Biology subjects

Leunissen, I.

Publications and source records attributed to Leunissen, I..

10 recordsLinked to original sources

bioRxiv2026

Theta-Phase Targeted Encoding Gates Memory Sensitivity

Theta phase has been proposed to play an important role in memory. It may gate encoding and retrieval, such that certain phases are more favorable for memory processing than others, or become part of the memory representation, such that reinstating the encoding phase benefits retrieval. To test and distinguish these competing accounts, we used a closed-loop EEG system, allowing us to control the phase at which items were presented at encoding and retrieval. In an associative memory task, visual targets were presented at predefined phases of the ongoing mid-frontal theta rhythm, thereby pairing individual memory items with specific encoding phases. During retrieval, targets appeared either at the same phase as during encoding or at an alternative phase. We show that theta phase during encoding predicted subsequent memory sensitivity, while finding no evidence that retrieval phase nor the match between encoding and retrieval phases influenced performance. Therefore, our findings are consistent with a gating account, in which the rhythmic state at the moment of encoding influences the efficacy of memory formation.

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bioRxiv2026

Predictable Timing Enhances the Use of Predictable Content

As events unfold, they carry structure in both their timing and content, with these dimensions often interrelated. Most research has treated these dimensions separately, although processing them jointly may provide important computational benefits. It is an open question whether the brain processes a sequence's timing and predictable content structure independently, or integrates these two sources of information to guide prediction. We hypothesised that predictable timing would allow listeners to better exploit structure in the content, with this effect increasing as content structure becomes stronger. To test this, we presented tone sequences with pitch trajectories following a 1/f^{beta} structure, where {beta} determines how strongly the content of each tone persists, while independently varying the temporal periodicity of the sequence. Performance was quantified using response errors relative to outcome predictions of a Gaussian Process Regression model and a model-free measure of how strongly preceding tones influenced responses. Response error decreased and reliance on preceding tones increased with higher {beta} and periodic timing. Moreover, the influence of preceding tones showed an interaction between timing and content, such that the effect of periodicity grew with increasing {beta}. The response error showed no such interaction, although the effect of periodic timing was reliable only for the most structured sequences. Our findings suggest an interdependency between content and timing, where predictable timing helps listeners make greater use of predictable content.

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bioRxiv2026

Effect of dopamine D2 blockade on behavioural and electrophysiological measures of inhibitory control

Inhibitory control is an essential executive function that encompasses both the stopping of an action in response to an unexpected stop signal (reactive response inhibition) and slowing of responses in anticipation of stopping (proactive response inhibition). Fronto-basal-ganglia circuits are thought to differentially contribute to response inhibition, with the indirect pathway implicated in proactive inhibition. Given the high expression of dopamine D2 receptors in the indirect pathway, pharmacological blockade of D2 receptors is expected to impact proactive inhibition, as indicated by response times on Go trials. The current study aimed to investigate this experimentally and study the effect of 600 mg of sulpiride, a D2 receptor antagonist, on behavioural and electrophysiological measures of proactive and reactive inhibition in humans. Human participants (N=24) completed an anticipated response version of the stop-signal task on either sulpiride or placebo in a double-blind within-subjects design. Sulpiride led to increased variability of Go response times and attenuation of the frontocentral negativity/readiness potential, considered to be a signature of proactive inhibition. In contrast, sulpiride had no effect on stop-signal reaction time or event-related potential components associated with reactive inhibition. These findings suggest that D2 receptor blockade selectively alters processes involved in proactive inhibition while leaving reactive inhibition unaffected, consistent with a key role for the indirect basal ganglia pathway in proactive response inhibition.

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bioRxiv2025

tACS induces state-dependent shifts in inhibitory phase preference consistent with phase precession

Phase-dependent modulation of motor inhibition suggests that oscillatory timing plays a key role in inhibitory control. Here we show that rhythmic brain stimulation can selectively alter this timing in a manner consistent with phase precession. Participants performed an anticipatory stop-signal task while receiving 20 Hz transcranial alternating current stimulation (tACS) over the pre-supplementary motor area, with stop signals presented at defined phases of the stimulation waveform. An additional control experiment with no tACS was conducted, in which the stop signal phase was derived post-hoc from the ongoing EEG. In both tACS and control sessions, stopping efficacy varied sinusoidally with beta phase, confirming that inhibitory control is intrinsically phase-dependent. During tACS, however, the phase associated with the strongest inhibition advanced progressively across the session by about 180{degrees}, and this effect was specific to failed-stop trials. No comparable shift occurred without stimulation. These findings indicate that rhythmic drive can bias the temporal phase at which inhibition is most effective when the brain is in an error-prone state, revealing a state-dependent, precession-like reorganization of inhibitory timing. We propose that tACS interacts with error-related plasticity to promote gradual phase advancement, placing the system within spike-timing-dependent learning windows, whereas intrinsic fluctuations alone appear insufficient to facilitate cumulative precession. More broadly, these results suggest that phase precession may represent a general coding principle extending beyond hippocampal circuits, enabling the motor system to adaptively adjust inhibitory control through oscillatory timing mechanisms. HighlightsO_LIBeta tACS over preSMA induces shifts in phase preference during motor inhibition C_LIO_LIPrecession-like phase shifts emerge selectively during failed but not successful stops C_LIO_LIPhase precession was absent in a control experiment without tACS C_LIO_LItACS might provide a method to probe phase precession mechanisms in cognition C_LI

