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Why can’t I meditate? Discussion of the neurobiological obstacles faced by those with ME/CFS (and other inflammatory / energetic / stress disorders)

Western medicine may be late to the party but, in recent years, as begun to cultivate a relationship with meditation. And the early signs are decidedly positive; as more and more randomized controlled trials are performed, researchers are finding that meditation reduces inflammation, reduces anxiety, improves attention span and even interpersonal interactions.

However, most people I work with see dismal results. This is itself is not what worries me, instead it’s the pervasive advice that individuals often encounter when they fail to get going with meditative practices: “it’s just your ego… it doesn’t want to let go. I used to have the same problem”. The advice is often followed with an unrequested anecdote that outlines how this superior being achieved their ego-less state and deep acceptance of everyone they encounter, complete with the gratifying details of their gap year, use of terms like moksha and satori and their disdain for people who are ‘unenlightened’.


Meditation – My definition

More than most areas, there is a need to be clear in what I mean by meditation. The subjective nature of the process lends itself to individual interpretation and, as a result, miscommunication. So, from this point on until the end of the article, please accept this as my working definition for meditation: a mental process that deliberately employs one part of the body/brain/mind to tactically quieten other structures, with the goal of removing inhibitory activity of core sensory signals so that such content can be processed (ie. allocated meaning and timelined) and maladaptive rules associated with such content can be updated.

This definition expressly includes a wide variety of approaches. I point this out as it is a common perception that meditation equals mindfulness meditation. However, while this may be the most popular, it is worth noting that there is a wide range of techniques that have been developed across the world and that individuals can enter meditative zones through a wide variety of entry points (some of which focus heavily on bodily movement while others on total stillness, some that aim to increase focus on a specific subject and others on the breath or on maintaining absence of thought, some with mantras and others in silence, some assisted by plant medicines and others without, etc).


Meditation from a neurobiological perspective: Basics

Any discussion of the neurobiology of meditation is best begun with an introduction of two networks that drive brain function in a passive (‘daydreaming’) and active state, respectively. Enter the Default Mode Network and the Task Positive Network. The Default Mode Network is a collection of hubs that are located across the brain, that work together to allow us to function in life without second-guessing every single choice we make. To do so, the network permits connections between circuits that convey sensory input in our environment and those that hold ‘rules’ and values on what to make of such input. This is done with basic, association-based rules that are initiated reflexively. This allows us to open doors without having to study the mechanism of handle and lock, allows us to know what dishes we like when ordering off a restaurant menu and whether something is safe or dangerous. It also plays a central role in determining our values and sense of identity and becomes hyperactive when our belief systems are challenged.

It is through this effect that the Default Mode Network can see us become ‘stuck’ in our beliefs and irrationally reject new information that disagrees with our pre-held perceptions (aka cognitive dissonance). Just as importantly, the reflexive recruitment of the amygdala means that we can respond quickly to threats but, if this network is not tamed, sensory signals that are even mildly associated with danger can result in the deployment of a pronounced stress response. Such a stress response forces us into a threat perception mode, whereby we are externally-focused, hypervigilant and scanning for the threat. The consequences of this action are twofold:


  1. Everyday sensations, transmitted regularly throughout a standard day, now activate the stress response (inducing the release of adrenaline, plus the diversion of valuable resources away from health-related tasks and towards emergency readiness)
  2. Each time we get close to accessing content for which we have laid down a maladaptive association, we become hypervigilant and enter an external, ‘scanning’ mode (terminating the introspective state needed to process and rewire such associations), sustaining this maladaptive pattern

The second effect is key in why traumatic memories can become inaccessible. Indeed, the Default Mode Network is repeatedly shown to be overactive in PTSD and depression. One of the most powerful mechanisms of meditation is the quietening effect on the Default Mode Network. This helps overcome the ‘hijack’ above – less default mode network activity means less maldaptive ‘tagging’ of incoming sensory stimuli, less activation of the stress response, and less barriers into introspective processes.


Neurobiological mechanisms

A 2014 review assessed the accumulative findings of 248 studies that measured the impact of meditation though imaging techniques. The various research teams repeatedly found that the impact of meditation is mediated by changes in the prefrontal cortex, posterior cingulate cortex (the seat of the default mode network), insula, amygdala, basal ganglia and thalamus.

