Biology subjects

Kragel, J. E.

Publications and source records attributed to Kragel, J. E..

12 recordsLinked to original sources

bioRxiv2026

Hippocampal ripples are distinguishable from aperiodic activity

High-frequency "ripple" oscillations support learning and memory across species, yet it has been argued that putative ripples in awake human recordings are false positives produced when algorithms misread aperiodic (1/f) fluctuations as ripple-band oscillations. We show that this conclusion arises from an artifact of evaluating detection algorithms on surrogate data containing only aperiodic activity. Ripple detectors are adaptive, setting their threshold from the amplitude statistics of the signal, so applying them to surrogate data that contains only aperiodic activity lowers the threshold and inflates false positives (median 62%). Adding real ripple-band events back to the surrogate corrects this threshold shift and eliminates most false detections across multiple standard algorithms. Using multi-variate classifiers, we show aperiodic fluctuations can reproduce the power of ripples but not their timing or spectral content. These findings indicate care needs to be taken when using surrogates to evalute ripple detection algorithms. Thus, under realistic signal properties, human hippocampal ripples remain distinguishable from aperiodic activity.

neuroscience↗

bioRxiv2026

Visuospatial coding by theta oscillations in human hippocampus

The hippocampus has been proposed to support visual processing and perception, challenging longstanding accounts that emphasize navigation or declarative memory. A key prediction of visual-processing accounts is that the hippocampus should exhibit similar visuospatial coding properties to those of higher-order visual neocortical areas, such as sensitivity to the size of visual stimuli and contralateral visual field biases. We tested for these properties using intracranial EEG to measure hippocampal neural activity during a retinotopic mapping task. The hippocampus exhibited characteristic slow ([~]2 Hz) and fast ([~]8 Hz) theta oscillations throughout the task. Fast theta was responsive to the presence but not the amount of visual stimulation. In contrast, slow theta did not generally respond to stimulus presence but scaled with the size of the visual stimulus, consistent with larger receptive fields. Slow theta also showed a contralateral bias, an effect that was specific to the right hippocampus. None of these effects were attributable to microsaccades or performance of the concurrent vigilance task. These findings provide electrophysiological evidence for visual field coding by human hippocampus, supporting accounts of hippocampal function that emphasize its role atop the visual hierarchy. Visual processing of this kind may combine with self-motion, memory, and other signals to support the broader spatial and mnemonic functions with which hippocampal theta oscillations have long been associated.

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bioRxiv2026

Fixation-locked hippocampal activity reflects semantic content and temporal order of visual exploration during scene encoding

Memory formation relies on the hippocampus and unfolds over time across experience, such as during the visual exploration of complex, naturalistic scenes. Eye movements evoke hippocampal activity, including fixation-locked field potentials and phase resets of theta oscillations. This suggests that hippocampal encoding is temporally structured by the sequence of visual fixations. Because eye-movement sequences sample semantically meaningful portions of scenes, they provide temporal structure to semantic content in memory. However, it remains unclear how the semantic content and temporal order of fixations jointly shape medial temporal lobe activity. We therefore tested whether intracranial EEG recordings from human hippocampus and amygdala reflect the semantic content and temporal order of individual fixations during encoding of naturalistic scenes. Relative to other semantic content, fixations on people were particularly relevant for memory, with the first fixation on a person predicting subsequent scene recognition. Fixation-locked hippocampal responses were enhanced for fixations to people relative to other semantic content, expressed in both larger fixation-evoked potentials and stronger theta phase locking. These effects were strongest for the first fixation relative to subsequent fixations. Theta phase locking was also enhanced in both hippocampus and amygdala for first fixations on people relative to later fixations and to other semantic content. These findings indicate that medial temporal lobe activity is structured by discrete fixation-level events during scene encoding, suggesting that theta-paced sampling contributes to the transformation of semantic and temporal components of visual experiences into memory. Significance StatementThis study shows that the semantic content and order of eye fixations jointly influence human hippocampal activity during memory encoding. Combining intracranial recordings, eye-movement tracking, and deconvolutional modeling, we show that the first glance at a person within naturalistic scenes is a privileged event, associated with increased hippocampal activity, theta-phase resetting in hippocampus and amygdala, and subsequent memory success. These findings recast eye movements not as mere motor acts, but as an important process that helps medial-temporal structures prioritize and integrate behaviorally relevant information into episodic memory.

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bioRxiv2025

Spatial and semantic memory reorganize a hippocampal long-axis gradient

The hippocampus supports episodic memory by binding spatial and semantic information, yet how this information is simultaneously organized along its long axis remains debated. Gradient accounts propose a continuous shift in representational scale, from coarse coding in anterior to fine coding in posterior regions, whereas modular accounts posit discrete subregions specialized for distinct functions. Using high-resolution fMRI together with eye tracking as a readout of spatial and semantic memory during sequence learning, we directly tested these competing models. During predictable sequences, hippocampal activity continuously varied along the long axis. In contrast, modular organization emerged when sequences mismatched memory. Subregions in the anterior and posterior hippocampus were sensitive to semantic and spatial mismatches, respectively. Notably, the intermediate hippocampus was specifically sensitive to concurrent mismatches in both dimensions, but not to mismatches in either dimension alone. These content-sensitive subregions were embedded within distinct cortical networks that reorganized according to memory demands. Together, our findings show the hippocampus flexibly combines gradient and modular dynamics to simultaneously represent the spatial and semantic content that defines episodic memory.

neuroscience↗

bioRxiv2025

Targeting intracranial electrical stimulation to network regions defined within individuals causes network-level effects

Intracranial electrical stimulation (ES) is routinely used therapeutically, diagnostically, and to provide causal evidence in neuroscience studies. However, our understanding of the brain network-level effects of ES remains limited. We applied precision functional mapping (PFM), based on functional magnetic resonance imaging (fMRI), to define large-scale networks within individual epilepsy patients. We show that single-pulse electrical stimulation (SPES) and high-frequency electrical stimulation (HFES) are more likely to evoke within-network responses and elicit network-related behavioral effects, respectively, when applied near to a PFM-defined network region. Network-level effects were more likely when stimulating sites in white matter, in close proximity to the targeted network, and within a region predominantly occupied by the targeted network. Further, network-specific modulation may be achievable by applying lower current intensities at these sites. Our findings support that modulation of specific networks is achievable by targeting ES to a functional anatomic "sweet spot" that can be identified using PFM.

