Biology subjects

Sahel, J.-A.

Publications and source records attributed to Sahel, J.-A..

At least 19 recordsLinked to original sources

bioRxiv2026

Wavelet Transform improves time-frequency characterization of the Electroretinographic Oscillatory Potentials as compared to Short-Time Fourier Transform across experimental and clinical models

Purpose: To compare continuous wavelet transform (CWT) and short-time Fourier transform (STFT) analyses of the oscillatory potentials (OPs) of the dark-adapted full-field electroretinogram (FFERG). Methods: FFERG recordings from Royal College of Surgeons (RCS) and healthy Brown Norway (BN) rats, wild-type and Atoh7 enhancer-knockout (KO) mice, and patients with diabetic retinopathy and healthy controls were analyzed with STFT and with CWT employing the real Morlet wavelet, after 60 Hz high-pass and sharp 60 Hz notch filtering. Time- and frequency-localized OP features were quantified and the methods compared on detection of transient OP signals. Both were additionally validated using synthetic OP-like bursts of known frequency embedded in each cohort's recorded noise. Results: CWT revealed distinct time-frequency patterns and disease-specific OP alterations across all rat, mouse, and human cohorts, with improved temporal localization and frequency resolution, whereas STFT merged transient features and was more susceptible to noise. CWT-derived dominant-frequency differences reached significance in all three models; the corresponding STFT difference reached significance only in rats (separate tests; methods not directly compared). In synthetic bursts, both methods recovered injected frequencies to within 1-2.5 Hz, but only CWT resolved two bursts separated by 15 ms. Conclusions: CWT employing the real Morlet wavelet provides a robust, physiologically relevant evaluation of OPs, with improved temporal localization and reduced spectral dispersion relative to STFT in clinical and experimental settings. Translational Relevance: CWT analysis may improve the characterization of inner retinal dysfunction by preserving transient OP time-frequency structure, as illustrated in preclinical rodent models and diabetic retinopathy patients.

physiology↗

bioRxiv2026

Systemic, RPE-directed AAV-Tyrosinase therapy restores ocular pigmentation in an OCA1 mouse model

Oculocutaneous albinism type 1 (OCA1) is a pigmentation disorder caused by biallelic tyrosinase (TYR) mutations, an essential enzyme for melanin synthesis. TYR inactivity results in loss of hair, skin, and eye pigment, which is detrimental for ocular function. Hypopigmentation of iris, retinal pigment epithelium (RPE), and choroid results in severe photosensitivity and low visual acuity. There are currently no FDA-approved pigment restoring therapies for OCA1, making therapeutic development an unmet clinical need. To address this gap, we have advanced an adeno-associated viral (AAV)-mediated Tyr replacement approach for OCA1 ocular pigment restoration. We evaluated the optimal viral delivery strategy and vector cell-type specificity for iris, RPE, and choroid pigmentation in an OCA1 mouse model, testing intraocular and systemic viral delivery methods in conjunction with viral constructs of varying RPE-specificity. Early, systemic delivery of an RPE-directed AAV-Tyr construct, AAV9.2yf-VMD2-Tyr, achieved widespread ocular pigment rescue with minimal off-target expression in non-ocular tissues. Animals treated with AAV9.2yf-VMD2-Tyr demonstrated reduced photophobic behavior compared to untreated controls, indicating that ocular pigmentation restores a debilitating functional consequence of OCA1. Our findings establish a foundation for clinical translation of an AAV-TYR therapy aimed at improving light sensitivity, glare, and low vision through pigment restoration in patients with OCA1.

molecular biology↗

bioRxiv2026

Structural dynamics insights into principles underlying the fitness of new broadly potent AAVs

