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The role of ventral medial prefrontal cortex in social decisions: Converging evidence from fMRI and frontotemporal lobar degeneration
Abstract
The ventral medial prefrontal cortex (vmPFC) has been implicated in social and affectively influenced decision-making. Disease in this region may have clinical consequences for social judgments in patients with frontotemporal lobar degeneration (FTLD). To test this hypothesis, regional cortical activation was monitored with fMRI while healthy adults judged the acceptability of brief social scenarios such as cutting into a movie ticket line or going through a red light at 2 AM. The scenarios described: (i) a socially neutral condition, (ii) a variant of each scenario containing a negatively valenced feature, and (iii) a variant containing a positively valenced feature. Results revealed that healthy adults activated vmPFC during judgments of negatively valenced scenarios relative to positive scenarios and neutral scenarios. In a comparative behavioral study, the same social decision-making paradigm was administered to patients with a social disorder due to FTLD. Patients differed significantly from healthy controls, specifically showing less sensitivity to negatively valenced features. Comparative anatomical analysis revealed considerable overlap of vmPFC activation in healthy adults and vmPFC cortical atrophy in FTLD patients. These converging results support the role of vmPFC in social decision-making where potentially negative consequences must be considered.
... Brain regions associated with processing of objects (occipital), actions (posterior parietal and IFG), and others' mental states (VMPFC) were context-dependently activated when experiment subjects watched another person search for hidden objects, thus providing insights beyond findings obtained using artificial stimuli by suggesting that action comprehension in social contexts activates mental state processing areas in addition to the mirror neuron system ( Ramsey and Hamilton, 2012 ). The VMPFC was also activated in healthy subjects during perception of social actions with potentially negative consequences such as cutting in line ( Grossman et al., 2010 ). Furthermore, this activation overlapped with damaged brain areas in neurological patients with reduced sensitivity to negative consequences of inappropriate actions ( Grossman et al., 2010 ). ...
... The VMPFC was also activated in healthy subjects during perception of social actions with potentially negative consequences such as cutting in line ( Grossman et al., 2010 ). Furthermore, this activation overlapped with damaged brain areas in neurological patients with reduced sensitivity to negative consequences of inappropriate actions ( Grossman et al., 2010 ). Detecting errors committed by others in movie clips activated the striatum, TPJ, and IFG ( Jaaskelainen et al., 2016a ). ...
Using movies and narratives as naturalistic stimuli in human neuroimaging studies has yielded significant advances in understanding of cognitive and emotional functions. The relevant literature was reviewed, with emphasis on how the use of naturalistic stimuli has helped advance scientific understanding of human memory, attention, language, emotions, and social cognition in ways that would have been difficult otherwise. These advances include discovering a cortical hierarchy of temporal receptive windows, which supports processing of dynamic information that accumulates over several time scales, such as immediate reactions vs. slowly emerging patterns in social interactions. Naturalistic stimuli have also helped elucidate how the hippocampus supports segmentation and memorization of events in day-to-day life and have afforded insights into attentional brain mechanisms underlying our ability to adopt specific perspectives during natural viewing. Further, neuroimaging studies with naturalistic stimuli have revealed the role of the default-mode network in narrative-processing and in social cognition. Finally, by robustly eliciting genuine emotions, these stimuli have helped elucidate the brain basis of both basic and social emotions apparently manifested as highly overlapping yet distinguishable patterns of brain activity.
... Generally speaking, social cognition impairments have been identified in bvFTD patients including deficits in emotional expression [11], emotional recognition [12], theory of mind [13], empathy [14], and social decisions [15]. Some authors have suggested that bvFTD patients more specifically demonstrate impairments of moral cognition impacting cooperative behaviors [16,17], moral judgments [18,19], and the ability to respect moral and legal codes [18][19][20][21], therefore leading to antisocial and sometimes criminal behavior [22,23]. ...
... General impairment of emotional processing in bvFTD, as suggested by deficient performance in both the extra-moral and moral condition of the experimental test, is coherent with studies showing deficits in the expression of emotions [11] and of emotion recognition [36]. Similarly, deficits in social cognition have been shown in bvFTD including empathy [14], theory of mind [13] and social decisions [15]. In addition, our correlation analyses indicate that, in bvFTD, the processing of more general 'extra-moral' emotions and social cognition capacities (as measured by the SEA) deteriorate concomitantly with the decline of moral emotion processing. ...
... Generally speaking, social cognition impairments have been identified in bvFTD patients including deficits in emotional expression [11], emotional recognition [12], theory of mind [13], empathy [14], and social decisions [15]. Some authors have suggested that bvFTD patients more specifically demonstrate impairments of moral cognition impacting cooperative behaviors [16,17], moral judgments [18,19], and the ability to respect moral and legal codes [18][19][20][21], therefore leading to antisocial and sometimes criminal behavior [22,23]. ...
... General impairment of emotional processing in bvFTD, as suggested by deficient performance in both the extra-moral and moral condition of the experimental test, is coherent with studies showing deficits in the expression of emotions [11] and of emotion recognition [36]. Similarly, deficits in social cognition have been shown in bvFTD including empathy [14], theory of mind [13] and social decisions [15]. In addition, our correlation analyses indicate that, in bvFTD, the processing of more general 'extra-moral' emotions and social cognition capacities (as measured by the SEA) deteriorate concomitantly with the decline of moral emotion processing. ...
Background:
Emotions, with or without moral valence, appear to be altered in the behavioral variant of frontotemporal dementia (bvFTD) but the relative degree of moral emotion breakdown, which could be a marker of bvFTD diagnosis, remains unexplored.
Objective:
To assess moral emotions in bvFTD, to differentiate bvFTD from typical Alzheimer's disease (AD) based on moral emotion processing, and to provide a sensitive and specific assessment tool contributing to bvFTD diagnosis.
Methods:
We investigated moral emotions in 22 bvFTD patients, 15 patients with typical AD having positive CSF AD biomarkers, and 45 healthy controls. The 'Moral Emotions Assessment' task consisted in 42 scenarios exploring positive and negative moral emotions. To control for moral-specificity, we contrasted the 42 moral scenarios with 18 extra-moral scenarios eliciting the emotions without involving any inter-human moral context.
Results:
bvFTD patients were more impaired in emotion processing than AD patients and healthy controls and had significantly poorer performance in the processing of moral emotions than of emotions without moral valence. ROC analyses of data on moral scenarios showed a high area under the curve (83%), and indicated a cut-off score (< 37/42) for differentiating bvFTD from AD with a sensitivity of 82% and specificity of 73%.
Conclusion:
Our findings demonstrate that bvFTD patients have disorders in emotion processing which is mainly related to failure regarding moral emotions. They also show that this deficit is reliably detected by the 'Moral Emotions Assessment' which represents a sensitive and specific diagnostic tool detecting bvFTD and differentiating it from AD.
... Neuroimaging studies in FTLD report varying degrees of asymmetry in cortical disease burden in patients with a specific molecular pathology (Whitwell et al., 2005;Rohrer et al., 2011), including those with underlying tauopathy (FTLD-Tau) or TDP-43 proteinopathy (FTLD-TDP) (Mackenzie et al., 2010) and those constrained to clinical bvFTD suggest that the disease may have a propensity for affecting the right hemisphere, particularly ventral frontal regions (Seeley et al., 2008;Whitwell et al., 2009). Further, measures of social cognition in bvFTD, such as behavioural disinhibition (Mychack et al., 2001;Liu et al., 2004;Massimo et al., 2009;Grossman et al., 2010;Eslinger et al., 2011;Powers et al., 2014), loss of empathy and perspective-taking (Rankin et al., 2006;Eslinger et al., 2011;McMillan et al., 2013a;Healey et al., 2015), hyperorality (Woolley et al., 2007) and apathy (Massimo et al., , 2015Powers et al., 2014) have neuroimaging correlates in frontotemporal regions largely in the right hemisphere. However, patients with bvFTD also frequently have clinical deficits in executive functioning such as category naming fluency, and these impairments appear to be less clearly lateralized, with findings associated with frontal and temporal regions in both right and left hemispheres, depending on the specific task (Rascovsky et al., 2007;Libon et al., 2009;Cook et al., 2014). ...
... Exploratory clinical-pathological correlations examined more closely the relationship between FTD phenotype during life and asymmetric FTLD pathology. Neurodegeneration in the right OFC has been associated with early symptoms of behavioural disinhibition (Liu et al., 2004;Viskontas et al., 2007;Seeley et al., 2008;Grossman et al., 2010) and may be one of the earliest sites for the deposition of TDP-43 pathology in bvFTD (Brettschneider et al., 2014) and an early region of pathologic involvement in Pick's disease (Irwin et al., 2016a). Our finding of increased social disinhibition during life in patients with more right-predominant pathology in OFC grey matter at autopsy suggests these patients may have had right-predominant OFC dysfunction during life, which remained evident microscopically at end-stage disease. ...
Antemortem behavioural and anatomic abnormalities have largely been associated with right hemisphere disease in behavioural-variant frontotemporal dementia, but post-mortem neuropathological examination of bilateral hemispheres remains to be defined. Here we measured the severity of post-mortem pathology in both grey and white matter using a validated digital image analysis method in four cortical regions sampled from each hemisphere in 26 patients with behavioural-variant frontotemporal dementia, including those with frontotemporal degeneration (i.e. tau = 9, TDP-43 = 14, or FUS = 1 proteinopathy) or Alzheimer's pathology (n = 2). We calculated an asymmetry index based on the difference in measured pathology from each left-right sample pair. Analysis of the absolute value of the asymmetry index (i.e. degree of asymmetry independent of direction) revealed asymmetric pathology for both grey and white matter in all four regions sampled in frontototemporal degeneration patients with tau or TDP-43 pathology (P ≤ 0.01). Direct interhemispheric comparisons of regional pathology measurements within-subjects in the combined tauopathy and TDP-43 proteinopathy group found higher pathology in the right orbitofrontal grey matter compared to the left (P < 0.01) and increased pathology in ventrolateral temporal lobe grey matter of the left hemisphere compared to the right (P < 0.02). Preliminary group-wise comparisons between tauopathy and TDP-43 proteinopathy groups found differences in patterns of interhemispheric burden of grey and white matter regional pathology, with greater relative white matter pathology in tauopathies. To test the association of pathology measurement with ante-mortem observations, we performed exploratory analyses in the subset of patients with imaging data (n = 15) and found a direct association for increasing pathologic burden with decreasing cortical thickness in frontotemporal regions on ante-mortem imaging in tauopathy (P = 0.001) and a trend for TDP-43 proteinopathy (P = 0.06). Exploratory clinicopathological correlations demonstrated an association of socially-inappropriate behaviours with asymmetric right orbitofrontal grey matter pathology, and reduced semantically-guided category naming fluency was associated asymmetric white matter pathology in the left ventrolateral temporal region. We conclude that pathologic disease burden is distributed asymmetrically in behavioural-variant frontotemporal dementia, although not universally in the right hemisphere, and this asymmetry contributes to the clinical heterogeneity of the disorder. The basis for this asymmetric profile is enigmatic but may reflect distinct species or strains of tau and TDP-43 pathologies with propensities to spread by distinct cell- and region-specific mechanisms. Patterns of region-specific pathology in the right hemisphere as well as the left hemisphere may play a role in antemortem clinical observations, and these observations may contribute to antemortem identification of molecular pathology in frontotemporal degeneration.
... Sin embargo, todos los estudios reflejan una diferencia considerable entre los enfermos con EA y con vfDFT cuando son evaluados con dilemas morales personales. Así, parece que los pacientes con vfDFT conservan los conocimientos morales en teoría, expresados de manera impersonal, pero fracasan cuando los ponen en práctica a través de pruebas de dilemas morales personales, porque toman decisiones utilitarias (Baez et al., 2014;Bosch-Domenech, Nagel & Sanchez-Andres, 2010;Gleichgerrcht et al., 2011;Grossman et al., 2010;Kéri, 2014;Lough et al., 2006;Mendez, 2010) y sin activación de los marcadores somáticos (Damasio, Tranel & Damasio, 1990), en comparación con los pacientes que sufren una EA (Eslinger et al., 2007;Kéri, 2014;Mendez & Anderson, 2005;Rankin et al., 2006;), los cuales realizan correctamente las pruebas. Los pobres resultados en las pruebas de dilemas morales se correlacionaron significativamente con la atrofia de las regiones frontoorbital, temporal superior, asociativa visual y cingular posterior del hemisferio derecho, lo que confirma la implicación del hemisferio derecho en el razonamiento social (Zhou et al., 2010). ...
... Además, los pacientes con vfDFT, en particular los que tienen un daño en la región temporal anterior del hemisferio derecho, presentan un déficit semántico de los conceptos sociales (Zahn et al., 2009), pero no está claro si los errores en los juicios morales son debidos a un deterioro semántico del conocimiento social o a una disminución al acceso a dicho conocimiento (Grossman et al., 2010;Mendez & Shapira, 2009). No obstante, se han descrito casos de pacientes con vfDFT que a pesar de poseer un conocimiento de las reglas sociales intactas, cometían actos criminales, asociados a un hipometabolismo temporal anterior derecho (Mendez, 2010). ...
Hemos elaborado una revisión del estado actual del concepto emergente denominado consciencia del otro en la enfermedad de Alzheimer y la demencia frontotemporal de variante frontal. La consciencia del otro es la consciencia que uno mismo tiene de los otros congéneres y podría considerarse clave para la comprensión de las alteraciones del comportamiento en patologías neurodegenerativas tales como la enfermedad de Alzheimer y las demencias frontotemporales. La consciencia del otro es multifactorial e incluye los siguientes componentes: reconocimiento emocional del rostro, prosodia emocional, pragmática del lenguaje, mentalización, empatía y razonamiento social. Los distintos tipos de demencias afectan de forma heterogénea a los diferentes componentes de la consciencia del otro. En general, los estudios con pacientes de demencia frontotemporal de variante frontal observan más alteraciones de la consciencia del otro que los de los enfermos de Alzheimer. En concreto, en estos últimos se encuentran mayores dificultades en el componente de la pragmática del lenguaje, asociándolo a la severidad de su deterioro cognitivo, pero que no les impide tener un adecuado sentido social. Sin embargo, los estudios con pacientes con demencia frontotemporal de variante frontal observan importantes dificultades en cada uno de los componentes de la consciencia del otro y muestran graves problemas para regular adecuadamente su conducta social. Se necesitarían más estudios para comprender las relaciones de los distintos componentes de la consciencia del otro en las demencias para comprender sus trastornos del comportamiento.
... Participants also perform a "reward" condition where they receive points for responding more rapidly than during the initiation condition (reward and penalty conditions were administered in a randomly ordered manner across participants). In this study, we use the penalty condition to obtain a motivation score because previous work has shown that bvFTD patients are insensitive to negative feedback relative to positive feedback (Grossman et al., 2010). Unbeknownst to participants, all receive the same final amount for participation by adjusting the dollar value of a monetary unit. ...
... Poor motivation can occur in these patients because they have decreased reactivity to positive "reward" and negative "punishment" signals, thereby making goal-selection difficult (Levy and Dubois, 2006). Experimental evidence, however, has emphasized that patients with bvFTD and other diseases affecting OFC have the greatest difficulty interpreting "punishment" signals (Grossman et al., 2010). Impaired processing of negatively valenced emotional stimuli, such as failure to recognize anger or sadness in others, can contribute to poor empathy (Kipps et al., 2009) which has also been associated with disease in the OFC in FTD (Kamminga et al., 2015). ...
Background: Apathy, the major manifestation of impaired goal-directed behavior (GDB), is the most common neuropsychiatric syndrome associated with behavioral variant frontotemporal degeneration (bvFTD). The behavioral and biological mechanisms of apathy, however, are not well understood. We hypothesized that GDB has multiple components—including at least initiation, planning and motivation—and that GDB is supported by a network of multiple frontal brain regions. In this study, we examined this hypothesis by evaluating the selective breakdown of GDB in bvFTD, and relating these deficits to gray matter (GM) atrophy and white matter (WM) integrity.
Methods: Eighteen apathetic bvFTD participants and 17 healthy controls completed the Philadelphia Apathy Computerized Test (PACT). This test quantifies each of three components of GDB hypothesized to contribute to apathy. We then used regression analyses to relate PACT scores to GM atrophy and reduced white matter (WM) fractional anisotropy (FA) in bvFTD.
