License, which permits unrestricted use, distribution, and reproduction in any medium, provided t... more License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Numerous studies have reported that plasticity induced in the motor cortex by transcranial magnetic stimulation (TMS) is attenuated in older adults. Those investigations, however, have focused solely on the stimulated hemisphere. Compared to young adults, older adults exhibit more widespread activity across bilateral motor cortices during the performance of unilateral motor tasks, suggesting that the manifestation of plasticity might also be altered. To address this question, twenty young (<35 years old) and older adults (>65 years) underwent intermittent theta burst stimulation (iTBS) whilst attending to the hand targeted by the plasticity-inducing procedure. The amplitude of motor evoked potentials (MEPs) elicited by single pulse TMS was used to quantify cortical excitability before and after iTBS. Individual responses to iTBS were highly varia...
which permits unrestricted use, distribution, and reproduction in any medium, provided the origin... more which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Repetitive performance of a task can result in learning. The neural mechanisms underpinning such use-dependent plasticity are influenced by several neuromodulators. Variations in neuromodulator levels may contribute to the variability in performance outcomes following training. Circulating levels of the neuromodulator cortisol change throughout the day. High cortisol levels inhibit neuroplasticity induced with a transcranial magnetic stimulation (TMS) paradigm that has similarities to use-dependent plasticity.Thepresent study investigatedwhether performance changes following amotor training task aremodulated by time of day and/or changes in endogenous cortisol levels. Motor training involving 30minutes of repeatedmaximum left thumb abduction was undertaken by twenty-two participants twice, once in the morning (8AM) and once in the evening (8 PM) on separate occasions. Saliva was assayed for cortisol concentration. Motor performance, quantified by measuring maximum left thumb abduction acceleration, significantly increased by 28 % following training. Neuroplastic changes in corticomotor excitability of abductor pollicis brevis, quantified with TMS, increased significantly by 23 % following training. Training-related motor performance improvements and neuroplasticity were unaffected by time of day and salivary cortisol concentration. Although similar neural
Physical exercise and neurorehabilitation involve repetitive training that can induce changes in ... more Physical exercise and neurorehabilitation involve repetitive training that can induce changes in motor performance arising from neuroplasticity. Retention of these motor changes occurs via an encoding process, during which rapid neuroplastic changes occur in response to training. Previous studies show that transcranial alternating current stimulation (tACS), a form of non-invasive brain stimulation, can enhance encoding of a cognitive learning task during wakefulness. However, the effect of tACS on motor processes in the awake brain is unknown. In this study, forty-two healthy 18–35 year old participants received either 0.75 Hz (active) tACS (or sham stimulation) for 30 min during a ballistic thumb abduction motor training task. Training-related behavioural effects were quantified by assessing changes in thumb abduction acceleration, and neuroplastic changes were quantified by measuring motor evoked potential (MEP) amplitude of the abductor pollicis brevis muscle. These measures wer...
Cortex; a journal devoted to the study of the nervous system and behavior, 2017
Plasticity can be induced in human cortex using paired associative stimulation (PAS), which repea... more Plasticity can be induced in human cortex using paired associative stimulation (PAS), which repeatedly and predictably pairs a peripheral electrical stimulus with transcranial magnetic stimulation (TMS) to the contralateral motor region. Many studies have reported small or inconsistent effects of PAS. Given that uncertain stimuli can promote learning, the predictable nature of the stimulation in conventional PAS paradigms might serve to attenuate plasticity induction. Here, we introduced stimulus uncertainty into the PAS paradigm to investigate if it can boost plasticity induction. Across two experimental sessions, participants (n = 28) received a modified PAS paradigm consisting of a random combination of 90 paired stimuli and 90 unpaired (TMS-only) stimuli. Prior to each of these stimuli, participants also received an auditory cue which either reliably predicted whether the upcoming stimulus was paired or unpaired (no uncertainty condition) or did not predict the upcoming stimulus...
We have reported reliable changes in behaviour, brain structure and function in 24 healthy right-... more We have reported reliable changes in behaviour, brain structure and function in 24 healthy right-handed adults who practiced a finger-thumb opposition sequence task with their left hand for 10 mins daily, over four weeks. Here we extend these findings by employing diffusion MRI to investigate white-matter changes in the corticospinal tract, basal-ganglia, and connections of the dorsolateral prefrontal cortex. Twenty-three participant datasets were available with pre-training and post-training scans. Task performance improved in all participants (mean: 52.8%, SD: 20.0%; group p<0.01 FWE) and widespread microstructural changes were detected across the motor system of the 'trained' hemisphere. Specifically, region-of-interest based analyses of diffusion MRI (n=21) revealed significantly increased fractional anisotropy in the right caudate nucleus (4.9%; p<0.05 FWE), and decreased mean diffusivity in the left nucleus accumbens (-1.3%; p<0.05 FWE). Diffusion MRI tractogr...
