David A. Ziegler

Localization of white matter volume increase in autism and developmental language disorder

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.

Labels and event processes in the asbestos operating system

Asbestos, a new prototype operating system, provides novel labeling and isolation mechanisms that help contain the effects of exploitable software flaws. Applications can express a wide range of policies with Asbestoss kernel-enforced label mechanism, including controls on inter-process communication and system-wide information flow. A new event process abstraction provides lightweight, isolated contexts within a single process, allowing the same process to act on behalf of multiple users while preventing it from leaking any single users data to any other user. A Web server that uses Asbestos labels to isolate user data requires about 1.5 memory pages per user, demonstrating that additional security can come at an acceptable cost.

Language-association cortex asymmetry in autism and specific language impairment

Language deficits are among the core impairments of autism. We previously reported asymmetry reversal of frontal language cortex in boys with autism. Specific language impairment (SLI) and autism share similar language deficits and may share genetic links. This study evaluated asymmetry of frontal language cortex in a new, independent sample of right‐handed boys, including a new sample of boys with autism and a group of boys with SLI. The boys with autism were divided into those with language impairment (ALI) and those with normal language ability (ALN). Subjects (right‐handed, aged 6.2–13.4 years) included 22 boys with autism (16 ALI and 6 ALN), 9 boys with a history of or present SLI, and 11 normal controls. MRI brain scans were segmented into grey and white matter; then the cerebral cortex was parcellated into 48 gyral‐based divisions per hemisphere. Group differences in volumetric asymmetry were predicted a priori in language‐related regions in inferior lateral frontal (Brocas area) and posterior superior temporal cortex. Language impaired boys with autism and SLI both had significant reversal of asymmetry in frontal language‐related cortex; larger on the right side in both groups of language impaired boys and larger on the left in both unimpaired language groups, strengthening a phenotypic link between ALI and SLI. Thus, we replicated the observation of reversed asymmetry in frontal language cortex reported previously in an independent autism sample, and observed similar reversal in boys with SLI, further strengthening a phenotypic link between SLI and a subgroup of autism. Linguistically unimpaired boys with autism had similar asymmetry compared with the control group, suggesting that Brocas area asymmetry reversal is related more to language impairment than specifically to autism diagnosis. Ann Neurol 2004

Abnormal asymmetry in language association cortex in autism

Autism is a neurodevelopmental disorder affecting cognitive, language, and social functioning. Although language and social communication abnormalities are characteristic, prior structural imaging studies have not examined language‐related cortex in autistic and control subjects. Subjects included 16 boys with autism (aged 7–11 years), with nonverbal IQ greater than 80, and 15 age‐ and handedness‐matched controls. Magnetic resonance brain images were segmented into gray and white matter; cerebral cortex was parcellated into 48 gyral‐based divisions per hemisphere. Asymmetry was assessed a priori in language‐related inferior lateral frontal and posterior superior temporal regions and assessed post hoc in all regions to determine specificity of asymmetry abnormalities. Boys with autism had significant asymmetry reversal in frontal language‐related cortex: 27% larger on the right in autism and 17% larger on the left in controls. Only one additional region had significant asymmetry differences on post hoc analysis: posterior temporal fusiform gyrus (more left‐sided in autism), whereas adjacent fusiform gyrus and temporooccipital inferior temporal gyrus both approached significance (more right‐sided in autism). These inferior temporal regions are involved in visual face processing. In boys with autism, language and social/face processing–related regions displayed abnormal asymmetry. These structural abnormalities may relate to language and social disturbances observed in autism.

Amygdala Volume Associated With Alcohol Abuse Relapse and Craving

OBJECTIVE Amygdala volume has been associated with drug craving in cocaine addicts, and amygdala volume reduction is observed in some alcohol-dependent subjects. This study sought an association in alcohol-dependent subjects between volumes of reward-related brain regions, alcohol craving, and the risk of relapse. METHOD Besides alcohol craving, the authors assessed amygdala, hippocampus, and ventral striatum volumes in 51 alcohol-dependent subjects and 52 age- and education-matched healthy comparison subjects after detoxification. After imaging and clinical assessment, patients were followed for 6 months and alcohol intake was recorded. RESULTS Alcohol-dependent subjects showed reduced amygdala, hippocampus, and ventral striatum volumes and reported stronger craving in relation to healthy comparison subjects. However, only amygdala volume and craving differentiated between subsequent relapsers and abstainers. A significant decrease of amygdala volume in alcohol-dependent subjects was associated with increased alcohol craving before imaging and an increased alcohol intake during the 6-month follow-up period. CONCLUSIONS These findings suggest a relationship between amygdala volume reduction, alcohol craving, and prospective relapse into alcohol consumption.

