Biology subjects

Nitsche, M. A.

Publications and source records attributed to Nitsche, M. A..

11 recordsLinked to original sources

bioRxiv2026

Testing the reliability of novel Voxel Placement approaches for Magnetic Resonance Spectroscopy

BackgroundSingle-voxel magnetic resonance spectroscopy (MRS) is a non-invasive method for measuring clinically and cognitively relevant metabolites. Reliable measurements require precise voxel placement across sessions and participants. We developed a scanner-console-based approach to improve voxel placement precision. MethodsIn a crossover design (n=7; six sessions each), we compared test-retest reliability of three voxel placement methods in a reference benchmark (left parietal cortex) and a technically challenging region (left ventromedial prefrontal cortex). Methods included (1) conventional anatomy-based placement, (2) mask-guided real-time positioning (MGRP), and (3) semiautomated session-locked voxel repositioning (SSVR). Resting-state MRS data were acquired using PRESS and MEGA-PRESS. Within-subject reliability of voxel placement and metabolite concentrations, namely, total N-acetylaspartate (tNAA), total Creatine (tCr), GABA (gamma-aminobutyric acid), and Glx (glutamate + glutamine) are reported using the coefficient of variation (CV), the intraclass correlation coefficient (ICC), minimal detectable change (MDC), and the spatial overlap. ResultsSSVR markedly improved voxel placement reliability, increasing spatial overlap (up to 88%) and achieving near-perfect geometric reproducibility (ICC = 0.99) compared to conventional anatomy-based placement and MGRP. SSVR improved tissue composition consistency and reduced metabolite variability in the technically challenging region (variability reduction of [~]70% tCr, [~]59% tNAA, and [~]51% Glx) while further refining already stable measurements in the benchmark region (tNAA from [~]15% to [~]10%). ConclusionBoth MGRP and SSVR improved voxel placement and metabolite measurement reproducibility compared with conventional anatomy-based placement. SSVR further enhanced within-subject reproducibility across repeated sessions, particularly in the technically challenging region, providing a robust approach for longitudinal single-voxel MRS studies.

neuroscience↗

bioRxiv2026

Age-dependent Effects of Titrating Anodal Transcranial Direct Current Stimulation (tDCS) Intensity on Motor Sequence Learning

Optimising the currently heterogenous efficacy of transcranial direct current stimulation (tDCS) interventions for motor learning requires identifying stimulation parameters facilitating performance while accounting for age-related differences in baseline performance and mechanisms underlying neuroplasticity. We systematically explored anodal tDCS intensity effects on implicit motor sequence learning (IMSL) in young and older adults. The study utilised a randomised, double-blind, counterbalanced crossover design. Ninety-six healthy participants (48 young adults, 48 older adults) completed a serial reaction time task (SRTT) with online sham or anodal tDCS over M1 at intensities of 1, 2, and 3 mA. The next day, memory consolidation was assessed in a recall test. Both age groups demonstrated IMSL and consolidation across conditions. While 1 mA tDCS improved IMSL in young adults by reducing reaction times, higher intensities had no significant benefit compared to sham. In older adults, anodal tDCS did not affect general task performance compared to sham, but 1mA tDCS acutely impaired selective sequence learning. The results demonstrate age-dependent and non-linear dose-dependent effects of anodal tDCS on IMSL. This underscores the necessity for age-adapted protocols for experimental and clinical tDCS applications. Future research should explore neurophysiological reasons for reduced tDCS efficacy in older adults found in the present study.

neuroscience↗

bioRxiv2026

Optimizing Network-Level TMS-fMRI: Benchmarking a Novel TMS-Compatible "Sushi" MR Coil

Concurrent TMS-fMRI can map how stimulation affects both the targeted cortex and connected brain-wide networks, but this requires MR receive hardware that allows TMS coil placement while preserving reliable whole-brain BOLD sensitivity. We developed and benchmarked a practical TMS-compatible "Sushi" MR receive setup assembled from two flexible 18-channel body arrays. Across six experiments, we tested functional readout validity, signal quality, and active TMS-fMRI compatibility. Resting-state fMRI (n = 12) and verbal N-back task-fMRI (n = 8) were acquired with Sushi, a commercially available 2x7-channel Surface setup, and a standard 64-channel head/neck array. Functional similarity to the 64-channel reference was quantified with spatial overlap, and multi-echo combination (MEcomb) was tested as a post-acquisition signal optimization strategy. Sushi recovered subject-specific resting-state networks that more closely matched the 64-channel reference than Surface, with no significant difference from the 64-channel test-retest reference. For task-fMRI, MEcomb increased task-map similarity for Sushi, whereas setup comparisons within each pipeline were not significant. MEcomb also improved resting-state similarity and increased temporal signal-to-noise ratio (tSNR) across receive setups. In phantom measurements, TMS coil placement produced spatially graded tSNR reductions relative to the no-TMS-coil condition, strongest near the coil. In one participant, active interleaved single-pulse TMS-fMRI over two cortical sites showed no detectable pulse-locked image artifacts; whole-brain MEcomb tSNR during active TMS-fMRI was reduced by 2.6-6.9% relative to the no-coil/no-stimulation reference. Together, Sushi and MEcomb provide complementary hardware and processing tools for TMS-compatible whole-brain fMRI. This combination supports network-level functional readouts while preserving feasibility for active interleaved TMS-fMRI.