Within the primate visual system, areas at lower levels of the cortical hierarchy process basic v... more Within the primate visual system, areas at lower levels of the cortical hierarchy process basic visual features, whereas those at higher levels, such as the frontal eye fields (FEF), are thought to modulate sensory processes via feedback connections. Despite these functional exchanges during perception, there is little shared activity between early and late visual regions at rest. How interactions emerge between regions encompassing distinct levels of the visual hierarchy remains unknown. Here we combined neuroimaging, non-invasive cortical stimulation and computational modelling to characterize changes in functional interactions across widespread neural networks before and after local inhibition of primary visual cortex or FEF. We found that stimulation of early visual cortex selectively increased feedforward interactions with FEF and extrastriate visual areas, whereas identical stimulation of the FEF decreased feedback interactions with early visual areas. Computational modelling ...
Numerous studies have reported that plasticity induced in the motor cortex by transcranial magnet... more Numerous studies have reported that plasticity induced in the motor cortex by transcranial magnetic stimulation (TMS) is attenuated in older adults. Those investigations, however, have focused solely on the stimulated hemisphere. Compared to young adults, older adults exhibit more widespread activity across bilateral motor cortices during the performance of unilateral motor tasks, suggesting that the manifestation of plasticity might also be altered. To address this question, twenty young (<35 years old) and older adults (>65 years) underwent intermittent theta burst stimulation (iTBS) whilst attending to the hand targeted by the plasticity-inducing procedure. The amplitude of motor evoked potentials (MEPs) elicited by single pulse TMS was used to quantify cortical excitability before and after iTBS. Individual responses to iTBS were highly variable, with half the participants showing an unexpected decrease in cortical excitability. Contrary to predictions, however, there were...
Repetitive performance of a task can result in learning. The neural mechanisms underpinning such ... more Repetitive performance of a task can result in learning. The neural mechanisms underpinning such use-dependent plasticity are influenced by several neuromodulators. Variations in neuromodulator levels may contribute to the variability in performance outcomes following training. Circulating levels of the neuromodulator cortisol change throughout the day. High cortisol levels inhibit neuroplasticity induced with a transcranial magnetic stimulation (TMS) paradigm that has similarities to use-dependent plasticity. The present study investigated whether performance changes following a motor training task are modulated by time of day and/or changes in endogenous cortisol levels. Motor training involving 30 minutes of repeated maximum left thumb abduction was undertaken by twenty-two participants twice, once in the morning (8 AM) and once in the evening (8 PM) on separate occasions. Saliva was assayed for cortisol concentration. Motor performance, quantified by measuring maximum left thumb...
The critical lesion site responsible for the syndrome of unilateral spatial neglect has been deba... more The critical lesion site responsible for the syndrome of unilateral spatial neglect has been debated for more than a decade. Here we performed an activation likelihood estimation (ALE) to provide for the first time an objective quantitative index of the consistency of lesion sites across anatomical group studies of spatial neglect. The analysis revealed several distinct regions in which damage has consistently been associated with spatial neglect symptoms. Lesioned clusters were located in several cortical and subcortical regions of the right hemisphere, including the middle and superior temporal gyrus, inferior parietal lobule, intraparietal sulcus, precuneus, middle occipital gyrus, caudate nucleus, and posterior insula, as well as in the white matter pathway corresponding to the posterior part of the superior longitudinal fasciculus. Further analyses suggested that separate lesion sites are associated with impairments in different behavioral tests, such as line bisection and targ...
The purpose of the study was to quantify the strength of motor-unit coherence from the left and r... more The purpose of the study was to quantify the strength of motor-unit coherence from the left and right first dorsal interosseous muscles in untrained, skill-trained (musicians), and strength-trained (weightlifters) individuals who had long-term specialized use of their hand muscles. The strength of motor-unit coherence was quantified from a total of 394 motor-unit pairs in 13 subjects using data from a previous study in which differences were found in the strength of motor-unit synchronization depending on training status. In the present study, we found that the strength of motor-unit coherence was significantly greater in the left compared with the right hand of untrained right-handed subjects with the largest differences observed between 21 and 24 Hz. The strength of motor-unit coherence was lower in both hands of skill-trained subjects (21–27 Hz) and the right (skilled) hand of untrained subjects (21–24 Hz), whereas the largest motor-unit coherence was observed in both hands of st...