What do we need to know about these areas?

Prefrontal cortex – a key area for executive function, making sense of things, mood, emotional processing but also an important ‘top-down’ regulator of emotionality. The cerebral cortex can be subdivided into the frontal, parietal, occipital and temporal lobes, although the frontal (especially the prefrontal cortex) is front and centre, both in physical location and in function. The prefrontal cortex aids in planning, in interpreting reality and making choices. It is also crucial to exert a ‘brake’ on the activation of the stress response. Meditation activates the prefrontal cortex to improve emotional regulation.

Amygala – the famous ‘fight or flight’ centre. The amygdala, so-called because it resembles the shape of an almond. It sits at the centre of the brain and, while it also plays an important role in regulating emotion and memory, its primary role is as reflexive response centre to danger (real or perceived), hijacking the brain’s normal operation through activation of the sympathetic nervous system. Such activity goes onto activate the adrenal response (including the release of adrenaline) and changing vagal tone. Meditation has repeatedly shown to reduce activation of the amygdala.

Thalamus – the central relay station for sensory transmission. A rule of thumb is that, if it produces sensations, it runs through the thalamus to be sent to the relevant cortex (auditory, visual, etc) to turn create consciousness. When we are experiencing a sensation / event, this is mediated by firing of circuits that connect these relevant area of the cerebral cortex and the thalamus (“cortico-thalamic loops”). The thalamus exerts the role not just of relay but also as a filter of information; central to the effects of psilocybin (the active chemical in “magic mushrooms”) is suspension of the thalamic activity. This allow for unrestrained flow of thoughts, synesthesia (the sensory inputs to be experienced by another sensory pathway, aka ‘seeing music’ or ‘tasting colours’) and improved free association. Meanwhile, meditation modifies the way the thalamus connects with other areas of the brain in a way that appears to improve emotional regulation, attention, self-awareness, pain management and perspective-forming.

Hippocampus – the reflexive memory centre. The hippocampus stores experiential (episodic) memories, doing so in an association-based manner. This area is particularly central to learning in toddlers, who may not understand the behaviour of electrical wiring but know to not stick their fingers in a live socket a second time (touching wall-mounted white box = pain = bad = aversion). What is particularly key about the hippocampus is that, should it have experienced key aspects of a situation previously without negative consequences, it can limit amygdala activity; the hippocampus is rich in cortisol receptors and cortisol activity here has a powerful impact on reducing activation of the HPA axis. Reduced hippocampal activity is unsurprisingly found to be a risk factor for PTSD although the relationship is circular, with long-term stress a driver of reduced hippocampal volume. Research demonstrates how the trauma response can be deactivated when traumatic memories have been processed and assigned into the hippocampal timeline, allowing them to become ‘just a memory’ and no longer triggering physiological readiness in the present moment. Meditation has been shown to increase activation of the hippocampus.

Posterior Cingulate Cortex (PCC) – the ‘seat’ of the Default Mode Network. As mentioned above, this area is key in establishing consistency in our preferences and beliefs, but can become overactive when such beliefs are challenged. Meditation is shown to improve connectivity between a hub of the prefrontal cortex/insula and the PCC, permitting improved regulation of this key network.

Insula – the relay station that provides information on the inner environment and is therefore the centre of bodily awareness. It is therefore an important component in transmitting signals that convey pain and letting us know how we feel. The insula is one area where region-specific activity is key, with right and left regions subject to ‘seesaw’ regulation of one another. Excessive activity of the right insula is known to activate sympathetic activity but excessive activity in the left insula is shown to induce alexithymia (a condition where we do not know what emotion we are feeling). Meditation has a regulating/balancing effect on the activity of the insula, allowing for both improved bodily awareness without emotional dysregulation.

Basal Ganglia – the ‘go’ zone of the brain. The basal ganglia was once considered ‘just’ a relay station that linked decisions in the prefrontal cortex to voluntary movement, a finding that helped explain the role of this area in Parkinsons disease. However, it is clear the basal ganglia’s role goes beyond this and has big say in switching gears within the brain, specifically switching off the default mode network and activating parts of the task-positive network. This would naturally be a vital aspect of entering a meditative state and, in a finding that comes as no surprise, the basal ganglia is particularly active when entering a meditative state, supporting its role as a key inducer of this state.


