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1.
PLoS One ; 19(5): e0299352, 2024.
Article in English | MEDLINE | ID: mdl-38728238

ABSTRACT

We developed a self-report measure of psychological well-being for teens and adults, the Healthy Minds Index, based on a novel theory that four trainable pillars underlie well-being: awareness, connection, insight, and purpose. Ninety-seven items were developed and revised by experts and guided by qualitative testing with teens (n = 32; average age = 16.0 years). After assessing the internal validity and factor structure in teens (n = 1607; average age = 16.7 years) and adults (n = 420; average age = 45.6 years), we reduced the survey to 17 items. We then validated the factor structure, internal and convergent and divergent validity, and retest reliability of the 17-item Healthy Minds Index in two new teen samples (study 1: n = 1492, average age = 15.7 years; study 2: n = 295, average age = 16.1 years), and one adult sample (n = 285; average age = 45.3 years). The Healthy Minds Index demonstrated adequate validity and provided a comprehensive measure of a novel theory of psychological well-being that includes two domains not found in other conceptualizations of this construct-awareness and insight. This measure will be invaluable for primary research on well-being and as a translational tool to assess the impact and efficacy of widely used behavioral training programs on these core dimensions of wellbeing.


Subject(s)
Self Report , Humans , Adolescent , Female , Male , Adult , Middle Aged , Surveys and Questionnaires , Mental Health , Reproducibility of Results , Young Adult , Psychometrics/methods
2.
Brain Behav Immun ; 115: 480-493, 2024 01.
Article in English | MEDLINE | ID: mdl-37924961

ABSTRACT

BACKGROUND: The staggering morbidity associated with chronic inflammatory diseases can be reduced by psychological interventions, including Mindfulness-Based Stress Reduction (MBSR). Proposed mechanisms for MBSR's beneficial effects include changes in salience network function. Salience network perturbations are also associated with chronic inflammation, including airway inflammation in asthma, a chronic inflammatory disease affecting approximately 10% of the population. However, no studies have examined whether MBSR-related improvements in disease control are related to changes in salience network function. METHODS: Adults with asthma were randomized to 8 weeks of MBSR or a waitlist control group. Resting state functional connectivity was measured using fMRI before randomization, immediately post-intervention, and 4 months post-intervention. Using key salience network regions as seeds, we calculated group differences in change in functional connectivity over time and examined whether functional connectivity changes were associated with increased mindfulness, improved asthma control, and decreased inflammatory biomarkers. RESULTS: The MBSR group showed greater increases in functional connectivity between salience network regions relative to the waitlist group. Improvements in asthma control correlated with increased functional connectivity between the salience network and regions important for attention control and emotion regulation. Improvements in inflammatory biomarkers were related to decreased functional connectivity between the salience network and other networks. CONCLUSIONS: Increased resting salience network coherence and connectivity with networks that subserve attention and emotion regulation may contribute to the benefits of MBSR for patients with asthma. Understanding the neural underpinnings of MBSR-related benefits in patients is a critical step towards optimizing brain-targeted interventions for chronic inflammatory disease management.


Subject(s)
Asthma , Mindfulness , Adult , Humans , Chronic Disease , Asthma/therapy , Inflammation , Biomarkers , Magnetic Resonance Imaging
3.
Sci Rep ; 13(1): 15953, 2023 09 24.
Article in English | MEDLINE | ID: mdl-37743388

