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Mindfulness-based randomized controlled trials led to brain structural changes: an anatomical likelihood meta-analysis

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• Published: 27 October 2023

Mindfulness-based randomized controlled trials led to brain structural changes: an anatomical likelihood meta-analysis

• Savannah Siew & 
• Junhong Yu 

Scientific Reports volume 13, Article number: 18469 (2023) Cite this article

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Abstract

Mindfulness has become increasingly popular and the practice presents in many different forms. Research has been growing extensively with benefits shown across various outcomes. However, there is a lack of consensus over the efficacy of randomized controlled mindfulness interventions, both traditional and mind–body formats. This study aimed to investigate the structural brain changes in mindfulness-based interventions through a meta-analysis. Scopus, PubMed, Web of Science, and PsycINFO were searched up to April 2023. 11 studies (n = 581) assessing whole-brain voxel-based grey matter or cortical thickness changes after a mindfulness RCT were included. Anatomical likelihood estimation was used to carry out voxel-based meta-analysis with leave-one-out sensitivity analysis and behavioural analysis as follow-ups. One significant cluster (p < 0.001, Z = 4.76, cluster size = 632 mm3) emerged in the right insula and precentral gyrus region (MNI = 48, 10, 4) for structural volume increases in intervention group compared to controls. Behavioural analysis revealed that the cluster was associated with mental processes of attention and somesthesis (pain). Mindfulness interventions have the ability to affect neural plasticity in areas associated with better pain modulation and increased sustained attention. This further cements the long-term benefits and neuropsychological basis of mindfulness-based interventions.

초록

마음 챙김은 점점 더 대중화되고 있으며,

다양한 형태로 실천되고 있습니다.

여러 연구에서 다양한 결과와 함께 그 이점이 광범위하게 입증되고 있습니다.

그러나

전통적인 방식과 심신 양면 방식 모두에서

무작위 통제 마음 챙김 개입의 효과에 대한 합의가 이루어지지 않고 있습니다.

이 연구는 메타 분석을 통해

마음 챙김 기반 개입의

구조적 뇌 변화를 조사하는 것을 목표로 합니다.

2023년 4월까지 Scopus, PubMed, Web of Science, PsycINFO를 검색했습니다.

마음 챙김 RCT 후 전뇌 복셀 기반 회백질 또는 대뇌 피질 두께 변화를 평가하는 11개의 연구(n=581)가 포함되었습니다. 해부학적 가능성 추정법을 사용하여 1개를 제외한 민감도 분석과 후속 조치로 행동 분석을 수행하는 복셀 기반 메타 분석을 수행했습니다.

한 가지 중요한 클러스터(p < 0.001, Z = 4.76, 클러스터 크기 = 632 mm3)가

오른쪽 내측섬과 전두엽(MNI = 48, 10, 4)에서 나타났는데,

이는 중재 그룹의 구조적 부피가 대조군에 비해 증가한 것을 의미합니다.

행동 분석 결과, 이 클러스터는

주의력과 통각(통증)의 정신적 과정과 관련이 있는 것으로 나타났습니다.

마음 챙김 개입은

통증 조절 능력과 지속적 주의력 향상에 관련된 영역의

신경 가소성에 영향을 미칠 수 있는 능력을 가지고 있습니다.

이것은

마음 챙김 기반 개입의 장기적인 이점과

신경심리학적 근거를 더욱 확고히 해줍니다.

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Introduction

Mindfulness has become increasingly popular in today’s wellness culture with it gaining popularity in the West with roots in Buddhism and Hinduism. Kabat-Zinn1 coined the modern definition of mindfulness which means “paying attention in a particular way: on purpose, in the present moment, and nonjudgmentally” (p. 4). There have been several conceptualizations of mindfulness and one widely-cited operational definition is a two-component model involving the self-regulation of attention to the present moment and orientation of acceptance towards that moment2. This definition strongly parallels one conceptualized within the Relational Frame Theory, in terms of four psychological processes of acceptance, defusion, present-moment awareness, and the observer self3. It seems that mindfulness can be characterized broadly by attention to the present moment and non-judgemental acceptance and this definition will be relied upon in this study.

The practice of mindfulness can look very different4, ranging from meditative religious practices of Vipassana and Zen to structured programs like mindfulness-based stress reduction (MBSR), and therapeutic modalities such as dialectical behaviour therapy and mindfulness-based cognitive therapy. Vipassana—A meditative practice from Buddhism, involves a constant body scan from head to toe while maintaining a stance of non-reactive observation5. This is sometimes referred to as open monitoring meditation which also includes Zen meditation, which focuses on regulating attention. MBSR is a structured programme developed by Kabat-Zinn6 where participants undergo an eight-week intensive mindfulness practice. Mind–body practices, such as yoga and the Chinese ancient art of Tai Chi Chuan (TCC) and Baduanjin, incorporate mindfulness into movement. Yoga focuses on the regulation of the breath and being aware of one’s thoughts while engaging in physical movement and stretches and the practice has now been widely accepted as secular and is popular around the world. TCC and Baduanjin are less well-known globally but these are widely practised in China as well as countries that inherited Confucius cultural heritage such as Singapore. TCC involves meditative and cognitive components in addition to physical movements and is often practised with a group. Baduanjin uses the breath to guide slow coordinated physical movements to cultivate one’s internal energy, called “Qi”. This shares similarities with Ashtanga yoga, where poses are executed in synchrony with each breath, and Hatha yoga which involves both yoga postures and breathing techniques and is traditionally used to preserve the vital “force” within one’s body. Thus, these mind–body practices can be viewed to involve similar components with each other as well as the traditional mindfulness practices without the physical component. Often, present-moment awareness is the key concept during these practices.

