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Background. Impaired spatial working memory (SWM) is a robust feature of schizophrenia and has been linked to the risk of developing psychosis in people with an at-risk mental state (ARMS). We used functional magnetic resonance imaging (fMRI) to examine the neural substrate of SWM in the ARMS and in patients who had just developed schizophrenia. Method. fMRI was used to study 17 patients with an ARMS, 10 patients with a first episode of psychosis and 15 age- matched healthy comparison subjects. The blood oxygen level-dependent (BOLD) response was measured while subjects performed an object-location paired-associate memory task, with experimental manipulation of mnemonic load. Results. In all groups, increasing mnemonic load was associated with activation in the medial frontal and medial posterior parietal cortex. Significant between-group differences in activation were evident in a cluster spanning the medial frontal cortex and right precuneus, with the ARMS groups showing less activation than controls but greater activation than first-episode psychosis (FEP) patients. These group differences were more evident at the most demanding levels of the task than at the easy level. In all groups, task performance improved with repetition of the conditions. However, there was a significant group difference in the response of the right precuneus across repeated trials, with an attenuation of activation in controls but increased activation in FEP and little change in the ARMS. Conclusions. Abnormal neural activity in the medial frontal cortex and posterior parietal cortex during an SWM task may be a neural correlate of increased vulnerability to psychosis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The authors sought to elucidate the functional neural basis of the neurobiological abnormalities underlying the vulnerability to suicidal behavior. METHOD: Event-related functional MRI was used to measure neural activity in response to angry and happy versus neutral faces. Thirteen currently euthymic men with a history of major depressive disorder and suicidal behavior were compared with 14 currently euthymic men with a history of major depressive disorder but not of suicidal acts (affective comparison subjects) and 16 healthy male comparison subjects. RESULTS: Relative to affective comparison subjects, suicide attempters showed greater activity in the right lateral orbitofrontal cortex (Brodmann's area 47) and decreased activity in the right superior frontal gyrus (area 6) in response to prototypical angry versus neutral faces, greater activity in the right anterior cingulate gyrus (area 32 extending to area 10) to mild happy versus neutral faces, and greater activity in the right cerebellum to mild angry versus neutral faces. However, activation in these frontal regions did not differ between healthy individuals and either patient group. Relative to healthy comparison subjects, both patient groups showed reduced activity in the right cerebellum to neutral faces and to mild happy versus neutral faces. CONCLUSIONS: Suicide attempters were distinguished from nonsuicidal patients by responses to angry and happy faces that may suggest increased sensitivity to others' disapproval, higher propensity to act on negative emotions, and reduced attention to mildly positive stimuli. These patterns of neural activity and cognitive processes may represent vulnerability markers of suicidal behavior in men with a history of depression. [ABSTRACT FROM AUTHOR]

Objective: Processing affective facial expressions is an important component of interpersonal relationships. However, depressed patients show impairments in this system. The present study investigated the neural correlates of implicit processing of happy facial expressions in depression and identified regions affected by antidepressant therapy.Method: Two groups of subjects participated in a prospective study with functional magnetic resonance imaging (fMRI). The patients were 19 medication-free subjects (mean age, 43.2 years) with major depression, acute depressive episode, unipolar subtype. The comparison group contained 19 matched healthy volunteers (mean age, 42.8 years). Both groups underwent fMRI scans at baseline (week 0) and at 8 weeks. Following the baseline scan, the patients received treatment with fluoxetine, 20 mg daily. The fMRI task was implicit affect recognition with standard facial stimuli morphed to display varying intensities of happiness. The fMRI data were analyzed to estimate the average activation (overall capacity) and differential response to variable intensity (dynamic range) in brain systems involved in processing facial affect.Results: An attenuated dynamic range of response in limbic-subcortical and extrastriate visual regions was evident in the depressed patients, relative to the comparison subjects. The attenuated extrastriate cortical activation at baseline was increased following antidepressant treatment, and symptomatic improvement was associated with greater overall capacity in the hippocampal and extrastriate regions.Conclusions: Impairments in the neural processing of happy facial expressions in depression were evident in the core regions of affective facial processing, which were reversed following treatment. These data complement the neural effects observed with negative affective stimuli. [ABSTRACT FROM AUTHOR]

At what levels of brain organization might pathological change in schizophrenia be anatomically expressed: global, regional or supra-regional? We hypothesized that brain structure reflects a set of supra-regional anatomical systems with common developmental influences. We conducted an exploratory analysis to identify supra-regional brain systems and to investigate whether abnormal brain architecture in schizophrenia is manifested within one or more of these systems. Magnetic resonance (MR) images were acquired from 27 patients with schizophrenia and 37 control subjects. After segmentation and registration of each individual MRI dataset in the standard space of Talairach and Tournoux, grey matter and ventricular-cerebrospinal fluid (CSF) maps were automatically parcellated into 104 regions. We used principal components analysis of the multiple regional grey matter and ventricular-CSF measurements, on all 64 subjects, to extract the five main normative supra-regional systems. The first two of these components represented global variation in grey matter and ventricular-CSF regional measures. We interpreted the other three components as representing supra-regional systems comprising: a frontal-parietal system, a frontal-temporal system and a frontal-basal ganglia system. Schizophrenic group mean scores on the first component (global grey matter-ventricular contrast) and fourth component (frontal-temporal system) were significantly reduced compared to controls. These results suggest that pathological changes in schizophrenia may be expressed at two mutually independent levels of anatomical organization: global change in a grey matter/ventricular system and supra-regional change in a frontal-temporal system. [ABSTRACT FROM AUTHOR]

Background: Difficulties in social communication are a defining clinical feature of autism. However, the underlying neurobiological heterogeneity has impeded targeted therapies and requires new approaches to identifying clinically relevant bio-behavioural subgroups. In the largest autism cohort to date, we comprehensively examined difficulties in facial expression recognition, a key process in social communication, as a bio-behavioural stratification biomarker, and validated them against clinical features and neurofunctional responses., Methods: Between 255 and 488 participants aged 6-30 years with autism, typical development and/or mild intellectual disability completed the Karolinska Directed Emotional Faces task, the Reading the Mind in the Eyes Task and/or the Films Expression Task. We first examined mean-group differences on each test. Then, we used a novel intersection approach that compares two centroid and connectivity-based clustering methods to derive subgroups based on the combined performance across the three tasks. Measures and subgroups were then related to clinical features and neurofunctional differences measured using fMRI during a fearful face-matching task., Results: We found significant mean-group differences on each expression recognition test. However, cluster analyses showed that these were driven by a low-performing autistic subgroup (~ 30% of autistic individuals who performed below 2SDs of the neurotypical mean on at least one test), while a larger subgroup (~ 70%) performed within 1SD on at least 2 tests. The low-performing subgroup also had on average significantly more social communication difficulties and lower activation in the amygdala and fusiform gyrus than the high-performing subgroup., Limitations: Findings of autism expression recognition subgroups and their characteristics require independent replication. This is currently not possible, as there is no other existing dataset that includes all relevant measures. However, we demonstrated high internal robustness (91.6%) of findings between two clustering methods with fundamentally different assumptions, which is a critical pre-condition for independent replication., Conclusions: We identified a subgroup of autistic individuals with expression recognition difficulties and showed that this related to clinical and neurobiological characteristics. If replicated, expression recognition may serve as bio-behavioural stratification biomarker and aid in the development of targeted interventions for a subgroup of autistic individuals., (© 2022. The Author(s).)

