Biology subjects

Oya, H.

Publications and source records attributed to Oya, H..

14 recordsLinked to original sources

bioRxiv2026

Safety of Subdural Direct Current Stimulation: A Histological Study in the Ovine Brain

BackgroundDirect current (DC) stimulation can modulate neuronal activity in ways that differ from pulsatile stimulation, but its intracranial use has been limited by concerns about tissue injury at the electrode/tissue interface. Quantitative safety limits for DC delivered through metal electrodes directly to the brain remain poorly defined. ObjectiveTo estimate histological safety boundaries for DC stimulation delivered through metal electrodes in a large-brain gyrencephalic animal model. MethodsCathodal DC stimulation was applied to the exposed cortical surface of ten anesthetized sheep using platinum-iridium disc electrodes typically used in clinical applications (surface area [≤] 4.15 mm2). Currents of 5 to 1000 {micro}A were delivered for 10 to 15 minutes at 36 cortical sites. Stimulation dose was quantified as charge density. Brains were removed shortly after stimulation and examined histologically for tissue damage, including necrosis, inflammation, gliosis, and demyelination. Lesion volumes were quantified and related to charge density. ResultsNo lesions were observed at sites where no current or a low charge density (0.7 mC/mm2) was delivered. With stimulation, lesion probability and volume increased with charge density, although variability was substantial. Lesions occurred in 3 of 18 sites at lower charge densities (1.4 to 10 mC/mm2) and in 5 of 9 sites at higher charge densities (14.4 to 144.4 mC/mm2). Linear regression of lesion volume against charge density yielded an estimated zero-lesion intercept of 2.3 mC/mm2, whereas alternative nonlinear models predicted thresholds up to 8.7 mC/mm2. ConclusionThese findings suggest that it may be possible to apply cathodal DC stimulation directly to the cortical surface through metal electrodes without detectable histological damage when current intensity, duration, and electrode size are appropriately constrained. These findings provide quantitative guidance for the safe application of DC directly to neural tissue in experimental and translational neuromodulation studies.

neuroscience↗

bioRxiv2025

High-Frequency Spinal Cord Stimulation Reorganizes Cortical Cross-Frequency Coupling in a Region- and Time-Dependent Manner

Pain management strategies have progressed beyond traditional pharmacologic and physical interventions, integrating advanced neuromodulation techniques such as deep brain stimulation, peripheral nerve stimulation, and high-frequency spinal cord stimulation (hSCS). Despite its clinical efficacy, the supraspinal mechanisms underlying hSCS remain poorly understood. Prior work in sheep demonstrated that hSCS modulates gamma ({gamma}) band (70-150 Hz) activity in the primary somatosensory and association cortices, implicating cortical involvement in pain modulation. Given, the interaction between low and high oscillations, we hypothesized that hSCS modulates {gamma} activity in a region- and time-dependent manner through specific coupling with theta ({square}) rhythms (4-8 Hz). Using 96-channel subdural electrocorticography (ECoG), we computed {square}-{gamma} phase-amplitude coupling (PAC) and the corresponding modulation index (MI) to quantify the effects of hSCS. While the preferred {square}phase of {gamma} activity remained consistent across conditions and regions, MI increased significantly post-stimulation--most prominently in the association cortex, where robust -{gamma} phase locking was observed. In contrast, the somatosensory cortex exhibited weaker and more variable locking. Temporally, both cortices demonstrated an early, rapid increase in MI post-hSCS, accompanied by a shift (association) and attenuation (somatosensory) of the secondary peak. These findings reveal distinct regional and temporal dynamics in PAC following hSCS and suggest complementary roles of somatosensory and association cortices in processing neuromodulatory input. hSCS appears to reorganize cortical cross-frequency interactions, supporting its role in reorganizing functional network dynamics relevant to sensory processing and the subjective pain experience.

