Biology subjects

Yazdan-Shahmorad, A.

Publications and source records attributed to Yazdan-Shahmorad, A..

11 recordsLinked to original sources

bioRxiv2025

Multimodal optical imaging and modulation through Smart Dura in non-human primates

Multimodal neural interfaces that integrate electrical and optical functionalities are promising tools for neuroscientific and clinical applications that involve recording and manipulating neuronal activity. However, most technologies for multimodal implementation are largely restricted to small animal models and lack the ability to translate to the larger brains of non-human primates (NHPs). Smart Dura, a recently developed large-scale neural interface for NHPs, enables high-density electrophysiological recordings and broad optical accessibility, providing multiscale information with enhanced spatiotemporal resolution. In this paper, the multimodal capabilities of Smart Dura are demonstrated through integration with multiphoton imaging, optical coherence tomography angiography (OCTA), and intrinsic signal optical imaging (ISOI), as well as optical manipulations such as photothrombotic lesioning and optogenetics. Through the transparent Smart Dura, in vivo fluorescence vascular imaging is achieved down to depths of 200 and 550 m using two-photon and three-photon microscopy, respectively. When combined with simultaneous electrophysiology, Smart Dura also enables assessment of vascular and neural dynamics via OCTA and ISOI, the induction of ischemic stroke, and the application of optogenetic neuromodulation across a wide cortical area of 20 mm in diameter. These capabilities support comprehensive investigations of brain dynamics in NHPs, advancing translational neurotechnology for human applications.

neuroscience↗

bioRxiv2025

Smart Dura: a functional artificial dura for multimodal neural recording and modulation

A multi-modal neural interface capable of long-term recording and stimulation is essential for advancing brain monitoring and developing targeted therapeutics. Among the traditional electrophysiological methods, micro-electrocorticography (ECoG) is appealing for chronic applications because it provides a good compromise between invasiveness and high-resolution neural recording. When combining ECoG with optical technologies, such as calcium imaging and optogenetics, this multi-modal approach enables the simultaneous collection of neural activity from individual neurons and the ability to perform cell-specific manipulation. While previous efforts have focused on multi-modal interfaces for small animal models, scaling these technologies to larger brains, of primates, remains challenging. In this paper, we present a multi-modal neural interface, named Smart Dura, a functional version of the commonly used artificial dura with integrated electrophysiological electrodes for large cortical area coverage for the NHP brain. The Smart Dura is fabricated using a thin-film microfabrication process to monolithically integrate a micron-scale electrode array into a soft, flexible, and transparent substrate with high-density electrodes (up to 256 electrodes) while providing matched mechanical compliance with the native tissue and achieving high optical transparency (exceeding 97%). Our in vivo experiments demonstrate electrophysiological recording capabilities combined with neuromodulation, as well as optical transparency via multiphoton imaging. This work paves the way toward a chronic neural interface that can provide large-scale, bidirectional interfacing for multimodal and closed-loop neuromodulation capabilities to study cortical brain activity in non-human primates, with the potential for translation to humans.

neuroscience↗

bioRxiv2024

Flexible modeling of large-scale neural network stimulation: electrical and optical extensions to The Virtual Electrode Recording Tool for EXtracellular Potentials (VERTEX)

BackgroundComputational models that predict effects of neural stimulation can be used as a preliminary tool to inform in-vivo research, reducing the costs, time, and ethical considerations involved. However, current models do not support the diverse neural stimulation techniques used in-vivo, including the expanding selection of electrodes, stimulation modalities, and stimulation paradigms. New MethodTo develop a more comprehensive software, we created several extensions to The Virtual Electrode Recording Tool for EXtracellular Potentials (VERTEX), the MATLAB-based neural stimulation tool from Newcastle University. VERTEX simulates input currents in a large population of multi-compartment neurons within a small cortical slice to model electric field stimulation, while recording local field potentials (LFPs) and spiking activity. Our extensions to its existing electric field stimulation framework include allowing multiple pairs of parametrically defined electrodes and biphasic, bipolar stimulation delivered at programmable delays. To support the growing use of optogenetic approaches for targeted neural stimulation, we introduced a feature that models optogenetic stimulation through an additional VERTEX input function that converts irradiance to currents at optogenetically responsive neurons. Finally, we added extensions to allow complex stimulation protocols including paired-pulse, spatiotemporal patterned, and closed-loop stimulation. ResultsWe demonstrated our novel features using VERTEXs built-in functionalities, with results in alignment with other models and experimental work. ConclusionsOur extensions provide an all in one platform to efficiently and systematically test diverse, targeted, and individualized stimulation patterns.

neuroscience↗

bioRxiv2024

A large-scale optogenetic neurophysiology platform for improving accessibility in NHP behavioral experiments

