Memory impairment is commonly found in multiple sclerosis (MS), presented in between 40 to 75% of patients. It is accepted that hippocampus plays a critical role in memory function therefore studying this brain structure is crucial to understand the nature of memory deficits. However, there is a lack of knowledge regarding how functional connectivity changes in memory-related brain regions, such as the hippocampus, exist between MS subtypes.
To investigate hippocampal resting-state functional connectivity changes between MS subtypes and healthy controls, and associations with the presence of total white matter (WM) lesions.
30 healthy controls and 78 MS patients (34 relapsing-remitting (RRMS)), 24 primary or secondary progressive subtypes (PMS) and 20 clinical or radiological isolated syndrome (CIS/RIS)) underwent a magnetic resonance imaging session. Univariate ANOVA models in SPM12 were used to assess whole-brain differences in the seed-based functional connectivity (FC) of the bilateral hippocampus, between controls and MS subtypes. Regression models then assessed whether the FC strength in the identified hippocampal networks showed a significant association with total WM lesions.
Mean total WM lesion volume was different among MS subtypes (F=18.493; p<0.001), with PMS showing the highest lesioned volume (16.32±14.09ml), followed by RRMS (8.93±9.46ml) and CIS/RIS (2.07±2.67ml). Compared to controls, both the PMS and RRMS showed lower FC in the hippocampi-right middle frontal gyrus network, while RRMS additionally showed lower FC with the rostral anterior cingulate cortex. Conversely, CIS/RIS showed higher FC in the hippocampi-right angular gyrus network. The lower FC in the hippocampi-right middle frontal gyrus network in PMS and RRMS was also significant compared with CIS/RIS, with PMS additionally showing lower FC in the hippocampi-dorsomedial frontal cortex. Finally, RRMS showed lower FC in the hippocampi-left insula network when directly compared to PMS. The strength of FC in the hippocampi-dorsomedial prefrontal cortex network was negatively associated with the total WM lesion volume (R2= 0.085, F= 6.76, p= 0.011) across the MS patients.
Hippocampal FC differences exist depending on MS subtypes, and the highest presence of total WM lesions impacts the FC with medial prefrontal cortex regions. Future studies are necessary to link such hippocampal changes with specific memory impairment.