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Effect of direct eye contact in women with PTSD related to interpersonal trauma: Psychophysiological interaction analysis of connectivity of an innate alarm system
Abstract
In healthy individuals, direct eye contact is thought to modulate a cortical route eliciting social cognitive processes via activation of a fast subcortical pathway. This study aimed to examine functional brain connectivity during direct eye contact in women with posttraumatic stress disorder (PTSD) related to childhood abuse as compared with healthy controls. We conducted psychophysiological interaction (PPI) analyses in Statistical Parametric Mapping-8 (SPM8) using the superior colliculus (SC) and locus coeruleus (LC) as seed regions while 16 healthy subjects and 16 patients with a primary diagnosis of PTSD related to childhood maltreatment viewed a functional magnetic resonance imaging (fMRI) paradigm involving direct (D) versus averted (A) gaze (happy, sad, neutral). The PTSD group showed a significantly enhanced connectivity between the SC and the anterior cingulate, and between the LC and the thalamus, caudate, putamen, insula, cingulate gyrus, and amygdala, as compared with healthy individuals. Symptom severity scores on the Clinician-Administered PTSD Scale (CAPS) showed significant positive correlations with superior colliculus connectivity with the perigenual and posterior cingulate, insula, and sublenticular extended amygdala. Functional connectivity data suggest increased recruitment of brain regions involved in emotion processing during direct gaze in PTSD in association with the fast subcortical pathway. The interpretation of eye contact as a signal of threat may require more emotion regulatory capacities in patients with PTSD.
Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
... The progression of PTSD may have brought enhancements in connections between thalamus and autonomic systems. Enhanced functional connectivity between the thalamus and the locus coeruleus has also been reported in PTSD [63]. Simultaneous enhancement of neural activity in the periaqueductal nuclei and in the midline thalamic nuclei has been reported in an animal PTSD model [64]. ...
... This circuit may be necessary for the development of PTSD. It has been reported that trauma survivors with a smaller pulvinar exhibit lower morbidity rates for PTSD [79], and fMRI studies indicated enhanced connectivity between the SC and the ACC in PTSD patients [63]. In addition, depletion of left pulvinar seed functional connectivity to sensory regions (left superior parietal lobule, left middle temporal gyrus, and right postcentral gyrus) in PTSD patients [80] and depletion of right pulvinar seed connectivity to primary visual and higher sensory regions (left superior frontal gyrus, left superior parietal lobule, bilateral precuneus, right inferior parietal lobule, right precentral gyrus medial segment) in dissociative PTSD patients was reported [80]. ...
... Increased coactivity with ACC, posterior cingulate cortex, and thalamus [55] Increase in effective connectivity from thalamus to amygdala [56][57][58][59] Increase in effective connectivity from thalamus to ACC, striatum, and occipital cortex [56] Positive correlation between thalamus−amygdala and PTSD severity [58] Depletion of connectivity between thalamus and ACC [19,52,60,61] Emotional processing correlation between thalamus and ACC/PCC [55] Alteration of connectivity from VLT to other sensory areas in dissociative PTSD patients [62] Enhanced connectivity of pedunculopontine nuclei (reticular activation system) and anterior thalamic nucleus in dissociative PTSD [48] Enhanced connectivity between thalamus and locus coeruleus [63] Simultaneous enhancement of activity in midline thalamus and periaqueductal nuclei in animal PTSD model [64] Diminished correlation between CAN and HRV [65] Enhanced connectivity between thalamus and VTA [66] Positive correlation between thalamus activity and alexithymia [68] Pulvinar lesions disrupt implicit fear-related visual processing [75] Pulvinar and V1 cortex contribute to fear anticipation [74] Contribution of retinotectal pathway to implicit fear processing [76,77] Contribution of retinotectal pathway to fear learning [78] Smaller pulvinar in traumatized control [79] Depletion of right pulvinar seed connectivity to sensory area in dissociative PTSD [80] ...
Post-traumatic stress disorder (PTSD) has a high lifetime prevalence and is one of the more serious challenges in mental health care. Fear-conditioned learning involving the amygdala has been thought to be one of the main causative factors; however, recent studies have reported abnormal-ities in the thalamus of PTSD patients, which may explain the mechanism of interventions such as eye movement desensitization and reprocessing (EMDR). I therefore conducted a mini literature review on the potential contribution of the thalamus to the pathogenesis of PTSD and the valida-tion of therapeutic approaches. As a result, we noticed the importance of the retinotectal pathway (superior colliculus−pulvinar−amygdala connection) and discussed therapeutic indicators.
... Characterization of basic resting-state brain networks in persons with mental illness or at-risk may help to identify perturbations of underlying neural oscillations and changed brain dynamics. Within trauma research, only a few studies to date have examined intrinsic functional connectivity (FC) but with much heterogeneity in findings (Olive et al., 2018;Philip et al., 2013;Steuwe et al., 2015;Thomason et al., 2015;van der Werff et al., 2013). Decreased FC between the amygdala and other brain areas such as the putamen, insula, or subgenual anterior cingulate cortex has been documented in maltreated adults (van der Werff et al., 2013) and children (Thomason et al., 2015). ...
... Decreased FC between the amygdala and other brain areas such as the putamen, insula, or subgenual anterior cingulate cortex has been documented in maltreated adults (van der Werff et al., 2013) and children (Thomason et al., 2015). Directly contrasting these findings, a task-based study reported increased (rather than decreased) FC for traumatized participants relative to comparisons specifically between midbrain structures (e.g., locus coeruleus) and subcortical brain areas including the amygdala or the thalamus (Steuwe et al., 2015). In their (Steuwe et al., 2015) study, participants viewed animated video sequences of faces with varying emotional expressions and direct or averted gaze. ...
... Directly contrasting these findings, a task-based study reported increased (rather than decreased) FC for traumatized participants relative to comparisons specifically between midbrain structures (e.g., locus coeruleus) and subcortical brain areas including the amygdala or the thalamus (Steuwe et al., 2015). In their (Steuwe et al., 2015) study, participants viewed animated video sequences of faces with varying emotional expressions and direct or averted gaze. The authors argued that this increased FC may reflect preferential recruitment of a fast subcortical processing route indicative of an innate threat system that is quickly (and probably standardly) active in traumatized persons. ...
Background: Experience of childhood maltreatment significantly increases the risk for the development of psychopathology and is associated with impairments in socio-cognitive skills including theory-of-mind (ToM). In turn, neural alterations in ToM processing might then influence future interpersonal interaction and social-emotional understanding.
Objective: To assess resting-state activity in the theory-of-mind network in traumatized and non-traumatized persons.
Methods: Thirty-five women with a history of childhood maltreatment and 31 unaffected women completed a resting-state scan and a ToM localizer task. The peak coordinates from the localizer were used as the seed regions for the resting-state functional connectivity (RSFC) analyses (temporo-parietal junction, dorsomedial prefrontal cortex, middle temporal gyrus and precuneus).
Results: Child abuse was associated with increased RSFC between various ToM regions including the precuneus and the brainstem suggesting altered hierarchical processing in ToM regions. Number of types of abuse was driving the effect for the temporo-parietal junction and the brainstem, while the severity of abuse was linked to increased RSFC between the middle temporal gyrus and the frontal cortex. Post-hoc analyses of brainstem regions indicated the involvement of the serotonergic system (dorsal raphe).
Conclusions: The data indicate a lasting impact of childhood maltreatment on the neural networks involved in social information processing that are integral to understanding others’ emotional states. Indeed, such altered neural networks may account for some of the interpersonal difficulties victims of childhood maltreatment experience.
... 6,50e52 SC and PAG projections to the pulvinar within the thalamus allow for coordination of orienting and alerting mechanisms involving further the amygdala in producing an immediate response to threat. 15,24,48,51,53,54 The amygdala, in turn, can communicate with prefrontal cortical regions for appraisal of incoming danger. 6,55 The amygdala, however, is also able to drive independently an immediate response to threat. ...
... The SC is also central to innate defense responses and the IAS where this region is responsible for fast, lower-order multisensory integration and threat-detection mechanisms. 50,54 A recent investigation of SC functional connectivity in PTSD at rest revealed hyperconnectivity between the left SC and the right dorsolateral PFC in participants with PTSD, as well as increased connectivity between the right SC and the left temporoparietal junction (TPJ) in individuals with PTSD þ DS. 52 These results have been linked to overmodulation of emotional responses in PTSD (top-down prefrontal modulation) and to passive defensive reaction involving depersonalization symptoms in PTSD þ DS due to increased TPJ connectivity with the SC, where the TPJ plays a key role in bodily self-consciousness and depersonalization symptomatology. 52,103 One final, unique method of studying subconscious threat processing involves investigation of neural responses to direct eye contact. ...
... 51 Moreover, increased functional connectivity of the SC and LC with the insula, the inferior frontal cortex, and the anterior cingulum has been observed during processing of direct eye gaze in PTSD. 54 Taken together, these findings point toward a hyperactive subcortical pathway in PTSD that is engaged in response to direct eye contact and appears to trigger a subconscious defense response operating independently from regulatory cortical structures. ...
... Characterization of resting-state brain networks in persons with mental illness or at-risk may help to identify perturbations of underlying neural oscillations and changed brain dynamics. Within trauma research, only a few studies to date have examined intrinsic functional connectivity (FC) but with much heterogeneity in findings (8)(9)(10)(11)(12). Decreased FC between the amygdala and other brain areas such as the putamen, insula, or subgenual anterior cingulate cortex have been documented in maltreated adults (10) and children (8). ...
... Decreased FC between the amygdala and other brain areas such as the putamen, insula, or subgenual anterior cingulate cortex have been documented in maltreated adults (10) and children (8). Directly contrasting these findings, a task-based study reported increased (rather than decreased) FC for traumatized participants relative to comparisons specifically between midbrain structures (superior colliculus (SC) and locus coeruleus (LC)) and subcortical brain areas including the amygdala, the anterior cingulate, the thalamus, and the striatum (12). In their (12) study, participants viewed animated video sequences of faces with varying emotional expressions and direct or averted gaze. ...
... Indeed, a hallmark symptom of PTSD is a constant level of alert (hypervigilance), an issue that clinicians aim to moderate before commencing other therapy (13). However, the findings by Steuwe et al. (12) have to be considered tentative as they were 1) task-based and consisted of a re-analysis of a prior fMRI study (14), and 2) were comprised of a relatively small sample (N=16 per group). ...
Background: Early life stressful events, such as childhood maltreatment, significantly increase risk for the development of psychopathology and are associated with impairments in socio-cognitive skills including theory-of-mind (ToM). However, to date, no study has examined the resting-state activity of the ToM network in adults with maltreatment history. Methods: Thirty-five women with a history of childhood maltreatment and 31 unaffected women completed a resting-state scan and a ToM localizer task. The peak coordinates from the localizer were used as the seed regions for the resting-state functional connectivity (RSFC) analyses (temporoparietal junction, dorsomedial prefrontal cortex, middle temporal gyrus and precuneus). Results: Child abuse was associated with increased RSFC between various ToM regions including the precuneus and the brainstem suggesting altered hierarchical processing in ToM regions. In addition, RSFC was also changed between the dorsomedial prefrontal cortex and the cerebellum. Limitations. A small and heterogeneous sample. Conclusions: The data indicate a lasting influence of early life stress on neural networks involved in social processing and may underlie the social difficulties reported by maltreated individuals.
... Five functional connectivity studies used the LC as their seed region. Location coordinates for the seed region were obtained from different sources, including a previous study by Keren et al. (2009) (Kline et al., 2016;Zhang et al., 2016), a previous study published by the same author (Steuwe et al., 2015), and an anatomical atlas of the human brainstem (Duvornoy's Atlas of the Human Brainstem and Cerebellum by Naidich et al., 2009;Bär et al., 2016). ...
... The majority of fMRI studies of the LC investigated executive functions, including attention (Mohanty et al., 2008;Murphy et al., 2014;Neufang et al., 2015;Raizada and Poldrack, 2007;Xuan et al., 2016), cognitive or inhibitory control (Köhler et al., 2016;Minzenberg et al., 2008;Schilbach et al., 2011;von der Gablentz et al., 2015) and decision-making (Kahnt and Tobler, 2013;Laureiro-Martínez et al., 2015;Payzan-LeNestour et al., 2013). Other studies assessed the impact of novelty (Krebs et al., 2017(Krebs et al., , 2013(Krebs et al., , 2011, emotion (Lerner et al., 2009;Sterpenich et al., 2006), stress/anger (Gilam et al., 2017;Henckens et al., 2012;van Marle et al., 2010), pain (Brooks et al., 2017;Erpelding et al., 2014;Hubbard et al., 2011;Schulte et al., 2016;Sclocco et al., 2016) and fear/threat (Liddell et al., 2005;Morey et al., 2015;Steuwe et al., 2015Steuwe et al., , 2014. Studies also investigated the effect of specific interventions on the LC such as vagal nerve stimulation (VNS) (Kraus et al., 2013), light exposure (Vandewalle et al., 2007) and psychotropic medications (Kline et al., 2016;Metzger et al., 2015;Minzenberg et al., 2008). ...
