Online citations, reference lists, and bibliographies.
Please confirm you are human
(Sign Up for free to never see this)
← Back to Search

Acute Dopamine Boost Has A Negative Effect On Plasticity Of The Primary Motor Cortex In Advanced Parkinson's Disease.

A. Kishore, T. Popa, B. Velayudhan, T. Joseph, A. Balachandran, S. Meunier
Published 2012 · Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Share
Plasticity of primary motor cortex is severely impaired in Parkinson's disease and chronic dopaminergic treatment is reported not to rescue it. The effect of an acute dose of levodopa on cortical plasticity reported so far is variable. In this study, it was hypothesized that cortical plasticity would be restored in Parkinson's disease as a long duration response to treatment in stable responders while those with motor complications would have a reduction or loss of plasticity similar to the decay of long duration response of motor signs. Patients were carefully stratified based on their motor response to levodopa into stable responders (n=17), fluctuating non-dyskinetics (n=18) and fluctuating dyskinetics (n=20). Theta burst stimulation was applied to the motor cortex to induce long-term potentiation and long-term depression-like plasticity in both OFF and ON conditions. In OFF, stable responders could express both types of plasticity, fluctuating non-dyskinetics had long-term potentiation, but no long-term depression and both types of plasticity were lost in fluctuating dyskinetics. This suggests the presence of a long duration response in early stages of levodopa treatment and a gradual loss of chronic treatment benefit on plasticity, particularly for long-term depression, when motor complications develop. An acute dose of levodopa led to a worsening of long-term potentiation in fluctuating non-dyskinetic patients, and it did not have any effect on the plasticity that was absent in OFF in the fluctuating dyskinetic patients. Acute dosing led to a worsening of long-term depression in all the groups. In the fluctuating dyskinetic patients, there was a paradoxical potentiation instead of depression. Our results suggest that an acute non-physiological dopamine boost has a negative effect on cortical plasticity as disease advances. We propose that the loss of long duration response and the negative effect of acute doses on cortical plasticity with progression of disease may contribute to the pathophysiology of motor complications. Repeated non-physiological surges in synaptic dopamine during acute levodopa dosing could potentially lead to persistent dysfunction of key enzymes of the intracellular signalling cascade that are involved in the induction and maintenance of both forms of plasticity.
This paper references
10.1136/jnnp.55.3.181
Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases.
A. Hughes (1992)
10.1093/brain/awr158
Abnormal bidirectional plasticity-like effects in Parkinson's disease.
Y. Huang (2011)
Synaptic plasticity of motor cortex M1 is symmetric in right-handed healthy volunteers
A Kishore (2011)
10.1016/S1474-4422(10)70218-0
Levodopa-induced dyskinesias in patients with Parkinson's disease: filling the bench-to-bedside gap
P. Calabresi (2010)
10.1016/j.tins.2007.03.001
Dopamine-mediated regulation of corticostriatal synaptic plasticity
P. Calabresi (2007)
10.1007/s00415-010-5597-1
Theta burst stimulation over the primary motor cortex does not induce cortical plasticity in Parkinson’s disease
C. Eggers (2010)
10.1001/ARCHNEUR.1992.00530350037016
Effect of long-term therapy on the pharmacodynamics of levodopa. Relation to on-off phenomenon.
J. Nutt (1992)
Recent Developments in Parkinson's Disease
S. Fahn (1986)
10.1002/ANA.410370208
Changes in excitability of motor cortical circuitry in patients with parkinson's disease
M. C. Ridding (1995)
10.1016/S0896-6273(00)80632-7
NMDA Induces Long-Term Synaptic Depression and Dephosphorylation of the GluR1 Subunit of AMPA Receptors in Hippocampus
H. Lee (1998)
10.1093/BRAIN/AWL031
Motor cortex plasticity in Parkinson's disease and levodopa-induced dyskinesias.
