Lee Ryan

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• Grilli, M. D., Ryan, L., & Ryan, T. L. (2020). Autobiographical Memory and the Self-Concept. In Neuroscience of Enduring Change(pp 189-212). Oxford University Press. doi:10.1093/OSO/9780190881511.003.0008
• Ryan, L., Alexander, G. E., & Ryan, T. L. (2008). Neuroimaging: Overview of methods and applications. In Handbook of Physiological Research Methods in Health Psychology(pp 371-394). SAGE Publications Inc. doi:10.4135/9781412976244.N17
• Moscovitch, M., Westmacott, R., Gilboa, A., Viskontas, I., Priselac, S., Svoboda, E., Ziegler, M., Black, S. E., Gao, F., Grady, C. L., Freedman, M., Kohler, S., Leach, L., Levine, B., Nadel, L., Proulx, G. B., Richards, B., Ryan, L., Stokes, K. A., , Winocur, G., et al. (2005). Hippocampal Complex Contribution to Retention and Retrieval of Recent and Remote Episodic and Semantic Memories: Evidence from Behavioral and Neuroimaging Studies of Healthy and Brain-Damaged People. In Dynamic Cognitive Processes(pp 333-380). Springer, Tokyo. doi:10.1007/4-431-27431-6_14
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  For over a hundred years, it has been accepted that remote memories are less vulnerable to disruption than are recent memories. The standard consolidation model posits that the hippocampus and related structures are temporary memory structures, necessary for acquisition, retention, and retrieval of all explicit (declarative) memories until they are consolidated elsewhere in the brain. We review lesion and neuroimaging evidence showing that important distinctions exist among different types of explicit memory and the structures that mediate them. We argue that retention and retrieval of detailed, vivid autobiographical memories depend on the hippocampal system no matter how long ago they were acquired. Semantic memories, on the other hand, benefit from hippocampal contribution for some time before they can be retrieved independently of the hippocampus. Even semantic memories, however, can have episodic elements associated with them which continue to depend on the hippocampus. In short, the evidence reviewed suggests strongly that the function of the hippocampus (and possibly of related limbic structures) is to help encode, retain, and retrieve experiences, no matter how long ago the events comprising the experience occurred. We conclude that the evidence favors a multiple trace theory (MTT) of memory over the traditional model, and we indicate what future work is needed to resolve disputes.
• Heaton, R. K., Heaton, R. K., Ryan, L., Grant, I., Grant, I., Matthews, C. G., & Ryan, T. L. (1996). Demographic influences on neuropsychological test performance.. In Neuropsychological assessment of neuropsychiatric disorders(pp 141–163). Oxford University Press.
• Macaulay, D., Eich, E., & Ryan, T. L. (1993). Mood Dependence in Implicit and Explicit Memory. In Implicit memory: New directions in cognition, development, and neuropsychology(pp 75–94). Lawrence Erlbaum Associates, Inc. doi:10.4324/9781315807034-9

Journals/Publications

• Matijevic, S., Andrews-Hanna, J. R., Wank, A. A., Ryan, L., & Grilli, M. D. (2022). Individual differences in the relationship between episodic detail generation and resting state functional connectivity vary with age. Neuropsychologia, 166, 108138.
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  The ability to generate episodic details while recollecting autobiographical events is believed to depend on a collection of brain regions that form a posterior medial network (PMN). How age-related differences in episodic detail generation relate to the PMN, however, remains unclear. The present study sought to examine individual differences, and the role of age, in PMN resting state functional connectivity (rsFC) associations with episodic detail generation. Late middle-aged and older adults (N = 41, ages 52-81), and young adults (N = 21, ages 19-35) were asked to describe recent personal events, and these memory narratives were coded for episodic, semantic and 'miscellaneous' details. Independent components analysis and regions-of-interest analyses were used to assess rsFC within the PMN separately for anterior connections (hippocampal and medial prefrontal) and posterior connections (hippocampal, parahippocampal and parieto-occipital), as these connections purportedly serve different functional roles in episodic detail generation. Compared to younger adults, older adults produced memory narratives with lower episodic specificity (ratio of episodic:total details) and a greater amount of semantic detail. Among the older adults, episodic detail amounts and episodic specificity were reduced with increasing age. There were no significant age differences in PMN rsFC. Stronger anterior PMN rsFC was related to lower episodic detail in the older adult group, but not in the young. Among the older adults, increasing age brought on an association between increased anterior PMN rsFC and reduced episodic specificity. In contrast, increasing age brought on an association between increased posterior PMN rsFC and increased semantic detail. The present study provides evidence that functional connectivity within the PMN, particularly anterior PMN, tracks individual differences in the amount of episodic details retrieved by older adults. Furthermore, these brain-behavior relationships appear to be age-specific, indicating that some process within aging alters the nature of how anterior PMN rsFC and episodic detail relate to each other. Whether this process entails an age-related loss of integrity to the PMN, or an age-related shift toward semantic retrieval, remains to be determined.
• Grilli, M. D., Wank, A. A., Huentelman, M. J., & Ryan, L. (2021). Autobiographical Memory Fluency Reductions in Cognitively Unimpaired Middle-Aged and Older Adults at Increased Risk for Alzheimer's Disease Dementia. Journal of the International Neuropsychological Society : JINS, 1-11.
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  Recent research has revealed that cognitively unimpaired older adults who are at higher risk for developing Alzheimer's disease (AD) dementia often exhibit subtle cognitive alterations in their neuropsychological profiles. Emerging evidence suggests that autobiographical memory, which is memory for personal events and knowledge, may be sensitive to early AD-related cognitive alterations. In the present study, we investigated whether the rapid generation of autobiographical memory category exemplars, a retrieval process that taxes the neural network that is vulnerable to early AD, is compromised in cognitively unimpaired middle-aged and older carriers of the e4 allele of the apolipoprotein E gene (APOE4), which increases risk for AD dementia.
