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Envy or schadenfreude? Reduced malicious pleasure in Huntington's disease families
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Counterfactual thinking (CFT) refers to the generation of mental simulations of alternatives to past events, actions and outcomes. CFT is a pervasive cognitive feature in every-day life and is closely related to decision-making, planning and problem-solving - all of which are cognitive processes linked to unimpaired frontal lobe functioning. Huntington's Disease (HD) is a neurodegenerative disorder characterised by motor, behavioral and cognitive dysfunctions. Because an impairment in frontal and executive functions has been described in HD, we hypothesised that HD patients may have a CFT impairment.
Tests of spontaneous counterfactual thoughts and counterfactual-derived inferences were administered to 24 symptomatic HD patients and 24 age- and sex-matched healthy subjects.
Our results show a significant impairment in the spontaneous generation of CFT and low performance on the Counterfactual Inference Test (CIT) in HD patients. Low performance on the spontaneous CFT test significantly correlates with impaired attention abilities, verbal fluency and frontal lobe efficiency, as measured by Trail Making Test - Part A, Phonemic Verbal Fluency Test and FAB.
Spontaneous CFT and the use of this type of reasoning are impaired in HD patients. This deficit may be related to frontal lobe dysfunction, which is a hallmark of HD. Because CFT has a pervasive role in patients' daily lives regarding their planning, decision making and problem solving skills, cognitive rehabilitation may improve HD patients' ability to analyse current behaviors and future actions.
Social cognition—the basis of all communicative and otherwise interpersonal relationships—is embedded in specific contextual circumstances which shape intrinsic meanings. This domain is compromised in the autism spectrum disorders (ASDs), including Asperger's syndrome (AS) (DSM-V). However, the few available reports of social cognition skills in adults with AS have largely neglected the effects of contextual factors. Moreover, previous studies on this population have also failed to simultaneously (a) assess multiple social cognition domains, (b) examine executive functions, (c) follow strict sample selection criteria, and (d) acknowledge the cognitive heterogeneity typical of the disorder. The study presently reviewed (Baez et al., 2012), addressed all these aspects in order to establish the basis of social cognition deficits in adult AS patients. Specifically, we assessed the performance of AS adults in multiple social cognition tasks with different context-processing requirements. The results suggest that social cognition deficits in AS imply a reduced ability to implicitly encode and integrate contextual cues needed to access social meaning. Nevertheless, the patients' performance was normal when explicit social information was presented or when the situation could be navigated with abstract rules. Here, we review the results of our study and other relevant data, and discuss their implications for the diagnosis and treatment of AS and other neuropsychiatric conditions (e.g., schizophrenia, bipolar disorder, frontotemporal dementia). Finally, we analyze previous results in the light of a current neurocognitive model of social-context processing.
We examined whether counterfactual thinking influences the experience of envy. Counterfactual thinking refers to comparing the situation as it is to what it could have been, and these thought processes have been shown to lead to a variety of emotions. We predicted that for envy the counterfactual thought "it could have been me" would be important. In four studies we found a clear link between such counterfactual thoughts and the intensity of envy. Furthermore, Studies 3 and 4 revealed that a manipulation known to affect the extent of counterfactual thinking (the perception of being close to obtaining the desired outcome oneself), had an effect on the intensity of envy via counterfactual thoughts. This relationship between counterfactual thinking and the experience of envy allows for new predictions concerning situations under which envy is likely be more intense.
Traditionally, Huntington's disease (HD) has been known as a movement disorder, characterized by motor, psychiatric, and cognitive impairments. Recent studies have shown that motor and action-language processes are neurally associated. The cognitive mechanisms underlying this interaction have been investigated through the action compatibility effect (ACE) paradigm, which induces a contextual coupling of ongoing motor actions and verbal processing. The present study is the first to use the ACE paradigm to evaluate action-word processing in HD patients (HDP) and their families. Specifically, we tested three groups: HDP, healthy first-degree relatives (HDR), and non-relative healthy controls. The results showed that ACE was abolished in HDP as well as HDR, but not in controls. Furthermore, we found that the processing deficits were primarily linguistic, given that they did not correlate executive function measurements. Our overall results underscore the role of cortico-basal ganglia circuits in action-word processing and indicate that the ACE task is a sensitive and robust early biomarker of HD and familial vulnerability.
Background
The ability to integrate contextual information with social cues to generate social meaning is a key aspect of social cognition. It is widely accepted that patients with schizophrenia and bipolar disorders have deficits in social cognition; however, previous studies on these disorders did not use tasks that replicate everyday situations.
Methodology/Principal Findings
This study evaluates the performance of patients with schizophrenia and bipolar disorders on social cognition tasks (emotional processing, empathy, and social norms knowledge) that incorporate different levels of contextual dependence and involvement of real-life scenarios. Furthermore, we explored the association between social cognition measures, clinical symptoms and executive functions. Using a logistic regression analysis, we explored whether the involvement of more basic skills in emotional processing predicted performance on empathy tasks. The results showed that both patient groups exhibited deficits in social cognition tasks with greater context sensitivity and involvement of real-life scenarios. These deficits were more severe in schizophrenic than in bipolar patients. Patients did not differ from controls in tasks involving explicit knowledge. Moreover, schizophrenic patients’ depression levels were negatively correlated with performance on empathy tasks.
Conclusions/Significance
Overall performance on emotion recognition predicted performance on intentionality attribution during the more ambiguous situations of the empathy task. These results suggest that social cognition deficits could be related to a general impairment in the capacity to implicitly integrate contextual cues. Important implications for the assessment and treatment of individuals with schizophrenia and bipolar disorders, as well as for neurocognitive models of these pathologies are discussed.
Deficits in social cognition are an evident clinical feature of the Asperger syndrome (AS). Although many daily life problems of adults with AS are related to social cognition impairments, few studies have conducted comprehensive research in this area. The current study examined multiple domains of social cognition in adults with AS assessing the executive functions (EF) and exploring the intra and inter-individual variability. Fifteen adult's diagnosed with AS and 15 matched healthy controls completed a battery of social cognition tasks. This battery included measures of emotion recognition, theory of mind (ToM), empathy, moral judgment, social norms knowledge, and self-monitoring behavior in social settings. We controlled for the effect of EF and explored the individual variability. The results indicated that adults with AS had a fundamental deficit in several domains of social cognition. We also found high variability in the social cognition tasks. In these tasks, AS participants obtained mostly subnormal performance. EF did not seem to play a major role in the social cognition impairments. Our results suggest that adults with AS present a pattern of social cognition deficits characterized by the decreased ability to implicitly encode and integrate contextual information in order to access to the social meaning. Nevertheless, when social information is explicitly presented or the situation can be navigated with abstract rules, performance is improved. Our findings have implications for the diagnosis and treatment of individuals with AS as well as for the neurocognitive models of this syndrome.
