Meditation. In: Boison D and Masino SA, editors. Homeostatic Control of Brain Function. Oxford University Press, 2015.

Homeostatic Control of Brain Function

Part III: Homeostatic Manipulators: Preventative and Restorative Opportunities

Chapter 8: Meditation

Abstract

Meditation practices can yield objective, measurable health benefits, especially in protecting

against the deleterious effects of chronic stress. Chronic stress engenders a dysregulation of

homeostatic processes and can lead to serious health disorders. The brain is both affected by and

centrally involved in the regulation of chronic stress. It has been proposed that meditation

practice is a form of mind training that can enhance health by promoting enduring, beneficial

changes in the brain and increasing resiliency to stress. In this chapter we review the current

body of literature on the short- and long-term effects of meditation practice on the central

nervous system and on peripheral systems that are directly or indirectly involved in homeostatic

regulation of the brain, including: (i) blood pressure; (ii) immune function; (iii) telomeres; (iv)

autonomic regulation of the heart; (v) Hypothalamic–pituitary–adrenal (HPA) axis regulation;

and (vi) neuroplasticity.

Keywords: meditation, stress, allostatic load, immune system, telomere, autonomic nervous

system, HPA axis, cortisol, neuroplasticity

Citation

Desbordes G. Meditation. In: Boison D and Masino SA, editors. Homeostatic Control of Brain

Function. Part III, Chapter 8. Oxford University Press. Forthcoming.

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1. Introduction

Meditation has been practiced for centuries by people across the world to improve well-being

and reduce suffering. Scientific research from the past several decades suggests that meditation

practice can yield objective, measurable health benefits. In particular, evidence is growing that

meditation practice may offer protection against the deleterious effects of chronic stress, which

engenders a dysregulation of homeostatic and allostatic processes and can lead to serious health

disorders. The brain is both affected by and centrally involved in the regulation of chronic stress

(Maier, 2003). It has been proposed that meditation practice is a form of mind training that can

enhance health by improving emotional regulation and increasing resiliency to stress (Benson,

1975; Kabat-Zinn, 1990), possibly via the generation of enduring, beneficial changes in the brain

through better regulation of inflammation and neuroplasticity mechanisms (Davidson and

McEwen, 2012; Lutz et al., 2007; Ornish et al., 2008, 2013; Slagter et al., 2011).

Allostasis (“stability through change”) is a model of physiological regulation that is a

generalization of the well-known concept of homeostasis and accounts for cases in which

physiological set points are not constant, but vary as a function of bodily needs and competing

motivation. Allostatic regulation necessitates the extensive involvement of the central nervous

system as the main coordinator of regulatory responses—both behavioral and physiological

(Schulkin, 2004; Sterling and Eyer, 1988).

While the stress response is adaptive in the short term, chronic stress exacts a cost on the

organism known as “allostatic load,” the cumulative physiological burden enacted on the body

through attempts to adapt to life’s demands which can accelerate disease processes (McEwen,

1998, 2004; McEwen and Stellar, 1993; Schulkin, 2004). Allostatic load has been proposed as a

marker of cumulative biological risk and a predictor of mortality and decline in physical

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functioning status (McEwen and Seeman, 1999; Seeman et al., 2001, 2010). Allostatic load

adversely affects multiple physiological systems in the organism (including the nervous,

endocrine, and immune systems) and can manifest in the form of chronic inflammation,

overactivation of the sympathetic nervous system, underactivation of the parasympathetic

nervous system, and premature cellular aging (e.g., shorter telomeres). Allostatic load has been

proposed as a major contributor to the increased occurrence of a broad range of modern-day

illnesses, including brain disorders such as major depression, post-traumatic stress disorder

(PTSD), and other chronic anxiety disorders (McEwen, 2003). Recent studies support the

intriguing possibility that these deleterious effects may be counteracted by specific “brain

training” programs (Bryck and Fisher, 2012), including meditation-based interventions designed

to promote well-being and prosocial behavior (Davidson and McEwen, 2012).

While the field of meditation science has not yet directly addressed how meditation may

affect homeostatic control of the brain, a growing number of studies suggest that meditation

affects physiological mechanisms that can disrupt or restore homeostasis in the brain. In this

chapter we review the current body of literature relating to the short- and long-term effects of

meditation practice on the central nervous system and on peripheral systems that are directly or

indirectly involved in homeostatic—or allostatic—regulation of the brain. Specifically, the topics

covered include the effects of meditation training on: (i) blood pressure; (ii) immune function;

(iii) telomeres; (iv) autonomic regulation of the heart; (v) HPA axis regulation; and (vi)

neuroplasticity.

2. What are meditation practices?

Meditation practices have existed since prehistoric times (Johnson, 1982) and are currently

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practiced globally by many people, both in religious and secular (including clinical) contexts.

