ASD involves a fundamental impairment in processing social-communicative information from faces. Several recent studies have challenged earlier findings that individuals with autism spectrum disorder (ASD) have no activation of the fusiform gyrus (fusiform face area, FFA) when viewing faces. In this study, we examined activation to faces in the broader network of face-processing modules that comprise what is known as the social brain. Using 3T functional resonance imaging, we measured BOLD signal changes in 10 ASD subjects and 7 healthy controls passively viewing nonemotional faces. We replicated our original findings of significant activation of face identity-processing areas (FFA and inferior occipital gyrus, IOG) in ASD. However, in addition, we identified hypoactivation in a more widely distributed network of brain areas involved in face processing [including the right amygdala, inferior frontal cortex (IFC), superior temporal sulcus (STS), and face-related somatosensory and premotor cortex]. In ASD, we found functional correlations between a subgroup of areas in the social brain that belong to the mirror neuron system (IFC, STS) and other face-processing areas. The severity of the social symptoms measured by the Autism Diagnostic Observation Schedule was correlated with the right IFC cortical thickness and with functional activation in that area. When viewing faces, adults with ASD show atypical patterns of activation in regions forming the broader face-processing network and social brain, outside the core FFA and IOG regions. These patterns suggest that areas belonging to the mirror neuron system are involved in the face-processing disturbances in ASD.

Although both frontal (Broca) and temporal (Wernicke) language-related heteromodal association cortex regions displayed a reversal of asymmetry in boys with autism compared with normal control boys, the frontal abnormality was substantially more extreme, and these differences were statistically significant.

Here we report fMRI results showing that individuals with autism failed to activate superior temporal sulcus voice selective regions in response to vocal sounds, whereas they showed a normal activation pattern in response to nonvocal sounds.

BACKGROUND: Autism is a syndrome of unknown cause, marked by abnormal development of social behavior. Attempts to link pathological features of the amygdala, which plays a key role in emotional processing, to autism have shown little consensus. OBJECTIVE: To evaluate amygdala volume in individuals with autism spectrum disorders and its relationship to laboratory measures of social behavior to examine whether variations in amygdala structure relate to symptom severity. DESIGN: We conducted 2 cross-sectional studies of amygdala volume, measured blind to diagnosis on high-resolution, anatomical magnetic resonance images. Participants were 54 males aged 8 to 25 years, including 23 with autism and 5 with Asperger syndrome or pervasive developmental disorder not otherwise specified, recruited and evaluated at an academic center for developmental disabilities and 26 age- and sex-matched community volunteers. The Autism Diagnostic Interview-Revised was used to confirm diagnoses and to validate relationships with laboratory measures of social function. MAIN OUTCOME MEASURES: Amygdala volume, judgment of facial expressions, and eye tracking. RESULTS: In study 1, individuals with autism who had small amygdalae were slowest to distinguish emotional from neutral expressions (P=.02) and showed least fixation of eye regions (P=.04). These same individuals were most socially impaired in early childhood, as reported on the Autism Diagnostic Interview-Revised (P<.04). Study 2 showed smaller amygdalae in individuals with autism than in control subjects (P=.03) and group differences in the relation between amygdala volume and age. Study 2 also replicated findings of more gaze avoidance and childhood impairment in participants with autism with the smallest amygdalae. Across the combined sample, severity of social deficits interacted with age to predict different patterns of amygdala development in autism (P=.047). CONCLUSIONS: These findings best support a model of amygdala hyperactivity that could explain most volumetric findings in autism. Further psychophysiological and histopathological studies are indicated to confirm these findings.

Autism is a neurodevelopmental disorder affecting sociocommunicative behavior, but also sensorimotor skill learning, oculomotor control, and executive functioning. Some of these impairments may be related to abnormalities of the caudate nuclei, which have been reported for autism. Our sample was comprised of 8 high-functioning males with autism and 8 handedness, sex, and age-matched controls. Subjects underwent functional MRI scanning during performance on simple visuomotor coordination tasks. Functional connectivity MRI (fcMRI) effects were identified as interregional blood oxygenation level dependent (BOLD) signal cross-correlation, using the caudate nuclei as seed volumes. In the control group, fcMRI effects were found in circuits with known participation of the caudate nuclei (associative, orbitofrontal, oculomotor, motor circuits). Although in the autism group fcMRI effects within these circuits were less pronounced or absent, autistic subjects showed diffusely increased connectivity mostly in pericentral regions, but also in brain areas outside expected anatomical circuits (such as visual cortex). These atypical connectivity patterns may be linked to developmental brain growth disturbances recently reported in autism and suggest inefficiently organized functional connectivity between caudate nuclei and cerebral cortex, potentially accounting for stereotypic behaviors and executive impairments.

Poor communication between brain areas may explain why people with autism do not interact well with other people, say researchers from the University of London. Weak links between brain areas could mean that people with Autism do not benefit from social situations as well as other people.

New research from Melbourne's Howard Florey Institute helps to explain why children with autism spectrum disorders (autism) have problem-solving difficulties. Using functional magnetic resonance imaging technology (fMRI) the Florey scientists have shown that children with autism have less activation in the deep parts of the brain responsible for executive function (attention, reasoning and problem solving).

The first major research paper to emerge from the studies, published this month in the British journal Brain, suggests that different areas of the brains of autism patients don't work with each other in the coordinated manner necessary for most high-level thinking.

The typical brain activity that occurs when most people are resting or daydreaming is impaired or absent in individuals with autism, new research suggests. The activity in this so-called "resting network" normally aids in the processing of emotional and social cues, "the very things that are abnormal in autism," lead investigator Daniel P. Kennedy noted in comments to Reuters Health. Through functional magnetic resonance imaging, Kennedy and colleagues observed that the resting network of the autistic brain does not deactivate, likely because this high resting activity is not there during rest. "We think that this finding makes sense in terms of understanding the social and emotional aspects of the disorder," Kennedy said. "We found that a network of brain regions important for social and emotional processing is abnormal in a disorder of social and emotional processing," he said.

