Marie St-Laurent

Determinants of autobiographical memory in patients with unilateral temporal lobe epilepsy or excisions

Patients with unilateral temporal lobe epilepsy from hippocampal origin and patients with unilateral surgical excision of an epileptic focus located in the medial temporal lobe were compared to healthy controls on a version of the Autobiographical Interview (AI) adapted to assess memory for event-specific and generic personal episodes. For both types of episodes, patients with unilateral (left and right) temporal lobe epilepsy or excision (TLE) reported fewer internal details, which are bits of information pertaining to the recollected episode. The source of this deficit was mainly the paucity of perceptual information about the personal episodes, but temporal and spatial information was also deficient. Information about the episodes story elements was preserved in both AM conditions. Participants were also tested on a script generation task to assess retrieval of semantic information. Patients with TLE excision, but not pre-surgical patients, reported significantly fewer actions per script in comparison to controls, suggesting that the temporal neocortex is more involved than mesial temporal structures in recall of this type of information. Together, these results indicate that the hippocampus is essential to the recollection of sensory perceptual aspects of past experiences. Detailed story elements and gist information, as collected during the AI and the script generation task, respectively, are more resilient to hippocampal damage. The similarity of the impairment between the event-specific and the generic memory conditions also suggests that temporal specificity is not a key determinant of hippocampal engagement in autobiographical retrieval.

Influence of aging on the neural correlates of autobiographical, episodic, and semantic memory retrieval

We used fMRI to assess the neural correlates of autobiographical, semantic, and episodic memory retrieval in healthy young and older adults. Participants were tested with an event-related paradigm in which retrieval demand was the only factor varying between trials. A spatio-temporal partial least square analysis was conducted to identify the main patterns of activity characterizing the groups across conditions. We identified brain regions activated by all three memory conditions relative to a control condition. This pattern was expressed equally in both age groups and replicated previous findings obtained in a separate group of younger adults. We also identified regions whose activity differentiated among the different memory conditions. These patterns of differentiation were expressed less strongly in the older adults than in the young adults, a finding that was further confirmed by a barycentric discriminant analysis. This analysis showed an age-related dedifferentiation in autobiographical and episodic memory tasks but not in the semantic memory task or the control condition. These findings suggest that the activation of a common memory retrieval network is maintained with age, whereas the specific aspects of brain activity that differ with memory content are more vulnerable and less selectively engaged in older adults. Our results provide a potential neural mechanism for the well-known age differences in episodic/autobiographical memory, and preserved semantic memory, observed when older adults are compared with younger adults.

Spatial conditional associative learning: effects of thalamo-hippocampal disconnection in rats.

Unilateral lesions to the anterior thalamic nuclei (ATN) and the hippocampus (H) were made in opposite hemispheres in the rat to examine whether these brain structures form part of a functional neural pathway underlying spatial learning and memory. In the first experiment, rats were tested on a spatial-visual conditional associative task in which they had to learn to approach one of two stimuli depending on the spatial context in which the stimuli were embedded. The rats were subsequently trained on delayed forced alternation, a spatial working memory task known to be sensitive to the effects of ATNxH damage. Rats with ATNxH lesions were impaired in the acquisition of both tasks in comparison with normal control animals. The findings support the idea that the anterior thalamic nuclei and the hippocampus are critical components of an anatomical system subserving spatial memory and suggest that these brain regions work in a dependent fashion during the performance of certain spatial learning tasks.

Functional and Effective Hippocampal–Neocortical Connectivity During Construction and Elaboration of Autobiographical Memory Retrieval

