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There is growing concern about a potential decline in empathy among medical students over time. Despite the importance of empathy toward patients in medicine, it remains unclear the nature of the changes in empathy among medical students. Thus, we systematically investigated affective and cognitive empathy for patients among medical students using neuroscientific approach. Nineteen medical students who completed their fifth-year medical curriculum and 23 age- and sex-matched nonmedical students participated in a functional magnetic resonance imaging study. Inside a brain scanner, all participants read empathy-eliciting scenarios while adopting either the patient or doctor perspective. Brain activation and self-reported ratings during the experience of empathy were obtained. Behavioral results indicated that all participants reported greater emotional negativity and empathic concern in association with the patient perspective condition than with the doctor perspective condition. Functional brain imaging results indicated that neural activity in the posterior superior temporal region implicated in goal-relevant attention reorienting was overall increased under the patient perspective than the doctor perspective condition. Relative to nonmedical students, medical students showed decreased activity in the temporoparietal region implicated in mentalizing under the patient perspective versus doctor perspective condition. Notably, this same region showed increased activity under the doctor versus patient condition in medical students relative to nonmedical students. This study is among the first to investigate the neural mechanisms of empathy among medical students and the current findings point to the cognitive empathy system as the locus of the primary brain differences associated with empathy toward patients.

Human fathers often form strong attachments to their infants that contribute to positive developmental outcomes. However, fathers are also the most common perpetrators of infant abuse, and infant crying is a known trigger. Research on parental brain responses to infant crying have typically employed passive listening paradigms. However, parents usually engage with crying infants. Therefore, we examined the neural responses of 20 new fathers to infant cries both while passively listening, and while actively attempting to console the infant by selecting soothing strategies in a video game format. Compared with passive listening, active responding robustly activated brain regions involved in movement, empathy and approach motivation, and deactivated regions involved in stress and anxiety. Fathers reporting more frustration had less activation in basal forebrain areas and in brain areas involved with emotion regulation (e.g., prefrontal cortex and the supplementary motor area). Successful consolation of infant crying activated regions involved in both action-outcome learning and parental caregiving (anterior and posterior cingulate cortex). Overall, results suggest that active responding to infant cries amplifies activation in many brain areas typically activated during passive listening. Additionally, paternal frustration during active responding may involve a combination of low approach motivation and low engagement of emotion regulation.

Mounting evidence has shown disrupted brain network architecture across the psychosis spectrum. However, whether these changes relate to the development of psychosis is unclear. Here, we used graph theoretical analysis to investigate longitudinal changes in resting-state brain networks in samples of 72 subjects at clinical high risk (including 8 cases who converted to full psychosis) and 48 healthy controls drawn from the North American Prodrome Longitudinal Study (NAPLS) consortium. We observed progressive reduction in global efficiency (P = 0.006) and increase in network diversity (P = 0.001) in converters compared with non-converters and controls. More refined analysis separating nodes into nine key brain networks demonstrated that these alterations were primarily driven by progressively diminished local efficiency in the default-mode network (P = 0.004) and progressively enhanced node diversity across all networks (P < 0.05). The change rates of network efficiency and network diversity were significantly correlated (P = 0.003), suggesting these changes may reflect shared underlying neural mechanisms. In addition, change rates of global efficiency and node diversity were significantly correlated with change rate of cortical thinning in the prefrontal cortex in converters (P < 0.03) and could be predicted by visuospatial memory scores at baseline (P < 0.04). These results provide preliminary evidence for longitudinal reconfiguration of resting-state brain networks during psychosis development and suggest that decreased network efficiency, reflecting an increase in path length between nodes, and increased network diversity, reflecting a decrease in the consistency of functional network organization, are implicated in the progression to full psychosis.

Compassion is closely associated with prosocial behavior. Although there is growing interest in developing strategies that cultivate compassion, most available strategies rely on effortful reflective processes. Furthermore, few studies have investigated neurocognitive mechanisms underlying compassion-dependent improvement of prosocial responses. We devised a novel implicit compassion promotion task that operates based on association learning and examined its prosocial effects in two independent experiments. In Experiment 1, healthy adults were assigned to either the compassion or control group. For the intervention task, the compassion group completed word fragments that were consistently related to compassionate responses toward others; in contrast, the control group completed word fragments related to emotionally neutral responses toward others. Following the intervention task, we measured attentional biases to fearful, sad, and happy faces. Prosocial responses were assessed using two measures of helping: the pen-drop test and the helping intentions rating test. In Experiment 2, independent groups of healthy adults completed the same intervention tasks used in Experiment 1. Inside a functional MRI scanner, participants rated empathic care and distress based on either distressful or neutral video clips. Outside the scanner, we assessed the degree of helping intentions toward the victims depicted in the distressful clips. The results of Experiment 1 showed that the compassion promotion task reduced attentional vigilance to fearful faces, which in turn mediated a compassion promotion task-dependent increase in helping intentions. In Experiment 2, relative to the control group, the compassion group showed reduced empathic distress and increased activity in the medial orbitofrontal cortex in response to others' suffering. Furthermore, increased functional connectivity of the medial orbitofrontal and inferior parietal cortex, predicted by reduced empathic distress, explained the increase in helping intentions. These results suggest the potential of implicit compassion promotion intervention to modulate compassion-related and prosocial responses as well as highlight the brain activation and connectivity related to these responses, contributing to our understanding of the neurocognitive mechanisms underlying compassion-dependent prosocial improvement.

