Activation In Right Amygdala Research Articles

Deterioration in cognitive control related mPFC function underlying development of treatment resistance in early psychosis

One third of people with psychosis become antipsychotic treatment-resistant and the underlying mechanisms remain unclear. We investigated whether altered cognitive control function is a factor underlying development of treatment resistance. We studied 50 people with early psychosis at a baseline visit (mean < 2 years illness duration) and follow-up visit (1 year later), when 35 were categorized at treatment-responsive and 15 as treatment-resistant. Participants completed an emotion-yoked reward learning task that requires cognitive control whilst undergoing fMRI and MR spectroscopy to measure glutamate levels from Anterior Cingulate Cortex (ACC). Changes in cognitive control related activity (in prefrontal cortex and ACC) over time were compared between treatment-resistant and treatment-responsive groups and related to glutamate. Compared to treatment-responsive, treatment-resistant participants showed blunted activity in right amygdala (decision phase) and left pallidum (feedback phase) at baseline which increased over time and was accompanied by a decrease in medial Prefrontal Cortex (mPFC) activity (feedback phase) over time. Treatment-responsive participants showed a negative relationship between mPFC activity and glutamate levels at follow-up, no such relationship existed in treatment-resistant participants. Reduced activity in right amygdala and left pallidum at baseline was predictive of treatment resistance at follow-up (67% sensitivity, 94% specificity). The findings suggest that deterioration in mPFC function over time, a key cognitive control region needed to compensate for an initial dysfunction within a social-emotional network, is a factor underlying development of treatment resistance in early psychosis. An uncoupling between glutamate and cognitive control related mPFC function requires further investigation that may present a future target for interventions.

Emotion processing in youths with conduct problems: an fMRI meta-analysis

Functional magnetic resonance imaging (fMRI) studies consistently indicate differences in emotion processing in youth with conduct problems. However, no prior meta-analysis has investigated emotion-specific responses associated with conduct problems. This meta-analysis aimed to generate an up-to-date assessment of socio-affective neural responding among youths with conduct problems. A systematic literature search was conducted in youths (ages 10–21) with conduct problems. Task-specific seed-based d mapping analyses examined responses to threatening images, fearful and angry facial expressions, and empathic pain stimuli from 23 fMRI studies, which included 606 youths with conduct problems and 459 comparison youths. Whole-brain analyses revealed youths with conduct problems relative to typically developing youths, when viewing angry facial expressions, had reduced activity in left supplementary motor area and superior frontal gyrus. Additional region of interest analyses of responses to negative images and fearful facial expressions showed reduced activation in right amygdala across youths with conduct problems. Youths with callous-unemotional traits also exhibited reduced activation in left fusiform gyrus, superior parietal gyrus, and middle temporal gyrus when viewing fearful facial expressions. Consistent with the behavioral profile of conduct problems, these findings suggest the most consistent dysfunction is found in regions associated with empathic responding and social learning, including the amygdala and temporal cortex. Youth with callous-unemotional traits also show reduced activation in the fusiform gyrus, consistent with reduced attention or facial processing. These findings highlight the potential role of empathic responding, social learning, and facial processing along with the associated brain regions as potential targets for interventions.

Combination therapy with exenatide decreases the dapagliflozin-induced changes in brain responses to anticipation and consumption of palatable food in patients with type 2 diabetes: A randomized controlled trial.

AimsSodium‐glucose cotransporter‐2 inhibitors induce less weight loss than expected. This may be explained by sodium‐glucose cotransporter‐2 inhibitor‐induced alterations in central reward‐ and satiety circuits, leading to increased appetite and food intake. Glucagon‐like peptide‐1 receptor agonists reduce appetite and body weight because of direct and indirect effects on the brain. We investigated the separate and combined effects of dapagliflozin and exenatide on the brain in response to the anticipation and consumption of food in people with obesity and type 2 diabetes.Materials and MethodsAs part of a larger study, this was a 16 week, double‐blind, randomized, placebo‐controlled trial. Subjects with obesity and type 2 diabetes were randomized (1:1:1:1) to dapagliflozin 10 mg with exenatide‐matched placebo, exenatide twice‐daily 10 μg with dapagliflozin‐matched placebo, dapagliflozin plus exenatide, or double placebo. Using functional magnetic resonance imaging, the effects of treatments on brain responses to the anticipation of food and food receipt were assessed after 10 days and 16 weeks.ResultsAfter 10 days, dapagliflozin increased activation in right amygdala and right caudate nucleus in response to the anticipation of food, and tended to decrease activation in right amygdala in response to actual food receipt. After 16 weeks, no changes in brain activation were observed with dapagliflozin. Dapagliflozin plus exenatide reduced activation in right caudate nucleus and amygdala to the anticipation of food, and decreased activation in the right amygdala in response to food receipt after 16 weeks.ConclusionsThe dapagliflozin‐induced changes in brain activation may contribute to the discrepancy between observed and expected weight loss with dapagliflozin. Exenatide blunted the dapagliflozin‐induced changes in brain activation, which may contribute to the additional weight loss with combined treatment.