Depression is the most common psychiatric disorder in Huntington's disease (HD) patients. In the general population, women are more prone to develop depression and such susceptibility might be related to serotonergic dysregulation. There is yet to be a study of sexual dimorphism in the development and presentation of depression in HD patients. We investigated whether 8-week-old male and female R6/1 transgenic HD mice display depressive-like endophenotypes associated with serotonergic impairments. We also studied the behavioral effects of acute treatment with sertraline. We found that only female HD mice exhibited a decreased preference for saccharin as well as impaired emotionality-related behaviors when assessed on the novelty-suppressed feeding test (NSFT) and the forced-swimming test (FST). The exaggerated immobility time displayed by female HD in the FST was reduced by acute administration of sertraline. We also report an increased response to the 5-HT(1A) receptor agonist 8-OH-DPAT in inducing hypothermia and a decreased 5-HT(2A) receptor function in HD animals. While tissue levels of serotonin were reduced in both male and female HD mice, we found that serotonin concentration and hydroxylase-2 (TPH2) mRNA levels were higher in the hippocampus of males compared to female animals. Finally, the antidepressant-like effects of sertraline in the FST were blunted in male HD animals. This study reveals sex-specific depressive-related behaviors during an early stage of HD prior to any cognitive and motor deficits. Our data suggest a crucial role for disrupted serotonin signaling in mediating the sexually dimorphic depression-like phenotype in HD mice.
HD entails damage of the WM. Our aim was to explore in vivo the regional volume and microstructure of the brain WM in HD and to correlate such findings with clinical status of the patients.
Fifteen HD gene carriers in different clinical stages of the disease and 15 healthy controls were studied with T1-weighted images for VBM and DTI for TBSS. Maps of FA, MD, and λ∥ and λ⊥ were reconstructed.
Compared with controls, in addition to neostriatum and cortical GM volume loss, individuals with HD showed volume loss in the genu of the internal capsule and subcortical frontal WM bilaterally, the right splenium of the corpus callosum, and the left corona radiata. TBSS revealed symmetrically decreased FA in the corpus callosum, fornix, external/extreme capsule, inferior fronto-occipital fasciculus, and inferior longitudinal fasciculus. Areas of increased MD were more extensive and included arciform fibers of the cerebral hemispheres and cerebral peduncles. Increase of the λ∥ and a comparatively more pronounced increase of the λ⊥ underlay the decreased FA of the WM in HD. Areas of WM atrophy, decreased FA, and increased MD correlated with the severity of the motor and cognitive dysfunction, whereas only the areas with increased MD correlated with disease duration.
Microstructural damage accompanies volume decrease of the WM in HD and is correlated with the clinical deficits and disease duration. MR imaging-based measures could be considered as a biomarker of neurodegeneration in HD gene carriers.
Emotions like regret and envy share a common origin: they are motivated by the counterfactual thinking of what would have happened had we made a different choice. When we contemplate the outcome of a choice we made, we may use the information on the outcome of a choice we did not make. Regret is the purely private comparison between two choices that we could have taken, envy adds to this the information on outcome of choices of others. However, envy has a distinct social component, in that it adds the change in the social ranking that follows a difference in the outcomes. We study the theoretical foundation and the experimental test of this view.
Attention-deficit hyperactivity disorder (ADHD) is associated with a range of cognitive deficits and social cognition impairments, which might be interpreted in the context of fronto-striatal dysfunction. So far only few studies have addressed the issue of social cognition deficits in ADHD.
Medline and Psyclit searches were performed for a 30-year period (1979-2009) using the words 'ADHD' and 'social cognition', 'theory of mind', 'prosody', 'face perception', 'humour' or 'social information processing'. Inclusion criteria consisted of a diagnosis according to DSM as well as the inclusion of a control group or a follow-up assessment following the treatment with methylphenidate.
ADHD is clearly associated with social cognition impairments involving emotional face and prosody perception. Although the database is sparse so far, there is some evidence for theory of mind deficits and reduced empathy in ADHD.
In summary, the social cognition impairments are consistent with fronto-striatal dysfunction in ADHD, but other functional networks of brain areas also appear to be implicated.
Numerous studies have demonstrated that Huntington's disease mutation-carriers have deficient explicit recognition of isolated facial expressions. There are no studies, however, which have investigated the recognition of facial expressions embedded within an emotional body and scene context. Real life facial expressions are typically embedded in contexts which may dramatically change the emotion recognized in the face. Moreover, a recent study showed that the magnitude of the contextual bias is modulated by the similarity between the actual expression of the presented face and the facial expression that would typically fit the context, e.g. disgust faces are more similar to anger than to sadness faces and, consequently, are more strongly influenced by contexts expressing anger than by contexts expressing sadness. Since context effects on facial expression perception are not explicitly controlled, their pattern serves as an implicit measure of the processing of facial expressions. In this study we took advantage of the face-in-context design to compare explicit recognition of face-expressions by Huntington's disease mutation-carriers, with evidence for processing the expressions deriving from implicit measures. In an initial experiment we presented a group of 21 Huntington's disease mutation-carriers with standard tests of face-expression recognition. Relative to controls, they displayed deficits in recognizing disgust and anger faces despite intact recognition of these emotions from non-facial images. In a subsequent experiment, we embedded the disgust faces on images of people conveying sadness and anger as expressed by body language and additional paraphernalia. In addition, sadness and anger faces were embedded on context images conveying disgust. In both cases participants were instructed to categorize the facial expressions, ignoring the context. Despite the deficient explicit recognition of isolated disgust and anger faces, the perception of the emotions expressed by the faces was affected by context in Huntington's disease mutation-carriers in a similar manner as in control participants. Specifically, they displayed the same sensitivity to face-context pairings. These findings suggest that, despite their impaired explicit recognition of facial expressions, Huntington's disease mutation-carriers display relatively preserved processing of the same facial configurations when embedded in context. The results also show intact utilization of the information elicited by contextual cues about faces expressing disgust even when the actually presented face expresses a different emotion. Overall, our findings shed light on the nature of the deficit in facial expression recognition in Huntington's disease mutation-carriers as well as underscore the importance of context in emotion perception.