Neurobiological deficits in ME/CFS

We know that it is impossible to meditate while running from a tiger and this can account for difficulty any of us may have in entering a meditative state following episodes of acute stress. But how does this play out when the entire system is subject to multiple/ongoing disturbances from within? Disturbances that result in ongoing activation of the amygdala (and subsequent hypervigilance)? To this end, there are several obstacles that call for discussion for individuals with ME/CFS, which centre on neuroinflammation, stress responses and problems with energy metabolism.

Neuroinflammation has long been a focus for researchers seeking to understand the mechanisms driving ME/CFS. Indeed, recent decades have seen improved understanding of inflammatory dysregulation in this condition, with research demonstrating overactivation of microglia (the main immune cell of the brain) as a common factor in these syndromes. Such overactivates often culminates in self-perpetuating cycles that play out between neuroinflammation, glutamate, oxidative stress and mitochondrial energy production (see Pall & Satterlee, 2001, and Morris and Maes, 2012). In 2014, Japanese researchers provided clarity on exactly how such inflammatory-driven issues impact on brain function, becoming the first team to locate the precise areas driving dysfunction through PET imaging. They found particularly high inflammation in the cingulate cortex, hippocampus, amygdala, thalamus, brain stem.

Inflammation has a habit of limiting the function of cells while, as a result of the excess glutamate, creating an ‘always-on’ response. The end result being that key centres never fully switch on when they should and neither do they fully switch off. Chaos abounds. Without sufficient activity in the cingulate cortex, we can expect difficulty controlling our stress response.  Without the hippocampus performing its job effectivity, we may react to threats that aren’t there. If the amygdala is always subject to stimulation, it may be near-impossible to come down a notch. If the thalamus function is disturbed, integrating sensory signalling will become much harder.

Central to the pathology found in ME/CFS is a maladaptive stress response. Stress is known to be a risk factor (accumulated life stressors and stress burden of the last 12 months are predicative of developing the condition) but one of the defining factors is the metabolic interplay between such loading and the metabolic response to it; individuals with ME/CFS show increased oxidative/nitrosative stress that not only increases the activation of the stress machinery, but also impairs their cortisol response (meaning that they are unable to switch it off). A continuously activated stress response can result in endoxemia which not only drives inflammation but can then downregulate cortisol receptors, further compromising their stress-regulating effects and further contributing to a self-perpetuating cycle.  Stress responses have shown reliable effects on the prefrontal cortex, insula and especially the amygdala.

Another major feature of ME/CFS are energy deficits.  Studies have shown ME/CFS patients have impaired PDK activity, which limits their ability to extract energy from carbohydrates. A 2020 paper provided further nuance, showing that mitochondrial dysfunction was universal across ME/CFS patients but impairments in glycolysis were a feature of those with more severe illness. Research on 612 different metabolic markers found that, compared to controls, ME/CFS patients showed abnormalities in 20 different metabolic pathways. Energy deficits can impact on physical performance (most notably, tolerance to physical exercise) and a wide range of challenges in brain function. The literature shows how low energy status ties in with reduced activation of the prefrontal cortex, vagal tone, and control of glutamate activity. Low energy also results in excess activation of the paraventricular nuclei (and therefore the HPA axis). Low energy states go well beyond simply leaving us with brain fog or low mood; researchers have demonstrated that poor energy production can contribute to the development of psychiatric disorders, with particular focus on the reduced ability of the prefrontal cortex to modulate the stress circuitry (such as the amygdala and thalamus, highly relevant when considering the role of energy availability in meditation).