neuroscience↗

bioRxiv2023

Activity-induced gene expression in the human brain

Direct electrical stimulation (eSTIM) is widely used clinically, from neurosurgical mapping to therapeutic interventions for neurological and neuropsychiatric disorders1-10. Despite over a century of application, its molecular and cellular underpinnings remain unknown. Here, using state-of-the-art single-nuclei multiomic profiling, we map changes in cell-type-specific gene expression and chromatin accessibility in vivo in the human cortex following eSTIM of neurosurgery patients. eSTIM impacts a network of cells that extends beyond excitatory neurons to include inhibitory neurons, astrocytes, oligodendrocytes and microglia. We observed an upregulation of canonical immediate-early genes (IEGs: FOS, NPAS4, EGR4) in excitatory and inhibitory neurons and induction of cytokine-related genes CCL3 and CCL4 in microglia. The cross-species conservation of this gene signature, together with our examination of a cohort of both epilepsy and cancer patients, underscores the fundamental role of these changes in stimulation-driven plasticity while controlling for disease and environmental confounds. Our study of changes in chromatin accessibility reveals a common code that involves a cell-type specific signature of transcription factor binding motifs for members of the EGR family. By addressing these previously unexplored questions about activity-induced gene expression in vivo in the human brain, our findings challenge the long-standing neuron-centric view of eSTIM, highlighting the broader role of non-neuronal cells, including microglia, in mediating the impact of brain stimulation.

neuroscience↗

bioRxiv2023

TMS provokes target-dependent intracranial rhythms across human cortical and subcortical sites

Transcranial magnetic stimulation (TMS) is increasingly deployed in the treatment of neuropsychiatric illness, under the presumption that stimulation of specific cortical targets can alter ongoing neural activity and cause circuit-level changes in brain function. While the electrophysiological effects of TMS have been extensively studied with scalp electroencephalography (EEG), this approach is most useful for evaluating low-frequency neural activity at the cortical surface. As such, little is known about how TMS perturbs rhythmic activity among deeper structures - such as the hippocampus and amygdala - and whether stimulation can alter higher-frequency oscillations. Recent work has established that TMS can be safely used in patients with intracranial electrodes (iEEG), allowing for direct neural recordings at sufficient spatiotemporal resolution to examine localized oscillatory responses across the frequency spectrum. To that end, we recruited 17 neurosurgical patients with indwelling electrodes and recorded neural activity while patients underwent repeated trials of single-pulse TMS at several cortical sites. Stimulation to the dorsolateral prefrontal cortex (DLPFC) drove widespread low-frequency increases (3-8Hz) in frontolimbic cortices, as well as high-frequency decreases (30-110Hz) in frontotemporal areas, including the hippocampus. Stimulation to parietal cortex specifically provoked low-frequency responses in the medial temporal lobe. While most low-frequency activity was consistent with brief evoked responses, anterior frontal regions exhibited induced theta oscillations following DLPFC stimulation. Taken together, we established that non-invasive stimulation can (1) provoke a mixture of low-frequency evoked power and induced theta oscillations and (2) suppress high-frequency activity in deeper brain structures not directly accessed by stimulation itself.

neuroscience↗

bioRxiv2023

Temporally organized representations of reward and risk in the human brain

AO_SCPLOWBSTRACTC_SCPLOWThe value and uncertainty associated with choice alternatives constitute critical features along which decisions are made. While the neural substrates supporting reward and risk processing have been investigated, the temporal organization by which these computations are encoded remains elusive. Here we leverage the high spatiotemporal precision of intracranial electroencephalography (iEEG) to uncover how representations of decision-related computations unfold in time. We present evidence of locally distributed representations of reward and risk variables that are temporally organized across multiple regions of interest. Reward outcome representations across wide-spread regions follow a temporally cascading order along the anteroposterior axis of the brain. In contrast, expected value can be decoded from multiple regions at the same time, and error signals in both reward and risk domains reflect a mixture of sequential and parallel encoding. We highlight the role of the anterior insula in generalizing between reward prediction error (RePE) and risk prediction error (RiPE), within which the encoding of RePE in the distributed iEEG signal predicts RiPE. Together our results emphasize the utility of uncovering temporal dynamics in the human brain for understanding how computational processes critical for value-based decisions under uncertainty unfold.

neuroscience↗

bioRxiv2022

Effects of transcranial magnetic stimulation on the human brain recorded with intracranial electrocorticography: First-in-human study