Autistic-spectrum disorder is approximately half as common as schizophrenia but its cause remains unknown. Recent studies have begun to clarify the underlying neuroanatomical abnormalities and brain-behaviour relationships in autism. In the past decade, great advances have been made in our understanding of the neurobiological basis of autism.

A functional magnetic resonance imaging (fMRI) study was performed on a 4-year-old girl with autism. While sedated, she listened to three utterances (numbers, hello, her own first name) played through headphones. Based on analyses of the fMRI data, the amount of total brain activation varied with the content of the utterance. The greatest volume of overall activation was in response to numbers, followed by the word 'hello', with the least activation to her name. Frontal cortex activation was greatest in response to her name, with less activation for numbers, and the least for the word 'hello.' These findings indicate that fMRI can identify and quantify the brain regions that are activated in response to words in children with autism under sedation.

There are few studies on brain anatomy of Asperger's syndrome, and no focal anatomical abnormality has been reliably reported from brain imaging studies of autism, although there is increasing evidence for differences in limbic circuits. These brain regions are important in sensorimotor gating, and impaired 'gating' may partly explain the failure of people with autistic disorders to inhibit repetitive thoughts and actions. Thus, we compared brain anatomy and sensorimotor gating in healthy people with Asperger's syndrome and controls. We found significant age-related differences in volume of cerebral hemispheres and caudate nuclei (controls, but not people with Asperger's syndrome, had age-related reductions in volume). Also, people with Asperger's syndrome had significantly less grey matter in fronto-striatal and cerebellar regions than controls, and widespread differences in white matter. Moreover, sensorimotor gating was significantly impaired in Asperger's syndrome. People with Asperger's syndrome most likely have generalized alterations in brain development, but this is associated with significant differences from controls in the anatomy and function of specific brain regions implicated in behaviours characterizing the disorder. We hypothesize that Asperger's syndrome is associated with abnormalities in fronto-striatal pathways resulting in defective sensorimotor gating, and consequently characteristic difficulties inhibiting repetitive thoughts, speech and actions.

We report a whole-brain MRI morphometric survey of asymmetry in children with high-functioning autism and with developmental language disorder (DLD). Autism and DLD were much more similar to each other in patterns of asymmetry throughout the cerebral cortex than either was to controls; this similarity suggests systematic and related alterations rather than random neural systems alterations. We review these findings in relation to previously reported volumetric features in these two samples of brains, including increased total brain and white matter volumes and lack of increase in the size of the corpus callosum. Larger brain volume has previously been associated with increased lateralization. The sizeable right-asymmetry increase reported here may be a consequence of early abnormal brain growth trajectories in these disorders, while higher-order association areas may be most vulnerable to connectivity abnormalities associated with white matter increases.

Heather Cody Hazlett, Ph.D., of the University of North Carolina, Chapel Hill, and colleagues examined brain volume and head circumference in children with and without autism. They analyzed data from an ongoing MRI study on 51 children with autism -- aged 18 to 35 months -- and a comparison group made up of 25 children without autism (14 with typical development, and 11 with developmental delay without evidence of a pervasive developmental disorder). Retrospective longitudinal HC measurements were also gathered from medical records on a larger sample of 113 children with autism and 189 control children, from birth to age three years. "Significant enlargement was detected in cerebral cortical volumes but not cerebellar volumes in individuals with autism," the authors report. "Enlargement was present in both white and gray matter, and it was generalized throughout the cerebral cortex."

Children with ASD were found to have significantly increased cerebral volumes compared with TD and DD children. Cerebellar volume for the ASD group was increased in comparison with the TD group, but this increase was proportional to overall increases in cerebral volume. The DD group had smaller cerebellar volumes compared with both of the other groups. Measurements of amygdalae and hippocampi in this group of young children with ASD revealed enlargement bilaterally that was proportional to overall increases in total cerebral volume. There were similar findings of cerebral enlargement for both girls and boys with ASD. For subregion analyses, structural abnormalities were observed primarily in boys, although this may reflect low statistical power issues because of the small sample (seven girls with ASD) studied. Among the ASD group, structural findings were independent of nonverbal IQ. In a subgroup of children with ASD with strictly defined autism, amygdalar enlargement was in excess of increased cerebral volume.

The brain's fear hub likely becomes abnormally small in the most severely socially impaired males with autism spectrum disorders, researchers funded by the National Institutes of Health's (NIH) National Institute of Mental Health (NIMH) and National Institute on Child Health and Human Development (NICHD) have discovered. Teens and young men who were slowest at distinguishing emotional from neutral expressions and gazed at eyes least -- indicators of social impairment -- had a smaller than normal amygdala, an almond-shaped danger-detector deep in the brain. The researchers also linked such amygdala shrinkage to impaired nonverbal social behavior in early childhood.

The new findings led the researchers to propose a new theory of the basis of autism, called underconnectivity theory, which holds that autism is a system-wide brain disorder that limits the coordination and integration among brain areas.

The results converge with previous findings of white matter abnormalities in autism. (White matter consists of the "cables" that connect the various parts of the brain to each other). The new findings led the researchers to propose a new theory of the basis of autism, called underconnectivity theory, which holds that autism is a system-wide brain disorder that limits the coordination and integration among brain areas. This theory helps explain a paradox of autism: Some people with autism have normal or even superior skills in some areas, while many other types of thinking are disordered.

Previous studies have demonstrated a lower degree of synchronization among activated brain areas in people with autism, as well as smaller size of the corpus callosum, the white matter that acts as cables to wire the parts of the brain together. This latest research shows for the first time that the abnormality in synchronization is related to the abnormality in the cabling. The results suggest that the connectivity among brain areas is among the central problems in autism. The researchers have also found that people with autism rely heavily on the parts of the brain that deal with imagery, even when completing tasks that would not normally call for visualization.