Results: Compared to controls, bvFTD participants demonstrated significant impairments in each of the three hypothesized components of GDB that contribute to apathy. Regression analyses related each component to disease in specific GM structures and associated WM tracts. Poor initiation thus was related to GM atrophy in anterior cingulate and reduced FA in the cingulum. Planning impairment was related to GM atrophy in dorsolateral prefrontal cortex and reduced FA in superior longitudinal fasciculus. Poor motivation was related to GM atrophy in orbitofrontal cortex (OFC) and reduced FA in uncinate fasciculus (UNC).
Conclusions: bvFTD patients have difficulty with initiation, planning and motivation components of GDB. These findings are consistent with the hypotheses that GDB encompasses at least three processes, that these are supported by a large-scale neural network within specific portions of the frontal lobe, and that degradation of any one of these prefrontal regions in bvFTD may contribute to apathy.
... These patients have difficulty on tasks requiring inference-making such as Theory of Mind (Adenzato et al., 2010;Gregory et al., 2002;Pardini et al., 2013;Torralva et al., 2007), although inference-making has rarely been assessed explicitly. Nevertheless, imaging studies (Adenzato et al., 2010;Eslinger et al., 2007;Gregory et al., 2002;Grossman, 2007;Grossman et al., 2010;Kipps and Hodges, 2006) and autopsy reports (e.g., Brettschneider et al., 2014;Hu et al., 2007) have shown that bvFTD affects dorsolateral, ventral and medial regions of the frontal lobe, and these regions have been implicated in several fMRI studies of social cognition (e.g., Amodio and Frith, 2006;Enrici et al., 2011;Frith and Frith, 2006;Mitchell, 2009;Saxe, 2006;Van Overwalle and Baetens, 2009) and reasoning (e.g., Bhatt et al., 2010;Bhatt and Camerer, 2005;Coricelli and Nagel, 2009;Goel, 2007;Prado and Noveck, 2007;Prado et al., 2014;Rypma et al., 2005). ...
... In this context, bvFTD patients appear to have minimal self-evaluation (Massimo et al., 2013;Rosen et al., 2010), and thus they may be less likely to evaluate the reasonableness of their responses. Likewise, they may have limited concern about the reward associated with a correct response or a penalty associated with an incorrect response (Grossman et al., 2010;McMillan et al., 2012a). Additional work is needed to evaluate these possibilities. ...
... Other studies concluded that the OFC plays a role in decision-making based on the valence of the stimuli (64,65). Additionally, the vmPFC is active when subjects feel socially accepted and comprehend rewarding social cues (66). Interestingly, specific impairments in the tendency of ASD patients to find social stimuli incentivizing or motivating are similar to those seen in humans with vmPFC lesions (67). ...
Social interaction is a complex behavior which requires the individual to integrate various internal processes, such as social motivation, social recognition, salience, reward, and emotional state, as well as external cues informing the individual of others’ behavior, emotional state and social rank. This complex phenotype is susceptible to disruption in humans affected by neurodevelopmental and psychiatric disorders, including autism spectrum disorder (ASD). Multiple pieces of convergent evidence collected from studies of humans and rodents suggest that the prefrontal cortex (PFC) plays a pivotal role in social interactions, serving as a hub for motivation, affiliation, empathy, and social hierarchy. Indeed, disruption of the PFC circuitry results in social behavior deficits symptomatic of ASD. Here, we review this evidence and describe various ethologically relevant social behavior tasks which could be employed with rodent models to study the role of the PFC in social interactions. We also discuss the evidence linking the PFC to pathologies associated with ASD. Finally, we address specific questions regarding mechanisms employed by the PFC circuitry that may result in atypical social interactions in rodent models, which future studies should address.
... A frontal lesion, especially when involving the orbitofrontal cortex, could impact these emotional mechanisms and consequently the generation of social emotions (Beer et al., 2006), such as pity or compassion that are underlined by such a distinction. These social emotions also play a role in decision-making (e.g., Grossman et al., 2010;Tasso et al., 2017), by supporting appropriate social behaviors and prosocial intentions (e.g., Goetz et al., 2010). ...
Introduction. – Although frequently observed in neurological disorders, social-cognitive deficits, which contribute to social behavior dysfunction, remain poorly assessed in clinical neuropsychology. A new task has been developed to better screen for these deficits.
Objectives. – REALSoCog was used in two case studies (SL, 41-years-old, severe head injury; DP, 66- years-old, Alzheimer’s disease) in order to pretest the task sensitivity to social-cognitive deficits due to neurological disorders.
Method. – Participants encountered several social situations in a virtual city allowing the assessment of (i) moral cognition, (ii) theory of mind (TOM; cognitive and affective), (iii) emotional empathy, and (iv) inappropriate behavioral intentions. SL’s performance was compared to 47 young adults and DP’s performance was compared to 45 older adults.
Results. – Results showed incongruence in patients’ felt emotions and a clear increase in inappropri- ate behavioral intentions despite relatively preserved transgression detection and TOM abilities in both patients.
Conclusion. – REALSoCog may help detect social behavioral disorders related to socio-cognitive deficits. Future studies are required for further validation.
... essa consente il controllo dell'impulsività e dell'aggressività permettendo all'individuo di modulare i comportamenti sociali (Carlson, 2016). La corteccia prefrontale ventromediale (vmPFC) si attiva soprattutto in situazioni in cui, nel contesto sociale, la presa di decisione potrebbe avere conseguenze negative (Grossman et al., 2010). La vmPFC ha attratto particolare attenzione per la possibilità di condurre studi su lesioni focali a carico di queste zone. ...
Because of their complexity, emotions are a very difficult phenomenon to define. For this reason, many theories have been proposed and different models have been developed to try to understand them better. In this review, we will limit ourselves to six main components that contribute to the emergence of emotions: environmental actors, attentional capacity, encoding, memory of events, appraisal, and emotional regulation.
Using the metaphor of a cube whose sides are interconnected and interact, we analyze each of these six elements and show how their articulation, starting from an affective core, enables the development of human emotions.
... Fifteen of these works studied the ToM domain: 13 employed a transverse design, and two used a longitudinal design. Among the first group, 11 (85%) studies documented significantly lower scores for patients than for healthy controls (Torralva et al., 2009(Torralva et al., , 2015Grossman et al., 2010;Custodio et al., 2015;Sedeno et al., 2016;Tabernero and Politis, 2016;Tabernero et al., 2017;Schroeter et al., 2018;Giovagnoli et al., 2019;Van den Stock et al., 2019;Lillo et al., 2020). The findings of the longitudinal studies were contradictory, since one study found that patients with bvFTD showed a greater deterioration than patients with other types of dementia , while the other study did not observe changes in ToM over time (Reus et al., 2018). ...
Background: Neurodegenerative diseases might affect social cognition in various ways depending on their components (theory of mind, emotional processing, attribution bias, and social perception) and the subtype of dementia they cause. This review aims to explore this difference in cognitive function among individuals with different aetiologies of dementia.
Methods:The following databases were explored: MEDLINE via PubMed, Cochrane Library, Lilacs, Web of Science, and PsycINFO. We selected studies examining social cognition in individuals with neurodegenerative diseases in which dementia was the primary symptom that was studied. The neurodegenerative diseases included Alzheimer's disease, Lewy body disease and frontotemporal lobar degeneration. The search yielded 2,803 articles.
Results: One hundred twenty-two articles were included in the present review. The summarised results indicate that people with neurodegenerative diseases indeed have deficits in social cognitive performance. Both in populations with Alzheimer's disease and in populations with frontotemporal dementia, we found that emotional processing was strongly affected. However, although theory of mind impairment could also be observed in the initial stages of frontotemporal dementia, in Alzheimer's disease it was only appreciated when performing highly complex task or in advanced stages of the disease.
Conclusions: Each type of dementia has a differential profile of social cognition deterioration. This review could provide a useful reference for clinicians to improve detection and diagnosis, which would undoubtedly guarantee better interventions.
Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020152562, PROSPERO, identifier: CRD42020152562.
... can lead to aberrant emotional responses (Koenigs et al., 2007;Zald and Andreotti, 2010;Hiser and Koenigs, 2018) and maladaptive decision-making in environments where emotional regulation may be useful (Grossman et al., 2010;Spaniol et al., 2019). Numerous studies suggest that subjective reward values are represented by vmPFC neural activity. ...
Standard economic indicators provide an incomplete picture of what we value both as individuals and as a society. Furthermore, canonical macroeconomic measures, such as GDP, do not account for non-market activities (e.g., cooking, childcare) that nevertheless impact well-being. Here, we introduce a computational tool that measures the affective value of experiences (e.g., playing a musical instrument without errors). We go on to validate this tool with neural data, using fMRI to measure neural activity in male and female human subjects performing a reinforcement learning task that incorporated periodic ratings of subjective affective state. Learning performance determined level of payment (i.e., extrinsic reward). Crucially, the task also incorporated a skilled performance component (i.e., intrinsic reward) which did not influence payment. Both extrinsic and intrinsic rewards influenced affective dynamics, and their relative influence could be captured in our computational model. Individuals for whom intrinsic rewards had a greater influence on affective state than extrinsic rewards had greater ventromedial prefrontal cortex (vmPFC) activity for intrinsic than extrinsic rewards. Thus, we show that computational modeling of affective dynamics can index the subjective value of intrinsic relative to extrinsic rewards, a “computational hedonometer” that reflects both behavior and neural activity that quantifies the affective value of experience.
... The effects of VMPC damage on emotion processing depend on context (Koenigs et al., 2007). Previous studies have shown that VMPFC activation appears to play a crucial role in evaluating the negative consequences of social decisionmaking (Grossman et al., 2010). In the current study, the cost of preventing one person from receiving a shock or helping one person prevent them from receiving a painful shock is equal to 5 CNY (approximately 0.77 US dollars). ...
Numerous experimental studies have replicated the social framing effect-the observation that people’s decisions related to economic benefits and feelings depend on the method of presentation. Previous neuroimaging studies have shown that the ventromedial prefrontal cortex (VMPFC) plays a part in the influence of framing and how individuals think about the feelings of others. Based on this, we used transcranial direct current stimulation (tDCS) to modulate neuronal activity in the VMPFC to determine the likelihood of a direct association between VMPFC activity and the social framing effect. Subsequently, in three stimulation treatments, we assessed the presence of the social framing effect, as demonstrated by a disparity between harm degree and help degree. The findings revealed a social framing effect in the participants in the control group and the sham treatment but no social framing effect in the participants in the anodal or cathodal treatments. Furthermore, sex differences were observed in the sham treatment’s social framing effect, whereas no sex differences were observed in the anodal or cathodal treatments. The participants tended to harm the victim after receiving anodal or cathodal tDCS over the VMPFC and did not change their helping behaviour in any stimulations. Consequently, a clear causal link between the behaviour of the VMPFC and the social framing effect was found in the present research.
... Ventromedial FC lesions that included subgenual sectors of the OFC were associated with a lack of guilt reported by caregivers (Koenigs et al., 2007). A study using fMRI and lesion information from patients with FTD showed that the ventromedial FC relates to the anticipation of negative consequences of social behaviour (Grossman et al., 2010), which is an important pre-requisite for experiencing guilt. ...
Social feelings have conceptual and empirical connections with affect and emotion. In this review, we discuss how they relate to cognition, emotion, behavior and well-being. We examne the functional neuroanatomy and neurobiology of social feelings and their role in adaptive social functioning. Existing neuroscience literature is reviewed to identify concepts, methods and challenges that might be addressed by social feelings research. Specific topic areas highlight the influence and modulation of social feelings on interpersonal affiliation, parent-child attachments, moral sentiments, interpersonal stressors, and emotional communication. Brain regions involved in social feelings were confirmed by meta-analysis using the Neurosynth platform for large-scale, automated synthesis of functional magnetic resonance imaging data. Words that relate specifically to social feelings were identfied as potential research variables. Topical inquiries into social media behaviors, loneliness, trauma, and social sensitivity, especially with recent physical distancing for guarding public and personal health, underscored the increasing importance of social feelings for affective and second person neuroscience research with implications for brain development, physical and mental health, and lifelong adaptive functioning.
... Second, we applied one of the standard co-registration methods, the mutual information matching algorithm, provided by a single tool (PNEURO) (35)(36)(37). Other co-registration algorithms, such as MRtrix and ANTs, may improve or lead to different results (38)(39)(40)(41). Further investigations utilizing multiple pipelines should be conducted. ...
Aims: This study aimed to analyze the performance of multi-atlas MRI-based parcellation for ¹²³ I-FP-CIT SPECT (DAT-SPECT) in healthy volunteers. The proposed method was compared with the SPECT-atlas-based and Bolt methods. ¹⁸ F-FE-PE2I-PET (DAT-PET) was used as a reference.
Methods: Thirty healthy subjects underwent DAT-SPECT, DAT-PET, and 3D-T1WI-MRI. We calculated the striatum uptake ratio (SUR/SBR), caudate uptake ratio (CUR), and putamen uptake ratio (PUR) for DAT-SPECT using the multi-atlas MRI-based method, SPECT-atlas-based method, and Bolt method. In the multi-atlas MRI-based method, the cerebellum, occipital cortex, and whole-brain were used as reference regions. The correlation of age with DAT-SPECT activity and the correlations of SUR/SBR, CUR, and PUR between DAT-SPECT and DAT-PET were calculated by each of the three methods.
Results: The correlation between age and SUR/SBR for DAT-SPECT based on the multi-atlas MRI-based method was comparable to that based on the SPECT-atlas-based method ( r = −0.441 to −0.496 vs. −0.488). The highest correlation between DAT-SPECT and DAT-PET was observed using the multi-atlas MRI-based method with the occipital lobe defined as the reference region compared with the SPECT-atlas-based and Bolt methods (SUR, CUR, and PUR: 0.687, 0.723, and 0.676 vs. 0.698, 0.660, and 0.616 vs. 0.655).
Conclusion: Multi-atlas MRI-based parcellation with the occipital lobe defined as the reference region was at least comparable to the clinical methods.
... In bvFTD associated with FTLD-Tau pathology, we observed greater GM pathology burden in ACG. ACG is a limbic region within the paralimbic salience network associated with bvFTD [63,64] and it appears to be associated with apathy [40] and limited self-appraisal [22,39]. Thus, both WM heterogeneity and GM heterogeneity appeared to contribute to clinical phenotype in FTLD-Tau. ...
Abstract Frontotemporal lobar degeneration proteinopathies with tau inclusions (FTLD-Tau) or TDP-43 inclusions (FTLD-TDP) are associated with clinically similar phenotypes. However, these disparate proteinopathies likely differ in cellular severity and regional distribution of inclusions in white matter (WM) and adjacent grey matter (GM), which have been understudied. We performed a neuropathological study of subcortical WM and adjacent GM in a large autopsy cohort (n = 92; FTLD-Tau = 37, FTLD-TDP = 55) using a validated digital image approach. The antemortem clinical phenotype was behavioral-variant frontotemporal dementia (bvFTD) in 23 patients with FTLD-Tau and 42 with FTLD-TDP, and primary progressive aphasia (PPA) in 14 patients with FTLD-Tau and 13 with FTLD-TDP. We used linear mixed-effects models to: (1) compare WM pathology burden between proteinopathies; (2) investigate the relationship between WM pathology burden and WM degeneration using luxol fast blue (LFB) myelin staining; (3) study regional patterns of pathology burden in clinico-pathological groups. WM pathology burden was greater in FTLD-Tau compared to FTLD-TDP across regions (beta = 4.21, SE = 0.34, p
... The vmPFC has been demonstrated to play a role in affect with subjective emotional experiences elicited by images and pleasurable music leading to changes in both vmPFC BOLD activity and regional cerebral blood flow (43)(44)(45). Damage to the vmPFC can lead to aberrant emotional responses (46)(47)(48) and maladaptive decisionmaking in environments where emotional regulation may be useful (49,50). Numerous studies suggest that subjective reward values are represented by vmPFC neural activity. ...
Standard economic indicators provide an incomplete picture of what we value both as individuals and as a society. Furthermore, canonical macroeconomic measures, such as GDP, do not account for non-market activities (e.g., cooking, childcare) that nevertheless impact well-being. Here, we introduce a computational tool that measures the affective value of experiences (e.g., playing a musical instrument without errors). We go on to validate this tool with neural data, using fMRI to measure neural activity in male and female human subjects performing a reinforcement learning task that incorporated periodic ratings of subjective affective state. Learning performance determined level of payment (i.e., extrinsic reward). Crucially, the task also incorporated a skilled performance component (i.e., intrinsic reward) which did not influence payment. Both extrinsic and intrinsic rewards influenced affective dynamics, and their relative influence could be captured in our computational model. Individuals for whom intrinsic rewards had a greater influence on affective state than extrinsic rewards had greater ventromedial prefrontal cortex (vmPFC) activity for intrinsic than extrinsic rewards. Thus, we show that computational modelling of affective dynamics can index the subjective value of intrinsic relative to extrinsic rewards, a ‘computational hedonometer’ that reflects both behavior and neural activity that quantifies the affective value of experience.