... This is consistent with the known reciprocal connection and interaction between the LC and amygdala for the upregulation of arousal in response to salient or stressful events (Valentino and Van Bockstaele, 2008;Van Bockstaele et al., 1998). Other brain regions functionally connected to the LC included prefrontal cortex (PFC) (Köhler et al., 2016;Minzenberg et al., 2008), hypothalamus (Moulton et al., 2014), cerebellum (Kline et al., 2016;Zhang et al., 2016) hippocampus (Kline et al., 2016;Steuwe et al., 2015), and habenula (Erpelding et al., 2014). Studies have shown that the LC is an important modulator of the PFC, influencing working memory and attention (Berridge and Spencer, 2016;Chandler, 2016). ...
The locus coeruleus (LC), the major origin of noradrenergic modulation of the central nervous system, innervates extensive areas throughout the brain and is implicated in a variety of autonomic and cognitive functions. Alterations in the LC-noradrenergic system have been associated with healthy ageing and neuropsychiatric disorders including Parkinson's disease, Alzheimer's disease and depression. The last decade has seen advances in imaging the structure and function of the LC, and this paper systematically reviews the methodology and outcomes of sixty-nine structural and functional MRI studies of the LC in humans. Structural MRI studies consistently showed lower LC signal intensity and volume in clinical groups compared to healthy controls. Within functional studies, the LC was activated by a variety of tasks/stimuli and had functional connectivity to a range of brain regions. However, reported functional LC location coordinates were widely distributed compared to previously published neuroanatomical locations. Methodological and demographic factors potentially contributing to these differences are discussed, together with recommendations to optimize the reliability and validity of future LC imaging studies.
... 6,50e52 SC and PAG projections to the pulvinar within the thalamus allow for coordination of orienting and alerting mechanisms involving further the amygdala in producing an immediate response to threat. 15,24,48,51,53,54 The amygdala, in turn, can communicate with prefrontal cortical regions for appraisal of incoming danger. 6,55 The amygdala, however, is also able to drive independently an immediate response to threat. ...
... The SC is also central to innate defense responses and the IAS where this region is responsible for fast, lower-order multisensory integration and threat-detection mechanisms. 50,54 A recent investigation of SC functional connectivity in PTSD at rest revealed hyperconnectivity between the left SC and the right dorsolateral PFC in participants with PTSD, as well as increased connectivity between the right SC and the left temporoparietal junction (TPJ) in individuals with PTSD þ DS. 52 These results have been linked to overmodulation of emotional responses in PTSD (top-down prefrontal modulation) and to passive defensive reaction involving depersonalization symptoms in PTSD þ DS due to increased TPJ connectivity with the SC, where the TPJ plays a key role in bodily self-consciousness and depersonalization symptomatology. 52,103 One final, unique method of studying subconscious threat processing involves investigation of neural responses to direct eye contact. ...
... 51 Moreover, increased functional connectivity of the SC and LC with the insula, the inferior frontal cortex, and the anterior cingulum has been observed during processing of direct eye gaze in PTSD. 54 Taken together, these findings point toward a hyperactive subcortical pathway in PTSD that is engaged in response to direct eye contact and appears to trigger a subconscious defense response operating independently from regulatory cortical structures. ...
Background: In lieu of consciously appraising the threat via
cortical sensory processing, a subcortical ‘innate alarm
system’ originating in the superior colliculus (SC) may
activate innate defensive responses when threat is imminent.
Individuals with posttraumatic stress disorder (PTSD)
demonstrate supra- and subliminal threat detection, together
contributing to hyperarousal symptoms and increased
defensive responses. Here, the periaqueductal gray (PAG)
may work in tandem with the SC to initiate instinctual
defensive strategies. The current study was designed to
examine functional connectivity patterns with the PAG and
the SC at rest in PTSD and healthy controls.
Methods: We examined PAG and SC resting-state functional
connectivity in PTSD (n5107) and healthy controls (n561)
using a seed-based approach via PickAtlas and SPM12.
Results: Both healthy controls and PTSD patients showed
widespread SC functional connectivity patterns with pre-motor
and V1 cortical regions at rest. Notably, these SC connectivity
patterns were stronger in controls. By contrast, virtually no
PAG functional connectivity was observed in controls.
However, PTSD patients further demonstrated extensive
PAG functional connectivity with brain regions associated
with emotional reactivity and defensive posturing (e.g.,
anterior insula, cingulum, pre/post central gyrus).
Conclusions: These findings suggest that although the SC
has extensive connections at rest in both controls and PTSD,
the PAG may also be responsible for additional defensive
posturing at rest. These findings emphasize the importance of
identifying functional connectivity of the innate alarm system
and related brain stem structures in PTSD.
Supported By: Canadian Institutes of Health Research
#137150 and #97914
Keywords: Functional MRI, Resting State, Posttraumatic
Stress Disorder
... For example, increased positive connectivity of the amygdala has been reported to the supplemental motor area, presumably to facilitate faster motor responding (Olsavsky et al., 2021). Increased positive connectivity has also been reported between the amygdala and the brainstem (van Rooij et al., 2020), including with a locus coeruleus seed (Steuwe et al., 2015), potentially mediating heightened arousal and autonomic effector activity in response to threat, given that the amygdala has indirect and direct projections to the locus coeruleus as well as to autonomic brainstem nuclei (Roozendaal et al., 2009;Ulrich-Lai and Herman, 2009;Waraczynski, 2016;Barman and Yates, 2017;Hennessey et al., 2018). Additionally, increased negative connectivity has been reported to: the ventromedial prefrontal cortex (vmPFC), specifically the subgenual anterior cingulate cortex (sgACC) and medial orbitofrontal cortex (mOFC), possibly reflecting the amygdala suppressing its own inhibition Peverill et al., 2019). ...
... Regarding the amygdala, I hypothesized that RMS would increase its volume at all three time points, both because of findings of increased volume (Mehta et al., 2009;Tottenham et al., 2010;Pechtel et al., 2014;van Rooij et al., 2020) and increased functional reactivity or connectivity (Steuwe et al., 2015;Peverill et al., 2019;van Rooij et al., 2020;Olsavsky et al., 2021) following human ELS, as well as reports of increased amygdala neuronal count following RMS (Gondré-Lewis et al., 2016;Hegde et al., 2020). ...
Early life stress (ELS), primarily encompassing childhood neglect and abuse, is associated with many adverse psychiatric and physical health outcomes in later life. What remains unclear, however, is precisely how these links are mediated. Answering this question is challenging, partly because there are many other exposures that may accompany childhood maltreatment or neglect, but also because there are many physical, social, and other life events that occur between childhood and adulthood which could interact with the effects of early life stress to together result in adulthood pathology. Here, I conducted a large, controlled experiment in rats that sought to isolate key behavioural, immunological, and neurobiological effects into adulthood of early life stress itself. To do this, I used the repeated maternal separation (RMS) model of chronic early life stress, and I focused particularly on those effects of possible relevance to anxiety, depression, and inflammation-related physical disease. In Chapter 3, I describe the long-term effects of RMS on commonly used measures of anxiety- and depression-like behaviour, as well as on comparatively sophisticated tasks capable of providing detailed insights into reward and punishment sensitivity, as well as attentional control. The probabilistic reversal learning task revealed long-lasting effects of RMS on the degree to which negative outcomes shaped animals’ future decisions, as well as evidence suggesting that RMS animals were comparatively inefficient at directing their attention, even where they were equally accurate. Further, RMS animals exhibited a long-lasting sensitization to later-life stress on several behavioural metrics. These effects all persisted into late adulthood despite RMS having no effects on conventional measures of anxiety- or depression-like behaviour, even in early adulthood. In Chapter 4, I present findings from my experiment and from a systematic review examining the short-term and long-term effects of RMS on cytokine levels in blood and non-blood tissue, as well as on microglial activation and density. I show that RMS causes short-term increases in pro-inflammatory signalling, but only causes long-term increases in pro-inflammatory signalling if animals are subjected to a later-life stress. Thus, I demonstrate that RMS causes a long-lasting sensitisation of the neuroimmune pathway that links stressor perception ultimately to pro-inflammatory cytokine release. However, these effects were largely limited to non-blood tissue such as brain tissue: in plasma, serum, or whole blood, studies generally found no effect of RMS on cytokine levels in the short- or long-term, even following later-life stress. In Chapter 5, I present analyses of regional brain volumes determined from 9.4 Tesla structural magnetic resonance imaging scans at three timepoints following RMS. I show that RMS had no effect on the volume of any of six regions examined at post-natal day (PND) 20 or 62, but resulted in a larger amygdala during the scan at PND 285, which occurred after 9-13 days of adult stress. Given that the PND 62 and PND 285 scans both occurred in adulthood, this suggests that RMS may have interacted with later-life stress to increase amygdala volume. In the General Discussion, I describe how these findings are concordant and together provide valuable insight into how early life stress can alter physiology and behaviour in such a way that may directly increase risk for mental and physical pathology.
... Nineteen of the included studies examined FC from the amygdala in PTSD, eight used the posterior cingulate (PCC)/precuneus, seven utilized seeds within the medial prefrontal cortex (mPFC), five utilized the hippocampus/parahippocampus as a seed, five examined connectivity from the anterior cingulate cortex (ACC), three from the lateral prefrontal cortex (lPFC), and three from the insula ( Figure S1). Investigators also chose seeds in the thalamus (Yin et al., 2011), vestibular nuclei (Harricharan et al., 2017), superior colliculus and locus ceruleus (Steuwe et al., 2015), supplementary motor area (Misaki et al., 2018), and putamen (Linnman et al., 2011) for FC studies in PTSD (Table S1; Figure S2). A detailed summary of FC targets from each seed is provided in the Supplemental Material and Table 2. ...
... interpersonal violence, motor vehicle accidents, natural disasters, etc.) varied within and between studies. Eight studies utilized taskbased paradigms in fMRI, including processing of emotional facesSteuwe et al., 2015;Stevens et al., 2013) and other emotional or threatening stimuli ...
Classical neural circuitry models of posttraumatic stress disorder (PTSD) are largely derived from univariate activation studies and implicate the fronto-limbic circuit as a main neural correlate of PTSD symptoms. Though well-supported by human neuroimaging literature, these models are limited in their ability to explain the widely distributed neural and behavioral deficits in PTSD. Emerging interest in the application of large-scale network methods to functional neuroimaging provides a new opportunity to overcome such limitations and conceptualize the neural circuitry of PTSD in the context of network patterns. This review aims to evaluate both the classical neural circuitry model and a new, network-based model of PTSD neural circuitry using a breadth of functional brain organization research in subjects with PTSD. Taken together, this literature suggests global patterns of reduced functional connectivity (FC) in PTSD groups as well as altered FC targets that reside disproportionately in canonical functional networks, especially the default mode network. This provides evidence for an integrative model that includes elements of both the classical models and network-based models to characterize the neural circuitry of PTSD.
... The avoidance of multiple comparisons correction was strategic because the statistical power of PPI analyses tends to involve a high proportion of false negatives (O'Reilly et al., 2012). Conversely, the selected thresholding procedure balances the risk of type I and type II errors (Lieberman & Cunningham, 2009), and it has been successfully employed in previous studies using PPI analyses (Baeuchl, Meyer, Hoppstadter, Diener, & Flor, 2015;Li et al., 2018;Osumi et al., 2012;Steuwe et al., 2015) as well as other FC metrics (Geisler et al., 2017;Lee et al., 2014;Loitfelder et al., 2012;Yasuno et al., 2015). For all group-level analyses, the subjects' behavioral outcomes were included as covariates of interest (see Section 2.5.3 for details). ...
... and a minimal cluster size of k = 30. Although the same threshold has been employed in previous studies using PPI analyses (Baeuchl et al., 2015;Li et al., 2018;Osumi et al., 2012;Steuwe et al., 2015) to balance the risk of type I and type II errors (Lieberman & Cunningham, 2009), future studies should examine other potential FC differences between BT and FT using metrics that allow for more strict thresholding methods. Finally, it must be noted that our results may have been influenced by the size established for our ROIs (which had radiuses of 10 mm). ...
Comparisons between backward and forward translation (BT, FT) have long illuminated the organization of bilingual memory, with neuroscientific evidence indicating that FT would involve greater linguistic and atten-tional demands. However, no study has directly assessed the functional interaction between relevant mechanisms. Against this background, we conducted the first fMRI investigation of functional connectivity (FC) differences between BT and FT. In addition to yielding lower behavioral outcomes, FT was characterized by increased FC between a core semantic hub (the left anterior temporal lobe, ATL) and key nodes of attentional and vigilance networks (left inferior frontal, left orbitofrontal, and bilateral parietal clusters). Instead, distinct FC patterns for BT emerged only between the left ATL and the right thalamus, a region implicated in automatic relaying of sensory information to cortical regions. Therefore, FT seems to involve enhanced coupling between semantic and attentional mechanisms, suggesting that asymmetries in cross-language processing reflect dynamic interactions between linguistic and domain-general systems.
... dorsomedial prefrontal cortex, temperoparietal junction) associated with social cognition, in response to direct vs averted eye gaze [51 ]. A follow-up study revealed increased connectivity between the SC and LC with IAS regions, including the insula, inferior frontal cortex, amygdala, ACC, and striatum [52], findings thought related to sustained activation of the subcortical pathway of eye contact processing. These findings suggest that direct eye contact may be perceived subconsciously as threat by individuals with PTSD related to interpersonal trauma, where these patients show prominent activation of neural regions within the IAS rather than higher cortical regions involved in social cognition. ...