We often evaluate the self and others from social comparisons. We feel envy when the target person has superior and self-relevant
characteristics. Schadenfreude occurs when envied persons fall from grace. To elucidate the neurocognitive mechanisms of envy
and schadenfreude, we conducted two functional magnetic resonance imaging studies. In study one, the participants read information
concerning target persons characterized by levels of possession and self-relevance of comparison domains. When the target
person's possession was superior and self-relevant, stronger envy and stronger anterior cingulate cortex (ACC) activation
were induced. In study two, stronger schadenfreude and stronger striatum activation were induced when misfortunes happened
to envied persons. ACC activation in study one predicted ventral striatum activation in study two. Our findings document mechanisms
of painful emotion, envy, and a rewarding reaction, schadenfreude.
Organization in hierarchical dominance structures is prevalent in animal societies, so a strong preference for higher positions in social ranking is likely to be an important motivation of human social and economic behavior. This preference is also likely to influence the way in which we evaluate our outcome and the outcome of others, and finally the way we choose. In our experiment participants choose among lotteries with different levels of risk, and can observe the choice that others have made. Results show that the relative weight of gains and losses is the opposite in the private and social domain. For private outcomes, experience and anticipation of losses loom larger than gains, whereas in the social domain, gains loom larger than losses, as indexed by subjective emotional evaluations and physiological responses. We propose a theoretical model (interdependent utilities), predicting the implication of this effect for choice behavior. The relatively larger weight assigned to social gains strongly affects choices, inducing complementary behavior: faced with a weaker competitor, participants adopt a more risky and dominant behavior.
Investigation of motor function in a group of 17 patients with Huntington's disease reveals that, in addition to the chorea that many patients exhibit, defects in voluntary motor performance also are evident. Fast simple wrist flexion movements to 15 degrees or 60 degrees were slower, and individual movements showed greater variability than seen in normal subjects. This bradykinesia was most pronounced in those patients who were akinetic and rigid, but also was seen in those with chorea alone; bradykinesia was independent of the drug treatment that the patients were receiving (and was therefore not due to drug-induced parkinsonism). The electromyographic activity of the agonist muscles during such simple but slow movement differed from that seen in Parkinson's disease. The performance of complex movements revealed further deficits. Some patients were unable to combine two movements in a simultaneous or sequential movement task of squeezing the hand and flexing the elbow. Those who could perform these complex movements exhibited slowing of the velocity of the movement and prolongation of the interval between movements. These abnormalities were present in patients with chorea who were not taking neuroleptic drugs. It is argued that they represent an abnormality of motor programming of complex movements, over and above the defect in executing simple movements. The long latency stretch reflexes in wrist flexor muscles and flexor pollicis longus were reduced or absent, but this did not correlate with changes in motor performance, or with the reduced size of the early components of cortical sensory evoked potentials. Bradykinesia is thus shown to be an integral component of the motor disorder of Huntington's disease, in addition to the chorea. The coexistence of bradykinesia and chorea in this illness is compatible with current theories of the role of the basal ganglia in the control of movement.
To analyse grey matter changes in early stages of Huntington's disease using magnetic resonance imaging (MRI) and the technique of voxel based morphometry (VBM).
Forty four patients with a molecularly confirmed clinical diagnosis of Huntington's disease based on the presence of motor signs were included in the study. Patients were clinically rated using the Unified Huntington's Disease Rating Scale; all were in early clinical stages of the disease (that is, Shoulson stages I and II). High resolution volume rendering MRI scans (MP-RAGE) were acquired. MRI data were volumetrically analysed in comparison to an age matched normal database by VBM, using statistical parametric mapping (SPM99).
In Huntington's disease, robust regional decreases in grey matter density (p<0.001, corrected for multiple comparisons)-that is, atrophy-were found bilaterally in striatal areas as well as in the hypothalamus and the opercular cortex, and unilaterally in the right paracentral lobule. The topography of striatal changes corresponded to the dorso-ventral gradient of neuronal loss described in neuropathological studies. Stratification according to clinical severity showed a more widespread involvement extending into the ventral aspects of the striatum in the group of more severely affected patients.
The topography of cerebral volume changes associated with Huntington's disease can be mapped using VBM. It can be shown that cerebral grey matter changes co-vary with clinical severity and CAG repeat length.
Disturbances in recognizing facial expressions of disgust have been reported previously in pre-symptomatic and manifest Huntington's disease. Given the substantial role of the insula and basal ganglia in the perception of disgust as revealed by functional imaging, lesion studies and intracerebral recordings, we propose dysfunction within the insula and/or basal ganglia as the underlying neural substrate. Using functional MRI (fMRI), we studied a group of nine pre-symptomatic Huntington's disease gene carriers and nine healthy controls, matched for age, gender, intelligence and years of education, while they were viewing disgusted facial expressions. As control conditions, surprised and neutral expressions were presented. Compared with healthy controls, Huntington's disease gene carriers showed reduced responses within the left dorsal anterior insula during processing of disgusted facial expressions. Moreover, processing of disgust was associated with significant activation of the left dorsal anterior insula and putamen in healthy controls, but not in Huntington's disease gene carriers. Furthermore, behavioural assessment revealed a selective impairment in recognizing facial expressions displaying disgust in Huntington's disease gene carriers. Our finding of dysfunctional decreased insula activation in pre-symptomatic Huntington's disease provides an explanation for the clinical deficit in recognizing facial expression of disgust. Furthermore, it underscores the role of the insula in the emotion of disgust.
Previous research yielded conflicting results concerning the role of envy in predicting Schadenfreude (pleasure at another's misfortune). Some studies showed that envy predicts Schadenfreude, whereas others did not. Results of the present research reconcile these opposing findings, by showing that envy is a predictor of Schadenfreude when the target is similar to the observer in terms of gender. These results suggest that envy predicts Schadenfreude when people are confronted with the misfortune of a relevant social comparison other.
The optimal design and outcome measures for preventive clinical trials in neurodegenerative diseases are unknown.
To examine measures that may be associated with disease in the largest cohort ever recruited of prediagnosed individuals carrying the gene expansion for Huntington disease (HD).
The Predict-HD study is a multicenter observational research study in progress at 17 sites in the United States, 4 in Canada, and 3 in Australia.