This paper presents functional MRI work on emotional processing in depersonalization disorder (DPD). This relatively neglected disorder is hallmarked by a disturbing change in the quality of first-person experience, almost invariably encompassing a diminished sense of self and an alteration in emotional experience such that the sufferer feels less emotionally reactive, with emotions experienced as decreased or "damped down," so that emotional life seems to lack spontaneity and subjective validity. Here we explored responses to emotive visual stimuli to examine the functional neuroanatomy of emotional processing in DPD before and after pharmacological treatment. We also employed concurrent skin conductance measurement as an index of autonomic arousal. In common with previous studies we demonstrated that in DPD, there is attenuated psychophysiological response to emotional material, reflected in altered patterns of (i) regional brain response, (ii) autonomic responses. By scanning participants before and after treatment we were able to build on previous findings by examining the changes in functional MRI response in patients whose symptoms had improved at time 2. The attenuation of emotional experience was associated with reduced activity of the insula, whereas clinical improvement in DPD symptoms was associated with increased insula activity. The insula is known to be implicated in interoceptive awareness and the generation of feeling states. In addition an area of right ventrolateral prefrontal cortex emerged as particularly implicated in what may be "top-down" inhibition of emotional responses. The relevance of these findings to the wider study of emotion, self-related processes, and interoception is discussed.

Objective: The cerebral mechanisms of traits associated with depersonalization-derealization disorder (DPRD) remain poorly understood., Method: Happy and sad emotion expressions were presented to DPRD and non-referred control (NC) subjects in an implicit event-related functional magnetic resonance imaging (fMRI) design, and correlated with self report scales reflecting typical co-morbidities of DPRD: depression, dissociation, anxiety, somatization., Results: Significant differences between the slopes of the two groups were observed for somatization in the right temporal operculum (happy) and ventral striatum, bilaterally (sad). Discriminative regions for symptoms of depression were the right pulvinar (happy) and left amygdala (sad). For dissociation, discriminative regions were the left mesial inferior temporal gyrus (happy) and left supramarginal gyrus (sad). For state anxiety, discriminative regions were the left inferior frontal gyrus (happy) and parahippocampal gyrus (sad). For trait anxiety, discriminative regions were the right caudate head (happy) and left superior temporal gyrus (sad). Discussion The ascertained brain regions are in line with previous findings for the respective traits. The findings suggest separate brain systems for each trait., Conclusion: Our results do not justify any bias for a certain nosological category in DPRD.

Neuroimaging has been identified as a potentially powerful probe for the in vivo study of drug effects on the brain with utility across several phases of drug development spanning preclinical and clinical investigations. Specifically, neuroimaging can provide insight into drug penetration and distribution, target engagement, pharmacodynamics, mechanistic action and potential indicators of clinical efficacy. In this review, we focus on machine learning approaches for neuroimaging which enable us to make predictions at the individual level based on the distributed effects across the whole brain. Crucially, these approaches can be trained on data from one study and applied to an independent study and, unlike group-level statistics, can be readily use to assess the generalisability to unseen data. In this review, we present examples and suggestions for how machine learning could help answer fundamental questions spanning the drug discovery pipeline: (1) Who should I recruit for this study? (2) What should I measure and when should I measure it? (3) How does the pharmacological agent behave using an experimental medicine model?, and (4) How does a compound differ from and/or resemble existing compounds? Specifically, we present studies from the literature and we suggest areas for the focus of future development. Further refinement and tailoring of machine learning techniques may help realise their tremendous potential for drug discovery and drug validation.

Adults diagnosed with autism spectrum disorder (ASD) show a reduced sensitivity (degree of selective response) to social stimuli such as human voices. In order to determine whether this reduced sensitivity is a consequence of years of poor social interaction and communication or is present prior to significant experience, we used functional MRI to examine cortical sensitivity to auditory stimuli in infants at high familial risk for later emerging ASD (HR group, N = 15), and compared this to infants with no family history of ASD (LR group, N = 18). The infants (aged between 4 and 7 months) were presented with voice and environmental sounds while asleep in the scanner and their behaviour was also examined in the context of observed parent-infant interaction. Whereas LR infants showed early specialisation for human voice processing in right temporal and medial frontal regions, the HR infants did not. Similarly, LR infants showed stronger sensitivity than HR infants to sad vocalisations in the right fusiform gyrus and left hippocampus. Also, in the HR group only, there was an association between each infant's degree of engagement during social interaction and the degree of voice sensitivity in key cortical regions. These results suggest that at least some infants at high-risk for ASD have atypical neural responses to human voice with and without emotional valence. Further exploration of the relationship between behaviour during social interaction and voice processing may help better understand the mechanisms that lead to different outcomes in at risk populations., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: 22q11.2 deletion syndrome (22q11DS, velo-cardio-facial syndrome [VCFS]) is a genetic disorder associated with interstitial deletions of chromosome 22q11.2. In addition to high rates of neuropsychiatric disorders, children with 22q11DS have impairments of face processing, as well as IQ-independent deficits in visuoperceptual function and social and abstract reasoning. These face-processing deficits may contribute to the social impairments of 22q11DS. However, their neurobiological basis is poorly understood., Methods: We used event-related functional magnetic resonance imaging (fMRI) to examine neural responses when children with 22q11DS (aged 9-17 years) and healthy controls (aged 8-17 years) incidentally processed neutral expressions and mild (50%) and intense (100%) expressions of fear and disgust. We included 28 right-handed children and adolescents: 14 with 22q11DS and 14 healthy (including nine siblings) controls., Results: Within groups, contrasts showed that individuals significantly activated 'face responsive' areas when viewing neutral faces, including fusiform-extrastriate cortices. Further, within both groups, there was a significant positive linear trend in activation of fusiform-extrastriate cortices and cerebellum to increasing intensities of fear. There were, however, also between-group differences. Children with 22q11DS generally showed reduced activity as compared to controls in brain regions involved in social cognition and emotion processing across emotion types and intensities, including fusiform-extrastriate cortices, anterior cingulate cortex (Brodmann area (BA) 24/32), and superomedial prefrontal cortices (BA 6). Also, an exploratory correlation analysis showed that within 22q11DS children reduced activation was associated with behavioural impairment-social difficulties (measured using the Total Difficulties Score from the Strengths and Difficulties Questionnaire [SDQ]) were significantly negatively correlated with brain activity during fear and disgust processing (respectively) in the left precentral gyrus (BA 4) and in the left fusiform gyrus (FG, BA 19), right lingual gyrus (BA 18), and bilateral cerebellum., Conclusions: Regions involved in face processing, including fusiform-extrastriate cortices, anterior cingulate gyri, and superomedial prefrontal cortices (BA 6), are activated by facial expressions of fearful, disgusted, and neutral expressions in children with 22q11DS but generally to a lesser degree than in controls. Hypoactivation in these regions may partly explain the social impairments of children with 22q11DS.

