Neural function in DCC mutation carriers with and without mirror movements

Area of Science:

• Neuroscience
• Genetics
• Human Brain Imaging

Background:

• Mutations in the Deleted in Colorectal Carcinoma (DCC) gene, an axon guidance molecule receptor, offer insights into neural connectivity.
• Mirror movements, involuntary contralateral responses mirroring voluntary actions, are a key focus for understanding neural circuit function.

Purpose of the Study:

• To investigate the neural mechanisms underlying mirror movements in humans.
• To examine the effects of haploinsufficient DCC (DCC+/-) mutations on neural connectivity and motor control.
• To correlate DCC gene expression, corticospinal tract function, and brain activity with the presence of mirror movements.

Main Methods:

• Recruited 52 participants: DCC+/- mutation carriers with (n=13) and without (n=7) mirror movements, mutation-negative relatives (n=13), and healthy volunteers (n=19).
• Employed a multimodal approach including quantitative real-time polymerase chain reaction (PCR) for gene expression, transcranial magnetic stimulation (TMS) for corticospinal excitability, functional magnetic resonance imaging (fMRI) for brain activity, and white matter integrity assessment.

Main Results:

• Mirror movements were associated with reduced DCC mRNA expression and increased ipsilateral motor evoked potentials (MEPs) via TMS.
• fMRI revealed increased activity in motor cortex (M1) and cerebellum in individuals with mirror movements.
• Reduced interhemispheric inhibition and decreased functional connectivity/white matter integrity were observed in DCC+/- mutation carriers, irrespective of mirror movements.

Conclusions:

• Connectivity abnormalities are present in DCC mutation carriers, with corticospinal effects and reduced DCC mRNA specifically linked to the mirror movement phenotype.
• The study highlights the role of DCC in neural development and motor control, differentiating between mutation effects and phenotype-specific alterations.