BACKGROUND: The cerebellum is one of the most consistent sites of neuroanatomic abnormality in autism, yet it is still unclear how such pathology impacts cerebellar function. In normal subjects, we previously demonstrated with functional magnetic resonance imaging (fMRI) a dissociation between cerebellar regions involved in attention and those involved in a simple motor task, with motor activation localized to the anterior cerebellum ipsilateral to the moving hand. The purpose of the present investigation was to examine activation in the cerebella of autistic patients and normal control subjects performing this motor task. METHODS: We studied eight autistic patients and eight matched normal subjects, using fMRI. An anatomic region-of-interest approach was used, allowing a detailed examination of cerebellar function. RESULTS: Autistic individuals showed significantly increased motor activation in the ipsilateral anterior cerebellar hemisphere relative to normal subjects, in addition to atypical activation in contralateral and posterior cerebellar regions. Moreover, increased activation was correlated with the degree of cerebellar structural abnormality. CONCLUSIONS: These findings strongly suggest dysfunction of the autistic cerebellum that is a reflection of cerebellar anatomic abnormality. This neurofunctional deficit might be a key contributor to the development of certain diagnostic features of autism (e.g., impaired communication and social interaction, restricted interests, and stereotyped behaviors).

There is evidence that the cerebellum is involved in motor learning and cognitive function in humans. Animal experiments have found structural changes in the cerebellum in response to long-term motor skill activity. We investigated whether professional keyboard players, who learn specialized motor skills early in life and practice them intensely throughout life, have larger cerebellar volumes than matched non-musicians by analyzing high-resolution T1-weighted MR images from a large prospectively acquired database (n = 120). Significantly greater absolute (P = 0.018) and relative (P = 0.006) cerebellar volume but not total brain volume was found in male musicians compared to male non-musicians. Lifelong intensity of practice correlated with relative cerebellar volume in the male musician group (r = 0.595, P = 0.001). In the female group, there was no significant difference noted in volume measurements between musicians and non-musicians. The significant main effect for gender on relative cerebellar volume (F = 10.41, P < 0.01), with females having a larger relative cerebellar volume, may mask the effect of musicianship in the female group. We propose that the significantly greater cerebellar volume in male musicians and the positive correlation between relative cerebellar volume and lifelong intensity of practice represents structural adaptation to long-term motor and cognitive functional demands in the human cerebellum.

When considering the cognitive abilities of people with autism, the majority of studies have explored domains in which there are deficits. However, on tests of local processing and visual search, exemplified by the Embedded Figures Task (EFT), people with autism have been reported to demonstrate superiority over normal controls. This study employed functional MRI of subjects during the performance of the EFT to test the hypothesis that normal subjects and a group with autism would activate different brain regions and that differences in the patterns of these regional activations would support distinct models of cerebral processing underlying EFT performance in the two groups. It was found that several cerebral regions were similarly activated in the two groups. However, normal controls, as well as demonstrating generally more extensive task-related activations, additionally activated prefrontal cortical areas that were not recruited in the group with autism. Conversely, subjects with autism demonstrated greater activation of ventral occipitotemporal regions. These differences in functional anatomy suggest that the cognitive strategies adopted by the two groups are different: the normal strategy invokes a greater contribution from working memory systems while the autistic group strategy depends to an abnormally large extent on visual systems for object feature analysis. This interpretation is discussed in relation to a model of autism which proposes a predisposition towards local rather than global modes of information processing.

Attempted deception is associated with activation of executive brain regions (particularly prefrontal and anterior cingulate cortices), while truthful responding has not been shown to be associated with any areas of increased activation (relative to deception). Hence, truthful responding may comprise a relative 'baseline' in human cognition and communication.

The brain activation of a group of high-functioning autistic participants was measured using functional MRI during sentence comprehension and the results compared with those of a Verbal IQ-matched control group. The groups differed in the distribution of activation in two of the key language areas. The autism group produced reliably more activation than the control group in Wernicke's (left laterosuperior temporal) area and reliably less activation than the control group in Broca's (left inferior frontal gyrus) area. Furthermore, the functional connectivity, i.e. the degree of synchronization or correlation of the time series of the activation, between the various participating cortical areas was consistently lower for the autistic than the control participants. These findings suggest that the neural basis of disordered language in autism entails a lower degree of information integration and synchronization across the large-scale cortical network for language processing. The article presents a theoretical account of the findings, related to neurobiological foundations of underconnectivity in autism.

The cause of autistic spectrum disorder (i.e., autism and Asperger's syndrome) is unknown. The serotonergic (5-HT) system may be especially implicated. However, cortical 5-HT2A receptor density in adults with the disorder has not been examined, to the authors' knowledge. METHOD: The authors investigated cortical 5-HT2A receptor binding in eight adults with Asperger's syndrome and in 10 healthy comparison subjects with single photon emission computed tomography and the selective 5-HT2A receptor ligand 123I iodinated 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide (123I-5-I-R91150). People with Asperger's syndrome had a significant reduction in cortical 5-HT2A receptor binding in the total, anterior, and posterior cingulate; bilaterally in the frontal and superior temporal lobes; and in the left parietal lobe. Also, reduced receptor binding was significantly related to abnormal social communication. The authors' findings suggest that adults with Asperger's syndrome have abnormalities in cortical 5-HT2A receptor density and that this deficit may underlie some clinical symptoms.

This study presents the first three-dimensional mapping of cortical sulcal patterns in autism, a pervasive developmental disorder, the underlying neurobiology of which remains unknown. High-resolution T1-weighted MRI scans were acquired in 21 autistic (age 10.7 ± 3.1 years) and 20 normal control (age 11.3 ± 2.9) children and adolescents. Using parametric mesh-based analytic techniques, we created three-dimensional models of the cerebral cortex and detailed maps of 22 major sulci in stereotaxic space. These average maps revealed anatomic shifting of major sulci primarily in frontal and temporal areas. Specifically, we found anterior and superior shifting of the superior frontal sulci bilaterally (P = 0.0003), anterior shifting of the right Sylvian fissure (P = 0.0002), the superior temporal sulcus (P = 0.0006 right, P = 0.02 left) and the left inferior frontal sulcus (P = 0.002) in the autistic group relative to the normal group. Less significant sulcal shifts occurred in the intraparietal and collateral sulci. These findings may indicate delayed maturation in autistic subjects in these brain regions involved in functions including working memory, emotion processing, language and eye gaze.

