Sleep apnea: Altered brain connectivity underlying a working-memory challenge

Abstract

Obstructive sleep apnea (OSA) is characterized by the frequent presence of neuro-cognitive impairment. Recent studies associate cognitive dysfunction with altered resting-state brain connectivity between key nodes of the executive and default-mode networks, two anti-correlated functional networks whose strength of activation increases or decreases with cognitive activity, respectively. To date no study has investigated a relationship between cognitive impairment in OSA and brain connectivity during an active working-memory challenge. We thus investigated the effect of OSA on working-memory performance and underlying brain connectivity.OSA patients and matched healthy controls underwent functional magnetic resonance imaging (fMRI) scanning while performing a 2-back working-memory task. Standard fMRI analyses highlighted the brain regions activated at increasing levels of working-memory load, which were used as seeds in connectivity analyses. The latter were based on a multiregional Psycho-Physiological-Interaction (PPI) approach, to unveil group differences in effective connectivity underlying working-memory performance.Compared with controls, in OSA patients normal working-memory performance reflected in: a) reduced interhemispheric effective connectivity between the frontal “executive” nodes of the working-memory network, and b) increased right-hemispheric connectivity among regions mediating the “salience-based” switch from the default resting-state mode to the effortful cognitive activity associated with the executive network. The strength of such connections was correlated, at increasing task-demands, with executive (Stroop test) and memory (Digit Span test) performance in neuro-cognitive evaluations.The analysis of effective connectivity changes during a working-memory challenge provides a complementary window, compared with resting-state studies, on the mechanisms supporting preserved performance despite functional and structural brain modifications in OSA. Keywords: Obstructive sleep apnea, Executive functions, Working-memory, fMRI, Cognitive disorders, Brain connectivity