A volumetric magnetic resonance imaging study of brain structures in children with Down syndrome

BACKGROUND AND PURPOSE : Down syndrome (DS) is the most common genetic cause of mental retardation with deficits in language and memory. Mental retardation of varying degrees is the most consistent feature of DS. The objective of this study was to use high-resolution magnetic resonance imaging (MRI) techniques to investigate the volumes of the hippocampus, amygdala, and temporal and frontal lobes in children with DS compared with healthy children. MATERIAL AND METHODS : MRI of 49 patients was reviewed prospectively. The study included 23 children with DS (9 girls and 14 boys, mean age 6.7 ± 3.7 years) and 26 healthy children (11 girls and 15 boys, mean age 8.3 ± 2.4 years). Volumes of the right and left hippocampus, the right and left amygdala, temporal and frontal lobes and the total brain volume were measured by a radiologist who was unaware of the diagnosis. RESULTS : Total brain volume in children with DS was significantly lower compared with controls. It was associated with significantly lower volume of the frontal and temporal lobes. Children with DS had a significantly smaller right and left hippocampus volume and a significantly smaller right and left amygdala volume than did the control group. We also found a negative correlation between mental retardation and volume of the right hippocampus. CONCLUSIONS : The presence of these abnormalities from an early age contributes to the specific cognitive and developmental deficits seen in children with DS.     

Structural brain abnormalities in patients with schizophrenia, epilepsy, and epilepsy with chronic interictal psychosis.

Chronic interictal psychotic syndromes, often resembling schizophrenia, develop in some patients with epilepsy. Although widespread brain abnormalities are recognized as characteristic of schizophrenia, prevailing but controversial hypotheses on the co-occurrence of epilepsy and psychosis implicate left temporal lobe pathology. In this study, quantitative MRI methods were used to address the regional specificity of structural brain abnormalities in patients with epilepsy plus chronic interictal psychosis (E+PSY, n=9) relative to three comparison groups: unilateral temporal lobe epilepsy without chronic psychosis (TLE, n=18), schizophrenia (SCZ, n=46), and healthy control subjects (HC, n=57). Brain measures, derived from a coronal spin-echo MRI sequence, were adjusted for age and cerebral volume. Relative to HC, all patient groups had ventricular enlargement and smaller temporal lobe, frontoparietal, and superior temporal gyrus gray matter volumes, with the extent of these abnormalities greatest in E+PSY. Only TLE had temporal lobe white matter deficits, as well as smaller hippocampi, which were ipsilateral to the seizure focus. Structural brain abnormalities in E+PSY are not restricted to the left temporal lobe. The confluence of cortical gray matter deficits in E+PSY and SCZ suggests salience to chronic psychosis.     

Cortical and Hippocampal Volume Deficits in Temporal Lobe Epilepsy

Summary: Purpose : To use quantitative magnetic resonance imaging (MRI) methods to examine the extent of volume abnormalities in the hippocampus and in extrahippocampal brain regions in localization-related epilepsy of temporal lobe origin (TLE).
Methods : Hippocampal, temporal lobe, and extratemporal lobe volumes were examined with 3–mm spin-echo coronal MRI scans in patients with unilateral TLE who were candidates for temporal lobe resection. Measures were adjusted for normal variation due to intracranial volume and age based on 72 healthy male controls. Group differences between 14 male TLE [7 left TLE (LTLE), 7 right TLE (RTLE)] patients and a subset of 49 age range-matched controls were examined with analysis of variance (ANOVA).
Results : As compared with controls, patients with TLE had smaller temporal lobe and frontoparietal region gray matter volumes, bilaterally, smaller temporal lobe white matter volumes bilaterally, and larger ventricular volumes. In contrast to these bilateral tissue volume deficits, hippocampal volume deficits in TLE were ipsilateral to the epileptogenic temporal lobe.
Conclusions : Extrahippocampal volume abnormalities were bilateral and occurred in both temporal and extra-temporal cortical regions in TLE, whereas hippocampal deficits were related to the side of the epileptogenic focus. These data suggest that brain abnormalities in TLE are not limited to the epileptogenic region.     