Background: Psychostimulant medication, most commonly the catecholamine agonist methylphenidate, is the most effective treatment for attention-deficit/hyperactivity disorder (ADHD). However, relatively little is known on the mechanisms of action. Acute effects on brain function can elucidate underlying neurocognitive effects. We tested methylphenidate effects relative to placebo in functional magnetic resonance imaging (fMRI) during three disorder-relevant tasks in medication-naïve ADHD adolescents. In addition, we conducted a systematic review and meta-analysis of the fMRI findings of acute stimulant effects on ADHD brain function., Methods: The fMRI study compared 20 adolescents with ADHD under either placebo or methylphenidate in a randomized controlled trial while performing stop, working memory, and time discrimination tasks. The meta-analysis was conducted searching PubMed, ScienceDirect, Web of Knowledge, Google Scholar, and Scopus databases. Peak coordinates of clusters of significant effects of stimulant medication relative to placebo or off medication were extracted for each study., Results: The fMRI analysis showed that methylphenidate significantly enhanced activation in bilateral inferior frontal cortex (IFC)/insula during inhibition and time discrimination but had no effect on working memory networks. The meta-analysis, including 14 fMRI datasets and 212 children with ADHD, showed that stimulants most consistently enhanced right IFC/insula activation, which also remained for a subgroup analysis of methylphenidate effects alone. A more lenient threshold also revealed increased putamen activation., Conclusions: Psychostimulants most consistently increase right IFC/insula activation, which are key areas of cognitive control and also the most replicated neurocognitive dysfunction in ADHD. These neurocognitive effects may underlie their positive clinical effects., (© 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.)

Background/objectives: Rates of obesity are greatest in middle age. Obesity is associated with altered activity of brain networks sensing food-related stimuli and internal signals of energy balance, which modulate eating behaviour. The impact of healthy mid-life ageing on these processes has not been characterised. We therefore aimed to investigate changes in brain responses to food cues, and the modulatory effect of meal ingestion on such evoked neural activity, from young adulthood to middle age., Subjects/methods: Twenty-four healthy, right-handed subjects, aged 19.5-52.6 years, were studied on separate days after an overnight fast, randomly receiving 50 ml water or 554 kcal mixed meal before functional brain magnetic resonance imaging while viewing visual food cues., Results: Across the group, meal ingestion reduced food cue-evoked activity of amygdala, putamen, insula and thalamus, and increased activity in precuneus and bilateral parietal cortex. Corrected for body mass index, ageing was associated with decreasing food cue-evoked activation of right dorsolateral prefrontal cortex (DLPFC) and precuneus, and increasing activation of left ventrolateral prefrontal cortex (VLPFC), bilateral temporal lobe and posterior cingulate in the fasted state. Ageing was also positively associated with the difference in food cue-evoked activation between fed and fasted states in the right DLPFC, bilateral amygdala and striatum, and negatively associated with that of the left orbitofrontal cortex and VLPFC, superior frontal gyrus, left middle and temporal gyri, posterior cingulate and precuneus. There was an overall tendency towards decreasing modulatory effects of prior meal ingestion on food cue-evoked regional brain activity with increasing age., Conclusions: Healthy ageing to middle age is associated with diminishing sensitivity to meal ingestion of visual food cue-evoked activity in brain regions that represent the salience of food and direct food-associated behaviour. Reduced satiety sensing may have a role in the greater risk of obesity in middle age.

The diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) is based on subjective measures despite evidence for multisystemic structural and functional deficits. ADHD patients have consistent neurofunctional deficits in motor response inhibition. The aim of this study was to apply pattern classification to task-based functional magnetic resonance imaging (fMRI) of inhibition, to accurately predict the diagnostic status of ADHD. Thirty adolescent ADHD and thirty age-matched healthy boys underwent fMRI while performing a Stop task. fMRI data were analyzed with Gaussian process classifiers (GPC), a machine learning approach, to predict individual ADHD diagnosis based on task-based activation patterns. Traditional univariate case-control analyses were also performed to replicate previous findings in a relatively large dataset. The pattern of brain activation correctly classified up to 90% of patients and 63% of controls, achieving an overall classification accuracy of 77%. The regions of the discriminative network most predictive of controls included later developing lateral prefrontal, striatal, and temporo-parietal areas that mediate inhibition, while regions most predictive of ADHD were in earlier developing ventromedial fronto-limbic regions, which furthermore correlated with symptom severity. Univariate analysis showed reduced activation in ADHD in bilateral ventrolateral prefrontal, striatal, and temporo-parietal regions that overlapped with areas predictive of controls, suggesting the latter are dysfunctional areas in ADHD. We show that significant individual classification of ADHD patients of 77% can be achieved using whole brain pattern analysis of task-based fMRI inhibition data, suggesting that multivariate pattern recognition analyses of inhibition networks can provide objective diagnostic neuroimaging biomarkers of ADHD., (Copyright © 2013 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

Background: Although cognitive behavioral therapy (CBT) is an effective treatment for obsessive-compulsive disorder (OCD), few reliable predictors of treatment outcome have been identified. The present study examined the neural correlates of symptom improvement with CBT among OCD patients with predominantly contamination obsessions and washing compulsions, the most common OCD symptom dimension., Method: Participants consisted of 12 OCD patients who underwent symptom provocation with contamination-related images during functional magnetic resonance imaging (fMRI) scanning prior to 12 weeks of CBT., Results: Patterns of brain activity during symptom provocation were correlated with a decrease on the Yale-Brown Obsessive Compulsive Scale (YBOCS) after treatment, even when controlling for baseline scores on the YBOCS and the Beck Depression Inventory (BDI) and improvement on the BDI during treatment. Specifically, activation in brain regions involved in emotional processing, such as the anterior temporal pole and amygdala, was most strongly associated with better treatment response. By contrast, activity in areas involved in emotion regulation, such as the dorsolateral prefrontal cortex, correlated negatively with treatment response mainly in the later stages within each block of exposure during symptom provocation., Conclusions: Successful recruitment of limbic regions during exposure to threat cues in patients with contamination-based OCD may facilitate a better response to CBT, whereas excessive activation of dorsolateral prefrontal regions involved in cognitive control may hinder response to treatment. The theoretical implications of the findings and their potential relevance to personalized care approaches are discussed.