Optogenetics has been a powerful scientific tool for two decades, yet its integration with non-human primate (NHP) electrophysiology has been limited due to several technical challenges. These include a lack of electrode arrays capable of supporting large-scale and long-term optical access, inaccessible viral vector delivery methods for transfection of large regions of cortex, a paucity of hardware designed for large-scale patterned cortical illumination, and limited designs for multi-modal experimentation. To address these gaps, we introduce a highly accessible platform integrating optogenetics and electrophysiology for behavioral and neural modulation with neurophysiological recording in NHPs. We employed this platform in two rhesus macaques and showcased its capability of optogenetically disrupting reaches, while simultaneously monitoring ongoing electrocorticography activity underlying the stimulation-induced behavioral changes. The platform exhibits long-term stability and functionality, thereby facilitating large-scale electrophysiology, optical imaging, and optogenetics over months, which is crucial for translationally relevant multi-modal studies of neurological and neuropsychiatric disorders. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/600719v2_ufig1.gif" ALT="Figure 1"> View larger version (67K): org.highwire.dtl.DTLVardef@179542eorg.highwire.dtl.DTLVardef@85ab3aorg.highwire.dtl.DTLVardef@1ac8deeorg.highwire.dtl.DTLVardef@19a0831_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2024

Inferring Neural Communication Dynamics from Field Potentials Using Graph Diffusion Autoregression

Estimating dynamic functional connectivity (dFC) is attracting increased attention, spurred by rapid advancements in multi-site neural recording technologies and efforts to better understand cognitive processes. Yet, most studies focus on static estimates of functional connectivity that cannot capture highly dynamic neural processes, while also ignoring information about the structural organization of the brain. To address these issues, we introduce a class of network-constrained linear autoregressive models that give rise to a highly dynamic functional connectivity signal on the edges of a predefined structural connectivity graph. Furthermore, we demonstrate that adding an additional diffusion constraint improves the models performance. We successfully validated the resulting graph diffusion autoregressive (GDAR) model on simulated neural activity and recordings from subdural and intracortical micro-electrode arrays placed in macaque sensorimotor cortex demonstrating its ability to describe rapid communication dynamics induced by optogenetic stimulation, changes in resting state dFC following stroke and electrical stimulation, and neural correlates of behavior during a reach task.

neuroscience↗

bioRxiv2023

Early Intervention with Electrical Stimulation Reduces Neural Damage After Stroke in Non-human Primates

Ischemic stroke is a neurological condition that results in significant mortality and long-term disability for adults, creating huge health burdens worldwide. For stroke patients, acute intervention offers the most critical therapeutic opportunity as it can reduce irreversible tissue injury and improve functional outcomes. However, currently available treatments within the acute window are highly limited. Although emerging neuromodulation therapies have been tested for chronic stroke patients, acute stimulation is rarely studied due to the risk of causing adverse effects related to ischemia-induced electrical instability. To address this gap, we combined electrophysiology and histology tools to investigate the effects of acute electrical stimulation on ischemic neural damage in non-human primates. Specifically, we induced photothrombotic lesions in the monkey sensorimotor cortex while collecting electrocorticography (ECoG) signals through a customized neural interface. Gamma activity in ECoG was used as an electrophysiological marker to track the effects of stimulation on neural activation. Meanwhile, histological analysis including Nissl, cFos, and microglial staining was performed to evaluate the tissue response to ischemic injury. Comparing stimulated monkeys to controls, we found that theta-burst stimulation administered directly adjacent to the ischemic infarct at 1 hour post-stroke briefly inhibits peri-infarct neuronal activation as reflected by decreased ECoG gamma power and cFos expression. Meanwhile, lower microglial activation and smaller lesion volumes were observed in animals receiving post-stroke stimulation. Together, these results suggest that acute electrical stimulation can be used safely and effectively as an early stroke intervention to reduce excitotoxicity and inflammation, thus mitigating neural damage and enhancing stroke outcomes.

neuroscience↗

bioRxiv2023

Type-2 diabetes alters hippocampal neural oscillations and disrupts synchrony between hippocampus and cortex

Type 2 diabetes mellitus (T2DM) increases the risk of neurological diseases, yet how brain oscillations change as age and T2DM interact is not well characterized. To delineate the age and diabetic effect on neurophysiology, we recorded local field potentials with multichannel electrodes spanning the somatosensory cortex and hippocampus (HPC) under urethane anesthesia in diabetic and normoglycemic control mice, at 200 and 400 days of age. We analyzed the signal power of brain oscillations, brain state, sharp wave associate ripples (SPW-Rs), and functional connectivity between the cortex and HPC. We found that while both age and T2DM were correlated with a breakdown in long-range functional connectivity and reduced neurogenesis in the dentate gyrus and subventricular zone, T2DM further slowed brain oscillations and reduced theta-gamma coupling. Age and T2DM also prolonged the duration of SPW-Rs and increased gamma power during SPW-R phase. Our results have identified potential electrophysiological substrates of hippocampal changes associated with T2DM and age. The perturbed brain oscillation features and diminished neurogenesis may underlie T2DM-accelerated cognitive impairment.

