Michelle N. McDonnell

Suppression of LTP-like plasticity in human motor cortex by the GABAB receptor agonist baclofen

Previous experiments in slice preparations revealed that pharmacological activation of GABAB receptors down- or up-regulates long-term potentiation (LTP), depending on whether increase of GABAB receptor mediated inhibitory postsynaptic potentials or decrease of presynaptic auto-inhibition of GABAA receptor mediated inhibition predominates. The effects of GABAB receptor activation on LTP in humans in vivo are unknown. Here we show, by using transcranial magnetic stimulation, that the GABAB receptor agonist baclofen decreases paired associative stimulation induced LTP-like plasticity in human motor cortex. This suggests that increased GABAB mediated inhibitory postsynaptic potentials drive this effect, and that baclofen may have a negative impact on LTP-dependent behavioural processes such as motor learning.

Influence of Combined Afferent Stimulation and Task-Specific Training Following Stroke: A Pilot Randomized Controlled Trial

Background. Reorganization of the human motor cortex can be induced by specific patterns of peripheral afferent stimulation. The potential for afferent stimulation to facilitate the functional recovery associated with conventional rehabilitative techniques has not previously been investigated. Objective. The authors sought to determine whether combining appropriate afferent stimulation with task-specific training resulted in greater improvements than training alone in patients with impaired upper limb function in the subacute phase following stroke. Method. Twenty patients with hemiparesis due to stroke were allocated randomly to either a stimulation or control group. All received 9 sessions of task-specific physiotherapy training over 3 weeks. Prior to each training session, associative electrical stimulation of the motor point of 2 hand muscles was given in the stimulation group, whereas the control group received sham stimulation. Changes in dexterity were assessed using a grip-lift task, and standard measures of upper-limb function were made before and following the intervention. Corticospinal excitability was examined using transcranial magnetic stimulation. Results. Both groups showed comparable improvements in functional measures of upper-limb function. Of the 20 patients, only 14 could perform the grip-lift task, which is an objective measure of dexterity. Patients in the stimulation group From the Research Centre for Human Movement Control, School of exhibited significantly greater improvements in this task than the control group. There was no significant change in corticospinal excitability in either group. Conclusion. This pilot study provides preliminary data suggesting that targeted afferent stimulation may facilitate the response to conventional rehabilitation in patients with hemiparesis due to stroke, but these results need to be confirmed in a larger scale study.

Aerobic Exercise to Improve Cognitive Function in Adults With Neurological Disorders: A Systematic Review

OBJECTIVE To evaluate whether aerobic exercise improves cognition in adults diagnosed with neurologic disorders. DATA SOURCES The Cochrane Central Register of Controlled Clinical Trials, MEDLINE, CINAHL, PubMed, EMBASE, PEDro, AMED, SPORTDiscus, PsycINFO, ERIC, and Google Scholar, with the last search performed in December 2010. STUDY SELECTION We included controlled clinical trials and randomized controlled trials with adults diagnosed with a neurologic disorder. Studies were included if they compared a control group with a group involved in an aerobic exercise program to improve cardiorespiratory fitness and if they measured cognition as an outcome. DATA EXTRACTION Two reviewers independently extracted data and methodologic quality of the included trials. DATA SYNTHESIS From the 67 trials reviewed, a total of 7 trials, involving 249 participants, were included. Two trials compared the effectiveness of yoga and aerobic exercise in adults with multiple sclerosis. Two trials evaluated the effect of exercise on patients with dementia, and 2 trials evaluated the effectiveness of exercise to improve cognition after traumatic brain injury. One trial studied the effect of a cycling program in people with chronic stroke. Lack of commonality between measures of cognition limited meta-analyses. Results from individual studies show that aerobic exercise improved cognition in people with dementia, improved attention and cognitive flexibility in patients with traumatic brain injury, improved choice reaction time in people with multiple sclerosis, and enhanced motor learning in people with chronic stroke. CONCLUSIONS There is limited evidence to support the use of aerobic exercise to improve cognition in adults with neurologic disorders. Of the 67 studies retrieved, less than half included cognition as an outcome, and few studies continued the aerobic exercise program long enough to be considered effective. Further studies investigating the effect of aerobic exercise interventions on cognition in people with neurologic conditions are required.