Nostalgia enhances detection of death threat: neural and behavioral evidence

An experiment examined the potency of nostalgia—a sentimental longing for one’s past—to facilitate detection of death-related stimuli, using functional magnetic resonance imaging (fMRI) and behavioral techniques (i.e., judgmental accuracy, reaction times). We hypothesized and found that, at the neural level, nostalgic (relative to control) participants evinced more intense activation in right amygdala in response to death-related (vs. neutral) words. We also hypothesized and found that, at the behavioral level, nostalgic (relative to control) participants manifested greater accuracy in judging whether two death-related (vs. neutral) words belonged in the same category. Exploratory analyses indicated that nostalgic (relative to control) participants did not show faster reaction times to death-related (vs. neutral) words. In all, nostalgia appeared to aid in death threat detection. We consider implications for the relevant literatures.

The impact of familial risk and early life adversity on emotion and reward processing networks in youth at-risk for bipolar disorder.

A recently developed risk calculator for bipolar disorder (BD) accounts for clinical and parental psychopathology. Yet, it is understood that both familial predisposition and early life adversity contribute to the development of BD. How the interplay between these two factors influence emotion and reward processing networks in youth at risk for BD remains unclear. In this exploratory analysis, offspring of BD parents performed emotion and reward processing tasks while undergoing a fMRI scan. Risk calculator score was used to assess risk for developing BD in the next 5 years. Environmental risk was tabulated using the Stressful Life Events Schedule (SLES). Emotion and reward processing networks were investigated for genetic and/or environment interactions. Interaction effects were found between risk calculator scores, negative SLES score and activity in right amygdala and bilateral fusiform gyri during the emotion processing task, as well as activity in the fronto-, striatal, and parietal regions during the reward processing task. Our findings are preliminary; however, they support the unique and interactive contributions of both familial and environmental risk factors on emotion and reward processing within OBP. They also identify potential neural targets to guide development of interventions for youth at greatest risk for psychiatric disorders.

The burden of conscientiousness? Examining brain activation and cortisol response during social evaluative stress

Although conscientiousness has for a long time been considered generally adaptive, there are findings challenging this view, suggesting that conscientiousness might be less advantageous during uncontrollable stress. We here examined the impact of conscientiousness on brain activation during and the cortisol response following an uncontrollable social evaluative stress task in order to test this hypothesis.Brain activation and cortisol levels were measured during an fMRI stress task, where subjects (n=86) performed cognitive tasks containing preprogrammed failure under time pressure, while being monitored by a panel of experts inducing social-evaluative threat. The degree of conscientiousness was measured using the NEO-FFI.We observed a positive correlation between conscientiousness and salivary cortisol levels in response to the stressful task in male subjects only. In male subjects conscientiousness correlated positively with activation in right amygdala and left insula, and, moreover, mediated the influence of amygdala and insula activation on cortisol output. This pattern of brain activation can be interpreted as a disadvantageous response to uncontrollable stress to which highly conscientious individuals might be predisposed.This is the first study showing the effect of conscientiousness on physiology and brain activation to an uncontrollable psychosocial stressor. Our results provide neurobiological evidence for the hypothesis that conscientiousness should not just be seen as beneficial, but rather as a trait associated with either costs or benefits depending on the extent to which one is in control of the situation.

