Neurophysiology in the mirror: A tri-layer model of mirror movements informed by TMS evidence

  • Luca Sebastianelli
  • , Viviana Versace
  • , Davide Ferrazzoli
  • , Paola Ortelli
  • , Eugen Trinka
  • , Johann Sellner
  • , Raffaele Nardone

Research output: Journal article (peer-reviewed)Journal article

Abstract

OBJECTIVE: Mirror movements are involuntary, task-coupled contractions in contralateral homologous muscles during unilateral movement. While often described as a developmental remnant or rare clinical sign, mirror movements offer insight into the physiological mechanisms that underlie motor lateralization and interhemispheric balance. This review aimed to synthesize the available neurophysiological evidence-primarily from transcranial magnetic stimulation (TMS)-and propose a structured, mechanism-based framework for interpreting mirror movements across neurological conditions.

METHODS: A structured narrative review was conducted of studies published between 1966 and November 2025 using TMS in individuals with congenital, developmental, or acquired mirror movements. Studies using neuroimaging or peripheral electrophysiology were included selectively to support anatomical or functional interpretation of TMS findings. Data were organized into three mechanistic layers based on prevailing neurophysiological signatures rather than etiology alone.

RESULTS: Three non-mutually exclusive mechanisms were identified: (I) persistent fast-conducting ipsilateral corticospinal projections, primarily in congenital mirror movement syndromes and early brain injury; (II) deficient transcallosal inhibition, observed in conditions affecting interhemispheric balance such as amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, and callosal agenesis; and (III) bilateral overactivation of premotor and supplementary motor areas, especially under conditions of impaired motor program selection or increased task demands.

CONCLUSIONS: Mirror movements can be interpreted within a tri-layer model reflecting distinct disruptions in corticospinal connectivity, interhemispheric inhibition, and supraspinal motor control.

SIGNIFICANCE: This framework provides an integrative model for interpreting neurophysiological findings in mirror movements, offering insight into hierarchical motor control without implying specific diagnostic or therapeutic applications.

Original languageEnglish
Article number2111692
Pages (from-to)2111692
JournalClinical Neurophysiology
Volume184
Early online date03 Feb 2026
DOIs
Publication statusE-pub ahead of print - 03 Feb 2026

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