Any attempt to define “meditation” is fraught with debate, and this review is not the place to

enter into these academic considerations. As a starting point, most meditative practices discussed

in this chapter are more or less adequately described by the following working definition, offered

by Shapiro: “Meditation refers to a family of techniques which have in common a conscious

attempt to focus attention in a nonanalytical way and an attempt not to dwell on discursive,

ruminating thought” (Shapiro Jr., 1982). However, the reader should keep in mind that there

exist other types of meditation not covered by this definition, such as the loving-kindness and

compassion meditation practices described below. Different traditions and schools of thought

offer a wide variety of meditation practices and the interested reader is referred to the vast

literature dedicated to these topics. Overall, the full spectrum of meditation practices—which

vary in terms of their purpose, specific instructions, and expected results—is therefore extremely

broad. The generic term “meditation” (often used without further elaboration in the scientific

literature) can refer to widely diverse practices, likely with varying effects on physiology. Recent

attempts to organize these practices into a few categories for the purpose of scientific research

resulted in active debate (Awasthi, 2012; Josipovic, 2010; Lutz et al., 2008; Travis and Shear,

2010a, 2010b). In summary, the reader is invited to acknowledge that there is no such thing as

“meditation” as a single, monolithic practice. This important distinction can help explain the

variety of physiological effects reported in the scientific literature to date.

Some of the first meditation practices to be investigated scientifically, in non-expert as

well as expert practitioners, were Transcendental Meditation (TM) (Rosenthal, 2011; Wallace et

al., 1971) and the Relaxation Response (Benson, 1975; Benson et al., 1974a). Since the 1980s,

another increasingly popular type of meditation practice offered in the clinical context is

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“mindfulness,” first introduced by Kabat-Zinn (1982). Nowadays, numerous mindfulness-based

interventions exist which are centered on mindfulness meditation instruction and practice,

typically in the form of a six- to eight-week group intervention. These programs include:

Mindfulness-Based Stress Reduction (MBSR), which is the original format (Kabat-Zinn, 1990,

2013); Mindfulness-Based Cognitive Therapy (MBCT), which is a hybrid between MBSR and

cognitive behavioral therapy originally designed to prevent depression relapse in patients with a

history of major depression, but which has been increasingly applied to other clinical and non-

clinical populations (Segal et al., 2013; Teasdale et al., 1995); and other mindfulness-based

interventions with varying duration and components (Kabat-Zinn, 2003). Other practices derived

from mindfulness include “third-wave” forms of psychotherapy such as Acceptance and

Commitment Therapy (ACT) (Hayes, 2004; Hayes et al., 1999) and Dialectical Behavioral

Therapy (DBT) (Lau and McMain, 2005; Linehan, 1993; Robins et al., 2004). A growing

scientific literature points to wide ranging benefits from mindfulness-based programs, from

decreases in anxiety, depression, and chronic pain, to improvements in immune function, etc.

(Kabat-Zinn, 2013). However, the methodological quality of the scientific literature on

meditation for health has been criticized (Ospina et al., 2007). A recent review concludes that

mindfulness-based programs show moderate evidence of improved anxiety, depression, and pain,

but low evidence of improved stress/distress, mental health-related quality of life, and positive

mood (Goyal et al., 2014), even though participants in mindfulness-based interventions often

report an increase in well-being (reviewed in Chambers, Gullone, & Allen, 2009; Grossman,

2004; Rubia, 2009). Clearly more high-quality research is needed, but the preliminary evidence

to date is very encouraging, as we review below.

Other types of meditative or contemplative practices are receiving increasing interest

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from the scientific community. Practices collectively referred to as “loving-kindness” or

“compassion” meditation (which encompass several distinct forms of practices) are aimed at

cultivating loving-kindness—a form of unconditional love towards all beings (Salzberg, 1995)—

or compassion—the feeling that arises in witnessing another’s suffering and that motivates a

subsequent desire to help (Goetz et al., 2010). Unlike mere empathic resonance, which can lead

to burnout, secondary traumatic stress, or compassion fatigue (a deterioration of one’s resiliency,

coping and empathic abilities), true compassion is considered beneficial to the individual who

experiences it (Klimecki et al., 2014; Singer and Bolz, 2013). In recent years, a number of

programs have been proposed to train individuals in cultivating loving-kindness and compassion

via meditative practices presented in a secular format adapted to a modern lifestyle (Germer,

2009; Gilbert, 2005; Hofmann et al., 2011; Jazaieri et al., 2013; Makransky, 2007; Ozawa-de

Silva and Negi, 2013; Salzberg, 1995; Wallmark et al., 2012). Recent scientific studies indicate

that loving-kindness and compassion practices may have multiple beneficial effects, such as

improvements in chronic pain and psychological distress (Carson et al., 2005), reductions in

depression, anxiety, rumination, and self-criticism (Gilbert and Procter, 2006; Kemeny et al.,

2012), reduced inflammation response (Pace et al., 2009, 2010, 2013), and increased vagal tone

as assessed by heart rate variability (Kok et al., 2013). A few studies have also begun to

investigate the neural correlates of these practices, although much more work is needed in this

area (Desbordes et al., 2012a; Garrison et al., 2014; Klimecki et al., 2013, 2014; Lee et al., 2012;

Leung et al., 2013; Mascaro et al., 2013; Weng et al., 2013).

