Meditation – Proposed Mechanisms and Potential Clinical Application

Stress, anxiety and depression account for 11.7 million days of work-related stress, amounting to an average of 24 days per year and 488,000 cases in 2015/161,2. Job insecurity, work intensity and interpersonal conflicts all contribute as stressors, with the modern environment exposing us to many stressful conditions3. These have subsequent cardiovascular and neuroendocrine consequences from increasingly being in the sympathetic state, impacted by increased cortisol, catecholamines and vasopressin, and the decrease of gonadotropins, thyroid function and insulin activity4,5.

Mindfulness is a practice which changes how we respond and perceive stress, by cultivating coping skills and awareness of the mind-body connection. The inner focus is known as meditation4. Mindfulness is understood to stem from Hindu and Buddhist origins, but also has a history in the Jewish, Christian and Islamic faith systems. Western philosophers also use the same concept of mindfulness, with the universal aim to become present in a non-judgmental way6.

In this article, the terms ‘mindfulness’ and ‘meditation’ are used interchangeably, but there are three main categories:

1) Concentrating on a particular object of focus, using a mantra or breath, i.e. ‘concentrative meditation’;

2) Observing the thoughts and not reacting to them, where awareness is raised and experiences accepted, i.e. ‘mindfulness meditation’7,8; and

3) Transcendental meditation (TM), which is neither concentrative nor mindful, but one of ‘effortless transcending’, by the mind settling down to a calm and alert state to ‘experience consciousness’9.

The practice generally involves quiet sitting or lying, employing one of the above techniques10.

This article gives an overview of the proposed mechanisms and potential clinical applications for meditation.

Changes in cortical-thalamic activity in meditation

Research based on imaging studies indicate that in meditation types which require motivation and concentration, the pre-frontal cortex (PFC) (especially the right hemisphere) and the cingulate gyrus are activated (see figure 1). However, for meditation techniques which use external guided meditation, rather than internal repetition, there was a decrease in frontal activity11,12.

Figure 1. Anatomy of the brain. (BrightFocus Foundation (2016))13.

On activation (see figure 2), the PFC uses the excitatory neurotransmitter glutamate to activate the thalamus, and the thalamus relays sensory information, both spatial and visual, to the cortex. Visual information goes to the striate visual cortex, and spatial information transfers to the posterior superior parietal lobule (PSPL). The thalamic reticular nucleus uses the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), and GABA reduces input to the striate cortex and PSPL (particularly the right), referred to as ‘functional deafferentation’. Less input and stimuli to the striate cortex and PSPL increases concentration11,12.

Figure 2. PSPL deafferentation (Mohandas, E. 2008)14.

Limbic system

Research indicates that meditation also affects the limbic system. The hippocampus is connected to the PFC, other areas of the neocortex, the amygdala and hypothalamus. Based on increased hippocampal and amygdala activity in meditation, researchers propose that the right hippocampus is stimulated by the deafferentation of the right PSPL information in meditation, or directly stimulated by the thalamus using glutamate, to regulate cortical stimulation. Right hippocampal stimulation affects the right lateral amygdala, bringing experience of emotion, attention and some images in meditation11,12.

Stimulation of the right lateral amygdala leads to stimulation of the ventromedial hypothalamus, activating the peripheral parasympathetic nervous system (PNS). This causes a reduction in heart and respiratory rates, leading to lowered noradrenaline production which lowers input to the PSPL, causing deafferentation, and lowered input to the hypothalamic paraventricular nucleus. Lowered hypothalamic paraventricular nucleus stimulation means less Corticotrophic Releasing Hormone, resulting in lowered cortisol production11,12.

Change of awareness with neural and physiological consequences

During meditation, the process of awareness can be associated with the Default Mode Network (DMN), parts of the brain including the medial PFC and posterior cingulate cortex. These are active when the person is awake but they are not focused on the external world, i.e. in a passive state15,16,17. The DMN is associated with self-referential processing, mind-wandering, with the latter being associated with lower levels of happiness18.