Research in the field has been growing extensively over the years due to its wide-ranging effects. It is efficacious in reducing primary symptoms of various medical conditions7,8,9,10,11,12,13 and their associated psychological factors7,8,10,13,14,15,16. Apart from clinical populations, mindfulness extends benefits to the general population17,18,19,20,21,22. Other outcome variables such as biomarkers of immune functioning23 and stress regulation18, cognitive functions24, and neuroimaging measures25,26,27,28,29 have also been associated with mindfulness practice.

Researchers have turned to neuroimaging to explore the neurobiological basis of the mechanisms involved in the process. Mindfulness affects both functional connectivity and structural anatomy in the brain25,30. Eight brain regions, for example, the sensory cortices and insular, hippocampus and anterior cingulate cortex (ACC), are often correlated with mindfulness meditation across studies, with a moderate effect size26. These include grey matter (GM) and white matter (WM) volume differences between long-term meditators and meditation-naïve controls, and pre- and post-mindfulness interventions among meditation-naïve participants. Moreover, these regions are congruent with the purpose of mindfulness practice. The insular cortex, linked to the effects of mindfulness such as body awareness and emotional self-awareness, has shown structural and functional differences26. GM volume in the hippocampus is significantly larger in long-term meditators compared to those without experience31 and this is seen among yoga practitioners as well32. The hippocampus has a key role in the memory organization of new memories, converting them from short-term to long-term memory stores. It is proposed that the structural differences observed here could explain one’s ability to deal with the spontaneous thoughts that occur during the practice and the memory organization ability that is required26. Cortical thickness in pain-related brain regions, the secondary somatosensory cortex and dorsal ACC33, and attention-related brain regions such as the left superior frontal gyrus and bilateral superior parietal lobule34 were significantly larger in long term Zen meditators. The structural changes occur in areas associated with the benefits of mindfulness practice and range from increased GM volume25,29 to increased connectivity in the WM microstructure28.

There is much more literature available on functional neuroimaging. During meditation, the brain areas of neural networks associated with present-moment awareness were highly activated during meditation tasks in both novice and experienced participants25,35. Activations in the brain regions such as the ACC and insula were often observed during mindfulness practice27. Moreover, functional connectivity within and between specific brain networks, such as the default mode network and the sensorimotor network was altered by mindfulness practice during resting-state or meditation-state functional scans36.

소개

마음 챙김은

불교와 힌두교에 뿌리를 두고 서양에서 인기를 얻으면서

오늘날의 웰빙 문화에서 점점 더 인기를 얻고 있습니다.

카바트-진1은 마음 챙김의 현대적 정의를 만들었는데,

그것은 “특정 방식으로 주의 집중: 의도적으로, 현재 순간에, 비판 없이”를 의미합니다(p. 4).

마음 챙김에 대한 여러 가지 개념화가 이루어졌으며,

널리 인용되는 조작적 정의는 현재 순간에 대한 주의의 자기 조절과

그 순간에 대한 수용의 방향을 포함하는 두 가지 요소 모델입니다2.

이 정의는 수용, 해리, 현재 순간 인식, 관찰자 자아의 네 가지 심리적 과정의 측면에서 관계적 틀 이론(Relational Frame Theory) 내에서 개념화된 것과 매우 유사합니다3.

마음 챙김은

현재 순간에 대한 주의와 비판적 판단을 배제한 수용으로 특징지어질 수 있는 것으로 보이며,

이 정의는 이 연구에서 사용될 것입니다.

마음 챙김의 실천은

위빳사나(Vipassana)와 선(Zen)의 명상적 종교적 실천에서부터

마음 챙김 기반 스트레스 감소(MBSR)와 같은 체계적인 프로그램,

변증법적 행동 치료와 마음 챙김 기반 인지 치료와 같은 치료적 양식에 이르기까지

매우 다양하게 나타날 수 있습니다4.

위빳사나(Vipassana)—불교의 명상 수행법으로,

무반응적 관찰 자세를 유지하면서

머리부터 발끝까지 지속적으로 몸을 스캔하는 것이 포함됩니다5.

이것을 개방형 모니터링 명상이라고도 하는데,

여기에는 주의력 조절에 초점을 맞춘 선(禪) 명상도 포함됩니다.

MBSR은

카바트-진(Kabat-Zinn)이 개발한 체계적인 프로그램으로,

참가자들은 8주 동안 집중적인 마음 챙김 수행을 합니다6.

요가,

태극권(TCC),

바두안진(Baduanjin)과 같은 심신 수련법은

움직임에 마음 챙김을 통합합니다.

요가는

호흡 조절과 신체 움직임과 스트레칭을 하면서

자신의 생각을 인식하는 데 중점을 두고 있으며,

현재는 세속적인 것으로 널리 받아들여져 전 세계적으로 인기가 있습니다.

TCC와 바두안진은

세계적으로 잘 알려지지 않았지만,

중국과 싱가포르와 같이 유교 문화 유산을 계승한 국가에서 널리 행해지고 있습니다.

TCC는

신체적 움직임 외에도 명상과 인지적 요소를 포함하며,

종종 그룹으로 수행됩니다.

