E. Zewdie

Contralesional Corticomotor Neurophysiology in Hemiparetic Children With Perinatal Stroke: Developmental Plasticity and Clinical Function.

Background. Perinatal stroke causes most hemiparetic cerebral palsy. Ipsilateral connections from nonlesioned hemisphere to affected hand are common. The nonlesioned primary motor cortex (M1) determines function and is a potential therapeutic target but its neurophysiology is poorly understood. Objective. We aimed to characterize the neurophysiological properties of the nonlesioned M1 in children with perinatal stroke and their relationship to clinical function. Methods. Fifty-two participants with hemiparetic cerebral palsy and magnetic resonance imaging–confirmed perinatal stroke and 40 controls aged 8 to 18 years completed the same transcranial magnetic stimulation (TMS) protocol. Single-pulse TMS to nonlesioned M1 determined rest and active motor thresholds (RMT/AMT), motor-evoked potential (MEP) latencies, and stimulus recruitment curves (SRC: 100%-150% RMT). Paired-pulse TMS evaluated short-latency intracortical inhibition (SICI) and intracortical facilitation (ICF). Ipsilateral (IP) participants (ipsilateral MEP ≥0.05 mV in ≥5/20 trials) were compared with contralateral MEP only, nonipsilateral (NI) participants. Assisting Hand and Melbourne assessments quantified clinical function. Results. Twenty-five IP were compared with 13 NI (n = 38, median age 12 years, 66% male). IP had lower motor function. SRC to unaffected hand were comparable between IP and NI while IP had smaller ipsilateral SRC. Ipsilateral MEP latencies were prolonged (23.5 ± 1.8 vs 22.2 ± 1.5 ms contra, P < .001). Contralateral SICI was different between IP (−42%) and NI (−20%). Ipsilateral SICI was reduced (−20%). Contralateral ICF was comparable between groups (+43%) and ipsilaterally (+43%). Measures correlated between contralateral and ipsilateral sides. Conclusion. Neurophysiology of nonlesioned M1 and its relationship to motor function is measureable in children with perinatal stroke. Correlation of excitability and intracortical circuitry measures between contralateral and ipsilateral sides suggests common control mechanisms.

Developmental profile of motor cortex transcallosal inhibition in children and adolescents

Transcallosal fibers facilitate interhemispheric networks involved in motor tasks. Despite their clinical relevance, interhemispheric motor control systems have not been completely defined in the developing brain. The objective of this study was to examine the developmental profile of transcallosal inhibition in healthy children and adolescents. Nineteen typically developing right-handed participants were recruited. Two transcranial magnetic stimulation (TMS) paradigms assessed transcallosal inhibition: ipsilateral silent periods (iSP) and paired-pulse interhemispheric inhibition (IHI). TMS was applied to the motor hotspot of the first dorsal interosseous muscle. Resting motor threshold (RMT), iSP latency, duration and suppression strength, and paired-pulse IHI were measured from both hemispheres. The Purdue Pegboard Test assessed unimanual motor function. Hemispheric differences were evident for RMT and iSP latency and suppression strength, where the left hemisphere had a lower RMT, prolonged latency, and greater suppression strength. iSP duration showed hemispheric symmetry. RMT and iSP latency decreased with age, whereas iSP suppression strength increased. Girls showed shorter iSP latency. Children typically displayed IHI, although hemispheric differences were observed. iSP suppression strength was uniquely associated with IHI within individuals. iSP duration correlated with motor performance. TMS can characterize transcallosal inhibition in normal children and adolescents with effects of age, directionality, sex, and motor performance. Establishing this developmental profile of interhemispheric interactions may advance understanding and therapeutic strategies for pediatric motor disorders such as cerebral palsy.NEW & NOTEWORTHY Here we demonstrate that transcranial magnetic stimulation can characterize transcallosal inhibition in normal children and adolescents with effects of age, directionality, handedness, and motor performance. Interestingly, we also demonstrated sex effects, possibly related to the differing developmental profiles of boys and girls. Establishing this developmental profile of interhemispheric interactions may advance understanding and therapeutic strategies for pediatric motor disorders such as cerebral palsy.

Pilot study of supplementary motor area rTMS for Tourette's syndrome in children

of task irrelevant, competing stimuli (interference control) and in the inhibition of prepotent responses. The brain region most prominently associated with these aspects of inhibition control is the right inferior frontal gyrus (rIFG) which shows structural and functional alterations in ADHD. In our talk, we will give an overview over different approaches using transcranial direct current stimulation (tDCS) of the rIFG in healthy adults and will present findings from two of our own studies with ADHD youth targeting the rIFG.

