Cortical N-acetylaspartate concentrations are impacted in chronic stroke but do not relate to motor impairment: A magnetic resonance spectroscopy study.

Magnetic resonance spectroscopy (MRS) measures cerebral metabolite concentrations, which can inform our understanding of the neurobiological processes associated with stroke recovery. Here, we investigated whether metabolite concentrations in primary motor and somatosensory cortices (sensorimotor cortex) are impacted by stroke and relate to upper-extremity motor impairment in 45 individuals with chronic stroke. Cerebral metabolite estimates were adjusted for cerebrospinal fluid and brain tissue composition in the MRS voxel. Upper-extremity motor impairment was indexed with the Fugl-Meyer (FM) scale. N-acetylaspartate (NAA) concentration was reduced bilaterally in stroke participants with right hemisphere lesions (n = 23), relative to right-handed healthy older adults (n = 15; p = .006). Within the entire stroke sample (n = 45) NAA and glutamate/glutamine (GLX) were lower in the ipsilesional sensorimotor cortex, relative to the contralesional cortex (NAA: p < .001; GLX: p = .003). Lower ipsilesional NAA was related to greater extent of corticospinal tract (CST) injury, quantified by a weighted CST lesion load (p = .006). Cortical NAA and GLX concentrations did not relate to the severity of chronic upper-extremity impairment (p > .05), including after a sensitivity analysis imputing missing metabolite data for individuals with large cortical lesions (n = 5). Our results suggest that NAA, a marker of neuronal integrity, is sensitive to stroke-related cortical damage and may provide mechanistic insights into cellular processes of cortical adaptation to stroke. However, cortical MRS metabolites may have limited clinical utility as prospective biomarkers of upper-extremity outcomes in chronic stroke.

The influence of an acute bout of moderate-intensity cycling exercise on sensorimotor integration.

Acute cycling exercise can modulate motor cortical circuitry in the non-exercised upper-limb. Within the primary motor cortex, measures of intracortical inhibition are reduced and intracortical facilitation is enhanced following acute exercise. Further, acute cycling exercise decreases interhemispheric inhibition between the motor cortices and lowers cerebellar-to-motor cortex inhibition. Yet, investigations into the effects of acute exercise on sensorimotor integration, referring to the transfer of incoming afferent information from the primary somatosensory cortex to motor cortex, are lacking. The current work addresses this gap in knowledge with two experimental sessions. In the first session, we tested the exercise-induced changes in somatosensory and motor excitability by assessing somatosensory (SEP) and motor evoked potentials (MEPs). In the second session, we explored the effects of acute cycling exercise on short- (SAI) and long-latency afferent inhibition (LAI), and afferent facilitation. In both experimental sessions, neurophysiological measures were obtained from the non-exercised upper-limb muscle, tested at two time points pre-exercise separated by a 25-min period of rest. Next, a 25-min bout of moderate-intensity lower-limb cycling was performed with measures assessed at two time points post-exercise. Acute lower-limb cycling increased LAI, without modulation of SAI or afferent facilitation. Further, there were no exercise-induced changes to SEP or MEP amplitudes. Together, these results suggest that acute exercise has unique effects on sensorimotor integration, which are not accompanied by concurrent changes in somatosensory or motor cortical excitability.

Robotics-assisted visual-motor training influences arm position sense in three-dimensional space.

BACKGROUND: Performing activities of daily living depends, among other factors, on awareness of the position and movements of limbs. Neural injuries, such as stroke, might negatively affect such an awareness and, consequently, lead to degrading the quality of life and lengthening the motor recovery process. With the goal of improving the sense of hand position in three-dimensional (3D) space, we investigate the effects of integrating a pertinent training component within a robotic reaching task. METHODS: In the proof-of-concept study presented in this paper, 12 healthy participants, during a single session, used their dominant hand to attempt reaching without vision to two targets in 3D space, which were placed at locations that resembled the functional task of self-feeding. After each attempt, participants received visual and haptic feedback about their hand's position to accurately locate the target. Performance was evaluated at the beginning and end of each session during an assessment in which participants reached without visual nor haptic feedback to three targets: the same two targets employed during the training phase and an additional one to evaluate the generalization of training. RESULTS: Collected data showed a statistically significant [39.81% (p=0.001)] reduction of end-position reaching error when results of reaching to all targets were combined. End-position error to the generalization target, although not statistically significant, was reduced by 15.47%. CONCLUSIONS: These results provide support for the effectiveness of combining an arm position sense training component with functional motor tasks, which could be implemented in the design of future robot-assisted rehabilitation paradigms to potentially expedite the recovery process of individuals with neurological injuries.

