Imaging derived cortical thickness reduction in high-functioning autism: key regions and temporal slope.

Cortical thickness (CT) changes possibly contribute to the complex symptomatology of autism. The aberrant developmental trajectories underlying such differences in certain brain regions and their continuation in adulthood are a matter of intense debate. We studied 28 adults with high-functioning autism (HFA) and 28 control subjects matched for age, gender, IQ and handedness. A surface-based whole brain analysis utilizing FreeSurfer was employed to detect CT differences between the two diagnostic groups and to investigate the time course of age-related changes. Direct comparison with control subjects revealed thinner cortex in HFA in the posterior superior temporal sulcus (pSTS) of the left hemisphere. Considering the time course of CT development we found clusters around the pSTS and cuneus in the left and the paracentral lobule in the right hemisphere to be thinner in HFA with comparable age-related slopes in patients and controls. Conversely, we found clusters around the supramarginal gyrus and inferior parietal lobule (IPL) in the left and the precentral and postcentral gyrus in the right hemisphere to be thinner in HFA, but with different age-related slopes in patients and controls. In the latter regions CT showed a steady decrease in controls but no analogous thinning in HFA. CT analyses contribute in characterizing neuroanatomical correlates of HFA. Reduced CT is present in brain regions involved in social cognition. Furthermore, our results demonstrate that aberrant brain development leading to such differences is proceeding throughout adulthood. Discrepancies in prior morphometric studies may be induced by the complex time course of cortical changes.

Corpus callosum size in adults with high-functioning autism and the relevance of gender.

The goal of the study was to investigate the size of the corpus callosum (CC) and its subsegments in relation to total brain volume (TBV) as an empirical indicator of impaired connectivity in autism with special respect to gender. In MRI data sets of 29 adults with high-functioning autism (HFA) and 29 age-, gender- and IQ-matched control subjects, the TBV was measured and the CC was analyzed as a whole and in subsegments employing two different manual segmentation procedures. With respect to diagnosis, there were no significant differences in the dependent variables (CC, CC subsegments, and TBV). With respect to gender, only TBV was significantly increased in males compared with females, resulting in a significantly decreased CC/TBV ratio in males. This finding, however, was independent from gender and can be fully attributed to brain size. Our findings do not support the following hypotheses: (1) a hypothesis of impaired CC in HFA adults as a subgroup of patients with autism spectrum disorders, and (2) the sexual dimorphism hypothesis of the CC.

Investigation of mentalizing and visuospatial perspective taking for self and other in Asperger syndrome.

Mentalizing refers to making inferences about other people's mental states, whereas visuospatial perspective taking refers to inferring other people's viewpoints. Both abilities seem vital for social functioning; yet, their exact relationship is unclear. We directly compared mentalizing and visuospatial perspective taking in nineteen adults with Asperger syndrome (AS) and fifteen control participants with the same stimulus material. Stimuli depicted virtual characters surrounded by two different objects. Virtual characters expressed a preference for one of the objects indicated by facial expression, gestures or head/body orientation. Compared to controls, participants with AS showed significantly increased reaction times and decreased accuracy for mentalizing (i.e., when inferring the virtual character's preference from the character's nonverbal bodily cues). By contrast, there were no significant group differences in perspective taking (i.e., by mental own-body transformations). These findings demonstrate, first, specific deficits in AS when mental states have to be inferred from nonverbal social cues. Second, visuospatial perspective taking may not necessarily be related to social impairments occurring in autism spectrum disorders.

Novel KRIT1 mutation and no molecular evidence of anticipation in a family with cerebral and spinal cavernous malformations.

BACKGROUND: Cerebral cavernous malformations (CCM) are vascular brain anomalies which can result in a variety of neurological symptoms. Familial CCM is inherited as an autosomal-dominant trait. There is one study in the literature which reports statistical evidence for anticipation in familial CCM. METHODS: We reevaluated the clinical course of the disease and performed molecular analyses in a previously described three-generation CCM family with apparent anticipation. RESULTS: Disease started at a younger age in each generation, strongly suggesting anticipation. The patient in generation I showed no clinical symptoms by the age of 68, whereas his son became wheelchair-bound at the age of 43 due to an intramedullary cavernous malformation at the thoracolumbar transition of the spinal cord. The patient in generation III had a pons hemorrhage at the age of 11 due to a large brainstem cavernoma. The hemorrhage caused facial palsy and hemiparesis, persisting as Millard-Gubler syndrome. Sequencing of KRIT1 identified a novel frameshift mutation in exon 15 (c.1561delC or p.Leu551X) which cosegregated with the phenotype. Flow-FISH analysis of granulocyte and lymphocyte telomere length showed that telomeres were longest in the youngest affected family member. CONCLUSIONS: We could not find any evidence for either of the two currently known molecular mechanisms for genetic anticipation (i.e., expansion of repetitive DNA elements or progressive telomere shortening) in this family. However, the family presented here raises the important question whether surveillance of CCM families with gradient-echo MRI should not only include the cerebrum, but the spinal cord as well.

Early ischemic edema on cerebral computed tomography: its relation to diffusion changes and hypoperfusion within 6 h after human ischemic stroke. A comparison of CT, MRI and PET.

BACKGROUND: Brain tissue hypoattenuation on early computed tomography is frequently included in decision making in acute stroke management. However, its pathophysiological counterpart needs further evaluation. METHODS: By comparative imaging with diffusion-weighted imaging and 15O-water positron emission tomography we aimed to interpret early (<6 h) hypoattenuation. RESULTS: In 11 patients, the hypoattenuation corresponded to a decreased proton diffusion (median 115.9% relative DWI value) measured by magnetic resonance imaging and to a severe hypoperfusion (below 12 ml/100 g/ min) assessed by positron emission tomography. The volume of parenchymal hypoattenuation correlated to the tissue with disturbed diffusion (Spearman's rho=0.73), but largely underestimated the hypoperfusion below 20 ml/100 g/min. CONCLUSIONS: Early hypoattenuation reflects the coupling of the severity of ischemia and resulting diffusion changes. It allows an estimate of the infarct core but underestimates the penumbral hypoperfusion.