Simulating the situated-self drives hippocampo-cortical engagement during inner narration of events.

We often use inner narration when thinking about past and future events. The present paradigm explicitly addresses the influence of the language used in inner narration on the hippocampus-dependent event construction process. We assessed the language context effect during the inner narration of different event types: past, future, daydream, and self-unrelated fictitious events. The language context was assessed via a fluent bilingual population who used inner narration, either in their first language (L1) or second language (L2). Not all inner narration of events elicited hippocampo-cortical activity. In fact, only the angular gyrus and precuneus-retrosplenial cortex were activated by inner narration across all event types. More precisely, only inner narration of events which entailed the simulation of bodily self-location in space (whether or not they were time-marked: past, future, daydream) depended on the hippocampo-cortical system, while inner narration of events that did not entail bodily self-location (self-unrelated fictitious) did not. The language context of the narration influenced the bilinguals' hippocampo-cortical system by enhancing the co-activation of semantic areas with the hippocampus for inner narration of events in the L2. Overall, this study highlights 2 important characteristics of hippocampo-cortical-dependent inner narration of events: The core episodic hippocampal system is activated for inner narration of events simulating self-location in space (regardless of time-marking), and the inner language used for narration (L1 or L2) mediates hippocampal functional connectivity.

Decoding illusory self-location from activity in the human hippocampus.

Decades of research have demonstrated a role for the hippocampus in spatial navigation and episodic and spatial memory. However, empirical evidence linking hippocampal activity to the perceptual experience of being physically located at a particular place in the environment is lacking. In this study, we used a multisensory out-of-body illusion to perceptually 'teleport' six healthy participants between two different locations in the scanner room during high-resolution functional magnetic resonance imaging (fMRI). The participants were fitted with MRI-compatible head-mounted displays that changed their first-person visual perspective to that of a pair of cameras placed in one of two corners of the scanner room. To elicit the illusion of being physically located in this position, we delivered synchronous visuo-tactile stimulation in the form of an object moving toward the cameras coupled with touches applied to the participant's chest. Asynchronous visuo-tactile stimulation did not induce the illusion and served as a control condition. We found that illusory self-location could be successfully decoded from patterns of activity in the hippocampus in all of the participants in the synchronous (P < 0.05) but not in the asynchronous condition (P > 0.05). At the group-level, the decoding accuracy was significantly higher in the synchronous than in the asynchronous condition (P = 0.012). These findings associate hippocampal activity with the perceived location of the bodily self in space, which suggests that the human hippocampus is involved not only in spatial navigation and memory but also in the construction of our sense of bodily self-location.

Out-of-body-induced hippocampal amnesia.

Theoretical models have suggested an association between the ongoing experience of the world from the perspective of one's own body and hippocampus-based episodic memory. This link has been supported by clinical reports of long-term episodic memory impairments in psychiatric conditions with dissociative symptoms, in which individuals feel detached from themselves as if having an out-of-body experience. Here, we introduce an experimental approach to examine the necessary role of perceiving the world from the perspective of one's own body for the successful episodic encoding of real-life events. While participants were involved in a social interaction, an out-of-body illusion was elicited, in which the sense of bodily self was displaced from the real body to the other end of the testing room. This condition was compared with a well-matched in-body illusion condition, in which the sense of bodily self was colocalized with the real body. In separate recall sessions, performed ∼1 wk later, we assessed the participants' episodic memory of these events. The results revealed an episodic recollection deficit for events encoded out-of-body compared with in-body. Functional magnetic resonance imaging indicated that this impairment was specifically associated with activity changes in the posterior hippocampus. Collectively, these findings show that efficient hippocampus-based episodic-memory encoding requires a first-person perspective of the natural spatial relationship between the body and the world. Our observations have important implications for theoretical models of episodic memory, neurocognitive models of self, embodied cognition, and clinical research into memory deficits in psychiatric disorders.

The eye of the self: precuneus volume and visual perspective during autobiographical memory retrieval.

