02/04/2022 13:34 Randomized Controlled Trial of Mindfulness-Based Stress Reduction Versus Aerobic Exercise: Effects on the Self-Referentia…

Front Hum Neurosci. 2012; 6: 295.

Published online 2012 Nov 5. doi: 10.3389/fnhum.2012.00295

Randomized Controlled Trial of Mindfulness-Based Stress Reduction Versus Aerobic

Exercise: Effects on the Self-Referential Brain Network in Social Anxiety Disorder
Philippe Goldin,1,* Michal Ziv,1 Hooria Jazaieri,1 and James J. Gross1

Abstract

Background: Social anxiety disorder (SAD) is characterized by distorted self-views. The goal of this
study was to examine whether mindfulness-based stress reduction (MBSR) alters behavioral and brain
measures of negative and positive self-views. Methods: Fifty-six adult patients with generalized SAD
were randomly assigned to MBSR or a comparison aerobic exercise (AE) program. A self-referential en‐
coding task was administered at baseline and post-intervention to examine changes in behavioral and
neural responses in the self-referential brain network during functional magnetic resonance imaging.
Patients were cued to decide whether positive and negative social trait adjectives were self-descriptive or
in upper case font. Results: Behaviorally, compared to AE, MBSR produced greater decreases in negative
self-views, and equivalent increases in positive self-views. Neurally, during negative self versus case, com‐
pared to AE, MBSR led to increased brain responses in the posterior cingulate cortex (PCC). There were
no differential changes for positive self versus case. Secondary analyses showed that changes in endorse‐
ment of negative and positive self-views were associated with decreased social anxiety symptom severity
for MBSR, but not AE. Additionally, MBSR-related increases in dorsomedial prefrontal cortex (DMPFC) ac‐
tivity during negative self-view versus case were associated with decreased social anxiety related disabil‐
ity and increased mindfulness. Analysis of neural temporal dynamics revealed MBSR-related changes in
the timing of neural responses in the DMPFC and PCC for negative self-view versus case. Conclusion:
These findings suggest that MBSR attenuates maladaptive habitual self-views by facilitating automatic
(i.e., uninstructed) recruitment of cognitive and attention regulation neural networks. This highlights po‐
tentially important links between self-referential and cognitive-attention regulation systems and sug‐
gests that MBSR may enhance more adaptive social self-referential processes in patients with SAD.

Keywords: social anxiety, self-view, mindfulness, fMRI, exercise, brain, self, meditation

Introduction

Self-views can powerfully influence how a person thinks, feels, and behaves, particularly in social con‐
texts. The relationship of self-views to social functioning is especially salient in the clinical context of so‐
cial anxiety disorder (SAD). Cognitive models of social anxiety (Clark and Wells, 1995) suggest that dis‐
torted self-views, specifically, regarding the self as socially awkward, inadequate, or flawed are an essen‐
tial feature of SAD. Recent conceptualizations highlight distorted social self-views as the core problem in
SAD (Moscovitch, 2009). These models suggest that maladaptive social self-reflective processes are impli‐
cated in cognitively biased evaluations of self which generate negative emotions, disrupt emotion regula‐
tion, and interfere with social self-efficacy and performance (Spurr and Stopa, 2002).

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Meta-analyses of neuroimaging studies of self-referential processing in healthy adults have identified a

set of three cortical midline brain regions that comprise the self-referential network (SRN), including the
ventromedial prefrontal cortex (VMPFC), dorsomedial prefrontal cortex (DMPFC), and posterior cingu‐
late cortex/precuneus (hereafter abbreviated as PCC; Figure ​1; Northoff et al., 2006, 2011). To induce ac‐
tivation in the SRN, studies have used judgments of visually presented trait adjectives (Kelley et al.,
2002), aurally presented statements (Johnson et al., 2002), or mental reflection on self-traits (Kjaer et al.,
2002). Most studies have used tasks that require making a rapid judgment of whether or not a specific
trait applies to oneself. Specifically, neural activity in the VMPFC has been shown to be related to ratings
of self-relatedness (Phan et al., 2004; de Greck et al., 2008). Activation of the DMPFC and PCC has been
observed during self-endorsement of positive and negative traits in healthy adults (Fossati et al., 2003).

Figure 1

Self-referential network from Northoff et al. (2006).

Neuroimaging studies of self-referential processing have begun to investigate abnormal patterns of SRN
activity in a variety of clinical samples, however, results are mixed. In patients with major depressive dis‐
order, fMRI investigations have reported elevated VMPFC activation during event-related task designs
which is thought to be associated with more automatic alerting to self-relevant information, as well as el‐
evated transient DMPFC activation during block task designs which may represent more strategic evalua‐
tion (Lemogne et al., 2012). In patients with SAD, fMRI investigations have observed SRN activation dur‐
ing self-referential processing of trait adjectives, as well as brain regions implicated in language, memory,
affective, and visual processing during social trait self-endorsement (Goldin et al., 2009a), and decreased
VMPFC response for first (versus second) person self-referential statements which were associated with
increased social anxiety symptom severity (Blair et al., 2011). However, there are no randomized con‐
trolled trials (RCT) that have compared the impact of different psychosocial interventions on SRN activity
in patients with SAD. Conducting such RCTs may provide stronger evidence for the function and modula‐
tion of the SRN in clinical samples.

One especially intriguing psychosocial intervention that directly cultivates non-identification with self-
views is mindfulness-based stress reduction (MBSR; Kabat-Zinn, 1990). Meta-analyses of MBSR training
in healthy adults have shown reliable reductions in symptoms of anxiety, stress, and ruminative thinking
(Chiesa and Serretti, 2009). Among patients with anxiety disorders, meta-analysis indicates robust reduc‐
tion of anxiety, and depression symptoms (Vøllestad et al., 2012). An important fMRI study of self-refer‐
ence in a non-clinical sample of adults found that for the contrast of experiential (versus narrative) self-
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focus MBSR resulted in brain response decreases in anterior VMPFC and DMPFC regions and increases in
a right lateralized network including dorsolateral and ventrolateral PFC, insular cortex, supramarginal
gyrus, angular gyrus, inferior parietal lobule suggesting suppression of conceptual narrative self-process‐
ing, and enhancement of viscerosomatic processing and present-moment focused attention (Farb et al.,
2007). Inferences from this study are limited because brain responses were measured only at post-MBSR.
In the few studies of patients with SAD, there are preliminary positive results for MBSR training, includ‐
ing reduction of clinical symptoms and increased well-being (Koszycki et al., 2007; Jazaieri et al., 2012).
Proposed mechanisms of MBSR include modulation of attention regulation, body awareness, emotion
regulation, and self-views (Hö lzel et al., 2011). Thus, MBSR is expected to decrease grasping at concep‐
tual self-views (instantiated in the SRN and language brain networks) and to increase present-moment
experiential modes of self-processing (instantiated in viscerosomatic networks). The impact of MBSR on
the SRN in clinical populations, however, is not yet understood.