바두안진은

호흡을 통해 느리고 협응력 있는 신체적 움직임을 유도하여 '기'라고 불리는

내적 에너지를 기릅니다.

이것은 호흡에 맞춰 자세를 취하는 아슈탕가 요가와 유사하며,

요가 자세와 호흡법을 모두 포함하는 하타 요가는

전통적으로 몸 안에 있는 생명력인 “기”를 유지하는 데 사용됩니다.

따라서 이러한

심신 수련은

신체적 요소가 없는 전통적인 마음 챙김 수련뿐만 아니라

서로 유사한 요소를 포함하는 것으로 볼 수 있습니다.

이러한 수련에서 중요한 개념은 종종 현재에 대한 인식입니다.

이 분야의 연구는 광범위한 효과로 인해 수년에 걸쳐 광범위하게 성장해 왔습니다. 다양한 의학적 상태의 주요 증상7,8,9,10,11,12,13 및 관련 심리적 요인7,8,10,13,14,15,16을 줄이는 데 효과적입니다. 임상 집단을 제외하고, 마음 챙김은 일반 대중에게도 혜택을 제공합니다17,18,19,20,21,22.

면역 기능의 바이오 마커23, 스트레스 조절18, 인지 기능24, 신경 영상 측정25,26,27,28,29과 같은 다른 결과 변수도 마음 챙김 수행과 관련이 있습니다.

연구자들은 이 과정에 관여하는 메커니즘의 신경생물학적 근거를 탐구하기 위해 신경영상학에 관심을 돌렸습니다.

마음 챙김은

뇌의 기능적 연결성과 구조적 해부학에 모두 영향을 미칩니다25,30.

예를 들어,

감각피질과 섬피질, 해마, 전두엽피질(ACC) 등

여덟 개의 뇌 영역은 여러 연구에서 마음 챙김 명상과 상관관계가 있는 것으로 나타났으며,

중간 정도의 효과 크기를 보였습니다26.

여기에는

장기 명상가와 명상 경험이 없는 대조군 사이의 회백질(GM)과 백질(WM) 부피 차이,

명상 경험이 없는 참가자 사이의 마음 챙김 개입 전후 차이가 포함됩니다.

또한, 이러한 영역은 마음 챙김 수행의 목적과 일치합니다.

신체 인식 및 정서적 자기 인식과 같은 마음 챙김의 효과와 관련된 섬피질은

구조적, 기능적 차이를 보였습니다26.

해마의 GM 부피는

장기 명상가들이 초보 명상가들에 비해 훨씬 더 큰 것으로 나타났습니다31.

요가 수련자들 사이에서도

이와 같은 현상이 관찰됩니다32.

해마는

새로운 기억을

단기 기억에서 장기 기억으로 전환하는 기억 조직의 핵심 역할을 담당합니다.

여기서 관찰된 구조적 차이가

명상 수행 중 발생하는 자발적 사고를 처리하는 능력과

기억 조직 능력을 설명할 수 있을 것으로 제안됩니다26.

통증 관련 뇌 영역,

이차 체성 감각 피질 및 등쪽 ACC33,

그리고

좌측 전두엽 상부 회선 및 양측 상두엽 소엽과 같은 주의력 관련 뇌 영역의 피질 두께는

장기 선(禪) 명상가에서 유의하게 더 컸습니다34.

이러한 구조적 변화는

마음 챙김 명상의 이점과 관련된 영역에서 발생하며,

GM 부피 증가25,29,

WM 미세 구조의 연결성 증가28에 이르기까지 다양합니다.

기능적 신경 영상화에 관한 문헌은 훨씬 더 많이 존재합니다.

초보자와 경험자 모두 명상 작업 중에는

현재에 대한 인식과 관련된 신경망의 뇌 영역이 매우 활성화되었습니다25,35.

ACC와 insula와 같은 뇌 영역의 활성화는

명상 수행 중에 자주 관찰되었습니다27.

또한,

휴식 상태 또는 명상 상태의 기능적 스캔 동안에 기본 모드 네트워크와

감각 운동 네트워크와 같은 특정 뇌 네트워크 내 및 그 사이의 기능적 연결성이 명상 수행에 의해 변경되었습니다36.

Further establishing that the associated brain activations were indeed due to the mindfulness practice, dissociable patterns of activation were reliably observed in the different types of meditations, in line with the characteristics embodied by each type27.

As evidenced by research, the benefits of mindfulness have been relatively well-established across a variety of outcomes. However, with regard to neuroimaging outcomes, many studies focus on the GM differences between long-term practitioners compared to controls25,26,35. Within these meta-analyses, the lack of consolidation of studies that include an experimental method makes it difficult to isolate the impact of mindfulness since there is a chance that certain individual traits could predispose someone to be more likely to engage in mindfulness practice. In addition, mind–body interventions such as yoga and qigong practice are often excluded from the meta-analyses of the subject matter26,29, which often leaves out the popular MBSR programme because one of the sessions involves yoga practice. This means that we are overlooking a good opportunity to investigate the physical-mental interactions and benefits of these practices, of which mindfulness is a huge aspect. On the other hand, other reviews only focused on mind–body practices37 which does not allow us to sufficiently understand the full picture regarding all mindfulness-based interventions. Thus, there is a lack of consensus over the efficacy of rigorous mindfulness interventions, both traditional and mind–body formats, in the form of randomized controlled trials (RCT). This study aims to understand the current state of structural neuroimaging findings regarding mindfulness-based interventions. It is hypothesized that brain regions associated with the mechanisms and benefits of mindfulness will show significant changes after mindfulness practice in the intervention compared to the control groups across the studies included in this meta-analysis.

