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<p>Patients in the placebo arms of randomized controlled trials (RCT) often experience positive changes from baseline. While multiple theories concerning such “placebo effects” exist, peculiarly, none has been informed by actual interviews of patients undergoing placebo treatment. Here, we report on a qualitative study (n = 27) embedded within a RCT (n = 262) in patients with irritable bowel syndrome. Besides identical placebo acupuncture treatment in the RCT, the qualitative study patients also received an additional set of interviews at the beginning, midpoint, and end of the trial. Interviews of the 12 qualitative subjects who underwent and completed placebo treatment were transcribed. We found that patients (1) were persistently concerned with whether they were receiving placebo or genuine treatment; (2) almost never endorsed “expectation” of improvement but spoke of “hope” instead and frequently reported despair; (3) almost all reported improvement ranging from dramatic psychosocial changes to unambiguous, progressive symptom improvement to tentative impressions of benefit; and (4) often worried whether their improvement was due to normal fluctuations or placebo effects. The placebo treatment was a problematic perturbation that provided an opportunity to reconstruct the experiences of the fluctuations of their illness and how it disrupted their everyday life. Immersion in this RCT was a co-mingling of enactment, embodiment and interpretation involving ritual performance and evocative symbols, shifts in bodily sensations, symptoms, mood, daily life behaviors, and social interactions, all accompanied by self-scrutiny and re-appraisal. The placebo effect involved a spectrum of factors and any single theory of placebo – e.g. expectancy, hope, conditioning, anxiety reduction, report bias, symbolic work, narrative and embodiment – provides an inadequate model to explain its salubrious benefits.</p>
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The capacity to stabilize the content of attention over time varies among individuals, and its impairment is a hallmark of several mental illnesses. Impairments in sustained attention in patients with attention disorders have been associated with increased trial-to-trial variability in reaction time and event-related potential deficits during attention tasks. At present, it is unclear whether the ability to sustain attention and its underlying brain circuitry are transformable through training. Here, we show, with dichotic listening task performance and electroencephalography, that training attention, as cultivated by meditation, can improve the ability to sustain attention. Three months of intensive meditation training reduced variability in attentional processing of target tones, as indicated by both enhanced theta-band phase consistency of oscillatory neural responses over anterior brain areas and reduced reaction time variability. Furthermore, those individuals who showed the greatest increase in neural response consistency showed the largest decrease in behavioral response variability. Notably, we also observed reduced variability in neural processing, in particular in low-frequency bands, regardless of whether the deviant tone was attended or unattended. Focused attention meditation may thus affect both distracter and target processing, perhaps by enhancing entrainment of neuronal oscillations to sensory input rhythms, a mechanism important for controlling the content of attention. These novel findings highlight the mechanisms underlying focused attention meditation and support the notion that mental training can significantly affect attention and brain function.
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Abstract Mindfulness has been incorporated into several treatment approaches for psychopathology. Despite the popularity of this approach, relatively few empirical investigations have examined the relationship between mindfulness and autonomic indicators of flexible emotion regulation, such as heart rate variability (HRV). Generalized anxiety disorder (GAD) has been associated with both low levels of mindfulness and HRV. In this investigation, we examined the relationship between HRV and mindfulness in the context of elevated generalized anxiety (GA) symptoms—an analog for GAD—by examining whether GA level moderated this relationship. HRV was collected while participants completed self-report measures of GA and trait mindfulness. GA level interacted with mindfulness in the prediction of HRV; in the high GA, but not low GA group, mindfulness was positively associated with HRV. This suggests that for individuals with high GA, mindfulness may enhance parasympathetic influences on the heart rate. We address the limitations of the current investigation and suggest avenues for future research on mindfulness-related changes in tonic and phasic HRV over time.