Adeno-associated virus (AAV) is a leading platform for gene therapy, but current clinical-stage vectors require high doses associated with adverse events. Engineering of AAVs has produced more efficient vectors, although the mechanism underlying these improvements often remains poorly understood, limiting further development and raising potential safety concerns. Here, we leveraged a new workflow for AAV engineering with single-cell resolution, called scAAVengr-Hunt, to create best-in-class AAVs for gene delivery. ATX002, the top-performing vector, demonstrates broad potency across species, including nonhuman primate, mouse, and human, as well as across retina and brain. To understand the mechanism underlying this broad potency, we performed molecular dynamics simulations comparing AAV variants spanning a range of fitness levels. Structural dynamics analysis revealed a bifunctional molecular mechanism that confers potency through increased affinity of the capsid to the AAV receptor and regulation of heparan sulfate binding. This work provides critical insights relating structural mechanism to the fitness of engineered AAVs and establishes rich new avenues for AAV engineering through the integration of sequence-level analysis with computational biophysics.

bioengineering↗

bioRxiv2025

A non-canonical AKT1-TERT pathway coordinates autophagy and ERphagy

The retinal pigment epithelium (RPE) sustains lifelong proteostasis under chronic stress, yet how post-mitotic cells activate autophagy when canonical kinase pathways suppress it remains unresolved. Here we demonstrate that AKT1, conventionally regarded as an autophagy suppressor, drives autophagy through a non-canonical transcriptional mechanism triggered by isoform imbalance. In RPE and age-related macular degeneration (AMD) models, AKT2 hyperactivation destabilizes mTORC2 and engages S6K-mediated IRS-1 inhibition, creating a feedforward autophagic arrest. Compensatory AKT1 activation via mTORC2 phosphorylates telomerase reverse transcriptase (TERT) at Serine 824, driving nuclear translocation that is independent of telomere maintenance. In the nucleus, TERT assembles with FOXO3 and MYC into a tripartite transcriptional complex that occupies the EIF2AK3 promoter, enabling PERK transcriptional activation. This activity converts the unfolded protein response from pro-apoptotic to cytoprotective: PERK-ATF4 signaling drives biogenesis of core autophagy machinery while simultaneously inducing selective ERphagy through the receptors TEX264 and CCPG1, which prevents pathological PERK clustering and preserves tubular ER architecture in diseased RPE. Using C. elegans phosphorylation-deficient mutants, mouse models and AMD patient induced pluripotent stem cell-derived retinal pigment epithelium (iPSC-RPE), we establish that AKT1-mediated TERT phosphorylation is an evolutionarily conserved prerequisite for FOXO/DAF-16 nuclear function and lysosomal homeostasis in post-mitotic cells. Pharmacologic targeting of AKT2 with a first-in-class dual-pocket allosteric inhibitor selectively enhances AKT1 compensation, restoring macroautophagic and ERphagy flux across disease models. These findings reveal a kinase-to-transcription axis that reprograms organelle quality control and identify the AKT1-TERT-PERK-ATF4 pathway as a therapeutic target in proteostasis-driven disease.

cell biology↗

bioRxiv2023

The AKT2/SIRT5/TFEB pathway as a potential therapeutic target in atrophic AMD

Introductory paragraphAge-related macular degeneration (AMD), the leading cause of geriatric blindness, is a multi-factorial disease with retinal-pigmented epithelial (RPE) cell dysfunction as a central pathogenic driver. With RPE degeneration, lysosomal function is a core process that is disrupted. Transcription factors EB/E3 (TFEB/E3) tightly control lysosomal function; their disruption can cause aging disorders, such as AMD. Here, we show that induced pluripotent stem cells (iPSC)-derived RPE cells with the complement factor H variant [CFH (Y402H)] have increased AKT2, which impairs TFEB/TFE3 nuclear translocation and lysosomal function. Increased AKT2 can inhibit PGC1, which downregulates SIRT5, an AKT2 binding partner. SIRT5 and AKT2 co-regulate each other, thereby modulating TFEB-dependent lysosomal function in the RPE. Failure of the AKT2/SIRT5/TFEB pathway in the RPE induced abnormalities in the autophagy-lysosome cellular axis by upregulating secretory autophagy, thereby releasing a plethora of factors that likely contribute to drusen formation, a hallmark of AMD. Finally, overexpressing AKT2 in RPE cells in mice led to an AMD-like phenotype. Thus, targeting the AKT2/SIRT5/TFEB pathway could be a potential therapy for atrophic AMD.

