抑郁症患者对正性面部表情功能识别

目的：利用任务态功能核磁共振成像技术,初步探讨抗抑郁治疗对正性情绪识别脑区功能的影响。方法：检测19例抑郁症患者治疗前和治疗10周后在识别正性及中性面部表情视频时的激活脑区,并与19例匹配的健康者对照比较。结果：与正常对照组相比,治疗前抑郁症患者左右颞上回（BA39）、左后扣带回（BA23）、右后扣带回（BA30）、左丘脑、右岛叶（BA13）等脑区激活显著降低;治疗后患者左颞上回（BA39）、右颞上回（BA22）、左颞中回（BA37）、左右海马旁回（BA30）、右后扣带回（BA29）、右梭状回（BA36）、左额中回（BA8）、右额下回（BA47）、左顶下小叶（BA40）、右岛叶（BA13）等脑区激活较治疗前增强;但与正常组相比,左颞上回（BA22）、左额中回（BA10）、左梭状回（BA20）、左楔叶（BA19）、右顶上小叶（BA7）、右岛叶（BA13）等脑区激活仍存在一定程度的降低。结论：经抗抑郁治疗,抑郁症患者正性情绪识别脑区功能较治疗前有所改善,但与正常对照组相比,仍存在一定程度的功能损害。进一步证实了积极有效的抗抑郁治疗能够部分逆转正性情绪相关脑区损害。     

Brain mechanisms of expectation associated with insula and amygdala response to aversive taste: implications for placebo

The experience of aversion is shaped by multiple physiological and psychological factors including one's expectations. Recent work has shown that expectancy manipulation can alter perceptions of aversive events and concomitant brain activation. Accruing evidence indicates a primary role of altered expectancies in the placebo effect. Here, we probed the mechanism by which expectation attenuates sensory taste transmission by examining how brain areas activated by misleading information during an expectancy period modulate insula and amygdala activation to a highly aversive bitter taste. In a rapid event-related fMRI design, we showed that activations in the rostral anterior cingulate cortex (rACC), orbitofrontal cortex (OFC), and dorsolateral prefrontal cortex to a misleading cue that the taste would be mildly aversive predicted decreases in insula and amygdala activation to the highly aversive taste. OFC and rACC activation to the misleading cue were also associated with less aversive ratings of that taste. Additional analyses revealed consistent results demonstrating functional connectivity among the OFC, rACC, and insula. Altering expectancies of upcoming aversive events are shown here to depend on robust functional associations among brain regions implicated in prior work on the placebo effect.     

抑郁症患者情绪图片刺激早期低频脑磁图研究

目的：探讨抑郁症患者给予视觉情绪图片刺激早期0～100ms、100～200ms、200～300ms3个时段8～30Hz的神经磁场激活特征。方法：8例抑郁症患者及12例健康右利手对照者,在给予国际情绪图片库（IAPS）正性、中性、负性情绪图片刺激同时记录脑磁图信号,使用SPM8b软件进行数据分析：设两样本t检验P〈0.01（未校正）和K值≥10个体素范围为差异有统计学意义。结果：与对照组相比,抑郁组在正性情绪图片刺激下,100～200ms内的左侧额下回,右侧的终板旁回、额内侧回、海马回激活增强。在中性情绪图片刺激下,抑郁组在0～100ms的右侧豆状核、岛叶、额上回,左内侧额叶,100～200ms内的右侧岛叶、豆状核壳核及屏状核,左侧额下回、额上回、颞上回,200～300ms内的右侧岛叶、豆状核、尾状核体激活增强。负性情绪图片刺激下抑郁组在0～100ms内的右侧颞上回、岛叶、尾状核头部、额中下回激活增强,100～200ms内的右侧额中回、尾状核体,200～300ms内右额下回激活增强。此外还比较一致的发现抑郁组在楔前叶、后扣带回等顶叶脑区激活降低。结论：抑郁个体起注意调节功能的顶叶脑区如楔前叶功能不足,对视觉皮质向前部脑区情绪信息颞叶底部传递通路抑制不足,腹侧前额皮质、岛叶过度的激活,可能是抑郁症的一个发病基础。     

Neural correlates of prior expectations of motion in the lateral intraparietal and middle temporal areas

