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.