F. Morgante (2006)
10.1016/j.neucli.2010.04.002
Excitability of the lower-limb area of the motor cortex in Parkinson's disease
F. Vacherot (2010)
10.1371/journal.pone.0007082
Dopamine in Motor Cortex Is Necessary for Skill Learning and Synaptic Plasticity
K. Molina-Luna (2009)
Parkinson Study Group. Levodopa and the progression of Parkinson's disease
S Fahn (2004)
10.1523/JNEUROSCI.20-22-08443.2000
Dopamine and cAMP-Regulated Phosphoprotein 32 kDa Controls Both Striatal Long-Term Depression and Long-Term Potentiation, Opposing Forms of Synaptic Plasticity
P. Calabresi (2000)
10.1016/b0-44-306557-8/50234-3
Unified Parkinson's Disease Rating Scale
S. Fahn (1987)
10.1002/ANA.410390504
The response to levodopa in parkinson's disease: Imposing pharmacological law and order
J. Nutt (1996)
10.1007/s00221-007-1121-y
Motor intracortical inhibition in PD: L-DOPA modulation of high-frequency rTMS effects
B. Fierro (2007)
10.1038/nn1040
Loss of bidirectional striatal synaptic plasticity in L-DOPA–induced dyskinesia
B. Picconi (2003)
10.1523/JNEUROSCI.6258-10.2011
Dose-Dependent Nonlinear Effect of l-DOPA on Paired Associative Stimulation-Induced Neuroplasticity in Humans
N. Thirugnanasambandam (2011)
10.1159/000300647
When Do Levodopa Motor Fluctuations First Appear in Parkinson’s Disease?
F. Stocchi (2010)
10.1002/mds.1255
Repetitive magnetic stimulation of cortical motor areas in Parkinson's disease: Implications for the pathophysiology of cortical function
F. Gilio (2002)
10.1002/ana.20599
Pathways mediating abnormal intracortical inhibition in Parkinson's disease
C. MacKinnon (2005)
10.1016/j.neuron.2004.12.033
Theta Burst Stimulation of the Human Motor Cortex
Y. Huang (2005)
10.1056/NEJMOA033447
Levodopa and the progression of Parkinson's disease.
S. Fahn (2004)
10.1002/ana.21947
Dopamine‐dependent motor learning: Insight into levodopa's long‐duration response
J. Beeler (2010)
10.1016/j.parkreldis.2011.03.014
The long-duration response to levodopa: phenomenology, potential mechanisms and clinical implications.
E. Anderson (2011)
10.1097/00043764-196912000-00037
Modification of Parkinsonism--chronic treatment with L-dopa.
G. C. Cotzias (1969)
10.1212/01.wnl.0000343881.27524.e8
Impaired presynaptic inhibition in the motor cortex in Parkinson disease
J. Chu (2009)
10.1016/j.clinph.2011.06.034
Early, severe and bilateral loss of LTP and LTD-like plasticity in motor cortex (M1) in de novo Parkinson’s disease
A. Kishore (2012)
10.1093/BRAIN/119.1.71
Cortical inhibition in Parkinson's disease. A study with paired magnetic stimulation.
A. Berardelli (1996)
10.1093/brain/awq342
Inhibition of phosphodiesterases rescues striatal long-term depression and reduces levodopa-induced dyskinesia.
B. Picconi (2011)
10.1002/MDS.870090403
Utility of an objective dyskinesia rating scale for Parkinson's disease: Inter‐ and intrarater reliability assessment
C. Götz (1994)
10.1097/00004691-199201000-00014
Optimal Focal Transcranial Magnetic Activation of the Human Motor Cortex: Effects of Coil Orientation, Shape of the Induced Current Pulse, and Stimulus Intensity
J. Brasil-Neto (1992)
When do motor fluctuations first appear in Parkinson's disease
F Stocchi (2010)
Negative effect of acute dopamine boost
(2012)
L-dopa therapy of Parkinson's disease: plasma L-dopa concentration, therapeutic response, and side effects.
M. Muenter (1971)
10.1126/SCIENCE.276.5321.2042
Regulatory phosphorylation of AMPA-type glutamate receptors by CaM-KII during long-term potentiation.
A. Barría (1997)
Clinical pharmacology of levodopa-induced dyskinesia.
J. Nutt (2000)
10.1002/ana.20692
Altered plasticity of the human motor cortex in Parkinson's disease
Y. Ueki (2006)
10.1093/BRAIN/AWH290
Levodopa-induced changes in synaptic dopamine levels increase with progression of Parkinson's disease: implications for dyskinesias.