관련된 뇌 활성화가

실제로 마음 챙김 수행에 의한 것임을 더욱 확증하면서,

각 유형의 명상마다 각 유형이 구현하는 특성에 따라 분리 가능한 활성화 패턴이 확실하게 관찰되었습니다27.

연구에 의해 입증된 바와 같이,

마음 챙김의 이점은 다양한 결과에서 비교적 잘 확립되어 있습니다.

그러나

신경 영상 결과와 관련하여,

많은 연구가 장기 수행자와 대조군 간의 GM 차이를 비교하는 데 초점을 맞추고 있습니다25,26,35.

이러한 메타 분석에서

실험적 방법을 포함하는 연구의 통합이 부족하기 때문에

특정 개인적 특성이 누군가를 더 쉽게 명상 수행에 참여하도록 만들 수 있기 때문에

명상의 영향을 분리하기가 어렵습니다.

또한,

요가와 기공 연습과 같은 심신 개입은

해당 주제에 대한 메타 분석에서 종종 제외됩니다26,29.

요가 연습이 포함된 세션이 있기 때문에 인기 있는 MBSR 프로그램이 종종 제외됩니다.

이는 우리가 이러한 관행의 신체-정신 상호작용과 이점을 조사할 수 있는 좋은 기회를 간과하고 있다는 것을 의미합니다. 

다른 한편, 다른 리뷰들은 오직 심신 관행에만 초점을 맞추고37 있기 때문에,

모든 마음 챙김 기반 개입에 관한 전체적인 그림을 충분히 이해할 수 없습니다.

따라서 무작위 대조 시험(RCT)의 형태로 전통적 방식과 심신 양식 모두에 관한 엄격한 마음 챙김 개입의 효과에 대한 합의가 이루어지지 않고 있습니다. 이 연구는 마음 챙김 기반 중재에 관한 구조적 신경 영상 연구의 현재 상태를 이해하는 것을 목표로 합니다. 이 메타 분석에 포함된 연구 전반에 걸쳐, 마음 챙김의 메커니즘과 이점에 관련된 뇌 영역이 마음 챙김 중재군에서 대조군에 비해 유의미한 변화를 보일 것이라는 가설이 세워졌습니다.

Methodology

Study selectionSearch strategy

A systematic literature search was carried out in four databases, Scopus, PubMed, Web of Science, and APA PsycINFO from the earliest studies up till April 2023. This is to ensure that both the psychological and neuroscience aspects of the research topic are covered as well as any inter-disciplinary research. The keywords used for the search in both the title and abstract were: “voxel-based” or “morphometr*” or “voxelwise” or “VBM” or "brain structur*" or "structur* change*" or "structural MRI" or "structural scan*” or “gray matter” or “grey matter”, together with “Meditat*” or “Mindful*” or “mind–body” or “mind body” or “yoga”, and lastly with “RCT” or “intervention” or “trial”.

All records that surfaced were imported into Covidence38 which helped to flag studies that were duplicated. All the duplicated articles were checked manually before being removed from the review. Following this, the author did an abstract screen to remove articles that were clearly irrelevant to the research question. If the study was relevant or the relevance was uncertain, and it appears to have met the following eligibility criteria, the full-text article was retrieved. Additionally, the studies included in systematic reviews and meta-analysis that were relevant to our topic was checked to ensure that we did not miss out any studies. Then, a full-text screen was conducted to ensure that all eligibility criteria were met. In addition, all the references of the papers selected in the first round of full-text review were included in the meta-analysis.

Eligibility criteria

Included studies must be RCTs with either a random or quasi-random allocation, with a treatment and a control group. Control groups could be active or passive, with some studies including both types of control groups within the study design. Only RCTs were included to conduct a more rigorous meta-analysis of mindfulness-related structural changes and control for individual differences that could surface when comparing expert practitioners to those without mindfulness experience in cross-sectional studies. The outcome measure must be a voxel-based or vertex-based comparison of whole-brain GM. Thus, only studies of the GM volume and cortical thickness conducted with structural MRI were included. Regions-of-interest analysis could introduce biases in terms of different methods of choosing and including the brain regions to focus on. Study populations were not restricted to healthy subjects and clinical populations were included as well, regardless of gender and race. In addition, all interventions that meet the definition of mindfulness as a form of present-moment awareness were included since the aim of the study is to surface brain structures related to mindfulness practice. Thus, both the traditional forms of interventions that examined solely the effect of mindfulness and holistic mind–body forms of mindfulness were included.

Studies with less than 10 subjects were excluded due to the low validity of the study. In addition, studies will be excluded when the required information cannot be extracted or obtained from the corresponding authors. Studies that re-analysed previously published data, protocol papers, and abstract-only papers were not included. Studies with null findings were excluded as they do not provide spatial coordinates that were necessary for the analysis method used in this study. To provide more stringent findings, studies that do not employ correction for multiple comparisons or cluster-level family-wise error correction in determining statistically significant clusters were excluded.

Meta-analysis

The preferred reporting items for systematic reviews and meta-analysis (PRISMA)39 and the following neuroimaging meta-analysis guidelines40,41 were followed in this study.