Background Subcallosal cingulate deep brain stimulation (SCC DBS) is an experimental treatment for severe depression. Surgery is performed with awake patients and intraoperative stimulation produces acute behavioral responses in select contacts. While there have been reports on the relationship between acute intraoperative behaviors and their relation to the location of the contacts, there are no descriptions of the physiological changes that accompany them. Objective The present study sought to examine these physiological readouts, and their association with the anatomical substrates that generated them. Methods Nine patients with severe, treatment-resistant depression were tested intraoperatively. The stimulation protocol consisted of 12 three-minute, sham-controlled, double-blind trials. Changes in heart rate and skin conductance were recorded during each stimulation cycle. Probabilistic tractography between the stimulated contacts and predefined regions of the mood regulation network was performed. Results Acute intraoperative SCC stimulation produced increases in autonomic sympathetic response that correlated with the salience of the behavioral responses. The autonomic changes were observed within seconds of initiating acute stimulation and prior to verbalization of subjective experiences. The probabilistic tractography analysis suggested that structural connectivity between the stimulated area and the midcingulate cortex is the primary pathway that mediates autonomic responsivity to SCC DBS. Conclusions These findings demonstrate that acute SCC stimulation produces autonomic and behavioral changes in the operating room that are explained by the modulation of networks associated with long term antidepressant response. Intraoperative autonomic recordings paired with careful behavioral observations and precise anatomical mapping aid in the identification and classification of the intraoperative phenomena.

While functional neuroimaging studies typically focus on a particular paradigm to investigate network connectivity, the human brain appears to possess an intrinsic ���trait��� architecture that is independent of any given paradigm. We have previously proposed the use of ���cross-paradigm connectivity (CPC)��� to quantify shared connectivity patterns across multiple paradigms and have demonstrated the utility of such measures in clinical studies. Here, using generalizability theory and connectome fingerprinting, we examined the reliability, stability, and individual identifiability of CPC in a group of highly-sampled healthy traveling subjects who received fMRI scans with a battery of five paradigms across multiple sites and days. Compared with single-paradigm connectivity matrices, the CPC matrices showed higher reliability in connectivity diversity, lower reliability in connectivity strength, higher stability, and higher individual identification accuracy. All of these assessments increased as a function of number of paradigms included in the CPC analysis. In comparisons involving different paradigm combinations and different brain atlases, we observed significantly higher reliability, stability, and identifiability for CPC matrices constructed from task-only data (versus those from both task and rest data), and higher identifiability but lower stability for CPC matrices constructed from the Power atlas (versus those from the AAL atlas). Moreover, we showed that multi-paradigm CPC matrices likely reflect the brain���s ���trait��� structure that cannot be fully achieved from single-paradigm data, even with multiple runs. The present results provide evidence for the feasibility and utility of CPC in the study of functional ���trait��� networks and offer some methodological implications for future CPC studies.

Several studies have shown that direct brain stimulation can enhance memory in humans and animal models. Investigating the neurophysiological changes induced by brain stimulation is an important step towards understanding the neural processes underlying memory function. Furthermore, it paves the way for developing more efficient neuromodulation approaches for memory enhancement. In this study, we utilized a combination of unsupervised and supervised machine learning approaches to investigate how amygdala stimulation modulated hippocampal network activities during the encoding phase. Using a sliding window in time, we estimated the hippocampal dynamic functional network connectivity (dFNC) after stimulation and during sham trials, based on the covariance of local field potential recordings in 4 subregions of the hippocampus. We extracted different network states by combining the dFNC samples from 5 subjects and applying k-means clustering. Next, we used the between-state transition numbers as the latent features to classify between amygdala stimulation and sham trials across all subjects. By training a logistic regression model, we could differentiate stimulated from sham trials with 67% accuracy across all subjects. Using elastic net regularization as a feature selection method, we identified specific patterns of hippocampal network state transition in response to amygdala stimulation. These results offer a new approach to better understanding of the causal relationship between hippocampal network dynamics and memory-enhancing amygdala stimulation.

Recently, as entertainment programs have become more prevalent in the news media, there is a growing need to understand how entertainment appeal influences viewers' sociomoral evaluation of news content. We investigated neural and self-reported moral evaluation of antisocial news content in college students who viewed real-life news reports featuring moral violations inside a functional magnetic resonance imaging (fMRI) brain scanner. Each news report was preceded by a traditional or entertaining style of introduction. The behavioral results showed that antisocial severity was reduced for antisocial news content that was presented following entertaining news introductions versus traditional news introductions. The fMRI results showed that entertainment news introductions tax more cognitive control resources than traditional news introductions during news processing, as indicated by greater activation in the dorsolateral prefrontal region; however, they diminish moral saliency, as suggested by the reduced activation in the medial prefrontal region. We also found that greater dorsolateral prefrontal activation during the early phase of news reports was associated with more lenient moral acceptability ratings in the entertainment condition. Furthermore, reduced functional connectivity of the mentalizing brain network was observed in the entertainment condition when compared with the traditional condition. These results suggest that entertainment appeal may increase resource depletion, diminish moral sensitivity, and reduce functional integration of relevant social information during news processing, thus hindering viewers' moral scrutiny. This novel study contributes to a better understanding of how entertainment features influence viewers’ sociomoral evaluation of news stories.

Understanding the fundamental alterations in brain functioning that lead to psychotic disorders remains a major challenge in clinical neuroscience. In particular, it is unknown whether any state-independent biomarkers can potentially predict the onset of psychosis and distinguish patients from healthy controls, regardless of paradigm. Here, using multi-paradigm fMRI data from the North American Prodrome Longitudinal Study consortium, we show that individuals at clinical high risk for psychosis display an intrinsic “trait-like” abnormality in brain architecture characterized as increased connectivity in the cerebello–thalamo–cortical circuitry, a pattern that is significantly more pronounced among converters compared with non-converters. This alteration is significantly correlated with disorganization symptoms and predictive of time to conversion to psychosis. Moreover, using an independent clinical sample, we demonstrate that this hyperconnectivity pattern is reliably detected and specifically present in patients with schizophrenia. These findings implicate cerebello–thalamo–cortical hyperconnectivity as a robust state-independent neural signature for psychosis prediction and characterization.

In this special section, three target articles present three different perspectives on emotion and how it is implemented in the human brain. Fundamental issues are discussed such as the nature and organization of emotion’s representation in the brain and the best approaches for elucidating emotion’s neural basis. Comments and author replies further discuss these issues and explore their interconnections. A common theme of the target articles and commentaries is that multiple approaches and perspectives must be integrated across all levels of analysis to understand the neural basis of emotion.

