Antipsychotic drug effects on motor activation measured by functional magnetic resonance imaging in schizophrenic patients.

Brain function and laterality in schizophrenia were investigated by means of a simple motor task with a self-generated left-hand sequential finger opposition (SFO) using a whole-brain high-speed (100 ms per slice) functional imaging technique. Neuroleptic-na?ve, acutely ill schizophrenic patients were compared to schizophrenic patients under stable neuroleptic medication and matched controls. The goal was to evaluate both the motor function in first-episode patients and possible effects of different neuroleptic treatments on functional MRI results. Forty patients satisfying ICD 10 criteria (F20.x) for schizophrenia and sex- and age-matched healthy volunteers participated in this study. All subjects underwent fMRI examinations on a conventional 1.5 T MR unit. The primary sensorimotor cortex and the high-order supplementary motor area (SMA) were evaluated. There was a close similarity in the activation of the primary and high-order (SMA) sensorimotor areas between first-episode schizophrenic patients and controls. In contrast, a significant reduction in the overall blood oxygen level dependent (BOLD) response was seen in sensorimotor cortices (contra- and ipsilateral) in schizophrenic patients under stable medication with typical neuroleptics. This effect was not present in patients treated with atypical antipsychotics. Both antipsychotic treatments, however, led to a significant reduction in activation of the SMA region compared to controls and neuroleptic-na?ve subjects. Thus, the present study provides no evidence for the localized involvement of the primary motor cortex or the SMA as a relatively stable vulnerability marker in schizophrenia. There is, however, strong evidence that neuroleptics themselves influence fMRI activation patterns and that there are major differences between typical neuroleptics and atypical antipsychotics.     

Brain activation patterns during a selective attention test-a functional MRI study in healthy volunteers and patients with schizophrenia

Functional magnetic resonance imaging was used to compare cortical activation patterns in healthy volunteers with those in patients with schizophrenia during a modified verbal Stroop task. Healthy subjects (n=13) and patients with schizophrenia (n=13) on stable antipsychotic treatment, matched on demographic variables, were included. Patients were preselected on the basis of good performance on a selective attention test. Patients with schizophrenia showed a significantly increased pattern of activation in the left and right inferior frontal cortex and the anterior cingulate cortex. A significant negative correlation between activation of the left prefrontal cortex and accuracy in the modified Stroop test was observed for healthy controls but not schizophrenia patients. Although both groups recruited the prefrontal cortex during the modified Stroop task, for the schizophrenia patients this activation was bilateral, whereas for the controls this activation was primarily in the left hemisphere, suggesting that patients with schizophrenia recruited more prefrontal regions to perform the task with the same accuracy as healthy controls. Our findings of increased activity across multiple areas of the brain, including dorsolateral frontal cortex and anterior cingulate, in patients with schizophrenia who perform relatively well on a task of selective attention give further evidence that task performance may be a confounding factor in the interpretation of neuroimaging results.     

Ketamine alters neural processing of facial emotion recognition in healthy men: an fMRI study

Disruption of facial emotion perception occurs in neuropsychiatric disorders where the expression of emotion is dulled or blunted, for example depersonalization disorder and schizophrenia. It has been suggested that, in the clinical context of emotional blunting, there is a shift in the relative contribution of brain regions subserving cognitive and emotional processing. The non-competitive glutamate receptor antagonist ketamine produces such emotional blunting in healthy subjects. Therefore, we hypothesised that in healthy subjects ketamine would elicit neural responses to emotional stimuli which mimicked those reported in depersonalization disorder and schizophrenia. Thus, we predicted that ketamine would produce reduced activity in limbic and visual brain regions involved in emotion processing, and increased activity in dorsal regions of the prefrontal cortex and cingulate gyrus, both associated with cognitive processing and, putatively, with emotion regulation. Measuring BOLD signal change in fMRI, we examined the neural correlates of ketamine-induced emotional blunting in eight young right-handed healthy men receiving an infusion of ketamine or saline placebo while viewing alternating 30 s blocks of faces displaying fear versus neutral expressions. The normal pattern of neural response occurred in limbic and visual cortex to fearful faces during the placebo infusion. Ketamine abolished this: significant BOLD signal change was demonstrated only in left visual cortex. However, with ketamine, neural responses were demonstrated to neutral expressions in visual cortex, cerebellum and left posterior cingulate gyrus. Emotional blunting may be associated with reduced limbic responses to emotional stimuli and a relative increase in the visual cortical response to neutral stimuli.     

