Stimulating at the right time to recover network states in a model of the cortico-basal ganglia-thalamic circuit.

Synchronization of neural oscillations is thought to facilitate communication in the brain. Neurodegenerative pathologies such as Parkinson's disease (PD) can result in synaptic reorganization of the motor circuit, leading to altered neuronal dynamics and impaired neural communication. Treatments for PD aim to restore network function via pharmacological means such as dopamine replacement, or by suppressing pathological oscillations with deep brain stimulation. We tested the hypothesis that brain stimulation can operate beyond a simple "reversible lesion" effect to augment network communication. Specifically, we examined the modulation of beta band (14–30 Hz) activity, a known biomarker of motor deficits and potential control signal for stimulation in Parkinson's. To do this we setup a neural mass model of population activity within the cortico-basal ganglia-thalamic (CBGT) circuit with parameters that were constrained to yield spectral features comparable to those in experimental Parkinsonism. We modulated the connectivity of two major pathways known to be disrupted in PD and constructed statistical summaries of the spectra and functional connectivity of the resulting spontaneous activity. These were then used to assess the network-wide outcomes of closed-loop stimulation delivered to motor cortex and phase locked to subthalamic beta activity. Our results demonstrate that the spatial pattern of beta synchrony is dependent upon the strength of inputs to the STN. Precisely timed stimulation has the capacity to recover network states, with stimulation phase inducing activity with distinct spectral and spatial properties. These results provide a theoretical basis for the design of the next-generation brain stimulators that aim to restore neural communication in disease. Author summary: Diseases of the brain lead to a wide range of disabling symptoms for patients, by affecting their ability to move or think properly. These symptoms arise from disruption to both the organization of networks in the brain, but also the timing of neural activity that propagates around it. Treatments for disease with drugs can restore the organization of these networks to some extent, yet it is very difficult to deliver drugs with good spatial or temporal selectivity. Brain stimulation provides one way in which to improve the spatial specificity of treatment, yet understanding how to stimulate at the right time to achieve the best outcome for patients, remains an outstanding question. In this work we use simulations of an important circuit involved in Parkinson's disease that has parameters chosen to reflect recordings made in animal models of the disease. Using this computer model, we show how brain rhythms can act as signatures of underlying changes in networks. Further, we simulate intervention with temporally precise stimulation to show how future approaches to brain stimulation can act to restore or even augment neural networks following their degeneration in disease. [ABSTRACT FROM AUTHOR]