neuroscience↗

bioRxiv2025

Sleep stage-specific effects of 0.75 Hz phase-synchronized rTMS and tACS on delta frequency activity during sleep

Slow oscillatory activity during non-rapid-eye-movement (NREM) sleep plays a crucial role in both physical health and cognitive functions. Enhancing slow oscillatory activity during sleep has the potential to benefit these domains, yet an optimal stimulation protocol has not been established. This study aimed to investigate whether repetitive transcranial magnetic stimulation (rTMS), synchronized with the trough phase of 0.75 Hz transcranial alternating current stimulation (tACS) can modulate EEG activity in the delta frequency range during sleep and enhance cognitive functions. Healthy adults participated in a within-subject, counterbalanced study design comparing real and sham stimulation conditions. Combined rTMS and tACS was applied over the bilateral prefrontal cortex before sleep. We evaluated (1) power spectral density and functional connectivity within the delta frequency range during resting state and sleep, (2) retention of declarative memory learned before sleep, and (3) sleep parameters including spindle activity, sleep stage ratios, sleep onset latency and sleep efficiency. The combined rTMS and tACS protocol significantly increased delta oscillatory activity during the N3 sleep stage compared to sham. Functional connectivity, as measured by global efficiency, was enhanced during the N2 sleep stage. However, the stimulation did not improve declarative memory retention, spindle activity or other sleep parameters. These findings demonstrate the potential of combined rTMS and tACS as a non-invasive method to enhance delta oscillatory activity during sleep. While the stimulation did not improve memory performance, its ability to modulate delta activity during sleep suggests potential clinical applications for addressing pathological alterations in slow wave activity during sleep. State of SignificanceSlow oscillatory activity during non-rapid eye movement (NREM) sleep is relevant for declarative memory consolidation and overall sleep quality. However, noninvasive brain-stimulation methods to selectively modulate these oscillations remain elusive. In this study, we show that pre-sleep application of repetitive transcranial magnetic stimulation (rTMS) synchronized to the trough of 0.75 Hz transcranial alternating current stimulation (tACS) significantly enhances delta oscillatory activity during N3 sleep and increases global functional connectivity during N2 sleep in healthy humans without sleep disturbances without altering sleep structure. Our findings indicate that rTMS synchronized to the trough of the tACS exerts sleep-stage-specific effects on delta oscillatory activity. This stimulation protocol represents a promising approach for restoring pathological slow-wave activity during sleep in clinical populations.

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bioRxiv2025

An in vivo model for transcranial direct current stimulation of the motor cortex in awake mice.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique mainly used in humans, in which weak direct currents are applied over the scalp to alter cortical excitability and induce neuroplasticity. Previous studies have demonstrated the value of tDCS for modulating sensory, motor, and cognitive functions, nevertheless, knowledge about how externally applied electric fields affect different components of neuronal networks is still incomplete, and in vivo animal models, which are required for a deeper understanding, are not fully developed. To evaluate the impact of tDCS on cortical excitability, many human experiments assess motor evoked potentials elicited by motor cortex (M1) stimulation. To develop a related in vivo animal model, we recorded electrical activity in M1 of alert mice during and after administration of tDCS over M1. M1 excitability was chronically recorded from layers 2-3, layer 5 and layer 6, evoked by stimulation of the ventral lateral nucleus of the thalamus (VAL). M1-tDCS was applied at 100 and 200 {micro}A for 5 s to test the acute effects on neuronal excitability, and for 15 min to induce after-effects. Acute M1-tDCS increased and decreased the amplitude of VAL-evoked potentials in a polarity-, layer- and intensity-dependent manner. For 15 minutes of anodal or cathodal tDCS, a similar polarity- and intensity-dependent modulation of VAL-evoked potential amplitudes during the 15 minutes of stimulation was observed. After tDCS was switched off, the highest intensity of anodal stimulation induced a significant excitability enhancement during at least two hours after stimulation, whereas the after-effects of cathodal tDCS were less pronounced. The current study demonstrates the feasibility of a mouse model of M1-tDCS to accomplish similar modulatory effects of tDCS on cortical excitability as observed in human experiments. A proper adjustment of tDCS parameters, as compared to application in humans, is however required to obtain these translational effects.

