Neurobiological indicators of disinhibition in posttraumatic stress disorder

Deficits in impulse control are increasingly recognized in association with posttraumatic stress disorder (PTSD). To our further understanding of the neurobiology of PTSD‐related disinhibition, we examined alterations in brain morphology and network connectivity associated with response inhibition failures and PTSD severity. The sample consisted of 189 trauma‐exposed Operation Enduring Freedom/Operation Iraqi Freedom veterans (89% male, ages 19–62) presenting with a range of current PTSD severity. Disinhibition was measured using commission errors on a Go/No‐Go (GNG) task with emotional stimuli, and PTSD was assessed using a measure of current symptom severity. Whole‐brain vertex‐wise analyses of cortical thickness revealed two clusters associated with PTSD‐related disinhibition (Monte Carlo cluster corrected P < 0.05). The first cluster included portions of right inferior and middle frontal gyri and frontal pole. The second cluster spanned portions of left medial orbital frontal, rostral anterior cingulate, and superior frontal gyrus. In both clusters, commission errors were associated with reduced cortical thickness at higher (but not lower) levels of PTSD symptoms. Resting‐state functional magnetic resonance imaging analyses revealed alterations in the functional connectivity of the right frontal cluster. Together, study findings suggest that reductions in cortical thickness in regions involved in flexible decision‐making, emotion regulation, and response inhibition contribute to impulse control deficits in PTSD. Furthermore, aberrant coupling between frontal regions and networks involved in selective attention, memory/learning, and response preparation suggest disruptions in functional connectivity may also play a role. Hum Brain Mapp 36:3076–3086, 2015. © 2015 Wiley Periodicals, Inc.     

长期海洛因依赖者前额叶功能连接的变化

以前额叶为种子点,利用静息态fMRI进行全脑时域相关的功能连接分析,观察长期海洛因成瘾者前额叶功能连接的变化。结果发现相比于正常对照,以左侧前额叶为种子点进行功能连接分析,海洛因成瘾者左侧前额叶与左侧海马、右侧前扣带回、左侧额中回、右侧额中回、右侧楔前叶功能连接明显降低;以右侧前额叶为种子点进行功能连接分析,海洛因成瘾者右侧前额叶与左侧眶额叶、左侧额中回功能连接明显降低。提示长期海洛因成瘾者前额叶与相关脑区的功能连接减弱,可能与海洛因成瘾的维持与戒断后复吸相关。     

Functional brain connectivity at rest changes after working memory training

Networks of functional connectivity are highly consistent across participants, suggesting that functional connectivity is for a large part predetermined. However, several studies have shown that functional connectivity may change depending on instructions or previous experience. In the present study, we investigated whether 6 weeks of practice with a working memory task changes functional connectivity during a resting period preceding the task. We focused on two task‐relevant networks, the frontoparietal network and the default network, using seed regions in the right middle frontal gyrus (MFG) and the medial prefrontal cortex (PFC), respectively. After practice, young adults showed increased functional connectivity between the right MFG and other regions of the frontoparietal network, including bilateral superior frontal gyrus, paracingulate gyrus, and anterior cingulate cortex. In addition, they showed reduced functional connectivity between the medial PFC and right posterior middle temporal gyrus. Moreover, a regression with performance changes revealed a positive relation between performance increases and changes of frontoparietal connectivity, and a negative relation between performance increases and changes of default network connectivity. Next, to study whether experience‐dependent effects would be different during development, we also examined practice effects in a pilot sample of 12‐year‐old children. No practice effects were found in this group, suggesting that practice‐related changes of functional connectivity are age‐dependent. Nevertheless, future studies with larger samples are necessary to confirm this hypothesis. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Dissociation of inhibition from error processing using a parametric inhibitory task during functional magnetic resonance imaging

Inhibition, the process that overrides and reverses the execution of a thought, action, or emotion, is important in daily life. Sixteen healthy volunteers performed a parametrically modulated motor inhibition task during functional magnetic resonance imaging. Two results were observed: (1) increased error-related anterior cingulate cortex activation and, (2) increased inferior frontal gyrus and medial prefrontal cortex activation during inhibition, irrespective of errors. Thus, the parametric nature of the task elucidated a functional dissociation of brain structures involved in motor inhibition from those involved in error processing. Additionally, this task allowed the identification of unique areas of increased activation within specific subregions of the anterior cingulate cortex related to errors made during trials with a high (dorsal anterior cingulate cortex) and low (ventral anterior cingulate cortex) inhibitory load.     

