These findings support the hypothesis that the limbic system, in particular the hippocampus, may be involved in the pathophysiology of pediatric bipolar disorder. While this report may represent the largest MRI study of pediatric bipolar disorder to date, more work is needed to confirm these findings and to determine if they are unique to pediatric bipolar disorder.

Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 [corrected] families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.

Increased brain volume in autism appears to be driven mainly by an unexplained white matter enlargement, and we have reported a similar phenomenon in developmental language disorder (DLD). Localization of this enlargement would strongly guide research into its cause, tissue basis, and functional implications. We utilized a white matter parcellation technique that divides cerebral white matter into an outer zone containing the radiate compartment and an inner zone containing sagittal and bridging system compartments. In both high-functioning autism and DLD, enlargement localized to the radiate white matter (all lobes in autism, all but parietal in DLD), whereas inner zone white matter compartments showed no volume differences from controls. Furthermore, in both autism and DLD, later or longer-myelinating regions showed greater volume increases over controls. Neither group showed cerebral cortex, corpus callosum, or internal capsule volume differences from control. Radiate white matter myelinates later than deep white matter; this pattern of enlargement thus is consistent with striking postnatal head circumference percentile increases reported in autism. These findings suggest an ongoing postnatal process in both autism and DLD that is probably intrinsic to white matter, that primarily affects intrahemispheric and corticocortical connections, and that places these two disorders on the same spectrum.

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. We performed MRI-based morphometric analysis on the brains of 17 autistic and 15 control subjects, all male with normal intelligence, aged 7-11 years. Clinical neuroradiologists judged the brains of all subjects to be clinically normal. The entire brain was segmented into cerebrum, cerebellum, brainstem and ventricles. The cerebrum was subdivided into cerebral cortex, cerebral white matter, hippocampus-amygdala, caudate nucleus, globus pallidus plus putamen, and diencephalon (thalamus plus ventral diencephalon). Volumes were derived for each region and compared between groups both before and after adjustment for variation in total brain volume. Factor analysis was then used to group brain regions based on their intercorrelations. Volumes were significantly different between groups overall; and diencephalon, cerebral white matter, cerebellum and globus pallidus-putamen were significantly larger in the autistic group. Brain volumes were not significantly different overall after adjustment for total brain size, but this analysis approached significance and effect sizes and univariate comparisons remained notable for three regions, although not all in the same direction: cerebral white matter showed a trend towards being disproportionately larger in autistic boys, while cerebral cortex and hippocampus-amygdala showed trends toward being disproportionately smaller. Factor analysis of all brain region volumes yielded three factors, with central white matter grouping alone, and with cerebral cortex and hippocampus-amygdala grouping separately from other grey matter 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.

Long-range cortical functional connectivity is often reduced in autism spectrum disorders (ASD), but the nature of local cortical functional connectivity in ASD has remained elusive. We used magnetoencephalography to measure task-related local functional connectivity, as manifested by coupling between the phase of alpha oscillations and the amplitude of gamma oscillations, in the fusiform face area (FFA) of individuals diagnosed with ASD and typically developing individuals while they viewed neutral faces, emotional faces, and houses. We also measured task-related long-range functional connectivity between the FFA and the rest of the cortex during the same paradigm. In agreement with earlier studies, long-range functional connectivity between the FFA and three distant cortical regions was reduced in the ASD group. However, contrary to the prevailing hypothesis in the field, we found that local functional connectivity within the FFA was also reduced in individuals with ASD when viewing faces. Furthermore, the strength of long-range functional connectivity was directly correlated to the strength of local functional connectivity in both groups; thus, long-range and local connectivity were reduced proportionally in the ASD group. Finally, the magnitude of local functional connectivity correlated with ASD severity, and statistical classification using local and long-range functional connectivity data identified ASD diagnosis with 90% accuracy. These results suggest that failure to entrain neuronal assemblies fully both within and across cortical regions may be characteristic of ASD.coherence | parvalbumin O scillations in the brain underlie many key cortical functions and coordinate activity between distant brain areas. These rhythmic oscillations are typically studied in distinct frequency bands, often segregated as delta (1-2 Hz), theta (3-7 Hz), alpha (8-12 Hz), beta (13-30 Hz), low gamma (30-60 Hz), and high gamma (>60 Hz). Each frequency band has been associated with specific cognitive and synaptic processes, with some overlaps among bands (1). Substantial evidence indicates that abnormalities in long-range interregional functional connectivity, usually mediated by theta and alpha oscillations, are common in neurodevelopmental disorders (2), including autism spectrum disorders (ASD) (3).The nature of functional connectivity in ASD has been under intense investigation since the publication of a 2004 report showing reduced long-range functional connectivity in ASD (4). The prevailing hypothesis in the field is that ASD is characterized by reduced long-range functional connectivity and increased local functional connectivity (5-7). The hypothesis that local functional connectivity is increased in ASD is motivated primarily by genetic and histological evidence of reduced neuronal inhibition in ASD (8-10). Although a large body of functional evidence supports the hypothesis of generally reduced long-range functional connectivity in ASD (11), neurophysiological signatures of local functional connectivity in ASD have r...

We report a whole-brain MRI morphometric survey of asymmetry in children with high-functioning autism and with developmental language disorder (DLD). Subjects included 46 boys of normal intelligence aged 5.7-11.3 years (16 autistic, 15 DLD, 15 controls). Imaging analysis included grey-white segmentation and cortical parcellation. Asymmetry was assessed at a series of nested levels. We found that asymmetries were masked with larger units of analysis but progressively more apparent with smaller units, and that within the cerebral cortex the differences were greatest in higher-order association cortex. The larger units of analysis, including the cerebral hemispheres, the major grey and white matter structures and the cortical lobes, showed no asymmetries in autism or DLD and few asymmetries in controls. However, at the level of cortical parcellation units, autism and DLD showed more asymmetry than controls. They had a greater aggregate volume of significantly asymmetrical cortical parcellation units (leftward plus rightward), as well as a substantially larger aggregate volume of right-asymmetrical cortex in DLD and autism than in controls; this rightward bias was more pronounced in autism than in DLD. DLD, but not autism, showed a small but significant loss of leftward asymmetry compared with controls. Right : left ratios were reversed, autism and DLD having twice as much right- as left-asymmetrical cortex, while the reverse was found in the control sample. Asymmetry differences between groups were most significant in the higher-order association areas. 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.

Prevalence, genetic, exposure, and pathophysiological evidence all suggest a role for environmental factors in the inception and lifelong modulation of ASD. This supports the need for seeking targets for early and ongoing medical prevention and treatment of ASD.

Although Autism Spectrum Disorders (ASD) are generally assumed to be lifelong, we review evidence that between 3% and 25% of children reportedly lose their ASD diagnosis and enter the normal range of cognitive, adaptive and social skills. Predictors of recovery include relatively high intelligence, receptive language, verbal and motor imitation, and motor development, but not overall symptom severity. Earlier age of diagnosis and treatment, and a diagnosis of Pervasive Developmental Disorder-Not Otherwise Specified are also favorable signs. The presence of seizures, mental retardation and genetic syndromes are unfavorable signs, whereas head growth does not predict outcome. Controlled studies that report the most recovery came about after the use of behavioral techniques. Residual vulnerabilities affect higher-order communication and attention. Tics, depression and phobias are frequent residual co-morbidities after recovery. Possible mechanisms of recovery include: normalizing input by forcing attention outward or enriching the environment; promoting the reinforcement value of social stimuli; preventing interfering behaviors; mass practice of weak skills; reducing stress and stabilizing arousal. Improving nutrition and sleep quality is non-specifically beneficial.