***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: BACKGROUND Although inflammatory activity is known to play a role in depression , no work has examined whether experimentally induced systemic inflammation alters neural activity that is associated with anhedonia , a key diagnostic symptom of depression . To investigate this , we examined the effect of an experimental inflammatory challenge on the neural correlates of anhedonia-namely , reduced ventral striatum ( VS ) activity to reward cues . We also examined whether this altered neural activity related to inflammatory-induced increases in depressed mood . METHODS Participants ( n = 39 ) were r and omly assigned to receive either placebo or low-dose endotoxin , which increases proinflammatory cytokine levels in a safe manner . Cytokine levels were repeatedly assessed through hourly blood draws ; self-reported and observer-rated depressed mood were assessed regularly as well . Two hours after drug administration , neural activity was recorded as participants completed a task in which they anticipated monetary rewards . RESULTS Results demonstrated that subjects exposed to endotoxin , compared with placebo , showed greater increases in self-reported and observer-rated depressed mood over time , as well as significant reductions in VS activity to monetary reward cues . Moreover , the relationship between exposure to inflammatory challenge and increases in observer-rated depressed mood was mediated by between-group differences in VS activity to anticipated reward . CONCLUSIONS The data reported here show , for the first time , that inflammation alters reward-related neural responding in humans and that these reward-related neural responses mediate the effects of inflammation on depressed mood . As such , these findings have implication s for underst and ing risk of depression in persons with underlying inflammation Although social withdrawal is a prominent symptom of sickness , the mechanisms associated with this behavioral change remain unclear . In animals , the amygdala is a key neural region involved in sickness-induced social withdrawal . Consistent with this , in humans , heightened amygdala activity to negative social cues is associated with social avoidance tendencies . Based on these findings , we investigated whether an experimental inflammatory challenge selectively increased amygdala activity to socially threatening images as well as whether this activity related to feelings of social disconnection . Thirty-nine participants were r and omly assigned to receive either placebo or low-dose endotoxin  , which increases inflammatory activity . Pro-inflammatory cytokines were assessed at 7 hourly time points via blood draws ; self-reported feelings of social disconnection and physical sickness symptoms were assessed hourly as well . Two hours post-injection , participants underwent an fMRI procedure to assess amygdala reactivity during the presentation of socially threatening images ( fear faces ) as well as non-socially threatening images ( guns ) , socially non-threatening images ( happy faces ) , and non-social , non-threatening images ( household objects ) . Endotoxin led to greater amygdala activity in response to socially threatening vs. all other types of images . No such differences were found for placebo participants . Additionally , increased amygdala activity in endotoxin participants during the viewing of socially vs. non-socially threatening images was associated with increased feelings of social disconnection . These findings highlight the amygdala as a neural region that may be important for sickness-induced social withdrawal . The implication s of amygdalar involvement in sickness-induced social withdrawal are discussed Background Inflammation rapidly impairs mood and cognition and , when severe , can appear indistinguishable from major depression . These sickness responses are characterized by an acute reorientation of motivational state ; pleasurable activities are avoided , and sensitivity to negative stimuli is enhanced . However , it remains unclear how these rapid shifts in behavior are mediated within the brain . Methods Here , we combined computational modeling of choice behavior , experimentally induced inflammation , and functional brain imaging ( functional magnetic resonance imaging ) to describe these mechanisms . Using a double-blind , r and omized crossover study design , 24 healthy volunteers completed a probabilistic instrumental learning task on two separate occasions , one 3 hours after typhoid vaccination and one 3 hours after saline ( placebo ) injection . Participants learned to select high probability reward ( win £ 1 ) and avoid high probability punishment ( lose £ 1 ) stimuli . An action-value learning algorithm was fit to the observed behavior , then used within functional magnetic resonance imaging analyses to identify neural coding of prediction error signals driving motivational learning . Results Inflammation acutely biased behavior , enhancing punishment compared with reward sensitivity , through distinct actions on neural representations of reward and punishment prediction errors within the ventral striatum and