Successful decision making involves combining observations of the external world with prior knowledge. Recent studies suggest that neural activity in macaque lateral intraparietal area (LIP) provides a useful window into this process. This study examines how rapidly changing prior knowledge about an upcoming sensory stimulus influences the computations that convert sensory signals into plans for action. Two monkeys performed a cued direction discrimination task, in which an arrow cue presented at the start of each trial communicated the prior probability of the direction of stimulus motion. We hypothesized that the cue would either shift the initial level of LIP activity before sensory evidence arrived, or it would scale sensory responses according to the prior probability of each stimulus, manifesting as a change in slope of LIP firing rates. Neural recordings demonstrated a clear shift in the activity level of LIP neurons following the arrow cue, which persisted into the presentation of the motion stimulus. No significant change in slope of responses was observed, suggesting that sensory gain was not strongly modulated. To confirm the latter observation, middle temporal area (MT) neurons were recorded during a version of the cued direction discrimination task, and we found no change in MT responses resulting from the presentation of the directional cue. These results suggest that information about an immediately upcoming stimulus does not scale the sensory response, but rather changes the amount of evidence that must be accumulated to reach a decision in areas that are involved in planning action.     

Predictive top-down integration of prior knowledge during speech perception

A striking feature of human perception is that our subjective experience depends not only on sensory information from the environment but also on our prior knowledge or expectations. The precise mechanisms by which sensory information and prior knowledge are integrated remain unclear, with longstanding disagreement concerning whether integration is strictly feedforward or whether higher-level knowledge influences sensory processing through feedback connections. Here we used concurrent EEG and MEG recordings to determine how sensory information and prior knowledge are integrated in the brain during speech perception. We manipulated listeners' prior knowledge of speech content by presenting matching, mismatching, or neutral written text before a degraded (noise-vocoded) spoken word. When speech conformed to prior knowledge, subjective perceptual clarity was enhanced. This enhancement in clarity was associated with a spatiotemporal profile of brain activity uniquely consistent with a feedback process: activity in the inferior frontal gyrus was modulated by prior knowledge before activity in lower-level sensory regions of the superior temporal gyrus. In parallel, we parametrically varied the level of speech degradation, and therefore the amount of sensory detail, so that changes in neural responses attributable to sensory information and prior knowledge could be directly compared. Although sensory detail and prior knowledge both enhanced speech clarity, they had an opposite influence on the evoked response in the superior temporal gyrus. We argue that these data are best explained within the framework of predictive coding in which sensory activity is compared with top-down predictions and only unexplained activity propagated through the cortical hierarchy.     

Neural correlates of personally familiar faces: parents, partner and own faces

Investigations of the neural correlates of face recognition have typically used old/new paradigms where subjects learn to recognize new faces or identify famous faces. Familiar faces, however, include one's own face, partner's and parents' faces. Using event-related fMRI, we examined the neural correlates of these personally familiar faces. Ten participants were presented with photographs of own, partner, parents, famous and unfamiliar faces and responded to a distinct target. Whole brain, two regions of interest (fusiform gyrus and cingulate gyrus), and multiple linear regression analyses were conducted. Compared with baseline, all familiar faces activated the fusiform gyrus; own faces also activated occipital regions and the precuneus; partner faces activated similar areas, but in addition, the parahippocampal gyrus, middle superior temporal gyri and middle frontal gyrus. Compared with unfamiliar faces, only personally familiar faces activated the cingulate gyrus and the extent of activation varied with face category. Partner faces also activated the insula, amygdala and thalamus. Regions of interest analyses and laterality indices showed anatomical distinctions of processing the personally familiar faces within the fusiform and cingulate gyri. Famous faces were right lateralized whereas personally familiar faces, particularly partner and own faces, elicited bilateral activations. Regression analyses show experiential predictors modulated with neural activity related to own and partner faces. Thus, personally familiar faces activated the core visual areas and extended frontal regions, related to semantic and person knowledge and the extent and areas of activation varied with face type.     

Analysis of Altered Baseline Brain Activity in Drug-Naive Adult Patients with Social Anxiety Disorder Using Resting-State Functional MRI

Objective

We hypothesize that the amplitude of low-frequency fluctuations (ALFF) is involved in the altered regional baseline brain function in social anxiety disorder (SAD). The aim of the study was to analyze the altered baseline brain activity in drug-naive adult patients with SAD.

Methods

We investigated spontaneous and baseline brain activities by obtaining the resting-state functional magnetic resonance imaging data of 20 drug-naïve adult SAD patients and 19 healthy controls. Voxels were used to analyze the ALFF values using one- and two-sample t-tests. A post-hoc correlation of clinical symptoms was also performed.

