Using Point Process Models to Compare Neural Spiking Activity in the Subthalamic Nucleus of Parkinson's Patients and a Healthy Primate

Placement of deep brain stimulating electrodes in the subthalamic nucleus (STN) to treat Parkinson's disease (PD) also allows the recording of single neuron spiking activity. Analyses of these unique data offer an important opportunity to better understand the pathophysiology of PD. Despite the point process nature of PD neural spiking activity, point process methods are rarely used to analyze these recordings. We develop a point process representation of PD neural spiking activity using a generalized linear model to describe long- and short-term temporal dependencies in the spiking activity of 28 STN neurons from seven PD patients and 35 neurons from one healthy primate (surrogate control) recorded, while the subjects executed a directed-hand movement task. We used the point process model to characterize each neuron's bursting, oscillatory, and directional tuning properties during key periods in the task trial. Relative to the control neurons, the PD neurons showed increased bursting, increased 10-30 Hz oscillations, and increased fluctuations in directional tuning. These features, which traditional methods failed to capture accurately, were efficiently summarized in a single model in the point process analysis of each neuron. The point process framework suggests a useful approach for developing quantitative neural correlates that may be related directly to the movement and behavioral disorders characteristic of PD.

[1]  L. Paninski Maximum likelihood estimation of cascade point-process neural encoding models , 2004, Network.

[2]  Charles J. Wilson,et al.  Move to the rhythm: oscillations in the subthalamic nucleus–external globus pallidus network , 2002, Trends in Neurosciences.

[3]  Andrew P. Bradley,et al.  Estimation of neuronal firing rates with the three-state biological point process model , 2008, Journal of Neuroscience Methods.

[4]  Partha P. Mitra,et al.  Sampling Properties of the Spectrum and Coherency of Sequences of Action Potentials , 2000, Neural Computation.

[5]  Ziv M. Williams,et al.  Timing and direction selectivity of subthalamic and pallidal neurons in patients with Parkinson disease , 2005, Experimental Brain Research.

[6]  J. Donoghue,et al.  Collective dynamics in human and monkey sensorimotor cortex: predicting single neuron spikes , 2009, Nature Neuroscience.

[7]  T. J. Breen,et al.  Biostatistical Analysis (2nd ed.). , 1986 .

[8]  A B Schwartz,et al.  Direct cortical representation of drawing. , 1994, Science.

[9]  J. H. Schuenemeyer,et al.  Generalized Linear Models (2nd ed.) , 1992 .

[10]  Uri T Eden,et al.  Analysis of between-trial and within-trial neural spiking dynamics. , 2008, Journal of neurophysiology.

[11]  E. Brown Course 14 - Theory of Point Processes for Neural Systems , 2005 .

[12]  J. Penney,et al.  The functional anatomy of basal ganglia disorders , 1989, Trends in Neurosciences.

[13]  R. Reid,et al.  Predicting Every Spike A Model for the Responses of Visual Neurons , 2001, Neuron.

[14]  Hagai Bergman,et al.  Oscillatory activity in the basal ganglia--relationship to normal physiology and pathophysiology. , 2004, Brain : a journal of neurology.

[15]  H. Akaike A new look at the statistical model identification , 1974 .

[16]  J. Dostrovsky,et al.  Movement-related neurons of the subthalamic nucleus in patients with Parkinson disease. , 2002, Journal of neurosurgery.

[17]  J. Dostrovsky,et al.  Dependence of subthalamic nucleus oscillations on movement and dopamine in Parkinson's disease. , 2002, Brain : a journal of neurology.

[18]  Erwin B Montgomery Subthalamic nucleus neuronal activity in Parkinson's disease and epilepsy subjects. , 2008, Parkinsonism & related disorders.

[19]  Eric R. Ziegel,et al.  Generalized Linear Models , 2002, Technometrics.

[20]  A P Georgopoulos,et al.  On the relations between the direction of two-dimensional arm movements and cell discharge in primate motor cortex , 1982, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[21]  P. Brown Oscillatory nature of human basal ganglia activity: Relationship to the pathophysiology of Parkinson's disease , 2003, Movement disorders : official journal of the Movement Disorder Society.

[22]  Ziv M. Williams,et al.  Visually Guided Movements Suppress Subthalamic Oscillations in Parkinson's Disease Patients , 2004, The Journal of Neuroscience.

[23]  Uri T Eden,et al.  A point process framework for relating neural spiking activity to spiking history, neural ensemble, and extrinsic covariate effects. , 2005, Journal of neurophysiology.

[24]  Per Brodal,et al.  The Central Nervous System: Structure and Function , 2004, Journal of Neurology.

[25]  Donald L. Snyder,et al.  Random Point Processes in Time and Space , 1991 .

[26]  J C Houk,et al.  Context dependency in the globus pallidus internal segment during targeted arm movements. , 2001, Journal of neurophysiology.

[27]  G Rees Cosgrove,et al.  Experience with Microelectrode Guided Subthalamic Nucleus Deep Brain Stimulation , 2006, Neurosurgery.

[28]  M. Quirk,et al.  Construction and analysis of non-Poisson stimulus-response models of neural spiking activity , 2001, Journal of Neuroscience Methods.

[29]  M. Hoehn,et al.  Parkinsonism , 1967, Neurology.

[30]  M. D. Crutcher,et al.  Single cell studies of the primate putamen , 2004, Experimental Brain Research.

[31]  Robert E. Kass,et al.  A Spike-Train Probability Model , 2001, Neural Computation.

[32]  Carlos D. Brody,et al.  Correlations Without Synchrony , 1999, Neural Computation.

[33]  R. J. Allan,et al.  Neurophysiological identification of the subthalamic nucleus in surgery for Parkinson's disease , 1998, Annals of neurology.

[34]  H. Bergman,et al.  The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism. , 1994, Journal of neurophysiology.

[35]  Emery N. Brown,et al.  The Time-Rescaling Theorem and Its Application to Neural Spike Train Data Analysis , 2002, Neural Computation.

[36]  R. Kass,et al.  Multiple neural spike train data analysis: state-of-the-art and future challenges , 2004, Nature Neuroscience.

[37]  Guglielmo Foffani,et al.  Involvement of the human subthalamic nucleus in movement preparation , 2004, Neurology.

[38]  E. Vaadia,et al.  Firing Patterns and Correlations of Spontaneous Discharge of Pallidal Neurons in the Normal and the Tremulous 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Vervet Model of Parkinsonism , 2000, The Journal of Neuroscience.

[39]  M. D. Crutcher,et al.  Relations between parameters of step-tracking movements and single cell discharge in the globus pallidus and subthalamic nucleus of the behaving monkey , 1983, The Journal of neuroscience : the official journal of the Society for Neuroscience.