Melanie K. Fleming

Priming the motor system enhances the effects of upper limb therapy in chronic stroke.

After stroke, the function of primary motor cortex (M1) between the hemispheres may become unbalanced. Techniques that promote a re-balancing of M1 excitability may prime the brain to be more responsive to rehabilitation therapies and lead to improved functional outcomes. The present study examined the effects of Active-Passive Bilateral Therapy (APBT), a putative movement-based priming strategy designed to reduce intracortical inhibition and increase excitability within the ipsilesional M1. Thirty-two patients with upper limb weakness at least 6 months after stroke were randomized to a 1-month intervention of self-directed motor practice with their affected upper limb (control group) or to APBT for 10-15 min prior to the same motor practice (APBT group). A blinded clinical rater assessed upper limb function at baseline, and immediately and 1 month after the intervention. Transcranial magnetic stimulation was used to assess M1 excitability. Immediately after the intervention, motor function of the affected upper limb improved in both groups (P < 0.005). One month after the intervention, the APBT group had better upper limb motor function than control patients (P < 0.05). The APBT group had increased ipsilesional M1 excitability (P < 0.025), increased transcallosal inhibition from ipsilesional to contralesional M1 (P < 0.01) and increased intracortical inhibition within contralesional M1 (P < 0.005). None of these changes were found in the control group. APBT produced sustained improvements in upper limb motor function in chronic stroke patients and induced specific and sustained changes in motor cortex inhibitory function. We speculate that APBT may have facilitated plastic reorganization in the brain in response to motor therapy. The utility of APBT as an adjuvant to physical therapy warrants further consideration.

Lateralization of unimanual and bimanual motor imagery

Most studies of motor imagery have examined motor cortex function during imagery of dominant hand movement. The aim of this study was to examine the modulation of excitability in the dominant and non-dominant corticomotor pathways during kinesthetic motor imagery of unimanual and bimanual movement. Transcranial magnetic stimulation (TMS) was applied over the contralateral motor cortex (M1) to elicit motor-evoked potentials (MEPs) in the abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles of each hand, in two separate sessions. Transcutaneous electrical stimuli were also delivered to the median nerve at each wrist, to elicit F-waves from APB. Fifteen right-handed volunteers imagined unimanual and bimanual phasic thumb movements, paced with a 1-Hz auditory metronome. Stimuli were delivered at rest, and either 50 ms before (ON phase), or 450 ms after (OFF phase), the metronome beeps. Significant MEP amplitude facilitation occurred only in right APB, during the ON phase of motor imagery of the right hand and both hands. Significant temporal modulation of right APB MEP amplitude was observed during motor imagery of right, left and bimanual performance. F-wave persistence and amplitude were unaffected by imagery. These results demonstrate that the motor imagery is lateralized to the left (dominant) hemisphere, which is engaged by imagery of each hand separately, and bimanual imagery. This finding has implications for the use of motor imagery in rehabilitation.

The Effect of Coil Type and Navigation on the Reliability of Transcranial Magnetic Stimulation

The objective of this study was to investigate reliability of transcranial magnetic stimulation (TMS) parameters for three coil systems; hand-held circular and figure-of-eight and navigated figure-of-eight coils. Stimulus response curves, intracortical inhibition (SICI) and facilitation (ICF) were studied in the right first dorsal interosseus muscle of 10 healthy adults. Each coil system was tested twice per subject. Navigation was conducted by a custom built system. Cortical excitability showed moderate-to-good reliability for the hand-held and navigated figure-of-eight coils (Intraclass correlation coefficients (ICCs) 0.55-0.89). The circular coil showed poor reliability for motor evoked potential (MEP) amplitude at 120% resting motor threshold (RMT; MEP<;sub>;120<;/sub>;) and MEP sum (ICCs 0.09 & 0.48). Reliability for SICI was good for all coil systems when an outlier was removed (ICCs 0.87-0.93), but poor for ICF (ICCs <; 0.3). The circular coil had a higher MEP<;sub>;120<;/sub>; than the navigated figure-of-eight coil (p = 0.004). Figure-of-eight coils can be used confidently to investigate cortical excitability over time. ICF should be interpreted with caution. The navigation device frees the experimenter and enables tracking of the position of the coil and subject. The results help guide the choice of coil system for longitudinal measurements of motor cortex function.

Bilateral parietal cortex function during motor imagery.

The aim of this study was to investigate the involvement of the parietal cortex during motor imagery (MI). In experiment one, participants imagined a sequence of upper limb movements during FMRI scanning. Statistical parametric mapping revealed a network of activation consistent with previous MI research, including activation in right and left inferior and superior parietal cortex. In experiment two, participants imagined a sequence of upper limb movements while real or sham single-pulse TMS was delivered over the scalp area corresponding to each individual’s left or right superior parietal cortex. At the end of each trial, participants moved their upper limbs to the position that would result from executing the sequence of movements. TMS degraded accuracy of MI compared to sham stimulation, and both accuracy and confidence decreased with real and sham stimulation later in the MI sequence. The effects of TMS were similar when delivered to either hemisphere. The results of this study provide evidence of the crucial role of SPL in MI, and may have implications for rehabilitation from brain injury.