Default network connectivity during a working memory task

The default network exhibits correlated activity at rest and has shown decreased activation during performance of cognitive tasks. There has been little investigation of changes in connectivity of this network during task performance. In this study, we examined task‐related modulation of connectivity between two seed regions from the default network posterior cingulated cortex (PCC) and medial prefrontal cortex (mPFC) and the rest of the brain in 12 healthy adults. The purpose was to determine (1) whether connectivity within the default network differs between a resting state and performance of a cognitive (working memory) task and (2) whether connectivity differs between these nodes of the default network and other brain regions, particularly those implicated in cognitive tasks. There was little change in connectivity with the other main areas of the default network for either seed region, but moderate task‐related changes in connectivity occurred between seed regions and regions outside the default network. For example, connectivity of the mPFC with the right insula and the right superior frontal gyrus decreased during task performance. Increased connectivity during the working memory task occurred between the PCC and bilateral inferior frontal gyri, and between the mPFC and the left inferior frontal gyrus, cuneus, superior parietal lobule, middle temporal gyrus and cerebellum. Overall, the areas showing greater correlation with the default network seed regions during task than at rest have been previously implicated in working memory tasks. These changes may reflect a decrease in the negative correlations occurring between the default and task‐positive networks at rest. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.     

Functional connectivity during orthographic,phonological, and semantic processing of Chinese characters identifies distinct visuospatial and phonosemantic networks

While neuroimaging studies have identified brain regions associated with single word reading, its three constituents, namely, orthography, phonology, and meaning, and the functional connectivity of their networks remain underexplored. This study examined the neurocognitive underpinnings of these neural activations and functional connectivity of the identified brain regions using a within‐subject design. Thirty‐one native Mandarin speakers performed orthographic, phonological, and semantic judgment tasks during functional magnetic resonance imaging. The results indicated that the three processes shared a core network consisting of a large region in the left prefrontal cortex, fusiform gyrus, and medial superior frontal gyrus but not the superior temporal gyrus. Orthographic processing more strongly recruited the left dorsolateral prefrontal cortex, left superior parietal lobule and bilateral fusiform gyri; semantic processing more strongly recruited the left inferior frontal gyrus and left middle temporal gyrus, whereas phonological processing more strongly activated the dorsal part of the precentral gyrus. Functional connectivity analysis identified a posterior visuospatial network and a frontal phonosemantic network interfaced by the left middle frontal gyrus. We conclude that reading Chinese recruits cognitive resources that correspond to basic task demands with unique features best explained in connection with the individual reading subprocesses.     

Neural systems for executive and emotional processing are modulated by symptoms of posttraumatic stress disorder in Iraq War veterans

The symptom-provocation paradigms generally used in neuroimaging studies of posttraumatic stress disorder (PTSD) have placed high demands on emotion processing but lacked cognitive processing, thereby limiting the ability to assess alterations in neural systems that subserve executive functions and their interactions with emotion processing. Thirty-nine veterans from Iraq and Afghanistan underwent functional magnetic resonance imaging while exposed to emotional combat-related and neutral civilian scenes interleaved with an executive processing task. Contrast activation maps were regressed against PTSD symptoms as measured by the Davidson Trauma Scale. Activation for emotional compared with neutral stimuli was highly positively correlated with level of PTSD symptoms in ventral frontolimbic regions, notably the ventromedial prefrontal cortex, inferior frontal gyrus, and ventral anterior cingulate gyrus. Conversely, activation for the executive task was negatively correlated with PTSD symptoms in the dorsal executive network, notably the middle frontal gyrus, dorsal anterior cingulate gyrus, and inferior parietal lobule. Thus, there is a strong link between the subjectively assessed behavioral phenomenology of PTSD and objective neurobiological markers. These findings extend the largely symptom provocation-based functional neuroanatomy to provide evidence that interrelated executive and emotional processing systems of the brain are differentially affected by PTSD symptomatology in recently deployed war veterans.     

