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Troubles du contrôle des impulsions au cours de la maladie de Parkinson, étude électro-encéphalographique de l’intégration de la récompense et modifications de la connectivité fonctionnelle cérébrale de repos en imagerie par résonance magnétique

Abstract : BackgroundIn Parkinson’s disease, dopamine agonists are associated with an increased risk of impulse control disorders (ICD). Their occurrence is supposed to be related with a deregulation of the dopaminergic meso-limbic pathway, involved in the processing of the consequences of previous action to adapt future behaviors. Dopamine agonists, through a tonic stimulation of the dopamine receptors would lead to an overestimation of the positive consequences of actions, and therefore, continuation of a harmful behavior.Method:We investigated (i) the resting-state striato-cortical functional connectivity using functional MRI, and (ii) electro-encephalographic (EEG) markers of feedback processing during a gambling task : the feedback related negativity (FRN), the feedback related positivity, (FRP), and the theta band oscillations (4-7 Hz) in 20 Parkinson’s disease patients with an active ICD, 19 Parkinson’s disease patients without ICD, and 19 healthy subjects.Functional MRI: The ventral striatum, dorsal caudate, and anterior and posterior putamen were semi-automatically segmented. For each region of interest, a seed-based connectivity analysis was performed on preprocessed fMRI data mapped on the ipsilateral cortical surface.Neurophysiological approach: The subjects underwent an EEG while performing a gambling task. The EEG was averaged for each condition and each subject. The FRP amplitude was measured in Cz, and the FRN amplitude was measured in Fz on the difference wave between the potential evoked by losses and by gains. The power spectra were computed by using a sinusoidal Morlet wavelet transform and averaged by condition. The maximum power in the theta frequency band was computed for each participant and each condition.Results:Cortico-striatal connectivity analysis: The presence of an ICD in patients with PD was associated with functional disconnection between the left anterior putamen and both the left inferior temporal and anterior cingulate gyrus. ICD patients also displayed a trend toward a functional disconnection between (i) the left anterior putamen and the inferior frontal gyrus, (ii) the posterior putamen and the inferior temporal gyrus, superior frontal gyrus, posterior cingulate, and medial frontal gyrus on the left, as well as the medial frontal gyrus, middle frontal gyrus, and cingulate gyrus on the right, (iii) the dorsal caudate and the gyrus rectus and orbitofrontal cortex, and the middle frontal and inferior temporal gyrus on the left.Evoked potentials: In Parkinson’s disease patients without ICD and healthy controls, the FRP was greater after gains that after losses following a non-risky choice. There was no difference in FRP amplitude after losses and gains in Parkinson’s disease patients with ICD.Time-frequency analysis: At Cz, positive outcomes (gains) were associated with greater theta power than negative outcomes (losses) in Parkinson’s disease patients without ICD and in healthy controls, but not in Parkinson’s disease patients with ICD. There was an increase in theta power after unexpectedly high outcomes, at Fz in healthy controls and in FCz in Parkinson’s disease patients with ICD, whereas theta power was not modulated by the magnitude of the outcome in PD patients without ICDs.Conclusions:Parkinson’s disease patients with ICD have an alteration in EEG markers of reward in line with an altered discrimination of gains and losses and a greater sensitivity to unexpectedly high outcomes, supposed to lead to a significant activation in the dopaminergic meso-limbic pathways. These findings are in line with a dysfunction in reward processing in ICD in Parkinson’s disease. This dysfunction is associated, at rest, with an alteration in striato-cortical connectivity that goes beyond a pure dopaminergic meso-limbic dysfunction.
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Nicolas Carrière. Troubles du contrôle des impulsions au cours de la maladie de Parkinson, étude électro-encéphalographique de l’intégration de la récompense et modifications de la connectivité fonctionnelle cérébrale de repos en imagerie par résonance magnétique. Médecine humaine et pathologie. Université du Droit et de la Santé - Lille II, 2015. Français. ⟨NNT : 2015LIL2S060⟩. ⟨tel-01413965⟩

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