Biology subjects

Hanslmayr, S.

Publications and source records attributed to Hanslmayr, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Comparing re-referencing methods for human intracranial EEG

Stereo-electroencephalography (SEEG) involves the implantation of depth electrodes in the brain to monitor epileptic seizures for surgical feasibility. As the electrodes advance into deeper limbic structures, the macro contacts distributed along the shaft record electrical activity from more lateral sites, while a bundled array of microwires simultaneously captures highly localised signals from the tip of the electrode. In a clinical setting these electrical signals are recorded relative to a reference signal, which may be sub-optimal for subsequent analyses that are unrelated to clinical objectives. Therefore, a secondary re-referencing operation is often undertaken to transform the signal in relation to a specific hypothesis. Despite a recent surge in SEEG studies, comparative studies on the much-understudied issue of re-referencing are sparse. Here, we analyse data collected from 16 human patients during an episodic memory task and comparatively apply a range of re-referencing methods to both macro contact and micro-wire data. We find that the choice of method changes the proportion of trials that survive artefact rejection, low frequency power, and the aperiodic background against which that power is read. In the hippocampal recordings, however, no method differed from any other in the size of a memory effect in power or spike-field coherence. This early transformative decision therefore bears on how the signal is described. We found no evidence that it changes the detectability of the behavioural effects tested here, and no method reversed the direction of a memory effect.

neuroscience↗

bioRxiv2026

Beyond Rate: Hippocampal Phase Codes for Space and Memory

Place cells and concept neurons are defined by a rise in firing rate at a particular location or for a particular person or object. Neurons without such a rise remain unlabeled, although they keep firing during the task. Such neurons could still carry information in the timing of their spikes. Hippocampal theta provides a reference for this timing. We therefore asked whether the theta phase of a neuron's spikes depends on location or on the viewed image, even when its firing rate does not. We analysed hippocampal neurons in humans navigating a virtual city, rats running on a linear track, and humans viewing images of anima ls, faces, and places. In both navigation datasets, more neurons than expected by chance fired at a consistent theta phase at particular locations. This phase tuning remained after we excluded neurons whose firing rate depended on location. In human navigation, the spike phases of these remaining neurons improved location decoding beyond the firing rates of all neurons. More phase-tuned neurons than expected by chance also fired at progressively earlier theta phases as participants passed each neuron's preferred location. This pattern resembles phase precession, which classically occurs as an animal crosses the firing-rate field of a place cell. The neurons that showed it had no firing-rate field, so their phase shift was anchored to the location defined by phase tuning alone. During image viewing, more neurons than expected by chance changed the theta phase of their spikes after a particular image appeared. This effect remained after we removed, for each neuron, the images that changed its firing rate. Spike phases alone also predicted the image category above chance. Theta-relative spike timing therefore carries in formation about location and images that firing rate alone misses. We propose that weak input changes when a neuron fires with in the theta cycle, whereas strong input also raises its firing rate.

neuroscience↗

bioRxiv2026

Active control modulates memory-related activity during encoding and encoding-retrieval similarity

Self-directed learning allows learners to actively control their learning experience and has been shown to enhance memory compared with matched yoked learning. However, it remains unclear when and how active control modulates memory-related neural activity during learning and retrieval. We recorded electroencephalography (EEG) while participants encoded objects under active and yoked learning conditions and again during a delayed recognition test approximately 24 h later. We examined event-related potential (ERP) activity across earlier processing windows, including pre-stimulus slow potentials and early N2 activity, and later processing windows, including P300, late slow-wave, and post-stimulus slow-potential activity. We also examined encoding-retrieval similarity (ERS) between neural patterns during encoding and retrieval. Behaviorally, active control improved delayed recognition, with the advantage selectively expressed in detailed recognition. In the ERP analyses, earlier processing windows showed memory-related effects, with pre-stimulus slow-potential and N2 activity differentiating subsequently remembered from forgotten items, but were not modulated by active control. By contrast, active control modulated later memory-related ERP activity, with remembered-forgotten differences expressed during late stimulus-related and immediate post-stimulus processing only in the active condition. ERS showed a similar active-control modulation: memory-related encoding-retrieval pattern similarity was evident under active learning, but not under yoked learning, with this effect involving relatively late encoding and retrieval windows. Together, these findings support a constructive-processing account, suggesting that memory formation under active control depends more strongly on rich, detailed encoding representations that can be reinstated during retrieval.

neuroscience↗

bioRxiv2026

Assessing the longevity of the Theta-induced Memory Effect (TIME)