Regional Brain Abnormalities in 22q11.2 Deletion Syndrome: Association With Cognitive Abilities and Behavioral Symptoms

Children with 22q11.2 microdeletions (Velocardiofacial Syndrome; VCFS) have previously been shown to exhibit learning deficits and elevated rates of psychopathology. The aim of this study was to assess regional brain abnormalities in children with 22q11DS, and to determine the relationship of these measures to neurocognitive and behavioral function. Thirteen children with confirmed deletions and 9 demographically matched comparison subjects were assessed with a neurocognitive battery, behavioral measures, and high-resolution MRI. Twenty-two q11DS children showed a nonsignificant 4.3% global decrease in total brain volume as compared to healthy controls, with differential reduction in white matter, and significantly increased sulcal cerebrospinal fluid (CSF) in temporal and posterior brain regions. In 22q11DS subjects, but not controls, bilateral temporal gray and white matter volumes were significant predictors of overall cognitive performance. Further, reduced temporal gray matter was associated with elevated Thought Problems score on the CBCL. Results indicate that global alterations in brain volume are common in children with 22q deletions, particularly those with low IQ and/or behavioral disturbance. Although preliminary, these findings suggest a possible underlying pathophysiology of the cognitive deficits seen in this syndrome, and provide insight into complex gene-brain-behavior relationships.     

Regional brain abnormalities in 22q11.2 deletion syndrome: association with cognitive abilities and behavioral symptoms

Children with 22q11.2 microdeletions (Velocardiofacial Syndrome; VCFS) have previously been shown to exhibit learning deficits and elevated rates of psychopathology. The aim of this study was to assess regional brain abnormalities in children with 22q11DS, and to determine the relationship of these measures to neurocognitive and behavioral function. Thirteen children with confirmed deletions and 9 demographically matched comparison subjects were assessed with a neurocognitive battery, behavioral measures, and high-resolution MRI. Twenty-two qllDS children showed a nonsignificant 4.3% global decrease in total brain volume as compared to healthy controls,with differential reduction in white matter, and significantly increased sulcal cerebrospinal fluid (CSF) in temporal and posterior brain regions. In 22q11 DS subjects, but not controls, bilateral temporal gray and white matter volumes were significant predictors of overall cognitive performance. Further, reduced temporal gray matter was associated with elevated Thought Problems score on the CBCL. Results indicate that global alterations in brain volume are common in children with 22q deletions, particularly those with low IQ and/or behavioral disturbance. Although preliminary,these findings suggest a possible underlying pathophysiology of the cognitive deficits seen in this syndrome,and provide insight into complex gene-brain-behavior relationships.     

Children and adolescents with velocardiofacial syndrome: a volumetric MRI study

OBJECTIVE: Velocardiofacial syndrome is a common genetic condition often accompanied by mild cognitive impairment. Children and adolescents with velocardiofacial syndrome also are at greater risk for developing serious neuropsychiatric disorders in adulthood, particularly schizophrenia-like disorders. The purpose of this preliminary study was to 1) elucidate through brain imaging the neurobiological basis of cognitive and neuropsychiatric problems in velocardiofacial syndrome, and 2) consider the association between variations in neuroanatomy in velocardiofacial syndrome subjects and the associated neurobehavioral phenotype. METHOD: Fifteen children and adolescents with velocardiofacial syndrome were matched by age and gender with 15 comparison subjects. High-resolution magnetic resonance imaging scans were analyzed to provide quantitative measures of specified brain tissues and regions. Rater-blind morphometric analyses were conducted to examine tissue volumes of the four lobes and the cerebellum. RESULTS: Total brain volume was approximately 11% smaller in the children with velocardiofacial syndrome. Gray matter volume was reduced to a lesser extent (7.5%) than white matter volume (16.3%). Multivariate analyses of variance indicated a distinct pattern of regional morphological variation among the children with velocardiofacial syndrome. Specifically, frontal lobe tissue tended to be enlarged relative to the overall reduction in brain volume. Normal symmetry of parietal lobe tissue observed in the comparison group was not evident in the velocardiofacial syndrome group. This loss of symmetry was attributable to a significant reduction of gray matter in the left parietal lobe. CONCLUSIONS: Aberrant brain morphology is associated with velocardiofacial syndrome. These changes are potentially related to the language and learning deficits associated with the syndrome and may provide clues about neurodevelopmental pathways associated with schizophrenia.     

