Biology subjects

Jobst, B. C.

Publications and source records attributed to Jobst, B. C..

14 recordsLinked to original sources

bioRxiv2025

Neural components underlying successful free recall are specific to episodic memory

AbstractEpisodic memory depends upon activity distributed across the brain. However, the activity underlying memory has largely been examined within single tasks in isolation. Thus it is unclear to what extent prior findings reflect task-general rather than memory-specific cognitive processes. Here we address this question using data from 371 patients recorded intracranially who performed a free recall task with encoding and retrieval phases alongside an arithmetic distractor phase. We ask whether neural decoders fit to predict behavior from one phase transfer to the others. Encoding-retrieval transfer exceeds both arithmetic-encoding and arithmetic-retrieval transfer and therefore cannot be explained solely by processes supporting arithmetic. We further detect transfer between arithmetic and retrieval but not between arithmetic and encoding. The brain-behavioral relations observed in these tasks thus do not merely reflect a single task-general factor of activity. We propose cross-task decoding as a method for identifying the neural factor structure underlying distinct cognitive processes.

neuroscience↗

bioRxiv2025

Low and high frequency signatures of impaired consciousness in temporal lobe seizures

Impaired consciousness is a debilitating and unpredictable outcome of mesial temporal lobe seizures whose mechanisms to date remain unclear. Moreover, questions about the relationship between impaired consciousness and lateralization, hemispheric spread and electrophysiological characteristics of seizures are yet to be answered. To address these gaps, we conducted in-depth investigation of behavioral and intracranial EEG data from 186 mesial temporal lobe seizures of 51 patients with intractable mesial temporal lobe epilepsy. We found that bilateral mesial temporal spread of seizures is not a necessary condition for impaired consciousness, although seizures with bilateral mesial temporal involvement were significantly more likely to have impaired consciousness than unilateral seizures. Contrary to prior belief, we found no relationship between the onset side (left vs. right temporal lobe or language dominant vs. non-dominant lobe) of seizures and the probability of impaired consciousness. Lastly, we established that widespread increases in slow-wave activity (delta band) in extratemporal cortical areas, as well as increases in fast activity (beta band) in the temporal lobes were both robust markers of seizures with impaired consciousness and could predict ictal impairment with up to 86% accuracy. Our findings shed new light on networks that underlie impaired consciousness in temporal lobe epilepsy and may help guide deep brain stimulation of such systems (e.g. via thalamic nuclei) as a potential intervention to improve consciousness during seizures.

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bioRxiv2023

Study-Phase Reinstatement: Encoding Spontaneous Thoughts as Memories

Can the brain improve the retrievability of an experience after it has occurred? Systems consolidation theory proposes that item-specific cortical reactivation during post-encoding rest periods facilitates the formation of stable memory representations, a prediction supported by neural evidence in humans and animals. Such reactivation may also occur on shorter time scales, offering a potential account of classic list memory phenomena but lacking in support from neural data. Leveraging the high-temporal specificity of intracranial electroencephalography (iEEG), we investigate spontaneous reactivation of previously experienced items during brief intervals between individual encoding events. Across two large-scale free recall experiments, we show that reactivation during these periods, measured by spectral iEEG similarity, predicts subsequent recall. In a third experiment, we show that the same methodology can identify post-encoding reactivation that correlates with subsequent memory, consistent with previous results. Thus, spontaneous study-phase reinstatement reliably predicts memory behavior, linking psychological accounts to neural mechanisms and providing evidence for rapid consolidation processes during encoding.

neuroscience↗

bioRxiv2023

Functional and anatomical connectivity predict brain stimulation's mnemonic effects

Closed-loop direct brain stimulation is a promising tool for modulating neural activity and behavior. However, it remains unclear how to optimally target stimulation to modulate brain activity in particular brain networks that underlie particular cognitive functions. Here, we test the hypothesis that stimulations behavioral and physiological effects depend on the stimulation targets anatomical and functional network properties. We delivered closed-loop stimulation as 47 neurosurgical patients studied and recalled word lists. Multivariate classifiers, trained to predict momentary lapses in memory function, triggered stimulation of the lateral temporal cortex (LTC) during the study phase of the task. We found that LTC stimulation specifically improved memory when delivered to targets near white matter pathways. Memory improvement was largest for targets near white matter that also showed high functional connectivity to the brains memory network. These targets also reduced low-frequency activity in this network, an established marker of successful memory encoding. These data reveal how anatomical and functional networks mediate stimulations behavioral and physiological effects, provide further evidence that closed-loop LTC stimulation can improve episodic memory, and suggest a method for optimizing neuromodulation through improved stimulation targeting.

