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1.
J Cogn Neurosci ; 36(7): 1395-1411, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38683725

ABSTRACT

Past research has found that the speed of the action cancellation process is influenced by the sensory modality of the environmental change that triggers it. However, the effect on selective stopping processes (where participants must cancel only one component of a multicomponent movement) remains unknown, despite these complex movements often being required as we navigate our busy modern world. Thirty healthy adults (mean age = 31.1 years, SD = 10.5) completed five response-selective stop signal tasks featuring different combinations of "go signal" modality (the environmental change baring an imperative to initiate movement; auditory or visual) and "stop signal" modality (the environmental change indicating that action cancellation is required: auditory, visual, or audiovisual). EMG recordings of effector muscles allowed detailed comparison of the characteristics of voluntary action and cancellation between tasks. Behavioral and physiological measures of stopping speed demonstrated that the modality of the go signal influenced how quickly participants cancelled movement in response to the stop signal: Stopping was faster in two cross-modal experimental conditions (auditory go - visual stop; visual go - auditory stop), than in two conditions using the same modality for both signals. A separate condition testing for multisensory facilitation revealed that stopping was fastest when the stop signal consisted of a combined audiovisual stimulus, compared with all other go-stop stimulus combinations. These findings provide novel evidence regarding the role of attentional networks in action cancellation and suggest modality-specific cognitive resources influence the latency of the stopping process.


Subject(s)
Auditory Perception , Electromyography , Psychomotor Performance , Visual Perception , Humans , Adult , Male , Female , Young Adult , Auditory Perception/physiology , Psychomotor Performance/physiology , Visual Perception/physiology , Inhibition, Psychological , Reaction Time/physiology , Acoustic Stimulation , Photic Stimulation
2.
Cogn Psychol ; 149: 101628, 2024 03.
Article in English | MEDLINE | ID: mdl-38199181

ABSTRACT

Response inhibition is a key attribute of human executive control. Standard stop-signal tasks require countermanding a single response; the speed at which that response can be inhibited indexes the efficacy of the inhibitory control networks. However, more complex stopping tasks, where one or more components of a multi-component action are cancelled (i.e., response-selective stopping) cannot be explained by the independent-race model appropriate for the simple task (Logan and Cowan 1984). Healthy human participants (n=28; 10 male; 19-40 years) completed a response-selective stopping task where a 'go' stimulus required simultaneous (bimanual) button presses in response to left and right pointing green arrows. On a subset of trials (30%) one, or both, arrows turned red (constituting the stop signal) requiring that only the button-press(es) associated with red arrows be cancelled. Electromyographic recordings from both index fingers (first dorsal interosseous) permitted the assessment of both voluntary motor responses that resulted in overt button presses, and activity that was cancelled prior to an overt response (i.e., partial, or covert, responses). We propose a simultaneously inhibit and start (SIS) model that extends the independent race model and provides a highly accurate account of response-selective stopping data. Together with fine-grained EMG analysis, our model-based analysis offers converging evidence that the selective-stop signal simultaneously triggers a process that stops the bimanual response and triggers a new unimanual response corresponding to the green arrow. Our results require a reconceptualisation of response-selective stopping and offer a tractable framework for assessing such tasks in healthy and patient populations. Significance Statement Response inhibition is a key attribute of human executive control, frequently investigated using the stop-signal task. After initiating a motor response to a go signal, a stop signal occasionally appears at a delay, requiring cancellation of the response. This has been conceptualised as a 'race' between the go and stop processes, with the successful (or failed) cancellation determined by which process wins the race. Here we provide a novel computational model for a complex variation of the stop-signal task, where only one component of a multicomponent action needs to be cancelled. We provide compelling muscle activation data that support our model, providing a robust and plausible framework for studying these complex inhibition tasks in both healthy and pathological cohorts.


