***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: The ventral tegmental area ( VTA ) has been primarily implicated in reward-motivated behavior . Recently , aberrant dopaminergic VTA signaling has also been implicated in anxiety-like behaviors in animal models . These findings , however , have yet to be extended to anxiety in humans . Here we hypothesized that clinical anxiety is linked to dysfunction of the mesocorticolimbic circuit during threat processing in humans ; specifically , excessive or dysregulated activity of the mesocorticolimbic aversion circuit may be etiologically related to errors in distinguishing cues of threat versus safety , also known as “ overgeneralization of fear . ” To test this , we recruited 32 females with generalized anxiety disorder and 25 age-matched healthy control females . We measured brain activity using fMRI while participants underwent a fear generalization task consisting of pseudo-r and omly presented rectangles with systematic ally varying widths . A mid-sized rectangle served as a conditioned stimulus ( CS ; 50 % electric shock probability ) and rectangles with widths of CS ±20 % , ±40 % , and ±60 % served as generalization stimuli ( GS ; never paired with electric shock ) . Healthy controls showed VTA reactivity proportional to the cue 's perceptual similarity to CS ( threat ) . In contrast , patients with generalized anxiety disorder showed heightened and less discriminating VTA reactivity to GS , a feature that was positively correlated with trait anxiety , as well as increased mesocortical and decreased mesohippocampal coupling . Our results suggest that the human VTA and the mesocorticolimbic system play a crucial role in threat processing , and that abnormalities in this system are implicated in maladaptive threat processing in clinical anxiety The role of worry in generalized anxiety disorder ( GAD ) has been posited to serve as an avoidance of emotional experience , and emotion regulation deficits in GAD have been found in several previous studies . It remains unclear whether those with GAD experience more dysregulated emotions during periods of euthymia and positive affect or whether these deficits occur only during periods of worry . Individuals with GAD ( with and without co-occurring dysphoria ) and non-anxious controls were r and omly assigned to receive a worry , neutral , or relaxation induction . Following the induction , all participants viewed a film clip documented to elicit sadness . Intensity of emotions and emotion regulation were examined following the induction period and film clip . The results revealed that , regardless of co-occurring dysphoria , individuals with GAD in the worry condition experienced more intense depressed affect than GAD participants in the other conditions and controls participants . In contrast , presence of worry appeared to have less impact on indices of emotion dysregulation , which were greater in participants with GAD compared to controls , but largely insensitive to context ual effects of worry or of relaxation . Following film viewing , both GAD participants with and without dysphoria displayed poorer underst and ing , acceptance , and management of emotions than did controls . However , acceptance and management deficits were most pronounced in individuals with both GAD and co-occurring dysphoria . Implication s for the role of emotions in conceptualization and treatment of GAD are discussed Theory of Mind ( ToM ) , the ability to attribute mental states to others , and empathy , the ability to infer emotional experiences , are important processes in social cognition . Brain imaging studies in healthy subjects have described a brain system involving medial prefrontal cortex , superior temporal sulcus and temporal pole in ToM processing . Studies investigating networks associated with empathic responding also suggest involvement of temporal and frontal lobe regions . In this fMRI study , we used a cartoon task derived from Sarfati et al. ( 1997 ) [ Sarfati , Y. , Hardy-Bayle , M.C. , Besche , C. , Widlocher , D. 1997 . Attribution of intentions to others in people with schizophrenia : a non-verbal exploration with comic strips . Schizophrenia Research 25 , 199 - 209.]with both ToM and empathy stimuli in order to allow comparison of brain activations in these two processes . Results of 13 right-h and ed , healthy , male volunteers were included . Functional images were acquired using a 1.5 T Phillips Gyroscan . Our results confirmed that  ToM and empathy  stimuli are associated with overlapping but distinct neuronal networks . Common areas of activation included the medial prefrontal cortex , temporoparietal junction and temporal poles . Compared to the empathy condition , ToM stimuli revealed increased activations in lateral orbitofrontal cortex , middle frontal gyrus , cuneus and superior temporal gyrus . Empathy , on the other h and , was associated with enhanced activations of paracingulate , anterior and posterior cingulate and amygdala . We therefore suggest that ToM and empathy both rely on networks associated with making inferences about mental states of others . However , empathic responding requires the additional recruitment of networks involved in emotional processing . These results have implication s for our underst and ing of disorders characterized by impairments of social cognition , such as autism and psychopathy As a central fear processor of the brain , the amygdala initiates a cascade of critical physiological and behavioral responses . Neuroimaging studies have shown that the human amygdala responds not only to fearful and angry facial expressions but also to fearful and threatening scenes such as attacks , explosions , and mutilations . Given the relative importance of facial expressions in adaptive social behavior , we hypothesized that the human amygdala would exhibit a stronger response to angry and fearful facial expressions in comparison to other fearful and threatening stimuli . Twelve subjects completed two tasks while undergoing fMRI : matching angry or fearful facial expressions , and matching scenes depicting fearful or threatening situations derived from the International Affective Picture System ( IAPS ) . While there was an amygdala response to both facial expressions and IAPS stimuli , direct comparison revealed that the amygdala response to facial expressions was significantly greater than that to IAPS stimuli . Autonomic reactivity , measured by skin conductance responses , was also greater to facial expressions . These results suggest that the human amygdala shows a stronger response to affective facial expressions than to scenes , a bias that should be considered in the design of experimental paradigms interested in probing