Results

Our findings show decreased ALFF in the bilateral insula, left medial superior frontal gyrus, left precuneus, left middle temporal gyrus, right middle temporal pole, and left fusiform gyrus of the SAD group. The SAD patients exhibited significantly increased ALFF in the right inferior temporal gyrus, right middle temporal gyrus, bilateral middle occipital gyrus, orbital superior frontal gyrus, right fusiform gyrus, right medial superior frontal gyrus, and left parahippocampal gyrus. Moreover, the Liebowitz Social Anxiety Scale results for the SAD patients were positively correlated with the mean Z values of the right middle occipital and right inferior occipital but showed a negative correlation with the mean Z values of the right superior temporal gyrus and right medial superior frontal gyrus.

Conclusion

These results of the altered regional baseline brain function in SAD suggest that the regions with abnormal spontaneous activities are involved in the underlying pathophysiology of SAD patients.     

Different neural pathways to negative affect in youth with pediatric bipolar disorder and severe mood dysregulation

Questions persist regarding the presentation of bipolar disorder (BD) in youth and the nosological significance of irritability. Of particular interest is whether severe mood dysregulation (SMD), characterized by severe non-episodic irritability, hyper-arousal, and hyper-reactivity to negative emotional stimuli, is a developmental presentation of pediatric BD and, therefore, whether the two conditions are pathophysiologically similar. We administered the affective Posner paradigm, an attentional task with a condition involving blocked goal attainment via rigged feedback. The sample included 60 youth (20 BD, 20 SMD, and 20 controls) ages 8–17. Magnetoencephalography (MEG) examined neuronal activity (4–50 Hz) following negative versus positive feedback. We also examined reaction time (RT), response accuracy, and self-reported affect. Both BD and SMD youth reported being less happy than controls during the rigged condition. Also, SMD youth reported greater arousal following negative feedback than both BD and controls, and they responded to negative feedback with significantly greater activation of the anterior cingulate cortex (ACC) and medial frontal gyrus (MFG) than controls. Compared to SMD and controls, BD youth displayed greater superior frontal gyrus (SFG) activation and decreased insula activation following negative feedback. Data suggest a greater negative affective response to blocked goal attainment in SMD versus BD and control youth. This occurs in tandem with hyperactivation of medial frontal regions in SMD youth, while BD youth show dysfunction in the SFG and insula. Data add to a growing empirical base that differentiates pediatric BD and SMD and begin to elucidate potential neural mechanisms of irritability.     

Identification of human gustatory cortex by activation likelihood estimation

Over the last two decades, neuroimaging methods have identified a variety of taste-responsive brain regions. Their precise location, however, remains in dispute. For example, taste stimulation activates areas throughout the insula and overlying operculum, but identification of subregions has been inconsistent. Furthermore, literature reviews and summaries of gustatory brain activations tend to reiterate rather than resolve this ambiguity. Here, we used a new meta-analytic method [activation likelihood estimation (ALE)] to obtain a probability map of the location of gustatory brain activation across 15 studies. The map of activation likelihood values can also serve as a source of independent coordinates for future region-of-interest analyses. We observed significant cortical activation probabilities in: bilateral anterior insula and overlying frontal operculum, bilateral mid dorsal insula and overlying Rolandic operculum, and bilateral posterior insula/parietal operculum/postcentral gyrus, left lateral orbitofrontal cortex (OFC), right medial OFC, pregenual anterior cingulate cortex (prACC) and right mediodorsal thalamus. This analysis confirms the involvement of multiple cortical areas within insula and overlying operculum in gustatory processing and provides a functional "taste map" which can be used as an inclusive mask in the data analyses of future studies. In light of this new analysis, we discuss human central processing of gustatory stimuli and identify topics where increased research effort is warranted.     