Brain imaging studies of the hippocampus in autism have yielded inconsistent results. In this study, a computational mapping strategy was used to examine the three-dimensional profile of hippocampal abnormalities in autism. Twenty-one males with autism (age: 9.5+/-3.3 years) and 24 male controls (age: 10.3+/-2.4 years) underwent a volumetric magnetic resonance imaging scan at 3 Tesla. The hippocampus was delineated, using an anatomical protocol, and hippocampal volumes were compared between the two groups. Hippocampal traces were also converted into three-dimensional parametric surface meshes, and statistical brain maps were created to visualize morphological differences in the shape and thickness of the hippocampus between groups. Parametric surface meshes and shape analysis revealed subtle differences between patients and controls, particularly in the right posterior hippocampus. These deficits were significant even though the groups did not differ significantly with traditional measures of hippocampal volume. These results suggest that autism may be associated with subtle regional reductions in the size of the hippocampus. The increased statistical and spatial power of computational mapping methods provided the ability to detect these differences, which were not found with traditional volumetric methods.

Strong age-related increases were seen in the cross-sectional area of CAS, but autistic and normal subjects were not significantly different. This is the first direct evidence that anatomical abnormality within the limbic system exists from the earliest years of the disorder, and persists throughout development and to middle age.

We considered that fMRI may be a useful non-invasive method to evaluate the cerebral functional abnormality in autistic patients.

Impaired social cognition is a core feature of autism. There is much evidence showing people with autism use a different cognitive style than controls for face-processing. We tested if people with autism would show differential activation of social brain areas during a face-processing task. Thirteen adults with high-functioning autism or Asperger Syndrome (HFA/AS) and 13 matched controls. We used fMRI to investigate 'social brain' activity during perception of fearful faces. We employed stimuli known to reliably activate the amygdala and other social brain areas, and ROI analyses to investigate brain areas responding to facial threat as well as those showing a linear response to varying threat intensities. We predicted: (1) the HFA/AS group would show differential activation (as opposed to merely deficits) of the social brain compared to controls and (2) that social brain areas would respond to varied intensity of fear in the control group, but not the HFA/AS group. Both predictions were confirmed. The controls showed greater activation in the left amygdala and left orbito-frontal cortex, while the HFA/AS group showed greater activation in the anterior cingulate gyrus and superior temporal cortex. The control group also showed varying responses in social brain areas to varying intensities of fearful expression, including differential activations in the left and right amygdala. This response in the social brain was absent in the HFA/AS group. HFA/AS are associated with different patterns of activation of social brain areas during fearful emotion processing, and the absence in the HFA/AS brain of a response to varying emotional intensity.

OBJECTIVE: Recent years have seen a revolution in views regarding cerebellar function. New findings suggest that the cerebellum plays a role in multiple functional domains: cognitive, affective, and sensory as well as motor. These findings imply that developmental cerebellar pathology could play a role in certain nonmotor functional deficits, thereby calling for a broader investigation of the functional consequences of cerebellar pathology. Autism provides a useful model, since over 90% of autistic cerebella examined at autopsy have shown well-defined cerebellar anatomic abnormalities. The aim of the present study was to examine how such pathology ultimately impacts cognitive and motor function within the cerebellum. METHOD: Patterns of functional magnetic resonance imaging (fMRI) activation within anatomically defined cerebellar regions of interest were examined in eight autistic patients (ages 14�38 years) and eight matched healthy comparison subjects performing motor and attention tasks. For the motor task, subjects pressed a button at a comfortable pace, and activation was compared with a rest condition. For the attention task, visual stimuli were presented one at a time at fixation, and subjects pressed a button to every target. Activation was compared with passive visual stimulation. RESULTS: While performing these tasks, autistic individuals showed significantly greater cerebellar motor activation and significantly less cerebellar attention activation. CONCLUSIONS: These findings shed new light on the cerebellar role in attention deficits in autism and suggest that developmental cerebellar abnormality has differential functional implications for cognitive and motor systems.

The corpus callosum is the largest commissural white matter pathway that connects the hemispheres of the human brain. In this study, diffusion tensor imaging (DTI) was performed on subject groups with high-functioning autism and controls matched for age, handedness, IQ, and head size. DTI and volumetric measurements of the total corpus callosum and subregions (genu, body and splenium) were made and compared between groups. The results showed that there were significant differences in volume, fractional anisotropy, mean diffusivity, and radial diffusivity between groups. These group differences appeared to be driven by a subgroup of the autism group that had small corpus callosum volumes, high mean diffusivity, low anisotropy, and increased radial diffusivity. This subgroup had significantly lower performance IQ measures than either the other individuals with autism or the control subjects. Measurements of radial diffusivity also appeared to be correlated with processing speed measured during the performance IQ tests. The subgroup of autism subjects with high mean diffusivity and low fractional anisotropy appeared to cluster with the highest radial diffusivities and slowest processing speeds. These results suggest that the microstructure of the corpus callosum is affected in autism, which may be related to nonverbal cognitive performance.

For the purpose of identifying the relatively specific brain regions related to word and face recognition memory on the one hand and the regions common to both on the other, regional cerebral blood flow associated with different cognitive tasks for recognition memory was examined using [H215O]PET in healthy volunteers. The tasks consisted of recognizing two types of stimuli (faces and words) in two conditions (novel and familiar), and two baseline tasks (reading words and gender classification). The statistical analyses used to identify the specific regions consisted of three subtractions: novel words minus novel faces, familiar words minus familiar faces, and reading words minus gender classification. These analyses revealed relative differences in the brain circuitry used for recognizing words and for recognizing faces within a defined level of familiarity. In order to find the regions common to both face and word recognition, overlapping areas in four subtractions (novel words minus reading words, novel faces minus gender classification, familiar words minus reading words, and familiar faces minus gender classification) were identified. The results showed that the activation sites in word recognition tended to be lateralized to the left hemisphere and distributed as numerous small loci, and particularly included the posterior portion of the left middle and inferior temporal gyri. These regions may be related to lexical retrieval during written word recognition. In contrast, the activated regions for face recognition tended to be lateralized to the right hemisphere and located in a large aggregated area, including the right lingual and fusiform gyri. These findings suggest that strikingly different neural pathways are engaged during recognition memory for words and for faces, in which a critical role in discrimination is played by semantic cueing and perceptual loading, respectively. In addition, the investigation of the regions common to word and face recognition indicates that the anterior and posterior cingulate have dissociable functions in recognition memory that vary with familiarity, and that the cerebellum may serve as the co-ordinator of all four types of recognition memory processes.

