Clothing Aesthetics: Consistent Colour Choices to Match Fair and Tanned Skin Tones.

Fashion stylists advise clothing colours according to personal categories that depend on skin, hair and eye colour. These categories are not defined scientifically, and advised colours are inconsistent. Such caveats may explain the lack of formal tests of clothing colour aesthetics. We assessed whether observers preferred clothing colours that are linked to variation in melanin levels among White women. For this, we presented 12 women's faces: six with fair skin (relatively lower in melanin) and six with tanned skin (relatively higher in melanin). Across two experiments, observers (N = 96 and 75) selected the colour (hue and saturation or hue and value) of simulated clothing that most suited the skin tone of each face. Observers showed strong preferences for red and blue hues, and in addition favoured 'cool' blue hues to match fair skin and 'warm' orange/red hues to match tanned skin. This finding suggests that skin tone can determine colour preferences for clothes.

The neuropsychology of first impressions: Evidence from Huntington's disease.

Impairments of emotion recognition have been widely documented in Huntington's disease (HD), but little is known concerning how these relate to other aspects of social cognition, including first impressions of traits such as trustworthiness and dominance. Here, we introduce a novel and sensitive method to investigate the ability to evaluate trustworthiness and dominance from facial appearance, with control tasks measuring ability to perceive differences between comparable stimuli. We used this new method together with standard tests of face perception to investigate social cognition in HD. We found that a subgroup of people with HD was impaired at perceiving trustworthiness and dominance, and that perceiving trustworthiness and dominance were correlated with impaired facial expression recognition. In addition, we used diffusion tensor imaging (DTI) to provisionally identify candidate brain regions associated with social cognition by contrasting regional functional anisotropy (FA) measures between subgroups of HD participants showing normal or impaired perception of trustworthiness and dominance, and by correlating these regional brain abnormalities with behavioural performance on tests of emotion recognition. In this way we show for the first time alterations in perception of trustworthiness and dominance in people with HD and link these to regions which may map the boundaries of the social brain. The pattern of breakdown seen in this neurodegenerative disease can thus be used to explore potential inter-relationships between different components of social cognition.

A causal role for the anterior mid-cingulate cortex in negative affect and cognitive control.

Converging evidence has linked the anterior mid-cingulate cortex to negative affect, pain and cognitive control. It has previously been proposed that this region uses information about punishment to control aversively motivated actions. Studies on the effects of lesions allow causal inferences about brain function; however, naturally occurring lesions in the anterior mid-cingulate cortex are rare. In two studies we therefore recruited 94 volunteers, comprising 15 patients with treatment-resistant depression who had received bilateral anterior cingulotomy, which consists of lesions made within the anterior mid-cingulate cortex, 20 patients with treatment-resistant depression who had not received surgery and 59 healthy control subjects. Using the Ekman 60 faces paradigm and two Stroop paradigms, we tested the hypothesis that patients who received anterior cingulotomy were impaired in recognizing negative facial affect expressions but not positive or neutral facial expressions, and impaired in Stroop cognitive control, with larger lesions being associated with more impairment. Consistent with this hypothesis, we found that larger volume lesions predicted more impairment in recognizing fear, disgust and anger, and no impairment in recognizing facial expressions of surprise or happiness. However, we found no impairment in recognizing expressions of sadness. Also consistent with the hypothesis, we found that larger volume lesions predicted impaired Stroop cognitive control. Notably, this relationship was only present when anterior mid-cingulate cortex lesion volume was defined as the overlap between cingulotomy lesion volume and Shackman's meta-analysis-derived binary masks for negative affect and cognitive control. Given substantial evidence from healthy subjects that the anterior mid-cingulate cortex is part of a network associated with the experience of negative affect and pain, engaging cognitive control processes for optimizing behaviour in the presence of such stimuli, our findings support the assertion that this region has a causal role in these processes. While the clinical justification for cingulotomy is empirical and not theoretical, it is plausible that lesions within a brain region associated with the subjective experience of negative affect and pain may be therapeutic for patients with otherwise intractable mood, anxiety and pain syndromes.

Short-interval observational data to inform clinical trial design in Huntington's disease.