Anorexia nervosa (AN), obsessive-compulsive disorder (OCD), and obsessive-compulsive personality disorder (OCPD) are often co-morbid; however, the aetiology of such co-morbidity has not been well investigated. This study examined brain activation in women with AN and in healthy control (HC) women during the provocation of symmetry/ordering-related anxiety. During provocation, patients with AN showed more anxiety compared to HCs, which was correlated with the severity of symmetry/ordering symptoms. Activation in the right parietal lobe and right prefrontal cortex (rPFC) in response to provocation was reduced in the AN group compared with the HC group. The reduced right parietal activation observed in the AN group is consistent with parietal lobe involvement in visuospatial cognition and with studies of OCD reporting an association between structural abnormalities in this region and the severity of 'ordering' symptoms. Reduced rPFC activation in response to symmetry/ordering provocation has similarities with some, but not all, data collected from patients with AN who were exposed to images of food and bodies. Furthermore, the combination of data from the AN and HC groups showed that rPFC activation during symptom provocation was inversely correlated with the severity of symmetry/ordering symptoms. These data suggest that individuals with AN have a diminished ability to cognitively deal with illness-associated symptoms of provocation. Furthermore, our data also suggest that symptom provocation can progressively overload attempts by the rPFC to exert cognitive control. These findings are discussed in the context of the current neurobiological models of AN.

The stimulant methylphenidate (MPX) and the nonstimulant atomoxetine (ATX) are the most commonly prescribed medications for attention deficit hyperactivity disorder (ADHD). However, no functional magnetic resonance imaging (fMRI) study has as yet investigated the effects of ATX on inhibitory or any other brain function in ADHD patients or compared its effects with those of MPX. A randomized, double-blind, placebo-controlled, crossover pharmacological design was used to compare the neurofunctional effects of single doses of MPX, ATX, and placebo during a stop task, combined with fMRI within 19 medication-naive ADHD boys, and their potential normalization effects relative to 29 age-matched healthy boys. Compared with controls, ADHD boys under placebo showed bilateral ventrolateral prefrontal, middle temporal, and cerebellar underactivation. Within patients, MPX relative to ATX and placebo significantly upregulated right ventrolateral prefrontal activation, which correlated with enhanced inhibitory capacity. Relative to controls, both drugs significantly normalized the left ventrolateral prefrontal underactivation observed under placebo, while MPX had a drug-specific effect of normalizing right ventrolateral prefrontal and cerebellar underactivation observed under both placebo and ATX. The findings show shared and drug-specific effects of MPX and ATX on performance and brain activation during inhibitory control in ADHD patients with superior upregulation and normalization effects of MPX.

Objective: The neural correlates of body checking perceptions in eating disorders have not yet been identified. This functional Magnetic Resonance Imaging study examined the neuroanatomy involved in altered perception and identification with body checking in female with anorexia nervosa (AN)., Method: Brain activation while viewing images depicting normal weight individuals involved in either body checking behavior or a neutral (noneating disorder) body action, was compared between 20 females with AN and 15 matched healthy controls (HC)., Results: Females with AN reported higher anxiety compared to HC during the body checking task. The level of anxiety positively correlated with body shape concern scores. People with AN had less activation in the medial prefrontal cortex (PFC) and right fusiform gyrus compared to HC in response to body checking compared to neutral action images. Body shape concern scores correlated negatively with medial PFC activation in AN group., Discussion: This preliminary study with modest power suggests that AN patients have reduced activation in cortical areas associated with self-reference, body action perception, and social cognition in females with AN., (Copyright © 2013 Wiley Periodicals, Inc.)

It is unclear to what degree depersonalization disorder (DPD) and alexithymia share abnormal brain mechanisms of emotional dysregulation. We compared cerebral processing of facial expressions of emotion in individuals with DPD to normal controls (NC). We presented happy and sad emotion expressions in increasing intensities from neutral (0%) through mild (50%) to intense (100%) to DPD and non-referred NC subjects in an implicit event-related fMRI design, and correlated respective brain activations with responses on the 20-item Toronto Alexithymia Scale (TAS-20) and its three subscales F1-F3. The TAS-20 predicts clinical diagnosis of DPD with a unique variance proportion of 38%. Differential regression analysis was utilized to ascertain brain regions for each alexithymia subscale. Differential regions of total alexithymia severity for happy emotion were the globus pallidus externus; for identifying feelings (TAS-20 F1 subscale), the right anterior insula; for description of feelings (F2), the right dorsal mid-anterior cingulate gyrus (BA 24); and for externally oriented cognitive style (F3), the left paracingulate gyrus (BA 32). For sad emotion, the differential region for the total TAS-20 score was the dorsal anterior cingulate gyrus (BA 24); for TAS-20 F1, the left inferior anterior insula; for TAS-20 F2, the right PCC (BA 31); and for TAS-20 F3, the right orbital gyrus (BA 10). Supporting our hypotheses, the ascertained brain regions for TAS-20 subscales subserve interoception, monitoring and reflection of internal states and emotion. The presented analyses provide evidence that alexithymia plays a substantial role in emotional dysregulation in DPD, presumably based on restrictions in interoception., (© 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Pauses during speech may reflect the planning and monitoring of discourse, two processes putatively impaired in patients with schizophrenia, particularly those with formal thought disorder (FTD). We used functional MRI to examine the neural correlates of between-clause and of filled pauses, which are respectively associated with speech planning and speech monitoring., Methods: BOLD contrast was measured while six schizophrenia patients with FTD and six healthy subjects spoke about Rorshach inkblots. In an event-related design, we examined activity associated with pauses that occurred between clauses and with pauses that were filled., Results: There was no significant group difference in the frequency of between-clause pauses but patients with FTD made strikingly fewer filled pauses than controls. Between-clause pauses were associated with activation in the anterior part of the left superior temporal gyrus (STG) and the left insula in controls and the engagement of these regions was significantly attenuated in patients., Conclusion: The anterior part of the left STG and the left insula are normally involved in both the planning and monitoring of discourse. The attenuated engagement of these regions with between-clause pauses and the striking infrequency of filled pauses in the patients are consistent with cognitive models implicating defective speech planning and speech monitoring in schizophrenia, especially in relation to FTD.