The high likelihood of recurrence in depression is linked to a progressive increase in emotional reactivity to stress (stress sensitization). Mindfulness-based therapies teach mindfulness skills designed to decrease emotional reactivity in the face of negative affect-producing stressors. The primary aim of the current study was to assess whether Mindfulness-Based Cognitive Therapy (MBCT) is efficacious in reducing emotional reactivity to social evaluative threat in a clinical sample with recurrent depression. A secondary aim was to assess whether improvement in emotional reactivity mediates improvements in depressive symptoms. Fifty-two individuals with partially remitted depression were randomized into an 8-week MBCT course or a waitlist control condition. All participants underwent the Trier Social Stress Test (TSST) before and after the 8-week trial period. Emotional reactivity to stress was assessed with the Spielberger State Anxiety Inventory at several time points before, during, and after the stressor. MBCT was associated with decreased emotional reactivity to social stress, specifically during the recovery (post-stressor) phase of the TSST. Waitlist controls showed an increase in anticipatory (pre-stressor) anxiety that was absent in the MBCT group. Improvements in emotional reactivity partially mediated improvements in depressive symptoms. Limitations include small sample size, lack of objective or treatment adherence measures, and non-generalizability to more severely depressed populations. Given that emotional reactivity to stress is an important psychopathological process underlying the chronic and recurrent nature of depression, these findings suggest that mindfulness skills are important in adaptive emotion regulation when coping with stress.
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BACKGROUND: Many antidepressant medications (ADM) are associated with disruptions in sleep continuity that can compromise medication adherence and impede successful treatment. The present study investigated whether mindfulness meditation (MM) training could improve self-reported and objectively measured polysomnographic (PSG) sleep profiles in depressed individuals who had achieved at least partial remission with ADM, but still had residual sleep complaints. METHODS: Twenty-three ADM users with sleep complaints were randomized into an 8-week Mindfulness-Based Cognitive Therapy (MBCT) course or a waitlist control condition. Pre-post measurements included PSG sleep studies and subjectively reported sleep, residual depression symptoms. RESULTS: Compared to controls, the MBCT participants improved on both PSG and subjective measures of sleep. They showed a pattern of decreased wake time and increased sleep efficiency. Sleep depth, as measured by stage 1 and slow-wave sleep, did not change as a result of mindfulness training. CONCLUSIONS: MM is associated with increases in both objectively and subjectively measured sleep continuity in ADM users. MM training may serve as more desirable and cost-effective alternative to discontinuation or supplementation with hypnotics, and may contribute to a more sustainable recovery from depression.

<p>BACKGROUND: Many antidepressant medications (ADM) are associated with disruptions in sleep continuity that can compromise medication adherence and impede successful treatment. The present study investigated whether mindfulness meditation (MM) training could improve self-reported and objectively measured polysomnographic (PSG) sleep profiles in depressed individuals who had achieved at least partial remission with ADM, but still had residual sleep complaints. METHODS: Twenty-three ADM users with sleep complaints were randomized into an 8-week Mindfulness-Based Cognitive Therapy (MBCT) course or a waitlist control condition. Pre-post measurements included PSG sleep studies and subjectively reported sleep, residual depression symptoms. RESULTS: Compared to controls, the MBCT participants improved on both PSG and subjective measures of sleep. They showed a pattern of decreased wake time and increased sleep efficiency. Sleep depth, as measured by stage 1 and slow-wave sleep, did not change as a result of mindfulness training. CONCLUSIONS: MM is associated with increases in both objectively and subjectively measured sleep continuity in ADM users. MM training may serve as more desirable and cost-effective alternative to discontinuation or supplementation with hypnotics, and may contribute to a more sustainable recovery from depression.</p>
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Objective: Mindfulness-based stress reduction (MBSR) is a structured group program that employs mindfulness meditation to alleviate suffering associated with physical, psychosomatic and psychiatric disorders. The program, nonreligious and nonesoteric, is based upon a systematic procedure to develop enhanced awareness of moment-to-moment experience of perceptible mental processes. The approach assumes that greater awareness will provide more veridical perception, reduce negative affect and improve vitality and coping. In the last two decades, a number of research reports appeared that seem to support many of these claims. We performed a comprehensive review and meta-analysis of published and unpublished studies of health-related studies related to MBSR. Methods: Sixty-four empirical studies were found, but only 20 reports met criteria of acceptable quality or relevance to be included in the meta-analysis. Reports were excluded due to (I) insufficient information about interventions, (2) poor quantitative health evaluation, (3) inadequate statistical analysis, (4) mindfulness not being the central component of intervention, or (5) the setting of intervention or sample composition deviating too widely from the health-related MBSR program. Acceptable studies covered a wide spectrum of clinical populations (e.g., pain, cancer, heart disease, depression, and anxiety), as well as stressed nonclinical groups. Both controlled and observational investigations were included. Standardized measures of physical and mental well-being constituted the dependent variables of the analysis. Results: Overall, both controlled and uncontrolled studies showed similar effect sizes of approximately 0.5 (P <.0001) with homogeneity of distribution. Conclusion: Although derived from a relatively small number of studies, these results suggest that MBSR may help a broad range of individuals to cope with their clinical and nonclinical problems.

