Reduced prefrontal cortex and sympathetic nervous system activity correlate with fatigue after aHSCT

Erik Boberg,Myrto Sklivanioti Greenfield,Katarina Le Blanc,Ellen Iacobaeus,Yanlu Wang,Mussie Msghina

doi:10.1038/s41409-021-01539-9

Abstract

Long-term fatigue and cognitive dysfunction affects 35% of allogeneic haematopoietic stem cell transplantation (aHSCT) survivors, suggesting a dysfunctional prefrontal cortex. In this study, we assessed prefrontal cortex and sympathetic nervous system activity in aHSCT patients with fatigue (n = 12), non-fatigued patients (n = 12) and healthy controls (n = 27). Measurement of near-infrared spectroscopy and electrodermal activity was carried out at rest and during cognitive performance (Stroop, verbal fluency and emotion regulation tasks). Prefrontal cortex and sympathetic nervous system activity were also analyzed in response to dopamine and noradrenaline increase after a single dose of methylphenidate. Baseline cognitive performance was similar in the two patient groups. However, after methylphenidate, only non-fatigued patients improved in Stroop accuracy and had better verbal fluency task performance compared to the fatigued group. Task-related activation of prefrontal cortex in fatigued patients was lower compared to non-fatigued patients during all cognitive tests, both before and after methylphenidate administration. During the Stroop task, reaction time, prefrontal cortex activation, and sympathetic nervous system activity were all lower in fatigued patients compared to healthy controls, but similar in non-fatigued patients and healthy controls.Reduced prefrontal cortex activity and sympathetic arousal suggests novel treatment targets to improve fatigue after aHSCT.

Highlights

Improved patient care has increased survivorship after allogeneic haematopoietic stem cell transplantation, but sequelae remain common [1]
Persisting fatigue and cognitive dysfunction, such as executive dysfunction, memory loss, difficulties in concentration and completing tasks are commonly reported in cancer treated patients, including allogeneic haematopoietic stem cell transplantation (aHSCT) recipients [2,3,4]
We recently reported that long-term aHSCT survivors with persistent fatigue suffer from impaired executive functions [37]

Summary

Introduction

Improved patient care has increased survivorship after allogeneic haematopoietic stem cell transplantation (aHSCT), but sequelae remain common [1]. Persisting fatigue and cognitive dysfunction, such as executive dysfunction, memory loss, difficulties in concentration and completing tasks are commonly reported in cancer treated patients, including aHSCT recipients [2,3,4]. These impairments negatively impact the patients’ quality of life and ability to return to employment. Cognitive dysfunction is among the most common manifestations [7]. It is unknown if the allogenic transplantation itself directly impacts on processes involved in higher cortical functions. Alterations in gray matter volumes and white matter connectivity one year after aHSCT have been reported, suggesting that the transplant procedure affects CNS structures [8, 9]

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