Mindfulness Practice Increases Regional Brain Gray Matter Density PDF

NIH Public Access Author Manuscript Psychiatry Res. Author manuscript; available in PMC 2012 January 30. Published in final edited form as: NIH-PA Author Manuscript Psychiatry Res. 2011 Ja...

NIH Public Access Author Manuscript Psychiatry Res. Author manuscript; available in PMC 2012 January 30. Published in final edited form as: NIH-PA Author Manuscript Psychiatry Res. 2011 January 30; 191(1): 36–43. doi:10.1016/j.pscychresns.2010.08.006. Mindfulness practice leads to increases in regional brain gray matter density Britta K. Hölzel*,a,b, James Carmodyc, Mark Vangela, Christina Congletona, Sita M. Yerramsettia, Tim Garda,b, and Sara W. Lazara aMassachusetts General Hospital, Harvard Medical School, Boston, MA, USA bBender Institute of Neuroimaging, Justus Liebig Universität Giessen, Germany cUniversity of Massachusetts Medical School, Worcester, MA, USA Abstract Therapeutic interventions that incorporate training in mindfulness meditation have become increasingly popular, but to date, little is known about neural mechanisms associated with these NIH-PA Author Manuscript interventions. Mindfulness-Based Stress Reduction (MBSR), one of the most widely used mindfulness training programs, has been reported to produce positive effects on psychological well-being and to ameliorate symptoms of a number of disorders. Here, we report a controlled longitudinal study to investigate pre-post changes in brain gray matter concentration attributable to participation in an MBSR program. Anatomical MRI images from sixteen healthy, meditation- naïve participants were obtained before and after they underwent the eight-week program. Changes in gray matter concentration were investigated using voxel-based morphometry, and compared to a wait-list control group of 17 individuals. Analyses in a priori regions of interest confirmed increases in gray matter concentration within the left hippocampus. Whole brain analyses identified increases in the posterior cingulate cortex, the temporo-parietal junction, and the cerebellum in the MBSR group compared to the controls. The results suggest that participation in MBSR is associated with changes in gray matter concentration in brain regions involved in learning and memory processes, emotion regulation, self-referential processing, and perspective taking. Keywords NIH-PA Author Manuscript meditation; mindfulness; voxel based morphometry; gray matter; longitudinal; hippocampus; posterior cingulate 1. Introduction Mindfulness meditation has been reported to produce positive effects on psychological well- being that extend beyond the time the individual is formally meditating. Over the last three decades mindfulness meditation practices have been increasingly incorporated into © 2010 Elsevier Ireland Ltd. All rights reserved. * Correspondence should be addressed to Britta K. Hölzel: Massachusetts General Hospital, 120 2nd Avenue, Charlestown, 02129, MA; [email protected], phone: 617-724-2256, fax: 617-643-7340. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.  Hölzel et al. Page 2 psychotherapeutic programs, to take advantage of these benefits (cf., Baer, 2003; Grossman et al., 2004). A large body of research has established the efficacy of these mindfulness- based interventions in reducing symptoms of a number of disorders, including anxiety NIH-PA Author Manuscript (Roemer et al., 2008), depression (Teasdale et al., 2000), substance abuse (Bowen et al., 2006), eating disorders (Tapper et al., 2009), and chronic pain (Grossman et al., 2007), as well as improving well-being and quality of life (e.g., Carmody and Baer, 2008). Mindfulness meditation involves the development of awareness of present-moment experience with a compassionate, non-judgmental stance (Kabat-Zinn, 1990). It has been suggested that this process is associated with a perceptual shift (Carmody, 2009), in which one’s thoughts and feelings are recognized as events occurring in the broader field of awareness. Neuroimaging studies have begun to explore the neural mechanisms underlying mindfulness meditation practice with techniques such as EEG (Davidson et al., 2003; Slagter et al., 2007) and functional MRI (Farb et al., 2007; Lutz et al., 2008; Farb et al., 2010; Goldin and Gross, 2010). Recently, several cross-sectional anatomical MRI studies have demonstrated that experienced meditators exhibit a different gray matter morphometry in multiple brain regions when compared to non-meditating individuals (Lazar et al., 2005; Pagnoni and Cekic, 2007; Hölzel et al., 2008; Luders et al., 2009; Vestergaard-Poulsen et al., 2009; Grant et al., 2010;). While most of the brain regions identified have been reported in only one of these studies, the divergent results are likely due to differences in participant characteristics, NIH-PA Author Manuscript type of meditation, and data analysis methods (see Table 1). Group differences in the hippocampus and the right anterior insula, however, have each been identified in at least two of the studies. Furthermore, activation in both regions has been reported during meditative states (hippocampus (Lazar et al., 2000; Hölzel et al., 2007); insula (Farb et al., 2007; Lutz et al., 2008)). The hippocampus is known to be critically involved in learning and memory processes (Squire, 1992), and in the modulation of emotional control (Corcoran et al., 2005; Milad et al., 2007), while the insula has been postulated to play a key role in the process of awareness (Craig, 2009) - functions which have been shown to be important in the process and outcomes of mindfulness training (Bishop et al., 2004; Shapiro et al., 2006; Ortner et al., 2007). A growing body of literature has demonstrated that neural systems are modifiable networks and changes in the neural structure can occur in adults as a result of training. For example, longitudinal studies have shown task-specific increases in brain gray matter as an effect of acquisition of abstract information (Draganski et al., 2006), motor skills (Draganski et al., 2004), aerobic training (Colcombe et al., 2006), and cognitive skills (Ilg et al., 2008). Cross- sectional studies have established that differences in regional gray matter are associated with performance abilities (Mechelli et al., 2004; Milad et al., 2005), suggesting that an increase NIH-PA Author Manuscript in gray matter corresponds to improved functioning in the relevant area. Studies of experienced meditators have also suggested the possibility of structural plasticity, but their cross-sectional designs did not exclude the possibility of pre-existing group differences, precluding causal conclusions. Here we report a longitudinal study of gray matter changes associated with a mindfulness-based intervention. The focus of the study was to identify brain regions that changed in association with participation in an eight-week Mindfulness- Based Stress Reduction course (MBSR; Kabat-Zinn, 1990). This group program aims to improve participants’ mindfulness and well-being, and reduce their levels of perceived stress. The study was an attempt to find objectively measurable neurological changes that could underlie the trait-changes associated with mindfulness practice. Changes in gray matter concentration were investigated using voxel-based morphometry. Focused analyses were conducted for the hippocampus and insula as our predefined regions of interest. Exploratory analyses were then performed on the entire brain and compared to a control group. Psychiatry Res. Author manuscript; available in PMC 2012 January 30.  Hölzel et al. Page 3 2. Methods 2.1 Participants NIH-PA Author Manuscript MBSR participants were recruited among individuals enrolled in four MBSR courses held at the Center for Mindfulness at the University of Massachusetts Medical School. The courses included physician- and self-referred individuals from across New England who were seeking stress reduction. Individuals were included in the study if they self-reported as physically and psychologically healthy and not taking any medications. Further inclusion criteria were: no meditation classes in the past six months, no more than four classes in the past five years, or ten classes in their lifetime; 25 to 55 years old; no contra-indications for MRI scanning (i.e., metallic implants, claustrophobia); commitment to attend all eight classes and perform the prescribed daily homework. Eighteen healthy, right-handed individuals were enrolled in the study, 8 male and 10 female, with a mean age of: 37.89 years (SD: 4.04 years). Due to discomforts during the first MRI scanning session, two participants did not return for the second session. The resulting sample consisted of 6 male and 10 female participants with a mean age of 38.0 years (SD: 4.1 years). Ethnicities were: 13 Caucasians, one Asian, one African American, and one multi-ethnic. Participants had an average of 17.7 years of education (SD: 1.9 years). Reimbursement for study participation was a discounted MBSR course fee. The control sample consisted of 17 participants (11 male and 6 female) with a mean age of NIH-PA Author Manuscript 39.0 years (SD: 9.2 years) and an average of 17.3 years of education (SD: 1.8 years). Ethnicities were: 13 Caucasians, two Asians, two African American, and one Hispanic. The groups did not differ in age (t (22.3) =.56; p =.58), or education (t (30) = −.56, p =.58). The study protocol was approved by the IRBs of Massachusetts General Hospital and the University of Massachusetts Medical School, and written informed consent was obtained from all participants. A previous publication that investigated neural correlates of changes in perceived stress (Hölzel et al., 2009) included data from this sample. 2.2 Intervention The MBSR program has been described extensively elsewhere (Kabat-Zinn, 1990). Briefly, it consists of eight weekly group meetings lasting two and a half hours each, plus one full day (6.5 hours) during the sixth week of the course. Formal mindfulness training exercises aim at developing the capacity for mindfulness (awareness of present-moment experiences with a compassionate, non-judgmental stance) and include a body scan, mindful yoga, and sitting meditation. During the body scan attention is sequentially guided through the entire body, observing with non-judgmental awareness the sensations in each region and ending with an awareness of the body “as a complete whole”. The mindful yoga typically contains NIH-PA Author Manuscript gentle stretching exercises and slow movements that are often coordinated with the breath, with emphasis placed on bringing full awareness to the moment-to-moment experience and a non-harming attitude towards the body. Participants are encouraged to investigate what feels appropriate for themselves and to honor their body’s limitations. Sitting meditation practices typically begin with awareness of the sensations of breathing, then evolve to include awareness of different modalities (such as sounds, sight, taste, other body sensations, thoughts and emotions). Later, emphasis is given to open awareness meditation, where the field of awareness is expanded to include anything that appears in consciousness, or a simple awareness of one’s presence in the here and now. Participants received audio recordings containing 45-minute guided mindfulness exercises (body scan, yoga, and sitting meditation) that they were instructed to practice daily at home. To facilitate the integration of mindfulness into daily life, they were also taught to practice mindfulness informally in everyday activities such as eating, walking, washing the dishes, Psychiatry Res. Author manuscript; available in PMC 2012 January 30.  