Exercise increases caudate dopamine release and ventral striatal activation in Parkinson's disease.

BACKGROUND: The objective of this study was to examine the effects of aerobic exercise on evoked dopamine release and activity of the ventral striatum using positron emission tomography and functional magnetic resonance imaging in Parkinson's disease (PD). METHODS: Thirty-five participants were randomly allocated to a 36-session aerobic exercise or control intervention. Each participant underwent an functional magnetic resonance imaging scan while playing a reward task before and after the intervention to determine the effect of exercise on the activity of the ventral striatum in anticipation of reward. A subset of participants (n = 25) completed [11 C] raclopride positron emission tomography scans to determine the effect of aerobic exercise on repetitive transcranial magnetic stimulation-evoked release of endogenous dopamine in the dorsal striatum. All participants completed motor (MDS-UPDRS part III, finger tapping, Timed-up-and-go) and nonmotor assessments (Starkstein Apathy Scale, Beck Depression Inventory, reaction time, Positive and Negative Affect Schedule, Trail Making Test [A and B], and Montreal Cognitive Assessment) before and after the interventions. RESULTS: The aerobic group exhibited increased activity in the ventral striatum during functional magnetic resonance imaging in anticipation of 75% probability of reward (P = 0.01). The aerobic group also demonstrated increased repetitive transcranial magnetic stimulation-evoked dopamine release in the caudate nucleus (P = 0.04) and increased baseline nondisplaceable binding potential in the posterior putamen of the less affected repetitive transcranial magnetic stimulation-stimulated hemisphere measured by position emission tomography (P = 0.03). CONCLUSIONS: Aerobic exercise alters the responsivity of the ventral striatum, likely related to changes to the mesolimbic dopaminergic pathway, and increases evoked dopamine release in the caudate nucleus. This suggests that the therapeutic benefits of exercise are in part related to corticostriatal plasticity and enhanced dopamine release. © 2019 International Parkinson and Movement Disorder Society.

The effects of acute exercise on visuomotor adaptation, learning, and inter-limb transfer.

Pairing an acute bout of lower-limb cycling exercise with skilled motor practice enhances acquisition and learning. However, it is not known whether an acute bout of exercise enhances a specific form of motor learning, namely motor adaptation, and if subsequent inter-limb transfer of this adaptation is enhanced. Seventeen young healthy participants performed a bout of cycling exercise and rest, on separate days, prior to right-arm reaching movements to visual targets under 45° rotated feedback of arm position (acquisition), followed by an immediate test of inter-limb transfer with the untrained left arm. After a 24-h delay, participants returned for a no-exercise retention test using the right and left arm with the same rotated visual feedback as acquisition. Results demonstrated that exercise enhanced right-arm adaptation during the acquisition and retention phases, and transiently enhanced aspects of inter-limb transfer, irrespective of usual levels of physical activity. Specifically, exercise enhanced movement accuracy, decreased reaction and movement time during acquisition, and increased accuracy during retention. Exercise shortened reaction time during the inter-limb transfer test immediately after right-arm acquisition but did not influence left-arm performance assessed at retention. These results indicate that an acute bout of exercise before practice enhances right-arm visuomotor adaptation (acquisition) and learning, and decreases reaction time during untrained left arm performance. The current results may have implications for the prescription of exercise protocols to enhance motor adaptation for healthy individuals and in clinical populations.

Selectivity of conventional electrodes for recording motor evoked potentials: An investigation with high-density surface electromyography.