An fMRI study of theory of mind in schizophrenic patients with "passivity" symptoms

Several studies have shown that patients with schizophrenia underactivate brain regions involved in theory of mind relative to controls during functional brain imaging. However, in most studies the samples were fairly heterogeneous in terms of clinical symptomatology. We examined a group of nine patients with first episode or recurrent episodes, who clinically presented with predominant "passivity" symptoms such as third-person auditory hallucinations or delusion of control, using a cartoon-based theory of mind task and compared activation patterns with a group of 13 healthy controls. All patients responded well to antipsychotic treatment and were only mildly symptomatic at the time of testing. The patient group showed significantly less activation of the right anterior cingulate cortex (ACC) and right insula compared with controls, but greater activation in dorsal areas of the medial prefrontal cortex, right temporal areas and left temporo-parietal junction. Patients with schizophrenia with predominant "passivity" symptoms and good response to antipsychotic treatment show a markedly diverging pattern of brain activation during theory of mind task performance compared with healthy controls. These findings suggest abnormal activation of those brain areas involved in the evaluation of self-reference during mental state attribution.     

Effects of psychological stress on the cerebral processing of visceral stimuli in healthy women

Abstract  The aim of the study was to analyse effects of psychological stress on the neural processing of visceral stimuli in healthy women. The brain functional magnetic resonance imaging blood oxygen level-dependent response to non-painful and painful rectal distensions was recorded from 14 healthy women during acute psychological stress and a control condition. Acute stress was induced with a modified public speaking stress paradigm. State anxiety was assessed with the State-Trait-Anxiety Inventory; chronic stress was measured with the Perceived Stress Questionnaire. During non-painful distensions, activation was observed in the right posterior insular cortex (IC) and right S1. Painful stimuli revealed activation of the bilateral anterior IC, right S1, and right pregenual anterior cingulate cortex. Chronic stress score was correlated with activation of the bilateral amygdala, right posterior IC (post-IC), left periaqueductal grey (PAG), and right dorsal posterior cingulate gyrus (dPCC) during non-painful stimulation, and with activation of the right post-IC, right PAG, left thalamus (THA), and right dPCC during painful distensions. During acute stress, state anxiety was significantly higher and the acute stress – control contrast revealed activation of the right dPCC, left THA and right S1 during painful stimulation. This is the first study to demonstrate effects of acute stress on cerebral activation patterns during visceral pain in healthy women. Together with our finding that chronic stress was correlated wit the neural response to visceral stimuli, these results provide a framework for further studies addressing the role of chronic stress and emotional disturbances in the pathophysiology of visceral hyperalgesia.     

Event-related fMRI of frontotemporal activity during word encoding and recognition in schizophrenia

OBJECTIVE: Neuropsychological studies have demonstrated verbal episodic memory deficits in schizophrenia during word encoding and retrieval. This study examined neural substrates of memory in an analysis that controlled for successful retrieval. METHOD: Event-related blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was used to measure brain activation during word encoding and recognition in 14 patients with schizophrenia and 15 healthy comparison subjects. An unbiased multiple linear regression procedure was used to model the BOLD response, and task effects were detected by contrasting the signal before and after stimulus onset. RESULTS: Patients attended during encoding and had unimpaired reaction times and normal response biases during recognition, but they had lower recognition discriminability scores, compared with the healthy subjects. Analysis of contrasts was restricted to correct items. Previous findings of a deficit in bilateral prefrontal cortex activation during encoding in patients were reproduced, but patients showed greater parahippocampal activation rather than deficits in temporal lobe activation. During recognition, left dorsolateral prefrontal cortex activation was lower in the patients and right anterior prefrontal cortex activation was preserved, as in the authors' previous study using positron emission tomography. Successful retrieval was associated with greater right dorsolateral prefrontal cortex activation in the comparison subjects, whereas orbitofrontal, superior frontal, mesial temporal, middle temporal, and inferior parietal regions were more active in the patients during successful retrieval. CONCLUSIONS: The pattern of prefrontal cortex underactivation and parahippocampal overactivation in the patients suggests that functional connectivity of dorsolateral prefrontal and temporal-limbic structures is disrupted by schizophrenia. This disruption may be reflected in the memory strategies of patients with schizophrenia, which include reliance on rote rehearsal rather than associative semantic processing.     