Genetics and HD outpatient clinics.
Five hundred five at-risk individuals who had previously undergone elective DNA analyses for the CAG expansion in the HD gene (predictive testing) and did not currently have a clinical diagnosis of HD.
Basal ganglia volumes on magnetic resonance images, estimated probability of diagnosis (based on CAG repeat length), performances on 21 standardized cognitive tasks, total scores on 3 scales of psychiatric distress, and motor diagnosis based on the Unified Huntington's Disease Rating Scale.
Several variables showed progressive decline as the diagnostic ratings advanced toward manifest disease. Estimated probability of diagnosis was associated with Unified Huntington's Disease Rating Scale prediagnostic stages and varied from 15% in persons with no motor abnormalities to nearly 40% in those with abnormalities suggestive of probable disease. Striatal volumes, cognitive performances, and even psychiatric ratings declined significantly with motor manifestations of disease.
The documentation of biological and refined clinical markers suggests several clinical end points for preventive clinical trials. Longitudinal study is critical to further validate possible markers for prediagnosed HD.
Objectives:
Behavioral variant frontotemporal dementia (bvFTD) is characterized by early atrophy in the frontotemporoinsular regions. These regions overlap with networks that are engaged in social cognition-executive functions, two hallmarks deficits of bvFTD. We examine (i) whether Network Centrality (a graph theory metric that measures how important a node is in a brain network) in the frontotemporoinsular network is disrupted in bvFTD, and (ii) the level of involvement of this network in social-executive performance.
Methods:
Patients with probable bvFTD, healthy controls, and frontoinsular stroke patients underwent functional MRI resting-state recordings and completed social-executive behavioral measures.
Results:
Relative to the controls and the stroke group, the bvFTD patients presented decreased Network Centrality. In addition, this measure was associated with social cognition and executive functions. To test the specificity of these results for the Network Centrality of the frontotemporoinsular network, we assessed the main areas from six resting-state networks. No group differences or behavioral associations were found in these networks. Finally, Network Centrality and behavior distinguished bvFTD patients from the other groups with a high classification rate.
Conclusions:
bvFTD selectively affects Network Centrality in the frontotemporoinsular network, which is associated with high-level social and executive profile.
Eighteen patients with early Huntington's disease were compared with age-and IQ-matched control volunteers on tests of executive and mnemonic function taken from the Cambridge Neuropsychological Test Automated Battery. Tests of pattern and spatial recognition memory, spatial span, spatial working memory, spatial planning and visual discrimination learning/attentional set shifting were employed. These tests have previously been found to be sensitive to the later stages of Huntington 's disease. Patients with early Huntington's disease were found to have a wide range of cognitive impairments encompassing both visuo-spatial memory and executive functions, a pattern distinct from those seen in other basal ganglia disorders. In contrast to patients with more advanced Huntington's disease, early Huntington's disease patients were not impaired at simple reversal learning, but were impaired at performing an extradimensional shift (EDS). The results will be discussed in relation to the hypothesized neuropathological staging of Huntington's disease and to the anatomical connectivity of the striatum.
The role of contextual modulations has been extensively studied in basic sensory and cognitive processes. However, little is known about their impact on social cognition, let alone their disruption in disorders compromising such a domain. In this chapter, we flesh out the social context network model (SCNM), a neuroscientific proposal devised to address the issue. In SCNM terms, social context effects rely on a fronto-temporo-insular network in charge of (a) updating context cues to make predictions, (b) consolidating context-target associative learning, and (c) coordinating internal and external milieus. First, we characterize various social cognition domains as context-dependent phenomena. Then, we review behavioral and neural evidence of social context impairments in behavioral variant frontotemporal dementia (bvFTD) and autism spectrum disorder (ASD), highlighting their relation with key SCNM hubs. Next, we show that other psychiatric and neurological conditions involve context-processing impairments following damage to the brain regions included in the model. Finally, we call for an ecological approach to social cognition assessment, moving beyond widespread abstract and decontextualized methods.
Background:
Moral judgment has been proposed to rely on a distributed brain network. This function is impaired in behavioral variant frontotemporal dementia (bvFTD), a condition involving damage to some regions of this network. However, no studies have investigated moral judgment in bvFTD via structural neuroimaging.
Methods:
We compared the performance of 21 bvFTD patients and 19 controls on a moral judgment task involving scenarios that discriminate between the contributions of intentions and outcomes. Voxel-based morphometry was used to assess (a) the atrophy pattern in bvFTD patients, (b) associations between gray matter (GM) volume and moral judgments, and (c) structural differences between bvFTD subgroups (patients with relatively preserved moral judgment and patients with severer moral judgment impairments).
Results:
Patients judged attempted harm as more permissible and accidental harm as less permissible than controls. The groups' performance on accidental harm was associated with GM volume in the precuneus. In controls, it was al- so associated with the ventromedial prefrontal cortex (VMPFC). Also, both groups' performance on attempted harm was associated with GM volume in the temporoparietal junction. Patients exhibiting worse performance displayed smaller GM volumes in the precuneus and temporal pole.
Conclusions:
Results suggest that moral judgment abnormalities in bvFTD are associated with impaired integration of intentions and outcomes, which depends on an extended brain network. In bvFTD, moral judgment seems to critically depend on areas beyond the VMPFC.
Perceiving and evaluating intentional harms in an interpersonal context engages both cognitive and emotional domains. This process involves inference of intentions, moral judgment, and, crucially, empathy towards others' suffering. This latter skill is notably impaired in behavioral variant frontotemporal dementia (bvFTD). However, the relationship between regional brain atrophy in bvFTD and deficits in the above-mentioned abilities is not well understood. The present study investigated how gray matter (GM) atrophy in bvFTD patients correlates with the perception and evaluation of harmful actions (attribution of intentionality, evaluation of harmful behavior, empathic concern, and moral judgment). First, we compared the behavioral performance of 26 bvFTD patients and 23 healthy controls on an experimental task (ET) indexing intentionality, empathy, and moral cognition during evaluation of harmful actions. Second, we compared GM volume in patients and controls using voxel-based morphometry (VBM). Third, we examined brain regions where atrophy might be associated with specific impairments in the patient group. Finally, we explored whether the patients' deficits in intentionality comprehension and empathic concern could be partially explained by regional GM atrophy or impairments in other relevant factors, such as executive functions (EFs). In bvFTD patients, atrophy of limbic structures (amygdala and anterior paracingulate cortex - APC) was related to impairments in intentionality comprehension, while atrophy of the orbitofrontal cortex (OFC) was associated with empathic concern deficits. Intentionality comprehension impairments were predicted by EFs and orbitofrontal atrophy predicted deficits in empathic concern. Thus, although the perception and evaluation of harmful actions are variously compromised in bvFTD, deficits in empathic concern may be central to this syndrome as they are associated with one of the earliest atrophied region. More generally, our results shed light on social cognition deficits in bvFTD and may have important clinical implications.