... Moreover, during direct eye gaze, as compared to controls [51 ], women with PTSD related to interpersonal trauma show heightened activation within and increased connectivity between IAS regions (e.g. SC and LC with amygdala, frontal cortex, ACC) [52]. Here, IAS may be associated with aberrant social responding observed in this patient population [51 ,52]. ...
... Indeed, accumulating evidence suggests that social cognition, the ability to interact optimally and to navigate the social world, may be altered in adults exposed to psychological trauma. Previous studies, including work conducted by our laboratory, have shown alterations in empathic responding (Nietlisbach, Maercker, Rö ssler, & Haker, 2010;Parlar et al., 2014), recognition of speech prosody (Nazarov, Frewen, et al., 2015), theory of mind (Mazza et al., 2012;Nazarov et al., 2014), and direct gaze processing (Steuwe et al., 2015) in this population. A reoccurring theme surrounding alterations in social cognition among individuals with PTSD is alterations in its performance in emotionally salient social contexts. ...
... As demonstrated by Parlar et al. (2014), women with PTSD exposed to chronic childhood trauma displayed reduced empathic concern and heightened personal distress. The sustained states of stress, anxiety, and fear may exacerbate the development of selffocused (potentially survival) behavior and competitiveness in trauma-exposed individuals as a result of being chronically engaged in subcortically-driven primitive defensive responses (Steuwe et al., 2014(Steuwe et al., , 2015. Individuals who develop under abusive, neglectful, and traumatic circumstances may not develop optimal socio-cognitive processes that in turn mediate altruistic behavior. ...
Background:
Preliminary evidence suggests that relative to healthy controls, patients with posttraumatic stress disorder (PTSD) show deficits on several inter-related social cognitive tasks, including theory of mind, and emotion comprehension. Systematic investigations examining other aspects of social cognition, including moral reasoning, have not been conducted in PTSD stemming from childhood trauma.
Objective:
To conduct a comprehensive assessment of moral reasoning performance in individuals with PTSD stemming from childhood abuse.
Method:
Moral reasoning performance was assessed in 28 women with PTSD related to prolonged childhood trauma and 19 matched healthy controls. Performance was assessed using 12 modified moral dilemmas and was queried in three domains: utilitarian/deontological sacrificial dilemmas (personal and impersonal), social order vs. compassion, and altruism vs. self-interest. Participants were asked whether a proposed action was morally acceptable or unacceptable and whether or not they would perform this action under the circumstances described.
Results:
Women with PTSD were less likely to carry out utilitarian actions in personal, sacrificial moral dilemmas, a choice driven primarily by consequential intrapersonal disapproval. Increased concern regarding intrapersonal disapproval was related to higher symptoms of guilt in the PTSD group. Patients with PTSD demonstrated less altruistic moral reasoning, primarily associated with decreased empathic role-taking for beneficiaries.
Conclusions:
Women with PTSD due to childhood trauma show alterations in moral reasoning marked by decreased utilitarian judgment and decreased altruism. Childhood trauma may continue to impact moral choices made into adulthood.
... PTSD patients are often triggered by stimuli of which they have no conscious awareness, where altered patterns of neural activity underlying subconscious processing of fearful or trauma-related material are thought to contribute to this symptom presentation [18][19][20][21]. Here, aberrant alerting mechanisms in PTSD have been associated with altered neural activity within key regions of the innate alarm system (a network of areas involved in rapid alerting to threat, including the brainstem, amygdala, pulvinar, and mPFC, see [22]), and increased brainstem-amygdala connectivity [20,[23][24][25][26] . To date, only two studies have investigated functional connectivity during subconscious threat processing in PTSD, revealing aberrant amygdala functional connectivity within the default mode network (comprising prefrontal and posterior regions [27]) and altered amygdala-mPFC connectivity [24]. ...
... In line with emerging reports, we expected to find differential functional connectivity between the BLA and CMA with the mPFC, parietal and insular cortex as a function of conscious and subconscious levels of awareness in PTSD. Finally, we sought to define the role of each specific amygdala subregion within the innate alarm circuit in PTSD, particularly with reference to brainstem-amygdala connectivity [26] during subconscious and conscious threat processing. ...
Post-traumatic stress disorder (PTSD) is characterized by altered functional connectivity of the amygdala complexes at rest. However, amygdala complex connectivity during conscious and subconscious threat processing remains to be elucidated. Here, we investigate specific connectivity of the centromedial amygdala (CMA) and basolateral amygdala (BLA) during conscious and subconscious processing of trauma-related words among individuals with PTSD (n = 26) as compared to non-trauma-exposed controls (n = 20). Psycho-physiological interaction analyses were performed using the right and left amygdala complexes as regions of interest during conscious and subconscious trauma word processing. These analyses revealed a differential, context-dependent responses by each amygdala seed during trauma processing in PTSD. Specifically, relative to controls, during subconscious processing, individuals with PTSD demonstrated increased connectivity of the CMA with the superior frontal gyrus, accompanied by a pattern of decreased connectivity between the BLA and the superior colliculus. During conscious processing, relative to controls, individuals with PTSD showed increased connectivity between the CMA and the pulvinar. These findings demonstrate alterations in amygdala subregion functional connectivity in PTSD and highlight the disruption of the innate alarm network during both conscious and subconscious trauma processing in this disorder.
... These findings provide a biological mechanism that may explain how experiences of RD may influence inflammation and subsequent response to threat. Given that heightened threat responses characterize stress-related disorders such as PTSD [68,69], these data reveal a pathway through which RD may increase vulnerability to brain health problems in Black Americans. To our knowledge, this is the first empirical study to show links between RD, CRP, and response in emotion regulation circuitry. ...
Prior research has shown that racial discrimination (RD) impacts activation in threat network regions, including the ventromedial prefrontal cortex (vmPFC) and middle occipital cortex during attention to threat-relevant stimuli. However, little is known about the biological mechanisms that may modulate these effects; inflammation may be a pathway linking RD and threat network activation. As such, the current study aimed to explore whether systemic inflammation, measured by C-reactive protein (CRP) levels, may moderate the relationship between RD and activation in the vmPFC and middle occipital cortex during attention to threat. Blood samples for inflammatory marker (CRP) assays were obtained from forty Black American women (mean [SD] age, 39.93 [9.97] years; range, 22-58 years) recruited from an ongoing trauma study; participants also viewed threat-relevant stimuli as part of an attention task during fMRI. We found that CRP moderated the relationship between RD and vmPFC activation during attention to threat, such that participants with relatively higher concentrations of CRP ( ≥ 23.97 mg/L) demonstrated significant positive associations between RD and vmPFC activation [β = 0.18, CI (0.04, 0.32), t = 2.65, p = 0.01]. No significant associations were observed for participants who showed moderate (10.89 mg/L) or low (0.20 mg/L) CRP concentrations. CRP did not moderate the relationship between RD and middle occipital cortex activation. Our data present a mechanism through which RD may influence immune system activation and, in turn, threat network activation. Inflammation may contribute to brain health vulnerabilities in Black Americans via its effects on threat circuits; this merits further investigation in large-scale studies.
... Thus, the thalamus can be regarded as a brain region commonly affected by child maltreatment. Recent brain imaging studies on PTSD have revealed a consistent decrease in thalamic activity [49][50][51][52]. Given that eye movement desensitization and reprocessing (EMDR), which is clinically effective in trauma therapy, addresses sensory integration, repeated traumatic exposure to maltreatment may create vulnerabilities in the thalamus, which regulates sensory integration. ...
Individuals who experienced childhood maltreatment reportedly have atypical gray matter structures in their primary visual cortex (V1). Thus, we hypothesized that the sensory structures of vision may also be affected by these influences and are related to each other. General ophthalmologic examinations, visual cognitive tasks, retinal imaging, and brain structural magnetic resonance imaging (MRI) were performed to compare the differences between children and adolescents aged 9–18 years with maltreatment experiences (CM) and typically developing (TD) children. The retinal nerve fiber layer (RNFL) and the segment (GCL++) summed with the RNFL and ganglion cell layer with the inner plexiform layer of the macular were significantly thinner in both eyes in CM. Although whole-brain analysis of Voxel-Based Morphometry revealed a significantly larger gray matter volume (GMV) in the thalamus compared to TD, there was no significant correlation with RNFL and GCL + + thickness. Based on the region-of-interest analysis, the thinner RNFL and GCL + + were associated with a larger GMV in the right V1. Owing to abusive experiences, CM showed subclinical structural atypicality in the retina, which may account for the immature V1 development since brain regions remain larger. Examination of retinal thickness could be a new clinical approach to capture CM characteristics.
... These effects were observed in many subcortical and limbic regions including the insula, claustrum, putamen, caudate, anterior cingulate, parahippocampal gyrus and the STG. Findings within areas such as the insula (Steuwe et al., 2014(Steuwe et al., , 2015, and (dorsal) anterior cingulate cortex (dACC; Klumpers et al., 2017;Piray et al., 2019) the BOLD signal in the dACC correlated with learning rate across all trials and participants, this was not the case for those high in social trait anxiety. Despite our focus on learning accuracy instead of learning rates, and that we used transient, mildly-elevated anxious states (compared to high trait social anxiety), we also found that in the ACC, threat led to loss of volatility-attuning (and attenuation) of neural surprise responses. ...
Anxiety can alter an individual's perception of their external sensory environment. Previous studies suggest that anxiety can increase the magnitude of neural responses to unexpected (or surprising) stimuli. Additionally, surprise responses are reported to be boosted during stable compared to volatile environments. Few studies, however, have examined how learning is impacted by both threat and volatility. To investigate these effects, we used threat-of-shock to transiently increase subjective anxiety in healthy adults while they performed an auditory oddball task under stable and volatile environments and while undergoing functional Magnetic Resonance Imaging (fMRI) scanning. We then used Bayesian Model Selection (BMS) mapping to identify the brain areas where different models of anxiety displayed the highest evidence. Behaviourally, we found that threat-of-shock eliminated the accuracy advantage conferred by environmental stability over volatility. Neurally, we found that threat-of-shock led to attenuation and loss of volatility-attuning of brain activity evoked by surprising sounds across most subcortical and limbic regions including the thalamus, basal ganglia, claustrum, insula, anterior cingulate, hippocampal gyrus and the superior temporal gyrus. Taken together, our findings suggest that threat eliminates learning advantages conferred by statistical stability compared to volatility. Thus, we propose that anxiety disrupts behavioural adaptation to environmental statistics, and that multiple subcortical and limbic regions are implicated in this process.
... The optic tectum (an evolutionary homolog of the superior colliculus in mammals) plays a critical role in the behavioral decision making that underlies avoidance and approach behavior. Imaging (Javanmard et al. 1999;Cornwell et al. 2012;Kessler et al. 2012), physiological (de Almeida et al. 2006Baek et al. 2019), and pharmacological studies (Azevedo et al. 2020) indicate that this brain area is more involved in post-limbic processing of a variety of anxiogenic stimuli than previously thought (Forcelli et al. 2016) and may play a central role in post-traumatic stress disorder (Steuwe et al. 2015;McFadyen et al. 2019). Despite growing evidence for a role of the optic tectum/superior colliculus in mediating anxiety-like behavior, little is known about the tectal neuromodulators and neurotransmitters involved in such control, especially in relation to a predator. ...
Animals often halt foraging in the presence of predator cues, an ecological phenomenon known as the foraging/predator avoidance tradeoff. Although some have proposed that anxiety may exist in animals exposed to predator cues, few studies have examined whether such interactions lead to anxiety-like behavior in animals other than laboratory rodents and zebrafish. In this experiment, a foraging/predator avoidance tradeoff task was modified using adult male African clawed frogs (Xenopus laevis) and a looming visual predator stimulus to determine if (1) visual predator cues reduce appetitive behavior, (2) visual predator cues lead to predator avoidance behavior, and (3) if visual predator cues alter the abundance of transcripts in the optic tectum known to be modulated in other brain areas during anxiety. Frogs exposed to the predator stimulus did not reduce their food intake, although sweeping, a foraging behavior, was significantly reduced by the predator stimulus. Predator-exposed animals spent significantly more time stationary and entered the predator zone less compared controls. There were no statistically significant changes in relative transcript abundance of anxiety-related peptides between the groups in the optic tectum. Collectively, this tradeoff task was able to induce discrete avoidance and appetitive behaviors that are similar to anxiety-like behaviors observed in other predator avoidance models; however, the effects of visual threats on feeding and anxiety-related transcript abundance requires further study.
Significance statement
Halting foraging activities to increase vigilance and engage avoidance behaviors has been proposed to play an adaptive role in survival of predator encounters in a number of animal species. Some have proposed that anxiety evolved as a state associated with the engagement of avoidance and antipredator behavior. However, few studies have examined whether such foraging/predator avoidance tradeoffs result in anxiety-like behavior in animals other than rodents. We developed a foraging/predator avoidance tradeoff task in an aquatic frog species to determine if the sight of a looming visual threat interferes with feeding and causes anxiety-like behavior in an amphibian. Our data suggest that some, but not other (feeding, for example), behavioral aspects of foraging/predator avoidance tradeoffs mimic anxiety-like behavior when a visual threat is present. These data contribute to a growing body of literature indicating that anxiety may be an adaptive response to predator threats in non-mammalian species.
... These effects were observed in many subcortical and limbic regions including the insula, claustrum, putamen, caudate, anterior cingulate, parahippocampal gyrus and the STG. Findings within areas such as the insula (Steuwe et al., 2014(Steuwe et al., , 2015, and (dorsal) ACC (Klumpers et al., 2010) are in support of previous literature showing these areas are engaged in threat processing. ...