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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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bioRxiv2022

Human hippocampal responses to network stimulation vary with theta phase

Hippocampal-dependent memory is thought to be supported by distinct connectivity states, with strong input to the hippocampus benefitting encoding and weak input benefitting retrieval. Previous research in rodents suggests that the hippocampal theta oscillation orchestrates the transition between these states, with opposite phase angles predicting minimal versus maximal input. We investigated whether this phase dependence exists in humans using network-targeted intracranial stimulation. Intracranial local field potentials were recorded from individuals with epilepsy undergoing medically necessary stereotactic electroencephalographic recording. In each subject, biphasic bipolar direct electrical stimulation was delivered to lateral temporal sites with demonstrated connectivity to hippocampus. Lateral temporal stimulation evoked ipsilateral hippocampal potentials with distinct early and late components. Using evoked component amplitude to measure functional connectivity, we assessed whether the phase of hippocampal theta predicted relatively high versus low connectivity. We observed an increase in the continuous phase-amplitude relationship selective to the early and late components of the response evoked by lateral temporal stimulation. The maximal difference in these evoked component amplitudes occurred across 180 degrees of separation in the hippocampal theta rhythm; i.e., the greatest difference in component amplitude was observed when stimulation was delivered at theta peak versus trough. The pattern of theta phase dependence observed for hippocampus was not identified for control locations. These findings demonstrate that hippocampal receptivity to input varies with theta phase, suggesting that theta phase reflects connectivity states of human hippocampal networks. These findings confirm a putative mechanism by which neural oscillations modulate human hippocampal function.

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bioRxiv2020

Rapid coordination of effective learning by the human hippocampus

Although the human hippocampus is necessary for long-term memory, controversial findings suggest that hippocampal computations support short-term memory in the service of guiding effective behaviors during learning. We tested the counterintuitive theory that the hippocampus contributes to long-term memory through remarkably short-term processing, as reflected in the sequence of eye movements during encoding of naturalistic scenes. While viewing scenes for the first time, participants generated patterns of eye movements that reflected a shift from stimulus-driven to memory-driven viewing and signaled effective spatiotemporal memory formation. Hippocampal theta oscillations recorded from depth electrodes predicted this viewing pattern. Moreover, effective viewing patterns were preceded by shifts towards top-down influence of hippocampal theta on activity within cortical networks that support visual perception and visuospatial attention. The hippocampus thus supports short-term memory processing that coordinates perception, attention, and behavior in the service of effective spatiotemporal learning. These findings motivate re-interpretation of long-term memory disorders as reflecting loss of the organizing influence of hippocampal short-term memory on learning.

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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

Enhanced reinstatement of naturalistic event memories due to hippocampal-network-targeted stimulation

Episodic memory involves the reinstatement of distributed patterns of brain activity present when events were initially experienced. The hippocampus is thought to coordinate reinstatement via its interactions with a network of brain regions, but this hypothesis has not been causally tested in humans. The current study directly tested the involvement of the hippocampal network in reinstatement using network-targeted noninvasive stimulation. We measured reinstatement of multi-voxel patterns of fMRI activity during encoding and retrieval of naturalistic video clips depicting everyday activities. Reinstatement of video-specific activity patterns was robust in posterior-parietal and occipital areas previously implicated in event reinstatement. Theta-burst stimulation targeting the hippocampal network increased videospecific reinstatement of fMRI activity patterns in occipital cortex and improved memory accuracy relative to stimulation of a control out-of-network location. Furthermore, stimulation targeting the hippocampal network influenced the trial-by-trial relationship between hippocampal activity during encoding and later reinstatement in occipital cortex. These findings implicate the hippocampal network in the reinstatement of spatially distributed patterns of event-specific activity, and identify a role for the hippocampus in encoding complex naturalistic events that later undergo cortical reinstatement.

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bioRxiv2019

Hippocampal theta coordinates memory processing during visual exploration

The hippocampus supports memory encoding and retrieval, with distinct phases of theta oscillations modulating the amplitude of gamma-band activity during each process. Encoding and retrieval operations dynamically interact over rapid timescales, especially when sensory information conflicts with memory. The ability to link hippocampal dynamics to specific memory-guided behaviors has been limited by experiments that lack the temporal resolution to segregate when encoding and retrieval occur. To resolve this issue, we simultaneously tracked eye movements and hippocampal field potentials while neurosurgical patients performed a spatial memory task. Novelty-driven fixations increased phase-locking to the theta rhythm, which predicted successful memory performance. Theta to gamma phase amplitude coupling increased during these viewing behaviors and predicted forgetting of conflicting memories. In contrast, theta phase-locking preceded fixations initiated by memory retrieval, indicating that the hippocampus coordinates memory-guided eye movements. These findings suggest that theta oscillations in the hippocampus support learning through two interleaved processes: strengthening the encoding of novel information and guiding exploration based on prior experience.

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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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