***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: R and omized controlled trials have yielded promising results for internet-delivered cognitive behavior therapy ( iCBT ) for patients with social anxiety disorder ( SAD ) . The present study investigated anxiety-related neural changes after iCBT  for SAD . The amygdala is a critical hub in the neural fear network , receptive to change using emotion regulation strategies and a putative target for iCBT .  Twenty-two subjects were included in pre- and post-treatment functional magnetic resonance imaging at 3 T assessing neural changes during an affective face processing task . Treatment outcome was assessed using social anxiety self-reports and the Clinical Global Impression-Improvement ( CGI-I ) scale .  ICBT yielded better outcome than ABM ( 66 % vs. 25 % CGI-I responders ) . A significant differential activation of the left amygdala was found with relatively decreased reactivity after iCBT . Changes in the amygdala were related to a behavioral measure of social anxiety . Functional connectivity analysis in the iCBT group showed that the amygdala attenuation was associated with increased activity in the medial orbitofrontal cortex and decreased activity in the right ventrolateral and dorsolateral ( dlPFC ) cortices . Treatment-induced neural changes with iCBT were consistent with previously reported studies on regular CBT and emotion regulation in general BACKGROUND We investigated whether the combination of multi-modal behaviour therapy ( BT ) with fluvoxamine is superior to BT and placebo in the acute treatment of severely ill in- patients with obsessive-compulsive disorder ( OCD ) . METHOD In a r and omised , double-blind design , 30 patients were treated for nine weeks with BT plus placebo and 30 patients with BT plus fluvoxamine  ( maximum dosage 300 mg , mean dose 288.1 mg ) . BT included exposure with response prevention , cognitive restructuring and development of alternative behaviours . RESULTS Both groups showed a highly significant symptom reduction after treatment . There were no significant differences between the groups concerning compulsions . Obsessions were significantly more reduced in the fluvoxamine and BT group than in the placebo and BT group . Furthermore , the group BT plus fluvoxamine showed a significantly higher response rate ( 87.5 v. 60 % ) according to a previously defined response criterion . Severely depressed patients with OCD receiving BT plus placebo presented a significantly worse treatment outcome ( Y-BOCS scores ) than all other groups . CONCLUSIONS The results suggest that BT should be combined with fluvoxamine when obsessions dominate the clinical picture and when a secondary depression is present IMPORTANCE Cognitive behavioral therapy ( CBT ) for social anxiety disorder ( SAD ) is thought to enhance cognitive re appraisal in patients with SAD . Such improvements should be evident in cognitive re appraisal -related prefrontal cortex responses . OBJECTIVE To determine whether CBT for SAD modifies cognitive re appraisal -related prefrontal cortex neural signal magnitude and timing when implementing cognitive re appraisal with negative self-beliefs . DESIGN R and omized clinical trial of CBT for SAD vs wait-list control group during a study that enrolled patients from 2007 to 2010 . SETTING University psychology department . PARTICIPANTS Seventy-five patients with generalized SAD r and omly assigned to  CBT or wait list . INTERVENTION Sixteen sessions of individual CBT for SAD . MAIN OUTCOME MEASURES Negative emotion ratings and functional magnetic resonance imaging blood oxygen-level dependent signal when reacting to and cognitively reappraising negative self-beliefs embedded in autobiographical social anxiety situations . RESULTS During reactivity trials , compared with wait list , CBT produced ( 1 ) greater reduction in negative emotion ratings and ( 2 ) greater blood oxygen-level dependent signal magnitude in the medial prefrontal cortex . During cognitive re appraisal trials , compared with wait list , CBT produced ( 3 ) greater reduction in negative emotion ratings , ( 4 ) greater blood oxygen level-dependent signal magnitude in the dorsolateral and dorsomedial prefrontal cortex , ( 5 ) earlier temporal onset of dorsomedial prefrontal cortex activity , and ( 6 ) greater dorsomedial prefrontal cortex-amygdala inverse functional connectivity . CONCLUSIONS AND RELEVANCE Modulation of cognitive re appraisal -related brain responses , timing , and functional connectivity may be important brain changes that contribute to the effectiveness of CBT for social anxiety . This study demonstrates that clinical ly applied neuroscience investigations can eluci date neurobiological mechanisms of change in psychiatric conditions . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00380731 Cognitive behavioral therapy ( CBT ) is efficacious for panic disorder with agoraphobia ( PD/A ) . Nevertheless , the active ingredients of treatment and the mechanisms through which CBT achieves its effects remain largely unknown . The mechanisms of action in CBT  ( MAC ) study was established to investigate these questions in 369 patients diagnosed with PD/A. The MAC study utilized a multi-center , r and omized controlled design , with two active treatment conditions in which the administration of exposure was varied , and a wait-list control group . The special feature of MAC is the way in which imbedded experimental , psychophysiological , and neurobiological paradigms were included to eluci date therapeutic and psychopathological processes . This paper describes the aims and goals of the MAC study and the methods utilized to achieve them . All aspects of the research design ( e.g. , assessment s , treatment , experimental procedures ) were implemented so as to facilitate the detection of active therapeutic components , and the mediators and moderators of therapeutic change . To this end , clinical , behavioral , physiological , experimental , and genetic data were collected and will be integrated BACKGROUND Learning by conditioning is a key ability of animals and humans for acquiring novel behavior necessary for survival in a changing environment . Aberrant conditioning has been considered a crucial factor in the etiology and maintenance of panic disorder with agoraphobia ( PD/A ) . Cognitive-behavioral therapy ( CBT ) is an effective treatment for PD/A. However , the neural mechanisms underlying the effects of CBT on conditioning processes in PD/A are unknown . METHODS In a r and omized , controlled , multicenter clinical trial in medication-free patients with PD/A who were treated with 12 sessions of manualized CBT , functional magnetic resonance imaging ( fMRI ) was used during fear conditioning before and after CBT . Quality -controlled fMRI data from 42 patients and 42 healthy subjects were obtained . RESULTS After CBT , patients compared to control subjects revealed reduced activation for the conditioned response ( CS+ > CS- ) in the left inferior frontal gyrus ( IFG ) . This activation reduction was correlated with reduction in agoraphobic symptoms from t1 to t2 . Patients compared to control subjects also demonstrated increased connectivity between the IFG and regions of the " fear network " ( amygdalae , insulae , anterior cingulate cortex ) across time . CONCLUSIONS This study demonstrates the link between cerebral correlates of cognitive ( IFG ) and emotional ( " fear network " ) processing during symptom improvement across time in PD/A. Further research along this line has promising potential to support the development and further optimization of targeted treatments Mindfulness-based stress reduction ( MBSR ) is thought to reduce emotional reactivity and enhance emotion regulation in patients with social anxiety disorder ( SAD ) . The goal of this study was to examine the neural correlates of deploying attention to regulate responses to negative self-beliefs using functional magnetic resonance imaging . Participants were 56 patients with generalized SAD in a r and omized controlled trial who were assigned to MBSR or a comparison aerobic exercise ( AE ) stress reduction program . Compared to AE , MBSR yielded greater ( i ) reductions in negative emotion when implementing regulation and ( ii ) increases in attention-related parietal cortical regions . Meditation practice was associated with decreases in negative emotion and social anxiety symptom severity , and increases in attention-related parietal cortex neural responses when implementing attention regulation of negative self-beliefs . Changes in attention regulation during MBSR may be an important psychological factor that helps to explain how mindfulness meditation training benefits patients with anxiety disorders Mindfulness training aims to impact emotion regulation . Generalized anxiety disorder ( GAD ) symptoms can be successfully addressed through mindfulness-based interventions . This preliminary study is the first to investigate neural mechanisms of symptom improvements in GAD following mindfulness training . Furthermore , we compared brain activation between GAD patients and healthy participants at baseline . 26 patients with a current DSM-IV GAD diagnosis were r and omized to an 8-week Mindfulness Based Stress Reduction ( MBSR , N = 15 ) or a stress management education ( SME , N = 11 ) active control program .  