Data extraction

Study characteristics including the author, year of publication and country of study, subject characteristics of age, gender, education, and health or clinical status, and intervention details such as the type of mindfulness practice, length of intervention, type of randomization and control group, and sample size were extracted from the study articles. Statistical data of the analysis design, the cluster-based statistical thresholds used to determine which voxels were statistically significant, and the software, which can be Statistical Parametric Mapping, FMRIB Software Library or other packages, and stereotactic space, which can be Montreal Neurological Institute (MNI), raw Talairach, or MNI converted to Talairach using Brett transform, were also noted. Lastly, the significant brain regions with their peak coordinates, and the direction of change, which can increase or decrease for the intervention group in comparison to the control group were extracted.

Statistical analysis

Voxel-based meta-analysis were carried out with Anatomical Likelihood Estimation (ALE). ALE is derived from activation likelihood estimation principles and detects convergence among the significant coordinates reported across studies that are above chance-levels. ALE was carried out using BrainMap’s GingerALE v3.0.2. Studies that reported coordinates in Talairach space were transformed to MNI space using the Lancaster transform icbm2tal provided in GingerALE. First, ALE uses a Gaussian function to model the coordinates of the studies that were included by accommodating the spatial uncertainty of significant coordinates that could be caused by differences in the neuroanatomy or by using different normalization techniques and brain templates, and by taking into account the sample size of each study. Second, each study has a whole-brain map constructed, where each voxel is assigned a number that corresponds to the probability that a difference in volume between the treatment and control groups occurs within the voxel. These maps from all the studies were then combined and yielded the ALE image where the likelihood of a particular voxel having difference in volumes found minimally for one study was represented in ALE values. Then, the statistical significance of these ALE values were analyzed with a cluster-level family-wise error (FWE) correction threshold of p < 0.05 with 1000 permutations. The cluster-level FWE correction is known to be the most appropriate method for inferring the statistical significance of ALE analyses42.

Following which, the Behavioural Analysis Plugin 3.1 for Mango 4.1 was used to access the behavioural profiles and mental processes that are associated with the identified significant ALE clusters. Based on the functional metadata from the BrainMap Database, the significant ALE clusters were compared against this map to generate the behavioural domains that could fall under Interoception, Cognition, Action, Emotion, and Perception, and is further divided into 60 sub-domains. The significant ALE clusters was transformed to the Talairach space using the transform tool MNI-to-Tal provided in Mango. The region of interest of the significant ALE cluster was selected and the proportion of behavioural domains found within this cluster was compared to the proportions of the behavioural domains across the whole functional database. A behavioural domain profile of the significant cluster was thus generated where Z-scores above 3.0 were considered significant. Sensitivity analysis will be conducted using a leave-one-out method to test the replicability of the results.

Results

Study search and characteristics

In the first round of search, a total of 254 articles were retrieved from the selected databases (PsycINFO = 44, Scopus = 88, Web of Science = 64, PubMed = 58). Duplicates were surfaced by Covidence and manually checked before deleting, which resulted in 109 studies to be screened. Following the eligibility criteria, 48 studies were found to be irrelevant during the title and abstract screening stage. Thus, 61 full-text articles were closely assessed for eligibility, leading to 10 included studies which met all the inclusion criteria. After which, all the references of the 10 included studies were entered into the selection process but only one article met all the inclusion criteria. Thus, the final number of included studies was 11. The full selection process and reasons for exclusion can be found in the PRISMA flow chart in Fig. 1 while the characteristics of the 11 included studies can be found in Table 1. Studies that were excluded for null findings were by Wolf, et al.43, Kral, et al.44, Seminowicz, et al.45 and Mooneyham, et al.46 while Pickut, et al.47 was excluded for using an uncorrected threshold.

Figure 1

PRISMA flow chart of selection process. Selection process of included studies for this meta-analysis according to PRISMA guidelines.

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Table 1 Characteristics of included studies.

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In summary, this meta-analysis had 581 participants (N = 11 studies) from various regions such as Asia (n = 5), Europe (n = 3) and North America (n = 3). All studies reported significant intervention > control contrasts while three studies reported significant control > intervention contrasts. Roughly half of the studies (n = 5) had physical components together with the mindfulness aspect such as Yoga, TCC and Baduanjin. Majority of the studies used a passive control group (n = 6), compared to an active control group (n = 3), while two studies had both an active and passive control groups. The active control groups ranged from memory enhancement training and aerobic exercise to health education programmes. Lastly, about half the studies (n = 6) were on healthy participants while the rest were on patient populations such as those with Mild Cognitive Impairment (MCI) or chronic neuropathic pain.

Risk of bias of included studies

The revised tool to assess the risk of bias in randomized trials were used in this assessment59. Availability of outcome data for nearly all participants randomized were considered when drop-out rates after the intervention were less than 10%. All included studies were assessed to be of low risk, as seen in Fig. 2.

Figure 2

Risk of bias assessment. Results of the risk of bias assessment for all included studies.

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Significant ALE clusters

One significant cluster, as seen in Fig. 3, emerged from the intervention > control ALE contrast and covered the right insula and precentral gyrus in the Brodmann area 13 (BA13) and 44 (BA44) respectively. The cluster size was 632 mm3 with one peak voxel MNI coordinates at 48, 10, 4. The ALE value for this cluster was 0.017 (p < 0.001, Z = 4.76) with two contributing experiments by Santarnecchi, et al.56 and Krause-Sorio, et al.53. There were no significant clusters from the intervention < control ALE contrast. Moreover, since both GM and cortical thickness measures were included, we re-conducted the ALE meta-analysis without the cortical thickness measures to see if that affected the results and no clusters remained significant.