While graph theoretical modeling has dramatically advanced our understanding of complex brain systems, the feasibility of aggregating connectomic data in large imaging consortia remains unclear. Here, using a battery of cognitive, emotional and resting fMRI paradigms, we investigated the generalizability of functional connectomic measures across sites and sessions. Our results revealed overall fair to excellent reliability for a majority of measures during both rest and tasks, in particular for those quantifying connectivity strength, network segregation and network integration. Processing schemes such as node definition and global signal regression (GSR) significantly affected resulting reliability, with higher reliability detected for the Power atlas (vs. AAL atlas) and data without GSR. While network diagnostics for default-mode and sensori-motor systems were consistently reliable independently of paradigm, those for higher-order cognitive systems were reliable predominantly when challenged by task. In addition, based on our present sample and after accounting for observed reliability, satisfactory statistical power can be achieved in multisite research with sample size of approximately 250 when the effect size is moderate or larger. Our findings provide empirical evidence for the generalizability of brain functional graphs in large consortia, and encourage the aggregation of connectomic measures using multisite and multisession data.

Hippocampal structure is particularly sensitive to trauma and other stressors. However, previous findings linking hippocampal function with trauma-related psychopathology have been mixed. Heterogeneity in psychological responses to trauma has not been considered with respect to hippocampal function and may contribute to mixed findings. To address these issues, we examined associations between data-driven symptom dimensions and episodic memory formation, a key function of the hippocampus, in a trauma-exposed sample. Symptom dimensions were defined using principal components analysis (PCA) in 3881 trauma-exposed African-American women recruited from primary care waiting rooms of a large urban hospital. Hippocampal and amygdala function were subsequently investigated in an fMRI study of episodic memory formation in a subset of 54 women. Participants viewed scenes with neutral, negative, and positive content during fMRI, and completed a delayed cued recall task. PCA analysis produced five symptom dimensions interpreted as reflecting negative affect, somatic symptoms, re-experiencing, hyper-arousal, and numbing. Re-experiencing was the only symptom type associated with hippocampal function, predicting increased memory encoding-related activation in the hippocampus as well as the amygdala. In contrast, the negative affect component predicted lower amygdala activation for subsequently recalled scenes, and lower functional coupling with other important memory-related regions including the precuneus, inferior frontal gyrus, and occipital cortex. Symptom dimensions were not related to hippocampal volume. The fMRI findings for re-experiencing versus negative affect parallel differences in behavioral memory phenomena in PTSD versus MDD, and highlight a need for more complex models of trauma-related pathology., Highlights • PTSD and MDD are equally likely post trauma, but differ in episodic memory features. • Examined post-trauma stress & depressive symptoms with respect to memory encoding. • Re-experiencing predicted greater hippocampus, amygdala involvement in encoding. • Negative affect predicted less amygdala involvement in encoding. • Negative affect predicted amygdala de-coupling from sensory and elaborative regions.

By implementing a low-temperature plasma pretreatment step in the processing procedure for separating different sulfide mineral mixtures, it has been possible to improve the efficiency of froth flotation. Two powder mixtures consisting of pyrite/chalcopyrite and chalcopyrite/molybdenite were selectively oxidized in an Ar/O2 microwave plasma. The oxide/sulfur mixture obtained was separated by using an oxide collector. The recovery of each mixture component was measured and the results were compared with the untreated material. For separating the pyrite/chalcopyrite mixture, high selectivity could be achieved after plasma pretreatment using the oxide collector Flotinor FS-2. One hundred percent of chalcopyrite could be recovered whilst the recovery rate of pyrite remained below eight percent. Additionally, major improvements could be achieved in the efficiency of separating the chalcopyrite/molybdenite mixtures. In all cases, it was possible to avoid the use of activating and depressant reagents, which successfully demonstrates that the surface oxidation selectivity of the plasma pretreatment ensures high flotation efficiencies by using an oxide collector to separate the sulfide mixture. Additional XPS measurements have been carried out to investigate the oxidation of the sulfide surface.

Autobiographical memory (AM) is a critically important form of memory for life events that undergoes substantial developmental changes from childhood to adulthood. Relatively little is known regarding the functional neural correlates of AM retrieval in children as assessed with fMRI, and how they may differ from adults. We investigated this question with 14 children ages 8-11 years and 14 adults ages 19-30 years, contrasting AM retrieval with semantic memory (SM) retrieval. During scanning, participants were cued by verbal prompts to retrieve previously selected recent AMs or to verify semantic properties of words. As predicted, both groups showed AM retrieval-related increased activation in regions implicated in prior studies, including bilateral hippocampus, and prefrontal, posterior cingulate, and parietal cortices. Adults showed greater activation in the hippocampal/parahippocampal region as well as prefrontal and parietal cortex, relative to children; age-related differences were most prominent in the first 8 sec versus the second 8 sec of AM retrieval and when AM retrieval was contrasted with semantic retrieval. This study is the first to characterise similarities and differences during AM retrieval in children and adults using fMRI.

In adults and children, sleep loss is associated with affective dysregulation and increased responsivity to negative stimuli. Adult functional neuroimaging (fMRI) studies have demonstrated associations between restricted sleep and neural alterations in the amygdala and reward circuitry when viewing emotional picture and face stimuli. Despite this, few studies have examined the associations between short sleep duration and emotional responsivity in typically developing children, and no studies have investigated this relationship using fMRI. The current study examined the relationship between sleep duration and fMRI activation to emotional facial expressions in 15 male children (ages 7-11 years). During fMRI scanning, subjects viewed and made perceptual judgments regarding negative, neutral, and positive emotional faces. Maternal reported child sleep duration was negatively associated with (a) activation in the bilateral amygdala, left insula, and left temporal pole activation when viewing negative (i.e., fearful, disgust) vs. neutral faces, (b) right orbitofrontal and bilateral prefrontal activation when viewing disgust vs. neutral faces, and (c) bilateral orbitofrontal, right anterior cingulate, and left amygdala activation when viewing happy vs. neutral faces. Consistent with our prediction, we also noted that emotion-dependent functional connectivity between the bilateral amygdala and prefrontal cortex, cingulate, fusiform, and occipital cortex was positively associated with sleep duration. Paralleling similar studies in adults, these findings collectively suggest that decreased sleep duration in school-aged children may contribute to enhanced reactivity of brain regions involved in emotion and reward processing, as well as decreased emotion-dependent functional connectivity between the amygdala and brain regions associated with emotion regulation.

