Nigel C. Rogasch

Background: Suprathreshold paired-pulse transcranial magnetic stimulation (TMS) at interstimulus intervals (ISIs) of 20–30 ms evokes cumulative online increases in corticospinal excitability. Whether these changes persist beyond stimulation remains unclear. This study investigated whether repetitive paired-pulse TMS targeting periods of net excitation or inhibition induces offline changes in corticospinal excitability. Methods: Nineteen healthy participants completed three sessions, separated by at least one week, involving 40 pairs of repetitive paired-pulse TMS delivered to the left primary motor cortex at an ISI of 20 ms (rPPS20) or 100 ms (rPPS100), or a single-pulse control condition (rSPS). Offline changes in corticospinal excitability were assessed using motor evoked potential (MEP) amplitudes recorded before and after stimulation. Results: During stimulation, MEP amplitudes decreased across trials in the rPPS100 condition, although online changes did not differ significantly between conditions. Following stimulation, MEP amplitudes were significantly reduced for up to 40 minutes after rPPS100 (p = 0.017) but were not changed following rPPS20 or rSPS (all p > 0.05). Conclusion: Contrary to our hypothesis, repetitive paired-pulse TMS targeting periods of net excitation did not induce offline changes in corticospinal excitability. In contrast, stimulation targeting long-interval intracortical inhibition (LICI) produced sustained reductions in corticospinal excitability, suggesting that repetitive LICI-inducing stimulation can induce lasting plasticity within the corticospinal system.

Working memory is a fundamental process that underlies cognition. Accordingly, the neural mechanisms that support working memory performance are of great interest in cognitive neuroscience. We present a publicly accessible dataset comprising 123 healthy adults (mean age = 28.58 years, SD = 7.56; age range = 18–46 years; 75 females) to facilitate investigation of the neural mechanisms underlying working memory performance in humans. Across two days of assessment, participants underwent a battery of cognitive tasks assessing working memory and other cognitive domains (day 1), followed by 62-channel EEG recordings (day 2). EEG data were acquired at rest, during a visual working memory task, and following single-pulse transcranial magnetic stimulation (TMS-EEG) targeting key brain regions involved in working memory. This article provides a detailed overview of the study design, methodology, and data characteristics.

Transcranial magnetic stimulation (TMS) is widely used to assess inhibitory and facilitatory circuits within the primary motor cortex. However, accumulating evidence suggests that even brief TMS paradigms may induce unintended changes in corticospinal excitability. Here, we examined whether suprathreshold paired-pulse TMS delivered at inter-stimulus intervals (ISIs) associated with intracortical facilitation or long-interval cortical inhibition (LICI) elicits cumulative changes in motor-evoked potential (MEP) amplitude. In experiment 1, we reanalysed data from 17 participants who received 20 suprathreshold paired-pulses at eight ISIs (10–200 ms) and 40 unconditioned single pulses. Stimulation was pseudo-randomised and distributed evenly across four blocks. A linear mixed-effects model assessed trial-wise changes in MEP amplitude across ISIs. We replicated the design in an independent sample (n = 10, experiment 2). A significant trial-by-ISI interaction was observed in both cohorts. Specifically, MEP amplitudes increased across trials for ISIs of 20 and 30 ms ( p < 0.05), but remained stable at LICI-related ISIs (100–150 ms). A similar increase was also seen with single-pulse TMS. These findings demonstrate that suprathreshold paired-pulse TMS at short ISIs can cumulatively enhance corticospinal excitability during stimulation.

Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) enables direct measurement of cortical reactivity via TMS-evoked potentials (TEPs). Interpretation of early TEP components however, is highly sensitive to stimulation and hardware-related artifacts. We identified and characterised a persistent, non-neural ‘step-drift’ artifact unexpectedly present in recent TMS-EEG recordings from our group. We show that the artifact is distinct from previously described TMS pulse and discharge/decay artifacts and likely reflects a hardware interaction phenomenon. We demonstrated that amplifier settings, but not TMS pulse shape, substantially influenced artifact expression, with DC-coupled recordings with no online high-pass filter reducing step amplitude compared with AC-coupled recordings with a high-pass filter. Simulations additionally revealed that filtering over the step-drift artifact introduced pronounced ringing and edge artifacts, highlighting the need to address this artifact prior to data processing. We propose a processing pipeline incorporating robust polynomial detrending and a modified Butterworth filter with autoregressive extrapolation that minimised TEP distortion in both simulated and real data containing the step-drift artifact. Together, these findings provide practical recommendations for both preventing and correcting step-drift artifacts and underscore the need for formal definition and routine recognition of this artifact to improve reproducibility and data quality in TMS-EEG research.

