Recent anatomical studies on macaque brains have revealed that 80% of the network connectivity occurs at the millimetre/centimetre, i.e. mesoscopic, scale, within brain areas (Markov). However, due to technical limitations, this scale remains by far the less studied (Chemla et al 2017). Most neuronal recording techniques are indeed restricted to microscopic (neuron, intra/extracellular recordings) or macroscopic scales (whole brain).

Recording brain activity at the mesoscopic scale has thus a strong potential to unveil many new fundamental neuronal operations and innovative clinical applications.

Optical imaging offers a unique opportunity to measure brain activity over a large field-of-view (up to 1cm for flat surfaces) with high spatio-temporal resolutions (20μmx1ms). Such technics can allow to better understand neuronal processing in fundamental research or improve development of clinical therapeutic approaches such as neurosurgery or retinal implants.

However, in neuroscience, there are two major limitations of this imaging technique, which partly explains the poor development of its use.

First, the cortex is non-planar, which, due to the field’s depth, limits the optical access to a small cortical region close to the center of the field-of-view. This is even worst for more curved cortex of small animals (rodents or other small monkeys such as the marmoset) used in neuroscience. In such animal models, the brain is lissencephalic and all visual cortical areas are located on the surface but inaccessible at once with standard methods. Methods compensating for such curvature would enable the recording of the whole visual system at once, from the primary to the fifth visual cortices bringing such imaging tools closer to the “ideal” technique.

The second limitation is the signal-to-noise ratio which is strongly degraded by the dynamic evolution of the brain curvature due to physiological rhythms (heartbeat, breath, etc.), creating perturbation at 0.1-20Hz. This strongly limits our ability to work at single-trial and unravel the real dynamics of neuronal processing, such as spatio-temporal waves (Muller et al 2018).

We propose an interdisciplinary approach at the border between brain imaging and technologies from astronomic instrumentation (curved detector, adaptive optics, real-time wave front control), to overcome technological limits and explore single-trial brain activity at expanded scales.

Our project will offer innovative research perspectives by imaging for the first-time multiple cortical areas with high spatio-temporal resolution and at the single trial. Such breakthrough will open new unexplored lines of research such as how neuronal interactions distributed at multiple scales and areas are dynamically shaping the parallel processing and representation of sensory information. This will interest a wide neuroscientific audience but also impact the clinical community interested in cartography of the nervous activity at the mesoscopic scale.