In patients with SAD, MBSR has been shown to modulate attention regulation, emotion regulation, and
self-views (Goldin et al., 2009a, 2012; Goldin and Gross, 2010). Neurally, during self-referential process‐
ing in patients with SAD, MBSR has been shown to decrease neural responses in brain regions related to
self-referential and language processing for positive self-views, and increase responses in brain regions
linked to attention engagement and regulation for negative self-views (Goldin et al., 2009a). This study
also reported associations of pre-to-post-MBSR increases in attention engagement related parietal brain
regions and decreases in anxiety symptoms. However, important caveats of these studies include a small
sample size, participant self-selection, and no active comparison intervention. Thus, the implementation
of a RCT with two active and dose matched stress reduction programs should support stronger inferences
about the effects of MBSR on self-views.

In addition to modulation of brain response magnitude, there is growing evidence of abnormal neural
temporal dynamics during social cognition and emotion regulation in patients with SAD (Campbell et al.,
2007; Goldin et al., 2009b). One study has reported MBSR-related changes in neural temporal dynamics
of emotional reactivity to negative self-views in adults with SAD (Goldin and Gross, 2010). Currently,
nothing is known about how MBSR impacts the neural temporal dynamics of brain responses within the
SRN. Analysis of neural temporal dynamics might elucidate the effects of MBSR on other cognitive pro‐
cesses that come online in patients with SAD when engaging to self-referential processing, such as shifts
in attention regulation and cognitive regulation of emotional reactivity to self-views.

Considered together, these changes suggest that MBSR likely modulates multiple cognitive processes.
MBSR is hypothesized to increase the ability to decenter from habitual patterns of reactivity. However, in
the case of adults with SAD, MBSR may have more specific effects such as modifying some of the core cog‐
nitive biases (e.g., distorted self-views, maladaptive attention, and emotional processing, deficient cogni‐
tive regulation) that are fundamental features of social anxiety.

The goal of the present study was to investigate the differential effects of MBSR versus an active control
condition [aerobic exercise (AE) stress reduction] on the neural bases of self-referential processing in pa‐
tients with generalized SAD in the context of a RCT. MBSR cultivates a non-judgmental, pliable present-
moment awareness that decreases habitual patterns of evaluation and reactivity, and increases psycho‐
logical flexibility. In patients with SAD, MBSR is associated with reduced symptoms of anxiety, depression
and self-deprecation, and increased quality of life and functionality (Koszycki et al., 2007). A recent re‐
view suggests that the brain-based mechanisms underlying MBSR include attention regulation, body
awareness, emotion regulation, and changes in the self-views (Hö lzel et al., 2011). Few studies, however,
have investigated these proposed brain-based mechanisms in the context of a RCT. To do this, we choose
AE as a control condition for several reasons. Like MBSR, AE has been shown to improve both physical
and mental health (Penedo and Dahn, 2005), especially symptoms of stress, depression, and anxiety
(Petruzzello et al., 1991; Stich, 1998; Strö hle, 2009) in clinical samples of mixed anxiety (e.g., Merom et
al., 2007), panic disorder (e.g., Broocks et al., 1998; Dratcu, 2001), and generalized anxiety disorder (e.g.,

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Steptoe et al., 1989; McEntee and Halgin, 1999). As implemented in this study, we matched the amount of
individual and group practice for MBSR and AE. Presently, there are no studies describing the impact of
AE on self-views in patients with SAD.

We conducted a RCT in which we obtained behavioral and neural measures of self-views during an fMRI
assessment in patients with generalized SAD before and after MBSR or AE. For behavioral responses, we
expected that, compared to AE, MBSR would result in self-endorsement of more adaptive self-views,
namely, greater decreases in negative and greater increases in positive self-views. For neural responses,
based on prior studies that reported reduction in cortical midline brain region responses during experi‐
ential (versus narrative) self-focus (Farb et al., 2007) and during self-referential processing in patients
with SAD (Goldin et al., 2009a), we expected that, compared to AE, MBSR would result in greater reduc‐
tions during negative and positive self-referential processing in the VMPFC and DMPFC. Based on previ‐
ous reports of MBSR-related increased activity in parietal cortex regions associated with attention en‐
gagement and regulation in general (Farb et al., 2007; Hö lzel et al., 2011) and specifically in patients with
SAD (Goldin et al., 2009a; Goldin and Gross, 2010), we expected that, compared to AE, MBSR would result
in greater increases in PCC during negative and positive self-referential processing. In secondary analyses,
we examined whether MBSR and AE-related changes in behavioral and brain responses related to
changes in clinical symptoms and mindfulness, and how MBSR impacted the neural temporal dynamics in
the three SRN brain regions.

Materials and Methods

Participants

Participants were unmedicated patients seeking treatment for SAD who met DSM-IV (American
Psychiatric Association, 1994) criteria for generalized SAD. Of 316 individuals assessed for eligibility, 260
were excluded (173 for not meeting study criteria, 66 for other reasons, and 21 declined to participate).
The remaining 56 participants were randomly assigned to either MBSR (n = 31) or AE (n = 25; Figure ​2).
Groups did not differ in gender, age, ethnicity, or education (Table ​1). fMRI assessments at both baseline
and post-intervention were available for 24 MBSR and 18 AE participants.

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Figure 2

Consolidated standards of reporting trials diagram for randomized controlled trial of mindfulness-based stress
reduction (MBSR) versus aerobic exercise (AE).

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Table 1

Demographic characteristics at baseline for patients randomized to mindfulness-based stress reduction versus
aerobic exercise.