The amygdala is a key structure mediating emotional processing. Few studies have used direct electrical stimulation of the amygdala in humans to examine stimulation-elicited physiological and emotional responses, and the nature of such effects remains unclear. Determining the effects of electrical stimulation of the amygdala has important theoretical implications for current discrete and dimensional neurobiological theories of emotion, which differ substantially in their predictions about the emotional effects of such stimulation. To examine the effects of amygdala stimulation on physiological and subjective emotional responses we examined epilepsy patients undergoing intracranial EEG monitoring in which depth electrodes were implanted unilaterally or bilaterally in the amygdala. Nine subjects underwent both sham and acute monopolar electrical stimulation at various parameters in electrode contacts located in amygdala and within lateral temporal cortex control locations. Stimulation was applied at either 50 Hz or 130 Hz, while amplitudes were increased stepwise from 1 to 12 V, with subjects blinded to stimulation condition. Electrodermal activity (EDA), heart rate (HR), and respiratory rate (RR) were simultaneously recorded and subjective emotional response was probed after each stimulation period. Amygdala stimulation (but not lateral control or sham stimulation) elicited immediate and substantial dose-dependent increases in EDA and decelerations of HR, generally without affecting RR. Stimulation elicited subjective emotional responses only rarely, and did not elicit clinical seizures in any subject. These physiological results parallel stimulation findings with animals and are consistent with orienting/defensive responses observed with aversive visual stimuli in humans. In summary, these findings suggest that acute amygdala stimulation in humans can be safe and can reliably elicit changes in emotion physiology without significantly affecting subjective emotional experience, providing a useful approach for investigation of amygdala-mediated modulatory effects on cognition.

Episodic memory for emotional events is typically enhanced and engages additional brain mechanisms relative to episodic memory for neutral events. Many functional magnetic resonance imaging (fMRI) studies have probed the neural basis of this emotional enhancement effect on encoding processes, while relatively fewer studies have examined retrieval. Neuroimaging meta-analysis methods can summarize the brain regions associated with emotional episodic memory that are consistently activated across multiple studies. A previous ALE (Activation Likelihood Estimation) meta-analysis identified consistent activations associated with successful encoding of episodic emotional memory in the amygdala, hippocampus, and in multiple neocortical regions (Murty et al., 2010). However, since that study, meta-analysis methods have improved, and many new relevant neuroimaging studies have been published. Moreover, although qualitative reviews have summarized brain activations related to the successful retrieval of emotional episodic memory, no corresponding quantitative meta-analyses have yet been reported. Here we conducted neuroimaging meta-analyses of successful emotional memory encoding and rretrieval using Seed-based d Mapping (SDM). Relevant neuroimaging studies reporting whole-brain fMRI correlates of successful encoding and retrieval of emotional episodic memory were selected for analysis. For successful emotional memory encoding, SDM activations were found bilaterally in the medial temporal lobe (amygdala, hippocampus, entorhinal cortex, perirhinal cortex, and parahippocampal cortex), bilaterally in visual processing regions (middle temporal, gyrus, fusiform gyrus and occipital cortex) and bilaterally in the temporal pole, orbitofrontal cortex, insula, putamen, and the inferior and middle temporal gyri. In contrast to the prior meta-analysis, SDM activations were not observed in the inferior frontal gyrus or in parietal regions. For successful emotional episodic memory retrieval, SDM activations were observed in the medial temporal lobe (bilateral amygdala, left hippocampus, and left entorhinal cortex and perirhinal cortex), visual processing regions (bilateral occipital cortex and right middle temporal gyrus), prefrontal cortex (bilateral orbitofrontal cortex, bilateral inferior frontal gyrus, bilateral precentral gyrus, left middle frontal gyrus, right frontal pole) and other regions in the left hemisphere including the temporal pole, insula, putamen, angular gyrus, and parietal opercular cortex. Considerable overlap was observed between the encoding and retrieval meta-analysis maps in the medial temporal lobe (bilateral amygdala, left hippocampus, entorhinal, and perirhinal cortex), visual processing regions (bilateral occipital cortex, right middle temporal gyrus), and other regions including the left orbitofrontal cortex, left insula, left putamen, left pallidum, and left temporal pole. The current findings add to current understanding of the role of the amygdala, hippocampus, and neocortical regions in the successful encoding and retrieval of emotional episodic memory, clarify and provide an important summary of the current literature in this area, and have implications for current theories of emotional episodic memory encoding and retrieval.

Memory deficits are a hallmark of psychotic disorders such as schizophrenia. However, whether the neural dysfunction underlying these deficits is present before the onset of illness and potentially predicts conversion to psychosis is unclear. In this study, we investigated brain functional alterations during memory processing in a sample of 155 individuals at clinical high risk (including 18 subjects who later converted to full psychosis) and 108 healthy controls drawn from the second phase of the North American Prodrome Longitudinal Study (NAPLS-2). All participants underwent functional magnetic resonance imaging with a paired-associate memory paradigm at the point of recruitment and were clinically followed up for approximately 2 years. We found that at baseline, subjects at high risk showed significantly higher activation during memory retrieval in the prefrontal, parietal, and bilateral temporal cortices (PFWE < .035). This effect was more pronounced in converters than nonconverters and was particularly manifested in unmedicated subjects (P < .001). The hyperactivation was significantly correlated with retrieval reaction time during scan in converters (P = .009) but not in nonconverters and controls, suggesting an exaggerated retrieval effort. These findings suggest that hyperactivation during memory retrieval may mark processes associated with conversion to psychosis, and such measures have potential as biomarkers for psychosis prediction.

