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Neural function in DCC mutation carriers with and without mirror movements.

Daniel E Vosberg1,2, Vincent Beaulé3, Angélica Torres-Berrío2,4

  • 1Department of Psychiatry, McGill University, Montreal, Quebec, Canada.

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Summary
This summary is machine-generated.

Mutations in the DCC gene are linked to mirror movements, affecting neural connectivity. These movements correlate with reduced DCC mRNA and altered brain activity, impacting motor control.

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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.