• Hay, M., Ryan, L., Huentelman, M., Konhilas, J., Hoyer-Kimura, C., Beach, T. G., Serrano, G. E., Reiman, E. M., Blennow, K., Zetterberg, H., & Parthasarathy, S. (2021). Serum Neurofilament Light is elevated in COVID-19 Positive Adults in the ICU and is associated with Co-Morbid Cardiovascular Disease, Neurological Complications, and Acuity of Illness. Cardiology and cardiovascular medicine, 5(5), 551-565.
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  In critically ill COVID-19 patients, the risk of long-term neurological consequences is just beginning to be appreciated. While recent studies have identified that there is an increase in structural injury to the nervous system in critically ill COVID-19 patients, there is little known about the relationship of COVID-19 neurological damage to the systemic inflammatory diseases also observed in COVID-19 patients. The purpose of this pilot observational study was to examine the relationships between serum neurofilament light protein (NfL, a measure of neuronal injury) and co-morbid cardiovascular disease (CVD) and neurological complications in COVID-19 positive patients admitted to the intensive care unit (ICU). In this observational study of one-hundred patients who were admitted to the ICU in Tucson, Arizona between April and August 2020, 89 were positive for COVID-19 (COVID-pos) and 11 was COVID-negative (COVID-neg). A healthy control group (n=8) was examined for comparison. The primary outcomes and measures were subject demographics, serum NfL, presence and extent of CVD, diabetes, sequential organ failure assessment score (SOFA), presence of neurological complications, and blood chemistry panel data. COVID-pos patients in the ICU had significantly higher mean levels of Nfl (229.6 ± 163 pg/ml) compared to COVID-neg ICU patients (19.3 ± 5.6 pg/ml), Welch's t-test, p =.01 and healthy controls (12.3 ± 3.1 pg/ml), Welch's t-test p =.005. Levels of Nfl in COVID-pos ICU patients were significantly higher in patients with concomitant CVD and diabetes (n=35, log Nfl 1.6±.09), and correlated with higher SOFA scores (r=.5, p =.001). These findings suggest that in severe COVID-19 disease, the central neuronal and axonal damage in these patients may be driven, in part, by the level of systemic cardiovascular disease and peripheral inflammation. Understanding the contributions of systemic inflammatory disease to central neurological degeneration in these COVID-19 survivors will be important to the design of interventional therapies to prevent long-term neurological and cognitive dysfunction.
• Hooyman, A., Talboom, J. S., DeBoth, M. D., Ryan, L., Huentelman, M. J., & Schaefer, S. Y. (2021). Remote, Unsupervised Functional Motor Task Evaluation in Older Adults across the United States Using the MindCrowd Electronic Cohort. Developmental neuropsychology, 46(6), 435-446.
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  COVID-19 has impacted the ability to evaluate motor function in older adults, as motor assessments typically require face-to-face interaction. One hundred seventy-seven older adults nationwide completed an unsupervised functional upper-extremity assessment at home. Data were compared to data from an independent sample of community-dwelling older adults (N = 250) assessed in lab. The effect of age on performance was similar between the in-lab and at-home groups. Practice effects were also similar. Assessing upper-extremity motor function remotely is feasible and reliable in community-dwelling older adults. This test offers a practical solution for telehealth practice and other research involving remote or geographically isolated individuals.
• Hooyman, A., Talboom, J. S., DeBoth, M. D., Ryan, L., Huentelman, M., & Schaefer, S. Y. (2021). Remote, unsupervised functional motor task evaluation in older adults across the United States using the MindCrowd electronic cohort. medRxiv : the preprint server for health sciences.
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  The COVID-19 pandemic has impacted the ability to evaluate motor function in older adults, as motor assessments typically require face-to-face interaction. This study tested whether motor function can be assessed at home. One hundred seventy-seven older adults nationwide (recruited through the MindCrowd electronic cohort) completed a brief functional upper-extremity assessment at home and unsupervised. Performance data were compared to data from an independent sample of community-dwelling older adults (N=250) assessed by an experimenter in-lab. The effect of age on performance was similar between the in-lab and at-home groups for both the dominant and non-dominant hand. Practice effects were also similar between the groups. Assessing upper-extremity motor function remotely is feasible and reliable in community-dwelling older adults. This test offers a practical solution in response to the COVID-19 pandemic and telehealth practice and other research involving remote or geographically isolated individuals.
• Lewis, C. R., Talboom, J. S., De Both, M. D., Schmidt, A. M., Naymik, M. A., Håberg, A. K., Rundek, T., Levin, B. E., Hoscheidt, S., Bolla, Y., Brinton, R. D., Hay, M., Barnes, C. A., Glisky, E., Ryan, L., & Huentelman, M. J. (2021). Smoking is associated with impaired verbal learning and memory performance in women more than men. Scientific reports, 11(1), 10248.
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  Vascular contributions to cognitive impairment and dementia (VCID) include structural and functional blood vessel injuries linked to poor neurocognitive outcomes. Smoking might indirectly increase the likelihood of cognitive impairment by exacerbating vascular disease risks. Sex disparities in VCID have been reported, however, few studies have assessed the sex-specific relationships between smoking and memory performance and with contradictory results. We investigated the associations between sex, smoking, and cardiovascular disease with verbal learning and memory function. Using MindCrowd, an observational web-based cohort of ~ 70,000 people aged 18-85, we investigated whether sex modifies the relationship between smoking and cardiovascular disease with verbal memory performance. We found significant interactions in that smoking is associated with verbal learning performance more in women and cardiovascular disease more in men across a wide age range. These results suggest that smoking and cardiovascular disease may impact verbal learning and memory throughout adulthood differently for men and women.
• Matijevic, S., & Ryan, L. (2021). Tract Specificity of Age Effects on Diffusion Tensor Imaging Measures of White Matter Health. Frontiers in aging neuroscience, 13, 628865.
