Akineto-rigid vs. tremor syndromes in Parkinsonism

Purpose of reviewAkinesia, rigidity and low-frequency rest tremor are the three cardinal motor signs of Parkinson's disease and some Parkinson's disease animal models. However, cumulative evidence supports the view that akinesia/rigidity vs. tremor reflect different pathophysiological phenomena in the basal ganglia. Here, we review the recent physiological literature correlating abnormal neural activity in the basal ganglia with Parkinson's disease clinical symptoms. Recent findingsThe subthalamic nucleus of Parkinson's disease patients is characterized by oscillatory activity in the beta-frequency (∼15 Hz) range. However, Parkinson's disease tremor is not strictly correlated with the abnormal synchronous oscillations of the basal ganglia. On the other hand, akinesia and rigidity are better correlated with the basal ganglia beta oscillations. SummaryThe abnormal basal ganglia output leads to akinesia and rigidity. Parkinson's disease tremor most likely evolves as a downstream compensatory mechanism.

[1]  L. Poirier.  Experimental and histological study of midbrain dyskinesias. , 1960, Journal of neurophysiology.

[2]  H. Kwan,et al.  Single unit analysis of the human ventral thalamic nuclear group. Tremor-related activity in functionally identified cells. , 1994, Brain : a journal of neurology.

[3]  P. James.  An Essay on the Shaking Palsy , 1817, The Medico-Chirurgical Journal and Review.

[4]  D. Surmeier,et al.  D1 and D2 dopamine-receptor modulation of striatal glutamatergic signaling in striatal medium spiny neurons , 2007, Trends in Neurosciences.

[5]  J. Wickens,et al.  Space, time and dopamine , 2007, Trends in Neurosciences.

[6]  H. Kita,et al.  Neostriatal and globus pallidus stimulation induced inhibitory postsynaptic potentials in entopeduncular neurons in rat brain slice preparations , 2001, Neuroscience.

[7]  L. Tremblay,et al.  Effects of dopamine agonists on the spontaneous activity of globus pallidus neurons in monkeys with MPTP-induced parkinsonism , 1991, Brain Research.

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

[9]  A. Parent,et al.  The striatofugal fiber system in primates: a reevaluation of its organization based on single-axon tracing studies. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[10]  S. Haber,et al.  Evidence for interconnections between the two segments of the globus pallidus in primates: a PHA-L anterograde tracing study , 1990, Brain Research.

[11]  P. Calabresi,et al.  ACh/Dopamine Crosstalk in Motor Control and Reward: A Crucial Role for α6-Containing Nicotinic Receptors? , 2008, Neuron.

[12]  H. Bergman,et al.  Neurons in the globus pallidus do not show correlated activity in the normal monkey, but phase-locked oscillations appear in the MPTP model of parkinsonism. , 1995, Journal of neurophysiology.

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

[14]  H. Narabayashi,et al.  Long-term follow-up study of nucleus ventralis intermedius and ventrolateralis thalamotomy using a microelectrode technique in parkinsonism. , 1987, Applied neurophysiology.

[15]  Aviva Abosch,et al.  Thalamic deep brain stimulation for essential tremor: relation of lead location to outcome. , 2008, Neurosurgery.

[16]  K. Sigvardt,et al.  Temporal evolution of oscillations and synchrony in GPi/muscle pairs in Parkinson's disease. , 2005, Journal of neurophysiology.

[17]  Jozsef Csicsvari,et al.  Disrupted Dopamine Transmission and the Emergence of Exaggerated Beta Oscillations in Subthalamic Nucleus and Cerebral Cortex , 2008, The Journal of Neuroscience.

[18]  Erwan Bezard,et al.  Phenotype of Striatofugal Medium Spiny Neurons in Parkinsonian and Dyskinetic Nonhuman Primates: A Call for a Reappraisal of the Functional Organization of the Basal Ganglia , 2006, The Journal of Neuroscience.

[19]  A. Nambu,et al.  Functional significance of the cortico–subthalamo–pallidal ‘hyperdirect’ pathway , 2002, Neuroscience Research.

[20]  Anne Boomsma,et al.  On the structure of motor symptoms of Parkinson's disease , 2008, Movement disorders : official journal of the Movement Disorder Society.

[21]  O. Hornykiewicz,et al.  Effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on the regional distribution of brain monoamines in the rhesus monkey , 1991, Neuroscience.

[22]  L A Beckett,et al.  Prevalence of parkinsonian signs and associated mortality in a community population of older people. , 1996, The New England journal of medicine.

[23]  E. Vaadia,et al.  Midbrain Dopaminergic Neurons and Striatal Cholinergic Interneurons Encode the Difference between Reward and Aversive Events at Different Epochs of Probabilistic Classical Conditioning Trials , 2008, The Journal of Neuroscience.

[24]  P. Calabresi,et al.  Dopamine, Acetylcholine and Nitric Oxide Systems Interact to Induce Corticostriatal Synaptic Plasticity , 2003, Reviews in the neurosciences.

[25]  S. Haber.  The primate basal ganglia: parallel and integrative networks , 2003, Journal of Chemical Neuroanatomy.