Decreased neural response for facial emotion processing in subjects with high genetic load for schizophrenia

BackgroundPatients with schizophrenia show impairment in facial emotion processing which is essential for successful social cognition. Using a functional magnetic resonance imaging (fMRI), this study aimed to investigate the implicit facial emotion recognition processing in participants with high genetic load for schizophrenia (GHR) as a possible trait marker of developing schizophrenia. MethodsBlock design fMRI of implicit facial emotion processing was used in 20 participants with GHR aged 16–35, and 17 age, sex, and education year-matched healthy controls (HC). During the facial emotional processing for fearful, happy, and neutral face stimuli, participants were asked to explicitly determine the gender per stimuli. ResultsOccipito-temporo-limbic area in fearful face condition and involvement of broader region including prefrontal cortex in neutral face condition revealed significant attenuation of BOLD signal activation in GHR compared to HC. The GHR demonstrated less activity in right amygdala during fearful and neutral face condition. ConclusionThe study presented that GHR displayed abnormal brain activity in occipito-temporo-limbic-frontal network implicated in facial emotion processing. It indicates that abnormal facial emotion processing may be influenced by a genetic factor and could be a trait marker in schizophrenia.

FMRI evidence for a reduction in affective processing of thermal pain in responders of transcutaneous vagal nerve stimulation (TVNS)

Background Although the transcutaneous vagal nerve stimulation (TVNS) is increasingly used in treatment of chronic pain, the underlying mechanism is unclear. The goal of this study was to analyse the cerebral effects of TVNS under experimental pain in fMRI. Methods Twenty healthy volunteers took part in two separate fMRI sessions (3 Tesla) with experimental pain, which was applied to the right forearm with MEDOC Sensory Analyser. During TVNS session the electrical stimulation was applied bilaterally to auricular concha with rectangle impulses (8 Hz frequency; 200 μs wave length); the intensity was maximal but not painful. During placebo session the stimulation device was switched off. The order of the sessions was randomised. Individual sensory thresholds were registered before and after each fMRI session. fMRI data was afterwards processed with standard settings in SPM8 and differences in BOLD effects between verum and placebo session were calculated. We used region of interest (ROI) based analysis on ROIs, which were previously identified in association with thermal pain. Results Cerebral pain processing areas were activated bilaterally under thermal stimulation. The group analysis did not show the differences in sensory parameters but revealed stronger activation of right amygdala under TVNS. The group of responders (subjects with increased pain threshold after TVNS, n = 8), showed a reduction in BOLD signal in the right nucleus caudate, the middle frontal cortex and left hypothalamus under TVNS in comparison to placebo. Conclusion Thermal stimulation elicited bilateral fMRI activation in pain processing regions of the brain in healthy volunteers. Responders to TVNS showed decreased activation in cerebral areas associated with affective processing of pain.

Neuroanatomical substrates for the volitional regulation of heart rate.

The control of physiological arousal can assist in the regulation of emotional state. A subset cortical and subcortical brain regions are implicated in autonomic control of bodily arousal during emotional behaviors. Here, we combined human functional neuroimaging with autonomic monitoring to identify neural mechanisms that support the volitional regulation of heart rate, a process that may be assisted by visual feedback. During functional magnetic resonance imaging (fMRI), 15 healthy adults performed an experimental task in which they were prompted voluntarily to increase or decrease cardiovascular arousal (heart rate) during true, false, or absent visual feedback. Participants achieved appropriate changes in heart rate, without significant modulation of respiratory rate, and were overall not influenced by the presence of visual feedback. Increased activity in right amygdala, striatum and brainstem occurred when participants attempted to increase heart rate. In contrast, activation of ventrolateral prefrontal and parietal cortices occurred when attempting to decrease heart rate. Biofeedback enhanced activity within occipito-temporal cortices, but there was no significant interaction with task conditions. Activity in regions including pregenual anterior cingulate and ventral striatum reflected the magnitude of successful task performance, which was negatively related to subclinical anxiety symptoms. Measured changes in respiration correlated with posterior insula activation and heart rate, at a more lenient threshold, change correlated with insula, caudate, and midbrain activity. Our findings highlight a set of brain regions, notably ventrolateral prefrontal cortex, supporting volitional control of cardiovascular arousal. These data are relevant to understanding neural substrates supporting interaction between intentional and interoceptive states related to anxiety, with implications for biofeedback interventions, e.g., real-time fMRI, that target emotional regulation.