Transcranial magnetic stimulation (TMS) is increasingly used as a noninvasive technique for neuromodulation in research and clinical applications, yet its mechanisms are not well understood. Here, we present the first in-human study evaluating the effects of TMS using intracranial electrocorticography (iEEG) in neurosurgical patients. We first evaluated safety in a gel-based phantom. We then performed TMS-iEEG in 20 neurosurgical participants with no adverse events. Next, we evaluated brain-wide intracranial responses to single pulses of TMS to the dorsolateral prefrontal cortex (dlPFC) (N=10, 1414 electrodes). We demonstrate that TMS preferentially induces neuronal responses locally within the dlPFC at sites with higher electric field strength. Evoked responses were also noted downstream in the anterior cingulate and anterior insular cortex, regions functionally connected to the dlPFC. These findings support the safety and promise of TMS-iEEG in humans to examine local and network-level effects of TMS with higher spatiotemporal resolution than currently available methods.

neuroscience↗

bioRxiv2021

Distribution of multi-unit pitch responses recorded intracranially from human auditory cortex

The perception of pitch requires the abstraction of stimulus properties related to the spectrotemporal structure of sound. Previous studies utilizing both animal electrophysiology and human imaging have indicated the presence of a center for pitch representation in the auditory cortex. Recent data from our own group - examining local field potentials (LFPs) in humans - indicate more widely distributed pitch-associated responses within the auditory cortex (Gander et al., 2019). To probe this with greater spatial resolution, we examined multi-unit activity related to three different auditory stimuli, in seven epilepsy patients who were implanted with high-impedance electrodes in auditory cortex for the clinical purpose of localizing seizures. The stimuli were regular-interval noise (RIN) with a pitch strength that is related to the temporal regularity, and pitch value determined by repetition rate, and harmonic complexes with missing fundamentals. We demonstrated increases in spiking activity in 69 of 104 (66%) responsive multiunit activity in auditory cortex due to pitch-associated stimuli. Importantly, these responses were distributed across the entire extent of Heschls gyrus (HG), in both primary and non-primary areas, rather than isolated to a specific region, and this finding was evident regardless of the stimulus presented. These findings are the first multi-unit pitch responses recorded from humans, and align with a recent study in macaques (Kikuchi et al., 2019) demonstrating that both local field potential and unit responses to pitch-inducing stimuli are distributed throughout auditory cortex. Significance StatementThe perception of pitch is a fundamental acoustic attribute that is mediated by the auditory system. Despite its importance, there is still debate as to the precise areas responsible for its encoding, which may be due to differences in the recording measures and choices of stimuli used in previous studies. Here, we present the first study to measure multi-unit pitch responses in the auditory cortices of intracranially-implanted humans. Importantly, we demonstrate reliable responses to three different pitch-inducing paradigms that are distributed throughout Heschls gyrus, rather than being localized to a particular region. These data provide a bridge across animal and human studies, and aid in our understanding of the processing of a critical attribute of acoustic stimuli.

neuroscience↗

bioRxiv2021

Intracranial electrical stimulation alters meso-scale network integration as a function of network topology

Human brain dynamics are organized into a multi-scale network structure that contains multiple tight-knit, meso-scale communities. Recent work has demonstrated that many psychological capacities, as well as impairments in cognitive function secondary to damage, can be mapped onto organizing principles at this mesoscopic scale. However, we still dont know the rules that govern the dynamic interactions between regions that are constrained by the topology of the broader network. In this preregistered study, we utilized a unique human dataset in which whole brain BOLD-fMRI activity was recorded simultaneously with intracranial electrical stimulation, to characterize the effects of direct neural stimulation on the dynamic reconfiguration of the broader network. Direct neural stimulation increased the extent to which the stimulation sites own mesoscale community integrated with the rest of the brain. Further, we found that these network changes depended on the topological role of the stimulation site itself: stimulating regions with high participation coefficients led to global integration, whereas stimulating sites with low participation coefficients integrated that regions own community with the rest of the brain. These findings provide direct causal evidence for how network topology shapes and constrains inter-regional coordination, and suggest applications for targeted therapeutic interventions in patients with deep-brain stimulation.

neuroscience↗

bioRxiv2020

Oscillatory correlates of auditory working memory examined with human electrocorticography