Frontal Atrophy and Attention Deficits in Older Adults with a History of Elevated Depressive Symptoms

Studies of older adults with depressive disorders indicate greater cognitive deficits and brain alterations than would be expected for their age. There is some evidence that these findings are present after a single episode of depression, but this work has been cross-sectional in nature. We investigated both cross-sectional and longitudinal associations between a history of elevated depressive symptoms (HDS), frontal lobe volumes, and cognitive performance within the context of normal age-related changes over time in the Baltimore Longitudinal Study of Aging. After controlling for age, HDS was associated with smaller total frontal gray matter volumes and with smaller regional volumes in the cingulate gyrus and orbitofrontal cortex. Men, but not women, with HDS showed deficits in auditory attention span at older ages. Results confirm previous reports that even a single episode of depression is associated with adverse outcomes in older adults but suggest that HDS does not affect longitudinal trajectories of cognitive and brain volume change.     

Tc-99m HMPAO brain perfusion imaging in young Down's syndrome patients

Down's syndrome (DS) is characterized by moderate mental retardation and a variety of abnormalities involving multiple organ systems. There is a high incidence of Alzheimer's disease (AD) type dementia beyond the age of 35. In this study, single photon emission computed tomography (SPECT) brain perfusion imaging of young Down's syndrome patients was performed to define the perfusion pattern. Tc-99m HMPAO brain perfusion SPECT was performed on 17 young DS patients, aged 3-24 years (mean: 10.9+/-5.9 years). None of the patients had dementia symptoms. Brain perfusion scans were acquired 15 min after i.v. injection of 12 MBq/kg of Tc-99m HMPAO using a single head rotating gamma camera. Images were analyzed visually and semiquantitatively by defining side-to-side asymmetry index. Nine DS cases showed normal brain perfusion. Eight of the 17 cases revealed mostly unilateral parieto-temporal, parieto-occipital and frontal hypoperfusions. The side-to-side asymmetry indices for these visually interpreted regional brain perfusion abnormalities ranged from 6 to 15%. These findings revealing mostly unilateral parieto-temporal and frontal hypoperfusions may not be considered as predictive patterns of dementia related Alzheimer type perfusion deficits in DS. However, such findings may connect to other functional imaging studies related to the higher cortical dysfunction in mental retardation.     

Smaller frontal gray matter volume in postmortem schizophrenic brains

OBJECTIVE: The prefrontal cortex exhibits prominent functional, biochemical, and anatomic abnormalities in schizophrenic patients. However, smaller than normal volume of the frontal lobe has not been found in previous postmortem studies of schizophrenic subjects, and magnetic resonance imaging (MRI) scans of schizophrenic subjects have not consistently revealed frontal volumetric deficits. The variability in MRI findings may be related partly to difficulty in defining the posterior border of the frontal lobe. In this study, precise measurements of frontal lobe volume from postmortem brains were derived by defining the posterior border according to the brain atlas of Talairach and Tournoux and by applying stereologic methods to estimate gray and white matter volumes. METHOD: Whole, or nearly whole, formalin-fixed left hemispheres from 14 schizophrenic and 19 normal comparison subjects were analyzed. Total cortical gray and white matter volumes, as well as frontal cortical gray and white matter volumes, were measured by using the Cavalieri method. RESULTS: Only frontal gray matter volume was significantly smaller in the schizophrenic subjects than in the comparison subjects (12% difference). The differences between groups in total gray and white matter volumes and frontal white matter volume (6%-8% smaller in the schizophrenic subjects than in the comparison subjects) did not reach statistical significance. CONCLUSIONS: The smaller frontal gray matter volume observed in schizophrenic brains suggests that pathology of the frontal lobe may be more severe than that of the three posterior lobes and may account for the prominence of prefrontal dysfunction associated with schizophrenia.     

