Thalamic Injury and Cognition in Multiple Sclerosis

Abstract

Multiple sclerosis (MS) produces demyelination and degeneration in both gray and white matter. Both cortical and deep gray matter injury is observed during the course of MS. Among deep gray matter structures, the thalamus has received special attention, as it undergoes volume loss in different MS subtypes and is involved in the earliest form of the disease, radiologically isolated syndrome. The thalamus plays an important role as an information relay center, and involvement of the thalamus in MS has been associated with a variety of clinical manifestations in MS, including fatigue, movement disorders, pain, and cognitive impairment (CI). Similar to thalamic volume loss, CI is seen from the earliest stages of MS and is potentially one of the most debilitating manifestations of the disease. The thalamus, particularly the dorsomedial nucleus as part of the basolateral limbic circuit and anterior thalamic nuclei through connections with the prefrontal cortex, has been shown to be involved in CI. Specifically, several cognitive performance measures such as processing speed and memory correlate with thalamic volume. Thalamic atrophy is one of the most important predictors of CI in MS, and both thalamic volume, diffusion tensor imaging measures, and functional activation correlate with the degree of CI in MS. Although the exact mechanism of thalamic atrophy is not well-understood, it is hypothesized to be secondary to degeneration following white matter injury resulting in secondary neurodegeneration and neuronal loss. The thalamus may represent an ideal biomarker for studies aiming to test neuroprotective or restorative therapies aimed at cognition.

Dynamics and Predictors of Cognitive Impairment along the Disease Course in Multiple Sclerosis

“…This region is involved in the fronto-parietal network, and it plays a key role in executive functions, as well as participating in the working memory network [32,33]. Moreover, the thalamus, a highly connected nucleus, has been associated with learning and memory function, and it seems to be a good predictor for CI in MS [5,34], although here, it was more specifically associated with verbal memory impairment. All these areas are part of the limbic system, which plays a crucial role in various cognitive functions [35].…”

Deformation-based morphometry identifies deep brain structures protected by ocrelizumab

“…Given the likely non-random spatial distribution of brain atrophy ( Steenwijk et al, 2016 ) and variable treatment response across brain structures, a suppression of volume loss in specific brain regions may reflect the treatment effect at a finer scale. Among the identified brain structures, involvement of the thalamus in multiple sclerosis has attracted significant attention in recent years ( Amin and Ontaneda, 2020 , Fadda et al, 2019 , Zivadinov et al, 2013 ). The thalamus has extensive neural connections with major cortical and subcortical structures, which makes it relevant to a wide range of brain functions including sensory, motor, and cognitive functions.…”

Gender differences in MS related pain, correlation with MRI lesion localization and burden of disease

“…15 Previous studies demonstrated gender differences in the prevalence of chronic pain in non-MS patient. 16 Other studies of patients with chronic pain syndromes utilizing brain imaging studies revealed abnormalities in pain processing areas of the brain. These areas include the thalamus, amygdala, prefrontal cortex, cingulate cortex and somatosensory cortex.…”

“…As mentioned in a recent research, the thalamus plays an important role as an information relay center, and involvement of the thalamus in MS has been linked with a variety of clinical symptoms including fatigue, movement disorders, pain, and cognitive impairment. 16 There are limitations in the day to day clinical practice regarding MS pain and imaging techniques. For better evaluation of these anatomical and connectivity subregions there are limitations in spatial resolution, which could improve with advances in imaging techniques.…”