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bioRxiv2025

Closed-loop anti-phase tACS over preSMA reduced oscillatory beta synchronization and modulated motor inhibition performance

Neural oscillations dynamically coordinate communication across distributed brain networks, and their pathological synchronization is a common feature of neurological and psychiatric disease. In Parkinsons disease, excessive beta-band synchronization within cortico-basal ganglia-thalamo-cortical loops is closely linked to motor impairment, highlighting the need for neuromodulation strategies that can selectively and adaptively reshape this brain synchrony online. Transcranial alternating current stimulation (tACS) offers a non-invasive approach to modify endogenous oscillatory activity, yet it is typically delivered in an open-loop manner, limiting control over the timing, direction, and functional network consequences of oscillatory modulation. Here, we developed an online adaptive EEG-guided closed-loop system that continuously tracked the instantaneous phase of ongoing cortical oscillations and delivered stimulation either aligned (in-phase) or 180 degrees opposed (anti-phase) to the endogenous beta rhythm. Thirty-eight right-handed healthy participants performed a stop-signal task while receiving adaptive closed-loop 4 x 1 HD-tACS over pre-supplementary motor cortex (preSMA) targeting beta-band activity (15-30 Hz) implicated in motor inhibition, under in-phase, anti-phase, or sham stimulation. Anti-phase tACS produced a robust suppression of beta synchrony relative to both in-phase and sham stimulation, consistent with destructive interference of the endogenous rhythm. Behaviorally, anti-phase tACS reduced inhibition performance by impairing the stopping process, whereas in-phase stimulation reduced peak force rate during go trials and decreased variability of the go response, consistent with increased inhibitory tone and stabilization of ongoing motor states. These results provide converging behavioral and neurophysiological evidence for destructive interference of anti-phase tACS and establish a mechanistic framework for phase-specific closed-loop neuromodulation, paving the way to implement a non-invasive therapeutic strategy aimed at desynchronizing pathological beta in neurological conditions such as Parkinsons disease.

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bioRxiv2025

Alpha Oscillatory Imbalance Predicts Attention Deficits in Visuospatial Neglect

Background and ObjectivesVisuospatial neglect (VSN) is a common consequence of unilateral stroke, characterized by reduced awareness on the contralesional side of space. This study examines resting-state electrophysiological mechanisms underlying VSN, with a focus on interhemispheric differences in alpha-band oscillations and their association with deficits in visual perception and attention. MethodsResting-state EEG was recorded during three-minute eyes-closed and eyes-open periods in VSN patients. Participants also completed a battery of perceptual and attentional assessments, including the Star Cancellation Task, the Computerized Visual Detection Task, and the Line Bisection Task. Measures of alpha activity, specifically amplitude, peak frequency, and fronto-parietal connectivity,were compared between VSN patients and age- and gender-matched healthy controls. Within the VSN group, alpha activity in the lesioned and non-lesioned hemispheres was used to predict task performance. ResultsCompared to healthy controls, VSN patients displayed a distinct resting-state alpha profile, characterized by slower and less synchronized alpha oscillations and reduced fronto-parietal alpha connectivity in the lesioned hemisphere. In contrast, controls showed symmetrical alpha activity across hemispheres. Crucially, the degree of interhemispheric alpha asymmetry in VSN patients consistently predicted attentional impairments across all behavioral tasks. DiscussionVSN is linked to disrupted alpha oscillatory dynamics and interhemispheric imbalance. The extent of alpha desynchronization between hemispheres predicts symptom severity, supporting the interhemispheric competition model of attention. These findings suggest that hyperactive alpha activity in the non-lesioned hemisphere may suppress the lesioned hemisphere, contributing to attentional bias away from the contralesional space.

