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PLOS Biology

Diffusion MRI reveals the neuronal activity associated with waking and anesthetized states

​A CEA research team, headed by Denis Le Bihan, has just used diffusion MRI* to reveal the connection between the level of neuronal activity in regions concerned by wake-sleep states in anesthetized rats, and the degree of neuronal swelling in these regions. This research amplifies the significance of diffusion MRI for understanding how the brain works, and improves knowledge of the brain mechanisms underlying anesthesia and states of consciousness. This research will be published in PLOS Biology on April 14, 2017.

Published on 30 November 2017

Diffusion MRI is a medical imaging technique that provides images in which contrast depends on the water diffusion coefficient. As water diffusion is impeded by the components of brain tissue, any change in how this tissue is organized affects diffusion. According to the CEA researchers, water diffusion and neuronal activity are closely interrelated. This assumption has now been strengthened by research results that show that water diffusion is modulated by the activity of the regions of the brain involved in the wake-sleep cycle in anesthetized rats. This can only be observed using diffusion functional MRI. Standard functional MRI has only revealed overall, nonspecific changes to the brain as a whole, showing only the systemic effects of anesthesia on brain blood flow.

The research team induced variations in states of anesthesia in rats and, using MRI, observed that water diffusion was modified as a result in the specific regions of the brain concerned by the wake-sleep cycle. The team began by electrically stimulating the centromedian nucleus of the thalamus, which led to a transitory waking state in the animals in spite of their being anesthetized. The researchers then administered a furosemide injection (used as a diuretic in medicine) to inhibit neuronal swelling in this nucleus, which made waking more difficult (with deeper anesthesia) and led to a further increase in water diffusion. Conversely, provoking cellular swelling simply by local infusion of diluted cerebrospinal fluid reduced water diffusion and countered the effects of the anesthetic, making it easier for the animals to wake.

These results confirm that cellular swelling is closely related to the functioning of neurons, to which diffusion MRI is sensitive. They are along the same lines as the assumption made by the researchers that diffusion MRI directly reveals neuronal activity through the swelling of the active neurons (neuromechanical coupling), a mechanism that is radically different from that used until now for standard functional MRI.

In the longer term, this discovery could have significant repercussions, not only for functional neuroimaging, but for understanding the brain mechanisms underlying anesthesia and states of consciousness.


*Diffusion MRI is used to obtain millimeter resolution quantitative images showing the microscopic movement of molecules (mainly of water) in tissues. The diffusion movement of water molecules provides information about the obstacles they encounter and, therefore, the microscopic structure of biological tissue, resulting in a sort of "virtual biopsy". When cells swell, the water molecules diffuse more slowly and their movement is reduced, and vice versa. The assumption underlying this published research is that neuronal activity is accompanied by the swelling of neuronal structures (dendritic spines) and that the inactivity induced by anesthesia is associated with their retraction. This is shown by MRI diffusion measurements.


Standard (or BOLD = Blood Oxygen Level Dependent) *functional MRI  is used to observe areas of the brain that are activated by a stimulus presented or applied to the subject. For example, when the subject is asked to look at an image, the blood flow to the activated areas of the brain will increase locally, bringing more oxygen than without the stimulus. The blood oxygenation state modifies the MRI signal. The MRI images with the higher signal correspond to the area of the brain involved in responding to the stimulus. Although BOLD fMRI is widely used, it has a number of drawbacks: its connection with neuronal activity is indirect (via blood circulation) and delayed, and it has limited spatial localization and poor specificity.

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