Another model based on imaging studies (see figure 3), proposes that during and after mindfulness meditation, the DMN is deactivated, there is increased PFC activity, increased activity in the PNS, and lowered activity in the thalamus (sensory) and amygdala (emotional relay centre), and increased cortical function connectivity. DMN deactivation is linked to synchronization of the cardiac and respiratory centres, and may be possible even after only 5 days of meditation training15, 19.

Effort or concentration lowers activation of the DMN, while DMN activity is increased when there is low cognitive load. TM increases DMN activity compared to just closing the eyes15, 20, 21. Regular activation of the DMN may help to promote neuroplasticity (see below)15.

Figure 3. Mind-body response before and after mindfulness meditation22.


With continued wilful meditation practice, PFC activation should continue. PFC stimulation leads to more free glutamate, which can stimulate the hypothalamus to produce Beta-endorphin, an opioid which reduces pain, fear, respiration and promotes feelings of pleasure, which are reported experiences in meditation. Other neurochemicals are also likely involved11.

Glutamate stimulates N-methyl-D-aspartate receptors (NMDAr) but high levels are neurotoxic. During intense meditation, researchers suggest that the brain may, as a protective mechanism, decrease the enzyme N-acetylated-a-linked-acidic dipeptidase, which converts N-acetylaspartylglutamate (NAAG) into glutamate; increased NAAG, an NMDAr inhibitor, may protect the cells, albeit it may cause states described as “mystical…out-of-body and near-death experiences” acting in the same way as the disassociative hallucinogens such as ketamine and nitrous oxide, where ketamine is understood to block NMDAr11,23.

Activation of the lateral hypothalamus can also stimulate the serotonergic pathway, where increased levels of the serotonin metabolite, 5-HT have been found. Increased serotonin can affect dopamine, creating feelings of joy11. Increased levels of melatonin have also been observed, due to stimulation of the pineal gland via the lateral hypothalamus, perhaps reducing pain12.

Brain waves

Brainwaves are produced by the electrical impulses from the neurons interacting in the brain, with specific bandwidths relating to particular functions and mood, and observed in different types of meditation: increased alpha coherence (related to calmness and alertness) in TM, increased theta wave activity (learning and memory) in a concentrative Zen meditation and increased gamma activity (processing information from different brain areas) in a mindfulness meditation15, 24,25,26.


Telomeres, the DNA-protein protective caps at the end of chromosomes, shorten during each cell division, and when they become too short, the chromosome degrades and the cell dies. The rate of shortening relates to the rate of aging, which may be increased by inflammation and oxidative stress. Telomerase, a reverse transcriptase enzyme, elongates telomeres and is linked to regulating NF-κB activity, the transcription factor found in aging cells27,28,29. Chronic stress has been found to reduce telomerase activity, speeding up telomere shortening and early aging29,30.

A study on participants after a 3-month meditation retreat, with a daily 6 hour practice, showed an increase in telomerase activity, while a separate study involving 3 months of lifestyle changes including diet, exercise, stress management and social support increased telomere length after a 5 year follow up31,32. Concentrative meditation techniques from the yogic tradition were found to reduce NF-κB and inflammatory cytokines in a group of caregivers who practiced for 12 minutes a day over 8 weeks33. 20 minutes of guided meditation before a stressful event was sufficient to reduce the stress response in another study34.


A study from 2005 on Western practitioners indicated, using MRI, that regular mindfulness meditation may affect the physical structure of the brain, by increasing the thickness of the cerebral cortex for areas involved in concentration, interoception and sensory processing, including the PFC and right anterior insula. Other forms of mediation and yoga may also affect the cortex but in a different way, depending on the technique12,35.

A 2012 study indicates that rather than just focussing on thickness, the gyrification, or pattern or degree of cortical folding was larger for meditators, and increased for the number of years meditating in the right anterior dorsal insula. Increased insula gyrification may help with autonomic, affective and cognitive processes36.