SIGNIFICANCE STATEMENT
Traditional economic indicators are increasingly recognized to provide an incomplete picture of what we value as a society. Standard economic approaches struggle to accurately assign values to non-market activities that nevertheless may be intrinsically rewarding, prompting a need for new tools to measure what really matters to individuals. Using a combination of neuroimaging and computational modeling, we show that despite their lack of instrumental value, intrinsic rewards influence subjective affective state and ventromedial prefrontal cortex activity. The relative degree to which extrinsic and intrinsic rewards influence affective state is predictive of their relative impacts on neural activity, confirming the utility of our approach for measuring the affective value of experiences and other non-market activities in individuals.
... There are a number of studies that have reported various social cognitive abnormalities in bvFTD patients, including abnormalities in Theory of Mind (ToM) detection of gaze direction, and recognition of facial and/or prosodic emotional expressions, in particular negative emotions such as fear and anger (Gregory et al., 2002;Keane et al., 2002;Rosen et al., 2004;Lavenu and Pasquier, 2005;Diehl-Schmid et al., 2007;Eslinger et al., 2007;Kessels et al., 2007;Werner et al., 2007;Bediou et al., 2009). There is evidence that bvFTD patients have difficulty identifying social concepts, judging appropriate actions in social dilemmas, recognizing sarcasm, and differentiating minor social transgressions from serious moral violations (Mendez et al., 2005;Lough et al., 2006;Eslinger et al., 2007;Grossman et al., 2010;Shany-Ur et al., 2012). Although svPPA and nfvPPA are primarily identified as language disorders, social cognition can also be affected (Neary et al., 1998;Hodges and Miller, 2001;Multani et al., 2017) and loss of emotion detection and decreased empathy has been reported in svPPA and nvPPA (Multani et al., 2017). ...
Objective
To determine the relationship between alterations in resting state functional connectivity and social cognition dysfunction among patients with frontotemporal dementia (FTD), Alzheimer’s disease (AD), Parkinson’s disease (PD), and healthy controls (HC).
Methods
Fifty-seven participants (FTD = 10, AD = 18, PD = 19, and HC = 10) underwent structural and functional imaging and completed the Awareness of Social Inference Test-Emotion Evaluation Test (TASIT-EET), Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) scale, Revised Self-Monitoring Scale (RSMS), Interpersonal Reactivity Index (IRI), and Social Norms Questionnaire (SNQ). A multi-variate pattern analysis (MVPA) was carried out to determine activation differences between the groups. The clusters from the MVPA were used as seeds for the ROI-to-voxel analysis. Relationship between social cognition deficits and uncinate integrity was also investigated.
Results
BOLD signal activation differed among the four groups of AD, PD, FTD, and HC in the left inferior temporal gyrus-anterior division [L-ITG (ant)], right central opercular cortex (R-COp), right supramarginal gyrus, posterior division (R-SMG, post), right angular gyrus (R-AG), and R-ITG. The BOLD co-activation of the L-ITG (ant) with bilateral frontal pole (FP) and paracingulate gyrus was positively associated with IRI-perspective taking (PT) (r = 0.38, p = 0.007), SNQ total (r = 0.37, p = 0.009), and TASIT-EET (r = 0.47, p < 0.001).
Conclusion
Patients with neurodegenerative diseases showed alterations in connectivity in brain regions important for social cognition compared with HCs. Functional connectivity correlated with performance on social cognition tasks and alterations could be responsible for some of the social cognition deficits observed in all neurodegenerative diseases.
... Loss of guilt was also reported by caregivers (Koenigs et al., 2007), and associated with decreased prosocial decisions in economic games (Krajbich et al., 2009) in patients with ventromedial FC lesions that included subgenual sectors of the orbitofrontal cortex. Converging evidence from fMRI and patients with FTD linked the ventromedial FC to the anticipation of negative consequences of social behaviour (Grossman et al., 2010). Less evidence is available on the behavioural effects of the subcortical parts of the basal forebrain in humans, but hypothalamic lesions were associated with aggressive behaviour (Haugh and Markesbery, 1983;Weissenberger et al., 2001), although endocrine disturbances may have played a role. ...
... This has not been observed in our group of bvFTD patients. Such a default of the valuation system has been clearly demonstrated in bvFTD patients as well as in human and non-human primates with ventromedial focal lesions (19,(36)(37)(38). (2) Regardless of their reward valuation abilities, bvFTD patients would have an inability to transfer this value into action. ...
Apathy is one of the six clinical criteria for the behavioral variant of frontotemporal dementia (bvFTD), and it is almost universal in this disease. Although its consequences in everyday life are debilitating, its underlying mechanisms are poorly known, its assessment is biased by subjectivity and its care management is very limited. In this context, we have developed “ECOCAPTURE,” a method aimed at providing quantifiable and objective signature(s) of apathy in order to assess it and identify its precise underlying mechanisms. ECOCAPTURE consists of the observation and recording of the patient's behavior when the participant is being submitted to a multiple-phase scenario reproducing a brief real-life situation. It is performed in a functional exploration platform transformed into a fully furnished waiting room equipped with a video and sensor-based data acquisition system. This multimodal method allowed video-based behavior analyses according to predefined behavioral categories (exploration behavior, sustained activities or inactivity) and actigraphy analyses from a 3D accelerometer. The data obtained were also correlated with behavioral/cognitive tests and scales assessing global cognitive efficiency, apathy, cognitive disinhibition, frontal syndrome, depression and anxiety. Here, bvFTD patients (n = 14) were compared to healthy participants (n = 14) during the very first minutes of the scenario, when the participants discovered the room and were encouraged to explore it. We showed that, in the context of facing a new environment, healthy participants first explored it and then engaged in sustained activities. By contrast, bvFTD patients were mostly inactive and eventually explored this new place, but in a more irregular and less efficient mode than normal subjects. This exploration deficit was correlated with apathy, disinhibition and cognitive and behavioral dysexecutive syndromes. These findings led us to discuss the presumed underlying mechanisms responsible for the exploration deficit (an inability to self-initiate actions, to integrate reward valuation and to inhibit involuntary behavior). Altogether, these results pave the way for simple and objective assessment of behavioral changes that represents a critical step for the evaluation of disease progression and efficacy of treatment in bvFTD.
... This has not been observed in our group of bvFTD patients. Such a default of the valuation system has been clearly demonstrated in bvFTD patients as well as in human and non-human primates with ventromedial focal lesions (19,(36)(37)(38). (2) Regardless of their reward valuation abilities, bvFTD patients would have an inability to transfer this value into action. ...
Apathy is one of the six clinical criteria for the behavioral variant of frontotemporal dementia (bvFTD), and it is almost universal in this disease. Although its consequences in everyday life are debilitating, its underlying mechanisms are poorly known, its assessment is biased by subjectivity and its care management is very limited. In this context, we have developed “ECOCAPTURE,” a method aimed at providing quantifiable and objective signature(s) of apathy in order to assess it and identify its precise underlying mechanisms. ECOCAPTURE consists of the observation and recording of the patient's behavior when the participant is being submitted to a multiple-phase scenario reproducing a brief real-life situation. It is performed in a functional exploration platform transformed into a fully furnished waiting room equipped with a video and sensor-based data acquisition system. This multimodal method allowed video-based behavior analyses according to predefined behavioral categories (exploration behavior, sustained activities or inactivity) and actigraphy analyses from a 3D accelerometer. The data obtained were also correlated with behavioral/cognitive tests and scales assessing global cognitive efficiency, apathy, cognitive disinhibition, frontal syndrome, depression and anxiety. Here, bvFTD patients (n = 14) were compared to healthy participants (n = 14) during the very first minutes of the scenario, when the participants discovered the room and were encouraged to explore it. We showed that, in the context of facing a new environment, healthy participants first explored it and then engaged in sustained activities. By contrast, bvFTD patients were mostly inactive and eventually explored this new place, but in a more irregular and less efficient mode than normal subjects. This exploration deficit was correlated with apathy, disinhibition and cognitive and behavioral dysexecutive syndromes. These findings led us to discuss the presumed underlying mechanisms responsible for the exploration deficit (an inability to self-initiate actions, to integrate reward valuation and to inhibit involuntary behavior). Altogether, these results pave the way for simple and objective assessment of behavioral changes that represents a critical step for the evaluation of disease progression and efficacy of treatment in bvFTD.
... It has been suggested that the gray matter and white matter structures in frontal and temporal parts of the brain comprise the critical components of a large scale network which is important in regulating the GDB (Brown and Pluck 2000). The role of orbital and medial regions of inferior temporal lobe in value and reward-related information has been demonstrated previously (Grossman et al. 2010). Thus, it is possible that the degeneration of these frontal white matter projections to temporal areas may interfere with motivation and GDB. ...
Neuroanatomical correlates of apathy and disinhibition, behavioral abnormalities in behavioral variant Frontotemporal dementia (bvFTD) remain unclear. In this study 45 participants (25 bvFTD patients and 20 controls) provided data on clinical, neuropsychological, behavioral (on Frontal Systems Behavior (FrSBe) Scale), cortical volume (on voxel-based morphometry (VBM)) and tract based spatial fractional anisotropy ((FA) on magnetic resonance imaging (MRI), allowing examination of the neural correlates of apathy and disinhibition. The patients with bvFTD had predominant grey matter loss and corresponding white matter fractional anisotropy reduction in the frontal and temporal lobe compared to the controls. Grey matter loss in frontal, temporal and limbic structures correlated with apathy and degeneration in temporal limbic brain areas correlated with disinhibition. FA changes in inferior fronto-occipital fasciculus and forceps minor correlated with apathy and fibre integrity changes in the superior longitudinal fasciculus correlated with disinhibition. The current study suggests that apathy and disinhibition arises due to changes in the frontal, temporal and limbic brain areas in bvFTD.
... This led to the hypothesis that such hypoconnectivity might contribute to SCH patients' social-cognitive impairment (Holt et al., 2011). The ventromedial prefrontal cortex (vmPFC) forms projections to the limbic regions (Ongür and Price, 2000;Young et al., 1994), which play an important role in social and emotional decision-making (Bechara, 2000;Grossman et al., 2010;Koenigs and Tranel, 2007;Moretti et al., 2009;van den Bos and Guroglu, 2009). Indeed, one study revealed an association between hypoconnectivity within the vmPFC and abnormal emotion regulation in chronic SCH patients (Fan et al., 2013). ...
Patients with schizophrenia often demonstrate impairment in social-cognitive functions as well as disturbances in large-scale network connectivity. The ventro-medial prefrontal cortex (vmPFC) is a core region of the default mode network, with projections to limbic structures. It plays an important role in social and emotional decision making. We investigated whether resting-state functional connectivity (FC) relates to the cognitive and affective domains of Theory of mind (ToM). Twenty-three schizophrenia patients (SCH) and 19 healthy controls (HC) underwent resting-state fMRI scanning. vmPFC seed connectivity was correlated with behavioral measures assessing ToM domains. SCH performed less well than HC in both ToM task domains. An analysis of the resting-state FC revealed that SCH had reduced connectivity from the vmPFC to the subcallosal cortex, right amygdala, and right hippocampus as a function of behavioral scores in both ToM domains. Within-group analyses indicated that in HC, the performance in ToM was positively associated with fronto-amygdalar resting-state connectivity, whereas in SCH, the performance in ToM was negatively associated with the fronto-subcallosal connectivity. Differences in the pattern of the resting-state fronto-limbic connectivity and its associations with performance in ToM tasks between the two study groups might represent a different setup for processing social information in patients with schizophrenia.
... BvFTD patients also show reduced sensitivity to negative social outcomes in social scenarios (e.g. cutting in line at a movie theatre) (Grossman et al., 2010) and reduced prosocial behaviour (e.g. sharing resources when personal gain is not at stake, or giving money to less-fortunate others) (O'Callaghan et al., 2016;Sturm et al., 2017). ...
Behavioural-variant frontotemporal dementia is characterized by a number of ostensibly disparate clinical features, which have largely been considered independently. This Update proposes an integrated conceptual framework for these symptoms, by bringing together findings from animal studies, functional neuroimaging and behavioural neurology. The combined evidence indicates that many of the clinical symptoms--such as altered eating behaviour; overspending and susceptibility to scams; reduced empathy and socially inappropriate behaviour; apathy and stereotyped/ritualistic behaviour--can be conceptualized as a common underlying deficiency in goal-directed behaviour and the concomitant emergence of habits. This view is supported by similarities between the characteristic patterns of frontostriatal and insular atrophy in behavioural-variant frontotemporal dementia and the circuitry of homologous brain regions responsible for goal-directed and habitual behaviour in animals. Appreciating the impact of disturbance in goal-directed behaviour provides a new, integrated understanding of the common mechanisms underpinning prototypical clinical symptoms in behavioural-variant frontotemporal dementia. Furthermore, by drawing parallels between animal and clinical research, this translational approach has important implications for the development and evaluation of novel therapeutic treatments, from animal models through to behavioural interventions and clinical trials in humans.
... A more complete understanding of the stimulus correlates of deficient internal consistency may also carry implications for theories of the cognitive ontology (Poldrack, 2010) of decision-making and its neural correlates. For example, this would add to a growing body of research suggesting the presence of two distinct executive function systems: a dorsal "cognitive" system and a ventral "socialaffective" system (Barbey, Koenigs, & Grafman, 2013;Floden et al., 2008;Gläscher et al., 2012;Grossman et al., 2010;Robinson, Calamia, Gläscher, Bruss, & Tranel, 2014;Stuss & Levine, 2002;Tsuchida & Fellows, 2009). ...
Objective:
A well-documented effect of focal ventromedial prefrontal cortex (vmPFC) damage is a deficit in real-world decision making. An important aspect of this deficit may be a deficiency in "internal consistency" during social decision making-that is, impaired congruence between expressed preferences versus actual behavioral choices. An example of low internal consistency would be if one expressed the desire to marry someone with impeccable moral character, yet proceeded to marry someone convicted of multiple felonies. Here, we used a neuropsychological approach to investigate neural correlates of internal consistency in complex decision making.
Method:
Sixteen individuals with focal vmPFC lesions, 16 brain damage comparison individuals, and 16 normal comparison individuals completed a 3-option forced-choice preference task in which choices were made using attribute sets. Participants also completed visual-analogue preference ratings to indicate how much they liked each option, and rated the influence of each attribute on their decision making. Options were either social (potential spouses) or nonsocial (potential houses). Internal consistency for a trial was defined as agreement between the choice and the most positively rated option.
Results:
A mixed design analysis of variance revealed that internal consistency between choices and preferences derived from summed attribute ratings was significantly lower for the vmPFC group relative to comparison participants, but only in the social condition (pη2 = .09), 95% CI [.002, .163].
Conclusions:
Internal consistency during social decisions may be deficient in patients with vmPFC damage, leading to a discrepancy between preferences and choices. The vmPFC may provide an important neural mechanism for aligning behavioral choices with expressed preferences. (PsycINFO Database Record
... Evidence from functional studies (fMRI) implicates the dorsolateral PFC (dlPFC) and anterior cingulate areas in the performance of metacognitive tasks such as the Tower of Hanoi (Unterrainer et al., 2004), digit span (Yoon et al., 2007) and WCST (Wilmsmeier et al., 2010). On the other hand, fMRI studies with patients with frontotemporal degeneration implicate the ventromedial PFC in the mechanisms of emotional/social decision (Grossman et al., 2010; for a review of the PFC involvement in social EF, see Bicks et al., 2015). ...
Executive function (EF) has been defined as a multifaceted construct that involves a variety of high-level cognitive abilities such as planning, working memory, mental flexibility, and inhibition. Being able to identify deficits in EF is important for the diagnosis and monitoring of several neurodegenerative disorders, and thus their assessment is a topic of much debate. In particular, there has been a growing interest in the development of neuropsychological screening tools that can potentially provide a reliable quick measure of EF. In this review, we critically discuss the four screening tools of EF currently available in the literature: Executive Interview-25 (EXIT 25), Frontal Assessment Battery (FAB), INECO Frontal Screening (IFS), and FRONTIER Executive Screen (FES). We first describe their features, and then evaluate their psychometric properties, the existing evidence on their neural correlates, and the empirical work that has been conducted in clinical populations. We conclude that the four screening tools generally present appropriate psychometric properties, and are sensitive to impairments in EF in several neurodegenerative conditions. However, more research will be needed mostly with respect to normative data and neural correlates, and to determine the extent to which these tools add specific information to the one provided by global cognition screening tests. More research directly comparing the available tools with each other will also be important to establish in which conditions each of them can be most useful.