MBSR AE t-Test

n = 31 n = 25 or χ2

Females, n (%) 19 (61.3%) 10 (40%) χ2 = 2.88

Age (M years ± SD) 32.87 ± 8.83 32.88 ± 7.97 t = 0.42

Ethnicity, n (%) χ2 = 0.43

Caucasian 13 (41.9%) 10 (40%)

Asian 14 (45.2%) 11 (44%)

Hispanic 3 (9.7%) 1 (4%)

Multiracial 1 (3.2%) 3 (12%)

Education (M years ± SD) 16.40 ± 2.00 16.84 ± 2.64 t = 0.34

Current axis-I comorbidity χ2 = 4.88

Generalized anxiety disorder 10 (32%) 8 (32%)

Major depressive disorder 5 (16%) 6 (24%)

Dysthymia 2 (6%) 3 (12%)

Specific phobia 3 (10%) 2 (8%)

Panic disorder 2 (6%) 2 (8%)

Agoraphobia 1 (3%) 2 (8%)

Obsessive-compulsive disorder 1 (3%) 0

Past axis-I comorbidity χ2 = 1.49

Major depressive disorder 9 (29%) 2 (8%)

Dysthymia 1 (3%) 0

Panic disorder 1 (3%) 0

Obsessive-compulsive disorder 0 1 (4%)

Substance abuse 0 1 (4%)

Eating disorder 3 (10%) 1 (4%)

Past psychotherapy 15 (48%) 9 (36%) χ2 = 1.84

Past pharmacotherapy 7 (23%) 5 (20%) χ2 = 1.56

GAF (M ± SD) 53.36 ± 5.87 55.38 ± 4.06 t = 1.02

CGI (M ± SD) 4.93 ± 1.23 5.22 ± 0.60 t = 1.33

n, Sample size, M, mean; SD, standard deviation; GAF, global assessment of functioning; CGI, clinical global impression.

Patients passed an MR safety screen and had to be medication and psychotherapy-free for at least 6
months with no history of medical disorders or head trauma. Patients had to have a primary diagnosis of
generalized SAD and no evidence of thought disorders, bipolar depression, alcohol, or drug dependence.
Patients were not permitted to be currently in any form of pharmacological or psychological treatment.
Patients were excluded if they had previously completed an MBSR course or if they had a regular medita‐
tion practice or AE regime (defined as three or more times per week, for more than 2 months). Patients

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randomized to MBSR and AE did not differ in current or past Axis-I comorbidity, current Global
Assessment of Functioning or Clinical Global Impression, and past psychotherapy or past pharmacother‐
apy (Table ​1).

Procedure

Patients were recruited through web-based community listings and referrals from mental health
providers. After passing a telephone screening, potential participants were administered the ADIS-IV-L
(Di Nardo et al., 1994) by a clinical psychologist. We enrolled patients with a principal diagnosis of gener‐
alized SAD operationalized as (a) moderate or higher severity (≥4 on a scale of 0–8) on the ADIS-IV-L
Clinician’s Severity Rating for SAD and (b) social fear for five or more distinct social or performance situa‐
tions in the SAD section. Patients were randomly assigned to MBSR or AE using a biased coin randomiza‐
tion procedure (Efron, 1971) which entails higher probability of allocation to the group with fewer par‐
ticipants. This method controls for potential confounds encountered when a greater number of partici‐
pants are assigned at specific time points during a trial to one of two interventions. Patients were admin‐
istered self-report clinical and fMRI scanning assessments before and after MBSR and AE. All participants
provided informed consent in accordance with the Stanford University Human Subjects Committee and
federal guidelines.

Mindfulness-based stress reduction

Mindfulness-based stress reduction consisted of eight, weekly 2.5 h group classes, a 1-day meditation re‐
treat, and daily home practice. Patients were trained in formal meditation, informal practice, and Hatha
yoga. Daily logs were collected each week to measure group and individual meditation and yoga practice.
Patients attended MBSR courses offered by seven different teachers in eight healthcare settings through‐
out the San Francisco Bay Area. Instructors had an average of 15.7 years (SD = 4.1 years, range = 10–20
years) of MBSR teaching experience.

Aerobic exercise

To match the individual and group components of MSBR, participants in the 8-week AE intervention were
provided a 2-month gym membership and were required to complete weekly at least two individual AE
sessions and one group AE session (other than meditation or yoga).

Self-referential encoding task

The self-referential encoding task (SRET; Derry and Kuiper, 1981) is considered an information process‐
ing measure of self-schema. Stimuli consisted of 25 positive and 25 negative social trait adjectives from
the Affective Norms of Emotion Words database (Bradley and Lang, 1999), balanced (all ps > 0.51) on
word frequency (positive adjectives = 40.5, negative adjectives = 33.6) and number of letters (positive ad‐
jectives = 6.9, negative adjectives = 7.2), as well as on arousal (positive adjectives = 5.54, negative adjec‐
tives = 5.43 on a scale of 1 = low to 9 = high using) and valence (deviation from neutral: positive adjectives
= 2.66, negative adjectives = 2.58 on a scale of 1 = most negative, 5 = neutral, 9 = most positive) based on
the nine-point Self-Assessment Manikin rating system (Lang, 1980).

The SRET was 5 min and 39 s in length. Each adjective was presented twice, once in each of two condi‐
tions. The self-referential condition assessed self-focused social-evaluative processing. Case identification
was used as a comparison condition to control for reading negative and positive adjectives while deter‐
mining whether the word consisted of upper or lower case letters. Each of the four trial types (two condi‐

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tions by two valences) included five blocks. Each block consisted of fixation, question (either “Describes
ME?” or “UPPER case?”), and five adjectives of the same valence presented one at a time for 3 s each
(Figure ​3).

Figure 3

Trial structure for self-referential encoding task.

Stimulus order included a pseudo-random block sequence with no more than two blocks of the same con‐
dition in a row and a random sequence of words and upper/lower case within each block. Patients
pressed buttons to indicate whether or not a word was self-descriptive or in uppercase letters.

Measures of clinical symptoms and mindfulness

To measure severity of social anxiety symptoms, we used the 24-item Liebowitz Social Anxiety Scale-Self-
Report (LSAS-SR; Liebowitz, 1987; Fresco et al., 2001), which consists of questions that assess social in‐
teraction situations (11 items) and performance situations (13 items). A four-point Likert-type scale is
used for ratings of fear and of avoidance, with a range from 0 (none and never, respectively) to 3 (severe
and usually, respectively) for situations during the past week. Ratings are summed for a total LSAS-SR
score (range = 0–144). The LSAS-SR has reliability and construct validity (Rytwinski et al., 2009) and its
internal consistency (Cronbach’s alpha) for this study was 0.90 in MBSR and 0.90 in AE.