Hölzel et al. Page 4 taking a shower etc. During classes the formal mindfulness exercises were practiced, questions relating to the practice of mindfulness in everyday life were clarified and didactic instruction given on using mindfulness for coping with stress in daily life. Historically, NIH-PA Author Manuscript MBSR participants have reported a wide range of home practice compliance and for this reason study participants recorded the amount of time they spent engaged in mindfulness exercises each day. 2.3 Five facet mindfulness questionnaire The Five Facet Mindfulness Questionnaire (FFMQ; Baer et al., 2006) is a 39-item scale to measure five factors of mindfulness: Observing (attending to or noticing internal and external stimuli, such as sensations, emotions, cognitions, sights, sounds, and smells), describing (noting or mentally labeling these stimuli with words), acting with awareness (attending to one’s current actions, as opposed to behaving automatically or absent- mindedly), non-judging of inner experience (refraining from evaluation of one’s sensations, cognitions, and emotions) and non-reactivity to inner experience (allowing thoughts and feeling to come and go, without attention getting caught up in them). Responses to the items are given on a 5-point Likert-type scale (1 = never or very rarely true, 5 = very often or always true). The five subscales have shown adequate to good internal consistency (Baer et al., 2006). Useable data from both time-points was obtained from 14 MBSR and 14 control participants. NIH-PA Author Manuscript 2.4 MRI data collection and analysis All participants were scanned at the Martinos Center for Biomedical Imaging in Charlestown, MA. MBSR participants were scanned during the 2 weeks before (Pre) and after (Post) participation in the program. Control participants were also scanned twice, approximately two months apart. There was an average time of 56.25 days (SD: 4.5 days) in between scanning sessions for the MBSR group and 65.67 days (SD: 11.22 days) for the control group. High-resolution MRI data were acquired with a Siemens Magnetom Avanto 1.5 T scanner with standard head coil. Data sets of the whole brain were collected using a T1 weighted MPRAGE-sequence, consisting of 128 sagittal slices (1.0 × 1.0 × 1.3 mm, TI = 1000 ms; TE = 3.39 ms; TR = 2730 ms). Image analysis was performed with voxel-based morphometry (VBM) tools within the SPM5 neuroimaging statistical software (Wellcome Department of Cognitive Neurology, London, www.fil.ion.ucl.ac.uk/spm/software/spm5/) based in MATLAB 7.1, release 14 (Mathworks Inc., Natick, MA, USA), using default settings unless otherwise specified. VBM permits an automated voxel-wise whole-brain statistical comparison of MRI scan (Ashburner and Friston, 2000). Images were manually aligned to the anterior commissure then segmented into gray and white matter in native space (i.e., before normalization, using the ‘Native Space’ segmentation option implemented NIH-PA Author Manuscript in SPM5). For each individual, the (unmodulated) gray matter segmentations of the Pre and Post images were spatially co-registered. Normalization parameters were calculated for the Pre scan and were applied to both time points (trilinear interpolation, 2 × 2 × 2 mm), to make sure that regional differences between the images were not removed by scan-specific spatial normalization (Driemeyer et al., 2008; Ilg et al., 2008). Images were smoothed using an 8 mm full width at half maximum Isotropic Gaussian Kernel. We computed exploratory whole brain analyses as well as region of interest (ROI) analyses. The ROI contained the bilateral hippocampi and bilateral insulae and was created using the WFU Pickatlas software (Maldjian et al., 2003) and based on the parcellation of Tzourio- Mazoyer et al. (Tzourio-Mazoyer et al., 2002). A paired t-test within the MBSR group was first performed in SPM5, in order to identify those brain regions with significantly increased gray matter concentration following participation in the MBSR program. Since our ROI analysis was spatially focused, we chose to correct for multiple comparisons within the ROI Psychiatry Res. Author manuscript; available in PMC 2012 January 30.  Hölzel et al. Page 5 (bilateral hippocampi and insulae) using the voxel-wise method implemented in SPM5. Given the very large number of voxels in the whole brain analysis, a voxel-wise method for preventing false positives seemed too conservative and leads to a substantial loss of NIH-PA Author Manuscript statistical power (Forman et al., 1995; Friston et al., 1996). We therefore chose to use a cluster-wise method for the exploratory whole-brain analysis and corrected for multiple comparisons across the entire brain using the method implemented in SPM5 (Friston et al., 1994). In order to exceed the threshold of p