ORCID Profile
0000-0001-7771-7569
Current Organisation
University of Adelaide
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Biological psychology | Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology) | Psychology | Psychophysiology | Psychology of ageing | Developmental Psychology and Ageing
Health Related to Ageing | Expanding Knowledge in the Biological Sciences |
Publisher: Springer Science and Business Media LLC
Date: 15-06-2022
DOI: 10.1038/S41598-022-14271-1
Abstract: Transcranial magnetic stimulation (TMS) is used to probe inhibitory intracortical neurotransmission and has been used to infer the neurobiological dysfunction that may underly several neurological disorders. One technique, short-interval intracortical inhibition (SICI), indexes gamma-aminobutyric acid (GABA) mediated inhibitory activity and is a promising biomarker. However emerging evidence suggests SICI does not exclusively represent GABAergic activity because it may be influenced by inter-in idual differences in the specific excitatory neural populations activated by TMS. Here we used the latency of TMS motor evoked potentials (MEPs) to index these inter-in idual differences, and found that a significant proportion of the observed variability in SICI magnitude was accounted for by MEP latency, r = − 0.57, r 2 = 0.33, p = .014. We conclude that SICI is influenced by inter-in idual differences in the excitatory neural populations activated by TMS, reducing the precision of this GABAergic probe. Interpreting SICI measures in the context of MEP latency may facilitate a more precise assessment of GABAergic intracortical inhibition. The reduced cortical inhibition observed in some neuropathologies could be influenced by reduced activity in specific excitatory neural populations. Including MEP latency assessment in research investigating SICI in clinical groups could assist in differentiating the cortical circuits impacted by neurological disorders.
Publisher: Elsevier BV
Date: 06-2022
Publisher: Elsevier BV
Date: 07-2021
DOI: 10.1111/NER.13314
Publisher: Elsevier BV
Date: 06-2021
Publisher: American Physiological Society
Date: 10-2022
DOI: 10.1152/JAPPLPHYSIOL.00213.2022
Abstract: We use a novel form of repetitive transcranial magnetic stimulation to show that motor cortex plasticity is increased after acute exercise and that this effect is bolstered in endurance-trained cyclists. These findings indicate that participation in regular endurance exercise (involving lower limb muscles) has widespread effects on cortical plasticity (assessed in unexercised upper limb muscles) following acute lower-limb cycling exercise. It also highlights that exercise history is an important factor in exercise-induced cortical plasticity.
Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.BRS.2015.04.001
Abstract: Previous research has shown age-related differences in short- (SICI) and long-interval intracortical inhibition (LICI) in both resting and active hand muscles, suggesting that healthy ageing influences post-synaptic motor cortex inhibition. However, it is not known how the ageing process effects the pre-synaptic interaction of SICI by LICI, and how these pre- and post-synaptic intracortical inhibitory circuits are modulated by the performance of different motor tasks in older adults. To examine age-related differences in pre- and post-synaptic motor cortex inhibition at rest, and during index finger abduction and precision grip. In 13 young (22.3 ± 3.8 years) and 15 old (73.7 ± 4.0 years) adults, paired-pulse transcranial magnetic stimulation (TMS) was used to measure SICI (2 ms inter-stimulus interval ISI) and LICI (100 and 150 ms ISI), whereas triple-pulse TMS was used to investigate SICI when primed by LICI. We found no age-related difference in SICI at rest or during index finger abduction, but significantly greater SICI in older subjects during precision grip. Older adults showed reduced LICI in resting muscle (at an ISI of 150 ms), with no age-related differences in LICI during either task. When SICI was primed by LICI, disinhibition of motor cortex was reduced in older adults at rest (100 ms ISI) and during index finger abduction (150 ms ISI), but not during precision grip. Our results support age-related differences in pre- and post-synaptic motor cortex inhibition, which may contribute to impaired hand function during task performance in older adults.
Publisher: Cold Spring Harbor Laboratory
Date: 17-10-2023
Publisher: Cold Spring Harbor Laboratory
Date: 16-02-2022
DOI: 10.1101/2022.02.14.480458
Abstract: Cerebellar-brain inhibition (CBI) is a transcranial magnetic stimulation (TMS) paradigm indexing excitability of cerebellar projections to motor cortex (M1). Stimulation involved with CBI is often considered to be uncomfortable, and alternative ways to index connectivity between cerebellum and the cortex would be valuable. Utilising electroencephalography in conjunction with TMS (combined TMS-EEG) to record the response to CBI has the potential to achieve this, but has not been attempted previously. To investigate the utility of TMS-EEG for characterising cerebellar-cortical interactions recruited by CBI. A total of 33 volunteers (25.7 ± 4.9 years, 20 females) participated across three experiments. These investigated EEG responses to CBI induced with a figure-of-eight (F8 experiment 1) or double cone (DC experiment 2) conditioning coil over cerebellum, in addition to multisensory sham stimulation (experiment 3). Both F8 and DC coils suppressed early TMS-evoked EEG potentials (TEPs) produced by TMS to M1 ( P 0.05). Furthermore, the TEP produced by CBI stimulation was related to the motor inhibitory response to CBI recorded in a hand muscle ( P 0.05), but only when using the DC coil. Multisensory sham stimulation failed to modify the M1 TEP. Cerebellar conditioning produced changes in the M1 TEP that were not apparent following sham stimulation, and that were related to the motor inhibitory effects of CBI. Our findings therefore suggest it is possible to index the response to CBI using TMS-EEG. In addition, while both F8 and DC coils appear to recruit cerebellar projections, the nature of these may be different.