To measure social anxiety related disability, we administered the Sheehan Disability Scale (SDS; Sheehan,
1983) which measures work, social life, and family life impairment as a function of SAD and comorbid
conditions, and has demonstrated good internal consistency and validity (Hambrick et al., 2004), and its
internal consistency in this study was 0.68 in MBSR and 0.68 in AE.

To measure mindfulness, we used the Kentucky Inventory of Mindfulness Skills (FFMQ; Baer, 2003). It is a
39-item self-report measure which measures mindfulness, and includes four components: observing, de‐
scribing, acting with awareness, and accepting without judgment. Items are rated on a five-point Likert
scale. The instrument has good internal consistency and validity (Baer et al., 2004), and its internal con‐
sistency in this study was 0.76 in MBSR and 0.85 in AE.

To measure the potential confound of social desirability, we administered the 10-item Marlowe–Crowne
Social Desirability Scale (MCSDS; Crowne and Marlowe, 1960). The instrument consists of true-false items
with four reverse coded items, with higher scores reflecting a greater tendency to give a socially desirable
response. It has shown adequate internal consistency and reliability (Crino et al., 1983).

fMRI acquisition

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Imaging was performed on a General Electric 3 T Signa magnet using a custom-built quadrature “dome”
elliptical bird cage head coil and a T2*-weighted gradient echo spiral-in/out pulse sequence that used
blood oxygenation level-dependent (BOLD) contrast. Head movement was minimized using a bite bar
and padding. During a single run, 226 volumes (each consisting of 22 sequential axial slices) were ob‐
tained (TR = 1500 ms, TE = 30 ms, flip angle = 60, FOV = 22 cm, frequency encoding = 64, voxel = 3.438 mm
× 4.5 mm). A high-resolution anatomical scan was acquired using a fast spin-echo spoiled grass pulse se‐
quence (voxel = 0.85942 mm × 1.2 mm; FOV = 22 cm, frequency encoding = 256).

fMRI data preprocessing

Analysis of functional neuroimages (AFNI) software (Cox, 1996) was used for preprocessing and statisti‐
cal analysis. Preprocessing included an analysis of potential outliers, volume registration to a base image,
motion correction, 4 mm3 isotropic Gaussian spatial smoothing, high-pass filtering (0.011 Hz), linear de‐
trending, and conversion into percentage change in each voxel. No volumes demonstrated motion in the
x, y, or z directions in excess of ±0.8 mm. There was no stimulus-correlated motion, as assessed by corre‐
lations between condition-specific reference functions and x, y, z motion correction parameters (all ps >
0.48).

fMRI statistical analysis

Multiple-regression was implemented with AFNI 3dDeconvolve and included baseline parameters to re‐
move mean, linear, and quadratic trends, and motion-related variance in the BOLD signal. Regressors for
the negative self, negative case, positive self, and positive case were convolved with the gamma variate
model (Cohen, 1997) of the hemodynamic response function. Functional MRI BOLD signal intensity was
computed as percentage of signal change [(MR signal per voxel per time point/mean MR signal in that
voxel for the entire functional run) × 100]. Brain maps were converted to Talairach atlas space (Talairach
and Tournoux, 1988) and second-level group statistical parametric maps were produced according to a
random-effects model.

Repeated-measures analysis of variance with planned follow-up t-tests was conducted to examine aver‐
age BOLD responses in masks for each of the three cortical midline SRN regions (VMPFC, DMPFC, and
PCC). The a priori rectangular region-of-interest masks were defined by a meta-analysis of 27 neuroimag‐
ing studies (Northoff et al., 2006). The Talairach coordinates of the boundaries of the three rectangular
masks are: VMPFC x = −12 to 8, y = 38–60, z = −7 to 21, DMPFC: x = −14 to 12, y = −11 to 31, z = 37–61, and
PCC: x = −14 to 8, y = −74 to −48, z = 10–52.

For the examination of pre-to-post-intervention changes in the temporal dynamics in each region we
used repeated-measures ANOVA with the Greenhouse–Geisser correction for potential violations of
sphericity in the time course of 10 time points (or 15 s per trial).

We also conducted whole-brain t-tests to examine within-group changes pre-to-post-MBSR and AE, sepa‐
rately, on negative and positive self-views. We used AlphaSim, a Monte Carlo simulation bootstrapping
program in the AFNI library, to protect against false positive cluster detection (Forman et al., 1995). The
program determined that a voxel-wise p < 0.001 threshold and cluster volume threshold of ≤213 mm3 (4
voxels × 3.438 mm × 4.5 mm) provided protection against false positive cluster detection at p < 0.01.

Results

Clinical responses

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As shown in Table ​2, both MBSR and AE yielded significant reductions in social anxiety symptom severity
(LSAS-SR; ts > 4.05, ps < 0.001), SAD-related disability (SDS; ts > 2.29, ps < 0.05), and increases in mindful‐
ness (KIMS; ts > 2.26, ps < 0.05). However, there were no between-group differences in pre-to-post change
(all ps > 0.34). A full account of the treatment-related self-reported changes in clinical and well-being
measures has been published elsewhere (Jazaieri et al., 2012).

Table 2

Self-endorsement and clinical variables.

MBSR n = 31 AE n = 25

Mean ± SD Mean ± SD

LIEBOWITZ SOCIAL ANXIETY SCALE-SELF-REPORT

Pre 87.3 ± 20.6 90.1 ± 17.1

Post 56.7 ± 19.0 61.4 ± 28.6

SHEEHAN DISABILITY SCALE

Pre 17.8 ± 7.1 18.0 ± 6.8

Post 9.2 ± 3.8 13.5 ± 8.5

KENTUCKY INVENTORY OF MINDFULNESS SKILLS

Pre 110.9 ± 12.9 110.9 ± 14.9

Post 126.5 ± 13.2 117.5 ± 14.6

NEGATIVE SELF-ENDORSEMENT

Pre 66.8 ± 18.4 65.3 ± 18.7

Post 33.6 ± 22.0 49.8 ± 27.0

POSITIVE SELF-ENDORSEMENT

Pre 32.3 ± 16.7 35.5 ± 20.3

Post 50.7 ± 28.1 46.2 ± 20.0

To rule out the possibility of a social desirability response bias on self-report measures, we examined the
relationship of the MCSDS and the clinical variables listed in Table ​2. We found no relationship (rs: −0.20
to +0.11, all ps > 0.09) between the MCSDS and baseline SRET negative self-endorsement, SRET positive
self-endorsement, social anxiety symptom severity (LSAS), SAD-related disability (SDS), and mindfulness
skills (Kentucky Inventory of Mindfulness Skills). There was also no relationship between the MC and the
same measures at post-intervention (rs: −0.08 to 0.21, all ps > 0.21).