OBJECTIVES: To evaluate candidate outcomes for disease-modifying trials in Huntington's disease (HD) over 6-month, 9-month and 15-month intervals, across multiple domains. To present guidelines on rapid efficacy readouts for disease-modifying trials. METHODS: 40 controls and 61 patients with HD, recruited from four EU sites, underwent 3 T MRI and standard clinical and cognitive assessments at baseline, 6 and 15 months. Neuroimaging analysis included global and regional change in macrostructure (atrophy and cortical thinning), and microstructure (diffusion metrics). The main outcome was longitudinal effect size (ES) for each outcome. Such ESs can be used to calculate sample-size requirements for clinical trials for hypothesised treatment efficacies. RESULTS: Longitudinal changes in macrostructural neuroimaging measures such as caudate atrophy and ventricular expansion were significantly larger in HD than controls, giving rise to consistently large ES over the 6-month, 9-month and 15-month intervals. Analogous ESs for cortical metrics were smaller with wide CIs. Microstructural (diffusion) neuroimaging metrics ESs were also typically smaller over the shorter intervals, although caudate diffusivity metrics performed strongly over 9 and 15 months. Clinical and cognitive outcomes exhibited small longitudinal ESs, particularly over 6-month and 9-month intervals, with wide CIs, indicating a lack of precision. CONCLUSIONS: To exploit the potential power of specific neuroimaging measures such as caudate atrophy in disease-modifying trials, we propose their use as (1) initial short-term readouts in early phase/proof-of-concept studies over 6 or 9 months, and (2) secondary end points in efficacy studies over longer periods such as 15 months.

Longitudinal Diffusion Tensor Imaging Shows Progressive Changes in White Matter in Huntington's Disease.

BACKGROUND: Huntington's disease is marked by progressive neuroanatomical changes, assumed to underlie the development of the disease's characteristic symptoms. Previous work has demonstrated longitudinal macrostructural white-matter atrophy, with some evidence of microstructural change focused in the corpus callosum. OBJECTIVE: To more accurately characterise longitudinal patterns, we examined white matter microstructural change using Diffusion Tensor Imaging (DTI) data from three timepoints over a 15 month period. METHODS: In 48 early-stage HD patients and 36 controls from the multi-site PADDINGTON project, diffusion tensor imaging (DTI) was employed to measure changes in fractional anisotropy (FA) and axial (AD) and radial diffusivity (RD) in 24 white matter regions-of-interest (ROIs). RESULTS: Cross-sectional analysis indicated widespread baseline between-group differences, with significantly decreased FA and increased AD and RD found in HD patients across multiple ROIs. Longitudinal rates of change differed significantly between HD patients and controls in the genu and body of corpus callosum, corona radiata and anterior limb of internal capsule. Change in RD in the body of the corpus callosum was significantly associated with baseline disease burden, but other clinical associations were not significant. CONCLUSIONS: We detected subtle longitudinal white matter changes in early HD patients. Progressive white matter abnormalities in HD may not be uniform throughout the brain, with some areas remaining static in the early symptomatic phase. Longer assessment periods across disease stages will help map this progressive trajectory.

Inconsistent emotion recognition deficits across stimulus modalities in Huntington׳s disease.

BACKGROUND: Recognition of negative emotions is impaired in Huntington׳s Disease (HD). It is unclear whether these emotion-specific problems are driven by dissociable cognitive deficits, emotion complexity, test cue difficulty, or visuoperceptual impairments. This study set out to further characterise emotion recognition in HD by comparing patterns of deficits across stimulus modalities; notably including for the first time in HD, the more ecologically and clinically relevant modality of film clips portraying dynamic facial expressions. METHODS: Fifteen early HD and 17 control participants were tested on emotion recognition from static facial photographs, non-verbal vocal expressions and one second dynamic film clips, all depicting different emotions. RESULTS: Statistically significant evidence of impairment of anger, disgust and fear recognition was seen in HD participants compared with healthy controls across multiple stimulus modalities. The extent of the impairment, as measured by the difference in the number of errors made between HD participants and controls, differed according to the combination of emotion and modality (p=0.013, interaction test). The largest between-group difference was seen in the recognition of anger from film clips. CONCLUSIONS: Consistent with previous reports, anger, disgust and fear were the most poorly recognised emotions by the HD group. This impairment did not appear to be due to task demands or expression complexity as the pattern of between-group differences did not correspond to the pattern of errors made by either group; implicating emotion-specific cognitive processing pathology. There was however evidence that the extent of emotion recognition deficits significantly differed between stimulus modalities. The implications in terms of designing future tests of emotion recognition and care giving are discussed.