Publisher: MDPI AG
Date: 03-01-2023
Abstract: The late indirect (I)-waves recruited by transcranial magnetic stimulation (TMS) over primary motor cortex (M1) can be modulated using I-wave periodicity repetitive TMS (iTMS). The purpose of this study was to determine if the response to iTMS is influenced by different interstimulus intervals (ISIs) targeting late I-waves, and whether these responses were associated with in idual variations in intracortical excitability. Seventeen young (27.2 ± 6.4 years, 12 females) healthy adults received iTMS at late I-wave intervals (4.0, 4.5, and 5.0 ms) in three separate sessions. Changes due to each intervention were examined with motor evoked potential (MEP) litudes and short-interval intracortical facilitation (SICF) using both posterior-anterior (PA) and anterior-posterior (AP) TMS current directions. Changes in MEP litude and SICF were influenced by iTMS ISI, with the greatest facilitation for ISIs at 4 and 5 ms with PA TMS, and 4 ms with AP TMS. Maximum SICF at baseline (irrespective of ISI) was associated with increased iTMS response, but only for PA stimulation. These results suggest that modifying iTMS parameters targeting late I-waves can influence M1 plasticity. They also suggest that maximum SICF may be a means by which responders to iTMS targeting the late I-waves could be identified.
Publisher: Cold Spring Harbor Laboratory
Date: 14-10-2020
DOI: 10.1101/2020.10.13.338350
Abstract: Combined single-pulse transcranial magnetic stimulation (TMS) and electroencephalography (EEG) has been used to probe the features of local networks in the cerebral cortex. Here we investigate whether we can use this approach to explore long-range connections between the cerebellum and cerebral cortex. To assess the feasibility of using cerebellar TMS-EEG for the exploration of cerebellar-cerebral network dynamics. Ten healthy adults received single-pulse suprathreshold TMS to the cerebellum and an occipital arietal control site with double-cone and figure-of-eight coils while cerebral activity was recorded. A multisensory electrical control condition was used to simulate the sensation of the double-cone coil at the cerebellar site. Two cleaning pipelines were compared, and the spatiotemporal relationships of the EEG output between conditions were examined at sensor and source levels. Cerebellar stimulation with the double-cone coil resulted in large artefacts in the EEG trace. The addition of SOUND filtering to the cleaning pipeline improved the signal such that further analyses could be undertaken. The cortical potentials evoked by the active TMS conditions showed strong relationships with the responses to the multisensory control condition after ~50 ms. A distinct parietal component at ~42 ms was found following cerebellar double-cone stimulation. Cerebellar double-cone stimulation produces large artefacts in the EEG. Cerebellar-specific responses could not be reliably differentiated from sensory evoked potentials after ~50 ms. While evoked potentials differed across conditions at early latencies, it is unclear as to whether these represented TMS-related network activation of the cerebellarthalamocortical tract, or whether components were dominated by sensory contamination and/or coil-driven artefacts. Further work will be required to clarify the specific contribution of cerebellar-cortical connectivity to the observed early latency signals.
Publisher: American Physiological Society
Date: 03-2018
Abstract: Recent research has demonstrated a task-related modulation of postsynaptic intracortical inhibition within primary motor cortex for tasks requiring isolated (abduction) or synergistic (precision grip) muscle activation. The current study sought to investigate task-related changes in pre- and postsynaptic intracortical inhibition in motor cortex. In 13 young adults (22.5 ± 3.5 yr), paired-pulse transcranial magnetic stimulation (TMS) was used to measure short (SICI)- and long-interval intracortical inhibition (LICI) (i.e., postsynaptic motor cortex inhibition) in first dorsal interosseous muscle, and triple-pulse TMS was used to investigate changes in SICI-LICI interactions (i.e., presynaptic motor cortex inhibition). These measurements were obtained at rest and during muscle activation involving isolated abduction of the index finger and during a precision grip using the index finger and thumb. SICI was reduced during abduction and precision grip compared with rest, with greater reductions during precision grip. The modulation of LICI during muscle activation depended on the interstimulus interval (ISI 100 and 150 ms) but was not different between abduction and precision grip. For triple-pulse TMS, SICI was reduced in the presence of LICI at both ISIs in resting muscle (reflecting presynaptic motor cortex inhibition) but was only modulated at the 150-ms ISI during index finger abduction. Results suggest that synergistic contractions are accompanied by greater reductions in postsynaptic motor cortex inhibition than isolated contractions, but the contribution of presynaptic mechanisms to this disinhibition is limited. Furthermore, timing-dependent variations in LICI provide additional evidence that measurements using different ISIs may not represent activation of the same cortical process.
