Default mode network changes in multiple sclerosis: a link between depression and cognitive impairment?

Background and purpose In multiple sclerosis ( MS ), depression is a common disorder whose pathophysiology is still debated. To gain insights into the pathophysiology of depression in MS , resting‐state ( RS ) functional connectivity ( FC ) changes of the default mode network ( DMN ), salience network ( SN ) and executive control network ( ECN ) were assessed in a group of depressed MS (D‐ MS ) patients and in appropriately matched control groups. Methods Sixteen D‐ MS patients, 17 non‐depressed MS ( ND ‐ MS ) patients, 17 non‐depressed healthy controls and 15 depressed subjects (D‐S), age, sex and education matched, cognitively preserved and non‐fatigued, were enrolled. All participants underwent a neuropsychological evaluation and RS functional magnetic resonance imaging study. Results Comparing D‐ MS patients with D‐S, within the DMN , a significant RS ‐ FC suppression was found in the posterior cingulate cortex ( PCC ); comparing D‐ MS with ND ‐ MS, FC was significantly increased in the anterior cingulate cortex and significantly reduced in the PCC . Within the SN increased FC in the right supramarginal gyrus and right middle frontal gyrus was found in D‐ MS patients compared to D‐S and to ND ‐ MS ; within the ECN increased FC in the right inferior parietal cortex was found in D‐ MS patients compared to ND ‐ MS patients. Conclusions In cognitively preserved D‐ MS patients, FC derangement occurs in the SN , ECN and DMN . In the latter, changes occurring both in the anterior cingulate cortex and PCC suggest that depression in MS may be linked to MS itself and, in particular, to a peculiar pattern of network abnormalities favored by MS pathology through disconnection mechanisms. Reduced FC in the PCC , similar to MS patients with cognitive impairment, suggests a functional link between depression and cognitive impairment in MS .