Acquired self‐control of insula cortex modulates emotion recognition and brain network connectivity in schizophrenia

Real‐time functional magnetic resonance imaging (rtfMRI) is a novel technique that has allowed subjects to achieve self‐regulation of circumscribed brain regions. Despite its anticipated therapeutic benefits, there is no report on successful application of this technique in psychiatric populations. The objectives of the present study were to train schizophrenia patients to achieve volitional control of bilateral anterior insula cortex on multiple days, and to explore the effect of learned self‐regulation on face emotion recognition (an extensively studied deficit in schizophrenia) and on brain network connectivity. Nine patients with schizophrenia were trained to regulate the hemodynamic response in bilateral anterior insula with contingent rtfMRI neurofeedback, through a 2‐weeks training. At the end of the training stage, patients performed a face emotion recognition task to explore behavioral effects of learned self‐regulation. A learning effect in self‐regulation was found for bilateral anterior insula, which persisted through the training. Following successful self‐regulation, patients recognized disgust faces more accurately and happy faces less accurately. Improvements in disgust recognition were correlated with levels of self‐activation of right insula. RtfMRI training led to an increase in the number of the incoming and outgoing effective connections of the anterior insula. This study shows for the first time that patients with schizophrenia can learn volitional brain regulation by rtfMRI feedback training leading to changes in the perception of emotions and modulations of the brain network connectivity. These findings open the door for further studies of rtfMRI in severely ill psychiatric populations, and possible therapeutic applications. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Neural correlates of treatment response in depressed bipolar adolescents during emotion processing

Depressive mood in adolescents with bipolar disorder (BDd) is associated with significant morbidity and mortality, but we have limited information about neural correlates of depression and treatment response in BDd. Ten adolescents with BDd (8 females, mean age = 15.6?±?0.9) completed two (fearful and happy) face gender labeling fMRI experiments at baseline and after 6-weeks of open treatment. Whole-brain analysis was used at baseline to compare their neural activity with those of 10 age and sex-matched healthy controls (HC). For comparisons of the neural activity at baseline and after treatment of youth with BDd, region of interest analysis for dorsal/ventral prefrontal, anterior cingulate, and amygdala activity, and significant regions identified by wholebrain analysis between BDd and HC were analyzed. There was significant improvement in depression scores (mean percentage change on the Child Depression Rating Scale-Revised 57 %?±?28). Neural activity after treatment was decreased in left occipital cortex in the intense fearful experiment, but increased in left insula, left cerebellum, and right ventrolateral prefrontal cortex in the intense happy experiment. Greater improvement in depression was associated with baseline higher activity in ventral ACC to mild happy faces. Study sample size was relatively small for subgroup analysis and consisted of mainly female adolescents that were predominantly on psychotropic medications during scanning. Our results of reduced negative emotion processing versus increased positive emotion processing after treatment of depression (improvement of cognitive bias to negative and away from positive) are consistent with the improvement of depression according to Beck’s cognitive theory.     

Neural long-term effects of emotion regulation on episodic memory processes

Emotions can enhance memory which is on the one hand advantageous, but on the other hand may be detrimental in the long term, for example in the case of traumatic events. Although cognitive emotion regulation may reduce emotion experience and corresponding neural activation, at present little is known about its influence on long-term memory. We investigated memory for emotional pictures in healthy female subjects 1 year after voluntary emotion regulation using fMRI. Whereas memory performance was not affected by regulation, our data revealed a dissociation of brain regions involved in memory encoding and recognition depending on whether emotional engagement during encoding had been downregulated. Emotional engagement during encoding resulted in a long-term subsequent memory effect in mesolimbic brain regions and hippocampus, and in recognition-related activation in the amygdala. In contrast, when negative emotions had been downregulated during encoding memory performance was predicted by prefrontal activation. Our data suggest that memory for emotionally encoded stimuli is supported by emotional re-activation, whereas memory for successfully encoded items during emotion regulation is rather supported by recognition of features and cognitive contents. These results contribute to research on long-term effects of emotion regulation in everyday life and open new avenues to understand and possibly influence traumatic memory traces.     

