Autobiographical Cerebral Network Activation in Older Adults Before and After Reminiscence Therapy: A Preliminary Report.

INTRODUCTION: Reminiscence therapy (RT), which engages individuals to evoke positive memories, has been shown to be effective in improving psychological well-being in older adults suffering from PTSD, depression, and anxiety. However, its impact on brain function has yet to be determined. This paper presents functional magnetic resonance imaging (fMRI) data to describe changes in autobiographical memory networks (AMN) in community-dwelling older adults. METHODS: This pilot study used a within-subject design to measure changes in AMN activation in 11 older adults who underwent 6 weeks of RT. In the scanner, participants retrieved autobiographical memories which were either recent or remote, rehearsed or unrehearsed. Participants also underwent a clinical interview to assess changes in memory, quality of life, mental health, and affect. FINDINGS: Compared to pretreatment, anxiety decreased (z = -2.014, p = .040) and activated significant areas within the AMN, including bilateral medial prefrontal cortex, left precuneus, right occipital cortex, and left anterior hippocampus. CONCLUSION: Although RT had subtle effects on psychological function in this sample with no evidence of impairments, including depression at baseline, the fMRI data support current thinking of the effect RT has on the AMN. Increased activation of right posterior hippocampus following RT is compatible with the Multiple Trace Theory Theory (Nadel & Moscovitch, 1997).

Self-referential processes and resting-state connectivity in breast cancer patients before and 1 year after chemotherapy.

Modifications in the processing of information relevant to oneself have been reported in breast cancer (BC) patients. Here, we characterize the longitudinal changes to self-representations in BC patients and how they are related to intrinsic functional brain connectivity. We tested 16 BC patients before (T1) and 1 year after the end of chemotherapy (T2) along with 24 healthy control participants (HC) at similar time points. Participants underwent resting-state fMRI and completed the Questionnaire of Self-Representation (QSR), which evaluates self-assertion and self-esteem. Resting-state functional connectivity (RSFC) was calculated for regions implicated in self-referential processes (dorsomedial prefrontal cortex [dmPFC], posterior cingulate cortex [PCC], and dorsal anterior cingulate cortex [dACC]) and correlated with QSR scores. QSR scores were on average larger in patients compared with HC and did not vary over time. RSFC between the dACC and regions supporting body awareness (precentral/postcentral and supramarginal gyri, superior parietal lobule) decreased more between T1 and T2 in BC patients than in HC. BC patients had lower RSFC than HC between the dmPFC and the PCC, and regions supporting mental imagery (precuneus, lingual gyrus), at each time point, and a greater decrease from T1 and T2. QSR scores negatively correlated with RSFC. Patients described themselves as having greater self-awareness and positive self-image, reflecting a fighting spirit. In parallel, patients presented a decrease in cortical activity related to body awareness and mental imagery of self-representations over time that may be related to the positive self-image patients have and could reflect a temporary adaptive strategy.

History of Magnetic Resonance Imaging: A Trip Down Memory Lane.

The history of magnetic resonance imaging (MRI) is closely linked to our improved understanding of memory systems, be it in normal functioning or altered due to pathologies. Over the years, brain imaging using MRI has moved from simple volumetric imaging to complex analysis using multiple sequences, allowing the measurement of microstructural integrity and brain activation through a dedicated task or at rest. This review aims at showing how the advent and evolution of magnetic resonance imaging has shaped a better understanding of memory and brain function in humans. We will give a brief overview on the history of MRI, how its evolution brought about concomitant improvement in our understanding of memory systems, going from final-stage observation to risk-prediction via the detection of subtle, but important, alterations in normal brain functioning.

Boosting Autobiographical Memory and the Sense of Identity of Alzheimer Patients Through Repeated Reminiscence Workshops?