OBJECTIVES: This study investigated the relationships between a mindfulness-based stress reduction meditation program for early stage breast and prostate cancer patients and quality of life, mood states, stress symptoms, lymphocyte counts, and cytokine production. METHODS: Forty-nine patients with breast cancer and 10 with prostate cancer participated in an 8-week MBSR program that incorporated relaxation, meditation, gentle yoga, and daily home practice. Demographic and health behavior variables, quality of life (EORTC QLQ C-30), mood (POMS), stress (SOSI), and counts of NK, NKT, B, T total, T helper, and T cytotoxic cells, as well as NK and T cell production of TNF, IFN-γ, IL-4, and IL-10 were assessed pre- and postintervention. RESULTS: Fifty-nine and 42 patients were assessed pre- and postintervention, respectively. Significant improvements were seen in overall quality of life, symptoms of stress, and sleep quality. Although there were no significant changes in the overall number of lymphocytes or cell subsets, T cell production of IL-4 increased and IFN-γ decreased, whereas NK cell production of IL-10 decreased. These results are consistent with a shift in immune profile from one associated with depressive symptoms to a more normal profile. CONCLUSIONS: MBSR participation was associated with enhanced quality of life and decreased stress symptoms in breast and prostate cancer patients. This study is also the first to show changes in cancer-related cytokine production associated with program participation.

<p>Mindfulness-based approaches are among the most innovative and interesting new approaches to mental health treatment. Mindfulness refers to patients developing an "awareness of present experience with acceptance." Interest in them is widespread, with presentations and workshops drawing large audiences all over the US and many other countries. This book provides a comprehensive introduction to the best-researched mindfulness-based treatments. It emphasizes detailed clinical illustration providing a close-up view of how these treatments are conducted, the skills required of therapists, and how they work. The book also has a solid foundation in theory and research and shows clearly how these treatments can be understood using accepted psychological principles and concepts. The evidence base for these treatments is concisely reviewed.* Comprehensive introduction to the best-researched mindfulness-based treatments* Covers wide range of problems &amp; disorders (anxiety, depression, eating, psychosis, personality disorders, stress, pain, relationship problems, etc)* Discusses a wide range of populations (children, adolescents, older adults, couples)* Includes wide range of settings (outpatient, inpatient, medical, mental health, workplace)* Clinically rich, illustrative case study in every chapter* International perspectives represented (authors from US, Canada, Britain, Sweden)</p>

Twenty-seven adult survivors of childhood sexual abuse participated in a pilot study comprising an 8-week mindfulness meditation-based stress reduction (MBSR) program and daily home practice of mindfulness skills. Three refresher classes were provided through final follow-up at 24 weeks. Assessments of depressive symptoms, post-traumatic stress disorder (PTSD), anxiety, and mindfulness, were conducted at baseline, 4, 8, and 24 weeks. At 8 weeks, depressive symptoms were reduced by 65%. Statistically significant improvements were observed in all outcomes post-MBSR, with effect sizes above 1.0. Improvements were largely sustained until 24 weeks. Of three PTSD symptom criteria, symptoms of avoidance/numbing were most greatly reduced. Compliance to class attendance and home practice was high, with the intervention proving safe and acceptable to participants. These results warrant further investigation of the MBSR approach in a randomized, controlled trial in this patient population. © 2009 Wiley Periodicals, Inc. J Clin Psychol 66: 1–18, 2010.