Subject(s)
Executive Function , Psychomotor Performance , Humans , Male , Reaction Time/physiology , Psychomotor Performance/physiology , Executive Function/physiology , Inhibition, Psychological
3.
Cogn Affect Behav Neurosci ; 23(1): 84-99, 2023 02.
Article in English | MEDLINE | ID: mdl-36385251

ABSTRACT

Response-selective stopping requires cancellation of only one component of a multicomponent action. While research has investigated how delays to the continuing action components ("stopping interference") can be attenuated by way of contextual cues of the specific stopping demands ("foreknowledge"), little is known of the underlying neural mechanisms. Twenty-seven, healthy, young adults undertook a multicomponent stop-signal task. For two thirds of trials, participants responded to an imperative (go) stimulus (IS) with simultaneous button presses using their left and right index fingers. For the remaining one third of trials, the IS was followed by a stop-signal requiring cancellation of only the left, or right, response. To manipulate foreknowledge of stopping demands, a cue preceded the IS that informed participants which hand might be required to stop (proactive) or provided no such information (reactive). Transcranial magnetic stimulation (TMS) assessed corticospinal excitability (CSE) as well as short- and long-interval interhemispheric inhibition (SIHI, LIHI) between the primary motor cortices. Proactive cues reduced, but did not eliminate, stopping interference relative to the reactive condition. Relative to TMS measures at cue onset, decreases in CSE (both hands and both cue conditions) and LIHI (both hands, proactive condition only) were observed during movement preparation. During movement cancellation, LIHI reduction in the continuing hand was greater than that in the stopping hand and greater than LIHI reductions in both hands during execution of multicomponent responses. Our results indicate that foreknowledge attenuates stopping interference and provide evidence for a novel role of LIHI, mediated via prefrontal regions, in facilitating continuing action components.


Subject(s)
Cues , Motor Cortex , Young Adult , Humans , Transcranial Magnetic Stimulation/methods , Motor Cortex/physiology , Evoked Potentials, Motor/physiology , Hand , Reaction Time/physiology
4.
BMC Neurol ; 22(1): 266, 2022 Jul 18.
Article in English | MEDLINE | ID: mdl-35850660

ABSTRACT

BACKGROUND: The worldwide prevalence of dementia is rapidly rising. Alzheimer's disease (AD), accounts for 70% of cases and has a 10-20-year preclinical period, when brain pathology covertly progresses before cognitive symptoms appear. The 2020 Lancet Commission estimates that 40% of dementia cases could be prevented by modifying lifestyle/medical risk factors. To optimise dementia prevention effectiveness, there is urgent need to identify individuals with preclinical AD for targeted risk reduction. Current preclinical AD tests are too invasive, specialist or costly for population-level assessments. We have developed a new online test, TAS Test, that assesses a range of motor-cognitive functions and has capacity to be delivered at significant scale. TAS Test combines two innovations: using hand movement analysis to detect preclinical AD, and computer-human interface technologies to enable robust 'self-testing' data collection. The aims are to validate TAS Test to [1] identify preclinical AD, and [2] predict risk of cognitive decline and AD dementia. METHODS: Aim 1 will be addressed through a cross-sectional study of 500 cognitively healthy older adults, who will complete TAS Test items comprising measures of motor control, processing speed, attention, visuospatial ability, memory and language. TAS Test measures will be compared to a blood-based AD biomarker, phosphorylated tau 181 (p-tau181). Aim 2 will be addressed through a 5-year prospective cohort study of 10,000 older adults. Participants will complete TAS Test annually and subtests of the Cambridge Neuropsychological Test Battery (CANTAB) biennially. 300 participants will undergo in-person clinical assessments. We will use machine learning of motor-cognitive performance on TAS Test to develop an algorithm that classifies preclinical AD risk (p-tau181-defined) and determine the precision to prospectively estimate 5-year risks of cognitive decline and AD. DISCUSSION: This study will establish the precision of TAS Test to identify preclinical AD and estimate risk of cognitive decline and AD. If accurate, TAS Test will provide a low-cost, accessible enrichment strategy to pre-screen individuals for their likelihood of AD pathology prior to more expensive tests such as blood or imaging biomarkers. This would have wide applications in public health initiatives and clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05194787 , 18 January 2022. Retrospectively registered.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Aged , Alzheimer Disease/diagnosis , Alzheimer Disease/epidemiology , Alzheimer Disease/psychology , Amyloid beta-Peptides , Biomarkers , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/psychology , Cross-Sectional Studies , Humans , Neuropsychological Tests , Prospective Studies , tau Proteins
5.
Neuroimage ; 185: 490-512, 2019 01 15.
Article in English | MEDLINE | ID: mdl-30342977