Transcranial magnetic stimulation (TMS) was used to assess the relative contribution of the corti... more Transcranial magnetic stimulation (TMS) was used to assess the relative contribution of the corticospinal (CS) pathway in activating the first dorsal interosseous (FDI) muscle in each hand of 16 right- (RH) and 16 left-handed (LH) subjects with varied degrees of hand preference. It was hypothesised that asymmetry in corticospinal activation of the two hands may be related to hand preference and interlimb differences in manual performance. Subjects performed isometric index finger abduction at force levels of 0.5 N, 1 N and 2 N while TMS was applied at resting threshold intensity (T), 0.9T, or 0.8T. The amount of contraction-induced facilitation of the muscle evoked potential (MEP) was used as an estimate of corticospinal involvement in the task. Patterns of MEP facilitation in each hand were compared with measures of manual performance (finger tapping speed, Purdue pegboard, maximal FDI strength). Threshold TMS intensities for an MEP in FDI at rest were similar in LH and RH subjects, and did not vary between hands. Facilitation of the MEP with voluntary activation was larger overall on the left side (P&lt;0.05), but the asymmetry was dependent on the degree of lateralisation of hand preference. For subjects with consistent hand preference (either LH or RH), MEP facilitation in active FDI was larger for the left hand. For non-consistent RH subjects, contraction-induced MEP facilitation was larger in the right FDI muscle than the left. Asymmetry of MEP facilitation was not correlated with differences between hands in finger tapping speed or performance in the pegboard task, but was associated with relative differences in FDI strength. MEP facilitation tended to be larger in the stronger FDI muscle of the pair. We conclude that corticospinal involvement in the command for index finger abduction is generally greater when the left hand is used, although in RH subjects the asymmetry is influenced by the degree of lateralisation of hand preference. The corticospinal asymmetry is not related to speed or dexterity of finger movements, but the association with muscle strength suggests that it may be influenced in part by preferential use of one hand for tasks which strengthen the FDI muscle.
License, which permits unrestricted use, distribution, and reproduction in any medium, provided t... more License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Numerous studies have reported that plasticity induced in the motor cortex by transcranial magnetic stimulation (TMS) is attenuated in older adults. Those investigations, however, have focused solely on the stimulated hemisphere. Compared to young adults, older adults exhibit more widespread activity across bilateral motor cortices during the performance of unilateral motor tasks, suggesting that the manifestation of plasticity might also be altered. To address this question, twenty young (<35 years old) and older adults (>65 years) underwent intermittent theta burst stimulation (iTBS) whilst attending to the hand targeted by the plasticity-inducing procedure. The amplitude of motor evoked potentials (MEPs) elicited by single pulse TMS was used to quantify cortical excitability before and after iTBS. Individual responses to iTBS were highly varia...
which permits unrestricted use, distribution, and reproduction in any medium, provided the origin... more which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Repetitive performance of a task can result in learning. The neural mechanisms underpinning such use-dependent plasticity are influenced by several neuromodulators. Variations in neuromodulator levels may contribute to the variability in performance outcomes following training. Circulating levels of the neuromodulator cortisol change throughout the day. High cortisol levels inhibit neuroplasticity induced with a transcranial magnetic stimulation (TMS) paradigm that has similarities to use-dependent plasticity.Thepresent study investigatedwhether performance changes following amotor training task aremodulated by time of day and/or changes in endogenous cortisol levels. Motor training involving 30minutes of repeatedmaximum left thumb abduction was undertaken by twenty-two participants twice, once in the morning (8AM) and once in the evening (8 PM) on separate occasions. Saliva was assayed for cortisol concentration. Motor performance, quantified by measuring maximum left thumb abduction acceleration, significantly increased by 28 % following training. Neuroplastic changes in corticomotor excitability of abductor pollicis brevis, quantified with TMS, increased significantly by 23 % following training. Training-related motor performance improvements and neuroplasticity were unaffected by time of day and salivary cortisol concentration. Although similar neural
Physical exercise and neurorehabilitation involve repetitive training that can induce changes in ... more Physical exercise and neurorehabilitation involve repetitive training that can induce changes in motor performance arising from neuroplasticity. Retention of these motor changes occurs via an encoding process, during which rapid neuroplastic changes occur in response to training. Previous studies show that transcranial alternating current stimulation (tACS), a form of non-invasive brain stimulation, can enhance encoding of a cognitive learning task during wakefulness. However, the effect of tACS on motor processes in the awake brain is unknown. In this study, forty-two healthy 18–35 year old participants received either 0.75 Hz (active) tACS (or sham stimulation) for 30 min during a ballistic thumb abduction motor training task. Training-related behavioural effects were quantified by assessing changes in thumb abduction acceleration, and neuroplastic changes were quantified by measuring motor evoked potential (MEP) amplitude of the abductor pollicis brevis muscle. These measures wer...