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bioRxiv2025

Electrophysiological resting-state signatures link polygenic scores to general intelligence

Intelligence is associated with important life outcomes. Behavioral, genetic, structural, and functional brain correlates of intelligence have been studied for decades, but questions remain as to how genetics are related to trait expression and what intermediary role brain properties play. This study investigated these mediations in a representative sample of 434 individuals, comprising young and older adults. Polygenic scores (PGS) for intelligence were calculated. Resting-state EEG recordings were analyzed using graph theory quantifying functional connectivity across different frequencies. We tested whether global and local graph metrics like efficiency and clustering mediated the association between PGS and intelligence. PGS significantly predicted variance in intelligence and were related to frequency-specific graph metrics in areas predominantly located in parieto-frontal regions, which in turn were associated with intelligence. These findings, which are based on the first study linking PGS to intelligence using EEG-derived graph metrics, advance our understanding of the neurogenetics of intelligence.

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bioRxiv2024

Dual-site transcranial alternating current stimulation over the primary motor cortices increases interhemispheric inhibition and improves bimanual dexterity: A triple-blind, randomised, sham-controlled study

Concurrent application of transcranial alternating current stimulation (tACS) over distant cortical regions has been shown to modulate functional connectivity between stimulated regions; however, the precise mechanisms remain unclear. Here, we investigated how dual-site tACS (ds-tACS) applied over the bilateral primary motor cortices (M1s) modulates connectivity between M1s. Using a cross-over sham-controlled triple-blind within- subject design, 37 (27 female, age 18-37yrs) healthy participants received tACS (1.0mA, 20Hz) over the bilateral M1s for 20 min. Before and after tACS, functional connectivity between M1s was assessed using imaginary coherence (ImCoh) measured via resting-state electroencephalography (EEG) and interhemispheric inhibition (IHI) via dual-site transcranial magnetic stimulation (TMS) protocol. Additionally, manual dexterity was assessed using the Purdue pegboard task. While ImCoh remained unchanged after simulation, spectral power analysis showed a significant decrease in beta (20 Hz) power during the tACS session. ds-tACS but not sham strengthened IHI between the M1s and improved bimanual assembly performance. These results suggest that improvement in bimanual performance may be explained by modulation in M1-M1 IHI, rather than by coupling in the oscillatory activity. As functional connectivity underlies many clinical symptoms in neurological and psychiatric disorders, these findings are invaluable in developing non-invasive therapeutic interventions that target neural networks to alleviate symptoms.

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bioRxiv2024

Modulating Prefrontal Cortex Activity to Alleviate Stress-Induced Working Memory Deficits: A Transcranial Direct Current (tDCS) Study

This study explores the impact of stress on working memory (WM) performance, and the potential mitigating effects of transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC). The study had a crossover, randomized, single-blind, sham-controlled design, with stress induction as within-subject and stimulation condition as between-subject factors. We assessed stress-induced WM deficits using aversive video clips to induce stress and a verbal n-back task to assess WM performance. We analyzed physiological (cortisol and heart rate), behavioral, and electroencephalographic (EEG) changes due to stress before, during, and after WM task performance and their modulation by tDCS. Stress impaired WM performance in the sham stimulation condition for the 3-back load, but not for 2-back or 4-back loads in the WM task, and was associated with elevated physiological stress markers. tDCS over the vmPFC led to better WM task performance while stimulation over the dlPFC did not. Active tDCS with both dlPFC and vmPFC stimulation blunted cortisol release in stress conditions compared to sham. The EEG analysis revealed potential mechanisms explaining the behavioral effects of vmPFC stimulation. vmPFC stimulation led to a decreased P200 event-related potential (ERP) component compared to the sham stimulation condition and resulted in higher task-related alpha desynchronization, indicating reduced distractions and better focus during task performance. This study thus shows that the vmPFC might be a potential target for mitigating the effects of stress on WM performance, and contributes to the development of targeted interventions for stress-related cognitive impairments. Significance StatementThis study investigates how stress impacts working memory performance and whether non-invasive brain stimulation can mitigate these effects. Using transcranial direct current stimulation (tDCS), we targeted specific brain areas in participants stressed by watching aversive videos. Stress reduced working memory performance and increased cortisol levels. However, tDCS applied to the ventromedial prefrontal cortex (vmPFC) improved task performance and blunted the cortisol response compared to a sham treatment. EEG data suggest that stimulation also enhanced focus during task performance and reduced emotional distraction. Our findings suggest that tDCS over the vmPFC could be a promising non-invasive brain stimulation method to counteract the negative effects of stress on cognitive functions.

