***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: Area-specific and stimulation-dependent changes of human brain activation by selective serotonin reuptake inhibitors ( SSRI ) are an important issue for improved underst and ing of treatment mechanisms , given the frequent prescription of these drugs in depression and anxiety disorders . The aim of this neuroimaging study was to investigate differences in BOLD-signal caused by administration of the SSRIs escitalopram and citalopram using pharmacological functional magnetic resonance imaging ( pharmaco-fMRI ) . Eighteen healthy subjects participated in a placebo-controlled , r and omized , double-blind study in cross-over repeated measures design . Each volunteer performed facial emotional discrimination and a sensorimotor control paradigm during three scanning sessions . Citalopram ( 20 mg/d ) , escitalopram ( 10 mg/d ) and placebo were administered for 10 days each with a drug-free period of at least 21 days . Significant pharmacological effects on BOLD-signal were found in the amygdala , medial frontal gyrus , parahippocampal , fusiform and middle temporal gyri . Post-hoc t-tests revealed decreased BOLD-signal in the right amygdala and left parahippocampal gyrus in both pharmacological conditions , compared to placebo . Escitalopram , compared to citalopram , induced a decrease of BOLD-signal in the medial frontal gyrus and an increase in the right fusiform and left parahippocampal gyri . Drug effects were concentrated in brain regions with dense serotonergic projections . Both escitalopram and citalopram  attenuated BOLD-signal in the amygdala and parahippocampal cortex to emotionally significant stimuli compared to control stimuli . We believe that reduced reactivity in the medial frontal gyrus found for escitalopram compared to citalopram administration might explain the response differences between study drugs as demonstrated in previous clinical trials BACKGROUND Anhedonia , a reduced ability to experience pleasure , is a chief symptom of major depressive disorder and is related to reduced frontostriatal connectivity when attempting to upregulate positive emotion . The present study examined another facet of positive emotion regulation associated with anhedonia-namely , the downregulation of positive affect- and its relation to prefrontal cortex ( PFC ) activity . METHODS Neuroimaging data were collected from 27 individuals meeting criteria for major depressive disorder as they attempted to suppress positive emotion during a positive emotion regulation task . Their PFC activation pattern was compared with the PFC activation pattern exhibited by 19 healthy control subjects during the same task . Anhedonia scores were collected at three time points : at baseline ( time 1 ) , 8 weeks after time 1 ( i.e. , time 2 ) , and 6 months after time 1 ( i.e. , time 3 ) . Prefrontal cortex activity at time 1 was used to predict change in anhedonia over time . Analyses were conducted utilizing hierarchical linear modeling software . RESULTS Depressed individuals who could not inhibit positive emotion-evinced by reduced right ventrolateral prefrontal cortex activity during attempts to dampen their experience of positive emotion in response to positive visual stimuli-exhibited a steeper anhedonia reduction slope between baseline and 8 weeks of treatment with antidepressant medication ( p < .05 ) . Control subjects showed a similar trend between baseline and time 3 . CONCLUSIONS To reduce anhedonia , it may be necessary to teach individuals how to counteract the functioning of an overactive pleasure-dampening prefrontal inhibitory system Background Antidepressant drugs such as selective serotonin re-uptake inhibitors ( SSRIs ) remediate negative biases in emotional processing in depressed patients in both behavioural and neural outcome measures . However , it is not clear if these effects occur before , or as a consequence of , changes in clinical state . Method In the present study , we investigated the effects of short-term SSRI treatment in depressed patients on the neural response to fearful faces prior to clinical improvement in mood . Altogether , 42 unmedicated depressed patients received SSRI treatment ( 10 mg escitalopram daily ) or placebo in a r and omised , parallel-group design . The neural response to fearful and happy faces was measured on day 7 of treatment using functional magnetic resonance imaging .  A group of healthy controls was imaged in the same way . Results Amygdala responses to fearful facial expressions were significantly greater in depressed patients compared to healthy controls . However , this response was normalised in patients receiving 7 days treatment with escitalopram . There was no significant difference in clinical depression ratings at 7 days between the escitalopram and placebo-treated patients . Conclusions Our results suggest that short-term SSRI treatment in depressed patients remediates amygdala hyperactivity in response to negative emotional stimuli prior to clinical improvement in depressed mood . This supports the hypothesis that the clinical effects of antidepressant treatment may be mediated in part through early changes in emotional processing . Further studies will be needed to show if these early effects of