Individual differences in alexithymia and brain response to masked emotion faces

Alexithymia is considered a dimensional personality trait that refers to a cluster of deficits in the recognition, differentiation, and verbalization of emotions. Research on the neurobiology of alexithymia has focused hitherto on impairments in the controlled processing of emotional information. In the present study automatic brain reactivity to facial emotion was investigated as a function of alexithymia (as assessed by the 20-Item Toronto Alexithymia Scale - TAS-20). During 3 T fMRI scanning, pictures of sad, happy, and neutral facial expression masked by neutral faces were presented to 33 healthy women. A priori regions of interest in the whole brain analysis were cerebral structures that are known to be crucially involved in the emotion perception from the face. Independently from trait anxiety and depression TAS-20 alexithymia was negatively correlated with activation to masked sad and happy faces in several regions of interest (in particular, insula, superior temporal gyrus, middle occipital and parahippocampal gyrus). In addition, the TAS-20 score was negatively correlated with response of the left amygdala to masked sad faces. A reduced automatic reactivity of the amygdala and visual occipito-temporal areas could implicate less automated engagement in the encoding of emotional stimuli in high alexithymia. In addition, a low spontaneous insular and amygdalar responsivity in high alexithymia individuals could be related to an attenuation of basic emotional experiences which may contribute to problems in identifying and differentiating one's feelings.     

Visual self-recognition in patients with schizophrenia

Self-processing is associated with distinct patterns of behavior and neural activity in healthy individuals. Self-monitoring deficits have been reported in schizophrenia in auditory and tactile modalities but it is unknown whether they generalize to all sensory domains. We investigated self-face recognition in patients with schizophrenia, using a visual search paradigm with three types of targets: objects, famous faces and self-faces. Schizophrenic patients showed increased reaction time (RT) for detecting targets overall compared to normal controls but they showed faster RT for self-face compared with the Famous-face condition. For healthy controls, there was no difference between Self- and Famous-face conditions. Thus, visual search for self-face is more efficient than for famous faces and self-face recognition is spared in schizophrenia. These findings suggest that impaired self-processing in schizophrenia may be task-dependent rather than ubiquitous.     

Recapitulating emotional context: activity of amygdala, hippocampus and fusiform cortex during recollection and familiarity

The amygdala is thought to enhance long-term memory for emotionally arousing events by modulating memory formation and storage in the hippocampus and in neocortical areas. Recent animal studies have raised the possibility that cooperativity between amygdala and hippocampus contributes to the retrieval of fear memories. The functional contributions of the amygdala to the retrieval of emotional memories in humans are less well known. Here, in a functional magnetic resonance imaging experiment, 20 healthy subjects studied neutral words in the context of a fearful or a neutral human face. In a subsequent test, they made 'remember' (conscious recollection of the study context), 'know' (familiarity in the absence of conscious recollection) and 'new' judgements on the studied and newly presented neutral words, in the absence of face stimuli. At test, bilateral amygdala, hippocampus and fusiform face area (FFA) were more strongly activated during recollection than during familiarity. Higher activity for fearful than for neutral study context was found in bilateral FFA during recollection but not during familiarity. This difference recapitulated higher activity for fearful than for neutral context in the FFA during study. These data suggest that the amygdalae and hippocampi contribute to the retrieval of emotion-laden context memories by coordinating the reactivation of stored representations in neocortical areas, such as the FFA. However, there also was a recapitulation of emotional study context in the right amygdala during familiarity only, which might therefore be related to affective implicit memory.     

Amygdala activation during recognition of emotions in a foreign ethnic group is associated with duration of stay

Abstract

Cultural differences in emotion recognition performance have frequently been reported, whereby duration of stay in a foreign culture seems to be a crucial factor. Furthermore, cultural aspects influence the neural correlates of face and emotion processing thereby also affecting the response of the amygdala. Here, the exposure to a foreign culture and its influence on the cerebral correlates of facial emotion recognition were examined in 24 Asian and 24 age-matched European males. Subjects performed an explicit emotion recognition task and were imaged with a 3 T MR-scanner. Results demonstrate a significant cultural influence on the specific recognition of disgust and anger, with higher accuracy among the Europeans, while the functional data indicate generally elevated amygdala activation in Asians compared to Europeans. Moreover, a significant inverse correlation between duration of stay and amygdala response emerged, with stronger activation in those subjects with shorter duration of stay in Europe. The observed amygdala hyperactivation in Asians may reflect novelty aspects but might also be associated with greater effort and motivation in immigrants, thus it possibly reflects one neural correlate of the “alien-effect”. We conclude that exposure to a foreign culture and duration of stay affect the behavioral and neural response to facial expressions of emotions.     

