RAD51 deficiency disrupts the corticospinal lateralization of motor control.
Mirror movements are involuntary symmetrical movements of one side of the body that mirror voluntary movements of the other side. Congenital mirror movement disorder is a rare condition characterized by mirror movements that persist throughout adulthood in subjects with no other clinical abnormalities. The affected individuals have mirror movements predominating in the muscles that control the fingers and are unable to perform purely unimanual movements. Congenital mirror movement disorder thus provides a unique paradigm for studying the lateralization of motor control. We conducted a multimodal, controlled study of patients with congenital mirror movements associated with RAD51 haploinsufficiency (n = 7, mean age 33.3 ± 16.8 years) by comparison with age- and gender-matched healthy volunteers (n = 14, mean age 33.9 ± 16.1 years). We showed that patients with congenital mirror movements induced by RAD51 deficiency had: (i) an abnormal decussation of the corticospinal tract; (ii) abnormal interhemispheric inhibition and bilateral cortical activation of primary motor areas during intended unimanual movements; and (iii) an abnormal involvement of the supplementary motor area during both unimanual and bimanual movements. The lateralization of motor control thus requires a fine interplay between interhemispheric communication and corticospinal wiring. This fine interplay determines: (i) the delivery of appropriate motor plans from the supplementary motor area to the primary motor cortex; (ii) the lateralized activation of the primary motor cortex; and (iii) the unilateral transmission of the motor command to the limb involved in the intended movement. Our results also unveil an unexpected function of RAD51 in corticospinal development of the motor system.
1 Centre de Neuro-imagerie de Recherche (CENIR) de l'Institut du Cerveau et de la Moëlle Epiniere (ICM), Paris, France.
Cécile
C
Gallea
Traian
T
Popa
Cécile
C
Hubsch
Romain
R
Valabregue
Vanessa
V
Brochard
Prantik
P
Kundu
Benoît
B
Schmitt
Eric
E
Bardinet
Eric
E
Bertasi
Constance
C
Flamand-Roze
Nicolas
N
Alexandre
Christine
C
Delmaire
Aurélie
A
Méneret
Christel
C
Depienne
Cyril
C
Poupon
Lucie
L
Hertz-Pannier
Massimo
M
Cincotta
Marie
M
Vidailhet
Stéphane
S
Lehericy
Sabine
S
Meunier
Emmanuel
E
Roze
D000293:Adolescent; D000328:Adult; D020820:Dyskinesias / Q000151:congenital / Q000235:genetics / Q000503:physiopathology*; D004525:Efferent Pathways / Q000503:physiopathology*; D019054:Evoked Potentials, Motor; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006225:Hand / Q000503:physiopathology*; D057895:Haploinsufficiency / Q000235:genetics; D006801:Humans; D015225:Magnetoencephalography; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology*; D064847:Multimodal Imaging; D051135:Rad51 Recombinase / Q000235:genetics*; D050781:Transcranial Magnetic Stimulation; D055815:Young Adult
C495153:RAD51 protein, human; D051135:Rad51 Recombinase
corticospinal pathways; genetics; motor disorders; movement coordination; transcallosal inhibition