antidepressant medication predict eventual clinical outcome BACKGROUND The amygdala has a central role in processing emotions , particularly fear . During functional magnetic resonance imaging ( fMRI ) amygdala activation has been demonstrated outside of conscious awareness using masked emotional faces . METHODS We applied the masked faces paradigm to patients with major depression ( n = 11 ) and matched control subjects ( n = 11 ) during  fMRI to compare amygdala activation in response to masked emotional faces before and after antidepressant treatment . Data were analyzed using left and right amygdala a priori regions of interest , in an analysis of variance block analysis and r and om effects model . RESULTS Depressed patients had exaggerated left amygdala activation to all faces , greater for fearful faces . Right amygdala did not differ from control subjects . Following treatment , patients had bilateral reduced amygdala activation to masked fearful faces and bilateral reduced amygdala activation to all faces . Control subjects had no differences between the two scanning sessions . CONCLUSIONS Depressed patients have left amygdala hyperarousal , even when processing stimuli outside conscious awareness . Increased amygdala activation normalizes with antidepressant treatment Serotonergic and noradrenergic pathways are the main targets of antidepressants . Their differential effects on emotion processing-related brain activation are , however , to be further characterized . We aim ed at elucidating the neural sites of action of an acute differential serotonergic and noradrenergic influence on an emotion-processing task , which was earlier shown to be associated with depressiveness . In a single-blind pseudo-r and omized crossover study , 21 healthy subjects ( 16 subjects finally included in the analysis ) participated to ingest a single dose at three time points of either 40 mg citalopram , a selective serotonin-reuptake inhibitor , 8 mg reboxetine , a selective noradrenaline-reuptake inhibitor , or placebo 2–3 h before functional magnetic resonance imaging ( fMRI ) . During fMRI , subjects performed a task comprising the anticipation and perception of pictures of either ‘ known ’ ( positive , negative , neutral ) or ‘ unknown ’ valence ( r and omly 50 % positive or negative ) . In direct comparison with citalopram and with placebo , reboxetine increased brain activity in the medial thalamus . Citalopram modulated certain prefrontal and insular areas more prominently . Other frontal and parieto-occipital areas were modulated by both drugs . In conclusion , the functional network involved in emotional information processing could be modulated by the acute application of selective noradrenergic and serotonergic drugs revealing a noradrenergic effect in thalamic and frontal areas , and a prefrontal and insular focus of serotonergic modulation . These findings could have implication s for future selection criteria concerning personalized antidepressant medication in depression Rationale The amygdala and insular cortex are integral to the processing of emotionally salient stimuli . We have shown in healthy volunteers that an anxiolytic agent , lorazepam , dose-dependently attenuates activation of limbic structures . Objective The current study investigated whether administration of a selective serotonin reuptake inhibitor ( SSRI ) , escitalopram , alters the activation of limbic structures . We hypothesized that subchronic ( 21 days ) SSRI treatment attenuates the activation of the amygdala and insula during processing of emotional faces . Material s and methods Thirteen healthy volunteers participated in a double-blind ,  placebo-controlled  , crossover , r and omized study . After 21 days of treatment with either escitalopram or placebo , participants underwent functional magnetic resonance imaging ( fMRI ) during which all subjects completed an emotion face assessment task , which has been shown to elicit amygdala and insula activation . Results Subjects activated the bilateral insula and amygdala after treatment with both escitalopram and placebo . In subjects who were adherent to the protocol ( as evidence d by sufficiently high urine concentrations of escitalopram ) , a reduction in amygdala activation was seen in the escitalopram condition compared to placebo . Conclusion The current investigation provides further evidence for the mechanism of action of SSRIs through the attenuation of activation in brain regions responsible for emotion processing and provides support for the use of blood oxygenation level-dependent fMRI with pharmacological probes to help identify the specific therapeutic effect of these agents in patients with anxiety and mood disorders It has been hypothesized that one of the effects of antidepressants is to increase functional connectivity between the cortical mood-regulating and the limbic mood-generating regions . One consequence of this antidepressant effect is thought to be decreased limbic activation in response to negative emotional stimuli . Twelve unmedicated unipolar depressed patients and 11 closely matched healthy comparison subjects completed two magnetic resonance imaging ( MRI ) scanning sessions at baseline and after 6 weeks . Depressed patients received treatment with sertraline