Publisher: Mary Ann Liebert Inc
Date: 10-2019
Abstract: While the potential long-term side effects of mild traumatic brain injury (mTBI) are becoming increasingly recognized, the associated neurophysiological mechanisms remain poorly understood. However, changes in cortical inhibitory function and neuroplasticity have been suggested as possible contributing factors. The current study applied transcranial magnetic stimulation (TMS) in conjunction with electroencephalography (combined TMS-EEG) to investigate further the effects of mTBI on these processes. In 17 patients with a history of mTBI and 15 healthy control subjects with no mTBI history, paired-pulse TMS-EEG measures of short- (SICI) and long-interval intracortical inhibition (LICI) were used to assess intracortical inhibitory function. Single-pulse TMS-EEG was used to assess neuroplastic changes in cortical excitability after application of continuous theta burst stimulation (cTBS, a plasticity inducing TMS paradigm). Inhibition of the TMS-evoked EEG potential after application of SICI and LICI was not different between groups. In contrast, the inhibitory effects of cTBS on both P30 (
Publisher: Wiley
Date: 29-05-2023
DOI: 10.1113/JP284204
Abstract: Previous research using transcranial magnetic stimulation (TMS) has demonstrated weakened connectivity between dorsal premotor cortex (PMd) and motor cortex (M1) with age. While this alteration is probably mediated by changes in the communication between the two regions, the effect of age on the influence of PMd on specific indirect (I) wave circuits within M1 remains unclear. The present study therefore investigated the influence of PMd on early and late I‐wave excitability in M1 of young and older adults. Twenty‐two young (mean ± SD, 22.9 ± 2.9 years) and 20 older (66.6 ± 4.2 years) adults participated in two experimental sessions involving either intermittent theta burst stimulation (iTBS) or sham stimulation over PMd. Changes within M1 following the intervention were assessed with motor‐evoked potentials (MEPs) recorded from the right first dorsal interosseous muscle. We applied posterior–anterior (PA) and anterior–posterior (AP) current single‐pulse TMS to assess corticospinal excitability (PA 1mV AP 1mV PA 0.5mV , early AP 0.5mV , late), and paired‐pulse TMS short intracortical facilitation for I‐wave excitability (PA SICF, early AP SICF, late). Although PMd iTBS potentiated PA 1mV and AP 1mV MEPs in both age groups (both P 0.05), the time course of this effect was delayed for AP 1mV in older adults ( P = 0.001). Furthermore, while AP 0.5mV , PA SICF and AP SICF were potentiated in both groups (all P 0.05), potentiation of PA 0.5mV was only apparent in young adults ( P 0.0001). While PMd influences early and late I‐wave excitability in young adults, direct PMd modulation of the early circuits is specifically reduced in older adults. image Interneuronal circuits responsible for late I‐waves within primary motor cortex (M1) mediate projections from dorsal premotor cortex (PMd), but this communication probably changes with advancing age. We investigated the effects of intermittent theta burst stimulation (iTBS) to PMd on transcranial magnetic stimulation (TMS) measures of M1 excitability in young and older adults. We found that PMd iTBS facilitated M1 excitability assessed with posterior–anterior (PA, early I‐waves) and anterior–posterior (AP, late I‐waves) current TMS in young adults, with a stronger effect for AP TMS. M1 excitability assessed with AP TMS also increased in older adults following PMd iTBS, but there was no facilitation for PA TMS responses. We conclude that changes in M1 excitability following PMd iTBS are specifically reduced for the early I‐waves in older adults, which could be a potential target for interventions that enhance cortical excitability in older adults.
Publisher: American Physiological Society
Date: 02-2018
Abstract: Fatiguing intermittent single-joint exercise causes an increase in corticospinal excitability and a decrease in intracortical inhibition when measured with peripherally recorded motor evoked potentials (MEPs) after transcranial magnetic stimulation (TMS). Combined TMS and electroencephalography (TMS-EEG) allows for more direct recording of cortical responses through the TMS-evoked potential (TEP). The aim of this study was to investigate the changes in the excitatory and inhibitory components of the TEP during fatiguing single-joint exercise. Twenty-three young (22 ± 2 yr) healthy subjects performed intermittent 30-s maximum voluntary contractions of the right first dorsal interosseous muscle, followed by a 30-s relaxation period repeated for a total of 15 min. Six single-pulse TMSs and one peripheral nerve stimulation (PNS) to evoke maximal M wave (M max ) were applied during each relaxation period. A total of 90 TMS pulses and 5 PNSs were applied before and after fatiguing exercise to record MEP and TEP. The litude of the MEP (normalized to M max ) increased during fatiguing exercise ( P 0.001). There were no changes in local and global P30, N45, and P180 of TEPs during the development of intermittent single-joint exercise-induced fatigue. Global analysis, however, revealed a decrease in N100 peak of the TEP during fatiguing exercise compared with before fatiguing exercise ( P = 0.02). The decrease in N100 suggests a fatigue-related decrease in global intracortical GABA B -mediated inhibition. The increase in corticospinal excitability typically observed during single-joint fatiguing exercise may be mediated by a global decrease in intracortical inhibition. NEW & NOTEWORTHY Fatiguing intermittent single-joint exercise causes an increase in corticospinal excitability and a decrease in intracortical inhibition when measured with transcranial magnetic stimulation (TMS)-evoked potentials from the muscle. The present study provides new and direct cortical evidence, using TMS-EEG to demonstrate that during single-joint fatiguing exercise there is a global decrease in intracortical GABA B -mediated inhibition.
Publisher: Frontiers Media SA
Date: 31-03-2017
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.NEUROSCIENCE.2019.05.049
Abstract: The response to motor training is improved when preceded by a bout of aerobic exercise. However, the effect of exercise at different intensities on motor performance is not well understood. The aim of the current study was therefore to compare the neurophysiological and functional response to training with a ballistic abduction task following a single 30-min bout of low intensity continuous cycling exercise, high-intensity interval cycling exercise, or rest. In 13 healthy young subjects, transcranial magnetic stimulation (TMS) was used to assess changes in the motor evoked potential (MEP), in addition to short-interval intracortical inhibition (SICI), whereas performance was assessed by changes in thumb abduction acceleration performed over two consecutive days. High-intensity exercise resulted in increased MEP litude and decreased SICI immediately after exercise. Following training, the increased MEP litude that reflects training-dependent plasticity was not different between exercise conditions. In contrast, reductions in SICI following training on day 1 were increased following high-intensity exercise, but decreased following low-intensity exercise, whereas cortical disinhibition was abolished after training on day 2. Finally, low-intensity exercise resulted in improved ballistic motor performance on both days. Our findings provide some evidence to suggest that low-intensity aerobic cycling is beneficial for performance during subsequent ballistic training. Furthermore, the effects of exercise intensity on motor training may depend on the type of task performed.
