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.

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.

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.

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.

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.

Amygdala Stimulation Leads to Functional Network Connectivity State Transitions in the Hippocampus.

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.

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.

Progressive reconfiguration of resting-state brain networks as psychosis develops: Preliminary results from the North American Prodrome Longitudinal Study (NAPLS) consortium.

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 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, may be implicated in the progression to full psychosis.

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.

Autonomic arousal elicited by subcallosal cingulate stimulation is explained by white matter connectivity.

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.

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.

Altered Brain Activation During Memory Retrieval Precedes and Predicts Conversion to Psychosis in Individuals at Clinical High Risk.

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.

Cerebello-thalamo-cortical hyperconnectivity as a state-independent functional neural signature for psychosis prediction and characterization.

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.

Dynamic changes in large-scale functional network organization during autobiographical memory retrieval.

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.

Potential effects of severe bilateral amygdala damage on psychopathic personality features: A case report.

The fearlessness model posits that psychopathy is underpinned by a deficiency in the capacity to experience fear, predisposing to other features of the condition, such as superficial charm, guiltlessness, callousness, narcissism, and dishonesty. Nevertheless, it is unclear whether fearlessness is irrelevant, necessary, sufficient, or merely contributory to psychopathy. In the present case study, we sought to examine the fearlessness model by studying an extensively investigated female patient-S. M.-who experienced early emerging bilateral calcifications of the amygdala, resulting in a virtual absence of fear. We aimed to replicate findings regarding S. M.'s deficient experience of self-reported fear and examine her levels of triarchic psychopathy dimensions (boldness, meanness, disinhibition). We also examined S. M.'s history of heroic behaviors given conjectures that fearlessness contributes to both heroism and psychopathy. Compared with population-based norms, S. M. reported deficient levels of self-reported fear and self-control, as well as elevated levels of heroism. She did not, however, exhibit elevated levels of the core affective deficits of psychopathy, as reflected in measures of coldheartedness and meanness. These findings suggest that severe fear deficits may be insufficient to yield the full clinical picture of psychopathy, although they do not preclude the possibility that these deficits are necessary. (PsycINFO Database Record

Episodic memory after trauma exposure: Medial temporal lobe function is positively related to re-experiencing and inversely related to negative affect symptoms.

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.

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.