Despite severe amnesia, some studies showed that Alzheimer Disease (AD) patients with moderate to severe dementia keep a consistent, but impoverished representation of themselves, showing preservation of the sense of identity even at severe stages of the illness. Some studies suggest that listening to music can facilitate the reminiscence of autobiographical memories and that stimulating autobiographical memory would be relevant to support the self of these patients. Consequently, we hypothesized that repeated participation to reminiscence workshops, using excerpts of familiar songs as prompts would participate to the enrichment of autobiographical memories, self-representation and sense of identity. We included a group of 20 AD patients with severe dementia residing in nursing homes. Their performances were compared to a control group of 20 matched (age, education, mood) healthy residents living in the same institutions. The experiment was conducted in three phases over a 2-week period. On phase 1, an individual assessment of sense of identity was proposed to each participant. On phase 2, participants joined musical reminiscence workshops (six sessions over 2 weeks for AD patients and 3 sessions over a week for controls). During the third phase (12 days after the first assessment), individual evaluation of autobiographical memory and a second assessment of sense of identity were proposed. Our results showed that, despite their massive amnesia syndrome, autobiographical memories of AD reached at the end of the 2 weeks the number and quality of those of matched controls. Moreover, we confirmed a continuity of self-representation in AD patients with a stable profile of the answers between the first and second individual assessments of sense of identity. However, the increase in number and episodic quality of autobiographical memories was not accompanied by an enrichment of the sense of identity. In a complementary study, new patients participated in the same paradigm, but using movie extracts as prompts, and showed very similar effects. We discuss all of these results with regard to the literature showing the significant impact of repetition on the reactivation of memory traces even in very amnestic AD patients at severe stages of the disease.

Longitudinal investigation of cognitive deficits in breast cancer patients and their gray matter correlates: impact of education level.

Cognitive deficits are a major complaint in breast cancer patients, even before chemotherapy. Comprehension of the cerebral mechanisms related to cognitive impairment in breast cancer patients remains difficult due to the scarcity of studies investigating both cognitive and anatomical imaging changes. Furthermore, only some of the patients experienced cognitive decline following chemotherapy, yet few studies have identified risk factors for cognitive deficits in these patients. It has been shown that education level could impact cognitive abilities during the recovery phase following chemotherapy. Our main aim was to longitudinally evaluate cognitive and anatomical changes associated with cancer and chemotherapy in breast cancer patients. Our secondary aim was to assess the impact of education level on cognitive performances and gray matter (GM) atrophy in these patients. Twenty patients were included before chemotherapy (T1), 1 month (T2) and 1 year (T3) after chemotherapy. Twenty-seven controls without a history of cancer were assessed at T1 and T3 only. Cluster groups based on education level were defined for both groups and were further compared. Comparison between patients and controls revealed deficits in patients on verbal episodic memory retrieval at T1 and T3 and on executive functions at T3. After chemotherapy, breast cancer patients had GM atrophy that persisted or recovered 1 year after chemotherapy depending on the cortical areas. Increase in GM volumes from T1 to T3 were also found in both groups. At T2, patients with a higher level of education compared to lower level exhibited higher episodic memory retrieval and state anxiety scores, both correlating with cerebellar volume. This higher level of education group exhibited hippocampal atrophy. Our results suggest that, before chemotherapy, cancer-related processes impact cognitive functioning and that this impact seems exacerbated by the effect of chemotherapy on certain brain regions. Increase in GM volumes after chemotherapy were unexpected and warrant further investigations. Higher education level was associated, 1 month after the end of chemotherapy, with greater anxiety and hippocampal atrophy despite a lack of cognitive deficits. These results suggest, for the first time, the occurrence of compensation mechanisms that may be linked to cognitive reserve in relationship to state anxiety. This identification of factors, which may compensate cognitive impairment following chemotherapy, is critical for patient care and quality of life.

Influence of emotional complexity on the neural substrates of affective theory of mind.