ABSTRACT

Mind-body interventions such as mindfulness-based stress reduction (MBSR) may improve well-being by increasing awareness and regulation of physiological and cognitive states. However, it is unclear how practice may alter long-term, baseline physiological processes, and whether these changes reflect improved well-being. Using respiration rate (RR), which can be sensitive to effects of meditation, and 3 aspects of self-reported well-being (psychological well-being [PWB], distress, and medical symptoms), we tested pre-registered hypotheses that: (1) Lower baseline RR (in a resting, non-meditative state) would be a physiological marker associated with well-being, (2) MBSR would decrease RR, and (3) Training-related decreases in RR would be associated with improved well-being. We recruited 245 adults (age range = 18-65, M = 42.4): experienced meditators (n = 42), and meditation-naïve participants randomized to MBSR (n = 72), active control (n = 41), or waitlist control (n = 66). Data were collected at pre-randomization, post-intervention (or waiting), and long-term follow-up. Lower baseline RR was associated with lower psychological distress among long-term meditators (p* = 0.03, b = 0.02, 95% CI [0.01, 0.03]), though not in non-meditators prior to training. MBSR decreased RR compared to waitlist (p = 0.02, Cohen's d = - 0.41, 95% CI [- 0.78, - 0.06]), but not the active control. Decreased RR related to decreased medical symptoms, across all participants (p* = 0.02, b = 0.57, 95% CI [0.15, 0.98]). Post-training, lower RR was associated with higher PWB across training groups compared to waitlist (p* = 0.01, b = 0.06, 95% CI [0.02, 0.10]), though there were no significant differences in change in PWB between groups. This physiological marker may indicate higher physical and/or psychological well-being in those who engage in wellness practices.


Subject(s)
Meditation , Psychological Distress , Adult , Humans , Adolescent , Young Adult , Middle Aged , Aged , Self Report , Respiratory Rate , Physical Examination
4.
Am J Psychiatry ; 179(10): 758-767, 2022 10.
Article in English | MEDLINE | ID: mdl-35899379

ABSTRACT

OBJECTIVE: Mindfulness-based interventions are widely used to target pain, yet their neural mechanisms of action are insufficiently understood. The authors studied neural and subjective pain response in a randomized active-control trial of mindfulness-based stress reduction (MBSR) alongside long-term meditation practitioners. METHODS: Healthy participants (N=115) underwent functional neuroimaging during a thermal acute pain task before and after random assignment to MBSR (N=28), an active control condition (health enhancement program [HEP]) (N=32), or a waiting list control condition (N=31). Long-term meditators (N=30) completed the same neuroimaging paradigm. Pain response was measured via self-reported intensity and unpleasantness, and neurally via two multivoxel machine-learning-derived signatures: the neurologic pain signature (NPS), emphasizing nociceptive pain processing, and the stimulus intensity independent pain signature-1 (SIIPS1), emphasizing stimulus-independent neuromodulatory processes. RESULTS: The MBSR group showed a significant decrease in NPS response relative to the HEP group (Cohen's d=-0.43) and from pre- to postintervention assessment (d=-0.47). The MBSR group showed small, marginal decreases in NPS relative to the waiting list group (d=-0.36), and in SIIPS1 relative to both groups (HEP group, d=-0.37; waiting list group, d=-0.37). In subjective unpleasantness, the MBSR and HEP groups also showed modest significant reductions compared with the waiting list group (d=-0.45 and d=-0.55). Long-term meditators reported significantly lower pain than nonmeditators but did not differ in neural response. Within the long-term meditator group, cumulative practice during intensive retreat was significantly associated with reduced SIIPS1 (r=-0.65), whereas daily practice was not. CONCLUSIONS: Mindfulness training showed associations with pain reduction that implicate differing neural pathways depending on extent and context of practice. Use of neural pain signatures in randomized trials offers promise for guiding the application of mindfulness interventions to pain treatment.