Other types of meditative practices have been scientifically studied, for instance

visualization practices (Kozhevnikov et al., 2009), gTummo or “inner heat” yoga (Benson et al.,

1982; Kozhevnikov et al., 2013), and body awareness practices such as yoga, qigong, tai-chi, the

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Alexander Technique, the Feldenkrais Method, etc. (Mehling et al., 2011; Schmalzl et al., 2014)

which are beyond the scope of this review.

3. Effects of meditation on allostatic markers

Early scientific experiments on meditators seemed to suggest that meditative states were

associated with a hypometabolic state and had calming, relaxing, stress-reducing effects (Benson

et al., 1974b; Wallace et al., 1971; Young and Taylor, 1998), even though it was recognized

early on that some types of meditation could also increase arousal (Amihai and Kozhevnikov,

2014; Corby et al., 1978; Shapiro Jr., 1982; Shapiro Jr. and Walsh, 1984).

The benefits of meditation practice for stress reduction purposes have been widely

reported. In this section we will review some of the most notable studies to date showing the

effects of meditation practices on some allostatic biomarkers. Allostatic load can be estimated

from markers of inflammation, metabolism, blood pressure, telomeres, as well as by measuring

the integrity of several inter-correlated physiological systems such as the sympathetic and

parasympathetic nervous systems and the hypothalamic–pituitary–adrenal (HPA) axis (McEwen

and Seeman, 1999; Seeman et al., 2001, 2010).

3.a. Blood pressure

Early studies suggested that TM and the related Relaxation Response practice could reduce

blood pressure and normalize hypertension (Benson et al., 1974a; Wallace et al., 1971). Later

studies seem to confirm this finding, albeit amid some controversy (Canter and Ernst, 2004;

Orme-Johnson et al., 2005; Parati and Steptoe, 2004). A more recent meta-analysis of nine

randomized controlled trials concluded that TM could decrease blood pressure, with an effect

size of −4.7 mm Hg (95% confidence interval: −7.4 to −1.9 mm Hg) for systolic blood pressure

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and −3.2 mm Hg (95% confidence interval: −5.4 to −1.3 mm Hg) for diastolic blood pressure,

respectively—effect sizes which are considered clinically meaningful (Anderson et al., 2008).

There is also preliminary evidence suggesting that the MBSR intervention can reduce blood

pressure as well. A single-arm study of breast and prostate cancer patients undergoing MBSR

found a significant pre- to post-intervention 2.1 mm Hg decrease in systolic blood pressure, but

no effect on diastolic blood pressure (Carlson et al., 2007). A randomized controlled trial of

MBSR in prehypertensive patients, with an active control condition consisting of progressive

muscle relaxation training, found that MBSR could significantly reduce blood pressure in this

population compared to the control intervention, with a 4.8-mm Hg reduction in systolic blood

pressure and a 1.9-mm Hg reduction in diastolic blood pressure (Hughes et al., 2013).

3.b. Immune function

Some evidence suggests that meditation training may improve immune function in healthy

individuals. Based on previous studies indicating that chronic stress can diminish antibody

response to vaccines (Glaser et al., 1998; Kiecolt-Glaser et al., 1996; Yang and Glaser, 2002),

Davidson et al. (2003) conducted a randomized controlled trial of MBSR in a workforce

population in which subjects in both the intervention group and the waitlist control group

received the influenza vaccine at the end of the 8-week period. Subjects who had received

MBSR (N = 25) showed small but statistically significant increases in antibody titers to influenza

vaccine compared with control subjects (N = 16).

