A positron emission tomographic study of subthalamic nucleus stimulation in Parkinson disease: enhanced movement-related activity of motor-association cortex and decreased motor cortex resting activity.

BACKGROUND Long-term high-frequency stimulation of the subthalamic nucleus (STN) improves akinesia in Parkinson disease. The neural correlates of STN stimulation are not well understood. Positron emission tomography can be applied to the in vivo study of the mechanisms of deep brain stimulation. OBJECTIVE To study changes in regional cerebral blood flow as an index of synaptic activity in patients with Parkinson disease with effective STN stimulation on and off during rest and movement. METHODS Eight patients with Parkinson disease who had electrodes implanted in the STN underwent 12 measurements of regional cerebral blood flow with water O 15 positron emission tomography at rest and during performance of paced freely selected joystick movements, both with and without STN stimulation (3 scans per experimental condition). Motor performance and reaction and movement times were monitored. Statistical parametric mapping was used to compare changes in regional cerebral blood flow between conditions and differences in activation. RESULTS All patients showed improvement in reaction and movement times during scans with the stimulator on. As predicted, increases in activation of rostral supplementary motor area and premotor cortex ipsilateral to stimulation were observed when stimulation was on during contralateral movement (P<.001). Unpredicted observations included decreases in regional cerebral blood flow in primary motor cortex at rest induced by STN stimulation. CONCLUSION Stimulation of the STN reduces the movement-related impairment of frontal motor association areas and the inappropriate motor cortex resting activity in Parkinson disease.

[1]  A L Benabid,et al.  Abnormal involuntary movements induced by subthalamic nucleus stimulation in parkinsonian patients , 1996, Movement disorders : official journal of the Movement Disorder Society.

[2]  T Uema,et al.  Evidence for lateral premotor and parietal overactivity in Parkinson's disease during sequential and bimanual movements. A PET study. , 1997, Brain : a journal of neurology.

[3]  N P Quinn,et al.  Pallidotomy in Parkinson's disease increases supplementary motor area and prefrontal activation during performance of volitional movements an H2(15)O PET study. , 1997, Brain : a journal of neurology.

[4]  C D Marsden,et al.  Motor reorganization in acquired hemidystonia , 1995, Annals of neurology.

[5]  A. Benabid,et al.  Effect on parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation , 1995, The Lancet.

[6]  Karl J. Friston.  Analysing brain images: principles and overview , 1997 .

[7]  Karl J. Friston,et al.  Role of the human rostral supplementary motor area and the basal ganglia in motor sequence control: investigations with H2 15O PET. , 1998, Journal of neurophysiology.

[8]  Scott T. Grafton,et al.  Tracing the brain's circuitry with functional imaging , 1997, Nature Medicine.

[9]  C. Marsden,et al.  Overactive prefrontal and underactive motor cortical areas in idiopathic dystonia , 1995, Annals of neurology.

[10]  J. Dostrovsky,et al.  Effect of GPi pallidotomy on motor function in Parkinson's disease , 1995, The Lancet.

[11]  M Loyo-Varela,et al.  Pallidotomy in Parkinson's disease. , 1996, Neurosurgery.

[12]  U Sabatini,et al.  Supplementary and primary sensory motor area activity in Parkinson's disease. Regional cerebral blood flow changes during finger movements and effects of apomorphine. , 1992, Archives of neurology.

[13]  Sylvain Houle,et al.  Globus pallidus stimulation activates the cortical motor system during alleviation of parkinsonian symptoms , 1997, Nature Medicine.

[14]  J. Obeso,et al.  The subthalamic nucleus: A possible target for stereotaxic surgery in parkinson's disease , 1993, Movement disorders : official journal of the Movement Disorder Society.

[15]  M. Chesselet,et al.  Basal ganglia and movement disorders: an update , 1996, Trends in Neurosciences.

[16]  J R Moeller,et al.  Regional metabolic correlates of surgical outcomes following unilateral pallidotomy for parkinson's disease , 1996, Annals of neurology.

[17]  Scott T. Grafton,et al.  Pallidotomy increases activity of motor association cortex in parkinson's disease: A positron emission tomographic study , 1995, Annals of neurology.

[18]  E. Hoffman,et al.  Fully three-dimensional reconstruction for a PET camera with retractable septa , 1991 .

[19]  Karl J. Friston,et al.  Spatial registration and normalization of images , 1995 .

[20]  B. Lippitz,et al.  Bilateral chronic electrostimulation of ventroposterolateral pallidum: a new therapeutic approach for alleviating all parkinsonian symptoms. , 1994, Neurosurgery.

[21]  J. A. Obeso,et al.  Restoration of thalamocortical activity after posteroventral pallidotomy in Parkinson's disease , 1994, The Lancet.

[22]  U Sabatini,et al.  Normal activation of the supplementary motor area in patients with Parkinson's disease undergoing long-term treatment with levodopa. , 1994, Journal of neurology, neurosurgery, and psychiatry.

[23]  Positron emission tomography studies on regional cerebral control of voluntary movement , 1993 .

[24]  A. Parent,et al.  Functional anatomy of the basal ganglia. II. The place of subthalamic nucleus and external pallidium in basal ganglia circuitry , 1995, Brain Research Reviews.

[25]  M. Hariz,et al.  Leksell's posteroventral pallidotomy in the treatment of Parkinson's disease. , 1992, Journal of neurosurgery.

[26]  T. Aziz,et al.  Lesion of the subthalamic nucleus for the alleviation of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced parkinsonism in the primate , 1991, Movement disorders : official journal of the Movement Disorder Society.

[27]  H. Bergman,et al.  Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. , 1990, Science.

[28]  Richard S. J. Frackowiak,et al.  Impaired mesial frontal and putamen activation in Parkinson's disease: A positron emission tomography study , 1992, Annals of neurology.

[29]  Karl J. Friston,et al.  Assessing the significance of focal activations using their spatial extent , 1994, Human brain mapping.

[30]  Richard S. J. Frackowiak,et al.  Changes in cerebral activity pattern due to subthalamic nucleus or internal pallidum stimulation in Parkinson's disease , 1997, Annals of neurology.

[31]  Karl J. Friston,et al.  P449 The role of rostral supplementary motor area and basal ganglia in motor sequence control , 1996 .