Default network activity is a sensitive and specific biomarker of memory in multiple sclerosis.
ABSTRACT Background: Patients with multiple sclerosis (MS) suffer memory impairment but the link between MS-related neuroanatomical changes (brain atrophy) and memory is relatively weak.Objective: The purpose of this study was to use functional magnetic resonance imaging (fMRI) to investigate task-induced default network (DN) deactivation as a neurophysiologic biomarker of memory functioning in MS.Methods: Twenty-eight MS patients underwent high-resolution MRIs to measure brain atrophy (third ventricle width, cerebral gray matter, cerebral white matter, parenchymal fraction, and thalamic, caudate, hippocampal, and amygdala volumes), and fMRI blood oxygen level dependent (BOLD) signal to measure DN deactivation during sustained attention relative to rest. Neuropsychological assessment of episodic memory was performed on a separate day. We used hierarchical regression to predict memory, with age, education, and depression in step one, brain atrophy within step two, DN activity within step three, and the interaction between brain atrophy and DN activity in step four.Results: Brain atrophy predicted worse memory but DN activity independently predicted memory over-and-above measurements of brain atrophy (R(2)=0.108), with greater DN activity (lesser deactivation) linked to better memory. A significant brain atrophy by DN activity interaction indicated a stronger relationship between memory and DN activity among patients with more advanced disease, at which point higher DN activity protects patients from disease/atrophy-related memory impairment. To establish specificity, we showed no relationship between DN activity and non-memory cognition, and no relationship between non-DN brain activity and memory.Conclusion: Maintenance of DN activity during sustained attention was supported as a sensitive and specific neurophysiologic biomarker of episodic memory functioning in MS, even when controlling for neuroanatomical changes (brain atrophy).