26 healthy participants were included for baseline comparisons . BOLD response was assessed with fMRI during affect labeling of angry and neutral facial expressions . At baseline , GAD patients showed higher amygdala activation than healthy participants in response to neutral , but not angry faces , suggesting that ambiguous stimuli reveal stronger reactivity in GAD patients . In patients , amygdala activation in response to neutral faces decreased following both interventions . BOLD response in ventrolateral prefrontal regions ( VLPFC ) showed greater increase in MBSR than SME participants . Functional connectivity between amygdala and PFC regions increased significantly pre- to post-intervention within the MBSR , but not SME group . Both , change in VLPFC activation and amygdala – prefrontal connectivity were correlated with change in Beck Anxiety Inventory ( BAI ) scores , suggesting clinical relevance of these changes . Amygdala – prefrontal connectivity turned from negative coupling ( typically seen in down-regulation of emotions ) , to positive coupling ; potentially suggesting a unique mechanism of mindfulness . Findings suggest that in GAD , mindfulness training leads to changes in fronto-limbic areas crucial for the regulation of emotion ; these changes correspond with reported symptom improvements IMPORTANCE Although neuroimaging research has made substantial progress in identifying the large-scale neural substrate of anxiety disorders , its value for clinical application lags behind expectations . Machine-learning approaches have predictive potential for individual-patient prognostic purpose s and might thus aid translational efforts in psychiatric research . OBJECTIVE To predict treatment response to cognitive behavioral therapy ( CBT ) on an individual-patient level based on functional magnetic resonance imaging data in patients with panic disorder with agoraphobia ( PD/AG ) . DESIGN , SETTING , AND PARTICIPANTS We included 49 patients free of medication for at least 4 weeks and with a primary diagnosis of PD/AG in a longitudinal study performed at 8 clinical research institutes and outpatient centers across Germany . The functional magnetic resonance imaging study was conducted between July 2007 and March 2010 . INTERVENTIONS Twelve CBT sessions conducted 2 times a week focusing on behavioral exposure . MAIN OUTCOMES AND MEASURES Treatment response was defined as exceeding a 50 % reduction in Hamilton Anxiety Rating Scale scores . Blood oxygenation level-dependent signal was measured during a differential fear-conditioning task . Regional and whole-brain gaussian process classifiers using a nested leave-one-out cross-validation were used to predict the treatment response from data acquired before CBT . RESULTS Although no single brain region was predictive of treatment response , integrating regional classifiers based on data from the acquisition and the extinction phases of the fear-conditioning task for the whole brain yielded good predictive performance ( accuracy , 82 % ; sensitivity , 92 % ; specificity , 72 % ; P < .001 ) . Data from the acquisition phase enabled 73 % correct individual-patient classifications ( sensitivity , 80 % ; specificity , 67 % ; P < .001 ) , whereas data from the extinction phase led to an accuracy of 74 % ( sensitivity , 64 % ; specificity , 83 % ; P < .001 ) . Conservative reanalyses under consideration of potential confounders yielded nominally lower but comparable accuracy rates ( acquisition phase , 70 % ; extinction phase , 71 % ; combined , 79 % ) . CONCLUSIONS AND RELEVANCE Predicting treatment response to CBT based on functional neuroimaging data in PD/AG is possible with high accuracy on an individual-patient level . This novel machine-learning approach brings personalized medicine within reach , directly supporting clinical decisions for the selection of treatment options , thus helping to improve response rates The possibility of individualized treatment prediction has profound implication s for the development of personalized interventions for patients with anxiety disorders . Here we utilize r and om forest classification and pre-treatment functional magnetic resonance imaging ( fMRI ) data from individuals with generalized anxiety disorder ( GAD ) and panic disorder ( PD ) to generate individual subject treatment outcome predictions . Before cognitive behavioral therapy ( CBT ) , 48 adults ( 25 GAD and 23 PD ) reduced ( via cognitive re appraisal ) or maintained their emotional responses to negative images during fMRI scanning .  CBT responder status was predicted using activations from 70 anatomically defined regions . The final r and om forest model included 10 predictors contributing most to classification accuracy . A similar analysis was conducted using the clinical and demographic variables . Activations in the hippocampus during maintenance and anterior insula , superior temporal , supramarginal , and superior frontal gyri during re appraisal were among the best predictors , with greater activation in responders than non-responders . The final fMRI-based model yielded 79 % accuracy , with good sensitivity ( 0.86 ) , specificity ( 0.68 ) , and positive and negative likelihood ratios ( 2.73 , 0.20 ) . Clinical and demographic variables yield 
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We conclude that , although each of these related disorders is mediated by somewhat different neural circuitry , CBT may act in a similar way to increase prefrontal control of subcortical structures .
These findings are consistent with an emphasis in cognitive-affective neuroscience on the potential therapeutic value of enhancing emotional regulation in various psychiatric conditions