Affective theory of mind (ToM) depends on both the decoding of emotional expressions and the reasoning on emotional mental states from social situations. While previous studies characterized the neural substrates underlying these processes, it remains unclear whether the nature of the emotional state inferred from others can influence the brain activation associated with affective ToM. In the present study, we focused on two types of emotions: basic emotions (BEs) (e.g., anger and surprise), which are innate and universal and self-conscious emotions (e.g., pride and embarrassment), which correspond to a special class of emotions involving the self and including a representation of one's relative reactions to internal and external standards. Specifically, we used an ecological functional MRI paradigm, on 21 healthy young subjects, to compare brain activations during the decoding of and the reasoning on others' self-conscious, basic and neutral mental states. Our results showed that compared to neutral states, the inference of self-conscious and basic emotional states from others elicited more activation in several core regions of affective ToM. Direct comparisons between emotional conditions revealed more activation for self-conscious than BEs in the right temporoparietal junction during the reasoning process and in left middle occipital regions during the decoding process. Further analyses using a localizer task showed that the extrastriate body area was more recruited for decoding others' self-conscious versus BEs, which emphasize the importance of body clues to properly infer these emotions. Using an original task allowing for an ecological assessment of the affective ToM, these results demonstrate that the complexity of the emotion inferred to others can influence the recruitment of ToM network. This study also validates the use of our task as an ecological tool to assess the affective ToM, constituting an avenue for the characterization of ToM impairments in neurological conditions.

Neurocognitive determinants of theory of mind across the adult lifespan.

Although theory of mind (ToM) has been extensively explored in aging, few studies have used the same tool to simultaneously assess and compare its cognitive and affective components. When we administered the Movie for Assessment of Social Cognition, a dynamic sequence of social scenes, to 60 healthy participants (20-75 years), we observed no different age-related decreases in both cognitive and affective ToM. While each component was associated with cognitive measures (i.e., episodic memory and processing speed were predictive of cognitive ToM, and recognition of facial emotion expressions and inhibition were predictive of affective ToM), mediation analyses showed that these measures only mediated the effect of age on affective ToM. Voxelwise regressions with grey-matter volume showed that the components partly rely on the same neural substrates, reflecting either ToM per se or other cognitive processes elicited by this multi-determinant task. We discuss the specific substrates of each ToM component, emphasising the importance of considering the impact of other aspects of cognition, present in more ecological situations, on ToM functioning.

Altered default mode network connectivity in adolescents with post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is characterized by intrusions, re-experiencing, avoidance and hyperarousal. These symptoms might be linked to dysfunction in core neurocognitive networks subserving self-referential mental processing (default mode network, DMN), detection of salient stimuli (salience network, SN) and cognitive dysfunction (central executive network, CEN). Resting state studies in adolescent PTSD are scarce and findings are inconsistent, probably due to differences in patient symptom severity. Resting state brain activity was measured in 14 adolescents with severe PTSD and 24 age-matched controls. Seed-based connectivity analyses were used to examine connectivity between the DMN and the whole brain, including regions from other networks (SN and CEN). The relationships of network properties with symptom dimensions (severity, anxiety and depression) and episodic memory were also examined. Analyses revealed decreased within-DMN connectivity (between PCC and occipital cortex) in patients compared to controls. Furthermore, within-DMN connectivity (between PCC and hippocampus) correlated negatively with symptom dimensions (severity and anxiety), while increased connectivity (DMN-SN and DMN-CEN) correlated positively with episodic memory measures. These abnormal network properties found in adolescent PTSD corroborate those previously reported in adult PTSD. Decreased within-DMN connectivity and disrupted DMN-SN and DMN-CEN coupling could form the basis for intrusive trauma recollection and impaired episodic autobiographical recall in PTSD.

Hippocampal subfields alterations in adolescents with post-traumatic stress disorder.