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  Well-established literature indicates that older adults have poorer cerebral white matter integrity, as measured through diffusion tensor imaging (DTI). Age differences in DTI have been observed widely across white matter, although some tracts appear more sensitive to the effects of aging than others. Factors like APOE ε4 status and sex may contribute to individual differences in white matter integrity that also selectively impact certain tracts, and could influence DTI changes in aging. The present study explored the degree to which age, APOE ε4, and sex exerted global vs. tract specific effects on DTI metrics in cognitively healthy late middle-aged to older adults. Data from 49 older adults (ages 54-92) at two time-points separated by approximately 2.7 years were collected. DTI metrics, including fractional anisotropy (FA) and mean diffusivity (MD), were extracted from nine white matter tracts and global white matter. Results showed that across timepoints, FA and MD increased globally, with no tract-specific changes observed. Baseline age had a global influence on both measures, with increasing age associated with lower FA and higher MD. After controlling for global white matter FA, age additionally predicted FA for the genu, callosum body, inferior fronto-occipital fasciculus (IFOF), and both anterior and posterior cingulum. Females exhibited lower global FA on average compared to males. In contrast, MD was selectively elevated in the anterior cingulum and superior longitudinal fasciculus (SLF), for females compared to males. APOE ε4 status was not predictive of either measure. In summary, these results indicate that age and sex are associated with both global and tract-specific alterations to DTI metrics among a healthy older adult cohort. Older women have poorer white matter integrity compared to older men, perhaps related to menopause-induced metabolic changes. While age-related alterations to white matter integrity are global, there is substantial variation in the degree to which tracts are impacted, possibly as a consequence of tract anatomical variability. The present study highlights the importance of accounting for global sources of variation in DTI metrics when attempting to investigate individual differences (due to age, sex, or other factors) in specific white matter tracts.
• McKinnon, A. C., Stickel, A., & Ryan, L. (2021). Cardiovascular risk factors and APOE-ε4 status affect memory functioning in aging via changes to temporal stem diffusion. Journal of neuroscience research, 99(2), 502-517.
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  Prior research investigating associations between hypertension, obesity, and apolipoprotein (APOE) genotype status with memory performance among older adults has yielded inconsistent results. This may reflect, in part, a lack of first accounting for the effects these variables have on structural brain changes, that in turn contribute to age-related memory impairment. The current study sought to clarify the relationships between these factors via path modeling. We hypothesized that higher body mass index (BMI), hypertension, and being an APOE-ε4 allele carrier would predict poorer memory scores, with much of these effects accounted for by indirect effects operating via differences in the integrity of temporal stem white matter. Participants included 125 healthy older adults who underwent neuropsychological assessment and diffusion-weighted MRI scanning. Direct effects were found for hypertension and demographic variables including age, sex, and education. Importantly, indirect effects were found for BMI, hypertension, APOE-ε4 status, age, and sex, where these factors predicted memory scores via their impact on temporal stem diffusion measures. There was also a dual effect of sex, with a direct effect indicating that females had better memory performance overall, and an indirect effect indicating that females with greater temporal stem diffusion had poorer memory performance. Results suggest that changes to the integrity of temporal white matter in aging may underpin reduced memory performance. These results highlight that accounting for variables that not only directly impact cognition, but also for those that indirectly impact cognition via structural brain changes, is crucial for understanding the impact of risk factors on cognition.
• Stickel, A. M., McKinnon, A. C., Matijevic, S., Grilli, M. D., Ruiz, J., & Ryan, L. (2021). Apolipoprotein E ε4 Allele-Based Differences in Brain Volumes Are Largely Uniform Across Late Middle Aged and Older Hispanic/Latino- and Non-Hispanic/Latino Whites Without Dementia. Frontiers in aging neuroscience, 13, 627322.
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  Hispanics/Latinos are at an equal or a greater risk for Alzheimer's disease (AD), yet risk factors remain more poorly characterized as compared to non-Hispanic/Latino Whites. Among non-Hispanic/Latino White cohorts, the apolipoprotein E (APOE) ε4 allele is one of the strongest risk factors for AD with subtle declines in episodic memory and brain volumes detectable in the preclinical stages. We examined whether the APOE ε4 status had a differential impact on cognition and brain volumes among cognitively healthy and mild cognitively impaired Hispanics/Latinos ( = 86; ε4 = 23) compared to a well-matched group of non-Hispanic/Latino Whites ( = 92; ε4 = 29). Neither the APOE ε4 status nor the interaction between the ε4 status and ethnicity was associated with cognitive performance. The APOE ε4 status was associated with white matter and not with gray matter volumes. APOE ε4 carriers had a significantly smaller total brain white matter volumes, as well as smaller right middle temporal and left superior temporal volumes. The Hispanics/Latinos had significantly smaller left middle frontal gray matter volumes, yet marginally larger overall white matter volumes, than the non-Hispanic/Latino Whites. Exploratory analysis within the Hispanic/Latino sample found that those people whose primary language was Spanish had larger total brain white matter volumes compared primarily to the English speakers. Importantly, primary language differences only held for Hispanic/Latino ε4 carriers and did not differentiate Hispanic/Latino non-carriers, underscoring the need for further investigation into the impacts of language and acculturation on cognitive aging among the fastest growing ethnic minority group in the United States.
• Talboom, J. S., De Both, M. D., Naymik, M. A., Schmidt, A. M., Lewis, C. R., Jepsen, W. M., Håberg, A. K., Rundek, T., Levin, B. E., Hoscheidt, S., Bolla, Y., Brinton, R. D., Schork, N. J., Hay, M., Barnes, C. A., Glisky, E., Ryan, L., & Huentelman, M. J. (2021). Two separate, large cohorts reveal potential modifiers of age-associated variation in visual reaction time performance. NPJ aging and mechanisms of disease, 7(1), 14.