We show that despite putative processing similarities at the cognitive level, binding in Williams syndrome and autism can be dissociated at the neurophysiological level by different abnormalities in underlying brain oscillatory activity.

High-functioning autistic and normal school-age boys were compared using a whole-brain morphometric profile that includes both total brain volume and volumes of all major brain regions. This morphometric profile of the autistic brain suggests that there is an overall increase in brain volumes compared with controls. Additionally, results suggest that there may be differential effects driving white matter to be larger and cerebral cortex and hippocampus-amygdala to be relatively smaller in the autistic than in the typically developing brain. The cause of this apparent dissociation of cerebral cortical regions from subcortical regions and of cortical white from grey matter is unknown, and merits further investigation.

"We will look for a relationship between gene variation and variation in the brain," says John Gabrieli, an MIT neuroscientist. Gabrieli will use fMRI, a type of MRI that shows which areas of the brain are active when people think about specific problems, to compare brain activity in normal individuals and in those with different forms of the suspected autism genes. Specifically, his group will look at how people deal with social functions, by imaging brain activity in response to faces and facial expressions.

Functional magnetic resonance imaging (fMRI) was used to compare brain activation to static facial displays versus dynamic changes in facial identity or emotional expression. Static images depicted prototypical fearful, angry and neutral expressions. Identity morphs depicted identity changes from one person to another, always with neutral expressions. Emotion morphs depicted expression changes from neutral to fear or anger, creating the illusion that the actor was 'getting scared' or 'getting angry' in real-time. Brain regions implicated in processing facial affect, including the amygdala and fusiform gyrus, showed greater responses to dynamic versus static emotional expressions, especially for fear. Identity morphs activated a dorsal fronto-cingulo-parietal circuit and additional ventral areas, including the amygdala, that also responded to the emotion morphs. Activity in the superior temporal sulcus discriminated emotion morphs from identity morphs, extending its known role in processing biologically relevant motion. The results highlight the importance of temporal cues in the neural coding of facial displays.

We conclude that the differences observed in the visual capacities of individuals with autism are likely to arise from higher-level cognitive areas and functions, and are the result of top-down processes.

Even with the enhanced emotional salience of facial stimuli, adults with autism showed lower activity in the fusiform cortex and differed from the comparison subjects in activation of other brain regions. The authors suggested that the recognition of emotion by adults with autism is achieved through recruitment of brain regions concerned with allocation of attention, sensory gating, the referencing of perceptual knowledge, and categorization.

In this context of high certainty about normal functional patterns, Schultz et al7 conducted the first neuroimaging study to test whether autism involves abnormal neurofunctional activation during face processing.

It appears that, as compared with normal individuals, autistic individuals `see' faces utilizing different neural systems, with each patient doing so via a unique neural circuitry. Such a pattern of individual-specific, scattered activation seen in autistic patients in contrast to the highly consistent FG activation seen in normals, suggests that experiential factors do indeed play a role in the normal development of the FFA.

Abnormal hypoactivation in the amygdala and fusiform gyrus, brain areas that participate in face processing and social cognition, has consistently been demonstrated in persons with autism. We investigated activity in these areas in a boy with autism, DD, who had a special interest in "Digimon" cartoon characters. DD individuates Digimon faster than familiar faces and objects, but he individuates familiar faces no faster than objects. In contrast, a typically developing boy with an interest in "Pokemon" cartoon characters is equally fast at individuating faces and Pokemon and faster at individuating faces and Pokemon than objects and Digimon. In addition, using functional magnetic resonance imaging (fMRI), we show that DD activates his amygdala and fusiform gyrus for perceptual discriminations involving Digimon but not for those involving familiar or unfamiliar faces. This pattern of activation is not seen in the typically developing control with an interest in Pokemon or in a second comparison case who has autism but no interest in Digimon. These results have important implications for our understanding of autism, cortical face specialization, and the possible role of the amygdala in the development of perceptual expertise.

We suggest that in autism during conditions that demand rapid change in attentional set, generalised arousal substitutes for impaired early selective attention, leaving irrelevant stimuli to be suppressed at a later stage.

The aim of this investigation was to identify neural systems supporting the processing of intentional and unintentional transgressions of social norms. Using event-related fMRI, we addressed this question by comparing neural responses to stories describing normal behaviour, embarrassing situations or violations of social norms. Processing transgressions of social norms involved systems previously reported to play a role in representing the mental states of others, namely medial prefrontal and temporal regions. In addition, the processing of transgressions of social norms involved systems previously found to respond to aversive emotional expressions (in particular angry expressions); namely lateral orbitofrontal cortex (Brodmann area 47) and medial prefrontal cortex. The observed responses were similar for both intentional and unintentional social norm violations, albeit more pronounced for the intentional norm violations. These data suggest that social behavioural problems in patients with frontal lobe lesions or fronto-temporal dementia may be a consequence of dysfunction within the systems identified in light of their possible role in processing whether particular social behaviours are, or are not, appropriate.

Recent neuroimaging studies have reported that regions of the frontal lobes appear to be active during theory of mind tasks, suggesting that these may be part of a theory of mind circuit.

Brain activity in people with high-functioning autism has been shown to be atypical in a number of ways, including reduced synchronization across areas of activation measured by functional magnetic resonance imaging. This activation atypicality has been observed mostly during the performance of cognitive tasks. This study compares the resting-state network of 57 participants with autism and 57 control participants matched for age and intelligence quotient. The results indicate that both groups have a resting-state network that is very similar both in volume and in organization, but in autism this network is much more loosely connected. This functional underconnectivity was observed in the anterior-posterior connections. The results expand the theory of cortical underconnectivity in autism to the resting state of the brain.