Cortex; a journal devoted to the study of the nervous system and behavior, 2017
Plasticity can be induced in human cortex using paired associative stimulation (PAS), which repea... more Plasticity can be induced in human cortex using paired associative stimulation (PAS), which repeatedly and predictably pairs a peripheral electrical stimulus with transcranial magnetic stimulation (TMS) to the contralateral motor region. Many studies have reported small or inconsistent effects of PAS. Given that uncertain stimuli can promote learning, the predictable nature of the stimulation in conventional PAS paradigms might serve to attenuate plasticity induction. Here, we introduced stimulus uncertainty into the PAS paradigm to investigate if it can boost plasticity induction. Across two experimental sessions, participants (n = 28) received a modified PAS paradigm consisting of a random combination of 90 paired stimuli and 90 unpaired (TMS-only) stimuli. Prior to each of these stimuli, participants also received an auditory cue which either reliably predicted whether the upcoming stimulus was paired or unpaired (no uncertainty condition) or did not predict the upcoming stimulus...
We have reported reliable changes in behaviour, brain structure and function in 24 healthy right-... more We have reported reliable changes in behaviour, brain structure and function in 24 healthy right-handed adults who practiced a finger-thumb opposition sequence task with their left hand for 10 mins daily, over four weeks. Here we extend these findings by employing diffusion MRI to investigate white-matter changes in the corticospinal tract, basal-ganglia, and connections of the dorsolateral prefrontal cortex. Twenty-three participant datasets were available with pre-training and post-training scans. Task performance improved in all participants (mean: 52.8%, SD: 20.0%; group p<0.01 FWE) and widespread microstructural changes were detected across the motor system of the 'trained' hemisphere. Specifically, region-of-interest based analyses of diffusion MRI (n=21) revealed significantly increased fractional anisotropy in the right caudate nucleus (4.9%; p<0.05 FWE), and decreased mean diffusivity in the left nucleus accumbens (-1.3%; p<0.05 FWE). Diffusion MRI tractogr...
Within the primate visual system, areas at lower levels of the cortical hierarchy process basic v... more Within the primate visual system, areas at lower levels of the cortical hierarchy process basic visual features, whereas those at higher levels, such as the frontal eye fields (FEF), are thought to modulate sensory processes via feedback connections. Despite these functional exchanges during perception, there is little shared activity between early and late visual regions at rest. How interactions emerge between regions encompassing distinct levels of the visual hierarchy remains unknown. Here we combined neuroimaging, non-invasive cortical stimulation and computational modelling to characterize changes in functional interactions across widespread neural networks before and after local inhibition of primary visual cortex or FEF. We found that stimulation of early visual cortex selectively increased feedforward interactions with FEF and extrastriate visual areas, whereas identical stimulation of the FEF decreased feedback interactions with early visual areas. Computational modelling ...
Numerous studies have reported that plasticity induced in the motor cortex by transcranial magnet... more Numerous studies have reported that plasticity induced in the motor cortex by transcranial magnetic stimulation (TMS) is attenuated in older adults. Those investigations, however, have focused solely on the stimulated hemisphere. Compared to young adults, older adults exhibit more widespread activity across bilateral motor cortices during the performance of unilateral motor tasks, suggesting that the manifestation of plasticity might also be altered. To address this question, twenty young (<35 years old) and older adults (>65 years) underwent intermittent theta burst stimulation (iTBS) whilst attending to the hand targeted by the plasticity-inducing procedure. The amplitude of motor evoked potentials (MEPs) elicited by single pulse TMS was used to quantify cortical excitability before and after iTBS. Individual responses to iTBS were highly variable, with half the participants showing an unexpected decrease in cortical excitability. Contrary to predictions, however, there were...