R. de la Fuente-Fernández (2004)
10.1523/JNEUROSCI.0852-07.2007
Critical Involvement of cAMP/DARPP-32 and Extracellular Signal-Regulated Protein Kinase Signaling in l-DOPA-Induced Dyskinesia
Emanuela Santini (2007)
10.1038/35016089
Regulation of distinct AMPA receptor phosphorylation sites during bidirectional synaptic plasticity
H. Lee (2000)
10.1016/j.expneurol.2010.11.020
Lack of LTP-like plasticity in primary motor cortex in Parkinson's disease
A. Suppa (2011)
10.1007/s00415-010-5731-0
The role of the long-duration response to levodopa in Parkinson’s disease
M. Zappia (2010)
10.1093/BRAIN/AWG183
Short and long latency afferent inhibition in Parkinson's disease.
A. Sailer (2003)
10.1002/mds.1090
Frequency of levodopa‐related dyskinesias and motor fluctuations as estimated from the cumulative literature
J. Ahlskog (2001)
10.1016/S0896-6273(00)80798-9
Beyond the Dopamine Receptor the DARPP-32/Protein Phosphatase-1 Cascade
P. Greengard (1999)
10.1016/0028-3932(71)90067-4
The assessment and analysis of handedness: the Edinburgh inventory.
R. Oldfield (1971)
10.1016/S1388-2457(00)00316-3
Effects of chronic levodopa and pergolide treatment on cortical excitability in patients with Parkinson's disease: a transcranial magnetic stimulation study
A. Strafella (2000)
10.1002/ANA.65.ABS
Biochemical variations in the synaptic level of dopamine precede motor fluctuations in Parkinson's disease: PET evidence of increased dopamine turnover.
R. de la Fuente-Fernández (2001)
Lack of long-term potentiation-like plasticity in primary motor cortex in Parkinson's disease
A Suppa (2011)
10.1016/S0165-0173(01)00158-8
Transcranial magnetic stimulation and Parkinson’s disease
R. Cantello (2002)
10.1136/jnnp.57.4.430
Motor response to levodopa in patients with parkinsonian motor fluctuations: a follow-up study over three years.
A. Hughes (1994)
10.1152/JN.1999.82.6.3575
Unilateral dopamine denervation blocks corticostriatal LTP.
D. Centonze (1999)
10.1016/j.clinph.2011.07.051
Effects of theta burst stimulation on motor cortex excitability in Parkinson’s disease
Orit Zamir (2012)
10.1212/WNL.44.7.1287
Longitudinal monitoring of the levodopa concentration‐effect relationship in Parkinson's disease
M. Contin (1994)
10.1093/CERCOR/BHM087
Effect of physiological activity on an NMDA-dependent form of cortical plasticity in human.
Y. Huang (2008)
10.1002/mds.23289
Tremor—some controversial aspects
N. Quinn (2011)
10.1002/mds.23429
Systematic review of levodopa dose equivalency reporting in Parkinson's disease
C. L. Tomlinson (2010)
10.1093/brain/awn340
Synaptic plasticity, dopamine and Parkinson's disease: one step ahead.
P. Calabresi (2009)



This paper is referenced by
10.1007/s00415-014-7572-8
Theta burst stimulation over the supplementary motor area in Parkinson’s disease
C. Eggers (2014)
10.1016/j.jneumeth.2020.108957
Non-invasive brain stimulation for Parkinson’s disease: Clinical evidence, latest concepts and future goals: A systematic review
J. Madrid (2021)
10.1007/s12311-016-0763-3
Consensus Paper: Towards a Systems-Level View of Cerebellar Function: the Interplay Between Cerebellum, Basal Ganglia, and Cortex
D. Caligiore (2016)
10.1097/WNF.0000000000000186
Switching L-dopa Therapy from Pulsatile to Pulse Administration Reduces Motor Complications in Parkinson's Disease
G. Mostile (2017)
10.1093/cercor/bht058
Cerebellar sensory processing alterations impact motor cortical plasticity in Parkinson's disease: clues from dyskinetic patients.
A. Kishore (2014)
10.3389/fneur.2014.00049
Maladaptive Plasticity in Levodopa-Induced Dyskinesias and Tardive Dyskinesias: Old and New Insights on the Effects of Dopamine Receptor Pharmacology
A. Cerasa (2014)
10.1016/j.gaitpost.2015.08.001
Active assistive forced exercise provides long-term improvement to gait velocity and stride length in patients bilaterally affected by Parkinson's disease.