ABSTRACT

Response inhibition, the ability to withhold a dominant and prepotent response following a change in circumstance or sensory stimuli, declines with advancing age. While non-invasive brain stimulation (NiBS) has shown promise in alleviating some cognitive and motor functions in healthy older individuals, NiBS research focusing on response inhibition has mostly been conducted on younger adults. These extant studies have primarily focused on modulating the activity of distinct neural regions known to be critical for response inhibition, including the right inferior frontal gyrus (rIFG) and the pre-supplementary motor area (pre-SMA). However, given that changes in structural and functional connectivity have been associated with healthy aging, this review proposes that NiBS protocols aimed at modulating the functional connectivity between the rIFG and pre-SMA may be the most efficacious approach to investigate-and perhaps even alleviate-age-related deficits in inhibitory control.


Subject(s)
Brain , Inhibition, Psychological , Neural Pathways , Transcranial Direct Current Stimulation/methods , Aged , Aged, 80 and over , Humans , Middle Aged
6.
J Neurophysiol ; 116(2): 575-86, 2016 08 01.
Article in English | MEDLINE | ID: mdl-27169508

ABSTRACT

Performance benefits conferred in the untrained limb after unilateral motor practice are termed cross-limb transfer. Although the effect is robust, the neural mechanisms remain incompletely understood. In this study we used noninvasive brain stimulation to reveal that the neural adaptations that mediate motor learning in the trained limb are distinct from those that underlie cross-limb transfer to the opposite limb. Thirty-six participants practiced a ballistic motor task with their right index finger (150 trials), followed by intermittent theta-burst stimulation (iTBS) applied to the trained (contralateral) primary motor cortex (cM1 group), the untrained (ipsilateral) M1 (iM1 group), or the vertex (sham group). After stimulation, another 150 training trials were undertaken. Motor performance and corticospinal excitability were assessed before motor training, pre- and post-iTBS, and after the second training bout. For all groups, training significantly increased performance and excitability of the trained hand, and performance, but not excitability, of the untrained hand, indicating transfer at the level of task performance. The typical facilitatory effect of iTBS on MEPs was reversed for cM1, suggesting homeostatic metaplasticity, and prior performance gains in the trained hand were degraded, suggesting that iTBS interfered with learning. In stark contrast, iM1 iTBS facilitated both performance and excitability for the untrained hand. Importantly, the effects of cM1 and iM1 iTBS on behavior were exclusive to the hand contralateral to stimulation, suggesting that adaptations within the untrained M1 contribute to cross-limb transfer. However, the neural processes that mediate learning in the trained hemisphere vs. transfer in the untrained hemisphere appear distinct.


Subject(s)
Adaptation, Physiological/physiology , Evoked Potentials, Motor/physiology , Extremities/physiology , Learning/physiology , Motor Cortex/physiology , Transfer, Psychology/physiology , Adult , Analysis of Variance , Electromyography , Female , Functional Laterality , Humans , Male , Psychomotor Performance , Regression Analysis , Transcranial Magnetic Stimulation , Young Adult
7.
Exp Brain Res ; 234(12): 3411-3423, 2016 12.
Article in English | MEDLINE | ID: mdl-27450080

ABSTRACT

Despite holding significant promise for counteracting the deleterious effects of ageing on cognitive and motor function, little is known of the effects of facilitatory non-invasive brain stimulation (NBS) techniques on corticospinal excitability (CSE) in older adults. Thirty-three older adults (≥60 years) participated in four NBS sessions on separate days, receiving 10- and 20-min anodal transcranial direct current stimulation (atDCS), and 300 and 600 pulses of intermittent theta burst stimulation (iTBS) over the left M1. Motor-evoked potentials measured in the contralateral hand served as a measure of CSE before and for 30 min following each NBS intervention. At the group level, generalized post-stimulation CSE increases were observed (p < 0.001) with no significant differences between the two durations of each stimulation type (atDCS: p = 0.5; iTBS: p = 0.9). For individuals exhibiting overall facilitatory change to atDCS ('responders', n = 10), 20-min atDCS resulted in longer lasting CSE facilitation than 10 min. No such difference was observed between the two iTBS protocols. Considerable variability was observed inter-individually, where 52-58 % of the cohort exhibited the expected facilitation after each of the NBS protocols-as well as intra-individually, where 45-48 % of the cohort maintained consistent post-stimulation responses across the varying durations and types of stimulation. In conclusion, as shown previously in young adults, older adults demonstrate substantial variability in response to different facilitatory NBS protocols. Studies to assess the intra-individual reliability of these protocols are critical to progress towards translation of appropriate protocols (i.e. those that elicit the greatest response for each individual) into clinical practice.