Studies of functional MRI data are increasingly concerned with the estimation of differences in spatio-temporal networks across groups of subjects or experimental conditions. Unsupervised clustering and independent component analysis (ICA) have been used to identify such spatio-temporal networks. While these approaches have been useful for estimating these networks at the subject-level, comparisons over groups or experimental conditions require further methodological development. In this paper, we tackle this problem by showing how self-organizing maps (SOMs) can be compared within a Frechean inferential framework. Here, we summarize the mean SOM in each group as a Frechet mean with respect to a metric on the space of SOMs. The advantage of this approach is twofold. Firstly, it allows the visualization of the mean SOM in each experimental condition. Secondly, this Frechean approach permits one to draw inference on group differences, using permutation of the group labels. We consider the use of different distance functions, and introduce one extension of the classical sum of minimum distance (SMD) between two SOMs, which take into account the spatial pattern of the fMRI data. The validity of these methods is illustrated on synthetic data. Through these simulations, we show that the two distance functions of interest behave as expected, in the sense that the ones capturing temporal and spatial aspects of the SOMs are more likely to reach significance under simulated scenarios characterized by temporal, spatial [and spatio-temporal] differences, respectively. In addition, a re-analysis of a classical experiment on visually-triggered emotions demonstrates the usefulness of this methodology. In this study, the multivariate functional patterns typical of the subjects exposed to pleasant and unpleasant stimuli are found to be more similar than the ones of the subjects exposed to emotionally neutral stimuli. In this re-analysis, the group-level SOM output units with the smallest sample Jaccard indices were compared with standard GLM group-specific z-score maps, and provided considerable levels of agreement. Taken together, these results indicate that our proposed methods can cast new light on existing data by adopting a global analytical perspective on functional MRI paradigms., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Pattern recognition approaches to the analysis of neuroimaging data have brought new applications such as the classification of patients and healthy controls within reach. In our view, the reliance on expensive neuroimaging techniques which are not well tolerated by many patient groups and the inability of most current biomarker algorithms to accommodate information about prior class frequencies (such as a disorder's prevalence in the general population) are key factors limiting practical application. To overcome both limitations, we propose a probabilistic pattern recognition approach based on cheap and easy-to-use multi-channel near-infrared spectroscopy (fNIRS) measurements. We show the validity of our method by applying it to data from healthy controls (n = 14) enabling differentiation between the conditions of a visual checkerboard task. Second, we show that high-accuracy single subject classification of patients with schizophrenia (n = 40) and healthy controls (n = 40) is possible based on temporal patterns of fNIRS data measured during a working memory task. For classification, we integrate spatial and temporal information at each channel to estimate overall classification accuracy. This yields an overall accuracy of 76% which is comparable to the highest ever achieved in biomarker-based classification of patients with schizophrenia. In summary, the proposed algorithm in combination with fNIRS measurements enables the analysis of sub-second, multivariate temporal patterns of BOLD responses and high-accuracy predictions based on low-cost, easy-to-use fNIRS patterns. In addition, our approach can easily compensate for variable class priors, which is highly advantageous in making predictions in a wide range of clinical neuroimaging applications., (Copyright © 2012 Wiley Periodicals, Inc.)

Women demonstrate higher pain sensitivity and prevalence of chronic visceral pain conditions such as functional gastrointestinal disorders than men. The role of sex differences in the brain processing of visceral pain is still unclear. In 16 male and 16 female healthy subjects we compared personality, anxiety levels, skin conductance response (SCR), and brain processing using functional MRI during anticipation and pain induced by esophageal distension at pain toleration level. There was no significant difference in personality scores, anxiety levels, SCR, and subjective ratings of pain between sexes. In group analysis, both men and women demonstrated a similar pattern of brain activation and deactivation during anticipation and pain consistent with previous reports. However, during anticipation women showed significantly greater activation in the cuneus, precuneus, and supplementary motor area (SMA) and stronger deactivation in the right amygdala and left parahippocampal gyrus, whereas men demonstrated greater activation in the cerebellum. During pain, women demonstrated greater activation in the midcingulate cortex, anterior insula, premotor cortex, and cerebellum and stronger deactivation in the caudate, whereas men showed increased activity in the SMA. The pattern of brain activity suggests that, during anticipation, women may demonstrate stronger limbic inhibition, which is considered to be a cognitive modulation strategy for impending painful stimulation. During pain, women significantly activate brain areas associated with the affective and motivation components of pain. These responses may underlie the sex differences that exist in pain conditions, whereby women may attribute more emotional importance to painful stimuli compared with men.