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  To identify potential factors influencing age-related cognitive decline and disease, we created MindCrowd. MindCrowd is a cross-sectional web-based assessment of simple visual (sv) reaction time (RT) and paired-associate learning (PAL). svRT and PAL results were combined with 22 survey questions. Analysis of svRT revealed education and stroke as potential modifiers of changes in processing speed and memory from younger to older ages (n = 75,666, n = 47,700, n = 27,966; ages 18-85 years old, mean (M) = 46.54, standard deviation (SD) = 18.40). To complement this work, we evaluated complex visual recognition reaction time (cvrRT) in the UK Biobank (n = 158,249 n = 89,333 n = 68,916; ages 40-70 years old, M = 55.81, SD = 7.72). Similarities between the UK Biobank and MindCrowd were assessed using a subset of MindCrowd (UKBb MindCrowd) selected to mirror the UK Biobank demographics (n = 39,795, n = 29,640, n = 10,155; ages 40-70 years old, M = 56.59, SD = 8.16). An identical linear model (LM) was used to assess both cohorts. Analyses revealed similarities between MindCrowd and the UK Biobank across most results. Divergent findings from the UK Biobank included (1) a first-degree family history of Alzheimer's disease (FHAD) was associated with longer cvrRT. (2) Men with the least education were associated with longer cvrRTs comparable to women across all educational attainment levels. Divergent findings from UKBb MindCrowd included more education being associated with shorter svRTs and a history of smoking with longer svRTs from younger to older ages.
• Barnes, C. A., Ryan, L., & Peterson, M. A. (2020). Nadel special issue introduction. Hippocampus, 30(8), 773-775.
• Glisky, E. L., Alexander, G. E., Hou, M., Kawa, K., Woolverton, C. B., Zigman, E. K., Nguyen, L. A., Haws, K., Figueredo, A. J., & Ryan, L. (2021). Differences between young and older adults in unity and diversity of executive functions. Neuropsychology, development, and cognition. Section B, Aging, neuropsychology and cognition, 1-26.
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  Miyake and colleagues (2000) identified three independent but correlated components of executive function in young adults - set shifting, inhibition, and updating. The present study compared the factor structure in young adults to two groups of older adults (ages 60-73 and 74-98). A three-factor model of shifting, inhibition and updating was confirmed in young adults, but the factors were weakly or uncorrelated. In both older groups, a two-factor solution was indicated, updating/inhibition and shifting, which were moderately correlated in young-older adults, and strongly correlated in the old-older group. A nested factors model in the oldest group revealed a common factor, which loaded on all but one of the tests, and a shifting-specific factor. We concluded that in young adulthood, shifting, updating and inhibition may operate relatively independently. As people age and processing becomes less efficient, they may rely increasingly on general executive control processes, reallocating their limited resources to optimize performance.
• Hay, M., Barnes, C., Huentelman, M., Brinton, R., & Ryan, L. (2020). Hypertension and Age-Related Cognitive Impairment: Common Risk Factors and a Role for Precision Aging. Current hypertension reports, 22(10), 80.
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  Precision Aging® is a novel concept that we have recently employed to describe how the model of precision medicine can be used to understand and define the multivariate risks that drive age-related cognitive impairment (ARCI). Hypertension and cardiovascular disease are key risk factors for both brain function and cognitive aging. In this review, we will discuss the common mechanisms underlying the risk factors for both hypertension and ARCI and how the convergence of these mechanisms may be amplified in an individual to drive changes in brain health and accelerate cognitive decline.
• Lawrence, A. V., Cardoza, J., & Ryan, L. (2020). Medial temporal lobe regions mediate complex visual discriminations for both objects and scenes: A process-based view. Hippocampus, 30(8), 879-891.
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  Debate continues regarding the role of medial temporal lobe regions in object and scene processing. Considerable evidence indicates that the perirhinal cortex (PRC) plays an important role in the perception of objects-namely, in disambiguating complex objects that share conjunctions of features. These findings support a content-specific view of medial temporal lobe functioning in which PRC is critically important for processing complex objects, while the parahippocampal cortex (PHC) and hippocampus (HC) may be selectively engaged during scene processing. However, emerging evidence from both animal and human studies suggest that the PRC is sensitive to spatial configural information as well as object information. In this fMRI study, we observed preliminary evidence for BOLD activation in the PRC during a complex visual discrimination task for objects and scenes, as well as robust activation for both stimulus types in PHC and HC. The results are discussed in light of a recent process-based model of medial temporal lobe functioning.
• Memel, M., Wank, A. A., Ryan, L., & Grilli, M. D. (2020). The relationship between episodic detail generation and anterotemporal, posteromedial, and hippocampal white matter tracts. Cortex; a journal devoted to the study of the nervous system and behavior, 123, 124-140.
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  Episodic details populate autobiographical memories with vivid representations of people, objects, and event happenings, and they link events to a specific time and place. Episodic detail generation is believed to be a function of medial temporal lobe (MTL)-cortical interaction, but much remains unclear about how this retrieval process unfolds. In the present study, we combined an autobiographical interview and diffusion magnetic resonance imaging to investigate the relationships of two types of episodic detail, namely details about entities of an event (people and objects) or "event elements" and details about spatiotemporal context, to the integrity of anterotemporal (uncinate fasciculus; UF) and posteromedial (cingulum bundle; CB) cortical pathways. We also measured the relationships of these detail types to the fornix, and the relationship between non-episodic details and these tracts. We found that only episodic detail generation was significantly related to cortical and hippocampal pathways. Notably, the UF was more strongly related to event element details than it was to spatiotemporal context details. In contrast, CB was significantly and similarly related to the generation of event element and spatiotemporal context details (when not controlling for age and global diffusion). The fornix was also significantly related to both types of episodic detail, although the relationship to spatiotemporal context was particularly robust. These findings support the idea that anterotemporal cortical regions are related to the retrieval of episodic details about the entities that are incorporated into autobiographical events. Our findings also align with the notion that posteromedial and hippocampal-cortical involvement support the retrieval of episodic details.
• Tang, Y., & Ryan, L. (2020). Music Performance Anxiety: Can Expressive Writing Intervention Help?. Frontiers in psychology, 11, 1334.
