Research Report Compensatory cortical mechanisms in Parkinson's disease evidenced with fMRI during the performance of pre-learned sequential movements Rosella Mallol a , Alfonso Barrós-Loscertales b , Mario López a , Vicente Belloch c , Maria Antònia Parcet b , César Ávila b, ⁎ a Sección de Neurología. Hospital General de Castellón Castelló, Spain b Dep. Psicología Bàsica, Clínica i Psicobiología. Universitat Jaume I, Castelló, Spain c Servicio de Radiología: ERESA, Valencia, Spain ARTICLE INFO ABSTRACT Article history: Accepted 4 February 2007 Available online 27 February 2007 We used fMRI to study brain activity associated with the performance of a pre-learned sequence of complex movements of the hand-made unimanually in a group of 13 Parkinson's disease patients and a group of 11 control volunteers. Patients were scanned “off” medication. In controls, sequential movements led to the activation of bilateral sensorimotor and premotor cortex, bilateral inferior parietal cortex, supplementary motor area, bilateral putamen and globus pallidus, and the left ventral lateral nucleus of the thalamus. Sequential movements in the Parkinson's disease group were associated with a similar pattern of activation, although relative decrease of activation in striatum and thalamic areas was observed. Patients in comparison with controls showed a hyperactivation in ipsilateral premotor areas and a hypoactivation in structures of the frontostriatal motor loop. Furthermore, patient scores in the motor scale of the UPDRS correlated positively with the activation thalamus and motor cortical areas during the sequential motor task. We concluded that in Parkinson's disease there is a compensatory mechanism of the dopamine deficit in frontostriatal motor circuits that increases participation in the execution of motor tasks of parietal–lateral premotor circuits. © 2007 Elsevier B.V. All rights reserved. Keywords: Parkinson's disease Fronto-striatal motor circuit Dopamine Complex movement fMRI Compensatory mechanism 1. Introduction Parkinson's disease (PD) is characterized by a loss of dopamine projections to the striatum. The basal ganglia are integral components in a complex system of cortico-subcortical loops, and they are linked to cortical premotor and prefrontal areas via the ventral and dorsomedial thalamus (Alexander et al., 1986). At least five separate parallel loops have been proposed to mediate motor behavior, eye movements and cognition. The motor circuit has been the subject of most investigations in PD. However, fMRI studies that investigate motor behavior have focused more on cortical brain structures rather than subcortical brain structures related to this circuitry. The basal ganglia are thought to mediate stimulus–response (S–R) learning, in which performance improves according to sensory feedback obtained as a result of a response. Evidence BRAIN RESEARCH 1147 (2007) 265 – 271 ⁎ Corresponding author. E-mail address: avila@psb.uji.es (C. Ávila). 0006-8993/$ – see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2007.02.046 available at www.sciencedirect.com www.elsevier.com/locate/brainres