Elucidating the Neural Mechanisms of Cognitive-Behavioral Therapy: A Commentary on Treatment Changes in Neural Correlates of Subliminal and Supraliminal Threat in Individuals With Spider Phobia

Understanding how clinical interventions work is a fundamental task of clinical science. In particular, elucidating the brain and behavioral mechanisms of therapeutic change is essential to develop more refined and effective interventions and to understand why they work. One of the promises of functional neuroimaging is to provide a powerful window into the underlying psychological mechanisms instantiated in distributed brain networks that are modified with specific types of clinical interventions. In this issue of Biological Psychiatry ,L ipkaet al. (1) used functional magnetic resonance imaging to investigate the impact of brief (2 3–5 hours of) small group cognitive-behavioral therapy (CBT) versus a waitlist control group on the neurocircuitry involved in subliminal (preconscious) and supraliminal (conscious) threat processing in 28 female patients with spider phobia and 16 healthy control female participants. This study used a two-backward masking functional magnetic resonance imaging task with spider (vs. bird and mushroom) visual target stimuli to determine distinct brain responses to automatic versus conscious elaborative processing of threat cues, both of which represent mechanisms that may trigger and maintain hyperactive fear responses in individuals with spider phobia. Behaviorally, this study demonstrated that, compared with the waitlist control group, CBT resulted in significant decreases in selfreported negative valence and arousal to spider target stimuli, symptom severity, spider-related beliefs, self-related beliefs, and increases in behavioral approach. However, there was no evidence of reduction for vigilance suggesting that this may be an incontrovertible trait in individuals with spider phobia. Reductions in clinical symptoms and distorted beliefs related to CBT can occur despite no change in phobic hypervigilance in individuals with spider phobia. Neurally, pretreatment analyses focused on a priori brain regions of interest identified greater activation in participants with phobia versus healthy control participants in right amygdala and fusiform gyrus for subliminal threat processing with no detection of spiders and even more robust activations in bilateral amygdala, fusiform gyrus, anterior insula, dorsal anterior cingulate cortex (ACC), pregenual ACC, and dorsomedial prefrontal cortex (PFC) for supraliminal correct conscious detection of spiders. This finding suggests a hyperactive network implicated in affective, visual, visceral, and cognitive control mechanisms during conscious threat processing in individuals with spider phobia that may be a target of clinical interventions. With respect to the impact of clinical treatment, CBT produced no changes during subliminal threat processing. However, compared with the waitlist control group, CBT was associated with greater reduction in activation of right amygdala and dorsal ACC during supraliminal threat processing. Pre- to post-CBT and waitlist group changes across all participants with spider phobia revealed habituation-related reductions in bilateral amygdala, anterior insula, dorsal and pregenual ACC, and dorsomedial PFC. This pattern of results suggests that CBT for spider phobia may not have an impact on automatic preconscious processing of subliminal threat processing and that the impact of CBT on supraliminal threat processing may be accounted for solely by habituation processes. These findings are in contrast to models of psychopathology that emphasize an inverse relationship between exaggerated emotional reactivity–related amygdala responses and top-down emotion regulation deficits reflected in diminished recruitment of cognitive control mechanisms instantiated in PFC and resolution of such abnormalities after CBT, specifically, increased PFC and decreased amygdala responses (2). Models of CBT emphasize increases in cognitive reappraisal ability and self-efficacy based on the extensive training in implementing cognitive restructuring in the context of fear exposure. Neurally, CBT training has been shown to enhance cognitive reappraisal via increases in integrated recruitment of

Functional effects of chronic paroxetine versus placebo on the fear, stress and anxiety brain circuit in Social Anxiety Disorder: Initial validation of an imaging protocol for drug discovery

