Pattern separation performance is decreased in patients with early multiple sclerosis

Abstract

Background: Hippocampal-dependent memory impairment is frequent and occurs

Regional hippocampal vulnerability in early multiple sclerosis: Dynamic pathological spreading from dentate gyrus to CA1

“…Although we have to take into account that the memory abilities of the PwCIS included in this study were not severely affected (regarding the median z ‐scores and the percentage of impaired patients), we postulate that CA4/dentate gyrus atrophy at the stage of CIS is “not enough” to explain the memory decline observed in “global” episodic memory tests such as the SRT or the BVMT‐R. Perhaps more specific tests such as the behavioral pattern separation task (Stark, Yassa, Lacy, & Stark, ) would have allowed us to pinpoint such a subtle memory decline related to CA4/dentate gyrus damage (Planche et al, ) and future studies should address this point. On the other hand, we found that CA1 atrophy explained part of the “global” episodic verbal memory decline one year after inclusion, when diagnosis of MS was finally observed in 65.2% of the patients.…”

“…Our main finding of a “natural history” of hippocampal subfield degeneration in MS, from dentate gyrus to CA1, is supported by anatomical and functional studies in both human and animal models of the disease. First, we previously reported that pattern separation performance—a cognitive task critically dependant on dentate gyrus function (Bakker, Kirwan, Miller, & Stark, )—was decreased in patients with CIS and early MS, when conventional visuospatial episodic memory tests (BVMT‐R) were not yet altered, suggesting an early and isolated dentate gyrus dysfunction during the course of the disease (Planche et al, ). Such functional alterations suggested by the pattern separation task are therefore consolidated by the anatomical alterations observed in this MRI study.…”

“…The 3D‐T1‐weighted images of the subjects considered in this study (1 × 1 × 1 mm 3 ) were up‐sampled to the image resolution of the training library (0.5 × 0.5 × 0.5 mm 3 ) using the local adaptive super‐resolution (LASR) method (Coupé, Manjón, Chamberland, Descoteaux, & Hiba, ). The method finally provided automatic segmentation of hippocampal subfields gathered into 5 labels: subiculum, CA1‐SP (stratum pyramidale), CA1‐SRLM (stratum radiatum‐lacunosum‐moleculare), CA2/3 and CA4/dentate gyrus (Figure ), allowing us to test our a priori hypotheses regarding the selective vulnerability of the dentate gyrus or CA1, as suggested in the literature from animal, neuropsychological (using pattern separation tasks) and MRI studies (Planche et al, ; Rocca et al, ; Sicotte et al, ). In our previous paper, the hippocampal subfield segmentation accuracy using T1‐weighted has been estimated to be 62% for the Winterburn protocol in terms of average DICE coefficient.…”

The hippocampus in multiple sclerosis

“…5 Recently, decreased performance in a pattern separation task was demonstrated in a cross-sectional study of 19 patients with early relapsing-remitting (RR) MS (within 6-to-18 months after a first neurological episode suggestive of MS), in comparison to healthy controls matched for age, gender and education level, in the absence of information processing speed (evaluated with the Computerized Speed Cognitive Test ) and visuospatial memory (evaluated with the Brief Visuospatial Memory Test) impairment. 6 Since it has been shown a critical role of the DG in pattern separation, 7 impaired performance in this task could be seen as evidence that brain areas implicated in pattern separation, for which the DG is crucial, are involved in early MS.…”

Pupil size changes signal hippocampus-related memory functions

“…label them as 'similar'). A similar dissociation between intact recognition memory performance and impaired lure discrimination emerged in psychiatric and neurological disorders as well (Schizophrenia: 22,23 Early multiple sclerosis: 24 ).…”