Behavioral responses

For self-endorsement of negative social traits, a 2 Group (MBSR, AE) × 2 Time (pre, post) repeated-mea‐
sures ANOVA yielded no main effect of group (p > 0.25), a main effect of time (F = 46.31, p < 0.0001, η = 2
p

0.63), and an interaction of group by time (F = 4.50, p < 0.05, η = 0.14). Follow-up paired t-tests showed
2
p

decreases in negative self-endorsement from pre-to-post-MBSR (change = −33.2, t = 5.72, p < 0.001, η = 2
p

0.70) and AE (change = −15.5, t = 3.84, p < 0.002, η = 0.53). Compared to AE, MBSR led to greater de‐
2
p

creases in negative self-endorsement (t = 2.10, p < 0.05, η = 0.16; Figure ​4; Table ​2).
2
p

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Figure 4

Blood oxygenation level-dependent signal at baseline for negative self versus case and positive self versus case
for all patients with SAD. T-maps were thresholded at t > 3.65, voxel-wise p < 0.001 and cluster volume >6 voxels in or‐
der to obtain a cluster-wise p < 0.05. *p < 0.05; error bars = SEM.

For self-endorsement of positive social traits, a 2 Group × 2 Time repeated-measures ANOVA yielded no
main effect of group (p > 0.84), a main effect of time (F1,28 = 25.75, p < 0.001, η = 0.49), and no interaction
2
p

of group by time (p > 0.33). Follow-up paired t-tests revealed increases in positive self-endorsement from
pre-to-post-MBSR (change = 18.4, t = 4.14, p < 0.001, η = 0.51) and AE (change = 10.7, t = 3.02, p < 0.01, η
2
p
2
p

= 0.41) that were not statistically different (t = 0.97, p > 0.34).

Brain responses

Manipulation check

To confirm that the SRET task induced activation of the cortical midline SRN, we examined BOLD re‐
sponses for negative and positive self-views, separately, across all patients at baseline. There was evi‐
dence of robust activations in VMPFC, DMPFC, and PCC regions for the contrasts of negative self versus
case and positive self versus case (Figure ​5).

Figure 5

Pre-to-post change in self-endorsement of negative and positive self-views.

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Treatment-related changes in the self-referential network

We conducted a 2 Group (MBSR, AE) × 2 Time (pre, post) repeated-measures ANOVA of BOLD responses
in each of the three SRN a priori ROIs (DMPFC, VMPFC, PCC) for the contrasts of negative self (versus
case) and positive self (versus case), separately.

Negative self-view

For the DMPFC, there were no main effects of time (p > 0.14) or group (p > 0.89), but there was a signifi‐
cant interaction of group by time (F = 8.87, p < 0.005, η = 0.18). Follow-up paired t-tests showed no sig‐
2
p

nificant change in BOLD signal from pre-to-post-MBSR (change = 0.03, p > 0.29, η = 0.4) and a decrease
2
p

from pre-to-post-AE (change = −0.10, t = 3.62, p = 0.002, η = 0.45; Figure ​6). For the VMPFC, there were
2
p

no main or interaction effects (all ps > 0.35). For the PCC, there were no main effects of time (p > 0.82) or
group (p > 0.17), and a significant interaction of group by time (F = 6.29, p < 0.05, η = 0.13). Follow-up t-
2
p

tests showed an increase from pre-to-post-MBSR (change = 0.09, t = 2.16, p < 0.05, η = 0.16) and no sig‐ 2
p

nificant change in AE (change = −0.07, p > 0.15, η = 0.12). 2

p

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Figure 6

Blood oxygenation level-dependent signal in the three self-referential network brain regions pre- and post-
mindfulness-based stress reduction and aerobic exercise in patients with social anxiety disorder for positive self
versus case and negative self versus case (A) Dorsomedial Prefrontal Cortex. (B) Ventromedial Prefrontal Cortex.
(C) Posterior Cingulate Cortex. *p < 0.05; error bars = SEM.

Positive self-view

There were no main or interaction effects (all ps > 0.10) in the VMPFC, DMPFC, and PCC.

Secondary analyses

We examined whether MBSR and AE-related changes in behavioral and brain responses were related to
changes in clinical symptoms and mindfulness, and also tested how MBSR impacted the neural temporal
dynamics in the three SRN brain regions for the contrast of negative self versus case. For completeness,
we also report the within-group effects of MBSR and AE, separately, on whole-brain responses for nega‐
tive and positive self-referential processing.

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Association of behavioral responses and clinical symptoms

For behavioral responses, decrease in self-endorsement of negative self-views was associated with de‐
crease in social anxiety symptom severity (LSAS-SR) from pre-to-post-MBSR (r = 0.85, p < 0.001), but not
AE (r = 0.00, p > 0.99; Zdiff = 2.48, p = 0.013). Increase in self-endorsement of positive self-views was asso‐
ciated with decrease in social anxiety symptom severity from pre-to-post-MBSR (r = −0.94, p < 0.001), but
not from pre-to-post-AE (r = −0.11, p > 0.73; Zdiff = 3.25, p = 0.001). There was no relationship with mind‐
fulness (KIMS).

Association of brain responses and clinical symptoms/mindfulness

For the contrast of self-endorsement of negative self (versus case), increases in DMPFC activity were as‐
sociated with (a) decreased social anxiety related disability (SDS) from pre-to-post-MBSR (r = −0.58, p <
0.05; Figure ​A1 in Appendix) and AE (r = −0.63, p < 0.05) and (b) increased mindfulness (KIMS) in MBSR
(r = 0.60, p < 0.05; Figure ​A2 in Appendix), but not in AE (r = 0.35, p > 0.43; Zdiff = 0.80, p > 0.42). For the
contrast of self-endorsement of positive self (versus case), decreases in DMPFC activity were associated
with increased mindfulness (KIMS) in MBSR (r = −0.53, p < 0.05; Figure ​A3 in Appendix) but not in AE (r
= 0.21, p > 0.65; Zdiff = 1.98, p < 0.05).

Neural temporal dynamics

For the contrast of negative self (versus case) in the MBSR group, we conducted a 2 Group (MBSR, AE) × 2
Time (pre, post) × 10 TRs (ten 1.5 s TRs or brain volume acquisitions) repeated-measures ANOVA with
Greenhouse–Geisser correction on BOLD responses for each of the three SRN brain regions.