INTRODUCTION: The objective of this study was to determine whether motor evoked potentials (MEPs) elicited with transcranial magnetic stimulation and measured with conventional bipolar electromyography (EMG) are influenced by crosstalk from non-target muscles. METHODS: MEPs were recorded in healthy participants using conventional EMG electrodes placed over the extensor carpi radialis muscle (ECR) and high-density surface EMG (HDsEMG). Fifty MEPs at 120% resting and active motor threshold were recorded. To determine the contribution of ECR to the MEPs, the amplitude distribution across HDsEMG channels was correlated with EMG activity recorded during a wrist extension task. RESULTS: Whereas the conventional EMG identified MEPs from ECR in >90% of the stimulations, HDsEMG revealed that spatial amplitude distribution representative of ECR activation was observed less frequently at rest than while holding a contraction (P < 0.001). CONCLUSIONS: MEPs recorded with conventional EMG may contain crosstalk from non-target muscles, especially when the stimulation is applied at rest. Muscle Nerve 55: 828-834, 2017.

Interhemispheric Pathways Are Important for Motor Outcome in Individuals with Chronic and Severe Upper Limb Impairment Post Stroke.

Background: Severity of arm impairment alone does not explain motor outcomes in people with severe impairment post stroke. Objective: Define the contribution of brain biomarkers to upper limb motor outcomes in people with severe arm impairment post stroke. Methods: Paretic arm impairment (Fugl-Meyer upper limb, FM-UL) and function (Wolf Motor Function Test rate, WMFT-rate) were measured in 15 individuals with severe (FM-UL ≤ 30/66) and 14 with mild-moderate (FM-UL > 40/66) impairment. Transcranial magnetic stimulation and diffusion weight imaging indexed structure and function of the corticospinal tract and corpus callosum. Separate models of the relationship between possible biomarkers and motor outcomes at a single chronic (≥6 months) time point post stroke were performed. Results: Age (ΔR20.365, p = 0.017) and ipsilesional-transcallosal inhibition (ΔR20.182, p = 0.048) explained a 54.7% (p = 0.009) variance in paretic WMFT-rate. Prefrontal corpus callous fractional anisotropy (PF-CC FA) alone explained 49.3% (p = 0.007) variance in FM-UL outcome. The same models did not explain significant variance in mild-moderate stroke. In the severe group, k-means cluster analysis of PF-CC FA distinguished two subgroups, separated by a clinically meaningful and significant difference in motor impairment (p = 0.049) and function (p = 0.006) outcomes. Conclusion: Corpus callosum function and structure were identified as possible biomarkers of motor outcome in people with chronic and severe arm impairment.

Promoting Motor Cortical Plasticity with Acute Aerobic Exercise: A Role for Cerebellar Circuits.

Acute aerobic exercise facilitated long-term potentiation-like plasticity in the human primary motor cortex (M1). Here, we investigated the effect of acute aerobic exercise on cerebellar circuits, and their potential contribution to altered M1 plasticity in healthy individuals (age: 24.8 ± 4.1 years). In Experiment   1, acute aerobic exercise reduced cerebellar inhibition (CBI) (n = 10, p = 0.01), elicited by dual-coil paired-pulse transcranial magnetic stimulation. In Experiment   2, we evaluated the facilitatory effects of aerobic exercise on responses to paired associative stimulation, delivered with a 25 ms (PAS25) or 21 ms (PAS21) interstimulus interval (n = 16 per group). Increased M1 excitability evoked by PAS25, but not PAS21, relies on trans-cerebellar sensory pathways. The magnitude of the aerobic exercise effect on PAS response was not significantly different between PAS protocols (interaction effect: p = 0.30); however, planned comparisons indicated that, relative to a period of rest, acute aerobic exercise enhanced the excitatory response to PAS25 (p = 0.02), but not PAS21 (p = 0.30). Thus, the results of these planned comparisons indirectly provide modest evidence that modulation of cerebellar circuits may contribute to exercise-induced increases in M1 plasticity. The findings have implications for developing aerobic exercise strategies to "prime" M1 plasticity for enhanced motor skill learning in applied settings.

Acute exercise enhances the response to paired associative stimulation-induced plasticity in the primary motor cortex.