Differential effects of hunger and satiety on insular cortex and hypothalamic functional connectivity

The insula cortex and hypothalamus are implicated in eating behaviour, and contain receptor sites for peptides and hormones controlling energy balance. The insula encompasses multi‐functional subregions, which display differential anatomical and functional connectivities with the rest of the brain. This study aimed to analyse the effect of fasting and satiation on the functional connectivity profiles of left and right anterior, middle, and posterior insula, and left and right hypothalamus. It was hypothesized that the profiles would be altered alongside changes in homeostatic energy balance. Nineteen healthy participants underwent two 7‐min resting state functional magnetic resonance imaging scans, one when fasted and one when satiated. Functional connectivity between the left posterior insula and cerebellum/superior frontal gyrus, and between left hypothalamus and inferior frontal gyrus was stronger during fasting. Functional connectivity between the right middle insula and default mode structures (left and right posterior parietal cortex, cingulate cortex), and between right hypothalamus and superior parietal cortex was stronger during satiation. Differences in blood glucose levels between the scans accounted for several of the altered functional connectivities. The insula and hypothalamus appear to form a homeostatic energy balance network related to cognitive control of eating; prompting eating and preventing overeating when energy is depleted, and ending feeding or transferring attention away from food upon satiation. This study provides evidence of a lateralized dissociation of neural responses to energy modulations.     

Frontoparietal attentional network activation differs between smokers and nonsmokers during affective cognition

Smoking withdrawal-induced disruption of affect and cognition is associated with dysregulated prefrontal brain function, although little is known regarding the neural foci of smoker–nonsmoker differences during affective cognition. Thus, the current study used functional magnetic resonance imaging (fMRI) to identify smoker–nonsmoker differences in affective cognition. Thirty-four healthy volunteers (17 smokers, 17 nonsmokers) underwent fMRI during an affective Stroop task (aST). The aST includes emotional cue-reactivity trials, and response selection trials that contain either neutral or negative emotional distractors. Smokers had less activation during negative cue-reactivity trials in regions subserving emotional awareness (i.e., posterior cingulate), inhibitory control (i.e., inferior frontal gyrus) and conflict resolution (i.e., anterior cingulate); during response-selection trials with negative emotional distractors, smokers had greater activation in a frontoparietal attentional network (i.e., middle frontal and supramarginal gyri). Exploratory analyses revealed that task accuracy was positively correlated with anterior cingulate cortex and inferior frontal gyrus response on fMRI. These findings suggests that chronic nicotine use may reduce inhibitory control and conflict resolution of emotional distraction, and result in recruiting additional attentional resources during emotional interference on cognition.     

Alterations of Functional Connectivity Among Resting‐State Networks in Hypothyroidism

Hypothyroidism affects brain functioning as suggested by various neuroimaging studies. The primary focus of the present study was to examine whether hypothyroidism would impact connectivity among resting‐state networks (RSNs) using resting‐state functional magnetic resonance imaging (rsfMRI). Twenty‐two patients with hypothyroidism and 22 healthy controls were recruited and scanned using rsfMRI. The data were analysed using independent component analysis and a dual regression approach that was applied on five RSNs that were identified using fsl software ( http://fsl.fmrib.ox.ac.uk ). Hypothyroid patients showed significantly decreased functional connectivity in the regions of the right frontoparietal network (frontal pole), the medial visual network (lateral occipital gyrus, precuneus cortex and cuneus) and the motor network (precentral gyrus, postcentral gyrus, precuneus cortex, paracingulate gyrus, cingulate gyrus and supramarginal gyrus) compared to healthy controls. The reduced functional connectivity in the right frontoparietal network, the medial visual network and the motor network suggests neurocognitive alterations in hypothyroid patients in the corresponding functions. However, the study would be further continued to investigate the effects of thyroxine treatment and correlation with neurocognitive scores. The findings of the present study provide further interesting insights into our understanding of the action of thyroid hormone on the adult human brain.     