In the DMPFC, there was not a three-way interaction (p > 0.18). However, there was a group by time inter‐
action (F = 8.87, p < 0.005, η = 0.18; Figure ​7). Paired t-tests comparing BOLD response at each time
2
p

point in the 15-s blocks showed significant increases from pre-to-post-MBSR in the middle of the 15-s
blocks and significant decreases from pre-to-post-AE in the early and later segments of blocks.

Figure 7

Blood oxygen level-dependent signal time series in the (A) dorsomedial prefrontal cortex (DMPFC) and (B) pos‐
terior cingulate cortex (PCC) across each 15 s block for the contrast of negative self-view versus case pre- and
post-MSBR and AE. *p < 0.05, **p < 0.01; error bars = SEM.

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In the VMPFC, there were no three- or two-way interactions (all ps > 0.35).

In the PCC, there was not a three-way interaction (p > 0.08). However, there was an interaction of group
by time (F = 6.29, p < 0.05, η = 0.13). Paired t-tests comparing BOLD response at each time point in the
2
p

15-s blocks again showed significant increases from pre-to-post-MBSR in the middle of the 15-s blocks
and significant decreases from pre-to-post-AE in the early segment of blocks.

Treatment-related changes in whole-brain

For MBSR, a paired t-test yielded pre-to-post BOLD signal increases for negative self (versus case) in ven‐
tromedial, left ventrolateral, and bilateral dorsolateral PFC, PCC/precuneus, left inferior parietal lobule,
and left posterior superior temporal gyrus (Table ​A1 in Appendix). The contrast of positive self (versus
case) yielded BOLD signal increases in anterior and posterior ventromedial, dorsomedial, right ventrolat‐
eral, and left anterior dorsolateral PFC, as well as subcortical uncus. For AE, a paired t-test revealed no
significant pre-to-post BOLD signal increases for negative self (versus case), and increased responses in
only the left mid-insula for positive self (versus case Table ​A2 in Appendix).

Discussion

The primary goal of this study was to investigate in the context of a RCT how MBSR, compared to an ac‐
tive comparison program (AE stress reduction), impacted behavioral and neural indicators of self-views
in unmedicated adult patients with generalized SAD.

Clinically, both MBSR and AE significantly reduced social anxiety symptoms and disability, and enhanced
mindfulness skills. Previous studies have shown similar MBSR-related improvements in patients with
SAD (Goldin et al., 2009a; Goldin and Gross, 2010). While resistance and AE training have shown promise
in reducing worry symptoms in patients with generalized anxiety disorders (Herring et al., 2012), this is
the first study to demonstrate in an RCT that short-term (2 months) AE training reduces social anxiety
symptom severity and disability inpatients with generalized SAD. The increase in mindfulness skills may
be related to enhanced attention to and awareness of sensations related to instantiating a regular physi‐
cal exercise practice. Some portion of the effect of AE in this study may also be related to social fear expo‐
sure occurring when exercising in a public gym facility. Ostensibly, patients with SAD may have experi‐
enced habituation or extinction of their social fears over repeated incidental exposures in the gym.
Importantly, none of the self-report measures were associated with a measure of social desirability re‐
sponse bias, which excludes the potential confounds associated with self-report questionnaires and treat‐
ment efficacy expectations.

For the self-referential processing task (i.e., SRET), we examined self-endorsement and neural responses
during positive and negative self-views. Behaviorally, MBSR and AE yielded significant self-endorsement
decreases in negative and increases in positive self-views. However, compared to AE, MBSR resulted in
(a) greater reduction in self-endorsement of negative self-views, (b) which was related to reduction in so‐
cial anxiety symptom severity. Interestingly, increased mindfulness was not associated with changes in
self-views. These findings suggest that chronically distorted social self-views in patients with SAD are
modified during MSBR and that more adaptive self-views are related to clinical symptom improvement.
Prior studies have also observed MBSR-related enhancement of more adaptive social self-views in pa‐
tients with SAD (Goldin et al., 2009a).

Several mindfulness skills are trained in MBSR. One specific mindfulness skill that may modify self-views
is decentering. This refers to non-identification with thoughts and beliefs, and active disengagement from
ruminative self-evaluations and judgments (Fresco et al., 2007). Decentering can be understood as a cog‐
nitive process that results in attenuating habitual grasping at thoughts and beliefs as accurate reflections
of the self. It has been proposed as a core mechanism of mindfulness meditation training (Segal et al.,
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2002; Ramel et al., 2004), that may account for the MBSR-related modification of self-views. However, the
effects of decentering may manifest in different ways in different populations. In non-anxious healthy
controls, decentering may appear as less identification with any self-concept. In the clinical context of
SAD, however, MBSR-related increases in decentering may have a different initial impact. Specifically, in
patients with SAD who have had life-long problems with inaccurate (i.e., exaggerated negative self-be‐
liefs) and maladaptive (i.e., viewing the self as unworthy and incapable of change) self-views, MBSR
might first re-establish more adaptive self-views (i.e., lesser negative, greater positive self-views) as a
foundation for later inducing more subtle changes related to decentering and non-identification with any
and all conceptual self-views (which is one of several more advanced result of mindfulness meditation
practice).

Neurally, the manipulation check of the SRET task at baseline confirmed robust BOLD signal for positive
and negative self-views in the expected cortical midline brain regions implicated in the SRN. Examination
of differential change as a function of treatment modality revealed significant interactions during nega‐
tive self (versus case) characterized by MBSR-related increased responses in the PCC and DMPFC.
Examination of BOLD signal time series data showed greater recruitment of DMPFC and PCC activity in
the middle portion of each 15 s block during negative self-processing from pre-to-post-MBSR. There was
no significant effect of positive self (versus case). Thus, in alignment with our predictions, we did find in‐
creased attention-related PCC/precuneus response following MBSR, but did not find decreased BOLD re‐
sponse in more conceptual and cognitive control brain regions, as hypothesized, in the VMPFC and
DMPFC.

Interestingly, recent research in developmental cognitive neuroscience suggests that SRN activation dur‐
ing self-reflection is considered a sign of healthy cognitive functioning and reflects the ability to sustain
internal self-focused attention – an important component of self-regulation. In contrast, low levels of SRN
activation have been identified as a risk factor for the development of psychological disorders and im‐
paired social functioning (Schneider et al., 2012). Furthermore, insufficient activation of the SRN and
brain networks that support socioemotional processes (specifically mentalizing, emotion, and emotion
regulation) may represent disorganization and/or lack of adequate development of the self-concept
(Pfeifer and Peake, 2012). Thus, activation of the SRN appears to reflect adaptive self-referential process‐
ing which may be an important component of self-development, social functioning, and self-regulation.