There is evidence that a single session of aerobic exercise can modulate intracortical inhibition. While decreases in inhibition appear to be a necessary precursor to the induction of long-term potentiation (LTP)-like plasticity, it is not known whether aerobic exercise can enhance the response to LTP induction. We investigated whether the addition of a preceding bout of exercise would modulate the response to paired associative stimulation (PAS) of the upper limb. It was hypothesized that exercise would enhance motor cortical (M1) excitability following PAS compared to a session of PAS alone. Ten healthy individuals underwent a control session involving PAS alone and an exercise session where PAS was preceded by 20 min of moderate-intensity stationary biking. PAS involved 180 pairs of stimuli (right median nerve, left M1) delivered at 0.1 Hz to the right abductor pollicis brevis representation. Excitability changes were measured by the area under a stimulus-response curve, and intracortical circuits were probed by testing short-interval intracortical inhibition (SICI), long-interval intracortical inhibition and intracortical facilitation. Two-way ANOVAs were conducted to compare excitability changes between sessions. PAS-induced increases in M1 excitability were enhanced in the exercise session (p < 0.026). In addition, SICI was differentially modulated between the two sessions, with greater decreases in SICI observed immediately after PAS when it was preceded by the exercise session (p < 0.03). Aerobic exercise enhances the effectiveness of PAS and may be a useful adjunct to traditional therapies and interventions that aim to promote neuroplasticity in cortical networks.

Evaluation of microglia activation related markers following a clinical course of TBS: A non-human primate study.

While the applicability and popularity of theta burst stimulation (TBS) paradigms remain, current knowledge of their neurobiological effects is still limited, especially with respect to their impact on glial cells and neuroinflammatory processes. We used a multimodal imaging approach to assess the effects of a clinical course of TBS on markers for microglia activation and tissue injury as an indirect assessment of neuroinflammatory processes. Healthy non-human primates received continuous TBS (cTBS), intermittent TBS (iTBS), or sham stimulation over the motor cortex at 90% of resting motor threshold. Stimulation was delivered to the awake subjects 5 times a week for 3-4 weeks. Translocator protein (TSPO) expression was evaluated using Positron Emission Tomography and [11C]PBR28, and myo-inositol (mI) and N-acetyl-aspartate (NAA) concentrations were assessed with Magnetic Resonance Spectroscopy. Animals were then euthanized, and immunofluorescence staining was performed using antibodies against TSPO. Paired t-tests showed no significant changes in [11C]PBR28 measurements after stimulation. Similarly, no significant changes in mI and NAA concentrations were found. Post-mortem TSPO evaluation showed comparable mean immunofluorescence intensity after active TBS and sham delivery. The current study suggests that in healthy brains a clinical course of TBS, as evaluated with in-vivo imaging techniques (PET and MRS), did not measurably modulate the expression of glia related markers and metabolite associated with neural viability.

Visuomotor adaptation and generalization with repeated and varied training.

Many studies have shown that reaching movements to visual targets can rapidly adapt to altered visual feedback of hand motion (i.e., visuomotor rotation) and generalize to new target directions. This generalization is thought to reflect the acquisition of a neural representation of the novel visuomotor environment that is localized to the particular trained direction. In these studies, participants perform movements to a small number of target locations repeatedly. However, it is unclear whether adaptation and generalization are comparable when target locations are constantly varied and participants reach to visual targets one time only. Here, we compared performance for reaches to a 30° counter-clockwise visuomotor rotation to four targets, spaced 90° apart across four areas of workspace 18 times each (repeated practice (RP)) with one time only reaching movements to 72 targets, spaced 5° apart (varied practice (VP)). For both training groups, participants performed 18 reaches to radial targets (either at the repeated or varied location) in a specific area of the workspace (i.e., one of four quadrants) before reaching in the adjacent workspace. We found that the RP group adapted more completely compared to the VP group. Conversely, the VP group generalized to new target directions more completely when reaching without cursor feedback compared to the RP group. This suggests that RP and VP follow a mainly common pattern of adaptation and generalization represented in the brain, with benefits of faster adaptation with RP and more complete generalization with VP.

Improved processing speed and decreased functional connectivity in individuals with chronic stroke after paired exercise and motor training.