Figure 3

Results of the ALE meta-analysis. The highlighted cluster represent significant convergence of structural increase in mindfulness intervention participants compared to controls. The cluster is depicted on an MNI standard brain template and the colour indicates the ALE values. L = left; R = right, A = anterior, P = posterior.

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Sensitivity and behavioural analysis

Using the leave-one-out method, the stability of the findings were tested. The region of interest that emerged above remains significant in all except two of the repetitions, when the studies that contributed to the clusters were excluded. These occurred when we left out the two studies that contributed to the significant cluster above.

Behavioural analysis of the significant ALE cluster above indicated that the cognitive subdomain of attention (Z = 3.77) and the perception subdomains of somesthesis, in particular pain (Z = 3.01) were the mental processes associated in the region.

Discussion

Across the intervention groups, there was a significant structural increase in the right insula and precentral gyrus region. Using behavioural analysis, this cluster was found to be associated with the cognitive process of attention and the perception process of pain-sensing. This region of interest remained significant in all but two of the repetitions, occurring when the studies contributing to the significant clusters were removed53,56. This signifies that the ALE cluster was due to a small set of studies. However, this brain region was consistently activated even though the type of mindfulness practice was varied, with one using yoga as the intervention while the other used MBSR. Interestingly, one sample was healthy while the other used participants who were at risk for Alzheimer’s disease.

The insula is often implicated in both sensorimotor and emotional processing, especially during interoceptive experiences60. The insula is also involved in top-down control of pain expression‎ and transmission61 which could explain findings of improved pain symptoms amongst those suffering from chronic pain following mindfulness interventions62,63. The posterior insula, where Brodmann area 13 is located, is crucial in processes like emotion regulation and attentional control64. The neural plasticity in this brain region with engagements in mindfulness practice could be the mediating factor for the well-being outcomes often observed. The right insula in particular has shown more involvement in self-related processing than the left due to specific neural features65. With mindfulness practice largely focused on an awareness of the self, it could explain this observation of a unilateral structural change in the insula.

The precentral gyrus, similar to the insula is often activated during interoceptive attention66. The right precentral gyrus especially is activated during awareness of the self67 and the right side of prefrontal activation is often observed during sustained attention tasks68. Overall, it seems that the mechanisms underlying mindfulness-based interventions stem from improvements in attention, especially attention inward to the self, and pain processing. Given the research surrounding the overlap of brain regions activated during both emotional and physical pain69, an increase in the structural volume of the right insula and precentral gyrus could contribute to the benefits of mindfulness practice as a therapeutic tool.

In the most recent meta-analysis on GM changes relating to mindfulness meditation, only structural change in the right anterior ventral insula was found to be consistent across studies29. The study excluded any mindfulness interventions with physical components, such as yoga and the popular MBSR programmes and the brain region found to be significant was similar but more in the anterior region, compared to the findings of this study which saw more structural changes in the posterior insula. The selection of included studies was also mentioned as a weakness since most were cross-sectional. The studies compared structural volume differences in the brains of meditators and non-meditators at a single timepoint or looked at the association of meditation experience with structural brain volume in meditators only. Thus, the stringent inclusion criteria set in this meta-analysis helped to address issues relating to experimental biases in previous meta-analyses. The insula was also consistently activated across fMRI studies during meditation tasks among participants with no experience in mindfulness35. It seems that the benefits of the intervention could be enduring given the structural change observed in this same region.

Another comprehensive and widely cited meta-analysis on morphometric changes associated with mindfulness practice mainly looked at significant differences between long-term practitioners and participants with no prior experience26. Only five studies used a mindfulness intervention on participants with no prior experience. Thus, there were more significant structural differences in brain regions observed in the anterior- and mid-cingulate cortex, middle frontal gyrus, anterior precuneus, fusiform gyrus, orbitofrontal cortex, inferior temporal gyrus, somatomotor cortices, and anterior insula. These additional brain regions could be attributed to either longer-term effects of consistent mindfulness practice, or biases arising from the cross-sectional design of the study. In contrast, the findings from our meta-analysis shows that even short-term mindfulness practice can effect structural changes in the brain. The two studies that contributed to the significant cluster found had mindfulness intervention durations between 8 to 12 weeks with 1 session per week. 8 weeks of mindfulness intervention was also the most common intervention duration used and could be the minimum period for mindfulness interventions to reflect effectiveness in terms of structural brain changes. This provides more convincing support for the benefits of mindfulness practice and allows us to allude the improvements in awareness and pain processing to the practice itself. Moreover, it seems that the benefits do not require years of mindfulness practice before appearing but we should take caution in interpreting the longevity of these changes since post-intervention follow-ups are usually not carried out in the studies.

The number of studies included in this meta-analysis did not meet the recommended good practice amount of 17 by40. However, we believe that it is crucial to explore what the current landscape of high-quality RCTs provides in terms of the evidence of the benefits of mindfulness intervention as interest in the area grows. This also surfaces multiple future research directions. With an increased sample size of included studies, future subgroup analysis could compare the effects of an active versus passive control group, or the effects of including a physical component to the mindfulness intervention, potentially isolating the unique mechanisms of the various components of mindfulness practices. Additionally, differential effects on a healthy versus patient population could also be explored. It is interesting that the patient populations in this meta-analysis have impairments in areas such as pain-processing and cognitive deficits which overlaps with the mental processes associated with the significant brain regions found. There is a possibility that the effectiveness of mindfulness interventions only pertains to clinical populations where deficits are seen in attention and pain-processing. However, future studies are needed to confirm‎ that.

