Abstract
Excessive neuronal synchrony is a hallmark of several neurological disorders, e.g., Parkinson's disease. An established treatment for medically refractory Parkinson's disease is high-frequency deep brain stimulation. However, it provides only acute relief, and symptoms return shortly after cessation of stimulation. A theory-based approach called coordinated reset (CR) has shown great promise in achieving long-lasting effects. During CR stimulation, phase-shifted stimuli are delivered to multiple stimulation sites to counteract neuronal synchrony. Computational studies in plastic neuronal networks reported that synaptic weights reduce during stimulation, which may cause sustained structural changes leading to stabilized desynchronized activity even after stimulation ceases. Corresponding long-lasting effects were found in recent preclinical and clinical studies. We study long-lasting desynchronization by CR stimulation in excitatory recurrent neuronal networks of integrate-and-fire neurons with spike-timing-dependent plasticity (STDP). We focus on the impact of the stimulation frequency and the number of stimulation sites on long-lasting effects. We compare theoretical predictions to simulations of plastic neuronal networks. Our results are important regarding CR calibration for two reasons. We reveal that long-lasting effects become most pronounced when stimulation parameters are adjusted to the characteristics of STDP-rather than to neuronal frequency characteristics. This is in contrast to previous studies where the CR frequency was adjusted to the dominant neuronal rhythm. In addition, we reveal a nonlinear dependence of long-lasting effects on the number of stimulation sites and the CR frequency. Intriguingly, optimal long-lasting desynchronization does not require larger numbers of stimulation sites.
Highlights
Synchronization phenomena are observed in various fields of the natural sciences.[9,10,11,12,13,14,15,16,17] Often, synchronization is critical for functional performance
We study long-lasting desynchronization by coordinated reset (CR) stimulation in excitatory recurrent neuronal networks of integrate-and-fire neurons with spike-timing-dependent plasticity (STDP)
We find that long-lasting desynchronization is most pronounced when CR parameters are adjusted to the STDP and not to the dominant neuronal rhythm, as suggested by prior studies.[4,6,8]
Summary
Synchronization phenomena are observed in various fields of the natural sciences.[9,10,11,12,13,14,15,16,17] Often, synchronization is critical for functional performance. Limitations of demand-controlled single pulse stimulation and complex stimuli combining a strong phase reset followed by a desynchronizing single pulse[28,39] led to the development of CR stimulation, a multisite stimulation technique that does not require precisely timed stimulus delivery (e.g., targeting a vulnerable phase of the synchronized oscillation).[4] As predicted by computational studies in neuronal networks with STDP,[40,41] acute effects of CR stimulation may entail long-lasting desynchronization and therapeutic after-effects.[5,6,7] Acute effects denote stimulation-induced effects observed during stimulus administration, whereas long-lasting aftereffects refer to sustained effects emerging after cessation of stimulus delivery for t → ∞. We briefly review current research on acute and long-lasting desynchronization by CR stimulation and present novel results on the impact of the number of stimulation sites on long-lasting effects
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