... They have trouble even recognizing negative emotion (Goodkind et al., 2015). They are less sensitive to negatively valenced contextual features in social decisions (Grossman et al., 2010). These behaviours could represent different facets of the same problem with reduced sensitivity to negative valence. ...
During reward processing individuals weigh positive and negative features of a stimulus to determine whether they will pursue or avoid it. Though patients with behavioural variant frontotemporal dementia display changes in their pursuit of rewards, such as food, alcohol, money, and sex, the basis for these shifts is not clearly established. In particular, it is unknown whether patients' behaviour results from excessive focus on rewards, insensitivity to punishment, or to dysfunction in a particular stage of reward processing, such as anticipation, consumption, or action selection. Our goal was to determine the nature of the reward deficit in behavioural variant frontotemporal dementia and its underlying anatomy. We devised a series of tasks involving pleasant, unpleasant, and neutral olfactory stimuli, designed to separate distinct phases of reward processing. In a group of 25 patients with behavioural variant frontotemporal dementia and 21 control subjects, diagnosis by valence interactions revealed that patients with behavioural variant frontotemporal dementia rated unpleasant odours as less aversive than did controls and displayed lower skin conductance responses when anticipating an upcoming aversive odour. Subjective pleasantness ratings and skin conductance responses did not differ between behavioural variant frontotemporal dementia and controls for pleasant or neutral smells. In a task designed to measure the effort subjects would expend to smell or avoid smelling a stimulus, patients with behavioural variant frontotemporal dementia were less motivated, and therefore less successful than control subjects, at avoiding what they preferred not to smell, but had equivalent success at obtaining stimuli they found rewarding. Voxel-based morphometry of patients with behavioural variant frontotemporal dementia revealed that the inability to subjectively differentiate the valence of pleasant and unpleasant odours correlated with atrophy in right ventral mid-insula and right amygdala. High pleasantness ratings of unpleasant stimuli correlated with left dorsal anterior insula and frontal pole atrophy. These findings indicate that insensitivity to negative information may be a key component of the reward-seeking behaviours in behavioural variant frontotemporal dementia, and may relate to degeneration of structures that are involved in representing the emotional salience of sensory information.
... Here, we focus on behavioural-variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD). Patients with bvFTD show progressive changes in personality and social interactions, with disturbance in emotion processing (Kumfor, Irish, Hodges, & Piguet, 2013a), empathy (Dermody et al., 2016), Theory of Mind (Le Bouc et al., 2012), social reward processing and decision making (Grossman et al., 2010;Perry, Sturm, Wood, Miller, & Kramer, 2015), compliance with social norms (O'Callaghan et al., 2016) and strategic social bargaining (Melloni et al., 2016). Of particular relevance, overly friendly or gullible behaviours are frequently reported in bvFTD (Pressman & Miller, 2014), suggesting distinct alterations in processing socially relevant information. ...
... We extracted the voxel grey matter volumes in our two a priori regions of interest (ROIs): frontopolar cortex (Brodmann Area[BA]10; MNI:-2, 66, 20) and right superior ATL (MNI: 58, 0,-12) and our two control regions: subgenual cingulate cortex (MNI:-4, 23,-5) and left superior ATL (mirror region of the right) using 6 mm radius spheres around centre coordinates from our previous paper revealing functional connectivity changes in this network in major depressive disorder which is associated with overgeneralized interpretations of social behaviour (Green et al., 2012) using the Marsbar toolbox (Brett et al., 2002). The subgenual cingulate was chosen as a control region because it is part of a posterior ventromedial frontal region that has been associated with impaired judgments of acceptability of social rule violations in patients with frontotemporal lobar degeneration(Grossman et al., 2010) and is functionally connected with our right superior ATL region whilst evaluating social behaviour (Green et al., 2010). ...
Inappropriate social behaviour is an early symptom of frontotemporal lobar degeneration (FTLD) in both behavioural variant frontotemporal dementia (bvFTD) and semantic dementia (SD) subtypes. Knowledge of social behaviour is essential for appropriate social conduct. The superior anterior temporal lobe (ATL) has been identified as one key neural component for the conceptual knowledge of social behaviour, but it is unknown whether this is dissociable from knowledge of the consequences of social behaviour. Here, we used a newly-developed test of knowledge about long-term and short-term consequences of social behaviour to investigate its impairment in patients with FTLD relative to a previously-developed test of social conceptual knowledge. We included 19 healthy elderly control participants and 19 consecutive patients with features of bvFTD or SD and defined dissociations as performance differences between tasks for each patient (Bonferroni-corrected p<.05). Knowledge of long-term consequences was selectively impaired relative to short-term consequences in five patients and the reverse dissociation occurred in one patient. Six patients showed a selective impairment of social concepts relative to long-term consequences with the reverse dissociation occurring in one patient. These results corroborate the hypothesis that knowledge of long-term consequences of social behaviour is dissociable from knowledge of short-term consequences, as well as of social conceptual knowledge. Confirming our hypothesis, we found that patients with more marked grey matter volume loss in frontopolar relative to right superior ATL regions of interest exhibited poorer knowledge of the long-term consequences of social behaviour relative to the knowledge of its conceptual meaning and vice versa (n=15). These findings support the hypothesis that frontopolar and ATL regions represent distinct aspects of social knowledge. This suggests that rather than being unable to suppress urges to behave inappropriately, FTLD patients often lose the knowledge of what appropriate social behaviour is and can therefore not be expected to behave accordingly.
... She also used social rules incorrectly as half of her justifications were inappropriate. Her deficits can be attributed either to anterior temporal atrophy, which correlates with loss of social semantic knowledge [30] or to frontal atrophy related to impaired social reasoning [31]. ...
Although frontal presentations of Alzheimer’s disease (fv-AD) have already been described in the literature, we still know little about patients’ social cognitive abilities, especially their theory of mind (ToM). We report the case of FT, a 61-year-old woman who was diagnosed with fv-AD. Two assessments of social cognition, using a false-belief task, the Reading the Mind in the Eyes test, and a task probing knowledge of social norms, were performed one year apart. FT exhibited cognitive ToM and social knowledge deficits from the onset. Affective ToM was initially preserved, but deteriorated as the disease progressed.
... 125 Accordingly, such patients can show seemingly dis inhibited and bizarre behavior when making decisions, owing in part to their insensiti vity to negative feedback and risky consequences. 126 In contrast to the literature on economic decision making in bvFTD, the evidence regarding this process in semantic dementia is scarce. Again, this may reflect the challenge of designing complex tasks that are not constrained by the semantic comprehension deficits in this patient population. ...
Converging evidence suggests that when individuals are left to think to themselves, a so-called default network of the brain is engaged, allowing the individual to daydream, reflect on their past, imagine possible future scenarios, and consider the viewpoints of others. These flexible self-relevant mental explorations enable the anticipation and evaluation of events before they occur, and are essential for successful social interactions. Such self-projective efforts are particularly vulnerable to disruption in frontotemporal dementia (FTD), a neurodegenerative disorder involving damage to the frontal and temporal lobes of the brain. In this Review, we explore how the progressive degeneration of the neural networks in two subtypes of FTD—the behavioral variant and semantic dementia—affects key structures of the default network and putative self-projective functions. We examine the available evidence from studies of autobiographical memory, episodic future thinking, theory of mind, moral reasoning, and economic decision-making in these neurodegenerative diseases. Finally, we propose that the mapping of default-network functions onto discrete subsystems of the default network may need revision in light of neuropsychological and clinical evidence from studies in patients with FTD.
... Investigations of the mechanisms of social and interpersonal behavior in bvFTD have employed a range of methods. These include social perception and recognition of emotions and mental states through facial and verbal expressions (Keane, Calder, Hodges, & Young, 2002;Kessels et al., 2007;Kipps, Nestor, Acosta-Cabronero, Arnold, & Hodges, 2009;Werner et al., 2007), mentalizing or Theory of Mind (the attribution of thoughts, feelings, and beliefs) (Adenzato, Cavallo, & Enrici, 2010;Fernandez-Duque, Baird, & Black, 2009;Gregory et al., 2002), assessment of emotional and cognitive empathy (Baez et al., 2014;Eslinger et al., 2011;Lough et al., 2006;Rankin et al., 2006), and corresponding aspects of executive functions (Eslinger et al., 2007;Gleichgerrcht, Torralva, Roca, & Manes, 2010;Grossman et al., 2010;Torralva, Roca, Gleichgerrcht, Bekinschtein, & Manes, 2009). However, there have been few studies on social attribution abilities in bvFTD, specifically animacy, or the attribution of being alive, and the related agency, or the attribution of intrinsically-driven action with or without animacy. ...
Impaired attribution of animacy (state of living or being sentient) and of agency (capability of intrinsically-driven action) may underlie social behavior disturbances in behavioral variant frontotemporal dementia (bvFTD). We presented the Heider and Simmel film of moving geometric shapes to 11 bvFTD patients, 11 Alzheimer’s disease (AD) patients, and 12 healthy controls (HCs) and rated their recorded verbal responses for animacy attribution and agency attribution. All participants had skin conductance (SC) continuously recorded while viewing the film, and all dementia participants underwent magnetic resonance imaging (MRI) for regions of interest. The bvFTD patients, but not the AD patients, were impaired in animacy attribution, compared to the HCs. In contrast, both bvFTD and AD groups were impaired in agency attribution, compared to the HCs, and only the HCs had increasing SC responsiveness during viewing of the film. On MRI analysis of cortical thicknesses, animacy scores significantly correlated across groups with the right pars orbitalis and opercularis; agency scores with the left inferior and superior parietal cortices and the supramarginal gyrus; and both scores with the left cingulate isthmus involved in visuospatial context. These findings suggest that bvFTD is specifically associated with impaired animacy attribution from right inferior frontal atrophy. In contrast, both dementias may have impaired agency attribution from left parietal cortical atrophy and absent SC increases during the film, a sympathetic indicator of attribution of a social “story” to the moving shapes. These findings clarify disease-related changes in social attribution and corroborate the neuroanatomical origins of animacy and agency.
... The motivational subtype would improve less in response (measured by total latency) to financial incentive-and particularly the penalty condition-than the initiation and planning patients under the simpler planning condition, but would not have slowed initiation times, and would not have disproportionally slowed performance for the complex planning condition. This insensitivity to penalty is supported by previous studies that show bvFTD patients are insensitive to negative consequences but respond to a reward (Farag et al., 2010;Grossman et al., 2010;Torralva, Roca, Gleichgerrcht, Bekinschtein, & Manes, 2009 Web-based data-management system. I anonymized data through the use of alpha numeric identification numbers, and kept the key for the identification in a separate password-protected site. ...
The syndrome of apathy, defined as a reduction in goal-directed behavior (GDB), has profound consequences for morbidity and mortality in the patient and for family-caregiver burden. Apathy is one of the primary neuropsychiatric syndromes associated with the disruption of the frontal-striatal system, but the behavioral and biological mechanisms underlying apathy are not well understood. Apathy is especially prevalent in behavioral variant frontotemporal degeneration (bvFTD). In a sample of 20 apathetic adults with bvFTD and 17 normal controls (NC), impairments in three components of GDB--initiation, planning and motivation--were examined using a novel computerized reaction time test. Employing structural neuroimaging techniques, I then examined the neural basis of GDB in these apathetic bvFTD participants. I found evidence that apathy is associated with an impairment in any of the three GDB components. Initiation, planning, and motivation each map onto three distinct brain regions in the frontal lobe that work together in a large-scale neural network. Furthermore, I was able to identify participants with specific subtypes of apathy, depending on the impaired GDB mechanism. I developed and submitted a proposal for continued study of the phenomenon; the proposal was awarded. The long-term potential impact of this beginning program of research is profound for patients with neurodegenerative disease, their caregivers, and families. Current treatment of apathy has been hindered due to poor understanding of the mechanisms underlying this condition. This work will lead to a better understanding of these mechanisms and structures fundamental to the behavior, and, with this knowledge, tailored interventions can be designed and implemented by professional and lay caregivers. Thus, a more precise characterization of apathy will allow providers to implement the most appropriate therapy for a given patient.
... 125 Accordingly, such patients can show seemingly dis inhibited and bizarre behavior when making decisions, owing in part to their insensiti vity to negative feedback and risky consequences. 126 In contrast to the literature on economic decision making in bvFTD, the evidence regarding this process in semantic dementia is scarce. Again, this may reflect the challenge of designing complex tasks that are not constrained by the semantic comprehension deficits in this patient population. ...
... We hypothesized that guilt and shame could be dissociated in terms of distinct neurodevelopmental correlates within social brain regions. Specifically, we hypothesized that guilt would be uniquely associated with the development of SGC/vmPFC, by virtue of the role of these regions in empathy (Zahn et al., 2009a), and anticipation of the social-emotional consequences (e.g., feeling guilty) in social decision-making (Grossman et al., 2010;Harrison et al., 2012;Moll et al., 2011). We also hypothesized that guilt would be associated with the development of the lOFC, given evidence for activation of this region when social cues initiate a change of current behavior (Blair and Cipolotti, 2000). ...
Investigating how brain development during adolescence and early adulthood underlies guilt- and shame-proneness may be important for understanding risk processes for mental disorders. The aim of this study was to investigate the neurodevelopmental correlates of interpersonal guilt- and shame-proneness in healthy adolescents and young adults using structural magnetic resonance imaging (sMRI). Sixty participants (age range: 15 to 25) completed sMRI and self-report measures of interpersonal guilt- and shame-proneness. Independent of interpersonal guilt, higher levels of shame-proneness were associated with thinner posterior cingulate cortex (PCC) thickness and smaller amygdala volume. Higher levels of shame-proneness were also associated with attenuated age-related reductions in thickness of lateral orbitofrontal cortex (lOFC). Our findings highlight the complexities in understanding brain-behavior relationships during the adolescent/young adult period. Results were consistent with growing evidence that accelerated cortical thinning during adolescence may be associated with superior socioemotional functioning. Further research is required to understand the implications of these findings for mental disorders characterized by higher levels of guilt and shame.
... She also used social rules incorrectly as half of her justifications were inappropriate. Her deficits can be attributed either to anterior temporal atrophy, which correlates with loss of social semantic knowledge [30] or to frontal atrophy related to impaired social reasoning [31]. ...
Introduction
Le diagnostic de démence fronto-temporale (DFT) repose sur une altération du comportement associée à une atteinte des structures cérébrales frontales ou temporales. Les patients présentent des troubles exécutifs et de la cognition sociale. Ce profil est distinct du tableau sémiologique classique de maladie d’Alzheimer (MA). Les critères diagnostiques de MA soulignent, toutefois, l’existence de variantes atypiques aphasiques ou visuo-constructives. Nous rapportons ici le cas d’une patiente présentant des troubles comportementaux au premier plan.
Matériel et méthode
Madame T, 61 ans, comptable, a consulté pour des troubles mnésiques et un manque du mot évoluant depuis 2 ans. Spontanément, elle rapporte un changement d’humeur et une baisse de motivation confirmés par ses proches avec des conséquences dans sa vie personnelle et professionnelle. Le bilan neuropsychologique révèle un syndrome dysexécutif associé à des performances déficitaires de mémoire. Le diagnostic de DFT a été posé et Madame T a participé à un protocole de recherche sur la cognition sociale.
Résultats
Le score au Frontal Behavioral Inventory de Madame T (27/72) confirme les troubles comportementaux. Comparativement à un groupe de sujets sains apparié (N=20), Madame T présente des capacités altérées de théorie de l’esprit cognitive (test des Fausses croyances TOM-15) de premier (3/8) et de deuxième ordre (3/7) mais pas affective (test du regard [1], score=16/20). Madame T présente une atteinte des connaissances des règles sociales (21/44). Ce profil cognitivo-comportemental est cohérent avec le diagnostic de DFT. Ses performances aux épreuves de cognition sociale diffèrent de celles d’un groupe apparié de patients DFT (n=6) uniquement pour la théorie de l’esprit affective. Les marqueurs biologiques montrent 1) IRM : atrophie des régions cingulaires postérieures, temporales et hippocampiques et discrète atrophie frontale médiane 2) LCR : index Bêta-amyloïde, Tau et Phospho-Tau en faveur d’une MA.