Unfortunately, it was also not possible to verify the effect of potential confounding variables such as age, gender, and length of intervention using meta-regressions with the ALE method, and the exclusion of studies without significant results also causes a selection bias. An important study that was excluded because of non-significant results was a large-scale and rigorously controlled study by Kral et al.44. It is possible that they did not detect significant GM changes due to their stringent exclusion criteria which included anyone with expertise in nutrition, music or physical activity. Additionally, participants had to undergo various other assessments as part of a larger multi-project study with each visit taking 2–4 h which could introduce other variabilities. These are all potential areas that future studies should take into account.

In conclusion, this meta-analysis has found evidence for structural brain changes following mindfulness interventions. These interventions, both traditional and mind–body formats, have the ability to affect neural plasticity in the brain regions associated with pain modulation and sustained attention. During the mindfulness intervention, the repeated practice of engaging one’s attention and awareness to the self repeatedly activates these regions of the brain. Over time, neural plasticity could lead to an increase in the volume of these regions. This further cements the long-term benefits and neuropsychological basis of mindfulness-based interventions.

토론

개입 그룹 전체에서 오른쪽 내측 도랑과 전두엽 전두엽 피질 영역에서 상당한 구조적 증가가 있었습니다. 행동 분석을 통해 이 클러스터는 주의의 인지 과정과 통각 지각 과정과 관련이 있는 것으로 밝혀졌습니다. 이 관심 영역은 유의미한 클러스터에 기여하는 연구가 제거되었을 때 발생하는 두 번의 반복을 제외한 모든 반복에서 유의미한 것으로 남아 있었습니다53,56. 이는 ALE 클러스터가 소수의 연구에 기인한다는 것을 의미합니다. 그러나 이 뇌 영역은 요가를 중재로 사용하는 것과 MBSR을 사용하는 것 등 마음 챙김 연습의 유형이 다양함에도 불구하고 일관되게 활성화되었습니다. 흥미롭게도 한 샘플은 건강한 반면 다른 샘플은 알츠하이머병 위험이 있는 참가자를 사용했습니다.

내측섬은 감각운동과 감정 처리,

특히 내인성 감각 경험에 관여하는 경우가 많습니다60. 

내측섬은 통증 표현과 전달에 대한 하향식 통제에 관여하기도 하는데61,

이는 명상 중재 후 만성 통증 환자의 통증 증상이 개선되었다는

연구 결과를 설명할 수 있습니다62,63.

브로드만 영역 13이 위치한 후방 내측섬은

감정 조절과 주의력 조절과 같은 과정에서 매우 중요합니다64.

이 뇌 영역의 신경 가소성은

마음 챙김 수행과 관련되어 종종 관찰되는 웰빙 결과의 매개 요인이 될 수 있습니다.

특히 오른쪽 내측 도랑은 왼쪽보다 자기 관련 처리에 더 많이 관여하는 것으로 나타났습니다. 이는 특정 신경 기능 때문일 수 있습니다65. 마음 챙김 수행이 주로 자기 인식에 초점을 맞추고 있기 때문에 내측 도랑의 일방적인 구조적 변화에 대한 이러한 관찰을 설명할 수 있습니다.

내부감각지각주의에 집중하는 마음챙김 수행은

내측전두엽과 유사한 전두전두엽을 활성화시킨다66.

특히

우측 전두전두엽은 자아에 대한 인식 과정에서 활성화된다67.

그리고 전두엽의 우측 활성화는 지속적인 주의 집중 작업 중에 관찰되는 경우가 많다68.

전반적으로, 마음 챙김 기반 중재의 기전은 주의력, 특히 자기 자신에 대한 내적 주의력, 그리고 통증 처리의 개선에서 비롯된 것으로 보입니다. 정서적 고통과 신체적 고통 모두에서 활성화되는 뇌 영역의 중복을 둘러싼 연구를 고려할 때, 오른쪽 내측 도랑과 전두엽의 구조적 부피의 증가는 치료 도구로서의 마음 챙김 수행의 이점에 기여할 수 있습니다.69

마음 챙김 명상과 관련된 GM 변화에 대한 가장 최근의 메타 분석에서, 오른쪽 전방 복부 내피의 구조적 변화만이 연구 전반에 걸쳐 일관된 것으로 나타났습니다29. 이 연구는 요가나 인기 있는 MBSR 프로그램과 같은 신체적 요소를 포함하는 마음 챙김 개입을 제외했으며, 유의미한 것으로 밝혀진 뇌 영역은 이 연구의 결과와 유사했지만, 후방 내피의 구조적 변화가 더 많이 나타난 이 연구의 결과와 비교했을 때 전방 영역에 더 집중되어 있었습니다. 포함된 연구의 선택 또한 단점이었습니다. 대부분의 연구가 단면 연구였기 때문입니다. 이 연구는 한 시점에서 명상가와 비명상가의 뇌의 구조적 부피 차이를 비교하거나 명상 경험과 명상가의 뇌 구조적 부피의 연관성을 조사했습니다. 따라서 이 메타분석에서 엄격한 포함 기준을 설정함으로써 이전 메타분석에서 실험적 편향과 관련된 문제를 해결하는 데 도움이 되었습니다. 또한, 명상 경험이 없는 참가자를 대상으로 한 fMRI 연구에서 명상 작업 중에도 편도체가 지속적으로 활성화되는 것으로 나타났습니다35. 이 같은 구조적 변화를 고려할 때, 명상 개입의 이점은 지속될 수 있는 것으로 보입니다.