Students with learning disabilities (LD; defined by compromised academic performance) often have higher levels of anxiety, school-related stress, and less optimal social skills compared with their typically developing peers. Previous health research indicates that meditation and relaxation training may be effective in reducing anxiety and promoting social skills. This pilot study used a pre—post no-control design to examine feasibility of, attitudes toward, and outcomes of a 5-week mindfulness meditation intervention administered to 34 adolescents diagnosed with LD. Postintervention survey responses overwhelmingly expressed positive attitudes toward the program. All outcome measures showed significant improvement, with participants who completed the program demonstrating decreased state and trait anxiety, enhanced social skills, and improved academic performance. Although not directly assessed, the outcomes are consistent with a cognitive-interference model of learning disability and suggest that mindfulness meditation decreases anxiety and detrimental self-focus of attention, which, in turn, promotes social skills and academic outcomes.

Mindfulness practice is an ancient tradition in Eastern philosophy that forms the basis for meditation, and it is increasingly making its way into Western approaches to health care. Although it has been applied to the treatment of many different mental health disorders, it has not been discussed in the context of therapy for sexual problems. In a previous qualitative study of female meditation practitioners who did not have sexual concerns, mindfulness practice was found to be associated with greater sexual response and higher levels of sexual satisfaction. We have recently developed a psychoeducational program for women with sexual arousal disorder subsequent to gynecologic cancer and have included a component of mindfulness training in the intervention. In this paper, we will attempt to provide a rationale for the use of mindfulness in the treatment of women with sexual problems, and will include transcript excerpts from women who participated in our research trial that illustrate how mindfulness was effective in improving their sexuality and quality of life. Although these findings are preliminary, they suggest that mindfulness may have a place in the treatment of sexual concerns.

A review of behavioral and neurobiological data on mood and mood regulation as they pertain to an understanding of mood disorders is presented. Four approaches are considered: 1) behavioral and cognitive; 2) neurobiological; 3) computational; and 4) developmental. Within each of these four sections, we summarize the current status of the field and present our vision for the future, including particular challenges and opportunities. We conclude with a series of specific recommendations for National Institute of Mental Health priorities. Recommendations are presented for the behavioral domain, the neural domain, the domain of behavioral-neural interaction, for training, and for dissemination. It is in the domain of behavioral-neural interaction, in particular, that new research is required that brings together traditions that have developed relatively independently. Training interdisciplinary clinical scientists who meaningfully draw upon both behavioral and neuroscientific literatures and methods is critically required for the realization of these goals.
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Anxiety is a debilitating symptom of many psychiatric disorders including generalized anxiety disorder, mood disorders, schizophrenia, and autism. Anxiety involves changes in both central and peripheral biology, yet extant functional imaging studies have focused exclusively on the brain. Here we show, using functional brain and cardiac imaging in sequential brain and cardiac magnetic resonance imaging (MRI) sessions in response to cues that predict either threat (a possible shock) or safety (no possibility of shock), that MR signal change in the amygdala and the prefrontal and insula cortices predicts cardiac contractility to the threat of shock. Participants with greater MR signal change in these regions show increased cardiac contractility to the threat versus safety condition, a measure of the sympathetic nervous system contribution to the myocardium. These findings demonstrate robust neural-cardiac coupling during induced anxiety and indicate that individuals with greater activation in brain regions identified with aversive emotion show larger magnitude cardiac contractility increases to threat.
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Children with an anxious temperament (AT) are at risk for developing psychiatric disorders along the internalizing spectrum, including anxiety and depression. Like these disorders, AT is a multidimensional phenotype and children with extreme anxiety show varying mixtures of physiological, behavioral, and other symptoms. Using a well-validated juvenile monkey model of AT, we addressed the degree to which this phenotypic heterogeneity reflects fundamental differences or similarities in the underlying neurobiology. The rhesus macaque is optimal for studying AT because children and young monkeys express the anxious phenotype in similar ways and have similar neurobiology. Fluorodeoxyglucose (FDG)-positron emission tomography (FDG-PET) in 238 freely behaving monkeys identified brain regions where metabolism predicted variation in three dimensions of the AT phenotype: hypothalamic-pituitary-adrenal (HPA) activity, freezing behavior, and expressive vocalizations. We distinguished brain regions that predicted all three dimensions of the phenotype from those that selectively predicted a single dimension. Elevated activity in the central nucleus of the amygdala and the anterior hippocampus was consistently found across individuals with different presentations of AT. In contrast, elevated activity in the lateral anterior hippocampus was selective to individuals with high levels of HPA activity, and decreased activity in the motor cortex (M1) was selective to those with high levels of freezing behavior. Furthermore, activity in these phenotype-selective regions mediated relations between amygdala metabolism and different expressions of anxiety. These findings provide a framework for understanding the mechanisms that lead to heterogeneity in the clinical presentation of internalizing disorders and set the stage for developing improved interventions.