The Effect of Combined Somatosensory Stimulation and Task-Specific Training on Upper Limb Function in Chronic Stroke A Double-Blind Randomized Controlled Trial

Background. Somatosensory stimulation (SS) is a potential adjuvant to stroke rehabilitation, but the effect on function needs further investigation. Objective. To explore the effect of combining SS with task-specific training (TST) on upper limb function and arm use in chronic stroke survivors and determine underlying mechanisms. Methods. In this double-blinded randomized controlled trial (ISRCTN 05542931), 33 patients (mean 37.7 months poststroke) were block randomized to 2 groups: active or sham SS. They received 12 sessions of 2 hours of SS (active or sham) to all 3 upper limb nerves immediately before 30 minutes of TST. The primary outcome was the Action Research Arm Test (ARAT) score. Secondary outcomes were time to perform the ARAT, Fugl-Meyer Assessment score (FM), Motor Activity Log (MAL), and Goal Attainment Scale (GAS). Underlying mechanisms were explored using transcranial magnetic stimulation stimulus–response curves and intracortical inhibition. Outcomes were assessed at baseline, immediately following the intervention (mean 2 days), and 3 and 6 months (mean 96 and 190 days) after the intervention. Results. The active group (n = 16) demonstrated greater improvement in ARAT score and time immediately postintervention (between-group difference; P < .05), but not at 3- or 6-month follow-ups (P > .2). Within-group improvements were seen for both groups for ARAT and GAS, but for the active group only for FM and MAL (P < .05). Corticospinal excitability did not change. Conclusions. Long-lasting improvements in upper limb function were observed following TST. Additional benefit of SS was seen immediately post treatment, but did not persist and the underlying mechanisms remain unclear.

Self-perceived utilization of the paretic arm in chronic stroke requires high upper limb functional ability.

Objective To explore potential predictors of self-reported paretic arm use at baseline and after task-specific training (TST) in survivors of stroke. Design Data were obtained from a randomized controlled trial of somatosensory stimulation and upper limb TST in chronic stroke. Setting University laboratory. Participants Chronic (≥3mo) survivors of stroke (N=33; mean age, 62y; mean stroke duration, 38mo). Interventions Participants received 12 sessions of TST preceded by either active (n=16) or sham (n=17) somatosensory stimulation to all 3 peripheral nerves. Main Outcome Measures Demographic and clinical characteristics were entered stepwise into multiple linear regression analyses to determine the factors that best predict baseline Motor Activity Log (MAL) amount of use rating and change 3 months after TST. Results The Action Research Arm Test (ARAT) score predicted the amount of use at baseline (R2=.47, P<.001); in using this model, an ARAT score of 54 (maximum of 57) is required to score 2.5 on the MAL (use described as between rarely and sometimes). After TST the change in the ARAT score predicted the change in the amount of use (R2=.31, P=.001). The predictive power of the model for change at 3 months increased if the Fugl-Meyer Assessment wrist component score was added (R2=.41, P=.001). Conclusions Utilization of the paretic upper limb in activities of daily living requires high functional ability. The increase in self-reported arm use after TST is dependent on the change in functional ability. These results provide further guidance for rehabilitation decisions.

Reliability of Transcallosal Inhibition in Healthy Adults.

Transcallosal inhibition (TCI), assessed using transcranial magnetic stimulation, can provide insight into the neurophysiology of aging and of neurological disorders such as stroke. However, the reliability of TCI using the ipsilateral silent period (iSP) has not been formally assessed, despite its use in longitudinal studies. This study aimed to determine the reliability of iSP onset latency, duration and depth in healthy young and older adults. A sample of 18 younger (mean age 27.7 years, range: 19–42) and 13 older healthy adults (mean age 68.1 years, range: 58–79) attended four sessions whereby the iSP was measured from the first dorsal interosseous (FDI) muscle of each hand. 20 single pulse stimuli were delivered to each primary motor cortex at 80% maximum stimulator output while the participant maintained an isometric contraction of the ipsilateral FDI. The average onset latency, duration of the iSP, and depth of inhibition relative to baseline electromyography activity was calculated for each hand in each session. Intraclass correlation coefficients (ICCs) were calculated for all four sessions, or the first two sessions only. For iSP onset latency the reliability ranged from poor to good. For iSP duration there was moderate to good reliability (ICC > 0.6). Depth of inhibition demonstrated variation in reproducibility depending on which hand was assessed and whether two or four sessions were compared. Bland and Altman analyses showed wide limits of agreement between the first two sessions, particularly for iSP depth. However, there was no systematic pattern to the variability. These results indicate that although iSP duration is reliable in healthy adults, changes in longitudinal studies should be interpreted with caution, particularly for iSP depth. Future studies are needed to determine reliability in clinical populations.