Neurodevelopmental and behavioral issues in Williams syndrome

Much existing research on Williams syndrome (WS) has focused on the individuals' unusual cognitive profile, with less emphasis placed on the developmental and neural underpinnings of the disorder. We review recent findings from brain imaging and begin to discuss links from these data to the behavioral phenotype. Overall brain size is significantly reduced in individuals with WS, as it is in many mental retardation syndromes. However, the specific profile of deficits in WS, particularly the visuospatial deficits, appears to be linked to parietal lobe abnormalities. Results from both genetic and brain imaging studies have provided useful insights into WS neurobiology. However, future work needs to remediate the lack of studies investigating developmental processes.     

Velocardiofacial syndrome: are structural changes in the temporal and mesial temporal regions related to schizophrenia?

OBJECTIVE: Velocardiofacial syndrome results from a microdeletion on chromosome 22 (22q11.2). Clinical studies indicate that more than 30% of children with the syndrome will develop schizophrenia. The authors sought to determine whether neuroanatomical features in velocardiofacial syndrome are similar to those reported in the literature on schizophrenia by measuring the volumes of the temporal lobe, superior temporal gyrus, and mesial temporal structures in children and adolescents with velocardiofacial syndrome. METHOD: Twenty-three children and adolescents with velocardiofacial syndrome and 23 comparison subjects, individually matched for age and gender, received brain magnetic resonance imaging (MRI) scans. Analysis of covariance models were used to compare regional brain volumes. Correlations between residualized brain volumes and age were standardized and compared with the Fisher r-to-z transformation. RESULTS: Children with velocardiofacial syndrome had significantly smaller average temporal lobe, superior temporal gyrus, and hippocampal volumes than normal comparison children, although these differences were commensurate with a lower overall brain size in the affected children. In a cross-sectional analysis, children with velocardiofacial syndrome exhibited aberrant volumetric reductions with age that were localized to the temporal lobe and left hippocampal regions. CONCLUSIONS: Abnormal temporal lobe and hippocampal development in velocardiofacial syndrome is potentially concordant with MRI findings in the schizophrenia literature. Temporal lobe and mesial temporal structures may represent a shared substrate for the effects of the 22q11.2 deletion and for the complex etiological pathways that lead to schizophrenia. Longitudinal research may help determine which children with velocardiofacial syndrome are at risk for serious psychiatric illness in adulthood.     

Growth disturbance of frontal lobe in BCECTS presenting with frontal dysfunction

A considerable proportion of children with benign childhood epilepsy with centrotemporal spikes (BCECTS) have increasingly been found to show neuropsychiatric deficits such as cognitive impairment and impulsivity, possibly associated with frontal lobe dysfunctions. We performed 3-dimensional magnetic resonance imaging (MRI)-based brain volumetry to characterize serial changes in frontal and prefrontal lobe volumes and compare volumetric changes with clinical symptoms. Serial changes in regional cerebral volumes were measured in a 5-year-old boy with BCECTS. Seizures were not easily controlled, and he demonstrated oromotor deficits, cognitive impairments and behavioral problems. Cognitive and behavioral deficits persisted even after remission of seizure disorder and oromotor deficits. Two BCECTS patients (5–6 years old) without neuropsychological disorders served as typical BCECTS, and nine normal subjects (4–10 years old) served as controls. Volumes of the frontal and prefrontal lobes were determined using a workstation, and prefrontal to frontal lobe volume ratio was calculated. Frontal and prefrontal lobe volumes showed no growth even after remission of seizure disorders. Prefrontal to frontal lobe volume ratio reduced slightly even after remission of both seizure disorders and EEG abnormalities. The result suggests that BCECTS presenting with atypical course may be associated with frontal lobe dysfunction resulting in cognitive and behavioral deficits.     