Impact of the control for corrupted diffusion tensor imaging data in comparisons at the group level: an application in Huntington disease.

BACKGROUND: Corrupted gradient directions (GD) in diffusion weighted images may seriously affect reliability of diffusion tensor imaging (DTI)-based comparisons at the group level. In the present study we employed a quality control (QC) algorithm to eliminate corrupted gradient directions from DTI data. We then assessed effects of this procedure on comparisons between Huntington disease (HD) subjects and controls at the group level. METHODS: Sixty-one HD patients in early stages and forty matched healthy controls were studied in a longitudinal design (baseline and two follow-ups at three time points over 15 months), in a multicenter setting with similar acquisition protocols on four different MR scanners at four European study sites. A QC algorithm was used to identify corrupted GD in DTI data sets. Differences in fractional anisotropy (FA) maps at the group level with and without elimination of corrupted GD were analyzed. RESULTS: The elimination of corrupted GD had an impact on individual FA maps as well as on cross-sectional group comparisons between HD subjects and controls. Following application of the QC algorithm, less small clusters of FA changes were observed, compared to the analysis without QC. However, the main pattern of regional reductions and increases in FA values with and without QC-based elimination of corrupted GD was unchanged. CONCLUSION: An impact on the result patterns of the comparison of FA maps between HD subjects and controls was observed depending on whether QC-based elimination of corrupted GD was performed. QC-based elimination of corrupted GD in DTI scans reduces the risk of type I and type II errors in cross-sectional group comparison of FA maps contributing to an increase in reliability and stability of group comparisons.

Visual system integrity and cognition in early Huntington's disease.

Posterior cortical volume changes and abnormal visuomotor performance are present in patients with Huntington's disease (HD). However, it is unclear whether posterior cortical volume loss contributes to abnormal neural activity, and whether activity changes predict cognitive dysfunction. Using magnetic resonance imaging (MRI), we investigated brain structure and visual network activity at rest in patients with early HD (n = 20) and healthy controls (n = 20). The symbol digit modalities test (SDMT) and subtests of the Visual Object and Space Perception Battery were completed offline. For functional MRI data, a group independent component analysis was used. Voxel-based morphometry was employed to assess regional brain atrophy, and 'biological parametric mapping' analyses were included to investigate the impact of atrophy on neural activity. Patients showed significantly worse visuomotor and visual object performance than controls. Structural analyses confirmed occipitotemporal atrophy. In patients and controls, two spatiotemporally distinct visual systems were identified. Patients showed decreased activity in the left fusiform cortex, and increased left cerebellar activity. These findings remained stable after correction for brain atrophy. Lower fusiform cortex activity was associated with lower SDMT performance and with higher disease burden scores. These associations were absent when cerebellar function was related to task performance and disease burden. The results of this study suggest that regionally specific functional abnormalities of the visual system can account for the worse visuomotor cognition in HD patients. However, occipital volume changes cannot sufficiently explain abnormal neural function in these patients.

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.

Social judgement in borderline personality disorder.

BACKGROUND: Borderline personality disorder (BPD) is a common and serious mental illness, associated with a high risk of suicide and self harm. Those with a diagnosis of BPD often display difficulties with social interaction and struggle to form and maintain interpersonal relationships. Here we investigated the ability of participants with BPD to make social inferences from faces. METHOD: 20 participants with BPD and 21 healthy controls were shown a series of faces and asked to judge these according to one of six characteristics (age, distinctiveness, attractiveness, intelligence, approachability, trustworthiness). The number and direction of errors made (compared to population norms) were recorded for analysis. RESULTS: Participants with a diagnosis of BPD displayed significant impairments in making judgements from faces. In particular, the BPD Group judged faces as less approachable and less trustworthy than controls. Furthermore, within the BPD Group there was a correlation between scores on the Childhood Trauma Questionnaire (CTQ) and bias towards judging faces as unapproachable. CONCLUSION: Individuals with a diagnosis of BPD have difficulty making appropriate social judgements about others from their faces. Judging more faces as unapproachable and untrustworthy indicates that this group may have a heightened sensitivity to perceiving potential threat, and this should be considered in clinical management and treatment.

