Sequences and their shuffling may crucially impact coordinated reset stimulation.

Standard deep brain stimulation is an established treatment for Parkinson’s disease (PD). Symptom suppression requires permanent stimulation, furthering side effects. Coordinated reset (CR) stimulation was developed to specifically counteract PD-related neuronal synchrony, and entails long-lasting desynchronization and therapeutic effects in animal models and PD patients. For CR, a sequence of phase-shifted stimuli is delivered to multiple stimulation sites. Recent studies in Parkinsonian monkeys reported that shuffling of this CR sequence led to better therapeutic aftereffects than non-shuffled CR, suggesting benefits of shuffling for clinical outcomes in PD patients.

To study how shuffling affects desynchronization aftereffects, we performed simulations of shuffled and non-shuffled CR in plastic networks of leaky integrate-and-fire neurons with different spatial arrangements of synaptic connections. Aftereffects of non-shuffled CR with different sequences varied substantially in networks with spatially dependent connections, but not in networks with spatially homogeneous connections. In contrast, shuffled CR caused long-term desynchronization regardless of synaptic connectivity. Our results suggest that shuffling reduces the dependence of long-lasting outcomes of CR on the (often uncharted) synaptic network structure in target brain areas.



J.A. Kromer & P.A. Tass, Brain Stimul. 17, P194 (2024).

J.A. Kromer & P.A. Tass, Front. Netw. Physiol. 4, 1351815 (2024).