[26]  M R DeLong,et al.  The primate subthalamic nucleus. III. Changes in motor behavior and neuronal activity in the internal pallidum induced by subthalamic inactivation in the MPTP model of parkinsonism. , 1994, Journal of neurophysiology.

[27]  Peter Brown,et al.  Parkinsonian Beta Oscillations in the External Globus Pallidus and Their Relationship with Subthalamic Nucleus Activity , 2008, The Journal of Neuroscience.

[28]  C. Marsden.  Origins of normal and pathological tremor , 1984 .

[29]  P. Greengard,et al.  Dichotomous Dopaminergic Control of Striatal Synaptic Plasticity , 2008, Science.

[30]  Aviva Abosch,et al.  Thalamic Deep Brain Stimulation for Essential Tremor: Relation of Lead Location to Outcome , 2004, Neurosurgery.

[31]  K. Doya.  Modulators of decision making , 2008, Nature Neuroscience.

[32]  André Parent,et al.  Chemical anatomy of primate basal ganglia , 1995, Progress in Neurobiology.

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

[34]  T. Kita,et al.  Number, origins, and chemical types of rat pallidostriatal projection neurons , 2001, The Journal of comparative neurology.

[35]  C. Gerfen,et al.  D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. , 1990, Science.

[36]  Peter Dayan,et al.  A Neural Substrate of Prediction and Reward , 1997, Science.

[37]  G. Deuschl,et al.  Pathophysiology of Parkinson's disease: From clinical neurology to basic neuroscience and back , 2002, Movement disorders : official journal of the Movement Disorder Society.

[38]  C. Rebert,et al.  Selective nigral toxicity after systemic administration of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyrine (MPTP) in the squirrel monkey , 1984, Brain Research.

[39]  D. Jacobowitz,et al.  A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[40]  H. Kita.  Globus pallidus external segment. , 2007, Progress in brain research.

[41]  H. Freund,et al.  The cerebral oscillatory network of parkinsonian resting tremor. , 2003, Brain : a journal of neurology.

[42]  Hagai Bergman,et al.  Dopamine Replacement Therapy Reverses Abnormal Synchronization of Pallidal Neurons in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Primate Model of Parkinsonism , 2002, The Journal of Neuroscience.

[43]  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.

[44]  Hitoshi Kita,et al.  Motor cortical control of internal pallidal activity through glutamatergic and GABAergic inputs in awake monkeys , 2007, The European journal of neuroscience.

[45]  M. Butz,et al.  Levodopa affects functional brain networks in parkinsonian resting tremor , 2009, Movement disorders : official journal of the Movement Disorder Society.

[46]  L. Timmermann,et al.  Pathological cerebral oscillatory activity in Parkinson’s disease: a critical review on methods, data and hypotheses , 2007, Expert review of medical devices.

[47]  H. Kwan,et al.  Statistical prediction of the optimal site for thalamotomy in parkinsonian tremor , 1995, Movement disorders : official journal of the Movement Disorder Society.

[48]  L. Tremblay,et al.  Abnormal spontaneous activity of globus pallidus neurons in monkeys with MPTP-induced parkinsonism , 1991, Brain Research.

[49]  H. Bergman,et al.  Pathological synchronization in Parkinson's disease: networks, models and treatments , 2007, Trends in Neurosciences.

[50]  F. A. Lenz,et al.  Tremor-frequency (3–6 Hz) activity in the sensorimotor arm representation of the internal segment of the globus pallidus in patients with Parkinson's disease , 1999, Neuroscience Letters.

[51]  E. Vaadia,et al.  Coincident but Distinct Messages of Midbrain Dopamine and Striatal Tonically Active Neurons , 2004, Neuron.

[52]  J. Bolam,et al.  Synaptic organisation of the basal ganglia , 2000, Journal of anatomy.

[53]  K. Jellinger,et al.  The Neuropathologic Basis of Different Clinical Subgroups of Parkinson's Disease , 1991, Journal of neuropathology and experimental neurology.

[54]  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.

[55]  Peter Brown,et al.  Effects of low-frequency stimulation of the subthalamic nucleus on movement in Parkinson's disease , 2007, Experimental Neurology.

[56]  J. Wickens.  Synaptic plasticity in the basal ganglia , 2009, Behavioural Brain Research.

[57]  Suzanne N Haber,et al.  Dopamine Replacement Therapy Does Not Restore the Full Spectrum of Normal Pallidal Activity in the 1-Methyl-4-Phenyl-1,2,3,6-Tetra-Hydropyridine Primate Model of Parkinsonism , 2006, The Journal of Neuroscience.

[58]  Joshua L Plotkin,et al.  Differential Excitability and Modulation of Striatal Medium Spiny Neuron Dendrites , 2008, The Journal of Neuroscience.

[59]  P. Lavallée,et al.  Single-axon tracing study of neurons of the external segment of the globus pallidus in primate. , 2000, The Journal of comparative neurology.

[60]  Poirier Lj.  The development of animal models for studies in Parkinson's disease. , 1971 .

[61]  D. Surmeier,et al.  Dichotomous Anatomical Properties of Adult Striatal Medium Spiny Neurons , 2008, The Journal of Neuroscience.