Further evidence for the functional relevance of the Northoff meta-analysis derived ROIs used in this
study is reflected by the double dissociation of DMPFC responses (decreased during positive and in‐
creased during negative self-processing) and increased mindfulness. Increased DMPFC during negative
self-processing was also related to decreases in SAD-related disability. The MBSR-related increases in
DMPFC activity during negative self-processing may be related to greater ability to greater recruitment of
cognitive control mechanisms that regulate habitual patterns of emotional reactivity and attention alloca‐
tion. This pattern of results highlights the importance of investigating both BOLD signal magnitude and
timing, as well as their relationship to individual difference measures in order to elucidate how MBSR
might enhance adaptive self-focus, increase psychological flexibility and reduce clinical dysfunction.

The psychological functions instantiated in DMPFC and PCC that are recruited during the SRET following
MBSR training might reveal the features of SAD that are specifically amenable to change with mindfulness
meditation training. In general, increased SRN activation in this clinical context may reflect a greater en‐
gagement in the external stimulus (i.e., enhanced ability to monitor the external stimulus) without shift‐
ing to habitual automatic avoidance which is a hallmark feature of anxiety disorder. This psychological
change may be a foundation for the adaptive changes in self-views as well as clinical and social function‐
ing observed in this study.

The DMPFC has been implicated in multiple executive cognitive functions, including strategic evaluation
(Lemogne et al., 2012), introspection, evaluation and decision-making (Northoff and Bermpohl, 2004;
Schmitz and Johnson, 2007; van der Meer et al., 2010), cognitive discernment and explicit appraisal of

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self-relatedness, and cognitive reappraisal of emotional reactivity in healthy adults (Ochsner and Gross,
2005; Northoff et al., 2009). DMPFC responses have also been linked to greater ability to down-regulate
negative emotions in patients with SAD (Goldin et al., 2009b). Here, increased DMPFC (along with PCC)
activity during negative self (versus case) following MBSR may reflect increased ability to monitor
present-moment experience and a concomitant reduction in prepotent cognitive biases, including attend
to followed by distract away attention biases, negative interpretations, and distorted self-evaluations.
Additionally, phasic increases in DMPFC may also reflect transient increases in spontaneous (i.e., uncued)
cognitive reappraisal of emotional reactivity to negative self-views. Recent models suggest that enhanced
MBSR-related psychological flexibility, for example, mindful coping with perceived stressors, involves the
process of disengaging and withdrawing from automatic negative appraisals into a transitory metacogni‐
tive state that attenuates semantic evaluations and enhances positive cognitive reappraisal (Garland et
al., 2009).

Increases in PCC/precuneus activity during negative self (versus case) following MBSR in adults with SAD
has been reported previously (Goldin et al., 2009a). PCC/precuneus has been implicated in multiple
higher-order cognitive functions, including visual-spatial imagery, episodic memory retrieval, first-per‐
son perspective taking, experience of agency, self-relevance, and personal identity (Cavanna and Trimble,
2006; Hö lzel et al., 2011). Furthermore, subdivisions of the PCC/precuneus suggest different patterns of
functional connectivity. In particular, the PCC and the central precuneus are known to be functionally con‐
nected with PFC regions including the DMPFC in a circuit that is related to higher-order executive pro‐
cessing (Margulies et al., 2009). A recent review suggests that the MPFC and PCC are part of a brain net‐
work with other brain regions implicated in mentalizing (i.e., theory of mind), emotion awareness and
emotion regulation, and that the functioning of these psychological functions are fundamental in the de‐
velopment of socioemotional skills and self-concept (Pfeifer and Peake, 2012). Clinically, concomitant in‐
creases in DMPFC and PCC have been linked to successful pharmacologic treatment (Samson et al., 2011)
and interpersonal therapy for major depression (Martin et al., 2001). This is the first demonstration of
increased DMPFC and PCC being linked to clinical improvement in patients with SAD following MBSR.

The whole-brain analysis was not the primary focus of this study. However, the whole-brain results pro‐
vided further support that MBSR training increased activity in brain regions involved in cognitive regula‐
tion (medial PFC, bilateral dorsolateral PFC, left ventrolateral PFC), and attention regulation (right
DLPFC, PCC/precuneus, inferior parietal lobule; Fan et al., 2005). Here, even though there was no explicit
instruction to implement top-down regulation during the SRET task, these brain changes suggest that
MBSR enhanced the recruitment of cognitive and attention regulation brain networks that reduce habit‐
ual automatic emotional (i.e., anxiety and fear) and behavioral (e.g., avoidance, attention disengagement)
patterns. This converges with proposed mechanisms of MBSR, namely, enhanced attention regulation and
cognitive regulation of emotion, as well as modulation of self-views (Hö lzel et al., 2011). It further sug‐
gests that increases in cognitive regulation-related PFC regions (as was seen in the Farb et al., 2007 study
during experiential versus narrative self-focus), might facilitate modification of habitual self-views.

With regard to the effect of AE, there was clear evidence of enhanced positive and reduced negative self-
views, albeit less than MBSR, as well as similar AE and MBSR improvement in clinical symptoms and
mindfulness skills. What is less clear, however, is what psychological and neural mechanisms are modu‐
lated by AE that account for these changes. Given the completely different pattern of pre-to-post-AE and
MBSR SRN ROIs (Figures ​6 and ​7) and whole-brain (Tables ​A1 and ​A2 in Appendix) changes, different
brain mechanisms must be at play. Clearly, MBSR-related processes such as decentering or non-identifica‐
tion with thought and beliefs are not likely to be the skills actively cultivated with AE. The increased left
insula activity for positive self versus case could suggest greater viscerosomatic awareness following AE.
From our previous published report (Jazaieri et al., 2012), we know that AE (and MBSR) were associated
with significant increases in self-esteem, and that increased self-esteem is associated with pre-to-post-AE
decreases in social anxiety symptoms (r = 0.58, p < 0.05) increases in use of cognitive reappraisal (r =

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0.57, p < 0.05) and increases in cognitive reappraisal self-efficacy (r = 0.68, p < 0.01). As noted above, re‐
peated social fear exposure during regular visits to the gym facility may also be related to the changes in
self-esteem and associations with social anxiety symptoms, cognitive reappraisal, and self-views.