Evidence for the triadic model of adolescent brain development: Cognitive load and task-relevance of emotion differentially affect adolescents and adults

In adults, cognitive control is supported by several brain regions including the limbic system and the dorsolateral prefrontal cortex (dlPFC) when processing emotional information. However, in adolescents, some theories hypothesize a neurobiological imbalance proposing heightened sensitivity to affective material in the amygdala and striatum within a cognitive control context. Yet, direct neurobiological evidence is scarce. Twenty-four adolescents (12–16) and 28 adults (25–35) completed an emotional n-back working memory task in response to happy, angry, and neutral faces during fMRI. Importantly, participants either paid attention to the emotion (task-relevant condition) or judged the gender (task-irrelevant condition). Behaviorally, for both groups, when happy faces were task-relevant, performance improved relative to when they were task-irrelevant, while performance decrements were seen for angry faces. In the dlPFC, angry faces elicited more activation in adults during low relative to high cognitive load (2-back vs. 0-back). By contrast, happy faces elicited more activation in the amygdala in adolescents when they were task-relevant. Happy faces also generally increased nucleus accumbens activity (regardless of relevance) in adolescents relative to adults. Together, the findings are consistent with neurobiological models of adolescent brain development and identify neurodevelopmental differences in cognitive control emotion interactions.     

Amygdala reactivity to sad faces in preschool children: An early neural marker of persistent negative affect

BackgroundElevated negative affect is a highly salient risk factor for later internalizing disorders. Very little is known about the early neurobiological correlates of negative affect and whether they associate with developmental changes in negative emotion. Such information may prove critical for identifying children deviating from normative developmental trajectories of negative affect and at increased risk for later internalizing disorders. The current study examined the relationship between amygdala activity and negative affect measured concurrently and approximately 12 months later in preschool-age children.MethodAmygdala activity was assessed using functional magnetic resonance imaging in 31 medication-naive preschool age children. Negative affect was measured using parent report both at the time of scan and 12 months later.ResultsNegative affect at baseline was positively correlated with right amygdala activity to sad faces, right amygdala activity to happy faces, and left amygdala activity to happy faces. Right amygdala activity to sad faces also positively predicted parent-reported negative affect 12 months later even when negative affect reported at baseline was controlled.ConclusionsThe current findings provide preliminary evidence for amygdala activity as a potential biomarker of persistent negative affect during early childhood and suggest future work examining the origins and long-term implications of this relationship is necessary.     

The voice of emotion: an FMRI study of neural responses to angry and happy vocal expressions

The human voice is one of the principal conveyers of socialand affective communication. Yet relatively little is knownabout the neural circuitry that supports the recognition ofdifferent vocally expressed emotions. We conducted an FMRI studyto examine the brain responses to vocal expressions of angerand happiness, and to test whether specific brain regions showedpreferential engagement in the processing of one emotion overthe other. We also tested the extent to which simultaneouslypresented facial expressions of the same or different emotionswould enhance brain responses, and to what degree such responsesdepend on attention towards the vocal expression. Forty healthyindividuals were scanned while listening to vocal expressionsof anger or happiness, while at the same time watching congruentor discrepant facial expressions. Happy voices elicited significantlymore activation than angry voices in right anterior and posteriormiddle temporal gyrus (MTG), left posterior MTG and right inferiorfrontal gyrus. Furthermore, for the left MTG region, happy voiceswere related to higher activation only when paired with happyfaces. Activation in the left insula, left amygdala and hippocampus,and rostral anterior cingulate cortex showed an effect of selectivelyattending to the vocal stimuli. Our results identify a networkof regions implicated in the processing of vocal emotion, andsuggest a particularly salient role for vocal expressions ofhappiness.     

The influence of personality on neural mechanisms of observational fear and reward learning

