Our lives unfold in space and time—we are able to be aware not only of the present instant but also to recollect the past and imagine the future, and our memories tend to be not instantaneous snapshots but rather bear a temporal, sequential dimension. This faculty of time travel allows us to adjust our current actions in light of what we have previously learned and with respect to what we aspire to become. It depends upon faithful records of our personal experiences, termed episodic memory. While over the last century we have learned a great deal about the molecular changes that support this kind of learning, the circuit-level mechanisms with which the brain implements the formation of episodic memory remain to be discovered. Failures of episodic memory can be catastrophic, and unfortunately, such dysfunction is commonplace in a number of human pathologies. In the neuropsychiatric syndrome of schizophrenia, the capacity to form and utilize episodic memory is compromised, a state of affairs that likely contributes to the difficulty people with schizophrenia have adjusting their actions to meet desired goals. Attempts to understand the pathogenesis of schizophrenia’s memory deficits at the molecular level have yielded frustratingly few leads, making circuit-level inquiries a rational next step. Utilizing a genetic mouse model of schizophrenia susceptibility (Df(16)A+/- mice), we have taken a three-pronged approach to the analysis of the circuit mechanisms and missteps of episodic memory. We first developed a behavioral model of episodic memory, a variation on classical ‘trace’ fear conditioning, which involves the formation of an association between an innocuous stimulus (conditioned stimulus, CS) and a temporally separate aversive stimulus (unconditioned stimulus, US). Next, we turned to a region of the brain known to be required for trace fear conditioning and implicated in the pathogenesis of schizophrenia, dorsal CA1 of the hippocampus. Because network coordination and plasticity in dorsal hippocampal CA1 relies heavily on the activity of soma-targeting, parvalbumin-positive interneurons (PV+ INs), we hypothesized that they may be mediators of the associations built during trace fear conditioning. We therefore sought to characterize their activity during temporal association learning in both wild-type (WT) and Df(16)A+/- mice using two-photon calcium imaging. We simultaneously recorded local field potentials in the contralateral dorsal hippocampus to pair the discrete transformations captured through imaging with information about more global states of hippocampal activity. Finally, we manipulated the activity PV+ INs during various epochs of freely-moving trace fear conditioning to test hypotheses regarding their necessity for trace fear conditioning in healthy and schizophrenia-susceptible mice. We found that Df(16)A+/- mice have severe deficits in trace fear conditioning when compared to mice that do not carry their defining mutation. Calcium imaging of PV+, peri-somatic boutons in dorsal CA1 over the course of trace fear conditioning revealed a marked increase in the number of detected boutons that initiate activity during the presentation of the CS and that sustain their activity across the time gap preceding delivery of the US. This shift in activity was notably absent in recordings from Df(16)A+/- mice. Consistent with the observations of others, analysis of local field potentials indicated that successful learning was associated with modulation of amplitude and theta-phase relation in mid- and fast-gamma frequency oscillations. This modulation was compromised in Df(16)A+/- mice. Finally, we found that inhibition of PV+ INs during encoding in Df(16)A+/- mice restores their response to the CS to near-WT levels of fear expression. Our results support the thesis that temporary downregulation of PV+ IN activity during encoding is essential for the formation of complex, hippocampus-dependent associations including temporal association memory. We suggest that this transient disinhibition may serve to allow for the generation of new pyramidal cell ensembles to represent the associated stimuli. The heightened, sustained inhibition observed during post-learning trials in the calcium imaging experiments is consistent with a transition of the PV+ INs into a role of stabilizing the fledgling memory trace during consolidation. Our results also support the hypothesis that in our model of schizophrenia susceptibility, impairments in learning complex associations may be due to the inability of PV+ INs to modulate their activity appropriately over the changing phases of memory formation. We identify PV+ INs as a promising therapeutic target for schizophrenia as we were able to restore behavior of the susceptible mice during our assay of temporal association memory. Further studies combining pharmacogenetic or optogenetic manipulations with calcium imaging and LFP recording could shed light on the mechanisms of these shifts in network plasticity and may help to identify new approaches to the treatment of the debilitating cognitive deficits associated with schizophrenia.