On a broader level, it has been proposed that meditation practice might help regulate

chronic inflammation (e.g., Oke and Tracey, 2009). Chronic inflammation is especially relevant

to homeostatic regulation of the brain, as the immune system and the central nervous system

form a bi-directional communication network (Maier, 2003; McEwen, 2006). Chronic

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inflammation has been associated with a number of diseases that can affect the brain (Anthony

and Pitossi, 2013), including inflammatory diseases of the blood vessel wall (with increased risk

of thrombotic stroke) and other cardiovascular diseases, Alzheimer’s disease (Ferreira et al.,

2014; Maccioni et al., 2009; Rubio-Perez and Morillas-Ruiz, 2012), Parkinson’s disease (Hirsch

et al., 2012; More et al., 2013), brain metastasis (Hamilton and Sibson, 2013), and type II

diabetes (Donath and Shoelson, 2011)—which can be associated with brain dysfunction

(Biessels et al., 2014). Chronic inflammation may also be involved in the process of age-related

cognitive decline (Simen et al., 2011) and normal aging (Pizza et al., 2011; Sparkman and

Johnson, 2008). Chronic inflammation is believed to be caused by a combination of genetic

predisposition, lifestyle, and psychosocial factors; it is, therefore, susceptible to sociobehavioral

changes such as those promoted by meditation-based interventions, and perhaps by other

meditation-specific neuroplasticity mechanisms (Coe and Laudenslager, 2007; Davidson and

McEwen, 2012).

Some recent studies indicate that meditation interventions may indeed reduce

inflammation. In a randomized controlled trial in a population of foster care adolescents (N = 71)

exposed to early life adversity (a known risk factor for increased inflammation), a six-week

compassion meditation intervention had some effects on salivary concentration in C-reactive

protein (CRP), an inflammatory marker. While there was no significant difference between the

intervention group and the control group in CRP levels overall, the number of practice sessions

attended by the subjects in the meditation group was correlated with a pre- to post-intervention

reduction in CRP, suggesting a possible dose-response relationship (Pace et al., 2013).

Inflammation can also be assessed in response to an acute stressor, such as the Trier

Social Stress Test (TSST), a commonly used standardized protocol for reproducibly inducing

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psychological stress in the laboratory. The TSST consists of a public speaking and mental

arithmetic task performed in front of a panel of emotionally non-responsive confederates

presented as “behavioral experts.” Even though the stressor itself only lasts for a few minutes,

the TSST reliably activates the autonomic nervous system, HPA axis, and innate immune

inflammatory response over a time course of several hours (Dickerson and Kemeny, 2004;

Kirschbaum et al., 1993).

Several studies of meditation have used the TSST to assess changes in inflammatory

response to stress after several weeks of meditation training. In a randomized controlled trial of

compassion meditation compared to an active control intervention (based on health discussion

groups) conducted in healthy college students, Pace et al. (2009) found a post-hoc association

between compassion meditation practice time and decreased plasma levels of interleukin-6 (a

pro-inflammatory cytokine), although there was no group difference between the two

interventions. In a randomized controlled trial of MBSR compared to the Health Enhancement

Program (an ad-hoc active control intervention), Rosenkranz et al. (2013) also found comparable

cortisol responses to the TSST after both interventions, but significantly smaller flare in the

MBSR group in response to topical application of capsaicin cream to forearm skin, indicating

reduced inflammation response. In another randomized controlled trial of MBSR with active

control group, levels of adrenocorticotrophin hormone (ACTH, the hormone that stimulates

cortisol release) during the TSST were lower in the MBSR group than in the control group (Hoge

et al., 2012).

Several recent studies also suggest that meditative states may have immediate effects on

inflammatory gene expression. In a recent study conducted on experienced meditators taking part

in a meditation retreat, Kaliman et al. (2014) found a downregulation of the pro-inflammatory

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genes RIPK2 and COX2 and of several histone deacetylase (HDAC) genes after engaging in

mindfulness meditation for eight hours. In addition, the extent to which some of those genes

were downregulated was associated with faster cortisol recovery to a TSST. In a study of both

experienced and novice practitioners of the Relaxation Response, Bhasin et al. (2013) found that

immediately after engaging in the Relaxation Response practice, the expression of genes

associated with energy metabolism, mitochondrial function, insulin secretion and telomere

maintenance was enhanced, whereas the expression of genes linked to inflammatory response

and stress-related pathways was reduced, with stronger effects in experienced practitioners than

in novices. While these recent findings are very promising, more research is needed to determine

whether meditation affects inflammatory gene expression over the long term.

3.c. Telomeres

Telomeres are protective “caps” at the ends of chromosomes. Their maintenance requires the

action of the ribonucleoprotein enzyme known as telomerase. The degradation, or shortening, of

telomeres threatens chromosome integrity and is implicated in the process of aging as well as

cancer (Aubert and Lansdorp, 2008; Corey, 2009; Eitan et al., 2014; Falandry et al., 2014; Kong

et al., 2013; Oeseburg et al., 2010; Zhu et al., 2011). Measures of telomere length and telomerase

activity have been used to assess cellular aging (Aubert and Lansdorp, 2008; Mather et al., 2011;

Njajou et al., 2009). Importantly, stress can accelerate telomere shortening (reviewed in

Starkweather et al., 2014). Epel et al. (2004) found that women with the highest levels of

perceived stress had telomeres shorter on average by the equivalent of at least one decade of

additional aging compared to low stress women. In addition, telomerase activity in peripheral-

blood mononuclear cells, although not telomere length, was inversely associated with six major

cardiovascular disease risk factors in healthy women, suggesting that telomerase activity may be

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a more direct and potentially earlier predictor than telomere length of long-term cellular viability,

genomic stability, and disease processes (Epel et al., 2006).

