Thalamic–hippocampal–prefrontal disruption in relapsing–remitting multiple sclerosis

Abstract

BackgroundCortical, thalamic and hippocampal gray matter atrophy in relapsing–remitting MS (RRMS) is associated cognitive deficits. However, the role of interconnecting white matter pathways including the fornix, cingulum, and uncinate fasciculus (UF) is less well studied.ObjectiveTo assess MS damage to a hippocampal–thalamic–prefrontal network and the relative contributions of its components to specific cognitive domains.MethodsWe calculated diffusion tensor fractional anisotropy (FA) in the fornix, cingulum and UF as well as thalamic and hippocampal volumes in 27 RRMS patients and 20 healthy controls. A neuropsychological battery was administered and 4 core tests known to be sensitive to MS changes were used to assess cognitive impairment. To determine the relationships between structure and cognition, all tests were grouped into 4 domains: attention/executive function, processing speed, verbal memory, and spatial memory. Univariate correlations with structural measures and depressive symptoms identified potential contributors to cognitive performance and subsequent linear regression determined their relative effects on performance in each domain. For significant predictors, we also explored the effects of laterality and axial versus radial diffusivity.ResultsRRMS patients had worse performance on the Symbol Digit Modalities Test, but no significant impairment in the 4 cognitive domains. RRMS had reduced mean FA of all 3 pathways and reduced thalamic and hippocampal volumes compared to controls. In RRMS we found that thalamic volume and BDI predicted attention/executive function, UF FA predicted processing speed, thalamic volume predicted verbal memory, and UF FA and BDI predicted spatial memory.ConclusionsHippocampal–thalamic–prefrontal disruption affects cognitive performance in early RRMS with mild to minimal cognitive impairment, confirming both white and gray matter involvement in MS and demonstrating utility in assessing functional networks to monitor cognition.

Multiple sclerosis and depressive manifestations: can diffusion tensor MR imaging help in the detection of microstructural white matter changes?

“…The damage induced by MS in the hippocampal-thalamic-prefrontal network and its contributions to depression and specific cognitive domains was assessed by Kern et al [26]. These authors found that compared to healthy controls, patients with RRMS had a reduced mean FA of the UF, fornix and cingulum which agreed with our findings.…”

“…The fornix has been associated with differences in MS on verbal memory tests, including CVLT-II [23,24] and BVRT [25]. A link between the FA of the fornix and verbal memory performance was identified in a previous study [26], but this relationship was not independent of thalamic volume. Additionally, the thalamic volume and FA of the fornix were strongly associated, which has been previously shown [25].…”

Neuroinflammatory component of gray matter pathology in multiple sclerosis

“…Increased TSPO levels in thalamus, hippocampus, and NAWM were associated with impaired SDMT function, a measure of information processing speed, which is frequently affected in MS and, thus, commonly evaluated in clinical setting. Diffusion imaging data highlighted that hippocampal-thalamic-prefrontal disruption affects SDMT performance in RRMS 47 . An association between depression and hippocampal neuroinflammation, as measured 18 F-PBR11, has been recently reported in RRMS 39 .…”

Pathology and MRI: exploring cognitive impairment in MS

“…113 A strong association of damage to strategically crucial deep gray matter nuclei such as thalamus or putamen with impaired cognitive processing has been demonstrated by multiple studies. 50,[114][115][116][117][118][119][120][121] Moreover, gray matter damage of the hippocampus which is especially relevant for memory performance has been revealed by various imaging techniques and was shown to be related to memory-related aspects of cognitive performance in MS.…”