Anxiety can alter an individual's perception of their external sensory environment. Previous studies suggest that anxiety can increase the magnitude of neural responses to unexpected (or surprising) stimuli. Additionally, surprise responses are reported to be boosted during stable compared to volatile environments. Few studies, however, have examined how learning is impacted by both threat and volatility. To investigate these effects, we used threat-of-shock to transiently increase subjective anxiety in healthy adults during an auditory oddball task, in which the regularity could be stable or volatile, while undergoing functional Magnetic Resonance Imaging (fMRI) scanning. We then used Bayesian Model Selection (BMS) mapping to pinpoint the brain areas where different models of anxiety displayed the highest evidence. Behaviourally, we found that threat-of-shock eliminated the accuracy advantage conferred by environmental stability over volatility in the task at hand. Neurally, we found that threat-of-shock led to both attenuation and loss of volatility-attuning of neural activity evoked by surprising sounds across most subcortical and limbic brain regions including the thalamus, basal ganglia, claustrum, insula, anterior cingulate, hippocampal gyrus and also the superior temporal gyrus. Conversely, within two small clusters in the left medial frontal gyrus and extrastriate area, threat-of-shock boosted the neural activity (relative to the safe and volatile condition) to the levels observed during the safe and stable condition, while also inducing a loss of volatility-attuning. Taken together, our findings suggest that threat eliminates the learning advantage conferred by statistical stability compared to volatility. Thus, we propose that anxiety disrupts behavioural adaptation to environmental statistics, and that multiple subcortical and limbic regions are implicated in this process.
... Taken together, the neuroimaging studies reviewed here support the hypothesis of an atypical representation of the PPS in PTSD, where neural structures related to bodily selfconsciousness, self-location, motor planning, and multisensory integration show altered neural activity and/or functional connectivity in PTSD and its dissociative subtype when compared to controls. This neural pattern can be interpreted as a general reorganization of neural networks in PTSD that favors innate alarm responses to potential threats and preparation for defense responses, thus affecting the integration of multisensory afferent and efferent inputs, with the resulting representation of the bodily self and its surroundings being biased toward potential incoming threats (Rabellino et al., 2015(Rabellino et al., , 2016a(Rabellino et al., , 2019Steuwe et al., 2015;Lanius et al., 2016;Frewen et al., 2017). ...
Peripersonal space (PPS) is defined as the space surrounding the body where we can reach or be reached by external entities, including objects or other individuals. PPS is an essential component of bodily self-consciousness that allows us to perform actions in the world (e.g., grasping and manipulating objects) and protect our body while interacting with the surrounding environment. Multisensory processing plays a critical role in PPS representation, facilitating not only to situate ourselves in space but also assisting in the localization of external entities at a close distance from our bodies. Such abilities appear especially crucial when an external entity (a sound, an object, or a person) is approaching us, thereby allowing the assessment of the salience of a potential incoming threat. Accordingly, PPS represents a key aspect of social cognitive processes operational when we interact with other people (for example, in a dynamic dyad). The underpinnings of PPS have been investigated largely in human models and in animals and include the operation of dedicated multimodal neurons (neurons that respond specifically to co-occurring stimuli from different perceptive modalities, e.g., auditory and tactile stimuli) within brain regions involved in sensorimotor processing (ventral intraparietal sulcus, ventral premotor cortex), interoception (insula), and visual recognition (lateral occipital cortex). Although the defensive role of the PPS has been observed in psychopathology (e.g., in phobias) the relation between PPS and altered states of bodily consciousness remains largely unexplored. Specifically, PPS representation in trauma-related disorders, where altered states of consciousness can involve dissociation from the body and its surroundings, have not been investigated. Accordingly, we review here: (1) the behavioral and neurobiological literature surrounding trauma-related disorders and its relevance to PPS; and (2) outline future research directions aimed at examining altered states of bodily self-consciousness in trauma related-disorders.
... The connectivity observed in areas consistently engaged in moral behaviour and social interaction depended highly on intention and on whether the pain was self-inflicted or not, providing an empirical framework for studies of social cognition disorders in children. Steuwe et al. (2015) showed that subcortical limbic and frontal loci become more connected to the locus coeruleus in female post-traumatic stress disorder patients when facing direct eye contact rather than averted gaze, potentially indicating an innate alarm system. More recently, a PPI analysis revealed that music intervention for preterm-born babies in neonatal intensive care units induces functional connectivity changes which suggest that music induces a more arousing and pleasant state (Lordier et al., 2018). ...
Preterm birth is a major risk factor for neurodevelopment impairments often only appearing later in life. The brain is still at a high rate of development during adolescence, making this a promising window for intervention. It is thus crucial to understand the mechanisms of altered brain function in this population. The aim of this thesis is to investigate how the brain dynamically reconfigures its own organisation over time in preterm-born young adolescents. Research to date has mainly focused on structural disturbances or in static features of brain function in this population. However, recent studies have shown that brain activity is highly dynamic, both spontaneously and during performance of a task, and that small disruptions in its complex architecture may interfere with normal behaviour and cognitive abilities.
This thesis explores the dynamic nature of brain function in preterm-born adolescents in three steps: First, we investigate changes in spontaneous brain activity over time using a resting-state paradigm. Here, we study how the variability of the blood oxygenation level dependent signal (BOLD), a measure previously linked to cognitive performance, develops in a preterm- and a term-born groups. We find that preterm participants show an altered trajectory of BOLD variability development during early adolescence. We also show that the dynamic patterns of co-activation with the dorsal anterior cingulate cortex (ACC), a key node of the salience network, also develop differently between the preterm and control groups. Secondly, we examine task-driven changes in brain activation. To this end, we select a reality filtering task known to engage the orbitofrontal cortex (OFC), a region that is particularly vulnerable in the preterm. We find that, although the preterm group is able to perform the task successfully, OFC activation is significantly higher in the control participants. Finally, inspired by the successful field of dynamic functional connectivity which has mainly flourished in resting-state paradigms, we develop a novel method to look into task-driven modulations of brain connectivity in a time-resolved way. We then apply this new approach to a third data set involving a movie watching and emotion regulation task. We find several subtle but significant seed; task; and group effects that characterise each of the dynamic co-activation patterns.
In short, we introduce a method for time-resolved evaluation of task-driven changes in brain connectivity and provide evidence of altered brain dynamics in preterm-born young adolescents. Our results thus highlight the importance of considering the dynamic aspects of brain function when studying clinical populations.
... In support of this model, PTSD patients show more exaggerated heart-rate responses, skin conductance, eye blink responses and LC blood-oxygen-level-dependent (BOLD) activation to loud sounds (Naegeli et al., 2018), as well as higher LC and insula BOLD responses to fearful stimuli (Morey et al., 2015) compared to trauma-exposed controls. There is also evidence linking PTSD with distorted fear learning governed by overactive of LC and insula to fearful stimuli and with increased LC connectivity with amygdala, striatum and insula during direct threatening eye gaze (Steuwe et al., 2015). Contradictory to this model is evidence that patients with PTSD show reduced LC size and reduced LC-NE reuptake availability (Arango et al., 1996;Bracha et al., 2005). ...
This review aims to synthesise a large pre-clinical and clinical literature related to a hypothesised role of the locus coeruleus norepinephrine system in responses to acute and chronic threat, as well as the emergence of pathological anxiety. The locus coeruleus has widespread norepinephrine projections throughout the central nervous system, which act to globally modulate arousal states and adaptive behavior, crucially positioned to play a significant role in modulating both ascending visceral and descending cortical neurocognitive information. In response to threat or a stressor, the locus coeruleus–norepinephrine system globally modulates arousal, alerting and orienting functions and can have a powerful effect on the regulation of multiple memory systems. Chronic stress leads to amplification of locus coeruleus reactivity to subsequent stressors, which is coupled with the emergence of pathological anxiety-like behaviors in rodents. While direct in vivo evidence for locus coeruleus dysfunction in humans with pathological anxiety remains limited, recent advances in high-resolution 7-T magnetic resonance imaging and computational modeling approaches are starting to provide new insights into locus coeruleus characteristics.
... Aberrant amygdala FC in response to threat also occurs in those with PTSD and spans a broad neural network. For instance, in response to threat, individuals with PTSD exhibit aberrant amygdala-brainstem (Steuwe et al., 2015), amygdala-thalamus (Morey et al., 2015;Rabellino et al., 2016), amygdala-medial prefrontal cortex (MPFC) and amygdala-anterior cingulate cortex (ACC) connectivity (Cisler, Scott Steele, Smitherman, Lenow, & Kilts, 2013; Keding & Herringa, 2016;Neumeister et al., 2016;Rabellino et al., 2016;Stevens et al., 2013;White, Costanzo, Blair, & Roy, 2015;Wolf & Herringa, 2016). Both healthy controls and traumatized controls are used as comparison groups throughout the literature, with no clear relationship between the directionality of findings and the type of control group employed. ...
Introduction
Resting state functional magnetic resonance imaging (rsfMRI) studies demonstrate that individuals with posttraumatic stress disorder (PTSD) exhibit atypical functional connectivity (FC) between the amygdala, involved in the generation of emotion, and regions responsible for emotional appraisal (e.g., insula, orbitofrontal cortex [OFC]) and regulation (prefrontal cortex [PFC], anterior cingulate cortex). Consequently, atypical amygdala FC within an emotional processing and regulation network may be a defining feature of PTSD, although altered FC does not seem constrained to one brain region. Instead, altered amygdala FC involves a large, distributed brain network in those with PTSD. The present study used a machine‐learning data‐driven approach, multi‐voxel pattern analysis (MVPA), to predict PTSD severity based on whole‐brain patterns of amygdala FC.
Methods
Trauma‐exposed adults (N = 90) completed the PTSD Checklist‐Civilian Version to assess symptoms and a 5‐min rsfMRI. Whole‐brain FC values to bilateral amygdala were extracted and used in a relevance vector regression analysis with a leave‐one‐out approach for cross‐validation with permutation testing (1,000) to obtain significance values.
Results
Results demonstrated that amygdala FC predicted PCL‐C scores with statistically significant accuracy (r = .46, p = .001; mean sum of squares = 130.46, p = .001; R ² = 0.21, p = .001). Prediction was based on whole‐brain amygdala FC, although regions that informed prediction (top 10%) included the OFC, amygdala, and dorsolateral PFC.
Conclusion
Findings demonstrate the utility of MVPA based on amygdala FC to predict individual severity of PTSD symptoms and that amygdala FC within a fear acquisition and regulation network contributed to accurate prediction.
... Similarly, effective connectivity between the pulvinar and the visual and frontal cortices is greater in people with social anxiety disorder while viewing faces 52 . Women with post-traumatic stress disorder (PTSD) (which is characterized by a hypervigilant attentional bias to threat) exhibit a greater blood oxygen level-dependent (BOLD) signal in the SC, PAG and locus coeruleus 53 , as well as enhanced functional connectivity between the SC and the cingulate cortex, insula and amygdala, while viewing faces 54 . Overall, these studies support a bottom-up exaggeration of threatening stimuli in people with greater attentional bias to threat, such as those with clinical anxiety. ...
The very earliest stages of sensory processing have the potential to alter how we perceive and respond to our environment. These initial processing circuits can incorporate subcortical regions, such as the thalamus and brainstem nuclei, which mediate complex interactions with the brain’s cortical processing hierarchy. These subcortical pathways, many of which we share with other animals, are not merely vestigial but appear to function as ‘shortcuts’ that ensure processing efficiency and preservation of vital life-preserving functions, such as harm avoidance, adaptive social interactions and efficient decision-making. Here, we propose that functional interactions between these higher-order and lower-order brain areas contribute to atypical sensory and cognitive processing that characterizes numerous neuropsychiatric disorders.
... The connectivity observed in areas consistently engaged in moral behaviour and social interaction depended highly on intention and on whether the pain was self-inflicted or not, providing an empirical framework for studies of social cognition disorders in children. Steuwe et al. et al. (2015) showed that subcortical limbic and frontal loci become more connected to the locus coeruleus in female post-traumatic stress disorder patients when facing direct eye contact rather than averted gaze, potentially indicating an innate alarm system. More recently, a PPI analysis revealed that music intervention for preterm-born babies in neonatal intensive care units induces functional connectivity changes which suggest that music induces a more arousing and pleasant state (Lordier et al., 2018). ...
Investigating context-dependent modulations of Functional Connectivity (FC) with functional magnetic resonance imaging is crucial to reveal the neurological underpinnings of cognitive processing. Most current analysis methods hypothesise sustained FC within the duration of a task, but this assumption has been shown too limiting by recent imaging studies. While several methods have been proposed to study functional dynamics during rest, task-based studies are yet to fully disentangle network modulations.
Here, we propose a seed-based method to probe task-dependent modulations of brain activity by revealing Psychophysiological Interactions of Co-activation Patterns (PPI-CAPs). This point process-based approach temporally decomposes task-modulated connectivity into dynamic building blocks which cannot be captured by current methods, such as PPI or Dynamic Causal Modelling. Additionally, it identifies the occurrence of co-activation patterns at single frame resolution as opposed to window-based methods.
In a naturalistic setting where participants watched a TV program, we retrieved several patterns of co-activation with a posterior cingulate cortex seed whose occurrence rates and polarity varied depending on the context; on the seed activity; or on an interaction between the two. Moreover, our method exposed the consistency in effective connectivity patterns across subjects and time, allowing us to uncover links between PPI-CAPs and specific stimuli contained in the video.