Evaluating multicenter DTI data in Huntington's disease on site specific effects: An ex post facto approach.

PURPOSE: Assessment of the feasibility to average diffusion tensor imaging (DTI) metrics of MRI data acquired in the course of a multicenter study. MATERIALS AND METHODS: Sixty-one early stage Huntington's disease patients and forty healthy controls were studied using four different MR scanners at four European sites with acquisition protocols as close as possible to a given standard protocol. The potential and feasibility of averaging data acquired at different sites was evaluated quantitatively by region-of-interest (ROI) based statistical comparisons of coefficients of variation (CV) across centers, as well as by testing for significant group-by-center differences on averaged fractional anisotropy (FA) values between patients and controls. In addition, a whole-brain based statistical between-group comparison was performed using FA maps. RESULTS: The ex post facto statistical evaluation of CV and FA-values in a priori defined ROIs showed no differences between sites above chance indicating that data were not systematically biased by center specific factors. CONCLUSION: Averaging FA-maps from DTI data acquired at different study sites and different MR scanner types does not appear to be systematically biased. A suitable recipe for testing on the possibility to pool multicenter DTI data is provided to permit averaging of DTI-derived metrics to differentiate patients from healthy controls at a larger scale.

Aesthetic and incentive salience of cute infant faces: studies of observer sex, oral contraception and menstrual cycle.

Infant cuteness can influence adult-infant interaction and has been shown to activate reward centres in the brain. In a previous study, we found men and women to be differentially sensitive to small differences in infant facial cuteness, with reproductive hormone status as the potential underlying cause. It is unclear, however, whether reproductive hormone status impacts on the aesthetic and incentive salience of infant faces. To address this question, we conducted two interlinked studies. We used static images of the same smiling and neutral-looking infant faces in both a rating task, in which participants had to rate the cuteness of infant faces (aesthetic salience - 'liking'), and a key-press task, in which participants could prolong or shorten viewing time of infant faces by rapid alternating key-presses (incentive salience - 'wanting'). In a first study, we compared the performance of men, women who are taking oral contraceptives, and regularly cycling women. In this study, we found a significant correlation between cuteness ratings within and between groups, which implies that participants had the same concept of cuteness. Cuteness ratings and effort to look at faces was linked regardless of sex and reproductive hormone status, in that cute faces were looked at for longer than less cute faces. A happy facial expression contributed only marginally to the incentive salience of the face. To explore the potential impact of reproductive hormone status in more detail, we followed a subset of regularly cycling women during the menstrual, follicular and luteal phases of their cycle. The aesthetic and incentive salience of infant faces did not change across the menstrual cycle. Our findings suggest that reproductive hormone status does not modulate the aesthetic and incentive value of infant faces.

Gender differences in the incentive salience of adult and infant faces.

Facial appearance can motivate behaviour and elicit activation of brain circuits putatively involved in reward. Gender differences have been observed for motivation to view beauty in adult faces--heterosexual women are motivated by beauty in general, while heterosexual men are motivated to view opposite-sex beauty alone. Although gender differences have been observed in sensitivity to infant cuteness, infant faces appear to hold equal incentive salience among men and women. In the present study, we investigated the incentive salience of attractiveness and cuteness in adult and infant faces, respectively. We predicted that, given alternative viewing options, gender differences would emerge for motivation to view infant faces. Heterosexual participants completed a "pay-per-view" key-press task, which allowed them to control stimulus duration. Gender differences were found such that infants held greater incentive salience among women, although both sexes differentiated infant faces based on cuteness. Among adult faces, men exerted more effort than women to view opposite-sex faces. These findings suggest that, contrary to previous reports, gender differences do exist in the incentive salience of infant faces as well as opposite-sex faces.

