Primed low frequency repetitive transcranial magnetic stimulation rebalances cortical excitatory-inhibitory circuitry and improves functional outcomes in infantile cerebral palsy patients: A randomized controlled trial

Multiple prenatal and postnatal etiologies in cerebral palsy (CP) patients cause neural tissue damage and alterations in cortical neuronal activity and plasticity, leading to motor and cognitive deficits early in life. Repetitive transcranial magnetic stimulation (rTMS) to the lesioned or contralesional hemisphere has been shown to alleviate these functional deficits. However, the underlying mechanisms of the beneficial effects of rTMS via realigning intracortical and interhemispheric circuitry and excitability remain unclear. The present study explored the ability of primed low-frequency rTMS to modulate intracortical excitatory-inhibitory circuitry, interhemispheric and corticospinal integrity, and plasticity in infantile hemiplegic CP. The current study was a randomized, placebo-controlled trial with infantile hemiplegic CP patients. The active group received 6 Hz primed low-frequency 1Hz rTMS delivered to the contralesional primary motor cortex for 4 weeks, in 10 sessions. The placebo group received sham stimulation. Both groups also underwent 10 sessions of modified-constraint induced movement therapy (mCIMT). Pre- and post-intervention assessments were conducted using the Quality of Upper Extremity Skills Test to evaluate sensory and motor function, and the Modified Ashworth Scale (MAS) to assess spasticity. Additionally, cortical excitability and plasticity were measured using single- and paired-pulse TMS. We found a significant increase in Quality of Upper Extremity Skills Test scores, CP Quality of Life Child (CP QOL-Child) scores, and grip strength, and a decrease in MAS scores in the active rTMS group compared with the sham group. Single- and paired-pulse paradigms revealed a significant decrease in resting and active motor threshold, a reduction in the cortical silent period, and short- and long-interval intracortical inhibition in the intervention group compared with the sham group. Primed low-frequency rTMS in the contralesional hemisphere combined with mCIMT shows potential for modulating motor neuronal excitability, rebalancing intracortical excitatory-inhibitory circuitry, and enhancing functional outcomes in children with infantile hemiparetic CP. Effect of Contralesional TMS on Excitatory-Inhibitory Neural Circuitry in Cerebral Palsy Patients.