Biology subjects

Voss, J. L.

Publications and source records attributed to Voss, J. L..

13 recordsLinked to original sources

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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bioRxiv2026

Non-invasive Neuromodulation Targeting Approach by Mapping Stimulations and Lesions That Modify Visual Memory

Therapeutic brain stimulation is believed to target specific networks, but targeting approaches for memory remain debated. For other symptoms, neuromodulation targets have been localized by mapping connectivity of lesions and stimulation sites to specific symptoms. This approach has yielded networks for global memory, but it remains unclear whether it applies to specific types of memory. Here, we mapped connectivity of stimulation sites, lesions, and atrophy patterns associated with different memory types. We included 544 individuals across three datasets: transcranial magnetic stimulation (N=262), penetrating head trauma (N=169), and ischemic stroke (N=113). We identified a network preferentially connected to lesions and stimulation sites specifically associated with changes in visual memory. Of note, the direction of this effect was inverted depending on whether lesions or stimulation occurred at younger age or an older age, consistent with prior results. This age effect was replicated in an independent dataset of patients with preclinical Alzheimers disease (N=1240). To examine neuromodulation targets, we computed electrical field models for potential TMS sites that overlap with the networks derived from each stimulation or lesion dataset; the resulting targets intersected with established targets that demonstrated efficacy for treating memory impairment - precuneus, cortical-hippocampal network, and dorsolateral prefrontal cortex - with peak intersection at medial posterior parietal lobe, angular gyrus, and left anterior middle frontal gyrus, respectively. Future head-to-head clinical trials are needed to systematically compare these proposed neuromodulation targets against each other. One Sentence SummaryNeuromodulation targets for visual memory diverge by age at the time of injury or stimulation.

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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.

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bioRxiv2025

Distinct contributions of anterior and posterior orbitofrontal cortex to outcome-guided behavior

The lateral orbitofrontal cortex (OFC) is critical for flexibly adjusting choices when outcome values change. Anterior and posterior parts of the human lateral OFC differ in cytoarchitecture and connectivity, but whether these subregions make differential contributions to outcome-guided (i.e., goal-directed) behavior remains unclear. Outcome-guided behavior requires (a) representations of stimulus-outcome associations and (b) inferring the current value of options when making decisions. Here, we test whether these two functions are differentially supported by the posterior (pOFC) and anterior (aOFC) parts of the lateral OFC, using transcranial magnetic stimulation (TMS) to selectively disrupt activity in functional networks centered on the pOFC and aOFC during a two-day outcome devaluation task. Participants (n = 48) received pOFC or aOFC network-targeted TMS either on day 1 before learning associations between visual stimuli and sweet or savory food odors, or on day 2 before a meal that selectively devalued one of these outcomes, followed by a choice test. TMS targeting pOFC, but not aOFC, before the meal on day 2 disrupted outcome-guided behavior, as measured by choices of stimuli predicting non-sated rewards in the post-meal choice test. In contrast, TMS targeting aOFC, but not pOFC, before learning on day 1 similarly impaired behavior in the post-meal choice test on day 2. These findings demonstrate that anterior and posterior parts of the lateral OFC make distinct contributions to outcome-guided behavior by supporting learning of stimulus-outcome associations and inferring the current value of options, respectively.

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bioRxiv2022

Neural similarity between overlapping events at learning differentially affects reinstatement across the cortex

Episodic memory often involves high overlap between the actors, locations, and objects of everyday events. Under some circumstances, it may be beneficial to distinguish, or differentiate, neural representations of similar events to avoid interference at recall. Alternatively, forming overlapping representations of similar events, or integration, may aid recall by linking shared information between memories. It is currently unclear how the brain supports these seemingly conflicting functions of differentiation and integration. We used multivoxel pattern similarity analysis (MVPA) of fMRI data and neural-network analysis of visual similarity to examine how highly overlapping naturalistic events are encoded in patterns of cortical activity, and how the degree of differentiation versus integration at encoding affects later retrieval. Participants performed an episodic memory task in which they learned and recalled naturalistic video stimuli with high feature overlap. Visually similar videos were encoded in overlapping patterns of neural activity in temporal, parietal, and occipital regions, suggesting integration. We further found that encoding processes differentially predicted later reinstatement across the cortex. In visual processing regions in occipital cortex, greater differentiation at encoding predicted later reinstatement. Higher-level sensory processing regions in temporal and parietal lobes showed the opposite pattern, whereby highly integrated stimuli showed greater reinstatement. Moreover, integration in high-level sensory processing regions during encoding predicted greater accuracy and vividness at recall. These findings provide novel evidence that encoding-related differentiation and integration processes across the cortex have divergent effects on later recall of highly similar naturalistic events.

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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

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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bioRxiv2020

Human orbitofrontal cortex is necessary for behavior based on inferred, not experienced outcomes

When direct experience is unavailable, animals and humans can imagine or infer the future to guide decisions. Behavior based on direct experience versus inference may recruit distinct but overlapping brain circuits. In rodents, the orbitofrontal cortex (OFC) contains neural signatures of inferred outcomes, and OFC is necessary for behavior that requires inference but not for responding driven by direct experience. In humans, OFC activity is also correlated with inferred outcomes, but it is unclear whether OFC activity is required for inference-based behavior. To test this, we used non-invasive network-based continuous theta burst stimulation (cTBS) to target lateral OFC networks in the context of a sensory preconditioning task that was designed to isolate inference-based behavior from responding that can be based on direct experience alone. We show that relative to sham, cTBS targeting this network impairs reward-related behavior in conditions in which outcome expectations have to be mentally inferred. In contrast, OFC-targeted stimulation does not impair behavior that can be based on previously experienced stimulus-outcome associations. These findings suggest that activity in the targeted OFC network supports decision making when outcomes have to be mentally simulated, providing converging cross-species evidence for a critical role of OFC in model-based but not model-free control of behavior.

