Chronic Fatigue Syndrome
You wake up already feeling exhausted. Even after getting enough sleep, the fatigue persists. Concentrating is a struggle, daily activities require more and more energy, and sometimes you feel as though your body and brain are no longer recovering properly.
Persistent fatigue is a condition where physical or mental exhaustion limits daily functioning and is not always sufficiently relieved by rest.
The causes can vary, ranging from sleep disorders and long-term stress to chronic pain, neurological conditions, or changes in energy metabolism.
Scientific research shows that fatigue can also be linked to changes in the activity and interaction of brain networks involved in stress regulation, attention, and cognitive control.
At BRAI3N, we investigate these brain processes and the possibilities of non-invasive neuromodulation.
Using targeted electrical or magnetic stimulation, we aim to influence brain networks that may play a role in certain forms of fatigue.
What is it?
Why does fatigue sometimes persist?
Fatigue is normal after physical or mental exertion. It is a signal that the body needs to recover.
But what if rest doesn't help enough? What if you are completely exhausted after a conversation, a short walk, or a regular workday?
Persistent fatigue can involve various biological processes. Sometimes the cause lies in a physical condition, disrupted sleep, medication, or a deficiency in certain nutrients. In other cases, long-term stress, chronic pain, or changes in the functioning of the nervous system play a significant role.
Fatigue can manifest in several ways:
- Mental fatigue: difficulty concentrating, thinking clearly, processing information, or making decisions.
- Physical fatigue: a feeling of exhaustion or reduced capacity for daily activities.
- Non-restorative sleep: waking up feeling unrefreshed, even after a full night's sleep.
- Increased sensitivity to stimuli: noise, crowds, and social activities require more energy than they used to.
- Reduced exercise tolerance: physical or cognitive exertion can exacerbate symptoms.
Not everyone experiences the same combination of symptoms. That is why it is important to carefully investigate the underlying cause.
What happens in the brain during persistent fatigue?
Our brains are constantly active. Even when we rest, they process information, regulate bodily functions, and help us cope with change and stress.
Prolonged strain can lead to changes in brain networks involved in attention, sensory processing, and the regulation of mental effort.
A key brain region in this process is the pregenual anterior cingulate cortex (pgACC).
This brain region is involved in, among other things, processing emotions and regulating responses to internal and external stimuli.
The pgACC works in tandem with other brain regions, including the prefrontal cortex, which is important for concentration, planning, and cognitive control.
What does the research from BRAI3N teach us?
In 2026, Sven Vanneste, Jan Ost, and Dirk De Ridder published a scientific study in the journal Neuroscience regarding the relationship between chronic stress, brain activity, and fatigue.
In a group of 589 participants, they examined, among other factors, the electrical brain activity in the pgACC.
The researchers found that more severe fatigue was associated with changes in the alpha activity of this brain region and its communication with other brain networks.
Alpha activity refers to electrical brain rhythms that are involved in, among other things, attention and the regulation of information processing.
In participants with pronounced fatigue, lower alpha activity was observed in certain brain regions. The functional connections between the pgACC and other brain areas were also altered.
These results support the hypothesis that chronic stress and persistent mental strain may be associated with changes in how brain networks process information.
The researchers view this brain activity as a potential future biomarker for certain forms of stress-related fatigue. Further studies are needed to determine whether these measurements are also useful for individual diagnostics or treatment decisions.
What conditions can cause fatigue?
Persistent fatigue can occur in conditions including:
- Chronic stress and burnout.
- Depression and anxiety disorders.
- Fibromyalgia and chronic pain.
- Sleep disorders, including sleep apnea.
- Neurological conditions, such as multiple sclerosis.
- Persistent symptoms following infections, including long COVID.
- Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
- Anemia, thyroid disorders, and other physical conditions.
In ME/CFS and some patients with long COVID, a characteristic worsening of symptoms can occur after physical, cognitive, or emotional exertion. This is called post-exertional malaise (PEM).
It is important to recognize this form of exercise intolerance, as exceeding individual capacity can lead to a long-term worsening of symptoms.
Fatigue is therefore not a standalone diagnosis.
It is a symptom that can have various causes and mechanisms.
How to treat
A broad approach to fatigue
At BRAI3N, we examine persistent fatigue from various perspectives.
We investigate not only the symptoms themselves but also potential physical causes and the underlying brain processes involved.
When chronic stress or altered brain network function appears to play a role, neuromodulation can be an additional treatment option.
Neuromodulation: influencing brain networks involved in fatigue
Neuromodulation is a treatment approach in which we aim to specifically influence the activity of nerves and brain networks.
For fatigue, scientific research focuses on, among other things, networks involved in attention, cognitive control, and stress regulation.
The possibilities of neuromodulation are being explored using various techniques, including transcranial electrical stimulation (tES) and transcranial magnetic stimulation (TMS).
Researchers involved with BRAI3N have contributed to several studies on this treatment approach.
For example, a randomized, placebo-controlled study of 42 patients with fibromyalgia found an improvement in fatigue following targeted electrical stimulation of the prefrontal cortex.
