The neural basis of behavioral recovery of chronic visuo-spatial neglect using repetitive transcranial magnetic stimulation

High frequency repetitive Transcranial Magnetic Stimulation (rTMS) has been used clinically on perilesional cortex to attenuate the neurological consequences of cerebral injuries. Presently the clinical benefits of rTMS remain controversial due to the high level of inter-individual variability in response to treatment. We explored the behavioral efficacy of multisession rTMS and studied the structural and metabolic characteristics underlying the recovery of visuo-spatial functions after unilateral parietal injury.;A group of adult cats (n=12) underwent focal lesions in a region of the posterior parietal cortex (pMS, posterior middle suprasylvian area ) leading to contralesional visuo-spatial deficits. Two and a half months post-injury, cats were treated with 7 consecutive rounds of 10 daily session of high frequency rTMS applied on an intact perilesional area (aMS, anterior middle suprasylvian area). We characterized two populations of animals: a group of 'Responders' (n=6) displaying significant visual detection improvements in contralesional hemispace and a group of 'Non-responders' (n=6) that did not show significant improvements and suffered unexpected decreases in ipsilesional performance.;Detailed lesion analyses revealed no differences between the two groups neither in the amount of total spared cortex nor in the level of residual metabolic activity within areas of perilesional tissue. Additionally, we used 14C-2-deoxyglucose (2DG) to measure the metabolic impact of the aMS area on discrete nodes of the visuo-spatial network. When compared individually, none of the 60 regions proved to have significantly higher metabolic uptake in either group. Interestingly however, a cross-correlation analysis of metabolic activity throughout all sampled cortical and subcortical areas revealed that 'Responders' displayed a more metabolically cross-correlated visuo-spatial network than 'Non-responders'. Furthermore, we found the aMS cortex in the 'Non-responders' group to hold no significant cross-correlations within the visuo-spatial network, indicating that the site of rTMS stimulation held no functional relationship with network regions.;We conclude that multisession perilesional rTMS has the potential to induce behavioral ameliorations in chronic brain injury but the ability to consistently induce adaptive outcomes remains highly variable across animals. In addition, functional correlations indicate that rTMS-mediated recovery is dependent on the stimulated aMS cortex and its metabolic coupling with other nodes within visuo-spatial networks.