Autobiographical memory (AM) provides the opportunity to study interactions among brain areas that support the search for a specific episodic memory (construction), and the later experience of mentally reliving it (elaboration). While the hippocampus supports both construction and elaboration, it is unclear how hippocampal-neocortical connectivity differs between these stages, and how this connectivity involves the anterior and posterior segments of the hippocampus, as these have been considered to support the retrieval of general concepts and recollection processes, respectively. We acquired fMRI data in 18 healthy participants during an AM retrieval task in which participants were asked to access a specific AM (construction) and then to recollect it by recovering as many episodic details as possible (elaboration). Using multivariate analytic techniques, we examined changes in functional and effective connectivity of hippocampal-neocortical interactions during these phases of AM retrieval. We found that the left anterior hippocampus interacted with frontal areas during construction and bilateral posterior hippocampi with visual perceptual areas during elaboration, indicating key roles for both hippocampi in coordinating transient neocortical networks at both AM stages. Our findings demonstrate the importance of direct interrogation of hippocampal-neocortical interactions to better illuminate the neural dynamics underlying complex cognitive tasks such as AM retrieval.

Distributed patterns of reactivation predict vividness of recollection

According to the principle of reactivation, memory retrieval evokes patterns of brain activity that resemble those instantiated when an event was first experienced. Intuitively, one would expect neural reactivation to contribute to recollection (i.e., the vivid impression of reliving past events), but evidence of a direct relationship between the subjective quality of recollection and multiregional reactivation of item-specific neural patterns is lacking. The current study assessed this relationship using fMRI to measure brain activity as participants viewed and mentally replayed a set of short videos. We used multivoxel pattern analysis to train a classifier to identify individual videos based on brain activity evoked during perception and tested how accurately the classifier could distinguish among videos during mental replay. Classification accuracy correlated positively with memory vividness, indicating that the specificity of multivariate brain patterns observed during memory retrieval was related to the subjective quality of a memory. In addition, we identified a set of brain regions whose univariate activity during retrieval predicted both memory vividness and the strength of the classifiers prediction irrespective of the particular video that was retrieved. Our results establish distributed patterns of neural reactivation as a valid and objective marker of the quality of recollection.

Does the cingulate cortex contribute to spatial conditional associative learning in the rat

Rats with lesions to the anterior or posterior (retrosplenial) region of the cingulate cortex and rats with lesions that included both the anterior and posterior cingulate cortex were tested on a visual–spatial conditional task in which they had to learn to approach one of the two objects depending on the spatial context within which they were embedded. Lesions restricted to either the anterior or the retrosplenial cingulate region did not impair learning of this task which is known to be very sensitive to the effects of hippocampal lesions. Complete lesions of the cingulate cortex gave rise to only a minor retardation in learning. In contrast, lesions to the retrosplenial cortex impaired performance on a spatial navigation task and the classic radial maze. These results suggest that the retrosplenial portion of the cingulate region forms part of a hippocampal circuit underlying learning about spatial responses. The dissociation between the effects of lesions of the cingulate region on different classes of behavior known to be associated with hippocampal function suggests that, although this neural structure does play a role in an extended hippocampal circuit underlying spatial learning, its role in such learning may be a selective one.

Social inference deficits in temporal lobe epilepsy and lobectomy: risk factors and neural substrates

In temporal lobe epilepsy and lobectomy, deficits in emotion identification have been found consistently, but there is limited evidence for complex social inference skills such as theory of mind. Furthermore, risk factors and the specific neural underpinnings of these deficits in this population are unclear. We investigated these issues using a comprehensive range of social inference tasks (emotion identification and comprehension of sincere, deceitful and sarcastic social exchanges) in individuals with temporal lobe epilepsy or lobectomy (n = 87). We observed deficits across patient groups which were partly related to the presence of mesial temporal lobe sclerosis, early age of seizure onset and left lobectomy. A voxel-based morphometry analysis conducted in the pre-operative group confirmed the importance of the temporal lobe by showing a relationship between left hippocampal atrophy and overall social inference abilities, and between left anterior neocortex atrophy and sarcasm comprehension. These findings are in keeping with theoretical proposals that the hippocampus is critical for binding diverse elements in cognitive domains beyond canonical episodic memory operations, and that the anterior temporal cortex is a convergence zone of higher-order perceptual and emotional processes, and of stored representations. As impairments were frequent, we require further investigation of this behavioural domain and its impact on the lives of people with epilepsy.