Neural substrates of olfactory processing in schizophrenia patients and their healthy relatives

Odorants represent powerful stimuli capable of eliciting various emotional responses. In schizophrenia patients and their non-affected relatives, olfactory and emotional functions are impaired, revealing a familial influence on these deficits. We aimed at determining the neural basis of emotional olfactory dysfunctions using odors of different emotional valence for mood induction and functional magnetic resonance imaging (fMRI) by comparing 13 schizophrenia patients, their non-affected brothers and 26 matched healthy controls. Blood-oxygen-level-dependent (BOLD) effects and subjective mood changes were assessed during negative (rotten yeast), positive (vanilla) and neutral (ambient air) olfactory stimulation. Group comparisons of brain activation were performed in regions of interest. Subjective ratings were comparable between groups and indicated successful mood induction. However, during stimulation with the negative odor, hypofunctional activity emerged in regions of the right frontal and temporal cortex in the patients. A familial influence in the neural substrates of negative olfactory dysfunction was indicated by a similar reduced frontal brain activity in relatives. Dysfunctions therefore appeared to be located in regions involved in higher cognitive processes associated with olfaction. No familial influences were indicated for cerebral dysfunctions during positive olfactory stimulation. Results point to a differentiation between trait and state components in cerebral dysfunctions during emotional olfactory processing in schizophrenia.     

Brain activation during eye gaze discrimination in stable schizophrenia

OBJECTIVE: Earlier studies described gaze discrimination impairment in schizophrenia. The purpose of this study was to compare gaze discrimination abilities and associated brain activation in persons with stable schizophrenia and matched controls. METHODS: 13 schizophrenia and 12 healthy participants underwent a gaze discrimination task with face stimuli rotated at 0, 4 and 8 degrees deviation. During fMRI with BOLD imaging, subjects were asked to identify whether a face was making eye contact. Subject-level parameter estimates for BOLD signal change were entered into an orientation by group mixed effect repeated measures ANOVA. RESULTS: Gaze discrimination performance did not differ between groups. Patients showed decreased activation in areas of bilateral inferior frontal and occipital areas, and select temporo-limbic regions, including amygdala. Groups differed by activation patterns according to gaze deviation. In controls, faces with 4 degrees deviation produced higher activation in frontal and temporal regions. In patients, 0 degrees deviation produced increased activation in amygdala and areas of temporal neocortex. CONCLUSIONS: Despite similar gaze discrimination abilities, schizophrenia patients exhibit decreased brain activation in areas associated with executive, emotional and visual processing. Controls exhibited increased activation associated with the more difficult task in select frontal and temporal regions. Patients exhibited increased activation associated with direct gaze in temporal regions, which may relate to common symptoms.     

Brain dysfunctions during facial discrimination in schizophrenia: Selective association to affect decoding

Schizophrenia patients exhibit impaired facial affect perception, yet the exact nature of this impairment remains unclear. We investigated neural activity related to processing facial emotional and non-emotional information and complex images in 12 schizophrenia patients and 15 healthy controls using functional magnetic resonance imaging. All subjects performed a facial information processing task with three conditions: matching facial emotion, matching facial identity, and matching complex visual patterns. Patients and controls showed comparable behavioral performance in all task conditions. The neural activation patterns in schizophrenia patients and healthy controls were distinctly different while processing affect-related facial information but not other non-emotional facial features. During emotion matching, orbital frontal cortex and left amydala activations were found in controls but not in patients. When comparing emotion versus identity matching, controls activated the fusiform and middle temporal gyri, left superior temporal gyrus, and right inferior and middle frontal gyrus, whereas schizophrenia patients only activated the middle and inferior frontal gyri, the frontal operculi and the right insular cortex. Our findings suggest that schizophrenia patients and healthy controls may utilize different neural networks when processing facial emotional information.     

