Biology subjects

Goldsworthy, M. R.

Publications and source records attributed to Goldsworthy, M. R..

12 recordsLinked to original sources

bioRxiv2026

Repetitive suprathreshold paired-pulse transcranial magnetic stimulation alters corticospinal excitability

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.

neuroscience↗

bioRxiv2026

Characterising and Minimising Step and Filtering Artifacts in TMS-EEG Recordings

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.

neuroscience↗

bioRxiv2025

Cumulative timing-dependent changes in corticospinal excitability during suprathreshold paired-pulse transcranial magnetic stimulation

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. Furthermore, the results suggest potential for using these protocols not just for probing cortical circuits, but also as interventions to modulate motor system excitability.

neuroscience↗

bioRxiv2025

Investigating the Influence of Anti-Seizure Medications on Aperiodic EEG Activity

ObjectiveElectroencephalography (EEG) signals comprise both oscillatory (periodic) and non-oscillatory (aperiodic) components. Aperiodic activity forms the 1/f-like background of the EEG power spectrum and can be characterised by parameters describing the offset and slope (1/f exponent). This study examined the effects of two antiseizure medications (ASMs), which reduce cortical excitability through different mechanisms of action, on aperiodic and periodic EEG activity. MethodsResting EEG was recorded with eyes open and closed from 13 healthy male volunteers at baseline and two hours after administration of lamotrigine (300 mg), levetiracetam (3000 mg), or placebo. Power spectra were computed using Welchs method. Aperiodic parameters were estimated using the specparam algorithm, and periodic activity was quantified after subtraction of the aperiodic component. ResultsIn the eyes-open condition, lamotrigine significantly reduced both aperiodic offset and exponent relative to placebo, consistent with a flattening of the aperiodic spectrum, whereas levetiracetam reduced the exponent without significantly altering the offset. Neither drug significantly altered aperiodic exponent or offset during eyes-closed. Lamotrigine reduced corrected theta power in both conditions and alpha power during eyes-open, whereas levetiracetam increased beta power in both conditions and reduced gamma power during eyes-closed. ConclusionsBoth lamotrigine and levetiracetam altered aperiodic and periodic EEG activity, with aperiodic effects observed only during eyes-open. SignificanceAperiodic EEG measures may provide a non-invasive approach for characterising ASM-related neurophysiological effects and may help elucidate how distinct pharmacological mechanisms influence large-scale cortical activity.

neuroscience↗

bioRxiv2025

The relationship between task-related aperiodic EEG activity, neural inefficiency and verbal working memory in younger and older adults

Working memory (WM) decline in ageing may be related to increases in "neural noise", potentially reflected in the EEG aperiodic exponent. We reanalysed previously published data to investigate age-related differences in the aperiodic exponent during verbal WM and its relationship with neural inefficiency. EEG was recorded from 24 younger (18-35 years) and 30 older adults (50-86 years) during a modified Sternberg task with 1-letter, 3-letter, and 5-letter load conditions. Younger adults consistently demonstrated steeper aperiodic slopes than older adults, though this difference was less pronounced in frontal regions during retention. Unexpectedly, both age groups showed decreased (i.e. flattened) aperiodic exponents during retention relative to fixation, with minimal load-dependent effects. Notably, the relationship between task-related exponent changes and WM performance was complex and dependent on the exponent at fixation, particularly in older adults. Finally, flatter exponents during fixation and late retention were associated with greater neural inefficiency during stimulus processing, reflected by increased P3b amplitudes without corresponding WM performance improvements. These findings suggest that flatter exponents are associated with less efficient neural processing and that older adults flexibly modulate their aperiodic exponent during retention to support WM performance.

neuroscience↗

bioRxiv2024

Metaplastic neuromodulation via transcranial direct current stimulation has no effect on corticospinal excitability and neuromuscular fatigue

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation tool with potential for managing fatigue, possibly due to alterations in corticospinal excitability. However, inconsistencies in intra- and inter-individual variability responsiveness to tDCS limit its clinical use. Emerging evidence suggests harnessing homeostatic metaplasticity induced via tDCS may reduce variability and boost its outcomes, yet little is known regarding its influence on fatigue in healthy adults. We explored whether cathodal tDCS (ctDCS) prior to exercise combined with anodal tDCS (atDCS) could augment corticospinal excitability and attenuate fatigue. 15 young healthy adults (6 males, 22 {+/-} 4 years) participated in four pseudo-randomised neuromodulation sessions: sham stimulation prior and during exercise, sham stimulation prior and atDCS during exercise, ctDCS prior and atDCS during exercise, ctDCS prior and sham stimulation during exercise. The exercise constituted an intermittent maximal voluntary contraction (MVC) of the right first dorsal interosseous (FDI) for 10 minutes. Fatigue was quantified as an attenuation in MVC force, while motor evoked potential (MEP) amplitude provided an assessment of corticospinal excitability. MEP amplitude increased during the fatiguing exercise, whilst across time, force decreased. There were no differences in MEP amplitudes or force between neuromodulation sessions. These outcomes highlight the ambiguity of harnessing metaplasticity to ameliorate fatigue in young healthy individuals.

