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

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.

Cognitive impairments correlate with increased central nervous system immune activation after allogeneic haematopoietic stem cell transplantation

“…The immune activation correlated with decreased neurogenesis and impaired synaptic plasticity. These findings are in line with prefrontal cortex dysfunction observed in our previous imaging studies performed on the same patients [6].…”

“…Neurobiological aberrations underlying the previously demonstrated reduced prefrontal cortex activity in these patients [6], may ultimately lead to a persistent and relevant clinical phenotype of fatigue and cognitive dysfunction. Pathophysiological understanding of CNS disorders is limited by the invasiveness of brain biopsies.…”

“…A selected battery of items from the Cambridge Neuropsychological Test Automated Battery (CANTAB), combined with validated fatigue questionnaires, was used to define a distinct cohort of long-term survivors with mental fatigue and cognitive impairment. Using functional near-infrared spectroscopy (fNIRS) and electrodermal activity, we demonstrated that prefrontal cortex activity and sympathetic nervous system activity was lower in the fatigued group compared to both non-fatigued and healthy controls during cognitive testing, suggesting an underlying abnormality in neural connectivity [6].…”

“…Compelling evidence suggests that the aHSCT procedure can affect brain structure and function [5,6]: Reductions in both grey and white matter volume during the first year post transplant have been demonstrated on magnetic resonance imaging [5,7].…”

Fatigue as Mediator Factor in PTSD-Symptoms after Allogeneic Hematopoietic Stem Cell Transplantation

“…Neuroimaging studies on patients with chronic fatigue have used functional connectivity, showing lower functional connectivity at the prefrontal cortex, both during rest and cognitive task [53,54]. Other evidence also shows an inefficient increase in resting-state functional connectivity linked to the psychological factors observed in the syndrome [55].…”