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bioRxiv2020

Evidence for immediate enhancement of medial-temporal lobe memory processing by network-targeted theta-burst stimulation during concurrent fMRI

The hippocampus supports episodic memory via interaction with a distributed brain network. Previous experiments using network-targeted noninvasive brain stimulation have identified episodic memory enhancements and modulation of activity within the hippocampal network. However, mechanistic insights were limited because these effects were measured long after stimulation and therefore could have reflected various neuroplastic aftereffects with extended timecourses. In this experiment with human subjects of both sexes, we tested for immediate stimulation impact on encoding-related activity of the hippocampus and immediately adjacent medial-temporal cortex by delivering theta-burst transcranial magnetic stimulation (TBS) concurrent with fMRI, as an immediate impact of stimulation would suggest an influence on neural activity. We reasoned that TBS would be particularly effective for influencing the hippocampus because rhythmic neural activity in the theta band is associated with hippocampal memory processing. First, we demonstrated that it is possible to obtain robust fMRI correlates of task-related activity during concurrent TBS. We then identified immediate effects of TBS on encoding of visual scenes. Brief volleys of TBS targeting the hippocampal network increased activity of the targeted (left) hippocampus during scene encoding and increased subsequent recollection. Stimulation did not influence activity during an intermixed numerical task with no memory demand. Control conditions using beta-band and out-of-network stimulation also did not influence hippocampal activity or recollection. TBS targeting the hippocampal network therefore immediately impacted hippocampal memory processing. This suggests direct, beneficial influence of stimulation on hippocampal neural activity related to memory and supports the role of theta-band activity in human episodic memory. Significance StatementCan noninvasive stimulation directly impact function of indirect, deep-brain targets such as the hippocampus? We tested this by targeting an accessible region of the hippocampal network via transcranial magnetic stimulation during concurrent fMRI. We reasoned that theta-burst stimulation would be particularly effective for impacting hippocampal function, as this stimulation rhythm should resonate with the endogenous theta-nested-gamma activity prominent in hippocampus. Indeed, theta-burst stimulation targeting the hippocampal network immediately impacted hippocampal activity during encoding, improving memory formation as indicated by enhanced later recollection. Rhythm- and location-control stimulation conditions had no such effects. These findings suggest a direct influence of noninvasive stimulation on hippocampal neural activity and highlight that the theta-burst rhythm is relatively privileged in its ability to influence hippocampal memory function.

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bioRxiv2019

Targeted stimulation of human orbitofrontal networks disrupts outcome-guided behavior

Outcome-guided behavior requires knowledge about the current value of expected outcomes. Such behavior can be isolated in the reinforcer devaluation task, which assesses the ability to infer the current value of rewards after devaluation. Animal lesion studies demonstrate that orbitofrontal cortex (OFC) is necessary for normal behavior in this task, but a causal role for human OFC in outcome-guided behavior has not been established. Here we used sham-controlled non-invasive continuous theta-burst stimulation (cTBS) to temporarily disrupt human OFC network activity prior to devaluation of food odor rewards in a between-subjects design. Subjects in the sham group appropriately avoided Pavlovian cues associated with devalued food odors. However, subjects in the stimulation group persistently chose those cues, even though devaluation of food odors themselves was unaffected by cTBS. This behavioral impairment was mirrored in changes in resting-stated functional magnetic resonance imaging (rs-fMRI) activity, such that subjects in the stimulation group exhibited reduced global OFC network connectivity after cTBS, and the magnitude of this reduction was correlated with choices after devaluation. These findings demonstrate the feasibility of indirectly targeting the human OFC with non-invasive cTBS, and indicate that OFC is specifically required for inferring the value of expected outcomes.

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bioRxiv2019

Increased task-dependent functional connectivity by stimulation of the hippocampal network predicts memory enhancement

Successful episodic memory involves dynamic increases in the coordination of activity across distributed hippocampal networks, including the posterior-medial network (PMN) and the anterior-temporal network (ATN). We tested whether this up-regulation of functional connectivity during memory processing can be enhanced within hippocampal networks by noninvasive stimulation, and whether such task-dependent connectivity enhancement predicts episodic memory improvement. Participants received stimulation targeting either the PMN or an out-of-network control location. We compared the effects of stimulation on fMRI connectivity measured during an autobiographical memory retrieval task versus during rest within the PMN and the ATN. PMN-targeted stimulation significantly increased connectivity during memory retrieval versus rest within the PMN. This effect was not observed in the ATN, or in either network due to control out-of-network stimulation. Task-dependent increases in connectivity due to PMN-targeted stimulation within the medial temporal lobe predicted improved performance of a separate episodic memory test. It is therefore possible to enhance the task-dependent regulation of hippocampal network connectivity that supports memory processing using noninvasive stimulation.

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