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bioRxiv2021

Minimal functional alignment of ventromedial prefrontal cortex intracranial EEG signals during naturalistic viewing

The ventromedial prefrontal cortex (vmPFC) has been thought to play an important role in processing endogenous information such as generating subjective affective meaning. Unlike sensory cortex, which processes exogenous information about the external world similarly across individuals, prior work has posited that vmPFC activity may be idiosyncratic to each individual, even when exposed to the same external stimulus. In this study, we recorded local field potentials (LFPs) from intracranial stereotactic electrodes implanted in patients with intractable epilepsy while they watched an emotionally engaging television show episode and evaluated temporal synchronization of these signals across participants in auditory cortex and vmPFC. Overall, we observed markedly lower intersubject synchronization of signals recorded from electrodes implanted in vmPFC compared to auditory cortex. A subset of patients, however, appeared to share similar vmPFC states during the more emotionally salient scenes. This work suggests that the vmPFC is involved in processing affective responses to ongoing experience in a state-like manner, but the specific states and temporal sequences are idiosyncratic to each individual, even when viewing the same television episode.

neuroscience↗

bioRxiv2020

Distinct cortical systems reinstate the content and context of episodic memories

Episodic recall depends upon the reinstatement of cortical activity present during the formation of a memory. We identified dissociable cortical networks via functional connectivity that uniquely reinstated semantic content and temporal context of previously studied stimuli during free recall. Network-specific reinstatement predicted the temporal and semantic organization of recall sequences, demonstrating how specialized cortical systems enable the human brain to target specific memories.

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bioRxiv2020

Biomarkers of Memory Variability in Traumatic Brain Injury

Traumatic brain injury (TBI) is a leading cause of cognitive disability and is often associated with significant impairment in episodic memory. In TBI survivors, as in healthy controls, there is marked variability between individuals in memory ability. Using recordings from indwelling electrodes, we characterized and compared the oscillatory biomarkers of mnemonic variability in two cohorts of epilepsy patients: a group with a history of moderate-to-severe TBI (n = 37) and a group of non-TBI controls (n = 111) closely matched for demographics and electrode coverage. Analysis of these recordings demonstrated that increased high frequency power and decreased theta power across a broad set of brain regions mark periods of successful memory formation in both groups. As features in a logistic-regression classifier, spectral power biomarkers effectively predicted recall probability, with little difference between TBI and non-TBI controls. The two groups also displayed similar patterns of theta-frequency connectivity during successful encoding periods. These biomarkers of successful memory, highly conserved between TBI patients and controls, could serve as the basis for novel therapies that target disordered memory across diverse forms of neurological disease.

neuroscience↗

bioRxiv2019

The effects of direct brain stimulation in humans depend on frequency, amplitude, and white-matter proximity.

Researchers have used direct electrical brain stimulation to treat a range of neurological and psychiatric disorders. However, for brain stimulation to be maximally effective, clinicians and researchers should optimize stimulation parameters according to desired outcomes. To examine how different kinds of stimulation affect human brain activity, we compared the changes in neuronal activity that resulted from stimulation at a range of frequencies, amplitudes, and locations with direct human brain recordings. We recorded human brain activity directly with electrodes that were implanted in widespread regions across 106 neurosurgical epilepsy patients while systematically stimulating across a range of parameters and locations. Overall, stimulation most often had an inhibitory effect on neuronal activity, consistent with earlier work. When stimulation excited neuronal activity, it most often occurred from high-frequency stimulation. These effects were modulated by the location of the stimulating electrode, with stimulation sites near white matter more likely to cause excitation and sites near gray matter more likely to inhibit neuronal activity. By characterizing how different stimulation parameters produced specific neuronal activity patterns on a large scale, our results help guide clinicians and researchers when designing stimulation protocols to cause precisely targeted changes in human brain activity.