Subject(s)
Motor Cortex/physiology , Neuronal Plasticity/physiology , Transcranial Direct Current Stimulation , Transcranial Magnetic Stimulation/methods , Aged , Analysis of Variance , Biophysics , Electromyography , Evoked Potentials, Motor/physiology , Functional Laterality , Humans , Locomotion , Male , Middle Aged , Muscle Contraction , Muscle Strength , Pyramidal Tracts/physiology , Time Factors
8.
Neural Plast ; 2015: 578620, 2015.
Article in English | MEDLINE | ID: mdl-26167305

ABSTRACT

Intermittent theta burst stimulation (iTBS) has the potential to enhance corticospinal excitability (CSE) and subsequent motor learning. However, the effects of iTBS following motor learning are unknown. The purpose of the present study was to explore the effect of iTBS on CSE and performance following motor learning. Therefore twenty-four healthy participants practiced a ballistic motor task for a total of 150 movements. iTBS was subsequently applied to the trained motor cortex (STIM group) or the vertex (SHAM group). Performance and CSE were assessed before motor learning and before and after iTBS. Training significantly increased performance and CSE in both groups. In STIM group participants, subsequent iTBS significantly reduced motor performance with smaller reductions in CSE. CSE changes as a result of motor learning were negatively correlated with both the CSE changes and performance changes as a result of iTBS. No significant effects of iTBS were found for SHAM group participants. We conclude that iTBS has the potential to degrade prior motor learning as a function of training-induced CSE changes. That means the expected LTP-like effects of iTBS are reversed following motor learning.


Subject(s)
Learning/physiology , Motor Activity , Motor Cortex/physiology , Pyramidal Tracts/physiology , Adult , Evoked Potentials, Motor , Female , Humans , Male , Psychomotor Performance/physiology , Transcranial Magnetic Stimulation/methods , Young Adult
9.
J Neurophysiol ; 111(5): 897-9, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24285870

ABSTRACT

Seminal work in animals indicates that learning a motor task results in long-term potentiation (LTP) in primary motor cortex (M1) and a subsequent occlusion of LTP induction (Rioult-Pedotti et al. J Neurophysiol 98: 3688-3695, 2007). Using various forms of noninvasive brain stimulation in conjunction with a motor learning paradigm, Cantarero et al. (J Neurosci 33: 12862-12869, 2013) recently provided novel evidence to support the hypothesis that retention of motor skill is contingent upon this postlearning occlusion.


Subject(s)
Learning/physiology , Long-Term Synaptic Depression/physiology , Motor Skills/physiology , Pyramidal Tracts/physiology , Retention, Psychology/physiology , Female , Humans , Male
10.
Neuropsychol Rehabil ; 24(6): 936-57, 2014.
Article in English | MEDLINE | ID: mdl-24894429

ABSTRACT

Provision of a mirror image of a hand undertaking a motor task (i.e., mirror therapy) elicits behavioural improvements in the inactive hand. A greater understanding of the neural mechanisms underpinning this phenomenon is required to maximise its potential for rehabilitation across the lifespan, e.g., following hemiparesis or unilateral weakness. Young and older participants performed unilateral finger abductions with no visual feedback, with feedback of the active or passive hands, or with a mirror image of the active hand. Transcranial magnetic stimulation was used to assess feedback-related changes in two neurophysiological measures thought to be involved in inter-manual transfer of skill, namely corticospinal excitability (CSE) and intracortical inhibition (SICI) in the passive hemisphere. Task performance led to CSE increases, accompanied by decreases of SICI, in all visual feedback conditions relative to rest. However, the changes due to mirror feedback were not significantly different to those observed in the other (more standard) visual conditions. Accordingly, the unimanual motor action itself, rather than modifications in visual feedback, appears more instrumental in driving changes in CSE and SICI. Therefore, changes in CSE and SICI are unlikely to underpin the behavioural benefits of mirror therapy. We discuss implications for rehabilitation and directions of future research.