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OBJECTIVE: The purpose of this study was to use functional magnetic resonance imaging (fMRI) to probe the neural circuitry associated with reactivity to negative and positive affective stimuli in patients with major depressive disorder before treatment and after 2 and 8 weeks of treatment with venlafaxine. Relations between baseline neural activation and response to treatment were also evaluated. METHOD: Patients with major depressive disorder (N=12) and healthy comparison subjects (N=5) were scanned on three occasions, during which trials of alternating blocks of affective and neutral pictorial visual stimuli were presented. Symptoms were evaluated at each testing occasion, and both groups completed self-report measures of mood. Statistical parametric mapping was used to examine the fMRI data with a focus on the group-by-time interactions. RESULTS: Patients showed a significant reduction in depressive symptoms with treatment. Group-by-time interactions in response to the negative versus neutral stimuli were found in the left insular cortex and the left anterior cingulate. At baseline, both groups showed bilateral activation in the visual cortices, lateral prefrontal cortex, and amygdala in response to the negative versus neutral stimuli, with patients showing greater activation in the visual cortex and less activation in the left lateral prefrontal cortex. Patients with greater relative anterior cingulate activation at baseline in response to the negative versus neutral stimuli showed the most robust treatment response. CONCLUSIONS: The findings underscore the importance of the neural circuitry activated by negative affect in depression and indicate that components of this circuitry can be changed within 2 weeks of treatment with antidepressant medication.
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In children, behavioral inhibition (BI) in response to potential threat predicts the development of anxiety and affective disorders, and primate lesion studies suggest involvement of the orbitofrontal cortex (OFC) in mediating BI. Lesion studies are essential for establishing causality in brain-behavior relationships, but should be interpreted cautiously because the impact of a discrete lesion on a complex neural circuit extends beyond the lesion location. Complementary functional imaging methods assessing how lesions influence other parts of the circuit can aid in precisely understanding how lesions affect behavior. Using this combination of approaches in monkeys, we found that OFC lesions concomitantly alter BI and metabolism in the bed nucleus of stria terminalis (BNST) region and that individual differences in BNST activity predict BI. Thus it appears that an important function of the OFC in response to threat is to modulate the BNST, which may more directly influence the expression of BI.
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Davidson and Schwartz (1) have proposed a psychobiological analysis of anxiety that emphasizes the patterning of multiple processes in the generation and self-regulation of this state. The present article specifically reviews recent research on cognitive and somatic components of anxiety. A dual component scale which separately assesses cognitive and somatic trait anxiety is described and applied to the study of the differential effects of a somatic (physical exercise) and a cognitive (meditation) relaxation procedure. A total of 77 subjects was employed; 44 regularly practiced physical exercise and 33 regularly practiced meditation for comparable periods of time. As predicted, subjects practicing physical exercise reported relatively less somatic and more cognitive anxiety than meditators. These data suggest that specific subcomponents of anxiety may be differentially associated with relaxation techniques engaging primarily cognitive versus somatic subsystems. It is proposed that relaxation consists of (1) a generalized reduction to multiple physiological systems (termed the relaxation response by Benson) and (2) a more specific pattern of changes superimposed upon this general reduction, which is elicited by the particular techniques employed. The data from this retrospective study need to be followed up by prospective studies to establish the precise mechanisms for these effects.
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Children with a cancer diagnosis experience symptom distress, including anxiety, because of the disease and its treatment. Parents experience stress and anxiety because of the uncertainty of the disease as well as the suffering of their children. Yoga is a complementary intervention that has physiological and psychological benefits in healthy children and healthy and chronically ill adults. On an inpatient hematology/oncology unit, 11 children aged 6 to 12 years, 5 adolescents aged 13 to 18 years, and 33 parents participated in a single yoga session tailored to the needs and abilities of the patients and parents. Sense of well-being pre- and postclass was measured with the Spielberger State Anxiety Scale. Children had normal anxiety scores preclass that did not change. Adolescents and parents experienced significant decreases in anxiety scores, and all cohorts gave positive feedback about the experience. The authors conclude that yoga is a feasible intervention for this population and is beneficial to adolescents and parents.