Publisher: Elsevier BV
Date: 05-2018
DOI: 10.1016/J.BRS.2017.12.013
Abstract: Alterations in inhibitory processes mediated by gamma-aminobutyric acid type B (GABA To utilise electroencephalography and TMS coregistration (TMS-EEG) to more directly assess age-related changes in GABA In 17 young (24.2 ± 1.1 years) and 17 older (71.4 ± 1.4 years) subjects, the TMS-evoked potential (TEP) was used to assess the global scalp response to single-pulse TMS and LICI applied at two interstimulus intervals of 100 ms (LICI For single-pulse stimulation, P30 litude was unaffected by age. Despite this, N45 litude was increased in older adults and both N100 and P180 showed altered spatial distributions. Furthermore, the latency of P30 was shorter, while the latency of P180 was longer, in the elderly. In addition, inhibition of the N100 and P180 was increased in older adults following both LICI These findings with TMS-EEG suggest that the ageing process is associated with a potentiation of GABAergic inhibition, particularly for the GABA
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.CLINPH.2015.04.062
Abstract: All previous studies using TMS to assess short-interval intracortical inhibition (SICI) in older adults have used a conventional coil orientation, which produces posterior-to-anterior (PA) current flow in the motor cortex. However, no studies have examined SICI in older adults by reversing the coil to induce anterior-to-posterior (AP) current flow, which is considered more sensitive at detecting SICI. Therefore, we investigated age-related changes in SICI using both PA and AP TMS across different conditioning stimulus intensities and muscle activation states. In 22 young and 20 older adults, SICI was assessed using PA and AP coil orientations, across a range of conditioning stimulus intensities (70-90% active motor threshold), and whilst participants kept their first dorsal interosseous (FDI) muscle either relaxed or active (2N force). There were no age-related differences in SICI using conventional PA TMS in resting or active FDI muscle. However, SICI was increased in elderly participants when assessed with reverse coil AP TMS in resting FDI. Coil orientation is a key factor to consider when assessing age-related differences in SICI. Reverse coil AP TMS can reveal age-related changes in SICI, which were previously not evident with conventional PA TMS. This may have implications for the assessment of SICI in some clinical populations that may show subtle differences in SICI circuitry.
Publisher: Wiley
Date: 23-05-2018
DOI: 10.1113/JP274641
Publisher: Wiley
Date: 26-10-2017
DOI: 10.1111/EJN.13729
Abstract: The ability of priming non-invasive brain stimulation (NIBS) to modulate neuroplasticity induction (i.e. metaplasticity) within primary motor cortex (M1) may be altered in older adults. Previous studies in young subjects suggest that consecutive NIBS protocols interact in a time-dependent manner and involve homoeostatic metaplasticity mechanisms. This was investigated in older adults by assessing the response to consecutive blocks of paired-associative stimulation (PAS) separated by different inter-PAS intervals (IPIs). Fifteen older (62-82 years) subjects participated in four sessions, with each session involving two PAS blocks separated by IPIs of 10 (IPI
Publisher: Elsevier BV
Date: 09-2019
DOI: 10.1016/J.NEUROBIOLAGING.2019.05.017
Abstract: Transcranial magnetic stimulation may represent an effective means for improving motor function in the elderly. The aim of this study was therefore to investigate the effects of paired associative stimulation (PAS a plasticity-inducing transcranial magnetic stimulation paradigm) on acquisition of a novel visuomotor task in young and older adults. Fourteen young (20.4 ± 0.6 years) and 13 older (69.0 ± 1.6 years) adults participated in 3 experimental sessions during which training was preceded (primed) by PAS. Within each session, the interstimulus interval used for PAS was set at either the N20 latency plus 5 ms (PAS
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.BRS.2017.01.003
Abstract: Primary motor cortex neuroplasticity is reduced in old adults, which may contribute to the motor deficits commonly observed in the elderly. Previous research in young subjects suggests that the neuroplastic response can be enhanced using non-invasive brain stimulation (NIBS), with a larger plastic response observed following priming with both long-term potentiation (LTP) and depression (LTD)-like protocols. However, it is not known if priming stimulation can also modulate plasticity in older adults. To investigate if priming NIBS can be used to modulate motor cortical plasticity in old subjects. In 16 young (22.3 ± 1.0 years) and 16 old (70.2 ± 1.7 years) subjects, we investigated the response to intermittent theta burst stimulation (iTBS LTP-like) when applied 10 min after sham stimulation, continuous TBS (cTBS LTD-like) or an identical block of iTBS. Corticospinal plasticity was assessed by recording changes in motor evoked potential (MEP) litude. In young subjects, priming with cTBS (cTBS + iTBS) resulted in larger MEPs than priming with either iTBS (iTBS + iTBS P = 0.001) or sham (sham + iTBS P < 0.0001), while larger MEPs were seen following iTBS + iTBS than sham + iTBS (P 0.9), whereas the response to cTBS + iTBS was reduced relative to iTBS + iTBS (P = 0.02) and sham + iTBS (P = 0.04). Priming TBS is ineffective for modifying M1 plasticity in older adults, which may limit the therapeutic use of priming stimulation in neurological conditions common in the elderly.
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.NEUROBIOLAGING.2017.03.024
Abstract: It is unclear how old age affects the neuronal mechanisms of motor learning. We reviewed the neuronal mechanisms of how healthy old and young adults acquire motor skills as assessed with transcranial magnetic stimulation. Quantitative meta-analyses of 11 studies, involving ballistic and visuomotor tasks performed by upper extremity muscles in 132 healthy old and 128 young adults, revealed that the motor practice-induced increase in corticospinal excitability (CSE) is task-dependent but not age-dependent, with an increase in CSE in both age groups after visuomotor but not ballistic training. In addition, short-interval intracortical inhibition (SICI) is reduced in old but not young adults, but only after visuomotor practice. In addition, correlation analyses in 123 old and 128 young adults showed that the magnitude of motor skill acquisition did not correlate with increases in CSE or decreases in SICI in either age group. Thus, there are subtle age-related differences in use-dependent plasticity but increases in CSE or decreases in SICI are not related to motor skill acquisition in healthy young or old adults.