Subject(s)
Feedback, Sensory/physiology , Motor Cortex/physiology , Psychomotor Performance/physiology , Pyramidal Tracts/physiology , Adult , Aged , Evoked Potentials, Motor , Female , Fingers/physiology , Humans , Male , Motor Activity/physiology , Photic Stimulation , Transcranial Magnetic Stimulation , Young Adult
11.
Cortex ; 177: 235-252, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38875737

ABSTRACT

The ability to inhibit movements is an essential component of a healthy executive control system. Two distinct but commonly used tasks to assess motor inhibition are the stop signal task (SST) and the anticipated response inhibition (ARI) task. The SST and ARI tasks are similar in that they both require cancelation of a prepotent movement; however, the SST involves cancelation of a speeded reaction to a temporally unpredictable signal, while the ARI task involves cancelation of an anticipated response that the participant has prepared to enact at a wholly predictable time. 33 participants (mean age = 33.3 years, range = 18-55 years) completed variants of the SST and ARI task. In each task, the majority of trials required bimanual button presses, while on a subset of trials a stop signal indicated that one of the presses should be cancelled (i.e., motor selective inhibition). Additional variants of the tasks also included trials featuring signals which were to be ignored, allowing for insights into the attentional component of the inhibitory response. Electromyographic (EMG) recordings allowed detailed comparison of the characteristics of voluntary action and cancellation. The speed of the inhibitory process was not influenced by whether the enacted movement was reactive (SST) or anticipated (ARI task). However, the ongoing (non-cancelled) component of anticipated movements was more efficient than reactive movements, as a result of faster action reprogramming (i.e., faster ongoing actions following successful motor selective inhibition). Older age was associated with both slower inhibition and slower action reprogramming across all reactive and anticipated tasks.


Subject(s)
Electromyography , Inhibition, Psychological , Movement , Psychomotor Performance , Reaction Time , Humans , Adult , Male , Female , Middle Aged , Adolescent , Young Adult , Psychomotor Performance/physiology , Movement/physiology , Reaction Time/physiology , Executive Function/physiology , Attention/physiology , Anticipation, Psychological/physiology
12.
Sci Rep ; 14(1): 9119, 2024 04 20.
Article in English | MEDLINE | ID: mdl-38643224

ABSTRACT

In everyday life, we constantly make decisions about actions to be performed subsequently. Research on motor decision making has provided empirical evidence for an influence of decision uncertainty on movement execution in young adults. Further, decision uncertainty was suggested to be increased in older adults due to limited cognitive resources for the integration of information and the prediction of the decision outcomes. However, the influence of cognitive aging on decision uncertainty during motor decision making and movement execution has not been investigated, yet. Thus, in the current study, we presented young and older adults with a motor decision making task, in which participants had to decide on pointing towards one out of five potential targets under varying cognitive demands. Statistical analyses revealed stronger decreases in correctly deciding upon the pointing target, i.e. task performance, from low to higher cognitive demand in older as compared to young adults. Decision confidence also decreased more strongly in older adults with increasing cognitive demand, however, only when collapsing across correct and incorrect decision trials, but not when considering correct decision trials, only. Further, older adults executed reaching movements with longer reaction times and increased path length, though the latter, again, not when considering correct decision trials, only. Last, reaction time and variability in movement execution were both affected by cognitive demand. The outcomes of this study provide a differentiated picture of the distinct and joint effects of aging and cognitive demand during motor decision making.


Subject(s)
Goals , Psychomotor Performance , Young Adult , Humans , Aged , Uncertainty , Reaction Time , Movement , Cognition , Decision Making
13.
Sci Rep ; 14(1): 2023, 2024 01 23.
Article in English | MEDLINE | ID: mdl-38263414

ABSTRACT

The prefrontal cortex (PFC) governs the ability to rapidly cancel planned movements when no longer appropriate (motor inhibition) and ignore distracting stimuli (perceptual inhibition). It is unclear to what extent these processes interact, and how they are impacted by age. The interplay between perceptual and motor inhibition was investigated using a Flanker Task, a Stop Signal Task and a combined Stop Signal Flanker Task in healthy young (n = 33, Mean = 24 years) and older adults (n = 32, Mean = 71 years). PFC activity was measured with functional near-infrared spectroscopy (fNIRS), while electromyography (EMG) measured muscle activity in the fingers used to respond to the visual cues. Perceptual inhibition (the degree to which incongruent flankers slowed response time to a central cue) and motor inhibition (the speed of cancellation of EMG activation following stop cues) independently declined with age. When both processes were engaged together, PFC activity increased for both age groups, however only older adults exhibited slower motor inhibition. The results indicate that cortical upregulation was sufficient to compensate for the increased task demands in younger but not older adults, suggesting potential resource sharing and neural limitations particularly in older adults.