Reliability of MRI-derived cortical and subcortical morphometric measures: Effects of pulse sequence, voxel geometry, and parallel imaging

Advances in magnetic resonance imaging (MRI) have contributed greatly to the study of neurodegenerative processes, psychiatric disorders, and normal human development, but the effect of such improvements on the reliability of downstream morphometric measures has not been extensively studied. We examined how MRI-derived neurostructural measures are affected by three technological advancements: parallel acceleration, increased spatial resolution, and the use of a high bandwidth multiecho sequence. Test-retest data were collected from 11 healthy participants during 2 imaging sessions occurring approximately 2 weeks apart. We acquired 4 T1-weighted MP-RAGE sequences during each session: a non-accelerated anisotropic sequence (MPR), a non-accelerated isotropic sequence (ISO), an accelerated isotropic sequence (ISH), and an accelerated isotropic high bandwidth multiecho sequence (MEM). Cortical thickness and volumetric measures were computed for each sequence to assess test-retest reliability and measurement bias. Reliability was extremely high for most measures and similar across imaging parameters. Significant measurement bias was observed, however, between MPR and all isotropic sequences for all cortical regions and some subcortical structures. These results suggest that these improvements in MRI acquisition technology do not compromise data reproducibility, but that consistency should be maintained in choosing imaging parameters for structural MRI studies.

Decreased Absolute Amygdala Volume in Cocaine Addicts

The amygdala is instrumental to a set of brain processes that lead to cocaine consumption, including those that mediate reward and drug craving. This study examined the volumes of the amygdala and hippocampus in cocaine-addicted subjects and matched healthy controls and determined that the amygdala but not the hippocampus was significantly reduced in volume. The right-left amygdala asymmetry in control subjects was absent in the cocaine addicts. Topological analysis of amygdala isosurfaces (population averages) revealed that the isosurface of the cocaine-dependent group undercut the anterior and superior surfaces of the control group, implicating a difference in the corticomedial and basolateral nuclei. In cocaine addicts, amygdala volume did not correlate with any measure of cocaine use. The amygdala symmetry coefficient did correlate with baseline but not cocaine-primed craving. These findings argue for a condition that predisposes the individual to cocaine dependence by affecting the amygdala, or a primary event early in the course of cocaine use.

Cognition in healthy aging is related to regional white matter integrity, but not cortical thickness

It is well established that healthy aging is accompanied by structural changes in many brain regions and functional decline in a number of cognitive domains. The goal of this study was to determine (1) whether the regional distribution of age-related brain changes is similar in gray matter (GM) and white matter (WM) regions, or whether these two tissue types are affected differently by aging, and (2) whether measures of cognitive performance are more closely linked to alterations in the cerebral cortex or in the underlying WM in older adults (OA). To address these questions, we collected high-resolution magnetic resonance imaging (MRI) data from a large sample of healthy young adults (YA; aged 18-28) and OA (aged 61-86 years). In addition, the OA completed a series of tasks selected to assess cognition in three domains: cognitive control, episodic memory, and semantic memory. Using advanced techniques for measuring cortical thickness and WM integrity, we found that healthy aging was accompanied by deterioration of both GM and WM, but with distinct patterns of change: Cortical thinning occurred primarily in primary sensory and motor cortices, whereas WM changes were localized to regions underlying association cortices. Further, in OA, we found a striking pattern of region-specific correlations between measures of cognitive performance and WM integrity, but not cortical thickness. Specifically, cognitive control correlated with integrity of frontal lobe WM, whereas episodic memory was related to integrity of temporal and parietal lobe WM. Thus, age-related impairments in specific cognitive capacities may arise from degenerative processes that affect the underlying connections of their respective neural networks.

Adjustment for Whole Brain and Cranial Size in Volumetric Brain Studies: A Review of Common Adjustment Factors and Statistical Methods

In this article we address analytic challenges inherent in brain volumetrics (i.e., the study of volumes of brains and brain regions). It has sometimes been assumed in the literature that deviations in regional brain size in clinical samples are directly related to maldevelopment or pathogenesis. However, this assumption may be incorrect; such volume differences may, instead, be wholly or partly attributable to individual differences in overall dimension (e.g., for head, brain, or body size). What quantitative approaches can be used to take these factors into account? Here, we provide a review of volumetric and nonvolumetric adjustment factors. We consider three examples of common statistical methods by which one can adjust for the effects of body, head, or brain size on regional volumetric measures: the analysis of covariance, the proportion, and the residual approaches. While the nature of the adjustment will help dictate which method is most appropriate, the choice is context sensitive, guided by numerous considerations-chiefly the experimental hypotheses, but other factors as well (including characteristic features of the disorder and sample size). These issues come into play in logically framing the assessment of putative abnormalities in regional brain volumes.

Larger brain and white matter volumes in children with developmental language disorder

Developmental language disorder (DLD) is predominantly a language disorder, but children with DLD also manifest nonlanguage impairments, and neuroanatomical abnormalities have been found in multiple areas of the brain, not all languageassociated. We therefore performed a whole brain general segmentation analysis of all major brain regions on MRI scans of 24 DLD subjects (16M, 8F) and 30 controls (15M, 15F), ages 5.7 to 11.3 years. Children with DLD showed increased total brain volume, driven predominantly by a substantial increase in the volume of cerebral white matter. Cerebral cortex and caudate were relatively but not absolutely smaller in DLD. These findings are discussed in relation to issues of specificity vs. generality as they arise in debates about (1) modular vs. general processing deficits and connectionist modeling in DLD, (2) languagespecific vs. pervasive, non-specific deficits in DLD and (3) specificity of the disorder vs. overlap with other disorders, notably autism.