Winston D. Byblow

Consensus: Motor cortex plasticity protocols

Noninvasive transcranial stimulation is being increasingly used by clinicians and neuroscientists to alter deliberately the status of the human brain. Important applications are the induction of virtual lesions (for example, transient dysfunction) to identify the importance of the stimulated brain network for a certain sensorimotor or cognitive task, and the induction of changes in neuronal excitability, synaptic plasticity or behavioral function outlasting the stimulation, for example, for therapeutic purposes. The aim of this article is to review critically the properties of the different currently used stimulation protocols, including a focus on their particular strengths and weaknesses, to facilitate their appropriate and conscientious application.

The PREP algorithm predicts potential for upper limb recovery after stroke.

Stroke is a leading cause of adult disability and the recovery of motor function is important for independence in activities of daily living. Predicting motor recovery after stroke in individual patients is difficult. Accurate prognosis would enable realistic rehabilitation goal-setting and more efficient allocation of resources. The aim of this study was to test and refine an algorithm for predicting the potential for recovery of upper limb function after stroke. Forty participants were prospectively enrolled within 3 days of ischaemic stroke. First, shoulder abduction and finger extension strength were graded 72 h after stroke onset to compute a shoulder abduction and finger extension score. Secondly, transcranial magnetic stimulation was used to assess the functional integrity of descending motor pathways to the affected upper limb. Third, diffusion-weighted magnetic resonance imaging was used to assess the structural integrity of the posterior limbs of the internal capsules. Finally, these measures were combined in the PREP algorithm for predicting an individuals potential for upper limb recovery at 12 weeks, measured with the Action Research Arm Test. A cluster analysis was used to independently group patients according to Action Research Arm Test score at 12 weeks, for comparison with predictions from the PREP algorithm. There was excellent correspondence between the cluster analysis of Action Research Arm Test score at 12 weeks and predictions made with the PREP algorithm. The algorithm had positive predictive power of 88%, negative predictive power of 83%, specificity of 88% and sensitivity of 73%. This study provides preliminary data in support of the PREP algorithm for the prognosis of upper limb recovery in individual patients. PREP may enable tailored planning of rehabilitation and more accurate stratification of patients in clinical trials.

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.

Rhythmic Bilateral Movement Training Modulates Corticomotor Excitability and Enhances Upper Limb Motricity Poststroke: A Pilot Study

The recovery of coordinated motor function after stroke onset has been associated with the practice of upper limb movements that required the activation of homologous muscles. This pilot study investigated whether repetitive bimanual coordinated movements enhanced upper limb corticomotor (CM) excitability and motor function poststroke. Patients practiced driving their paretic wrist through passive rhythmical flexion-extension by active flexion-extension of their unaffected wrist using purpose-built manipulanda over a 4-week period. Both preintervention and postintervention motricity was assessed using the upper limb Fugl-Meyer rating scale, and cortical maps of wrist flexor and extensor representations were derived from potentials evoked by transcranial magnetic stimulation. Five of nine subjects improved upper limb motricity in response to this novel active-passive bimanual movement therapy (APBT). Unaffected cortical map volume decreased, especially for a subgroup of five patients who had a postintervention increase in motricity. No change in unaffected map volume was revealed for the four patients who did not improve their postintervention motricity. No consistent shifts in cortical map center of gravity were revealed. These findings suggest that APBT can initiate an improvement in motricity that is accompanied by a balancing of between-hemisphere CM excitability. The findings justify the assessment of the rehabilitative effects of APBT in a homogeneous sample of patients poststroke.

Excitability changes in human forearm corticospinal projections and spinal reflex pathways during rhythmic voluntary movement of the opposite limb.

Rhythmic movements brought about by the contraction of muscles on one side of the body give rise to phase‐locked changes in the excitability of the homologous motor pathways of the opposite limb. Such crossed facilitation should favour patterns of  bimanual coordination in which homologous muscles are engaged simultaneously, and disrupt those in which the muscles are activated in an alternating fashion. In order to examine these issues, we obtained responses to transcranial magnetic stimulation (TMS), to stimulation of the cervicomedullary junction (cervicomedullary‐evoked potentials, CMEPs), to peripheral nerve stimulation (H‐reflexes and f‐waves), and elicited stretch reflexes in the relaxed right flexor carpi radialis (FCR) muscle during rhythmic (2 Hz) flexion and extension movements of the opposite (left) wrist. The potentials evoked by TMS in right FCR were potentiated during the phases of movement in which the left FCR was most strongly engaged. In contrast, CMEPs were unaffected by the movements of the opposite limb. These results suggest that there was systematic variation of the excitability of the motor cortex ipsilateral to the moving limb. H‐reflexes and stretch reflexes recorded in right FCR were modulated in phase with the activation of left FCR. As the f‐waves did not vary in corresponding fashion, it appears that the phasic modulation of the H‐reflex was mediated by presynaptic inhibition of Ia afferents. The observation that both H‐reflexes and f‐waves were depressed markedly during movements of the opposite indicates that there may also have been postsynaptic inhibition or disfacilitation of the largest motor units. Our findings indicate that the patterned modulation of excitability in motor pathways that occurs during rhythmic movements of the opposite limb is mediated primarily by interhemispheric interactions between cortical motor areas.