Subject(s)
Cues , Psychophysiology , Electromyography , Fingers , Reaction Time , Humans , Young Adult
14.
Trials ; 25(1): 598, 2024 Sep 08.
Article in English | MEDLINE | ID: mdl-39245707

ABSTRACT

BACKGROUND: Multiple sclerosis (MS) is a chronic neurological condition and the leading cause of non-traumatic disability in young adults. MS pathogenesis leads to the death of oligodendrocytes, demyelination, and progressive central nervous system neurodegeneration. Endogenous remyelination occurs in people with MS (PwMS) but is insufficient to repair the damage. Our preclinical studies in mice indicate that endogenous remyelination can be supported by the delivery of repetitive transcranial magnetic stimulation (rTMS). Our phase I trial concluded that 20 sessions of rTMS, delivered over 5 weeks, are safe and feasible for PwMS. This phase II trial aims to investigate the safety and preliminary efficacy of rTMS for PwMS. METHODS: Participants must be aged 18-65 years, diagnosed with MS by a neurologist, stable and relapse free for 6 months, have an Extended Disability Status Scale (EDSS) between 1.5 and 6 (inclusive), willing to travel to a study site every weekday for 4 consecutive weeks, and able to provide informed consent and access the internet. Participants from multiple centres will be randomised 2:1 (rTMS to sham) stratified by sex. The intervention will be delivered with a Magstim Rapid2 stimulator device and circular 90-mm coil or MagVenture MagPro stimulator device with C100 circular coil, positioned to stimulate a broad area including frontal and parietal cortices. For the rTMS group, pulse intensity will be set at 18% (MagVenture) or 25% (Magstim) of maximum stimulator output (MSO), and rTMS applied as intermittent theta burst stimulation (iTBS) (~ 3 min per side; 600 pulses). For the sham group, the procedure will be the same, but the intensity is set at 0%. Each participant will attend 20 intervention sessions over a maximum of 5 weeks. Outcome measures include MS Functional Composite Score (primary), Fatigue Severity Scale, Hospital Anxiety and Depression Scale, Quality of Life, and Pittsburgh Sleep Quality Index/Numeric Rating Scale and adverse events (secondary) and advanced MRI metrics (tertiary). Outcomes will be measured at baseline and after completing the intervention. DISCUSSION: This study will determine if rTMS can improve functional outcomes or other MS symptoms and determine whether rTMS has the potential to promote remyelination in PwMS. TRIAL REGISTRATION: Registered with Australian New Zealand Clinical Trials Registry, 20 January 2022; ACTRN12622000064707.


Subject(s)
Clinical Trials, Phase II as Topic , Multiple Sclerosis , Transcranial Magnetic Stimulation , Humans , Transcranial Magnetic Stimulation/methods , Transcranial Magnetic Stimulation/adverse effects , Adult , Middle Aged , Multiple Sclerosis/therapy , Treatment Outcome , Male , Female , Adolescent , Young Adult , Aged , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Time Factors , Disability Evaluation , Quality of Life
15.
Mult Scler J Exp Transl Clin ; 10(2): 20552173241252571, 2024.
Article in English | MEDLINE | ID: mdl-38756414

ABSTRACT

Background: Low-intensity repetitive transcranial magnetic stimulation (rTMS), delivered as a daily intermittent theta burst stimulation (iTBS) for four consecutive weeks, increased the number of new oligodendrocytes in the adult mouse brain. Therefore, rTMS holds potential as a remyelinating intervention for people with multiple sclerosis (MS). Objective: Primarily to determine the safety and tolerability of our rTMS protocol in people with MS. Secondary objectives include feasibility, blinding and an exploration of changes in magnetic resonance imaging (MRI) metrics, patient-reported outcome measures (PROMs) and cognitive or motor performance. Methods: A randomised (2:1), placebo controlled, single blind, parallel group, phase 1 trial of 20 rTMS sessions (600 iTBS pulses per hemisphere; 25% maximum stimulator output), delivered over 4-5 weeks. Twenty participants were randomly assigned to 'sham' (n = 7) or active rTMS (n = 13), with the coil positioned at 90° or 0°, respectively. Results: Five adverse events (AEs) including one serious AE reported. None were related to treatment. Protocol compliance was high (85%) and blinding successful. Within participant MRI metrics, PROMs and cognitive or motor performance were unchanged over time. Conclusion: Twenty sessions of rTMS is safe and well tolerated in a small group of people with MS. The study protocol and procedures are feasible. Improvement of sham is warranted before further investigating safety and efficacy.

