Biology subjects

Curtin, D.

Publications and source records attributed to Curtin, D..

4 recordsLinked to original sources

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.

neuroscience↗

bioRxiv2024

Default mode and motor networks facilitate early learning of implicit motor sequences: a multimodal MR spectroscopy and fMRI study

Learning new motor skills is a fundamental process that involves the sequencing of actions. Skill develops with practice and time, and manifests as performance that is fast and accurate. Although we know that learning can occur through an implicit process in the absence of conscious awareness, and across multiple temporal scales, the precise neural mechanisms mediating implicit motor sequence learning remain poorly understood. Similarly, the capacity for interventions with known influence on learning and memory, such as cardiovascular exercise, to facilitate implicit learning is yet to be clearly established. Here, we investigated the neuroplasticity of implicit motor sequence learning and the effect of acute exercise priming. Healthy adults (39.5% female) aged 22.55 {+/-} 2.69 years were allocated to either a high-intensity exercise (HIIT) group (n = 16) or to a very low-intensity control group (n = 17). Following exercise, participants performed a serial reaction time task. MR spectroscopy estimates of sensorimotor gamma-aminobutyric acid (GABA) were acquired before and after exercise, and during task performance, and resting-state fMRI was acquired at the end of the protocol. We show that early stages of learning are linked to default mode network connectivity, while the overall degree of learning following sustained practice is associated with motor network connectivity. Sensorimotor GABA concentration was linked to the early stages of learning, and GABA concentration was modulated following HIIT, although the two were not related. Overall, via integration of multiple neuroimaging modalities we demonstrate that interactions between hippocampal and motor networks underlie implicit motor sequence learning. Key points summary- Motor learning occurs across different temporal scales and can arise implicitly in the absence of conscious awareness. - Explicit motor learning is linked to the brains primary inhibitory neurotransmitter, GABA, and interactions across motor and hippocampal networks. - Whether these same neural mechanisms are implicated in implicit learning is unclear. Similarly, the capacity to influence learning via priming with cardiovascular exercise is yet to be clearly established. - We show that early implicit learning is underpinned by default mode network connectivity and sensorimotor GABA concentration, while total learning following sustained practice is linked to motor network connectivity. We also found that HIIT exercise elevated sensorimotor GABA concentration, but not the magnitude of implicit learning. - Overall, our results highlight shared involvement of default mode and motor networks in implicit motor sequence learning.

neuroscience↗

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.

neuroscience↗

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

neuroscience↗