Discussion
Des troubles de la cognition sociale ont été rapportés dans la MA [2]. Toutefois, chez Madame T, ces troubles sont au premier plan et associés à d’importantes modifications comportementales comparables à celles des patients DFT. Cette forme de MA avec des troubles comportementaux prédominants a récemment été décrite [3] mais les capacités de cognition sociale de ces patients n’ont pas été étudiées. Le profil cognitif de Madame T semble uniquement se distinguer de celui des patients DFT pour la théorie de l’esprit affective. Le profil d’atrophie diffère de celui des patients DFT avec une atrophie frontale modeste et une importante atteinte des régions temporo-pariétales et cingulaires, classique de la MA.
... bvFTD is a neurodegenerative disease associated with progressive frontal and anterior-inferior temporal atrophy that results in inappropriate social behavior and executive difficulty (Rascovsky et al., 2011;Mendez et al., 2014). Imaging studies (Gregory et al., 2002;Kipps and Hodges, 2006;Eslinger et al., 2007;Grossman, 2007;Adenzato et al., 2010;Grossman et al., 2010) and autopsy reports (Hu et al., 2007;Brettschneider et al., 2014) have shown that bvFTD affects dorsolateral, ventral and medial regions of the frontal lobe. These prefrontal regions have been implicated in functional MRI (fMRI) studies of social cognition (e.g., Amodio and Frith, 2006;Frith and Frith, 2006;Saxe, 2006;Mitchell, 2009;Van Overwalle and Baetens, 2009;Enrici et al., 2011) and reasoning (e.g., Bhatt and Camerer, 2005;Rypma et al., 2005;Goel, 2007;Prado and Noveck, 2007;Coricelli and Nagel, 2009;Bhatt et al., 2010;Prado et al., 2015). ...
Some extent of ambiguity is ubiquitous in everyday conversations. For example, words have multiple meaning and very common pronouns, like “he” and “she” (anaphoric pronouns), have little meaning on their own and refer to a noun that has been previously introduced in the discourse. Ambiguity triggers a decision process that is not a subroutine of language processing but rather a more general domain resource. Therefore non-aphasic patients with limited decision-making capability can encounter severe limitation in language processing due to extra linguistic limitations. In the present study, we test patients with behavioral variant frontotemporal degeneration (bvFTD), focusing on anaphora as a paradigmatic example of ambiguity resolution in the linguistic domain. bvFTD is characterized by gray matter (GM) atrophy in prefrontal cortex, but relative sparing of peri-Sylvian cortex. A group of patients with parietal disease due to corticobasal syndrome (CBS) was also tested here in order to investigate the specific role of prefrontal cortex in the task employed in the current study. Participants were presented with a pair of sentences in which the first sentence contained two nouns while the second contained a pronoun. In the experimental (ambiguous) condition, both nouns are plausible referents of the pronoun, thus requiring decision-making resources. The results revealed that bvFTD patients are significantly less accurate than healthy seniors in identifying the correct referent of a pronoun in the ambiguous condition, although CBS patients were as accurate as healthy seniors. Imaging analyses related bvFTD patients’ performance to GM atrophy in ventromedial prefrontal cortex (vmPFC). These results suggest that bvFTD patients have difficulties in decision processes that involve the resolution of an ambiguity.
... Brown and Pluck (2000) suggested that frontal and temporal gray matter and white matter structures constitute critical components of a large-scale neural network that is important in regulating goal-directed behavior. From this perspective, orbital and medial regions of the inferior frontal lobe have been shown to contribute to the interpretation of value-and reward-related information (Grossman et al, 2010;Kable and Glimcher, 2007;Kringelbach and Rolls, 2004). Thus, degradation of the white matter projections between orbital and medial regions of the inferior frontal lobe and other areas of the temporal lobe may interfere with motivation and goal-directed behavior. ...
To relate changes in fractional anisotropy associated with behavioral variant frontotemporal dementia to measures of apathy and disinhibition.
Apathy and disinhibition are the 2 most common behavioral features of behavioral variant frontotemporal dementia, and these symptoms are associated with accelerated patient decline and caregiver stress. However, little is known about how white matter disease contributes to these symptoms.
We collected neuropsychiatric data, volumetric magnetic resonance imaging, and diffusion-weighted imaging in 11 patients who met published criteria for behavioral variant frontotemporal dementia and had an autopsy-validated cerebrospinal fluid profile consistent with frontotemporal lobar degeneration. We also collected imaging data on 34 healthy seniors for analyses defining regions of disease in the patients. We calculated and analyzed fractional anisotropy with a white matter tract-specific method. This approach uses anatomically guided data reduction to increase sensitivity, and localizes results within canonically defined tracts. We used nonparametric, cluster-based statistical analysis to relate fractional anisotropy to neuropsychiatric measures of apathy and disinhibition.
The patients with behavioral variant frontotemporal dementia had widespread reductions in fractional anisotropy in anterior portions of frontal and temporal white matter, compared to the controls. Fractional anisotropy correlated with apathy in the left uncinate fasciculus and with disinhibition in the right corona radiata.
In patients with behavioral variant frontotemporal dementia, apathy and disinhibition are associated with distinct regions of white matter disease. The implicated fiber tracts likely support frontotemporal networks that are involved in goal-directed behavior.
Frontotemporal dementia (FTD) is a cruel disease, robbing patients of core human characteristics and wreaking havoc with relationships. Clinical and scientific interest in FTD and related disorders continues to grow rapidly, with major advances having occurred since this book's last publication. New clinical diagnostic criteria were published in 2011; new pathological discoveries have led to new diagnostic criteria; and major genetic discoveries have been made. This new edition covers these developments, providing the leading resource on FTD, PPA, PSP, CBD, FTD-ALS, and related disorders, now written by a more internationally representative group of authors than before. Providing an in-depth and expert synthesis of the status of our knowledge of FTD and related syndromes, the content includes chapters reviewing clinical, neuropsychiatric, neuropsychological, imaging, and other features of FTD and multidisciplinary approaches to patient management. Essential reading for specialist and generalist neurologists, psychiatrists, geriatricians, neuropsychologists, neuropathologists, and basic scientists in relevant fields.
Negative and positive emotions are known to shape decision-making towards more or less impulsive responses respectively. Decision-making and emotion processing are underpinned by shared brain regions including the ventromedio-prefrontal cortex (vmPFC) and the amygdala. How these processes interact at the behavioural and brain levels is still unclear. We used a lesion model to address this question. Study participants included individuals diagnosed with behavioural-variant frontotemporal dementia (bvFTD, n=18), who typically present deficits in decision-making/emotion processing and atrophy of the vmPFC, individuals with Alzheimer's disease (AD, n=12) who present with atrophy in limbic structures, and age-matched healthy controls (CTRL, n=15). Prior to each choice on the delay discounting task participants were cued with a positive, negative or neutral picture and asked to vividly imagine witnessing the event. As hypothesised, our findings showed that, bvFTD patients were more impulsive than AD and CTRL and did not show any emotion-related modulation of delay discounting rate. In contrast, AD patients showed increased impulsivity when primed by negative emotion. This increased impulsivity was associated with reduced integrity of bilateral amygdala in AD but not in bvFTD. Altogether, our results indicate that decision-making and emotion interact at the level of the amygdala supporting findings from animal studies.
Bribery is perhaps the most visible and most frequently studied form of corruption. Very little research, however, examines the individual decision to offer or accept a bribe, or how understanding that decision can help to effectively control bribery. This book brings together research by scholars from a variety of disciplines studying the mind and morality, who use their research to explain how and why decisions regarding participation in bribery are made. It first examines bribery from the perspective of brain structure, then approaches the decision to engage in bribery from a cognitive perspective. It examines the psychological costs imposed on a person who engages in bribery, and studies societal and organizational norms and their impact on bribery. This is an ideal read for scholars and other interested persons studying business ethics, bribery and corruption, corruption control, and the applications of neuroscience in a business environment.
Bribery is perhaps the most visible and most frequently studied form of corruption. Very little research, however, examines the individual decision to offer or accept a bribe, or how understanding that decision can help to effectively control bribery. This book brings together research by scholars from a variety of disciplines studying the mind and morality, who use their research to explain how and why decisions regarding participation in bribery are made. It first examines bribery from the perspective of brain structure, then approaches the decision to engage in bribery from a cognitive perspective. It examines the psychological costs imposed on a person who engages in bribery, and studies societal and organizational norms and their impact on bribery. This is an ideal read for scholars and other interested persons studying business ethics, bribery and corruption, corruption control, and the applications of neuroscience in a business environment.
Social norms regulate behavior, and changes in norms have a great impact on society. In most modern
societies, norms change through interpersonal communication and persuasive messages found in
media. Here, we examined the neural basis of persuasion-induced changes in attitude toward and
away from norms using fMRI. We measured brain activity while human participants were exposed
to persuasive messages directed toward specific norms. Persuasion directed toward social norms
specifically activated a set of brain regions including temporal poles, temporo-parietal junction,
and medial prefrontal cortex. Beyond these regions, when successful, persuasion away from an
accepted norm specifically recruited the left middle temporal and supramarginal gyri. Furthermore, in
combination with data from a separate attitude-rating task, we found that left supramarginal gyrus
activity represented participant attitude toward norms and tracked the persuasion-induced attitude
changes that were away from agreement.
Deficits in decision-making are thought to contribute significantly to socio-behavioral impairments of patients with frontal lobe damage. The purpose of this study was to test the hypothesis of whether the inappropriate social behavior of patients with frontal lesions can be viewed as the product of a general failure of decision-making ability or as the result of socio-cognitive impairment. We studied a group of patients with prefrontal lesions (FL patients, n = 15) and a group of matched healthy controls (n = 30) on the Iowa Gambling task (IGT) of non-social decision-making, environmental dependency phenomena (EDP) during social interaction, and the "reading the mind in the eyes" and "character intention task" of theory of mind (TOM) tasks. The FL patients were impaired in both TOM and EDP protocols but, surprisingly, they behaved appropriately in the IGT. In addition, FL patients with EDP did not differ in executive functioning, IGT and TOM measures from those who did not demonstrate these behavioral disorders. The right orbitofrontal cortex was associated with social decision-making deficits. By adopting an interactionist approach, this study raises the possibility of identifying components of social and non-social decision-making, which could be helpful in understanding the behavioral disorders of FL patients.
Résumé
L’avancée des connaissances médicales et scientifiques a mis en lumière de nouvelles pathologies à expression neuropsychiatrique. Ces pathologies, à la frontière de la neurologie et de la psychiatrie, représentent un réel enjeu tant sur le plan du diagnostic, car il s’agit souvent de pathologies génétiques familiales, que sur le plan de la prise en charge, qui doit tenir compte de la résistance aux traitements pharmacologiques usuels. En partant de la description de deux patients qui présentent un syndrome délirant à début tardif dans le cadre d’une démence fronto-temporale liée à une mutation du gène C9ORF72, nous essayerons de mettre en évidence des marqueurs cliniques spécifiques permettant de distinguer ces pathologies neurologiques à expression psychiatrique des pathologies schizophréniques prototypiques. Parmi ces marqueurs cliniques, l’existence d’un syndrome frontal cognitif et comportemental pourrait faire suspecter un diagnostic neurologique et inciter à la réalisation d’imagerie cérébrale anatomique et fonctionnelle. À l’inverse, l’existence d’une désorganisation mentale, ou dissociation, apparaîtrait comme un critère spécifique de la schizophrénie, rarement observé dans les schizophrénies à début tardif ou dans les autres syndromes délirants chroniques. Ces observations permettent ainsi d’ouvrir une réflexion plus large sur la physiopathologie des syndromes délirants chroniques et incitent à une redéfinition de la sémiologie neuropsychiatrique, visant l’optimisation de la prise en charge diagnostique et thérapeutique.
The behavioural variant of frontotemporal dementia (bvFTD) is a rare disease mainly affecting the social brain. FDG-PET fronto-temporal hypometabolism is a supportive feature for the diagnosis. It may also provide specific functional metabolic signatures for altered socio-emotional processing. In this study, we evaluated the emotion recognition and attribution deficits and FDG-PET cerebral metabolic patterns at the group and individual levels in a sample of sporadic bvFTD patients, exploring the cognitive-functional correlations. Seventeen probable mild bvFTD patients (10 male and 7 female; age 67.8±9.9) were administered standardized and validated version of social cognition tasks assessing the recognition of basic emotions and the attribution of emotions and intentions (i.e., Ekman 60-Faces test-Ek60F and Story-based Empathy task-SET). FDG-PET was analysed using an optimized voxel-based SPM method at the single-subject and group levels. Severe deficits of emotion recognition and processing characterized the bvFTD condition. At the group level, metabolic dysfunction in the right amygdala, temporal pole, and middle cingulate cortex was highly correlated to the emotional recognition and attribution performances. At the single-subject level, however, heterogeneous impairments of social cognition tasks emerged, and different metabolic patterns, involving limbic structures and prefrontal cortices, were also observed. The derangement of a right limbic network is associated with altered socio-emotional processing in bvFTD patients, but different hypometabolic FDG-PET patterns and heterogeneous performances on social tasks at an individual level exist.
This meta-analytic connectivity modeling (MACM) study explores the functional connectivity of the cerebellum with the cerebrum in social cognitive processes. In a recent meta-analysis, Van Overwalle, Baetens, Mariën, and Vandekerckhove () documented that the cerebellum is implicated in social processes of "body" reading (mirroring; e.g., understanding other persons' intentions from observing their movements) and "mind" reading (mentalizing, e.g., inferring other persons' beliefs, intentions or personality traits, reconstructing persons' past, future, or hypothetical events). In a recent functional connectivity study, Buckner et al. () offered a novel parcellation of cerebellar topography that substantially overlaps with the cerebellar meta-analytic findings of Van Overwalle et al. (). This overlap suggests that the involvement of the cerebellum in social reasoning depends on its functional connectivity with the cerebrum. To test this hypothesis, we explored the meta-analytic co-activations as indices of functional connectivity between the cerebellum and the cerebrum during social cognition. The MACM results confirm substantial and distinct connectivity with respect to the functions of (a) action understanding ("body" reading) and (b) mentalizing ("mind" reading). The consistent and strong connectivity findings of this analysis suggest that cerebellar activity during social judgments reflects distinct mirroring and mentalizing functionality, and that these cerebellar functions are connected with corresponding functional networks in the cerebrum. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.
For social interactions to be successful, individuals must establish shared mental representations that allow them to reach a common understanding and "get on the same page". We refer to this process as social coordination. While examples of social coordination are ubiquitous in daily life, relatively little is known about the neuroanatomic basis of this complex behavior. This is particularly true in a language context, as previous studies have used overly complex paradigms to study this. Although traditional views of language processing and the recent interactive-alignment account of conversation focus on peri-Sylvian regions, our model of social coordination predicts prefrontal involvement. To test this hypothesis, we examine the neural basis of social coordination during conversational exchanges in non-aphasic patients with behavioral variant frontotemporal degeneration (bvFTD). bvFTD patients show impairments in executive function and social comportment due to disease in frontal and anterior temporal regions. To investigate social coordination in bvFTD, we developed a novel language-based task that assesses patients' ability to convey an object's description to a conversational partner. Experimental conditions manipulated the amount of information shared by the participant and the conversational partner, and the associated working memory demands. Our results indicate that, although patients did not have difficulty identifying the features of the objects, they did produce descriptions that included insufficient or inappropriate adjectives and thus struggled to communicate effectively. Impaired performance was related to gray matter atrophy particularly in medial prefrontal and orbitofrontal cortices. Our findings suggest an important role for non-language brain areas that belong to a large-scale neurocognitive network for social coordination.
Copyright © 2015. Published by Elsevier Ltd.
SUMMARY There is an overlap between amyotrophic lateral sclerosis and frontotemporal dementia. Approximately 15% of amyotrophic lateral sclerosis patients suffer from frontotemporal dementia characterized by behavioral change while a further third experience subtle executive dysfunction (typically letter fluency deficits) and corresponding prefrontal changes. Behavior change appears prevalent with apathy being the most prominent feature. Reports of social and emotional cognition deficits are increasing. Deficits have been described on theory of mind tasks including interpretation of stories and cartoons, faux pas detection and in the judgment of preference based on direction of eye-gaze. Impairments in emotional face and prosody perception and emotional enhancement of memory have been reported, and decision making (with and without risk) appears affected. The role of executive dysfunction in this social cognition deficit remains unresolved and more direct evidence of oribitofrontal involvement has yet to ...
