MAP-FAT – MAP-FAT

Persistent fatigue (PF) is a highly prevalent transdiagnostic symptom across countries and cultures, and an important cause of disability and reduced quality of life. Acute infection is a common trigger of PF, as exemplified by the ‘Long COVID’ phenomenon. Despite substantial burden for the suffering individuals as well as their next-of-kins, the healthcare systems and the economy, PF is an under-researched field, with scarce knowledge of disease mechanisms as well as treatment and preventive measures.
Existing knowledge on PF pathophysiology suggests complex interactions between functional brain alterations, immunological aberrations and disturbances of autonomic nervous system activity. Previous findings have been interpreted in light of two alternative models: A body-to-brain mechanism highlighting immunological aberrations as the primary mechanism, and a brain-to-body mechanism where functional brain alteration is seen as the central element whereas immunological alterations are regarded secondary phenomena mediated by autonomic disturbances.
The multinational and collaborative Mechanism of Persistent Fatigue (MAP-FAT) project is determined to scrutinize both these potential brain-body interactions in PF. The main objectives are: a) To determine the relationship between PF, brain network dynamics, sympathetic nervous activity and immunological alterations; b) To determine whether PF is primarily dependent upon strong priors or current interoceptive input within a central inferential model. To achieve these objectives, MAP-FAT will exploit an existing health registry on post-infective fatigue (preparatory part) and conduct a de novo post-infective cohort study (main part) of n=150 individuals with acute Epstein-Barr virus (EBV) infection and n=150 healthy controls followed for six months. Investigations include: a) Clinical and demographic assessment; b) Questionnaire charting; c) Multimodal brain MRI; d) Autonomic cardiovascular assessment; e) Deep immunological profiling; and f) Behavioral experiments (The Affective Picture Paradigm (APP), The Virtual Hill Bicycling Paradigm, and The Belief Updating Task Paradigm). The behavioral experiments are specifically designed to disentangle the relative contributions of priors and sensory input for the experience of PF. In addition, the APP set-up, which includes concurrent brain fMRI, autonomic assessment, and immunological profiling during pharmacological manipulations, is key for addressing the causal association between functional brain alterations, autonomic activity and immunological aberrations.