Two experiments are presented in this dissertation to investigate the effect a schema may have on mnemonic discrimination. We developed stimuli composed of a foreground item on a background that was either schematically congruent or incongruent. For the encoding phase of both experiments, these stimuli were presented to 98 participants, who were tasked with determining the congruency of each foreground-background pair. Next, the two experiments diverged for the retrieval phase, where participants were presented with either the same object as before (Target) or one that was similar (Lure). Forty-six participants in Experiment 1 saw stimuli with the same background as initially presented during the retrieval phase. For Experiment 2, fifty-two participants saw the foreground item presented only on a white background. Behavioral, eye tracking, and whole-brain, high-resolution fMRI data were acquired for both experiments and both phases of the task. We found memory discriminability (d-prime) scores were larger for incongruent stimuli when target-lure pairs were less similar and only when the background was present during retrieval. Critically, we found evidence of recognition in the hippocampal subregions as opposed to lure detection. These findings support the notion of a congruency benefit due to the "generate-and-recognize" model and an incongruency benefit due to increased initial attention.

Two projects are presented in this dissertation. First, we investigated the impact of false memories on the original trace and whether recovery of the original is possible. Second, we tested whether mnemonic discrimination for temporal duration is possible. Both projects incorporated fMRI techniques in order to implicate any potential neural correlates of these memory behaviors. Project One. To elicit false memories and study a potential recovery therefrom, thirty-five healthy, young adults performed multiple recognition memory tests where they were induced to make errors in a first test and then participants were tested again in a surprise, second test. These two tests allowed us to determine which memory error would be corrected, if any. Further, fMRI signal associated with the encoding and retrieval processes during the experiment allowed us to implicate the regions associated with false memory correction. We found that false memories do not overwrite the original trace in all instances, as recovery of the original information was possible. Critically, we determined that recovery of the original information was dependent on activity in regions associated with retrieval, saliency attention, and bottom-up attention during the formation of the false memory, and not on processing at the time of encoding or the second test episode. Project Two. We developed a novel paradigm to test episodic memory for temporal duration. Thirty-five healthy, young adults completed a temporal discrimination task that consisted of a continuous-recognition paradigm in which visual objects were presented one at a time for either 1 or 1.5 seconds. Certain items repeated (Targets and Lures) where Targets were presented for the same duration while the duration of Lures was altered by ±0.5 seconds. Participants were asked to identify whether the stimulus duration changed. Whole-brain high-resolution fMRI data were acquired. Behavioral results indicate that participants were sensitive to both increases and decreases in duration. Further, fMRI analyses revealed that the left entorhinal and perirhinal cortices were differentially involved in encoding and retrieval, respectively, of correct duration representations. These findings support the notion of the entorhinal cortex supporting temporal representations in memory as well as the perirhinal cortex representing the conjunction of item and context.

The purpose of this study was to describe the relationship between mental, physical, and social activity, and episodic memory (EM) of cognitively intact older persons. The specific aims were (a) to describe the relationship between EM and mental, physical, and social activity, (b) to describe the role of gender, marital status, and race on EM, (c) to describe the moderating effects of each activity on the relationship between each of the remaining two activities and EM, and (d) to describe the moderating effects of gender, marital status, and race on the relationship between each activity and EM. Two theoretical frameworks: Cognitive Reserve Theory (Stern, 2002) and Theory of Nursing as Caring (Boykin & Schoenhofer, 1993) guided the study. This study was designed as a correlational and retrospective secondary analysis of data sets from the Health and Retirement Study. The sample consisted of 3,903 cognitively intact persons who were 50 years and older and completed immediate and delayed recall tests in the 2016 HRS and the 2015 Consumptions and Activities Mail Survey. Descriptive statistics included the means for age: 67 (SD 9.54), education:13.85 (SD 5.89), and total cognition 16.86 (SD 3.11). The sample was predominantly Caucasian (78.3%), female (59.8%), and married (60.9%). / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2020. / FAU Electronic Theses and Dissertations Collection