Reexperiencing symptoms in adolescent Post-Traumatic Stress Disorder (PTSD) are characterized by the apparition of vivid intrusive images of the traumatic event. The emergence of these intrusions is thought to be related to a deficiency in context processing and could then be related to hippocampal alterations. The hippocampus is a complex structure which can be divided into several subfields, namely, the Cornu Ammonis (CA1, CA2, and CA3), the subiculum, and the dentate gyrus (DG). As each subfield presents different histological characteristics and functions, it appears more relevant to consider hippocampal subfields, instead of only assessing the whole hippocampus, to understand the neurobiology of PTSD. Hence, this study presents the first investigation of structural alterations within hippocampal subfields and their links to reexperiencing symptoms in adolescent PTSD. Hippocampal subfields were manually delineated on high-resolution MRI images in 15 adolescents (13-18 years old) with PTSD and 24 age-matched healthy controls. The volume of the region CA2-3/DG region was significantly smaller in the PTSD group compared to controls in both hemispheres. No other significant difference was found for other subfields. Moreover, the volume of the left CA2-3/DG was negatively correlated with the intrusion score (as measured by the Impact of Events Scale-Revised) in the PTSD group. To conclude, an alteration in the hippocampal subregion CA2-3/DG, known to resolve interferences between new and similar stored memories, could participate in the apparition of intrusive trauma memories in adolescents with PTSD.

Functional brain alterations during self-reference processing in adolescents with sexual abuse-related post-traumatic stress disorder: A preliminary report.

We proposed to explore the functional brain changes during a self-reference processing (SRP) task in adolescents with sexual abuse-related post-traumatic stress disorder (N = 10), compared with healthy adolescents (N = 10). While patients showed no behavioral disturbances in (SRP), they exhibited changes in activity and connectivity in regions involved in emotional regulation (amygdala and dorsal prefrontal cortex) and semantic memory (temporal and ventrolateral prefrontal regions). These preliminary results suggest that these alterations may have an effect on self-esteem which may contribute to a possible retention and impairment of symptoms in adulthood.

Social Cognition in the Frontal Variant of Alzheimer's Disease: A Case Study.

Although frontal presentations of Alzheimer's disease (fv-AD) have already been described in the literature, we still know little about patients' social cognitive abilities, especially their theory of mind (ToM). We report the case of FT, a 61-year-old woman who was diagnosed with fv-AD. Two assessments of social cognition, using a false-belief task, the Reading the Mind in the Eyes test, and a task probing knowledge of social norms, were performed one year apart. FT exhibited cognitive ToM and social knowledge deficits from the onset. Affective ToM was initially preserved, but deteriorated as the disease progressed.

The MNESIS model: Memory systems and processes, identity and future thinking.

The Memory NEo-Structural Inter-Systemic model (MNESIS; Eustache and Desgranges, Neuropsychology Review, 2008) is a macromodel based on neuropsychological data which presents an interactive construction of memory systems and processes. Largely inspired by Tulving's SPI model, MNESIS puts the emphasis on the existence of different memory systems in humans and their reciprocal relations, adding new aspects, such as the episodic buffer proposed by Baddeley. The more integrative comprehension of brain dynamics offered by neuroimaging has contributed to rethinking the existence of memory systems. In the present article, we will argue that understanding the concept of memory by dividing it into systems at the functional level is still valid, but needs to be considered in the light of brain imaging. Here, we reinstate the importance of this division in different memory systems and illustrate, with neuroimaging findings, the links that operate between memory systems in response to task demands that constrain the brain dynamics. During a cognitive task, these memory systems interact transiently to rapidly assemble representations and mobilize functions to propose a flexible and adaptative response. We will concentrate on two memory systems, episodic and semantic memory, and their links with autobiographical memory. More precisely, we will focus on interactions between episodic and semantic memory systems in support of 1) self-identity in healthy aging and in brain pathologies and 2) the concept of the prospective brain during future projection. In conclusion, this MNESIS global framework may help to get a general representation of human memory and its brain implementation with its specific components which are in constant interaction during cognitive processes.

Neural Correlates of Self and Its Interaction With Memory in Healthy Adolescents.