Visual perspective (i.e. first-person versus third-person perspective) during autobiographical memory (AM) retrieval plays a role in both emotional regulation and self-related processes. However, its neural underpinnings remain mostly unexplored. Visual perspective during AM retrieval was assessed in two independent datasets of 45 and 20 healthy young adults with two different AM retrieval tasks. Diffeomorphic anatomical registration using exponentiated lie algebra and voxel-based morphometry were used to assess individual differences in the precuneus grey matter volume. The spontaneous tendency to recall memories from a first-person perspective was positively correlated with the right precuneus volume among the two independent datasets. Whole-brain analyses revealed that these results were relatively specific to the anterior part of the right precuneus. Our results provide first evidence for the role of the precuneus in egocentric spatial processing in the context of AM retrieval among healthy subjects.

A shared representation of the space near oneself and others in the human premotor cortex.

Interactions between people require shared high-level cognitive representations of action goals, intentions, and mental states, but do people also share their representation of space? The human ventral premotor (PMv) and parietal cortices contain neuronal populations coding for the execution and observation of actions, analogous to the mirror neurons identified in monkeys. This neuronal system is tuned to the location of the acting person relative to the observer and the target of the action. Therefore, it can be theorized that the observer's brain constructs a low-level, body-centered representation of the space around others similar to one's own peripersonal space representation. Single-cell recordings have reported that parietal visuotactile neurons discharge for objects near specific parts of a monkey's own body and near the corresponding body parts of another individual. In humans, no neuroimaging study has investigated this issue. Here, we identified neuronal populations in the human PMv that encode the space near both one's own hand and another person's hand. The shared peripersonal space representation could support social interactions by coding sensory events, actions, and cognitive processes in a common spatial reference frame.

Breast cancer affects both the hippocampus volume and the episodic autobiographical memory retrieval.

BACKGROUND: Neuroimaging studies show the hippocampus is a crucial node in the neural network supporting episodic autobiographical memory retrieval. Stress-related psychiatric disorders, namely Major Depression and Post Traumatic Stress Disorder (PTSD), are related to reduced hippocampus volume. However, this is not the case for remitted breast cancer patients with co-morbid stress-related psychiatric disorders. This exception may be due to the fact that, consequently to the cancer experience as such, this population might already be characterized by a reduced hippocampus with an episodic autobiographical memory deficit. METHODOLOGY: We scanned, with a 3T Siemens TRIO, 16 patients who had lived through a "standard experience of breast cancer" (breast cancer and a standard treatment in remission since 18 month) in the absence of any associated stress-related psychiatric or neurological disorder and 21 matched controls. We then assessed their episodic autobiographical memory retrieval ability. PRINCIPAL FINDINGS: Remitted breast cancer patients had both a significantly smaller hippocampus and a significant deficit in episodic autobiographical memory retrieval. The hippocampus atrophy was characterized by a smaller posterior hippocampus. The posterior hippocampus volume was intimately related to the ability to retrieve negative memories and to the past experience of breast cancer or not. CONCLUSIONS/SIGNIFICANCE: These results provide two main findings: (1) we identify a new population with a specific reduction in posterior hippocampus volume that is independent of any psychiatric or neurological pathology; (2) we show the intimate relation of the posterior hippocampus to the ability to retrieve episodic autobiographical memories. These are significant findings as it is the first demonstration that indicates considerable long-term effects of living through the experience of breast cancer and shows very specific hippocampal atrophy with a functional deficit without any presence of psychiatric pathology.

Brain effects of antidepressants in major depression: a meta-analysis of emotional processing studies.

BACKGROUND: A consistent brain activity pattern has been identified in major depression across many resting positron emission tomography (PET) studies. This dysfunctional pattern seems to be normalized by antidepressant treatment. The aim of this meta-analysis was to identify more clearly the pattern associated with clinical improvement of depression following an antidepressant drug treatment, in emotional activation studies using functional magnetic resonance imaging (fMRI). METHODS: A quantitative Activation Likelihood Estimation (ALE) meta-analysis was performed across 9 emotional activation fMRI and PET studies (126 patients) using the Activation Likelihood Estimation technique. RESULTS: Following the antidepressant drug treatment, the activation of dorsolateral, dorsomedial and ventrolateral prefrontal cortices was increased whereas the activation of the amygdala, hippocampus, parahippocampal region, ventral anterior cingulate cortex, orbitofrontal cortex, and insula was decreased. Additionally, there was a decreased activation in the anterior (BA 32) and posterior cingulate cortices, as well as in the precuneus and inferior parietal lobule, which could reflect a restored deactivation of the default mode network. LIMITATIONS: The small number of emotional activation studies, using heterogeneous tasks, included in the ALE analysis. CONCLUSIONS: The activation of several brain regions involved in major depression, in response to emotional stimuli, was normalized after antidepressant treatment. To refine our knowledge of antidepressants' effect on the neural bases of emotional processing in major depression, neuroimaging studies should use consistent emotional tasks related to depressive symptoms and that involve the default mode network, such as self-referential processing tasks.