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bioRxiv2025

In-phase and anti-phase dual-site beta tACS differentially influence functional connectivity and motor inhibition

Inhibitory control relies on coordinated beta-band activity within a fronto-basal ganglia network, which implements inhibition via downstream effects on (pre)motor areas. In this study, we employed dual-site transcranial alternating current stimulation (tACS) targeting the right inferior frontal gyrus (rIFG) and primary motor cortex (M1) to directly manipulate phase relationships in the beta band and assess their effects on both functional connectivity and motor inhibition. Fifty-two healthy participants received in-phase, anti-phase and sham stimulation while performing a stop-signal task. The results revealed that connectivity between rIFG and lM1 increased following in-phase but decreased after anti-phase stimulation. Although no direct modulation of task performance was observed, the greater connectivity increase between the targets during in-phase stimulation was predictive of faster inhibitory performance. In contrast, greater connectivity decreases during anti-phase stimulation were related to faster go responses, suggesting a shift towards less inhibition on the motor system. These findings provide evidence that dual-site beta-tACS can both enhance and impair inhibitory control depending on phase alignment, highlighting its potential as a non-invasive intervention for disorders marked by impaired inhibition.

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bioRxiv2024

Using TMS-EEG to study the intricate interplay between GABAergic inhibition and glutamatergic excitation during reactive and proactive motor inhibition

Transcranial magnetic stimulation (TMS) studies have provided insight into the neurotransmission underlying motor inhibition but are limited to the primary motor cortex (M1). To investigate {gamma}-aminobutyric acid (GABA) and glutamatergic neurotransmission across the broader motor inhibition network, we combined TMS with electroencephalography (EEG). The N45 and N100 components of the TMS-evoked potentials (TEPs) have been liked to GABAa and GABAb signaling, respectively, whereas the N15, P30 and P60 TEPs are believed to reflect glutamatergic neurotransmission. This study investigates how these components are modulated during reactive and proactive motor inhibition. Twenty-four healthy participants completed two TMS-EEG sessions targeting either the left M1 or the pre-supplementary motor area (preSMA) at rest and during a stop-signal task. We compared TEP amplitudes across TMS conditions (active/sham) and trial types and assessed their relationship with task performance. Participants with a higher N45 amplitude over M1 at rest demonstrated a faster stop-signal reaction time. Active TMS during successful motor inhibition evoked higher N15 amplitudes over preSMA than during uncertain go trials, suggesting that an early excitatory signal from preSMA is crucial for reactive inhibition. In contrast, proactive inhibition was linked to lower P30 amplitudes in M1, possibly reflecting reduced motor facilitation. These findings provide novel empirical insights into the neurophysiological mechanisms underpinning motor inhibition, emphasizing the importance of a coordinated balance between inhibitory processes in M1 and early glutamatergic excitatory signals from preSMA for effective inhibition.

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bioRxiv2023

The phase of tACS-entrained pre-SMA beta oscillations modulates motor inhibition

Inhibitory control has been linked to beta oscillations in the fronto-basal ganglia network. Here we aim to investigate the functional role of the phase of this oscillatory beta rhythm for successful motor inhibition. We applied 20 Hz transcranial alternating current stimulation (tACS) to the pre-supplementary motor area (pre-SMA) while presenting stop signals at 4 (Experiment 1) and 8 (Experiment 2) equidistant phases of the tACS entrained beta oscillations. Participants showed better inhibitory performance when stop signals were presented at the trough of the beta oscillation whereas their inhibitory control performance decreased with stop signals being presented at the oscillatory beta peak. These results are consistent with the communication through coherence theory, in which postsynaptic effects are thought to be greater when an input arrives at an optimal phase within the oscillatory cycle of the target neuronal population. The current study provides mechanistic insights into the neural communication principles underlying successful motor inhibition and may have implications for phase-specific interventions aimed at treating inhibitory control disorders such as PD or OCD.

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bioRxiv2020

Effects of beta- and gamma-band rhythmic stimulation on motor inhibition

Voluntary movements are accompanied by an increase in gamma-band oscillatory activity (60-100Hz) and a strong desynchronization of beta-band activity (13-30Hz) in the motor system at both the cortical and subcortical level. Conversely, successful motor inhibition is associated with increased beta power in a fronto-basal-ganglia network. Intriguingly, gamma activity also increases in response to a stop-signal. In this study, we used transcranial alternating current stimulation to drive beta and gamma oscillations to investigate whether these frequencies are causally related to motor inhibition. We found that 20Hz stimulation targeted at the pre-supplementary motor area enhanced inhibition and increased beta oscillatory activity around the time of the stop-signal in trials directly following stimulation. In contrast, 70Hz stimulation seemed to slow down the braking process, and predominantly affected go task performance. These results demonstrate that the effects of tACS are state-dependent and that especially fronto-central beta activity is a functional marker for successful motor inhibition.

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