Cognitive compensation failure in multiple sclerosis

Compensatory processes involving the recruitment of additional cerebral areas can limit cognitive impairment caused by brain damage as revealed by fMRI. Multiple sclerosis (MS) is characterized by frequent cognitive deficiencies and diffuse brain damage. Understanding the missing or disturbed processes resulting in cognitive compensation failure is a major challenge in MS. Fifteen patients with relapsing-remitting (RR) MS and 20 healthy controls underwent an fMRI paradigm based on Go/No-go task with increasing complexity and neuropsychological and morphologic MRI examinations. To perform all the Go/No-go conditions, patients with RRMS exhibited supplementary cerebral recruitment compared to controls. For the most complex condition, patients presented both collapse of additional cerebral recruitment and significant lower cognitive performance compared to controls. In patients, both response times and diffuse tissue damage were correlated with medial frontal activations. Functional connectivity analysis demonstrated strong correlation between dorsolateral prefrontal cortex and medial frontal region activations. High cognitive demand causes beneficial cerebral recruitment failure, leading to cognitive impairment in patients with RRMS. Functional compensatory mechanisms preserving good cognitive performances operate by a new cerebral strategy involving medial prefrontal regions recruitment, instead of cerebellar regions seen in controls. This new recruitment is diffuse tissue damage-dependent. Missing cerebellar involvement argues for an inability to generate proficient cognitive automation processes in patients, directly leading to recruitment of high-level decision-making areas. Recurrent mobilization of cortical regions could explain the limiting effect of the cognitive load on the cognitive compensatory phenomena in patients with MS.