After stroke, impaired motor performance is linked to an increased demand for cognitive resources. Aerobic exercise improves cognitive function in neurologically intact populations and may be effective in altering cognitive function post-stroke. We sought to determine if high-intensity aerobic exercise paired with motor training in individuals with chronic stroke alters cognitive-motor function and functional connectivity between the dorsolateral prefrontal cortex (DLPFC), a key region for cognitive-motor processes, and the sensorimotor network. Twenty-five participants with chronic stroke were randomly assigned to exercise (n = 14; 66 ± 11 years; 4 females), or control (n = 11; 68 ± 8 years; 2 females) groups. Both groups performed 5-days of paretic upper limb motor training after either high-intensity aerobic exercise (3 intervals of 3 min each, total exercise duration of 23-min) or watching a documentary (control). Resting-state fMRI, and trail making test part A (TMT-A) and B were recorded pre- and post-intervention. Both groups showed implicit motor sequence learning (p < 0.001); there was no added benefit of exercise for implicit motor sequence learning (p = 0.738). The exercise group experienced greater overall cognitive-motor improvements measured with the TMT-A. Regardless of group, the changes in task score, and dwell time during TMT-A were correlated with a decrease in DLPFC-sensorimotor network functional connectivity (task score: p = 0.025; dwell time: p = 0.043), which is thought to reflect a reduction in the cognitive demand and increased automaticity. Aerobic exercise may improve cognitive-motor processing speed post-stroke.

Insight Into the Effects of Clinical Repetitive Transcranial Magnetic Stimulation on the Brain From Positron Emission Tomography and Magnetic Resonance Imaging Studies: A Narrative Review.

Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a therapeutic tool to alleviate symptoms for neurological and psychiatric diseases such as chronic pain, stroke, Parkinson's disease, major depressive disorder, and others. Although the therapeutic potential of rTMS has been widely explored, the neurological basis of its effects is still not fully understood. Fortunately, the continuous development of imaging techniques has advanced our understanding of rTMS neurobiological underpinnings on the healthy and diseased brain. The objective of the current work is to summarize relevant findings from positron emission tomography (PET) and magnetic resonance imaging (MRI) techniques evaluating rTMS effects. We included studies that investigated the modulation of neurotransmission (evaluated with PET and magnetic resonance spectroscopy), brain activity (evaluated with PET), resting-state connectivity (evaluated with resting-state functional MRI), and microstructure (diffusion tensor imaging). Overall, results from imaging studies suggest that the effects of rTMS are complex and involve multiple neurotransmission systems, regions, and networks. The effects of stimulation seem to not only be dependent in the frequency used, but also in the participants characteristics such as disease progression. In patient populations, pre-stimulation evaluation was reported to predict responsiveness to stimulation, while post-stimulation neuroimaging measurements showed to be correlated with symptomatic improvement. These studies demonstrate the complexity of rTMS effects and highlight the relevance of imaging techniques.

Continuous but not intermittent theta burst stimulation decreases striatal dopamine release and cortical excitability.

Dopamine modulation is thought to underpin some of the therapeutic effects associated with repetitive transcranial magnetic stimulation (rTMS). However, patient studies have failed to demonstrate consistent changes in the dopamine system in vivo after a therapeutic course of rTMS. Here, we evaluated acute and chronic changes in striatal dopamine release elicited by a clinically relevant course of theta burst (TBS) or sham stimulation using [11C]raclopride in healthy non-human primates (n = 11). Subjects were scanned immediately after the first session of TBS and the day after a 3 week course of daily TBS delivery. After experiment completion, animals were euthanized, and immunofluorescence staining was carried out using antibodies targeting D2 receptors (D2R). Continuous TBS (cTBS, an inhibitory form of rTMS) over the left primary motor cortex acutely decreased dopamine release bilaterally in the putamen. However, no significant changes in dopamine receptors nor D2R immunoreactivity were noted 24 h after the last stimulation, while a decrease in cortical excitability, as measured by an increase in resting motor threshold, could still be quantified. On the opposite, intermittent TBS (iTBS, an excitatory form of rTMS) did not affect dopamine release, acutely or chronically, D2R immunoreactivity or cortical excitability. These findings suggest that the long-term therapeutic effects of TBS might be facilitated through the modulation of different neurotransmission systems beyond the dopamine system. However, given the small sample size, these results should be interpreted with caution.

Acute High-Intensity Interval Exercise Modulates Corticospinal Excitability in Older Adults.