Emotional events are often remembered better than neutral events, a benefit that many studies have hypothesized to depend on the amygdala's interactions with memory systems. These studies have indicated that the amygdala can modulate memory-consolidation processes in other brain regions such as the hippocampus and perirhinal cortex. Indeed, rodent studies have demonstrated that direct activation of the amygdala can enhance memory consolidation even during nonemotional events. However, the premise that the amygdala causally enhances declarative memory has not been directly tested in humans. Here we tested whether brief electrical stimulation to the amygdala could enhance declarative memory for specific images of neutral objects without eliciting a subjective emotional response. Fourteen epilepsy patients undergoing monitoring of seizures via intracranial depth electrodes viewed a series of neutral object images, half of which were immediately followed by brief, low-amplitude electrical stimulation to the amygdala. Amygdala stimulation elicited no subjective emotional response but led to reliably improved memory compared with control images when patients were given a recognition-memory test the next day. Neuronal oscillations in the amygdala, hippocampus, and perirhinal cortex during this next-day memory test indicated that a neural correlate of the memory enhancement was increased theta and gamma oscillatory interactions between these regions, consistent with the idea that the amygdala prioritizes consolidation by engaging other memory regions. These results show that the amygdala can initiate endogenous memory prioritization processes in the absence of emotional input, addressing a fundamental question and opening a path to future therapies.

In this functional neuroimaging study, we investigated neural activations during the process of learning to gain monetary rewards and to avoid monetary loss, and how these activations are modulated by individual differences in reward and punishment sensitivity. Healthy young volunteers performed a reinforcement learning task where they chose one of two fractal stimuli associated with monetary gain (reward trials) or avoidance of monetary loss (avoidance trials). Trait sensitivity to reward and punishment was assessed using the behavioral inhibition/activation scales (BIS/BAS). Functional neuroimaging results showed activation of the striatum during the anticipation and reception periods of reward trials. During avoidance trials, activation of the dorsal striatum and prefrontal regions was found. As expected, individual differences in reward sensitivity were positively associated with activation in the left and right ventral striatum during reward reception. Individual differences in sensitivity to punishment were negatively associated with activation in the left dorsal striatum during avoidance anticipation and also with activation in the right lateral orbitofrontal cortex during receiving monetary loss. These results suggest that learning to attain reward and learning to avoid loss are dependent on separable sets of neural regions whose activity is modulated by trait sensitivity to reward or punishment.

Recent evidence suggests that emotions have a distributed neural representation, which has significant implications for our understanding of the mechanisms underlying emotion regulation and dysregulation as well as the potential targets available for neuromodulation-based emotion therapeutics. This work adds to this evidence by testing the distribution of neural representations underlying the affective dimensions of valence and arousal using representational models that vary in both the degree and the nature of their distribution. We used multi-voxel pattern classification (MVPC) to identify whole-brain patterns of functional magnetic resonance imaging (fMRI)-derived neural activations that reliably predicted dimensional properties of affect (valence and arousal) for visual stimuli viewed by a normative sample (n=32) of demographically diverse, healthy adults. Inter-subject leave-one-out cross-validation showed whole-brain MVPC significantly predicted (p

While graph theoretical modeling has dramatically advanced our understanding of complex brain systems, the feasibility of aggregating brain graphic data in large imaging consortia remains unclear. Here, using a battery of cognitive, emotional and resting fMRI paradigms, we investigated the reproducibility of functional connectomic measures across multiple sites and sessions. Our results revealed overall fair to excellent reliability for a majority of measures during both rest and tasks, in particular for those quantifying connectivity strength, network segregation and network integration. Higher reliabilities were detected for cognitive tasks (vs rest) and for weighted networks (vs binary networks). While network diagnostics for several primary functional systems were consistently reliable independently of paradigm, those for cognitive-emotional systems were reliable predominantly when challenged by task. Different data aggregation approaches yielded significantly different reliability. In addition, we showed that after accounting for observed reliability, satisfactory statistical power can be achieved in the multisite context with a total sample size of approximately 250 when the effect size is at least moderate. Our findings provide direct evidence for the generalizability of brain graphs for both resting and task paradigms in large consortia and encourage the use of multisite, multisession scans to enhance power for human functional connectomic studies.

Autobiographical memory (AM), episodic memory for life events, involves the orchestration of multiple dynamic cognitive processes, including memory access and subsequent elaboration. Previous neuroimaging studies have contrasted memory access and elaboration processes in terms of regional brain activation and connectivity within large, multi-region networks. Although interactions between key memory-related regions such as the hippocampus and prefrontal cortex (PFC) have been shown to play an important role in AM retrieval, it remains unclear how such connectivity between specific, individual regions involved in AM retrieval changes dynamically across the retrieval process and how these changes relate to broader memory networks throughout the whole brain. The present functional magnetic resonance imaging (fMRI) study sought to assess the specific changes in interregional connectivity patterns across the AM retrieval processes to understand network level mechanisms of AM retrieval and further test current theoretical accounts of dynamic AM retrieval processes. We predicted that dynamic connections would reflect two hypothesized memory processes, with initial processes reflecting memory-access related connections between regions such as the anterior hippocampal and ventrolateral PFC regions, and later processes reflecting elaboration-related connections between dorsolateral frontal working memory regions and parietal-occipital visual imagery regions. One week prior to fMRI scanning, fifteen healthy adult participants generated AMs using personally selected cue words. During scanning, participants were cued to retrieve the AMs. We used a moving-window functional connectivity analysis and graph theoretic measures to examine dynamic changes in the strength and centrality of connectivity among regions involved in AM retrieval. Consistent with predictions, early, access-related processing primarily involved a ventral frontal to temporal-parietal network associated with strategic search and initial reactivation of specific episodic memory traces. In addition, neural network connectivity during later retrieval processes was associated with strong connections between occipital-parietal regions and dorsal fronto-parietal regions associated with mental imagery, reliving, and working memory processes. Taken together, these current findings help refine and extend dynamic neural processing models of AM retrieval by providing evidence of the specific connections throughout the brain that change in their synchrony with one another as processing progresses from access of specific event memories to elaborative reliving of the past event.

