Distinct hemodynamic and functional connectivity features of fatigue in clinically isolated syndrome and multiple sclerosis: accounting for the confounding effect of concurrent depression symptoms

Abstract

Purpose This study aims to identify common and distinct hemodynamic and functional connectivity (FC) features for self-rated fatigue and depression symptoms in patients with clinically isolated syndrome (CIS) and relapsing–remitting multiple sclerosis (RR-MS). Methods Twenty-four CIS, 29 RR-MS patients, and 39 healthy volunteers were examined using resting-state fMRI (rs-fMRI) to obtain whole-brain maps of (i) hemodynamic response patterns (through time shift analysis), (ii) FC (via intrinsic connectivity contrast maps), and (iii) coupling between hemodynamic response patterns and FC. Each regional map was correlated with fatigue scores, controlling for depression, and with depression scores, controlling for fatigue. Results In CIS patients, the severity of fatigue was associated with accelerated hemodynamic response in the insula, hyperconnectivity of the superior frontal gyrus, and evidence of reduced hemodynamics–FC coupling in the left amygdala. In contrast, depression severity was associated with accelerated hemodynamic response in the right limbic temporal pole, hypoconnectivity of the anterior cingulate gyrus, and increased hemodynamics–FC coupling in the left amygdala. In RR-MS patients, fatigue was associated with accelerated hemodynamic response in the insula and medial superior frontal cortex, increased functional role of the left amygdala, and hypoconnectivity of the dorsal orbitofrontal cortex, while depression symptom severity was linked to delayed hemodynamic response in the medial superior frontal gyrus; hypoconnectivity of the insula, ventromedial thalamus, dorsolateral prefrontal cortex, and posterior cingulate; and decreased hemodynamics–FC coupling of the medial orbitofrontal cortex. Conclusion There are distinct FC and hemodynamic responses, as well as different magnitude and topography of hemodynamic connectivity coupling, associated with fatigue and depression in early and later stages of MS.

Eye movement desensitization and reprocessing for depressed individuals with multiple sclerosis: A pilot study

“…Functional brain patterns analysis demonstrated no changes in the activation pattern when exploring positive valence stimuli post-treatment, but modulation was observed in the parietal and premotor areas when examining negative valence stimuli. The herein-presented data differ from previous works showing increased activation in prefrontal cortex, and decreased functional connectivity between the amygdala and prefrontal cortex 9,10 in people with MS and depression. It is worth noting that discrepancies between studies may arise due to variances in stimulation paradigms 9 or the utilization of resting state instead of task fMRI.…”

“…It is worth noting that discrepancies between studies may arise due to variances in stimulation paradigms 9 or the utilization of resting state instead of task fMRI. 10 However, these parietal and premotor areas are linked to the mirror neuron system (MNS), which plays a role in empathetic emotional mirroring that can be influenced by stressful memories. Our results should be considered in need of further confirmation in larger MS samples with more severe depressive symptoms (HADS scores at baseline were relatively low) and involving control group comparisons.…”

Functional connectivity-hemodynamic (un)coupling changes in chronic mild brain injury are associated with mental health and neurocognitive indices: a resting state fMRI study

“…The voxel BOLD time series consisted of 150 dynamic volumes, while the voxel size was 3 × 3 × 3 mm (3 mm isotropic). Initial fMRI data preparation steps are in line with previous work of our team on data from the same MRI system [ 28 , 42 – 44 , 56 , 57 ] (see supplementary material ).…”

“…Time-shift analysis maps were calculated as described in several previous studies [ 36 – 44 ] using MATLAB scripts (see also supplementary material ). Firstly, a mask of the major venous sinuses was created based on the standard brain.…”

“…To date, this technique has been applied not only to neurological conditions characterized by severe perfusion disturbances, such as stroke [ 36 – 40 ], but also in patients with Alzheimer’s dementia or mild cognitive impairment [ 41 ], systemic lupus erythematosus [ 42 , 43 ], clinically isolated syndrome and multiple sclerosis [ 44 ], displaying more subtle hemodynamic impairment. By utilizing TSA on rs-fMRI data, it becomes possible to combine hemodynamic and functional connectivity metrics and assess the degree of their coupling (or uncoupling) within specific regions of the brain with the same technique and without the use of contrast agents.…”