Sex differences in neural responses to stress and alcohol context cues

Stress and alcohol context cues are each associated with alcohol-related behaviors, yet neural responses underlying these processes remain unclear. This study investigated the neural correlates of stress and alcohol context cue experiences and examined sex differences in these responses. Using functional magnetic resonance imaging, brain responses were examined while 43 right-handed, socially drinking, healthy individuals (23 females) engaged in brief guided imagery of personalized stress, alcohol-cue, and neutral-relaxing scenarios. Stress and alcohol-cue exposure increased activity in the cortico-limbic-striatal circuit (P < 0.01, corrected), encompassing the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), left anterior insula, striatum, and visuomotor regions (parietal and occipital lobe, and cerebellum). Activity in the left dorsal striatum increased during stress, while bilateral ventral striatum activity was evident during alcohol-cue exposure. Men displayed greater stress-related activations in the mPFC, rostral ACC, posterior insula, amygdala, and hippocampus than women, whereas women showed greater alcohol-cue-related activity in the superior and middle frontal gyrus (SFG/MFG) than men. Stress-induced anxiety was positively associated with activity in emotion-modulation regions, including the medial OFC, ventromedial PFC, left superior-mPFC, and rostral ACC in men, but in women with activation in the SFG/MFG, regions involved in cognitive processing. Alcohol craving was significantly associated with the striatum (encompassing dorsal, and ventral) in men, supporting its involvement in alcohol "urge" in healthy men. These results indicate sex differences in neural processing of stress and alcohol-cue experiences and have implications for sex-specific vulnerabilities to stress- and alcohol-related psychiatric disorders.     

Neural correlates of informational cascades: brain mechanisms of social influence on belief updating

Informational cascades can occur when rationally acting individuals decide independently of their private information and follow the decisions of preceding decision-makers. In the process of updating beliefs, differences in the weighting of private and publicly available social information may modulate the probability that a cascade starts in a decisive way. By using functional magnetic resonance imaging, we examined neural activity while participants updated their beliefs based on the decisions of two fictitious stock market traders and their own private information, which led to a final decision of buying one of two stocks. Computational modeling of the behavioral data showed that a majority of participants overweighted private information. Overweighting was negatively correlated with the probability of starting an informational cascade in trials especially prone to conformity. Belief updating by private information was related to activity in the inferior frontal gyrus/anterior insula, the dorsolateral prefrontal cortex and the parietal cortex; the more a participant overweighted private information, the higher the activity in the inferior frontal gyrus/anterior insula and the lower in the parietal-temporal cortex. This study explores the neural correlates of overweighting of private information, which underlies the tendency to start an informational cascade.     

Using subjective expectations to model the neural underpinnings of proactive inhibition

Proactive inhibition – the anticipation of having to stop a response – relies on objective information contained in cue‐related contingencies in the environment, as well as on the subjective interpretation derived from these cues. To date, most studies of brain areas underlying proactive inhibition have exclusively considered the objective predictive value of environmental cues, by varying the probability of stop‐signals. However, by only taking into account the effect of different cues on brain activation, the subjective component of how cues affect behavior is ignored. We used a modified stop‐signal response task that includes a measurement for subjective expectation, to investigate the effect of this subjective interpretation. After presenting a cue indicating the probability that a stop‐signal will occur, subjects were asked whether they expected a stop‐signal to occur. Furthermore, response time was used to retrospectively model brain activation related to stop‐expectation. We found more activation during the cue period for 50% stop‐signal probability, when contrasting with 0%, in the mid and inferior frontal gyrus, inferior parietal lobe and putamen. When contrasting expected vs. unexpected trials, we found modest effects in the mid frontal gyrus, parietal, and occipital areas. With our third contrast, we modeled brain activation during the cue with trial‐by‐trial variances in response times. This yielded activation in the putamen, inferior parietal lobe, and mid frontal gyrus. Our study is the first to use the behavioral effects of proactive inhibition to identify the underlying brain regions, by employing an unbiased task‐design that temporally separates cue and response.     

Listening under difficult conditions: An activation likelihood estimation meta‐analysis

The brain networks supporting speech identification and comprehension under difficult listening conditions are not well specified. The networks hypothesized to underlie effortful listening include regions responsible for executive control. We conducted meta‐analyses of auditory neuroimaging studies to determine whether a common activation pattern of the frontal lobe supports effortful listening under different speech manipulations. Fifty‐three functional neuroimaging studies investigating speech perception were divided into three independent Activation Likelihood Estimate analyses based on the type of speech manipulation paradigm used: Speech‐in‐noise (SIN, 16 studies, involving 224 participants); spectrally degraded speech using filtering techniques (15 studies involving 270 participants); and linguistic complexity (i.e., levels of syntactic, lexical and semantic intricacy/density, 22 studies, involving 348 participants). Meta‐analysis of the SIN studies revealed higher effort was associated with activation in left inferior frontal gyrus (IFG), left inferior parietal lobule, and right insula. Studies using spectrally degraded speech demonstrated increased activation of the insula bilaterally and the left superior temporal gyrus (STG). Studies manipulating linguistic complexity showed activation in the left IFG, right middle frontal gyrus, left middle temporal gyrus and bilateral STG. Planned contrasts revealed left IFG activation in linguistic complexity studies, which differed from activation patterns observed in SIN or spectral degradation studies. Although there were no significant overlap in prefrontal activation across these three speech manipulation paradigms, SIN and spectral degradation showed overlapping regions in left and right insula. These findings provide evidence that there is regional specialization within the left IFG and differential executive networks underlie effortful listening.     