Self-perspective leads to increased activation of pain processing brain regions in fibromyalgia

BackgroundDysfunction of central nervous pain processing is assumed to play a key role in primary fibromyalgia (FM) syndrome. This pilot study examined differences of pain processing associated with adopting different interpersonal perspectives.MethodsEleven FM patients and 11 healthy controls (HC) were scanned with functional magnetic resonance imaging. Participants were trained to take either a self-perspective or another person's perspective when viewing the visual stimuli. Stimuli showed body parts in painful situations of varying intensity (low, medium, and high) and visually similar but neutral situations.ResultsPatients with FM showed a higher increase in blood oxygen level dependent (BOLD) response, particularly in the supplementary motor area (SMA). All pain-related regions of interest (anterior insula, somatosensory cortices, anterior cingulate cortex, and SMA) showed stronger modulation of BOLD responses in FM patients in the self-perspective. In contrast to pain processing regions, perspective-related regions (e.g. temporoparietal junction) did not differ between FM and HC.ConclusionsThe stronger response of all four pain processing cerebral regions during self-perspective is discussed in the light of disturbed bottom-up processing. Furthermore, the results confirm earlier reports of augmented pain processing in FM, and provide evidence for sensitization of central nervous pain processing.     

Common neural systems for contact heat and laser pain stimulation reveal higher-level pain processing

Our current knowledge of pain-related neuronal responses is largely based on experimental pain studies using contact heat or nontactile laser painful stimulation. Both stimuli evoke pain, yet they differ considerably in their physical and perceptual properties. In sensory cortex, cerebral responses to either stimulus should therefore substantially differ. However, given that both stimuli evoke pain, we hypothesized that at a certain subset of cortical regions the different physical properties of the stimuli become less important and are therefore activated by both stimuli. In contrast, regions with clearly dissociable activity may belong to "lower-level" pain processing mechanisms depending on the physical properties of the administered stimuli. We used functional magnetic resonance (fMRI) to intraindividually compare pain-related activation patterns between laser and contact heat stimulation using four different intensities of laser and contact heat stimuli. Common and dissociable neural responses were identified by correlating perceived pain intensities with blood oxygenation level dependent (BOLD) signal changes. Only neuronal responses to stimuli that were perceived as painful were analyzed. Pain-related BOLD signal increases independent of stimulus modality were detected in the anterior insula, anterior cingulate cortex, medial secondary somatosensory cortex, and the prefrontal cortex. These similarities are likely to reflect higher-level pain processing, which is largely independent of the single physical parameters that determine the painful nature of the stimuli.     

No amygdala attenuation in schizophrenic patients treated with atypical antipsychotics

Functional magnetic resonance (fMRI) imaging was used to measure amygdala activation in an emotional valence discrimination task in clinically stable patients with schizophrenia treated with atypical antipsychotics and healthy controls. No difference was detected between patients with schizophrenia and controls.     

Cerebral responses to pain in patients with atypical facial pain measured by positron emission tomography.

The localised PET cerebral correlates of the painful experience in the normal human brain have previously been demonstrated. This study examined whether these responses are different in patients with chronic atypical facial pain. The regional cerebral responses to non-painful and painful thermal stimuli in six female patients with atypical facial pain and six matched female controls were studied by taking serial measurements of regional blood flow by PET. Both groups displayed highly significant differences in responses to painful heat compared with non-painful heat in the thalamus, anterior cingulate cortex (area 24), lentiform nucleus, insula, and prefrontal cortex. These structures are closely related to the "medial pain system". The atypical facial pain group had increased blood flow in the anterior cingulate cortex and decreased blood flow in the prefrontal cortex. These findings show the importance of the anterior cingulate cortex and the reciprocal (possibly inhibitory) connections with the prefrontal cortex in the processing of pain in patients with this disorder. A hypothesis is proposed to explain the mechanisms of cognitive and pharmacological manipulation of these pain processes.     

Investigation of anatomical thalamo-cortical connectivity and FMRI activation in schizophrenia

The purpose of this study was to examine measures of anatomical connectivity between the thalamus and lateral prefrontal cortex (LPFC) in schizophrenia and to assess their functional implications. We measured thalamocortical connectivity with diffusion tensor imaging (DTI) and probabilistic tractography in 15 patients with schizophrenia and 22 age- and sex-matched controls. The relationship between thalamocortical connectivity and prefrontal cortical blood-oxygenation-level-dependent (BOLD) functional activity as well as behavioral performance during working memory was examined in a subsample of 9 patients and 18 controls. Compared with controls, schizophrenia patients showed reduced total connectivity of the thalamus to only one of six cortical regions, the LPFC. The size of the thalamic region with at least 25% of model fibers reaching the LPFC was also reduced in patients compared with controls. The total thalamocortical connectivity to the LPFC predicted working memory task performance and also correlated with LPFC BOLD activation. Notably, the correlation with BOLD activation was accentuated in patients as compared with controls in the ventral LPFC. These results suggest that thalamocortical connectivity to the LPFC is altered in schizophrenia with functional consequences on working memory processing in LPFC.     