Theta-phase synchronisation between visual and auditory rhythmically modulated sensory stimuli during encoding has been shown to enhance associative memory, an effect known as Theta-Induced Memory Effect (TIME). However, whether this advantage is short-lived or persists over time remains unknown. To address this, we examined the TIME effect in 52 participants randomly assigned to a short-delay group (immediate retrieval) or a long-delay group (retrieval after 24 hours). Electroencephalography (EEG) was recorded during incidental encoding of audio-video pairs. The luminance of the video clips and the amplitude of the sounds were modulated at theta frequency (4 Hz) and presented either in-synchrony (0{degrees} phase offset between audio and video) or out-of-synchrony (the sound 180{degrees} phase-shifted relative to the video). Source reconstruction was used to estimate the actual phase difference between visual and auditory cortices for every trial. At the behavioural level, no significant difference in memory accuracy was found between the synchronous and asynchronous conditions in either group. However, after reconstructing the actual phase difference at the source level, the TIME effect was replicated in the short-delay group, with significantly higher memory accuracy at the optimal reconstructed theta phase compared to out-of-phase. In contrast, the long-delay group showed a reversed pattern, with higher accuracy in the asynchronous condition, though this difference did not reach significance. These findings suggest that the TIME effect is time-limited and may not survive or even reverse after overnight consolidation.

neuroscience↗

bioRxiv2026

Phase similarity between similar objects indicates representational merging across retrieval training but not sleep

Retrieval training (i.e., cued recall) is theorised to induce rapid memory consolidation, similarly to sleep. Across consolidation, related neural representations become increasingly similar; yet, this representational change has never been directly compared between sleep and retrieval training. In this study, 30 subjects (27F, 18-34, M=22.17) completed four separate sessions in which they (1) learnt object-word pairs, followed by (2) immediate recognition testing, (3) one of four 120-min interventions (retrieval training, restudy, sleep, or wake), and (4) delayed recognition testing. We compared EEG phase similarity between similar and different objects to assess the time, frequency, and anatomical distribution of representational similarity across encoding (learning to immediate recognition), and each intervention (immediate to delayed recognition). We hypothesised that EEG phase patterns for similar objects would become more similar (i.e., representational merging) across retrieval training and sleep interventions, and predict a greater endorsement of similar-object lures. Indeed, we found increased representational similarity between similar objects across the encoding shift in the theta-band and occipital sources. Crucially, additional representational merging was only observed across the retrieval training intervention, in the alpha-band and parieto-occipital sources. Despite retrieval training leading to reduced performance in discriminating similar-objects lures, greater representational merging across retrieval training predicted greater discrimination of similar-object lures. Together, these findings suggest that sleep and retrieval training induce different memory transformations across the same timescale. Retrieval training may generally provoke rapid gist extraction, with greater neocortical integration supporting episodic discrimination. Conversely, sleep may selectively maintain task-relevant episodic and semantic details in the short-term.

neuroscience↗

bioRxiv2026

Non-invasive tracking of hippocampal theta oscillations

Hippocampal theta oscillations play a crucial role in the formation of episodic memories by binding multisensory information into coherent episodes. Brain stimulation studies suggest that memory performance can be modulated by targeting these oscillations, offering a potential way of treating memory disorders. However, to effectively engage these rhythms, precise knowledge about their presence, frequency, phase and location is required, which has been a challenge, particularly for non-invasive methods such as magnetoencephalography (MEG). Here, we first asked if hippocampal signals are detectable in MEG recordings. Using simultaneous MEG-intracranial EEG (iEEG) data, we show that invasively recorded hippocampal activity is reflected in MEG sensor signals, demonstrating the feasibility of detecting deep-brain activity non-invasively. Building on this, we introduce a MEG-based analysis pipeline to track hippocampal theta frequency over time. Applied across three independent datasets, the pipeline captured characteristic hippocampal theta frequency patterns in both rodents and humans, and MEG-derived hippocampal frequencies were consistent with those observed simultaneously in intracranial EEG. These findings provide evidence that MEG can reliably track individual hippocampal oscillatory dynamics, paving the way for future non-invasive closed-loop interventions that adapt stimulation frequency and timing to ongoing oscillations.

