Modafinil treatment modulates functional connectivity in stroke survivors with severe fatigue

Abstract

Post-stroke fatigue has a significant impact on stroke survivors’ mental and physical well-being. Our recent clinical trial showed significant reduction of post-stroke fatigue with modafinil treatment, however functional connectivity changes in response to modafinil have not yet been explored in stroke survivors with post-stroke fatigue. Twenty-eight participants (multidimensional fatigue inventory-20 ≥ 60) had MRI scans at baseline, and during modafinil and placebo treatment. Resting-state functional MRI data were obtained, and independent component analysis was used to extract functional networks. Resting-state functional connectivity (rsFC) was examined between baseline, modafinil and placebo treatment using permutation testing with threshold-free cluster enhancement. Overall twenty-eight participants (mean age: 62 ± 14.3, mean baseline MFI-20: 72.3 ± 9.24) were included. During modafinil treatment, increased rsFC was observed in the right hippocampus (p = 0.004, 11 voxels) compared to placebo. This coincided with lower rsFC in the left frontoparietal (inferior parietal lobule, p = 0.023, 13 voxels), somatosensory (primary somatosensory cortex; p = 0.009, 32 voxels) and mesolimbic network (temporal pole, p = 0.016, 35 voxels). In conclusion, modafinil treatment induces significant changes in rsFC in post-stroke fatigue. This modulation of rsFC may relate to a reduction of post-stroke fatigue; however, the relationship between sensory processing, neurotransmitter expression and fatigue requires further exploration.

Cognitive enhancement: Effects of methylphenidate, modafinil, and caffeine on latent memory and resting state functional connectivity in healthy adults

“…However, Iidaka et al have shown evidence that this network is also associated with successful retrieval in episodic memory (Iidaka et al, 2006 ). FC within the FPN has been shown to be modulated by different stimulants such as MOD (Esposito et al, 2012 ; Visser et al, 2019 ); CAF (Haller et al, 2013 ; Koppelstaetter et al, 2008 ) and MPH (Mehta et al, 2000 ; Mueller et al, 2014 ). In fact, Schmidt and colleagues report a broad recruitment of frontoparietal regions when MOD and MPH are consumed compared with placebo (Schmidt et al, 2017 ).…”

Neuroimaging correlates of post-stroke fatigue: A systematic review and meta-analysis

“…38 A third small study (n = 12) used fMRI to show that reduced network functional connectivity in the ipsilesional rostral middle frontal cortex was associated with higher fatigue severity. 52 Two studies assessed the effect of modafinil on fMRI functional connectivity (FC) in PSF, 55,56 using data from the double-blind MIDAS-II trial (n = 36), which showed modafinil 200 mg daily reduced PSF compared to placebo. 62 In a subgroup of 28 who had fMRI, modafinil treatment was associated with increased resting-state functional connectivity (rsFC) in the right hippocampus compared to placebo, and lower rsFC in the left frontoparietal, somatosensory, and mesolimbic network.…”

Fatigue, physical activity and associated factors in 779 patients with myasthenia gravis

“…The MFI-20 has been validated and/or used in several clinical and healthy populations since 1995, including patients with neurological diseases, e.g. multiple sclerosis, stroke, polio and spinal muscular atrophy [19][20][21][22][23][24][25]. The MFI-20 was in 2000, in a study of fatigue in the Danish background population, validated and translated into Danish [26,27].…”