***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 We tested the hypothesis that endothelial dysfunction underlies the association between an acute inflammatory episode and the transiently increased risk of a cardiovascular event by examining the effects of an experimental inflammatory stimulus on endothelium-dependent vasodilation . Methods and Results Salmonella typhi vaccine was used to generate a systemic inflammatory response in healthy volunteers . In 12 subjects , dilatation of the brachial artery to flow and to sublingual nitroglycerin ( NTG ) was recorded ( conduit vessel response ) , and in 6 subjects , venous occlusion plethysmography was used to measure forearm blood flow during intrabrachial infusion of the endothelium-dependent dilators acetylcholine ( ACh ) and bradykinin ( BK ) and the endothelium-independent dilators NTG and verapamil ( resistance vessel response ) . Responses were assessed 16 hours before and 8 and 32 hours after vaccination . Vaccination result ed in elevations in white cell count and serum levels of interleukin-6 and interleukin-1 receptor antagonist . Eight hours after vaccination , resistance vessel responses to BK ( P = 0.0099 ) and ACh ( P = 0.0414 ) were markedly attenuated , and brachial artery flow-mediated dilatation was depressed . Resistance vessel responses to verapamil and NTG were unchanged , as was the conduit vessel response to NTG . Thirty-two hours after vaccination , resistance vessel responses to BK and ACh had returned to normal . Conclusions S typhi vaccine generates a mild inflammatory reaction associated with temporary but profound dysfunction of the arterial endothelium in both resistance and conduit vessels to both physical and pharmacological dilator stimuli . This finding might explain the association between infection and inflammation and the enhanced risk of an acute cardiovascular event Significance Functional MRI ( fMRI ) is 25 years old , yet surprisingly its most common statistical methods have not been vali date d using real data . Here , we used  resting-state fMRI data from 499 healthy controls to conduct 3 million task group analyses . Using this null data with different experimental design s , we estimate the incidence of significant results . In theory , we should find 5 % false positives ( for a significance threshold of 5 % ) , but instead we found that the most common software packages for fMRI analysis ( SPM , FSL , AFNI ) can result in false-positive rates of up to 70 % . These results question the validity of a number of fMRI studies and may have a large impact on the interpretation of weakly significant neuroimaging results . The most widely used task functional magnetic resonance imaging ( fMRI ) analyses use parametric statistical methods that depend on a variety of assumptions . In this work , we use real resting-state data and a total of 3 million r and om task group analyses to compute empirical familywise error rates for the fMRI software packages SPM , FSL , and AFNI , as well as a nonparametric permutation method . For a nominal familywise error rate of 5 % , the parametric statistical methods are shown to be conservative for voxelwise inference and invalid for clusterwise inference . Our results suggest that the principal cause of the invalid cluster inferences is spatial autocorrelation functions that do not follow the assumed Gaussian shape . By comparison , the nonparametric permutation test is found to produce nominal results for voxelwise as well as clusterwise inference . These findings speak to the need of validating the statistical methods being used in the field of neuroimaging 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 BACKGROUND Infectious , autoimmune , and neurodegenerative diseases are associated with profound psychological disturbances . Studies in animals clearly demonstrate that cytokines mediate illness-associated behavioral changes . However , the mechanisms underlying the respective psychological alterations in humans have not been established yet . Therefore , we investigated the effects of low-dose endotoxemia , a well-established and safe model of host-defense activation , on emotional , cognitive , immunological , and endocrine parameters . METHODS In a double-blind , crossover study , 20 healthy male volunteers completed psychological question naires and neuropsychological tests 1 , 3 , and 9 hours after intravenous injection of Salmonella abortus equi endotoxin ( 0.8 ng/kg ) or saline in 2 experimental sessions . Blood sample s were collected hourly , and rectal temperature and heart rate were monitored continuously . RESULTS