amygdala function 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 BACKGROUND Functional magnetic resonance imaging ( fMRI ) holds promise as a noninvasive means of identifying neural responses that can be used to predict treatment response before beginning a drug trial . Imaging paradigms employing facial expressions as presented stimuli have been shown to activate the amygdala and anterior cingulate cortex ( ACC ) . Here , we sought to determine whether pretreatment amygdala and rostral ACC ( rACC ) reactivity to facial expressions could predict treatment outcomes in patients with generalized anxiety disorder ( GAD ) . METHODS Fifteen subjects ( 12 female subjects ) with GAD participated in an open-label venlafaxine treatment trial . Functional magnetic resonance imaging responses to facial expressions of emotion collected before subjects began treatment were compared with changes in anxiety following 8 weeks of venlafaxine administration . In addition , the magnitude of fMRI responses of subjects with GAD were compared with that of 15 control subjects ( 12 female subjects ) who did not have GAD and did not receive venlafaxine treatment .  RESULTS The magnitude of treatment response was predicted by greater pretreatment reactivity to fearful faces in rACC and lesser reactivity in the amygdala . These individual differences in pretreatment rACC and amygdala reactivity within the GAD group were observed despite the fact that 1 ) the overall magnitude of pretreatment rACC and amygdala reactivity did not differ between subjects with GAD and control subjects and 2 ) there was no main effect of treatment on rACC-amygdala reactivity in the GAD group . CONCLUSIONS These findings show that this pattern of rACC-amygdala responsivity could prove useful as a predictor of venlafaxine treatment response in patients with GAD Although the role of emotion in socioeconomic decision making is increasingly recognised , the impact of specific emotional disorders , such as anxiety disorders , on these decisions has been surprisingly neglected . Twenty anxious patients and twenty matched controls completed a commonly used socioeconomic task ( the Ultimatum Game ) , in which they had to accept or reject monetary offers from other players .  Anxious patients accepted significantly more unfair offers than controls . We discuss the implication s of these findings in light of recent models of anxiety , in particular the importance of interpersonal factors and assertiveness in an integrated model of decision making . Finally , we were able to show that pharmacological serotonin used to treat anxious symptomatology tended to normalise decision making , further confirming and extending the role of serotonin in co-operation , prosocial behaviour , and social decision making . These results show , for the first time , a different pattern of socioeconomic behaviour in anxiety disordered patients , in addition to the known memory , attentional and emotional biases that are part of this pathological condition More than half of anxiety and depression patients treated with an adequate course of antidepressants fail to fully improve . We retrospectively examined whether treatment-resistant depression and anxiety disorder patients responded to and tolerated augmentation with the atypical antipsychotic , aripiprazole . We report on patients with depression and anxiety disorders , including panic disorder , generalized anxiety disorder , social anxiety and post-traumatic stress disorder , who had an incomplete response to a variety of selective serotonin reuptake inhibitors ( SSRIs ) and who received augmentation with aripiprazole .  The primary outcome measure was the Clinical Global Impression of Improvement ( CGI-I ) . In the intent-to-treat analysis , the mean±SD CGI-S was 3.8±1.3 at endpoint . Fifty-nine percent of subjects received CGI-I ratings of 1 or 2 , ‘ much improved ’ or ‘ very much improved , ’ in terms of their depression and anxiety symptoms at the end of 12 weeks . Several patients showed an early ( weeks 1–5 ) , as well as sustained , response to augmentation with doses of aripiprazole between 15 and 30 mg/day . The results suggest that aripiprazole may be effective as an augmentation for patients with persistent depressive and anxiety disorders despite initial SSRI treatment . Because this is a retrospective case review , further prospect i ve studies are required to confirm these findings This study investigated the temporal pattern of brain response to emotional stimuli during 28 days of alprazolam treatment among patients with generalized anxiety disorder ( GAD ) r and omized 2:1 to drug or placebo in a double-blind design . Functional magnetic resonance imaging scans obtained during an emotion face matching task ( EFMT ) and an affective stimulus expectancy task ( STIMEX ) were performed at baseline , one hour after initial drug administration and 28 days later . Alprazolam significantly reduced scores on the Hamilton Anxiety Scale and the Penn State Worry Question naire after one week and 28 days of treatment . Brain activation in the amygdala during the EFMT and in the insula during the STIMEX was reduced one hour after alprazolam administration but returned to baseline levels at Day 28 . Exploratory analyses revealed significant treatment differences in brain activity during the STIMEX on Day 28 in frontal lobe , cau date nucleus , middle temporal gyrus , secondary visual cortex , and supramarginal gyrus . These results are consistent with the notion that the neural mechanisms supporting sustained treatment effects of benzodiazepines in GAD differ from those underlying their acute effects Some research ers have recently suggested that antidepressants may be superior to benzodiazepines in the alleviation of generalized anxiety . In a 6-week , double-blind , parallel- design study with flexible dosage scheduling , the authors compared the effects of alprazolam with those of imipramine in 60 patients who had generalized anxiety disorder . On rating scales that contained both psychic and somatic symptoms , patients in both treatment groups improved to a similar degree after 2 weeks . However , alprazolam was more effective in attenuating somatic symptoms , and imipramine was more effective in attenuating psychic symptoms such as dysphoria and negative anticipatory thinking . The authors ' results suggest that , in generalized anxiety , somatic symptoms and hyperarousal selectively respond to drugs acting on the gamma 
    Output:
    
RESULTS The available studies have shown impairments in ventrolateral and dorsolateral prefrontal cortex , anterior cingulate , posterior parietal regions , and amygdala in both pediatric and adult GAD patients , mostly in the right hemisphere .