A neglected question regarding cognitive control is how control processes might detect situations calling for their involvement. The authors propose here that the demand for control may be evaluated in part by monitoring for conflicts in information processing. This hypothesis is supported by data concerning the anterior cingulate cortex, a brain area involved in cognitive control, which also appears to respond to the occurrence of conflict. The present article reports two computational modeling studies, serving to articulate the conflict monitoring hypothesis and examine its implications. The first study tests the sufficiency of the hypothesis to account for brain activation data, applying a measure of conflict to existing models of tasks shown to engage the anterior cingulate. The second study implements a feedback loop connecting conflict monitoring to cognitive control, using this to simulate a number of important behavioral phenomena.
[reviews] 6 chapters that comprise varied perspectives and approaches to executive functions / each chapter deals in some way with the following critical issues and questions about executive functions / what theoretical context and theoretical model guide each conceptual view of executive function and its relationship to attention and memory / what are the primary constructs within the model of executive functions / how can the model and the constructs be operationalized / what are a series of testable hypotheses that provide an opportunity for disconfirmation of the executive function model / what experimental designs and experiments would be applied and conducted
these questions [emphasize] definition, measurement, and specific hypotheses to be tested [on executive function] / the organization of this chapter is centered around these guiding questions / the definition and measurement of executive function as well as future research directions of each approach are covered, with subsequent discussion of their commonalities and differences, relationship to neurobiological and neuropsychological aspects of typical and altered brain development, and new research directions in this area
importance of executive functions for human development and adaptation / information processing approach: Borkowski and Burke / neuropsychological approach: Pennington, Bennetto, McAleer, and Roberts / neuropsychological approach: Denckla / behavioral approach: Hayes, Gifford, and Ruckstuhl / self-regulated strategy development: Graham and Harris / attention and executive function: Barkley (PsycINFO Database Record (c) 2012 APA, all rights reserved)
To investigate the neural basis for the behavioral symptoms of frontotemporal lobar degeneration (FTLD) that cause the greatest caregiver distress.
FTLD is a progressive neurodegenerative disease associated with behavioral disturbances. Group studies have related these behaviors to volume loss on MRI.
Forty caregivers of patients with the clinical diagnosis of FTLD completed the Neuropsychiatric Inventory. Twelve neuropsychiatric symptoms and the associated caregiver distress were assessed. Optimized voxel-based morphometry identified significant atrophy in subgroups of FTLD patients with isolated behavioral symptoms corresponding to the most distressing behaviors, and we correlated cortical atrophy directly with these distressing behavioral disorders in an unbiased group analysis.
The greatest stressors for caregivers were apathy and disinhibition (p < 0.005 for both contrasts). Partially distinct areas of cortical atrophy were associated with these behaviors in both individual patients with these symptoms and group-wide analyses, including the dorsal anterior cingulate cortex and dorsolateral prefrontal cortex in apathetic patients, and the medial orbital frontal cortex in disinhibited patients.
Caregiver stress in families of FTLD patients is due in large part to apathy and disinhibition. The anatomic distribution of cortical loss corresponding to these distressing social behaviors includes partially distinct areas within the frontal lobe.
Inappropriate social behaviours are early and distinctive symptoms of the temporal and frontal variants of frontotemporal lobar degeneration (FTLD). Knowledge of social behaviour is essential for appropriate social conduct. It is unknown, however, in what way this knowledge is degraded in FTLD. In a recent functional MRI study, we have identified a right-lateralized superior anterior temporal lobe (aTL) region showing selective activation for 'social concepts' (i.e. concepts describing social behaviour: e.g. 'polite', 'stingy') as compared with concepts describing less socially relevant animal behaviour ('animal function concepts': e.g. 'trainable', 'nutritious'). In a further fMRI study, superior aTL activation was independent of the context of actions and feelings associated with these social concepts. Here, we investigated whether the right superior sector of the aTL is necessary for context-independent knowledge of social concepts. We assessed neuronal glucose uptake using 18-fluoro-deoxy-glucose-positron emission tomography (FDG-PET) and a novel semantic discrimination task which probed knowledge of social and animal function concepts in patients with FTLD (n = 29) and corticobasal syndrome (n = 18). FTLD and corticobasal syndrome groups performed equally poorly on animal function concepts but FTLD patients showed more pronounced impairments on social concepts than corticobasal syndrome patients. FTLD patients with right superior aTL hypometabolism, as determined on individual ROI analyses, were significantly more impaired on social concepts than on animal function concepts. FTLD patients with selective impairments for social concepts, as determined on individual neuropsychological profiles, showed higher levels of inappropriate social behaviours ('disinhibition') and demonstrated more pronounced hypometabolism in the right superior aTL, the left temporal pole and the right lateral orbitofrontal and dorsomedial prefrontal cortex as compared with FTLD patients showing selective impairments of animal function concepts. Combining both FTLD subgroup analyses, based on anatomical and neuropsychological criteria, by using inclusive masks, revealed the right superior aTL as associated with selective impairments of social concepts in both analyses. These results corroborate the hypothesis that the right aTL is necessary for representing conceptual social knowledge. Further, we provide first evidence for the potential importance of conceptual social knowledge impairments as contributing to behavioural symptoms of FTLD.
Social interaction is profoundly affected in the behavioural form of frontotemporal dementia (bvFTD) yet there are few means of objectively assessing this. Diagnosis of bvFTD is based on informant report, however a number of individuals with a clinical profile consistent with the disease have no imaging abnormality and seem to remain stable, with doubt about the presence of underlying neurodegenerative pathology. We aimed to quantify aspects of the behavioural disorder and link it to the underlying level of atrophy in socially relevant brain regions. We tested individuals with either bvFTD (N = 26) or Alzheimer's disease (N = 9) and 16 controls using The Awareness of Social Inference Test (TASIT) to assess their ability to identify emotion and sarcasm in video vignettes. A subset of bvFTD patients (N = 21) and controls (N = 12) were scanned using MRI within 6 months of assessment. There was marked impairment in the ability of bvFTD patients whose scans showed abnormalities to recognize sarcastic, but not sincere statements. Their capacity to interpret negative emotion was also impaired, and this appeared to be a major factor underlying the deficit in sarcasm recognition. Clinically diagnosed bvFTD patients whose scans were normal, Alzheimer's disease patients and controls had no difficulty in appreciating both types of statement. In a multivariate imaging analysis it was shown that the sarcasm (and emotion recognition) deficit was dependent on a circuit involving the lateral orbitofrontal cortex, insula, amygdala and temporal pole, particularly on the right. Performance on a more global test of cognitive function, the Addenbrooke's Cognitive Examination did not have a unique association with these regions. The TASIT is an objective test of social dysfunction in bvFTD which indexes the frontotemporal volume loss in bvFTD patients and provides an objective measure for separating behavioural patients who are likely to decline from those who may remain stable. These results provide additional evidence for the role of the orbitofrontal cortex and related structures in the processing of socially relevant signals, particularly those where negative emotion recognition is important.
A group of patients with damage to the ventral part of the frontal lobes was severely impaired relative to a group of patients without damage in this area (the non-ventral group) in the reversal and in the extinction of simple visual discrimination tests. In these tests they continued to make responses to a previously rewarded stimulus. Patients often reported verbally that the contingencies had changed, but were unable to alter their behaviour appropriately. These impairments occurred independently of IQ or verbal memory impairments. The perseverative touching of a previously rewarded stimulus is consistent with work with non-human primates showing impaired reversal and extinction after orbitofrontal lesions. Performance on these reversal and extinction tests was highly correlated with scores obtained on a behaviour questionnaire, which reflected the degree of disinhibited and socially inappropriate behaviour exhibited by patients. It is suggested that a difficulty in modifying responses, especially when followed by negative consequences, as manifested in these simple laboratory tests, may contribute to the inappropriate behaviour shown in daily life by patients with frontal lobe damage.
The ability of normal children and adults to attribute independent mental states to self and others in order to explain and predict behaviour ("theory of mind") has been a focus of much recent research. Autism is a biologically based disorder which appears to be characterised by a specific impairment in this "mentalising" process. The present paper reports a functional neuroimaging study with positron emission tomography in which we studied brain activity in normal volunteers while they performed story comprehension tasks necessitating the attribution of mental states. The resultant brain activity was compared with that measured in two control tasks: "physical" stories which did not require this mental attribution, and passages of unlinked sentences. Both story conditions, when compared to the unlinked sentences, showed significantly increased regional cerebral blood flow in the following regions: the temporal poles bilaterally, the left superior temporal gyrus and the posterior cingulate cortex. Comparison of the "theory of mind" stories with "physical" stores revealed a specific pattern of activation associated with mental state attribution: it was only this task which produced activation in the medial frontal gyrus on the left (Brodmann's area 8). This comparison also showed significant activation in the posterior cingulate cortex. These surprisingly clear-cut findings are discussed in relation to previous studies of brain activation during story comprehension. The localisation of brain regions involved in normal attribution of mental states and contextual problem solving is feasible and may have implication for the neural basis of autism.
Theories of the regulation of cognition suggest a system with two necessary components: one to implement control and another to monitor performance and signal when adjustments in control are needed. Event-related functional magnetic resonance imaging and a task-switching version of the Stroop task were used to examine whether these components of cognitive control have distinct neural bases in the human brain. A double dissociation was found. During task preparation, the left dorsolateral prefrontal cortex (Brodmann's area 9) was more active for color naming than for word reading, consistent with a role in the implementation of control. In contrast, the anterior cingulate cortex (Brodmann's areas 24 and 32) was more active when responding to incongruent stimuli, consistent with a role in performance monitoring.
To test predictions that frontotemporal dementia and semantic dementia give rise to distinct patterns of behavioural change.
An informant based semistructured behavioural interview, covering the domains of basic and social emotions, social and personal behaviour, sensory behaviour, eating and oral behaviour, repetitive behaviours, rituals, and compulsions, was administered to carers of 41 patients with semantic dementia and with apathetic (FTD-A) and disinhibited (FTD-D) forms of frontotemporal dementia.
Consistent with prediction, emotional changes differentiated FTD from semantic dementia. Whereas lack of emotional response was pervasive in FTD, it was more selective in semantic dementia, affecting particularly the capacity to show fear. Social avoidance occurred more often in FTD and social seeking in semantic dementia. Patients with FTD showed reduced response to pain, whereas patients with semantic dementia more often showed exaggerated reactions to sensory stimuli. Gluttony and indiscriminate eating were characteristic of FTD, whereas patients with semantic dementia were more likely to exhibit food fads. Hyperorality, involving inedible objects, was unrelated to gluttony, indicating different underlying mechanisms. Repetitive behaviours were common in both FTD and semantic dementia, but had a more compulsive quality in semantic dementia. Behavioural differences were greater between semantic dementia and FTD-A than FTD-D. A logistic regression analysis indicated that emotional and repetitive, compulsive behaviours discriminated FTD from semantic dementia with 97% accuracy.
The findings confirm predictions regarding behavioural differences in frontotemporal and semantic dementia and point to differential roles of the frontal and temporal lobes in affect, social functioning, eating, and compulsive behaviour.
Responses to monetary reward in humans have been assessed in a number of recent functional imaging studies, and it is clear that the neuronal substrates of financial reinforcement overlap extensively with regions responding to primary reinforcers, such as food. Money has the practical advantage of being an objectively quantifiable reinforcer. In this study, we exploit this advantage using a parametric functional magnetic resonance imaging design to look at the patterns of responding to systematically varying reward values. Twelve healthy volunteers were scanned during performance of a rewarded target detection task, in which the reward value varied between task blocks. We observed three distinct patterns of responding in different regions. Amygdala, striatum, and dopaminergic midbrain responded to the presence of rewards, regardless of value. In contrast, premotor cortex showed a linear increase in response with increasing reward value. Finally, medial and lateral foci of orbitofrontal cortex responded nonlinearly, such that response was enhanced for the lowest and highest reward values relative to the midrange. These results suggest functional distinction in response patterns within a distributed reward system.
To analyse the functions of different parts of the prefrontal cortex in emotion, patients with different prefrontal surgical excisions were compared on four measures of emotion: voice and face emotional expression identification, social behaviour, and the subjective experience of emotion. Some patients with bilateral lesions of the orbitofrontal cortex (OFC) had deficits in voice and face expression identification, and the group had impairments in social behaviour and significant changes in their subjective emotional state. Some patients with unilateral damage restricted to the OFC also had deficits in voice expression identification, and the group did not have significant changes in social behaviour or in their subjective emotional state. Patients with unilateral lesions of the antero-ventral part of the anterior cingulate cortex (ACC) and/or medial Brodmann area (BA) 9 were, in some cases, impaired on voice and face expression identification, had some change in social behaviour, and had significant changes in their subjective emotional state. Patients with unilateral lesions of the OFC and of the ACC and/or medial BA 9 were, in some cases, impaired on voice and face expression identification, had some changes in social behaviour, and had significant changes in their subjective emotional state. Patients with dorsolateral prefrontal cortex lesions or with medial lesions outside ACC and medial BA 9 areas (dorsolateral/other medial group) were unimpaired on any of these measures of emotion. In all cases in which voice expression identification was impaired, there were no deficits in control tests of the discrimination of unfamiliar voices and the recognition of environmental sounds. Thus bilateral or unilateral lesions circumscribed surgically within the OFC can impair emotional voice and/or face expression identification, but significant changes in social behaviour and in subjective emotional state are related to bilateral lesions. Importantly, unilateral lesions of the ACC (including some of medial BA 9) can produce voice and/or face expression identification deficits, and marked changes in subjective emotional state. These findings with surgically circumscribed lesions show that within the prefrontal cortex, both the OFC and the ACC/medial BA 9 region are involved in a number of aspects of emotion in humans including emotion identification, social behaviour and subjective emotional state, and that the dorsolateral prefrontal areas are not involved in emotion in these ways.
Event-related functional magnetic resonance imaging was used to measure blood oxygenation level-dependent responses in 16 young healthy human volunteers during performance of an attentional switching task. The task allowed the separate investigation of lower-order switching between concrete objects and higher-order switching between abstract task rules. Significant signal change in the ventral striatum was demonstrated on trials when subjects switched between objects but not when subjects switched between abstract task rules. In contrast, signal change in the lateral prefrontal cortex (PFC) was observed during all switch trials. The switch-related responses were not contaminated by task difficulty, because the greatest signal change was observed during the relatively easy switch trials, which required both lower-order and higher-order switching at the same time. The present data suggest that mechanisms of inhibitory response control in frontostriatal systems are organized according to distinct levels of abstraction. Specifically, the response selection computation carried by the ventral striatum, which projects to the orbitofrontal cortex and the medial PFC, is restricted to the transformation of concrete stimulus exemplar information into motor responses, whereas the adaptive function of the lateral PFC extends to the transformation of abstract task-rule representations into action.
Psychologists and economists have long appreciated the contribution of reward history and expectation to decision-making.
Yet we know little about how specific histories of choice and reward lead to an internal representation of the “value” of
possible actions. We approached this problem through an integrated application of behavioral, computational, and physiological
techniques. Monkeys were placed in a dynamic foraging environment in which they had to track the changing values of alternative
choices through time. In this context, the monkeys' foraging behavior provided a window into their subjective valuation. We
found that a simple model based on reward history can duplicate this behavior and that neurons in the parietal cortex represent
the relative value of competing actions predicted by this model.
To discern behavioral problems that co-occur in frontotemporal dementia (FTD) patients, and to investigate the relation between behavioral clusters and the burden for caregivers.
Baseline data of 63 FTD patients and their respective caregivers were used to detect the behavioral clusters in the Neuropsychiatric Inventory (NPI) and the accompanying distress evoked in caregivers. To detect the clusters in behavior of the FTD patients, we performed multidimensional scaling (procedure: PROXSCAL). Multiple regression analysis was used to determine the association between behavior of patients and the distress experienced by caregivers.
This was the first study that found behavioral clusters for FTD. Two behavioral clusters were found: agitation/psychosis (comprising delusions, hallucinations, irritability and agitation) and mood (made up of anxiety and depression). The remaining NPI domains (euphoria, disinhibition, aberrant motor behavior and apathy were found to be autonomous. After controlling for relevant confounding factors, caregiver distress was strongest related to agitation/psychosis, followed by mood. Disinhibition and aberrant motor behavior were mildly related to caregiver distress. Euphoria and apathy were not significantly related to distress. Caregivers of patients living at home were more distressed by the behavioral problems of the FTD patients than caregivers of hospitalized patients.
The high prevalence of psychopathology in FTD patients and the associated caregiver distress was confirmed in this study. Clustering behavioral symptoms allows investigation of the relationship between structural or functional cerebral deficits and neuropsychiatric symptoms.
