Abstract
In Parkinson’s disease (PD), there are alterations of the basal ganglia (BG) thalamocortical networks, primarily due to degeneration of nigrostriatal dopaminergic neurons. These changes in subcortical networks lead to plastic changes in primary motor cortex (M1), which mediates cortical motor output and is a potential target for treatment of PD. Studies investigating the motor cortical plasticity using non-invasive transcranial magnetic stimulation (TMS) have found altered plasticity in PD, but there are inconsistencies among these studies. This is likely because plasticity depends on many factors such as the extent of dopaminergic loss and disease severity, response to dopaminergic replacement therapies, development of l-DOPA-induced dyskinesias (LID), the plasticity protocol used, medication, and stimulation status in patients treated with deep brain stimulation (DBS). The influences of LID and DBS on BG and M1 plasticity have been explored in animal models and in PD patients. In addition, many other factors such age, genetic factors (e.g., brain derived neurotropic factor and other neurotransmitters or receptors polymorphism), emotional state, time of the day, physical fitness have been documented to play role in the extent of plasticity induced by TMS in human studies. In this review, we summarize the studies that investigated M1 plasticity in PD and demonstrate how these afore-mentioned factors affect motor cortical plasticity in PD. We conclude that it is important to consider the clinical, demographic, and technical factors that influence various plasticity protocols while developing these protocols as diagnostic or prognostic tools in PD. We also discuss how the modulation of cortical excitability and the plasticity with these non-invasive brain stimulation techniques facilitate the understanding of the pathophysiology of PD and help design potential therapeutic possibilities in this disorder.
Highlights
PLASTICITY – LONG-TERM POTENTIATION AND LONG-TERM DEPRESSION The word plasticity is derived from Spanish word “plasticina” meaning “play-doh” describing the property of a substance being impressionable or changes the structure or function depending on the situation
A rapid increase in post-synaptic calcium concentration binds the C-terminal of calmodulin and triggers a kinase pathway that increases the density and conductance surface α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors leading to long-term potentiation (LTP) (Figure 1)
The management strategies of Parkinson’s disease (PD) involve the use of dopaminergic medications and deep brain stimulation (DBS) which alter plasticity in both basal ganglia (BG) and M1, and these will be discussed
Summary
There are three main pathways of information processing in the cortico-BG loop (Figure 2A), the direct (cortico-striatopallidal/nigral) and indirect (cortico-striato-pallido-subthalamopallidal/nigral) pathways via the striatum and the hyperdirect (cortico-subthalamo-pallidal/nigral) pathway via the subthalamic nucleus (STN) [12]. Α-calcium-calmodulin-dependent protein kinase II (α-CaMKII) functions as signal integrator [27] for these two neurotransmitters (glutamate and dopamine) related pathways and increased autophosphorylation of this molecule was associated with defective synaptic plasticity which parallels the development of motor abnormalities in Parkinsonian rats [28] This alteration of plasticity involved the absence of both LTP [29, 30] and LTD [31] in striatum and was postulated as the molecular mechanisms responsible for motor and cognitive symptoms of PD [6]. Plasticity induced by protocols that activate multiple sets of synapses (such as PAS acting through sensory-motor communications and intracortical circuits of M1) is termed as heterosynaptic plasticity This type of plasticity depends on spike-timing-dependent mechanisms of activating pre and post-synaptic terminals within a time window www.frontiersin.org as discussed earlier. Picconi et al [29]
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