Neurocognitive mechanisms underlying improvement of prosocial responses by a novel implicit compassion promotion task.

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.

Differences in empathy toward patients between medical and nonmedical students: an fMRI study.

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.

Direct electrical stimulation of the amygdala enhances declarative memory in humans.

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.

The neural correlates of paternal consoling behavior and frustration in response to infant crying.

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.

Toward Leveraging Human Connectomic Data in Large Consortia: Generalizability of fMRI-Based Brain Graphs Across Sites, Sessions, and Paradigms.

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.

Multisite reliability of MR-based functional connectivity.

Recent years have witnessed an increasing number of multisite MRI functional connectivity (fcMRI) studies. While multisite studies provide an efficient way to accelerate data collection and increase sample sizes, especially for rare clinical populations, any effects of site or MRI scanner could ultimately limit power and weaken results. Little data exists on the stability of functional connectivity measurements across sites and sessions. In this study, we assess the influence of site and session on resting state functional connectivity measurements in a healthy cohort of traveling subjects (8 subjects scanned twice at each of 8 sites) scanned as part of the North American Prodrome Longitudinal Study (NAPLS). Reliability was investigated in three types of connectivity analyses: (1) seed-based connectivity with posterior cingulate cortex (PCC), right motor cortex (RMC), and left thalamus (LT) as seeds; (2) the intrinsic connectivity distribution (ICD), a voxel-wise connectivity measure; and (3) matrix connectivity, a whole-brain, atlas-based approach to assessing connectivity between nodes. Contributions to variability in connectivity due to subject, site, and day-of-scan were quantified and used to assess between-session (test-retest) reliability in accordance with Generalizability Theory. Overall, no major site, scanner manufacturer, or day-of-scan effects were found for the univariate connectivity analyses; instead, subject effects dominated relative to the other measured factors. However, summaries of voxel-wise connectivity were found to be sensitive to site and scanner manufacturer effects. For all connectivity measures, although subject variance was three times the site variance, the residual represented 60-80% of the variance, indicating that connectivity differed greatly from scan to scan independent of any of the measured factors (i.e., subject, site, and day-of-scan). Thus, for a single 5min scan, reliability across connectivity measures was poor (ICC=0.07-0.17), but increased with increasing scan duration (ICC=0.21-0.36 at 25min). The limited effects of site and scanner manufacturer support the use of multisite studies, such as NAPLS, as a viable means of collecting data on rare populations and increasing power in univariate functional connectivity studies. However, the results indicate that aggregation of fcMRI data across longer scan durations is necessary to increase the reliability of connectivity estimates at the single-subject level.

Neural correlates of autobiographical memory retrieval in children and adults.

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.

Reliability of an fMRI paradigm for emotional processing in a multisite longitudinal study.

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.

Reliability of functional magnetic resonance imaging activation during working memory in a multi-site study: analysis from the North American Prodrome Longitudinal Study.

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.

Brain responses to sexual images in 46,XY women with complete androgen insensitivity syndrome are female-typical.

Androgens, estrogens, and sex chromosomes are the major influences guiding sex differences in brain development, yet their relative roles and importance remain unclear. Individuals with complete androgen insensitivity syndrome (CAIS) offer a unique opportunity to address these issues. Although women with CAIS have a Y chromosome, testes, and produce male-typical levels of androgens, they lack functional androgen receptors preventing responding to their androgens. Thus, they develop a female physical phenotype, are reared as girls, and develop into women. Because sexually differentiated brain development in primates is determined primarily by androgens, but may be affected by sex chromosome complement, it is currently unknown whether brain structure and function in women with CAIS is more like that of women or men. In the first functional neuroimaging study of (46,XY) women with CAIS, typical (46,XX) women, and typical (46, XY) men, we found that men showed greater amygdala activation to sexual images than did either typical women or women with CAIS. Typical women and women with CAIS had highly similar patterns of brain activation, indicating that a Y chromosome is insufficient for male-typical human brain responses. Because women with CAIS produce male-typical or elevated levels of testosterone which is aromatized to estradiol these results rule out aromatization of testosterone to estradiol as a determinate of sex differences in patterns of brain activation to sexual images. We cannot, however, rule out an effect of social experience on the brain responses of women with CAIS as all were raised as girls.

FMRI correlates of autobiographical memory: Comparing silent retrieval with narrated retrieval.

FMRI studies of autobiographical memory (AM) retrieval typically ask subjects to retrieve memories silently to avoid speech-related motion artifacts. Recently, some fMRI studies have started to use overt (spoken) retrieval to probe moment-to-moment retrieved content. However, the extent to which the overt retrieval method alters fMRI activations during retrieval is unknown. Here we examined this question by eliciting unrehearsed AMs during fMRI scanning either overtly or silently, in the same subjects, in different runs. Differences between retrieval modality (silent vs. narrated) included greater activation for silent retrieval in the anterior hippocampus, left angular gyrus, PCC, and superior PFC, and greater activation for narrated retrieval in speech production regions, posterior hippocampus, and the DLPFC. To probe temporal dynamics, we divided each retrieval period into an initial search phase and a later elaboration phase. The activations during the search and elaboration phases were broadly similar regardless of modality, and these activations were in line with previous fMRI studies of AM temporal dynamics employing silent retrieval. For both retrieval modalities, search activated the hippocampus, mPFC, ACC, and PCC, and elaboration activated the left DLPFC and middle temporal gyri. To examine content-specific reactivation during retrieval, the timecourse of narrated memory content was transcribed and modeled. We observed dynamic activation associated with object content in the lateral occipital complex, and activation associated with scene content in the retrosplenial cortex. The current findings show that both silent and narrated AMs activate a broadly similar memory network, with some key differences, and add to current knowledge regarding the content-specific dynamics of AM retrieval. However, these observed differences between retrieval modality suggest that studies using overt retrieval should carefully consider this method's possible effects on cognitive and neural processing.