Publisher: Frontiers Media SA
Date: 29-04-2015
Publisher: Cold Spring Harbor Laboratory
Date: 29-05-2023
DOI: 10.1101/2023.05.28.542670
Abstract: Although transcranial magnetic stimulation (TMS) research demonstrates that dorsal premotor cortex (PMd) influences neuroplasticity within primary motor cortex (M1), it is unclear how ageing modifies this communication. The present study investigated the influence of PMd on different indirect (I) wave inputs within M1 that mediate cortical plasticity in young and older adults. 15 young and 15 older participants completed two experimental sessions that examined the effects of intermittent theta burst stimulation (iTBS) to M1 when preceded by iTBS (PMd iTBS-M1 iTBS) or sham stimulation (PMd sham-M1 iTBS) to PMd. Changes in corticospinal excitability post-intervention were assessed with motor evoked potentials (MEP) recorded from right first dorsal interosseous using posterior-anterior (PA) and anterior-posterior (AP) current single-pulse TMS (PA 1mV AP 1mV PA 0.5mV , early I-wave AP 0.5mV , late I-wave). Although PA 1mV did not change post-intervention ( P = 0.628), PMd iTBS-M1 iTBS disrupted the expected facilitation of AP 1mV (to M1 iTBS) in young and older adults ( P = 0.002). Similarly, PMd iTBS-M1 iTBS disrupted PA 0.5mV facilitation in young and older adults ( P = 0.030), whereas AP 0.5mV facilitation was not affected in either group ( P = 0.218). This suggests that while PMd specifically influences the plasticity of early I-wave circuits, this communication is preserved in older adults.
Publisher: Wiley
Date: 07-04-2013
DOI: 10.1111/EJN.12203
Abstract: Obstructive sleep apnoea (OSA) is a respiratory condition occurring during sleep characterised by repeated collapse of the upper airway. Patients with OSA show altered brain structure and function that may manifest as impaired neuroplasticity. We assessed this hypothesis in 13 patients with moderate-to-severe OSA and 11 healthy control subjects. Transcranial magnetic stimulation was used to induce and measure neuroplastic changes in the motor cortex by assessing changes in motor-evoked potentials (MEPs) in a hand muscle. Baseline measurements of cortical excitability included active (AMT) and resting motor thresholds (RMT), and the maximal stimulator output producing a 1-mV MEP. Intracortical inhibition (ICI) was investigated with short- and long-interval ICI paradigms (SICI and LICI, respectively), and neuroplastic changes were induced using continuous theta burst stimulation (cTBS). At baseline, differences were found between groups for RMT (9.5% maximal stimulator output higher in OSA) and 1-mV MEPs (10.3% maximal stimulator output higher in OSA), but not AMT. No differences were found between groups for SICI or LICI. The response to cTBS was different between groups, with control subjects showing an expected reduction in MEP litude after cTBS, whereas the MEPs in patients with OSA did not change. The lack of response to cTBS suggests impaired long-term depression-like neuroplasticity in patients with OSA, which may be a consequence of sleep fragmentation or chronic blood gas disturbance in sleep. This reduced neuroplastic capacity may have implications for the learning, retention or consolidation of motor skills in patients with OSA.
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1016/J.CLINPH.2017.02.011
Abstract: To examine the effect of priming paired associative stimulation (PAS) on the modulation of motor cortex (M1) plasticity in young and old adults. Fifteen young (20-27yrs) and 15 old (61-79yrs) subjects participated in 3 experimental sessions, with each session involving two consecutive PAS protocols separated by 10mins. The first (priming) protocol was either PAS In young subjects, MEPs were larger after PAS Data show that priming with PAS These findings suggest a limited utility of priming PAS for augmenting plasticity induction in old adults.
Publisher: Springer Science and Business Media LLC
Date: 12-05-0009
DOI: 10.1007/S12311-021-01278-Z
Abstract: Interactions between cerebellum (CB) and primary motor cortex (M1) are critical for effective motor function. Although the associated neurophysiological processes are yet to be fully characterised, a growing body of work using non-invasive brain stimulation (NIBS) techniques has significantly progressed our current understanding. In particular, recent developments with both transcranial magnetic (TMS) and direct current (tDCS) stimulation suggest that CB modulates the activity of local excitatory interneuronal circuits within M1. These circuits are known to be important both physiologically and functionally, and understanding the nature of their connectivity with CB therefore has the potential to provide important insight for NIBS applications. Consequently, this mini-review provides an overview of the emerging literature that has investigated interactions between CB and the intracortical excitatory circuits of M1.
Publisher: Frontiers Media SA
Date: 14-04-2023
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.CLINPH.2013.11.015
Abstract: The aim of the current study was to investigate the effect of increasing test motor evoked potential (MEP) litude on short- (SICI) and long-interval intracortical inhibition (LICI) at rest and during activation of the first dorsal interosseous (FDI) muscle. In 22 young subjects, a conditioning-test transcranial magnetic stimulation (TMS) paradigm was used to assess SICI and LICI at 5 different test TMS intensities (110-150% motor threshold) in resting and active FDI. In 9 additional subjects, SICI and LICI data were quantified when the test MEP litude represented specific proportions of the maximal compound muscle action potential (Mmax) in each subject. Test TMS intensity influenced SICI and LICI in rest and active FDI muscle. The normalised test MEP litude (%Mmax) did not influence SICI at rest, whereas there was a decrease in LICI at rest and an increase in SICI in active FDI with an increased normalised test MEP litude (%Mmax). Our results demonstrate differential effects of normalised test MEP litude (%Mmax) on SICI and LICI in resting and active FDI muscle. Estimation of SICI and LICI under some circumstances may be influenced by the normalised test MEP litude in subject populations with different Mmax characteristics.