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  Performance is an essential part of music education; however, many music professionals and students suffer from music performance anxiety (MPA). The purpose of this study was to investigate whether a 10-min expressive writing intervention (EWI) can effectively reduce performance anxiety and improve overall performance outcomes in college-level piano students. Two groups of music students (16 piano major students and 19 group/secondary piano students) participated in the study. Piano major students performed a solo work from memory, while group/secondary piano students took a sight-reading exam of an eight-measure piano musical selection. All students performed twice, at baseline and post-EWI, with 2 or 3 days between performances. During the EWI phase, students were randomly divided into two groups: an expressive writing group and a control group. Students in the expressive writing group wrote down feelings and thoughts about their upcoming performances, while students in the control group wrote about a topic unrelated to performing. Each student's pulse was recorded immediately before performing, and each performance was videotaped. Three independent judges evaluated the recordings using a modified version of the Observational Scale for Piano Practicing (OSPP) by Gruson (1988). The results revealed that, by simply writing out their thoughts and feelings right before performing, students who had high MPA improved their performance quality significantly and reduced their MPA significantly. Our findings suggest that EWI may be a viable tool to alleviate music performance anxiety.
• Ryan, L., Hay, M., Huentelman, M. J., Duarte, A., Rundek, T., Levin, B., Soldan, A., Pettigrew, C., Mehl, M. R., & Barnes, C. A. (2019). Precision Aging: Applying Precision Medicine to the Field of Cognitive Aging. Frontiers in aging neuroscience, 11, 128.
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  The current "one size fits all" approach to our cognitive aging population is not adequate to close the gap between cognitive health span and lifespan. In this review article, we present a novel model for understanding, preventing, and treating age-related cognitive impairment (ARCI) based on concepts borrowed from precision medicine. We will discuss how multiple risk factors can be classified into because of their interrelatedness in real life, the that increase sensitivity to, or ameliorate, risk for ARCI, and the or common mechanisms mediating brain aging. Rather than providing a definitive model of risk for ARCI and cognitive decline, the Precision Aging model is meant as a starting point to guide future research. To that end, after briefly discussing key risk categories, genetic risks, and brain drivers, we conclude with a discussion of steps that must be taken to move the field forward.
• Stickel, A., McKinnon, A., Ruiz, J., Grilli, M. D., & Ryan, L. (2019). The impact of cardiovascular risk factors on cognition in Hispanics and non-Hispanic whites. Learning & memory (Cold Spring Harbor, N.Y.), 26(7), 235-244.
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  Among non-Hispanic whites, cardiovascular risk factors are associated with increased mortality and poorer cognition. Prevalence of cardiovascular risk factors among aging Hispanics is also high and Hispanics generally have poorer access to healthcare, yet they tend to have advantageous cardiovascular disease rates and outcomes and live longer than non-Hispanic whites, an epidemiological phenomenon commonly referred to as the Hispanic or Latino health paradox. Although robust data support these ethnic benefits on physical health and mortality, it is unknown if it extends to include cognition resilience advantages in older adulthood. The present study compared relationships between cardiovascular risk and cognition (executive functions and episodic memory) in late middle age and older Hispanics ( = 87) and non-Hispanic whites ( = 81). Participants were selected from the National Alzheimer's Coordinating Center and Alzheimer's Disease Neuroimaging Initiative databases. Hispanics and non-Hispanic white groups were matched on age (50-94 yr, mean age = 72 yr), education, gender, cognitive status (i.e., cognitively healthy versus mildly cognitively impaired), and apolipoprotein E4 status. History of hypertension and higher body mass index were both associated with poorer executive functions among Hispanics but not non-Hispanic whites. Our findings suggest greater vulnerability to impairments in executive functions among Hispanics with hypertension and obesity, contrary to the notion of a Hispanic health paradox for cognitive aging.
• Talboom, J. S., Håberg, A., De Both, M. D., Naymik, M. A., Schrauwen, I., Lewis, C. R., Bertinelli, S. F., Hammersland, C., Fritz, M. A., Myers, A. J., Hay, M., Barnes, C. A., Glisky, E., Ryan, L., & Huentelman, M. J. (2019). Family history of Alzheimer's disease alters cognition and is modified by medical and genetic factors. eLife, 8.
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  In humans, a first-degree family history of dementia (FH) is a well-documented risk factor for Alzheimer's disease (AD); however, the influence of FH on cognition across the lifespan is poorly understood. To address this issue, we developed an internet-based paired-associates learning (PAL) task and tested 59,571 participants between the ages of 18-85. FH was associated with lower PAL performance in both sexes under 65 years old. Modifiers of this effect of FH on PAL performance included age, sex, education, and diabetes. The Apolipoprotein E ε4 allele was also associated with lower PAL scores in FH positive individuals. Here we show, FH is associated with reduced PAL performance four decades before the typical onset of AD; additionally, several heritable and non-heritable modifiers of this effect were identified.
• Burke, S. N., Gaynor, L. S., Barnes, C. A., Bauer, R. M., Bizon, J. L., Roberson, E. D., & Ryan, L. (2018). Shared Functions of Perirhinal and Parahippocampal Cortices: Implications for Cognitive Aging. Trends in neurosciences, 41(6), 349-359.
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  A predominant view of perirhinal cortex (PRC) and postrhinal/parahippocampal cortex (POR/PHC) function contends that these structures are tuned to represent objects and spatial information, respectively. However, known anatomical connectivity, together with recent electrophysiological, neuroimaging, and lesion data, indicate that both brain areas participate in spatial and nonspatial processing. Instead of content-based organization, the PRC and PHC/POR may participate in two computationally distinct cortical-hippocampal networks: one network that is tuned to process coarse information quickly, forming gist-like representations of scenes/environments, and a second network tuned to process information about the specific sensory details that are necessary for discrimination across sensory modalities. The available data suggest that the latter network may be more vulnerable in advanced age.
• Grilli, M. D., Wank, A. A., Bercel, J. J., & Ryan, L. (2018). Evidence for Reduced Autobiographical Memory Episodic Specificity in Cognitively Normal Middle-Aged and Older Individuals at Increased Risk for Alzheimer's Disease Dementia. Journal of the International Neuropsychological Society : JINS, 24(10), 1073-1083.
