Cognitive rehabilitation of working memory in juvenile multiple sclerosis-effects on cognitive functioning, functional MRI and network related connectivity

Purpose: To assess possible effects of working memory (WM) training on cognitive functionality, functional MRI and brain connectivity in patients with juvenile MS. Methods: Cognitive status, fMRI and inter-network connectivity were assessed in 5 cases with juvenile MS aged between 12 and 18 years. Afterwards they received a computerizedWMtraining for four weeks. Primary cognitive outcome measures were WM(visual and verbal) and alertness. Activation patterns related toWMwere assessed during fMRI using an N-Back task with increasing difficulty. Inter-network connectivity analyses were focused on fronto-parietal (left and right), default-mode (dorsal and ventral) and the anterior salience network. Cognitive functioning, fMRI and inter-network connectivity were reassessed directly after the training and again nine months following training. Results: Response to treatment was seen in two patients. These patients showed increased performance in WM and alertness after the training. These behavioural changes were accompanied by increased WM network activation and systematic changes in inter-network connectivity. The remaining participants were non-responders to treatment. Effects on cognitive performance were maintained up to nine months after training, whereas effects observed by fMRI disappeared. Conclusions: Responders revealed training effects on all applied outcome measures. Disease activity and general intelligence may be factors associated with response to treatment.