title: Differential patterns of interhemispheric functional disconnection in mild and advanced multiple sclerosis.
abstract: BACKGROUND
  Patients with multiple sclerosis may present altered patterns of connectivity between the two brain hemispheres. To date, only transcallosal connectivity between the two primary motor cortices (M1) has been investigated functionally in patients with multiple sclerosis.
  
  
  OBJECTIVE
  The aim of this study was to investigate whether connectivity between the dorsal premotor cortex and the contralateral M1 was altered in patients with multiple sclerosis, and to see whether clinical progression is accompanied by exacerbated dorsal premotor cortex-M1 disconnectivity.
  
  
  METHODS
  A twin-coil transcranial magnetic stimulation approach was used to investigate both excitatory and inhibitory interhemispheric connections between the left dorsal premotor cortex and the contralateral M1 in 18 multiple sclerosis patients without disability, in 18 multiple sclerosis patients with advanced disease and in 12 age-matched healthy subjects. To activate distinct inhibitory and facilitatory transcallosal pathways, the intensity of dorsal premotor cortex stimulation was adjusted to be either suprathreshold (110% of resting motor threshold) or subthreshold (80% of active motor threshold).
  
  
  RESULTS
  Our sample of patients with multiple sclerosis showed altered patterns of interhemispheric dorsal premotor cortex-M1 functional connectivity even in the absence of clinical deficits. Facilitatory connections originating from dorsal premotor cortex were reduced in multiple sclerosis patients with or without disability, while inhibitory dorsal premotor cortex-M1 connections were altered only in disabled patients.
  
  
  CONCLUSIONS
  The current study demonstrates that functional excitatory connectivity originating from non-primary motor areas is compromised in multiple sclerosis patients even in the absence of clinical disability. Clinical disease progression leads to an impairment of both excitatory and inhibitory transcallosal connections.
authors: Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, Rome, Italy.
authors: Claudia
authors: C
authors: Codecà
authors: Francesco
authors: F
authors: Mori
authors: Hajime
authors: H
authors: Kusayanagi
authors: Fabrizia
authors: F
authors: Monteleone
authors: Laura
authors: L
authors: Boffa
authors: Andrea
authors: A
authors: Paolillo
authors: Giorgio
authors: G
authors: Bernardi
authors: Giacomo
authors: G
authors: Koch
authors: Diego
authors: D
authors: Centonze
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D001931:Brain Mapping; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology / Q000503:physiopathology*; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology*; D050781:Transcranial Magnetic Stimulation