Quantitative Limbic System Mapping of Main Cognitive Domains in Multiple Sclerosis

Abstract

Background and objectiveCognitive impairment (CI) is common in multiple sclerosis (MS), but underlying mechanisms and their imaging correlates are not completely understood. The gray and white matter structures of the limbic system (LS) play crucial roles in different aspects of cognition. To investigate their role in MS related CI, and since a detailed evaluations are lacking in the literature, we used a comprehensive neuroimaging approach to evaluate CI’s correlations with the main components of the LS.MethodsTen non-cognitively impaired MS patients and 30 MS patients with diagnosed CI, who underwent a comprehensive neuropsychological evaluation were included in the analysis. Microstructural integrity, volumetry of main limbic gray and white matter structures and cortical thickness were assessed for associations with CI.ResultsFornix and cingulum/cingulate cortices were found to be the strongest correlates of CI in MS. As expected, LS’ gray and white matter structures were involved in various cognitive functions. Uncinate fasciculi showed significant correlation with verbal and visuospatial learning and memory, phonemic and semantic fluency; hippocampi with visuospatial skills, phonemic and semantic fluency, executive functions, and processing speed; thalami with verbal learning, visuospatial skills, semantic fluency; and amygdala with verbal recognition discrimination.ConclusionThis comprehensive neuroimaging approach elucidated the role of the main limbic structures in cognitive functions associated with MS-related CI.

Yakovlev's Basolateral Limbic Circuit in Multiple Sclerosis Related Cognitive Impairment

“…21 However, later it was shown to contribute to the neural basis of learning and memory. 4 Additionally, recent MS studies showing the importance of the amygdala and OFC 10,22 in cognition support our findings.…”

“…Yakovlev described the circuit of orbitofrontal cortex-dorsomedial thalamus-amygdala as basolateral limbic circuit in addition to Papez circuit. 3 This circuit has two main white matter loops; 1) anteriorly uncinate fasciculus, previously studied in MS related CI 10–11 connecting amygdala or temporal pole to orbitofrontal frontal cortex and 2) posteriorly bisynaptic orbitofrontoamygdalar loop including bidirectional and ipsilateral orbitfrontothalamic and amygdalothalamic projection pathways. From the cortex, this loop arises from OFC travels posteriorly through the anterior limb of the internal capsule and synapses in the dorsomedial nucleus of the thalamus.…”

“…Recent studies have revealed the involvement of limbic structures in MS-related cognitive impairment (CI). 10,11…”

Association Between White Matter Microstructure and Verbal Fluency in Patients With Multiple Sclerosis

“…Specifically, these studies showed patterns of reduced left lateralization when verbal fluency tasks were performed by patients with Alzheimer’s disease, epilepsy and schizophrenia (Weiss et al, 2004; Metternich et al, 2014; Rodríguez-Aranda et al, 2016). A recent study, focusing primarily on the limbic system in MS patients, showed associations between verbal fluency and the UF, bilaterally, and in particular, an association between category-based fluency and the right UF (Keser et al, 2018). The correlation we found in the right IFOF, a neighboring right hemispheric ventral pathway, aligns with this overall tendency for reduced left lateralization in clinical populations.…”

A general role for ventral white matter pathways in morphological processing: going beyond reading

“…Still, this finding provides supporting evidence for the involvement of the ventral tracts in morphological processing sampled with production tasks. Other studies reported associations between letter-or categorybased fluency and properties of several white matter tracts, in clinical patients suffering from multiple sclerosis, aphasia or stroke (Blecher et al, 2019;Griffis et al, 2017;Keser et al, 2018;Li et al, 2017; but see Vallesi and Babcock (2020) for null results in healthy adults). Morpheme-based fluency may be more challenging than standard fluency tasks, as it requires using metalinguistic knowledge for lexical search and applying more restrictive response selection criteria.…”