The investigation of neural substrates of autism spectrum disorder using neuroimaging has been the focus of recent literature. In addition, machine-learning approaches have also been used to extract relevant information from neuroimaging data. There are only few studies directly exploring the inter-regional structural relationships to identify and characterize neuropsychiatric disorders. In this study, we concentrate on addressing two issues: (i) a novel approach to extract individual subject features from inter-regional thickness correlations based on structural magnetic resonance imaging (MRI); (ii) using these features in a machine-learning framework to obtain individual subject prediction of a severity scores based on neurobiological criteria rather than behavioral information. In a sample of 82 autistic patients, we have shown that structural covariances among several brain regions are associated with the presence of the autistic symptoms. In addition, we also demonstrated that structural relationships from the left hemisphere are more relevant than the ones from the right. Finally, we identified several brain areas containing relevant information, such as frontal and temporal regions. This study provides evidence for the usefulness of this new tool to characterize neuropsychiatric disorders., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Suggestions of limb paralysis in highly hypnotically suggestible subjects have been employed to successfully model conversion disorders, revealing similar patterns of brain activation associated with attempted movement of the affected limb. However, previous studies differ with regard to the executive regions involved during involuntary inhibition of the affected limb. This difference may have arisen as previous studies did not control for differences in hypnosis depth between conditions and/or include subjective measures to explore the experience of suggested paralysis. In the current study we employed functional magnetic resonance imaging (fMRI) to examine the functional anatomy of left and right upper limb movements in eight healthy subjects selected for high hypnotic suggestibility during (i) hypnosis (NORMAL) and (ii) attempted movement following additional left upper limb paralysis suggestions (PARALYSIS). Contrast of left upper limb motor function during NORMAL relative to PARALYSIS conditions revealed greater activation of contralateral M1/S1 and ipsilateral cerebellum, consistent with the engagement of these regions in the completion of movements. By contrast, two significant observations were noted in PARALYSIS relative to NORMAL conditions. In conjunction with reports of attempts to move the paralysed limb, greater supplementary motor area (SMA) activation was observed, a finding consistent with the role of SMA in motor intention and planning. The anterior cingulate cortex (ACC, BA 24) was also significantly more active in PARALYSIS relative to NORMAL conditions - suggesting that ACC (BA 24) may be implicated in involuntary, as well as voluntary inhibition of prepotent motor responses., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Somatisation is a frequent problem in various psychiatric disorders, yet the cerebral mechanisms of somatisation remain unexamined. To test if somatisation is susceptible to emotional states, we investigated relationships between somatisation severity, neural effective connectivity, and autonomic responses to emotional facial expressions. Volunteering participants (N = 20) were presented with facial expressions of happy and sad emotion at three intensity levels (0%-50%-100%) in a fast implicit ER-fMRI design with concurrent derivation of skin conductance levels (SCL). Self-reported somatisation severity as assessed with Rief's SOMS-2 index was correlated with neural response controlling for other clinical traits to ascertain brain bases of somatisation. Regression analyses estimated effective connectivity of main clusters so determined with peripheral autonomic responses. Regions in which magnitude of activity correlated with somatisation severity consisted in both happy and sad conditions of the anterior ventral precuneus (BA7), along with posterior cingulate gyrus (PCC, BA23, sad condition) and anteromedial thalamus (happy condition).

Background: Lack of insight is a core feature of schizophrenia and is associated with structural brain abnormalities. The functional neuroanatomy of insight has only recently been investigated. When people evaluate their personality traits compared to those of another, activation is seen in central midline structures (CMS) of the brain. This study set out to compare cerebral activation in schizophrenia patients versus controls during a self-evaluation task which included positive and negative traits as well as mental and physical illness terms., Methods: Eleven schizophrenia patients and 8 healthy controls, matched for age were studied. Insight was assessed using the Schedule for the Assessment of Insight-expanded version (SAI-E). FMRI data were obtained with a 1.5 Tesla GE system and interactions between participant group, self versus other, significant at the cluster level, were recorded., Results: Significant hypoactivation in the medial superior frontal gyrus (dorsomedial prefrontal cortex) was observed in patients vs. controls during self-evaluation of all traits combined. A second cluster of hypoactivation in the posterior cingulate was also detected. When the response to individual traits was explored, underactivation in other frontal regions plus right inferior parietal lobule emerged and this tended to correlate, albeit weakly with lower insight scores. Further, there were areas of hyperactivation relative to controls in anterior cingulate, frontal and parietal regions (especially precuneus) which showed moderate inverse correlations with insight scores., Conclusions: We have demonstrated that the CMS, identified as a key system underpinning self-evaluation, is dysfunctional in patients with schizophrenia, particularly dorso-medial PFC. This may have implications for lack of insight in schizophrenia. Hypofunction within the dorsomedial prefrontal region seems to be particularly important although other posterior and lateral cortical regions play a part and may modulate self-evaluative responses depending on the type of trait under consideration.

Advances in machine learning as applied to functional magnetic resonance imaging (fMRI) data offer the possibility of pretesting and classifying marketing communications using unbiased pattern recognition algorithms. By using these algorithms to analyze brain responses to brands, products, or existing marketing communications that either failed or succeeded in the marketplace and identifying the patterns of brain activity that characterize success or failure, future planned campaigns or new products can now be pretested to determine how well the resulting brain responses match the desired (successful) pattern of brain activity without the need for verbal feedback. This major advance in signal processing is poised to revolutionize the application of these brain-imaging techniques in the marketing sector by offering greater accuracy of prediction in terms of consumer acceptance of new brands, products, and campaigns at a speed that makes them accessible as routine pretesting tools that will clearly demonstrate return on investment.

The extraction of information about neural activity timing from BOLD signal is a challenging task as the shape of the BOLD curve does not directly reflect the temporal characteristics of electrical activity of neurons. In this work, we introduce the concept of neural processing time (NPT) as a parameter of the biophysical model of the hemodynamic response function (HRF). Through this new concept we aim to infer more accurately the duration of neuronal response from the highly nonlinear BOLD effect. The face validity and applicability of the concept of NPT are evaluated through simulations and analysis of experimental time series. The results of both simulation and application were compared with summary measures of HRF shape. The experiment that was analyzed consisted of a decision-making paradigm with simultaneous emotional distracters. We hypothesize that the NPT in primary sensory areas, like the fusiform gyrus, is approximately the stimulus presentation duration. On the other hand, in areas related to processing of an emotional distracter, the NPT should depend on the experimental condition. As predicted, the NPT in fusiform gyrus is close to the stimulus duration and the NPT in dorsal anterior cingulate gyrus depends on the presence of an emotional distracter. Interestingly, the NPT in right but not left dorsal lateral prefrontal cortex depends on the stimulus emotional content. The summary measures of HRF obtained by a standard approach did not detect the variations observed in the NPT., (Copyright © 2010 Wiley Periodicals, Inc.)

Objective: Repetitive transcranial magnetic stimulation (rTMS) has been shown to have clinically beneficial effects in altering the perception of auditory hallucinations (AH) in patients with schizophrenia. However, the mode of action is not clear. Recent neuroimaging findings indicate that rTMS has the potential to induce not only local effects but also changes in remote, functionally connected brain regions. Frontotemporal dysconnectivity has been proposed as a mechanism leading to psychotic symptoms in schizophrenia. The current study examines functional connectivity between temporal and frontal brain regions after rTMS and the implications for AH in schizophrenia., Method: A connectivity analysis was conducted on the fMRI data of 11 healthy controls receiving rTMS, compared with 11 matched subjects receiving sham TMS, to the temporoparietal junction, before engaging in a task associated with robust frontotemporal activation., Results: Compared to the control group, the rTMS group showed an altered frontotemporal connectivity with stronger connectivity between the right temporoparietal cortex and the dorsolateral prefrontal cortex and the angular gyrus., Conclusion: This finding provides preliminary evidence for the hypothesis that normalizing the functional connectivity between the temporoparietal and frontal brain regions may underlie the therapeutic effect of rTMS on AH in schizophrenia.