Intervention-Induced Motor Cortex Plasticity in Hemiparetic Children With Perinatal Stroke

Background. Clinical trials are suggesting efficacy of intensive therapy combined with brain stimulation to improve hand function in hemiparetic children with perinatal stroke. However, individual variability exists and the underlying neuroplasticity mechanisms are unknown. Exploring primary motor cortex (M1) neurophysiology, and how it changes with such interventions, may provide valuable biomarkers for advancing personalized neurorehabilitation. Methods. Forty-five children (age 6-19 years) with hemiparesis participated in PLASTIC CHAMPS, a blinded, sham-controlled, factorial clinical trial. All received 80 hours of goal-directed intensive upper extremity therapy. They were randomized into 4 groups: repetitive transcranial magnetic stimulation (rTMS) of contralesional M1, constraint therapy, both, or neither. Stimulus recruitment curves (SRC), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) for lesioned and contralesional M1 were investigated using TMS. Clinical assessments including the Assisting Hand Assessment (AHA) and Canadian Occupational Performance Measure (COPM) were conducted pre- and postintervention. Results. All children completed the intervention and both function (AHA) and goal performance (COPM) improved with additive effects of rTMS and constraint (P < .01). After intervention, motor-evoked potential (MEP) amplitudes from the contralesional M1 to the less-affected hand increased (n = 16, P < .02). SRC from the contralesional M1 to the less-affected hand increased (n = 25, P < .01). SICI of the contralesional M1 to the less-affected hand decreased (n = 30, P < .04). No changes were observed for ICF in either hemisphere (P > .12). Conclusion. TMS applied before/after intensive neuromodulation therapies can explore M1 neurophysiology and plasticity in children with cerebral palsy. Increased MEP sizes and decreased SICI may reflect mechanisms of interventional plasticity and be potential biomarkers of individualized medicine.

P034 Lesioned motor cortex neurophysiology in children with perinatal stroke

Introduction Perinatal stroke (PS) causes most hemiparetic cerebral palsy. Motor recovery is highly dependent on developmental plasticity in bilateral motor cortex. The fundamental neurophysiology of the lesioned motor cortex (M1) is poorly understood. Objective To characterize lesioned corticomotor neurophysiological properties in hemiparetic children with perinatal stroke. Methods Children 6–18years with MRI-confirmed PS and hemiparesis were recruited (Alberta Perinatal Stroke Project). Transcranial magnetic stimulation (TMS) protocols applied to the lesioned M1 measured rest and active motor thresholds (RMT/AMT) and stimulus response curves (SRC:100-150RMT). Paired-pulse TMS explored short-latency intracortical inhibition and intracortical facilitation (SICI/ICF; 2/10ms ISI). Measures were compared to the non-lesioned hemisphere and healthy controls ( n =40, median 12.2years, range 8–18). Motor outcomes by blinded occupational therapists were Assisting Hand (AHA), Melbourne (MA) assessments and Box and Block (BB). Safety and tolerability were assessed. Results Of 45 children (median 11.3years, 25 male; 65% arterial, 35% PVI), TMS of lesioned M1 evoked contralateral MEPs in only 12 (27%). No ipsilateral MEPs were recorded. Thresholds for evoking a stroke-side MEP were higher than the non-lesioned side ( p =0.04).The s-shaped SRC indicated that the morphology and responsiveness to increases in TMS intensities was preserved but shifted down compared to non-lesioned side or controls contralateral SRC. Contralateral SICI (−39.2%, −42.1%) and ICF (42.5%, 43.6%) effects were comparable between lesioned and non-lesioned sides ( p =0.43, p =0.54, respectively), as well as controls SICI ( p =0.30) and ICF ( p =0.22). Latencies of MEPs from the lesion side (24.3ms) were longer than contralateral, non-lesioned MEP (24.3ms versus 21.6ms, p =0.003). The area under the SRC curve is correlated with all AHA ( r =0.9, p =0.01), MEL ( r =0.9, p =0.02) and BB ( r =0.8, p =0.05). Protocols were well tolerated with no adverse events. Conclusion Cortical physiology of contralateral projections from the lesion side can be measured in hemiparetic children with PS using TMS. Individualized neurophysiology will further inform recently demonstrated therapeutic neuromodulation interventions in this population.