***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: In contrast to the wealth of data describing the neural mechanisms underlying classical conditioning , we know remarkably little about the mechanisms involved in acquisition of explicit contingency awareness . Subjects variably acquire contingency awareness in classical conditioning paradigms , in which they are able to describe the temporal relationship between a conditioned cue and its outcome . Previous studies have implicated the hippocampus and prefrontal cortex in the acquisition of explicit knowledge , although their specific roles remain unclear . We used functional magnetic resonance imaging to track the trial-by-trial acquisition of explicit knowledge in a concurrent trace and delay conditioning paradigm . We show that activity in bilateral middle frontal gyrus and parahippocampal gyrus correlates with the accuracy of explicit contingency awareness on each trial . In contrast , amygdala activation correlates with conditioned responses indexed by skin conductance responses ( SCRs ) . These results demonstrate that brain regions known to be involved in other aspects of learning and memory also play a specific role , reflecting on each trial the acquisition and representation of contingency awareness Anticipation of pain is a complex state that may influence the perception of subsequent noxious stimuli . We used functional magnetic resonance imaging ( fMRI ) to study changes of activity of cortical nociceptive networks in healthy volunteers while they expected the somatosensory stimulation of one foot , which might be painful ( subcutaneous injection of ascorbic acid ) or not . Subjects had no previous experience of the noxious stimulus .  Mean fMRI signal intensity increased over baseline values during anticipation and during actual stimulation in the putative foot representation area of the contralateral primary somatosensory cortex ( SI ) . Mean fMRI signals decreased during anticipation in other portions of the contralateral and ipsilateral SI , as well as in the anteroventral cingulate cortex . The activity of cortical clusters whose signal time courses showed positive or negative correlations with the individual psychophysical pain intensity curve was also significantly affected during the waiting period . Positively correlated clusters were found in the contralateral SI and bilaterally in the anterior cingulate , anterior insula , and medial prefrontal cortex . Negatively correlated clusters were found in the anteroventral cingulate bilaterally . In all of these areas , changes during anticipation were of the same sign as those observed during pain but less intense ( ∼30–40 % as large as peak changes during actual noxious stimulation ) . These results provide evidence for top-down mechanisms , triggered by anticipation , modulating cortical systems involved in sensory and affective components of pain even in the absence of actual noxious input and suggest that the activity of cortical nociceptive networks may be directly influenced by cognitive factors Transient reductions in serotonin levels during tryptophan depletion ( TD ) are thought to impair reward processing in healthy volunteers , while another facet of the serotonergic system , the serotonin transporter ( 5-HTTLPR ) short allele polymorphism , is implicated in augmented processing of aversive stimuli . We examined the impact and interactions of TD and the serotonin promoter polymorphism genotype on reward and punishment via two forms of instrumental learning : passive avoidance and response reversal . In this study , healthy volunteers ( n=35 ) underwent rapid TD or control procedures and genotyping ( n=26 ) of the 5-HTTLPR for long and short allele variants . In the passive avoidance task , tryptophan-depleted volunteers failed to respond sufficiently to rewarded stimuli compared to the control group . Additionally , long allele homozygous individuals ( n=11 ) were slower to learn to avoid punished stimuli compared to short allele carriers ( n=15 ) . TD alone did not produce measurable deficits in probabilistic response reversal errors . However , a significant drug group by genotype interaction was found indicating that in comparison to short allele carriers , tryptophan-depleted individuals homozygous for the long allele failed to appropriately use punishment information to guide responding . These findings extend prior reports of impaired reward processing in TD to include instrumental learning . Furthermore , they demonstrate behavioral differences in responses to punishing stimuli between long allele homozygotes and short allele carriers when serotonin levels are acutely reduced Laterality of changes in regional cerebral blood flow ( rCBF ) during classical conditioning of the human eyeblink response was studied and changes in rCBF were correlated with conditioned responses . In 10 normal volunteers , rCBF was mapped with positron emission tomography and H2(15)O during pairings of a binaural tone conditioned stimulus and an air puff unconditioned stimulus to the left eye . Control conditions consisted of explicitly unpaired presentations of the tone and air puff before ( control ) and after ( extinction ) pairings . During pairings , rCBF increased significantly in right primary auditory cortex ( contralateral to air puff ) and decreased significantly in left and right cerebellar cortex . There were also increases in rCBF in right auditory association cortex and left temporoccipital cortex . Decreases in rCBF were noted bilaterally in the temporal