Alterations of brain activity and functional connectivity in transition from acute to chronic tinnitus

The objective of this study was to investigate alterations to brain activity and functional connectivity in patients with tinnitus, exploring neural features in the transition from acute to chronic phantom perception. Twenty‐four patients with acute tinnitus, 23 patients with chronic tinnitus, and 32 healthy controls were recruited. High‐density electroencephalography (EEG) was used to explore changes in brain areas and functional connectivity in different groups. When compared with healthy subjects, acute tinnitus patients had a significant reduction in superior frontal cortex activity across all frequency bands, whereas chronic tinnitus patients had a significant reduction in the superior frontal cortex at beta 3 and gamma frequency bands as well as a significant increase in the inferior frontal cortex at delta‐band and superior temporal cortex at alpha 1 frequency band. When compared to the chronic tinnitus group, the acute tinnitus group activity was significantly increased in the middle frontal and parietal gyrus at the gamma‐band. Functional connectivity analysis showed that the chronic tinnitus group had increased connections between the parahippocampus gyrus, posterior cingulate cortex, and precuneus when compared with the healthy group. Alterations of local brain activity and connections between the parahippocampus gyrus and other nonauditory areas appeared in the transition from acute to chronic tinnitus. This indicates that the appearance and development of tinnitus is a dynamic process involving aberrant local neural activity and abnormal connectivity in multifunctional brain networks.     

Baseline functional connectivity may predict placebo responses to accelerated rTMS treatment in major depression

Although in theory sham repetitive transcranial magnetic stimulation (rTMS) has no inherent therapeutic value, nonetheless, such placebo stimulations may have relevant therapeutic effects in clinically depressed patients. On the other hand, antidepressant responses to sham rTMS are quite heterogeneous across individuals and its neural underpinnings have not been explored yet. The current brain imaging study aims to detect baseline neural fingerprints resulting in clinically beneficial placebo rTMS treatment responses. We collected resting‐state functional magnetic resonance imaging data prior to a registered randomized clinical trial of accelerated placebo stimulation protocol in patients documented with treatment‐resistant depression ( http://clinicaltrials.gov/show/NCT01832805 ). In addition to global brain connectivity and rostral anterior cingulate cortex (rACC) seed‐based functional connectivity (FC), elastic‐net regression and cross‐validation procedures were used to identify baseline intrinsic brain connectivity biomarkers for sham‐rTMS responses. Placebo responses to accelerated sham rTMS were correlated with baseline global brain connectivity in the rACC/ventral medial prefrontal cortex (vmPFC). Concerning the rACC seed‐based FC analysis, the placebo response was associated positively with the precuneus/posterior cingulate (PCun/PCC) cortex and negatively with the middle frontal gyrus. Our findings provide first brain imaging evidence for placebo responses to sham stimulation being predictable from rACC rsFC profiles, especially in brain areas implicated in (re)appraisal and self‐focus processes.     

Differentiating between self and others: an ALE meta-analysis of fMRI studies of self-recognition and theory of mind

The perception of self and others is a key aspect of social cognition. In order to investigate the neurobiological basis of this distinction we reviewed two classes of task that study self-awareness and awareness of others (theory of mind, ToM). A reliable task to measure self-awareness is the recognition of one’s own face in contrast to the recognition of others’ faces. False-belief tasks are widely used to identify neural correlates of ToM as a measure of awareness of others. We performed an activation likelihood estimation meta-analysis, using the fMRI literature on self-face recognition and false-belief tasks. The brain areas involved in performing false-belief tasks were the medial prefrontal cortex (MPFC), bilateral temporo-parietal junction, precuneus, and the bilateral middle temporal gyrus. Distinct self-face recognition regions were the right superior temporal gyrus, the right parahippocampal gyrus, the right inferior frontal gyrus/anterior cingulate cortex, and the left inferior parietal lobe. Overlapping brain areas were the superior temporal gyrus, and the more ventral parts of the MPFC. We confirmed that self-recognition in contrast to recognition of others’ faces, and awareness of others involves a network that consists of separate, distinct neural pathways, but also includes overlapping regions of higher order prefrontal cortex where these processes may be combined. Insights derived from the neurobiology of disorders such as autism and schizophrenia are consistent with this notion.     

Color Stroop and negative priming in schizophrenia: An fMRI study

Disturbances in selective attention represent a core characteristic of schizophrenia, whose neural underpinnings have yet to be fully elucidated. Consequently, we recorded brain activation using functional magnetic resonance imaging (fMRI) while 15 patients with schizophrenia and 15 age-matched controls performed a well-established measure of selective attention—the color Stroop negative priming task. We focused on two aspects of performance: overriding pre-potent responses (Stroop effect) and inhibition of prior negatively primed trials (negative priming effect). Behaviorally, controls demonstrated both significant Stroop and negative priming effects, while schizophrenic subjects only showed the Stroop effect. For the Stroop effect, fMRI indicated significantly greater activation in frontal regions–medial frontal gyrus/anterior cingulate gyrus and middle frontal gyrus for controls–but greater activation in medial parietal regions (posterior cingulate gyrus/precuneus) for patients. Negative priming elicited significant activation in right dorsolateral prefrontal cortex for both groups, but also in left dorsolateral prefrontal cortex for patients. These different patterns of fMRI activation may reflect faulty interaction in schizophrenia within networks of brain regions that are vital to selective attention.     

