***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 : Cognitive behavioral therapy ( CBT ) is an effective treatment for panic disorder with agoraphobia ( PD/AG ) . It is unknown , how variants of CBT differentially modulate brain networks involved in PD/AG . This study was aim ed to evaluate the effects of therapist-guided ( T+ ) versus self-guided ( T- ) exposure on the neural correlates of fear conditioning in PD/AG . Method : In a r and omized , controlled multicenter clinical trial in medication-free patients with PD/AG who were treated with 12 sessions of manualized CBT , functional magnetic resonance imaging ( fMRI ) was used during fear conditioning before ( t1 ) and after CBT ( t2 ) . Quality -controlled fMRI data from 42 patients and 42 healthy subjects ( HS ) were obtained . Patients were r and omized to two variants of CBT ( T+ , n = 22 , and T- , n = 20 ) . Results : The interaction of diagnosis ( PD/AG , HS ) , treatment group ( T+ , T- ) , time point ( t1 , t2 ) and stimulus type ( conditioned stimulus : yes , no ) revealed activation in the left hippocampus and the occipitotemporal cortex . The T+ group demonstrated increased activation of the hippocampus at t2 ( t2 > t1 ) , which was positively correlated with treatment outcome , and a decreased connectivity between the left inferior frontal gyrus and the left hippocampus across time ( t1 > t2 ) . Conclusion : After T+ exposure , contingency-encoding processes related to the posterior hippocampus are augmented and more decoupled from processes of the left inferior frontal gyrus , previously shown to be dysfunctionally activated in PD/AG . Linking single procedural variants to neural substrates offers the potential to inform about the optimization of targeted psychotherapeutic interventions 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 Social anxiety disorder patients suffer from excessive anxious responses in social interaction leading to avoidance behavior and social impairment . Although the amygdala has a central role in perception and processing of threatening cues , little is known about the involved networks and corresponding dysfunctions in social anxiety . Therefore , this study aims to investigate the functional connectivity network of the amygdala in patients with social anxiety disorder and to identify regions that might influence amygdalar reactivity via modulatory pathways . Ten patients with anxiety disorders ( social and /or panic ) and 27 healthy controls underwent a facial emotion processing task as well as 6-min functional MRI at resting state . Individual voxel-wise functional connectivity maps were calculated using the amygdala as seed region . Group comparisons were done by r and om-effects analysis in SPM . Patients exhibited an amygdala hyperactivation during the emotional task and decreased functional coupling of the left amygdala with the medial orbitofrontal cortex and the posterior cingulate cortex/precuneus . The strength of this functional connectivity showed a negative association with the severity of state anxiety . In addition , an exploratory analysis revealed further reduced functional connectivity and a marked functional separation between the medial orbitofrontal and anterior cingulate cortices in the patient group . Our results suggest alterations within the amygdalar functional connectivity network in social anxiety disorder . Combined with the amygdalar hyperactivation our findings corroborate the proposed dysfunction of the fronto-amygdalar inhibition in anxiety disorders and indicate a modulatory influence of the anterior and posterior cingulate cortices on threat perception and processing 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 One component of mindfulness training ( MT ) is the development of interoceptive attention ( IA ) to visceral bodily sensations , facilitated through daily practice s such as breath monitoring . Using functional magnetic resonance imaging ( fMRI ) , we examined experience-dependent functional plasticity in accessing interoceptive representations by comparing graduates of a Mindfulness-Based Stress Reduction course to a  waitlisted control group .  IA to respiratory sensations was contrasted against two visual tasks , controlling for attentional requirements non-specific to IA such as maintaining sensation and suppressing distraction . In anatomically partitioned analyses of insula activity , MT predicted greater IA-related activity in anterior dysgranular insula regions , consistent with greater integration of interoceptive sensation with external context . MT also predicted decreased recruitment of the dorsomedial prefrontal cortex ( DMPFC ) during IA , and altered functional connectivity between the DMPFC and the posterior insula , putative primary interoceptive cortex . Furthermore , meditation practice compliance predicted greater posterior insula and reduced visual pathway recruitment during IA . These findings suggest that interoceptive training modulates task-specific cortical recruitment , analogous to training-related plasticity observed in the external senses . Further , DMPFC modulation of IA networks may be an important mechanism by which MT alters information processing in the brain , increasing the contribution of interoception to perceptual experience Background Given the variable response to cognitive – behavioral therapy ( CBT ) when added to antipsychotic medication in psychosis and the evidence for a role of pretherapy level of frontal lobe – based cognitive function in responsiveness to CBT in other disorders , this study examined whether pretherapy brain activity associated with working memory neural network predicts clinical responsiveness to CBT in schizophrenia . Methods Fifty-two out patients stable on medication with at least one distressing symptom of schizophrenia and willing to receive CBT in addition to their usual treatment and 20 healthy participants underwent functional magnetic resonance imaging during a parametric n-back task . Subsequently , 26 patients received CBT for psychosis ( CBT+treatment-as-usual [ TAU ] , 19 completers ) for 6–8 months , and 26 continued with TAU alone ( 17 completers ) . Symptoms in both patient groups were assessed ( blindly ) at entry and follow-up . Results The CBT+TAU and TAU-alone groups did not differ clinical ly or in performance at baseline . The CBT+TAU group showed significant improvement in relation to the TAU-alone group , which showed no change , at follow-up . Stronger dorsolateral prefrontal cortex ( DLPFC ) activity ( within the normal range ) and DLPFC – cerebellum connectivity during the highest memory load condition ( 2-back > 0-back ) were associated with post-CBT clinical improvement . Conclusions DLPFC activity and its connectivity with the cerebellum predict responsiveness to CBT for psychosis in schizophrenia . These effects may be mediated by PFC – cerebellum contributions to executive processing Neuroimaging research has demonstrated that ventromedial prefrontal cortex ( vmPFC ) encodes value signals that can be modulated by top-down cognitive input such as semantic knowledge , price incentives , and monetary favors suggesting that such biases may have an identified biological basis . It has been hypothesized that mindfulness training ( MT ) provides one path for gaining control over such top-down influences ; yet , there have been no direct tests of this hypothesis . Here , we probe the behavioral and neural effects of MT on value signals in vmPFC in a r and omized longitudinal design of 8 weeks of MT on an initially naïve subject cohort . The impact of this within-subject training was assessed using two paradigms : one that employed primary rewards ( fruit juice ) in a simple conditioning task and another that used a well-vali date d art-viewing paradigm to test bias of monetary favors on preference . We show that MT behaviorally censors the top-down bias of monetary favors through a measurable influence on value signals in vmPFC . MT also modulates value signals in vmPFC to primary reward delivery . Using a separate cohort of subjects we show that 8 weeks of active control training ( ACT ) generates the same behavioral impact also through an effect on signals in the vmPFC . Importantly , functional connectivity analyses show that value signals in vmPFC are coupled with bilateral posterior insula in the MT groups in both paradigms , but not in the ACT groups . These results suggest that MT integrates interoceptive input from insular cortex in the context of value computations of both primary and secondary rewards 
    Output:
    
Conclusion : While the evidence base is still in its infancy for other therapy approaches , there was clearer evidence that functional connectivity both predicts and is altered by cognitive behavioural therapy .
Connections from prefrontal cortex appear especially key , perhaps given their role in cognitive appraisal of lower order affective , motivational and cognitive processes .