Motor cortex plasticity in Parkinson's disease and levodopa-induced dyskinesias

Abstract

Experimental models of Parkinson's disease have demonstrated abnormal synaptic plasticity in the corticostriatal system, possibly related to the development of levodopa-induced dyskinesias (LID). We tested the hypothesis that LID in Parkinson's disease is associated with aberrant plasticity in the human motor cortex (M1). We employed the paired associative stimulation (PAS) protocol, an experimental intervention involving transcranial magnetic stimulation (TMS) and median nerve stimulation capable of producing long-term potentiation (LTP) like changes in the sensorimotor system in humans. We studied the more affected side of 16 moderately affected patients with Parkinson's disease (9 dyskinetic, 7 non-dyskinetic) and the dominant side of 9 age-matched healthy controls. Motor-evoked potential (MEP) amplitudes and cortical silent period (CSP) duration were measured at baseline before PAS and for up to 60 min (T0, T30 and T60) after PAS in abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles. PAS significantly increased MEP size in controls (+74.8% of baseline at T30) but not in patients off medication (T30: +0.07% of baseline in the non-dyskinetic, +27% in the dyskinetic group). Levodopa restored the potentiation of MEP amplitudes by PAS in the non-dyskinetic group (T30: +64.9% of baseline MEP) but not in the dyskinetic group (T30: -9.2% of baseline). PAS prolonged CSP duration in controls. There was a trend towards prolongation of CSP in the non-dyskinetic group off medications but not in the dyskinetic group. Levodopa did not restore CSP prolongation by PAS in the dyskinetic group. Our findings suggest that LTP-like plasticity is deficient in Parkinson's disease off medications and is restored by levodopa in non-dyskinetic but not in dyskinetic patients. Abnormal synaptic plasticity in the motor cortex may play a role in the development of LID.

Interaction of BDNF and COMT Polymorphisms on Paired-Associative Stimulation-Induced Cortical Plasticity

“…Other intrinsic differences in protocols used to induce cortical plasticity in humans, e.g., stimulation mode or pulse frequency (Ziemann, 2004), may additionally contribute to differential findings between studies. We chose the PAS protocol (Stefan et al, 2000) for the present study as a frequently used and sensitive tool to investigate cortical plasticity and its relation to age and cognitive function in healthy subjects and neurological patients (Morgante et al, 2006;Weise et al, 2006;Frantseva et al, 2008;Muller-Dahlhaus et al, 2008;Castel-Lacanal et al, 2009;Fathi et al, 2010;Zeller et al, 2010;List et al, 2011List et al, , 2012.…”

Neuromodulatory Neurotransmitters Influence LTP-Like Plasticity in Human Cortex: A Pharmaco-TMS Study

“…Impaired PAS-induced LTP-like plasticity is typically observed in disorders associated with a dysfunctional dopaminergic system such as Parkinson's disease (Morgante et al, 2006;Ueki et al, 2006;Schwingenschuh et al, 2010) or schizophrenia (Frantseva et al, 2008), or a deficient central cholinergic system such as Alzheimer's disease (Battaglia et al, 2007), whereas exaggerated PASinduced LTP-like plasticity can be observed in states of increased endogenous central cholinergic tone such as dystonia (Quartarone et al, 2003(Quartarone et al, , 2008Weise et al, 2006;Schwingenschuh et al, 2010).…”

Stimulus uncertainty enhances long-term potentiation-like plasticity in human motor cortex

“…Indeed, some studies have shown that MEP changes following PAS reach their maximum 30-60 minutes following PAS (Frantseva et al, 2008;Morgante, Espay, Gunraj, Lang, & Chen, 2006). Our choice of measuring MEPs up to 15 minutes following PAS was motivated by the earlier work of Stefan et al (2000), which suggested that the largest changes in cortical excitability occur at approximately this time point, before gradually returning to baseline at 60 minutes post-PAS.…”