Au cours de cette thèse, nous nous sommes intéressés au fonctionnement de la mémoire autobiographique, permettant de rappeler nos souvenirs personnels. L’autobiographie d’une personne fonde son identité et comporte, outre les souvenirs personnels d’événements singuliers, phénoménologiquement riches et détaillés (souvenirs épisodiques), des connaissances personnelles détachées de tout contexte particulier. Cette dernière composante stocke un ensemble de connaissances très abstraites sur soi et des souvenirs d’événements généraux répétés ou étendus (souvenirs et connaissances sémantisés), issus de sources d’encodage multiples et sans accès spontané à un contexte d’encodage particulier. L’effet de l’âge sur ces différents types de matériels autobiographiques fait l’objet d’études récentes qui ont permis de montrer que les difficultés des sujets âgés sains portent principalement sur les souvenirs épisodiques dont la restitution nécessite une recherche active en mémoire, préservant les souvenirs sémantisés et quelques souvenirs épisodiques, le tout maintenant un sentiment d’identité et de continuité dans le temps. Une autre spécificité du vieillissement cognitif réside dans la nécessité de faire face à certains changements liés à l’identité qui peuvent être déstabilisant, pendant la vieillesse. Dans ce cadre, les souvenirs personnels constituent le matériel brut grâce auquel notre identité peut graduellement se modifier aux grés des différentes étapes de la vie. Le but de ce travail était de spécifier les processus sous-tendant ces modifications liées au vieillissement. Dans ce cadre, nous avons tenté de mieux comprendre la distinction épisodique/sémantique en mémoire autobiographique et le lien entre cette mémoire et le concept d’identité dans le vieillissement normal et dans la maladie d’Alzheimer par le biais du concept de souvenirs définissant le Soi. Nous avons également mené une méta-analyse nous permettant de préciser au niveau neural le processus d’abstraction des souvenirs et de différencier les substrats cérébraux correspondant à la récupération de matériels autobiographiques, mais aussi à la récupération d’informations plus élaborées liées directement à l’identité (jugements personnels liés aux traits de personnalités). Pour terminer, nous présentons des résultats permettant de déterminer les modifications cérébrales liées au vieillissement lors de la récupération de souvenirs autobiographiques épisodiques et sémantisés. L’ensemble de ces résultats nous a permis de proposer de nouvelles pistes de recherche concernant les causes du déclin cognitif associé à la mémoire autobiographique dans le vieillissement, notamment en termes de lien entre mémoire autobiographique et Soi mais également par rapport au rôle des fonctions exécutives et de leurs substrats cérébraux lors du processus de récupération / In this work, we investigated the functioning of autobiographical memory which enables the recall of personal past. Autobiographical memory provides the raw material from which identity is constructed and encompasses various types of knowledge from the general knowledge (i.e., semantic component) of a person’s past comprising abstracted personal information as well as repeated and extended events to very specific personal events (i.e., episodic component) situated in a particular time and space, for which the subject can mentally travel back through subjective time, reliving the encoding context. Several behavioral studies could show that episodic (which necessitate an active research) but not semantic retrieval become less easy to access in aging. Based on their capacity to retrieve semantic memories and some episodic memories, older people ensure a sense of identity and continuity in time. AM contributes to different aspects of identity and the access to personal memories enable the gradual changes of identity throughout lifespan and aging is a particular phase of change. The aim of this work was to investigate the processes underlying cognitive changes in aging. In this framework, we tried to understand more precisely the link between memory retrieval and the Self in normal aging and Alzheimer’s disease studying the Self-defining memories. We also conducted a meta-analysis determining the neural substrates of autobiographical episodic memories, autobiographical semantic memories and self-trait judgments. Finally, we propose fMRI results concerning aging effects on the neural substrates of episodic and semantic autobiographical memory retrieval. Taken together, these results set us on several causes of cognitive decline with aging in the context of autobiographical retrieval; in particular concerning the link between autobiographical memory and the Self and also concerning the role of executive functions during autobiographical retrieval

Cache County and the Wasatch Front, Utah have persistently experienced some of the nation’s worst air quality over the past decade. Elevated PM2.5 concentrations during wintertime “red air day” episodes frequently exceed the National Ambient Air Quality Standards (NAAQS). We investigate the possible effects of two different economic policies in controlling these regional problems. Adapting a model originally developed to calculate the social investment necessary to control nationwide disease outbreaks, we estimate an optimal preventative capital stock (for example, investment in public transportation) of between $4.1 million and $14.1 million to control red air day episodes in Cache County, and $133 million to $1.6 billion dollars to control such episodes in the Wasatch Front. Further, we find that a seasonal gasoline tax rate of roughly $8 per gallon is necessary for policy makers in the Wasatch Front to impose at the pump if their goal is to maintain concentrations below the NAAQS on average during a typical winter-inversion season. This rate is roughly $2 more than the rate calculated for Cache County in a previously published study.