16.
J Neurophysiol ; 109(12): 2963-71, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23536709

ABSTRACT

Bilateral movement rehabilitation is gaining popularity as an approach to improve the recovery not only of bimanual function but also of unilateral motor tasks. While the neural mechanisms mediating the transfer of bilateral training gains into unimanual contexts are not fully understood, converging evidence from behavioral, neurophysiological, and imaging studies suggests that bimanual movements are not simply the superposition of unimanual tasks undertaken with both (upper) limbs. Here we investigated the neural responses in both hemispheres to bilateral ballistic motor training and the extent to which performance improvements transferred to a unimanual task. Since aging influences interhemispheric interactions during movement production, both young (n = 9; mean age 19.4 yr; 6 women, 3 men) and older (n = 9; 66.3 yr; 7 women, 2 men) adults practiced a bilateral motor task requiring simultaneous "fast-as-possible" abductions of their left and right index fingers. Changes in bilateral and unilateral performance, and in corticospinal excitability and intracortical inhibition, were assessed. Strong transfer was observed between bimanual and unimanual contexts for both age groups. However, in contrast to previous reports of substantial bilateral cortical adaptations following unilateral training, increases in corticospinal excitability following bilateral training were not statistically reliable, and a release of intracortical inhibition was only observed for older adults. The results indicate that the neural mechanisms of motor learning for bilateral ballistic tasks differ from those that underlie unimanual ballistic performance improvement but that aging results in a greater overlap of the neural mechanisms mediating bilateral and unilateral ballistic motor performance.


Subject(s)
Adaptation, Physiological , Adaptation, Psychological , Aging , Functional Laterality , Motor Skills , Muscle Stretching Exercises , Aged , Female , Fingers/innervation , Fingers/physiology , Humans , Learning , Male , Motor Cortex/growth & development , Motor Cortex/physiology , Pyramidal Tracts/physiology , Task Performance and Analysis , Young Adult
17.
J Neurophysiol ; 110(5): 1062-9, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23761694

ABSTRACT

A disruptive transcranial magnetic stimulation (TMS) approach was used to determine whether the increased frontal activation and reduced hemispheric laterality brain activation patterns observed in older adults during motor tasks play a functional role. Young and older adults abducted their left index finger as soon as possible after a visual imperative signal presented 500 ms after a warning signal. TMS was applied to the dorsal premotor (PMd) or primary motor (M1) cortex in the left or right hemisphere at seven times during response preparation and execution. Both groups exhibited faster reaction times in their left hand after stimulation of the left PMd (i.e., ipsilateral to the responding hand) relative to trials with no TMS, indicating a functional role of the left PMd in the regulation of impulse control. This result also suggests that the function of the left PMd appears to be unaffected by the healthy aging process. Right M1 TMS resulted in a response time delay in both groups. Only for older adults did left M1 stimulation delay responses, suggesting the involvement of ipsilateral motor pathways in the preparation of motor actions in older adults.


Subject(s)
Functional Laterality , Hand/physiology , Motor Cortex/physiology , Movement , Muscle, Skeletal/physiology , Aged , Evoked Potentials, Motor , Female , Humans , Male , Muscle, Skeletal/innervation , Psychomotor Performance , Transcranial Magnetic Stimulation , Young Adult
18.
Exp Brain Res ; 227(1): 19-29, 2013 May.
Article in English | MEDLINE | ID: mdl-23535836