An fMRI study was used to measure the brain activation of a group of adults with high-functioning autism compared to a Full Scale and Verbal IQ and age-matched control group during an n-back working memory task with letters. The behavioral results showed comparable performance, but the fMRI results suggested that the normal controls might use verbal codes to perform the task, while the adults with autism might use visual codes. The control group demonstrated more activation in the left than the right parietal regions, whereas the autism group showed more right lateralized activation in the prefrontal and parietal regions. The autism group also had more activation than the control group in the posterior regions including inferior temporal and occipital regions. The analysis of functional connectivity yielded similar patterns for the two groups with different hemispheric correlations. The temporal profile of the activity in the prefrontal regions was more correlated with the left parietal regions for the control group, whereas it was more correlated with the right parietal regions for the autism group.

An fMRI study was used to measure the brain activation of a group of adults with high-functioning autism compared to a Full Scale and Verbal IQ and age-matched control group during an n-back working memory task with letters. The behavioral results showed comparable performance, but the fMRI results suggested that the normal controls might use verbal codes to perform the task while the adults with autism might use visual codes.

Positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and computed tomography (CT, also referred to as computed axial tomography, CAT) are the most common techniques currently used in functional imaging.

Structural neuroimaging, which consists of computed tomography (CT) and magnetic resonance imaging (MRI), can only show gross anatomic details. Functional neuroimaging scans show some activity of the brain, and they often provide more information.

When viewing a movie laden with social interaction, most people naturally focus on eyes; people with autism, however, appear unable to focus on eyes and fix their gaze instead on mouths, thus missing much of the visual social information.

Results confirm that the left amygdala plays a general role in the interpretation of eye gaze direction, and that the activity of the right amygdala of the subject increases when another individual's gaze is directed towards him. This suggests that the human amygdala plays a role in reading social signals from the face.

these data suggest that regions of temporal cortex actively integrate form and motion information, a process largely independent of low-level visual processes such as changes in local luminance and contrast.

Children with attention deficit-hyperactivity disorder (ADHD) may have significantly altered levels of important neurotransmitters (biochemicals that carry signals to and from cells) in the frontal region of the brain.

Future imaging studies should attempt to investigate more homogeneous subgroups of patients such as those with �the lesser variant of PDD� and high-functioning patients with PDD who do not have comorbid medical conditions.

It is clear that brain mapping and neuroimaging will continue to be ever more important parts of clinical neuroscience and may ultimately serve as the bridge between the molecular and clinical domains of this field.

This review provides a brief description of spectroscopy, followed by a literature review of key spectroscopy findings in schizophrenia, affective disorders, and autism.

In autism, the pervasive and persistent cognitive deficits which characterize the disorder may be the consequence of concurrent anatomical abnormality not just in the frontal lobe, but also in the cerebellum and possibly also in other brain regions. It remains to be determined whether a similar increase in volume exists elsewhere in the brain (particularly the cerebrum) and whether such abnormalities also correlate with the cerebellar abnormalities.

Intersite differences were seen for subject age, IQ, and cerebellum measures. Cerebral gray matter volume was enlarged in both HFA and LFA compared with controls (P = .009 and P = .04, respectively). Cerebral gray matter volume in ASP was intermediate between that of HFA and controls, but nonsignificant. Exploratory analyses revealed a negative correlation between cerebral gray matter volume and performance IQ within HFA but not ASP. A positive correlation between cerebral white matter volume and performance IQ was observed within ASP but not HFA.

Compared with age- and sex-matched healthy volunteers, patients with autism spectrum disorders showed significantly decreased metabolism in both the anterior and posterior cingulate gyri.

By incorporating MRI analysis in neuropathological investigations, studies may benefit from a record of the intact brain.

The orbitofrontal cortex is involved in multiple psychologic functions, such as emotional and cognitive processing, learning, and social behavior. These functions are variably impaired in individuals with autism. The present study examined the size of the orbitofrontal cortex, and its medial and lateral subdivisions, using magnetic resonance imaging (MRI) scans obtained from 40 non�mentally retarded individuals with autism and 41 healthy controls. No differences were observed between the two groups on any of the orbitofrontal cortex measurements. However, when compared with controls, a smaller right lateral orbitofrontal cortex was observed in children and adolescents with autism, whereas a larger right lateral orbitofrontal cortex was found in adult patients. Interestingly, a positive relationship was found in the patient group between circumscribed interests and all orbitofrontal cortex structures. The present study suggests the absence of global volumetric abnormalities in the orbitofrontal cortex in autism and indicates that the functional disturbances in this structure might not be related to anatomic alterations.

We will use a multivoxel proton MRS as our neuroimaging method to measure the brain metabolites of macrocephalic autistic children and their non-autistic macrocephalic parents. Multivoxel technique allows a number of voxels to be simultaneously positioned in the brain. However, the more voxels of interest (VOIs) formed, the longer the scan time. Due to restrictions of cost and time, we have chosen to limit this study to the temporal lobe (including hippocampus-amygdala region), the cerebellum, and the frontal lobe, based on previous neuroimaging findings.

Children with autism had a significant reduction in total grey matter volume and significant increase in CSF volume. They had significant localized grey matter reductions within fronto-striatal and parietal networks similar to findings in our previous study, and additional decreases in ventral and superior temporal grey matter. White matter was reduced in the cerebellum, left internal capsule and fornices. Correlation analysis revealed significantly more numerous and more positive grey matter volumetric correlations in controls compared with children with autism. Our data suggest abnormalities in the anatomy and connectivity of limbic-striatal 'social' brain systems which may contribute to the brain metabolic differences and behavioural phenotype in autism.

Stopped at a red light or waiting in a doctor's office, people's idle thoughts may focus on themselves, other people in their lives, nearby strangers or their plans for the day. But a new brain-imaging study suggests the minds of autistic individuals do not engage in these "daydreams" about themselves or other people whenever their brains are free to wander.