neuroscience↗

bioRxiv2021

A toolbox for studying cortical physiology in primates

Lesioning and neurophysiological studies have facilitated the elucidation of cortical functions and mechanisms of functional recovery following injury. Clinical translation of such studies is contingent on their employment in non-human primates (NHPs), yet tools for monitoring and modulating cortical physiology are incompatible with conventional NHP lesioning techniques. To address these challenges, we developed a toolbox demonstrated in seven macaques. We introduce the photothrombotic method to induce focal cortical lesions alongside a quantitative model for the design of lesion profiles based on experimental needs. Large-scale ([~]5 cm2) vascular and neural dynamics can be monitored and lesion induction can be validated in vivo with optical coherence tomography angiography and our electrocorticographic array, the latter of which also enables testing stimulation-based interventions. By combining optical and electrophysiological techniques in NHPs, we can enhance our understanding of cortical functions, investigate functional recovery mechanisms, integrate physiological and behavioral findings, and develop treatments for neurological disorders.

neuroscience↗

bioRxiv2021

Cortical network structure mediates response to stimulation: an optogenetic study in non-human primates

As aberrant network-level functional connectivity underlies a variety of neural disorders, the ability to induce targeted functional reorganization would be a profound development towards therapies for neural disorders. Brain stimulation has been shown to alter large-scale network-wide functional connectivity, but the mapping from stimulation to the modification is unclear. Here, we leverage advances in neural interfaces, interpretable machine learning, and graph theory to arrive at a model which accurately predicts stimulation-induced network-wide functional reorganization. The model jointly considers the stimulation protocol and the cortical network structure, departing from the standard approach which only considers the stimulation protocol. We validate our approach in the primary sensorimotor cortex of non-human primates using paired optogenetic stimulation through a large-scale optogenetic interface. We observe that the stimulation protocol only predicts a small portion of the induced functional connectivity changes while the network structure predicts much more, indicating that the underlying network is the primary mediator of the response to stimulation. We extract the relationships linking the stimulation and network characteristics to the functional connectivity changes and observe that the mappings diverge over frequency bands and successive stimulations. Finally, we uncover shared processes governing real-time and longer-term effects of stimulation. Our framework represents a paradigm shift for targeted neural stimulation and can be used to interrogate, improve, and develop stimulation-based interventions for neural disorders. TeaserBrain stimulation rewires the brain, but the pre-existing network structure of the brain controls the rewiring.

neuroscience↗

bioRxiv2021

Environmental enrichment mitigates stroke-induced change in sharp-wave associated ripple characteristics

Cognitive and memory impairments are common sequelae after stroke, yet how middle cerebral artery (MCA) stroke chronically affects the neural activity of the hippocampus, a brain region critical for memory but remote from the stroke epicenter, is poorly understood. Environmental enrichment (EE) improves cognition following stroke; however, the electrophysiology that underlies this behavioral intervention is still elusive. We recorded local field potentials simultaneously from sensorimotor cortex and hippocampus in rats following MCA occlusion and subsequent EE treatment. We found that MCA stroke significantly impacted the electrophysiology in the hippocampus, in particular it disrupted characteristics of sharp-wave associated ripples (SPW-Rs) which are known correlates of memory and cognition. Importantly, we show that EE mitigates stroke-induced changes to SPW-R characteristics. These results begin to uncover the complex interaction between cognitive deficit following stroke and EE treatment, providing a testbed to assess different strategies for therapeutics following stroke.

neuroscience↗

bioRxiv2021

Multi-modal artificial dura for simultaneous large-scale optical access and large-scaleelectrophysiology in non-human primate cortex

ObjectiveNon-human primates (NHPs) are critical for development of translational neural technologies because of their neurological and neuroanatomical similarities to humans. Large-scale neural interfaces in NHPs with multiple modalities for stimulation and data collection poise us to unveil network-scale dynamics of both healthy and unhealthy neural systems. We aim to develop a large-scale multi-modal interface for NHPs for the purpose of studying large-scale neural phenomena including neural disease, damage, and recovery. ApproachWe present a multi-modal artificial dura (MMAD) composed of flexible conductive traces printed into transparent medical grade polymer. Our MMAD provides simultaneous neurophysiological recordings and optical access to large areas of the cortex (~3 cm2) and is designed to mitigate photo-induced electrical artifacts. The MMAD is the centerpiece of the interfaces we have designed to support electrocorticographic recording and stimulation, cortical imaging, and optogenetic experiments, all at the large-scales afforded by the brains of NHPs. We performed electrical and optical experiments bench-side and in vivo with macaques to validate the utility of our MMAD. Main resultsUsing our MMAD we present large-scale electrocorticography from sensorimotor cortex of three macaques. Furthermore, we validated surface electrical stimulation in one of our animals. Our bench-side testing showed up to 90% reduction of photo-induced artifacts with our MMAD. The transparency of our MMAD was confirmed both via bench-side testing (87% transmittance) and via in vivo imaging of blood flow from the underlying microvasculature using optical coherence tomography angiography. SignificanceOur results indicate that our MMAD supports large-scale electrocorticography, large-scale cortical imaging, and, by extension, large-scale optical stimulation. The MMAD prepares the way for both acute and long-term chronic experiments with complimentary data collection and stimulation modalities. When paired with the complex behaviors and cognitive abilities of NHPs, these assets prepare us to study large-scale neural phenomena including neural disease, damage, and recovery.

neuroscience↗