cell biology↗

bioRxiv2022

The vertical position of visual information conditions spatial memory performance in healthy aging

Memory for objects and their location is a cornerstone of adequate cognitive functioning across the lifespan. Considering that human visual perception is dependent upon the position of stimuli within the visual field, we posit that the position of objects in the environment may be a determinant aspect of mnemonic performance. In this study, a population of young and older adults completed a source monitoring task with objects presented either in the upper or lower visual field. Using multinomial processing tree modeling, we revealed that while item memory remained intact in older age, spatial memory was impaired but only for objects that had been presented in the upper visual field. Spatial memory is therefore conditioned by the vertical position of information. These findings put into question the traditional view that age-related spatial mnemonic deficits are primarily attributable to high-order associative dysfunctions and suggest that they could also originate from altered encoding of object attributes.

neuroscience↗

bioRxiv2022

Imaging the structure and dynamic activity of retinal microglia and macrophage-like cells in the living human eye

PurposeWe recently showed how a refined sequential detection pattern and image processing pipeline for multi-offset adaptive optics scanning light ophthalmoscopy (AOSLO) can increase the contrast of weakly scattering inner retinal structures, including microglia. However, sequential detection was still time-consuming, preventing dynamics from being monitored over short intervals (< 3 mins). Here we show that simultaneous fiber-bundle (FB) detection can overcomes this limitation to reveal the structure and dynamic activity of microglia and macrophage-like cells in healthy and diseased retinae. MethodsWe designed and implemented a custom 7-fiber optical FB with one central confocal fiber and six larger fibers for multi-offset detection in AOSLO at a single focal plane. We imaged the ganglion cell layer at several locations at multiple timepoints (from minutes to weeks) in 8 healthy participants and in 4 patients with ocular infections or inflammation, including ocular syphilis and posterior uveitis. Microglia and immune cells were manually segmented to quantify cell morphometry and motility. ResultsFiber-bundle detection reduced single acquisition time to 20-30 seconds, enabling imaging over larger areas and monitoring of dynamics over shorter intervals. Presumed microglia in healthy retinas had an average diameter of 12.8 m and with a spectrum of morphologies including circular cells and elongated cells with visible processes. We also detected the somas of putative macroglia, potentially astrocytes, near the optic nerve head. Microglia moved slowly in normal eyes (0.02m/sec, on average) but speed increased in patients with active infections or inflammation (up to 2.37m/sec). Microglia activity was absent in a patient with chronic uveitis that was quiescent but apparent over short intervals in an active uveitis retina. In a patient with ocular syphilis imaged at multiple timepoints during treatment, macrophage-like cells containing granular internal structures were seen. Decreases in the quantity and motility of these immune cells were correlated with improvements to vision and other structural and systemic biomarkers. ConclusionsFB-AOSLO enable simplified optical setup with easy alignment and implementation. We imaged the fine-scale structure and dynamics of microglia and macrophage-like cells during active infection and inflammation in the living eye for the first time. In healthy eyes we also detected putative glia cell near the optic nerve head. FB-AOSLO offers promise as a powerful tool for detecting and monitoring retinal inflammation and infection in the living eye over short response to treatment.

