Title: Transcranial Magnetic Stimulation (TMS) Evaluation of Corticospinal Circuitry in Babies with Early Life Brain Injuries.
Legend: Cameron Casey, Alina Grimaldo, Ellen Sutter, Veronika Mak, Preston Christopher, Bernadette Gillick. “Assessment of Corticospinal Tract Circuitry Through Transcranial Magnetic Stimulation and Motor Evoked Potentials” UW Pediatric Research Week Symposium, May 2023, Madison, WI.
Citation: Graphical representation of the motor pathways activated by transcranial magnetic stimulation (TMS) in seven babies with early-life brain injuries. Arrows show the ipsilateral (same side) and contralateral (opposite side) connections from primary motor brain regions to the wrist muscles. Solid red arrows indicate that TMS activated a motor pathway. Dashed black arrows indicate that TMS did not activate a motor pathway. Dark blue ovals indicate which hemisphere of the brain was more affected by the brain injury for each baby. TMS assessments demonstrated diverse circuitry patterns in babies who had experienced an early-life brain injury. Prior work suggests that loss of contralateral connections from the more affected hemisphere is predictive of higher risk of cerebral palsy. This association between motor connectivity patterns and cerebral palsy will be further investigated in this developing dataset.
Background – Perinatal brain injury is a primary cause of cerebral palsy (CP). Research has shown that the first two years of life are critical for brain development and exhibit heightened neuroplasticity. However, the specific influence of perinatal injury on cortical excitability and nervous system development remains poorly understood. Previous studies have implicated altered corticospinal tract (CST) development as an important indicator of future motor function in CP. Hence, longitudinal assessment of CST circuitry during the first two years of life may provide crucial insights into the development of CP and enable future therapies targeted to an individual’s brain development. Transcranial magnetic stimulation (TMS), a form of non-invasive brain stimulation, offers an assessment of CST circuitry by stimulating the motor cortex and monitoring the presence or absence of motor evoked potentials (MEPs) in the upper extremities, allowing for individualized assessment of the developing and recovering brain. Methods – Children with a radiologically confirmed diagnosis of perinatal stroke or brain bleed were assessed for neuroexcitability and CST circuitry using single-pulse TMS. TMS pulses were targeted to the motor cortex (M1) using each participant’s T1-weighted MRI on a neuronavigational system or an MRI template if needed. Resting motor thresholds and MEPs were assessed bilaterally using electrodes placed over wrist flexor musculature. Data were collected under the Perinatal Stroke: Longitudinal Assessment of Infant Brain Organization and Recovery through Neuroexcitability, Neuroimaging and Motor Development study (NIH 7R01HD098202-02 PI:Gillick). Results – Seven children, with ages between 3 and 13 months (adjusted for prematurity), were assessed. Five showed evidence of bilateral MEPs, 1 unilateral MEPs, and 1 with indeterminate responses. A total of 461 TMS pulses were delivered across all infants. Infant safety and comfort were prioritized while maintaining accuracy in data acquisition with no adverse events. Conclusions – TMS assessments can be used to characterize patterns of early brain connectivity and may identify neurophysiologic biomarkers of motor function that could guide future investigation and interventions. TMS assessments were well tolerated and safely administered within this pediatric population. Further analysis of MEPs may elucidate patterns of neurodevelopment related to CP occurrence and severity.
About the Lab: Bernadette Gillick’s Pediatric Neuromodulation Laboratory at the Waisman Center investigates how the brain simultaneously develops and recovers after perinatal stroke in early infancy. Further, Gillick’s team investigates interventions using combined non-invasive brain stimulation with neurorehabilitation to optimize functional outcomes in children with cerebral palsy due to perinatal stroke. By understanding the patterns of brain recovery and the optimal timing of intervention, Gillick aims to improve functional outcomes early in life, for improved lifelong activity and participation.
Investigator: Bernadette Gillick, PhD, MSPT, PT