Cortical Stimulation Induces Network-Wide Coherence Change In Non-Human Primate Somatosensory Cortex

Bloch, Julien; Khateeb, Karam; Silversmith, Daniel B.; O’Doherty, Joseph E.; Sabes, Philip N.; Yazdan-Shahmorad, Azadeh

doi:10.1109/embc.2019.8856633

Cited by 12 publications

(27 citation statements)

References 8 publications

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“…Moving forward, we plan to capitalize on our previous optogenetic (Ledochowitsch et al ., 2015; Yazdan-Shahmorad et al ., 2015, 2016, 2018b, 2018a, 2018c; Khateeb et al ., 2019a; Ojemann et al ., 2020; Tremblay et al ., 2020) and imaging (Khateeb et al ., 2019b; Macknik et al ., 2019) experience as we pioneer the experimental spaces unveiled by the merging of large-scale ECoG and large-scale optical access to the NHP cortex. The synergistic power of these technologies poise us to build on our past work investigating neural plasticity (Yazdan-Shahmorad et al ., 2018a; Bloch et al ., 2019) as we study large-scale, chronic neural phenomena including neural disease, damage, and recovery. To specifically mention one example research pursuit, we plan to use the MMAD to study the effects of stimulation during recovery from our photothrombotic stroke model (Khateeb et al ., 2019b).…”

Section: Discussionmentioning

confidence: 99%

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

Griggs

Khateeb

Zhou

et al. 2021

Preprint

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Objective. Non-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. Approach. We 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 results. Using 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. Significance. Our 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.

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Section: Discussionmentioning

confidence: 99%

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

Griggs

Khateeb

Zhou

et al. 2021

Preprint

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“…The dominant framework for stimulation-induced targeted connectivity change was developed in vitro , a setting in which the cortical network is largely nonexistent and the stimulation protocol can be extremely precise. Attempts to translate the in vitro findings to in vivo have been largely inconsistent, with some reporting promising results [16] and others reporting effects such as off-target (unstimulated) connectivity changes and a lack of response to the protocols [20, 23, 36, 39].…”

Section: Discussionmentioning

confidence: 99%

“…In line with the original in vitro studies, these experiments hypothesized that pairwise stimulation would drive FCC only between the stimulation targets. Some reported successful induction of targeted FCC [13][14][15][16] while others reported inconsistent results across stimulation targets [10,11]. Notably, these studies also reported a novel finding: stimulation-induced FCC were found to extend beyond the stimulation sites to other recorded regions [10,11,[14][15][16].…”

Section: Introductionmentioning

confidence: 97%

“…Interventions targeting real-time activity are already in clinical use, with deep brain stimulators (DBS) alone implanted in over one hundred thousand individuals to date [34]. Interventions targeting neural connectivity have encountered more difficulties in their transition to clinical practice, as clinical trials [32] and in vivo studies [20, 23, 36, 39] have reported inconsistent results. Very little is known about the underlying mechanisms governing the therapeutic outcomes of either approach.…”

Section: Introductionmentioning

confidence: 99%

“…While STDP was initially observed between monosynaptically connected pairs of neurons in vitro , later studies attempted to recreate the phenomenon in vivo . Some reported successful induction of targeted connectivity changes, but others reported inconsistent effects, most notably off-target (unstimulated) connectivity changes and a lack of response to the protocols [20, 23, 36, 39]. The difficulty in translation from in vitro models to in vivo models corresponds to a stark contrast in experimental settings: in real brains, connections between neurons are mediated by a highly interconnected network.…”

Section: Introductionmentioning

confidence: 99%

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

Bloch

Greaves-Tunnell

Shea‐Brown

et al. 2021

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Brain stimulation interventions are used for the treatment of neurological disorders such as Parkinson's and depression. Despite some success, the effects of stimulation are poorly understood, as evidenced by unknown mechanisms governing therapeutic outcomes, widespread side-effects, and inconsistent results in clinical translation. This incomplete understanding may originate from incomplete treatment of the effects of stimulation, as most studies limit their scale and subject of analysis to local effects of various stimulation protocols. Indeed, in a recent paper we demonstrated that neural stimulation impacts the brain at the network scale; here, we leverage advances in neural interfaces and interpretable machine learning to reveal that the cortical network is the primary controlling factor of the response to stimulation. Using optogenetic stimulation and micro-electrocorticography (μECoG) recording in two awake rhesus macaques, we induce and record widespread functional connectivity changes over large-scale sensorimotor cortical networks. We then use a novel nonparametric modeling framework to predict these changes from the stimulation protocol and from characteristics of the underlying cortical network. We observe that the stimulation protocol only explains a small portion of the network response to stimulation while the network structure characteristics explain much more of the response, implicating the underlying network as 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, demonstrating that all neural stimulation interventions must consider both timescales for their effects to be fully understood. The insights and developments generated in this work represent a paradigm shift for the field of neural stimulation.

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Convection Enhanced Delivery of Viral Vectors

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Cortical Stimulation Induces Network-Wide Coherence Change In Non-Human Primate Somatosensory Cortex

Cited by 12 publications

References 8 publications

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

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

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

Convection Enhanced Delivery of Viral Vectors

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