Time-Varying Functional Connectivity of the Hippocampus Is Associated With Cognitive Performance in Multiple Sclerosis Patients
Monica Margoni1, Paola Valsasina1, Paolo Preziosa2, Olga Marchesi1, Carmen Vizzino1, Damiano Mistri1, Massimo Filippi3, Maria Rocca4
1Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 2Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute; Neurology Unit, IRCCS San Raffaele Scientific Institute; Vita-Salute San Raffaele University, 3Neuroimaging Research Unit, Division of Neuroscience, Neurology Unit, Neurorehabilitation Unit, and Neurophysiology Service, 4Neuroimaging Research Unit, Division of Neuroscience, and Neurology Unit, IRCCS San Raffaele Scientific Institute; Vita-Salute San Raffaele University
Objective:
To explore hippocampal static (sFC) and time-varying functional connectivity (TVFC) and assess their association with cognition in multiple sclerosis (MS).
Background:
The hippocampus has a key role in cognition. Hippocampal TVFC in MS needs to be further explored.
Design/Methods:
3T structural and resting-state (RS) functional MRI scans were acquired from 108 MS patients and 63 healthy controls (HC). Subjects underwent neuropsychological evaluation. Sliding-window correlation analysis using the left (L) and right (R) hippocampus as seed regions assessed TVFC, quantified by the standard deviation of connectivity across windows. Mean connectivity indicated sFC.
Results:
MS patients had decreased sFC vs HC between L hippocampus and temporo-parietal regions, and increased sFC between L and R hippocampus and thalamus, precuneus and superior frontal regions. TVFC was decreased in MS patients between L hippocampus and temporo-parietal regions. Conversely, TVFC was increased in MS patients between L and R hippocampus and L pre- and postcentral gyri, cuneus, orbitofrontal cortex and inferior temporal gyrus (ITG). In MS patients, better global cognition correlated with higher TVFC between L hippocampus and L pre- and postcentral gyri (r=0.21-0.28; p=0.04-0.006). Better verbal memory correlated with higher TVFC between L hippocampus and L precentral gyrus (r=0.21, p=0.03), and better visuospatial memory correlated with higher TVFC between L and R hippocampus and L cuneus, pre- and postcentral gyri and ITG (r=0.19-0.23, p=0.02-0.04). Better information processing speed correlated with higher TVFC between L hippocampus and L postcentral gyrus (r=0.21, p=0.03) and with higher sFC between R hippocampus and L superior frontal cortex (SFC) (r=0.21, p=0.03). Finally, better attention scores correlated with higher TVFC between L hippocampus and L temporal cortex (r=0.24, p=0.01) and with higher sFC between R hippocampus and L SFC (r=0.20, p=0.05).
Conclusions:
Increased hippocampal connectivity contributed to explain better cognitive performances in MS, with a peculiar association between higher hippocampal TVFC and better memory scores.