Increased posterior cingulate cortex blood flow in cancer-related fatigue

David Raizen; Rupal Bhavsar; Brendan T Keenan; Patrick Z Liu; Timothy P Kegelman; Hann-Hsiang Chao; Neha Vapiwala; Hengyi Rao

doi:10.3389/fneur.2023.1135462

Increased posterior cingulate cortex blood flow in cancer-related fatigue

Front Neurol. 2023 Jul 27:14:1135462. doi: 10.3389/fneur.2023.1135462. eCollection 2023.

Authors

David Raizen^{1

2

3}, Rupal Bhavsar^{1

3}, Brendan T Keenan^{2

3}, Patrick Z Liu³, Timothy P Kegelman⁴, Hann-Hsiang Chao^{5

6}, Neha Vapiwala⁷, Hengyi Rao^{1

8}

Affiliations

¹ Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
² Division of Sleep Medicine, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
³ Chronobiology and Sleep Institute, University of Pennsylvania, Philadelphia, PA, United States.
⁴ Department of Radiation Oncology, ChristianaCare, Newark, DE, United States.
⁵ Radiation Oncology Service, Richmond VA Medical Center, Richmond, VA, United States.
⁶ Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA, United States.
⁷ Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
⁸ Shanghai Key Laboratory of Brain-Machine Intelligence for Information Behavior, Center for Magnetic Resonance Imaging Research, Shanghai International Studies University, Shanghai, China.

Abstract

Fatigue is a common symptom associated with cancer treatments. Brain mechanisms underlying cancer-related fatigue (CRF) and its progression following therapy are poorly understood. Previous studies have suggested a role of the default mode network (DMN) in fatigue. In this study we used arterial spin labeling (ASL) perfusion functional magnetic resonance imaging (fMRI) and compared resting cerebral blood flow (CBF) differences in the posterior cingulate cortex (PCC), a core hub of the DMN, between 16 patients treated with radiation therapy (RAT) for prostate (9 males) or breast (7 females) cancer and 18 healthy controls (HC). Resting CBF in patients was also measured immediately after the performance of a fatiguing 20-min psychomotor vigilance task (PVT). Twelve of 16 cancer patients were further followed between 3 and 7 months after completion of the RAT (post-RAT). Patients reported elevated fatigue on RAT in comparison to post-RAT, but no change in sleepiness, suggesting that the underlying neural mechanisms of CRF progression are distinct from those regulating sleep drive progression. Compared to HC, patients showed significantly increased resting CBF in the PCC and the elevated PCC CBF persisted during the follow up visit. Post-PVT, but not pre-PVT, resting CBF changes in the PCC correlated with fatigue changes after therapy in patients with CRF, suggesting that PCC CBF following a fatiguing cognitive task may be a biomarker for CRF recovery.

Keywords: arterial spin labeling; cancer; cerebral blood flow; default mode network; fatigue; functional MRI; posterior cingulate cortex; sleep.

Grants and funding

This research was supported by grants R21CA224267 (PI: DR), R21AG051981 (PI: HR), and P01 HL094307 (PI: Allan Pack) from the National Institutes of Health, a grant from the University of Pennsylvania Perelman School of Medicine Department of Radiation Oncology Translational Center of Excellence, and a University of Pennsylvania Perelman School of Medicine Institute for Translational Medicine and Therapeutics Translational Biomedical Imaging Center pilot grant.