Modeling the effects of Deep Brain Stimulation on sensorimotor cortex in normal and MPTP conditions

Deep Brain Stimulation (DBS) is an effective surgical therapy for the treatment of movement disorders in Parkinson's disease (PD) and other neurological pathologies. DBS is known to modulate the spiking activity of the neurons within the basal ganglia, but how such modulation impacts the primary sensorimotor cortex is still uncertain. In this study a monkey was stimulated with DBS at several frequencies in the subthalamic nucleus (STN) before and after treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to develop PD symptoms, while single unit recordings are simultaneously obtained from the sensorimotor cortex. We exploit such data to develop point-process input-output models of the cortical neurons. Our models describe the effects of stimulation in normal and MPTP conditions and investigate the influence of the stimulation frequency on the neuronal activity. Our models show increased synchronization of the cortical neurons in MPTP vs. normal conditions before stimulation, suggest that STN DBS impacts the cortical activity by antidromically eliciting spikes at the stimulation frequency, and support the hypothesis that high frequency DBS partially masks the effects of thalamo-cortical input.

[1]  L. Tremblay,et al.  Thalamic Neuronal Activity in Dopamine-Depleted Primates: Evidence for a Loss of Functional Segregation within Basal Ganglia Circuits , 2005, The Journal of Neuroscience.

[2]  Thomas Wichmann,et al.  Circuits and circuit disorders of the basal ganglia. , 2007, Archives of neurology.

[3]  Emery N. Brown,et al.  Using Point Process Models to Compare Neural Spiking Activity in the Subthalamic Nucleus of Parkinson's Patients and a Healthy Primate , 2010, IEEE Transactions on Biomedical Engineering.

[4]  Erwin B. Montgomery,et al.  Mechanisms of action of deep brain stimulation (DBS) , 2008, Neuroscience & Biobehavioral Reviews.

[5]  Matthew D. Johnson,et al.  Pallidal stimulation that improves parkinsonian motor symptoms also modulates neuronal firing patterns in primary motor cortex in the MPTP-treated monkey , 2009, Experimental Neurology.

[6]  W. Grill,et al.  Amplitude- and Frequency-Dependent Changes in Neuronal Regularity Parallel Changes in Tremor With Thalamic Deep Brain Stimulation , 2007, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[7]  John A. Nelder,et al.  Generalized linear models. 2nd ed. , 1993 .

[8]  S. Haber,et al.  The cortico-basal ganglia integrative network: The role of the thalamus , 2009, Brain Research Bulletin.

[9]  Emery N. Brown,et al.  Computational Neuroscience: A Comprehensive Approach , 2022 .

[10]  John T. Gale,et al.  Subthalamic nucleus discharge patterns during movement in the normal monkey and Parkinsonian patient , 2009, Brain Research.

[11]  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.

[12]  Andrea A. Kühn,et al.  Pathological synchronisation in the subthalamic nucleus of patients with Parkinson's disease relates to both bradykinesia and rigidity , 2009, Experimental Neurology.

[13]  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.

[14]  P. Starr,et al.  Treatment of dystonia with deep brain stimulation , 2008, Neurotherapeutics.

[15]  J. Vitek,et al.  Stimulation of the Subthalamic Nucleus Changes the Firing Pattern of Pallidal Neurons , 2003, The Journal of Neuroscience.

[16]  Brian Hyland,et al.  Cortical effects of subthalamic stimulation correlate with behavioral recovery from dopamine antagonist induced akinesia. , 2009, Cerebral cortex.

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

[18]  Erwin B. Montgomery,et al.  Effects of GPi stimulation on human thalamic neuronal activity , 2006, Clinical Neurophysiology.

[19]  A. Benabid,et al.  Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson's disease , 2009, The Lancet Neurology.

[20]  P. Brown Abnormal oscillatory synchronisation in the motor system leads to impaired movement , 2007, Current Opinion in Neurobiology.

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