Facial emotion recognition in Scottish prisoners.

BACKGROUND: Studies of antisocial populations have found that they show deficits in recognition of facial affect. Such deficits are also found in other populations with clinical conditions such as autism spectrum disorders, schizophrenia and obsessive compulsive disorder. AIMS: We aimed to investigate the hypothesis that facial affect recognition in the Scottish prison population would differ from matched controls. In addition, we aimed to investigate any relationship between facial affect recognition deficits and offence history. METHODS: A sample of serving convicted prisoners, drawn from a larger study, was assessed for ability to recognise facial affect. Other variables were also measured and a self-report offending history obtained. RESULTS: 127 prisoners were assessed in 11 prisons. Male prisoners were significantly worse than age, sex and IQ-matched controls at recognising negative facial emotions, specifically anger, fear, sadness and disgust. Within the sample of prisoners, deficits in fear recognition were associated with a history of previous prison sentences but not previous convictions. With respect to offending history, sex offenders were relatively better at recognising sadness and worse at recognising surprise than the other offenders. These relationships remain after controlling for IQ. CONCLUSIONS: Scottish convicted prisoners show deficits in recognising negative facial emotions in a pattern consistent with other antisocial populations. We also demonstrated a relationship between particular patterns of deficit and types of offending history not previously described.

Evaluation of multi-modal, multi-site neuroimaging measures in Huntington's disease: Baseline results from the PADDINGTON study.

BACKGROUND: Macro- and micro-structural neuroimaging measures provide valuable information on the pathophysiology of Huntington's disease (HD) and are proposed as biomarkers. Despite theoretical advantages of microstructural measures in terms of sensitivity to pathology, there is little evidence directly comparing the two. METHODS: 40 controls and 61 early HD subjects underwent 3 T MRI (T1- and diffusion-weighted), as part of the PADDINGTON study. Macrostructural volumetrics were obtained for the whole brain, caudate, putamen, corpus callosum (CC) and ventricles. Microstructural diffusion metrics of fractional anisotropy (FA), mean-, radial- and axial-diffusivity (MD, RD, AD) were computed for white matter (WM), CC, caudate and putamen. Group differences were examined adjusting for age, gender and site. A formal comparison of effect sizes determined which modality and metrics provided a statistically significant advantage over others. RESULTS: Macrostructural measures showed decreased regional and global volume in HD (p < 0.001); except the ventricles which were enlarged (p < 0.01). In HD, FA was increased in the deep grey-matter structures (p < 0.001), and decreased in the WM (CC, p = 0.035; WM, p = 0.053); diffusivity metrics (MD, RD, AD) were increased for all brain regions (p < 0.001). The largest effect sizes were for putamen volume, caudate volume and putamen diffusivity (AD, RD and MD); each was significantly larger than those for all other metrics (p < 0.05). CONCLUSION: The highest performing macro- and micro-structural metrics had similar sensitivity to HD pathology quantified via effect sizes. Region-of-interest may be more important than imaging modality, with deep grey-matter regions outperforming the CC and global measures, for both volume and diffusivity. FA appears to be relatively insensitive to disease effects.

Social cognition, the male brain and the autism spectrum.

Behavioral studies have shown that, at a population level, women perform better on tests of social cognition and empathy than men. Furthermore Autism Spectrum Disorders (ASDs), which are characterized by impairments in social functioning and empathy, occur more commonly in males than females. These findings have led to the hypothesis that differences in the functioning of the social brain between males and females contribute to the greater vulnerability of males to ASD and the suggestion that ASD may represent an extreme form of the male brain. Here we sought to investigate this hypothesis by determining: (i) whether males and females differ in social brain function, and (ii) whether any sex differences in social brain function are exaggerated in individuals with ASD. Using fMRI we show that males and females differ markedly in social brain function when making social decisions from faces (compared to simple sex judgements) especially when making decisions of an affective nature, with the greatest sex differences in social brain activation being in the inferior frontal cortex (IFC). We also demonstrate that this difference is exaggerated in individuals with ASD, who show an extreme male pattern of IFC function. These results show that males and females differ significantly in social brain function and support the view that sex differences in the social brain contribute to the greater vulnerability of males to ASDs.