INTRODUCTION: Acute exercise can modulate the excitability of the nonexercised upper limb representation in the primary motor cortex (M1). Measures of M1 excitability using transcranial magnetic stimulation (TMS) are modulated after various forms of acute exercise in young adults, including high-intensity interval training (HIIT). However, the impact of HIIT on M1 excitability in older adults is currently unknown. Therefore, the purpose of the current study was to investigate the effects of lower limb cycling HIIT on bilateral upper limb M1 excitability in older adults. METHODS: We assessed the impact of acute lower limb HIIT or rest on bilateral corticospinal excitability, intracortical inhibition and facilitation, and interhemispheric inhibition of the nonexercised upper limb muscle in healthy older adults (mean age 66 ± 8 yr). We used single and paired-pulse TMS to assess motor evoked potentials, short-interval intracortical inhibition, intracortical facilitation, and the ipsilateral silent period. Two groups of healthy older adults completed either HIIT exercise or seated rest for 23 min, with TMS measures performed before (T0), immediately after (T1), and 30 min after (T2) HIIT/rest. RESULTS: Motor evoked potentials were significantly increased after HIIT exercise at T2 compared with T0 in the dominant upper limb. Contrary to our hypothesis, we did not find any significant change in short-interval intracortical inhibition, intracortical facilitation, or ipsilateral silent period after HIIT. CONCLUSIONS: Our findings demonstrate that corticospinal excitability of the nonexercised upper limb is increased after HIIT in healthy older adults. Our results indicate that acute HIIT exercise impacts corticospinal excitability in older adults, without affecting intracortical or interhemispheric circuitry. These findings have implications for the development of exercise strategies to potentiate neuroplasticity in healthy older and clinical populations.

Observational Study of Neuroimaging Biomarkers of Severe Upper Limb Impairment After Stroke.

BACKGROUND AND OBJECTIVES: It is difficult to predict post-stroke outcome for people with severe motor impairment, as both clinical tests and corticospinal tract (CST) microstructure may not reliably indicate severe motor impairment. Here, we test whether imaging biomarkers beyond the CST relate to severe upper limb impairment post-stroke by evaluating white matter microstructure in the corpus callosum (CC). In an international, multisite hypothesis-generating observational study we determined if: a) CST asymmetry index can differentiate between individuals with mild-moderate and severe upper limb impairment; and b) CC biomarkers relate to upper limb impairment within individuals with severe impairment post-stroke. We hypothesised that CST asymmetry index would differentiate between mild-moderate and severe impairment, but CC microstructure would relate to motor outcome for individuals with severe upper limb impairment. METHODS: Seven cohorts with individual diffusion imaging and motor impairment (Fugl Meyer-Upper Limb) data were pooled. Hand-drawn regions-of-interest were used to seed probabilistic tractography for CST (ipsilesional/contralesional) and CC (prefrontal/premotor/motor/sensory/posterior) tracts. Our main imaging measure was mean fractional anisotropy. Linear mixed-effect regression explored relationships between candidate biomarkers and motor impairment, controlling for observations nested within cohorts, as well as age, sex, time post-stroke and lesion volume. RESULTS: Data from 110 individuals (30 mild-moderate, 80 with severe motor impairment) were included. In the full sample, greater CST asymmetry index (i.e., lower fractional anisotropy in the ipsilesional hemisphere, p<.001) and larger lesion volume (p=.139) were negatively related to impairment. In the severe subgroup, CST asymmetry index was not reliably associated with impairment across models. Instead, lesion volume and CC microstructure explained impairment in the severe group beyond CST asymmetry index (p's<.010). CONCLUSIONS: Within a large cohort of individuals with severe upper limb impairment, CC microstructure related to motor outcome post-stroke. Our findings demonstrate that CST microstructure does relate to upper limb outcome across the full range of motor impairment but was not reliably associated within the severe subgroup. Therefore, CC microstructure may provide a promising biomarker for severe upper limb outcome post-stroke, which may advance our ability to predict recovery in people with severe motor impairment after stroke.

Acute Exercise Modulates the Excitability of Specific Interneurons in Human Motor Cortex.