A single bout of aerobic exercise promotes motor cortical neuroplasticity

Regular physical activity is associated with enhanced plasticity in the motor cortex, but the effect of a single session of aerobic exercise on neuroplasticity is unknown. The aim of this study was to compare corticospinal excitability and plasticity in the upper limb cortical representation following a single session of lower limb cycling at either low or moderate intensity, or a control condition. We recruited 25 healthy adults to take part in three experimental sessions. Cortical excitability was examined using transcranial magnetic stimulation to elicit motor-evoked potentials in the right first dorsal interosseus muscle. Levels of serum brain-derived neurotrophic factor and cortisol were assessed throughout the experiments. Following baseline testing, participants cycled on a stationary bike at a workload equivalent to 57% (low intensity, 30 min) or 77% age-predicted maximal heart rate (moderate intensity, 15 min), or a seated control condition. Neuroplasticity within the primary motor cortex was then examined using a continuous theta burst stimulation (cTBS) paradigm. We found that exercise did not alter cortical excitability. Following cTBS, there was a transient inhibition of first dorsal interosseus motor-evoked potentials during control and low-intensity conditions, but this was only significantly different following the low-intensity state. Moderate-intensity exercise alone increased serum cortisol levels, but brain-derived neurotrophic factor levels did not increase across any condition. In summary, low-intensity cycling promoted the neuroplastic response to cTBS within the motor cortex of healthy adults. These findings suggest that light exercise has the potential to enhance the effectiveness of motor learning or recovery following brain damage.

Impairments in precision grip correlate with functional measures in adult hemiplegia.

OBJECTIVE Analysis of a precision grip-lift task provides measures to assess functional disability of the hand, but the correlation between these measures and accepted tests of motor function in stroke patients has not been established. METHODS Seventeen subacute stroke patients were studied to compare parameters of a precision grip-lift task between the affected and unaffected side, and to correlate them with function. Functional impairment was assessed with the Action Research Arm Test and the Fugl-Meyer assessment, as well as grip strength and maximal finger-tapping speed. The grip force (GF) and load force (LF) were recorded as patients lifted a custom-built manipulandum. All measures were recorded on two separate occasions, at least 1 week apart. RESULTS There was good reproducibility between testing sessions for the grip-lift and functional measures. The affected hand gripped the manipulandum for longer prior to lift-off than the unaffected hand, and the normal close temporal coupling between the rate of change of GF and LF during the lift was disrupted. These two measures correlated more highly with the ARAT than the FMA and, when combined with measures of grip strength and tapping speed, explained 71% of the variance of the ARAT. CONCLUSIONS The grip-lift task is a sensitive measure of impaired dexterity following stroke and provides measures which correlate well with a commonly applied functional assessment scale. SIGNIFICANCE This task may be used clinically to detect changes in the hemiplegic upper limb during rehabilitation and recovery.

Physical Activity Frequency and Risk of Incident Stroke in a National US Study of Blacks and Whites

Background and Purpose— Regular physical activity (PA) is an important recommendation for stroke prevention. We compared the associations of self-reported PA with incident stroke in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. Methods— REGARDS recruited 30 239 US blacks (42%) and whites, aged ≥45 years with follow-up every 6 months for stroke events. Excluding those with prior stroke, analysis involved 27 348 participants who reported their frequency of moderate to vigorous intensity PA at baseline according to 3 categories: none (physical inactivity), 1 to 3×, and ≥4× per week. Stroke and transient ischemic attack cases were identified during an average of 5.7 years of follow-up. Cox proportional hazards models were constructed to examine whether self-reported PA was associated with risk of incident stroke. Results— Physical inactivity was reported by 33% of participants and was associated with a hazard ratio of 1.20 (95% confidence intervals, 1.02–1.42; P=0.035). Adjustment for demographic and socioeconomic factors did not affect hazard ratio, but further adjustment for traditional stroke risk factors (diabetes mellitus, hypertension, body mass index, alcohol use, and smoking) partially attenuated this risk (hazard ratio, 1.14 [0.95–1.37]; P=0.17). There was no significant association between PA frequency and risk of stroke by sex groups, although there was a trend toward increased risk for men reporting PA 0 to 3× a week compared with ≥4× a week. Conclusions— Self-reported low PA frequency is associated with increased risk of incident stroke. Any effect of PA is likely to be mediated through reducing traditional risk factors.

Effect of human grip strategy on force control in precision tasks.

Alternate grip strategies are often used for object manipulation in individuals with sensorimotor deficits. To determine the effect of grip type on force control, ten healthy adult subjects were asked to grip and lift a small manipulandum using a traditional precision grip (lateral pinch), a pinch grip with the fingers oriented downwards (downward pinch) and a “key grip” between the thumb and the side of the index finger. The sequence of grip type and hand used was varied randomly after every ten lifts. Each of the three grips resulted in different levels of force, with the key grip strategy resulting in the greatest grip force and the downward pinch grip using the least amount of grip force to lift the device. Cross-correlation analysis revealed that the ability to scale accurately the rate of grip force and load force changes was lowest in the downward pinch grip. This was also associated with a more variable time-shift between the two forces, indicating that the precise anticipatory control when lifting an object is diminished in this grip strategy. There was a difference between hands across all grips, with the left non-dominant hand using greater grip force during the lift but not the hold phase. Further, in contrast with the right hand, the left hand did not reduce grip force during the lift or the hold phase over the ten lifts, suggesting that the non-dominant hand did not quickly learn to optimise grip force. These findings suggest that the alternate grip strategies used by patients with limited fine motor control, such as following stroke, may partly explain the disruption of force control during object manipulation.