Loss of empathy is an early central symptom and diagnostic criterion of the behavioral variant frontotemporal dementia (bvFTD). Although changes in empathy are evident and strongly affect the social functioning of bvFTD patients, few studies have directly investigated this issue by means of experimental paradigms. The current study assessed multiple components of empathy (affective, cognitive and moral) in bvFTD patients. We also explored whether the loss of empathy constitutes a primary deficit of bvFTD or whether it is explained by impairments in executive functions (EF) or other social cognition domains. Thirty-seven bvFTD patients with early/mild stages of the disease and 30 healthy control participants were assessed with a task that involves the perception of intentional and accidental harm. Participants were also evaluated on emotion recognition, theory of mind (ToM), social norms knowledge and several EF domains. BvFTD patients presented deficits in affective, cognitive and moral aspects of empathy. However, empathic concern was the only aspect primarily affected in bvFTD that was neither related nor explained by deficits in EF or other social cognition domains. Deficits in the cognitive and moral aspects of empathy seem to depend on EF, emotion recognition and ToM. Our findings highlight the importance of using tasks depicting real-life social scenarios because of their greater sensitivity in the assessment of bvFTD. Moreover, our results contribute to the understanding of primary and intrinsic empathy deficits of bvFTD and have important theoretical and clinical implications.
People often fail to empathize with others, and sometimes even experience schadenfreude-pleasure at others' misfortunes. One potent predictor of schadenfreude is envy, which, according to the stereotype content model, is elicited by high-status, competitive targets. Here we review our recent research program investigating the relationships among stereotypes, envy, schadenfreude, and harm. Experiment 1 demonstrates that stereotypes are sufficient to influence affective responses to targets' misfortunes; participants not only report feeling less negative when misfortunes befall high-status, competitive targets as compared to other targets, they also smile more (assessed with facial EMG). Experiment 2 replicates the self-report findings from Experiment 1 and assesses behavioral tendencies toward envied targets; participants are more willing to endorse harming high-status, competitive targets as compared to other targets. Experiment 3 turns off the schadenfreude response by manipulating status and competition-relevant information regarding envied targets. Finally, Experiment 4 investigates affective and neural markers of intergroup envy and schadenfreude in the context of a long-standing sports rivalry and the extent to which neurophysiological correlates of schadenfreude are related to self-reported likelihood of harming rival team fans. We conclude with implications and future directions.
© 2013 New York Academy of Sciences.
Background: Careful characterization of the phenotype and genotype of Huntington disease (HD) can foster better understanding of the condition.
Bipolar disorder (BD) and attention deficit hyperactivity disorder (ADHD) in adults share clinical symptoms. Both disorders present with executive functioning impairment. The detection of executive dysfunction usually requires the administration of an extensive neuropsychological battery. The Institute of Cognitive Neurology (INECO) Frontal Screening (IFS) is an efficient tool, which has been demonstrated to be useful for the detection of executive deficits in other diseases involving the prefrontal cortex. This study assessed the usefulness of the IFS in detecting the executive dysfunction of BD and ADHD adults, by means of a receiver-operating characteristic curve analysis and a multigroup discriminant function analysis. Twenty-four BD, 25 ADHD patients and 25 controls were assessed with a battery that included the IFS and other measures of executive functioning. Our results showed that both patient groups performed significantly lower than controls on the IFS total score. Using a 27.5 point cut-off score, the IFS showed good sensitivity and acceptable specificity to detect executive impairments in BD and ADHD patients. The IFS discriminated between controls and each patient group more reliably than other executive functions measures. Our results suggest that this tool could be a useful instrument to assess executive functions in BD and ADHD patients.
The significance of social situations is commonly context-embedded. Although the role of context has been extensively studied in basic sensory processing or simple stimulus-response settings, its relevance for social cognition is unknown. We propose the social context network model (SCNM), a fronto-insular-temporal network responsible for processing social contextual effects. The SCNM may 1) update the context and use it to make predictions, 2) coordinate internal and external milieus, and 3) consolidate context-target associative learning. We suggest the behavioral variant of frontotemporal dementia (bvFTD) as a specific disorder in which the reported deficits in social cognition (e.g., facial recognition, empathy, decision-making, figurative language, theory of mind) can be described as context impairments due to deficits in the SCNM. Disruption of orbitofrontal-amygdala circuit, as well as the frontal, temporal, and insular atrophy in bVFTD, suggests a relationship between context-sensitive social cognition and SCNM. In considering context as an intrinsic part of social cognition, we highlight the need for a situated cognition approach in social cognition research as opposed to an abstract, universal, and decontextualized approach. The assessment of context-dependent social cognition paradigms, the SCNM, and their possible application to neuropsychiatric disorders may provide new insight into bvFTD and other related frontal disorders.
Recent research using various neuroimaging methods revealed the crucial role of the striatum concerning the neuropathology of Huntington's disease. Degenerative changes located in the basal ganglia are already observable in premanifest stages of Huntington's disease (pre-HD), i.e., before the onset of manifest motor symptoms. Although the impact of the striatum on reward and punishment processing is well-established in healthy subjects, these processes have not been investigated in manifest and premanifest HD subjects using functional magnetic resonance imaging (fMRI) so far. We used the Monetary Incentive Delay Task to investigate valence discrimination in terms of rewarding and punishing cues in 30 pre-HD and 15 healthy subjects. According to the probability of disease onset within the next 5 years, pre-HD subjects were categorized as either near to motor symptom onset (pre-HD(near); 9.9 [±2.91] years to onset) or far from manifest disease onset (pre-HD(far); 23.49 [±5.99] years to onset). Compared to pre-HD(far) and healthy subjects, pre-HD(near) subjects showed a disturbed neuronal differentiation between reward and control anticipation located in the left ventral striatum. In contrast to pre-HD(far) and healthy subjects, no significant ventral striatal discrimination between punishing and control cues was detected in pre-HD(near) subjects. In the present study, we demonstrated for the first time significant differences in valence discrimination in pre-HD(near) subjects compared to pre-HD(far) subjects and healthy controls. Altered reward and punishment processing could therefore reflect a motivational deficit that may contribute to the pathogenesis of Huntington's disease.
