Cortical thinning in the anterior cingulate cortex predicts multiple sclerosis patients' fluency performance in a lateralised manner

Abstract

Cognitive impairment is as an important feature of Multiple Sclerosis (MS), and might be even more relevant to patients than mobility restrictions. Compared to the multitude of studies investigating memory deficits or basic cognitive slowing, executive dysfunction is a rarely studied cognitive domain in MS, and its neural correlates remain largely unexplored. Even rarer are topological studies on specific cognitive functions in MS. Here we used several structural MRI parameters – including cortical thinning and T2 lesion load – to investigate neural correlates of executive dysfunction, both on a global and a regional level by means of voxel- and vertex-wise analyses. Forty-eight patients with relapsing-remitting MS and 48 healthy controls participated in the study. Five executive functions were assessed, i.e. verbal and figural fluency, working memory, interference control and set shifting. Patients scored lower than controls in verbal and figural fluency only, and displayed widespread cortical thinning. On a global level, cortical thickness independently predicted verbal fluency performance, when controlling for lesion volume and central brain atrophy estimates. On a regional level, cortical thinning in the anterior cingulate region correlated with deficits in verbal and figural fluency and did so in a lateralised manner: Left-sided thinning was related to reduced verbal – but not figural – fluency, whereas the opposite pattern was observed for right-sided thinning. We conclude that executive dysfunction in MS patients can specifically affect verbal and figural fluency. The observed lateralised clinico-anatomical correlation has previously been described in brain-damaged patients with large focal lesions only, for example after stroke. Based on focal grey matter atrophy, we here show for the first time comparable lateralised findings in a white matter disease with widespread pathology.

Random number generation deficits in patients with multiple sclerosis: Characteristics and neural correlates

“…More precisely, MS patients showed more ascending counting behavior than control subjects. This corresponds well with previous reports of a deterioration of randomization performance in the presence of a neurological disorder Brugger et al, 1996;Ho et al, 2004) and with the observation of executive dysfunction in MS (Drew, Tippett, Starkey, & Isler, 2008;Geisseler et al, 2016). Patients did not differ from controls in the global measure of randomness (RNG index; 0.47 and 0.43, respectively), perhaps due to a "floor effect"; both groups scored far from the value obtained in 100 simulations of 66 dice throws, i.e.…”

“…MS, the most common autoimmune disorder affecting the central nervous system, is historically considered a white matter (WM) disease, with focal demyelinating lesions in the WM being the pathological hallmark. However, several recent neuropathological studies disclosed a relevant involvement of gray matter areas including the cerebral cortex (Calabrese et al, 2015;Geisseler et al, 2016). Brain integrity, captured by various imaging techniques, has been shown to correlate with cognitive impairment (for review see Rocca et al, 2015), which is recognized as an important feature of MS, prevalent in 43-70% of MS patients (Chiaravalloti & DeLuca, 2008;Pflugshaupt, Geisseler, Nyffeler, & Linnebank, 2016).…”

Volume versus surface-based cortical thickness measurements: A comparative study with healthy controls and multiple sclerosis patients

“…Corresponding cortical regions have been reported as well by previous studies [7, 10, 11]. It should be noted that, unlike other studies, we did not observe thinning in the anterior temporal areas [7].…”

Characterization of normal-appearing white matter in multiple sclerosis using quantitative susceptibility mapping in conjunction with diffusion tensor imaging

“…However, no significant correlation with clinical impairment (EDSS scores) was appreciated. It has been proposed that the CCG is involved in cognitive tasks such as emotion and memory, while also forming part of the default mode network [42, 43]. Therefore, clinical tests that focus on cognition such as the multiple sclerosis functional composite may be more appropriate for determining this relationship.…”