Brainstem motor loops in the control of movement

In recent years, the role of the area around the upper brainstem, particularly the pedunculopontine (PPN) region and the zona incerta (ZI), in the initiation and control of movement has generated much clinical interest. Using electrophysiological and pharmacological methods, we have further explored these structures and their influence in motor control in the nonhuman primate and in patients with proximal tremor. We have found that lesioning the PPN and electrical stimulation at high frequencies of the PPN region in the normal‐behaving primate induces akinesia, and low frequency stimulation can induce tremor. In the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine hydrochloride (MPTP) ‐treated parkinsonian primate model, bicuculline, a γ‐aminobutyric acid antagonist, can alleviate akinesia when infused into the PPN region. Further studies will elucidate the possible clinical implications of these observations. The ZI has reciprocal connections with several cortical areas, the upper brainstem, cerebellum, and thalamus. We have found that chronic, high‐frequency deep brain stimulation of the ZI suppresses proximal limb tremor. Field potential recordings from the ZI show significant coherence with concurrent proximal muscle electromyograms. This finding has potential clinical relevance as proximal tremor generally does not respond well to thalamic surgery and may be severely disabling. © 2002 Movement Disorder Society

[1]  A. Benabid,et al.  Subthalamic nucleus stimulation alleviates akinesia and rigidity in parkinsonian patients. , 1996, Advances in neurology.

[2]  D L Price,et al.  The pedunculopontine nucleus in Parkinson's disease , 1989, Annals of neurology.

[3]  A M Graybiel,et al.  Neuronal loss in the pedunculopontine tegmental nucleus in Parkinson disease and in progressive supranuclear palsy. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[4]  T. Aziz,et al.  The pallidotomy debate. , 1998, British Journal of Neurosurgery.

[5]  H Imai Clinicophysiological features of akinesia. , 1996, European neurology.

[6]  E. Hirsch,et al.  Functional Activity of Zona Incerta Neurons Is Altered after Nigrostriatal Denervation in Hemiparkinsonian Rats , 2000, Experimental Neurology.

[7]  W. W. Kaelber,et al.  Projections of the zona incerta in the cat, with stimulation controls , 1979, Experimental Neurology.

[8]  S. Sun,et al.  Surgical control of akinesia in Parkinson's disease. , 1996, European neurology.

[9]  F. Mundinger Stereotaxic interventions on the zona incerta area for treatment of extrapyramidal motor disturbances and their results. , 1965, Confinia neurologica.

[10]  M. Inase,et al.  Excitotoxic lesions of the pedunculopontine tegmental nucleus produce contralateral hemiparkinsonism in the monkey , 1997, Neuroscience Letters.

[11]  M. Sambrook,et al.  Experimental hemichorea/hemiballismus in the monkey. Studies on the intracerebral site of action in a drug-induced dyskinesia. , 1984, Brain : a journal of neurology.

[12]  T. Aziz,et al.  Subthalamic nucleotomy alleviates parkinsonism in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-exposed primate. , 1992, British journal of neurosurgery.

[13]  Michel Panisset,et al.  Freezing of gait in Parkinson's disease. , 2004, Neurologic clinics.

[14]  K. Jellinger,et al.  The pedunculopontine nucleus in Parkinson's disease, progressive supranuclear palsy and Alzheimer's disease. , 1988, Journal of neurology, neurosurgery, and psychiatry.

[15]  J. D. Parkes,et al.  "ON-OFF" EFFECTS IN PATIENTS WITH PARKINSON'S DISEASE ON CHRONIC LEVODOPA THERAPY , 1976, The Lancet.

[16]  D. Price,et al.  Loss of pedunculopontine neurons in progressive supranuclear palsy , 1987, Annals of neurology.

[17]  E. Garcia-Rill,et al.  The mesencephalic locomotor region (MLR) in the rat , 1984, Brain Research.

[18]  T. Kondo,et al.  Various aspects of motor fluctuations and their management in Parkinson's disease. , 1994, Neurology.

[19]  Y. Agid,et al.  Axial parkinsonian symptoms can be improved: the role of levodopa and bilateral subthalamic stimulation , 2000, Journal of neurology, neurosurgery, and psychiatry.

[20]  G. Mogenson,et al.  Electrical and chemical activation of the mesencephalic and subthalamic locomotor regions in freely moving rats , 1988, Brain Research.

[21]  P. Bain,et al.  A study of tremor in multiple sclerosis. , 2001, Brain : a journal of neurology.

[22]  M. Inase,et al.  Protection against dopaminergic nigrostriatal cell death by excitatory input ablation , 2000, The European journal of neuroscience.

[23]  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.

[24]  E. Garcia-Rill,et al.  Locomotion-inducing sites in the vicinity of the pedunculopontine nucleus , 1987, Brain Research Bulletin.

[25]  A. Lozano,et al.  Comparative effects of unilateral and bilateral subthalamic nucleus deep brain stimulation , 1999, Neurology.

[26]  I. Mitchell,et al.  Regional brain uptake of 2-deoxyglucose in N -methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)—induced parkinsonism in the macaque monkey , 1985, Neuropharmacology.

[27]  Tipu Z. Aziz,et al.  Deep brain stimulation of the pedunculopontine region in the normal non-human primate , 2002, Journal of Clinical Neuroscience.

[28]  R. Grossman,et al.  Effects of stimulation of non-specific thalamic system on locomotor movements in cat. , 1958, Journal of neurophysiology.

[29]  E. Garcia-Rill The basal ganglia and the locomotor regions , 1986, Brain Research Reviews.

[30]  R. Gerard,et al.  AUTONOMIC AND MOTOR LOCALIZATION IN THE HYPOTHALAMUS , 1938 .

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

[32]  I. Mitchell,et al.  Levodopa-induced dyskinesia and response fluctuations in primates rendered parkinsonian with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) , 1987, Journal of the Neurological Sciences.

[33]  A L Benabid,et al.  Treatment of tremor in Parkinson's disease by subthalamic nucleus stimulation , 1998, Movement disorders : official journal of the Movement Disorder Society.

[34]  E. Eidelberg,et al.  Locomotor control in macaque monkeys. , 1981, Brain : a journal of neurology.

[35]  C. Blaha,et al.  Modulation of dopamine efflux in the striatum following cholinergic stimulation of the substantia nigra in intact and pedunculopontine tegmental nucleus-lesioned rats , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[36]  William H. Waller,et al.  PROGRESSION MOVEMENTS ELICITED BY SUBTHALAMIC STIMULATION , 1940 .

[37]  J. Stein,et al.  The role of descending basal ganglia connections to the brain stem in parkinsonian akinesia. , 1998, British journal of neurosurgery.

[38]  M. S. Goldman,et al.  The symptomatic and functional outcome of stereotactic thalamotomy for medically intractable essential tremor. , 1992, Journal of neurosurgery.

[39]  J. Stein,et al.  The role of the pedunculopontine region in basal-ganglia mechanisms of akinesia , 1999, Experimental Brain Research.

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

[41]  A. Benabid,et al.  Chronic electrical stimulation of the ventralis intermedius nucleus of the thalamus as a treatment of movement disorders. , 1996, Journal of neurosurgery.