Recent studies suggest that pharmacologic effects of anxiolytic agents can be mapped as functional changes in the fear, stress and anxiety brain circuit. In this work we investigated the effects of a standard treatment, paroxetine (20mg/day), in subjects with Social Anxiety Disorder (SAD) versus placebo using different fMRI paradigms. The fMRI sessions, performed before and after the treatment, consisted of a public exposition of recorded performance task (PERPT), an emotional face processing task (EFPT) and a 6-min resting state followed by an off-scanner public speaking test. Paroxetine significantly improved the clinical conditions of SAD patients (n=17) vs. placebo (n=16) as measured with Clinical Global Inventory – Improvement (CGI-I) while no change was seen when using Liebowitz Social Anxiety Scale, as expected given the small size of the study population. Paroxetine reduced the activation of insula, thalamus and subgenual/anterior cingulate cortex (ACC) in PERPT. Resting-state fMRI assessment using Independent Component Analysis indicated that paroxetine reduced functional connectivity in insula, thalamus and ACC when compared with placebo. Both paradigms showed significant correlation with CGI-I in rostral prefrontal cortex. Conversely, paroxetine compared to placebo produced activation of right amygdala and bilateral insula and no effects in ACC when tested with EFPT. No treatment effects on distress scores were observed in the off-scanner Public Speaking Test. Overall this study supports the use of fMRI as sensitive approach to explore the neurobiological substrate of the effects of pharmacologic treatments and, in particular, of resting state fMRI given its simplicity and task independence.

When psychopathy impairs moral judgments: neural responses during judgments about causing fear.

Psychopathy is a disorder characterized by reduced empathy, shallow affect and behaviors that cause victims distress, like threats, bullying and violence. Neuroimaging research in both institutionalized and community samples implicates amygdala dysfunction in the etiology of psychopathic traits. Reduced amygdala responsiveness may disrupt processing of fear-relevant stimuli like fearful facial expressions. The present study links amygdala dysfunction in response to fear-relevant stimuli to the willingness of individuals with psychopathic traits to cause fear in other people. Thirty-three healthy adult participants varying in psychopathic traits underwent whole-brain fMRI scanning while they viewed statements that selectively evoke anger, disgust, fear, happiness or sadness. During scanning, participants judged whether it is morally acceptable to make each statement to another person. Psychopathy was associated with reduced activity in right amygdala during judgments of fear-evoking statements and with more lenient moral judgments about causing fear. No group differences in amygdala function or moral judgments emerged for other emotion categories. Psychopathy was also associated with increased activity in middle frontal gyrus (BA 10) during the task. These results implicate amygdala dysfunction in impaired judgments about causing distress in psychopathy and suggest that atypical amygdala responses to fear in psychopathy extend across multiple classes of stimuli.

Neural Responses to Affective and Cognitive Theory of Mind in Children With Conduct Problems and Varying Levels of Callous-Unemotional Traits

Reduced neural responses to others' distress is hypothesized to play a critical role in conduct problems coupled with callous-unemotional traits, whereas increased neural responses to affective stimuli may accompany conduct problems without callous-unemotional traits. Heterogeneity of affective profiles in conduct problems may account for inconsistent neuroimaging findings in this population. To broaden understanding of neural processing in conduct problems using an affective processing task including an empathy component as well as to explore dimensional contributions of conduct problems symptoms and callous-unemotional traits to variance in affective neural responses. Case-control study. On-campus neuroimaging facility. Thirty-one boys with conduct problems (mean age, 14.34 years) and 16 typically developing control subjects (mean age, 13.51 years) matched for age (range, 10-16 years), IQ, socioeconomic status, handedness, and race/ethnicity. Participants were recruited using screening questionnaires in a community-based volunteer sample. Functional magnetic resonance imaging of a task contrasting affective and cognitive theory of mind judgments. Relative to typically developing children, children with conduct problems showed reduced activation in right amygdala and anterior insula for affective vs cognitive theory of mind judgments. Furthermore, in the right amygdala, regression analysis within the conduct-problems group showed suppressor effects between ratings of conduct problems and callous-unemotional traits. Specifically, unique variance associated with conduct problems was positively correlated with amygdala reactivity, whereas unique variance associated with callous-unemotional traits was negatively correlated with amygdala reactivity. These associations were not explained by hyperactivity, depression/anxiety symptoms, or alcohol use ratings. Childhood conduct problems are associated with amygdala and anterior insula hypoactivity during a complex affective processing task including an empathy component. Suppressor effects between conduct problems and callous-unemotional traits in the amygdala suggest a potential neural substrate for heterogeneity in affective profiles associated with conduct problems.