neuroscience↗

bioRxiv2023

Age-Related Differences in Alpha Power for Distractor Inhibition During Visual Working Memory

As visual working memory (WM) is limited in capacity, it is important to direct neural resources towards task-relevant information and away from task-irrelevant information. Neural oscillations in the alpha frequency band (8-12 Hz) have been suggested to play a role in the inhibition of distracting information during WM retention in younger adults, but it is unclear if alpha power modulation also supports distractor inhibition in older adults. Here, we recorded electroencephalography (EEG) while 24 younger (aged 18-35) and 24 older (aged 60-86) adults completed a modified delay match-to-sample task in which distractors of varying strength appeared during the retention period. We found: (1) strong distractors impaired WM performance compared with weak and no distractors in both age groups, but there were no age-differences in WM performance; (2) while younger adults demonstrated significant increases in alpha power prior to the onset of the distractor in all conditions, decreases in alpha power were seen in all distractor conditions in older adults; (3) there was no difference in alpha power between the strong and no distractor conditions; and (4) alpha power in anticipation of the distractor was only associated with task performance in younger adults. Our results suggest that younger adults, but not older adults, modulate alpha power in anticipation of distractors during the visual WM retention period.

neuroscience↗

bioRxiv2019

Load-dependent modulation of alpha oscillations during working memory encoding and retention in young and older adults

Working memory (WM) is vulnerable to age-related decline, particularly under high loads. Visual alpha oscillations contribute to WM performance in younger adults, and although alpha decreases in power and frequency with age, it is unclear if alpha activity supports WM in older adults. We recorded electroencephalography (EEG) while 24 younger (aged 18-35 years) and 30 older (aged 50-86) adults performed a modified Sternberg task with varying load conditions. Older adults demonstrated slower reaction times at all loads, but there were no significant age differences in accuracy. Regardless of age, alpha power decreased, and alpha frequency increased with load during encoding, and the magnitude of alpha suppression during retention was larger at higher loads. While alpha power during retention was lower than fixation in older, but not younger adults, the relative change from fixation was not significantly different between age groups. Individual differences in alpha power did not predict performance for either age groups or at any WM loads. Future research should elaborate the functional significance of alpha power and frequency changes that accompany WM performance in cognitive ageing.

neuroscience↗

bioRxiv2019

Associations between EEG functional brain connectivity and a cognitive reserve proxy in healthy older adults

Cognitive reserve is a concept that explains individual differences in vulnerability to cognitive impairment due to age and dementia-related brain changes. Mechanisms underlying the cognitive reserve effect are poorly understood. We investigated associations between a comprehensive cognitive reserve proxy (Lifetime Experiences Questionnaire/LEQ) and functional connectivity of the prefrontal cortex across the whole scalp, covarying for the level of current cognitive functioning (Addenbrookes Cognitive Examination Revised/ACE-R), using multiblock parallel and orthogonalized partial least squares regression. EEG data were collected from 34 healthy older adults (63 to 83 years) in eyes-open and eyes-closed resting-states, and during 0-back and 1-back tasks. Functional connectivity was estimated using imaginary coherence in the theta and alpha frequency bands, as these bands have been heavily implicated in cognitive ageing, attention and executive function. We found three clusters of electrodes where the absolute values of the regression coefficient were above threshold when covarying for ACE-R: (1) a cluster approximating the right frontocentral region during the eyes-open condition in the theta band with seed electrodes approximating the left prefrontal cortex with positive associations of medium effect size; (2) a cluster approximating the right parietotemporal region during the 0-back task in the theta band with seed electrodes approximating the right prefrontal cortex with negative associations of medium to large effect sizes; and (3) a cluster approximating the occipitoparietal region in the eyes-closed condition in the alpha band with seed electrodes approximating the left prefrontal cortex with negative associations of medium effect size. These relationships between a cognitive reserve proxy and functional connectivity, within key networks and frequency bands associated with attention and executive function, may reflect greater neural capacity and efficiency.