Adolescence is marked by the development of personal identity and is associated with structural and functional changes in brain regions associated with Self processing. Yet, little is known about the neural correlates of self-reference processing and self-reference effect in adolescents. This functional magnetic resonance imaging study consists of a self-reference paradigm followed by a recognition test proposed to 30 healthy adolescents aged 13-18 years old. Results showed that the rostral anterior cingulate cortex is specifically involved in self-reference processing and that this specialization develops gradually from 13 to 18 years old. The self-reference effect is associated with increased brain activation changes during encoding, suggesting that the beneficial effect of Self on memory may occur at encoding of self-referential information, rather than at retrieval.

Emotional specificities of autobiographical memory after breast cancer diagnosis.

Cancer involves stressful events. One aspect of cognition that is impacted by stress is episodic autobiographical memory (EAM). EAM is intimately linked to self-representation. Some studies have revealed impairment of EAM in patients with breast cancer in remission. Yet, these studies failed to differentiate between the influence of adjuvant treatments and that of psychosocial factors. We therefore assessed the psychological impact of breast cancer diagnosis on EAM and self-representation profiles prior to any adjuvant treatment. Patients newly diagnosed with breast cancer (n=31) and women without any history of cancer (n=49) were compared on state anxiety, EAM and its emotional characteristics, and self-representations. The most anxious patients retrieved fewer emotional details for memories than the controls, and had lower self-representation scores than the least anxious patients, who had no deficits in emotional detail retrieval. Our results revealed distinct EAM profiles for patients, reflecting two contrasting modes of coping with breast cancer.

Episodic future thinking in semantic dementia: a cognitive and FMRI study.

Semantic dementia (SD) is characterized by gradual loss of semantic memory. While episodic autobiographical memory seems relatively preserved, behavioral studies suggest that episodic future thinking is impaired. We used fMRI to measure brain activity in four SD patients (JPL, EP, LL, EG) while they envisioned future events and remembered personal past events. Twelve healthy elders served as controls. Episodic quality, emotion, mental imagery and level of consciousness (via remember/know judgements) were checked at debriefing. We analyzed the future compared to the past for each patient. All patients presented lateral temporal atrophy, but varied in terms of frontal and anterior hippocampal atrophy. Patient JPL presented atrophy in bilateral superior medial frontal gyri and left anterior hippocampus and was unable to engage in episodic future thinking, despite hyperactivations in frontal and occipital regions. Patient EP presented no atrophy in the anterior hippocampus, but atrophy in bilateral superior medial frontal gyrus and had difficulties to engage in episodic future thinking. Patient LL presented atrophy in left anterior hippocampus, but hyperactivated its right counterpart for future compared to past thinking, permitting her to project efficiently in the future in an episodic way. Patient EG presented no atrophy in the superior medial frontal gyri or anterior hippocampi and was able to engage in episodic future thinking. Altogether, patients' future projections differed depending on the severity and localization of their atrophy. The functional integrity of bilateral superior medial frontal gyri and anterior hippocampus appear crucial for episodic future thinking: atrophy of both structures strongly impairs future projection, while integrity of these structures or hyperactivation of residual tissue normalizes episodic future projection.

Autobiographical memory in semantic dementia: new insights from two patients using fMRI.