Publisher: Cold Spring Harbor Laboratory
Date: 25-05-2022
DOI: 10.1101/2022.05.23.493173
Abstract: Repetitive paired-pulse transcranial magnetic stimulation (iTMS) at indirect (I) wave intervals increases motor-evoked potentials (MEPs) produced by TMS to primary motor cortex (M1). However, the effects of iTMS at early and late intervals on the plasticity of specific I-wave circuits remains unclear. The current study therefore aimed to assess how the timing of iTMS influences intracortical excitability within early and late I-wave circuits. To investigate the cortical effects of iTMS more directly, changes due to the intervention were also assessed using combined TMS-electroencephalography (EEG). Eighteen young adults (24.6 ± 4.2 years) participated in four sessions in which iTMS targeting early (1.5 ms interval iTMS 1.5 ) or late (4.0 ms interval iTMS 4.0 ) I-waves was applied over M1. Neuroplasticity was assessed using both posterior-to-anterior (PA) and anterior-to-posterior (AP) stimulus directions to record MEPs and TEPs before and after iTMS. SICF at inter-stimulus intervals of 1.5 and 4.0 ms was also used to index I-wave activity. MEP litude was increased after iTMS ( P 0.01) and this was greater for PA responses ( P 0.01), but not different between iTMS intervals ( P = 0.9). Irrespective of iTMS interval and coil current, SICF was facilitated after the intervention ( P 0.01). While the N45 produced by AP stimulation was reduced by iTMS 1.5 ( P = 0.04), no other changes in TEP litude were observed. The timing of iTMS failed to influence which I-wave circuits were potentiated by the intervention. In contrast, reductions in the N45 suggest that the neuroplastic effects of iTMS may include disinhibition of intracortical inhibitory processes.
Publisher: Frontiers Media SA
Date: 30-06-2021
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.BRS.2015.12.005
Abstract: The modulation of intracortical inhibition is thought to be impaired in older adults, which may contribute to their reduced fine motor control, particularly during lengthening muscle contractions. To quantify the magnitude of intracortical inhibition and movement performance during postural, shortening and lengthening contractions of a hand muscle in young and old adults. In 18 young (23.2 ± 4.2) and 16 old (70.6 ± 6.5) subjects, paired-pulse transcranial magnetic stimulation (TMS) was used to assess short-interval intracortical inhibition (SICI) and long-interval intracortical inhibition (LICI) during a movement task involving the first dorsal interosseous muscle. The task required a constant load (50 g) to be slowly lifted and lowered using the index finger while single- or paired-pulse TMS was delivered during the shortening or lengthening contraction. Relative to postural contractions, SICI during shortening contractions was reduced by 29% in young subjects (P < 0.0001) and 43% in old subjects (P < 0.0001), whereas SICI during lengthening contractions was reduced by 11% in young subjects (P = 0.0004) and 33% in old subjects (P < 0.0001). Furthermore, SICI was significantly less in older adults during lengthening contractions (P-values < 0.01). For LICI, inhibition was not influenced by contraction type in old subjects, but was increased by 11% during shortening contractions (P < 0.0001) and by 9% during lengthening contractions in young subjects (P = 0.0008). In addition, old subjects showed significantly less LICI than young subjects in each movement phase (both P-values < 0.05). Shortening and lengthening contractions with a constant load are associated with a modulation of GABAergic inhibition that is altered by healthy ageing.
Publisher: Elsevier BV
Date: 09-2014
DOI: 10.1016/J.BRS.2014.06.014
Abstract: Effects of age on the assessment of intracortical inhibition with paired-pulse transcranial magnetic stimulation (TMS) have been variable, which may be due to between-study differences in test TMS intensity and test motor evoked potential (MEP) litude. To investigate age-related differences in short- (SICI) and long-interval intracortical inhibition (LICI) across a range of test TMS intensities and test MEP litudes. In 22 young and 18 older subjects, SICI and LICI were recorded at a range of test TMS intensities (110%-150% of motor threshold) while the first dorsal interosseous (FDI) muscle was at rest, or producing a precision grip of the index finger and thumb. Data were subsequently compared according to the litude of the MEP produced by the test alone TMS. When pooled across all test TMS intensities, SICI in resting muscle and LICI in active muscle were similar in young and older adults, whereas SICI in active muscle and LICI in resting muscle were reduced in older adults. Regrouping data based on test MEP litude demonstrated similar effects of age for SICI and LICI in resting muscle, whereas more subtle differences between age groups were revealed for SICI and LICI in active muscle. Advancing age influences GABA-mediated intracortical inhibition, but the outcome is dependent on the experimental conditions. Age-related differences in SICI and LICI were influenced by test TMS intensity and test MEP litude, suggesting that these are important considerations when assessing intracortical inhibition in older adults, particularly in an active muscle.
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.NEUROSCIENCE.2019.11.022
Abstract: The effects of muscle fatigue are known to be altered in older adults, and age-related changes in the brain are likely to be a contributing factor. However, the neural mechanisms underlying these changes are not known. The aim of the current study was to use transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) to investigate age-related changes in cortical excitability with muscle fatigue. In 23 young (mean age ± SD: 22 ± 2 years) and 17 older (mean age ± SD: 68.3 ± 5.6 years) adults, single-pulse TMS-EEG was applied before, during and after the performance of fatiguing, intermittent isometric abduction of the index finger. Motor-evoked potential (MEP) measures of cortical excitability were increased during (estimated mean difference, 123.3% P 0.5). For TMS-EEG, the litude of the P30 and P180 potentials were unaffected by fatigue in older participants (P > 0.05). In contrast, the litude of the N45 potential in older adults was significantly reduced both during (positive cluster: mean voltage difference = 0.7 µV, P < 0.005 negative cluster: mean voltage difference = 0.9 µV, P < 0.0005) and after (mean voltage difference = 0.5 µV, P < 0.005) fatiguing exercise, whereas this response was absent in young participants. These results suggest that performance of maximal intermittent isometric exercise in old but not young adults is associated with modulation of cortical inhibition likely mediated by activation of gamma-aminobutyric acid type A receptors.