Individual differences in smoking-related cue reactivity in smokers: an eye-tracking and fMRI study

Measures of cue reactivity provide a means of studying and understanding addictive behavior. We wanted to examine the relationship between different cue reactivity measures, such as attentional bias and subjective craving, and functional brain responses toward smoking-related cues in smokers. We used eye-tracking measurements, a questionnaire for smoking urges-brief and functional magnetic resonance imaging to assess the responses to smoking-related and neutral visual cues from 25 male smokers after 36 h of smoking abstinence. Regression analyses were conducted to determine the correlation between cue-evoked brain responses and the attentional bias to smoking-related cues. The eye gaze dwell time percentage was longer in response to smoking-related cues than neutral cues, indicating significant differences in attentional bias towards smoking-related cues. The attentional bias to smoking-related cues correlated with subjective craving ratings (r=0.660, p<0.001). The dorsolateral prefrontal cortex, the putamen, the posterior cingulate cortex and the primary motor cortex were associated with the attentional bias to smoking-related cues, whereas the orbitofrontal cortex, the insula and the superior temporal gyrus were associated with smoking-related cue-induced craving and smoking urges. These results suggest that attentional mechanisms in combination with motivational and reward-related mechanisms play a role in smoking-related cue reactivity. We confirmed a positive correlation between different smoking-related cue reactivities, such as attentional bias and subjective craving, and functional brain responses in various individuals. Further studies in this field might contribute to a better individualized understanding of addictive behavior.     

Spatio-temporal dynamics of brain mechanisms in aversive classical conditioning: high-density event-related potential and brain electrical tomography analyses

Social cognition, including complex social judgments and attitudes, is shaped by individual learning experiences, where affect often plays a critical role. Aversive classical conditioning-a form of associative learning involving a relationship between a neutral event (conditioned stimulus, CS) and an aversive event (unconditioned stimulus, US)-represents a well-controlled paradigm to study how the acquisition of socially relevant knowledge influences behavior and the brain. Unraveling the temporal unfolding of brain mechanisms involved appears critical for an initial understanding about how social cognition operates. Here, 128-channel ERPs were recorded in 50 subjects during the acquisition phase of a differential aversive classical conditioning paradigm. The CS+ (two fearful faces) were paired 50% of the time with an aversive noise (CS upward arrow + /Paired), whereas in the remaining 50% they were not (CS upward arrow + /Unpaired); the CS- (two different fearful faces) were never paired with the noise. Scalp ERP analyses revealed differences between CS upward arrow + /Unpaired and CS- as early as approximately 120 ms post-stimulus. Tomographic source localization analyses revealed early activation modulated by the CS+ in the ventral visual pathway (e.g. fusiform gyrus, approximately 120 ms), right middle frontal gyrus (approximately 176 ms), and precuneus (approximately 240 ms). At approximately 120 ms, the CS- elicited increased activation in the left insula and left middle frontal gyrus. These findings not only confirm a critical role of prefrontal, insular, and precuneus regions in aversive conditioning, but they also suggest that biologically and socially salient information modulates activation at early stages of the information processing flow, and thus furnish initial insight about how affect and social judgments operate.     

fMRI auditory language differences between dyslexic and able reading children

During fMRI, dyslexic and control boys completed auditory language tasks (judging whether pairs of real and/or pseudo words rhymed or were real words) in 30 s 'on' conditions alternating with a 30 s 'off' condition (judging whether tone pairs were same). During phonological judgment, dyslexics had more activity than controls in right than left inferior temporal gyrus and in left precentral gyrus. During lexical judgment, dyslexics were less active than controls in bilateral middle frontal gyrus and more active than controls in left orbital frontal cortex. Individual dyslexics were reliably less active than controls in left insula and left inferior temporal gyrus. Dyslexic and control children differ in brain activation during auditory language processing skills that do not require reading.     

