‘Brain fog’ is a common and life-limiting symptom of ME/CFS. It is the term used to describe a range of cognitive difficulties which (in the new NICE guideline) include “problems finding words or numbers, difficulty in speaking, slowed responsiveness, short-term memory problems, and difficulty concentrating or multitasking”.
To work out what goes wrong in the brain to cause these problems, we first need to understand exactly what we mean by cognitive function and how it works.
In this series of two articles, Dr Eleanor Roberts explores those very questions, including what areas of the brain are involved in cognitive function, how information is transmitted between those areas, and (next week) research into cognitive dysfunction in ME/CFS.
Cognition includes all brain processing involved in our understanding of thoughts, processes, experiences and senses, as well as knowledge acquisition. One major facet of cognition, and the one concentrated on here, is executive function.
Executive function includes several components:
- Attention/goal-directed behaviour – focusing on what you are doing and what’s going on around you.
- Self-monitoring – monitoring your thoughts and behaviours to attain your goal.
- Cognitive flexibility – ability to switch how information is processed according to what’s going on at the time.
- Working memory – retaining information that’s used immediately to aid other cognitive functions such as attention, learning, reasoning and problem-solving.
- Initiation – ability to start a task without prompting.
- Interference control – filtering of irrelevant factors, both internal and external, that can interfere with a task.
- Planning/problem solving – ability to organise your thoughts logically and set a goal using known and incoming information; this can also require selective attention, cognitive flexibility, working memory and initiation.
- Sensory integration – coordinating internal and external tasks and thoughts with messages obtained from the senses.
- Emotional regulation – appropriately responding emotionally to current circumstances.
The diagram below shows the different regions of the brain, including those areas that control and coordinate executive function: the dorsolateral prefrontal cortex (dlPFC), the lateral orbitofrontal cortex (lOFC) and the anterior cingulate cortex (ACC), all of which are part of the frontal cortex.
For example, attention/goal-directed behaviour is controlled by the ACC, while self-monitoring is controlled by both the dIPFC and ACC, and initiation by the IOFC.
These three areas can connect to and influence, not only each other, but also other parts of the brain, as illustrated in the diagram below.
For instance, signals sent ‘down’ into the caudate and thalamus can be linked up with signals coming from the ‘lower’ parts of the brain such as the cerebellum and brainstem. This is important in understanding cognition as, while these frontal-lobe areas might seem to be structurally and functionally sound in an individual, they can be affected by problems in other parts of the brain, which would therefore have an impact on executive function.
One vital part of cognitive function outside of the cortex is the thalamus. This processes sensory information and relays it to the cortex, as well as receiving information from the cortex, which it can process and send throughout the brain. Under the thalamus is the hypothalamus, which provides a vital link between the brain and the body in that it helps maintain body temperature, blood pressure and calorie intake, partly through release of a variety of hormones.
The thalamus also has connections to the cerebellum, whose main function is motor coordination, as well as having a role in cognitive functions such as attention and language. The brainstem is vital to maintain consciousness as well as controlling basic functions such as heart rate and breathing. While it is not directly involved in executive functions, its connections to other areas (especially the thalamus) mean that damage here can still affect cognition.
The brain is made up of a number of different types of cell, but neurons are what most people are thinking of when they talk about ‘brain cells’. The diagram below shows that neurons consist of a central body; a tube-like projection called an axon, which sends signals; and branches called dendrites and neurites, which receive signals.
The body of the neuron sits in a particular structure, such as the cerebral cortex, which is known as grey matter. The axons that go from one brain area to another are covered in a fatty wrap known as myelin (think of the plastic around electrical wire), which is actually the extension of another cell type called an oligodendrocyte wrapping itself around the axon. Due to the light colour of this wrapping, it is known as white matter.
Messages within and between brain areas are passed from one neuron to another via a type of chemical called a neurotransmitter, which is held in packages at the ends of axons. A message generated in the central part of the neuron, which may originate in that neuron or be a translation of one ‘picked up’ by a dendrite from another neuron, is passed down the axon via a series of chemical exchanges. This causes a neurotransmitter to be released from the end of the axon (terminal) to send the message to neurons in the immediate neighbourhood.
Some messages are only passed locally (with axons acting like B-roads inside a town), while some travel to different brain regions along the axonal equivalent of motorways in bundles or tracts of several thousand axons.
Many executive-function circuits involve an excitatory neurotransmitter called glutamate, which is made from glucose primarily by another type of brain cell known as astrocytes. Other neurotransmitters involved in cognition are noradrenaline (also known as norepinephrine), dopamine and acetylcholine (which are made in brainstem neurons that connect to other brain areas), and histamine.
Cognitive function therefore involves a complex interaction between different brain areas and neurotransmitters. Because of this, the brain fog of ME/CFS is almost impossible to pin down to a problem in only one specific area of the brain.
In part 2 of this article, Eleanor looks at some of the research studies that have tried to improve our understanding of cognitive dysfunction in ME/CFS.
A comprehensive review of the brain and cognitive function can be found in these three articles from Jiawei Zhang at Cornell University: