Abstract
Accurately describing the spiking patterns of neurons in the subthalamic nucleus (STN) of patients suffering from Parkinson's disease (PD) is important for understanding the pathogenesis of the disease and for achieving the maximum therapeutic benefit from deep brain stimulation (DBS). We analyze the spiking activity of 24 subthalamic neurons recorded in Parkinson's patients during a directed hand movement task by using a point process generalized linear model (GLM). The model relates each neuron's spiking probability simultaneously to factors associated with movement planning and execution, directional selectivity, refractoriness, bursting, and oscillatory dynamics. The model indicated that while short-term history dependence related to refractoriness and bursting are most informative in predicting spiking activity, nearly all of the neurons analyzed have a structured pattern of long-term history dependence such that the spiking probability was reduced 20–30 ms and then increased 30–60 ms after a previous spike. This suggests that the previously described oscillatory firing of neurons in the STN of Parkinson's patients during volitional movements is composed of a structured pattern of inhibition and excitation. This point process model provides a systematic framework for characterizing the dynamics of neuronal activity in STN.
Highlights
Abnormal neural firing in the subthalamic nucleus (STN) of patients with Parkinson’s disease (PD) is postulated to play a role in the pathogenesis of the tremor, rigidity, and akinesia that characterize the disorder (Bergman et al, 1994; Lang and Lozano, 1998; Levy et al, 2000)
We present a point process generalized linear model (GLM) for characterizing the spiking activity of STN neurons, recorded from PD patients, that relates spiking probability simultaneously to factors associated with the time course of movement planning and execution, directional selectivity, refractoriness, bursting, and oscillatory dynamics
Previous analyses of aberrant spiking patterns of STN neurons in PD have focused on features of the spike train power spectrum
Summary
Abnormal neural firing in the subthalamic nucleus (STN) of patients with Parkinson’s disease (PD) is postulated to play a role in the pathogenesis of the tremor, rigidity, and akinesia that characterize the disorder (Bergman et al, 1994; Lang and Lozano, 1998; Levy et al, 2000). Studies employing microelectrode recordings from the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model of PD (Bergman et al, 1994) and from PD patients (Levy et al, 2000) have demonstrated an apparent increase in oscillatory and synchronized activity in STN neurons These abnormal oscillations have been posited to play a role in the pathogenesis of PD in several possible ways. Low frequency oscillations (3–10 Hz) may contribute to Parkinsonian tremor whereas beta band oscillations (12–30 Hz) may block the normal flow of information through the basal ganglia, or lead to a loss of neuronal selectivity resulting in akinesia or rigidity (Kopell et al, 2006) This oscillatory activity appears to be dynamic and can be attenuated by volitional movements (Cassidy et al, 2002; Levy et al, 2002; Amirnovin et al, 2004; Gale et al, 2009). Recent studies have suggested that one of the primary mechanisms of DBS maybe the disruption of abnormal beta-band oscillations (Kopell et al, 2006; Wingeier et al, 2006; Gale et al, 2008)
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