Multi-site neuroimaging studies offer an efficient means to study brain functioning in large samples of individuals with rare conditions; however, they present new challenges given that aggregating data across sites introduces additional variability into measures of interest. Assessing the reliability of brain activation across study sites and comparing statistical methods for pooling functional data are critical to ensuring the validity of aggregating data across sites. The current study used two samples of healthy individuals to assess the feasibility and reliability of aggregating multi-site functional magnetic resonance imaging (fMRI) data from a Sternberg-style verbal working memory task. Participants were recruited as part of the North American Prodrome Longitudinal Study (NAPLS), which comprises eight fMRI scanning sites across the United States and Canada. In the first study sample (n= 8), one participant from each home site traveled to each of the sites and was scanned while completing the task on two consecutive days. Reliability was examined using generalizability theory. Results indicated that blood oxygen level-dependent (BOLD) signal was reproducible across sites and was highly reliable, or generalizable, across scanning sites and testing days for core working memory ROIs (generalizability ICCs. = 0.81 for left dorsolateral prefrontal cortex, 0.95 for left superior parietal cortex). In the second study sample (n= 154), two statistical methods for aggregating fMRI data across sites for all healthy individuals recruited as control participants in the NAPLS study were compared. Control participants were scanned on one occasion at the site from which they were recruited. Results from the image-based meta-analysis (IBMA) method and mixed effects model with site covariance method both showed robust activation in expected regions (i.e. dorsolateral prefrontal cortex, anterior cingulate cortex, supplementary motor cortex, superior parietal cortex, inferior temporal cortex, cerebellum, thalamus, basal ganglia). Quantification of the similarity of group maps from these methods confirmed a very high (96%) degree of spatial overlap in results. Thus, brain activation during working memory function was reliable across the NAPLS sites and both the IBMA and mixed effects model with site covariance methods appear to be valid approaches for aggregating data across sites. These findings indicate that multi-site functional neuroimaging can offer a reliable means to increase power and generalizability of results when investigating brain function in rare populations and support the multi-site investigation of working memory function in the NAPLS study, in particular. © 2014 Elsevier Inc.

Prenatal cocaine exposure (PCE) is associated with arousal dysregulation, and alterations of amygdala activity in response to emotional arousal have previously been reported. However, voluntary regulation of emotional affect, enabling appropriate neural response to different streams of stimuli, must also engage prefrontal regions, yet the impact of PCE on these prefrontal mechanisms has not been investigated. Recent neuroimaging studies have shown the involvement of ventral prefrontal cortex (vPFC) in the modulation of amygdala reactivity and the mediation of effective emotional regulation. Based on these findings, using functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), the present study compared functional activations of the vPFC as well as its structural connectivity with the amygdala between groups of PCE and control adolescents. In a working memory task with emotional distracters, the PCE adolescents exhibited less capability of increasing their vPFC activation in response to increased memory load, which corresponded with their less suppressed amygdala activation. Reduced structural connectivity between the vPFC and the amygdala was also observed from DTI measurement in the PCE group. In addition, correlations between amygdala activation and (i) vPFC activation, as well as (ii) amygdala-vPFC structural connectivity, were observed in the control but not in the PCE group. These data complement previous findings of the impact of PCE on the activity of the amygdala and extend our understanding of the neurobiological mechanisms underlying the effect of PCE on arousal dysregulation reported in human and animal studies.

A longstanding controversy in the field of emotion research has concerned whether emotions are better conceptualized in terms of discrete categories, such as fear and anger, or underlying dimensions, such as arousal and valence. In the domain of neuroimaging studies of emotion, the debate has centered on whether neuroimaging findings support characteristic and discriminable neural signatures for basic emotions or whether they favor competing dimensional and psychological construction accounts. This review highlights recent neuroimaging findings in this controversy, assesses what they have contributed to this debate, and offers some preliminary conclusions. Namely, although neuroimaging studies have identified consistent neural correlates associated with basic emotions and other emotion models, they have ruled out simple one-to-one mappings between emotions and brain regions, pointing to the need for more complex, network-based representations of emotion.

Prenatal cocaine exposure (PCE) is associated with attention/arousal dysregulation and possible inefficiencies in some cognitive functions. However, the neurobiological bases of these teratogenic effects have not been well characterized. Because activities in the default mode network (DMN) reflect intrinsic brain functions that are closely associated with arousal regulation and cognition, alterations in the DMN could underlie cognitive effects related to PCE. With resting‐state and task activation functional magnetic resonance imaging (fMRI), this study investigated the possible PCE related changes in functional brain connectivity and brain activation in the DMN. In the resting state, the PCE group was found to have stronger functional connectivity in the DMN, as compared to the nonexposed controls. During a working memory task with emotional distracters, the PCE group exhibited less deactivation in the DMN and their fMRI signal was more increased by emotional arousal. These data revealed additional neural effects related to PCE, and consistent with previous findings, indicate that PCE may affect behavior and functioning by increasing baseline arousal and altering the excitatory/inhibitory balancing mechanisms involved in cognitive resource allocation. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.

Glucose enhances memory in a variety of species. In humans, glucose administration enhances episodic memory encoding, although little is known regarding the neural mechanisms underlying these effects. Here we examined whether elevating blood glucose would enhance functional MRI (fMRI) activation and connectivity in brain regions associated with episodic memory encoding and whether these effects would differ depending on the emotional valence of the material. We used a double-blind, within-participants, crossover design in which either glucose (50 g) or a saccharin placebo were administered before scanning, on days approximately 1 week apart. We scanned healthy young male participants with fMRI as they viewed emotionally arousing negative pictures and emotionally neutral pictures, intermixed with baseline fixation. Free recall was tested at 5 min after scanning and again after 1 day. Glucose administration increased activation in brain regions associated with successful episodic memory encoding. Glucose also enhanced activation in regions whose activity was correlated with subsequent successful recall, including the hippocampus, prefrontal cortex, and other regions, and these effects differed for negative vs. neutral stimuli. Finally, glucose substantially increased functional connectivity between the hippocampus and amygdala and a network of regions previously implicated in successful episodic memory encoding. These findings fit with evidence from nonhuman animals indicating glucose modulates memory by selectively enhancing neural activity in brain regions engaged during memory tasks. Our results highlight the modulatory effects of glucose and the importance of examining both regional changes in activity and functional connectivity to fully characterize the effects of glucose on brain function and memory.