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bioRxiv2019

Risk of Seizures Induced by Intracranial Research Stimulation: Analysis of 770 Stimulation Sessions

BackgroundPatients with medically refractory epilepsy often undergo intracranial electroencephalography (iEEG) monitoring to identify a seizure focus and determine their candidacy for surgical intervention. This clinically necessary monitoring period provides an increasingly utilized research opportunity to study human neurophysiology, however, ethical concerns demand a thorough appreciation of the associated risks.\n\nObjectiveWe measured the incidence of research stimulation-associated seizures in a large multi-institutional study on brain stimulations effect on memory in order to determine if brain stimulation was statistically associated with seizure incidence, and identify potential risk factors for stimulation-associated seizures.\n\nMethods188 subjects undergoing iEEG monitoring across 10 institutions participated in 770 research stimulation sessions over 3.5 years. Seizures within 30 minutes of a stimulation session were included in our retrospective analysis. We analyzed stimulation parameters, seizure incidence, and typical seizure patterns, to assess the likelihood that recorded seizures were stimulation-induced, rather than events that occurred by chance in epilepsy patients prone to seizing.\n\nResultsIn total, 14 seizures were included in our analysis. All events were single seizures, and no adverse events occurred. The mean amplitude of seizure-associated stimulation did not differ significantly from the mean amplitude delivered in sessions without seizures.\n\nIn order to determine the likelihood that seizures were stimulation induced, we used three sets of analyses: Visual iEEG analysis, statistical frequency, and power analyses. We determined that three of the 14 seizures were likely stimulation-induced, five were possibly stimulation-induced, and six were unlikely stimulation-induced. Overall, we estimate a rate of stimulation-induced seizures between 0.39% and 1.82% of sessions.\n\nConclusionsThe rarity of stimulation-associated seizures, and that none added morbidity or affected the clinical course of any patient, are important findings for understanding the feasibility and safety of intracranial stimulation for research purposes.

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bioRxiv2018

MTL functional connectivity predicts stimulation-induced theta power

Abstract/SummaryFocal electrical stimulation of the brain incites a cascade of neural activity that propagates from the stimulated region to both nearby and remote areas, offering the potential to control the activity of brain networks. Understanding how exogenous electrical signals perturb such networks in humans is key to its clinical translation. To investigate this, we applied electrical stimulation to subregions of the medial temporal lobe in 26 neurosurgical patients fitted with indwelling electrodes. Networks of low-frequency (5-13 Hz) spectral coherence predicted stimulation-evoked changes in theta (5-8 Hz) power, but only when stimulation was applied in or adjacent to white matter. Furthermore, these power changes aligned with control-theoretic predictions of how exogenous stimulation flows through complex networks, such as a dispersal of induced activity when functional hubs are targeted. Our results demonstrate that functional connectivity is predictive of causal changes in the brain, but that access to structural connections is necessary to observe such effects.

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bioRxiv2018

Predictive control of electrophysiological network architecture using direct, single-node neurostimulation in humans

Chronically implantable neurostimulation devices are becoming a clinically viable option for treating patients with neurological disease and psychiatric disorders. Neurostimulation offers the ability to probe and manipulate distributed networks of interacting brain areas in dysfunctional circuits. Here, we use tools from network control theory to examine the dynamic reconfiguration of functionally interacting neuronal ensembles during targeted neurostimulation of cortical and subcortical brain structures. By integrating multi-modal intracranial recordings and diffusion tensor imaging from patients with drug-resistant epilepsy, we test hypothesized structural and functional rules that predict altered patterns of synchronized local field potentials. We demonstrate the ability to predictably reconfigure functional interactions depending on stimulation strength and location. Stimulation of areas with structurally weak connections largely modulates the functional hubness of downstream areas and concurrently propels the brain towards more difficult-to-reach dynamical states. By using focal perturbations to bridge large-scale structure, function, and markers of behavior, our findings suggest that stimulation may be tuned to influence different scales of network interactions driving cognition.

