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Neural function in DCC mutation carriers with and without mirror movements
Author(s) -
Vosberg Daniel E.,
Beaulé Vincent,
TorresBerrío Angélica,
Cooke Danielle,
Chalupa Amanda,
Jaworska Natalia,
Cox Sylvia M. L.,
Larcher Kevin,
Zhang Yu,
Allard Dominique,
Durand France,
Dagher Alain,
Benkelfat Chawki,
Srour Myriam,
Tampieri Donatella,
La Piana Roberta,
Joober Ridha,
Lepore Franco,
Rouleau Guy,
PascualLeone Alvaro,
Fox Michael D.,
Flores Cecilia,
Leyton Marco,
Théoret Hugo
Publication year - 2019
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25418
Subject(s) - functional magnetic resonance imaging , neuroscience , mirroring , mutation , psychology , mirror neuron , white matter , transcranial magnetic stimulation , cerebellum , biology , magnetic resonance imaging , genetics , medicine , communication , stimulation , gene , radiology
Objective Recently identified mutations of the axon guidance molecule receptor gene, DCC, present an opportunity to investigate, in living human brain, mechanisms affecting neural connectivity and the basis of mirror movements, involuntary contralateral responses that mirror voluntary unilateral actions. We hypothesized that haploinsufficient DCC +/− mutation carriers with mirror movements would exhibit decreased DCC mRNA expression, a functional ipsilateral corticospinal tract, greater “mirroring” motor representations, and reduced interhemispheric inhibition. DCC +/− mutation carriers without mirror movements might exhibit some of these features. Methods The participants (n = 52) included 13 DCC +/− mutation carriers with mirror movements, 7 DCC +/− mutation carriers without mirror movements, 13 relatives without the mutation or mirror movements, and 19 unrelated healthy volunteers. The multimodal approach comprised quantitative real time polymerase chain reaction, transcranial magnetic stimulation (TMS), functional magnetic resonance imaging (fMRI) under resting and task conditions, and measures of white matter integrity. Results Mirror movements were associated with reduced DCC mRNA expression, increased ipsilateral TMS‐induced motor evoked potentials, increased fMRI responses in the mirroring M1 and cerebellum, and markedly reduced interhemispheric inhibition. The DCC +/− mutation, irrespective of mirror movements, was associated with reduced functional connectivity and white matter integrity. Interpretation Diverse connectivity abnormalities were identified in mutation carriers with and without mirror movements, but corticospinal effects and decreased peripheral DCC mRNA appeared driven by the mirror movement phenotype. ANN NEUROL 2019;85:433–442.