bioengineering↗

bioRxiv2021

IMMMUNE MEDIATORS IN IDIOPATHIC UVEITIS

To investigate which cytokines, chemokines and growth factors are involved in the immunopathogenesis of idiopathic uveitis, and whether cytokine profiles are associated with. Serum and aqueous humor (AH) samples of 75 patients with idiopathic uveitis were analyzed by multiplex immunoassay. Infectious controls consisted of 16 patients with ocular toxoplasmosis all confirmed by intraocular fluid analyses. Noninfectious controls consisted of 7 patients with Behcet disease related uveitis and 15 patients with sarcoidosis related uveitis. The control group consisted of AH and serum samples from 47 noninflammatory control patients with age-related cataract. In each sample, 27 immune mediators {+/-} IL-21 and IL-23 were measured. In idiopathic uveitis, 13 of the 29 mediators, including most proinflammatory and vascular mediators such as IL-6, IL-8, IL-12, G-CSF, GM-CSF, MCP-1, IP-10, TNF- and VEGF, were significantly elevated in the aqueous humor when compared to all controls. Moreover, IL-17, IP-10, and IL-21, were significantly elevated in the serum when compared to all controls. We clustered 4 subgroups of idiopathic uveitis using a statistical analysis of hierarchical unsupervised classification, characterized by the order of magnitude of concentrations of intraocular cytokines. The pathogenesis of idiopathic uveitis is characterized by the presence of predominantly proinflammatory cytokines and chemokines and vascular endothelial growth factor with high expression levels as compared to other causes of uveitis. There are indications for obvious Th-1/ IL21-Th17 pathways but also IL9-Th9 and increased IFN-{gamma}-inducing cytokine (IL12) and IFN-{gamma}-inducible CXC chemokine (IP-10). The combined data suggest that immune mediator expression is different among idiopathic uveitis. This study suggests various clusters among the idiopathic uveitis group rather than one specific uveitis entity.

immunology↗

bioRxiv2021

Selective neural coding of object, feature, and geometry spatial cues in humans

Orienting in space requires the processing and encoding of visual spatial cues. The dominant hypothesis about the brain structures mediating the coding of spatial cues stipulates the existence of a hippocampal-dependent system for the representation of geometry and a striatal-dependent system for the representation of landmarks. However, this dual-system hypothesis is based on paradigms that presented spatial cues conveying either conflicting or ambiguous spatial information and that amalgamated the concept of landmark into both discrete 3D objects and wall features. These confounded designs introduce difficulties in interpreting the spatial learning process. Here, we test the hypothesis of a complex interaction between the hippocampus and the striatum during landmark and geometry visual coding in humans. We also postulate that object-based and feature-based navigation are not equivalent instances of landmark-based navigation as currently considered in human spatial cognition. We examined the neural networks associated with geometry-, object-, and feature-based spatial navigation in an unbiased, two-choice behavioral paradigm using fMRI. We showed evidence of a synergistic interaction between hippocampal and striatal coding underlying flexible navigation behavior. The hippocampus was involved in all three types of cue-based navigation, whereas the striatum was more strongly recruited in the presence of geometric cues than object or feature cues. We also found that unique, specific neural signatures were associated with each spatial cue. Critically, object-based navigation elicited a widespread pattern of activity in temporal and occipital regions relative to feature-based navigation. These findings challenge and extend the current view of a dual, juxtaposed hippocampal-striatal system for visual spatial coding in humans. They also provide novel insights into the neural networks mediating object vs. feature spatial coding, suggesting a need to distinguish these two types of landmarks in the context of human navigation. Highlights O_LIComplex hippocampal-striatal interaction during visual spatial coding for flexible human navigation behavior. C_LIO_LIDistinct neural signatures associated with object-, feature-, and geometry-based navigation. C_LIO_LIObject- and feature-based navigation are not equivalent instances of landmark-based navigation. C_LI

neuroscience↗

bioRxiv2021

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↗

bioRxiv2021

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↗

bioRxiv2021

Mobile brain/body imaging of landmark-based navigation with high-density EEG

Coupling behavioral measures and brain imaging in naturalistic, ecological conditions is key to comprehend the neural bases of spatial navigation. This highly-integrative function encompasses sensorimotor, cognitive, and executive processes that jointly mediate active exploration and spatial learning. However, most neuroimaging approaches in humans are based on static, motion constrained paradigms and they do not account for all these processes, in particular multisensory integration. Following the Mobile Brain/Body Imaging approach, we aimed to explore the cortical correlates of landmark-based navigation in actively behaving young adults, solving a Y-maze task in immersive virtual reality. EEG analysis identified a set of brain areas matching state-of-the-art brain imaging literature of landmark-based navigation. Spatial behavior in mobile conditions additionally involved sensorimotor areas related to motor execution and proprioception usually overlooked in static fMRI paradigms. Expectedly, we located a cortical source in or near the posterior cingulate, in line with the engagement of the retrosplenial complex in spatial reorientation. Consistent with its role in visuo-spatial processing and coding, we observed an alpha power desynchronization while participants gathered visual information. We also hypothesized behavior-dependent modulations of the cortical signal during navigation. Despite finding few differences between the encoding and retrieval phases of the task, we identified transient time-frequency patterns attributed, for instance, to attentional demand, as reflected in the alpha/gamma range, or memory workload in the delta/theta range. We confirmed that combining mobile high-density EEG and biometric measures can help unravel the brain structures and the neural modulations subtending ecological landmark-based navigation.