Using multivariate data reduction to predict postsurgery memory decline in patients with mesial temporal lobe epilepsy

Predicting postsurgery memory decline is crucial to clinical decision-making for individuals with mesial temporal lobe epilepsy (mTLE) who are candidates for temporal lobe excisions. Extensive neuropsychological testing is critical to assess risk, but the numerous test scores it produces can make deriving a formal prediction of cognitive change quite complex. In order to benefit from the information contained in comprehensive memory assessment, we used principal component analysis (PCA) to simplify neuropsychological test scores (presurgical and pre- to postsurgical change) obtained from a cohort of 56 patients with mTLE into a few easily interpretable latent components. We next performed discriminant analyses using presurgery latent components to categorize seizure laterality and then regression analyses to assess how well presurgery latent components could predict postsurgery memory decline. Finally, we validated the predictive power of these regression models in an independent sample of 18 patients with mTLE. Principal component analysis identified three significant latent components that reflected IQ, verbal memory, and visuospatial memory, respectively. Together, the presurgery verbal and visuospatial memory components classified 80% of patients with mTLE correctly according to their seizure laterality. Furthermore, the presurgery verbal memory component predicted postsurgery verbal memory decline, while the presurgery visuospatial memory component predicted visuospatial memory decline. These regression models also predicted postsurgery memory decline successfully in the independent cohort of patients with mTLE. Our results demonstrate the value of data reduction techniques in identifying cognitive metrics that can characterize laterality of damage and risk of postoperative decline.

Age differences in brain activity related to unsuccessful declarative memory retrieval

Although memory recall is known to be reduced with normal aging, little is known about the patterns of brain activity that accompany these recall failures. By assessing faulty memory, we can identify the brain regions engaged during retrieval attempts in the absence of successful memory and determine the impact of aging on this functional activity. We used functional magnetic resonance imaging to examine age differences in brain activity associated with memory failure in three memory retrieval tasks: autobiographical (AM), episodic (EM) and semantic (SM). Compared to successful memory retrieval, both age groups showed more activity when they failed to recall a memory in regions consistent with the salience network (SLN), a brain network also associated with non-memory errors. Both groups also showed strong functional coupling among SLN regions during incorrect trials and in intrinsic patterns of functional connectivity. In comparison to young adults, older adults demonstrated (1) less activity within the SLN during unsuccessful AM trials; (2) weaker intrinsic functional connectivity between SLN nodes and dorsolateral prefrontal cortex; and (3) less differentiation of SLN functional connectivity during incorrect trials across memory conditions. These results suggest that the SLN is engaged during recall failures, as it is for non-memory errors, which may be because errors in general have particular salience for adapting behavior. In older adults, the dedifferentiation of functional connectivity within the SLN across memory conditions and the reduction of functional coupling between it and prefrontal cortex may indicate poorer inter-network communication and less flexible use of cognitive control processes, either while retrieval is attempted or when monitoring takes place after retrieval has failed. This article is part of a Special Issue entitled SI: Memory & Aging.

Changes in patterns of neural activity underlie a time-dependent transformation of memory in rats and humans

The dynamic process of memory consolidation involves a reorganization of brain regions that support a memory trace over time, but exactly how the network reorganizes as the memory changes remains unclear. We present novel converging evidence from studies of animals (rats) and humans for the time‐dependent reorganization and transformation of different types of memory as measured both by behavior and brain activation. We find that context‐specific memories in rats, and naturalistic episodic memories in humans, lose precision over time and activity in the hippocampus decreases. If, however, the retrieved memories retain contextual or perceptual detail, the hippocampus is engaged similarly at recent and remote timepoints. As the interval between the timepoint increases, the medial prefrontal cortex is engaged increasingly during memory retrieval, regardless of the context or the amount of retrieved detail. Moreover, these hippocampal‐frontal shifts are accompanied by corresponding changes in a network of cortical structures mediating perceptually‐detailed as well as less precise, schematic memories. These findings provide cross‐species evidence for the crucial interplay between hippocampus and neocortex that reflects changes in memory representation over time and underlies systems consolidation.