Threat of Punishment Motivates Memory Encoding via Amygdala, Not Midbrain, Interactions with the Medial Temporal Lobe

Neural circuits associated with motivated declarative encoding and active threat avoidance have both been described, but the relative contribution of these systems to punishment-motivated encoding remains unknown. The current study used functional magnetic resonance imaging in humans to examine mechanisms of declarative memory enhancement when subjects were motivated to avoid punishments that were contingent on forgetting. A motivational cue on each trial informed participants whether they would be punished or not for forgetting an upcoming scene image. Items associated with the threat of shock were better recognized 24 h later. Punishment-motivated enhancements in subsequent memory were associated with anticipatory activation of right amygdala and increases in its functional connectivity with parahippocampal and orbitofrontal cortices. On a trial-by-trial basis, right amygdala activation during the motivational cue predicted hippocampal activation during encoding of the subsequent scene; across participants, the strength of this interaction predicted memory advantages due to motivation. Of note, punishment-motivated learning was not associated with activation of dopaminergic midbrain, as would be predicted by valence-independent models of motivation to learn. These data are consistent with the view that motivation by punishment activates the amygdala, which in turn prepares the medial temporal lobe for memory formation. The findings further suggest a brain system for declarative learning motivated by punishment that is distinct from that for learning motivated by reward.

Fronto-limbic dysfunction in mania pre-treatment and persistent amygdala over-activity post-treatment in pediatric bipolar disorder

Neural deficits at the interface of affect and cognition may improve with pharmacotherapy in pediatric bipolar disorder (PBD). We examined lamotrigine treatment impact on the neural interface of working memory and affect in PBD. Un-medicated, acutely ill, patients with mania and hypomania (n = 17), and healthy controls (HC; n = 13; mean age = 13.36 ± 2.55) performed an affective two-back functional magnetic resonance imaging task with blocks of angry vs neutral faces (i.e., angry face condition) or happy vs neutral faces (i.e., happy face condition) before treatment and at follow-up, after 8-week treatment with second-generation antipsychotics followed by 6 weeks of lamotrigine monotherapy. At baseline, for the angry face condition, PBD, relative to HC, showed reduced activation in the left ventrolateral prefrontal cortex (VLPFC) and right caudate; for the happy face condition, PBD showed increased activation in bilateral PFC and right amygdala and middle temporal gyrus. Post-treatment, PBD showed greater activation in right amygdala relative to HC for both conditions. Patients, relative to HC, exhibited greater changes over time in the right VLPFC and amygdala, left subgenual anterior cingulate cortex and left caudate for the angry face condition, and in right middle temporal gyrus for the happy face condition. Pharmacotherapy resulted in symptom improvement and normalization of higher cortical emotional and cognitive regions in patients relative to HC, suggesting that the VLPFC dysfunction may be state-specific in PBD. Amygdala was overactive in PBD, relative to HC, regardless of reduction in manic symptoms, and may be a trait marker of PBD.

Effects of diazepam on BOLD activation during the processing of aversive faces

This study aimed to measure, using fMRI, the effect of diazepam on the haemodynamic response to emotional faces. Twelve healthy male volunteers (mean age = 24.83 ± 3.16 years), were evaluated in a randomized, balanced-order, double-blind, placebo-controlled crossover design. Diazepam (10 mg) or placebo was given 1 h before the neuroimaging acquisition. In a blocked design covert face emotional task, subjects were presented with neutral (A) and aversive (B) (angry or fearful) faces. Participants were also submitted to an explicit emotional face recognition task, and subjective anxiety was evaluated throughout the procedures. Diazepam attenuated the activation of right amygdala and right orbitofrontal cortex and enhanced the activation of right anterior cingulate cortex (ACC) to fearful faces. In contrast, diazepam enhanced the activation of posterior left insula and attenuated the activation of bilateral ACC to angry faces. In the behavioural task, diazepam impaired the recognition of fear in female faces. Under the action of diazepam, volunteers were less anxious at the end of the experimental session. These results suggest that benzodiazepines can differentially modulate brain activation to aversive stimuli, depending on the stimulus features and indicate a role of amygdala and insula in the anxiolytic action of benzodiazepines.