抑郁症患者静息状态的功能磁共振成像研究

目的 了解在静息状态下抑郁症患者脑区的局部一致性特点.方法 采用功能磁共振成像(fMRI)技术,检测静息状态下27例抑郁症患者(患者组)和性别、年龄、受教育程度均与患者相匹配的27名正常人(对照组)的脑功能活动,并对两组进行比较.利用局部一致性方法 分析fMRI数据,用SPM2软件进行配对t检验(P＜0.005).结果 与对照组相比,患者组双侧额中回、右额下回、右颞上回、左前扣带回、右后扣带回、右岛叶、双侧豆状核、双侧屏状核、左尾状核局部一致性显著增高(P＜0.005,未校正,体素值＞10);未显示脑区有明显的局部一致性减低.结论 抑郁症患者神经环路脑区局部在静息状态下具有很高的一致性,其局部一致性的增高可能参与了抑郁症的代偿机制.     

Behavioral and genetic correlates of the neural response to infant crying among human fathers

Although evolution has shaped human infant crying and the corresponding response from caregivers, there is marked variation in paternal involvement and caretaking behavior, highlighting the importance of understanding the neurobiology supporting optimal paternal responses to cries. We explored the neural response to infant cries in fathers of children aged 1–2, and its relationship with hormone levels, variation in the androgen receptor (AR) gene, parental attitudes and parental behavior. Although number of AR CAG trinucleotide repeats was positively correlated with neural activity in brain regions important for empathy (anterior insula and inferior frontal gyrus), restrictive attitudes were inversely correlated with neural activity in these regions and with regions involved with emotion regulation (orbitofrontal cortex). Anterior insula activity had a non-linear relationship with paternal caregiving, such that fathers with intermediate activation were most involved. These results suggest that restrictive attitudes may be associated with decreased empathy and emotion regulation in response to a child in distress, and that moderate anterior insula activity reflects an optimal level of arousal that supports engaged fathering.     

The role of the lateral prefrontal cortex and anterior cingulate in stimulus-response association reversals

Many complex tasks require us to flexibly switch between behavioral rules, associations, and strategies. The prefrontal cerebral cortex is thought to be critical to the performance of such behaviors, although the relative contribution of different components of this structure and associated subcortical regions are not fully understood. We used functional magnetic resonance imaging to measure brain activity during a simple task which required repeated reversals of a rule linking a colored cue and a left/right motor response. Each trial comprised three discrete events separated by variable delay periods. A colored cue instructed which response was to be executed, followed by a go signal which told the subject to execute the response and a feedback instruction which indicated whether to "hold" or "flip" the rule linking the colored cue and response. The design allowed us to determine which brain regions were recruited by the specific demands of preparing a rule contingent motor response, executing such a response, evaluating the significance of the feedback, and reconfiguring stimulus-response (SR) associations. The results indicate that an increase in neural activity occurs within the anterior cingulate gyrus under conditions in which SR associations are labile. In contrast, lateral frontal regions are activated by unlikely/unexpected perceptual events regardless of their significance for behavior. A network of subcortical structures, including the mediodorsal nucleus of the thalamus and striatum were the only regions showing activity that was exclusively correlated with the neurocognitive demands of reversing SR associations. We conclude that lateral frontal regions act to evaluate the behavioral significance of perceptual events, whereas medial frontal-thalamic circuits are involved in monitoring and reconfiguring SR associations when necessary.     

Pain anticipation recruits the mesolimbic system and differentially modulates subsequent recognition memory

The ability to encode information into long‐term memory is not a passive process but can be influenced by motivational factors. While the mesolimbic system has long been associated with reward‐driven memory enhancement, the precise neurobiology of processing aversive events and their effects on declarative learning remain unclear. To address this issue, human subjects encoded a series of scene images, which was combined with cues predicting an aversive electric shock with different probabilities (0.2, 0.5, 0.8). Subsequently, recognition memory for the scenes was tested using a remember/know procedure. In a behavioral experiment, shock probability had linear effects on familiarity and inverted u‐shaped effects on recollection. While the behavioral effect was absent in experiment 2 (fMRI), at the neural level encoding‐related activity in the hippocampus mimicked the recollection specific quadratic effect, whereas activity in the anterior parahippocampal gyrus mirrored the familiarity specific linear relationship that was evident in experiment 1. Importantly, the probability of upcoming shocks was linearly coded in the substantia nigra / ventral tegmental area, and pain associated brain regions, such as the insula, responded to shock delivery. Our results demonstrate that anticipating primary aversive events recruits the human mesolimbic system and differentially modulates declarative memory functions via medial temporal lobe structures. Hum Brain Mapp 35:4594–4606, 2014. © 2014 Wiley Periodicals, Inc.