While the above factors can be considered to have a ‘general’ effect on how individual brain sections are provided or denied resources, we should also integrate specific changes that are the culmination of such physiological obstacles, coping mechanisms and zone-specific metabolic disruption. A 2020 study conducted a meta-analysis on 63 research projects that investigated the differences found in ME/CFS patients upon neuroimaging. They noted a key theme, that ME/CFS patients not only showed different activation profiles upon baseline – reduced activity in the prefrontal cortex and brain stem – but also needed to work harder when subject to cognitive challenges, with the amygdala, hippocampus, basal ganglia and thalamus all hyper-activated in such circumstances:


Image from: Shan et al (2020): Neuroimaging characteristics of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review.

This study is pivotal in both our knowledge of the mechanisms involved but also in reconciling the apparent conflicts between some studies; it is a common to see widespread agreement that a certain area is relevant in chronic illness, but with some researchers finding high activity and those finding the opposite. While the tendency in Western medicine is to determine a fixed, black-and-white pattern for physical structures in any given disease state, we yield much better understanding through accepting that long-term overuse of a structure can result in damage (and subsequent loss of mass/function, via oxidative stress). As such, these findings can be considered different sides of the same coin.

Such perspective speaks to the need to understand how imbalances found in the chronically ill may adhere to a common template, but the pattern we see on the frontline may differ based on how long such issues have been present. It is also important to consider common factors that are commonly found in ME/CFS individuals, particularly those that are not necessarily determined to be part of the condition. And such individual differences always occur, although it appears the biggest discrepancies are found in the contributing factors that initiate problems we encounter, rather than the nature of the problems themselves. When it comes to meditation, the main issue is clear, and this in in the crossover between the neurobiological challenges found in ME/CFS and the structures that are employed in the process:


The more we examine the deficits found in ME/CFS, a disease state characterized by the self-perpetuating cycles that are driven by inflammation, stress and poor energy availability, the more clear it becomes that this is a group that a) stands to benefit most from the specific effects of meditation yet b) is less able to access the state and the benefits it offers. Ironically, this stands out as yet another self-perpetuating cycle whereby the physiological dysregulation limit their access to this healing state, and the lack of access leaves them unable to deploy their own self-corrective mechanisms and therefore subject to ongoing physiological dysregulation.


On the frontline: problems

I have spent many years tracking the outcomes achieved by those with ME/CFS, specifically in regards to what changes induced the improvements we seek; doing so has repeatedly demonstrated the powerful two-way connections between body and mind. The body influences the mind and the mind influences the body. A further, intriguing layer to this pattern, and one that has emerged repeatedly, is how physical problems that simply will not budge from the usual interventions often melt away when a psychological hurdle is tended to. But it also works the other way round.

Physical limitations on meditation practice are especially common in the early stages. They do not play our in an all-or-nothing pattern, instead presenting in shades of grey (depending on the number of obstacles and the severity), but it is exceedingly rare to see individuals at the start of their journey who have a ‘fair’ chance of benefitting from meditation, just as it is norm to see access to these states improve in line with physical progress.

These obstacles tend to centre on energy, inflammation and activation of the stress response. While this trifecta is something I expect to see in all chronic cases, the exact symptomology will vary and especially the contributing factors. Therefore, it is vital to undertake screening to determine the root causes for each individual. However, certain principles have emerged when it comes to tending to this fundamental issue.


On the frontline: solutions

While the multi-layered and self-perpetuating nature of the challenges described above can appear daunting, it is also important to stress that this leaves us with a multitude of ways that we can help. Such options are naturally too numerous to cover in full, although the most reliable means of removing these obstacles include:

Cortisol signalling – cortisol is a misunderstood hormone, with the public perception of it being as ‘bad’ due to its association with stress. However, cortisol is extremely helpful during times of stress and, whether directly or indirectly, can influence almost every key brain area discussed above. It is also relevant that ME/CFS individuals have propensities towards low cortisol production and reduced cortisol sensitivity, limiting the ability of this steroid hormone to control inflammation, maintain resilience to stress and regulate important brain processes. This is a concern; cortisol directly reduces activity in the amygdala and gives us better leverage in controlling it. It also has a fundamental effect on permitting serotonin trafficking, which can play a role in maintaining healthy activity across the frontal cortex and regulating the insula activity. Interestingly, the use of cortisol analogs has been shown to improve symptoms of PTSD after just one dose (both here and here). While dosing with hydrocortisone is limited due to its effects of downregulating receptors, we do have a number of reliable strategies to support cortisol signalling. Licorice Root, Korean Ginseng, and anything that limits endotoxemia (which may otherwise downregulate the cortisol receptors) are good starting points,

