Spatiotemporal visualization of deep brain stimulation-induced effects in the subthalamic nucleus.
Deep brain stimulation (DBS) is a successful surgical therapy used to treat the disabling symptoms of movement disorders such as Parkinson's disease. It involves the chronic stimulation of disorder-specific nuclei. However, the mechanisms that lead to clinical improvements remain unclear. Consequently, this slows the optimization of present-day DBS therapy and hinders its future development and application. We used a computational model to calculate the distribution of electric potential induced by DBS and study the effect of stimulation on the spiking activity of a subthalamic nucleus (STN) projection neuron. We previously showed that such a model can reveal detailed spatial effects of stimulation in the vicinity of the electrode. However, this multi-compartmental STN neuron model can fire in either a burst or tonic mode and, in this study, we hypothesized that the firing mode of the cell will have a major impact on the DBS-induced effects. Our simulations showed that the bursting model exhibits behaviour observed in studies of high-frequency stimulation of STN neurons, such as the presence of a silent period at stimulation offset and frequency-dependent stimulation effects. We validated the model by simulating the clinical parameter settings used for a Parkinsonian patient and showed, in a patient-specific anatomical model, that the region of affected tissue is consistent with clinical observations of the optimal DBS site. Our results demonstrated a method of quantitatively assessing neuronal changes induced by DBS, to maximize therapeutic benefit and minimize unwanted side effects.
Centre for Neuroscience, Imperial College London, Charing Cross Hospital, London, UK. n.yousif@imperial.ac.uk
Nada
N
Yousif
Roman
R
Borisyuk
Nicola
N
Pavese
Dipankar
D
Nandi
Peter
P
Bain
D000200:Action Potentials / Q000502:physiology; D058256:Brain Waves / Q000502:physiology; D046690:Deep Brain Stimulation; D006801:Humans; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology; D010300:Parkinson Disease / Q000503:physiopathology* / Q000628:therapy; D020531:Subthalamic Nucleus / Q000502:physiology / Q000503:physiopathology*