Research using electroencephalography (EEG) has shown that individual differences in visual working memory capacity are related to slow-wave event-related potentials (ERPs) and suppression of alpha-band oscillatory power during the delay period of memory tasks. However, recent evidence suggests that changes in non-oscillatory (aperiodic) features of the EEG signal are related to working memory performance. We assessed several features of task-related changes in aperiodic activity including its spatial distribution, the effect of memory load, and the relationships between aperiodic activity, memory capacity, slow-wave ERPs, and alpha suppression. Eighty-four healthy individuals performed a continuous recall working memory (WM) task consisting of 2, 4 or 6 coloured squares while EEG was recorded. Aperiodic activity during a baseline and WM delay period was quantified by fitting a model to the background of the EEG power spectra, which returned parameters describing the slope (exponent) and broadband offset of the spectra. The aperiodic exponent increased (i.e., slope steepened) in fronto-central electrodes during the WM delay period, whereas the offset decreased over parieto-occipital electrodes. These task-related changes in aperiodic activity did not differ between memory loads. Larger increases in the aperiodic exponent were associated with higher working memory capacity measured from both the WM task and a separate battery of complex span tasks, a relationship that was independent of slow-wave ERPs and alpha suppression. Our findings suggest that WM task-related changes in aperiodic activity are region specific and reflect an independent neural mechanism that is important for general working memory ability.

Transcranial magnetic stimulation (TMS) results in a series of deflections in electroencephalography (EEG) recordings known as a TMS-evoked potential (TEP). However, it remains unclear whether these responses reflect neural activity resulting from transcranial stimulation of the cortex, the sensory experiences of TMS, or a combination of the two. Across three experiments (total n = 135), we recorded EEG activity following TMS to the dorsolateral prefrontal cortex, premotor cortex, and parietal cortex as well as a sensory control condition (stimulation of the shoulder or electrical stimulation of the scalp with a click sound). We found that TEPs showed a stereotypical frontocentral N100/P200 complex following TMS of all cortical sites and control conditions, regardless of TMS intensity or the type of sensory control. In contrast, earlier TEPs (<60 ms) showed site-specific characteristics which were largest at the site of stimulation, although TEP topographies were distorted in a subgroup of individuals due to residual TMS-evoked muscle artefact despite cleaning with independent component analysis. Self-reported sensory experiences differed across sites, with prefrontal stimulation resulting in stronger auditory (click sound perception) and somatosensory input (scalp muscle twitch, discomfort) than premotor or parietal stimulation, a pattern that was reflected in the amplitude of later (N100/P200), but not earlier (<60 ms), TEP peak amplitudes. Later TEPs were also larger in individuals who experienced stronger click sound perception and, to a lesser extent, TMS-evoked scalp muscle twitches. Increasing click sound perception by removing auditory masking increased N100/P200 amplitudes without altering earlier peaks, an effect which was more prominent at sites with more successful masking. Together, these findings suggest that the frontocentral N100/P200 complex primarily represents a generalised sensory response resulting from TMS-related auditory and somatosensory input when present. In contrast, early TEP peaks likely primarily reflect activity resulting from transcranial stimulation of the cortex when artefacts were adequately accounted for. The results have important implications for designing and interpreting TEP studies, especially when comparing TEPs between stimulation sites and participant groups showing differences in sensory experiences following TMS.

Objective: Repetitive transcranial magnetic stimulation (rTMS) shows promise as an aphasia treatment, however its physiological mechanisms in people with aphasia (PWA) remain largely unclear. Electroencephalography (EEG) could be used to explore rTMS mechanisms. The present study investigated the acute effects of rTMS in PWA on: 1) an EEG measure of language (N400 event-related potential); and 2) picture naming. Methods: Eleven people with chronic non-fluent or anomic aphasia (64 ± 10.13 years old; 8 males; 37.27 ± 20.64 months since stroke) received one session of 1-Hz rTMS and one session of sham to the right pars triangularis at 80% resting motor threshold (RMT). N400 mean amplitude and picture naming accuracy were compared before and after each session. Results: No acute changes were observed in N400 mean amplitude or picture naming accuracy as compared to sham (p > 0.05; BF₁₀ < 0.33). Conclusions: Results suggest that language networks underlying the N400 are not altered following one session of 1-Hz rTMS in PWA. Significance: Although EEG could be useful for assessing physiological mechanisms of rTMS in PWA, the N400 does not appear to be a viable measure of acute 1-Hz rTMS effects, at least when delivered at 80% RMT in a single session.

Background: In primary motor cortex, changes in excitatory and inhibitory neurotransmission (E:I balance) accompany motor sequence learning. In particular, there is an early reduction in inhibition (i.e., disinhibition). The supplementary motor area (SMA) is a key brain region involved in the learning of sequences, however the neurophysiological mechanisms within SMA which support motor sequence learning remain poorly understood. Disinhibition may also occur in SMA, but this possibility remains unexamined. Objective: We investigated disinhibition within SMA during motor sequence learning using combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG). Methods: Twenty-nine healthy adults practiced a sequential motor task. TMS-evoked potentials (TEPs) resulting from SMA stimulation were measured with EEG before, during, and after practice. The N45 TEP peak was our primary measure of disinhibition. Furthermore, the slope of aperiodic EEG activity was included as an additional E:I balance measure. Results: Significant improvements in task performance (i.e., learning) occurred with practice. We observed smaller N45 amplitudes during early learning relative to baseline (both p < .01), indicative of disinhibition. Intriguingly, aperiodic exponents increased as learning progressed and were associated with greater sequence learning ( p < .05). Conclusion: Our results show disinhibition within SMA during the planning phase of motor sequence learning and thus provide novel understanding on the neurophysiological mechanisms within higher-order motor cortex that accompany new sequence learning.