Our study reveals that explicitly tracking connectivity pattern transients is paramount to advance our understanding of how different brain areas dynamically communicate when presented with a set of cues.
... Patients with PTSD show higher LC functional MRI activation, exaggerated heart-rate responses, skin conductance and eye blink responses to loud sounds (Naegeli et al., 2018) as well as higher LC and insula functional MRI activation to fearful stimuli (Morey et al., 2015) compared to trauma-exposed controls. There is also evidence linking PTSD with increased LC connectivity with amygdala, striatum and insula during threatening eye gaze (Steuwe et al., 2015). This enhanced functional activation and connectivity may relate to larger volume but further studies linking structure and function are needed. ...
The locus coeruleus (LC) has a long-established role in the attentional and arousal response to threat, and in the emergence of pathological anxiety in pre-clinical models. However, human evidence of links between LC function and pathological anxiety has been restricted by limitations in discerning LC with current neuroimaging techniques. We combined ultra-high field 7-Tesla and 0.4 × 0.4 × 0.5 mm quantitative MR imaging with a computational LC localization and segmentation algorithm to delineate the LC in 29 human subjects including subjects with and without an anxiety or stress-related disorder. Our automated, data-driven LC segmentation algorithm provided LC delineations that corresponded well with postmortem anatomic definitions of the LC. There was variation of LC size in healthy subjects (125.7 +/- 59.3 mm3), which recapitulates histological reports. Patients with an anxiety or stress-related disorder had larger LC compared to controls (Cohen's d = 1.08, p = 0.024). Larger LC was additionally associated with poorer attentional and inhibitory control and higher anxious arousal (FDR-corrected p's
... In addition to NM-MRI, there have been studies examining LC functional connectivity in healthy and clinical populations. These studies have primarily focused on psychiatric symptoms, showing that LC functional connectivity with certain limbic regions is increased in patients with generalized anxiety disorder (Meeten et al., 2016), post-traumatic stress disorder (Steuwe et al., 2015), or those at high risk for schizophrenia (Anticevic et al., 2014). Whether such changes are also present in AD patients with BPSD has yet to be determined. ...
The dearth of effective treatments for Alzheimer’s disease (AD) is one of the largest public health issues worldwide, costing hundreds of billions of dollars per year. From a therapeutic standpoint, research efforts to date have met with strikingly little clinical success. One major issue is that trials begin after substantial pathological change has occurred, and it is increasingly clear that the most effective treatment regimens will need to be administered earlier in the disease process. In order to identify individuals within the long preclinical phase of AD who are likely to progress to dementia, improvements are required in biomarker development. One potential area of research that might prove fruitful in this regard is the in vivo detection of brainstem pathology. The brainstem is known to undergo pathological changes very early and progressively in AD. With an updated and harmonized AD research framework, and emerging advances in neuroimaging technology, the potential to leverage knowledge of brainstem pathology into biomarkers for AD will be discussed.
... First, the early visual cortex (Brodmann's 17 and 18 areas) ROI (473 average voxels) was identified by the group results of neural activation for mask-only condition over baseline condition, masked by the template defined by automated anatomical labeling map (AAL) (Tzourio-Mazoyer et al., 2002). The priori ROIs, LGN, SC and pulvinar anatomical ROIs were created based on pertinent literature (Kastner et al., 2002;Morris, de Gelder, Weiskrantz, & Dolan, 2001) and defined as a sphere of 5 mm radius (133 voxels) respectively (Hsu, et al. 2013;Schmid et al., 2013;Steuwe, et al., 2015). ...
Introduction
“Where to begin” is a fundamental question of vision. A “Global‐first” topological approach proposed that the first step in object representation was to extract topological properties, especially whether the object had a hole or not. Numerous psychophysical studies found that the hole (closure) could be rapidly recognized by visual system as a primitive property. However, neuroimaging studies showed that the temporal lobe (IT), which lied at a late stage of ventral pathway, was involved as a dedicated region. It appeared paradoxical that IT served as a key region for processing the early component of visual information. Did there exist a distinct fast route to transit hole information to IT? We hypothesized that a fast noncortical pathway might participate in processing holes.
Methods
To address this issue, a backward masking paradigm combined with functional magnetic resonance imaging (fMRI) was applied to measure neural responses to hole and no‐hole stimuli in anatomically defined cortical and subcortical regions of interest (ROIs) under different visual awareness levels by modulating masking delays.
Results
For no‐hole stimuli, the neural activation of cortical sites was greatly attenuated when the no‐hole perception was impaired by strong masking, whereas an enhanced neural response to hole stimuli in non‐cortical sites was obtained when the stimulus was rendered more invisible.
Conclusions
The results suggested that whereas the cortical route was required to drive a perceptual response for no‐hole stimuli, a subcortical route might be involved in coding the hole feature, resulting in a rapid hole perception in primitive vision.
... 115 Similarly, the pulvinar nucleus of the thalamus is a key node of the innate alarm system (IAS), a network of interconnected brain regions involved in subconscious detection of threat, 116-119 allowing rapid activation of defensive responses conferring an evolutionary advantage by rapidly facilitating response to threat. 120,121 The IAS has recently been described as a brainnetwork that shows aberrant functional connectivity among individuals with PTSD during subconscious and conscious threat processing, [122][123][124][125][126] including heightened activity of the thalamus, amygdala and parahippocampal gyrus during subconscious threat processing in individuals with PTSD+DS in response to fearful faces, suggesting exaggerated IAS responding to subconscious threat. 64 Given the emerging role of thalamus connectivity to the DMN in mindfulness, it will also be important to determine the potential utility of mindfulnessbased interventions in targeting dissociative symptoms associated with PTSD. ...
Mindfulness-based treatments for posttraumatic stress disorder (PTSD) have emerged as promising adjunctive or alternative intervention approaches. A scoping review of the literature on PTSD treatment studies, including approaches such as mindfulness-based stress reduction, mindfulness-based cognitive therapy and metta mindfulness, reveals low attrition with medium to large effect sizes. We review the convergence between neurobiological models of PTSD and neuroimaging findings in the mindfulness literature, where mindfulness interventions may target emotional under- and overmodulation, both of which are critical features of PTSD symptomatology. Recent emerging work indicates that mindfulness-based treatments may also be effective in restoring connectivity between large-scale brain networks among individuals with PTSD, including connectivity between the default mode network and the central executive and salience networks. Future directions, including further identification of the neurobiological mechanisms of mindfulness interventions in patients with PTSD and direct comparison of these interventions to first-line treatments for PTSD are discussed.
... The SC is a powerful subcortical structure processing multisensory integration and sensorimotor transformations [King, 2004;May, 2006;Stein and Meredith, 1993]. Critically, extensive animal studies Comoli et al., 2012;Merker, 2013], more recently replicated in healthy humans [Gitelman et al., 2002;Krebs et al., 2010b;Steuwe et al., 2015;Vuilleumier, 2015], indicate that the SC is involved in a series of cognitive and motor processes relevant to threat-detection mechanisms. Its involvement is also associated with a cluster of symptoms observed clinically in both active (fight/flight) and passive (emotional detachment with accompanying symptoms of depersonalization/derealisation) defensive responses Kozlowska et al., 2015;Schauer and Elbert, 2010]. ...
Objectives:
The innate alarm system (IAS) models the neurocircuitry involved in threat processing in posttraumatic stress disorder (PTSD). Here, we investigate a primary subcortical structure of the IAS model, the superior colliculus (SC), where the SC is thought to contribute to the mechanisms underlying threat-detection in PTSD. Critically, the functional connectivity between the SC and other nodes of the IAS remains unexplored.
Experimental design:
We conducted a resting-state fMRI study to investigate the functional architecture of the IAS, focusing on connectivity of the SC in PTSD (n = 67), its dissociative subtype (n = 41), and healthy controls (n = 50) using region-of-interest seed-based analysis.
Principal observations:
We observed group-specific resting state functional connectivity between the SC for both PTSD and its dissociative subtype, indicative of dedicated IAS collicular pathways in each group of patients. When comparing PTSD to its dissociative subtype, we observed increased resting state functional connectivity between the left SC and the right dorsolateral prefrontal cortex (DLPFC) in PTSD. The DLPFC is involved in modulation of emotional processes associated with active defensive responses characterising PTSD. Moreover, when comparing PTSD to its dissociative subtype, increased resting state functional connectivity was observed between the right SC and the right temporoparietal junction in the dissociative subtype. The temporoparietal junction is involved in depersonalization responses associated with passive defensive responses typical of the dissociative subtype.
Conclusions:
Our findings suggest that unique resting state functional connectivity of the SC parallels the unique symptom profile and defensive responses observed in PTSD and its dissociative subtype. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.
... 115 Similarly, the pulvinar nucleus of the thalamus is a key node of the innate alarm system (IAS), a network of interconnected brain regions involved in subconscious detection of threat, 116-119 allowing rapid activation of defensive responses conferring an evolutionary advantage by rapidly facilitating response to threat. 120,121 The IAS has recently been described as a brainnetwork that shows aberrant functional connectivity among individuals with PTSD during subconscious and conscious threat processing, [122][123][124][125][126] including heightened activity of the thalamus, amygdala and parahippocampal gyrus during subconscious threat processing in individuals with PTSD+DS in response to fearful faces, suggesting exaggerated IAS responding to subconscious threat. 64 Given the emerging role of thalamus connectivity to the DMN in mindfulness, it will also be important to determine the potential utility of mindfulnessbased interventions in targeting dissociative symptoms associated with PTSD. ...
Mindfulness-based treatments for posttraumatic stress disorder (PTSD) have emerged as promising adjunctive or alternative intervention approaches. A scoping review of the literature on PTSD treatment studies, including approaches such as mindfulness-based stress reduction, mindfulness-based cognitive therapy and metta mindfulness, reveals low attrition with medium to large effect sizes. We review the convergence between neurobiological models of PTSD and neuroimaging findings in the mindfulness literature, where mindfulness interventions may target emotional under- and overmodulation, both of which are critical features of PTSD symptomatology. Recent emerging work indicates that mindfulness-based treatments may also be effective in restoring connectivity between large-scale brain networks among individuals with PTSD, including connectivity between the default mode network and the central executive and salience networks. Future directions, including further identification of the neurobiological mechanisms of mindfulness interventions in patients with PTSD and direct comparison of these interventions to first-line treatments for PTSD are discussed.
... While no BOLD changes occurred in this condition compared to placebo, we found an increased task-related functional connectivity between NAcc and left vmPFC using PPI analysis ( Figure 5). Recently, a growing recognition for task-related functional connectivity changes has been established in psychiatric research (Admon et al., 2015;Cisler et al., 2014;Steuwe et al., 2015), also in absence of direct BOLD alterations (Esslinger et al., 2009). A majority of the neural afferents to the NAcc originates from vmPFC, by which behavioral drives, mood states, direct or anticipated reward shape consecutive behaviors (Sesack and Grace, 2010). ...
Gamma-hydroxybutyrate (GHB) is a GHB-/GABAB-receptor agonist currently used as treatment for narcolepsy but also as a drug of abuse. Non-medical GHB users have repeatedly reported prosexual effects including libido-enhancement and lowering of attractiveness standards for partner selection. Here, we examined the putative prosexual effects of oral GHB in healthy males in two experiments both employing randomized, placebo-controlled, double-blind, balanced, and cross-over study designs. In experiment I, subjective effects of 20 and 35 mg/kg GHB vs. placebo were tested in 32 participants using the Sexual Arousal and Desire Inventory. In experiment II, brain reactivity towards erotic vs. neutral pictures was investigated in 15 participants using functional magnetic resonance imaging after 35 mg/kg GHB vs. placebo.
... This question has been investigated predominantly in combat veterans for traumata related to war, and partially also in survivors of traffic or mining accidents (Bremner et al., 1999;Hayes et al., 2011;Hou et al., 2007). Moreover, several important studies have investigated PTSD in female victims of IPV, mostly using unspecific threat stimuli (faces; Fonzo et al., 2010;eye contact;Steuwe et al., 2015; negative words; Thomaes et al., 2009), but also trauma-related and more complex stimuli (e.g. video clips; Moser et al., 2015). ...
Interpersonal violence (IPV) is one of the most frequent causes for the development of posttraumatic stress disorder (PTSD) in women. Trauma-related triggers have been proposed to evoke automatic emotional responses in PTSD. The present functional magnetic resonance study investigated the neural basis of trauma-related picture processing in women with IPV-PTSD (n = 18) relative to healthy controls (n = 18) using a new standardized trauma-related picture set and a nonemotional vigilance task. We aimed to identify brain activation and connectivity evoked by trauma-related pictures, and associations with PTSD symptom severity.We found hyperactivation during trauma-related vs. neutral pictures processing in both subcortical (basolateral amygdala (BLA), thalamus, brainstem) and cortical (anterior cingulate cortex (ACC), medial prefrontal cortex (mPFC), insula, occipital cortex) regions in IPV-PTSD. In patients, brain activation in amygdala, ACC, insula, occipital cortex and brainstem correlated positively with symptom severity. Furthermore, connectivity analyses revealed hyperconnectivity between BLA and dorsal ACC/mPFC.Results show symptom severity dependent brain activation and hyperconnectivity in response to trauma-related pictures in brain regions related to fear and visual processing in women suffering from IPV-PTSD. These brain mechanisms appear to be associated with immediate responses to trauma-related triggers presented in a non-emotional context in this PTSD subgroup.