neuroscience↗

bioRxiv2018

Functional wiring of the human medial temporal lobe

The medial temporal lobe (MTL) is a locus of episodic memory in the human brain. It is comprised of cytologically distinct subregions that, in concert, give rise to successful encoding and retrieval of context-dependent memories. However, the functional connections between these subregions are poorly understood. To determine functional connectivity among MTL subregions, we had 126 subjects fitted with indwelling electrodes perform a verbal memory task, and asked how encoding or retrieval correlated with interregional synchronization. Using phase-based measures of connectivity, we found that synchronous theta (4-8 Hz) activity underlies successful episodic memory, whereas high-frequencies exhibit desynchronization. Moreover, theta functional connectivity during encoding aligned with key anatomic connections, including critical links between the entorhinal cortex, dentate gyrus, and CA1 of the hippocampus. Retrieval-associated networks demonstrated enhanced involvement of the subiculum, reflecting a substantial reorganization of the encoding-associated network. We posit that coherent theta activity within the MTL marks periods of successful memory, but distinct patterns of connectivity dissociate key stages of memory processing.\n\nSignificance StatementThe brain functions through the interaction of its distinct parts, but little is known about how such connectivity dynamics relate to learning and memory. We used a large dataset of 126 human subjects with intracranial electrodes to assess patterns of electrical connectivity within the medial temporal lobe - a key region for memory processing - as they performed a memory task. We discovered that unique networks of time-varying, low-frequency interactions correlate with memory encoding and retrieval, specifically in the theta band. Simultaneously, we observed elevated spectral power at high frequencies in these same regions. The result is a complete map of physiological dynamics within the MTL, highlighting how a reorganization of theta networks support distinct memory operations.

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bioRxiv2017

Electrophysiological signatures of spatial boundaries in the human subiculum

Environmental boundaries play a crucial role in spatial navigation and memory across a wide range of distantly-related species. In rodents, boundary representations have been identified at the single-cell level in the subiculum and entorhinal cortex of the hippocampal formation. While studies of hippocampal function and spatial behavior suggest that similar representations might exist in humans, boundary-related neural activity has not been identified electrophysiologically in humans until now. Here we present direct intracranial recordings from the hippocampal formation of surgical epilepsy patients while they performed a virtual spatial navigation task. Our results suggest that encoding target locations near boundaries elicited stronger theta oscillations than for target locations near the center of the environment and that this difference cannot be explained by variables such as trial length, speed, or movement. These findings provide the first direct evidence of boundary-dependent neural activity localized in humans to the subiculum, the homologue of the hippocampal subregion in which most rodent boundary cells are found.\n\nSignificance StatementSpatial computations using environmental boundaries are an integral part of the brains spatial mapping system. In rodents, border/boundary cells in the subiculum and entorhinal cortex reveal boundary coding at the single-neuron level. Although there is good reason to believe that such representations also exist in humans, the evidence has thus far been limited to fMRI studies that broadly implicate the hippocampus in boundary-based navigation. By combining intracranial recordings with high-resolution imaging of hippocampal subregions we identified, for the first time in humans, a neural marker of boundary representation in the subiculum.

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bioRxiv2017

The medial temporal lobe organizes memory across time and space: Causal evidence from brain stimulation

The medial temporal lobe (MTL) is widely implicated in supporting episodic memory and navigation, but its precise functional role in organizing memory across time and space remains elusive. Here we examine the specific cognitive processes implemented by MTL structures (hippocampus and entorhinal cortex) to organize memory by using electrical brain stimulation, leveraging its ability to establish causal links between brain regions and features of behavior. We studied neurosurgical patients who performed spatial-navigation and verbal-episodic memory tasks while brain stimulation was applied in various regions during learning. During the verbal memory task, stimulation in the MTL disrupted the temporal organization of encoded memories such that items learned with stimulation tended to be recalled in a more randomized order. During the spatial task, MTL stimulation impaired subjects abilities to remember items using view-independent (allocentric) navigation strategies. These stimulation effects were specific to the MTL. Our findings thus provide the first causal demonstration in humans of the specific memory processes that are performed by the MTL to encode when and where events occurred.\n\nSignificance StatementNumerous studies have implicated the medial temporal lobe (MTL) in encoding spatial and temporal memories, but they have not been able to causally demonstrate the nature of the cognitive processes by which this occurs in real-time. Electrical brain stimulation is able to demonstrate causal links between a brain region and a given function with high temporal precision. By examining behavior in a memory task as subjects received MTL stimulation, we provide the first causal evidence demonstrating the role of the MTL in organizing the spatial and temporal aspects of episodic memory.

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