This work examines how sounds are held in auditory working memory (AWM) in humans by examining oscillatory local field potentials (LFPs) in candidate brain regions. Previous fMRI studies by our group demonstrated blood oxygenation level-dependent (BOLD) response increases during maintenance in auditory cortex, inferior frontal cortex and the hippocampus using a paradigm with a delay period greater than 10s. The relationship between such BOLD changes and ensemble activity in different frequency bands is complex, and the long delay period raised the possibility that long-term memory mechanisms were engaged. Here we assessed LFPs in different frequency bands in six subjects with recordings from all candidate brain regions using a paradigm with a short delay period of 3 s. Sustained delay activity was demonstrated in all areas, with different patterns in the different areas. Enhancement in low frequency (delta) power and suppression across higher frequencies (beta/gamma) were demonstrated in primary auditory cortex in medial Heschls gyrus (HG) whilst non-primary cortex showed patterns of enhancement and suppression that altered at different levels of the auditory hierarchy from lateral HG to superior- and middle-temporal gyrus. Inferior frontal cortex showed increasing suppression with increasing frequency. The hippocampus and parahippocampal gyrus showed low frequency increases and high frequency decreases in oscillatory activity. The work demonstrates sustained activity patterns that can only be explained by AWM maintenance, with prominent low-frequency increases in medial temporal lobe regions.

neuroscience↗

bioRxiv2020

Focal cortical surface cooling is a novel and safe method for intraoperative functional brain mapping

ObjectiveElectrical cortical stimulation (ECS) has been the gold standard for intraoperative functional mapping in neurosurgery, yet it carries the risk of induced seizures. Here we assess the safety of focal cortical cooling (CC) as a potential alternative to ECS for functional brain mapping. MethodsWe retrospectively reviewed 40 consecutive subjects (n=13 tumor, 27 mesial temporal lobe epilepsy (MTLE) resection) who underwent intraoperative CC during craniotomy at the University of Iowa Hospital and Clinics from 2007 through 2019 (CC group). Thirty-eight of the 40 subjects had ECS performed along with CC during the same procedure. To assess the safety of CC, intra- and post-operative seizure incidence and post-operative neurological deficits were collected together with new post-operative radiographic findings not related to the surgical procedure itself (i.e. non-mapping portions). As a control cohort, we collected 55 consecutive subjects (n=21 MTLE, 34 tumor/vascular pathology) who underwent awake ECS mapping without CC between 2006 and 2019 (ECS-alone group). To evaluate potential long term effects of mapping techniques (CC and/or ECS), we separately collected another 25 consecutive subjects who underwent anterior temporal lobectomy(ATL) without CC nor ECS between 2007 and 2019 (No ECS/No CC-ATL group). ResultsA total of 79 brain sites were cooled in the 40 CC subjects, including inferior frontal gyrus (44%), precentral gyrus (39%), postcentral gyrus (6%), subcentral gyrus (4%) and superior temporal gyrus (6%). No intraoperative seizures were reported in the CC group, whereas 3.6% of ECS-alone group had intraoperative seizures. The incidence of seizure(s) within the first post-operative week did not significantly differ amongst CC (7.9%), ECS-alone (9.0%) and No ECS/No CC-ATL groups (12%). There was no significante difference in the incidence of postoperative radiographic change between CC (7.5%) and ECS-alone groups (5.5 %). The long term seizure outcome for MTLE subjects did not statistically differ regarding good outcomes (Engel I+II): CC group (80%), ECS-alone (83.3%) and No ECS/No CC-ATL group (83.3%). ConclusionsCortical cooling when used as an intraoperative mapping technique is safe, and may complement traditional electrical cortical stimulation.

neuroscience↗

bioRxiv2020

Human es-fMRI Resource: Concurrent deep-brain stimulation and whole-brain functional MRI

Mapping the causal effects of one brain region on another (effective connectivity) is a challenging problem in neuroscience, since it requires invasive direct manipulation of brain function, together with whole-brain measurement of the effects produced. Here we establish a unique resource and present data from 26 human patients who underwent electrical stimulation during functional magnetic resonance imaging (es-fMRI). The patients had medically refractory epilepsy requiring surgically implanted intracranial electrodes in cortical and subcortical locations. One or multiple contacts on these electrodes were stimulated while simultaneously recording BOLD-fMRI activity in a block design. Multiple runs exist for patients with different stimulation sites. We describe the resource, data collection process, preprocessing using the fMRIPrep analysis pipeline and management of artifacts, and provide end-user analyses to visualize distal brain activation produced by site-specific electrical stimulation. The data are organized according to the brain imaging data structure (BIDS) specification, and are available for analysis or future dataset contributions on openneuro.org including both raw and preprocessed data.