Afferent stimulation facilitates performance on a novel motor task

Training on a motor task results in performance improvements that are accompanied by increases in motor cortex excitability. Moreover, periods of afferent stimulation result in increased motor cortex excitability. There is increasing evidence to suggest that raised motor cortical excitability may facilitate movement and learning. Here we examined whether a period of electrical stimulation of hand afferents (“associative stimulation”), known to increase motor cortex excitability, facilitated the performance of a complex sensorimotor task. Three groups of nine normal subjects participated in these studies. All subjects were trained on the grooved pegboard test (GPT). Training consisted of three blocks, each of five trials, of placing pegs as quickly as possible. The time to complete each block was recorded. One group of subjects had a 1-h period of associative stimulation prior to training on the GPT. A second group received non-associative stimulation (which does not change cortical excitability) of the same hand afferents while a third group received no stimulation prior to training. Motor evoked potentials (MEPs) were recorded from the first dorsal interosseous (FDI) and abductor digiti minimus (ADM) muscles both prior to and following stimulation and performance of the GPT. In contrast to non-associative stimulation, associative stimulation increased motor cortical excitability, as evidenced by an increase in the amplitude of MEPs evoked in the FDI, one of the stimulated muscles, but not the ADM. Training on the GPT resulted in significant improvements in the time taken to complete the task for all three groups. However, in subjects who had preconditioning associative stimulation, performance on the GPT improved more rapidly. Additionally, there was a strong trend for the improvement in the performance of the stimulated group to be greater than that of the control group. The results of the present study suggest that increased motor cortical excitability, induced by associative stimulation, may facilitate the performance of a novel complex sensorimotor task.

Anodal transcranial direct current stimulation to the cerebellum improves handwriting and cyclic drawing kinematics in focal hand dystonia

There is increasing evidence that the cerebellum has a role in the pathophysiology of primary focal hand dystonia and might provide an intervention target for non-invasive brain stimulation to improve function of the affected hand. The primary objective of this study was to determine if cerebellar transcranial direct current stimulation (tDCS) improves handwriting and cyclic drawing kinematics in people with hand dystonia, by reducing cerebellar-brain inhibition (CBI) evoked by transcranial magnetic stimulation (TMS). Eight people with dystonia (5 writer’s dystonia, 3 musician’s dystonia) and eight age-matched controls completed the study and underwent cerebellar anodal, cathodal and sham tDCS in separate sessions. Dystonia severity was assessed using the Writer’s Cramp Rating Scale (WRCS) and the Arm Dystonia Disability Scale (ADDS). The kinematic measures that differentiated the groups were; mean stroke frequency during handwriting and fast cyclic drawing and average pen pressure during light cyclic drawing. TMS measures of cortical excitability were no different between people with FHD and controls. There was a moderate, negative relationship between TMS-evoked CBI at baseline and the WRCS in dystonia. Anodal cerebellar tDCS reduced handwriting mean stroke frequency and average pen pressure, and increased speed and reduced pen pressure during fast cyclic drawing. Kinematic measures were not associated with a decrease in CBI within an individual. In conclusion, cerebellar anodal tDCS appeared to improve kinematics of handwriting and circle drawing tasks; but the underlying neurophysiological mechanism remains uncertain. A study in a larger homogeneous population is needed to further investigate the possible therapeutic benefit of cerebellar tDCS in dystonia.

Transient motor evoked potential suppression following a complex sensorimotor task

OBJECTIVE To investigate the mechanism involved in the transient suppression of the response to transcranial magnetic stimulation (TMS) following repeated performance of a complex sensorimotor training task (ST). METHODS A total of 19 healthy subjects participated in 4 experiments, all involving performance of the grooved pegboard test (GPT). The experiments investigated the effect of the ST on corticospinal and intracortical excitability, spinal excitability and maximal pinch grip force. RESULTS Motor evoked potential amplitude decreased significantly following the ST in both muscles tested and this was associated, but not correlated, with a decrease in the time taken to perform the GPT. There was no change in intracortical inhibition or facilitation (tested at interstimulus intervals of 3 and 10 ms, respectively). M wave amplitude was unchanged, as were F wave amplitude, latency and persistence and there was no evidence of muscle fatigue. CONCLUSIONS The reduction in corticospinal excitability was short lasting (<10 min) and was not accompanied by changes at the spinal or peripheral level, suggesting that other intracortical circuits may be involved. SIGNIFICANCE Repeated performance of motor tasks can result in both short- and long-term modulation of motor cortical excitability. However, the relationship between changes in corticospinal excitability and motor performance is complex and critically dependent upon task type and duration.