Episodic autobiographical memory (EAM) consists of personal events embedded within a specific spatiotemporal context. Patients with semantic dementia (SD) generally show preserved recent EAMs, but a controversy remains concerning their ability to retrieve remote ones. Only one fMRI study examined remote autobiographical memory in SD through a longitudinal case study (Maguire, Kumaran, Hassabis, & Kopelman, 2010). Here, we propose a cross-sectional study to test the hippocampo-neocortical up-regulation hypothesis, through a multimodal approach (gray matter volume, activation, connectivity analyses), directly comparing recent and remote autobiographical memory retrieval and collecting data to asses phenomelogical re-experiencing. EAM retrieval recruits a distributed network of brain regions, notably the hippocampus which is shown to be atrophied in SD, although some studies report no hippocampal atrophy in SD. Using fMRI, we examined recent and remote EAM retrieval in two SD patients with different profiles of hippocampal atrophy, compared to 12 healthy elders (HE). JPL presented severe bilateral hippocampal atrophy, while EP showed sparing of both hippocampi. Behaviourally, JPL was impaired at retrieving EAMs from both life periods and showed poorer use of visual mental imagery than HE, while EP retrieved memories which were as episodic as those of HE for both periods and relied on greater use of visual mental imagery than HE. Neuroimaging results showed that, for JPL, hyperactivations of the residual hippocampal tissue and of frontal, lateral temporal, occipital and parietal cortices did not efficiently compensate his autobiographical memory deficit. EP however presented hyperactivations in similar neocortical regions which appeared to be more efficient in compensating for atrophy elsewhere, since EP's EAM retrieval was preserved. Functional connectivity analyses focusing on the hippocampus showed how the residual hippocampal activity was connected to other brain areas. For JPL, recent autobiographical retrieval was associated with connectivity between the posterior hippocampus and middle occipital gyrus, while for EP, connectivity was detected between the anterior hippocampus and numerous regions (medial temporal, occipital, temporal, frontal, parietal) for both recent and remote periods. These findings suggest that intensification of hippocampal atrophy in SD strongly affects both recent and remote autobiographical recollection. Up-regulation of neocortical regions and functional hippocampal-neocortical connectivity within the autobiographical network may be insufficient to compensate the lifelong episodic memory deficit for patients with extensive hippocampal atrophy.

Autobiographical memory, self, and stress-related psychiatric disorders: which implications in cancer patients?

Autobiographical memory refers to information and memories of personal life events, accumulated since childhood, which enable the construction of a feeling of identity and continuity. Autobiographical memory retrieval is a dynamic and reconstructive process, as mental representations change with the passage of time. This flexible aspect of memory is linked to one's changing self and aspirations over time, that evolve according to our personal status and environment. Hence, any breakdown in the continuity of life involves a distortion of memory. Such distortions can be observed in stress-related psychiatric disorders, such as major depression or post-traumatic stress disorder, where autobiographical memory retrieval is characterized by overgenerality (i.e., the tendency to recall generic memories rather than specific events in response to cue words). Such memory disorders can be observed at different degrees in cancer patients. We will report studies focusing on the above-mentioned psychiatric disorders and cancer, and will attempt to establish a relation with autobiographical memory disturbances. The better understanding of such memory deficits could permit new pathophysiological hypotheses to emerge. Recommendations for future research that will enhance understanding of the factors that contribute to autobiographical memory in cancer are suggested.

"Disorganized in time": impact of bottom-up and top-down negative emotion generation on memory formation among healthy and traumatized adolescents.

"Travelling in time," a central feature of episodic memory is severely affected among individuals with Post Traumatic Stress Disorder (PTSD) with two opposite effects: vivid traumatic memories are unorganized in temporality (bottom-up processes), non-traumatic personal memories tend to lack spatio-temporal details and false recognitions occur more frequently that in the general population (top-down processes). To test the effect of these two types of processes (i.e. bottom-up and top-down) on emotional memory, we conducted two studies in healthy and traumatized adolescents, a period of life in which vulnerability to emotion is particularly high. Using negative and neutral images selected from the international affective picture system (IAPS), stimuli were divided into perceptual images (emotion generated by perceptual details) and conceptual images (emotion generated by the general meaning of the material). Both categories of stimuli were then used, along with neutral pictures, in a memory task with two phases (encoding and recognition). In both populations, we reported a differential effect of the emotional material on encoding and recognition. Negative perceptual scenes induced an attentional capture effect during encoding and enhanced the recollective distinctiveness. Conversely, the encoding of conceptual scenes was similar to neutral ones, but the conceptual relatedness induced false memories at retrieval. However, among individuals with PTSD, two subgroups of patients were identified. The first subgroup processed the scenes faster than controls, except for the perceptual scenes, and obtained similar performances to controls in the recognition task. The second subgroup group desmonstrated an attentional deficit in the encoding task with no benefit from the distinctiveness associated with negative perceptual scenes on memory performances. These findings provide a new perspective on how negative emotional information may have opposite influences on memory in normal and traumatized individuals. It also gives clues to understand how intrusive memories and overgeneralization takes place in PTSD.