Endotoxemia – endotoxemia refers to scenarios where fragments of dead bacteria (called endotoxins or lipopolysaccharides) move from the gut into the bloodstream. While they cause little problem in the gut, increased intestinal permeability can permit their movement across this barrier and cause a host of problems (and contribute to a self-perpetuating cycle that is a common in chronic disease, and discussed here). A subject that needs much more discussion is how there are two forms of ‘leaky gut’, paracellular and transcellular; the former relates to the separation of cells that maintain the integrity of the gut lining, the latter to the deliberate opening of the channels. The former can be driven by oxidative stress as a consequence of inflammation, with dysbiosis, hypoxia/physical tension, alcohol, gluten, allergies and food chemicals (lectins/oxalates/etc) frequent offenders. But just as important (and, often, more so) is the way that stress drivers the later, with sympathetic nerves triggering the opening of channels in the cells themselves (in an attempt to access more sugars and salts, but allowing in the endotoxins as a result).

Endotoxins are shown to have a direct role in the processes we have discussed above, with studies showing that injections induced depression via overactivation of the right insula (again speaking to the important of bilateral balance at this key structure). Endotoxins also contribute to overall inflammation that, as discussed above, can have such measurable disturbances in key areas (cingulate cortex, hippocampus, amygdala, thalamus, brain stem). Therefore, any steps that remove such obstacles are likely to have important effects on the frontline results we see. This is where it is necessary to carefully consider what factors are driving increased permeability in each individual (and where testing can be helpful; consider the Organic Acids test, GI stool tests, Intestinal permeability screens).

Physical tension – arguably one of the most vital concerns for successful meditation/introspection, and yet one of the least discussed. Physical tension activates the left insula (which, as discussed above, can inhibit sensory signals that allow us to appropriately check in on our inner environment and get a measure of our emotional state). It can also activate the brain (notably the insula, ACC and cerebellum) in a pattern that mirrors that found in pain conditions. Tension also has a reliable effect on proper breathing, which is important for pro-introspective effects at both the insula and in the frontal cortex. A growing field of evidence indicates that the movement of the diaphragm is key in modulating signals sent ‘upwards’ to the brain. Multiple options exist to help resolve stored tension,  although Tension Release Exercise (also called Trauma Release Exercise), somatic/’bodymind’ approaches (such as Somatic Experiencing, Reichian Therapy) or breathwork (holotropic breathwork, transformational breathowk) have proved most beneficial for the individuals I work with.

Energy production / signalling  – existing (dogmatic) scientific paradigms make it difficult for researchers to fairly measure the effects of improving mitochondrial performance on meditation (the reductionist approach allows for the measurement of, say, Co-Q10 supplementation, but not for a customized support package that would actually tend to the mitochondrial requirements of each individual). However, despite these hurdles, the frontline pattern I have observed is very clear and is supported by the data we have. This comes in the form of mechanistic support, showing clear links between low energy states and dysfunction in highly relevant brain areas, but perhaps the connection between energy availability and introspective processes comes from an Israeli study on hyperbaric treatment; the research showed that this oxidative therapy allowed for the recall of traumatic memories, as a result of restoring normal metabolism of key brain cells (in the prefrontal cortex). Such findings should have a profound impact on the way we understand the exquisite interplay between body and mind.

Energy signalling makes just as important a contribution as energy production. This is where insulin, thyroid and leptin sensitivity play a major role, with insulin resistance the most likely (now found in 88% of the wider population) and also easiest to resolve.  Insulin resistance can reek havoc with neuroplasticity and can contribute to poor memory recall as a result of reduced volume of both the prefrontal cortex and the hippocampus. Obese individuals show reduced engagement in the hippocampus and several cortical areas (notably at the parietal cortex, a contributor to sensory processing). However, hypothyroidism is well-linked with mental health disorders, demonstrating again how fundamental energy availability is when it comes to the workings of the mind, and low thyroid activity shows measurable changes in the workings of the anterior cingulate cortex, posterior cingulate cortex, basal ganglia and amygdala (all areas key in the meditation process).

