Apathy in Parkinson's disease: neurophysiological evidence of impaired incentive processing.
Apathy is one of the most common and debilitating nonmotor manifestations of Parkinson's disease (PD) and is characterized by diminished motivation, decreased goal-directed behavior, and flattened affect. Despite its high prevalence, its underlying mechanisms are still poorly understood, having been associated with executive dysfunction, and impaired emotional processing and decision making. Apathy, as a syndrome, has recently been associated with reduced activation in the ventral striatum, suggesting that early- to middle-stage Parkinson's disease patients with this manifestation may have a compromised mesocorticolimbic dopaminergic pathway and impaired incentive processing. To test this hypothesis, we measured the amplitude of the feedback-related negativity, an event-related brain potential associated with performance outcome valence, following monetary gains and losses in human PD patients (12 women) and healthy controls (6 women) performing a gambling task. Early- to middle-stage PD patients presenting clinically meaningful symptoms of apathy were compared with nonapathetic PD patients and healthy controls. Patients with cognitive impairment, depression, and other psychiatric disturbances were excluded. Results showed that the amplitude of the feedback-related negativity, measured as the difference wave in the event-related brain potential between gains and losses, was significantly reduced in PD patients with apathy compared with nonapathetic patients and healthy controls. These findings indicate impaired incentive processing and suggest a compromised mesocorticolimbic pathway in cognitively intact PD patients with apathy.
Neurology Department, Movement Disorders Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, 08025 Barcelona, Spain, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), 08025 Barcelona, Spain, Human Neuropsychopharmacology Group, Centre d'Investigació de Medicaments, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain, Departament de Farmacologia i Terapèutica, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Centro Investigación Biomedica en Red-Enfermedades Neurodegenerativas (CIBERNED), Spain, and Department of Automatic Control (ESAII), Biomedical Engineering Research Center (CREB), Universitat Politècnica de Catalunya, 08028 BarcelonaTech (UPC), CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain.
Saul
S
Martínez-Horta
Jordi
J
Riba
Ramón Fernández
RF
de Bobadilla
Javier
J
Pagonabarraga
Berta
B
Pascual-Sedano
Rosa Maria
RM
Antonijoan
Sergio
S
Romero
Miquel Àngel
MÀ
Mañanas
Carmen
C
García-Sanchez
Jaime
J
Kulisevsky
D000339:Affect / Q000502:physiology; D000368:Aged; D057565:Apathy / Q000502:physiology*; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D003657:Decision Making / Q000502:physiology; D005071:Evoked Potentials / Q000502:physiology*; D005260:Female; D005715:Gambling; D006801:Humans; D008297:Male; D008875:Middle Aged; D009042:Motivation / Q000502:physiology*; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000503:physiopathology* / Q000523:psychology; D011930:Reaction Time / Q000502:physiology
Parkinson's disease; apathy; feedback-related negativity; incentive processing