anterior insula . Consequently , choice options leading to potential rewards were less behaviorally attractive , and those leading to punishments were more aversive . Conclusions Our findings demonstrate the neural mediation of a rapid , state-dependent reorientation of reward versus punishment sensitivity during inflammation . This mechanism may aid the adaptive reallocation of metabolic re sources during acute sickness but might also account for maladaptive , motivational changes that underpin the association between chronic inflammation and depression Background Systemic infections commonly cause sickness symptoms including psychomotor retardation . Inflammatory cytokines released during the innate immune response are implicated in the communication of peripheral inflammatory signals to the brain . Methods We used functional magnetic resonance brain imaging ( fMRI ) to investigate neural effects of peripheral inflammation following  typhoid vaccination  in 16 healthy men , using a double-blind , r and omized , crossover-controlled design . Results Vaccination had no global effect on neurovascular coupling but markedly perturbed neural reactivity within substantia nigra during low-level visual stimulation . During a cognitive task , individuals in whom typhoid vaccination engendered higher levels of circulating interleukin-6 had significantly slower reaction time responses . Prolonged reaction times and larger interleukin-6 responses were associated with evoked neural activity within substantia nigra . Conclusions Our findings provide mechanistic insights into the interaction between inflammation and neurocognitive performance , specifically implicating circulating cytokines and midbrain dopaminergic nuclei in mediating the psychomotor consequences of systemic infection Increases in peripheral cytokines during acute inflammation may affect various neuropsychological functions . The aim of this functional magnetic resonance imaging ( fMRI ) study was to investigate the effects of acute endotoxemia on mood and the neural response to emotionally aversive visual stimuli in healthy human subjects . In a double-blind , r and omized crossover study , 18 healthy males received a bolus injection of bacterial lipopolysaccharide ( LPS ; 0.4 ng/kg ) or saline . Plasma levels of pro- and anti-inflammatory cytokines and cortisol as well as mood ratings were analyzed together with the blood-oxygen-level dependent ( BOLD ) response during the presentation of aversive versus neutral pictures . Endotoxin administration induced pronounced transient increases in plasma levels of TNF-α , IL-1ra , IL-6 , IL-10 , and cortisol . Positive mood was decreased and state anxiety increased . In addition , activation of right inferior orbitofrontal cortex ( OFC ) in response to emotional visual stimuli was significantly increased in the LPS condition . Increased prefrontal activation during the presentation of emotional material may reflect enhanced cognitive regulation of emotions as an adaptive response during an acute inflammation . These findings may have implication s for the putative role of inflammatory processes in the pathophysiology of depression Background Interferon-alpha ( IFN-α ) is a key mediator of antiviral immune responses used clinical ly for hepatitis C treatment . Though effective , IFN-α induces marked behavioral changes that , when severe , can appear indistinguishable from major depression . Curiously , fatigue and motivational impairment evolve rapidly , suggesting acute engagement of immune-brain communicatory pathways , yet mood impairments typically emerge later , after weeks of treatment . Whether this reflects prolonged modulation of motivational processes underpinning fatigue or separate neurobiological mechanisms is currently unclear . Methods Here , we used quantitative magnetization transfer ( qMT ) imaging , an advanced microstructural neuroimaging technique sensitive to effects of inflammation , in a prospect i ve study design to measure acute brain changes to IFN-α and relate these to later development of discrete behavioral changes . Twenty-three patients initiating IFN-α treatment for hepatitis C underwent qMT imaging and blood sampling at baseline and 4 hours after their first IFN-α injection . Comprehensive behavioral and psychological assessment s were completed at both scanning sessions and at treatment weeks 4 , 8 , 12 , and 24 . Results IFN-α injection stimulated an acute inflammatory cytokine response and evoked fatigue that peaked between 4 and 12 weeks , preceding mood change by 4 weeks . In the brain , IFN-α induced an acute change in striatal microstructure that additionally predicted development of fatigue but not mood symptoms . Conclusions Our findings highlight qMT as an in vivo biomarker of central effects of peripheral inflammation . We demonstrate exquisite sensitivity of the striatum to IFN-α , implicate striatal perturbation in IFN-α-induced fatigue , and dissociate this from mechanisms underlying IFN-α-induced mood symptoms , providing empirical support for distinct neural substrates mediating actions on motivation and mood Background Inflammatory cytokines are implicated in the pathophysiology