Using MRI, we found that a slowly diffusing water pool was expanding (1.7 ؎ 0.3%) upon activation on the human visual cortex at the detriment of a faster diffusing pool. The time course of this water phase transition preceded the activation-triggered vascular response detected by usual functional MRI by several seconds. The observed changes in water diffusion likely reflect early biophysical events that take place in the activated cells, such as cell swelling and membrane expansion. Although the exact mechanisms remain to clarify, access to such an early and direct physiological marker of cortical activation with MRI will provide opportunities for functional neuroimaging of the human brain.ur current model of neuronal activation places great importance on transient electrical and biochemical events associated with the excitation processes. However, there is compelling evidence that activation is accompanied by other important physical phenomena. Microstructural changes in excited tissues have been observed, first from optical birefringence measurements (1, 2) and later more directly by using piezoelectric transducers (3). Those studies have revealed, for instance, that in the brain cell swelling is one of the physiological responses associated with neuronal activation (4, 5).However, such biophysical events have been monitored at the microscopic level by using invasive techniques in neuronal cell cultures or slices, and do not necessarily reflect physiological conditions (6, 7). Observing changes in cortical cell configuration in animals or humans would, thus, have a tremendous impact, because they would be directly linked to neuronal events, such as membrane expansion, and bridge the gap with current approaches to obtain images of human brain activation. Those approaches, such as blood oxygen level-dependent (BOLD) MRI, are based on blood flow changes and only indirectly and remotely related to cortical activation (8,9).A small decrease of the water diffusion coefficient during activation of human visual cortex has been previously reported by using diffusion MRI (10). Diffusion MRI provides valuable information on the microscopic obstacles which hinder diffusing molecules, such as membranes or macromolecules, and in turn, on the tissue cellular structure (11). Based on other MRI reports of water diffusivity decrease during intense neuronal activation (12, 13) or during other physiological or pathological conditions inducing cell swelling (14-17), the observed diffusion findings have been putatively ascribed to a transient swelling of cortical cells and a shrinking of the extracellular space, increasing its tortuosity (18) for diffusing molecules. However, no confirmation has been found so far for this mechanism. The aim of this report is to demonstrate that a decrease in water mobility can readily been observed in the human brain with diffusion MRI upon activation, and to provide evidence that this effect results from an early neuronal activation event that precedes the blood flow response by a sizeable time am...

How does the bilingual brain distinguish and control which language is in use? Previous functional imaging experiments have not been able to answer this question because proficient bilinguals activate the same brain regions irrespective of the language being tested. Here, we reveal that neuronal responses within the left caudate are sensitive to changes in the language or the meaning of words. By demonstrating this effect in populations of German-English and Japanese-English bilinguals, we suggest that the left caudate plays a universal role in monitoring and controlling the language in use.

Background and Purpose-About one half of those who develop adult-onset moyamoya disease experience intracranial hemorrhage. Despite the extremely high frequency of rebleeding attacks and poor prognosis, measures to prevent rebleeding have not been established. The purpose of this study is to determine whether extracranial-intracranial bypass can reduce incidence of rebleeding and improve patient prognosis. Methods-This study was a multicentered, prospective, randomized, controlled trial conducted by 22 institutes in Japan.Adult patients with moyamoya disease who had experienced intracranial hemorrhage within the preceding year were given either conservative care or bilateral extracranial-intracranial direct bypass and were observed for 5 years. Primary and secondary end points were defined as all adverse events and rebleeding attacks, respectively. Results-Eighty patients were enrolled (surgical, 42; nonsurgical, 38). Adverse events causing significant morbidity were observed in 6 patients in the surgical group (14.3%) and 13 patients in the nonsurgical group (34.2%). Kaplan-Meier survival analysis revealed significant differences between the 2 groups (3.2%/y versus 8.2%/y; P=0.048). The hazard ratio of the surgical group calculated by Cox regression analysis was 0.391 (95% confidence interval, 0.148-1.029).Rebleeding attacks were observed in 5 patients in the surgical group (11.9%) and 12 in the nonsurgical group (31.6%), significantly different in the Kaplan-Meier survival analysis (2.7%/y versus 7.6%/y; P=0.042). The hazard ratio of the surgical group was 0.355 (95% confidence interval, 0.125-1.009). Conclusions-Although statistically marginal, Kaplan-Meier analysis revealed the significant difference between surgical and nonsurgical group, suggesting the preventive effect of direct bypass against rebleeding. Clinical Trial Registration