Schizotypal personality disorder and MRI abnormalities of temporal lobe gray matter.

BACKGROUND: Structural MRI data indicate schizophrenics have reduced left-sided temporal lobe gray matter volumes, especially in the superior temporal gyrus (STG) and medial temporal lobe. Our data further suggest a specificity to schizophrenia spectrum disorders of STG volume reduction. Interpretation of research studies involving schizophrenics may be complicated by the effects of exposure to neuroleptics and chronic illness. Sharing the same genetic diathesis of schizophrenics, subjects with schizotypal personality disorder (SPD) offer a unique opportunity to evaluate commonalities between schizophrenia and SPD, particularly as SPD subjects are characterized by cognitive and perceptual distortions, an inability to tolerate close friendships, and odd behavior, but they are not psychotic and so have generally not been prescribed neuroleptics nor hospitalized. Evaluation of brain structure in SPD may thus offer insight into the "endophenotype" common to both disorders. In addition, differences between groups may suggest which are the brain structures of schizophrenics that contribute to the development of psychosis. METHODS: To test the hypothesis of whether SPD subjects might show similar STG abnormalities, STG and medial temporal lobe regions of interest (ROI) were manually drawn on high resolution coronal MRI 1.5 mm thick slices. Images were derived from 16 right-handed male SPD subjects, without regard to family history, and 14 healthy, right-handed, comparison males who did not differ from the SPD group on parental socio-economic status, age, or verbal IQ. RESULTS: As predicted, SPD subjects showed a reduction in left STG gray matter volume compared with age and gender matched comparison subjects. SPD subjects also showed reduced parahippocampal left/right asymmetry and a high degree of disordered thinking. Comparisons with chronic schizophrenics previously studied by us showed the SPD group had a similarity of left STG gray matter volume reduction, but fewer medial temporal lobe abnormalities. CONCLUSIONS: These abnormalities strengthen the hypothesis of a temporal lobe abnormality in SPD, and the similarity of STG findings in schizophrenia and SPD suggest that STG abnormalities may be part of the spectrum "endophenotype." It is also possible that presence of medial temporal lobe abnormalities may help to differentiate who will develop schizophrenia and who will develop the less severe schizophrenia spectrum disorder, SPD.     

Age, rapid-cycling, and pharmacotherapy effects on ventral prefrontal cortex in bipolar disorder: a cross-sectional study.

BACKGROUND: Neuroimaging data suggest that deficits in ventral prefrontal cortex (VPFC) function in bipolar disorder (BD) progress during adolescence and young adulthood. However, the developmental trajectory of VPFC morphological abnormalities in BD is unknown. This study investigated potential age-dependent volume abnormalities in VPFC in BD. METHODS: Thirty-seven individuals diagnosed with BD I (14 adolescents, 10 young adults and 13 older adults) and 56 healthy comparison subjects (HC) participated in imaging. Gray and white matter volumes of VPFC were measured using high-resolution structural magnetic resonance imaging (MRI). We used a mixed model, repeated measures analysis to examine VPFC volumes across age groups while co-varying for total brain volume. Potential effects of illness features including rapid-cycling and medication were explored. RESULTS: VPFC volumes declined with age (p < .001). The diagnosis-by-age group interaction was significant (p = .01). Relative to HC subjects, VPFC gray and white matter volumes were significantly smaller in BD patients only in young adulthood (p = .04). In participants with BD, VPFC volumes were significantly smaller in participants with rapid-cycling than participants without rapid-cycling (p = .02). Conversely, current use of medication was associated with larger VPFC gray matter volumes (p = .005), independent of age. CONCLUSIONS: These preliminary findings suggest the presence of a more rapid initial decline in VPFC volumes with age in adolescents and young adults with BD than HC. These findings also suggest that the rapid-cycling subtype of BD is associated with larger VPFC volume deficits than the non-rapid-cycling subtype, and that pharmacotherapy may have trophic or protective effects on VPFC volumes in BD patients.     