Negative affectivity, self-referential processing and the cortical midline structures.

The neural bases of the association between negative affectivity and self-focus remain unknown in healthy subjects. Building on the role of the cortical midline structures (CMS) in self-referential processing, we hypothesized that negative affectivity in healthy subjects would be associated with an increased activation of the CMS during self-referential processing. We presented positive and negative pictures to 45 healthy subjects during fMRI and asked them to judge whether the pictures were related to themselves or not (self condition), or whether the pictures were positive or negative (general condition). Negative affectivity was measured by the level of harm avoidance (HA) with the Temperament and Character Inventory. Self-referential processing activated the CMS, including the dorsal and ventral medial prefrontal cortex (MPFC) and the posterior cingulate cortex (PCC). A higher HA score was associated with a greater activation of the dorsal MPFC and PCC during self-referential processing, this greater activation being more pronounced for negative pictures in the dorsal MPFC. This increased activation of the CMS may embody the association between negative affectivity and self-focus in healthy subjects, as previously observed in major depression. Within the CMS, the dorsal MPFC may play a key role in negative affectivity, integrating an increased attention to negative stimuli with an increased attention to the self.

Self-referential processing and the prefrontal cortex over the course of depression: a pilot study.

BACKGROUND: Depressed patients exhibit cognitive biases, including maladaptive self-focus. In a previous functional magnetic resonance imaging (fMRI) study, the dorsal medial prefrontal cortex (MPFC) activation during self-referential versus semantic processing was unique to patients, as was the left dorsolateral prefrontal cortex (DLPFC) activation. The aim of this pilot study was to examine whether this pattern was stable over the course of depression. METHODS: Sixteen participants (8 depressed inpatients, 8 healthy controls) viewed personality traits during fMRI and judged whether each trait described them or not ('self' condition), or whether it described a socially desirable trait or not ('general' condition). There were 2 scanning sessions with an interval of at least 6weeks, in which patients received an antidepressant treatment. RESULTS: After a mean duration of 9 weeks, depressed patients displayed a more balanced activation of the left DLPFC but a greater activation of the dorsal MPFC in 'self' versus 'general' condition remained. LIMITATIONS: The small sample size and heterogeneous clinical features prevented subgroups analyses between responders and non-responders. CONCLUSIONS: The change of the left DLPFC activation suggests that antidepressants are associated with a more balanced allocation of cognitive control across self-referential and non-self-referential processes. The apparent lack of effect on the dorsal MPFC activity is consistent with the specific effects of antidepressants versus cognitive behavior therapy (CBT) previously demonstrated in depression. Future studies could examine the relationships between the dorsal MPFC activity in depressed patients and the need to reduce self-focus through CBT to achieve remission and prevent relapse.

Genetics and personality affect visual perspective in autobiographical memory.

Major depression is associated with a decrease of 1st person (versus 3rd person) visual perspective in autobiographical memory, even after full remission. This study aimed to examine visual perspective in healthy never-depressed subjects presenting with either genetic or psychological vulnerability for depression. Sixty healthy participants performed the Autobiographical Memory Test with an assessment of visual perspective. Genetic vulnerability was defined by the presence of at least one S or L(G) allele of the polymorphism of the serotonin-transporter-linked promoter region (5-HTTLPR). Psychological vulnerability was defined by high scores of harm avoidance measured by the Temperament and Character Inventory. Life stress exposure, depressive mood, rumination, and familial history of depression were assessed through standardized procedures. Visual perspective for positive memories was independently predicted by both harm avoidance and a gene by environment interaction between the 5-HTTLPR polymorphism and life stress exposure. Visual perspective and vulnerability for depression may share some biological bases.

In search of the depressive self: extended medial prefrontal network during self-referential processing in major depression.

