Amygdala network reorganization mediates the theory of mind performances in multiple sclerosis

Abstract

Theory of mind (ToM) seems to be affected in multiple sclerosis (MS). MRI studies suggested a role of the amygdala in social cognitive performances. Therefore, we explored the role of the amygdala network in ToM using a multimodal MRI approach. In MS, patients with impaired ToM showed contradictory dysexecutive neuropsychological profile. Therefore, we compared neural networks involved in ToM and executive functions (EFs). Twenty patients with relapsing‐remitting MS and 15 matched healthy controls were selected. ToM (Faux Pas test and mind stories) and EFs were assessed within and outside the scanner. All subjects underwent a battery of neuropsychological tests. Multimodal MRI with structural (diffusion imaging) and functional (resting‐state and task‐based) sequences was used to analyze the role and connections of the amygdala in ToM functioning. Cognitive and ToM performances were similar between patients and controls. Resting‐state data revealed decreased connectivity of the left amygdala with frontal areas in patients compared to controls (p < 0.0001). During the task‐based functional MRI, patients demonstrated increased connectivity between the amygdala and several cerebellar and left temporal regions (all p < 0.05). The microstructural alterations between the left amygdala and left temporal regions were associated with increased functional connectivity within the same pathway (r = 0.74; p < 0.01). No overlap was observed between functional networks involved in ToM and EFs. Our study demonstrates more connectivity recruitment between the amygdala and cerebellar and temporal regions in MS patients to reach preserved ToM performance. Microstructural abnormalities have been related to this compensatory network. Finally, different networks were involved in EFs and ToM.

A systematic review and meta-analysis of socio-cognitive impairments in multiple sclerosis

“…In all studies, depression was described as mild because patients with severe symptoms were generally excluded. Several cognitive domains were reported as impaired in patients in MS compared to healthy controls, including executive functions 25 , 26 , semantic fluency 27 , and IQ scores 27 . Three studies 17 , 28 , 29 included depressive and fatigue scores as control variables in their analyses; two of them found that even after controlling for these variables, patients with MS performed significantly worse on aToM 28 and cToM tasks 28 , 29 , one study found no significant influence of these variables on impaired ToM performance 17 .…”

“…Four studies used task-free resting-state functional imaging 26 , 30 , 40 , 46 and three of these studies highlighted the contribution of frontal and temporal networks to aToM impairment in MS. Specifically, they demonstrated a negative correlation between implicit emotion recognition performance and functional connectivity of the fusiform gyrus with lateral occipital gyrus 40 , a positive association between RMET performance and functional connectivity between the left amygdala and frontal pole/paracingulate cortex 26 , or decreased functional connectivity between fronto-temporal regions in patients compared to controls during a facial affect recognition task 30 . On the other hand, Bisecco et al 46 did not find any correlations between the RMET performance and functional connectivity of the default mode, bilateral fronto-parietal executive, salience, cerebellar and limbic networks.…”

“…Using more regional approaches, two studies revealed association between aToM and white matter lesions 44 or other DTI derived metrics (e.g., fractional anisotropy, mean diffusivity 41 ), highlighting the potential role of disconnection of regions associated with socio-cognitive processing. Six studies that used voxel-based morphometry or assessed regional cortical thickness demonstrated positive correlations between aToM and integrity of the amygdala, fronto-temporal and other regions 26,28,44,45 , whereas two studies could not confirm these findings 46,47 . Four studies used task-free resting-state functional imaging 26,30,40,46 and three of these studies highlighted the contribution of frontal and temporal networks to aToM impairment in MS.…”

“…Six studies that used voxel-based morphometry or assessed regional cortical thickness demonstrated positive correlations between aToM and integrity of the amygdala, fronto-temporal and other regions 26,28,44,45 , whereas two studies could not confirm these findings 46,47 . Four studies used task-free resting-state functional imaging 26,30,40,46 and three of these studies highlighted the contribution of frontal and temporal networks to aToM impairment in MS. Specifically, they demonstrated a negative correlation between implicit emotion recognition performance and functional connectivity of the fusiform gyrus with lateral occipital gyrus 40 , a positive association between RMET performance and functional connectivity between the left amygdala and frontal pole/paracingulate cortex 26 , or decreased functional connectivity between fronto-temporal regions in patients compared to controls during a facial affect recognition task 30 .…”

Topological Alterations of the Brain Functional Network in Type 2 Diabetes Mellitus Patients With and Without Mild Cognitive Impairment

“…Previously, increased rs-fMRI signals have also been observed in various studies. For example, more connectivity recruitment between the amygdala and cerebellar regions and between the amygdala and temporal regions has been detected in multiple sclerosis patients ( Koubiyr et al, 2021 ); in addition, increased nodal centralities in the nodes of the cingulo-opercular network, occipital network, and the ventral lateral prefrontal cortex were detected in Parkinson’s disease patients with MCI ( Hou et al, 2020 ).…”