Fear and reward learning can occur through direct experience or observation. Both channels can enhance survival or create maladaptive behavior. We used fMRI to isolate neural mechanisms of observational fear and reward learning and investigate whether neural response varied according to individual differences in neuroticism and extraversion. Participants learned object-emotion associations by observing a woman respond with fearful (or neutral) and happy (or neutral) facial expressions to novel objects. The amygdala-hippocampal complex was active when learning the object-fear association, and the hippocampus was active when learning the object-happy association. After learning, objects were presented alone; amygdala activity was greater for the fear (vs. neutral) and happy (vs. neutral) associated object. Importantly, greater amygdala-hippocampal activity during fear (vs. neutral) learning predicted better recognition of learned objects on a subsequent memory test. Furthermore, personality modulated neural mechanisms of learning. Neuroticism positively correlated with neural activity in the amygdala and hippocampus during fear (vs. neutral) learning. Low extraversion/high introversion was related to faster behavioral predictions of the fearful and neutral expressions during fear learning. In addition, low extraversion/high introversion was related to greater amygdala activity during happy (vs. neutral) learning, happy (vs. neutral) object recognition, and faster reaction times for predicting happy and neutral expressions during reward learning. These findings suggest that neuroticism is associated with an increased sensitivity in the neural mechanism for fear learning which leads to enhanced encoding of fear associations, and that low extraversion/high introversion is related to enhanced conditionability for both fear and reward learning.     

Functional activation of the left amygdala and hippocampus during associative encoding

The human hippocampus is critical to episodic encoding, but the role of the amygdala in memory is less clear. Animal research suggests a role for the amygdala in associative memory, but this has not been examined systematically in humans. Using fMRI, we compared amygdala and hippocampus activation for seven healthy subjects during two visual encoding tasks: serially presented single faces and faces presented as pairs. Single faces activated bilateral hippocampi, but not the amygdala. Paired faces activated bilateral amygdala, but only the left hippocampus. Subtraction of the two conditions revealed greater activation within the left amygdala and hippocampus during paired face encoding, suggesting that associative encoding activates a left-lateralized limbic network including the hippocampus and amygdala.     

The neurobiology of emotion regulation in posttraumatic stress disorder: Amygdala downregulation via real‐time fMRI neurofeedback

Amygdala dysregulation has been shown to be central to the pathophysiology of posttraumatic stress disorder (PTSD) representing a critical treatment target. Here, amygdala downregulation was targeted using real‐time fMRI neurofeedback (rt‐fMRI‐nf) in patients with PTSD, allowing us to examine further the regulation of emotional states during symptom provocation. Patients (n = 10) completed three sessions of rt‐fMRI‐nf with the instruction to downregulate activation in the amygdala, while viewing personalized trauma words. Amygdala downregulation was assessed by contrasting (a) regulate trials, with (b) viewing trauma words and not attempting to regulate. Training was followed by one transfer run not involving neurofeedback. Generalized psychophysiological interaction (gPPI) and dynamic causal modeling (DCM) analyses were also computed to explore task‐based functional connectivity and causal structure, respectively. It was found that PTSD patients were able to successfully downregulate both right and left amygdala activation, showing sustained effects within the transfer run. Increased activation in the dorsolateral and ventrolateral prefrontal cortex (PFC), regions related to emotion regulation, was observed during regulate as compared with view conditions. Importantly, activation in the PFC, rostral anterior cingulate cortex, and the insula, were negatively correlated to PTSD dissociative symptoms in the transfer run. Increased functional connectivity between the amygdala‐ and both the dorsolateral and dorsomedial PFC was found during regulate, as compared with view conditions during neurofeedback training. Finally, our DCM analysis exploring directional structure suggested that amygdala downregulation involves both top‐down and bottom‐up information flow with regard to observed PFC‐amygdala connectivity. This is the first demonstration of successful downregulation of the amygdala using rt‐fMRI‐nf in PTSD, which was critically sustained in a subsequent transfer run without neurofeedback, and corresponded to increased connectivity with prefrontal regions involved in emotion regulation during the intervention. Hum Brain Mapp 38:541–560, 2017. © 2016 Wiley Periodicals, Inc.     

Amygdalar activation associated with happy facial expressions in adolescents: a 3-T functional MRI study

OBJECTIVE: To study the possible role of the amygdala in the recognition of happy and sad facial expressions in adolescents aged 13 to 17 years. METHOD: Twelve healthy adolescents (6 females and 6 males) underwent noninvasive 3-Tesla functional magnetic resonance imaging while viewing pictures of happy, sad, and neutral facial expressions. RESULTS: Happy faces produced significant bilateral amygdalar activation when compared with neutral faces (p <.05, corrected). Sad faces relative to neutral did not produce significant amygdalar activation. CONCLUSIONS: These results extend the role of the amygdala in adolescents to include the recognition of happy facial expressions. They demonstrate the feasibility of using happy facial expressions to noninvasively study amygdalar function in adolescents and establish a baseline against which the amygdalar response to emotional stimuli in several psychiatric conditions may be compared.     