Factors affecting medial temporal lobe engagement for past and future episodic events: an ALE meta-analysis of neuroimaging studies.

Remembering the past and envisioning the future are at the core of one's sense of identity. Neuroimaging studies investigating the neural substrates underlying past and future episodic events have been growing in number. However, the experimental paradigms used to select and elicit episodic events vary greatly, leading to disparate results, especially with respect to the laterality and antero-posterior localization of hippocampal and adjacent medial temporal activations (i.e., parahippocampal, entorhinal and perirhinal cortices, amygdala). Although a central concern in today's literature, the issue of hippocampal and medial temporal lobe laterality and antero-posterior segregation in past and future episodic events has not yet been addressed extensively. Using the activation likelihood estimation (ALE) procedure (Turkeltaub, Eden, Jones, & Zeffiro, 2002), we performed a meta-analysis of hippocampal and adjacent medial temporal coordinates extracted from neuroimaging studies examining past remembering and future envisioning. We questioned whether methodological choices could influence the laterality of activations, namely (1) the type of cue used (generic vs. specific), (2) the type of task performed (recognition vs. recall/imagine), (3) the nature of the information retrieved (episodic vs. "strictly" episodic events) and (4) the age of participants. We consider "strictly" episodic events as events which are not only spatio-temporally unique and personal like episodic events, but are also associated with contextual and phenomenological details. These four factors were compared two-by-two, generating eight whole-brain statistical maps. Results indicate that (1) specific cues tend to activate more the right anterior hippocampus compared to the use of generic cues, (2) recall/imagine tasks tend to recruit more the left posterior parahippocampal gyrus compared to recognition tasks, (3) (re/pre)experiencing strictly episodic events tends to activate more the bilateral posterior hippocampus compared to episodic events and (4) older subjects tend to activate more the right anterior hippocampus compared to younger subjects. Importantly, our results stress that strictly episodic events triggered by specific cues elicit greater left posterior hippocampal activation than episodic events triggered by specific cues. These findings suggest that such basic methodological choices have an impact on the conclusions reached regarding past and future (re/pre)experiencing and their neural substrates.

When Higher Activations Reflect Lower Deactivations: A PET Study in Alzheimer's Disease during Encoding and Retrieval in Episodic Memory.

The aim of the present study was to explore the cerebral substrates of episodic memory disorders in Alzheimer's disease (AD) and investigate patients' hyperactivations frequently reported in the functional imaging literature. It remains unclear whether some of these hyperactivations reflect real increased activity or deactivation disturbances in the default mode network (DMN). Using positron emission tomography ((15)O-H(2)O), cerebral blood flow was measured in 11 AD patients and 12 healthy elderly controls at rest and during encoding and stem-cued recall of verbal items. Subtractions analyses between the target and control conditions were performed and compared between groups. The average signal was extracted in regions showing hyperactivation in AD patients versus controls in both contrasts. To determine whether hyperactivations occurred in regions that were activated or deactivated during the memory tasks, we compared signal intensities between the target conditions versus rest. Our results showed reduced activation in AD patients compared to controls in several core episodic memory regions, including the medial temporal structures, during both encoding and retrieval. Patients also showed hyperactivations compared to controls in a set of brain areas. Further analyses conducted on the signal extracted in these areas indicated that most of these hyperactivations actually reflected a failure of deactivation. Indeed, whereas almost all of these regions were significantly more activated at rest than during the target conditions in controls, only one region presented a similar pattern of deactivation in patients. Altogether, our findings suggest that hyperactivations in AD must be interpreted with caution and may not systematically reflect increased activity. Although there has been evidence supporting the existence of genuine compensatory mechanisms, dysfunction within the DMN may be responsible for part of the apparent hyperactivations reported in the literature on AD.