Biology subjects

Coxon, J. P.

Publications and source records attributed to Coxon, J. P..

10 recordsLinked to original sources

bioRxiv2026

Beta power modulation supports micro-consolidation of implicit motor sequences

The consolidation of novel motor skills has traditionally been investigated over the timescale of hours-days following practice. However, a growing body of evidence has demonstrated that consolidation of skills occurs more rapidly across a scale of seconds - a process termed micro-consolidation. Micro-consolidation of explicitly cued motor sequences is supported by frontoparietal beta oscillations. Whether beta power modulation is a common mechanism supporting rapid consolidation of other forms of skill learning, such as implicit sequence learning, is yet to be elucidated. 72 healthy adults aged 18-35 (55% female) completed a serial reaction time task with concurrent electroencephalography recording. In line with our previous work, we show that the early fast learning on an implicit sequence task is primarily expressed as micro-offline gains during brief rest periods between periods of practice. Beta power was modulated as a function of active practice vs rest epochs (i.e., event-related synchronisation/desynchronisation), and here we demonstrate that micro-offline gains are associated with this modulation of beta power during the rest epochs. This relationship was specific to the beta frequency, and was not observed across either mu or gamma bands. Overall, in line with seminal work implicating beta in early explicit motor learning, our results indicate that beta is a shared neurophysiological signature of micro-consolidation of implicit sequences. Key points summary- Recent evidence demonstrates rapid consolidation of motor skills over seconds, termed micro-consolidation. - Seminal work has implicated beta oscillations in early explicit motor learning, though whether beta supports rapid consolidation of other forms of skill learning is unclear. - Using electroencephalography, we demonstrate that beta modulation is a neurophysiological signature of micro-consolidation of implicitly learnt motor sequences. - Lower beta at rest is associated with a higher degree of micro-consolidation. - Our findings shed critical new insight into the neurophysiological mechanisms mediating rapid consolidation of implicit motor skills during early fast learning.

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bioRxiv2025

Transcranial ultrasound stimulation induces white matter plasticity in the human corticospinal tract

Non-invasive methods to causally modulate human white matter tracts have proved elusive. In vitro and in vivo studies indicate that myelinated axons are sensitive to mechanical perturbations from ultrasound, providing a mechanistic rationale for targeting white matter tracts with ultrasound neuromodulation. Here, we demonstrate that transcranial ultrasound stimulation (TUS) targeted at the human corticospinal tract induces site-specific changes in motor neurophysiology. In a within-subject study, 15 healthy adults received 5 Hz repetitive TUS targeted at the left corticospinal tract at the level of the superior internal capsule. The homologous tract in the opposite hemisphere and the ipsilateral motor cortex were targeted as comparison conditions to confirm site specificity. Left corticospinal tract TUS increased corticomotor excitability and intracortical facilitation, whereas left motor cortex TUS reduced intracortical inhibition. Supporting analysis using diffusion tractography indicated that the magnitude of these changes depended jointly on ultrasound pressure and white matter microstructure (fractional anisotropy). These findings provide causal evidence that ultrasound can modulate white matter neurophysiology and establish TUS as a tool for non-invasive neuromodulation of white matter tracts in health and disorders of white matter. Significance statementWhite matter pathways are central to brain function and disease, yet causal tools to modulate these tracts in humans are lacking. We show that neuronavigated, low-intensity transcranial ultrasound targeted to the corticospinal white matter tract induces site-specific changes in motor neurophysiology. Supporting analyses using diffusion MRI tractography indicated that individual responses depended jointly on ultrasound pressure and local tissue properties, supporting an anatomy-informed, precision approach. These findings establish tract-targeted ultrasound as a non-invasive way to modulate human white matter neurophysiology, opening new opportunities for mechanistic tests of brain circuits and for developing circuit-guided interventions in neurological and psychiatric disorders.

