Recording brain activity at the mesoscopic scale has a strong potential to unveil many new fundamental neuronal operations. Optical imaging offers a unique opportunity to measure brain activity over a large area with high spatio-temporal resolutions (20 μm x 1 ms). However, two major limitations of this imaging technique partially explain the lack of development in this field. The cortex being non-planar, the field's depth limits the region in focus to a small region close to the center of the field of view. This is particularly significant for the highly curved lissencephalic small cortex of non-human primates that are becoming popular in neuroscience experiments. The ideal technique would be a method that compensates for such curvature; it would enable imaging the whole visual system at once, from the primary to the fifth visual cortices, in small non-human primates. Additionally, the signal-to-noise ratio is strongly degraded by the dynamic evolution of the brain curvature due to physiological rhythms (heartbeat, breathing, etc.). This strongly limits the ability to work at a single-trial level and to unravel the real dynamics of neuronal processing, such as spatio-temporal waves. Here in this project, we present an interdisciplinary approach for imaging of the non-human primate cortex, using technologies from astronomical instrumentation to overcome current technological limits. This will be of interest to a wide neuroscientific audience but also will impact the clinical community interested in mapping the nervous activity at the mesoscopic scale. Our current preliminary development involves redesigning the illumination source and the optical design.
KEYWORDS: Infrared radiation, Neurons, Calcium, Brain, Infrared imaging, In vivo imaging, Luminescence, Brain mapping, Neuroimaging, Signal to noise ratio
Functional mapping of the connectivity of the brain is an essential procedure for neurosurgeons aiming for maximal resection of a brain tumor, while minimizing damage to the eloquent cortex. Being able to delineate the location of critical cortical areas in individual patients allows the surgeon to preserve sensorimotor and cognitive functions. Several methods exist for functional mapping, however, none are capable of delivering fast, label free mapping of the cortex with millimeter precision. In this work, we investigate the potential use of infrared neural stimulation (λ=1470nm) as a means of focal stimulation of the mouse cortex in vivo. Here, we show that the application of infrared neural stimulation induces in vivo cortical intracellular calcium signals in Layer II/III mouse neurons, using intravital calcium imaging with the genetically encoded calcium indicator GCaMP6f.
Increasing evidence suggests that sensory stimulation not only changes the level of cortical activity with respect to baseline but also its structure. Despite having been reported in a multitude of conditions and preparations (for instance, as a quenching of intertrial variability, Churchland et al., 2010), such changes remain relatively poorly characterized. Here, we used optical imaging of voltage-sensitive dyes to explore, in V4 of an awake macaque, the spatiotemporal characteristics of both visually evoked and spontaneously ongoing neuronal activity and their difference. With respect to the spontaneous case, we detected a reduction in large-scale activity (cortical extent>1 mm) in the alpha range (5 to 12.5 Hz) during sensory inflow accompanied by a decrease in pairwise correlations. Moreover, the spatial patterns of correlation obtained during the different visual stimuli were on the average more similar one to another than they were to that obtained in the absence of stimulation. Finally, these observed changes in activity dynamics approached saturation already at very low stimulus contrasts, unlike the progressive, near-linear increase of the mean raw evoked responses over a wide range of contrast values, which could indicate a specific switching in the presence of a sensory inflow.
Depth selectivity is crucial for accurate depth volume probing in vivo in a large
number of medical applications such as brain monitoring. Polarization gating has been widely
used to analyze biological tissues. It is shown that using polarized light allows probing tissues
on a specific depth depending on the polarization illumination type (linearly, circularly) and
the tissues properties. However, accurate depth investigation of the tissue requires a high
selectivity of the probed depth. We propose and simulate the use of different elliptically
polarized illuminations for continuous depth examination between linearly and circularly
polarized illumination. Monte Carlo simulations verify that circularly polarized illumination
penetrates deeper than linearly polarized illumination in biological scattering media.
Furthermore, we show that elliptically polarized light can be tuned in its penetration depth
continuously between the penetration depth of linearly polarized light and circularly polarized
light. Experimental results obtained on phantoms mimicking in vivo situations are presented.
The method proposed here allows to perform a selection of a well defined
subsurface volume in a turbid medium allowing SNR enhancement for functional imaging of
the cortex. The principle consists in sequentially probing the biological tissue with light
polarized linearly or circularly. The method and preliminary results obtained on phantoms are
presented.
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