Although behavioral studies suggest that pain distress may alter the perception of somatic stimulation, neural correlates underlying such alteration remain to be clarified. The present study was aimed to test the hypothesis that expectation of pain might amplify brain responses to somatosensory stimulation in the anterior cingulate cortex (ACC) and the region including parietal operculum and posterior insula (PO/PI), both of which may play roles in regulating pain-dependent behavior. We compared brain responses with and subjective evaluation of physically identical nonpainful warm stimuli between two psychologically different contexts: one linked with pain expectation by presenting the nonpainful stimuli randomly intermixed with painful stimuli and the other without. By applying the event-related functional magnetic resonance imaging technique, brain responses to the stimuli were assessed with respect to signal changes and activated volume, setting regions of interest on activated clusters in ACC and bilateral PO/PI defined by painful stimuli. As a result, the uncertain expectation of painful stimulus enhanced transient brain responses to nonpainful stimulus in ACC and PO/PI. The enhanced responses were revealed as a higher intensity of signal change in ACC and larger volume of activated voxels in PO/PI. Behavioral measurements demonstrated that expectation of painful stimulus amplified perceived unpleasantness of innocuous stimulus. From these findings, it is suggested that ACC and PO/PI are involved in modulation of affective aspect of sensory perception by the uncertain expectation of painful stimulus.

In order to clarify the roles played by the primary motor cortex and the supplementary motor area in the execution of complex sequential and simple repetitive finger movements, regional cerebral blood flow (rCBF) was measured with PET using 15O-labelled water in five normal subjects. The PET data of each individual subject co-registered to his own MRI, was analysed. Compared with the resting condition, the mean rCBF was markedly increased in the contralateral sensorimotor cortex (M1-S1) and moderately increased in the contralateral cingulate gyrus and putamen in both the simple and complex motor tasks. During the complex motor task, in addition to the above, the mean rCBF was markedly increased in the supplementary motor area and the contralateral premotor area, and moderately increased in the ipsilateral M1-S1 and cerebellum. In the supplementary motor area, there was a moderate rCBF increase also during the simple task. However, comparison of the mean rCBF increase against the resting condition between the two tasks revealed a greater increase during the complex task than in the other only in the supplementary motor area and the ipsilateral M1-S1. Thus, in agreement with our previous electrophysiological findings, not only the supplementary motor area but also the M1-S1 seems to play an important role in the execution of complex sequential finger movements.

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Background and Purpose-We have previously described effects of chronic cerebral hypoperfusion in mice with bilateral common carotid artery stenosis (BCAS) using microcoils for 30 days. These mice specifically exhibit working memory deficits attributable to frontal-subcortical circuit damage without apparent gray matter changes, indicating similarities with subcortical ischemic vascular dementia. However, as subcortical ischemic vascular dementia progresses over time, the longer-term effects that characterize the mouse model are not known. Methods-Comprehensive behavioral test batteries and histological examinations were performed in mice subjected to BCAS for up to 8 months. Laser speckle flowmetry and 18 F-fluorodeoxyglucose positron emission tomography were performed to assess cerebral blood flow and metabolism at several time points. Results-At 2 hours after BCAS, cerebral blood flow in the cerebral cortex temporarily decreased to as much as 60% to 70% of the control value but gradually recovered to Ͼ80% at 1 to 3 months. At 5 to 6 months after BCAS, reference and working memory were impaired as demonstrated by the Barnes and radial arm maze tests, respectively. Furthermore,

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