The spacing principle for unlearning abnormal neuronal synchrony

Desynchronizing stimulation techniques were developed to specifically counteract abnormal neuronal synchronization relevant to several neurological and psychiatric disorders. The goal of our approach is to achieve an anti-kindling, where the affected neural networks unlearn abnormal synaptic connectivity and, hence, abnormal neuronal synchrony, by means of desynchronizing stimulation, in particular, Coordinated Reset (CR) stimulation. As known from neuroscience, psychology and education, learning effects can be enhanced by means of the spacing principle, i.e. by delivering repeated stimuli spaced by pauses as opposed to delivering a massed stimulus (in a single long stimulation session). To illustrate that the spacing principle may boost the anti-kindling effect of CR neuromodulation, in this computational study we carry this approach to extremes. To this end, we deliver spaced CR neuromodulation at particularly weak intensities which render permanently delivered CR neuromodulation ineffective. Intriguingly, spaced CR neuromodulation at these particularly weak intensities effectively induces an anti-kindling. In fact, the spacing principle enables the neuronal population to successively hop from one attractor to another one, finally approaching attractors characterized by down-regulated synaptic connectivity and synchrony. Our computational results might open up novel opportunities to effectively induce sustained desynchronization at particularly weak stimulation intensities, thereby avoiding side effects, e.g., in the case of deep brain stimulation.