This thoroughly revised new edition of a classic book provides a clinically inspired but scientifically guided approach to the biological foundations of human mental function in health and disease. It includes authoritative coverage of all the major areas related to behavioral neurology, neuropsychology, and neuropsychiatry. Each chapter, written by a world-renowned expert in the relevant area, provides an introductory background as well as an up-to-date review of the most recent developments. Clinical relevance is emphasized but is placed in the context of cognitive neuroscience, basic neuroscience, and functional imaging. Major cognitive domains such as frontal lobe function, attention and neglect, memory, language, prosody, complex visual processing, and object identification are reviewed in detail. A comprehensive chapter on behavioural neuroanatomy provides a background for brain-behaviour interactions in the cerebral cortex, limbic system, basal ganglia, thalamus, and cerebullum. Chapters on temperolimbic epilepsy, major psychiatric syndromes, and dementia provide in-depth analyses of these neurobehavioral entities and their neurobiological coordinates. Changes for this second edition include the reflection throughout the book of the new and flourishing alliance of behavioral neurology, neuropsychology, and neuropsychiatry with cognitive science;major revision of all chapters; new authorship of those on language and memory; and the inclusion of entirely new chapters on psychiatric syndromes and the dementias. Both as a textbook and a reference work, the second edition of Principles of Behavioral and Cognitive Neurology represents an invaluable resource for behavioural neurologists, neuropsychologists, neuropsychiatrists, cognitive and basic neuroscientists, geriatricians, physiatrists, and their students and trainees.
Structural brain imaging and neuropsychological data implicate the orbital aspects of prefrontal cortex in the developing neuropathology of fvFTD. Damage to this region is associated with deficient performance on laboratory tasks assessing theory of mind (ToM) and affective decision-making (DM), but the relationship between these two capacities in patients with prefrontal cortex dysfunction is unclear. We studied a group of patients with early/mild fvFTD (n = 20) and a group of matched normal controls (n = 10) on the Iowa gambling task (IGT) of affective decision-making, and the " reading the mind in the eyes " (MIE) and " faux pas " (FP) tests of ToM. The fvFTD group was impaired in both ToM tasks and the IGT. While performance measures from the two ToM tasks were significantly correlated, they were not associated with IGT performance. This suggests that whilst similar prefrontal circuitry is implicated in ToM and DM tasks, these cognitive domains may be independent. In clinical settings, the IGT may be useful as a complementary tool to the frontal test battery for patients with early/mild fvFTD. Deficits in decision-making and ToM observed in this study have distinct but additive effects upon the development of social behaviour in patients with prefrontal dysfunction.
Social cognition is crucial for human interaction, and is markedly impaired in the frontal variant of frontotemporal dementia (fvFTD). The relationship of various aspects of social functioning, however, remains controversial in this group.
Patients with fvFTD (n = 18), and matched controls (n = 13), were tested using tasks designed to assess their Theory of Mind (ToM), moral reasoning, emotion recognition and executive function. Caregivers documented changes in empathy compared to premorbid functioning.
We found marked impairments in the abilities of fvFTD patients, relative to controls, in ability to mentalise (ToM), which was evident on a cartoon test, but not on a story-based ToM task. Knowledge of social rules was intact, but moral reasoning was defective, and was due, in part, to an inability to rate the seriousness of moral and conventional transgressions appropriately. Executive function was impaired in this group, and compromised aspects of moral reasoning, but ToM performance was independent of this. Emotion recognition was globally impaired in fvFTD, but was particularly so for anger and disgust which may partly explain the difficulty these patients have with identifying social violations. Empathy, as rated by carers, was also shown to be abnormal.
It appears that social reasoning is disrupted in a number of ways in fvFTD, and the findings provide a basis for the understanding and further study of abnormal behaviour in this disease. The results are discussed in light of neuroimaging findings in studies of social cognition and the locus of pathology in fvFTD.
Patients with frontotemporal dementia (FTD) can present with the clinical syndrome of semantic dementia due to a progressive loss of semantic knowledge or a neuropsychiatric syndrome characterised by aberrant social behaviours although frequently both co-exist. It has been assumed that the former is underpinned by damage to the temporal lobes and the latter, predominantly, by damage to the frontal lobes. Using the technique of voxel-based morphometry, we studied a group of FTD cases (n = 18) with a range of cognitive and neuropsychiatric features to correlate loss of semantic knowledge (as measured by the sum of two semantic tests) and aberrant behaviour (as measured by the neuropsychiatric inventory, NPI) with regional loss of grey matter volume. Semantic breakdown correlated with extensive loss of grey matter volume throughout the left anterior temporal lobe and less significantly with right temporal pole and subcallosal gyrus. Aberrant behaviour correlated with loss of grey matter volume in the dorso-mesial frontal lobe—paracingulate region, Brodmann areas 6/8/ 9—more so on the right. The frontal paracingulate correlation suggests that damage to this region may significantly contribute to the genesis of the behavioural syndrome seen in FTD.
Lavenu et al. [Alzheimer Dis. Assoc. Disorder 5 (1999) 96] have shown that patients with frontotemporal dementia (FTD) show impaired recognition of facial expressions. It is not clear, however, whether these deficits arise from an impairment affecting face processing generally, emotion processing generally, or facial expression recognition alone. We address this issue by testing six patients with frontal variant frontotemporal dementia (fvFTD) on a series of face perception tasks (including facial identity and facial expression recognition), and a test of vocal emotion recognition. In general, the fvFTD participants showed impaired recognition of facial expressions in the context of preserved recognition of facial identity. In addition, however, deficits were also observed for the vocal emotion recognition task. These results are consistent with the idea that fvFTD affects the recognition of emotional signals from multiple modalities rather than facial expression processing alone. It is plausible that the emotion recognition impairments observed contribute to the abnormal social behaviour that is characteristic of this condition.
In this paper, we adopt a neurodevelopmental stance to examining frontal variant frontotemporal dementia (fv-FTD) by using experimental procedures from the literature on the growth of social behaviour in children to examine the deficits in social reasoning which may underpin behavioural disturbance in fv-FTD. We present the case of a 47-year-old man with a diagnosis of fv-FTD and severe antisocial behaviour. Tests of general neuropsychology and of executive function were performed. In addition, the patient, JM, was assessed on tasks which test theory of mind. Theory of mind develops in distinct stages through childhood and is a core ability to represent the thoughts and feelings of others, independent of the level of intellectual ability. The results indicate relatively intact general neuropsychological and executive function, but extremely poor performance on tasks of theory of mind. This indicates a dissociation of social cognition and executive function suggesting that in psychiatric presentations of fv-FTD there may be a fundamental deficit in theory of mind independent of the level of executive function. The implications of this finding for diagnostic procedures and possible behavioural management are discussed.
Objectives—To investigate the prevalence of changes in mood, personality, and behaviour in frontotemporal dementia (FTD) and Alzheimer's disease (AD) and hence, which features reliably distinguish between them. To establish whether the frontal and temporal variants of FTD are characterised by diVerent behavioural changes. Methods—A questionnaire was designed to assess a wide range of neuropsychiatric changes; it incorporated features reported in previous studies of FTD and components of the neuropsychiatric inventory. 1 This was completed by 37 carers of patients with Alzheimer's disease (AD) and 33 patients with frontotemporal de-mentia (FTD), comprising 20 with temporal variant FTD (tv FTD) or semantic dementia and 13 with frontal variant FTD (fv FTD). An exploratory principal components factor analysis and discriminant function analysis was applied. Results—Factor analysis showed four robust and meaningful symptom clusters: factor 1—stereotypic and eating behaviour ; factor 2—executive dysfunction and self care; factor 3—mood changes; factor 4—loss of social awareness. Only stere-otypic and altered eating behaviour and loss of social awareness reliably diVerenti-ated AD from FTD with no eVect of disease severity. By contrast, executive dysfunction, poor self care, and restless-ness showed a significant eVect of disease severity only, with the more impaired patients scoring more highly. Changes in mood were found to be equally prevalent in the three patient groups. Analysis of individual symptoms showed increased rates of mental rigidity and depression in the patients with semantic dementia compared with those with fv FTD. Conversely, the latter group showed greater disinhibi-tion. Discriminant function analysis correctly classified 71.4% overall and 86.5% of the patients with AD. Conclusions—This questionnaire disclosed striking diVerences between patients with FTD and AD, but only stereotypic behaviour, changes in eating preference, disinhibition, and features of poor social awareness reliably separated the groups. The patients with fv FTD and semantic dementia were behaviourally very similar, reflecting the involvement of a common network, the ventral frontal lobe, temporal pole, and amygdala. Dys-executive symptoms and poor self care were found to be aVected by the severity of the disease, reflecting perhaps spread to dorsolateral prefrontal areas relatively late in the course of both FTD and AD. This questionnaire may be of value in the diagnosis and the monitoring of therapies.
This chapter describes the connections of the orbital and medial prefrontal cortex. Intrinsic connections indicate the presence of distinct orbital and medial networks, with the orbital network concentrated in central OFC subregions, and the medial network involving medial structures, and some areas on the medial and lateral orbital surface. The medial and orbital networks show strikingly differential patterns of input and output. The orbital network receives substantial input from sensory systems including olfaction, taste, visceral, visual, and somatosensory systems, and may serve to assess sensory objects, especially food. The medial network has little direct sensory input, but provides output to the hypothalamus and periaqueductal gray, and is heavily connected with limbic regions such as the amygdala, entorhinal cortex, and hippocampus. The medial and orbital networks are also connected to distinct parts of the striatum and mediodorsal thalamic nucleus.
An unresolved question in neuroscience and psychology is how the brain monitors performance to regulate behavior. It has been proposed that the anterior cingulate cortex (ACC), on the medial surface of the frontal lobe, contributes to performance monitoring by detecting errors. In this study, event-related functional magnetic resonance imaging was used to examine ACC function. Results confirm that this region shows activity during erroneous responses. However, activity was also observed in the same region during correct responses under conditions of increased response competition. This suggests that the ACC detects conditions under which errors are likely to occur rather than errors themselves.
An international group of clinical and basic scientists participated in the Frontotemporal Dementia and Pick's Disease Criteria Conference at the National Institutes of Health in Bethesda, Md, on July 7, 2000, to reassess clinical and neuropathological criteria for the diagnosis of frontotemporal dementia (FTD). Previous criteria for FTD have primarily been designed for research purposes. The goal of this meeting was to propose guidelines that would enable clinicians (particularly neurologists, psychiatrists, and neuropsychologists) to recognize patients with FTD and, if appropriate, to expedite their referral to a diagnostic center. In addition, recommendations for the neuropathological criteria of FTD were reviewed, relative to classical neuropathology and modern molecular biology.
Theories of the regulation of cognition suggest a system with two necessary components: one to implement control and another to monitor performance and signal when adjustments in control are needed. Event-related functional magnetic resonance imaging and a task-switching version of the Stroop task were used to examine whether these components of cognitive control have distinct neural bases in the human brain. A double dissociation was found. During task preparation, the left dorsolateral prefrontal cortex (Brodmann's area 9) was more active for color naming than for word reading, consistent with a role in the implementation of control. In contrast, the anterior cingulate cortex (Brodmann's areas 24 and 32) was more active when responding to incongruent stimuli, consistent with a role in performance monitoring.
Summary A key aspect of social cognition is the ability to infer other people’s mental states, thoughts and feelings; referred to as ‘theory of mind’ (ToM). We tested the hypothesis that the changes in personality and behaviour seen in frontal variant frontotemporal dementia (fvFTD) may reflect impairment in this cognitive domain. Tests of ToM, executive and general neuropsychological ability were given to 19 fvFTD patients, a comparison group of Alzheimer’s disease patients (n = 12) and matched healthy controls (n = 16). Neuropsychiatric assessment was undertaken using the Neuropsychiatric Inventory (NPI). Patients with fvFTD were impaired on all tests of ToM (first-order false belief; second-order false belief; faux pas detection; and Reading the Mind in the Eyes), but had no difficulty with control questions designed to test general comprehension and memory. By contrast, the Alzheimer’s disease group failed only one ToM task (second-order false belief), which places heavy demands on working memory. Performance on the faux pas test revealed a double dissociation, with the fvFTD group showing deficits on ToM-based questions and the Alzheimer’s disease group failing memory-based questions only. Rank order of the fvFTD patients according to the magnitude of impairment on tests of ToM and their degree of frontal atrophy showed a striking concordance between ToM performances and ventromedial frontal damage. There was a significant correlation between the NPI score and more sophisticated tests of ToM in the fvFTD group. This study supports the hypothesis that patients with fvFTD, but not those with Alzheimer’s disease, are impaired on tests of ToM, and may explain some of the abnormalities in interpersonal behaviour that characterize fvFTD.
The frontal lobe has been viewed historically in very different ways, ranging from enigmatic and mystifying to the crucial neural substrate for higher cognition and social behavior. Frontal lobe damage poses a unique and difficult set of challenges to the patient, their family and the neurorehabilitation team. Because of the role of the frontal lobe in adaptation and adjustment, such damage adversely affects a patient's participation in the process and content of rehabilitation. To aid diagnosis and treatment planning, a model of frontal lobe organization is outlined, focusing on the specific cognitive and behavioral symptom clusters associated with superior mesial, inferior mesial, dorsolateral and orbital frontal lesions. A taxonomy of social executive processes is presented for identifying impairments in social behavior and personality, based upon the domains of social self-regulation, social self-awareness, social-sensitivity (empathy), and social-salience. Specific interventions are described that encompass dopamine agonist therapy for blunted affect, mutism and akinesia, cognitive strategies for improving organization and planning deficits, and evolving treatments for social impairments.
Dementia of frontal type(DFT) and the other focal lobar atrophies challenge the clinician to assess patients with dementia thoroughly. DFT presents with characteristic behavioural and personality changes, and operational criteria have recently been devised to assist in the assessment and diagnosis. A significant proportion of cases present with functional psychiatric disorders including mood disturbance. Diogenes syndrome may be a variant of DFT. A number of syndromes associated with focal lobar atrophy of other brain regions have also been described, most common of these is primary progressive aphasia (PPA). Bedside cognitive and formal neuropsychological testing, and neuroimaging—both functional (SPECT) and anatomical—may assist in the diagnosis of these disorders. At post-mortem, non-specific atrophy is present; in DFT, the frontal lobes are affected, and in PPA, the focus of pathology is the dominant temporal lobe. Only a minority of cases show Pick cells and Picks bodies, in the remainder non-specific neuronal loss and gliosis are present
Representing the affective value of a reward on a continuous scale may occur separately from making a binary, for example yes vs no, decision about whether to choose the reward. To investigate whether these are separable processes, we used functional magnetic resonance imaging to measure activations produced by pleasant warm, unpleasant cold, and affectively complex combinations of these stimuli applied to the hand. On some trials the affective value was rated on a continuous scale, and on different trials a yes-no decision was made about whether the stimulus should be repeated in future. Decision-making contrasted with just rating the affective stimuli revealed activations in the medial prefrontal cortex area 10, implicating this area in binary decision-making. Activations related to the pleasantness ratings and which were not influenced when a binary decision was made were found in the pregenual cingulate and parts of the orbitofrontal cortex, implicating these regions in the continuous representation of affective value. When a decision was yes vs. no, effects were found in the dorsal cingulate cortex, agranular (anterior) insula and ventral tegmental area, implicating these areas in initiating actions to obtain goals.
The clinical, neuropsychological, and cerebral blood flow characteristics of eight patients with frontal lobe degeneration (FLD) were studied. Social withdrawal and behavioral disinhibition were the earliest and most common clinical presentations, and psychiatric symptoms typically preceded the onset of dementia by several years. Neuropsychological testing showed selective impairment of frontal and memory tasks with relative sparing of attention, language, and visuospatial skills. Single-photon emission computerized tomography demonstrated frontal and temporal hypoperfusion with relative sparing of parietal and occipital blood flow. Previous studies suggest that the neuropathologic findings in patients with FLD are varied; some demonstrate frontal gliosis, neuronal loss, and Pick bodies while others show only gliosis and neuronal loss.
The behavioral, neuropsychological and single photon emission computerized tomography characteristics of 5 patients with progressive degeneration of the right hemisphere are described. In all, the brain regions with greatest involvement were right-frontal and temporal. Psychosis, compulsions and behavioral disinhibition were the dominant, and often first, symptoms. Affect was flattened and the patients seemed distant and remote. Neuropsychological testing did not reveal a consistent pattern that helped localize the abnormality to the right frontotemporal region. These patients contrast dramatically to those with left frontotemporal degeneration in whom behavior and psychiatric status is often normal. This study suggests that the right hemisphere may be primary for the control of social conduct.
