title: Dopamine Replacement Therapy, Learning and Reward Prediction in Parkinson's Disease: Implications for Rehabilitation.
abstract: The principal feature of Parkinson's disease (PD) is the impaired ability to acquire and express habitual-automatic actions due to the loss of dopamine in the dorsolateral striatum, the region of the basal ganglia associated with the control of habitual behavior. Dopamine replacement therapy (DRT) compensates for the lack of dopamine, representing the standard treatment for different motor symptoms of PD (such as rigidity, bradykinesia and resting tremor). On the other hand, rehabilitation treatments, exploiting the use of cognitive strategies, feedbacks and external cues, permit to "learn to bypass" the defective basal ganglia (using the dorsolateral area of the prefrontal cortex) allowing the patients to perform correct movements under executive-volitional control. Therefore, DRT and rehabilitation seem to be two complementary and synergistic approaches. Learning and reward are central in rehabilitation: both of these mechanisms are the basis for the success of any rehabilitative treatment. Anyway, it is known that "learning resources" and reward could be negatively influenced from dopaminergic drugs. Furthermore, DRT causes different well-known complications: among these, dyskinesias, motor fluctuations, and dopamine dysregulation syndrome (DDS) are intimately linked with the alteration in the learning and reward mechanisms and could impact seriously on the rehabilitative outcomes. These considerations highlight the need for careful titration of DRT to produce the desired improvement in motor symptoms while minimizing the associated detrimental effects. This is important in order to maximize the motor re-learning based on repetition, reward and practice during rehabilitation. In this scenario, we review the knowledge concerning the interactions between DRT, learning and reward, examine the most impactful DRT side effects and provide suggestions for optimizing rehabilitation in PD.
authors.affiliation: Department of Parkinson's disease, Movement Disorders and Brain Injury Rehabilitation, "Moriggia-Pelascini" Hospital Gravedona ed Uniti (Como), Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Ferrazzoli
authors.affiliation: UQ Centre for Clinical Research, The University of QueenslandBrisbane, QLD, Australia; School of Psychological Sciences and Monash Institute of Cognitive and Clinical Neurosciences, Monash UniversityMelbourne, VIC, Australia.
authors.forename: Adrian
authors.initials: A
authors.lastname: Carter
authors.affiliation: Neuroscience Graduate Program and National Magnetic Resonance Research Center (UMRAM), Bilkent University Ankara, Turkey.
authors.forename: Fatma S
authors.initials: FS
authors.lastname: Ustun
authors.affiliation: Department of Parkinson's disease, Movement Disorders and Brain Injury Rehabilitation, "Moriggia-Pelascini" Hospital Gravedona ed Uniti (Como), Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Palamara
authors.affiliation: Department of Parkinson's disease, Movement Disorders and Brain Injury Rehabilitation, "Moriggia-Pelascini" Hospital Gravedona ed Uniti (Como), Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Ortelli
authors.affiliation: Department of Biomedical Engineering, Scientific Institute of Montescano, S. Maugeri Foundation, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Montescano (Pavia), Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Maestri
authors.affiliation: School of Psychological Sciences and Monash Institute of Cognitive and Clinical Neurosciences, Monash University Melbourne, VIC, Australia.
authors.forename: Murat
authors.initials: M
authors.lastname: Yücel
authors.affiliation: Department of Parkinson's disease, Movement Disorders and Brain Injury Rehabilitation, "Moriggia-Pelascini" Hospital Gravedona ed Uniti (Como), Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Frazzitta
keywords: DRT side effects; dopamine replacement therapy; learning; rehabilitation; reward prediction