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bioRxiv2025

The role of human intraparietal sulcus in evidence accumulation revealed by EEG and model-informed fMRI

Sequential sampling models propose that the repeated sampling of sensory information is a fundamental component of perceptual decision-making. Electroencephalographic investigations in humans have demonstrated motor-independent representations of evidence accumulation, but such observations have seldom been made in neuroimaging studies exploring the neuroanatomical origins of evidence accumulation. Here, we aimed to reveal the neuroanatomical locus of sensory evidence accumulation in the human brain by regressing an electrophysiological marker of evidence accumulation (centroparietal positivity, CPP) against changes in blood oxygen level-dependent (BOLD) signal during perceptual decision-making. Our cross-modal imaging approach revealed a cluster within left intraparietal sulcus (IPS), located within putative lateral intraparietal area (region hIP3), for which BOLD signals scaled in relation to the slope of the CPP. Furthermore, the drift rate parameter of a drift diffusion model parametrically modulated BOLD activity within an overlapping region of left IPS. In contrast, parametric modulation by reaction time revealed a distributed fronto-parietal network, demonstrating the utility of our approach for isolating a discrete neuroanatomical locus of evidence accumulation. Together, our findings provide strong support for intraparietal sulcus involvement in the accumulation of sensory evidence during human perceptual decision-making.

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bioRxiv2024

Supplementary motor area disinhibition during motor sequence learning: A TMS-EEG study

BackgroundIn 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. ObjectiveWe investigated disinhibition within SMA during motor sequence learning using combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG). MethodsTwenty-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. ResultsSignificant 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). ConclusionOur 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.

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bioRxiv2023

The effect of dopamine D2 receptor blockade on human motor skill learning

Rationale: Dopamine signalling supports motor skill learning in a variety of ways, including through an effect on cortical and striatal plasticity. One neuromodulator that has been consistently linked to motor skill learning is dopamine. However, the specific role of dopamine D2 receptor in the acquisition and consolidation stages of motor learning remains unclear. ObjectivesTo examine the effect of a selective D2 receptor antagonist on human motor skill acquisition and consolidation. MethodsIn this randomised, double-blind, placebo-controlled design, healthy adult men and women (N = 23) completed a sequential motor skill learning task after taking either sulpiride (800mg) or placebo. A 20-minute bout of high-intensity interval cycling exercise was included to enhance experimental effects and counteract potentially confounding sedative effects of sulpiride. ResultsSulpiride reduced performance during motor skill acquisition relative to placebo in the first session, however this difference was abolished at the subsequent retention test. Sulpiride did not reduce consolidation of learning as expected, however it led to a reduction in speed of execution relative to placebo. ConclusionsOur results demonstrate that neuromodulation at the dopamine D2 receptor is critical in the early acquisition of a novel motor skill. These results may have functional relevance in motor rehabilitation as reduced dopamine transmission can impact performance during initial learning and slow subsequent performance of the skill.

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bioRxiv2023

Ageing attenuates exercise-enhanced motor cortical plasticity

Cardiorespiratory exercise is known to modulate motor cortical plasticity in young adults, but the influence of ageing on this relationship is unknown. Here, we compared the effects of a single session of cardiorespiratory exercise on motor cortical plasticity in young and older adults. We acquired measures of cortical excitatory and inhibitory activity of the primary motor cortex using transcranial magnetic stimulation (TMS) from 20 young (M {+/-} s.d. = 25.30 {+/-} 4.00 years) and 20 older (M {+/-} s.d. = 64.10 {+/-} 6.50 years) healthy adults. Single and paired pulse TMS measures were collected before and after a 20-minute bout of high-intensity interval cycling exercise or an equivalent period of rest, and again after intermittent theta burst stimulation (iTBS). In both young and older adults, exercise led to an increase in glutamatergic excitation and a reduction in gamma-aminobutyric acid (GABA) inhibition. However, in contrast to younger adults, older adults showed an attenuated plasticity response to iTBS following exercise. These results demonstrate an age-dependent decline in cortical plasticity and indicate that a preceding bout of high-intensity interval exercise may be less effective for enhancing primary motor cortex plasticity in older adults. Our findings align with the hypothesis that the capacity for cortical plasticity is altered in older age. Key pointsO_LIExercise enhances motor cortical plasticity in young adults, but how ageing influences this effect is unknown. C_LIO_LIHere, we compared primary motor cortical plasticity responses in young and older adults before and after a bout of high-intensity interval exercise, and again after a plasticity-inducing protocol - intermittent theta burst stimulation. C_LIO_LIIn both young and older adults, exercise led to an increase in glutamatergic excitation and a reduction in gamma-aminobutyric acid (GABAergic) inhibition. C_LIO_LIOur key result was that older adults showed an attenuated plasticity response to theta burst stimulation following exercise, relative to younger adults. C_LIO_LIOur findings demonstrate an age-dependent decline in exercise-enhanced cortical plasticity and indicate that a preceding bout of high-intensity interval exercise may be less effective for enhancing primary motor cortex plasticity in older adults. C_LI