In the field of meditation science, telomeres and telomerase activity are gaining interest

as possible objective markers of health improvements associated with meditation practice.

In a study of long-term meditation practitioners engaged in a three-month-long, intense

meditation retreat (known as the Shamatha project), telomerase activity was significantly greater

in retreat participants at the end of the retreat than in matched control subjects, and mediation

analyses based on longitudinal psychological assessments suggested that increases in perceived

control and decreases in negative affectivity contributed to increased telomerase activity (Jacobs

et al., 2011).

In a recent pilot study of mindfulness training for healthy eating in overweight and obese

women, both the mindfulness group and the waitlist control group showed an increase in

telomerase activity over four months, with negative correlations between changes in telomerase

activity and changes in chronic stress, anxiety, dietary restraint, dietary fat intake, cortisol, and

glucose (Daubenmier et al., 2012). This preliminary finding is in line with a previous study of

intensive lifestyle changes (including daily meditation practice) in prostate cancer patients that

showed significantly increased telomerase activity after three months, where the increases in

telomerase activity were significantly associated with decreases in low-density lipoprotein (LDL)

cholesterol and decreases in psychological distress (Ornish et al., 2008), and with increased

relative telomere length after five years of follow-up (Ornish et al., 2013).

Finally, a recent pilot study on a small number (N = 15) of experienced practitioners of

loving-kindness meditation and matched control subjects suggested that, in women, the amount

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of loving-kindness meditation practice over the lifetime was associated with longer telomeres

(Hoge et al., 2013).

Overall, these preliminary findings support the possibility that meditation training may

have positive impacts on telomere length and telomerase activity.

3.d. Autonomic regulation of the heart

One of the main markers of allostatic load is heart rate variability (HRV), the healthy beat-to-

beat fluctuations in heart rate that reflect autonomic (sympathetic and parasympathetic)

influences on cardiac activity (Malik et al., 1996). Diminished HRV is an independent risk factor

for mortality in patients with heart disease (Berntson et al., 1997; Freeman, 2006; Friedman and

Thayer, 1998; Malik et al., 1996; Malliani et al., 1991; Mujica-Parodi et al., 2009; Stein et al.,

1994) and has been associated with a variety of pathological states and dispositions, including

anxiety and depression (Gorman and Sloan, 2000). For instance, low HRV is associated with

both acute (“state”) anxiety (Fuller, 1992; Jönsson, 2007; Watkins et al., 1998) and with chronic

(“trait”) anxiety and clinical anxiety disorders (Cohen and Benjamin, 2006; Cohen et al., 2000;

Friedman, 2007; Klein et al., 1995; Licht et al., 2009; McCraty et al., 2001). HRV decreases in

relation to increased depression severity, even in the absence of cardiovascular disease (Brown et

al., 2009; Kemp et al., 2010). Consequently, high HRV has been proposed as an indicator of

good physical and psychological health (Porges, 2011; Thayer et al., 2009, 2012).

Meditative states are usually associated with higher vagal parasympathetic activity, as

indicated by higher HRV either during or immediately after engaging in a meditation practice

session (Cysarz and Büssing, 2005; Ditto et al., 2006; Kubota et al., 2001; Nesvold et al., 2012;

Peng et al., 1999, 2004; Phongsuphap et al., 2008; Takahashi et al., 2005; Tang et al., 2009;

Wolever et al., 2012; Wu and Lo, 2008). However, it should be noted that certain advanced

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forms of meditation practices seem to increase sympathetic activation in expert practitioners

(Corby et al., 1978; Kox et al., 2012). A review of the literature on the complex autonomic

changes associated with meditative states is beyond the scope of this chapter. The question of

interest here is whether the practice of meditation has lasting, beneficial influences on autonomic

functioning that may affect homeostatic regulation of the brain. In other words, is autonomic

function altered in meditation practitioners, even outside periods of formal meditation practice,

such as during normal resting conditions or during tasks that challenge the ANS? Recent studies

have linked even brief training in meditation (from five days to several weeks) to a longitudinal

increase in resting HRV. In a single-arm pilot study of patients presenting with depression and

anxiety six months after surgery for spontaneous subarachnoid hemorrhage, resting HRV was

found to significantly increase pre- to post-MBSR training, while depression scores significantly

decreased (Joo et al., 2010). Longitudinal increases in resting HRV have also been found with

meditation-based interventions other than MBSR. In a waitlist-controlled field experiment of

university workers taking part in a six-week program for learning loving-kindness meditation

