Damage to the default mode network disrupts autobiographical memory retrieval

Functional neuroimaging studies have implicated the default mode network (DMN) in autobiographical memory (AM). Convergent evidence from a lesion approach would help clarify the role of the DMN in AM. In this study, we used a voxelwise lesion-deficit approach to test the hypothesis that regions of the DMN are necessary for AM. We also explored whether the neural correlates of semantic AM (SAM) and episodic AM (EAM) were overlapping or distinct. Using the Iowa Autobiographical Memory Questionnaire, we tested AM retrieval in 92 patients with focal, stable brain lesions. In support of our hypothesis, damage to regions within the DMN (medial prefrontal cortex, mPFC; posterior cingulate cortex, PCC; inferior parietal lobule, IPL; medial temporal lobe, MTL) was associated with AM impairments. Within areas of effective lesion coverage, the neural correlates of SAM and EAM were largely distinct, with limited areas of overlap in right IPL. Whereas SAM deficits were associated with left mPFC and MTL damage, EAM deficits were associated with right mPFC and MTL damage. These results provide novel neuropsychological evidence for the necessary role of parts of the DMN in AM. More broadly, the findings shed new light on how the DMN participates in self-referential processing.     

Neural bases of learning and memory: functional neuroimaging evidence

Positron emission tomography and functional magnetic resonance imaging studies have identified brain regions associated with different forms of memory. Working memory has been associated primarily with the bilateral prefrontal and parietal regions; semantic memory with the left prefrontal and temporal regions; episodic memory encoding with the left prefrontal and medial temporal regions; episodic memory retrieval with the right prefrontal, posterior midline and medial temporal regions; and skill learning with the motor, parietal, and subcortical regions. Recent studies have provided higher specificity, by dissociating the neural correlates of different subcomponents of complex memory tasks, and the cognitive roles of different subregions of larger brain areas.     

Common and unique neural activations in autobiographical, episodic, and semantic retrieval

This study sought to explore the neural correlates that underlie autobiographical, episodic, and semantic memory. Autobiographical memory was defined as the conscious recollection of personally relevant events, episodic memory as the recall of stimuli presented in the laboratory, and semantic memory as the retrieval of factual information and general knowledge about the world. Our objective was to delineate common neural activations, reflecting a functional overlap, and unique neural activations, reflecting functional dissociation of these memory processes. We conducted an event-related functional magnetic resonance imaging study in which we utilized the same pictorial stimuli but manipulated retrieval demands to extract autobiographical, episodic, or semantic memories. The results show a functional overlap of the three types of memory retrieval in the inferior frontal gyrus, the middle frontal gyrus, the caudate nucleus, the thalamus, and the lingual gyrus. All memory conditions yielded activation of the left medial-temporal lobe; however, we found a functional dissociation within this region. The anterior and superior areas were active in episodic and semantic retrieval, whereas more posterior and inferior areas were active in autobiographical retrieval. Unique activations for each memory type were also delineated, including medial frontal increases for autobiographical, right middle frontal increases for episodic, and right inferior temporal increases for semantic retrieval. These findings suggest a common neural network underlying all declarative memory retrieval, as well as unique neural contributions reflecting the specific properties of retrieved memories.     

Integrated brain activity in medial temporal and prefrontal areas predicts subsequent memory performance: human declarative memory formation at the system level

After an era in which lesion studies have identified the declarative memory system and its essential anatomical structures, functional imaging and event-related potential studies have begun to delineate the neural underpinnings of declarative memory formation at the system level. By memory formation, we refer to those mnemonic processes present during encoding that transform perceptual representations into enduring memories. Recent studies have revealed that distinct regions in medial temporal and prefrontal areas exhibit more neural activity during successful than unsuccessful memory formation. We attempt to identify the nature of the processes underlying these subsequent memory effects. Reviewed data suggest specific mnemonic operations in the medial temporal lobe that may be integrated with semantic/perceptual operations and subserving operations in the prefrontal cortex. The formation of relational and non-relational memories may be supported by distinct subregions within these two brain regions. While the medial temporal lobe may have a serial organizational structure, with a processing hierarchy, interactions between medial temporal and prefrontal areas seem to occur in a parallel and bi-directional fashion. Interacting with this system, emotionally arousing events enhance neural activity in the amygdala, which in turn may modulate processing in other brain regions responsible for declarative memory formation.     