ABSTRACT

We recently reported considerably less inter-limb transfer in older, compared to young, adults following dominant (right) hand motor training (Hinder et al. in J Appl Physiol 110:166-175, 2011). This occurred despite the fact that both age groups exhibited similar performance improvements in the trained limb. However, asymmetries can exist with respect to the degree of transfer observed in some tasks, depending upon which limb undertakes the training. Accordingly, here we investigated inter-limb transfer following left hand ballistic motor training in young (n = 15; mean age 21.2 years) and older (n = 15; mean age 70.3 years) right handers. Following motor training that required participants to maximally abduct the left index finger, both groups exhibited significant performance improvements in the trained left hand. Moreover, the extent of inter-limb transfer was substantial and indistinguishable between the two age groups. Transcranial magnetic stimulation revealed that both age groups exhibited bilateral increases in cortical excitability following unilateral training, indicating that unilateral training affects both the trained and untrained hemisphere. However, only for young adults was the extent of the performance gain in the trained hand able to predict the degree of transfer. These findings suggest that different mechanisms may mediate inter-limb transfer of ballistic motor tasks for older and young adults. Because such tasks evoke similar neural responses to those observed following strength training (Selvanayagam et al. in J Appl Physiol 111:367-375, 2011; Carroll et al. in Acta Physiol 202:119-140, 2011), our findings have important implications for rehabilitation paradigms following stroke or limb immobilisation due to injury.


Subject(s)
Evoked Potentials, Motor/physiology , Functional Laterality/physiology , Motor Skills/physiology , Upper Extremity/physiology , Adolescent , Adult , Age Factors , Female , Humans , Male , Motor Cortex/physiology , Movement/physiology , Muscle, Skeletal/physiology , Resistance Training , Transcranial Magnetic Stimulation/methods , Upper Extremity/surgery , Young Adult
19.
Exp Brain Res ; 227(2): 289-300, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23591690

ABSTRACT

The present study investigated age-related changes in the attentional demands associated with interlimb coordination involving upper and lower limbs performed at three different movement frequencies. Younger and older adults performed rhythmical, 180° out-of-phase flexion-extension movements of the knee and elbow with either ipsilateral (right arm, right leg) or contralateral (right arm, left leg) limbs at 20, 60, and 100 % of each individual's maximum movement frequency. A concurrent vocal reaction time task (dual task) was used to assess attentional load. There were two major findings: (1) The attentional cost associated with undertaking the required coordination patterns was greatest at the slowest movement frequency, and this additional attentional load was most pronounced for older adults; (2) the manipulation of movement frequency had a distinct effect on the coordination performance: moving at the fastest frequency degraded the accuracy and stability of coordination, while moving at the slowest movement frequency led to increased temporal variability, particularly in older adults. Coordination performance at slowest movement frequency required the greatest cognitive demand in older adults relative to other movement frequencies, suggesting that going 'slow and steady' is not necessarily less attentionally demanding for older adults.


Subject(s)
Aging , Attention/physiology , Extremities/physiology , Movement/physiology , Psychomotor Performance/physiology , Sound , Acoustic Stimulation , Adolescent , Adult , Age Factors , Aged , Analysis of Variance , Female , Functional Laterality , Humans , Male , Middle Aged , Photic Stimulation , Reaction Time , Statistics, Nonparametric , Young Adult
20.
PLoS One ; 18(7): e0288085, 2023.
Article in English | MEDLINE | ID: mdl-37418378

ABSTRACT

Rapid-choice decision-making is biased by prior probability of response alternatives. Conventionally, prior probability effects are assumed to selectively affect, response threshold, which determines the amount of evidence required to trigger a decision. However, there may also be effects on the rate at which evidence is accumulated and the time required for non-decision processes (e.g., response production). Healthy young (n = 21) and older (n = 20) adults completed a choice response-time task requiring left- or right-hand responses to imperative stimuli. Prior probability was manipulated using a warning stimulus that informed participants that a particular response was 70% likely (i.e., the imperative stimulus was either congruent or incongruent with the warning stimulus). In addition, prior probability was either fixed for blocks of trials (block-wise bias) or varied from trial-to-trial (trial-wise bias). Response time and accuracy data were analysed using the racing diffusion evidence-accumulation model to test the selective influence assumption. Response times for correct responses were slower on incongruent than congruent trials, and older adults' responses were slower, but more accurate, than young adults. Evidence-accumulation modelling favoured an effect of prior probability on both response thresholds and nondecision time. Overall, the current results cast doubt on the selective threshold influence assumption in the racing diffusion model.


Subject(s)
Decision Making , Young Adult , Humans , Aged , Decision Making/physiology , Reaction Time/physiology , Probability
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