poles and in the left prefrontal cortex . Positive correlations between changes in rCBF and percent conditioned responses were located in middle cerebellum , right superior temporal cortex , left dorsal premotor cortex , right middle cingulate , and right superior temporal cortex . There were negative correlations in left inferior prefrontal cortex , left middle prefrontal cortex , and right inferior parietal cortex . The data replicate our previous findings of lateralized changes in rCBF following presentations of a binaural tone and air puff to the right eye and indicate that there are pairing-specific changes in primary auditory cortex and cerebellum that are not unique to the left or right hemisphere but are a function of the side of training . The commonalities as well as differences in regional involvement in our present and previous experiment as well as in other eyeblink studies illustrate the advantage of functional neuroimaging to quantify different strategies used by the brain to perform seemingly similar functions . Indeed , the data support the notion that learning-related changes can be detected in a number of specific , but not necessarily invariant , brain regions , and that the involvement of any one region is dependent on the characteristics of the particular learning situation The experience of pain is subjectively different from the fear and anxiety caused by threats of pain . Functional magnetic resonance imaging in healthy humans was applied to dissociate neural activation patterns associated with acute pain and its anticipation . Expectation of pain activated sites within the medial frontal lobe , insular cortex , and cerebellum distinct from , but close to , locations mediating pain experience itself . Anticipation of pain can in its own right cause mood changes and behavioral adaptations that exacerbate the suffering experienced by chronic pain patients . Selective manipulations of activity at these sites may offer therapeutic possibilities for treating chronic pain Only recently have neuroimaging studies moved away from describing regions activated by noxious stimuli and started to disentangle subprocesses within the nociceptive system . One approach to characterizing the role of individual regions is to record brain responses evoked by different stimulus intensities . We used such a parametric single-trial functional MRI design in combination with a thulium : yttrium-aluminium-granate infrared laser and investigated pain , stimulus intensity and stimulus awareness ( i.e. pain-unrelated ) responses in nine healthy volunteers . Four stimulus intensities , ranging from warm to painful ( 300 - 600 mJ ) , were applied in a r and omized order and rated by the subjects on a five-point scale ( P0 - 4 ) . Regions in the dorsolateral prefrontal cortex and the intraparietal sulcus differentiated between P0 ( not perceived ) and P1 but exhibited no further signal increase with P2 , and were related to stimulus perception and subsequent cognitive processing . Signal changes in the primary somatosensory cortex discriminated between non-painful trials ( P0 and P1 ) , linking this region to basic sensory processing . Pain-related regions in the secondary somatosensory cortex and insular cortex showed a response that did not distinguish between innocuous trials ( P0 and P1 ) but showed a positive linear relationship with signal changes for painful trials ( P2 - 4 ) . This was also true for the amygdala , with the exception that , in P0 trials in which the stimulus was not perceived ( i.e. ' uncertain ' trials ) , the evoked signal changes were as great as in P3 trials , indicating that the amygdala is involved in coding ' uncertainty ' , as has been suggested previously in relation to classical conditioning Previous functional neuroimaging studies have characterized brain systems mediating associative learning using classical delay conditioning paradigms . In the present study , we used event-related functional magnetic resonance imaging to characterize neuronal responses mediating aversive trace conditioning . During conditioning , neutral auditory tones were paired with an aversive sound [ unconditioned stimulus ( US ) ] . We compared neuronal responses evoked by conditioned ( CS+ ) and nonconditioned ( CS− ) stimuli in which a 50 % pairing of CS+ and the US enabled us to limit our analysis to responses evoked by the CS+ alone . Differential responses  ( CS+ vs CS− ) , related to conditioning , were observed in anterior cingulate and anterior insula , regions previously implicated in delay fear conditioning . Differential responses were also observed in the amygdala and hippocampus that were best characterized with a time × stimulus interaction , indicating rapid adaptation of CS+-specific responses in medial temporal lobe . These results are strikingly similar to those obtained with a previous delay conditioning experiment and are in accord with a preferential role for medial temporal lobe structures during the early phase of conditioning . However , an additional activation of anterior hippocampus in the present experiment supports a view that its role in trace conditioning is to maintain a memory trace between the offset of the CS+ and the delayed onset of the US to enable associative learning in trace conditioning Our subjective sensory experiences are thought to be heavily shaped by interactions between expectations and incoming sensory information . However , the neural mechanisms supporting these interactions remain poorly understood . By using combined