Functional imaging of cognition in Alzheimer's disease using positron emission tomography

Positron emission tomography in Alzheimer's disease (AD) demonstrates a metabolic decrease, predominantly in associative posterior cortices (comprising the posterior cingulate cortex), and also involving medial temporal structures and frontal regions at a lesser degree. The level of activity in this wide network is roughly correlated with dementia severity, but several confounds (such as age, education or subcortical ischemic lesions) may influence the brain-behaviour relationship. Univariate analyses allow one to segregate brain regions that are particularly closely related to specific neuropsychological performances. For example, a relationship was established between the activity in lateral associative cortices and semantic performance in AD. The role of semantic capacities (subserved by temporal or parietal regions) in episodic memory tasks was also emphasized. The residual activity in medial temporal structures was related to episodic memory abilities, as measured by free recall performance, cued recall ability and recognition accuracy. More generally, AD patients' performance on episodic memory tasks was correlated with the metabolism in several structures of Papez's circuit (including the medial temporal and posterior cingulate regions). Multivariate analyses should provide complementary information on impaired metabolic covariance in functional networks of brain regions and the consequences for AD patients' cognitive performance. More longitudinal studies are being conducted that should tell us more about the prognostic value of initial metabolic impairment and the neural correlates of progressive deterioration of cognitive performance in AD.     

Functional neuroimaging of sex differences in autobiographical memory recall

Autobiographical memory (AM) is episodic memory for personally experienced events. The brain areas underlying AM retrieval are known to include several prefrontal cortical and medial temporal lobe regions. Sex differences in AM recall have been reported in several behavioral studies, but the functional anatomical correlates underlying such differences remain unclear. This study used fMRI to compare the neural correlates of AM recall between healthy male and female participants (n = 20 per group). AM recall in response to positive, negative, and neutral cue words was compared to a semantic memory task involving the generation of examples from a category using emotionally valenced cues. Behaviorally, females recalled more negative and fewer positive AMs compared with males, while ratings of arousal, vividness, and memory age did not differ significantly between sexes. Males and females also did not differ significantly in their performance on control tasks. Neurophysiologically, females showed increased hemodynamic activity compared to males in the dorsolateral prefrontal cortex (DLPFC), dorsal anterior insula, and precuneus while recalling specific AMs (all valences combined); increased activity in the DLPFC, transverse temporal gyrus, and precuneus while recalling positive AMs; and increased activity in the anterior cingulate cortex, precuneus, amygdala, and temporopolar cortex when recalling negative AMs. When comparing positive to negative AMs directly, males and females differed in their BOLD responses in the hippocampus and DLPFC. We propose that the differential hemodynamic changes may reflect sex‐specific cognitive strategies during recall of AMs irrespective of the phenomenological properties of those memories. Hum Brain Mapp 34:3320–3332, 2013. © 2012 Wiley Periodicals, Inc.     

Gender differences in the functional neuroanatomy of emotional episodic autobiographical memory

Autobiographical memory is based on interactions between episodic memory contents, associated emotions, and a sense of self-continuity along the time axis of one's life. The functional neuroanatomy subserving autobiographical memory is known to include prefrontal, medial and lateral temporal, as well as retrosplenial brain areas; however, whether gender differences exist in neural correlates of autobiographical memory remains to be clarified. We reanalyzed data from a previous functional magnetic resonance imaging (fMRI) experiment to investigate gender-related differences in the neural bases of autobiographical memories with differential remoteness and emotional valence. On the behavioral level, there were no significant gender differences in memory performance or emotional intensity of memories. Activations common to males and females during autobiographical memory retrieval were observed in a bilateral network of brain areas comprising medial and lateral temporal regions, including hippocampal and parahippocampal structures, posterior cingulate, as well as prefrontal cortex. In males (relative to females), all types of autobiographical memories investigated were associated with differential activation of the left parahippocampal gyrus. By contrast, right dorsolateral prefrontal cortex was activated differentially by females. In addition, the right insula was activated differentially in females during remote and negative memory retrieval. The data show gender-related differential neural activations within the network subserving autobiographical memory in both genders. We suggest that the differential activations may reflect gender-specific cognitive strategies during access to autobiographical memories that do not necessarily affect the behavioral level of memory performance and emotionality.     