The projects are: Using new gene targeting, physiological and imaging techniques, the Sur team will develop tools for creating mouse and other animal models for autism and explore whether autism-related genes are involved in two key aspects of brain development and function in the cerebral cortex. Bear will look at mutations in the gene causing Fragile X syndrome, which shares similarities with autism. Bear's work indicates that by blocking a single brain chemical, many of the psychiatric and neurological disabilities associated with Fragile X and autism could be treated. Using state-of-the-art brain imaging techniques, Gabrieli will seek to understand how neurons play a role in autistic individuals' problems with social interaction and face recognition. Graybiel's team has cloned genes that may be related to autism or related disorders and will seek to understand the function of two molecules of a particular group. This information may lead to new mouse models. Sinha studies face processing ability in children with autism and is developing a methodology called VisTA (Visual Training and Assessment) to help them refine skills such as maintaining eye contact and reading facial expressions, body postures and gestures.Tonegawa's team will investigate the functional interaction between two genes that are implicated in both Fragile X syndrome and autism.

Analyses of brain structure in genetic speech and language disorders provide an opportunity to identify neurobiological phenotypes and further elucidate the neural bases of language and its development. Here we report such investigations in a large family, known as the KE family, half the members of which are affected by a severe disorder of speech and language, which is transmitted as an autosomal-dominant monogenic trait. The structural brain abnormalities associated with this disorder were investigated using two morphometric methods of MRI analysis. A voxel-based morphometric method was used to compare the amounts of grey matter in the brains of three groups of subjects: the affected members of the KE family, the unaffected members and a group of age-matched controls. This method revealed a number of mainly motor- and speech-related brain regions in which the affected family members had significantly different amounts of grey matter compared with the unaffected and control groups, who did not differ from each other. Several of these regions were abnormal bilaterally, including the caudate nucleus, which was of particular interest because this structure was also found to show functional abnormality in a related PET study. We performed a more detailed volumetric analysis of this structure. The results confirmed that the volume of this nucleus was reduced bilaterally in the affected family members compared with both the unaffected members and the group of age-matched controls. This reduction in volume was most evident in the superior portion of the nucleus. The volume of the caudate nucleus was significantly correlated with the performance of affected family members on a test of oral praxis, a test of non-word repetition and the coding subtest of the Wechsler Intelligence Scale. These results thus provide further evidence of a relationship between the abnormal development of this nucleus and the impairments in oromotor control and articulation reported in the KE family.

Our study clearly demonstrates that two different CNS structures, midbrain and corpus callosum, correlate with the results of psychological and behavioral tests.

There is a reduction in the volume of amygdala and hippocampus in people with autism, particularly in relation to total brain volume. The histopathology of autism suggests that these volume reductions are related to a reduction in dendritic tree and neuropil development, and likely reflect the underdevelopment of the neural connections of limbic structures with other parts of the brain, particularly cerebral cortex.

Impairments in executive cognitive processes in autism may be subserved by abnormalities in neocortical circuitry as evidenced by decreased activation in prefrontal and posterior cingulate circuitry during a spatial working memory task.

Brain imaging research has identified at least two regions in human extrastriate cortex responding selectively to faces. One of these is located in the mid-fusiform gyrus (FFA), the other in the inferior occipital gyrus (IOG). We studied activation of these areas using fMRI in three individuals with severely impaired face recognition (one pure developmental and two childhood prosopagnosics). None of the subjects showed the normal pattern of higher fMRI activity to faces than to objects in the FFA and IOG or elsewhere. Moreover, in two of the patients, faces and objects produced similar activations in the regions corresponding to where the FFA and IOG are found in normal subjects. Our study casts light on the important role of FFA and IOG in the network of areas involved in face recognition, and indicates limits of brain plasticity.

Neural activity was measured in 10 healthy volunteers by functional MRI while they viewed familiar and unfamiliar faces and listened to familiar and unfamiliar voices. The familiar faces and voices were those of people personally known to the subjects; they were not people who are more widely famous in the media. Changes in neural activity associated with stimulus modality irrespective of familiarity were observed in modules previously demonstrated to be activated by faces (fusiform gyrus bilaterally) and voices (superior temporal gyrus bilaterally). Irrespective of stimulus modality, familiarity of faces and voices (relative to unfamiliar faces and voices) was associated with increased neural activity in the posterior cingulate cortex, including the retrosplenial cortex. Our results suggest that recognizing a person involves information flow from modality-specific modules in the temporal cortex to the retrosplenial cortex. The latter area has recently been implicated in episodic memory and emotional salience, and now seems to be a key area involved in assessing the familiarity of a person. We propose that disturbances in the information flow described may underlie neurological and psychiatric disorders of the recognition of familiar faces, voices and persons (prosopagnosia, phonagnosia and Capgras delusion, respectively).

Autistic spectrum disorder (ASD) is a lifelong developmental disorder characterized by impairment in socialization and communication. Neuroimaging research has shown abnormalities in the frontal lobes, limbic systems, and cerebella of individuals with ASD. Recently, abnormal developmental trajectories of brain growth have been reported, with increases in brain volume (in both gray and white matter) seen in younger rather than older individuals with this disorder. Despite 30 years of research, a reliable marker for ASD has not been identified. Therefore, routine neuroimaging for individuals with ASD is not recommended.

I hypothesize that autism is a disorder of systems alteration or disruption and that systems can be impacted in multiple ways and yet yield a similar syndrome of behaviors. From this vantage point, the variability in biomarkers can be transformed from noise into signal, yielding insight into the multiple systems vulnerabilities that can lead to this type of disordered social-emotional functioning. We also need to characterize the limits to the variability of systems impact; that is, under what circumstances can systems disruption lead to a lesser or different syndrome than autism? Formulating the research challenge in these terms can allow a more parsimonious integration not only of variability in biologic findings but also of variability in the gene-environment interactions involved in underlying mechanisms.

Conclusion : Neuroimaging should be the standard clinical practice for a child with global developmental delay where no cause is apparent after examination and relevant investigations.

Objective: To test the hypothesis that a combination of magnetic resonance imaging (MRI) brain measures obtained during early childhood distinguish children with autism spectrum disorders (ASD) from typically developing children and is associated with functional outcome. Conclusions: These results indicate that variability in cerebellar and cerebral size is correlated with diagnostic and functional outcome in very young children with ASD.

We propose that the critical mechanism that allows humans to develop a theory of own and other minds results from the development of introspection (monitoring one's own mind) and an adaptation of a much older social brain concerned with monitoring the behaviour of others.

