Background and Purpose-Traditionally, cell death after cerebral ischemia was considered to be exclusively necrotic in nature, but research over the past decade has revealed that after a stroke, many neurons in the ischemic penumbra will undergo apoptosis. Summary of Review-This brief review provides a general overview and update of various signaling pathways in the development of apoptosis in ischemic lesions. Cerebral ischemia triggers two general pathways of apoptosis: the intrinsic pathway, originating from mitochondrial release of cytochrome c and associated stimulation of caspase-3; and the extrinsic pathway, originating from the activation of cell surface death receptors, resulting in the stimulation of caspase-8. Although many of the key apoptotic proteins have been identified, our understanding of the complex underlying mechanisms remains poor and hence treatment of stroke patients by manipulating apoptotic pathways remains a daunting task. However, recent advances in the field have helped broaden our knowledge of apoptosis after cerebral ischemia. Further to the simplistic concept that stroke-induced apoptosis occurs predominantly in neurons and is caspase-dependent, accumulating evidence now indicates that apoptosis is prevalent in nonneuronal cells and that caspase-independent mechanisms also play a key role. Conclusions-Although the ischemic penumbra is under threat of infarction, it is potentially salvageable and thus represents an opportunity for therapeutic intervention. (Stroke. 2009;40:e331-e339.)

This review critically examines the research findings which characterize the cognitive, behavioral, and neuroanatomical features of Williams syndrome (WS). This article analyzes 178 published studies in the WS literature covering the following areas: 1) General intelligence, 2) Language skills, 3) Visuospatial and face processing skills, 4) Behavior patterns and hypersociability, 5) Musical abilities, and 6) Brain structure and function. We identify methodological issues relating to small sample size, use and type of control groups, and multiple measures of task performance. Previously described 'peaks' within the cognitive profile are closely examined to assess their veracity. This review highlights the need for methodologically sound studies that utilize multiple comparison groups, developmental trajectories, and longitudinal analyses to examine the WS phenotype, as well as those that link brain structure and function to the cognitive and behavioral phenotype of WS individuals.

In the present study, we investigated changes in regional cerebral blood flow (rCBF) in humans during the progression from relaxed wakefulness through slow wave sleep (SWS). These changes were examined as a function of spindle (12-15 Hz) and ␦ (1.5-4.0 Hz) electroencephalographic (EEG) activity of SWS. rCBF was studied with positron emission tomography (PET) using the H 2 15 O bolus method. A maximum of six 60 sec scans were performed per subject during periods of wakefulness and stages 1-4 of SWS, as determined by on-line EEG monitoring. Spectral analysis was performed off-line on the EEG epochs corresponding to the scans for computation of activity in specific frequency bands. The relationship between EEG frequency band activity and normalized rCBF was determined by means of a voxel-by-voxel analysis of covariance. ␦ activity covaried negatively with rCBF most markedly in the thalamus and also in the brainstem reticular formation, cerebellum, anterior cingulate, and orbitofrontal cortex. After the effect of ␦ was removed, a significant negative covariation between spindle activity and the residual rCBF was evident in the medial thalamus. These negative covariations may reflect the disfacilitation and active inhibition of thalamocortical relay neurons in association with ␦ and spindles, as well as the neural substrates underlying the progressive attenuation of sensory awareness, motor responsiveness, and arousal that occur during SWS. ␦ activity covaried positively with rCBF in the visual and auditory cortex, possibly reflecting processes of dream-like mentation purported to occur during SWS.

Background and Purpose-The association between cerebral white matter lesions (WMLs) and the risk of falls in older people is uncertain, with no supporting prospective evidence. We aimed to determine the risk of incident falls associated with WML volume, and the interactions between WML volume, gait, and other sensorimotor factors leading to falls. Methods-We conducted a prospective, population-based study (nϭ294, mean age 72.3 years, independently mobile).Volumetric MRI, computerized gait measures, and sensorimotor measures of falls risk were obtained at baseline. Incident falls were recorded prospectively over a 12-month period. Using regression modeling, we estimated the risk of incident falls associated with baseline WML volume. Results-Increasing baseline WML volume was independently associated with any incident fall (Pϭ0.01) and multiple incident falls (Pϭ0.02). The risk of incident falls was doubled in people with lesion volumes in the highest quintile of its distribution compared with the lowest (adjusted relative risk, 2.32; 95% CI, 1.28 -4.14).Greater lesion volume was also associated with poorer gait and greater gait variability (both PϽ0.001).