Subject(s)
Meditation , Mindfulness , Functional Neuroimaging , Humans , Meditation/methods , Mindfulness/methods , Pain , Stress, Psychological
5.
J Cogn Neurosci ; 34(9): 1576-1589, 2022 08 01.
Article in English | MEDLINE | ID: mdl-35704552

ABSTRACT

Mindfulness meditation has been shown to increase resting-state functional connectivity (rsFC) between the posterior cingulate cortex (PCC) and dorsolateral prefrontal cortex (DLPFC), which is thought to reflect improvements in shifting attention to the present moment. However, prior research in long-term meditation practitioners lacked quantitative measures of attention that would provide a more direct behavioral correlate and interpretational anchor for PCC-DLPFC connectivity and was inherently limited by small sample sizes. Moreover, whether mindfulness meditation primarily impacts brain function locally, or impacts the dynamics of large-scale brain networks, remained unclear. Here, we sought to replicate and extend prior findings of increased PCC-DLPFC rsFC in a sample of 40 long-term meditators (average practice = 3759 hr) who also completed a behavioral assay of attention. In addition, we tested a network-based framework of changes in interregional connectivity by examining network-level connectivity. We found that meditators had stronger PCC-rostrolateral prefrontal cortex (RLPFC) rsFC, lower connector hub strength across the default mode network, and better subjective attention, compared with 124 meditation-naive controls. Orienting attention positively correlated with PCC-RLPFC connectivity and negatively correlated with default mode network connector hub strength. These findings provide novel evidence that PCC-RLPFC rsFC may support attention orienting, consistent with a role for RLPFC in the attention shifting component of metacognitive awareness that is a core component of mindfulness meditation training. Our results further demonstrate that long-term mindfulness meditation may improve attention and strengthen the underlying brain networks.


Subject(s)
Meditation , Mindfulness , Brain , Brain Mapping , Gyrus Cinguli/diagnostic imaging , Humans , Magnetic Resonance Imaging , Meditation/methods , Meditation/psychology , Mindfulness/methods , Prefrontal Cortex/diagnostic imaging , Rest
6.
Sci Adv ; 8(20): eabk3316, 2022 May 20.
Article in English | MEDLINE | ID: mdl-35594344

ABSTRACT

Studies purporting to show changes in brain structure following the popular, 8-week mindfulness-based stress reduction (MBSR) course are widely referenced despite major methodological limitations. Here, we present findings from a large, combined dataset of two, three-arm randomized controlled trials with active and waitlist (WL) control groups. Meditation-naïve participants (n = 218) completed structural magnetic resonance imaging scans during two visits: baseline and postintervention period. After baseline, participants were randomly assigned to WL (n = 70), an 8-week MBSR program (n = 75), or a validated, matched active control (n = 73). We assessed changes in gray matter volume, gray matter density, and cortical thickness. In the largest and most rigorously controlled study to date, we failed to replicate prior findings and found no evidence that MBSR produced neuroplastic changes compared to either control group, either at the whole-brain level or in regions of interest drawn from prior MBSR studies.

7.
Sci Rep ; 9(1): 18667, 2019 12 10.
Article in English | MEDLINE | ID: mdl-31822684

ABSTRACT

Mindfulness training has been shown to improve attention and change the underlying brain substrates in adults. Most mindfulness training programs involve a myriad of techniques, and it is difficult to attribute changes to any particular aspect of the program. Here, we created a video game, Tenacity, which models a specific mindfulness technique - focused attention on one's breathing - and assessed its potential to train an attentional network in adolescents. A combined analysis of resting state functional connectivity (rs-FC) and diffusion tensor imaging (DTI) yielded convergent results - change in communication within the left fronto-parietal network after two weeks of playing Tenacity compared to a control game. Rs-FC analysis showed greater connectivity between left dorsolateral prefrontal cortex (dlPFC) and left inferior parietal cortex (IPC) in the Tenacity group. Importantly, changes in left dlPFC - IPC rs-FC and changes in structural connectivity of the white matter tract that connects these regions -left superior longitudinal fasiculus (SLF) - were associated with changes in performance on an attention task. Finally, changes in left dlPFC - IPC rs-FC correlated with the change in left SLF structural connectivity as measured by fractional anisotropy (FA) in the Tenacity group only.