Huntington's Disease (HD) is a neurodegenerative disease caused by a CAG triplet-repeat expansion-mutation in the Huntingtin gene. Subjects at risk for HD can be identified by genetic testing in the prodromal phase. Structural changes of basal-ganglia nuclei such as the caudate nucleus are well-replicated findings observable early in prodromal-HD subjects and may be preceded by distinct functional alterations of cortico-striatal circuits. This study aims to assess functional integrity of the motor system as a cortico-striatal circuit with particular clinical relevance in HD. Ten subjects in the prodromal phase of HD and ten matched controls were administered blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) at rest (3T). Functional connectivity was measured as synchrony of BOLD activity between the caudate nucleus and thirteen cortical brain regions (seeds). Basal-ganglia volumes were assessed as established markers of disease progression in prodromal-HD. Linear regression analysis was performed to test for a relationship between structural changes and group differences in functional connectivity. Prodromal-HD subjects showed reduced BOLD synchrony between two seeds in the premotor cortex (BA6) and the caudate nucleus. While similar effect sizes could be observed for reduced basal-ganglia volumes and differences in functional connectivity, coefficients of determination indicate a moderate relationship between functional connectivity and striatal atrophy. Our data show reduced cortico-striatal functional connectivity at rest in prodromal-HD and suggest a relation to early structural brain changes. Additional longitudinal studies are necessary to elucidate the temporal relationship between functional alterations and earliest structural brain changes in prodromal-HD.
Huntington's disease is an autosomal dominant, progressive neurodegenerative disorder, for which there is no disease-modifying treatment. By use of predictive genetic testing, it is possible to identify individuals who carry the gene defect before the onset of symptoms, providing a window of opportunity for intervention aimed at preventing or delaying disease onset. However, without robust and practical measures of disease progression (ie, biomarkers), the efficacy of therapeutic interventions in this premanifest Huntington's disease population cannot be readily assessed. Current progress in the development of biomarkers might enable evaluation of disease progression in individuals at the premanifest stage of the disease; these biomarkers could be useful in defining endpoints in clinical trials in this population. Clinical, cognitive, neuroimaging, and biochemical biomarkers are being investigated for their potential in clinical use and their value in the development of future treatments for patients with Huntington's disease.
The neuroanatomic basis of affective processing deficits in Huntington disease is insufficiently understood. We investigated whether Huntington disease-related deficits in emotion recognition and experience are associated with specific changes in grey matter volume.
We assessed grey matter volume in symptomatic patients with Huntington disease and healthy controls using voxel-based morphometry, and we correlated regional grey matter volume with participants' affective ratings.
We enrolled 18 patients with Huntington disease and 18 healthy controls in our study. Patients with Huntington disease showed normal affective experience but impaired recognition of negative emotions (disgust, anger, sadness). The patients perceived the emotions as less intense and made more classification errors than controls. These deficits were correlated with regional atrophy in emotion-relevant areas (insula, orbitofrontal cortex) and in memory-relevant areas (dorsolateral prefrontal cortex, hippocampus).
Our study was limited by the small sample size and the resulting modest statistical power relative to the number of tests.
Our study sheds new light on the importance of a cognitive-affective brain circuit involved in the affect recognition impairment in patients with Huntington disease.
This study aims to understand the neurological manifestations of patients with an indeterminate CAG repeat length (36-39) of the Huntingtin gene, HTT.
A longitudinal evaluation of 10 patients was performed. Duration of follow-up was mean=4.23 years (standard deviation 1.068; 95% CI 3.466-4.994; range 3-6.4 years). Three patients had a CAG repeat length of 37, three 38 and four 39. Mean CAG repeat length=38 (standard deviation 0.88; 95% CI 37.47-38.73; range 37-39). Data from clinical histories, neurological examinations, the United Huntington's Disease Rating Scale (UHDRS) and MRI imaging were collected.
Four patients developed facial chorea, ataxia, impaired tongue protrusion, abnormal saccades and intermittent eye pursuits, dysarthria and impaired Luria 3 hand test. Early in its natural history the neurological syndrome is dominated by perioral chorea, subtle cognitive deficits and mild ataxia. Three patients developed a formal diagnosis of HD within 5 years. The illness progression was variable and associated with different co-morbidities. MRI scans showed ventricular dilatation as a common finding. Scores from UHDRS, Total Functional Capacity (TFC) and mini-mental state examination (MMSE) suggested significant behavioural and functional impairment with compromised cognitive abilities. Two patients had subtle manifestations and four remained asymptomatic (3 patients CAG=37; 1 patient CAG=39).
This study documents the disease manifestations and natural history of people with CAG repeat lengths within the indeterminate range. The findings reveal heterogeneity in disease progression and have implications on the advice that should be given to patients and families on risk assessment and prognosis. Long-term follow up of such patients is essential as the neurological presentation of indeterminate CAG repeat length mutation might be accelerated by associated medical disorders and treatments, environmental and modifying genetic factors.
Neuroimaging studies of subjects who are gene-expanded for Huntington Disease, but not yet diagnosed (termed prodromal HD), report that the cortex is "spared," despite the decrement in striatal and cerebral white-matter volume. Measurement of whole-cortex volume can mask more subtle, but potentially clinically relevant regional changes in volume, thinning, or surface area. The current study addressed this limitation by evaluating cortical morphology of 523 prodromal HD subjects. Participants included 693 individuals enrolled in the PREDICT-HD protocol. Of these participants, 523 carried the HD gene mutation (prodromal HD group); the remaining 170 were non gene-expanded and served as the comparison group. Based on age and CAG repeat length, gene-expanded subjects were categorized as "Far from onset," "Midway to onset," "Near onset," and "already diagnosed." MRI scans were processed using FreeSurfer. Cortical volume, thickness, and surface area were not significantly different between the Far from onset group and controls. However, beginning in the Midway to onset group, the cortex showed significant volume decrement, affecting most the posterior and superior cerebral regions. This pattern progressed when evaluating the groups further into the disease process. Areas that remained mostly unaffected included ventral and medial regions of the frontal and temporal cortex. Morphologic changes were mostly in thinning as surface area did not substantially change in most regions. Early in the course of HD, the cortex shows changes that are manifest as cortical thinning and are most robust in the posterior and superior regions of the cerebrum.
