Cortico-Striatal-Thalamic Network Functional Connectivity In Hemiparkinsonism (P2.001)

OBJECTIVE: To investigate functional connectivity of the cortico-striatal-thalamic networks in patients with early lateralized Parkinson’s disease (PD) (hemiparkinsonism), and the effects of levodopa (L-dopa) on the brain networks at the earliest stage of PD. BACKGROUND: In hemiparkinsonian patients, the cerebral hemisphere ipsilateral to the affected limbs can be considered “presymptomatic”. Resting state (RS) fMRI in mild/moderate stage of PD revealed an altered connectivity of the cortico-striatal-thalamic network, which is likely to be modulated by L-DOPA in both chronically treated (t-PD) and drug-naive (n-PD) patients. DESIGN/METHODS: RS fMRI was obtained from 69 patients with hemiparkinsonism (25 n-PD and 44 t-PD) and 27 healthy subjects. Functional connectivity analysis was performed using caudate, putamen, pallidus nucleus and thalamus bilaterally as seed regions of interest. The images of patients whose symptoms were on the left (L) side were left-right (R) flipped so that the hemisphere contralateral to the affected limbs was the L for all patients. RESULTS: Relative to controls, n-PD patients showed an increased basal ganglia reciprocal functional connectivity bilaterally, and a decreased connectivity of the affected caudate nucleus and thalamus with the ispilateral prefrontal, frontomedial, orbitofrontal and insular cortices. Compared with both controls and n-PD patients, t-PD patients showed a decreased functional connectivity among the striatal and thalamic regions, and an increased functional connectivity between the striatum and the temporal cortex and between the thalamus and several sensorimotor, parietal, temporal and occipital cortical regions. In both n-PD and t-PD groups, patients with more severe motor disability had an increased striatal/thalamic functional connectivity with temporal, parietal and occipital regions. CONCLUSIONS: Cortico-striatal-thalamic functional abnormalities occur in patients with hemiparkinsonism, antecede the onset of motor symptoms on the opposite body side, and are modulated by L-dopa. L-dopa is likely to facilitate a compensation of PD functional abnormalities possibly through an increased thalamic outflow. Study Supported by: Italian Ministry of Health (#GR-2009-1577482); Ministry of Science and Technology of the Republic of Serbia (#175095). Disclosure: Dr. Caso has nothing to disclose. Dr. Agosta has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec, Sanofi-Aventis Pharmaceuticals Inc., and Serono Symposia International Foundation. Dr. Agosta has received personal compensation in an editorial capacity for the Journal of Neurology. Dr. Agosta has received research support from the Italian Ministry of Health, and Teva Neuroscience. Dr. Stankovic has nothing to disclose. Dr. Inuggi has nothing to disclose. Dr. Petrovic has received personal compensation for activities with Lundbeck, GlaxoSmithKlein Inc., and Boehnringer Ingelheim Pharmaceuticals Inc. Dr. Svetel has received personal compensation for activities with Lundbeck, Novartis, GlaxoSmithKline Inc. and Boehringer Ingelheim Pharmaceuticals Inc. Dr. Comi has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals Inc., Novartis, Merck Serono, Biogen Idec, Bayer Pharmaceuticals Corp., Teva Neuroscience, and Actellion. Dr. Kostic has received personal compensation for activities with Boehringer Ingelheim Pharmaceuticals Inc., Pfizer Inc., Solvay Pharmaceuticals, Novartis, Abbott, Hemofarm Stada, and GlaxoSmithKline Inc. Dr. Kostic has received research support from Hemofarm Stada, Lundbeck, Novartis, GlaxoSmithKline Inc., Pharma Swiss, Boehringer Ingelheim Pharmaceuticals Inc., Bayer Pharmaceuticals Corp., and Pfizer Inc. Dr. Filippi has received personal compensation for activities with Teva Neuroscience and Genmab AS as a member of scientific advisory boards, and Bayer Pharmaceuticals Corp. as a consultant. Dr. Filippi has received research support from Bayer Schering, Biogen Idec, Genmab AS, Merck Serono, Teva Neuroscience, the Italian Ministry of Health, and the Fondazione Italiana Sclerosi Mult.