Subject(s)
Emotions , Frontal Lobe/diagnostic imaging , Mindfulness , Parietal Lobe/diagnostic imaging , Video Games , White Matter/diagnostic imaging , Adolescent , Anisotropy , Attention , Child , Diffusion Tensor Imaging , Female , Humans , Male , Multimodal Imaging
8.
Sci Rep ; 9(1): 11963, 2019 08 19.
Article in English | MEDLINE | ID: mdl-31427669

ABSTRACT

Interest has grown in using mindfulness meditation to treat conditions featuring excessive impulsivity. However, while prior studies find that mindfulness practice can improve attention, it remains unclear whether it improves other cognitive faculties whose deficiency can contribute to impulsivity. Here, an eight-week mindfulness intervention did not reduce impulsivity on the go/no-go task or Barratt Impulsiveness Scale (BIS-11), nor produce changes in neural correlates of impulsivity (i.e. frontostriatal gray matter, functional connectivity, and dopamine levels) compared to active or wait-list control groups. Separately, long-term meditators (LTMs) did not perform differently than meditation-naïve participants (MNPs) on the go/no-go task. However, LTMs self-reported lower attentional impulsivity, but higher motor and non-planning impulsivity on the BIS-11 than MNPs. LTMs had less striatal gray matter, greater cortico-striatal-thalamic functional connectivity, and lower spontaneous eye-blink rate (a physiological dopamine indicator) than MNPs. LTM total lifetime practice hours (TLPH) did not significantly relate to impulsivity or neurobiological metrics. Findings suggest that neither short- nor long-term mindfulness practice may be effective for redressing impulsive behavior derived from inhibitory motor control or planning capacity deficits in healthy adults. Given the absence of TLPH relationships to impulsivity or neurobiological metrics, differences between LTMs and MNPs may be attributable to pre-existing differences.


Subject(s)
Impulsive Behavior , Meditation/methods , Meditation/psychology , Mindfulness , Attention , Blinking , Brain Mapping , Female , Gray Matter/anatomy & histology , Gray Matter/physiology , Healthy Volunteers , Humans , Magnetic Resonance Imaging , Male , Psychomotor Performance , Rest , Time Factors
9.
Soc Cogn Affect Neurosci ; 14(7): 777-787, 2019 07 31.
Article in English | MEDLINE | ID: mdl-31269203

ABSTRACT

Mindfulness meditation training has been shown to increase resting-state functional connectivity between nodes of the frontoparietal executive control network (dorsolateral prefrontal cortex [DLPFC]) and the default mode network (posterior cingulate cortex [PCC]). We investigated whether these effects generalized to a Mindfulness-Based Stress Reduction (MBSR) course and tested for structural and behaviorally relevant consequences of change in connectivity. Healthy, meditation-naïve adults were randomized to either MBSR (N = 48), an active (N = 47) or waitlist (N = 45) control group. Participants completed behavioral testing, resting-state fMRI scans and diffusion tensor scans at pre-randomization (T1), post-intervention (T2) and ~5.5 months later (T3). We found increased T2-T1 PCC-DLPFC resting connectivity for MBSR relative to control groups. Although these effects did not persist through long-term follow-up (T3-T1), MBSR participants showed a significantly stronger relationship between days of practice (T1 to T3) and increased PCC-DLPFC resting connectivity than participants in the active control group. Increased PCC-DLPFC resting connectivity in MBSR participants was associated with increased microstructural connectivity of a white matter tract connecting these regions and increased self-reported attention. These data show that MBSR increases PCC-DLPFC resting connectivity, which is related to increased practice time, attention and structural connectivity.


