Intervention-related changes in motor cortex GABA in children with perinatal stroke

2387 

Abstract Submission 

Paulina Hart¹, Tiffany Bell¹, Ashley Harris¹, Helen Carlson¹, Adam Kirton¹

¹University of Calgary, Calgary, Alberta

Paulina Hart  
University of Calgary
Calgary, Alberta

Tiffany Bell  
University of Calgary
Calgary, Alberta

Ashley Harris  
University of Calgary
Calgary, Alberta

Helen Carlson, Ph.D.  
University of Calgary
Calgary, Alberta

Adam Kirton, MD  
University of Calgary
Calgary, Alberta

Perinatal stroke (PS) affects millions of children, damaging the motor system leading to lifelong motor disability in the form of hemiparetic cerebral palsy (Dunbar, 2020; Kirton, 2013). Most PS are either periventricular venous infarction (PVI) or arterial ischemic stroke (AIS). Magnetic resonance spectroscopy (MRS) has demonstrated differences in glutamate/glutamine and creatine levels between lesioned and non-lesioned hemisphere motor cortices in PS patients (Carlson, 2017). However, it is unknown if γ-aminobutyric acid (GABA), a primary inhibitory neurotransmitter critical for motor coordination, is altered. Current rehabilitation treatments for PS are limited but non-invasive neuromodulation is a promising adjuvant. Transcranial direct current stimulation (tDCS) uses weak electrical currents to modulate neuroplasticity and can enhance motor learning in children (Ciechanski, 2017) but effects on motor cortex chemistry are unknown. Studies have suggested that tDCS can induce changes to motor cortex GABA levels which are associated with improved cortical learning (Stagg, 2011). We aimed to quantify GABA levels in the lesioned and non-lesioned motor cortices in children with PS at baseline and following intensive motor learning paired with neurostimulation and explored associations with clinical function.

Participants (6-18 years) with unilateral, perinatal PVI or AIS were recruited to the Stimulation for Perinatal Stroke Optimizing Recovery Trajectory (SPORT) randomized, controlled, clinical trial. Participants attended a two-week day-camp including intensive, individualized, goal-directed therapy. Each received daily active or sham cathodal tDCS over the non-lesioned motor cortex. At baseline, post-camp, and 6-months later (follow-up), MRI was performed and motor function was assessed using the Assisting Hand Assessment (AHA), and Box and Blocks Test (affected hand, BBTA). MRI were performed on a 3.0 T GE MR750w MRI scanner. T1-weighted images were acquired. A ball-squeezing motor task-fMRI acquisition was used to localize the motor cortex bilaterally for MRS voxel placement. GABA-edited MEGA-PRESS was used to measure GABA levels (20x20x10mm³ voxels, TE=68ms, averages=128, 14ms editing pulses applied at 1.9ppm and 7.46 ppm). The MRS voxel was segmented by tissue type to maximize accuracy of tissue correction. GABA spectra (Figure 1) were processed using Gannet 9 (Edden, 2014). Statistical analyses were conducted using Jamovi.

Forty-nine participants (AIS n=24, mean age 11.0(2.97) years; PVI n=25, age 10.3(1.74) years) were included. Three participants were excluded for missing baseline measurements or an MRS linewidth value (obtained from Gannet analysis) greater than 15Hz. Age, sex, and stroke laterality were comparable between groups. Twenty participants received active and 29 received sham tDCS. Linear mixed models (using age as a co-variate) showed a decrease in non-lesioned hemisphere GABA levels across the three time points (p=0.048) regardless of tDCS condition (Figure 2). There was no significant change in GABA levels observed in the lesioned hemisphere across the three time points (p=0.765) or between tDCS treatment groups. Motor function (AHA and BBTA) increased (p<0.001) across the three time points, however, increases in motor function were not associated with changes in GABA levels in either hemisphere (p>0.05).

Bilateral motor cortex GABA is measurable in children with PS undergoing intensive therapy and neuromodulation. GABA levels may decrease in the non-lesioned motor cortex following intensive manual therapy with effects lasting 6 months or more. Simultaneous tDCS over the non-lesioned motor cortex does not appear to affect motor cortex GABA levels.

TDCS ²

Neurodevelopmental/ Early Life (eg. ADHD, autism)

Activation (eg. BOLD task-fMRI)

Motor Behavior Other

MR Spectroscopy ¹

FUNCTIONAL MRI

GABA

Magnetic Resonance Spectroscopy (MRS)

Neurotransmitter

PEDIATRIC

Pediatric Disorders

Therapy