Explicit motor sequence learning with the paretic arm after stroke

Abstract Purpose: Motor sequence learning is important for stroke recovery, but experimental tasks require dexterous movements, which are impossible for people with upper limb impairment. This makes it difficult to draw conclusions about the impact of stroke on learning motor sequences. We aimed to test a paradigm requiring gross arm movements to determine whether stroke survivors with upper limb impairment were capable of learning a movement sequence as effectively as age-matched controls. Materials and methods: In this case-control study, 12 stroke survivors (10–138 months post-stroke, mean age 64 years) attempted the task once using their affected arm. Ten healthy controls (mean 66 years) used their non-dominant arm. A sequence of 10 movements was repeated 25 times. The variables were: time from target illumination until the cursor left the central square (onset time; OT), accuracy (path length), and movement speed. Results: OT reduced with training (p < 0.05) for both groups, with no change in movement speed or accuracy (p > 0.1). We quantified learning as the OT difference between the end of training and a random sequence; this was smaller for stroke survivors than controls (p = 0.015). Conclusions: Stroke survivors can learn a movement sequence with their paretic arm, but demonstrate impairments in sequence specific learning. Implications for Rehabilitation Motor sequence learning is important for recovery of movement after stroke. Stroke survivors were found to be capable of learning a movement sequence with their paretic arm, supporting the concept of repetitive task training for recovery of movement. Stroke survivors showed impaired sequence specific learning in comparison with age-matched controls, indicating that they may need more repetitions of a sequence in order to re-learn movements. Further research is required into the effect of lesion location, time since stroke, hand dominance and gender on learning of motor sequences after stroke.

Fluoxetine Does Not Enhance Visual Perceptual Learning and Triazolam Specifically Impairs Learning Transfer

The selective serotonin reuptake inhibitor fluoxetine significantly enhances adult visual cortex plasticity within the rat. This effect is related to decreased gamma-aminobutyric acid (GABA) mediated inhibition and identifies fluoxetine as a potential agent for enhancing plasticity in the adult human brain. We tested the hypothesis that fluoxetine would enhance visual perceptual learning of a motion direction discrimination (MDD) task in humans. We also investigated (1) the effect of fluoxetine on visual and motor cortex excitability and (2) the impact of increased GABA mediated inhibition following a single dose of triazolam on post-training MDD task performance. Within a double blind, placebo controlled design, 20 healthy adult participants completed a 19-day course of fluoxetine (n = 10, 20 mg per day) or placebo (n = 10). Participants were trained on the MDD task over the final 5 days of fluoxetine administration. Accuracy for the trained MDD stimulus and an untrained MDD stimulus configuration was assessed before and after training, after triazolam and 1 week after triazolam. Motor and visual cortex excitability were measured using transcranial magnetic stimulation. Fluoxetine did not enhance the magnitude or rate of perceptual learning and full transfer of learning to the untrained stimulus was observed for both groups. After training was complete, trazolam had no effect on trained task performance but significantly impaired untrained task performance. No consistent effects of fluoxetine on cortical excitability were observed. The results do not support the hypothesis that fluoxetine can enhance learning in humans. However, the specific effect of triazolam on MDD task performance for the untrained stimulus suggests that learning and learning transfer rely on dissociable neural mechanisms.

Non-invasive brain stimulation for the lower limb after stroke: what do we know so far and what should we be doing next?

Abstract Background: Non-invasive brain stimulation (NIBS) is promising as an adjuvant to rehabilitation of motor function after stroke. Despite numerous studies and reviews for the upper limb, NIBS targeting the lower limb and gait recovery after stroke is a newly emerging field of research. Purpose: To summarize findings from studies using NIBS to target the lower limb in stroke survivors. Methods: This narrative review describes studies of repetitive transcranial magnetic stimulation, paired associative stimulation and transcranial direct current stimulation with survivors of stroke. Results: NIBS appears capable of inducing changes in cortical excitability and lower limb function, but stimulation parameters and study designs vary considerably making it difficult to determine effectiveness. Conclusions: Future research should systematically assess differences in response with different stimulation parameters, test measures for determining who would be most likely to benefit and assess effectiveness with large samples before NIBS can be considered for use in clinical practice. Implications for Rehabilitation Stroke is a leading cause of disability, often resulting in dependency in activities of daily living and reduced quality of life. Non-invasive brain stimulation has received considerable interest as a potential adjuvant to rehabilitation after stroke and this review summarizes studies targeting the lower limb and gait recovery. Non-invasive brain stimulation can be used to modulate excitability of lower limb muscle representations and can lead to improvements in motor performance in stroke survivors. Non-invasive brain stimulation for gait recovery needs further investigation before translation to clinical practice is possible.