What is the basic structure of emotional experience and how is it represented in the human brain? One highly influential theory, discrete basic emotions, proposes a limited set of basic emotions such as happiness and fear, which are characterized by unique physiological and neural profiles. Although many studies using diverse methods have linked particular brain structures with specific basic emotions, evidence from individual neuroimaging studies and from neuroimaging meta-analyses has been inconclusive regarding whether basic emotions are associated with both consistent and discriminable regional brain activations. We revisited this question, using activation likelihood estimation (ALE), which allows spatially sensitive, voxelwise statistical comparison of results from multiple studies. In addition, we examined substantially more studies than previous meta-analyses. The ALE meta-analysis yielded results consistent with basic emotion theory. Each of the emotions examined (fear, anger, disgust, sadness, and happiness) was characterized by consistent neural correlates across studies, as defined by reliable correlations with regional brain activations. In addition, the activation patterns associated with each emotion were discrete (discriminable from the other emotions in pairwise contrasts) and overlapped substantially with structure–function correspondences identified using other approaches, providing converging evidence that discrete basic emotions have consistent and discriminable neural correlates. Complementing prior studies that have demonstrated neural correlates for the affective dimensions of arousal and valence, the current meta-analysis results indicate that the key elements of basic emotion views are reflected in neural correlates identified by neuroimaging studies.

Functional neuroimaging has identified brain regions associated with voluntary regulation of emotion, including the prefrontal cortex and amygdala. The neural mechanisms underlying individual differences in emotion regulation have not been extensively studied. We investigated the neural correlates of neuroticism and psychopathic personality traits in the context of an emotion regulation task. Results showed that amygdala activity elicited by unpleasant pictures was positively correlated with neuroticism and negatively correlated with a specific psychopathic trait related to emotional underreactivity. During active attempts to decrease emotional responses to unpleasant pictures, superior and ventrolateral prefrontal activity was positively correlated with psychopathy, but not with neuroticism. In contrast, dorsolateral prefrontal activity was positively correlated with neuroticism, but not with psychopathy. Psychopathy was also negatively correlated with medial prefrontal activity in response to pictures depicting moral violations, suggesting reduced emotional responses to moral stimuli in individuals with high levels of psychopathic traits. These results demonstrate dissociable influences of different personality traits on neural activity associated with responses to emotional stimuli and on the recruitment of regulation-related brain activity during the active down-regulation of responses to negative emotional stimuli. These results have implications for the etiology of trait-based psychopathology involving emotional dysregulation.

The ability to cope adaptively with emotional events by volitionally altering one's emotional reactions is important for psychological and physical health as well as social interaction. Cognitive regulation of emotional responses to aversive events engages prefrontal regions that modulate activity in emotion-processing regions such as the amygdala. However, the neural correlates of the regulation of positive emotions remain largely unexplored. We used event-related functional magnetic resonance imaging to examine the neural correlates of cognitively increasing and decreasing emotional reactions to positive and negative stimuli. Participants viewed negative, positive, and neutral pictures while attempting to increase, decrease, or not alter their emotional reactions. Subjective reactions were assessed via on-line ratings. Consistent with previous studies, increasing negative and positive emotion engaged primarily left-lateralized prefrontal regions, whereas decreasing emotion activated bilateral prefrontal regions. Different activations unique to increasing versus decreasing emotion were observed for positive and negative stimuli: Unique increase-related activations were observed only for positive stimuli, whereas unique decrease-related activations were observed only for negative stimuli. Regulation also modulated activity in the amygdala, a key emotion-processing region. Regulation effects on amygdala activity were larger for positive than for negative stimuli, potentially reflecting a greater malleability of positive emotional reactions. Increasing and decreasing positive and negative emotion can thus increase and decrease subjective reactions and associated amygdala activity in line with regulatory goals, and is associated with different patterns of prefrontal activation as a function of emotional valence and regulatory goal.

Multisite neuroimaging studies can facilitate the investigation of brain-related changes in many contexts, including patient groups that are relatively rare in the general population. Though multisite studies have characterized the reliability of brain activation during working memory and motor functional magnetic resonance imaging tasks, emotion processing tasks, pertinent to many clinical populations, remain less explored. A traveling participants study was conducted with eight healthy volunteers scanned twice on consecutive days at each of the eight North American Longitudinal Prodrome Study sites. Tests derived from generalizability theory showed excellent reliability in the amygdala ( Eρ2 = 0.82), inferior frontal gyrus (IFG; Eρ2 = 0.83), anterior cingulate cortex (ACC; Eρ2 = 0.76), insula ( Eρ2 = 0.85), and fusiform gyrus ( Eρ2 = 0.91) for maximum activation and fair to excellent reliability in the amygdala ( Eρ2 = 0.44), IFG ( Eρ2 = 0.48), ACC ( Eρ2 = 0.55), insula ( Eρ2 = 0.42), and fusiform gyrus ( Eρ2 = 0.83) for mean activation across sites and test days. For the amygdala, habituation ( Eρ2 = 0.71) was more stable than mean activation. In a second investigation, data from 111 healthy individuals across sites were aggregated in a voxelwise, quantitative meta-analysis. When compared with a mixed effects model controlling for site, both approaches identified robust activation in regions consistent with expected results based on prior single-site research. Overall, regions central to emotion processing showed strong reliability in the traveling participants study and robust activation in the aggregation study. These results support the reliability of blood oxygen level-dependent signal in emotion processing areas across different sites and scanners and may inform future efforts to increase efficiency and enhance knowledge of rare conditions in the population through multisite neuroimaging paradigms.

Research on political judgment and decision-making has converged with decades of research in clinical and social psychology suggesting the ubiquity of emotion-biased motivated reasoning. Motivated reasoning is a form of implicit emotion regulation in which the brain converges on judgments that minimize negative and maximize positive affect states associated with threat to or attainment of motives. To what extent motivated reasoning engages neural circuits involved in “cold” reasoning and conscious emotion regulation (e.g., suppression) is, however, unknown. We used functional neuroimaging to study the neural responses of 30 committed partisans during the U.S. Presidential election of 2004. We presented subjects with reasoning tasks involving judgments about information threatening to their own candidate, the opposing candidate, or neutral control targets. Motivated reasoning was associated with activations of the ventromedial prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex, insular cortex, and lateral orbital cortex. As predicted, motivated reasoning was not associated with neural activity in regions previously linked to cold reasoning tasks and conscious (explicit) emotion regulation. The findings provide the first neuroimaging evidence for phenomena variously described as motivated reasoning, implicit emotion regulation, and psychological defense. They suggest that motivated reasoning is qualitatively distinct from reasoning when people do not have a strong emotional stake in the conclusions reached.