Subject(s)
Brain/physiology , Executive Function/physiology , Meditation/psychology , Mindfulness , Prefrontal Cortex/physiology , Adult , Brain/physiopathology , Female , Gyrus Cinguli/physiopathology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Rest , White Matter , Young Adult
10.
Annu Rev Clin Psychol ; 15: 285-316, 2019 05 07.
Article in English | MEDLINE | ID: mdl-30525995

ABSTRACT

Mindfulness meditation is increasingly incorporated into mental health interventions, and theoretical concepts associated with it have influenced basic research on psychopathology. Here, we review the current understanding of mindfulness meditation through the lens of clinical neuroscience, outlining the core capacities targeted by mindfulness meditation and mapping them onto cognitive and affective constructs of the Research Domain Criteria matrix proposed by the National Institute of Mental Health. We review efficacious applications of mindfulness meditation to specific domains of psychopathology including depression, anxiety, chronic pain, and substance abuse, as well as emerging efforts related to attention disorders, traumatic stress, dysregulated eating, and serious mental illness. Priorities for future research include pinpointing mechanisms, refining methodology, and improving implementation. Mindfulness meditation is a promising basis for interventions, with particular potential relevance to psychiatric comorbidity. The successes and challenges of mindfulness meditation research are instructive for broader interactions between contemplative traditions and clinical psychological science.


Subject(s)
Meditation , Mental Disorders/physiopathology , Mental Disorders/therapy , Mindfulness , Neurosciences , Humans , Mental Disorders/classification
11.
Soc Cogn Affect Neurosci ; 14(12): 1263-1272, 2019 12 30.
Article in English | MEDLINE | ID: mdl-31993663

ABSTRACT

While rodent research suggests that the bed nucleus of the stria terminalis (BNST) and centromedial amygdala (CM) coordinate the hormonal stress response, little is known about the BNST's role in the human stress response. The human BNST responds to negatively valenced stimuli, which likely subserves its role in responding to threat. Thus, variation in BNST reactivity to negatively valenced stimuli may relate to differences in the stress response. We measured participants' blood oxygenated level-dependent response to affective images and salivary cortisol and α-amylase (AA) levels in response to a subsequent Trier social stress test (TSST). Greater BNST activation to emotionally evocative images was associated with a larger TSST-evoked AA, but not cortisol response. This association remained after controlling for CM activation, which was not related to the cortisol or AA response. These results suggest that the BNST response to negatively valenced images subserves its role in coordinating the stress response, a BNST role in the stress response independent from the CM, and highlight the need for investigation of the conditions under which BNST activation predicts the cortisol response. Our findings are critical for the future study of mood and anxiety disorders, as dysregulation of the stress system plays a key role in their pathogenesis.


Subject(s)
Septal Nuclei/physiology , Stress, Psychological/metabolism , alpha-Amylases/metabolism , Amygdala/physiology , Animals , Anxiety Disorders , Female , Humans , Hydrocortisone/metabolism , Male
12.
Neuroimage ; 181: 301-313, 2018 11 01.
Article in English | MEDLINE | ID: mdl-29990584

ABSTRACT

Meditation training can improve mood and emotion regulation, yet the neural mechanisms of these affective changes have yet to be fully elucidated. We evaluated the impact of long- and short-term mindfulness meditation training on the amygdala response to emotional pictures in a healthy, non-clinical population of adults using blood-oxygen level dependent functional magnetic resonance imaging. Long-term meditators (N = 30, 16 female) had 9081 h of lifetime practice on average, primarily in mindfulness meditation. Short-term training consisted of an 8-week Mindfulness- Based Stress Reduction course (N = 32, 22 female), which was compared to an active control condition (N = 35, 19 female) in a randomized controlled trial. Meditation training was associated with less amygdala reactivity to positive pictures relative to controls, but there were no group differences in response to negative pictures. Reductions in reactivity to negative stimuli may require more practice experience or concentrated practice, as hours of retreat practice in long-term meditators was associated with lower amygdala reactivity to negative pictures - yet we did not see this relationship for practice time with MBSR. Short-term training, compared to the control intervention, also led to increased functional connectivity between the amygdala and a region implicated in emotion regulation - ventromedial prefrontal cortex (VMPFC) - during affective pictures. Thus, meditation training may improve affective responding through reduced amygdala reactivity, and heightened amygdala-VMPFC connectivity during affective stimuli may reflect a potential mechanism by which MBSR exerts salutary effects on emotion regulation ability.