psychophysical and functional MRI techniques , brain activation related to the intensity of expected pain and experienced pain was characterized . As the magnitude of expected pain increased , activation increased in the thalamus , insula , prefrontal cortex , anterior cingulate cortex ( ACC ) and other brain regions . Pain-intensity-related brain activation was identified in a widely distributed set of brain regions but overlapped partially with expectation-related activation in regions , including the anterior insula and ACC . When expected pain was manipulated , expectations of decreased pain powerfully reduced both the subjective experience of pain and activation of pain-related brain regions , such as the primary somatosensory cortex , insular cortex , and ACC . These results confirm that a mental representation of an impending sensory event can significantly shape neural processes that underlie the formulation of the actual sensory experience and provide insight as to how positive expectations diminish the severity of chronic disease states The neural mechanisms underlying the persistence and plasticity of human emotional learning are unknown . Here we describe dissociable neural responses in amygdala and orbitofrontal cortex during acquisition and reversal of discriminatory fear conditioning . During acquisition , increased responses in bilateral amygdala were elicited by a face stimulus ( A = CS+ ) predictive of an aversive noise compared to another nonpredictive face ( B = CS- ) . With subsequent reversal of the conditioning contingency , face B ( new CS+ ) elicited enhanced responses in right orbitofrontal cortex , while face A ( old CS+ ) continued to evoke increased responses in right ventral amygdala . Thus , while orbitofrontal cortex exhibited rapid reversal of acquired fear responses , ventral amygdala showed a persistent , nonreversing " memory " for previous fear-related stimulus associations Echoplanar functional magnetic resonance imaging ( fMRI ) was used in normal human subjects to investigate the role of the amygdala in conditioned fear acquisition and extinction . A simple discrimination procedure was employed in which activation to a visual cue predicting shock ( CS+ ) was compared with activation to another cue presented alone ( CS- ) . CS+ and CS- trial types were intermixed in a pseudor and om order . Functional images were acquired with an asymmetric spin echo pulse sequence from three coronal slices centered on the amygdala . Activation of the amygdala/periamygdaloid cortex was observed during conditioned fear acquisition and extinction . The extent of activation during acquisition was significantly correlated with autonomic indices of conditioning in individual subjects . Consistent with a recent electrophysiological recording study in the rat ( Quirk et al. , 1997 ) , the profile of the amygdala response was temporally grade d , although this dynamic was only statistically reliable during extinction . These results provide further evidence for the conservation of amygdala function across species and implicate an amygdalar contribution to both acquisition and extinction processes during associative emotional learning tasks Previous functional magnetic resonance imaging ( fMRI ) studies have characterized brain systems involved in conditional response acquisition during Pavlovian fear conditioning . However , the functional neuroanatomy underlying the extinction of human conditional fear remains largely undetermined . The present study used fMRI to examine brain activity during acquisition and extinction of fear conditioning . During the acquisition phase , participants were either exposed to light ( CS ) presentations that signaled a brief electrical stimulation ( paired group ) or received light presentations that did not serve as a warning signal ( control group ) . During the extinction phase , half of the paired group subjects continued to receive the same treatment , whereas the remainder received light alone . Control subjects also received light alone during the extinction phase . Changes in metabolic activity within the amygdala and hippocampus support the involvement of these regions in each of the procedural phases of fear conditioning . Hippocampal activity developed during acquisition of the fear response . Amygdala activity increased whenever experimental contingencies were altered , suggesting that this region is involved in processing changes in environmental relationships . The present data show learning-related amygdala and hippocampal activity during human Pavlovian fear conditioning and suggest that the amygdala is particularly important for forming new associations as relationships between stimuli change The amygdala plays a central role in the acquisition and expression of fear memories . Laboratory animal studies indicate that the amygdala both receives sensory information and produces learned behavioral and autonomic fear responses 
    Output:
    
A network consisting of fear-related brain areas , such as amygdala , insula , and anterior cingulate cortex , is activated independently of design parameters .
However , some neuroimaging studies do not report these findings in the presence of method ological heterogeneities .
Furthermore , other brain areas are differentially activated , depending on specific design parameters .
These include stronger hippocampal activation in trace conditioning and tactile stimulation .
Furthermore , tactile unconditioned stimuli enhance activation of pain related , motor , and somatosensory areas .