Combining Theta Burst Stimulation With Training After Subcortical Stroke

Background and Purpose— Repetitive transcranial magnetic stimulation of the primary motor cortex (M1) may improve outcomes after stroke. The aim of this study was to determine the effects of M1 theta burst stimulation (TBS) and standardized motor training on upper-limb function of patients with chronic stroke. Methods— Ten patients with chronic subcortical stroke and upper-limb impairment were recruited to this double-blind, crossover, sham-controlled study. Intermittent TBS of the ipsilesional M1, continuous TBS of the contralesional M1, and sham TBS were delivered in separate sessions in conjunction with standardized training of a precision grip task using the paretic upper limb. Results— Training after real TBS improved paretic-hand grip-lift kinetics, whereas training after sham TBS resulted in deterioration of grip-lift. Ipsilesional M1 excitability increased after intermittent TBS of the ipsilesional M1 but decreased after continuous TBS of the contralesional M1. Action Research Arm Test scores deteriorated when training followed continuous TBS of the contralesional M1, and this was correlated with reduced ipsilesional corticomotor excitability. Conclusions— Generally, TBS and training led to task-specific improvements in grip-lift. Specifically, continuous TBS of the contralesional M1 led to an overall decrement in upper-limb function, indicating that the contralesional hemisphere may play a pivotal role in recovery after stroke.

Proportional recovery after stroke depends on corticomotor integrity

For most patients, resolution of upper limb impairment during the first 6 months poststroke is 70% of the maximum possible. We sought to identify candidate mechanisms of this proportional recovery. We hypothesized that proportional resolution of upper limb impairment depends on ipsilesional corticomotor pathway function, is mirrored by proportional recovery of excitability in this pathway, and is unaffected by upper limb therapy dose.

Primary motor cortex and movement prevention: Where Stop meets Go

Processes that engage frontal cortex and the basal ganglia are responsible for the prevention of planned movements. Here, we review the role of primary motor cortex (M1) in this function. M1 receives and integrates input from a range of cortical and subcortical sites. It is also the final cortical processing site for voluntary motor commands, before they descend to the spinal cord. Inhibitory networks within M1 may be an important mechanism for the prevention or suppression of movement. Transcranial magnetic stimulation (TMS) has been used to evaluate corticospinal excitability and intracortical inhibition in humans, during the performance of a range of movement selection and prevention tasks. This review explores how M1 intracortical inhibition is selectively reduced to initiate desired voluntary movements, while movement prevention is associated with rapid, non-selective recruitment of inhibition within M1. The relationship between deficient intracortical inhibition and behavioural inhibition is also explored. Examples of neuropathology are reviewed, including focal dystonia, attention deficit hyperactivity disorder and Tourette syndrome. The strengths and limitations of TMS in the study of movement prevention are also discussed. While the precise functional links between M1 neuronal populations and the fronto-basal-ganglia network activated by movement prevention have yet to be elucidated, it is clear that M1 plays a critical role in the final processing stage of response inhibition.

Symmetric facilitation between motor cortices during contraction of ipsilateral hand muscles

Abstract. Using transcranial magnetic stimulation (TMS) over the contralateral motor cortex, motor evoked potentials (MEPs) were recorded from resting abductor pollicis brevis (APB) and first dorsal interosseous (FDI) muscles of eight subjects while they either rested or produced one of six levels of force with the APB ipsilateral to the TMS. F-waves were recorded from each APB at rest in response to median nerve stimulation while subjects either rested or produced one of two levels of force with their contralateral APB. Contraction of the APB ipsilateral to TMS produced facilitation of the MEPs recorded from resting APB and FDI muscles contralateral to TMS but did not modulate F-wave amplitude. Negligible asymmetries in MEP facilitation were observed between dominant and subdominant hands. These results suggest that facilitation arising from isometric contraction of ipsilateral hand muscles occurs primarily at supraspinal levels, and this occurs symmetrically between dominant and subdominant hemispheres.

Stop and go: The neural basis of selective movement prevention

Converging lines of evidence show that volitional movement prevention depends on the right prefrontal cortex (PFC), especially the right inferior frontal gyrus (IFG). Selective movement prevention refers to the rapid prevention of some, but not all, movement. It is unknown whether the IFG, or other prefrontal areas, are engaged when movement must be selectively prevented, and whether additional cortical areas are recruited. We used rapid event-related fMRI to investigate selective and nonselective movement prevention during performance of a temporally demanding anticipatory task. Most trials involved simultaneous index and middle finger extension. Randomly interspersed trials required the prevention of one, or both, finger movements. Regions of the right hemisphere, including the IFG, were active for selective and nonselective movement prevention, with an overlap in the inferior parietal cortex and the middle frontal gyrus. Selective movement prevention caused a significant delay in movement initiation of the other digit. These trials were associated with activation of the medial frontal cortex. The results provide support for a right-hemisphere network that temporarily “brakes” all movement preparation. When movement is selectively prevented, the supplementary motor cortex (SMA/pre-SMA) may participate in conflict resolution and subsequent reshaping of excitatory drive to the motor cortex.