Publisher: Cold Spring Harbor Laboratory
Date: 04-12-2020
DOI: 10.1101/2020.12.03.410944
Abstract: The late indirect (I) waves recruited by transcranial magnetic stimulation (TMS) over primary motor cortex (M1) can be modulated using I-wave periodicity repetitive TMS (iTMS). The purpose of this study was to determine if the response to iTMS is influenced by different interstimulus intervals (ISIs) targeting late I-waves, and whether these responses were associated with in idual variations in intracortical excitability. 17 young (27.2 ± 6.4 years, 12 females) healthy adults received iTMS at late I-wave intervals (4.0, 4.5 & 5.0 ms) in three separate sessions. Changes due to each intervention were examined with motor evoked potential (MEP) litudes and short-interval intracortical facilitation (SICF) using both posterior-anterior (PA) and anterior-posterior (AP) TMS current directions. Changes in MEP litude and SICF were influenced by iTMS ISI, with the greatest facilitation for ISIs at 4 and 5 ms with PA TMS, and 4 ms with AP TMS. Maximum SICF at baseline (irrespective of ISI) was associated with increased iTMS response, but only for PA stimulation. These results suggest that modifying iTMS parameters targeting late I-waves can influence M1 plasticity. They also suggest that maximum SICF may be a means by which responders to iTMS targeting the late I-waves could be identified.
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.NEUROSCIENCE.2016.06.002
Abstract: Short-term immobilization that reduces muscle use for 8-10h is known to influence cortical excitability and motor performance. However, the mechanisms through which this is achieved, and whether these changes can be used to modify cortical plasticity and motor skill learning, are not known. The purpose of this study was to investigate the influence of short-term immobilization on use-dependent cortical plasticity, motor learning and retention. Twenty-one adults were ided into control and immobilized groups, both of which underwent two experimental sessions on consecutive days. Within each session, transcranial magnetic stimulation (TMS) was used to assess motor-evoked potential (MEP) litudes, short- (SICI) and long-interval intracortical inhibition (LICI), and intracortical facilitation (ICF) before and after a grooved pegboard task. Prior to the second training session, the immobilized group underwent 8h of left hand immobilization targeting the index finger, while control subjects were allowed normal limb use. Immobilization produced a reduction in MEP litudes, but no change in SICI, LICI or ICF. While motor performance improved for both groups in each session, the level of performance was greater 24-h later in control, but not immobilized subjects. Furthermore, training-related MEP facilitation was greater after, compared with before, immobilization. These results indicate that immobilization can modulate use-dependent plasticity and the retention of motor skills. They also suggest that changes in intracortical excitability are unlikely to contribute to the immobilization-induced modification of cortical excitability.
Publisher: Elsevier BV
Date: 07-2020
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.BRS.2016.08.004
Abstract: Long-interval intracortical inhibition (LICI) is a transcranial magnetic stimulation (TMS) paradigm that uses paired magnetic stimuli separated by 100-200 ms to investigate the activity of cortical GABAergic interneurons. While commonly applied, the mechanisms contributing to LICI are not well understood, and growing evidence suggests that inhibition observed at different interstimulus intervals (ISI) may involve non-identical processes. This study aims to utilise combined TMS-EEG to more thoroughly characterise LICI at different ISIs, as the TMS-evoked EEG potential (TEP) can provide more direct insight into the cortical response to stimulation that is not subject to variations in spinal cord excitability that can confound the motor evoked potential (MEP). In 12 subjects (22.6 ± 0.9 years), LICI was applied using two ISIs of 100 ms (LICI Analysis of EEG data within a region of interest (C3 electrode) showed that test alone stimulation produced three consistent TEP peaks (corresponding to P30, N100 and P180) that were all significantly inhibited following paired-pulse stimulation. However, for P30, inhibition varied between LICI conditions, with reduced litude following LICI These findings suggest that LICI
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.BRS.2019.08.003
Abstract: Recent work suggests that the function of intracortical interneurons activated by transcranial magnetic stimulation (TMS) is modified in older adults, with the circuits generating short-interval intracortical facilitation (SICF) at longer intervals appearing to be particularly affected. To use SICF to quantify age-related changes in the excitability and recruitment of late synaptic inputs to corticospinal neurons, and investigate if changes within these circuits contribute to altered motor performance in older adults. SICF was recorded with 3 different conditioning intensities in 23 young (23.0 ± 4.2 years) and 21 older (67.1 ± 1.1 years) adults. These measures were performed with conventional (posterior-anterior, PA) and reverse (anterior-posterior, AP) current directions using interstimulus intervals targeting late synaptic inputs to corticospinal neurons (3.5-5.3 ms). Peak SICF recorded with a PA current (SICF These results suggest that there are age-related changes in late synaptic inputs to corticospinal neurons and that these changes influence fine motor performance.
Publisher: Public Library of Science (PLoS)
Date: 10-07-2020
Publisher: American Physiological Society
Date: 05-2013
DOI: 10.1152/JAPPLPHYSIOL.01378.2012
Abstract: Regular physical activity is associated with enhanced plasticity in the motor cortex, but the effect of a single session of aerobic exercise on neuroplasticity is unknown. The aim of this study was to compare corticospinal excitability and plasticity in the upper limb cortical representation following a single session of lower limb cycling at either low or moderate intensity, or a control condition. We recruited 25 healthy adults to take part in three experimental sessions. Cortical excitability was examined using transcranial magnetic stimulation to elicit motor-evoked potentials in the right first dorsal interosseus muscle. Levels of serum brain-derived neurotrophic factor and cortisol were assessed throughout the experiments. Following baseline testing, participants cycled on a stationary bike at a workload equivalent to 57% (low intensity, 30 min) or 77% age-predicted maximal heart rate (moderate intensity, 15 min), or a seated control condition. Neuroplasticity within the primary motor cortex was then examined using a continuous theta burst stimulation (cTBS) paradigm. We found that exercise did not alter cortical excitability. Following cTBS, there was a transient inhibition of first dorsal interosseus motor-evoked potentials during control and low-intensity conditions, but this was only significantly different following the low-intensity state. Moderate-intensity exercise alone increased serum cortisol levels, but brain-derived neurotrophic factor levels did not increase across any condition. In summary, low-intensity cycling promoted the neuroplastic response to cTBS within the motor cortex of healthy adults. These findings suggest that light exercise has the potential to enhance the effectiveness of motor learning or recovery following brain damage.
