Visually Guided Movements Suppress Subthalamic Oscillations in Parkinson's Disease Patients

There is considerable evidence that abnormal oscillatory activity in the basal ganglia contributes to the pathogenesis of Parkinson's disease. However, little is known regarding the relationship of oscillations to volitional movements. Our goal was to evaluate the dynamics of oscillatory activity at rest and during movement. We performed microelectrode recordings from the subthalamic nucleus (STN) of patients undergoing deep brain stimulation surgery. During recordings, the patients used a joystick to guide a cursor to one of four targets on a monitor. We recorded 184 cells and 47 pairs of cells in 11 patients. At rest, 26 cells (14%) demonstrated significant oscillatory activity, with a mean frequency of 18 Hz. During movement, this oscillatory activity was either reduced or completely abolished in all of the cells. At rest, 18 pairs (38%) of cells in five patients exhibited synchronized oscillatory activity, with a mean frequency of 15 Hz. In 17 of the 18 pairs, both of the cells exhibited oscillations, and, in one pair, only one of the cells was oscillatory. These synchronized oscillations were also significantly decreased with movement. There was a strong inverse correlation between firing rates and oscillatory activity. As the firing rates increased with movement, there was a decrease in oscillatory activity. These findings suggest that visually guided movements are associated with a dampening and desynchronization of oscillatory activity in STN neurons. One possible explanation for these observations is that the increased cortical drive associated with movement preparation and execution leads to a transient dampening of STN oscillations, hence facilitating movement.

[1]  M. Delong,et al.  Altered Tonic Activity of Neurons in the Globus Pallidus and Subthalamic Nucleus in the Primate MPTP Model of Parkinsonism , 1987 .

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

[3]  M. Delong,et al.  Primate models of movement disorders of basal ganglia origin , 1990, Trends in Neurosciences.

[4]  M. Glickstein,et al.  Paradoxical movement in Parkinson's disease , 1991, Trends in Neurosciences.

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

[6]  M. Inase,et al.  Dual somatotopical representations in the primate subthalamic nucleus: evidence for ordered but reversed body-map transformations from the primary motor cortex and the supplementary motor area , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[7]  Wiklund Ra,et al.  First of two parts , 1997 .

[8]  J. Donoghue,et al.  Neural discharge and local field potential oscillations in primate motor cortex during voluntary movements. , 1998, Journal of neurophysiology.

[9]  A. Lang,et al.  Parkinson's disease. First of two parts. , 1998, The New England journal of medicine.

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

[11]  A. Lang,et al.  Parkinson's disease. Second of two parts. , 1998, The New England journal of medicine.

[12]  D. Plenz,et al.  A basal ganglia pacemaker formed by the subthalamic nucleus and external globus pallidus , 1999, Nature.

[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]  E. Eskandar,et al.  Stereotactic pallidotomy performed without using microelectrode guidance in patients with Parkinson's disease: surgical technique and 2-year results. , 2000, Journal of neurosurgery.

[15]  J. Csicsvari,et al.  Accuracy of tetrode spike separation as determined by simultaneous intracellular and extracellular measurements. , 2000, Journal of neurophysiology.

[16]  B Bioulac,et al.  Ratio of inhibited-to-activated pallidal neurons decreases dramatically during passive limb movement in the MPTP-treated monkey. , 2000, Journal of neurophysiology.

[17]  J. Dostrovsky,et al.  High-frequency Synchronization of Neuronal Activity in the Subthalamic Nucleus of Parkinsonian Patients with Limb Tremor , 2000, The Journal of Neuroscience.

[18]  P. Krack,et al.  Deep-brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in Parkinson's disease. , 2001, The New England journal of medicine.

[19]  A. Lozano,et al.  Pallidotomy for parkinson disease: a review of contemporary literature. , 2001, Journal of neurosurgery.

[20]  J. Dostrovsky,et al.  Effects of apomorphine on subthalamic nucleus and globus pallidus internus neurons in patients with Parkinson's disease. , 2001, Journal of neurophysiology.

[21]  Emad N Eskandar,et al.  Distinct nature of directional signals among parietal cortical areas during visual guidance. , 2002, Journal of neurophysiology.

[22]  A. Oliviero,et al.  Movement-related changes in synchronization in the human basal ganglia. , 2002, Brain : a journal of neurology.

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

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

[25]  A. Graybiel,et al.  Synchronous, Focally Modulated β-Band Oscillations Characterize Local Field Potential Activity in the Striatum of Awake Behaving Monkeys , 2003, The Journal of Neuroscience.

[26]  J. Assad,et al.  Putaminal activity for simple reactions or self-timed movements. , 2003, Journal of neurophysiology.

[27]  Robert Chen,et al.  Involvement of the human subthalamic nucleus in movement preparation. , 2003 .

[28]  B. Bean,et al.  Subthreshold Sodium Currents and Pacemaking of Subthalamic Neurons Modulation by Slow Inactivation , 2003, Neuron.

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

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