Humans have a drive to evaluate themselves by examining their abilities and outcomes in comparison to others. The present study examined the emotional and neural correlates of upward social comparison (comparison with those who have more) and downward social comparison (comparison with those who have less). Two experiments were conducted with volunteers in an interactive game of chance, in which a putative player won or lost more money than the participant. The results showed that even when participants lost money, they expressed joy and schadenfreude (gloating) if the other player had lost more money. On the other hand when they actually won money, but the other player had won more they expressed envy. This pattern was also demonstrated in a differential BOLD response in the ventral striatum. Comparing the activations between an actual gain and a relative gain indicated that even when a person loses money, merely adding information about another person's greater loss may increase ventral striatum activations to a point where these activations are similar to those of an actual gain. We suggest that the ventral striatum plays a role in mediating the emotional consequences of social comparison.
Huntington's disease (HD) is an autosomal dominant, fully penetrant, neurodegenerative disease that most commonly affects adults in mid-life. Our aim was to identify sensitive and reliable biomarkers in premanifest carriers of mutated HTT and in individuals with early HD that could provide essential methodology for the assessment of therapeutic interventions.
This multicentre study uses an extensive battery of novel assessments, including multi-site 3T MRI, clinical, cognitive, quantitative motor, oculomotor, and neuropsychiatric measures. Blinded analyses were done on the baseline cross-sectional data from 366 individuals: 123 controls, 120 premanifest (pre-HD) individuals, and 123 patients with early HD.
The first participant was enrolled in January, 2008, and all assessments were completed by August, 2008. Cross-sectional analyses identified significant changes in whole-brain volume, regional grey and white matter differences, impairment in a range of voluntary neurophysiological motor, and oculomotor tasks, and cognitive and neuropsychiatric dysfunction in premanifest HD gene carriers with normal motor scores through to early clinical stage 2 disease.
We show the feasibility of rapid data acquisition and the use of multi-site 3T MRI and neurophysiological motor measures in a large multicentre study. Our results provide evidence for quantifiable biological and clinical alterations in HTT expansion carriers compared with age-matched controls. Many parameters differ from age-matched controls in a graded fashion and show changes of increasing magnitude across our cohort, who range from about 16 years from predicted disease diagnosis to early HD. These findings might help to define novel quantifiable endpoints and methods for rapid and reliable data acquisition, which could aid the design of therapeutic trials.
Functional neuroimaging studies have suggested a dysfunction of prefrontal regions in clinically pre-symptomatic individuals with the Huntington's disease (HD) gene mutation (pre-HD) during cognitive processing. The objective of this study was to test the impact of cognitive demand on prefrontal connectivity in pre-HD individuals.
Sixteen healthy controls and sixteen pre-HD subjects were studied using functional MRI and a verbal working memory task with increasing cognitive load. Load-dependent functional connectivity of the left dorsolateral prefrontal cortex (DLPFC) was investigated by means of psychophysiological interactions.
In pre-HD subjects, aberrant functional connectivity of the left DLPFC was found at high working memory load levels only. Compared with healthy controls, pre-HD individuals exhibited lower connectivity strength in the left putamen, the right anterior cingulate and the left medial prefrontal cortex. Pre-HD individuals close to the onset of motor symptoms additionally exhibited lower connectivity strength in the right putamen and the left superior frontal cortex. The connectivity strength in the left putamen was associated with several clinical measures including CAG repeat length, Unified Huntington's Disease Rating Scale motor score and predicted years to manifest symptom onset.
These findings suggest that early prefrontal connectivity abnormalities in pre-HD individuals are modulated by cognitive demand.
Symptomatic patients with Huntington's disease may have reduced glucose metabolism in the caudate nuclei. We used positron emission tomography and [18F]fluorodeoxyglucose to study cerebral glucose metabolism in 95 subjects: 58 clinically asymptomatic (chorea-free) subjects at risk for Huntington's disease, 10 symptomatic patients with the disease, and 27 controls. All the symptomatic patients had marked reductions in caudate glucose metabolism. Despite a normal structural appearance on computed tomography, caudate glucose metabolism was bilaterally reduced in 31 percent of the subjects at risk (18 of 58). Using each at-risk subject's age and the sex of the affected parent, we averaged individual risk estimates for the development of Huntington's disease for this group and predicted that the probability of having the clinically unexpressed Huntington's disease gene should be 33.9 +/- 6.0 percent for the group. Thus, there was excellent agreement between the predicted percentage of carriers of the Huntington's disease gene (33.9 +/- 6.0 percent) and the percentage with metabolic abnormalities of the caudate nuclei (31 percent). These results indicate that the measurement of glucose metabolism may allow the observation of the pathophysiologic effects of the Huntington's disease gene during the natural development of the disease. It may also provide a direct means to monitor the response to experimental treatments during both the clinically asymptomatic and the symptomatic phases of the disorder.
Clinical records were evaluated for 163 Huntington's disease patients in whom postmortem brain specimens had been graded for degree of neuropathologic involvement in the striatum. Juvenile/adolescent onset (4 to 19 years of age) was associated with very severe neuropathologic involvement produced by an apparent rapid degenerative process. Cases of early (20 to 34 years) and midlife (35 to 49 years) onset had respectively less severe striatal involvement, suggesting a slower degenerative progression. High correlations among the grade of neuropathologic involvement, cell counts of neurons, and a rating of physical disability suggest that each represents a common underlying degenerative process of the disease. The relationship between the age at onset and the extent of neuropathologic involvement suggests that a single mechanism may determine both onset and rate of degenerative disease progression.
Huntington disease (HD) is an autosomal dominant disorder in which the major gene expression occurs in the central nervous system. It is characterized by the appearance of progressive chorea and dementia, usually in adult life. One tragic aspect of the disorder, due to its late age of onset and, until recently, lack of a presymptomatic marker, is that transmission of the disease to offspring invariably occurs before symptoms develop in the parent. Although the onset of symptoms and the rate of progression may vary, the prognosis is one of relentless deterioration. The major pathological features of HD are a primary loss of cells in the caudate nucleus and putamen (striatum) but other regions of the basal ganglia, hypothalamus, and brain stem are also involved. Not only is there neuronal loss but there is also a decrease in the level of a number of neurotransmitters and associated enzymes, together with abnormalities in some receptor sites. Martin [1] described the disease as "genetically programmed cell death in the human central nervous system."
