Explore the impact of training time of day on clinical benefits achieved with programmed transcutaneous spinal cord stimulation (ARC-EX Therapy).

ARC-EX Therapy safely and effectively improves hand sensation and strength following spinal cord injury (SCI) when combined with focused rehabilitation. Circadian fluctuations of adenosine, a neuromodulator that impedes serotonin-dependent synaptic plasticity, may impact ARC-EX Therapy’s neuroplastic potential and therapeutic impact. We hypothesized that participants primarily training in the morning, when adenosine levels are lowest, would exhibit greater effects than those training primarily in the afternoon.

Sensorimotor data from Up-LIFT Trial participants with chronic, incomplete cervical SCI before and after two months of ARC-EX Therapy plus rehabilitation was performed. Assessments included the Capabilities of Upper Extremity Test (CUE-T), Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP), International Standards for Neurological Classification of SCI Upper Extremity Motor Score (UEMS) and Upper Extremity Sensory Score (UESS), and pinch/grasp force. Participants were classified into AM (≥75% of sessions before 12 PM, n=21) or PM (≥75% after 12 PM, n=26) subgroups. Within-group pre- vs. post-therapy effect sizes were calculated using Cohen’s d.

The AM subgroup experienced greater effects in CUE-T (AM d=0.27, PM d=0.17), GRASSP Prehension Performance (AM d=0.18, PM d=0.14), UEMS (AM d=0.23, PM d=0.18), GRASSP Strength (AM d=0.20, PM d=0.09), pinch force (AM d=0.17, PM d=0.03), grasp force (AM d=0.18, PM d=0.04), and UESS (AM d=0.42, PM d=0.19). GRASSP Sensibility effects were equivalent for both subgroups (d=0.10).

ARC-EX Therapy session timing influenced the degree of improvements achieved.  Morning therapy sessions produced greater effects, potentially due to reduced adenosine levels that facilitate serotonin-dependent neural plasticity, though further research is essential to determine if neuromodulator circadian fluctuations indeed play a contributory role. Incorporating session timing considerations into neurorehabilitation protocols could help optimize therapeutic outcomes.