Two distinct neural networks support the mapping of meaning to a novel word

Children can learn the meaning of a new word from context during normal reading or listening, without any explicit instruction. It is unclear how such meaning acquisition is supported and achieved in human brain. In this functional magnetic resonance imaging (fMRI) study we investigated neural networks supporting word learning with a functional connectivity approach. Participants were exposed to a new word presented in two successive sentences and needed to derive the meaning of the new word. We observed two neural networks involved in mapping the meaning to the new word. One network connected the left inferior frontal gyrus (LIFG) with the middle frontal gyrus (MFG), medial superior frontal gyrus, caudate nucleus, thalamus, and inferior parietal lobule. The other network connected the left middle temporal gyrus (LMTG) with the MFG, anterior and posterior cingulate cortex. The LIFG network showed stronger interregional interactions for new than real words, whereas the LMTG network showed similar connectivity patterns for new and real words. We proposed that these two networks support different functions during word learning. The LIFG network appears to select the most appropriate meaning from competing candidates and to map the selected meaning onto the new word. The LMTG network may be recruited to integrate the word into sentential context, regardless of whether the word is real or new. The LIFG and the LMTG networks share a common node, the MFG, suggesting that these two networks communicate in working memory. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.     

Working memory load modulation of parieto-frontal connections: evidence from dynamic causal modeling

Previous neuroimaging studies have shown that working memory load has marked effects on regional neural activation. However, the mechanism through which working memory load modulates brain connectivity is still unclear. In this study, this issue was addressed using dynamic causal modeling (DCM) based on functional magnetic resonance imaging (fMRI) data. Eighteen normal healthy subjects were scanned while they performed a working memory task with variable memory load, as parameterized by two levels of memory delay and three levels of digit load (number of digits presented in each visual stimulus). Eight regions of interest, i.e., bilateral middle frontal gyrus (MFG), anterior cingulate cortex (ACC), inferior frontal cortex (IFC), and posterior parietal cortex (PPC), were chosen for DCM analyses. Analysis of the behavioral data during the fMRI scan revealed that accuracy decreased as digit load increased. Bayesian inference on model structure indicated that a bilinear DCM in which memory delay was the driving input to bilateral PPC and in which digit load modulated several parieto‐frontal connections was the optimal model. Analysis of model parameters showed that higher digit load enhanced connection from L PPC to L IFC, and lower digit load inhibited connection from R PPC to L ACC. These findings suggest that working memory load modulates brain connectivity in a parieto‐frontal network, and may reflect altered neuronal processes, e.g., information processing or error monitoring, with the change in working memory load. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc     

Childhood maltreatment is associated with a sex‐dependent functional reorganization of a brain inhibitory control network

Childhood adversity represents a major risk factor for drug addiction and other mental disorders. However, the specific mechanisms by which childhood adversity impacts human brain organization to confer greater vulnerability for negative outcomes in adulthood is largely unknown. As an impaired process in drug addiction, inhibitory control of behavior was investigated as a target of childhood maltreatment (abuse and neglect). Forty adults without Axis‐I psychiatric disorders (21 females) completed a Childhood Trauma Questionnaire (CTQ) and underwent functional MRI (fMRI) while performing a stop‐signal task. A group independent component analysis identified a putative brain inhibitory control network. Graph theoretical analyses and structural equation modeling investigated the impact of childhood maltreatment on the functional organization of this neural processing network. Graph theory outcomes revealed sex differences in the relationship between network functional connectivity and inhibitory control which were dependent on the severity of childhood maltreatment exposure. A network effective connectivity analysis indicated that a maltreatment dose‐related negative modulation of dorsal anterior cingulate (dACC) activity by the left inferior frontal cortex (IFC) predicted better response inhibition and lesser attention deficit hyperactivity disorder (ADHD) symptoms in females, but poorer response inhibition and greater ADHD symptoms in males. Less inhibition of the right IFC by dACC in males with higher CTQ scores improved inhibitory control ability. The childhood maltreatment‐related reorganization of a brain inhibitory control network provides sex‐dependent mechanisms by which childhood adversity may confer greater risk for drug use and related disorders and by which adaptive brain responses protect individuals from this risk factor. Hum Brain Mapp 35:1654–1667, 2014. © 2013 Wiley Periodicals, Inc.     