neuroscience↗

bioRxiv2020

Spatial frequency-based image reconstruction to improve image contrast in multi-offset adaptive optics ophthalmoscopy

Off-axis detection methods in adaptive optics (AO) ophthalmoscopy can enhance image contrast of translucent retinal structures such as cone inner segments and retinal ganglion cells layer neurons. Here, we propose a 2D optical model showing that the phase contrast produced by these methods depends on the offset orientation. While one axis provides an asymmetric light distribution, hence a high phase contrast, the perpendicular axis provides a symmetric one, thus a substantially lower contrast. We support this model with in-vivo human data acquired with a multi-offset AO scanning light ophthalmoscope. Then, using this finding, we provide a post-processing method, named Spatial frequency-based iMAge ReconsTruction (SMART), to optimally combine images from different off-axis detector orientations, significantly increasing the structural cellular contrast of in-vivo human retinal neurons such as conne inner segment, putative rods and retinal ganglion cells.

bioengineering↗

bioRxiv2020

Improvements to multi-offset adaptive optics scanning laser ophthalmoscopy for in vivo imaging of individual retinal ganglion cell layer neurons in humans

Previous work has shown that multi-offset detection in adaptive optics scanning laser ophthalmoscopy (AOSLO) can be used to image retinal ganglion cells (RGCs) in monkeys and humans. However, though images of RGCs in anesthetized monkeys with high light levels produced high contrast images of RGCs, images from humans failed to reach the same contrast due to several drawbacks in the previous dual-wavelength multi-offset approach. Our aim here was to design and build a multi-offset detection pattern for humans at safe light levels that could reveal the retinal ganglion cell layer neurons with a contrast, robustness and acquisition time approaching results only previously obtained in monkeys. Here, we present a new imaging system using only one light source, compared to the previous dual-wavelength used on monkeys. Our single-wavelength solution allows for increased light power and eliminates problematic chromatic aberrations. Then, we demonstrate that a radial multi-offset detection pattern with an offset distance of 8-10 Airy Disk Diameter (ADD) is optimal to detect photons multiply scattered in all directions from RGCs thereby enhancing their contrast. This new setup and image processing pipeline led to improved imaging of retinal ganglion cells using multi-offset imaging in AOSLO.

bioengineering↗

bioRxiv2020

scAAVengr: Single-cell transcriptome-based quantification of engineered AAVs in non-human primate retina

Adeno-associated virus (AAV)-mediated gene therapies are rapidly advancing to the clinic, and AAV engineering has resulted in vectors with increased ability to deliver therapeutic genes. Although the choice of vector is critical, quantitative comparison of AAVs, especially in large animals, remains challenging. Here, we developed an efficient single-cell AAV engineering pipeline (scAAVengr) to quantify efficiency of AAV-mediated gene expression across all cell types. scAAVengr allows for definitive, head-to-head comparison of vectors in the same animal. To demonstrate proof-of-concept for the scAAVengr workflow, we quantified - with cell-type resolution - the abilities of naturally occurring and newly engineered AAVs to mediate gene expression in primate retina following intravitreal injection. A top performing variant, K912, was used to deliver SaCas9 and edit the rhodopsin gene in macaque retina, resulting in editing efficiency similar to infection rates detected by the scAAVengr workflow. These results validate scAAVengr as a powerful method for development of AAV vectors.

