Objective: Levodopa-induced dyskinesia (LID) in Parkinson’s disease (PD) are involuntary movements caused by long-term treatment with dopaminergic replacement therapy (levodopa). During the cause of PD, most patients develop LID. Little is known about how brain networks are disturbed in LID. To investigate this, we performed a systematic review of the functional neuroimaging literature on LID.

Background: Maladaptive plasticity at the cortico-striatal synapses and non-physiological oscillations in dopamine concentrations have both been implicated in the pathophysiology that underlies LID shown in animal models. These changes include changes in dopaminergic and non-dopaminergic receptors. Due to the intrusive nature of the procedures, these findings have not yet been demonstrated in humans. Yet, the behavioral and motor modifications identified in LID cannot be fully explained by the molecular changes in LID. By examining the changes in brain networks, neuroimaging techniques can be utilized to examine the pathology of LID on a global scale.

Method: Twenty-six studies of functional magnetic resonance imaging (fMRI), electroencephalography (EEG), transcranial magnetic stimulation (TMS)-EEG/ electromyography (EMG), positron emission tomography (PET), and single-photon emission computerized tomography (SPECT) met our pre-defined criteria and were included.

Results: The included studies showed increased activation of the putamen, premotor areas involved in motor planning and action selection, and the cerebellum. On the other hand, a decreased activation was found in the right inferior frontal gyrus (rIFG), involved in motor inhibition. TMS targeting the pre-supplementary motor area (preSMA), cerebellum, and rIFG have shown transient anti-dyskinetic effects suggesting these structures are involved in generating involuntary movements. Furthermore,TMS-EMG studies have shown increased cortical excitability and blunted cortical plasticity in patients with LID.

Conclusion: The changes seen in LID might result from pathophysiological processes but could also reflect compensatory mechanisms to balance the slowness of movement in PD. The compensatory changes might then ultimately result in LID. More studies are needed to elaborate on the pathophysiology and to find targets for effective and long-lasting treatment using non-invasive brain stimulation.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/functional-circuit-abnormalities-in-levodopa-induced-dyskinesia-in-parkinsons-disease-a-systematic-review/