Subject(s)
Amygdala/physiology , Emotions/physiology , Functional Neuroimaging/methods , Magnetic Resonance Imaging/methods , Meditation , Mindfulness , Pattern Recognition, Visual/physiology , Prefrontal Cortex/physiology , Adult , Amygdala/diagnostic imaging , Connectome/methods , Female , Humans , Male , Middle Aged , Prefrontal Cortex/diagnostic imaging , Time Factors
13.
NPJ Sci Learn ; 3: 13, 2018.
Article in English | MEDLINE | ID: mdl-30631474

ABSTRACT

The ability to understand emotional experiences of others, empathy, is a valuable skill for effective social interactions. Various types of training increase empathy in adolescents, but their impact on brain circuits underlying empathy has not been examined. Video games provide a unique medium familiar and engaging to adolescents and can be used to deliver training at scale. We developed an empathy training video game, Crystals of Kaydor (Crystals), and investigated whether playing Crystals increases empathic accuracy (EA) and related brain activation in adolescents (N = 74; 27 female; mean age(sd) = 12.8(0.7) years; age range 11-14 years). Participants completed a resting state functional MRI (rs-fMRI) scan and an EA task during an fMRI scan before and after 2 weeks of daily gameplay with either the empathy training game, Crystals (N = 34), or the commercial video game Bastion (N = 40), an active control condition. There were no group differences in EA improvement following gameplay, however, engagement with training aspects of Crystals was associated with a higher increase in EA-related activation in right temporoparietal junction following gameplay. Moreover, rs-fMRI connectivity in empathy-related brain circuits (posterior cingulate-medial prefrontal cortex; MPFC) was stronger after Crystals gameplay compared to Bastion. The more individuals' EA increased following Crystals versus Bastion, the stronger their rs-fMRI connectivity in brain circuits relevant for emotion regulation (amygdala-MPFC). These findings suggest that a video game designed to increase empathic accuracy produces behaviorally-relevant, functional neural changes in fewer than 6 h of gameplay in adolescents.

15.
Soc Cogn Affect Neurosci ; 12(11): 1701-1710, 2017 11 01.
Article in English | MEDLINE | ID: mdl-28981837

ABSTRACT

Empathy, the ability to understand others' emotions, can occur through perspective taking and experience sharing. Neural systems active when adults empathize include regions underlying perspective taking (e.g. medial prefrontal cortex; MPFC) and experience sharing (e.g. inferior parietal lobule; IPL). It is unknown whether adolescents utilize networks implicated in both experience sharing and perspective taking when accurately empathizing. This question is critical given the importance of accurately understanding others' emotions for developing and maintaining adaptive peer relationships during adolescence. We extend the literature on empathy in adolescence by determining the neural basis of empathic accuracy, a behavioral assay of empathy that does not bias participants toward the exclusive use of perspective taking or experience sharing. Participants (N = 155, aged 11.1-15.5 years) watched videos of 'targets' describing emotional events and continuously rated the targets' emotions during functional magnetic resonance imaging scanning. Empathic accuracy related to activation in regions underlying perspective taking (MPFC, temporoparietal junction and superior temporal sulcus), while activation in regions underlying experience sharing (IPL, anterior cingulate cortex and anterior insula) related to lower empathic accuracy. These results provide novel insight into the neural basis of empathic accuracy in adolescence and suggest that perspective taking processes may be effective for increasing empathy.