Brain morphology in Klinefelter syndrome: extra X chromosome and testosterone supplementation

OBJECTIVE: This study focuses on variation in brain morphology associated with supernumerary X chromosome and Klinefelter syndrome (KS). Using an unselected birth cohort of KS subjects and high-resolution MRI, the authors investigated the neuroanatomic consequences of the 47,XXY karyotype in the presence and absence of exogenous testosterone supplementation. METHODS: Regional brain volumes were measured in 10 subjects with KS and 10 age-matched control men. Five of the KS subjects had received testosterone supplementation since puberty (KS+T) and five had not (KS-T). RESULTS: KS subjects showed significant (p < 0.01) reduction in left temporal lobe gray matter volumes compared with normal control subjects. Differences in left temporal gray volumes were also significant between the KS+T and KS-T groups (p < 0.01). Verbal fluency scores were significantly different between the KS+T and KS-T groups as well. CONCLUSION: Supernumerary X chromosome material in men is associated with a reduction in left temporal lobe gray matter, a finding that is consistent with the verbal and language deficits associated with KS. Also, relative preservation of gray matter in the left temporal region is associated with exposure to exogenous androgen during development. A history of testosterone supplementation also appears to be associated with increased verbal fluency scores in KS patients.     

Quantitative MRI biomarkers of cognitive morbidity in temporal lobe epilepsy

PURPOSE: To determine the relation between neuropsychological morbidity, quantitative magnetic resonance imaging (MRI) measures of whole brain structure, and clinical seizure factors reflecting epilepsy cause, course, and treatment. METHODS: Quantitative MRI measurements of total (whole brain) cerebrospinal fluid (CSF) and gray- and white-matter volumes and clinical seizure features were examined in relation to summary indices of cognitive morbidity in 96 patients with temporal lobe epilepsy. MRI volumes were adjusted for intracranial volume (ICV), and cognitive scores were adjusted for age, education, and gender, based on a sample of 82 healthy controls. RESULTS: Whole-brain volumes (gray, white, and CSF) were abnormal in chronic temporal lobe epilepsy patients compared with controls and were related significantly to neuropsychological morbidity, especially total CSF. Statistical modeling demonstrated that markers of total atrophy (CSF) was the primary mediator of the relation between clinical seizure variables and neuropsychological morbidity. CONCLUSIONS: Quantitative measurements of overall brain abnormality (atrophy) in temporal lobe epilepsy are clinically meaningful markers that are associated with increased cognitive morbidity. These biomarkers appear to mediate the adverse effects of some clinical seizure variables on cognition.     

Autism Spectrum Disorder as Early Neurodevelopmental Disorder: Evidence from the Brain Imaging Abnormalities in 2–3 Years Old Toddlers