Reduced specificity of autobiographical memory and aging: Do the executive and feature binding functions of working memory have a role?

Autobiographical memory (AM) is built up from various kinds of knowledge, from general to specific, via generative processes. Aging seems to particularly affect the episodic autobiographical information while preserving information that is more semantic. However, the mechanism of this deficit has not yet been thoroughly tested in relation to working memory. This study is designed to investigate, in a group of 100 subjects, the relationships between age, accessibility to different levels of AM specificity, and two main components of working memory: the central executive and the episodic buffer. We used a new task composed of four embedded verbal autobiographical fluencies (VAF) - from low to highest specificity levels - exploring lifetime periods, general events, specific events, and details, plus tasks exploring free recall of episodic AM and updating, shifting, inhibition, and feature binding in working memory. The results demonstrate that age-related difficulties increase with level of specificity of autobiographical knowledge, i.e., from semantic to episodic aspects. Moreover, regression analyses mainly show that increase in age-related deficit with level of specificity of AM is largely mediated by performance on executive functions (updating and inhibition) and to a lesser extent feature binding in working memory. The results confirm in episodic AM the executive/working memory aging hypothesis, and for the first time highlight the role of episodic buffer in associating the various different details of specific events that elicit the conscious recollection.     

Retrieval mechanisms for autobiographical memories: insights from the frontal variant of frontotemporal dementia

Very few studies have investigated autobiographical memory in the frontal variant of frontotemporal dementia (fv-FTD). The aim of this study was therefore to unravel the mechanisms of autobiographical memory disruption in general and in the anterograde and retrograde components of amnesia in particular, in patients suffering from fv-FTD. An autobiographical memory task assessing overall (AM) and strictly episodic memories (EM) from five lifetime periods covering the entire lifespan revealed the absence of a temporal gradient for both scores, suggesting the existence of a retrieval deficit. An analysis of the correlation between these two scores and a general cognitive assessment of executive function, working, episodic (i.e. new learning ability) and semantic memory, and behavioural changes highlighted the considerable involvement of executive function, semantic memory and, to a lesser degree, episodic memory and behavioural changes. Moreover, step-wise regression analyses performed on the EM score revealed that the executive function was a better predictor of the retrograde component than of the anterograde component, which was linked principally to new episodic learning ability. All these results confirm the impact of executive dysfunction on autobiographical deficits in fv-FTD, and suggest that the mechanisms at the root of autobiographical memory disruption may also involve difficulties in new episodic learning and semantic storage, though this may be due to the fact that we studied an advanced form of fv-FTD.     

The role of the medial temporal lobe in autistic spectrum disorders

The neural basis of autistic spectrum disorders (ASDs) is poorly understood. Studies of mnemonic function in ASD suggest a profile of impaired episodic memory with relative preservation of semantic memory (at least in high-functioning individuals). Such a pattern is consistent with developmental hippocampal abnormality. However, imaging evidence for abnormality of the hippocampal formation in ASD is inconsistent. These inconsistencies led us to examine the memory profile of children with ASD and the relationship to structural abnormalities. A cohort of high-functioning individuals with ASD and matched controls completed a comprehensive neuropsychological memory battery and underwent magnetic resonance imaging for the purpose of voxel-based morphometric analyses. Correlations between cognitive/behavioural test scores and quantified results of brain scans were also carried out to further examine the role of the medial temporal lobe in ASD. A selective deficit in episodic memory with relative preservation of semantic memory was found. Voxel-based morphometry revealed bilateral abnormalities in several areas implicated in ASD including the hippocampal formation. A significant correlation was found between parental ratings reflecting autistic symptomatology and the measure of grey matter density in the junction area involving the amygdala, hippocampus and entorhinal cortex. The data reveal a pattern of impaired and relatively preserved mnemonic function that is consistent with a hippocampal abnormality of developmental origin. The structural imaging data highlight abnormalities in several brain regions previously implicated in ASD, including the medial temporal lobes.     