Subject(s)
Brain/physiology , Emotions/physiology , Empathy/physiology , Interpersonal Relations , Adolescent , Brain/diagnostic imaging , Child , Female , Humans , Magnetic Resonance Imaging , Male
16.
Soc Cogn Affect Neurosci ; 9(2): 176-81, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23160815

ABSTRACT

An individual's affective style is influenced by many things, including the manner in which an individual responds to an emotional challenge. Emotional response is composed of a number of factors, two of which are the initial reactivity to an emotional stimulus and the subsequent recovery once the stimulus terminates or ceases to be relevant. However, most neuroimaging studies examining emotional processing in humans focus on the magnitude of initial reactivity to a stimulus rather than the prolonged response. In this study, we use functional magnetic resonance imaging to study the time course of amygdala activity in healthy adults in response to presentation of negative images. We split the amygdala time course into an initial reactivity period and a recovery period beginning after the offset of the stimulus. We find that initial reactivity in the amygdala does not predict trait measures of affective style. Conversely, amygdala recovery shows predictive power such that slower amygdala recovery from negative images predicts greater trait neuroticism, in addition to lower levels of likability of a set of social stimuli (neutral faces). These data underscore the importance of taking into account temporal dynamics when studying affective processing using neuroimaging.


Subject(s)
Amygdala/physiology , Emotions/physiology , Personality/physiology , Visual Perception/physiology , Adult , Aged , Anxiety Disorders , Face , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neuropsychological Tests , Neuroticism , Photic Stimulation , Time Factors
17.
Arch Gen Psychiatry ; 69(9): 925-34, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22945621

ABSTRACT

CONTEXT: Emotion regulation deficits figure prominently in generalized anxiety disorder (GAD) and in other anxiety and mood disorders. Research examining emotion regulation and top-down modulation has implicated reduced coupling of the amygdala with prefrontal cortex and anterior cingulate cortex, suggesting altered frontolimbic white matter connectivity in GAD. OBJECTIVES: To investigate structural connectivity between ventral prefrontal cortex or anterior cingulate cortex areas and the amygdala in GAD and to assess associations with functional connectivity between those areas. DESIGN: Participants underwent diffusion-tensor imaging and functional magnetic resonance imaging. SETTING: University magnetic resonance imaging facility. PARTICIPANTS: Forty-nine patients with GAD and 39 healthy volunteer control subjects, including a matched subset of 21 patients having GAD without comorbid Axis I diagnoses and 21 healthy volunteers matched for age, sex, and education. MAIN OUTCOME MEASURES: The mean fractional anisotropy values in the left and right uncinate fasciculus, as measured by tract-based analysis for diffusion-tensor imaging data. RESULTS: Lower mean fractional anisotropy values in the bilateral uncinate fasciculus indicated reduced frontolimbic structural connectivity in patients with GAD. This reduction in uncinate fasciculus integrity was most pronounced for patients without comorbidity and was not observed in other white matter tracts. Across all participants, higher fractional anisotropy values were associated with more negative functional coupling between the pregenual anterior cingulate cortex and the amygdala during the anticipation of aversion. CONCLUSIONS: Reduced structural connectivity of a major frontolimbic pathway suggests a neural basis for emotion regulation deficits in GAD. The functional significance of these structural differences is underscored by decreased functional connectivity between the anterior cingulate cortex and the amygdala in individuals with reduced structural integrity of the uncinate fasciculus.


Subject(s)
Anxiety Disorders/physiopathology , Diffusion Magnetic Resonance Imaging/methods , Frontal Lobe/physiopathology , Image Interpretation, Computer-Assisted/methods , Imaging, Three-Dimensional/methods , Limbic System/physiopathology , Magnetic Resonance Imaging/methods , Neural Pathways/physiopathology , Adolescent , Adult , Amygdala/physiopathology , Anxiety Disorders/diagnosis , Anxiety Disorders/psychology , Arousal/physiology , Brain Mapping/methods , Comorbidity , Dominance, Cerebral/physiology , Emotions/physiology , Female , Gyrus Cinguli/physiopathology , Humans , Male , Reference Values , Temporal Lobe/physiopathology , Young Adult
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