T. Stuckenschneider (2015)
10.3389/fneur.2014.00068
Cerebellar Influence on Motor Cortex Plasticity: Behavioral Implications for Parkinson’s Disease
A. Kishore (2014)
10.1007/s11910-014-0449-5
Treatment and Physiology in Parkinson’s Disease and Dystonia: Using Transcranial Magnetic Stimulation to Uncover the Mechanisms of Action
A. Wagle Shukla (2014)
10.1007/978-3-319-25721-1_9
Clinical Applications of rTMS in Parkinson’s Disease
Y. Shirota (2016)
10.1016/j.clinph.2017.03.043
Cortical plasticity and levodopa-induced dyskinesias in Parkinson’s disease: Connecting the dots in a multicomponent network
R. Rajan (2017)
10.1016/j.clinph.2015.02.009
Are studies of motor cortex plasticity relevant in human patients with Parkinson’s disease?
M. Bologna (2016)
10.2298/BG20130429KACAR
Uticaj transkranijalne magnetne stimulacije na kliničke znake i elektrofiziološke parametre kod obolelih od Parkinsonove bolesti
A. Kačar (2013)
10.4103/0972-2327.167713
Research in Parkinson's disease in India: A review
Pratibha Surathi (2016)
10.1016/j.brs.2012.12.004
Study of Cerebello-Thalamocortical Pathway by Transcranial Magnetic Stimulation in Parkinson's Disease
F. Carrillo (2013)
10.1016/j.clinph.2012.09.016
History of exposure to dopaminergic medication does not affect motor cortex plasticity and excitability in Parkinson’s disease
A. Kacar (2013)
10.1016/j.brs.2016.01.006
Ten Years of Theta Burst Stimulation in Humans: Established Knowledge, Unknowns and Prospects
A. Suppa (2016)
10.1002/cpt.1542
Invasive and Noninvasive Brain Stimulation in Parkinson's Disease: Clinical Effects and Future Perspectives
Kai-Hsiang S Chen (2019)
The role of sensorimotor cortical plasticity in pathophysiology of Parkinson’s disease and dystonia
M. Kojović (2014)
ROLE OF FUNCTIONAL ELECTRICAL STIMULATION AND OF TRANSCRANIAL MAGNETIC STIMULATION IN IMPROVING MOTOR PEFORMANCE IN PARKINSONʼS DISEASE
Thesis (2013)
10.1016/j.neulet.2013.06.050
Alterations of mean diffusivity in brain white matter and deep gray matter in Parkinson's disease
H. Kim (2013)
10.1038/srep06027
Continuous dopaminergic stimulation (CDS)-based treatment in Parkinson's disease patients with motor complications: A systematic review and meta-analysis
C. Xie (2014)
10.1016/j.neurobiolaging.2014.05.004
Age-related decline in the responsiveness of motor cortex to plastic forces reverses with levodopa or cerebellar stimulation
A. Kishore (2014)
10.3389/fneur.2013.00134
The Enemy within: Propagation of Aberrant Corticostriatal Learning to Cortical Function in Parkinson’s Disease
J. Beeler (2013)
10.1111/ncn3.12031
Quantitative relationships of graded motor symptoms with thalamic activities monitored during thalamotomy for a population of patients with Parkinson's disease
Y. Narabayashi (2016)
10.1016/j.neulet.2017.11.064
Analysis of white matter characteristics with tract-based spatial statistics according to diffusion tensor imaging in early Parkinson’s disease
X. Li (2018)
10.1002/mds.27736
The interindividual variability of transcranial magnetic stimulation effects: Implications for diagnostic use in movement disorders
A. Latorre (2019)
10.1098/rstb.2014.0184
Levodopa-induced plasticity: a double-edged sword in Parkinson's disease?
P. Calabresi (2015)
10.1016/j.clinph.2013.04.154
P 76. Cerebellar sensory processing alterations impact motor cortical plasticity in Parkinson’s disease: Clues from dyskinetic patients
A. Kishore (2013)
10.1002/mds.28025
MRI of Motor and Nonmotor Therapy‐Induced Complications in Parkinson's Disease
G. Donzuso (2020)
10.1016/j.parkreldis.2012.08.012
Non-homogeneous effect of levodopa on inhibitory circuits in Parkinson's disease and dyskinesia.
L. Barbin (2013)
10.1371/journal.pone.0191839
Sensorimotor adaptation of voice fundamental frequency in Parkinson's disease
D. Abur (2018)
See more
Semantic Scholar Logo Some data provided by SemanticScholar