Neuroprotection and cognitive decline

Studies suggest that mediation can slow, delay or reverse age-related brain degeneration37,38. Possible mechanisms include:

1) Increasing grey matter through ‘environmental enrichment’, i.e. engaging the brain in new activities increases Neural Growth Factor, neurogenesis and synaptogenesis for both neural plasticity and cognitive plasticity, in conjunction with low dietary fat, dietary restriction, resveratrol and exercise39,40. The increases seen in cerebral grey matter in the left hippocampus, in the posterior cingulate cortex, the temporo-parietal junction and the cerebellum, may counter the normal loss in areas associated with learning and memory, emotional response, self-referring processing and perspective taking37,41; alongside

2) Cerebral grey matter conservation over time.  This may be due to lower stress levels, changing the immune response in cytokine production, and lowered HPA activation with subsequent cortisol production37,42,43. Reducing stress-induced cortisol may increase Brain-Derived Neurotrophic Factor, thereby having a neuroprotective role44. However, brain matter might be conserved due to healthier lifestyle habits, increased self-awareness, intelligence and other factors, including the types of people drawn to a long-term meditation practice may be of a certain disposition at the outset37.

Clinical application

Meditation has been found to have wide benefits and improve a wide range of conditions, including:

  • Developmental dyslexia and ADHD by reducing impulsivity, improved concentration and lowering stress and anxiety in ADHD through TM in particular9,45;
  • Anxiety through self-reflection by activation of the anterior cingulate cortex, ventromedial PFC and anterior insula46;
  • Addiction through strengthened DMN connections47;
  • Food cravings and unhealthy food choices, by viewing thoughts as transient48;
  • Other mental health disorders, such as bipolar disorder (using Mindfulness-Based Cognitive Therapy (MBCT) to improve cognitive function), depression and post-traumatic stress disorder49,50,51;
  • Pain management and depression through body awareness using MBCT, and increased cortical thickness may lead to lowered sensitivity to pain52,53;
  • Cardiovascular through regulation of the autonomic nervous system, reduced blood pressure and improved lipid profiles19,44,54;
  • Insomnia and melatonin levels55,56;
  • Neurodegeneration and improving memory, attention, verbal fluency, processing speed, executive function, cognition, and creativity7,37,57,58,59,60;
  • Chronic inflammatory conditions, immunity via increased natural killer cells as a result of improved psychosocial wellbeing and reduced Il-6 by increasing DMN resting-state functional connectivity61,62,63;
  • Decision making and prosocial behaviour64; and
  • Developing well-being and emotional balance7,60,65.

Although there has been positive research supporting the use of meditation for those with psychiatric disorders, there are some older reports showing that mediation can induce psychosis or make obsessive dispositions more severe, so as always, a personalised approach needs to be taken8.

Getting started

In my nutrition practice and as a yoga and meditation teacher, some people find it hard to begin the practice of meditation. There are various smartphone apps that can help, for example Headspace, although there are issues associated with blue light emission66,67. Encouraging clients to keep it simple, starting off with just one minute of daily self-practice, perhaps using these apps or joining local groups, some of which are free to attend, are a good start. Particular music may also help as an easy, passive and accessible activity68,69. Regularity of practice is important, as it may be the amount of daily meditation time, rather than total hours over lifetime that confers the benefits70.

Other clients may prefer a more movement based approach such as yoga, Tai Chi or Qigong, as a practice in itself, or before sitting down for meditation.

In summary

Meditation shows promising benefits for a range of conditions. Although more research is ongoing and required into the application of different types of meditation on different ranges of people, there is growing evidence for it to be considered as part of a client protocol37,59.



Atiya Khan has a BSc (Hons) in Biochemistry and Biological Chemistry and works as a Naturopathic Nutritional Therapist (Dip. CNM), yoga and meditation teacher.