(with one hour-long class per week that included guided meditation practice and group

discussion), the experimental condition (meditation versus waitlist control) significantly

predicted an increase in resting HRV (Kok et al., 2013). In our own recent study, healthy adults

were randomized to either mindful-attention meditation training, or compassion meditation

training, or an active control intervention based on health education classes (see Desbordes et al.,

2012a). One of our assessments measured resting HRV before and after each of the three eight-

week interventions. Preliminary analyses indicate that participants who underwent either type of

meditation training (mindful-attention or compassion) showed an increase in resting HRV pre- to

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post-intervention, with a significant correlation between increased HRV and decreased

depression score (Desbordes et al., 2012b).

In summary, while specific meditative states are associated with a variety of changes in

autonomic activation, recent evidence suggests that the regular practice of meditation may have

lasting, beneficial influences on autonomic functioning.

It should be noted that the autonomic nervous system and the HPA axis can be

independently affected by a psychosocial stressor such as the TSST (Schommer et al., 2003).

Therefore, it does not necessarily follow from the effects of meditation on autonomic function

that meditation will have comparable effects on the HPA axis (e.g., as assessed by cortisol

levels). Below we review how meditation may affect regulation of the HPA axis.

3.e. HPA axis regulation

One of the main systems involved in allostatic regulation is the HPA axis, a major

neuroendocrine subsystem that controls physiological responses to stress, such as increased

levels of cortisol (Dickerson and Kemeny, 2004; Hellhammer et al., 2009; Kirschbaum et al.,

1993; Marques et al., 2010; Steptoe et al., 2007). Cortisol levels have been proposed as an

objective measure of HPA axis activation in chronic stress (Herbert and Cohen, 1993) and as an

outcome measure for meditation interventions (Matousek et al., 2010). Salivary cortisol is

considered the method of choice for measuring free cortisol levels in the context of stress

research (Hellhammer et al., 2009). However, obtaining meaningful measures of cortisol can be

challenging. Cortisol levels exhibit wide variations throughout a 24-hour cycle, following a

circadian rhythm controlled by the hypothalamic suprachiasmatic nucleus (part of the HPA axis).

While the daily cortisol curve normally follows a stereotypical profile, with a sharp morning rise,

a slow descending slope in the afternoon, and reaching its minimum level during the night

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(Krieger et al., 1971), many factors can perturb this rhythm, and erratic cortisol patterns have

been associated with metabolic abnormalities, fatigue, depression, psychosocial factors, and poor

quality of life in general (Chida and Steptoe, 2009; Debono et al., 2009). In addition, flattened or

abnormal diurnal cortisol rhythms are a predictor of early mortality in some types of cancer

(Sephton et al., 2000, 2013).

To obtain meaningful cortisol measurements as part of a research study, it is therefore

necessary to measure cortisol at very specific times relative to subject waking time, if possible at

multiple time points during a 24-hour cycle, or at short intervals immediately after waking to

assess the cortisol awakening response (Clow et al., 2004; Fries et al., 2009; Hellhammer et al.,

2009; Pruessner et al., 1997). Alternatively, one can measure cortisol response to acute stressors

such as the TSST (Kirschbaum et al., 1993). Finally, it should be noted that cortisol levels vary

with age, gender, and certain pharmacological treatments, including oral contraceptives.

Previous reports of the effects of meditation training on cortisol levels showed mixed

results (for a review, see Matousek et al., 2010). Some studies in cancer patients found that

participation in MBSR was associated with a global decrease in cortisol levels (Carlson et al.,

2007; Witek-Janusek et al., 2008), while another study reported an increase in cortisol

awakening response (Matousek et al., 2011)—arguably an improvement in this patient

population since stressed individuals tend to exhibit a blunted (i.e., abnormally flat) cortisol daily

profile (Chida and Steptoe, 2009). Other studies found no significant changes in cortisol after

MBSR, although their methodological design has been criticized on the basis of inadequate

cortisol sampling (e.g., insufficient number of time points), small sample sizes, or lack of control

over confounding variables such as diet, physical exercise, or sleep–wake cycle (Matousek et al.,

2010). However, even carefully designed randomized controlled trials have also yielded unclear

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cortisol outcomes. For example, a longitudinal study of MBCT in remitted depression patients

with six-month follow-up showed no significant changes in any cortisol measure (cortisol

awakening response, diurnal slope, or area under the curve) (Gex-Fabry et al., 2012), although it

may be due to the fact that cortisol patterns are erratic and difficult to detect in depressed patients

(Peeters et al., 2004). In a non-clinical community sample, a randomized controlled trial of

MBSR compared to an active control intervention found no difference between the groups in

post-training cortisol response to a TSST, although the amount of mindfulness practice (i.e.,

dose) predicted a steeper (arguably more salubrious) diurnal cortisol slope following training

(Rosenkranz et al., 2013). More longitudinal studies with careful methodology for cortisol

assessments are needed to elucidate the effects of meditation training on HPA axis activation in

various populations.