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that occurs within the first 3 years of life, which is marked by social skills and communication deficits along with stereotyped repetitive behavior. Although great efforts have been made to clarify the underlying neuroanatomical abnormalities and brain-behavior relationships in adolescents and adults with ASD, literature is still limited in information about the neurobiology of ASD in the early age of life. Brain images of 50 toddlers with ASD and 28 age, gender, and developmental quotient matched toddlers with developmental delay (DD) (control group) between ages 2 and 3 years were captured using combined magnetic resonance-based structural imaging and diffusion tensor imaging (DTI). Structural magnetic resonance imaging was applied to assess overall gray matter (GM) and white matter (WM) volumes, and regional alterations were assessed by voxel-based morphometry. DTI was used to investigate the white matter tract integrity. Compared with DD, significant increases were observed in ASD, primarily in global GM and WM volumes and in right superior temporal gyrus regional GM and WM volumes. Higher fractional anisotropy value was also observed in the corpus callosum, posterior cingulate cortex, and limbic lobes of ASD. The converging findings of structural and white matter abnormalities in ASD suggest that alterations in neural-anatomy of different brain regions may be involved in behavioral and cognitive deficits associated with ASD, especially in an early age of 2–3 years old toddlers.     

MRI volumes of the hippocampus and amygdala in adults with Down's syndrome with and without dementia

OBJECTIVE: This study sought to determine whether volumes of the hippocampus and amygdala are disproportionately smaller in subjects with Down's syndrome than in normal comparison subjects and whether volume reduction is greater in Down's syndrome subjects with dementia. METHOD: The subjects were 25 adults with Down's syndrome (eight with dementia) and 25 cognitively normal adults who were individually matched on age, sex, and race. Magnetic resonance imaging measures included volumes of the hippocampus, amygdala, and total brain. Nineteen of the Down's syndrome subjects had follow-up scans (interscan interval = 9-41 months). RESULTS: Nondemented Down's syndrome subjects had significantly smaller volumes of the hippocampus, but not the amygdala, than their comparison subjects, even when total brain volume was controlled for. Volumes of both the hippocampus and the amygdala were smaller in the demented Down's syndrome subjects than in their comparison subjects, even when total brain volume was controlled for. Age was not correlated with volume of the hippocampus or amygdala among the nondemented Down's syndrome subjects and the comparison subjects; age was correlated with volume of the amygdala, but not the hippocampus, among the Down's syndrome subjects with dementia. Changes in volume over time were not statistically significant for either the demented or the nondemented subjects. CONCLUSIONS: Hippocampal volume, while disproportionately small for brain size in individuals with Down's syndrome, remains fairly constant through the fifth decade of life in those without dementia. All subjects over age 50 who had Down's syndrome demonstrated volume reduction in the hippocampus as well as clinical signs of dementia. Dementia was also associated with volume reductions in the amygdala that exceeded reductions in total brain volume.     

Anthroposophic therapy for chronic depression: a four-year prospective cohort study

Background

Although differences in brain anatomy in autism have been difficult to replicate using manual tracing methods, automated whole brain analyses have begun to find consistent differences in regions of the brain associated with the social cognitive processes that are often impaired in autism. We attempted to replicate these whole brain studies and to correlate regional volume changes with several autism symptom measures.

Methods

We performed MRI scans on 24 individuals diagnosed with DSM-IV autistic disorder and compared those to scans from 23 healthy comparison subjects matched on age. All participants were male. Whole brain, voxel-wise analyses of regional gray matter volume were conducted using voxel-based morphometry (VBM).

Results

Controlling for age and total gray matter volume, the volumes of the medial frontal gyri, left pre-central gyrus, right post-central gyrus, right fusiform gyrus, caudate nuclei and the left hippocampus were larger in the autism group relative to controls. Regions exhibiting smaller volumes in the autism group were observed exclusively in the cerebellum. Significant partial correlations were found between the volumes of the caudate nuclei, multiple frontal and temporal regions, the cerebellum and a measure of repetitive behaviors, controlling for total gray matter volume. Social and communication deficits in autism were also associated with caudate, cerebellar, and precuneus volumes, as well as with frontal and temporal lobe regional volumes.

Conclusion

Gray matter enlargement was observed in areas that have been functionally identified as important in social-cognitive processes, such as the medial frontal gyri, sensorimotor cortex and middle temporal gyrus. Additionally, we have shown that VBM is sensitive to associations between social and repetitive behaviors and regional brain volumes in autism.