Acute exercise can modulate the excitability of the non-exercised upper-limb representation in the primary motor cortex (M1). Accumulating evidence demonstrates acute exercise affects measures of M1 intracortical excitability, with some studies also showing altered corticospinal excitability. However, the influence of distinct M1 interneuron populations on the modulation of intracortical and corticospinal excitability following acute exercise is currently unknown. We assessed the impact of an acute bout of leg cycling exercise on unique M1 interneuron excitability of a non-exercised intrinsic hand muscle using transcranial magnetic stimulation (TMS) in young adults. Specifically, posterior-to-anterior (PA) and anterior-to-posterior (AP) TMS current directions were used to measure the excitability of distinct populations of interneurons before and after an acute bout of exercise or rest. Motor evoked potentials (MEPs) and short-interval intracortical inhibition (SICI) were measured in the PA and AP current directions in M1 at two time points separated by 25 min of rest, as well as immediately and 30 min after a 25-minute bout of moderate-intensity cycling exercise. Thirty minutes after exercise, MEP amplitudes were significantly larger than other timepoints when measured with AP current, whereas MEP amplitudes derived from PA current did not show this effect. Similarly, SICI was significantly decreased immediately following acute exercise measured with AP but not PA current. Our findings suggest that the excitability of unique M1 interneurons are differentially modulated by acute exercise. These results indicate that M1 interneurons preferentially activated by AP current may play an important role in the exercise-induced modulation of intracortical and corticospinal excitability.

Multiple bouts of high-intensity interval exercise reverse age-related functional connectivity disruptions without affecting motor learning in older adults.

Exercise has emerged as an intervention that may mitigate age-related resting state functional connectivity and sensorimotor decline. Here, 42 healthy older adults rested or completed 3 sets of high-intensity interval exercise for a total of 23 min, then immediately practiced an implicit motor task with their non-dominant hand across five separate sessions. Participants completed resting state functional MRI before the first and after the fifth day of practice; they also returned 24-h and 35-days later to assess short- and long-term retention. Independent component analysis of resting state functional MRI revealed increased connectivity in the frontoparietal, the dorsal attentional, and cerebellar networks in the exercise group relative to the rest group. Seed-based analysis showed strengthened connectivity between the limbic system and right cerebellum, and between the right cerebellum and bilateral middle temporal gyri in the exercise group. There was no motor learning advantage for the exercise group. Our data suggest that exercise paired with an implicit motor learning task in older adults can augment resting state functional connectivity without enhancing behaviour beyond that stimulated by skilled motor practice.

Robot-Aided Upper-limb Proprioceptive Training in Three-Dimensional Space.

Proprioception, the ability to sense body position and limb movements in space without visual feedback, is one of the key factors in controlling body movements and performing activities of daily living. However, this capability might be affected after neural injuries such as stroke. Robotic platforms can be used to monitor and promote arm movements and, therefore, can assist in developing rehabilitation protocols that aim to improve proprioception through repetitive reaching motions without vision. The objective of this paper is to investigate if a robotic training protocol improves the end-position reaching proprioceptive sense in three-dimensional (3D) space. As an initial step towards clinical application, a robotic platform was employed to train the end-position proprioceptive sense in six healthy participants. During the training phase, volunteers used their dominant hand to reach without vision to two different targets in 3D space. Positions of these targets were carefully chosen to create a hand movement pattern similar to that used when self-feeding, which is an important activity of daily living. At the end of each training trial, participants were provided with visual feedback to help them move their hands to the exact locations confirmed through haptic feedback. Their performance was evaluated before and after the training in an assessment phase during which participants were asked to move from the start position to the same two targets as well as an additional third one without any visual or haptic feedback. The results from this study show significant improvements in overall reaching accuracy and trajectory smoothness, demonstrated by 41% decrease in the average end-position error and 13% reduction in the average index of curvature after the training. This research suggests the potential of designing robotic rehabilitation protocols for improving 3D proprioception.

Individualized Challenge Point Practice as a Method to Aid Motor Sequence Learning.

We conducted two studies to investigate if and how: (1) the rate of skill acquisition was related to motor performance at retention of a serial RT task (Study 1); and (2) whether rate of skill acquisition and baseline performance could be used to design schedules of practice related to contextual interference (CI) to enhance motor learning (Study 2). In Study 1, a slower rate of skill acquisition of repeating sequences in practice was related to faster response times at retention. Based on performance in Study 1, three levels of individualized CI were created for Study 2. Compared to low and moderate levels of CI, the higher CI practice condition led to faster response times in retention. We conclude that an individualized 'challenge point', which generates high CI enhances motor learning by optimizing challenge.