The hypothesis that meditation practice may contribute to lower abnormally elevated

cortisol levels, at least in some clinical populations, should be of interest in the context of

homeostatic control of the brain since high concentrations of cortisol may have deleterious

effects on the brain, especially in the hippocampus. It is well known that the hippocampus

becomes atrophied and presents functional abnormalities in humans and animals exposed to

severe stress or depression (Bora et al., 2012; Bremner et al., 2000; Colla et al., 2007; Davidson

et al., 2002; Malykhin et al., 2010; Shah et al., 1998; Sheline et al., 1996, 1999). It has been

suggested that this hippocampal atrophy results from prolonged exposure to high concentrations

of cortisol (Lupien et al., 1998). While normal levels of cortisol activate mineralocorticoid

receptors and facilitate hippocampal long-term potentiation (and memory functions), high

concentrations of cortisol additionally activate glucocorticoid receptors which have debilitating

effects on hippocampal function, including a dampening of long-term potentiation (Kerr et al.,

17  

1989). Therefore, cortisol exerts a concentration-dependent biphasic (inverted U-shape)

influence on the expression of hippocampal plasticity (Diamond et al., 1992). While these

mechanisms have been investigated mostly in animal models, studies in humans also indicate

that elevated basal cortisol levels predict reduced hippocampal volume and deficits in

hippocampus-dependent memory tasks in the aging population (Lupien et al., 1998; Sapolsky,

1992). These complex interactions between cortisol levels and hippocampal structure and

function may underlie the connection between stressful experiences and dampening of

hippocampal neurogenesis (Gould and Tanapat, 1999; Gould et al., 1998; Rao et al., 2010). The

link between cortisol levels and hippocampus size in chronic stress may take the form of a

positive feedback loop between pathologically high levels of cortisol and neuronal damage in the

hippocampus, which may in turn further reduce HPA downregulation and promote

hypercortisolemia (reviewed in Davidson et al., 2002).

Most interestingly, hippocampal atrophy seems to be reversible to some extent (Gould et

al., 2000; Jacobs et al., 2000; Malykhin et al., 2010). For example, chronic treatment with

antidepressants increases neurogenesis in the hippocampus (Santarelli et al., 2003; Vermetten et

al., 2003). Since hippocampal atrophy can be reverted when stress is reduced, the question

naturally arises whether similar effects can be achieved by reducing perceived stress, via the

practice of meditation for example. Recent studies suggest that meditation practice may indeed

promote growth (or prevent shrinkage) in the hippocampus. Long-term meditation practitioners

have larger hippocampi and greater gray matter density in the hippocampal complex than

matched control subjects (Hölzel et al., 2008; Luders et al., 2009, 2013a, 2013b). Remarkably,

hippocampus growth was also observed longitudinally after only eight weeks of meditation

practice in meditation-naïve participants, in healthy subjects undergoing MBSR (Hölzel et al.,

18  

2011) and in healthy subjects undergoing mindful-attention or compassion meditation training

(Desbordes et al., 2014). In addition, neuroplastic effects of meditation have been reported not

only in the hippocampal complex but also in other brain regions, as reviewed below.

3.f. Neuroplasticity

In a seminal study of the effects on brain structure of lifetime meditation experience, Lazar et al.

(2005) found greater cortical thickness in the right anterior insula and dorsolateral prefrontal

cortex regions in Vipassana (a.k.a. Insight) meditation practitioners than in matched control

subjects, with a significant correlation between cortical thickness and years of meditation

experience. This study was the first to suggest that meditation practices might offset age-related

cortical thinning and gray matter loss.

Other studies have since extended these findings. In another cross-sectional study of

Vipassana meditators and matched controls, Hölzel et al. (2008) used voxel-based morphometry

(Ashburner and Friston, 2000) to assess gray matter concentration. This study confirmed the

earlier finding in Vipassana meditators of increased gray matter in the right anterior insula,

which is involved in interoceptive awareness, presumably reflecting the cultivation of bodily

awareness during this type of training. This study also reported greater gray matter concentration

in the left inferior temporal gyrus and right hippocampus in meditators compared to matched

controls. Pagnoni and Cekic (2007) investigated gray matter volume in relation to attentional

performance in Zen meditators compared with matched controls. They found that, contrary to the

control subjects, meditators did not display the expected effects of age on gray matter volume

and on performance in a computerized sustained attention task. Vestergaard-Poulsen et al. (2009)

found higher gray matter density in the brain stem of experienced practitioners of Tibetan