A cognitive chameleon: Lessons from a novel MAPT mutation case

We report a case of frontotemporal dementia caused by a novel MAPT mutation (Q351R) with a remarkably long amnestic presentation mimicking familial Alzheimer’s disease. Longitudinal clinical, neuropsychological and imaging data provide convergent evidence for predominantly bilateral anterior medial temporal lobe involvement consistent with previously established neuroanatomical signatures of MAPT mutations. This case supports the notion that the neural network affected in MAPT mutations is determined to a large extent by the underlying molecular pathology. We discuss the diagnostic significance of anomia in the context of atypical amnesia and the impact of impaired episodic and semantic memory systems on autobiographical memory.     

fMRI studies of successful emotional memory encoding: A quantitative meta-analysis

Over the past decade, fMRI techniques have been increasingly used to interrogate the neural correlates of successful emotional memory encoding. These investigations have typically aimed to either characterize the contributions of the amygdala and medial temporal lobe (MTL) memory system, replicating results in animals, or delineate the neural correlates of specific behavioral phenomena. It has remained difficult, however, to synthesize these findings into a systems neuroscience account of how networks across the whole-brain support the enhancing effects of emotion on memory encoding. To this end, the present study employed a meta-analytic approach using activation likelihood estimates to assess the anatomical specificity and reliability of event-related fMRI activations related to successful memory encoding for emotional versus neutral information. The meta-analysis revealed consistent clusters within bilateral amygdala, anterior hippocampus, anterior and posterior parahippocampal gyrus, the ventral visual stream, left lateral prefrontal cortex and right ventral parietal cortex. The results within the amygdala and MTL support a wealth of findings from the animal literature linking these regions to arousal-mediated memory effects. The consistency of findings in cortical targets, including the visual, prefrontal, and parietal cortices, underscores the importance of generating hypotheses regarding their participation in emotional memory formation. In particular, we propose that the amygdala interacts with these structures to promote enhancements in perceptual processing, semantic elaboration, and attention, which serve to benefit subsequent memory for emotional material. These findings may motivate future research on emotional modulation of widespread neural systems and the implications of this modulation for cognition.     

Reprint of: fMRI studies of successful emotional memory encoding: a quantitative meta-analysis

Over the past decade, fMRI techniques have been increasingly used to interrogate the neural correlates of successful emotional memory encoding. These investigations have typically aimed to either characterize the contributions of the amygdala and medial temporal lobe (MTL) memory system, replicating results in animals, or delineate the neural correlates of specific behavioral phenomena. It has remained difficult, however, to synthesize these findings into a systems neuroscience account of how networks across the whole-brain support the enhancing effects of emotion on memory encoding. To this end, the present study employed a meta-analytic approach using activation likelihood estimates to assess the anatomical specificity and reliability of event-related fMRI activations related to successful memory encoding for emotional versus neutral information. The meta-analysis revealed consistent clusters within bilateral amygdala, anterior hippocampus, anterior and posterior parahippocampal gyrus, the ventral visual stream, left lateral prefrontal cortex and right ventral parietal cortex. The results within the amygdala and MTL support a wealth of findings from the animal literature linking these regions to arousal-mediated memory effects. The consistency of findings in cortical targets, including the visual, prefrontal, and parietal cortices, underscores the importance of generating hypotheses regarding their participation in emotional memory formation. In particular, we propose that the amygdala interacts with these structures to promote enhancements in perceptual processing, semantic elaboration, and attention, which serve to benefit subsequent memory for emotional material. These findings may motivate future research on emotional modulation of widespread neural systems and the implications of this modulation for cognition.     

Encoding and retrieving faces and places: Distinguishing process- and stimulus-specific differences in brain activity

Among the most fundamental issues in cognitive neuroscience is how the brain may be organized into process-specific and stimulus-specific regions. In the episodic memory domain, most functional neuroimaging studies have focused on the former dimension, typically investigating the neural correlates of various memory processes. Thus, there is little information about what role stimulus-specific brain regions play in successful memory processes. To address this issue, the present event-related fMRI study used a factorial design to focus on the role of stimulus-specific brain regions, such as the fusiform face area (FFA) and parahippocampal place area (PPA) in successful encoding and retrieval processes. Searching within regions sensitive to faces or places, we identified areas similarly involved in encoding and retrieval, as well as areas differentially involved in encoding or retrieval. Finally, we isolated regions associated with successful memory, regardless of stimulus and process type. There were three main findings. Within face sensitive regions, anterior medial PFC and right FFA displayed equivalent encoding and retrieval success processes whereas left FFA was associated with successful encoding rather than retrieval. Within place sensitive regions, left PPA displayed equivalent encoding and retrieval success processes whereas right PPA was associated with successful encoding rather than retrieval. Finally, medial temporal and prefrontal regions were associated with general memory success, regardless of stimulus or process type. Taken together, our results clarify the contribution of different brain regions to stimulus- and process-specific episodic memory mechanisms.     