명상 수행과 관련된 형태학적 변화에 대한 또 다른 포괄적이고 널리 인용되는 메타 분석은 주로 장기 수행자와 이전 경험이 없는 참가자 간의 유의미한 차이를 조사했습니다26. 이전 경험이 없는 참가자를 대상으로 명상 개입을 실시한 연구는 5건뿐이었습니다. 따라서, 전방 및 중방피질, 중전두엽, 전두전두엽, 방추형피질, 전두전두엽피질, 하측측두엽, 체성운동피질, 전방섬유주위에서 관찰된 뇌 영역의 구조적 차이가 더 중요했습니다. 이러한 추가적인 뇌 영역은 지속적인 마음 챙김 수행의 장기적 효과 또는 연구의 단면 설계에서 비롯된 편향 때문일 수 있습니다. 반면에, 메타 분석의 결과는 단기간의 마음 챙김 수행도 뇌의 구조적 변화에 영향을 미칠 수 있음을 보여줍니다. 유의미한 클러스터 발견에 기여한 두 연구의 마음 챙김 개입 기간은 8~12주, 주 1회 세션이었습니다. 8주간의 마음 챙김 개입이 가장 많이 사용된 개입 기간이었으며, 이는 구조적 뇌 변화 측면에서 효과를 반영하기 위한 최소 기간일 수 있습니다. 이것은 마음 챙김 수행의 이점에 대한 보다 설득력 있는 근거를 제공하며, 수행 자체에 의해 인식과 통증 처리 능력이 향상되었음을 암시합니다. 또한, 이러한 이점은 수행을 수년간 지속해야만 나타나는 것이 아닌 것으로 보이지만, 연구에서 수행 후 추적 조사가 일반적으로 수행되지 않으므로 이러한 변화의 지속 기간을 해석할 때 주의해야 합니다.

이 메타분석에 포함된 연구의 수는 권장되는 우수 사례인 17개에서40개에 미치지 못했습니다. 그러나, 이 분야에 대한 관심이 증가함에 따라, 고품질 RCT의 현재 경관이 마음 챙김 개입의 이점에 대한 증거를 제공하는 것이 중요하다고 생각합니다. 이것은 또한 여러 미래 연구 방향을 제시합니다. 포함된 연구의 표본 크기가 증가함에 따라, 향후 하위 그룹 분석은 능동적 대 수동적 통제 그룹의 효과를 비교하거나, 마음 챙김 개입에 신체적 요소를 포함하는 효과를 비교하여 잠재적으로 마음 챙김 수행의 다양한 구성 요소의 고유한 메커니즘을 분리할 수 있습니다. 또한, 건강한 인구와 환자 집단에 대한 차별적 효과도 탐색할 수 있습니다. 이 메타 분석에서 환자 집단이 통증 처리 및 인지 결핍과 같은 영역에서 장애를 가지고 있다는 것은 흥미로운 사실입니다. 이는 발견된 중요한 뇌 영역과 관련된 정신적 과정과 겹치는 부분입니다. 마음 챙김 개입의 효과가 주의력 결핍과 통증 처리와 관련된 임상 집단에만 적용될 가능성이 있습니다. 그러나 이를 확인하기 위해서는 향후 연구가 필요합니다.

불행히도, 연령, 성별, 개입 기간과 같은 잠재적 교란 변수의 효과를 ALE 방법을 이용한 메타 회귀 분석을 통해 검증하는 것도 불가능했으며, 유의미한 결과가 없는 연구를 제외하는 것도 선택 편향을 야기합니다. 유의미한 결과가 없기 때문에 제외된 중요한 연구로는 Kral 등의 대규모의 엄격한 통제 연구가 있습니다44. 그들이 엄격한 제외 기준을 적용했기 때문에 영양, 음악 또는 신체 활동에 대한 전문 지식을 가진 사람을 포함시켰기 때문에 유의미한 GM 변화를 발견하지 못했을 가능성이 있습니다. 또한, 참가자들은 대규모 다중 프로젝트 연구의 일환으로 다양한 평가를 받아야 했고, 방문할 때마다 2-4시간이 소요되어 다른 변동성을 유발할 수 있었습니다. 이러한 모든 잠재적 영역은 향후 연구에서 고려해야 할 사항입니다.

결론적으로, 이 메타 분석은 마음 챙김 개입에 따른 구조적 뇌 변화의 증거를 발견했습니다. 전통적인 방식과 심신 양면 방식의 이러한 중재는 통증 조절과 지속적인 주의력과 관련된 뇌 영역의 신경 가소성에 영향을 미칠 수 있는 능력을 가지고 있습니다. 마음 챙김 중재 동안, 자기 자신에 대한 주의력과 인식을 반복적으로 사용하는 연습은 이러한 뇌 영역을 반복적으로 활성화시킵니다. 시간이 지남에 따라, 신경 가소성은 이러한 영역의 부피를 증가시킬 수 있습니다. 이것은 마음 챙김 기반 중재의 장기적인 이점과 신경심리학적 근거를 더욱 확고히 합니다.

Data availability

The data that support the findings of this study are available from the corresponding author upon request.

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