Post-stroke fatigue is associated with resting state posterior hypoactivity and prefrontal hyperactivity

Georgia Cotter; Mohamed Salah Khlif; Laura Bird; Mark E Howard; Amy Brodtmann; Natalia Egorova-Brumley

doi:10.1177/17474930211048323

Post-stroke fatigue is associated with resting state posterior hypoactivity and prefrontal hyperactivity

Int J Stroke. 2021 Sep 27:17474930211048323. doi: 10.1177/17474930211048323. Online ahead of print.

Authors

Georgia Cotter¹, Mohamed Salah Khlif², Laura Bird², Mark E Howard^{1

3

4

5}, Amy Brodtmann², Natalia Egorova-Brumley^{1

2}

Affiliations

¹ Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Australia.
² Dementia Theme, the Florey Institute of Neuroscience and Mental Health, Melbourne, Australia.
³ Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, Australia.
⁴ Institute for Breathing and Sleep, Melbourne, Australia.
⁵ Victorian Respiratory Support Service, Austin Health, Heidelberg, Australia.

PMID: 34569876
DOI: 10.1177/17474930211048323

Abstract

Background: Fatigue is associated with poor functional outcomes and increased mortality following stroke. Survivors identify fatigue as one of their key unmet needs. Despite the growing body of research into post-stroke fatigue, the specific neural mechanisms remain largely unknown.

Aim: This observational study aimed to identify resting state brain activity markers of post-stroke fatigue.

Method: Sixty-three stroke survivors (22 women; age 30-89 years; mean 67.5 ± 13.4 years) from the Cognition And Neocortical Volume After Stroke study, a cohort study examining cognition, mood, and brain volume in stroke survivors following ischemic stroke, underwent brain imaging three months post-stroke, including a 7-minute resting state functional magnetic resonance imaging. We calculated the fractional amplitude of low-frequency fluctuations, which is measured at the whole-brain level and can detect altered spontaneous neural activity of specific regions.

Results: Forty-five participants reported experiencing post-stroke fatigue as measured by an item on the Patient Health Questionnaire-9. Fatigued compared to non-fatigued participants demonstrated significantly lower resting-state activity in the calcarine cortex (p < 0.001, cluster-corrected p_FDR = 0.009, k = 63) and lingual gyrus (p < 0.001, cluster-corrected p_FDR = 0.025, k = 42) and significantly higher activity in the medial prefrontal cortex (p < 0.001, cluster-corrected p_FDR = 0.03, k = 45).

Conclusions: Post-stroke fatigue is associated with posterior hypoactivity and prefrontal hyperactivity reflecting dysfunction within large-scale brain systems such as fronto-striatal-thalamic and frontal-occipital networks. These systems in turn might reflect a relationship between post-stroke fatigue and abnormalities in executive and visual functioning. This whole-brain resting-state study provides new targets for further investigation of post-stroke fatigue beyond the lesion approach.

Keywords: Calcarine/lingual gyrus; fractional amplitude of low-frequency fluctuations; medial prefrontal cortex; post-stroke fatigue; resting state functional magnetic resonance imaging; stroke subtypes.