Research

When people are sick, their behaviour changes drastically. They get fatigued, and rather lie in bed than go for a run. This is called sickness behaviour. During acute sickness, this behaviour is adaptive, directing energy away from physical/mental activities and towards bodily processes that fight disease. However, it is not well understood what mechanisms underpin this form of fatigue and why it can persist after illness or medical treatment.

My research investigates how behavior and decision making changes during acute illness (using LPS), what neural mechanisms are involved, and how this might explain the development of long-term persisting fatigue and cognitive alterations after medical treatments or infectious disease.

I aim to use the latest biological insight on how inflammation affects the brain and metabolic function to explain fatigue and cognitive symptoms during and after disease.

We-Care project

@ Tilburg University

Inflammation and cancer-related fatigue

@ RadboudUMC, with Prof Sanne Schagen, Prof Roshan Cools, and Prof. Peter PickkersFunded by the Young Investigators Grant, Dutch Cancer Foundation, starting date: April 2019
Fatigue is one of the most prevalent and debilitating side effect of cancer treatment. A growing body of literature suggests that cancer-related fatigue result from treatment-induced inflammatory effects on brain function. However, as most studies have focused on effects of acute inflammatory manipulations, little is known about the mechanisms on how adaptive acute fatigue during treatment transitions into chronic maladaptive fatigue after curative treatment.
Fatigue is part of the sickness syndrome, a set of mood and motivational alterations, including alterations in effort-expenditure and cost-benefit decision making. This project investigates the relationship between inflammation, motivational behaviors (i.e. cost-benefit decision making) and neural mechanisms during acute inflammatory challenges in healthy subjects (i.e. LPS) as well as in cross-sectional and longitudinal studies with fatigued (ex-)cancer patients.
The identification of neural mechanisms that trigger or maintain fatigue can provide new treatment targets e.g. targeting the brain dopamine network or immune-to-brain pathways to counteract inflammation effects on the brain.

Key publications:1. Lambregts BIHM, Vasenna E, Scholing JM, Janssen A, Kox M, Aarts E, van der Schaaf ME*, Effects of lipopolysaccharide-induced systemic inflammation and fatigue on cognitive effort expenditure (Brain Behaviour and Immunity 2024)2. Draper A, Koch R, Pickkers P, Husain M, van der Schaaf ME*, Effort but not reward sensitivity is altered by acute sickness induced by experimental endotoxemia in humans(accepted for publication, Neuropsychopharmacology).3. Roerink ME, van der Schaaf ME, Knoop H, van der Meer JMW, Interleukin-1 as a mediator of fatigue in disease, Journal of Neuroinflammation, 2017

Neural correlates of chronic fatigue

Currently setting up projects within the Netherlands ME/CFS Biobank (NMCB) and Dutch Post-Covid Network. Previous projects were done within a Post Doc project (2014-2018) @ the Expert Centre for Chronic Fatigue and the Donders Institute for Brain, Cognition and Behaviour, with Prof. Hans Knoop, Prof. Ivan Toni, and Prof. Jos van der Meer.
Chronic fatigue syndrome (CFS) is characterized by profound disabling fatigue and increased fatigability after mild physical exertions. Its etiology is still being studied, but increasing evidence point towards a role for (neuro) immune-metabolic disturbances. Supported by previous (f)MRI studies, it has been suggested that central abnormalities may underlie fatigue symptoms, potentially involving immune-effects on glial and brain functions that regulate metabolic functioning energy-saving behaviours.
My research aims to further unravel the neural mechanisms that are involved in fatigue symptoms of patients with chronic fatigue syndrome. To do this, We use (micro) structural MRI, Spectroscopy, and fMRI to assess changes in neuroanatomy, brain metabolism, and functional connectivity.
One of the likely drivers of the historical psychological/biological discussion in this field, is that fatigue is complex with many different dimensions that can result from both biological e.g. inflammation/metabolic constraint/somatic disease and psychological stress which are too-often confused. Accordingly, one of biggest challenges to understanding fatigue symptoms is to find a way to better dissociate and identify the biological and psychological processes that underlie fatigue.
At the Expert Centre for Chronic Fatigue in Nijmegen, CFS is treated with cognitive behavioral therapy (CBT), which is effective in a subset of CFS patients, but not all patients. The post doc project aimed to investigate what neural mechanisms are modifiable by behavioral interventions, and what neural mechanisms are not. This will help dissociate fatigue-related neural alterations that have a psychological or a biological cause, and ultimately contribute to better individualized treatments that encompass both psychological and medical treatments.

Key publications:1. van der Schaaf ME, Roelofs K, de Lange FL, Geurts DEM, van der Meer JM, Knoop H, Toni I. Fatigue is associated with altered monitoring and preparation of physical effort in patients with chronic fatigue syndrome, Biological psychiatry: Cognitive neuroscience and neuroimaging
2. van der Schaaf, ME, De Lange, FP, Schmits, IC, Geurts, DEM, Roelofs, K, van der Meer, JWM, Toni, I, Knoop, J, Prefrontal structure varies as function of pain symptoms in patients with Chronic Fatigue Syndrome, Biological Psychiatry
Pre-registration of the full study can be found here: van der Schaaf ME, Toni I, Roelofs K, de Lange FL, Geurts DEM, van der Meer JM, Knoop H, Investigating neural mechanisms of change of cognitive behavioural therapy for chronic fatigue syndrome: a randomized controlled trial, BMC psychiatry (2015) pubmedNote: Over the years many new scientific developments in the field highlight the need to revise certain theories and hypotheses in this pre-registration, and develop a more balanced view on the biology/psychology aspects of the disease.

Dopamine, reward and punishment

@ the Donders Institute for Brain, Cognition and Behaviour with Prof. Roshan Cools.
I use pharmacological fMRI and DTI to investigate dopaminergic drug effects on brain mechanisms involved in the learning from rewards and punishments. Specifically, I focus on individual differences in dopaminergic modulation of striatal activity and fronto-limbic-striatal interactions during reward- and punishment-based reversal learning. My work is contributed to current models of dopaminergic functioning in fronto-limbic-striatal circuits. A better knowledge of these circuits can be valuable for the mechanistic understanding of motivated behaviour in various age groups and psychiatric disorders. Clinically, understanding of individual differences in drug responses can lead to better tailoring of individualized drug treatments.

Key publications:1. van der Schaaf ME, van Schouwenburg MR, Geurts DEM, Schellekens AFA, Buitelaar JK, Verkes RJ, Cools R, Establishing the dopamine‐dependency of human striatal signals during reward and punishment reversal learning, Cerebral Cortex (2014) pubmed2. van der Schaaf, ME, Fallon, SJ, ter Huurne, N, Buitelaar, J, & Cools, R, Working memory capacity predicts effects of methylphenidate on reversal learning, Neuropsychopharmacology (2013) pubmed3. Van der Schaaf, ME, Warmerdam, E, Crone, EA, & Cools, R, Distinct linear and non‐linear trajectories of reward and punishment reversal learning during development: Relevance for dopamine’s role in adolescent decision making. Developmental Cognitive Neuroscience (2011) pubmed

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