neuroscience↗

bioRxiv2020

Common Fronto-temporal Effective Connectivity in Humans and Monkeys

Cognitive pathways supporting human language and declarative memory are thought to have uniquely evolutionarily differentiated in our species. However, cross-species comparisons are missing on site-specific effective connectivity between regions important for cognition. We harnessed a new approach using functional imaging to visualize the impact of direct electrical brain stimulation in human neurosurgery patients. Applying the same approach with macaque monkeys, we found remarkably comparable patterns of effective connectivity between auditory cortex and ventro-lateral prefrontal cortex (vlPFC) and parahippocampal cortex in both species. Moreover, in humans electrical tractography revealed rapid evoked potentials in vlPFC from stimulating auditory cortex and speech sounds drove vlPFC, consistent with prior evidence in monkeys of direct projections from auditory cortex to vocalization responsive regions in vlPFC. The results identify a common effective connectivity signature that from auditory cortex is equally direct to vlPFC and indirect to the hippocampus (via parahippocampal cortex) in human and nonhuman primates. HighlightsO_LIPrivileged human auditory to inferior frontal connectivity, linked to monkeys C_LIO_LICommon auditory to parahippocampal effective connectivity in both species C_LIO_LIGreater lateralization in human effective connectivity, more symmetrical in monkeys C_LIO_LIHuman fronto-temporal network function rooted in evolutionarily conserved signature C_LI eTOC short summaryFunctional connectivity between regions crucial for language and declarative memory is thought to have substantially differentiated in humans. Using a new technique to similarly visualize directional effective connectivity in humans and monkeys, we found remarkably comparable connectivity patterns in both species between fronto-temporal regions crucial for cognition.

neuroscience↗

bioRxiv2018

FMRIPrep: a robust preprocessing pipeline for functional MRI

Preprocessing of functional MRI (fMRI) involves numerous steps to clean and standardize data before statistical analysis. Generally, researchers create ad hoc preprocessing workflows for each new dataset, building upon a large inventory of tools available for each step. The complexity of these workflows has snowballed with rapid advances in MR data acquisition and image processing techniques. We introduce fMRIPrep, an analysis-agnostic tool that addresses the challenge of robust and reproducible preprocessing for task-based and resting fMRI data. FMRIPrep automatically adapts a best-in-breed workflow to the idiosyncrasies of virtually any dataset, ensuring high-quality preprocessing with no manual intervention. By introducing visual assessment checkpoints into an iterative integration framework for software-testing, we show that fMRIPrep robustly produces high-quality results on a diverse fMRI data collection comprising participants from 54 different studies in the OpenfMRI repository. We review the distinctive features of fMRIPrep in a qualitative comparison to other preprocessing workflows. We demonstrate that fMRIPrep achieves higher spatial accuracy as it introduces less uncontrolled spatial smoothness than commonly used preprocessing tools. FMRIPrep has the potential to transform fMRI research by equipping neuroscientists with a high-quality, robust, easy-to-use and transparent preprocessing workflow which can help ensure the validity of inference and the interpretability of their results.

bioinformatics↗

bioRxiv2017

Causal Mapping of Emotion Networks in the Human Brain: Framework and Preliminary Findings

Emotions involve many cortical and subcortical regions, prominently including the amygdala. It remains unknown how these multiple network components interact, and it remains unknown how they cause the behavioral, autonomic, and experiential effects of emotions. Here we describe a framework for combining a novel technique, concurrent electrical stimulation with fMRI (es-fMRI), together with a novel analysis, inferring causal structure from fMRI data (causal discovery). We outline a research program for investigating human emotion with these new tools, and provide initial findings from two large resting-state datasets as well as case studies in neurosurgical patients with electrical stimulation of the amygdala. The overarching goal is to use causal discovery methods on fMRI data to infer causal graphical models of how brain regions interact, and then to further constrain these models with direct stimulation of specific brain regions and concurrent fMRI. We conclude by discussing limitations and future extensions. The approach could yield anatomical hypotheses about brain connectivity, motivate rational strategies for treating mood disorders with deep brain stimulation, and could be extended to animal studies that use combined optogenetic fMRI.

neuroscience↗