Endotoxin had no effects on physical sickness symptoms , blood pressure , or heart rate . Endotoxin caused a mild increase in rectal temperature ( 0.5 degrees C ) , and increased the circulating levels of tumor necrosis factor alpha ( TNF-alpha ) , soluble TNF receptors , interleukin (IL)-6 , IL-1 receptor antagonist , and cortisol . After endotoxin administration , the subjects showed a transient significant increase in the levels of anxiety ( effect size [ ES ] = 0.55 ) and depressed mood ( ES = 0.66 ) . Verbal and nonverbal memory functions were significantly decreased ( ES = 0.55 to 0.64 ) . Significant positive correlations were found between cytokine secretion and endotoxin-induced anxiety ( r = 0.49 to r = 0.60 ) , depressed mood ( r = 0.40 to r = 0.75 ) , and decreases in memory performance ( r = 0.46 to r = 0.68 ) . CONCLUSIONS In humans , a mild stimulation of the primary host defense has negative effects on emotional and memory functions , which are probably caused by cytokine release . Hence , cytokines represent a novel target for neuropsychopharmacological research 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 Significance The periaqueductal gray is a brainstem region that is critical for autonomic regulation and for defensive responses ( e.g. , “ fight , ” “ flight , ” “ freeze ” ) . It has been studied extensively in rodents and cats , but less is known about the human periaqueductal gray . The small size and shape of the periaqueductal gray makes it challenging to study using st and ard noninvasive MRI techniques . We used a high-field strength magnet to examine this region at high resolution while participants viewed emotionally aversive or neutral images . Emotion-related functional activity was concentrated in particular subregions and in ways that are consistent with neurobiological observations in nonhuman animals . This study establishes a technique to uncover the functional architecture of the periaqueductal gray in humans . The midbrain periaqueductal gray ( PAG ) region is organized into distinct subregions that coordinate survival-related responses during threat and stress [ B and ler R , Keay KA , Floyd N , Price J ( 2000 ) Brain Res 53 (1):95–104 ] . To examine PAG function in humans , research ers have relied primarily on functional MRI ( fMRI ) , but technological and method ological limitations have prevented research ers from localizing responses to different PAG subregions . We used high-field strength ( 7-T ) fMRI techniques to image the PAG at high resolution ( 0.75 mm isotropic ) , which was critical for dissociating the PAG from the greater signal variability in the aqueduct . Activation while participants were exposed to emotionally aversive images segregated into subregions of the PAG along both dorsal/ventral and rostral/caudal axes . In the rostral PAG , activity was localized to lateral and dorsomedial subregions . In caudal PAG , activity was localized to the ventrolateral region . This shifting pattern of activity from dorsal to ventral PAG along the rostrocaudal axis mirrors structural and functional neurobiological observations in nonhuman animals . Activity in lateral and ventrolateral subregions also grouped with distinct emotional experiences ( e.g. , anger and sadness ) in a factor analysis , suggesting that each subregion participates in distinct functional circuitry . This study establishes the use of high-field strength fMRI as a promising technique for revealing the functional architecture of the PAG . The techniques developed here also may be extended to investigate the functional roles of other brainstem nuclei Objective To investigate whether plasma interleukin- 
    Output:
    
Meta‐ analysis of 24 neuroimaging studies revealed consistently reported regions .
Some regions were specific to study design and task .
Patterns of regions resembled intrinsic brain networks and corticostriatal loops .
Co‐activated regions formed prefrontal‐brainstem and insula‐brainstem ensembles .
Multilevel kernel density analysis of 24 studies ( 37 statistical maps ; 264 coordinates ; 457 participants ) revealed consistent effects in the amygdala , hippocampus , hypothalamus , striatum , insula , midbrain , and brainstem , as well as prefrontal and temporal cortices .
Effects in some regions were specific to particular study design s and tasks .
Spatial pattern analysis revealed significant overlap of reported effects with limbic , default mode , ventral attention , and corticostriatal networks , and co‐activation analyses revealed functional ensembles encompassing the prefrontal cortex , insula , and midbrain/brainstem .