Neuroimaging and behavior: Probing brain behavior relationships in the 21st century

Functional neuroimaging over the past decade has provided a new way to examine brain behavior relationships. Current noninvasive neuroimaging techniques, which can examine structure and function, have begun to clarify the networks involved in cognitive processes and how these are affected in aging and disease. Functional magnetic resonance imaging (fMRI) has demonstrated the interaction between medial temporal and prefrontal regions in episodic memory. The anatomical correlates of various components of spatial attention and working memory have emerged from elegant event-related fMRI designs. Distinct neural networks for different emotions are being mapped out, and the role of the anterior cingulate in depressed mood has been documented. This review highlights key recent studies that have illuminated the neural substrates of these important cognitive and affective processes.     

Episodic memory,semantic memory,and amnesia

Episodic memory and semantic memory are two types of declarative memory. There have been two principal views about how this distinction might be reflected in the organization of memory functions in the brain. One view, that episodic memory and semantic memory are both dependent on the integrity of medial temporal lobe and midline diencephalic structures, predicts that amnesic patients with medial temporal lobe/diencephalic damage should be proportionately impaired in both episodic and semantic memory. An alternative view is that the capacity for semantic memory is spared, or partially spared, in amnesia relative to episodic memory ability. This article reviews two kinds of relevant data: 1) case studies where amnesia has occurred early in childhood, before much of an individual's semantic knowledge has been acquired, and 2) experimental studies with amnesic patients of fact and event learning, remembering and knowing, and remote memory. The data provide no compelling support for the view that episodic and semantic memory are affected differently in medial temporal lobe/diencephalic amnesia. However, episodic and semantic memory may be dissociable in those amnesic patients who additionally have severe frontal lobe damage. Hippocampus 1998;8:205–211. Published 1998 Wiley-Liss, Inc.

1 This article is a US Government work and, as such, is in the public domain in the United States of America.

     

Anosognosia and default mode subnetwork dysfunction in Alzheimer's disease

Research on the neural correlates of anosognosia in Alzheimer's disease varied according to methods and objectives: they compared different measures, used diverse neuroimaging modalities, explored connectivity between brain networks, addressed the role of specific brain regions or tried to give support to theoretical models of unawareness. We used resting‐state fMRI connectivity with two different seed regions and two measures of anosognosia in different patient samples to investigate consistent modifications of default mode subnetworks and we aligned the results with the Cognitive Awareness Model. In a first study, patients and their relatives were presented with the Memory Awareness Rating Scale. Anosognosia was measured as a patient‐relative discrepancy score and connectivity was investigated with a parahippocampal seed. In a second study, anosognosia was measured in patients with brain amyloid (taken as a disease biomarker) by comparing self‐reported rating with memory performance, and connectivity was examined with a hippocampal seed. In both studies, anosognosia was consistently related to disconnection within the medial temporal subsystem of the default mode network, subserving episodic memory processes. Importantly, scores were also related to disconnection between the medial temporal and both the core subsystem (participating to self‐reflection) and the dorsomedial subsystem of the default mode network (the middle temporal gyrus that might subserve a personal database in the second study). We suggest that disparity in connectivity within and between subsystems of the default mode network may reflect impaired functioning of pathways in cognitive models of awareness.     