Amygdala activity and prefrontal cortex-amygdala effective connectivity to emerging emotional faces distinguish remitted and depressed mood states in bipolar disorder

Perlman SB, Almeida JRC, Kronhaus DM, Versace A, LaBarbara EJ, Klein CR, Phillips ML. Amygdala activity and prefrontal cortex–amygdala effective connectivity to emerging emotional faces distinguish remitted and depressed mood states in bipolar disorder. Bipolar Disord 2012: 14: 162–174. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: Few studies have employed effective connectivity (EC) to examine the functional integrity of neural circuitry supporting abnormal emotion processing in bipolar disorder (BD), a key feature of the illness. We used Granger Causality Mapping (GCM) to map EC between the prefrontal cortex (PFC) and bilateral amygdala and a novel paradigm to assess emotion processing in adults with BD. Methods: Thirty‐one remitted adults with BD [(remitted BD), mean age = 32 years], 21 adults with BD in a depressed episode [(depressed BD), mean age = 33 years], and 25 healthy control participants [(HC), mean age = 31 years] performed a block‐design emotion processing task requiring color‐labeling of a color flash superimposed on a task‐irrelevant face morphing from neutral to emotional (happy, sad, angry, or fearful). GCM measured EC preceding (top‐down) and following (bottom‐up) activity between the PFC and the left and right amygdalae. Results: Our findings indicated patterns of abnormally elevated bilateral amygdala activity in response to emerging fearful, sad, and angry facial expressions in remitted‐BD subjects versus HC, and abnormally elevated right amygdala activity to emerging fearful faces in depressed‐BD subjects versus HC. We also showed distinguishable patterns of abnormal EC between the amygdala and dorsomedial and ventrolateral PFC, especially to emerging happy and sad facial expressions in remitted‐BD and depressed‐BD subjects. Discussion: EC measures of neural system level functioning can further understanding of neural mechanisms associated with abnormal emotion processing and regulation in BD. Our findings suggest major differences in recruitment of amygdala–PFC circuitry, supporting implicit emotion processing between remitted‐BD and depressed‐BD subjects, which may underlie changes from remission to depression in BD.     

Differential amygdala response during facial recognition in patients with schizophrenia: an fMRI study

Human lesion or neuroimaging studies suggest that amygdala is involved in facial emotion recognition. Although impairments in recognition of facial and/or emotional expression have been reported in schizophrenia, there are few neuroimaging studies that have examined differential brain activation during facial recognition between patients with schizophrenia and normal controls. To investigate amygdala responses during facial recognition in schizophrenia, we conducted a functional magnetic resonance imaging (fMRI) study with 12 right-handed medicated patients with schizophrenia and 12 age- and sex-matched healthy controls. The experiment task was a type of emotional intensity judgment task. During the task period, subjects were asked to view happy (or angry/disgusting/sad) and neutral faces simultaneously presented every 3 s and to judge which face was more emotional (positive or negative face discrimination). Imaging data were investigated in voxel-by-voxel basis for single-group analysis and for between-group analysis according to the random effect model using Statistical Parametric Mapping (SPM). No significant difference in task accuracy was found between the schizophrenic and control groups. Positive face discrimination activated the bilateral amygdalae of both controls and schizophrenics, with more prominent activation of the right amygdala shown in the schizophrenic group. Negative face discrimination activated the bilateral amygdalae in the schizophrenic group whereas the right amygdala alone in the control group, although no significant group difference was found. Exaggerated amygdala activation during emotional intensity judgment found in the schizophrenic patients may reflect impaired gating of sensory input containing emotion.     

Self‐regulation of ventromedial prefrontal cortex activation using real‐time fMRI neurofeedback—Influence of default mode network