Dzogchen meditation compared to matched controls, particularly in the medulla oblongata region

19  

of the dorsal brain stem which contains autonomic nuclei involved in cardiac and respiratory

functions. Grant et al. (2010) found that compared to matched controls, Zen meditators had both

lower pain sensitivity and greater cortical thickness in pain-related areas (the dorsal anterior

cingulate and secondary somatosensory cortex), with a positive correlation between cortical

thickness in the anterior cingulate and years of meditation practice. A series of studies by Luders

and colleagues conducted on long-term meditators from various traditions demonstrated

widespread differences between meditators and matched controls in several brain structural

measures. These measures included: larger gray matter volume in the right orbito-frontal cortex

(Luders et al., 2009), larger hippocampus and greater gray matter in the hippocampal complex

(Luders et al., 2013a, 2013b), greater structural connectivity within major white matter pathways

(Luders et al., 2011), local (voxel-wise) differences in gray matter asymmetry between left and

right hemispheres (Kurth et al., 2014), and greater cortical gyrification (a measure of cortical

folding curvature) in the fusiform gyrus, precentral gyrus, cuneus, and especially in the right

anterior dorsal insula (where gyrification was positively correlated with years of meditation

practice) (Luders et al., 2012), again pointing to an important role of the right anterior insula. In

a study of Theravadan Buddhist practitioners of loving-kindness meditation, Leung et al. (2013)

found significantly greater gray matter volume in meditators than in matched controls in the right

angular gyrus and right posterior parahippocampal gyrus. While neuroplastic effects of

meditation in the hippocampus had been found in several other studies (reviewed above), this

study was the first to highlight differences in the right angular gyrus, a region known to be

activated by cognitive empathy and perspective taking and thereby potentially involved in

compassion and care for others (Adolphs, 2009; Van Overwalle, 2009; Saxe and Kanwisher,

2003).

20  

While the above studies suggest that the brains of meditators show some structural

differences from the brains of non-meditators, the cross-sectional nature of these studies did not

allow testing of whether meditation practice caused these differences, or whether individuals

with particular brain features were more drawn to becoming long-term meditation practitioners.

However, recent longitudinal studies of subjects without prior meditation experience indicate

that changes in brain structure can be detected after only a few weeks of meditation practice.

After participating in the eight-week MBSR program, healthy subjects showed significantly

higher longitudinal increases in gray matter concentration in the amygdala, hippocampus,

posterior cingulate cortex, temporo-parietal junction, and cerebellum compared with waitlist

control subjects (Hölzel et al., 2010, 2011). After one month of integrative body-mind training (a

meditation training program based on traditional Chinese medicine, in the form of daily 30-min

sessions totaling only 11 hours of practice), a college student population exhibited increases in

fractional anisotropy (a measure of white matter integrity) in the corona radiata, a major white-

matter tract connecting multiple brain structures to the anterior cingulate cortex, a region

previously implicated in self-regulation (Tang et al., 2010, 2012). In our longitudinal meditation

study mentioned previously (Desbordes et al., 2012a), preliminary analyses of structural brain

data suggest changes in several subcortical regions (including increased hippocampal volume)

after eight weeks of training in either mindful-attention meditation or compassion meditation

(Desbordes et al., 2014). In the compassion meditation participants, we also found a significant

increase in cortical thickness in the dorsomedial prefrontal cortex (Singleton et al., 2014), a

region activated during empathy tasks which, in another study, showed increased activation

correlated with greater empathic accuracy after CBCT (Mascaro et al., 2013).

21  

Taken together, the above findings support the view that meditation practices, as a form

of “brain training,” may promote neuroplasticity and impact multiple brain functions, including

homeostatic and allostatic processes.

4. Conclusion

The scientific investigation of meditative practices is still at an early stage. Larger longitudinal

studies, ideally in the form of randomized controlled trials with active control interventions, are

warranted to rigorously test the effects of meditation-based interventions on different

physiological (and psychological) mechanisms that may improve health—in particular when it

comes to homeostatic and allostatic regulation processes in the brain and other physiological

systems. The field is rapidly progressing and maturing into a full-fledged multidisciplinary

research domain, with a growing number of investigators worldwide collectively building a

rigorous body of evidence supporting the view that meditation practices may offer wide-ranging

health benefits. The effects of meditation are especially remarkable in the context of allostatic

load—the cumulative, deleterious effects of chronic stress on our bodies which not only diminish

our quality of life, but can also promote chronic inflammation and accelerate aging and disease

processes. We expect that future research will further establish the legitimacy of meditation

practices as low-cost, accessible therapeutic interventions for a variety of illnesses and pre-

clinical conditions.

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