Debate regarding the neural basis of the hypnotic state continues, but a recent hypothesis suggests that it may produce alterations in the default mode network (DMN). DMN describes a network of brain regions more active during low-demand compared to high-demand task conditions and has been linked to processes such as task-independent thinking, episodic memory, semantic processing, and self-awareness. However, the experiential and cognitive correlates of DMN remain difficult to investigate directly. Using hypnosis as a means of altering the resting ("default") state in conjunction with subjective measures and brain imaging, the authors found that the state of attentional absorption following a hypnotic induction was associated with reduced activity in DMN and increased activity in prefrontal attentional systems, under invariant conditions of passive visual stimulation. The findings that hypnosis and spontaneous conceptual thought at rest were subjectively and neurally distinctive are also relevant to understanding hypnosis itself.

In this study, the first to explore the cortical correlates of signed language (SL) processing under point-light display conditions, the observer identified either a signer or a lexical sign from a display in which different signers were seen producing a number of different individual signs. Many of the regions activated by point-light under these conditions replicated those previously reported for full-image displays, including regions within the inferior temporal cortex that are specialised for face and body-part identification, although such body parts were invisible in the display. Right frontal regions were also recruited - a pattern not usually seen in full-image SL processing. This activation may reflect the recruitment of information about person identity from the reduced display. A direct comparison of identify-signer and identify-sign conditions showed these tasks relied to a different extent on the posterior inferior regions. Signer identification elicited greater activation than sign identification in (bilateral) inferior temporal gyri (BA 37/19), fusiform gyri (BA 37), middle and posterior portions of the middle temporal gyri (BAs 37 and 19), and superior temporal gyri (BA 22 and 42). Right inferior frontal cortex was a further focus of differential activation (signer>sign). These findings suggest that the neural systems supporting point-light displays for the processing of SL rely on a cortical network including areas of the inferior temporal cortex specialized for face and body identification. While this might be predicted from other studies of whole body point-light actions (Vaina, Solomon, Chowdhury, Sinha, & Belliveau, 2001) it is not predicted from the perspective of spoken language processing, where voice characteristics and speech content recruit distinct cortical regions (Stevens, 2004) in addition to a common network. In this respect, our findings contrast with studies of voice/speech recognition (Von Kriegstein, Kleinschmidt, Sterzer, & Giraud, 2005). Inferior temporal regions associated with the visual recognition of a person appear to be required during SL processing, for both carrier and content information., (Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.)

Background: Abnormalities in inhibitory control and underlying fronto-striatal networks is common to both attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive-disorder (OCD). The aim of this study was to investigate disorder-specific abnormalities in neural networks mediating interference inhibition and selective attention., Method: Event-related functional magnetic resonance imaging (fMRI) was used to compare brain activation of boys with ADHD (18), with OCD (10), and healthy boys during (20) during a Simon task that measures interference inhibition and controls for and therefore comeasures attention allocation., Results: During interference inhibition, both patient groups shared mesial frontal dysfunction compared to controls. Disorder-specific dysfunctions were observed in OCD patients in dorsolateral prefrontal cortex during the oddball condition and in ADHD patients in inferior parietal lobe during interference inhibition and in caudate and posterior cingulate during the simpler oddball condition. The decreased activation in caudate and cingulate in ADHD was furthermore negatively correlated with ADHD symptoms and positively with OCD behavioral traits., Conclusions: The study shows that ADHD and OCD patients have shared but also disorder-specific brain dysfunctions during interference inhibition and attention allocation. Both disorders shared dysfunction in mesial frontal cortex. Disorder-specific dysfunctions, however, were observed in dorsolateral prefrontal cortex in OCD patients and in caudate, cingulate, and parietal brain regions in ADHD patients. The disorder-specific dissociation of striato-cingulate activation that was increased in OCD compared to ADHD patients, was furthermore inversely related to the symptomatology of the two disorders, and may potentially reflect differential dopamine modulation of striatal brain regions., (Copyright © 2010 Wiley-Liss, Inc.)

Context: Although psychiatric disorders are, to date, diagnosed on the basis of behavioral symptoms and course of illness, the interest in neurobiological markers of psychiatric disorders has grown substantially in recent years. However, current classification approaches are mainly based on data from a single biomarker, making it difficult to predict disorders characterized by complex patterns of symptoms., Objective: To integrate neuroimaging data associated with multiple symptom-related neural processes and demonstrate their utility in the context of depression by deriving a predictive model of brain activation., Design: Two groups of participants underwent functional magnetic resonance imaging during 3 tasks probing neural processes relevant to depression., Setting: Participants were recruited from the local population by use of advertisements; participants with depression were inpatients from the Department of Psychiatry, Psychosomatics, and Psychotherapy at the University of Wuerzburg, Wuerzburg, Germany., Participants: We matched a sample of 30 medicated, unselected patients with depression by age, sex, smoking status, and handedness with 30 healthy volunteers., Main Outcome Measure: Accuracy of single-subject classification based on whole-brain patterns of neural responses from all 3 tasks., Results: Integrating data associated with emotional and affective processing substantially increases classification accuracy compared with single classifiers. The predictive model identifies a combination of neural responses to neutral faces, large rewards, and safety cues as nonredundant predictors of depression. Regions of the brain associated with overall classification comprise a complex pattern of areas involved in emotional processing and the analysis of stimulus features., Conclusions: Our method of integrating neuroimaging data associated with multiple, symptom-related neural processes can provide a highly accurate algorithm for classification. The integrated biomarker model shows that data associated with both emotional and reward processing are essential for a highly accurate classification of depression. In the future, large-scale studies will need to be conducted to determine the practical applicability of our algorithm as a biomarker-based diagnostic aid.

Objective: People with 'prodromal' symptoms have a very high risk of developing psychosis. We examined the neurocognitive basis of this vulnerability by using functional MRI to study subjects with an at-risk mental state (ARMS) while they performed a random movement generation task., Method: Cross-sectional comparison of individuals with an ARMS (n = 17), patients with first episode schizophreniform psychosis (n = 10) and healthy volunteers (n = 15). Subjects were studied using functional MRI while they performed a random movement generation paradigm., Results: During random movement generation, the ARMS group showed less activation in the left inferior parietal cortex than controls, but greater activation than in the first episode group., Conclusion: The ARMS is associated with abnormalities of regional brain function that are qualitatively similar to those in patients who have recently presented with psychosis but less severe.