Research suggests an association between frontal and temporal injury and antisocial conduct. We studied the frequency of antisocial behaviours in fronto-temporal dementia (FTD) where pathology is anterior frontal-temporal, compared with Alzheimer's disease (AD) where pathology is primarily posterior temporal-parietal.
The presence of antisocial conduct was compared in 22 FTD versus 22 AD subjects. All FTD patients had anterior frontal or temporal hypoperfusion with single photon emission computed tomography, whereas those with AD had posterior temporal-parietal hypoperfusion.
Ten FTD and one AD subject showed antisocial behaviours, which included assault, indecent exposure, shoplifting and hit-and-run driving. Three FTD subjects were arrested. This difference was highly significant (P = 0.004).
Degeneration of frontal and temporal lobes predisposes to antisocial behaviour. This study supports a relationship between frontal-temporal dysfunction and certain types of antisocial activities.
An unresolved question in neuroscience and psychology is how the brain monitors performance to regulate behavior. It has been proposed that the anterior cingulate cortex (ACC), on the medial surface of the frontal lobe, contributes to performance monitoring by detecting errors. In this study, event-related functional magnetic resonance imaging was used to examine ACC function. Results confirm that this region shows activity during erroneous responses. However, activity was also observed in the same region during correct responses under conditions of increased response competition. This suggests that the ACC detects conditions under which errors are likely to occur rather than errors themselves.
To improve clinical recognition and provide research diagnostic criteria for three clinical syndromes associated with frontotemporal lobar degeneration.
Consensus criteria for the three prototypic syndromes-frontotemporal dementia, progressive nonfluent aphasia, and semantic dementia-were developed by members of an international workshop on frontotemporal lobar degeneration. These criteria build on earlier published clinical diagnostic guidelines for frontotemporal dementia produced by some of the workshop members.
The consensus criteria specify core and supportive features for each of the three prototypic clinical syndromes and provide broad inclusion and exclusion criteria for the generic entity of frontotemporal lobar degeneration. The criteria are presented in lists, and operational definitions for features are provided in the text.
The criteria ought to provide the foundation for research work into the neuropsychology, neuropathology, genetics, molecular biology, and epidemiology of these important clinical disorders that account for a substantial proportion of cases of primary degenerative dementia occurring before the age of 65 years.
Event-related functional MRI and a version of the Stroop color naming task were used to test two conflicting theories of anterior cingulate cortex (ACC) function during executive processes of cognition. A response-related increase in ACC activity was present when strategic processes were less engaged, and conflict high, but not when strategic processes were engaged and conflict reduced. This is inconsistent with the widely held view that the ACC implements strategic processes to reduce cognitive conflicts, such as response competition. Instead, it suggests that the ACC serves an evaluative function, detecting cognitive states such as response competition, which may lead to poor performance, and representing the knowledge that strategic processes need to be engaged.
The somatic marker hypothesis provides a systems-level neuroanatomical and cognitive framework for decision making and the influence on it by emotion. The key idea of this hypothesis is that decision making is a process that is influenced by marker signals that arise in bioregulatory processes, including those that express themselves in emotions and feelings. This influence can occur at multiple levels of operation, some of which occur consciously and some of which occur non-consciously. Here we review studies that confirm various predictions from the hypothesis. The orbitofrontal cortex represents one critical structure in a neural system subserving decision making. Decision making is not mediated by the orbitofrontal cortex alone, but arises from large-scale systems that include other cortical and subcortical components. Such structures include the amygdala, the somatosensory/insular cortices and the peripheral nervous system. Here we focus only on the role of the orbitofrontal cortex in decision making and emotional processing, and the relationship between emotion, decision making and other cognitive functions of the frontal lobe, namely working memory.
To investigate the prevalence of changes in mood, personality, and behaviour in frontotemporal dementia (FTD) and Alzheimer's disease (AD) and hence, which features reliably distinguish between them. To establish whether the frontal and temporal variants of FTD are characterised by different behavioural changes.
A questionnaire was designed to assess a wide range of neuropsychiatric changes; it incorporated features reported in previous studies of FTD and components of the neuropsychiatric inventory.(1) This was completed by 37 carers of patients with Alzheimer's disease (AD) and 33 patients with frontotemporal dementia (FTD), comprising 20 with temporal variant FTD (tv FTD) or semantic dementia and 13 with frontal variant FTD (fv FTD). An exploratory principal components factor analysis and discriminant function analysis was applied.
Factor analysis showed four robust and meaningful symptom clusters: factor 1-stereotypic and eating behaviour; factor 2-executive dysfunction and self care; factor 3-mood changes; factor 4-loss of social awareness. Only stereotypic and altered eating behaviour and loss of social awareness reliably differentiated AD from FTD with no effect of disease severity. By contrast, executive dysfunction, poor self care, and restlessness showed a significant effect of disease severity only, with the more impaired patients scoring more highly. Changes in mood were found to be equally prevalent in the three patient groups. Analysis of individual symptoms showed increased rates of mental rigidity and depression in the patients with semantic dementia compared with those with fv FTD. Conversely, the latter group showed greater disinhibition. Discriminant function analysis correctly classified 71.4% overall and 86.5% of the patients with AD.
This questionnaire disclosed striking differences between patients with FTD and AD, but only stereotypic behaviour, changes in eating preference, disinhibition, and features of poor social awareness reliably separated the groups. The patients with fv FTD and semantic dementia were behaviourally very similar, reflecting the involvement of a common network, the ventral frontal lobe, temporal pole, and amygdala. Dysexecutive symptoms and poor self care were found to be affected by the severity of the disease, reflecting perhaps spread to dorsolateral prefrontal areas relatively late in the course of both FTD and AD. This questionnaire may be of value in the diagnosis and the monitoring of therapies.
Frontotemporal dementia (FTD) is associated with a variety of cognitive and behavioral dysfunctions. Symptoms may be influenced by the relative involvement of the right versus the left hemisphere, with left-sided FTD manifesting language changes and right-sided FTD presenting with aggressive, antisocial, and other socially undesirable behaviors.
To test the hypothesis that right-sided FTD is associated with socially undesirable behavior.
The authors assessed 41 patients with FTD diagnosed by the new research criteria for FTD(1) including behavioral, neuropsychologic, and neurologic testing as well as SPECT and MRI. Based on visual inspection of SPECT scans, 12 patients were classified as having predominantly right-sided and 19 patients were classified as having predominantly left-sided FTD. A clinician blinded to the imaging data reviewed medical records to tabulate the frequency of the following socially undesirable behaviors: criminal behavior, aggression, loss of job, alienation from family/friends, financial recklessness, sexually deviant behavior, and abnormal response to spousal crisis.
Eleven of 12 right-sided and 2 of 19 left-sided FTD patients had socially undesirable behavior as an early presenting symptom (chi = 23.3, p < 0.001).
The authors conclude that right-sided frontotemporal degeneration is associated with socially undesirable behavior. The early presence of socially undesirable behavior in FTD differentiates right-sided from left-sided degeneration. The results highlight the importance of the right hemisphere, especially frontotemporal regions, in the mediation of social behavior. The potential mechanism for these social losses with right-sided disease is discussed.
A neglected question regarding cognitive control is how control processes might detect situations calling for their involvement. The authors propose here that the demand for control may be evaluated in part by monitoring for conflicts in information processing. This hypothesis is supported by data concerning the anterior cingulate cortex, a brain area involved in cognitive control, which also appears to respond to the occurrence of conflict. The present article reports two computational modeling studies, serving to articulate the conflict monitoring hypothesis and examine its implications. The first study tests the sufficiency of the hypothesis to account for brain activation data, applying a measure of conflict to existing models of tasks shown to engage the anterior cingulate. The second study implements a feedback loop connecting conflict monitoring to cognitive control, using this to simulate a number of important behavioral phenomena.
To evaluate the frequency and types of change in "self" seen in frontotemporal dementia (FTD) and to determine the relative involvement of the nondominant and dominant frontal and temporal brain regions in FTD patients with or without changes in a sense of self using neuropsychology tests and neuroimaging.
The self has been defined as "the total, essential, or particular being of a person" involving "the essential qualities distinguishing one person from another." Some suggest that the frontal lobes play a dominant role in maintaining the self. FTD affects anterior frontal and temporal areas and can be associated with a loss of self.
Seventy-two consecutive FTD patients were evaluated with neuropsychiatric, neuropsychologic, and behavioral measures. Patients were imaged with MRI and SPECT. Charts were reviewed by a social psychologist to determine patients who exhibited a dramatic change in their self as defined by changes in political, social, or religious values. The brain areas with the most severe atrophy or hypoperfusion on neuroimaging were noted.
Seven of 72 patients exhibited a dramatic change in self. In six of the seven, the selective dysfunction involved the nondominant frontal region. In contrast, only one of the other 65 patients without selective nondominant frontal dysfunction showed a change in self.
FTD patients with asymmetric loss of function in the nondominant frontal lobe often exhibit a diminished maintenance of previously learned self-concepts despite intact memory and language. Normal nondominant frontal function is important for the maintenance of the self.
An international group of clinical and basic scientists participated in the Frontotemporal Dementia and Pick's Disease Criteria Conference at the National Institutes of Health in Bethesda, Md, on July 7, 2000, to reassess clinical and neuropathological criteria for the diagnosis of frontotemporal dementia (FTD). Previous criteria for FTD have primarily been designed for research purposes. The goal of this meeting was to propose guidelines that would enable clinicians (particularly neurologists, psychiatrists, and neuropsychologists) to recognize patients with FTD and, if appropriate, to expedite their referral to a diagnostic center. In addition, recommendations for the neuropathological criteria of FTD were reviewed, relative to classical neuropathology and modern molecular biology.
To identify and compare the patterns of cerebral atrophy associated with two clinical variants of frontotemporal lobar degeneration (FTLD): frontotemporal dementia (FTD) and semantic dementia (SemD).
Twenty patients with FTLD were classified as having FTD (N = 8) or SemD (N = 12) based on current clinical criteria. Both groups showed a similar spectrum of behavioral abnormalities, as indicated by the neuropsychiatric inventory. T1-weighted MRI was obtained for each patient and 20 control subjects. The regions of focal gray matter tissue loss associated with both FTD and SemD, as well as those differing between the two groups were examined using voxel-based morphometry.
Regions of significant atrophy seen in both groups were located in the ventromedial frontal cortex, the posterior orbital frontal regions bilaterally, the insula bilaterally, and the left anterior cingulate cortex. The FTD, but not the SemD, group showed atrophy in the right dorsolateral frontal cortex and the left premotor cortex. The SemD, but not the FTD, group showed tissue loss in the anterior temporal cortex and the amygdala/anterior hippocampal region bilaterally.
Although FTD and SemD are associated with different overall patterns of brain atrophy, regions of gray matter tissue loss in the orbital frontal, insular, and anterior cingulate regions are present in both groups. The authors suggest that pathology in the areas of atrophy associated with both FTD and SemD may underlie some the behavioral symptoms seen in the two disorders.
A key aspect of social cognition is the ability to infer other people's mental states, thoughts and feelings; referred to as 'theory of mind' (ToM). We tested the hypothesis that the changes in personality and behaviour seen in frontal variant frontotemporal dementia (fvFTD) may reflect impairment in this cognitive domain. Tests of ToM, executive and general neuropsychological ability were given to 19 fvFTD patients, a comparison group of Alzheimer's disease patients (n = 12) and matched healthy controls (n = 16). Neuropsychiatric assessment was undertaken using the Neuropsychiatric Inventory (NPI). Patients with fvFTD were impaired on all tests of ToM (first-order false belief; second-order false belief; faux pas detection; and Reading the Mind in the Eyes), but had no difficulty with control questions designed to test general comprehension and memory. By contrast, the Alzheimer's disease group failed only one ToM task (second-order false belief), which places heavy demands on working memory. Performance on the faux pas test revealed a double dissociation, with the fvFTD group showing deficits on ToM-based questions and the Alzheimer's disease group failing memory-based questions only. Rank order of the fvFTD patients according to the magnitude of impairment on tests of ToM and their degree of frontal atrophy showed a striking concordance between ToM performances and ventromedial frontal damage. There was a significant correlation between the NPI score and more sophisticated tests of ToM in the fvFTD group. This study supports the hypothesis that patients with fvFTD, but not those with Alzheimer's disease, are impaired on tests of ToM, and may explain some of the abnormalities in interpersonal behaviour that characterize fvFTD.
A recent flurry of neuroimaging and decision-making experiments in humans, when combined with single-unit data from orbitofrontal cortex, suggests major additions to current models of reward processing. We review these data and models and use them to develop a specific computational relationship between the value of a predictor and the future rewards or punishments that it promises. The resulting computational model, the predictor-valuation model (PVM), is shown to anticipate a class of single-unit neural responses in orbitofrontal and striatal neurons. The model also suggests how neural responses in the orbitofrontal-striatal circuit may support the conversion of disparate types of future rewards into a kind of internal currency, that is, a common scale used to compare the valuation of future behavioral acts or stimuli.
Efforts to characterize changes in social functioning in frontotemporal dementia (FTD) have failed to elicit clear dissociation between frontal and temporal variants of the disease based on behavioral measures.
This study obtained premorbid and current first-degree relative ratings using an established measure of interpersonal functioning, the Interpersonal Adjectives Scales, to measure personality change in 16 patients with frontal variant (FLV) and 13 with temporal variant (TLV) FTD, and in a control group of 16 patients with AD.
All three groups showed significant change over time in multiple domains, including increased introversion (FG) and submissiveness (HI). However, patients with both FTD subtypes evidenced significantly greater increases in overall interpersonal pathology vector length [VL] than did patients with AD, who remained within the normal range on all scores. Patients with FLV showed a 2 SD increase in submissiveness (HI), but their cold-heartedness (DE) change scores were not significantly different from those of patients with AD. Conversely, the TLV cold-heartedness (DE) score increased 2 SD compared to minimal change for the AD and FLV groups, yet change in submissiveness (HI) did not differentiate between AD and TLV groups.
The Interpersonal Adjectives Scales differentiated both FTD groups from patients with AD on the basis of both degree and direction of personality change. Also, the two subtypes of FTD showed distinctly different patterns of change in social functioning: patients with temporal variant shifted toward severe interpersonal coldness with mild loss of dominance, whereas patients with frontal variant showed the opposite pattern.
We are an intensely social species--it has been argued that our social nature defines what makes us human, what makes us conscious or what gave us our large brains. As a new field, the social brain sciences are probing the neural underpinnings of social behaviour and have produced a banquet of data that are both tantalizing and deeply puzzling. We are finding new links between emotion and reason, between action and perception, and between representations of other people and ourselves. No less important are the links that are also being established across disciplines to understand social behaviour, as neuroscientists, social psychologists, anthropologists, ethologists and philosophers forge new collaborations.
Prefrontal cortex (PFC) supports flexible behavior by mediating cognitive control, though the elemental forms of control supported by PFC remain a central debate. Dorsolateral PFC (DLPFC) is thought to guide response selection under conditions of response conflict or, alternatively, may refresh recently active representations within working memory. Lateral frontopolar cortex (FPC) may also adjudicate response conflict, though others propose that FPC supports higher order control processes such as subgoaling and integration. Anterior cingulate cortex (ACC) is hypothesized to upregulate response selection by detecting response conflict; it remains unclear whether ACC functions generalize beyond monitoring response conflict. The present fMRI experiment directly tested these competing theories regarding the functional roles of DLPFC, FPC, and ACC. Results reveal dissociable control processes in PFC, with mid-DLPFC selectively mediating resolution of response conflict and FPC further mediating subgoaling/integration. ACC demonstrated a broad sensitivity to control demands, suggesting a generalized role in modulating cognitive control.
Ventromedial prefrontal cortex (VMF) damage can lead to impaired decision-making. This has been studied most intensively with the Iowa gambling task (IGT), a card game that asks subjects to overcome an initial attraction to high-payoff decks as losses begin to accrue. VMF subjects choose from the high risk decks more often than controls, but the fundamental impairments driving poor performance on this complex task have yet to be established. There is also conflicting evidence regarding the role of the dorsolateral prefrontal cortex (DLF) in this task. The present study examined whether poor performance on the IGT was specific for VMF damage and whether fundamental impairments in reversal learning contributed to IGT performance. We found that both VMF and DLF damage leads to impaired IGT performance. The impairment of VMF subjects, but not of DLF subjects, seems to be largely explained by an underlying reversal learning deficit.