Ventral tegmental area dysfunction affects decision-making in patients with myotonic dystrophy type-1.


Journal

Cortex; a journal devoted to the study of the nervous system and behavior
ISSN: 1973-8102
Titre abrégé: Cortex
Pays: Italy
ID NLM: 0100725

Informations de publication

Date de publication:
07 2020
Historique:
received: 19 07 2019
revised: 16 12 2019
accepted: 05 03 2020
pubmed: 4 5 2020
medline: 22 6 2021
entrez: 4 5 2020
Statut: ppublish

Résumé

The clinical manifestations of Myotonic Dystrophy type-1 (DM1) are associated with a complex mixture of multisystem features including cognitive dysfunctions that strongly impact on patients' social and occupational functioning. Decision making, a function controlled by dopaminergic circuitry, is critical for succeeding in one's social and professional life. We tested here the hypothesis that altered connectivity of the ventral tegmental area (VTA), one of the major sources of diffuse dopaminergic projections in the brain, might account for some higher-level dysfunctions observed in patients with DM1. In this case-control study, we recruited 31 patients with DM1 and 26 healthy controls who underwent the IOWA Gambling task and resting-state functional MRI (RS-fMRI) at 3T. Functional connectivity of the VTA was assessed using RS-fMRI. VTA connectivity was compared between 25 DM1 patients and all the controls, and the presence of associations between VTA connectivity and IOWA Gambling task performance was also investigated. DM1 patients performed significantly worse than controls at the IOWA Gambling task. A significant increase of functional connectivity was observed between VTA and the left supramarginal and superior temporal gyri in DM1 patients. Patients' IOWA Gambling task net-scores were strictly associated with VTA-driven functional connectivity in the bilateral supplementary motor area and right precentral gyrus. This study demonstrates a prominent deficit of decision-making in patients with DM1. It might be related to increased connectivity between VTA and brain areas critically involved in the reward/punishment system and social cognition. These findings indicate that dopaminergic function is a potential target for pharmacological and non-pharmacological interventions in DM1.

Identifiants

pubmed: 32361267
pii: S0010-9452(20)30129-5
doi: 10.1016/j.cortex.2020.03.022
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

192-202

Informations de copyright

Copyright © 2020 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The Authors report no competing interests.

Auteurs

Laura Serra (L)

Neuroimaging Laboratory, IRCCS Fondazione Santa Lucia, Rome, Italy.

Marta Scocchia (M)

Neuroimaging Laboratory, IRCCS Fondazione Santa Lucia, Rome, Italy.

Giovanni Meola (G)

Department of Neurorehabilitation Sciences, Casa di Cura Policlinico, Milano, Italy.

Marcello D'Amelio (M)

Laboratory Molecular Neurosciences, IRCCS Fondazione Santa Lucia, Rome, Italy; Unit of Molecular Neurosciences, Department of Medicine, University Campus-Biomedico, Rome, Italy.

Michela Bruschini (M)

Neuroimaging Laboratory, IRCCS Fondazione Santa Lucia, Rome, Italy.

Gabriella Silvestri (G)

Area of Neuroscience, Institute of Neurology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Institute of Neurology, Catholic University of the Sacred Heart, Rome, Italy.

Antonio Petrucci (A)

UOC Neurologia e Neurofisiopatologia, AO San Camillo Forlanini, Rome, Italy.

Carlotta Di Domenico (C)

Neuroimaging Laboratory, IRCCS Fondazione Santa Lucia, Rome, Italy.

Carlo Caltagirone (C)

Department of Clinical and Behavioural Neurology, IRCCS Fondazione Santa Lucia, Rome Italy.

Giacomo Koch (G)

Department of Clinical and Behavioural Neurology, IRCCS Fondazione Santa Lucia, Rome Italy.

Mara Cercignani (M)

Neuroimaging Laboratory, IRCCS Fondazione Santa Lucia, Rome, Italy; Department of Neuroscience, Brighton & Sussex Medical School, University of Sussex, Brighton, East Sussex, United Kingdom.

Laura Petrosini (L)

Experimental and Behavioural Laboratory IRCCS Fondazione Santa Lucia, Rome, Italy.

Marco Bozzali (M)

Neuroimaging Laboratory, IRCCS Fondazione Santa Lucia, Rome, Italy; Department of Neuroscience, Brighton & Sussex Medical School, University of Sussex, Brighton, East Sussex, United Kingdom. Electronic address: m.bozzali@bsms.ac.uk.

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Classifications MeSH