... However, it should be noted that no differences in NET availability were noted between trauma-exposed individuals who developed PTSD and those who did not. Another set of interesting fMRI studies reported LC hyperactivity in PTSD patients relative to healthy controls (Steuwe et al. 2014), as well as a strengthening of functional connectivity between the LC and a distributed network that includes the thalamus, caudate putamen, insula, cingulate gyrus and amygdala (Steuwe et al. 2015). ...
Post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) are highly co-morbid in humans. Although we have some understanding of the structural and functional brain changes that define each of these disorders, and how those changes contribute to the behavioral symptoms that define them, little is known about the neurobiology of co-morbid PTSD and AUD, which may be due in part to a scarcity of adequate animal models for examining this research question. The goal of this review is to summarize the current state-of-the-science on co-morbid PTSD and AUD: we summarize epidemiological data documenting the prevalence of this co-morbidity, review what is known about the potential neurobiological basis for the frequent co-occurrence of PTSD and AUD, and discuss successes and failures of past and current treatment strategies. We also review animal models that aim to examine co-morbid PTSD and AUD, highlighting where the models parallel the human condition, and we discuss the strengths and weaknesses of each model. We end by discussing key gaps in our knowledge and strategies for addressing them: in particular, we 1) highlight the need for better animal models of the co-morbid condition and better clinical trial design, 2) emphasize the need for examination of subpopulation effects and individual differences, and 3) urge cross-talk between basic and clinical researchers that is reflected in collaborative work with forward and reverse translational impact.
... Social cognition, involving the ability to use, encode, and store information about others that we gain from social interactions (Brothers, 1990;Adolphs, 2001), is disrupted across a host of psychiatric conditions, including schizophrenia (Savla et al., 2013), mood disorders (Cusi et al., , 2011(Cusi et al., , 2013(Cusi et al., , 2012a(Cusi et al., , 2012bMcKinnon et al., 2010), borderline personality disorder (Domes et al., 2009), and PTSD (Nazarov et al., , 2015Parlar et al., 2014;Steuwe et al., 2015) Critically, alterations in social cognitive functions relying upon the joint contribution of cognitive and affective processing resources known to be disrupted in neuropsychiatric illness may contribute to the impairments in interpersonal functioning (e.g., relations with family and friends) seen in these conditions. ...
Dissociative experiences, involving altered states of consciousness, have long been understood as a consequence or response to traumatic experiences, where a reduced level of consciousness may aid in survival during and after a traumatic event. Indeed, the dissociative subtype of post-traumatic stress disorder (PTSD-DS) was added recently to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). Dissociative symptoms are present across a host of neuropsychiatric conditions, including PTSD, psychotic spectrum illnesses, anxiety and mood disorders. Transdiagnostically, the presence of dissociative symptoms is associated with a greater illness burden and reduced treatment outcomes. Critically, dissociative symptoms are related to impaired performance on measures of attention, executive functioning, memory, and social cognition and may contribute to the widespread cognitive dysfunction observed across psychiatric illnesses. Despite this knowledge, the relation between dissociative symptoms and reduced cognitive function remains poorly understood. Here, we review the evidence linking dissociative symptoms to cognitive dysfunction across neuropsychiatric disorders. In addition, we explore two potential neurobiological mechanisms that may underlie the relation between dissociative symptoms and cognitive dysfunction in trauma-related neuropsychiatric conditions. Specifically, we hypothesize that: 1) functional sensory deafferentation at the level of the thalamus as observed in the defense cascade model of dissociation may underlie reduced attention and arousal leading to progressive cognitive dysfunction and; 2) altered functional connectivity between key brain networks implicated in cognitive functioning among may represent a critical neurobiological mechanism linking dissociative symptoms and cognitive dysfunction in patients with PTSD-DS and transdiagnostically.
... Extremely stressful events during early childhood can alter a person's affective state decades after the triggering incident. Women in their early 30s often exhibit phobias and increased anxiety after maltreatment as a child [104]. In a cohort of depressed patients given antidepressant medication for the first time (mean age: 33.6 years), it was found that patients who had experienced childhood maltreatment were less likely to respond to the medication [105], suggesting a significant alteration to their neurochemistry relative to age matched, depressed controls. ...
The development of a persistent depressive affective state has for some time been thought to result from persistent alterations in neurotransmitter-mediated synaptic transmission. While the identity of those transmitters has changed over the years, the literature has lacked mechanistic connections between the neurophysiological mechanisms they regulate, and how these mechanisms alter neuronal function, and, hence, affective homeostasis. This review will examine recent work that suggests that both long-term activity-dependent changes in synaptic strength ("plasticity"), and shifting set points for the ease of induction of future long-term changes ("metaplasticity"), may be critical to establishing and reversing a depressive behavioral state. Activity-dependent long-term synaptic plasticity involves both strengthening and weakening of synaptic connections associated with a dizzying array of neurochemical alterations that include synaptic insertion and removal of a number of subtypes of AMPA, NMDA and metabotropic glutamate receptors, changes in presynaptic glutamate release, and structural changes in dendritic spines. Cellular mechanisms of metaplasticity are far less well understood. Here, we will review the growing evidence that long-term synaptic changes in glutamatergic transmission, in brain regions that regulate mood, are key determinants of affective homeostasis and therapeutic targets with immense potential for drug development.
... The concept of two visual systems, one a subconscious pathway that localizes objects and the second an evolutionarily newer visual system that identifies objects, dates back to the 1960s and work in hamsters by Schneider (1967Schneider ( , 1969 and work in frogs by Ingle (1973). More recent imaging studies showing that the SC plays a central role in the response to a wide variety of stressors (Javanmard et al., 1999;Cornwell et al., 2012;Kessler et al., 2012;Steuwe et al., 2015), and studies showing ascending projections to the amygdala that are relayed through the pulvinar nucleus (Morris et al., 1999(Morris et al., , 2002Liddell et al., 2005;Ohman et al., 2007), has re-focused this debate on the importance of the SC, in particular, in processing fear. Are visual threats processed consciously or in a more reflexive, subconscious, way by the brain? ...
Although there is general agreement that the central nucleus of the amygdala (CeA) is critical for triggering the neuroendocrine response to visual threats, there is uncertainty about the role of subcortical visual pathways in this process. Primates in general appear to depend less on subcortical visual pathways than other mammals. Yet, imaging studies continue to indicate a role for the superior colliculus and pulvinar nucleus in fear activation, despite disconnects in how these brain structures communicate not only with each other but with the amygdala. Studies in fish and amphibians suggest that the neuroendocrine response to visual threats has remained relatively unchanged for hundreds of millions of years, yet there are still significant data gaps with respect to how visual information is relayed to telencephalic areas homologous to the CeA, particularly in fish. In fact ray finned fishes may have evolved an entirely different mechanism for relaying visual information to the telencephalon. In part because they lack a pathway homologous to the lateral geniculate-striate cortex pathway of mammals, amphibians continue to be an excellent model for studying how stress hormones in turn modulate fear activating visual pathways. Glucocorticoids, melanocortin peptides, and CRF all appear to play some role in modulating sensorimotor processing in the optic tectum. These observations, coupled with data showing control of the hypothalamus-pituitary-adrenal axis by the superior colliculus, suggest a fear/stress/anxiety neuroendocrine circuit that begins with first order synapses in subcortical visual pathways. Thus, comparative studies shed light not only on how fear triggering visual pathways came to be, but how hormones released as a result of this activation modulate these pathways.
Eye contact with another person (social gaze) can evoke emotions, produce autonomic arousal, and influence behavior. Gaze cues can be evocative even when presented in static pictures of faces suggesting that responses depend on low-level visual features of gaze stimuli. The current study examined whether emotional gaze responses depend on the physical stimulus properties of an eye contact experience versus the cognitive evaluation of the social context of gaze. This was done by comparing skin conductance responses (SCR), an index of emotional arousal, during episodes of social gaze and 'self-gaze' (gazing at one's own eyes in a mirror), keeping other aspects of the viewing conditions constant. We compared SCRs during social gaze and self-gaze in forty participant pairs. Each participant engaged in ten, 20 second eye contact trials, alternating between social and self-gaze. Self-gaze episodes produced significant SCRs but social gaze SCR's were larger and occurred more reliably. SCRs decreased across trials (habituation effect) in both conditions. We speculated that social gaze between opposite sex partners might yield larger SCRs but this was not found. Overall, these results conceptually replicate previous findings of (likely top-town) cognitive regulation of autonomic gaze responses based on evaluation of the social context.
Appropriate expression of fear in the face of threats in the environment is essential for survival. The sustained expression of fear in the absence of threat signals is a central pathological feature of trauma- and anxiety-related disorders. Our understanding of the neural circuitry that controls fear inhibition coalesces around the amygdala, hippocampus, and prefrontal cortex. By discussing thalamic and sub-thalamic influences on fear-related learning and expression in this review, we suggest a more inclusive neurobiological framework that expands our canonical view of fear. First, we visit how fear-related learning and expression is influenced by the aforementioned canonical brain regions. Next, we review emerging data that shed light on new roles for thalamic and subthalamic nuclei in fear-related learning and expression. Then, we highlight how these neuroanatomical hubs can modulate fear via integration of sensory and salient stimuli, gating information flow and calibrating behavioral responses, as well as maintaining and updating memory representations. Finally, we propose that the presence of this thalamic and sub-thalamic neuroanatomy in parallel with the tripartite prefrontal cortex-amygdala-hippocampus circuit allows for dynamic modulation of information based on interoceptive and exteroceptive signals.
Social functioning is a key component of recovery after a potentially traumatic experience, and the buffering role of the social support in trauma resilience and recovery has been very well documented. Factors contributing to resilience and recovery are notable because although most people will experience a traumatic event during their lifetimes, only 6‐10% are diagnosed with post‐traumatic stress disorder (PTSD). The relationship between an individual and their social environment is determined both by the quality of the social environment itself, and by the individual’s perception and understanding of information conveyed by the other people around them. However, little research has considered the contribution of these internal social cognitive processes to PTSD risk or resilience. The current review draws on the existing literature on social cognitive functioning in trauma exposure and PTSD, identifying key questions and themes for future research. We utilized a meta‐analytic approach to assess the evidence for alterations in social cognition in PTSD, finding a consistent large deficit in social cognitive performance in PTSD groups relative to trauma‐exposed and healthy controls. We then reviewed the literature on the interaction of genes and the social environment, supporting the hypothesis that social cognitive deficits are a pre‐existing risk factor for PTSD. Finally, we reviewed relevant neuroimaging findings, which suggest that alterations in social cognition affect the perception of threat cues in PTSD. Overall, research on social cognition and PTSD is still emerging, but existing findings suggest this is an important and understudied area for the understanding of PTSD.
One of the major developments of the second year of human life is the emergence of the ability to pretend. A child's knowledge of a real situation is apparently contradicted and distorted by pretense. If, as generally assumed, the child is just beginning to construct a system for internally representing such knowledge, why is this system of representation not undermined by its use in both comprehending and producing pretense? In this article I present a theoretical analysis of the representational mechanism underlying this ability. This mechanism extends the power of the infant's existing capacity for (primary) representation, creating a capacity for metarepresentation. It is this, developing toward the end of infancy, that underlies the child's new abilities to pretend and to understand pretense in others. There is a striking isomorphism between the three fundamental forms of pretend play and three crucial logical properties of mental state expressions in language. This isomorphism points to a common underlying form of internal representation that is here called metarepresentation. A performance model, the decoupler, is outlined embodying ideas about how an infant might compute the complex function postulated to underlie pretend play. This model also reveals pretense as an early manifestation of the ability to understand mental states. Aspects of later preschool development, both normal and abnormal, are discussed in the light of the new model. This theory begins the task of characterizing the specific innate basis of our commonsense "theory of mind.".
Posttraumatic stress (PTSD) disorder has been associated with heightened threat sensitivity. Evidence suggests that direct eye gaze leads to sustained activation of the superior colliculus/periaqueductal grey within individuals with PTSD. The present analysis investigated functional connectivity within the salience network (SN) in the same sample as presented in a prior publication during direct versus averted gaze in adults with PTSD related to childhood maltreatment as compared to healthy individuals.
Functional connectivity within the SN was examined using functional magnetic resonance imaging while participants viewed avatars positioned in direct versus averted gaze relative to the participant in 16 individuals with PTSD related to childhood maltreatment and 16 healthy control subjects. Connectivity within the SN was assessed via Independent Component Analysis (ICA). Associations with symptom severity were explored with multiple regression analyses on individual subject components.
Temporal multiple regression analyses revealed higher connectivity within the SN during direct versus averted gaze which was more pronounced in individuals with PTSD as compared to healthy controls. Compared to controls, individuals with PTSD showed increased integration of the left amygdala and the right insula within the SN. PTSD symptom severity was positively associated with connectivity of the right mid-cingulate cortex within the SN in PTSD subjects only.
Participants with PTSD showed enhanced coupling of the amygdala and the insula within the SN as compared to healthy control subjects during gaze processing. Our results provide evidence for an increased sensitivity of the salience network to direct versus averted gaze in individuals with PTSD related to childhood maltreatment.