bioengineering↗

bioRxiv2018

Characterization of young and old adult brains: An EEG functional connectivity analysis

Brain connectivity studies have reported that functional networks change with older age. We aim to (1) investigate whether electroencephalography (EEG) data can be used to distinguish between individual functional networks of young and old adults; and (2) identify the functional connections that contribute to this classification. Two eyes-open resting-state EEG recording sessions with 64 electrodes for each of 22 younger adults (19-37 years) and 22 older adults (63-85 years) were conducted. For each session, imaginary coherence matrices in theta, alpha, beta and gamma bands were computed. A range of machine learning classification methods were utilized to distinguish younger and older adult brains. A support vector machine (SVM) classifier was 94% accurate in classifying the brains by age group. We report decreased functional connectivity with older age in theta, alpha and gamma bands, and increased connectivity with older age in beta band. Most connections involving frontal, temporal, and parietal electrodes, and approximately two-thirds of connections involving occipital electrodes, showed decreased connectivity with older age. Just over half of the connections involving central electrodes showed increased connectivity with older age. Functional connections showing decreased strength with older age had significantly longer electrode-to-electrode distance than those that increased with older age. Most of the connections used by the classifier to distinguish participants by age group belonged to the alpha band. Findings suggest a decrease in connectivity in key networks and frequency bands associated with attention and awareness, and an increase in connectivity of the sensorimotor functional networks with ageing during a resting state.

neuroscience↗

bioRxiv2018

Test-retest reliability of functional brain network characteristics using resting-state EEG and graph theory

Metrics of brain network organization can be derived from neuroimaging data using graph theory. We explored the test-retest reliability of graph metrics of functional networks derived from resting-state electroencephalogram (EEG) recordings. Data were collected within two designs: (1) within sessions (WS) design where EEG data were collected from 18 healthy participants in four trials within a few hours and (2) between sessions (BS) design where EEG data were collected from 19 healthy participants in three trials on three different days at least one week apart. Electrophysiological source activity was reconstructed and functional connectivity between pairs of sensors or brain regions was determined in different frequency bands. We generated undirected binary graphs and used intra-class correlation coefficient (ICC) to estimate reliability. We showed that reliabilities ranged from poor to good. Reliability at the sensor-level was significantly higher than source-level. The most reliable graph metric at the sensor-level was cost efficiency and at the source-level was global efficiency. At the sensor-level: WS reliability was significantly higher than BS reliability; high beta band in WS design had the highest reliability; in WS design reliability in gamma band was significantly lower than reliability in low and high beta bands. At the source-level: low beta band in BS design had the highest reliability; there was no significant main effect of frequency band on reliability; reliabilities of WS and BS designs were not significantly different. These results suggest that these graph metrics can provide reliable outcomes, depending on how the data were collected and analysed.

neuroscience↗

bioRxiv2017

The effect of stimulation interval on plasticity following repeated blocks of intermittent theta burst stimulation

IntroductionTheta burst stimulation (TBS) is a non-invasive brain stimulation paradigm capable of influencing cortical circuits in humans by inducing neural plasticity. Applying spaced blocks of TBS can affect both the direction and magnitude of plasticity, but the impact of interval duration on these interactions following intermittent TBS (iTBS) is unclear.\n\nObjectivesTo assess the effect of interval duration on plasticity magnitude/direction following spaced iTBS.\n\nMethods15 healthy participants received three different iTBS conditions on separate days: single iTBS; spaced iTBS with a 5 minute interval (iTBS-5); and spaced iTBS with a 15 minute interval (iTBS-15). Changes in cortical excitability and short-interval cortical inhibition (SICI) resulting from iTBS were assessed via motor-evoked potentials (MEPs) measured from the first dorsal interosseus muscle before and up to 60 mins following stimulation.\n\nResultsiTBS-15 increased MEP amplitude up to 60 mins post stimulation, whereas iTBS-5 decreased MEP amplitude. In contrast, MEP amplitude was not altered by single iTBS. Despite the significant effect of iTBS-15 on MEP amplitude at the group level, there was still considerable inter-individual variability, with only 53% of individuals meeting response criteria. Modulation of SICI did not differ between conditions.\n\nConclusionsThe interval duration between spaced iTBS plays an important role in determining the direction of plasticity on excitatory, but not inhibitory circuits in human motor cortex. While iTBS-15 can increase the magnitude of facilitation in some individuals compared to single iTBS, this approach still suffers from high inter-individual variability.

neuroscience↗