Energy availability is an area that call for personalized assessment of the areas that are running in a suboptimal fashion, and the factors that contribute to it (eg. some may experience impaired carbohydrate metabolism, some may suffer with mitochondrial hypoxia, while others may see challenges due to a lack of Carnitine, B vitamins, Magnesium or through altered redox status). While lipids, insulin-related markers and copper/iron status can be pivotal, the first step here is to run an Organic Acids Test to determine what obstacles are at play in the individual, and thus what supplement, dietary and lifestyle support are appropriate.

Stress – always the biggest factor, while also the most common and most misunderstood. When I speak of stress, I speak of the physiological response that is deployed to increase energy availability in circulation in order to deal with the challenges/threats our sympathetic nervous system expects to face. This is important to emphasize, as the post-it-note culture permits a pervasive message that a) stress is something that happens to us and b) the determinant of if we are ‘stressed’ or ‘not’ is how many hours we have been working. Such ideas are entirely inconsistent with the patterns seen in real humans and in the literature, which show that pronounced stress responses can be initiated by having our values/positions challenged (your limbic system does not enjoy identity politics) and through suppressing emotional impulses (eg. not crying during a job interview, being a ‘good wife/husband’, reflexively burying fear or sadness, etc). In any case, while these subjects call for detailed exploration in their own right, overactive stress responses in the absence of actual threat remains one of the defining features of ME/CFS. This speaks to both the need for those with ME/CFS to undertake additional steps to aid in processing (such as meditation) but also, in a cruel irony, why it is more difficult for them to access. This is where steps to address undue activation of the stress response should first include a thorough investigation of any burden that results from mitochondrial deficits, inflammatory triggers and undue postural tension. Next up comes cortisol support and, if appropriate, neurotransmitter support. At this stage, we can expect an improved passage into introspective states but that such progress will be substantially more efficient with external regulation and experienced guidance (ie. working with an appropriate practitioner/group).



When it comes to meditation, there is little controversy on how the practice can help. However, ideas may easily appear idealistic for those with multiple physiological obstacles in accessing such benefits. While clearly not the only group that are subject to barriers in entering a meditative state, ME/CFS patients stand out in both how they stand to benefit more from meditation but also in how they are subject to multiple challenges that directly impair function in the very brain areas that both help induce the desired state and allow us to benefit from the process. While addressing these obstacles may require a thorough analysis to ‘work backwards’ from the observed dysfunction to the root cause, doing so has freed up countless individuals to harness the benefits of meditation in literally rewiring the central nervous system, in doing so breaking some of the most deep-rooted self-perpetuating cycles that are so characteristic of the condition.




Because the scope of this article is on the ability of ‘regular’ individuals to engage in (and benefit from) meditation, it does not consider the impacts of long-term meditation (which, as we may expect, includes further changes beyond that seen in the short-term studies above).

The discussion also does not delve into the different regulation of neurotransmitters found in ME/CFS. Such differences relate to serotonin (such as a reduction in serotonin stores and altered 5HT1a binding), dopamine (low dopamine activity, reduced binding in the basal ganglia, reduced symptoms following use of dopaminergic agents) and in some cases glutamate/GABA and beyond, although these imbalances obviously have important interactions with the neurobiological differences outlined above.

Equally, it does not delve into the exquisite complexity of the effects that meditation has on the cerebral cortex. This area can be sub-divided into prefrontal, frontal, parietal, occipital and temporal lobes;  each provide different contributions to our mental state. The effects of meditation are heavily centred on the prefrontal cortex but typically work in concert with some of the other lobes to mediate effects. I have avoided deeper discussion here as this additional nuance does not impact on frontline recommendations while potentially diluting from the key message here, which is that removing metabolic obstacles that limit optimal regulation of the prefrontal cortex area is an important consideration for individuals with chronic inflammatory disorders that are struggling to meditate.

One last point is that is does not discuss scenarios whereby individual can successfully achieve introspection, but find the increase in sensory intensity and altered psychological state can have destabilizing effects (as seen in a small but significant number of individuals with PTSD).


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