neuroscience↗

bioRxiv2025

Higher baseline alpha power is associated with faster responses in visual search

Visual search models have long emphasised that task-relevant items must be prioritized for optimal performance. While it is known that search efficiency also benefits from active distractor inhibition, the underlying neuronal mechanisms are debated. Neuronal alpha oscillations (7-14 Hz) have been associated with functional inhibition of cortical excitability, as well as distractor suppression in spatial attention and visual working memory tasks. We therefore hypothesised that alpha oscillations similarly support the deselection of distractors in visual search. Using Magnetoencephalography (MEG), we here show that high alpha power before the onset of a complex search display is associated with faster search performance. Crucially, we used a General Linear Model (GLM) approach to control for confounds between alpha power and task duration, ruling out that this result was merely driven by practice effects paired with increased fatigue over time. In addition to spontaneous oscillatory activity, we quantified the cortical excitability to colours of the search stimuli based on Rapid Invisible Frequency Tagging (RIFT) responses. In contrast to our initial hypothesis, increased pre-search alpha power did not correlate with the RIFT response, providing no direct evidence for feature-specific inhibition of distracting stimuli by alpha. Our findings challenge the traditional view of alpha oscillations reducing visual processing, showing instead that increased occipital alpha power can enhance performance in a visual task. We propose that the increase in alpha power may reflect increased top-down control supporting visual search

neuroscience↗

bioRxiv2025

Pre-stimulus alpha power modulates trial-by-trial variability in theta rhythmic multisensory entrainment strength and theta-induced memory effect

Binding multisensory information into episodic memory depends partly on the timing of the hippocampal theta rhythm which provides time windows for synaptic modification. In humans, theta rhythmic sensory stimulation (RSS) enhances episodic memory when the stimuli are synchronised across the visual and auditory domain compared to when they are out-of-synchrony. However, recent studies show mixed evidence if the improvement in episodic memory is the result of modulating hippocampal theta activity. In the current study, we investigated whether pre-stimulus brain state could explain part of this variance in the neural and behavioural effects induced by the RSS, via recording participants brain activity with MEG during a multisensory theta RSS memory paradigm. Our findings suggest that pre-stimulus alpha power modulates entrainment strength in sensory regions, which in turn predicts subsequent memory formation. These findings suggest that for non-invasive brain stimulation tools to be effective it is crucial to consider brain-state dependent effects.

neuroscience↗

bioRxiv2024

Characterizing neuronal and population responses to electrical stimulation in the human hippocampo-cortical network

Direct electrical stimulation (DES) can advance our understanding of the intricate dynamics of the human hippocampo-neocortical network, which underlies complex cognitive processes such as spatial cognition and memory. This knowledge can help Neurotechnology to more effectively interface with this network and improve its functions. Here, we investigated the effects of DES in seven epilepsy patients under medical supervision recording single neuron activity alongside local field potentials to investigate neural responses to single pulses at different levels of granularity. Our results demonstrate that (i) single neurons respond to local electrical stimulation with a stereotypical pattern of short-lived increased excitation, followed by sustained inhibition, (ii) that input into the hippocampus from neocortex takes [~]100 ms, and (iii) that output from the hippocampus to the neocortex is gated by theta phase. These results are vital to inform the optimal choice of parameters for future electrical stimulation studies targeting the human memory system.

neuroscience↗

bioRxiv2024

Guided Visual Search is associated with a feature-based priority map in early visual cortex

Visual search models have long emphasised that task-relevant items must be prioritised for optimal performance. While it is known that search efficiency also benefits from active distractor inhibition, the underlying neuronal mechanisms are debated. Here, we used MEG in combination with Rapid Invisible Frequency Tagging (RIFT) to probe how neuronal excitability in early visual cortex is modulated during feature-guided visual search. Participants were instructed to indicate the presence or absence of a letter "T" presented amongst 16 and 32 "L"s. In the guided search condition, participants were informed about the colour of the "T" and could infer the colour of the irrelevant distractors. In the unguided search condition, the target colour was unknown. We found that guided search was associated with enhanced RIFT responses to the target colour, and decreased responses to the distractor colour compared to unguided search. These results conceptually replicated using both a conventional coherence approach, as well as with a General Linear Model approach based on a single-trial measure of the RIFT response. The present findings expand on previous reports based on electrophysiology and fMRI in humans and non-human primates by revealing that feature-guidance in visual search affects neuronal excitability as early as primary visual cortex.

neuroscience↗

bioRxiv2024

Neocortical and hippocampal theta oscillations track audiovisual integration and replay of speech memories