The insular cortex and the neuroanatomy of major depression.

BACKGROUND: The neuroanatomical substrate underlying Major Depressive Disorder (MDD) is incompletely understood. Recent reports have implicated the insular cortex. METHODS: Two cohorts of participants with MDD were tested. In the first MDD cohort, we used standardised facial expression recognition tasks. In the second cohort, we focused on facial disgust recognition, a function associated with the insular cortex. T1 weighted MR imaging was used in the second cohort to test the hypothesis of abnormal insular volume being associated with impaired disgust recognition. RESULTS: Disgust recognition was particularly impaired in both cohorts. In the second cohort, the magnitude of the disgust recognition deficit correlated with reduced insula grey matter volume. Exploring the idea of insula involvement in MDD further, we identified the insular cortex and the anterior cingulate cortex as key neural correlates of core symptoms, in that scores of 3 clinical scales (the Beck Depression Inventory, the Hamilton Depression Rating Scale, and the Snaith-Hamilton Pleasure Scale) correlated with grey matter volume in these structures. LIMITATIONS: MDD participants were clinically representative of specialist and academic psychiatric practice in the UK and presented with robust primary diagnoses; we did not exclude common co-morbidities such as anxiety and personality disorders. CONCLUSIONS: We propose that cognitive and emotional functions assumed to be associated with the insula are adversely affected in patients with MDD and that this may, therefore, represent the substrate for some core clinical features of MDD. Further exploration of the involvement of the insular cortex in MDD is warranted.

Disgust and fear recognition in paraneoplastic limbic encephalitis.

Paraneoplastic limbic encephalitis (PNLE) affects limbic portions of the brain associated with recognition of social signals of emotions. Yet it is not known whether this perceptual ability is impaired in individuals with PNLE. We therefore conducted a single case study to explore possible impairments in recognising facially, vocally and bodily expressed emotions, using standardised emotion recognition tests. Facial expression recognition was tested with two forced-choice emotion-labelling tasks using static faces with either prototypical or morphed blends of basic emotions. Recognition of vocally and bodily expressed emotions was also tested with forced-choice labelling tasks, one based on prosodic cues, the other on whole-body movement cues. We found a deficit in fear and disgust recognition from both face and voice, while recognition of bodily expressed emotions was unaffected. These findings are consistent with data from previous studies demonstrating critical roles for certain brain regions - particularly the amygdala and insular cortex - in processing facially and vocally displayed basic emotions, and furthermore, suggest that recognition of bodily expressed emotions may not depend on neural structures involved in facial and vocal emotion recognition. Impaired facial and vocal emotion recognition may form a further neuropsychological marker of limbic encephalitis, in addition to the already well-described mnestic deficits.

Overactivation of fear systems to neutral faces in schizophrenia.

BACKGROUND: The amygdala plays a central role in detecting and responding to fear-related stimuli. A number of recent studies have reported decreased amygdala activation in schizophrenia to emotional stimuli (such as fearful faces) compared with matched neutral stimuli (such as neutral faces). We investigated whether the apparent decrease in amygdala activation in schizophrenia could actually derive from increased amygdala activation to the neutral comparator stimuli. METHODS: Nineteen patients with schizophrenia and 24 matched control participants viewed pictures of faces with either fearful or neutral facial expressions, and a baseline condition, during functional magnetic resonance imaging scanning. RESULTS: Patients with schizophrenia showed a relative decrease in amygdala activation to fearful faces compared with neutral faces. However, this difference resulted from an increase in amygdala activation to the neutral faces in patients with schizophrenia, not from a decreased response to the fearful faces. CONCLUSIONS: Patients with schizophrenia show an increased response of the amygdala to neutral faces. This is sufficient to explain their apparent deficit in amygdala activation to fearful faces compared with neutral faces. The inappropriate activation of neural systems involved in fear to otherwise neutral stimuli may contribute to the development of psychotic symptoms in schizophrenia.