Publisher: American Physiological Society
Date: 05-2021
Abstract: Combined single-pulse transcranial magnetic stimulation (TMS) and electroencephalography (EEG) has been used to probe the features of local networks in the cerebral cortex. Here, we investigated whether we can use this approach to explore long-range connections between the cerebellum and cerebral cortex. Ten healthy adults received single-pulse suprathreshold TMS to the cerebellum and an occipital arietal control site with double-cone and figure-of-eight coils while cerebral activity was recorded. A multisensory electrical control condition was used to simulate the sensation of the double-cone coil at the cerebellar site. Two cleaning pipelines were compared, and the spatiotemporal relationships of the EEG output between conditions were examined at sensor and source levels. Cerebellar stimulation with the double-cone coil resulted in large artifact in the EEG trace. The addition of SOUND filtering to the cleaning pipeline improved the signal such that further analyses could be undertaken. The cortical potentials evoked by the active TMS conditions showed strong relationships with the responses to the multisensory control condition after ∼50 ms. A distinct parietal component at ∼42 ms was found following cerebellar double-cone stimulation. Although evoked potentials differed across all conditions at early latencies, it is unclear as to whether these represented TMS-related network activation of the cerebellarthalamocortical tract, or whether components were dominated by sensory contamination and/or coil-driven artifact. This study highlights the need for caution when interpreting outcomes from cerebellar TMS-EEG studies.
Publisher: Public Library of Science (PLoS)
Date: 12-07-2022
DOI: 10.1371/JOURNAL.PONE.0271311
Abstract: While previous research using transcranial magnetic stimulation (TMS) suggest that cerebellum (CB) influences the neuroplastic response of primary motor cortex (M1), the role of different indirect (I) wave inputs in M1 mediating this interaction remains unclear. The aim of this study was therefore to assess how CB influences neuroplasticity of early and late I-wave circuits. 22 young adults (22 ± 2.7 years) participated in 3 sessions in which I-wave periodicity repetitive transcranial magnetic stimulation (iTMS) was applied over M1 during concurrent application of cathodal transcranial direct current stimulation over CB (tDCS CB ). In each session, iTMS either targeted early I-waves (1.5 ms interval iTMS 1 . 5 ), late I-waves (4.5 ms interval iTMS 4 . 5 ), or had no effect (variable interval iTMS Sham ). Changes due to the intervention were examined with motor evoked potential (MEP) litude using TMS protocols measuring corticospinal excitability (MEP 1mV ) and the strength of CB-M1 connections (CBI). In addition, we indexed I-wave activity using short-interval intracortical facilitation (SICF) and low-intensity single-pulse TMS applied with posterior-anterior (MEP PA ) and anterior-posterior (MEP AP ) current directions. Following both active iTMS sessions, there was no change in MEP 1mV , CBI or SICF (all P 0.05), suggesting that tDCS CB broadly disrupted the excitatory response that is normally seen following iTMS. However, although MEP AP also failed to facilitate after the intervention ( P 0.05), MEP PA potentiated following both active iTMS sessions (both P 0.05). This differential response between current directions could indicate a selective effect of CB on AP-sensitive circuits.
Publisher: Springer Science and Business Media LLC
Date: 16-07-2021
Publisher: Elsevier BV
Date: 11-2020
Publisher: Cold Spring Harbor Laboratory
Date: 31-01-2022
DOI: 10.1101/2022.01.30.478397
Abstract: While previous research using transcranial magnetic stimulation (TMS) suggest that cerebellum (CB) influences the neuroplastic response of primary motor cortex (M1), the role of different indirect (I) wave inputs in M1 mediating this interaction remains unclear. The aim of this study was therefore to assess how CB influences neuroplasticity of early and late I-wave circuits. 22 young adults (22 ± 2.7 years) participated in 3 sessions in which I-wave periodicity repetitive transcranial magnetic stimulation (iTMS) was applied over M1 during concurrent application of cathodal transcranial direct current stimulation over CB (tDCS CB ). In each session, iTMS either targeted early I-waves (1.5 ms interval iTMS 1.5 ), late I-waves (4.5 ms interval iTMS 4.5 ), or had no effect (variable interval iTMS Sham ). Changes due to the intervention were examined with motor evoked potential (MEP) litude using TMS protocols measuring corticospinal excitability (MEP 1mV ) and the strength of CB-M1 connections (CBI). In addition, we indexed I-wave activity using short-interval intracortical facilitation (SICF) and low-intensity single-pulse TMS applied with posterior-anterior (MEP PA ) and anterior-posterior (MEP AP ) current directions. Following both active iTMS sessions, there was no change in MEP 1mV , CBI or SICF (all P 0.05), suggesting that tDCS CB broadly disrupted the excitatory response that is normally seen following iTMS. However, although MEP AP also failed to facilitate after the intervention ( P 0.05), MEP PA potentiated following both active iTMS sessions (both P 0.05). This differential response between current directions suggests that the disruptive effects of CB modulation on M1 plasticity may be selectively mediated by AP-sensitive circuits (also likely recruited with MEP 1mV , CBI, and SICF).
Start Date: 06-2020
End Date: 12-2024
Amount: $297,621.00
Funder: Australian Research Council
View Funded ActivityStart Date: 2023
End Date: 12-2025
Amount: $435,298.00
Funder: Australian Research Council
View Funded Activity