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bioRxiv2022

Beta tACS over rIFG and preSMA Improves Stopping Ability for Younger but not Older Adults

A growing body of research suggests that changes in both structural and functional connectivity in the aging brain contribute to declines in cognitive functions such as response inhibition. In recent years, transcranial alternating current stimulation (tACS) has garnered substantial research interest as a potential tool for the modulation of functional connectivity. Here, we report the findings from a double-blind crossover study that investigated the effects of dual-site beta tACS over the right inferior frontal gyrus (rIFG) and pre-supplementary motor area (preSMA) on functional connectivity measured with electroencephalography and response inhibition (stop-signal task performance) of healthy young (n = 18, aged 18-34 years) and older (n =15, aged 61-79 years) adults. Two tACS conditions were administered in separate sessions: in-phase tACS, where electrical currents delivered to the rIFG and preSMA had a 0{degrees} phase difference, and anti-phase tACS, where currents had a 180{degrees} phase difference. Stop-signal task performance was assessed before and after tACS. We found significant improvements in response inhibition that were not due to the phase of the tACS applied. There were also no significant changes in rIFG-preSMA phase connectivity in either age group from in- or anti-phase tACS. Furthermore, we did not observe significant differences in rIFG-preSMA phase connectivity between successful and unsuccessful inhibition, which suggests that rIFG-preSMA phase-coupling might not underlie effective response inhibition. The results offer insight into the neurophysiology of response inhibition and contribute to the future development of non-pharmacological interventions aimed at alleviating age-related declines in cognitive function.

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bioRxiv2021

Cognitive functions and respective parameters of human brain physiology are chronotype-dependent

Circadian rhythms have natural relative variations among humans known as chronotype. Chronotype or being a morning or evening person, has a specific physiological, behavioural, and also genetic manifestation. Whether and how chronotype modulates human brain physiology and cognition is, however, not well understood. Here we examine how cortical excitability, neuroplasticity, and cognition are associated with chronotype in early and late chronotype individuals. We monitor motor cortical excitability, brain stimulation-induced neuroplasticity, and examine motor learning and cognitive functions at circadian-preferred and non-preferred times of day in 32 individuals. Motor learning and cognitive performance (working memory, and attention) along with their electrophysiological components are significantly enhanced at the circadian-preferred, compared to the non-preferred time. This outperformance is associated with enhanced cortical excitability (prominent cortical facilitation, diminished cortical inhibition), and long-term potentiation/depression-like plasticity. Our data show convergent findings of chronotype can modulate human brain functions from basic physiological mechanisms to behaviour and higher cognitive functions.

neuroscience↗

bioRxiv2020

Prefrontal Transcranial Direct Current Stimulation globally improves learning, but does not selectively potentiate the benefits of Targeted Memory Reactivation on awake memory consolidation

Targeted Memory Reactivation (TMR) and transcranial Direct Current Stimulation (tDCS) can enhance memory consolidation. It is currently unknown whether TMR reinforced by simultaneous tDCS has superior efficacy. In this study, we investigated the complementary effect of TMR and bilateral tDCS on the consolidation of emotionally neutral and negative declarative memories. Participants learned neutral and negative word pairs. Each word pair was presented with an emotionally compatible sound. Following learning, participants spent a 20-minutes retention interval awake under 4 possible conditions: (1) TMR alone (i.e. replay of 50% of the associated sounds), (2) TMR combined with anodal stimulation of the left DLPFC, (3) TMR combined with anodal stimulation of the right DLPFC and (4) TMR with sham tDCS. Results evidenced selective memory enhancement for the replayed stimuli in the TMR-only and TMR-sham conditions, which confirms a specific effect of TMR on memory. However, memory was enhanced at higher levels for all learned items (irrespective of TMR) in the TMR-anodal right and TMR-anodal left tDCS conditions, suggesting that the beneficial effects of tDCS overshadow the specific effects of TMR. Emotionally negative memories were not modulated by tDCS hemispheric polarity. We conclude that electrical stimulation of the DLPFC during post-learning period globally benefits memory consolidation, but does not potentiate the specific benefits of TMR.

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