The ventromedial prefrontal cortex (vmPFC) is involved in regulation of negative emotion and decision‐making, emotional and behavioral control, and active resilient coping. This pilot study examined the feasibility of training healthy subjects (n = 27) to self‐regulate the vmPFC activity using a real‐time functional magnetic resonance imaging neurofeedback (rtfMRI‐nf). Participants in the experimental group (EG, n = 18) were provided with an ongoing vmPFC hemodynamic activity (rtfMRI‐nf signal represented as variable‐height bar). Individuals were instructed to raise the bar by self‐relevant value‐based thinking. Participants in the control group (CG, n = 9) performed the same task; however, they were provided with computer‐generated sham neurofeedback signal. Results demonstrate that (a) both the CG and the EG show a higher vmPFC fMRI signal at the baseline than during neurofeedback training; (b) no significant positive training effect was seen in the vmPFC across neurofeedback runs; however, the medial prefrontal cortex, middle temporal gyri, inferior frontal gyri, and precuneus showed significant decreasing trends across the training runs only for the EG; (c) the vmPFC rtfMRI‐nf signal associated with the fMRI signal across the default mode network (DMN). These findings suggest that it may be difficult to modulate a single DMN region without affecting other DMN regions. Observed decreased vmPFC activity during the neurofeedback task could be due to interference from the fMRI signal within other DMN network regions, as well as interaction with task‐positive networks. Even though participants in the EG did not show significant positive increase in the vmPFC activity among neurofeedback runs, they were able to learn to accommodate the demand of self‐regulation task to maintain the vmPFC activity with the help of a neurofeedback signal.     

Social anxiety predicts amygdala activation in adolescents viewing fearful faces

The amygdala is critically involved in the processing of anxiety in adults, but little is known about the neurogenesis of trait-anxiety during adolescence. We correlated amygdala activity during visual presentations of fearful and happy faces with scores on the Multidimensional Anxiety Scale for Children in 16 adolescents undergoing functional magnetic resonance imaging. During fear perception, amygdala activity positively correlated with several social dimensions of anxiety, including peer rejection, humiliation, performing in public, and being separated from loved ones, but was not correlated with most measured nonsocial dimensions of anxiety. Amygdala responses during happy face presentations correlated positively only with tension/restlessness. During adolescence, amygdala activity appears to be more strongly related to social/interpersonal than nonsocial dimensions of anxiety.     

Magical ideation associated social cognition in adolescents: signs of a negative facial affect recognition deficit

BackgroundStudies provide evidence for impaired social cognition in schizotypy and its association with negative symptoms. Cognitive features related to magical ideation – a component of the positive dimension of schizotypy – have been less investigated. We aimed to assess social cognitive functioning among adolescents with high magical ideation scores, mainly focusing on face and emotion recognition.Methods22 subjects with magical ideation scale scores above the cut off level and 22 controls with lowest scores from among 250 students screened with this scale were included in the study. A face and emotion recognition n-back test, the empathy quotient, theory of mind tests and the Physical Anhedonia Scale were applied to both magical ideation and control groups.ResultsThe magical ideation group performed significantly worse than controls on both face and emotion recognition tests. Emotion recognition performance was found to be affected by memory load, with sadness, among emotions, revealing a difference between the two groups. Empathy and theory of mind tests did not distinguish the magical ideation group from controls.ConclusionOur findings provide evidence for a deficit in negative emotion recognition affected by memory load associated with magical ideation in adolescents.     

Amygdala Habituation and Prefrontal Functional Connectivity in Youth With Autism Spectrum Disorders

ObjectiveAmygdala habituation, the rapid decrease in amygdala responsiveness to the repeated presentation of stimuli, is fundamental to the nervous system. Habituation is important for maintaining adaptive levels of arousal to predictable social stimuli and decreased habituation is associated with heightened anxiety. Input from the ventromedial prefrontal cortex (vmPFC) regulates amygdala activity. Although previous research has shown abnormal amygdala function in youth with autism spectrum disorders (ASD), no study has examined amygdala habituation in a young sample or whether habituation is related to amygdala connectivity with the vmPFC.MethodData were analyzed from 32 children and adolescents with ASD and 56 typically developing controls who underwent functional magnetic resonance imaging while performing a gender identification task for faces that were fearful, happy, sad, or neutral. Habituation was tested by comparing amygdala activation to faces during the first half versus the second half of the session. VmPFC-amygdala connectivity was examined through psychophysiologic interaction analysis.ResultsYouth with ASD had decreased amygdala habituation to sad and neutral faces compared with controls. Moreover, decreased amygdala habituation correlated with autism severity as measured by the Social Responsiveness Scale. There was a group difference in vmPFC-amygdala connectivity while viewing sad faces, and connectivity predicted amygdala habituation to sad faces in controls.ConclusionsSustained amygdala activation to faces suggests that repeated face presentations are processed differently in individuals with ASD, which could contribute to social impairments. Abnormal modulation of the amygdala by the vmPFC may play a role in decreased habituation.