Background Functional magnetic resonance imaging offers a compelling, new perspective on altered brain function but is sparsely used in studies of anesthetic effect. To examine effects on verbal memory encoding, the authors imaged human brain response to auditory word stimulation using functional magnetic resonance imaging at different concentrations of an agent not previously studied, and tested memory after recovery. Methods Six male volunteers were studied breathing 0.0, 2.0, and 1.0% end-tidal sevoflurane (awake, deep, and light states, respectively) via laryngeal mask. In each condition, they heard 15 two-syllable English nouns via closed headphones. Each word was repeated 15 times (1/s), followed by 15 s of rest. Blood oxygenation level-dependent brain activations during blocks of stimulation versus rest were assessed with a 3-T Siemens Trio scanner and a 20-voxel spatial extent threshold. Memory was tested approximately 1.5 h after recovery with an auditory recognition task (chance performance = 33% correct). Results Scans showed widespread activations (P < 0.005, uncorrected) in the awake state, including bilateral superior temporal, frontal, and parietal cortex, right occipital cortex, bilateral thalamus, striatum, hippocampus, and cerebellum; more limited activations in the light state (bilateral superior temporal gyrus, right thalamus, bilateral parietal cortex, left frontal cortex, and right occipital cortex); and no significant auditory-related activation in the deep state. During recognition testing, subjects correctly selected 77 +/- 12% of words presented while they were awake as "old," versus 32 +/- 15 and 42 +/- 8% (P < 0.01) correct for the light and deep stages, respectively. Conclusions Sevoflurane induces dose-dependent suppression of auditory blood oxygenation level-dependent signals, which likely limits the ability of words to be processed during anesthesia and compromises memory.

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Recent functional brain imaging studies of the neurobiology of emotion have investigated how individual differences among subjects modulate neural responses during emotion processing. Differences in personality, dispositional affect, biological sex, and genotype can all substantially modulate the neural bases of emotion processing in prefrontal, limbic, and other brain regions, across a variety of domains including emotional reactions, emotional memory, and emotion perception. Analysis of individual differences provides a new window into the neurobiology of emotion processing that complements traditional approaches.

Men are generally more interested in and responsive to visual sexually arousing stimuli than are women. Here we used functional magnetic resonance imaging (fMRI) to show that the amygdala and hypothalamus are more strongly activated in men than in women when viewing identical sexual stimuli. This was true even when women reported greater arousal. Sex differences were specific to the sexual nature of the stimuli, were restricted primarily to limbic regions, and were larger in the left amygdala than the right amygdala. Men and women showed similar activation patterns across multiple brain regions, including ventral striatal regions involved in reward. Our findings indicate that the amygdala mediates sex differences in responsiveness to appetitive and biologically salient stimuli; the human amygdala may also mediate the reportedly greater role of visual stimuli in male sexual behavior, paralleling prior animal findings.

In Vytal and Hamann (2010) we reported a neuroimaging meta-analysis that found that basic emotions can be distinguished by their brain activation correlates, in marked contrast to Lindquist et al.'s conclusions in the target article. Here, I discuss implications of these findings for understanding emotion, outline limitations of using meta-analyses and neuroimaging as the sole basis for deciding between emotion views, and suggest that these views are essentially compatible and could be adapted and combined into an integrated emotion framework.

Considerable evidence indicates that the amygdala plays a critical role in negative, aversive human emotions. Although researchers have speculated that the amygdala plays a role in positive emotion, little relevant evidence exists. We examined the neural correlates of positive and negative emotion using positron emission tomography (PET), focusing on the amygdala. Participants viewed positive and negative photographs, as well as interesting and uninteresting neutral photographs, during PET scanning. The left amygdala and ventromedial prefrontal cortex were activated during positive emotion, and bilateral amygdala activation occurred during negative emotion. High-interest, unusual photographs also elicited left-amygdala activation, a finding consistent with suggestions that the amygdala is involved in vigilance reactions to associatively ambiguous stimuli. The current results constitute the first neuroimaging evidence for a role of the amygdala in positive emotional reactions elicited by visual stimuli. Although the amygdala appears to play a more extensive role in negative emotion, it is involved in positive emotion as well.

Classical conditioning of the fear response is a basic form of nondeclarative (nonconscious) memory that mediates both normal and pathological responses to aversive stimuli. Because fear conditioning critically depends on the amygdala, a medial temporal lobe structure that frequently undergoes significant pathological changes early in the course of Alzheimer's disease (AD), we hypothesized that fear conditioning would be impaired in patients with mild to moderate AD. We examined simple classical fear conditioning in a group of 10 patients with probable AD and 14 demographically matched, neurologically intact elderly controls. During conditioning, one stimulus (e.g. a green rectangle, the conditioned stimulus (CS+)), was paired with an aversive stimulus (a loud noise, the unconditioned stimulus (US)) using a partial reinforcement conditioning schedule. The opponent color (e.g. red rectangle), the CS-, was never paired with the US. The elderly controls acquired robust fear responses as demonstrated by their differential skin-conductance responses to the CS+ and CS-. In contrast, the AD group showed a marked impairment in conditioning, failing to exhibit significant conditioned fear responses. This failure to acquire conditioned responses could not be attributed to diminished responding by patients, relative to controls, to the aversive US. The results indicate that fear conditioning, an amygdala-dependent form of memory, is impaired in AD. These findings complement previous reports of impairments in declarative emotional memory in AD by demonstrating that a basic form of nondeclarative emotional memory is also impaired in AD.

Summary A new neuropsychological study of a rare patient provides novel evidence that amygdala lesions can virtually abolish the experience of fear, illuminating neurobiological mechanisms of fear experience.