An individual has a theory of mind if he imputes mental states to himself and others. A system of inferences of this kind is properly viewed as a theory because such states are not directly observable, and the system can be used to make predictions about the behavior of others. As to the mental states the chimpanzee may infer, consider those inferred by our own species, for example, purpose or intention, as well as knowledge, belief, thinking, doubt, guessing, pretending, liking, and so forth. To determine whether or not the chimpanzee infers states of this kind, we showed an adult chimpanzee a series of videotaped scenes of a human actor struggling with a variety of problems. Some problems were simple, involving inaccessible food – bananas vertically or horizontally out of reach, behind a box, and so forth – as in the original Kohler problems; others were more complex, involving an actor unable to extricate himself from a locked cage, shivering because of a malfunctioning heater, or unable to play a phonograph because it was unplugged. With each videotape the chimpanzee was given several photographs, one a solution to the problem, such as a stick for the inaccessible bananas, a key for the locked up actor, a lit wick for the malfunctioning heater. The chimpanzee's consistent choice of the correct photographs can be understood by assuming that the animal recognized the videotape as representing a problem, understood the actor's purpose, and chose alternatives compatible with that purpose.
In healthy individuals, direct eye contact initially leads to activation of a fast subcortical pathway, which then modulates
a cortical route eliciting social cognitive processes. The aim of this study was to gain insight into the neurobiological
effects of direct eye-to-eye contact using a virtual reality paradigm in individuals with posttraumatic stress disorder (PTSD)
related to prolonged childhood abuse. We examined 16 healthy comparison subjects and 16 patients with a primary diagnosis
of PTSD using a virtual reality functional magnetic resonance imaging paradigm involving direct vs averted gaze (happy, sad, neutral) as developed by Schrammel et al. in 2009. Irrespective of the displayed emotion, controls exhibited an increased blood oxygenation level-dependent response
during direct vs averted gaze within the dorsomedial prefrontal cortex, left temporoparietal junction and right temporal pole. Under the same
conditions, individuals with PTSD showed increased activation within the superior colliculus (SC)/periaqueductal gray (PAG)
and locus coeruleus. Our findings suggest that healthy controls react to the exposure of direct gaze with an activation of
a cortical route that enhances evaluative ‘top–down’ processes underlying social interactions. In individuals with PTSD, however,
direct gaze leads to sustained activation of a subcortical route of eye-contact processing, an innate alarm system involving
the SC and the underlying circuits of the PAG.
Symptoms of anhedonia, or deficits in the ability to experience positive affect, are increasingly recognized as an outcome of traumatic stress. Herein we demonstrate a phenomenon of "negative affective interference", specifically, negative affective responses to positive events, in association with childhood trauma history. Young adults (n=99) completed a Hedonic Deficit & Interference Scale (HDIS), a self-report measure developed for this study, as well as a modified version of the Fawcette-Clarke Pleasure Capacity Scale that assessed not only positive but also negative affective responses to positive events. The two assessment approaches demonstrated convergent validity and predicted concurrent individual differences in trait positive and negative affect, and extraversion and neuroticism. Histories of childhood emotional and sexual abuse were differentially associated with negative affective responses to positive events. Future research and clinical directions are discussed.
The role of horizontal head tilt for the perceptions of emotional facial expressions was examined. For this, a total of 387
participants rated facial expressions of anger, fear, sadness, and happiness, as well as neutral expressions shown by two
men and two women in either a direct or an averted face angle. Decoding accuracy, attributions of dominance and affiliation,
emotional reactions of the perceivers, and the felt desire to approach the expresser were assessed. Head position was found
to strongly influence reactions to anger and fear but less so for other emotions. Direct anger expressions were more accurately
decoded, perceived as less affiliative, and elicited higher levels of anxiousness and repulsion, as well as less desire to
approach than did averted anger expressions. Conversely, for fear expressions averted faces elicited more negative affect
in the perceiver. These findings suggest that horizontal head position is an important cue for the assessment of threat.
Social neuroscience has shed light on the underpinnings of understanding other minds. The current study investigated the effect of self-involvement during social interaction on attention, arousal, and facial expression. Specifically, we sought to disentangle the effect of being personally addressed from the effect of decoding the meaning of another person's facial expression. To this end, eye movements, pupil size, and facial electromyographic (EMG) activity were recorded while participants observed virtual characters gazing at them or looking at someone else. In dynamic animations, the virtual characters then displayed either socially relevant facial expressions (similar to those used in everyday life situations to establish interpersonal contact) or arbitrary facial movements. The results show that attention allocation, as assessed by eye-tracking measurements, was specifically related to self-involvement regardless of the social meaning being conveyed. Arousal, as measured by pupil size, was primarily related to perceiving the virtual character's gender. In contrast, facial EMG activity was determined by the perception of socially relevant facial expressions irrespective of whom these were directed towards.
Traditionally, the cerebral cortex is considered the dominant player in understanding human brain functions, with subcortical structures relegated to a subservient role. In a recent Perspective article, Pessoa and Adolphs partly return to this traditional corticocentric view in the field of emotion processing (Emotion processing and the amygdala: from a 'low road' to 'many roads' of evaluating biological significance.
We examined whether amygdala responses to rapidly presented fear expressions are preferentially tuned to averted vs direct gaze fear and conversely whether responses to more sustained presentations are preferentially tuned to direct vs averted gaze fear. We conducted three functional magnetic resonance imaging (fMRI) studies to test these predictions including: Study 1: a block design employing sustained presentations (1 s) of averted vs direct gaze fear expressions taken from the Pictures of Facial Affect; Study 2: a block design employing rapid presentations (300 ms) of these same stimuli and Study 3: a direct replication of these studies in the context of a single experiment using stimuli selected from the NimStim Emotional Face Stimuli. Together, these studies provide evidence consistent with an early, reflexive amygdala response tuned to clear threat and a later reflective response tuned to ambiguous threat.
Using functional magnetic resonance imaging (fMRI) repetition suppression, we explored the selectivity of the human action
perception system (APS), which consists of temporal, parietal and frontal areas, for the appearance and/or motion of the perceived
agent. Participants watched body movements of a human (biological appearance and movement), a robot (mechanical appearance
and movement) or an android (biological appearance, mechanical movement). With the exception of extrastriate body area, which
showed more suppression for human like appearance, the APS was not selective for appearance or motion per se. Instead, distinctive responses were found to the mismatch between appearance and motion: whereas suppression effects for
the human and robot were similar to each other, they were stronger for the android, notably in bilateral anterior intraparietal
sulcus, a key node in the APS. These results could reflect increased prediction error as the brain negotiates an agent that
appears human, but does not move biologically, and help explain the ‘uncanny valley’ phenomenon.
Reduced amygdala activation in individuals with schizophrenia is thought to contribute to impairments in emotion recognition and social functioning. Recent work, however, suggests that amygdala abnormalities in schizophrenia are more nuanced than generalized hypoactivation and that modulation of amygdala responses across different stimulus types may be more closely related to social functioning than to overall levels of amygdala activation during a task. The authors investigated amygdala modulation during emotion recognition in patients by manipulating the gaze direction of threat-related expressions.
Blood-oxygen-level-dependent functional MRI was used to measure neural activation in 37 healthy volunteers and 35 schizophrenia patients while participants identified the emotion (anger or fear) displayed on facial stimuli that appeared with either direct or averted gaze.
Analysis of percent signal change in the amygdala bilaterally revealed a three-way interaction of emotion, gaze, and group, demonstrating significantly reduced amygdala responses to direct-gaze anger expressions in the patient group but comparable levels of activation across groups in all other conditions. Within the patient group, amygdala responses to direct-gaze anger expressions were positively correlated with level of functioning.
These findings extend previous reports of amygdala hypoactivation in schizophrenia by identifying abnormal amygdala modulation in response to varying emotional stimuli. Additionally, the strong relationship between amygdala activation and social and occupational functioning underscores the need for investigations of amygdala modulation in schizophrenia that further specify the nature of these impairments and that examine a potential causal link between amygdala activation and functioning.
A subcortical pathway through the superior colliculus and pulvinar to the amygdala is commonly assumed to mediate the non-conscious processing of affective visual stimuli. We review anatomical and physiological data that argue against the notion that such a pathway plays a prominent part in processing affective visual stimuli in humans. Instead, we propose that the primary role of the amygdala in visual processing, like that of the pulvinar, is to coordinate the function of cortical networks during evaluation of the biological significance of affective visual stimuli. Under this revised framework, the cortex has a more important role in emotion processing than is traditionally assumed.
Several recent studies have begun to examine the neurocognitive mechanisms involved in perceiving and responding to eye contact,
a salient social signal of interest and readiness for interaction. Laboratory experiments measuring observers' responses to
pictorial instead of live eye gaze cues may, however, only vaguely approximate the real-life affective significance of gaze
direction cues. To take this into account, we measured event-related brain potentials and subjective affective responses in
healthy adults while viewing live faces with a neutral expression through an electronic shutter and faces as pictures on a
computer screen. Direct gaze elicited greater face-sensitive N170 amplitudes and early posterior negativity potentials than
averted gaze or closed eyes, but only in the live condition. The results show that early-stage processing of facial information
is enhanced by another person's direct gaze when the person is faced live. We propose that seeing a live face with a direct
gaze is processed more intensely than a face with averted gaze or closed eyes, as the direct gaze is capable of intensifying
the feeling of being the target of the other's interest and intentions. These results may have implications for the use of
pictorial stimuli in the social cognition studies.
Emotion theory emphasizes the distinction between social vs non-social emotional-processing (E-P) although few functional neuroimaging studies have examined whether the neural systems
that mediate social vs non-social E-P are similar or distinct. The present fMRI study of script-driven imagery in 20 women demonstrates that social
E-P, independent of valence, more strongly recruits brain regions involved in social- and self-referential processing, specifically
the dorsomedial prefrontal cortex, posterior cingulate/precuneus, bilateral temporal poles, bilateral temporoparietal junction
and right amygdala. Functional response within brain regions involved in E-P was also significantly more pronounced during
negatively relative to positively valenced E-P. Finally, the effect for social E-P was increased for positive relative to
negative stimuli in many of these same regions. Future research directions for social and affective neuroscience are discussed.
Statistical thresholding (i.e. P-values) in fMRI research has become increasingly conservative over the past decade in an attempt to diminish Type I errors (i.e. false alarms) to a level traditionally allowed in behavioral science research. In this article, we examine the unintended negative consequences of this single-minded devotion to Type I errors: increased Type II errors (i.e. missing true effects), a bias toward studying large rather than small effects, a bias toward observing sensory and motor processes rather than complex cognitive and affective processes and deficient meta-analyses. Power analyses indicate that the reductions in acceptable P-values over time are producing dramatic increases in the Type II error rate. Moreover, the push for a mapwide false discovery rate (FDR) of 0.05 is based on the assumption that this is the FDR in most behavioral research; however, this is an inaccurate assessment of the conventions in actual behavioral research. We report simulations demonstrating that combined intensity and cluster size thresholds such as P < 0.005 with a 10 voxel extent produce a desirable balance between Types I and II error rates. This joint threshold produces high but acceptable Type II error rates and produces a FDR that is comparable to the effective FDR in typical behavioral science articles (while a 20 voxel extent threshold produces an actual FDR of 0.05 with relatively common imaging parameters). We recommend a greater focus on replication and meta-analysis rather than emphasizing single studies as the unit of analysis for establishing scientific truth. From this perspective, Type I errors are self-erasing because they will not replicate, thus allowing for more lenient thresholding to avoid Type II errors.
Haxby et al. (Haxby JV, Hoffman EA, Gobbini MI. 2000. The distributed human neural system for face perception. Trends Cogn Sci. 4:223-233.) proposed that eye gaze processing results from an interaction between a "core" face-specific system involved in visual analysis and an "extended" system involved in spatial attention, more generally. However, the full gaze perception network has remained poorly specified. In the context of a functional magnetic resonance imaging study, we used psychophysiological interactions (PPIs) to identify brain regions that showed differential connectivity (correlation) with core face perception structures (posterior superior temporal sulcus [pSTS] and fusiform gyrus [FG]) when viewing gaze shifts relative to control eye movements (opening/closing the eyes). The PPIs identified altered connectivity between the pSTS and MT/V5, intraparietal sulcus, frontal eye fields, superior temporal gyrus (STG), supramarginal gyrus, and middle frontal gyrus (MFG). The FG showed altered connectivity with the same areas of the STG and MFG, demonstrating the contribution of both dorsal and ventral core face areas to gaze perception. We propose that this network provides an interactive system that alerts us to seen changes in other agents' gaze direction, makes us aware of their altered focus of spatial attention, and prepares a corresponding shift in our own attention.
How the processing of emotional expression is influenced by perceived gaze remains a debated issue. Discrepancies between previous results may stem from differences in the nature of stimuli and task characteristics. Here we used a highly controlled set of computer-generated animated faces combining dynamic emotional expressions with varying intensity, and gaze shifts either directed at or averted from the observer. We predicted that perceived self-relevance of fearful faces would be higher with averted gaze-signaling a nearby danger; whereas conversely, direct gaze would be more relevant for angry faces-signaling aggressiveness. This interaction pattern was observed behaviorally for emotion intensity ratings, and neurally for functional magnetic resonance imaging activation in amygdala, as well as fusiform and medial prefrontal cortices, but only for mild- and not high-intensity expressions. These results support an involvement of human amygdala in the appraisal of self-relevance and reveal a crucial role of expression intensity in emotion and gaze interactions.
