Slowness in Movement Initiation is Associated with Proactive Inhibitory Network Dysfunction in Parkinson’s Disease

Article type: Research Article

Authors: Criaud, Marion^{a; b; c; d; e; f} | Poisson, Alice^{a; b; c; g} | Thobois, Stéphane^{a; b; c; g} | Metereau, Elise^{a; b; c} | Redouté, Jérôme^h | Ibarrola, Danièle^h | Baraduc, Pierre^{a; b; c} | Broussolle, Emmanuel^{a; b; c; g} | Strafella, Antonio P.^{d; e; f} | Ballanger, Bénédicte^{a; b; c; i; j; *; 1} | Boulinguez, Philippe^{a; b; c; *}

Affiliations: [a] Université de Lyon,, Lyon, France | [b] Université Lyon I, Villeurbanne, France | [c] Centre de Neuroscience Cognitive, Bron, France | [d] Morton and Gloria Shulman Movement Disorder Unit & E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario, Canada | [e] Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada | [f] Division of Brain, Imaging and Behaviour –Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto, Ontario, Canada | [g] Hospices civils de Lyon, hôpital neurologique Pierre Wertheimer, Bron, France | [h] CERMEP-Imagerie du Vivant, Lyon, France | [i] INSERM, U1028, Lyon Neuroscience Research Center, Neuroplasticity and Neuropathology of Olfactory Perception Team, Lyon, France | [j] CNRS, UMR5292, Lyon Neuroscience Research Center, Neuroplasticity and Neuropathology of Olfactory Perception Team, Lyon, France

Correspondence: [*] Correspondence to: Bénédicte Ballanger, Centre de Recherche en Neurosciences de Lyon Inserm U1028 - CNRS UMR5292, Equipe Neuroplasticité et neuropathologie de la perception olfactive, 50 avenue Tony Garnier 69366 Lyon Cedex 07, France. Tel.: +33 04 37 28 74 97; E-mail: [email protected].

Note: [1] Co-last authors

Abstract: Background: Impairment in initiating movements in PD might be related to executive dysfunction associated with abnormal proactive inhibitory control, a pivotal mechanism consisting in gating movement initiation in uncertain contexts. Objective: Testing this hypothesis on the basis of direct neural-based evidence. Methods: Twelve PD patients on antiparkinsonian medication and fifteen matched healthy controls performed a simple reaction time task during event-related functional MRI scanning. Results: For all subjects, the level of activation of SMA was found to predict RT on a trial-by-trial basis. The increase in movement initiation latency observed in PD patients with regard to controls was associated with pre-stimulus BOLD increases within several nodes of the proactive inhibitory network (caudate nucleus, precuneus, thalamus). Conclusions: These results provide physiological data consistent with impaired control of proactive inhibition over motor initiation in PD. Patients would be locked into a mode of control maintaining anticipated inhibition over willed movements even when the situation does not require action restraint. The functional and neurochemical bases of brain activity associated with executive settings need to be addressed thoroughly in future studies to better understand disabling symptoms that have few therapeutic options like akinesia.

Keywords: Response inhibition, fMRI, proactive control, reaction time, Parkinson’s disease

DOI: 10.3233/JPD-150750

Journal: Journal of Parkinson's Disease, vol. 6, no. 2, pp. 433-440, 2016