Growing up with bilateral hippocampal atrophy: from childhood to teenage

The respective roles of the medial temporal lobe (MTL) structures in memory are controversial. Some authors put forward a modular account according to which episodic memory and recollection-based processes are crucially dependent on the hippocampal formation whereas semantic acquisition and familiarity-based processes rely on the adjacent parahippocampal gyri. Others defend a unitary view.We report the case of VJ, a boy with developmental amnesia of most likely perinatal onset diagnosed at the age of 8. Magnetic resonance imaging (MRI), including quantitative volumetric measurements of the hippocampal formation and of the entorhinal, perirhinal, and temporopolar cortices, showed severe, bilateral atrophy of the hippocampal formation, fornix and mammillary bodies; by contrast, the perirhinal cortex was within normal range and the entorhinal and temporopolar cortex remained within two standard deviations (SDs) from controls’ mean. We examined the development of his semantic knowledge from childhood to teenage as well as his recognition and cued recall memory abilities. On tasks tapping semantic memory, VJ increased his raw scores across years at the same rate as children from large standardisation samples, except for one task; he achieved average performance, consistent with his socio-educational background. He performed within normal range on 74% of recognition tests and achieved average to above average scores on 42% of them despite very severe impairment on 82% of episodic recall tasks. Both faces and landscapes-scenes gave rise to above average scores when tested with coloured stimuli. Cued recall, although impaired, was largely superior to free recall.This case supports a modular account of the MTL with episodic, but not semantic memory depending on the hippocampal formation. Furthermore, the overall pattern of findings is consistent with evidence from both brain-damaged and neuroimaging studies indicating that recollection requires intact hippocampal formation and familiarity relies, at least partly, on the adjacent temporal lobe cortex.     

Exploring the roles of the executive and short-term feature-binding functions in retrieval of retrograde autobiographical memories in severe traumatic brain injury

Conway’s autobiographical memory (AM) model postulates that memories are not stored in a crystallised form in long-term memory but are reconstructed at time of retrieval via executive and binding processes, to create a temporary multimodal representation from different AM knowledge. Traumatic brain injury (TBI) impairs AM recollection. However, no study has yet considered the distinct roles of executive and short-term feature-binding functions in the retrieval deficits of retrograde AMs after TBI. Examining a group of 33 TBI patients and 33 controls, our study addresses these roles through a first-ever exploration of the links between performance on an AM verbal fluency evaluation that distinguishes four levels of representation, from semantic to episodic (lifetime periods, general events, specific events, specific details of a specific event), and three executive functions (shifting, inhibition and updating) and two short-term feature-binding functions (short-term formation and maintenance of multimodal representations). The results showed that TBI patients were impaired compared to controls in the retrieval of both semantic and episodic retrograde AM representations, but especially for the most episodic level of AM, in the three executive functions and the short-term maintenance of multimodal representations. Regression analyses indicated that the executive predictors (mainly updating) mediated a large proportion (over 70%) of TBI-related deficit on the retrieval of lifetime periods, general events and specific events, in contrast with the main impairment on generation of specific details which were only mildly (just 12%) predicted by the short-term maintenance of multimodal representations. Additional analyses in a subgroup of patients point to episodic memory abilities and time since injury in predicting the retrieval of specific events and details. In summary, the present study mainly emphasizes that the executive deficits in TBI are involved in the disruption of the first levels of AM generative processes that give access to the multiple episodic details recollection.     

Functional connectivity of hippocampal and prefrontal networks during episodic and spatial memory based on real‐world environments

Several recent studies have compared episodic and spatial memory in neuroimaging paradigms in order to understand better the contribution of the hippocampus to each of these tasks. In the present study, we build on previous findings showing common neural activation in default network areas during episodic and spatial memory tasks based on familiar, real‐world environments (Hirshhorn et al. (2012) Neuropsychologia 50:3094–3106). Following previous demonstrations of the presence of functionally connected sub‐networks within the default network, we performed seed‐based functional connectivity analyses to determine how, depending on the task, the hippocampus and prefrontal cortex differentially couple with one another and with distinct whole‐brain networks. We found evidence for a medial prefrontal‐parietal network and a medial temporal lobe network, which were functionally connected to the prefrontal and hippocampal seeds, respectively, regardless of the nature of the memory task. However, these two networks were functionally connected with one another during the episodic memory task, but not during spatial memory tasks. Replicating previous reports of fractionation of the default network into stable sub‐networks, this study also shows how these sub‐networks may flexibly couple and uncouple with one another based on task demands. These findings support the hypothesis that episodic memory and spatial memory share a common medial temporal lobe‐based neural substrate, with episodic memory recruiting additional prefrontal sub‐networks. © 2014 Wiley Periodicals, Inc.