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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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bioRxiv2020

Multi-day rTMS exerts site-specific effects on functional connectivity but does not influence associative memory performance

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique with the capacity to modulate brain network connectivity and cognitive function. Recent studies have demonstrated long-lasting improvements in associative memory and resting-state connectivity following multi-day repetitive TMS (rTMS) to individualised parietal-hippocampal networks. We aimed to assess the reproducibility and network- and cognitive-specificity of these effects following multi-day rTMS. Participants received four days of 20 Hz rTMS to a subject-specific region of left lateral parietal cortex exhibiting peak functional connectivity to the left hippocampus. In a separate week, the same stimulation protocol was applied to a subject-specific region of pre-supplementary motor area (pre-SMA) exhibiting peak functional connectivity to the left putamen. We assessed changes to associative memory before and after each week of stimulation (N = 39), and changes to resting-state functional connectivity before and after stimulation in week one (N = 36). We found no evidence of long-lasting enhancement of associative memory or increased parieto-hippocampal connectivity following multi-day rTMS to the parietal cortex, nor increased pre-SMA-putamen connectivity following multi-day rTMS to pre-SMA. Instead, we observed some evidence of site-specific modulations of functional connectivity lasting [~]24 hours, with reduced connectivity within targeted networks and increased connectivity across distinct non-targeted networks. Our findings suggest a complex interplay between multi-day rTMS and network connectivity. Further work is required to develop reliable rTMS paradigms for driving changes in functional connectivity between cortical and subcortical regions.

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bioRxiv2019

Do TMS evoked responses measured from scalp and hand represent the same cortical mechanisms?

Transcranial magnetic stimulation (TMS) is a powerful tool to investigate cortical circuits. Changes in cortical excitability following TMS are typically assessed by measuring changes in either conditioned motor-evoked potentials (MEPs) following paired-pulse TMS over motor cortex or evoked potentials measured with electroencephalography following single-pulse TMS (TEPs). However, it is unclear whether these two measures of cortical excitability index the same cortical response. Twenty-four healthy participants received local and interhemispheric paired-pulse TMS over motor cortex with eight inter-pulse intervals, suband suprathreshold conditioning intensities, and two different pulse waveforms, while MEPs were recorded from a hand muscle. TEPs were also recorded in response to single-pulse TMS using the conditioning pulse alone. The relationships between TEPs and conditioned-MEPs were evaluated using metrics sensitive to both their magnitude at each timepoint and their overall shape across time. The impacts of undesired sensory potentials resulting from TMS pulse and muscle contractions were also assessed on both measures. Both conditioned-MEPs and TEPs were sensitive to re-afferent somatosensory activity following motor-evoked responses, but over different post-stimulus timepoints. Moreover, the amplitude of low-frequency oscillations in TEPs was strongly correlated with the sensory potentials, whereas early and local high-frequency responses showed minimal relationships. Accordingly, conditioned-MEPs did not correlate with TEPs in the time domain but showed high shape similarity with the amplitude of high-frequency oscillations in TEPs. Therefore, despite the effects of sensory confounds, the TEP and MEP measures share a response component, suggesting that they index a similar cortical response and perhaps the same neuronal populations.

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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.

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