The natural variability of pitch naming ability in the population (known as absolute pitch or AP) provides an ideal method for investigating individual differences in pitch processing and auditory knowledge formation and representation. We have demonstrated the involvement of different cognitive processes in AP ability that reflects varying skill expertise in the presence of similar early age of onset of music tuition. These processes were related to different regions of brain activity, including those involved in pitch working memory (right prefrontal cortex) and the long-term representation of pitch (superior temporal gyrus). They reflected expertise through the use of context dependent pitch cues and the level of automaticity of pitch naming. They impart functional significance to structural asymmetry differences in the planum temporale of musicians and establish a neurobiological basis for an AP template. More generally, they indicate variability of knowledge representation in the presence of environmental fostering of early cognitive development that translates to differences in cognitive ability.

When used to measure blood flow in the brain, water leaves a residue in the vascular bed that influences the estimation of blood flow by current methods. To assess the magnitude of this influence, we developed a two-compartment model of blood flow with separate parameters for transport and vascular distribution of brain water. Maps of the water clearance, K1 into brain tissue, separated from the circulation by a measurably resistant blood-brain barrier (BBB), were generated by time-weighted integration. Depending on the validity of the assumptions underlying the two-compartment model presented here, the maps revealed a significant overestimation of the clearance of water when the vascular residue was ignored. Maps of Vo, the estimate of the apparent vascular distribution volume of tracer H2(15)O, clearly revealed major cerebral arteries. Thus, we claim that the accumulation of radioactive water in brain tissue also reflects the volume of the arterial vascular bed of the brain.

Background and Purpose-Knowledge of the topographic distribution of infarcts of the middle cerebral artery (MCA) may give insight into the limits of the arterial territory and infarct mechanism and may influence the decision to use thrombolytic therapy. We describe the creation of a digital atlas of MCA (DA-MCA) infarction associated with MCA branch and trunk occlusion using magnetic resonance (MR) techniques. Methods-Hemispheric infarcts, with evidence of MCA trunk or branch occlusion, were manually segmented into binary images, linearly registered into a common stereotaxic coordinate space, and averaged to yield the probability of involvement by infarction at each voxel. Comparisons were made with existing maps of the MCA territory. Results-Twenty-eight patients with median age of 74 years (range, 26 to 87 years) were studied. On the DA-MCA, the highest frequency of infarction was within the striatocapsular region, centrum semiovale, and the insula. The mean and maximal MCA infarct volumes were 195.5 cm 3 and 366.3 cm 3 , respectively. Comparison with published maps showed that the most common difference from the DA-MCA was in the superomedial extent of the MCA territory. Some maps showed the MCA territory reaching the interhemispheric fissure, whereas in the DA-MCA it did not. There was a lower variability in the anterior boundary of the MCA territory compared with its posterior counterpart. Conclusion-We

The neocortex is the largest component of the mammalian cerebral cortex. It integrates sensory inputs with experiences and memory to produce sophisticated responses to an organism's internal and external environment. While areal patterning of the mouse neocortex has been mapped using histological techniques, the neocortex has not been comprehensively segmented in magnetic resonance images. This study presents a method for systematic segmentation of the C57BL/6J mouse neocortex. We created a minimum deformation atlas, which was hierarchically segmented into 74 neocortical and cortical-related regions, making it the most detailed atlas of the mouse neocortex currently available. In addition, we provide mean volumes and relative intensities for each structure as well as a nomenclature comparison between the two most cited histological atlases of the mouse brain. This MR atlas is available for download, and it should enable researchers to perform automated segmentation in genetic models of cortical disorders.