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Non-Invasive Modulation and Robotic Mapping of Motor Cortex in the Developing Brain

Mapping the motor cortex with transcranial magnetic stimulation (TMS) has potential to interrogate motor cortex physiology and plasticity but carries ...

University of Calgary

Robotic therapy can improve upper limb function in hemiparesis. Excitatory transcranial direct current stimulation (tDCS) can prime brain motor circuits before therapy.

Combined transcranial direct current stimulation and robotic upper limb therapy improves upper limb function in an adult with cerebral palsy.

Children with unilateral spastic cerebral palsy (CP) often have mirror movements, i.e. involuntary imitations of unilateral voluntary movements of the contralateral upper extremity. The pathophysiology of mirror movements has been investigated in small and heterogeneous cohorts in the literature. Specific pathophysiology of mirror movements and their impact on upper extremity function require systematic investigation in larger and homogeneous cohorts of children with unilateral spastic CP. Here we review two possible neurophysiological mechanisms underlying mirror movements in children with CP and those with typical development: (1) an ipsilateral corticospinal tract projecting from the contralesional motor cortex (M1) to both upper extremities; (2) insufficient interhemispheric inhibition between the two M1s. We also discuss clinical implications of mirror movements in children with unilateral CP and suggest that a thorough examination of the relationship between the pathophysiology and clinical manifestations of mirror movements is warranted. We suggest two premises: (1) the presence of mirror movements is indicative of an ipsilateral corticospinal tract reorganization; and (2) the corticospinal tract organization may affect patients' responses to certain treatment. If these premises are supported through future research, mirror movements should be clinically evaluated for patient selection to maximize benefits of therapy, hence promoting individualized medicine in this population.

Neurophysiological mechanisms and functional impact of mirror movements in children with unilateral spastic cerebral palsy.

We tested the hypothesis that somatosensory system injury would more strongly affect movement than motor system injury in children with unilateral cerebral palsy (USCP). This hypothesis was based on how somatosensory and corticospinal circuits adapt to injury during development; whereas the motor system can maintain connections to the impaired hand from the uninjured hemisphere, this does not occur in the somatosensory system. As a corollary, cortical injury strongly impairs sensory function, so we hypothesized that cortical lesions would impair hand function more than subcortical lesions.

Effect of sensory and motor connectivity on hand function in pediatric hemiplegia.

In many children with unilateral spastic cerebral palsy (USCP), the corticospinal tract to the affected hand atypically originates in the hemisphere ipsilateral to the affected hand. Such ipsilateral connectivity is on average a predictor of poor hand function. However, there is high variability in hand function in these children, which might be explained by the complexity of motor representations of both hands in the contralesional hemisphere.

The Relationship Between Hand Function and Overlapping Motor Representations of the Hands in the Contralesional Hemisphere in Unilateral Spastic Cerebral Palsy.

 Transcranial direct current stimulation (tDCS) can improve motor learning in children. High-definition approaches (HD-tDCS) have not been examined in children.  We hypothesized that primary motor cortex HD-tDCS would enhance motor learning but be inferior to tDCS in children.  Twenty-four children were recruited for a randomized, sham-controlled, double-blinded interventional trial (NCT03193580, clinicaltrials.gov/ct2/show/NCT03193580) to receive (1) right hemisphere (contralateral) primary motor cortex (M1) 1 mA anodal conventional 1 × 1 tDCS (tDCS), (2) right M1 1 mA anodal 4 × 1 HD-tDCS (HD-tDCS), or (3) sham. Over five consecutive days, participants trained their left hand using the Purdue Pegboard Test (PPT). The Jebsen-Taylor Test, Serial Reaction Time Task, and right hand and bimanual PPT were also tested at baseline, post-training, and 6-week retention time (RT).  Both the tDCS and HD-tDCS groups demonstrated enhanced motor learning compared to sham with effects maintained at 6 weeks. Effect sizes were moderate-to-large for tDCS and HD-tDCS groups at the end of day 4 (Cohen's  tDCS = 0.960, HD-tDCS = 0.766) and day 5 (tDCS = 0.655, HD-tDCS = 0.851). Enhanced motor learning effects were also seen in the untrained hand. HD-tDCS was well tolerated and safe with no adverse effects.  HD-tDCS and tDCS can enhance motor learning in children. Further exploration is indicated to advance rehabilitation therapies for children with motor disabilities such as cerebral palsy.  clinicaltrials.gov, identifier NCT03193580.

Effects of High-Definition and Conventional Transcranial Direct-Current Stimulation on Motor Learning in Children.

We aimed to determine if the mirror movements that often result in children with unilateral cerebral palsy (CP) after perinatal stroke represent a clinical biomarker of developmental plasticity.

Mirror movements in children with unilateral cerebral palsy due to perinatal stroke: clinical correlates of plasticity reorganization.

To characterize fatigue in children with hemiparesis with perinatal stroke and explore associations with measures of motor performance and corticospinal excitability.

Article	Year
Combined transcranial direct current stimulation and robotic upper limb therapy improves upper limb function in an adult with cerebral palsy. NeuroRehabilitation\| PubMed ID: 28505986	2017
Neurophysiological mechanisms and functional impact of mirror movements in children with unilateral spastic cerebral palsy. Developmental medicine and child neurology\| PubMed ID: 28884806	2018
Effect of sensory and motor connectivity on hand function in pediatric hemiplegia. Annals of neurology\| PubMed ID: 29034483	2017
The Relationship Between Hand Function and Overlapping Motor Representations of the Hands in the Contralesional Hemisphere in Unilateral Spastic Cerebral Palsy. Neurorehabilitation and neural repair\| PubMed ID: 29303031	2018
Effects of High-Definition and Conventional Transcranial Direct-Current Stimulation on Motor Learning in Children. Frontiers in neuroscience\| PubMed ID: 30429768	2018
Mirror movements in children with unilateral cerebral palsy due to perinatal stroke: clinical correlates of plasticity reorganization. Developmental medicine and child neurology\| PubMed ID: 30690708	2019
Fatigue in children with perinatal stroke: clinical and neurophysiological associations. Developmental medicine and child neurology\| PubMed ID: 31222717	2019

Hsing-Ching Kuo

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