Patterns in response to facial expressions support the notion of involved neural substrates for processing different facial expressions.

No consistent focal brain abnormalities for Asperger Syndrome were detected. The reduced diameters of the mesencephalon in the Asperger group support the hypothesis that the mesencephalon may be involved in the pathogenesis of Asperger Syndrome.

Previous functional imaging studies have explored the brain regions activated by tasks requiring 'theory of mind'--the attribution of mental states. Tasks used have been primarily verbal, and it has been unclear to what extent different results have reflected different tasks, scanning techniques, or genuinely distinct regions of activation. Here we report results from a functional magnetic resonance imaging study (fMRI) involving two rather different tasks both designed to tap theory of mind. Brain activation during the theory of mind condition of a story task and a cartoon task showed considerable overlap, specifically in the medial prefrontal cortex (paracingulate cortex). These results are discussed in relation to the cognitive mechanisms underpinning our everyday ability to 'mind-read'.

Contrary to the prominence traditionally given to ventral frontal regions for response inhibition, the results suggest that response inhibition is accomplished by a distributed collection of primarily frontal and largely right hemisphere regions.

New findings indicate a deficiency in the coordination among brain areas. The results converge with previous findings of white matter abnormalities in autism. White matter consists of the "cables" that connect the various parts of the brain to each other.

Brain development during childhood and adolescence is characterized by both progressive myelination and regressive pruning processes. However, sex differences in brain maturation remain poorly understood. Magnetic resonance imaging was used to examine the relationships between age and sex with cerebral gray and white matter volumes and corpus callosal areas in 118 healthy children and adolescents (61 males and 57 females), aged 6�17 years. Gender groups were similar on measures of age, handedness, socioeconomic status and Full Scale IQ. Significant age-related reductions in cerebral gray and increases in white matter volumes and corpus callosal areas were evident, while intracranial and cerebral volumes did not change significantly. Significant sex by age interactions were seen for cerebral gray and white matter volumes and corpus callosal areas. Specifically, males had more prominent age-related gray matter decreases and white matter volume and corpus callosal area increases compared with females. While these data are from a cross-sectional sample and need to be replicated in a longitudinal study, the findings suggest that there are age-related sex differences in brain maturational processes. The study of age-related sex differences in cerebral pruning and myelination may aid in understanding the mechanism of several developmental neuropsychiatric disorders.

Visual attention can be primarily allocated to either where an object is in space (with little emphasis on the structure of the object itself) or to the structure of the object (with little emphasis on where in space the object is located). Using PET measures of regional cerebral blood flow (rCBF) to index neural activity, we investigated the shared and specific functional anatomy underlying both of these types of visual attention in a controlled non-cueing non-blocked paradigm that involved identical stimuli across the conditions of interest. The interaction of eye movements with these attentional systems was studied by introducing fixation or free vision as an additional factor. Relative to the control condition, object-based and space-based attention showed significant activations of the left and right medial superior parietal cortex and the left lateral inferior parietal cortex, the left prefrontal cortex and the cerebellar vermis. Significant differential activations were observed during object-based attention in the left striate and prestriate cortex. Space-based attention activated the right prefrontal cortex and the right inferior temporal-occipital cortex. Differential neural activity due to free vision or fixation was observed in occipital areas only. Significant interactions of free vision/fixation on activations due to object-based and space-based attention were observed in the right medial superior parietal cortex and left lateral inferior parietal cortex, respectively. The study provides direct evidence for the importance of the parietal cortex in the control of object-based and space-based visual attention. The results show that object-based and space-based attention share common neural mechanisms in the parietal lobes, in addition to task specific mechanisms in early visual processing areas of temporal and occipital cortices.

Researchers at the University of Washington School of Medicine in Seattle used magnetic resonance imaging (MRI) to examine transverse relaxation (T2) of cortical gray and white matter in the brains of 60 children with autism spectrum disorder (ASD) and found their brains were structurally different from children with typical brain development (TD) or those with idiopathic developmental delay (DD). "We've discovered that very young children with autism have larger brains that are less mature than children with typical [brain] development with respect to cortical gray matter," principal investigator Stephen Dager, MD, told Medscape. In addition, he said, these data, which show delayed development of gray matter, contradict previous theories that autism is characterized by accelerated normal brain growth.

Consistent with behavioural studies showing that basic face perception is abnormal in individuals with autism, activity in the fusiform gyrus is reduced during face perception tasks involving neutral faces.

The finding is surprising, as it is widely known that autistic individuals tend to avoid looking directly at faces. The research also counters previous published reports that the face-processing area at the back of the brain is under-responsive in people with autism, and it suggests that specific behavioral interventions may help people with autism improve their ability to interact socially. The study involved functional magnetic resonance imaging, or fMRI. Unlike standard MRI scans that show anatomical structures in black and white, fMRI offers digitally enhanced color images of brain function, depicting localized changes in blood flow and oxygenation.

The first autistic group had a highly significant hypoperfusion in both temporal lobes centered in associative auditory and adjacent multimodal cortex, which was detected in 76% of autistic children. Virtually identical results were found in the second autistic group in the extension study. PETand voxel-based image analysis revealed a localized dysfunction of the temporal lobes in school-aged children with idiopathic autism.

This chapter explores the contribution of neuroimaging in advancing our understanding how the human brain processes language generally, but discourse specifically.

Abnormal regulation of brain growth in autism results in early overgrowth followed by abnormally slowed growth. Hyperplasia was present in cerebral gray matter and cerebral and cerebellar white matter in early life in patients with autism.

Abnormal regulation of brain growth in autism results in early overgrowth followed by abnormally slowed growth. Hyperplasia was present in cerebral gray matter and cerebral and cerebellar white matter in early life in patients with autism.

Children with autism may have slower development of some neurons although their brains are often larger than normal, researchers say. Previously, some scientists thought the brain abnormalities in autism resulted from faster development. Brain scans confirmed children with autism tend to have brains that are enlarged by about 10 per cent, Stephen Dager of the University of Washington School of Medicine and his colleagues found.