"Are you talkin to me?!" If you ever watched the masterpiece "Taxi driver" directed by Martin Scorsese, you certainly recall the famous monologue during which Travis Bickle rehearses an imaginary confrontation in front of a mirror. While remembering this scene, you recollect a myriad of speech features across visual and auditory senses with a smooth sensation of unified memory. The aim of this study was to investigate how brain oscillations integrate the fine-grained synchrony between coinciding visual and auditory features when forming multisensory speech memories. We developed a memory task presenting participants with short synchronous or asynchronous movie clips focusing on the face of speakers engaged in real interviews. In the synchronous condition, the natural alignment between visual and auditory onsets was kept intact. In the asynchronous condition, auditory onsets were delayed to present lip movements and speech sounds in antiphase specifically with respect to the theta oscillation synchronising them in the original movie. We recorded magnetoencephalographic (MEG) activity to investigate brain oscillations in response to audiovisual asynchrony in the theta band. Our results first showed that theta oscillations in the neocortex and hippocampus were modulated by the level of synchrony between lip movements and syllables during audiovisual speech perception. Second, the accuracy of subsequent theta oscillation reinstatement during memory recollection was decreased when lip movements and the auditory envelope were encoded in asynchrony during speech perception. We demonstrate that neural theta oscillations in the neocortex and the hippocampus integrated lip movements and syllables during natural speech. We conclude that neural theta oscillations play a pivotal role in both aspects of audiovisual speech memories, i.e., encoding and retrieval.

neuroscience↗

bioRxiv2024

Top-down and bottom-up interactions rely on nested brain oscillations.

Adaptive visual processing is enabled through the dynamic interplay between top-down and bottom-up (feedback/feedforward) information exchange, presumably propagated through brain oscillations. Here we causally tested for the oscillatory mechanisms governing this interaction in the visual system. Using concurrent TMS-EEG, we emulated top-down signals by a single TMS-pulse over the Frontal Eye Field (right-FEF), while manipulating the strength of sensory input through the presentation of moving concentric gratings (compared to a control-TMS site). FEF-TMS without sensory input led to a top-down controlled occipital phase-realignment, alongside higher fronto-occipital phase-connectivity, in the alpha/beta-band. Sensory input in the absence of FEF-TMS increased occipital gamma activity. Crucially, testing the interaction between top-down and bottom-up processes (FEF-TMS during sensory input) revealed an increased nesting of the bottom-up gamma activity in the alpha/beta-band cycles. This establishes a causal link between phase-to-power coupling and top-down modulation of feedforward signals, providing novel mechanistic insights into how attention interacts with sensory input at the neural level, shaping rhythmic sampling.

neuroscience↗

bioRxiv2023

Gamma sensory stimulation and effects on the brain

Findings by the Tsai lab and others 1-8 demonstrate that 40 Hz frequency sensory stimulation induces electrophysiological responses and attenuates pathology in mouse models of Alzheimers disease (AD). A recent study in Nature Neurosciene 9 concluded that the stimulation does not affect endogenous gamma oscillations or amyloid burden. We welcome research investigating 40 Hz sensory stimulation, and the article by Soula et al enhances our understanding of the brains electrophysiological response to 40Hz. However, we respectfully suggest that the data in Soula et al are consistent with a neuronal response to 40 Hz, which we further support with new data in humans. Moreover we contend the non-significant effects on amyloid are due to technical limitations of the study.

neuroscience↗

bioRxiv2023

Alpha oscillations support the efficiency of guided visual search by inhibiting both target and distractor features in early visual cortex

Withdrawal StatementThe authors have withdrawn this manuscript owing to having received feedback that prompted a reconsideration of the findings in light of potential confounds associated with time-on-task effects, as highlighted by Benwell et al. (2019, NeuroImage). Subsequent in-depth analysis has led the authors to reassess the central assertions made in our original manuscript, and the main claims can no longer be supported. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

neuroscience↗

bioRxiv2023

Beta bursts correlate with synchronization of movements to rhythmic sounds

Accumulating evidence indicates transient beta bursts play an important role in the representation of temporal information and prediction. However, the role of beta bursts in sensorimotor synchronization (SMS) involving active interactions between motor and sensory systems to synchronize predictive movements to periodic events remains unclear. To answer this question, 15 participants were invited to complete a finger-tapping task whilst high-density EEG (128 channels) was recorded. Participants tapped with their right index finger in synchrony with 1 Hz and 0.5 Hz tone trains. In line with previous findings, we found a negative mean asynchrony between tone and tap time, i.e., taps preceded tones for both tone frequencies (1 and 0.5 Hz). In the EEG data, beta bursts were detected and their timing in relationship with tapping and auditory tracking was examined. Results revealed that beta bursts tracked tapping and were modulated by the low frequency phase of the tone frequency (i.e., 1 Hz or 0.5 Hz). Importantly, the locking of beta bursts to the phase of auditory tracking correlated with the behavioural variance on a single trial level that occurred while tapping to the tones. These results demonstrate a critical role for an interplay between beta bursts and low frequency phase in coordinating rhythmic behaviour.

