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Provansal, M.

Publications and source records attributed to Provansal, M..

5 recordsLinked to original sources

From Functional Organization to Vascular Structure in the Primate Visual Cortex Using Ultrasound Imaging

The primary visual cortex (V1) provides an exceptional structure to assess information encoding in the cortex thanks to its highly controlled visual input. However, optical measures and electrophysiology are limited to very superficial layers while fMRI provides low spatial resolution. Taking advantages of functional ultrasound imaging (fUSi), we examined large volumes of V1 in two awake non-human primates. We showed the conservation of retinotopic maps within deep sulcal regions and across cortical layers. We then assessed the cortical point image and compared it to its vasculature distribution through ultrasound localization microscopy (ULM). We further identified the smallest vascular compartment underlying the signal. Together, these results establish fUSi, complemented by ULM, as a minimally invasive mesoscale approach for resolving functional organization of the cortex in deep sulci.

neuroscience↗

Covariations of cerebral blood volume and single neurons discharge during resting state and behavioral visual cognitive tasks in non-human primates

To better understand how the brain allows primates to perform various set of tasks, the ability to simultaneously record the activity of the brain at multiple temporal and spatial scales is challenging but necessary. In non-human primates, combined fMRI and electrophysiological recordings have not disentangle the contributions of spiking activity to the neurovascular response. Here, we combined functional ultrasound imaging (fUS) of cerebral blood volume (CBV) and recording of single-unit activities (SUA) in visual and fronto-medial cortices of behaving macaques. We computed task-induced and SUA-induced CBV activation maps. We demonstrate that SUA provides a significant estimate of the neurovascular response below the typical fMRI voxel spatial resolution of 2mm3. Furthermore, our results also show that single unit and CBV activities are statistically uncorrelated during the resting states but correlate during behaving tasks. Conversely, during the resting states, CBV activities across known connected brain areas are correlated but decorrelate at the onset of the tasks as expected if participating in the default mode network (DMN). These results have important implications for interpreting functional imaging findings collected with fMRI or fUS while one constructs inferences of spiking activities during resting-state or while primates perform tasks.

neuroscience↗

Sonogenetic stimulation of the brain at a spatiotemporal resolution suitable for vision restoration

Remote, precisely controlled activation of the brain is a fundamental challenge in the development of brain-machine interfaces providing feasible rehabilitation strategies for neurological disorders. Low-frequency ultrasound stimulation can be used to modulate neuronal activity deep in the brain1-7, but this approach lacks spatial resolution and cellular selectivity and loads the brain with high levels of acoustic energy. The combination of the expression of ultrasound-sensitive proteins with ultrasound stimulation ( sonogenetic stimulation) can provide cellular selectivity and higher sensitivity, but such strategies have been subject to severe limitations in terms of spatiotemporal resolution in vivo8-10, precluding their use for real-life applications. We used the expression of large-conductance mechanosensitive ion channels (MscL) with high-frequency ultrasonic stimulation for a duration of milliseconds to activate neurons selectively at a relatively high spatiotemporal resolution in the rat retina ex vivo and the primary visual cortex of rodents in vivo. This spatiotemporal resolution was achieved at low energy levels associated with negligible tissue heating and far below those leading to complications in ultrasound neuromodulation6,11. We showed, in an associative learning test, that sonogenetic stimulation of the visual cortex generated light perception. Our findings demonstrate that sonogenetic stimulation is compatible with millisecond pattern presentation for visual restoration at the cortical level. They represent a step towards the precise transfer of information over large distances to the cortical and subcortical regions of the brain via an approach less invasive than that associated with current brain-machine interfaces and with a wide range of applications in neurological disorders.

neuroscience↗

In vivo optogenetic stimulation of the primate retina activates the visual cortex after long-term transfection

Over the last 15 years, optogenetics has changed fundamental research in neuroscience, and is now reaching toward therapeutic applications. Vision restoration strategies using optogenetics are now at the forefront of these new clinical opportunities. But applications to human patients suffering from retinal diseases leading to blindness rise important concerns on the long-term functional expression of optogenes and the efficient signal transmission to higher visual centers. Here we demonstrate in non-human primates, continued expression and functionality at the retina level [~]20 months after delivery of our construct. We also performed in-vivo recordings of visually evoked potentials in the primary visual cortex of anaesthetized animals. Using synaptic blockers, we isolated the in-vivo cortical activation resulting from the direct optogenetic stimulation of primate retina. In conclusion, our work indicates long-term transgene expression and transmission of the signal generated in the macaque retina to the visual cortex, two important features for future clinical applications.

neuroscience↗

Functional ultrasound imaging of the spreading activity following optogenetic stimulation of the rat visual cortex

Optogenetic stimulation of the primary visual cortex (V1) is a promising therapy for sight restoration, but it remains unclear what total cerebral volume is activated after surface stimulation. In this study, we expressed the red-shifted opsin ChrimsonR in excitatory neurons within V1 in rats, and used the fine spatial resolution provided by functional ultrasound imaging (fUS) over the whole depth of the brain to investigate the brain response to focal surface stimulation. We observed optogenetic activation of a high proportion of the volume of V1. Extracellular recordings confirmed the neuronal origin of this activation. Moreover, neuronal responses were even located in deep layers under conditions of low irradiance, spreading to the LGN and V2, consistent with a normal visual information process. This study paves the way for the use of optogenetics for cortical therapies, and highlights the value of coupling fUS with optogenetics.

neuroscience↗