The most important implications of this study are that MBSR can modulate self-views in ways that are
clearly detectable via self-report and brain networks, especially for negative self-views, and that the self-
report and neural changes are related to important indicators of social anxiety symptom severity and dis‐
ability. Furthermore, this study highlights that MBSR-related increases in the SRN may be an important
first step in re-establishing adaptive self-views and social functioning in patients with SAD.

The present study compared MBSR to AE, another active control stress reduction training intervention.
One disparity is that while MBSR involves learning new mindfulness skills, AE does not. Also, in future
studies, adding a no training waitlist control group could be useful to examine habituation to the SRET
task. Nonetheless, the significant group by time interactions of self-endorsement ratings and BOLD re‐
sponses only for negative self-views indicate meaningful differential changes from pre-to-post-MBSR ver‐
sus AE. The SRET task implemented here used experimenter-selected positive and negative social trait
adjectives selected for their relevance to SAD. Use of participant-generated (i.e., idiographic) stimuli may
result in more robust brain-behavioral responses in patients with SAD and perhaps larger differential ef‐
fects of MBSR versus AE. The duration of each word stimulus was only 3 s. Use of longer stimulus dura‐
tions will allow for examination of differences in self-focused attention, and rumination, as well as tempo‐
ral features of BOLD responses in the SRN. This study only used single adjectives as stimuli. Future stud‐
ies could explore adding non-verbal cues associated with positive and negative (and perhaps neutral)
self-views. The present study used binary yes/no responses for the target condition (self-descriptive) and
control condition (upper case letters). Future studies will benefit from using a continuous rating scale to
obtain more refined measurement of how self-descriptive a target social trait is perceived to be.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial rela‐
tionships that could be construed as a potential conflict of interest.

Acknowledgments

This work was supported by the National Center for Complementary and Alternative Medicine Institutes
of Health awarded to James Gross (Grant AT003644).

Appendix

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Table A1

Pre-to-post-mindfulness-based stress reduction changes in BOLD responses for negative and positive self versus
case.

Brain regions BA xyz % Vol mm3 t-Test

MBSR post versuspre

Negative self > case

FRONTAL LOBES

Rostromedial PFC 10 −3 62 8 0.16 957 3.56

Caudomedial PFC 10 7 52 −2 0.12 426 3.21

L middle frontal gyrus 8 −38 35 50 0.22 904 3.15

R middle frontal gyrus 8 31 31 46 0.12 1223 3.29

L Ventrolateral PFC 47 −38 31 −2 0.14 1011 3.47

TEMPORAL LOBES

L superior temporal gyrus 22 −69 −13 1 0.15 213 4.18

PARIETAL LOBES

PCC/precuneus 31/7 0 −61 29 0.10 1277 3.62

L inferior parietal lobule 40 −45 −61 46 0.21 426 3.66

Negative case > self None

Positive self > case

FRONTAL LOBES

Rostromedial PFC 10 0 62 12 0.18 851 4.64

Dorsomedial PFC 8 3 52 50 0.41 372 3.46

L rostral superior frontal gyrus 9 −17 52 29 0.08 319 3.65

Caudal rectal gyrus 25 7 4 −16 0.24 319 3.55

R ventrolateral PFC 46 58 31 12 0.14 213 3.36

SUBCORTICAL

L uncus 28 −31 4 −19 0.08 319 3.15

Positive case > self None

Italicized brain regions are located within the Northoff defined self-referential cortical midline network. xyz = Talairach co‐
ordinates for peak of cluster, % = BOLD percent signal change for contrast, t-value threshold ≥3.10, voxel p < 0.005, minimum
cluster volume threshold >213 mm3 (4 voxels × 3.438 mm × 4.5 mm), cluster-wise p < 0.01. BA, Brodmann area; BOLD, blood
oxygen level-dependent; L, left; MFG, middle frontal gyrus; PCC, posterior cingulate cortex; PFC, prefrontal cortex; R, right;
SAD, social anxiety disorder; Vol, volume.

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Table A2

Pre-to-post aerobic exercise changes in BOLD responses for negative and positive self versus case.

Brain regions BA xyz % Vol mm3 t-Test

AE post versuspre

Negative self > case None

Negative case > self

FRONTAL LOBES

Dorsal medial PFC 8 0 25 43 −0.17 479 −3.64

Medial PFC 9 0 49 15 −0.14 213 −3.34

Rostral anterior cingulate 24 3 27 1 −0.17 479 −3.59

L ventral lateral PFC 47 −31 25 −2 −0.10 319 −4.66

L ventral lateral PFC 47 −48 31 −9 −0.27 213 −3.27

R inferior frontal gyrus 45 41 21 12 −0.10 213 −4.17

PARIETAL LOBES

R lateral precuneus 7 28 −41 43 −0.14 266 −3.39

OCCIPITAL LOBES

R lingual gyrus 18 3 −79 −9 −0.20 798 −4.68

L lingual gyrus 18 −7 −65 5 −0.11 532 −3.28

L lingual gyrus 18 −3 −79 −6 −0.19 213 −4.16

SUBCORTICAL

R caudate 3 1 12 −0.17 745 −3.40

R caudate 14 11 5 −0.12 479 −4.84

R caudate 17 −10 22 −0.09 213 −3.71

R thalamus 14 −10 1 −0.10 426 −4.76

Negative case > self None

Positive self > case

L insula 13 −31 −10 15 0.07 213 3.65

Positive case > self None

Italicized brain regions are located within the Northoff defined self-referential cortical midline network. xyz = Talairach co‐
ordinates for peak of cluster, % = BOLD percent signal change for contrast, t-value threshold ≥3.10, voxel p < 0.005, minimum
cluster volume threshold >213 mm3 (4 voxels × 3.438 mm × 4.5 mm), cluster-wise p < 0.01. BA, Brodmann area; BOLD, blood
oxygen level-dependent; L, left; PFC, prefrontal cortex; R, right; SAD, social anxiety disorder; Vol, volume.

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Figure A1

Association of pre-to-post-MBSR changes in DMPFC during negative self versus case and social anxiety related
disability.

Figure A2

Association of pre-to-post-MBSR changes in DMPFC during negative self versus case and mindfulness skills.

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Figure A3

Association of pre-to-post-MBSR changes in DMPFC during positive self versus case and mindfulness skills.

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