The ability and motivation to share attention is a unique aspect of human cognition. Despite its significance, the neural basis remains elusive. To investigate the neural correlates of joint attention, we developed a novel, interactive research paradigm in which participants' gaze behavior--as measured by an eye tracking device--was used to contingently control the gaze of a computer-animated character. Instructed that the character on screen was controlled by a real person outside the scanner, 21 participants interacted with the virtual other while undergoing fMRI. Experimental variations focused on leading versus following the gaze of the character when fixating one of three objects also shown on the screen. In concordance with our hypotheses, results demonstrate, firstly, that following someone else's gaze to engage in joint attention resulted in activation of anterior portion of medial prefrontal cortex (MPFC) known to be involved in the supramodal coordination of perceptual and cognitive processes. Secondly, directing someone else's gaze toward an object activated the ventral striatum which--in light of ratings obtained from participants--appears to underlie the hedonic aspects of sharing attention. The data, therefore, support the idea that other-initiated joint attention relies upon recruitment of MPFC previously related to the "meeting of minds." In contrast, self-initiated joint attention leads to a differential increase of neural activity in reward-related brain areas, which might contribute to the uniquely human motivation to engage in the sharing of experiences.
This meta-analysis of 172 studies (N = 2,263 anxious, N = 1,768 nonanxious) examined the boundary conditions of threat-related attentional biases in anxiety. Overall, the results show that the bias is reliably demonstrated with different experimental paradigms and under a variety of experimental conditions, but that it is only an effect size of d = 0.45. Although processes requiring conscious perception of threat contribute to the bias, a significant bias is also observed with stimuli outside awareness. The bias is of
comparable magnitude across different types of anxious populations (individuals with different clinical disorders, high-anxious nonclinical individuals, anxious children and adults) and is not observed in nonanxious individuals. Empirical and clinical implications as well as future directions for research are discussed.
The interpretation of interpersonal gaze behavior requires the use of complex cognitive processes and guides social interactions. Among a variety of different gaze characteristics, gaze direction and gaze duration modulate crucially the meaning of the "social gaze". Nevertheless, prior neuroimaging studies disregarded the relevance of gaze duration by focusing on gaze direction only. The present functional magnetic resonance imaging (fMRI) study focused on the differentiation of these two gaze parameters. Therefore direct gaze displayed by virtual characters was contrasted with averted gaze and, additionally, systematically varied with respect to gaze duration (i.e., 1, 2.5 or 4 s). Consistent with prior findings, behavioral data showed that likeability was higher for direct than for averted gaze and increased linearly with increasing direct gaze duration. On the neural level, distinct brain regions were associated with the processing of gaze direction and gaze duration: (i) the comparison between direct and averted gaze revealed activations in bilateral occipito-temporal regions including the posterior superior temporal sulcus (pSTS); (ii) whereas increasing duration of direct gaze evoked differential neural responses in the medial prefrontal cortex (MPFC) including orbitofrontal and paracingulate regions. The results suggest two complementary cognitive processes related to different gaze parameters. On the one hand, the recruitment of multimodal sensory regions in the pSTS indicates detection of gaze direction via complex visual analysis. On the other hand, the involvement of the MPFC associated with outcome monitoring and mentalizing indicates higher-order social cognitive processes related to evaluation of the ongoing communicational input conveyed by direct gaze duration.
When subjects are required to reason about someone's false belief, a consistent pattern of brain regions are recruited including
the medial prefrontal cortex, medial precuneus and bilateral temporo-parietal junction. Previous group analyses suggest that
the two medial regions, but not the lateral regions, are also recruited when subjects engage in self-reflection. The current
study directly compared the results of the ‘false belief’ and ‘self’ tasks in individual subjects. Consistent with previous
reports, the medial prefrontal and medial precuneus regions recruited by the two tasks significantly overlap in individual
subjects, although there was also evidence for non-overlapping voxels in medial regions. The temporo-parietal regions are
only recruited for the ‘theory of mind’ task. Six possible models of the relationship between theory of mind, self-reflection
and autobiographical memory, all consistent with both neurobiological and developmental evidence to date, are discussed.
This article summarizes recent evidence indicating that individuals suffering from autism have a specific problem in understanding intentions and beliefs. We propose that this problem arises because they are incapable of forming a special kind of mental representation. A single cognitive deficit defines what is common to all autistic individuals. In contrast there is a wide range of proposals for the biological origins of the disorder.
Some investigators have argued that emotions, especially animal emotions, are illusory concepts outside the realm of scientific inquiry. With advances in neurobiology and neuroscience, however, researchers are proving this position wrong while moving closer to understanding the biology and psychology of emotion. In Affective Neuroscience, Jaak Panksepp argues that emotional systems in humans, as well as other animals, are necessarily combinations of innate and learned tendencies; there are no routine and credible ways to really separate the influences of nature and nurture in the control of behavior. The book shows how to move toward a new understanding by taking a psychobiological approach to the subject, examining how the neurobiology and neurochemistry of the mammalian brain shape the psychological experience of emotion. It includes chapters on sleep and arousal, pleasure and pain systems, the sources of rage and anger, and the neural control of sexuality. The book will appeal to researchers and professors in the field of emotion.
Objective
Although deficits in memory and cognitive processing are evident in post-traumatic stress disorder (PTSD), difficulties with social cognition and the impact of such difficulties on interpersonal functioning are poorly understood. Here, we examined the ability of women diagnosed with PTSD related to childhood abuse to discriminate affective prosody, a central component of social cognition.Method
Women with PTSD and healthy controls (HCs) completed two computer-based tasks assessing affective prosody: (i) recognition (categorizing foreign-language excerpts as angry, fearful, sad, or happy) and (ii) discrimination (identifying whether two excerpts played consecutively had the ‘same’ or ‘different’ emotion). The association of performance with symptom presentation, trauma history, and interpersonal functioning was also explored.ResultsWomen with PTSD were slower than HCs at identifying happiness, sadness, and fear, but not anger in the speech excerpts. The presence of dissociative symptoms was related to reduced accuracy on the discrimination task. An increased severity of childhood trauma was associated with reduced accuracy on the discrimination task and with slower identification of emotional prosody.Conclusion
Exposure to childhood trauma is associated with long-term, atypical development in the interpretation of prosodic cues in speech. The findings have implications for the intergenerational transmission of trauma.
This chapter discusses recent studies of the noradrenergic locus coeruleus (LC) system to consider its possible roles in emotion. It describes the recent studies of the effects of manipulating LC neurons on electroencephalographic (EEG) activity and attentional behavior. Emotional responses are typically measured by EEG or autonomic arousal. Emotionally arousing stimuli produce activation of the cortical EEG, and parallel activation of autonomic measures such as blood pressure, heart rate, or galvanic skin response (as commonly used in lie detector tests). Recent results link the LC both to the EEG and autonomic responses that accompany emotionally arousing events LC neuronal projections, effects of NE on LC target cells, and discharge characteristics of LC neurons in unanesthetized, unconditioned animals are reviewed. More recent studies on the effects of stress on LC neurons, and on activity of LC neurons in behaving monkeys during a conditioned attentional task are also examined. The chapter reviews new findings on afferents to the LC that indicate the status of this key noradrenergic system in brain circuitry. Although the LC is not typically considered in the context of emotion, the analysis suggests that the LC system could play an important role in the process of emotional activation.
The parahippocampal cortex (PHC) has been associated with many cognitive processes, including visuospatial processing and episodic memory. To characterize the role of PHC in cognition, a framework is required that unifies these disparate processes. An overarching account was proposed whereby the PHC is part of a network of brain regions that processes contextual associations. Contextual associations are the principal element underlying many higher-level cognitive processes, and thus are suitable for unifying the PHC literature. Recent findings are reviewed that provide support for the contextual associations account of PHC function. In addition to reconciling a vast breadth of literature, the synthesis presented expands the implications of the proposed account and gives rise to new and general questions about context and cognition.
The arrival of a book for review usually gives rise to pleasant anticipation, and whatever criticisms have to be made, it is that almost always possible to find some pleasant things to say. But finding praise for this tome is a problem — it is a volume too far. It is to be hoped that the authors
The clinical and psychopharmacological profile of panic disorder in human patients shows a remarkable similarity to the defensive behavioral response evoked in experimental animals by activation of neurons in the dorsal part of the midbrain periaqueductal gray matter (PAG). Studies of the neural circuitry within the PAG indicate that a subpopulation of GABAergic neurons in the dorsolateral sector may act as an amplifying stage that potentiates inhibitory serotonergic input to the "defense area" within the PAG. These neurons may function as a gain-control system that sets the level of excitability of efferent output neurons, which mediate the autonomic and somatomotor components of panic behavior. Dysfunctional activity within the dorsolateral PAG leading to a destabilization of this control system may be a factor underlying panic behavior and predisposes to the development of panic disorder in susceptible persons. NEUROSCIENTIST 6:48-59, 2000
Objective
Key questions remain unaddressed concerning the nature of interpersonal functioning in trauma survivors, including the ability to understand and interpret other people's thoughts and feelings. Here, we investigate theory of mind (ToM) performance of women with PTSD related to childhood abuse in comparison to healthy controls. Method
Participants completed two ToM tasks, the Interpersonal Perception Task-15 (IPT-15) and the Reading the Mind in the Eyes Task - Revised (RMET). ResultsRelative to controls, women with a history of childhood trauma had difficulty recognizing familial relationships depicted in the IPT-15 (P=0.005). No other category of the IPT-15 showed significant group differences. In addition, while healthy women displayed faster RMET reaction times to emotionally valenced mental states (positive: P=0.003; negative: P=0.016) compared with neutral mental states, the PTSD group showed similar reaction times across all valences. The presence of dissociative symptoms (e.g., disengagement, amnesia, identity dissociation) was strongly associated with hindered accuracy of complex mental state identification and altered perception of kinship interactions. Conclusion
Women with PTSD stemming from childhood trauma show changes in ToM abilities particularly those often involved in the interpretation of family interactions. In addition, individuals with PTSD showed slower reaction times during the recognition of complex mental states from emotionally salient facial/eye expressions in comparison with healthy subjects.
I have argued in other work that emotion, attentional functions, and executive functions are three interpenetrant global state variables, essentially differential slices of the consciousness pie. This paper will outline the columnar architecture and connectivities of the PAG (periaqueductal gray), its role in organizing prototype states of emotion, and the re-entry of PAG with the extended reticular thalamic activating system (“ERTAS). At the end we will outline some potential implications of these connectivities for possible functional correlates of PAG networks that are just starting to be mapped. Overall, we will look at many lines of evidence that PAG should be conceptualized as a peri-reticular structure that has a foundational role in emotion, in generating the meaningful organization of behavior by the brain through prototype emotional states, and in allowing the various emotional systems to globally influence and tune both the forebrain and brainstem. Finally, we address implications of these concepts for what is currently understood about consciousness, underlining the need for somewhat more humility within consciousness studies about our current level of understanding of consciousness in the brain, combined with a deeper appreciation of the intrinsic connections between emotion and consciousness. One hopes that more concerted empirical interest in structures underneath the thalamus, combined with a deeper appreciation for the fundamental role that organismic and social value must have in bootstrapping awareness in the developing brain, would begin more widely to influence the fundamental lines of neuroscientific research in both emotion studies and consciousness studies.
[discuss] human emotional neurophysiology / postulate on the existence of an emotional system consisting of an orienting complex, event integration, and response selection / a cortico-limbic-brainstem network is described as the neural instantiation of these processes (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Several interviews are available for assessing PTSD. These interviews vary in merit when compared on stringent psychometric and utility standards. Of all the interviews, the Clinician-Administered PTSD Scale (CAPS-1) appears to satisfy these standards most uniformly. The CAPS-1 is a structured interview for assessing core and associated symptoms of PTSD. It assesses the frequency and intensity of each symptom using standard prompt questions and explicit, behaviorally-anchored rating scales. The CAPS-1 yields both continuous and dichotomous scores for current and lifetime PTSD symptoms. Intended for use by experienced clinicians, it also can be administered by appropriately trained paraprofessionals. Data from a large scale psychometric study of the CAPS-1 have provided impressive evidence of its reliability and validity as a PTSD interview.
This study examined activation to facial expressions in youth with a history of interpersonal trauma and current posttraumatic stress symptoms (PTSS) compared to healthy controls (HC).
Twenty-three medication-naive youth with PTSS and 23 age- and gender-matched HC underwent functional magnetic resonance imaging (fMRI) while viewing fearful, angry, sad, happy, and neutral faces. Data were analyzed for group differences in location of activation, as well as timing of activation during the early versus late phase of the block. Using SPM5, significant activation (P < .05 FWE [Family-Wise Error] corrected, extent = 10 voxels) associated with the main effect of group was identified. Activation from selected clusters was extracted to SPSS software for further analysis of specific facial expressions and temporal patterns of activation.
The PTSS group showed significantly greater activation than controls in several regions, including the amygdala/hippocampus, medial prefrontal cortex, insula, and ventrolateral prefrontal cortex, and less activation than controls in the dorsolateral prefrontal cortex (DLPFC). These group differences in activation were greatest during angry, happy, and neutral faces, and predominantly during the early phase of the block. Post hoc analyses showed significant Group × Phase interactions in the right amygdala and left hippocampus.
Traumatic stress may impact development of brain regions important for emotion processing. Timing of activation may be altered in youth with PTSS.