Neural correlates of autobiographical memory retrieval: An SDM neuroimaging meta-analysis.

Autobiographical memory (AM) is a type of episodic memory that involves the recollection and re-experiencing of personal life events. AM retrieval is a complex process requiring the coordination of multiple memory processes across the brain. Important questions remain regarding the degree to which specific brain regions are consistently recruited during AM retrieval and the influence of methodological factors such as type of AM retrieval task and control task. Neuroimaging meta-analyses can summarize the brain regions associated with AM retrieval, addressing these questions by revealing consistent findings across multiple studies. We used a coordinate-based neuroimaging meta-analysis method, seed-based d mapping (SDM), to assess the largest set of neuroimaging studies of AM retrieval to date. An important advantage of SDM over other methods is that it factors in the effect sizes of the activation coordinates from studies, yielding a more representative summary of activations. Studies were selected if they elicited AM retrieval in the scanner, contrasted AM retrieval with a matched control task, and used univariate whole-brain analyses, yielding a set of 50 papers with 963 participants and 891 foci. The findings confirmed the recruitment of many previously identified core AM retrieval regions including the prefrontal cortex (PFC), hippocampus and parahippocampal cortex, retrosplenial cortex and posterior cingulate, and angular gyrus, and revealed additional regions, including bilateral inferior parietal lobule and greater activation extent through the PFC, including lateral PFC activation. Results were robust across different types of AM retrieval tasks (previously rehearsed cues vs. novel cues), and robust across different control tasks (visual/attention vs. semantic retrieval). To maximize the utility of the meta-analysis, all results image files are available online. In summary, the current meta-analysis provides an updated and more representative characterization of the neural correlates of autobiographical memory retrieval and how these neural correlates are affected by important experimental factors.

Altered resting-state effective connectivity of fronto-parietal motor control systems on the primary motor network following stroke.

Previous brain imaging work suggests that stroke alters the effective connectivity (the influence neural regions exert upon each other) of motor execution networks. The present study examines the intrinsic effective connectivity of top-down motor control in stroke survivors (n=13) relative to healthy participants (n=12). Stroke survivors exhibited significant deficits in motor function, as assessed by the Fugl-Meyer Motor Assessment. We used structural equation modeling (SEM) of resting-state fMRI data to investigate the relationship between motor deficits and the intrinsic effective connectivity between brain regions involved in motor control and motor execution. An exploratory adaptation of SEM determined the optimal model of motor execution effective connectivity in healthy participants, and confirmatory SEM assessed stroke survivors' fit to that model. We observed alterations in spontaneous resting-state effective connectivity from fronto-parietal guidance systems to the motor network in stroke survivors. More specifically, diminished connectivity was found in connections from the superior parietal cortex to primary motor cortex and supplementary motor cortex. Furthermore, the paths demonstrated large individual variance in stroke survivors but less variance in healthy participants. These findings suggest that characterizing the deficits in resting-state connectivity of top-down processes in stroke survivors may help optimize cognitive and physical rehabilitation therapies by individually targeting specific neural pathway.

What can neuroimaging meta-analyses really tell us about the nature of emotion?

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.

Increased "default mode" activity in adolescents prenatally exposed to cocaine.

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.

Identifying the neurophysiological effects of memory-enhancing amygdala stimulation using interpretable machine learning.

BACKGROUND: Direct electrical stimulation of the amygdala can enhance declarative memory for specific events. An unanswered question is what underlying neurophysiological changes are induced by amygdala stimulation. OBJECTIVE: To leverage interpretable machine learning to identify the neurophysiological processes underlying amygdala-mediated memory, and to develop more efficient neuromodulation technologies. METHOD: Patients with treatment-resistant epilepsy and depth electrodes placed in the hippocampus and amygdala performed a recognition memory task for neutral images of objects. During the encoding phase, 160 images were shown to patients. Half of the images were followed by brief low-amplitude amygdala stimulation. For local field potentials (LFPs) recorded from key medial temporal lobe structures, feature vectors were calculated by taking the average spectral power in canonical frequency bands, before and after stimulation, to train a logistic regression classification model with elastic net regularization to differentiate brain states. RESULTS: Classifying the neural states at the time of encoding based on images subsequently remembered versus not-remembered showed that theta and slow-gamma power in the hippocampus were the most important features predicting subsequent memory performance. Classifying the post-image neural states at the time of encoding based on stimulated versus unstimulated trials showed that amygdala stimulation led to increased gamma power in the hippocampus. CONCLUSION: Amygdala stimulation induced pro-memory states in the hippocampus to enhance subsequent memory performance. Interpretable machine learning provides an effective tool for investigating the neurophysiological effects of brain stimulation.

Cross-paradigm connectivity: reliability, stability, and utility.

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.

Neuroimaging support for discrete neural correlates of basic emotions: a voxel-based meta-analysis.

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.

Neural correlates of successful emotional episodic encoding and retrieval: An SDM meta-analysis of neuroimaging studies.

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.

Human amygdala stimulation effects on emotion physiology and emotional experience.

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.