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  Alzheimer's disease (AD) typically eludes clinical detection for years, if not decades. The identification of subtle cognitive decline associated with preclinical AD would not only advance understanding of the disease, but also provide clinical targets to assess preventative and early intervention treatments. Disrupted retrieval of detailed episodic autobiographical memories may be a sensitive indicator of subtle cognitive decline, because this type of memory taxes a core neural network affected by preclinical AD neuropathology.
• Memel, M., & Ryan, L. (2018). Visual integration of objects and scenes increases recollection-based responding despite differential MTL recruitment in young and older adults. Hippocampus, 28(12), 886-899.
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  Unitization, the process of encoding previously independent units as one coherent representation, improves associative memory in both young and older adults, or in some cases, differentially benefits older adults. Unitization of verbal associative pairs may reduce reliance on the hippocampus (HC) for successful encoding and recognition by shifting to familiarity-based processing mediated by perirhinal cortex (PRC). However, this shift was not observed in a recent study of visual associative memory, with equivalent activation in HC and PRC during encoding of visually integrated (unitized) and nonintegrated object and scene pairs. Furthermore, behavioral findings from this study suggested an increase in recollection rather than familiarity during recognition of visually integrated pairs. The present study extends our previous work by focusing on the influence of visual integration on fMRI activation during associative recognition, rather than encoding and these patterns between young and older adults. In contrast to our findings from encoding, visual integration reduced HC and PRC activation during retrieval of object and scene associative pairs across both age groups. However, visual integration increased the correlation between bilateral HC and left parahippocampal (PHC) activation and behavioral performance among older adults, consistent with an increased reliance on recollection. In contrast, visual integration reduced the correlation between HC activation and behavioral performance in young adults, more consistent with findings from the verbal unitization literature. Taken together, these results suggest that associative memory for visually integrated pairs may involve differential recruitment of medial temporal regions in young and older adults.
• Memel, M., & Ryan, T. L. (2017). Visual integration enhances associative memory equally for young and older adults without reducing hippocampal encoding activation. Neuropsychologia, 100, 195-206.
• Stickel, A., Kawa, K., Walther, K., Glisky, E., Richholt, R., Huentelman, M., & Ryan, L. (2017). Age-Modulated Associations between , Brain Volume, and Verbal Memory among Healthy Older Adults. Frontiers in aging neuroscience, 9, 431.
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  The resource modulation hypothesis suggests that the influence of genes on cognitive functioning increases with age. The single nucleotide polymorphism rs17070145, associated with episodic memory and working memory, has been suggested to follow such a pattern, but few studies have tested this assertion directly. The present study investigated the relationship between alleles (T carriers vs. CC homozygotes), cognitive performance, and brain volumes in three groups of cognitively healthy adults-middle aged (ages 52-64, = 38), young old (ages 65-72, = 45), and older old (ages 73-92, = 62)-who were carefully matched on potentially confounding variables including apolipoprotein ε4 status and hypertension. Consistent with our prediction, T carriers maintained verbal memory performance with increasing age while CC homozygotes declined. Voxel-based morphometric analysis of magnetic resonance images showed an advantage for T carriers in frontal white matter volume that increased with age. Focusing on the older old group, this advantage for T carriers was also evident in left lingual gyrus gray matter and several additional frontal white matter regions. Contrary to expectations, neither nor the interaction between and age predicted hippocampal volumes. None of the brain regions investigated showed a CC homozygote advantage. Taken together, these data suggest that results in decreased verbal memory performance and lower brain volumes in CC homozygotes compared to T carriers, particularly among the oldest old, consistent with the resource modulation hypothesis.
• Marquine, M. J., Grilli, M. D., Rapcsak, S. Z., Kaszniak, A. W., Ryan, L., Walther, K., & Glisky, E. L. (2016). Impaired personal trait knowledge, but spared other-person trait knowledge, in an individual with bilateral damage to the medial prefrontal cortex. Neuropsychologia, 89, 245-53.
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  Functional neuroimaging has revealed that in healthy adults retrieval of personal trait knowledge is associated with increased activation in the medial prefrontal cortex (mPFC). Separately, neuropsychology has shown that the self-referential nature of memory can be disrupted in individuals with mPFC lesions. However, it remains unclear whether damage to the mPFC impairs retrieval of personal trait knowledge. Therefore, in this neuropsychological case study we investigated the integrity of personal trait knowledge in J.S., an individual who sustained bilateral damage to the mPFC as a result of an anterior communicating artery aneurysm. We measured both accuracy and consistency of J.S.'s personal trait knowledge as well as his trait knowledge of another, frequently seen person, and compared his performance to a group of healthy adults. Findings revealed that J.S. had severely impaired accuracy and consistency of his personal trait knowledge relative to control participants. In contrast, J.S.'s accuracy and consistency of other-person trait knowledge was intact in comparison to control participants. Moreover, J.S. showed a normal positivity bias in his trait ratings. These results, albeit based on a single case, implicate the mPFC as critical for retrieval of personal trait knowledge. Findings also cast doubt on the likelihood that the mPFC, in particular the ventral mPFC, is necessary for storage and retrieval of trait knowledge of other people. Therefore, this case study adds to a growing body of evidence that mPFC damage can disrupt the link between self and memory.
• Lane, R., Ryan, L., Nadel, L., & Greenberg, L. (2015). Memory Reconsolidation, Emotional Arousal and the Process of Change in Psychotherapy: New Insights from Brain Science. Behavioral and Brain Sciences, 15, 1-80.
• Hoscheidt, S. M., Labar, K. S., Ryan, L., Jacobs, W. J., & Nadel, L. (2014). Encoding negative events under stress: High subjective arousal is related to accurate emotional memory despite misinformation exposure. Neurobiol Learn Mem, 112, 237-247.
• Ryan, L., & Walther, K. (2014). White matter integrity in older females is altered by increased body fat. Obesity, 22(9), 2039-2046.