This study investigated memory in children with temporal lobe epilepsy and the ability to discern hippocampal dysfunction with conventional memory tests that are typically used to detect more global memory impairment. All data was obtained retrospectively from the epilepsy surgery program at a local children’s hospital. The research population consisted of 54 children with intractable epilepsy of temporal onset, balanced across pathology types (with and without hippocampal disease) and other demographics. Each was given a clinical battery prior to surgical intervention, which included the WRAML/WRAML2 Verbal Learning subtest from which the dependent variables for this study were extracted. The research hypothesis had predicted that memory retention between verbal learning and recall would be worse for participants with pathology that included hippocampal sclerosis than for those with non-hippocampal temporal lobe pathology. A two-way mixed-design ANOVA was used to test the hypothesis, which allowed incorporation of variables of interest related to memory factors, pathology type, and hemispheric laterality, as well as their various interactions. There was a significant main effect for change in the number of words retained from the final learning trial to the delayed recall. Although the interaction between memory retention and pathology type was not statistically significant, the average of the memory scores as it related to pathology by side did show significance. Thus, results did not support the hypothetical relationship between retention and hippocampal function. However, additional exploratory analyses revealed that the final learning trial by itself was associated with hippocampal pathology, which applied only to those participants with left-hemisphere lesions. Logistic regression with the final learning trial correctly classified 74 percent of participants into the appropriate pathology category, with 81 percent sensitivity to hippocampal dysfunction. Mean participant memory scores were nearly one standard deviation below the normative mean for both delayed recall and total learning scaled scores, regardless of pathology type or lesion hemisphericity. Thus, while the conventionally used indices of the WRAML Verbal Learning test are useful for determining overall memory status, they are not specific to pathological substrate. The within-subject main effect showed an expected loss of information across the time of the delay, but overall the recall score showed no association with hippocampal functioning. This study revealed the possibility of measuring hippocampal function at statistically significant group levels using learning scores from a widely used measure of verbal memory, even in participants with intact contralateral mesial temporal structures. It also indicated that hippocampal structures do not play a role during recall measures given after a standard time delay. Data further demonstrated a role of the hippocampus for encoding and transferring information beyond short term/working memory into long term. During the learning process, the hippocampus appears to work in concert with short-term memory systems, but does not take over the encoding process until enough repetitions have occurred to saturate the working memory buffer. This research represents a small, yet important step forward in our understanding of the hippocampus, with potentially important implications for the future study of memory constructs and mensuration.

Gestures have been shown to enhance memory recall for children and adults, but little research has investigated the benefits of gesturing to recall in older adult populations. While theory suggests that older adults may be less embodied, that their cognitive and perceptual processes may be less grounded in their sensorimotor capacities, the literature is unclear on whether or not gesturing is still associated with memory in this population. To test the effect of gesturing on recall we compare 58 younger (20-29 yrs) and 62 older (60-85yrs) adults’ performance on an episodic memory recall task (immediately, and at a 3-week delay) after randomly assigning participants to two conditions (instructed gesture or free gesture). In the free gesture condition participants were allowed to freely gesture while describing 26 3-second-long vignettes. Participants in the instructed gesture condition were additionally asked to provide meaningful gestures while providing descriptions to vignettes. Analyzing observational data from the free gesture conditions, we found that both immediately and at a delay, younger and older adults recalled more of the vignettes that they had spontaneously gestured for than those that they had not gestured for. When looking at the effects of instructing gesture, we found that asking older adults to gesture increased their overall recall of vignettes at a delay when compared to older adults left to freely gesture. The same increase to recall was not found for younger adults. These findings suggest that spontaneous gesturing at encoding is just as significant to episodic memory recall for older adults as it is for younger adults, and that asking older adults to gesture may additionally benefit episodic memory for older adults.

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