Association between amygdala response to emotional faces and social anxiety in autism spectrum disorders

Difficulty interpreting facial expressions has been reported in autism spectrum disorders (ASD) and is thought to be associated with amygdala abnormalities. To further explore the neural basis of abnormal emotional face processing in ASD, we conducted an fMRI study of emotional face matching in high-functioning adults with ASD and age, IQ, and gender matched controls. In addition, we investigated whether there was a relationship between self-reported social anxiety and fMRI activation. During fMRI scanning, study participants were instructed to match facial expressions depicting fear or anger. The control condition was a comparable shape-matching task. The control group evidenced significantly increased left prefrontal activation and decreased activation in the occipital lobes compared to the ASD group during emotional face matching. Further, within the ASD group, greater social anxiety was associated with increased activation in right amygdala and left middle temporal gyrus, and decreased activation in the fusiform face area. These results indicate that level of social anxiety mediates the neural response to emotional face perception in ASD.

Regional cerebral glucose metabolism and anxiety symptoms in bipolar depression: Effects of levothyroxine

We examined the relationships between regional brain activity and anxiety in bipolar depressed patients receiving adjunctive treatment with levothyroxine. Regional brain activity was assessed with positron emission tomography and [ 18F]fluorodeoxyglucose in 10 euthyroid, depressed bipolar women before and after 7 weeks of adjunctive therapy with levothyroxine. The primary biological measures were relative (to global) regional radioactivity as a surrogate index of glucose metabolism in pre-selected brain regions. Relationships were assessed between regional brain activity and anxiety symptoms while controlling for depression severity. At baseline, Trait Anxiety Inventory measures covaried positively with relative brain activity bilaterally in the dorsal anterior cingulate, superior temporal gyri, parahippocampal gyri, amygdala, hippocampus, ventral striatum, and right insula; state anxiety showed a similar pattern. After treatment anxiety was improved significantly. Change in trait anxiety covaried positively with changes in relative activity in right amygdala and hippocampus. Change in state anxiety covaried positively with changes in relative activity in the hippocampus bilaterally and left thalamus, and negatively with changes in left middle frontal gyrus and right dorsal anterior cingulate. Results indicate that comorbid anxiety symptoms have specific regional cerebral metabolic correlates in bipolar depression and cannot only be explained exclusively by the depressive state of the patients.

Alterations in the processing of non-drug-related affective stimuli in abstinent heroin addicts

Long-term exposure to drug may alter the neural system associated with affective processing, as evidenced by both clinical observations and behavioral data documenting dysfunctions in emotional experiences and processing in drug addicts. Although many imaging studies examined neural responses to drug or drug-related cues in addicts, there have been few studies explicitly designed to reveal their neural abnormalities in processing non-drug-related natural affective materials. The present study asked abstinent heroin addicts and normal controls to passively view standardized affective pictures of positive, negative, or neutral valence and compared their brain activities with functional MRI. Compared to normal controls, addicts showed reduced activation in right amygdala in response to the affective pictures, consistent with previous reports of blunted subjective experience for affective stimuli in addicts. Furthermore, in two visual cortical areas BA 19 and 37, while the controls showed greater responses to positive pictures than to negative ones replicating literature findings, the addicts showed the opposite pattern. The results reveal a complex pattern of altered processing of non-drug-related affective materials in addicts showing both heightened and blunted neural responses in different brain regions and for different stimulus valence. The present study highlights the importance of brain imaging research on drug addicts' processing of affective stimuli in understanding disruptions in their emotion circuitry.

Age-related differences in brain regions supporting successful encoding of emotional faces

In an event-related functional Magnetic Resonance Imaging (fMRI) study, younger and older adults were presented with negative emotional (i.e., fearful) and neutral face pictures under incidental learning conditions. They were subsequently given a test of face recognition outside the scanner. Both age groups activated amygdala bilaterally as well as the right hippocampus during successful encoding of the fearful faces. Direct age comparisons revealed greater activation in right amygdala and bilateral hippocampus in the young, whereas older adults showed greater activation in the left insular and right prefrontal cortices. None of these brain areas was activated during successful encoding of neutral faces, suggesting specificity of these brain activation patterns. The results indicate an age-related shift in the neural underpinnings of negative emotional face processing from medial–temporal to neocortical regions.