How task demands shape brain responses to visual food cues

Several previous imaging studies have aimed at identifying the neural basis of visual food cue processing in humans. However, there is little consistency of the functional magnetic resonance imaging (fMRI) results across studies. Here, we tested the hypothesis that this variability across studies might – at least in part – be caused by the different tasks employed. In particular, we assessed directly the influence of task set on brain responses to food stimuli with fMRI using two tasks (colour vs. edibility judgement, between‐subjects design). When participants judged colour, the left insula, the left inferior parietal lobule, occipital areas, the left orbitofrontal cortex and other frontal areas expressed enhanced fMRI responses to food relative to non‐food pictures. However, when judging edibility, enhanced fMRI responses to food pictures were observed in the superior and middle frontal gyrus and in medial frontal areas including the pregenual anterior cingulate cortex and ventromedial prefrontal cortex. This pattern of results indicates that task sets can significantly alter the neural underpinnings of food cue processing. We propose that judging low‐level visual stimulus characteristics – such as colour – triggers stimulus‐related representations in the visual and even in gustatory cortex (insula), whereas discriminating abstract stimulus categories activates higher order representations in both the anterior cingulate and prefrontal cortex. Hum Brain Mapp 38:2897–2912, 2017. © 2017 Wiley Periodicals, Inc.     

偏头痛与静息态脑功能连接研究

目的本文研究采用静息态功能磁共振成像(rfMRI)技术描述偏头痛患者静息态脑功能连接改变,为探索偏头痛的发病机制提供影像学资料。方法收集16例偏头痛患者与16例健康对照,采集rfMRI成像,计算低频振幅,找出感兴趣区做功能连接进行统计分析。结果偏头痛患者左侧岛叶、左侧额下回低频振幅显著低于对照组,右侧视觉皮质低频振幅显著高于对照组;以左侧额下回、右侧枕中回为感兴趣区,发现左侧额下回与脑干之间的功能连接增强,与双侧枕叶之间的功能连接减弱;右侧枕中回与双侧楔前叶延伸至扣带回中部区域之间的功能连接增强,与双侧中央前回、双侧缘上回、双侧颞上回及双侧额下回之间的功能连接减弱。结论偏头痛患者无头痛发作时神经元活动强度改变,大脑功能连接异常,这导致大脑整合信息过程改变,并与偏头痛发病相关。     

Altered Amygdala Connectivity Within the Social Brain in Schizophrenia

Background: Impairments in social cognition have been described in schizophrenia and relate to core symptoms of the disorder. Social cognition is subserved by a network of brain regions, many of which have been implicated in schizophrenia. We hypothesized that deficits in connectivity between components of this social brain network may underlie the social cognition impairments seen in the disorder. Methods: We investigated brain activation and connectivity in a group of individuals with schizophrenia making social judgments of approachability from faces (n = 20), compared with a group of matched healthy volunteers (n = 24), using functional magnetic resonance imaging. Effective connectivity from the amygdala was estimated using the psychophysiological interaction approach. Results: While making approachability judgments, healthy participants recruited a network of social brain regions including amygdala, fusiform gyrus, cerebellum, and inferior frontal gyrus bilaterally and left medial prefrontal cortex. During the approachability task, healthy participants showed increased connectivity from the amygdala to the fusiform gyri, cerebellum, and left superior frontal cortex. In comparison to controls, individuals with schizophrenia overactivated the right middle frontal gyrus, superior frontal gyrus, and precuneus and had reduced connectivity between the amygdala and the insula cortex. Discussion: We report increased activation of frontal and medial parietal regions during social judgment in patients with schizophrenia, accompanied by decreased connectivity between the amygdala and insula. We suggest that the increased activation of frontal control systems and association cortex may reflect a compensatory mechanism for impaired connectivity of the amygdala with other parts of the social brain networks in schizophrenia.Key words: fMRI, social cognition, approachability, psychosis, neural, psychophysiological interaction