of depression . In rodents , systemically administered inflammatory cytokines induce depression-like behavior . Similarly in humans , therapeutic interferon-α induces clinical depression in a third of patients . Conversely , patients with depression also show elevated pro-inflammatory cytokines . Objectives To determine the neural mechanisms underlying inflammation-associated mood change and modulatory effects on circuits involved in mood homeostasis and affective processing . Methods In a double-blind , r and omized crossover study , 16 healthy male volunteers received  typhoid vaccination or saline ( placebo ) injection in two experimental sessions . Mood question naires were completed at baseline and at 2 and 3 hours . Two hours after injection , participants performed an implicit emotional face perception task during functional magnetic resonance imaging . Analyses focused on neurobiological correlates of inflammation-associated mood change and affective processing within regions responsive to emotional expressions and implicated in the etiology of depression . Results Typhoid but not placebo injection produced an inflammatory response indexed by increased circulating interleukin-6 and significant mood reduction at 3 hours . Inflammation-associated mood deterioration correlated with enhanced activity within subgenual anterior cingulate cortex ( sACC ) ( a region implicated in the etiology of depression ) during emotional face processing . Furthermore , inflammation-associated mood change reduced connectivity of sACC to amygdala , medial prefrontal cortex , nucleus accumbens , and superior temporal sulcus , which was modulated by peripheral interleukin-6 . Conclusions Inflammation-associated mood deterioration is reflected in changes in sACC activity and functional connectivity during evoked responses to emotional stimuli . Peripheral cytokines modulate this mood-dependent sACC connectivity , suggesting a common pathophysiological basis for major depressive disorder and sickness-associated mood change and depression Although stress-induced increases in inflammation have been implicated in several major disorders , including cardiovascular disease and depression , the neurocognitive pathways that underlie inflammatory responses to stress remain largely unknown . To examine these processes , we recruited 124 healthy young adult participants to complete a laboratory-based social stressor while markers of inflammatory activity were obtained from oral fluids . A subset of participants ( n = 31 ) later completed an fMRI session in which their neural responses to social rejection were assessed . As predicted , exposure to the laboratory-based social stressor was associated with significant increases in two markers of inflammatory activity , namely a soluble receptor for tumor necrosis factor-α ( sTNFαRII ) and interleukin-6 ( IL-6 ) . In the neuroimaging sub sample , greater increases in sTNFαRII ( but not IL-6 ) were associated with greater activity in the dorsal anterior cingulate cortex and anterior insula , brain regions that have previously been associated with processing rejection-related distress and negative affect . These data thus eluci date a neurocognitive pathway that may be involved in potentiated inflammatory responses to acute social stress . As such , they have implication s for underst and ing how social stressors may promote susceptibility to diseases with an inflammatory component Background Inflammation is associated with psychological , emotional , and behavioral disturbance , known as sickness behavior . Inflammatory cytokines are implicated in coordinating this central motivational reorientation accompanying peripheral immunologic responses to pathogens . Studies in rodents suggest an afferent interoceptive neural mechanism , although comparable data in humans are lacking . Methods In a double-blind , r and omized crossover study , 16 healthy male volunteers received typhoid vaccination or saline ( placebo ) injection in two experimental sessions . Profile of Mood State question naires were completed at baseline and at 2 and 3 hours . Two hours after injection , participants performed a high-dem and color word Stroop task during functional magnetic resonance imaging .  Blood sample s were performed at baseline and immediately after scanning . Results Typhoid but not placebo injection produced a robust inflammatory response indexed by increased circulating interleukin-6 accompanied by a significant increase in fatigue , confusion , and impaired concentration at 3 hours . Performance of the Stroop task under inflammation activated brain regions encoding representations of internal bodily state . Spatial and temporal characteristics of this response are consistent with interoceptive information flow via afferent autonomic fibers . During performance of this task , activity within interoceptive brain regions also predicted individual differences in inflammation-associated but not placebo-associated fatigue and confusion . Maintenance of cognitive 
    Output:
    
This review supports the view that peripheral inflammation is an etiological process that may influence depression via effects on brain function .