between the two sessions . During each MRI session , subjects completed a resting state functional connectivity scan and a conventional block- design negative vs. neutral pictures regional brain activation scan . After 6 weeks of sertraline treatment resting state , functional connectivity between the ACC and limbic regions increased while limbic activation in response to negative versus neutral pictures decreased . The results of this study are consistent with the hypothesis that antidepressant treatment has reciprocal effects on corticolimbic functional connectivity and limbic activation in response to emotional stimuli BACKGROUND The amygdala is believed to play a key role in processing emotionally salient , threat-relevant , events that require further online processing by cortical regions . Emotional disorders such as depression and anxiety have been associated with hyperactivity of the amygdala , but it is unknown whether antidepressant treatment directly affects amygdala responses to emotionally significant information . METHODS The current study assessed the effects of 7 days administration of the selective serotonin reuptake inhibitor ( SSRI ) , citalopram , on amygdala responses to masked presentations of fearful and happy facial expressions in never-depressed volunteers using blood oxygenation level-dependent ( BOLD ) functional magnetic resonance imaging . A double-blind , between-groups design was used with volunteers r and omized to 20 mg/day citalopram versus placebo . RESULTS Volunteers receiving citalopram showed decreased amygdala responses to masked presentations of threat compared with those receiving placebo . Citalopram also reduced responses within the hippocampus and medial prefrontal cortex ( mPFC ) specifically during the fear-relevant stimuli . These neural differences were accompanied by decreased recognition of fearful facial expressions assessed after the scan . By contrast , there was no effect of citalopram on the neural or behavioral response to the happy facial expressions . CONCLUSIONS These results suggest a direct effect of serotonin potentiation on amygdala response to threat-relevant stimuli in humans . Such effects may be important in the therapeutic actions of antidepressants in depression and anxiety OBJECTIVE To investigate neural activity in prefrontal cortex and amygdala during bipolar depression . METHODS Eleven bipolar I depressed and 17 normal subjects underwent functional magnetic resonance imaging ( fMRI ) while performing a task known to activate prefrontal cortex and amygdala . Whole brain activation patterns were determined using statistical parametric mapping ( SPM ) when subjects matched faces displaying neutral or negative affect ( match condition ) or matched a geometric form ( control condition ) . Contrasts for each group for the match versus control conditions were used in a second-level r and om effects analysis . RESULTS R and om effects between-group analysis revealed significant attenuation in right and left orbitofrontal cortex ( BA47 ) and right dorsolateral prefrontal cortex ( DLPFC ) ( BA9 ) in bipolar depressed subjects . Additionally , r and om effects analysis showed a significantly increased activation in left lateral orbitofrontal cortex ( BA10 ) in the bipolar depressed versus control subjects . Within-group contrasts demonstrated significant amygdala activation in the controls and no significant amygdala activation in the bipolar depressed subjects . The amygdala between-group difference , however , was not significant . CONCLUSIONS Bipolar depression is associated with attenuated bilateral orbitofrontal ( BA47 ) activation , attenuated right DLPFC ( BA9 ) activation and heightened left orbitofrontal ( BA10 ) activation . BA47 attenuation has also been reported in mania and may thus represent a trait feature of the disorder . Increased left prefrontal ( BA10 ) activation may be a state marker to bipolar depression . Our findings suggest dissociation between mood-dependent and disease-dependent functional brain abnormalities in bipolar disorder The mechanisms by which antidepressant-induced neurochemical changes lead to physiological changes in brain circuitry and ultimately an antidepressant response remain unclear . This study investigated the effects of sertraline , a selective ser 
    Output:
    
Automatic regulation subprocesses were shown to involve predominantly medial prefrontal cortical structures , in addition to the hippocampus and parahippocampus , while voluntary regulation processes additionally recruited lateral prefrontal cortical regions .
In conclusion , although the available data is limited , findings suggest that MDD subjects demonstrate abnormally reduced activity in lateral prefrontal cortices during explicit voluntary control of emotional experience .
During early , automatic stages of emotion regulation , on the other h and , MDD subjects appear to achieve successful emotion regulation by recruiting additional lateral prefrontal neural regions , that may be mediated by medial prefrontal , especially rostral/dorsal anterior cingulate gyrus ( ACG ) functioning .
Dysfunctional automatic regulation may impair successful voluntary emotion regulation , and may present a target for novel therapeutic approaches in MDD