To determine (1) whether the neuropsychological profiles of healthy individuals at risk (AR) for Huntington's disease who were positive (AR/+) or negative (AR/-) for the Huntington's disease genetic marker differed from those of symptomatic patients with Huntington's disease and normal control individuals and (2) whether the neuropsychological performance of the two AR groups differed from each other on three assessments during a 4-year span.
Case-control, double-blind study, with AR status determined by genetic linkage analysis (G8 probe), in addition to examination of trinucleotide repeats for most AR subjects.
The Neuropsychology Program in the Department of Psychiatry and the Department of Neurology at the University of Michigan Medical Center, Ann Arbor, a tertiary care center.
Eight subjects matched as closely as possible for age, gender, and education in each of the following groups: AR/+, AR/-, normal control, and Huntington's disease.
A battery of neuropsychological tasks, including measures of intelligence, memory, problem solving, and motor ability.
Although both AR groups demonstrated variability on select intellectual subtests relative to normal subjects, they did not differ from each other on the three assessments during a 4-year span. Patients with Huntington's disease performed more poorly than the other groups across a range of neuropsychological measures.
These results do not support previous evaluations concluding that AR/+ individuals demonstrate cognitive impairments as compared with AR/- individuals. Findings in earlier studies without genetic linkage analysis of lower performance of AR individuals, including children, as compared with normal controls may relate to extraneous environmental and familial issues that interfere with intellectual development.
Previous investigations using linear CT measures found no evidence of caudate atrophy in asymptomatic persons who have the DNA haplotype linked to the Huntington's disease (HD) gene. We measured volumes of the caudate, putamen, and globus pallidus on MRIs of 10 gene marker-positive and 18 gene marker-negative asymptomatic at-risk persons. The volumes of all basal ganglia structures were significantly reduced in the marker-positive group, even after controlling for age, total brain volume, and minor neurologic signs. Discriminant function analysis using basal ganglia volumes and age as predictor variables correctly identified genetic status in 86% of subjects. These results indicate that basal ganglia volume is reduced before individuals become symptomatic with HD.
An objective assessment of the clinical findings in patients with Huntington's disease (HD) is necessary for an evaluation of the longitudinal progression of the disease features. The Unified Huntington's Disease Rating Scale (UHDRS) is a scale to assess clinical performance and functional capacity. The authors examined the 1-year change in UHDRS scores in 78 patients with HD examined either in Leiden, the Netherlands (24 men, 25 women), or in Rochester, New York, United States (12 men, 17 women). A significant decline was seen in motor function, measured with the total motor scale. The total dystonia score increased significantly; the total chorea score did not. The frequency of behavioral disorders tended to increase. The scores on independence scale, functional assessment, total functional capacity, and symbol digit decreased significantly. No relation was observed between the UHDRS items and the age at onset or duration of illness. Thirteen patients with 2-year follow up showed a clear increase in score on the total motor scale and a decline on the independence scale and in total functional capacity. The UHDRS may also be used as a tool for determining therapeutic intervention. Annual evaluation of the total motor scale in every patient gives a clear description of the motor progression of the disease. The authors suggest performing a total UHDRS evaluation every second year for every HD patient as part of the routine longitudinal evaluation.
This study examined the first participants who registered for the Huntington's disease predictive testing program 1990-1995 in Stockholm, Sweden. A psychosocial investigation was performed to evaluate potential effects of the presymptomatic testing. The results showed no significant differences between 13 gene carriers and 21 noncarriers in pretest attitudes, expectations, general well-being, life satisfaction and lifestyle, the need for support, estimated sense of wellbeing or degree of health. However, both groups showed high suicidal ideation and self-injurious behavior. Noncarriers had a very high frequency of attempted suicide, and both groups had similarly pronounced psychiatric dysfunction. Their relatives also had high frequencies of psychiatric diseases, suicide or suicidal attempts. Most of the participants had a desire to meet a psychologist or a social worker. The need for counseling, using a well designed protocol, and the importance of focusing on suicide risk of participants in predictive testing programs is emphasized.
The early stages of Huntington's disease (HD) present with motor, cognitive, and emotional symptoms. Correspondingly, current models implicate dysfunction of the motor, associative, and limbic basal ganglia-thalamocortical circuits. Available data, however, indicate that in the early stages of the disease, striatal damage is mainly restricted to the associative striatum. Based on an open interconnected model of basal ganglia-thalamocortical organization, we provide a detailed account of the mechanisms by which associative striatal pathology may lead to the complex pattern of motor, cognitive, and emotional symptoms of early HD. According to this account, the degeneration of a direct and several indirect pathways arising from the associative striatum leads to impaired functioning of: (1) the motor circuit, resulting in chorea and bradykinesia, (2) the associative circuit, resulting in abnormal eye movements, "frontal-like" cognitive deficits and "cognitive disinhibition," and (3) the limbic circuit, resulting in affective and psychiatric symptoms. When relevant, this analysis is aided by comparing the symptomatology of HD patients to that of patients with mild to moderate Parkinson's disease, since in the latter there is similar dysfunction of direct pathways but opposite dysfunction of indirect pathways. Finally, we suggest a potential novel treatment of HD and provide supportive evidence from a rat model of the disease.
To develop a 10-minute cognitive screening tool (Montreal Cognitive Assessment, MoCA) to assist first-line physicians in detection of mild cognitive impairment (MCI), a clinical state that often progresses to dementia.
Validation study.
A community clinic and an academic center.
Ninety-four patients meeting MCI clinical criteria supported by psychometric measures, 93 patients with mild Alzheimer's disease (AD) (Mini-Mental State Examination (MMSE) score > or =17), and 90 healthy elderly controls (NC).
The MoCA and MMSE were administered to all participants, and sensitivity and specificity of both measures were assessed for detection of MCI and mild AD.
Using a cutoff score 26, the MMSE had a sensitivity of 18% to detect MCI, whereas the MoCA detected 90% of MCI subjects. In the mild AD group, the MMSE had a sensitivity of 78%, whereas the MoCA detected 100%. Specificity was excellent for both MMSE and MoCA (100% and 87%, respectively).
MCI as an entity is evolving and somewhat controversial. The MoCA is a brief cognitive screening tool with high sensitivity and specificity for detecting MCI as currently conceptualized in patients performing in the normal range on the MMSE.