• Chan, S., Ryan, L., & Bever, T. G. (2013). Role of the striatum in language: Syntactic and conceptual sequencing. Brain and Language, 125(3), 283-294.
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  PMID: 22200490;Abstract: The basal ganglia (BG) have long been associated with cognitive control, and it is widely accepted that they also subserve an indirect, control role in language. Nevertheless, it cannot be completely ruled out that the BG may be involved in language in some domain-specific manner. The present study aimed to investigate one type of cognitive control-sequencing, a function that has long been connected with the BG-and to test whether the BG could be specifically implicated in language. Participants were required to rearrange materials sequentially based on linguistic (syntactic or conceptual) or non-linguistic (order switching) rules, or to repeat a previously ordered sequence as a control task. Functional magnetic resonance imaging (fMRI) data revealed a strongly active left-lateralized corticostriatal network, encompassing the anterior striatum, dorsolaterial and ventrolateral prefrontal cortex and presupplementary motor area, while the participants were sequencing materials using linguistic vs. non-linguistic rules. This functional network has an anatomical basis and is strikingly similar to the well-known associative loop implicated in sensorimotor sequence learning. We concluded that the anterior striatum has extended its original sequencing role and worked in concert with frontal cortical regions to subserve the function of linguistic sequencing in a domain-specific manner. © 2011 Elsevier Inc.
• Nadel, L., Hoscheidt, S., & Ryan, L. R. (2013). Spatial cognition and the hippocampus: the anterior-posterior axis. Journal of Cognitive Neuroscience, 25(1), 22-8.
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  We discuss the question of differentiation along the anterior-posterior longitudinal axis of the hippocampus. Data from a recent fMRI study are reanalyzed to determine whether activations in these hippocampal regions are affected by the nature of the information being accessed during a scanning session in which participants thought about episodes from their lives. Retrieving detailed spatial relational information preferentially activated the posterior hippocampus, whereas retrieving information about locales (or contexts) preferentially activated the anterior hippocampus. These data support the view that there is functional differentiation along the longitudinal axis in humans that matches what has been seen in rats, namely, that the posterior (dorsal) hippocampus is crucial for precise spatial behavior, and the anterior (ventral) hippocampus is crucial for context coding.
• Burke, S. N., Ryan, L., & Barnes, C. A. (2012). Characterizing cognitive aging of recognition memory and related processes in animal models and in humans. Frontiers in Aging Neuroscience, 4(SEP).
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  PMID: 22988437;PMCID: PMC3439640;Abstract: Analyses of complex behaviors across the lifespan of animals can reveal the brain regions that are impacted by the normal aging process, thereby, elucidating potential therapeutic targets. Recent data from rats, monkeys, and humans converge, all indicating that recognition memory and complex visual perception are impaired in advanced age. These cognitive processes are also disrupted in animals with lesions of the perirhinal cortex, indicating that the the functional integrity of this structure is disrupted in old age. This current review summarizes these data, and highlights current methodologies for assessing perirhinal cortex-dependent behaviors across the lifespan. © 2012 Burke, Ryan and Barnes.
• Forbes, C. E., Cox, C. L., Schmader, T., & Ryan, L. (2012). Negative stereotype activation alters interaction between neural correlates of arousal, inhibition and cognitive control. Social Cognitive and Affective Neuroscience, 7(7), 771-781.
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  PMID: 21954239;PMCID: PMC3475352;Abstract: Priming negative stereotypes of African Americans can bias perceptions toward novel Black targets, but less is known about how these perceptions ultimately arise. Examining how neural regions involved in arousal, inhibition and control covary when negative stereotypes are activated can provide insight into whether individuals attempt to downregulate biases. Using fMRI, White egalitarian-motivated participants were shown Black and White faces at fast (32 ms) or slow (525 ms) presentation speeds. To create a racially negative stereotypic context, participants listened to violent and misogynistic rap (VMR) in the background. No music (NM) and death metal (DM) were used as control conditions in separate blocks. Fast exposure of Black faces elicited amygdala activation in the NM and VMR conditions (but not DM), that also negatively covaried with activation in prefrontal regions. Only in VMR, however, did amygdala activation for Black faces persist during slow exposure and positively covary with activation in dorsolateral prefrontal cortex while negatively covarying with activation in orbitofrontal cortex. Findings suggest that contexts that prime negative racial stereotypes seem to hinder the downregulation of amygdala activation that typically occurs when egalitarian perceivers are exposed to Black faces. © The Author (2011). Published by Oxford University Press.
• Ryan, L., Ryan, L., Cardoza, J. A., Cardoza, J. A., Barense, M. D., Barense, M. D., Kawa, K. H., Kawa, K. H., Wallentin-Flores, J., Wallentin-Flores, J., Arnold, W. T., Arnold, W. T., Alexander, G. E., & Alexander, G. E. (2012). Age-related impairment in a complex object discrimination task that engages perirhinal cortex. Hippocampus, 22(10), 1978-1989.
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  PMID: 22987676;Abstract: Previous lesion studies have shown compromised complex object discrimination in rats, monkeys, and human patients with damage to the perirhinal cortical region (PRC) of the medial temporal lobe. These findings support the notion that the PRC is involved in object discrimination when pairs of objects have a high degree of overlapping features but not when object discrimination can be resolved on the basis of a single feature (e.g., size or color). Recent studies have demonstrated age-related functional changes to the PRC in animals (rats and monkeys) resulting in impaired complex object discrimination and object recognition. To date, no studies have compared younger and older humans using paradigms previously shown to engage the PRC. To investigate the influence of age on complex object discrimination in humans, the present study used an object matching paradigm for blob-like objects that have previously been shown to recruit the PRC. Difficulty was manipulated by varying the number of overlapping features between objects. Functional MRI data was acquired to determine the involvement of the PRC in the two groups during complex object discrimination. Results indicated that while young and older adults performed similarly on the easy version of the task, most older adults were impaired relative to young participants when the number of overlapping features increased. fMRI results suggest that older adults do not engage bilateral anterior PRC to the same extent as young adults. Specifically, complex object matching performance in older adults was predicted by the degree to which they engage left anterior PRC. These results provide evidence for human age-related changes in PRC function that impact complex object discrimination. © 2012 Wiley Periodicals, Inc.