The identification, modeling, and analysis of interactions between nodes of neural systems in the human brain have become the aim of interest of many studies in neuroscience. The complex neural network structure and its correlations with brain functions have played a role in all areas of neuroscience, including the comprehension of cognitive and emotional processing. Indeed, understanding how information is stored, retrieved, processed, and transmitted is one of the ultimate challenges in brain research. In this context, in functional neuroimaging, connectivity analysis is a major tool for the exploration and characterization of the information flow between specialized brain regions. In most functional magnetic resonance imaging (fMRI) studies, connectivity analysis is carried out by first selecting regions of interest (ROI) and then calculating an average BOLD time series (across the voxels in each cluster). Some studies have shown that the average may not be a good choice and have suggested, as an alternative, the use of principal component analysis (PCA) to extract the principal eigen-time series from the ROI(s). In this paper, we introduce a novel approach called cluster Granger analysis (CGA) to study connectivity between ROIs. The main aim of this method was to employ multiple eigen-time series in each ROI to avoid temporal information loss during identification of Granger causality. Such information loss is inherent in averaging (e.g., to yield a single "representative" time series per ROI). This, in turn, may lead to a lack of power in detecting connections. The proposed approach is based on multivariate statistical analysis and integrates PCA and partial canonical correlation in a framework of Granger causality for clusters (sets) of time series. We also describe an algorithm for statistical significance testing based on bootstrapping. By using Monte Carlo simulations, we show that the proposed approach outperforms conventional Granger causality analysis (i.e., using representative time series extracted by signal averaging or first principal components estimation from ROIs). The usefulness of the CGA approach in real fMRI data is illustrated in an experiment using human faces expressing emotions. With this data set, the proposed approach suggested the presence of significantly more connections between the ROIs than were detected using a single representative time series in each ROI., (Copyright 2010 Elsevier Inc. All rights reserved.)

Very few studies have investigated to what extent different subtypes of specific phobia share the same underlying functional neuroanatomy. This study aims to investigate the potential differences in the anatomy and dynamics of the blood oxygen level-dependent (BOLD) responses associated with spider and blood-injection-injury phobias. We used an event-related paradigm in 14 untreated spider phobics, 15 untreated blood-injection-injury phobics and 17 controls. Phobic images successfully induced distress only in phobic participants. Both phobic groups showed a similar pattern of heart rate increase following the presentation of phobic stimuli, this being different from controls. The presentation of phobic images induced activity within the same brain network in all participants, although the intensity of brain responses was significantly higher in phobics. Only blood-injection-injury phobics showed greater activity in the ventral prefrontal cortex compared with controls. This phobia group also presented a lower activity peak in the left amygdala compared with spider phobics. Importantly, looking at the dynamics of BOLD responses, both phobia groups showed a quicker time-to-peak in the right amygdala than controls, but only spider phobics also differed from controls in this parameter within the left amygdala. Considering these and previous findings, both phobia subtypes show very similar responses regarding their immediate reaction to phobia-related images, but critical differences in their sustained responses to these stimuli. These results highlight the importance of considering complex mental processes potentially associated with coping and emotion regulation processes, rather than exclusively focusing on primary neural responses to threat, when investigating fear and phobias., (© 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.)

Autism spectrum disorder (ASD) is a neurodevelopmental condition with multiple causes, comorbid conditions, and a wide range in the type and severity of symptoms expressed by different individuals. This makes the neuroanatomy of autism inherently difficult to describe. Here, we demonstrate how a multiparameter classification approach can be used to characterize the complex and subtle structural pattern of gray matter anatomy implicated in adults with ASD, and to reveal spatially distributed patterns of discriminating regions for a variety of parameters describing brain anatomy. A set of five morphological parameters including volumetric and geometric features at each spatial location on the cortical surface was used to discriminate between people with ASD and controls using a support vector machine (SVM) analytic approach, and to find a spatially distributed pattern of regions with maximal classification weights. On the basis of these patterns, SVM was able to identify individuals with ASD at a sensitivity and specificity of up to 90% and 80%, respectively. However, the ability of individual cortical features to discriminate between groups was highly variable, and the discriminating patterns of regions varied across parameters. The classification was specific to ASD rather than neurodevelopmental conditions in general (e.g., attention deficit hyperactivity disorder). Our results confirm the hypothesis that the neuroanatomy of autism is truly multidimensional, and affects multiple and most likely independent cortical features. The spatial patterns detected using SVM may help further exploration of the specific genetic and neuropathological underpinnings of ASD, and provide new insights into the most likely multifactorial etiology of the condition.

Background: Autistic spectrum disorder (ASD) is characterized by stereotyped/obsessional behaviours and social and communicative deficits. However, there is significant variability in the clinical phenotype; for example, people with autism exhibit language delay whereas those with Asperger syndrome do not. It remains unclear whether localized differences in brain anatomy are associated with variation in the clinical phenotype., Method: We used voxel-based morphometry (VBM) to investigate brain anatomy in adults with ASD. We included 65 adults diagnosed with ASD (39 with Asperger syndrome and 26 with autism) and 33 controls who did not differ significantly in age or gender., Results: VBM revealed that subjects with ASD had a significant reduction in grey-matter volume of medial temporal, fusiform and cerebellar regions, and in white matter of the brainstem and cerebellar regions. Furthermore, within the subjects with ASD, brain anatomy varied with clinical phenotype. Those with autism demonstrated an increase in grey matter in frontal and temporal lobe regions that was not present in those with Asperger syndrome., Conclusions: Adults with ASD have significant differences from controls in the anatomy of brain regions implicated in behaviours characterizing the disorder, and this differs according to clinical subtype.

Studies of spoken and signed language processing reliably show involvement of the posterior superior temporal cortex. This region is also reliably activated by observation of meaningless oral and manual actions. In this study we directly compared the extent to which activation in posterior superior temporal cortex is modulated by linguistic knowledge irrespective of differences in language form. We used a novel cross-linguistic approach in two groups of volunteers who differed in their language experience. Using fMRI, we compared deaf native signers of British Sign Language (BSL), who were also proficient speechreaders of English (i.e., two languages) with hearing people who could speechread English, but knew no BSL (i.e., one language). Both groups were presented with BSL signs and silently spoken English words, and were required to respond to a signed or spoken target. The interaction of group and condition revealed activation in the superior temporal cortex, bilaterally, focused in the posterior superior temporal gyri (pSTG, BA 42/22). In hearing people, these regions were activated more by speech than by sign, but in deaf respondents they showed similar levels of activation for both language forms - suggesting that posterior superior temporal regions are highly sensitive to language knowledge irrespective of the mode of delivery of the stimulus material., (Copyright 2009 Elsevier Inc. All rights reserved.)