These results demonstrate that certain forms of neuromodulation can reduce fatigue symptoms in specific patient groups.
These scientific insights offer an interesting treatment perspective, but efficacy depends on the underlying condition and the chosen treatment.
Our four-phase treatment plan
1. Assessment
We begin with a comprehensive evaluation of your fatigue, medical history, and previous treatments.
We also focus on sleep, stress, concentration, physical resilience, and any accompanying symptoms.
Where appropriate, aqEEG measurement and analysis provide additional information about electrical brain activity and how certain brain networks interact.
In addition, we can determine if further blood work via Fidlab would be beneficial
For some patients, a more comprehensive blood analysis can help further investigate potential physical factors contributing to fatigue.
Through a blood draw, for example, a Fidlab Health Check can be performed. This analysis maps out various health parameters, including:
- Nutritional balance and specific nutrient deficiencies.
- Hormonal parameters, including thyroid function.
- Metabolic factors, such as insulin resistance.
- Certain inflammatory markers.
The results are interpreted by a physician and, where relevant, may lead to further investigation or targeted guidance.
A Fidlab analysis is not a standalone diagnostic test for chronic fatigue and does not replace standard medical diagnostics.
More information about Fidlab blood testing
2. Targeted treatment
Based on the test results, we will determine the most appropriate approach.
When a physical cause is identified, its treatment will receive the necessary attention.
If neuromodulation is appropriate for your situation, we will discuss how targeted stimulation of the involved brain networks may help reduce certain symptoms.
In doing so, we take into account the scientific evidence, any contraindications, and your personal treatment goals.
3. Stabilization
Throughout the treatment process, we monitor how your symptoms evolve.
We look at factors such as mental clarity, daily stamina, sleep quality, and the extent to which fatigue affects your functioning.
The approach is adjusted as needed. In cases of exercise intolerance, we take your individual energy limits into account.
4. Maintenance
When improvement occurs, we look at how to maintain it as effectively as possible.
Depending on the cause, further medical follow-up, sleep coaching, energy management, lifestyle adjustments, or other treatments may be important.
At BRAI3N, we look beyond just the fatigue.
We combine insights from neuroscience with a comprehensive medical assessment to investigate which factors may be contributing to your symptoms.
Contact us for a no-obligation consultation or to schedule an appointment
Scientific Background
The neuroscientific approach at BRAI3N is based on research into brain networks involved in stress regulation, cognitive control, and fatigue.
Researchers affiliated with BRAI3N have contributed to international publications on the neurobiological mechanisms of fatigue and the potential of electrical brain stimulation.
The Brain Signs of Wear and Tear: Chronic Stress Associated Alpha Oscillations in the Pregenual Anterior Cingulate Cortex Lead to Fatigue
Vanneste S, Ost J, De Ridder D. The brain signs of wear and tear: Chronic stress associated alpha oscillations in the pregenual anterior cingulate cortex lead to fatigue.Neuroscience. 2026;594:134–141.
Read the publication in Neuroscience
Differential Effects of Bifrontal and Occipital Nerve Stimulation on Pain and Fatigue Using Transcranial Direct Current Stimulation in Fibromyalgia Patients
To WT, James E, Ost J, Hart J Jr, De Ridder D, Vanneste S. Differential effects of bifrontal and occipital nerve stimulation on pain and fatigue using transcranial direct current stimulation in fibromyalgia patients. Journal of Neural Transmission. 2017;124(7):799–808.
Read the publication in Journal of Neural Transmission
Non-Invasive Brain Stimulation on Clinical Symptoms in Multiple Sclerosis Patients: A Systematic Review and Meta-Analysis
Uygur-Kucukseymen E, Pacheco-Barrios K, Yuksel B, Gonzalez-Mego P, Soysal A, Fregni F. Non-invasive brain stimulation on clinical symptoms in multiple sclerosis patients: a systematic review and meta-analysis. Multiple Sclerosis and Related Disorders. 2023;78:104927.
Read the publication in Multiple Sclerosis and Related Disorders
Authored by Prof. Dr. Sven Vanneste, Prof. Dr. Dirk De Ridder and Jan Ost - 09/10/2026
Other conditions that we treat
Auditory and vestibular disorders
These disorders are related to hearing and balance and can have a major impact on your daily life.
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Neurological and cognitive disorders
These disorders affect brain function, which can lead to problems with attention, memory, and motor skills.
Mental and emotional disorders
Mental illness can be deeply rooted in neurobiological dysfunctions.
Chronic Pain and Fatigue Syndromes
Chronic pain and fatigue are often difficult to treat with conventional methods, especially when there is no obvious physical cause.
Fatigue syndromes and sleep disorders
Sleep and energy management are essential for brain function. Problems in these areas can lead to severe tiredness and difficulty concentrating.
Headache and facial pain disorders
Headaches and facial pain can result from complex neurological processes.
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Our specialists are here to help you. Find out what treatments are possible or schedule a consultation.