Phase-specific brain change of spatial working memory processing in genetic and ultra-high risk groups of schizophrenia

Spatial working memory (WM) processing has 3 distinct phases: encoding, maintenance, and retrieval and its dysfunction is a core feature in schizophrenia. We examined phase-specific brain activations associated with spatial WM in first-degree relatives of schizophrenia (genetic high risk, GHR), ultra-high risk (UHR) subjects, patients with schizophrenia, and healthy controls. We used an event-related functional magnetic resonance imaging in 17 GHR subjects, 21 UHR subjects, 15 clinically stable patients with schizophrenia and 16 healthy controls, while subjects were performing a spatial delayed-response task. During the encoding phase, the GHR group showed increased activation in the fronto-parietal regions, whereas the UHR and schizophrenia groups showed significantly less activation in these regions than did the healthy control group. Especially, frontal activation was strongest in GHR subjects, followed by healthy controls, and occurred to a lesser degree in the UHR group, with the least activation occurring in the schizophrenia group. During the maintenance phase, the thalamus showed a differential activation, similar to frontal activation pattern during the encoding phase. During the retrieval phase, no prominent differential activations were found. Increased activations were observed in the superior temporal gyrus during the encoding and maintenance phases in the GHR, UHR, and schizophrenia groups relative to healthy controls. Our findings suggest that functional deficits associated with spatial WM processing emerge in the UHR before the onset of schizophrenia and compensatory neural processes exist in the GHR with genetic liability to schizophrenia.     

Distinct neural responses used to gain insight into hallucinatory perception in patients with schizophrenia

ObjectiveMost patients with schizophrenia suffer from various types of hallucinations, which commonly produce distress, functional disability or behavioral dyscontrol. The neural process of adapting to hallucinations in patients with schizophrenia remains unknown.MethodsFunctional magnetic resonance imaging (MRI) responses to an unusual threatening visual stimulus designed to simulate a hallucinatory experience were compared between 16 patients with schizophrenia and 17 healthy controls. Linear and quadratic repetition-variant as well as repetition-invariant responses to the stimulus were compared between the two groups.ResultsRepetition-invariant responses were similar between patients with schizophrenia and healthy controls. Patients with schizophrenia exhibited a linear activation pattern in the anterior cingulate, whereas healthy controls exhibited a parabolic activation pattern in the anterior prefrontal cortex, occipito-temporal junction and amygdala.ConclusionsThese results provide us with a better understanding of the neural processes involved in gaining insight into unreality. Patients with schizophrenia may use a salience-related region instead of reality monitoring-related regions to react to the unusual stimuli, and this peculiarity of the neural processes may be related to vulnerability to psychosis.     

Neural correlates of emotional recognition memory in schizophrenia: effects of valence and arousal

Schizophrenia patients are often impaired in their memory for emotional events compared with healthy subjects. Investigations of the neural correlates of emotional memory in schizophrenia patients are scarce in the literature. The present study aimed to compare cerebral activations in schizophrenia patients and healthy controls during memory retrieval of emotional images that varied in both valence and arousal. In a study with functional magnetic resonance imaging, 37 schizophrenia patients were compared with 37 healthy participants while performing a yes/no recognition paradigm with positive, negative (differing in arousal intensity) and neutral images. Schizophrenia patients performed worse than healthy controls in all experimental conditions. They showed less cerebral activation in limbic and prefrontal regions than controls during retrieval of negatively valenced stimuli, but had a similar pattern of brain activation compared with controls during retrieval of positively valenced stimuli (particularly in the high arousal condition) in the cerebellum, temporal lobe and prefrontal cortex. Both groups demonstrated increased brain activations in the high relative to low arousing conditions. Our results suggest atypical brain function during retrieval of negative pictures, but intact functional circuitry of positive affect during episodic memory retrieval in schizophrenia patients. The arousal data revealed that schizophrenia patients closely resemble the control group at both the behavioral and neurofunctional level.     