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Neuroimage phenotyping for psychiatric and neurological disorders is performed using voxelwise analyses also known as voxel based analyses or morphometry (VBM). A typical voxelwise analysis treats measurements at each voxel (e.g., fractional anisotropy, gray matter probability) as outcome measures to study the effects of possible explanatory variables (e.g., age, group) in a linear regression setting. Furthermore, each voxel is treated independently until the stage of correction for multiple comparisons. Recently, multi-voxel pattern analyses (MVPA), such as classification, have arisen as an alternative to VBM. The main advantage of MVPA over VBM is that the former employ multivariate methods which can account for interactions among voxels in identifying significant patterns. They also provide ways for computer-aided diagnosis and prognosis at individual subject level. However, compared to VBM, the results of MVPA are often more difficult to interpret and prone to arbitrary conclusions. In this paper, first we use penalized likelihood modeling to provide a unified framework for understanding both VBM and MVPA. We then utilize statistical learning theory to provide practical methods for interpreting the results of MVPA beyond commonly used performance metrics, such as leave-one-out-cross validation accuracy and area under the receiver operating characteristic (ROC) curve. Additionally, we demonstrate that there are challenges in MVPA when trying to obtain image phenotyping information in the form of statistical parametric maps (SPMs), which are commonly obtained from VBM, and provide a bootstrap strategy as a potential solution for generating SPMs using MVPA. This technique also allows us to maximize the use of available training data. We illustrate the empirical performance of the proposed framework using two different neuroimaging studies that pose different levels of challenge for classification using MVPA.
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OBJECTIVES: To examine whether mindfulness meditation (MM) was associated with changes in objectively measured polysomnographic (PSG) sleep profiles and to relate changes in PSG sleep to subjectively reported changes in sleep and depression within the context of a randomized controlled trial. Previous studies have indicated that mindfulness and other forms of meditation training are associated with improvements in sleep quality. However, none of these studies used objective PSG sleep recordings within longitudinal randomized controlled trials of naïve subjects. METHODS: Twenty-six individuals with partially remitted depression were randomized into an 8-week Mindfulness-Based Cognitive Therapy (MBCT) course or a waitlist control condition. Pre-post measurements included PSG sleep studies and subjectively reported sleep and depression symptoms. RESULTS: According to PSG sleep, MM practice was associated with several indices of increased cortical arousal, including more awakenings and stage 1 sleep and less slow-wave sleep relative to controls, in proportion to amount of MM practice. According to sleep diaries, subjectively reported sleep improved post MBCT but not above and beyond controls. Beck Depression Inventory scores decreased more in the MBCT group than controls. Improvements in depression were associated with increased subjective sleep continuity and increased PSG arousal. CONCLUSIONS: MM is associated with increases in objectively measured arousal during sleep with simultaneous improvements in subjectively reported sleep quality and mood disturbance. This pattern is similar to the profiles of positive responders to common antidepressant medications.
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Individuals with fragile X syndrome (FXS) commonly display characteristics of social anxiety, including gaze aversion, increased time to initiate social interaction, and difficulty forming meaningful peer relationships. While neural correlates of face processing, an important component of social interaction, are altered in FXS, studies have not examined whether social anxiety in this population is related to higher cognitive processes, such as memory. This study aimed to determine whether the neural circuitry involved in face encoding was disrupted in individuals with FXS, and whether brain activity during face encoding was related to levels of social anxiety. A group of 11 individuals with FXS (5 M) and 11 age- and gender-matched control participants underwent fMRI scanning while performing a face encoding task with online eye-tracking. Results indicate that compared to the control group, individuals with FXS exhibited decreased activation of prefrontal regions associated with complex social cognition, including the medial and superior frontal cortex, during successful face encoding. Further, the FXS and control groups showed significantly different relationships between measures of social anxiety (including gaze-fixation) and brain activity during face encoding. These data indicate that social anxiety in FXS may be related to the inability to successfully recruit higher level social cognition regions during the initial phases of memory formation.
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