Restoration of segregated, physiological neuronal connectivity by desynchronizing stimulation.

The loss of segregation of neuronal signal processing pathways is an important hypothesis for explaining the origin of functional deficits as associated with Parkinson's disease. Here we use a modeling approach which is utilized to study the influence of deep brain stimulation on the restoration of segregated activity in the target structures. Besides the spontaneous activity of the target network, the model considers a weak sensory input mimicking signal processing tasks, electrical deep brain stimulation delivered through a standard DBS electrode and synaptic plasticity. We demonstrate that the sensory input is capable of inducing a modification of the network structure which results in segregated microcircuits if the network is initialized in the healthy, desynchronized state. Depending on the strength and coverage, the sensory input is capable of restoring the functional sub-circuits even if the network is initialized in the synchronized, pathological state. Weak coordinated reset stimulation, applied to a network featuring a loss of segregation caused by global synchronization, is able to restore the segregated activity and to truncate the pathological, synchronized activity.