Repetitive performance of a task can result in learning. The neural mechanisms underpinning such ... more Repetitive performance of a task can result in learning. The neural mechanisms underpinning such use-dependent plasticity are influenced by several neuromodulators. Variations in neuromodulator levels may contribute to the variability in performance outcomes following training. Circulating levels of the neuromodulator cortisol change throughout the day. High cortisol levels inhibit neuroplasticity induced with a transcranial magnetic stimulation (TMS) paradigm that has similarities to use-dependent plasticity. The present study investigated whether performance changes following a motor training task are modulated by time of day and/or changes in endogenous cortisol levels. Motor training involving 30 minutes of repeated maximum left thumb abduction was undertaken by twenty-two participants twice, once in the morning (8 AM) and once in the evening (8 PM) on separate occasions. Saliva was assayed for cortisol concentration. Motor performance, quantified by measuring maximum left thumb...
The critical lesion site responsible for the syndrome of unilateral spatial neglect has been deba... more The critical lesion site responsible for the syndrome of unilateral spatial neglect has been debated for more than a decade. Here we performed an activation likelihood estimation (ALE) to provide for the first time an objective quantitative index of the consistency of lesion sites across anatomical group studies of spatial neglect. The analysis revealed several distinct regions in which damage has consistently been associated with spatial neglect symptoms. Lesioned clusters were located in several cortical and subcortical regions of the right hemisphere, including the middle and superior temporal gyrus, inferior parietal lobule, intraparietal sulcus, precuneus, middle occipital gyrus, caudate nucleus, and posterior insula, as well as in the white matter pathway corresponding to the posterior part of the superior longitudinal fasciculus. Further analyses suggested that separate lesion sites are associated with impairments in different behavioral tests, such as line bisection and targ...
The purpose of the study was to quantify the strength of motor-unit coherence from the left and r... more The purpose of the study was to quantify the strength of motor-unit coherence from the left and right first dorsal interosseous muscles in untrained, skill-trained (musicians), and strength-trained (weightlifters) individuals who had long-term specialized use of their hand muscles. The strength of motor-unit coherence was quantified from a total of 394 motor-unit pairs in 13 subjects using data from a previous study in which differences were found in the strength of motor-unit synchronization depending on training status. In the present study, we found that the strength of motor-unit coherence was significantly greater in the left compared with the right hand of untrained right-handed subjects with the largest differences observed between 21 and 24 Hz. The strength of motor-unit coherence was lower in both hands of skill-trained subjects (21–27 Hz) and the right (skilled) hand of untrained subjects (21–24 Hz), whereas the largest motor-unit coherence was observed in both hands of st...
Transcranial magnetic stimulation (TMS) was used to assess the relative contribution of the corti... more Transcranial magnetic stimulation (TMS) was used to assess the relative contribution of the corticospinal (CS) pathway in activating the first dorsal interosseous (FDI) muscle in each hand of 16 right- (RH) and 16 left-handed (LH) subjects with varied degrees of hand preference. It was hypothesised that asymmetry in corticospinal activation of the two hands may be related to hand preference and interlimb differences in manual performance. Subjects performed isometric index finger abduction at force levels of 0.5 N, 1 N and 2 N while TMS was applied at resting threshold intensity (T), 0.9T, or 0.8T. The amount of contraction-induced facilitation of the muscle evoked potential (MEP) was used as an estimate of corticospinal involvement in the task. Patterns of MEP facilitation in each hand were compared with measures of manual performance (finger tapping speed, Purdue pegboard, maximal FDI strength). Threshold TMS intensities for an MEP in FDI at rest were similar in LH and RH subjects, and did not vary between hands. Facilitation of the MEP with voluntary activation was larger overall on the left side (P&lt;0.05), but the asymmetry was dependent on the degree of lateralisation of hand preference. For subjects with consistent hand preference (either LH or RH), MEP facilitation in active FDI was larger for the left hand. For non-consistent RH subjects, contraction-induced MEP facilitation was larger in the right FDI muscle than the left. Asymmetry of MEP facilitation was not correlated with differences between hands in finger tapping speed or performance in the pegboard task, but was associated with relative differences in FDI strength. MEP facilitation tended to be larger in the stronger FDI muscle of the pair. We conclude that corticospinal involvement in the command for index finger abduction is generally greater when the left hand is used, although in RH subjects the asymmetry is influenced by the degree of lateralisation of hand preference. The corticospinal asymmetry is not related to speed or dexterity of finger movements, but the association with muscle strength suggests that it may be influenced in part by preferential use of one hand for tasks which strengthen the FDI muscle.
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