Influence of antipsychotic medication on pain perception in schizophrenia

A number of clinical observations indicate that pain processing might be disturbed in psychotic disorders such as schizophrenia. Only a few studies have investigated pain perception in schizophrenia. The main objective of this study was the investigation of thresholds of warmth perception (WP), thermal pain onset (TPO) and thermal pain tolerance (TPT) in acute schizophrenic patients and the influence of antipsychotic medication on the patients' responses. We investigated 23 schizophrenic subjects who had been not received antipsychotic treatment for 8 weeks, and we then reassessed them 3 days later after the introduction of neuroleptics. Acute symptoms of schizophrenia were measured using the Scales for the Assessment of Positive and Negative Symptoms. Thresholds were determined by a contact thermode on both volar wrists. Schizophrenic patients showed significantly increased thresholds of WP and TPO relative to healthy controls. Antipsychotics did not alter pain thresholds. We found no correlation between pain perception and psychometric scales. Our findings demonstrate altered warmth and heat pain perception in acute schizophrenia. We believe that our findings can be attributed to information-processing abnormalities of the disorder and that they are not specific to pain processing, per se, since both WP and TPO were significantly different. Future studies should evaluate attentional deficits in schizophrenia in relation to pain perception.     

Medial frontal hyperactivity in reality distortion.

BACKGROUND: Schizophrenia/schizoaffective disorder involves reality distortion (RD), which impairs the ability to process socioemotional information. Because this psychological capacity maps to the medial prefrontal cortex (MPFC) and schizophrenia involves abnormal MPFC function, we tested the hypothesis that treated schizophrenic/schizoaffective patients with persistent RD (RD+) would exhibit greater MPFC dysfunction than patients without significant RD (RD-). The amygdala interacts with MPFC, also carries out socioemotional processing, and has been implicated in schizophrenia; thus, we also tested the hypothesis that patients would exhibit aberrant amygdala activity. METHODS: Eleven RD+ patients, 12 RD- patients, and 15 healthy control subjects (HC) viewed emotionally salient pictures with neutral, aversive, and positive content during the acquisition of blood oxygenation level-dependent (BOLD) sensitive functional magnetic resonance imaging. RESULTS: All groups had similar behavioral responses to the pictures. The RD+ subjects had greater BOLD responses (compared with the RD- and HC groups) to the aversive pictures in the anterior MPFC. Both patient groups showed reduced activation in MPFC and the left amygdala (compared with HC) for neutral pictures (compared with blank condition), although this effect could be explained by medication. CONCLUSIONS: Reality distortion is associated with hyperactivity of the MPFC in schizophrenic/schizoaffective patients whose symptoms persist in spite of antipsychotic treatment.     

Neural bases for impaired social cognition in schizophrenia and autism spectrum disorders

Schizophrenia and autism both feature significant impairments in social cognition and social functioning, but the specificity and mechanisms of these deficits remain unknown. Recent research suggests that social cognitive deficits in both disorders may arise from dysfunctions in the neural systems that underlie social cognition. We explored the neural activation of discrete brain regions implicated in social cognitive and face processing in schizophrenia subgroups and autism spectrum disorders during complex social judgments of faces. Twelve individuals with autism spectrum disorders (ASD), 12 paranoid individuals with schizophrenia (P-SCZ), 12 non-paranoid individuals with schizophrenia (NP-SCZ), and 12 non-clinical healthy controls participated in this cross sectional study. Neural activation, as indexed by blood oxygenation level dependent (BOLD) contrast, was measured in a priori regions of interest while individuals rated faces for trustworthiness. All groups showed significant activation of a social cognitive network including the amygdala, fusiform face area (FFA), superior temporal sulcus (STS), and ventrolateral prefrontal cortex (VLPFC) while completing a task of complex social cognition (i.e. trustworthiness judgments). ASD and P-SCZ individuals showed significantly reduced neural activation in the right amygdala, FFA, and left VLPFC as compared to controls and in the left VLPFC as compared to NP-SCZ individuals during this task. These findings lend support to models hypothesizing well-defined neural substrates of social cognition and suggest a specific neural mechanism that may underlie social cognitive impairments in both autism and paranoid schizophrenia.