Hippocampal structural and functional integrity in multiple sclerosis patients with or without memory impairment: a multimodal neuroimaging study

Abstract

The increasing evidence for a pure amnestic-like profile in multiple sclerosis (MS) introduces the role of hippocampal formation in MS episodic memory function. The aim of the present study was to investigate structural and functional hippocampal changes in mildly-disabled MS patients with and without memory impairment. Thirty-one MS patients with or without memory impairment and 16 healthy controls (HC) underwent MRI in a 3.0 T MRI scanner. Patients were categorized as memory preserved (MP) and memory impaired (MI) based on verbal and visual memory scores extracted from the Brief Repeatable Neuropsychological Battery. The acquisition protocol included high-resolution 3D-T1-weighted, diffusion weighted imaging and echo-planar imaging sequences for the analysis of hippocampal gray matter (GM) density, perforant pathway area (PPA) tractography, and hippocampal functional connectivity (FC), respectively. Compared to HC, we found decreased left and bilateral hippocampal GM density in MP and MI patients, respectively, decreased fractional anisotropy and increased radial diffusivity on left PPA in MI patients, and reduced FC in MI between left hippocampus and left superior frontal gyrus, precuneus/posterior cingulated cortex and lateral occipital gyrus/angular gyrus. The only differences between MP and MI were found in FC. Specifically, MP patients showed FC changes between left hippocampus and right temporo-occipital fusiform/lingual gyrus (increased FC) as well as supramarginal gyrus (decreased FC). In conclusion, we highlight the early detection of structural hippocampal changes in MS without neuropsychologically-detected memory deficits and decreased hippocampal FC in MS patients with impaired memory performance, when both GM density and PPA integrity are affected.

Task- and resting-state fMRI studies in multiple sclerosis: From regions to systems and time-varying analysis. Current status and future perspective

“…CI variations in people with similar severities of structural damage could be related to the severity of increased RS FC Cocozza et al, 2018 29 people with progressive MS 22 HC Progressive MS showed reduced cerebellar RS FC for Crus II, but increased cerebellar FC for Lobule VIIb, which was related to memory impairment Fuchs et al, 2019 74 people with MS 29 HC Higher cognitive reserve was related to normal RS FC and cognition. This effect attenuated the impact of structural disconnection on CI Karavasilis et al, 2019 31 people with MS 16 HC Memory impairment was related to reduced hippocampal RS FC Lin et al, 2019 64 people with MS 26 HC Thalamic subnuclei showed different patterns of RS FC alterations, which were related to CI Carotenuto et al, 2020 19 people with MS 24 HC RS FC of specific neurotransmitter networks were related to CI Has Silemek et al, 2020 33 people with MS 29 HC Decreased structural FC was related to increased RS FC and worse cognitive performance. Effects were mostly seen in the DMN Meijer et al, 2020 133 people with MS 48 HC In people with MS and a long disease duration, structural connectivity loss was worst in long-distance connections, and was related to a more abnormal RS FC.…”

Structural and Functional Connectivity Substrates of Cognitive Impairment in Multiple Sclerosis

“…Hippocampus is the key region of memory in the human brain ( 107 , 108 ). In CIS and RRMS patients, a decrease in SC, expressed by reduced FA and increased axial diffusivity, along perforant pathways, which connect entorhinal cortex to hippocampus, was found in those patients with memory impairment ( 109 ). In another study on RRMS patients assessing tractography-derived hippocampal memory network, worse memory performance was associated with reduction in various SC measures [network efficiency, right hippocampus nodal strength, streamline count, and communicability (i.e., efficiency of the information spread) across network] at the level of the medial temporal lobe, thalamus, insula, and occipital cortex ( 110 ).…”

“…Altered hippocampal FC is also important for long-term memory deficit in MS. Indeed, RRMS patients with impairment in this cognitive domain showed, compared to healthy controls, decreased FC on the left hemisphere between hippocampus and various cortical regions (superior frontal gyrus, precuneus, posterior cingulate cortex lateral occipital gyrus, angular gyrus) ( 109 ) and, compared to memory-preserved MS patients, both increased FC between left hippocampus and right supramarginal gyrus and decreased FC between left hippocampus and right temporo-occipital fusiform/lingual gyrus ( 109 ). In another study on RR and SPMS, increased FC in the right posterior hippocampus turned out to be the best correlation of long-term memory impairment ( 111 ).…”

Cognitive Impairment and Brain Reorganization in MS: Underlying Mechanisms and the Role of Neurorehabilitation

“…The importance of structural and functional integrity of the hippocampus was highlighted by Sumowski et al (49), who investigated the neural basis of reserve against memory decline in PwMS, linking greater intellectual enrichment and better memory to larger hippocampal volume and supporting the argument that larger hippocampal volume is a key component of reserve against memory decline in MS. The hippocampus of PwMS usually has a high lesion load, demyelination, neuronal damage, synaptic dysfunction, neurotransmitter level reduction, and disconnection, linking hippocampus pathology not only to CI but also to the reorganization capacity of broader networks (48,(50)(51)(52)(53)(54)(55). A biomarker indicating deep GM structures, especially thalamus and hippocampus volume and status, could ideally give provision of the cognitive status, insights for reorganization dynamics, and cues for therapeutic decisions.…”