Major depression is associated with an excessive self-focus, a tendency to engage oneself in self-referential processing. The medial frontal gyrus (MFG) is central to self-referential processing. This study aimed to explore the neural bases of this excessive self-focus and to disambiguate the role of the MFG in the pathophysiology of major depression. We presented 15 depressed patients and 15 healthy subjects with personality traits during functional magnetic resonance imaging and asked them to judge whether each trait described them ('self' condition) or a generally desirable trait ('general' condition). Both patients and healthy subjects activated the MFG in 'self' vs 'general' condition. However, the activation of the dorsal part of the MFG and of the dorsolateral prefrontal cortex (DLPFC) in 'self' vs 'general' condition was unique to patients. Additionally, patients displayed an increased functional connectivity between the MFG, the dorsal anterior cingulate cortex and the DLPFC. These results provide evidence for an extended medial prefrontal network during self-referential processing in major depression, suggesting the involvement of a greater cognitive control.

Cognitive avoidance of intrusive memories and autobiographical memory: specificity, autonoetic consciousness, and self-perspective.

Autobiographical memory (AM) specificity is impaired in depression and post-traumatic stress disorder. Previous studies emphasised the role of cognitive avoidance of intrusive memories in this impairment. This study aimed to examine the association of cognitive avoidance of intrusive memories with specificity, autonoetic consciousness, and self-perspective. A total of 38 healthy participants were given the revised Impact of Event Scale (IES-R) and an AM task designed to assess positive and negative memories regarding specificity, autonoetic consciousness (remember/know procedure), and self-perspective (field/observer procedure). Taking into account age, verbal IQ, mood, harm avoidance, and executive resources, the IES-R avoidance subscale was negatively correlated with specificity and remember responses for positive memories, and with remember and field responses for negative memories. These findings suggest that cognitive avoidance of intrusive memories is associated with a decrease of the episodic components of AM retrieval.

Can voxel based morphometry, manual segmentation and automated segmentation equally detect hippocampal volume differences in acute depression?

CONTEXT: According to meta-analyses, depression is associated with a smaller hippocampus. Most magnetic resonance imaging (MRI) studies among middle aged acute depressed patients are based on manual segmentation of the hippocampus. Few studies used automated methods such as voxel-based morphometry (VBM) or automated segmentation that can overcome certain drawbacks of manual segmentation (essentially intra- and inter-rater variability and operator time consumption). OBJECTIVE: The aim of our study was to compare the sensitivity of manual segmentation, automated segmentation and VBM to detect hippocampal structural changes in middle aged acute depressed population. METHOD: Twenty-one middle aged depressed inpatients and 21 matched controls were compared regarding their hippocampal structure using VBM with SPM5, manual segmentation and an automated segmentation algorithm. The VBM-ROI analysis was performed using two different normalization methods: the standard approach implemented in SPM5 and the most recent DARTEL algorithm. RESULTS: Using VBM-DARTEL, when corrected for multiple comparisons, significant volume differences were detected between groups in different regions and more specifically in hippocampus with ROI analyses. Whereas using standard VBM (without DARTEL), ROI analyses did not show bilateral volume between group differences. Significant hippocampal volume reductions between patients and controls were also detected using manual segmentation (-11.6% volume reduction, p<0.05) and automated segmentation (-9.7% volume reduction, p<0.05). VBM-DARTEL and automated segmentation show equal sensitivity in detecting hippocampal differences in depressed patients, while standard VBM was unable to detect hippocampal changes. Both VBM-DARTEL and automated segmentation could be used to perform large scale volumetric studies in humans. The new automated segmentation technique could further explore and detect hippocampal subpart differences that could be very useful for clarifying physiopathology of psychiatric disorders.

Field perspective deficit for positive memories characterizes autobiographical memory in euthymic depressed patients.

Research on autobiographical memory (AM) and the ability to retrieve specific autobiographical events in euthymic depressed patients yielded divergent results. The main goal of the present study was to further explore episodic specificity of AM among fully remitted depressed patients. Twenty euthymic depressed patients and 20 matched healthy controls were given a semi-structured interview, which assesses episodic specificity of positive and negative autobiographical memories regarding event and details' specificity, autonoetic consciousness (remember/know procedure) and visual perspective (field/observer procedure). Results showed an impairment of episodic specificity of AM in euthymic depressed patients. This impairment was explained by a field perspective deficit for positive memories only. These results suggest that euthymic patients continue to exhibit discrepancy between their current self and their self for positive past behaviors, which maintains an unfavorable view of their current self. Specific cognitive interventions may improve the self-relevance of their positive memories.