neuroscience↗

bioRxiv2022

Altering stimulus timing via fast rhythmic sensory stimulation induces STDP-like recall performance in human episodic memory

Animal studies suggest that the strength of synaptic modification depends on spike timing between pre- and post-synaptic neurons on the order of tens of milliseconds, which is termed spike-timing-dependent plasticity (STDP). However, evidence for STDP in human episodic memory is lacking. We investigated this using rhythmic sensory stimulation to drive visual and auditory cortices at 37.5 Hz with four phase offsets. Visual relative to auditory cued recall accuracy was significantly enhanced in the 90{degrees} condition since the visual stimulus led at the shortest delay (6.67 ms). This pattern was reversed in the 270{degrees} condition when the auditory stimulus led the shortest delay. Within cue modality, recall was enhanced when a stimulus of the corresponding modality led the shortest delay as compared to the longest delay (20 ms). Our findings provide novel evidence for STDP in human memory, which builds an important bridge from in-vitro studies in animals to human behaviour.

neuroscience↗

bioRxiv2022

Rhythmic interactions between the mediodorsal thalamus and prefrontal cortex precede human visual perception

The thalamus is much more than a simple sensory relay. High-order thalamic nuclei, such as the mediodorsal thalamus, exert a profound influence over animal cognition. However, given the difficulty of directly recording from the thalamus in humans, next-to-nothing is known about thalamic and thalamocortical contributions to human cognition. To address this, we analysed simultaneously-recorded thalamic iEEG and whole-head MEG in six patients (four female, two male; plus MEG recordings from twelve healthy controls) as they completed a visual detection task. We observed that the phase of both ongoing mediodorsal thalamic and prefrontal low-frequency activity was predictive of perceptual performance. Critically however, mediodorsal thalamic activity mediated prefrontal contributions to perceptual performance. These results suggest that it is thalamocortical interactions, rather than cortical activity alone, that is predictive of upcoming perceptual performance and, more generally, highlights the importance of accounting for the thalamus when theorising about cortical contributions to human cognition.

neuroscience↗

bioRxiv2021

Interaction between theta-phase and spike-timing dependent plasticity simulates theta induced memory effects

Rodent studies suggest that spike timing relative to hippocampal theta activity determines whether potentiation or depression of synapses arise. Such changes also depend on spike timing between pre- and post-synaptic neurons, known as spike-timing-dependent plasticity (STDP). STDP, together with theta-phase-dependent learning, has inspired several computational models of learning and memory. However, evidence to elucidate how these mechanisms directly link to human episodic memory is lacking. In a computational model, we modulate long-term potentiation (LTP) and long-term depression (LTD) of STDP, by opposing phases of a simulated theta rhythm. We fit parameters to a hippocampal cell culture study in which LTP and LTD were observed to occur in opposing phases of a theta rhythm. Further, we modulated two inputs by cosine waves with synchronous and asynchronous phase offsets and replicate key findings in human episodic memory. Learning advantage was found for the synchronous condition, as compared to the asynchronous conditions, and was specific to theta modulated inputs. Importantly, simulations with and without each mechanism suggest that both STDP and theta-phase-dependent plasticity are necessary to replicate the findings. Together, the results indicate a role for circuit-level mechanisms, which bridges the gap between slice preparation studies and human memory. Author SummaryLong-lasting changes in synaptic connectivity between neurons have been suggested to support learning and memory processes at the cellular level in the brain. Such synaptic modifications depend on synchronous activation of neurons, which leads to generate brain oscillations. Human memory studies focus on the relationships between brain oscillations and memory processes. Direct evidence on how the cellular mechanism links to human memory behaviour is lacking. To investigate the direct link between synaptic plasticity mechanisms and human memory formation, we built a computational neural network that implements two synaptic plasticity mechanisms, which are well-established in the rodents hippocampus. One mechanism shows that strengthening or weakening in synaptic connectivity depends on the phases of ongoing brain oscillation at theta frequency (4 - 8 Hz), which is a dominant signal in the hippocampus. The other mechanism suggests that synaptic modification depends on the precise timing of action potentials between two neurons. Our model successfully reproduces results from rodents, as well as several human episodic memory studies which demonstrated that human associative memory performance depends on phase synchronisation in theta frequency. These findings suggest a link between specific learning mechanisms at cellular level and human memory behaviour.

neuroscience↗