bioengineering↗

bioRxiv2020

Optogenetic therapy: High spatiotemporal resolution and pattern recognition compatible with vision restoration in non-human primates

Restoring vision using optogenetics is an ideal medical application because the eye offers a direct window to access and stimulate the pathological area: the retina. Optogenetic therapy could be applied to diseases with photoreceptor degeneration such as retinitis pigmentosa. Here, we select the specific optogenetic construct that is now used in the clinical trial and assess the opsin functional efficacy on non-human primates retinal ganglion cells (RGCs). We chose the microbial opsin ChrimsonR and showed that the vector AAV2.7m8 produced greater transfection in RGCs compared to AAV2, and that ChrimsonR attached to tdTomato (ChR-tdT) is more efficiently expressed than ChrimsonR. The 600 nm light activates the RGCs transfected with the vector AAV2.7m8-ChR-tdT from an irradiance of 1015 photons.cm-2.s-1. Vector doses of 5.1010 and 5.1011 vg/eye transfect up to 7000 RGCs/mm2 in the perifovea, with no significant immune reaction. Furthermore, using a multielectrode array we recorded RGCs responses starting from 1ms stimulus duration. Using the recorded activity we were able to decode stimulus information and estimate a theoretical visual acuity of 20/249, above legal blindness. Altogether, our results pave the way for the ongoing clinical trial with the AAV2.7m8-ChrimsonR-tdT vector for vision restoration in patients affected by retinitis pigmentosa. One Sentence SummaryWe select here the vector and genetic construct best suited to provide vision restoration in patients suffering from retinopathies, we demonstrate temporal resolution compatible with high dynamic visual scenes and a visual acuity above legal blindness.

neuroscience↗

bioRxiv2020

Modulation of spatial cue processing across the lifespan: a geometric polarization of space restores allocentric navigation strategies in children and older adults

The impact of development and healthy aging on spatial cognition has been traditionally attributed to a difficulty in using allocentric strategies and a preference for egocentric ones. An alternative possibility, suggested by our previous works, is that this preference is actually conditioned by the spatial cues (e.g. geometric of landmark cues) present in the environment rather than a strategic choice per se. We tested this prediction by having 79 subjects (children, young and older adults) navigating a Y-maze composed either of landmarks or geometric cues, with an immersive head-mounted display that allows us to record both head and eye movements. Our results show that when the performance is based on landmarks solely, children and older adults exhibit a deficit in using allocentric strategies when compared to young adults. Hence, an inverted U-profile of allocentric strategies was observed across the lifespan. This was not due to a default of attention to the landmarks, as evidenced by analysis of gaze dynamics. When geometric were provided, however, older adults and children used allocentric strategies in the same proportion as young adults. They were, in addition, as efficient and quick to implement the strategy. We thus propose a reinterpretation of the previous data in the literature, whereby reference to geometric cues is the default mode for spatial representations, which is immune to age, whereas spatial representations fail to be anchored on landmarks early in development and later in aging. This new interpretation has the potential to reunify several data from the literature, ranging from spatial cues processing to strategy preference, and including other spatial skills like path integration and route learning.

neuroscience↗

bioRxiv2019

Functional ultrasound imaging of deep visual cortex in awake non-human primates

Deep regions of the brain are not easily accessible to investigation at the mesoscale level in awake animals or humans. We have recently developed functional Ultrasound (fUS) imaging fUS imaging technique to uncover deep hemodynamic functional responses. Applying fUS imaging on two awake non-human primates performing a passive fixation task, we reconstructed their retinotopic maps down to the deep calcarine and lunate sulci on visual areas (V1, V2 and V3). These maps were acquired in a single hour session with very few stimuli presentation. The spatial resolution of the technology is illustrated by mapping of Ocular Dominance (OD) columns within superficial and deep layers of the primary visual cortex. These acquisitions showed that OD selectivity is mostly present in layer IV but with evidence also in layers II/III and V. The fUS imaging technology therefore provides a new mesoscale approach to map brain activities at high spatiotemporal resolution in awake subjects within the whole depth of the cortex.

neuroscience↗