• Glisky, E. L., Ryan, L., Walther, K., Trouard, T. P., Ryan, L., Posever, J. O., Lisse, J. R., Glisky, E. L., & Bendlin, B. B. (2011). Anti-inflammatory drugs reduce age-related decreases in brain volume in cognitively normal older adults.. Neurobiology of aging, 32(3), 497-505. doi:10.1016/j.neurobiolaging.2009.03.006
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  Previous studies have indicated a decreased risk for developing Alzheimer's disease in anti-inflammatory (AI) drug users. Yet few studies have determined whether AI drug use provides a protective effect against normal age-related changes in the brains of older adults. Regional volume changes in gray and white matter were assessed cross-sectionally using optimized voxel-based morphometry in 36 females taking AI drugs as arthritis or pain medication and 36 age- and education-matched female controls. Although mean gray and white matter volume differences between AI drug users and the non-AI group were small, AI drug use interacted with age, such that the non-AI group showed significantly greater age-related volume changes in regions of both gray and white matter compared to the AI drug users. These regions included the superior and medial frontal gyri, middle and inferior temporal gyri, fusiform and parahippocampal gyri, and occipital gray matter as well as temporal, parietal, and midbrain white matter. The results are consistent with the notion that AI drugs provide protection against age-related changes in brain volume. It is possible that inflammation plays a role in volume decreases associated with normal aging, and that suppressing the inflammatory response moderates this decrease.
• Ryan, L., Glisky, E. L., Walther, K., Walker, D. G., Ryan, L., Lue, L., Glisky, E. L., & Bendlin, B. B. (2011). Age-related differences in white matter integrity and cognitive function are related to APOE status.. NeuroImage, 54(2), 1565-77. doi:10.1016/j.neuroimage.2010.08.052
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  While an extensive literature is now available on age-related differences in white matter integrity measured by diffusion MRI, relatively little is known about the relationships between diffusion and cognitive functions in older adults. Even less is known about whether these relationships are influenced by the apolipoprotein (APOE) ε4 allele, despite growing evidence that ε4 increases cognitive impairment in older adults. The purpose of the present study was to examine these relationships in a group of community-dwelling cognitively normal older adults. Data were obtained from a sample of 126 individuals (ages 52-92) that included 32 ε4 heterozygotes, 6 ε4 homozygotes, and 88 noncarriers. Two measures of diffusion, the apparent diffusion coefficient (ADC) and fractional anisotropy (FA), were obtained from six brain regions-frontal white matter, lateral parietal white matter, the centrum semiovale, the genu and splenium of the corpus callosum, and the temporal stem white matter-and were used to predict composite scores of cognitive function in two domains, executive function and memory function. Results indicated that ADC and FA differed with increasing age in all six brain regions, and these differences were significantly greater for ε4 carriers compared to noncarriers. Importantly, after controlling for age, diffusion measures predicted cognitive function in a region-specific way that was also influenced by ε4 status. Regardless of APOE status, frontal ADC and FA independently predicted executive function scores for all participants, while temporal lobe ADC additionally predicted executive function for ε4 carriers but not noncarriers. Memory scores were predicted by temporal lobe ADC but not frontal diffusion for all participants, and this relationship was significantly stronger in ε4 carriers compared to noncarriers. Taken together, age and temporal lobe ADC accounted for a striking 53% of the variance in memory scores within the ε4 carrier group. The results provide further evidence that APOE ε4 has a significant impact on the trajectory of age-related cognitive functioning in older adults. Possible mechanisms are discussed that could account for the associations between ε4, diffusion, and cognitive function, including the influence of ε4 on neural repair, oxidative stress, and the health of myelin-producing oligodendroglia.
• Ryan, T., Campbell, J., Nadel, L., Duke, D., & Ryan, T. L. (2011). Remembering all that and then some: recollection of autobiographical memories after a 1-year delay. Memory (Hove, England), 19(4).
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  We have previously shown that repeated retrievals of remote autobiographical memories over the course of one month led to an overall increase in reported detail (Nadel, Campbell, & Ryan, 2007). The current study examined the retrieval of those same memories 1 year later in order to determine whether the level of detail remained stable or whether the memories returned to their original state. Participants reported even more details than they had recalled at least 1 year earlier, including new details that were reported for the first time. This finding was consistent across both multiple and single retrieval conditions, suggesting that the critical factor leading to the increase in recall was the passage of time. These findings provide evidence for long-term effects of repeated retrieval on memory content.
• Ryan, L., Ryan, L., Ryan, L., Ryan, L., Nadel, L., Nadel, L., Lin, C. Y., Lin, C. Y., Ketcham, K., & Ketcham, K. (2010). The role of medial temporal lobe in retrieving spatial and nonspatial relations from episodic and semantic memory.. Hippocampus, 20(1), 11-8. doi:10.1002/hipo.20607
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  This study examined the involvement of medial temporal lobe, especially the hippocampus, in processing spatial and nonspatial relations using episodic and semantic versions of a relational judgment task. Participants studied object arrays and were tested on different types of relations between pairs of objects. Three prevalent views of hippocampal function were considered. Cognitive map theory (O'Keefe and Nadel (1978) The Hippocampus as a Cognitive Map. USA: Oxford University Press) emphasizes hippocampal involvement in spatial relational tasks. Multiple trace theory (Nadel and Moscovitch (1997) Memory consolidation, retrograde amnesia and the hippocampal complex Curr Opin Neurobiol 7:217-227) emphasizes hippocampal involvement in episodic tasks. Eichenbaum and Cohen's ((2001) From Conditioning to Conscious Recollection: Memory Systems of the Brain. USA: Oxford University Press) relational theory predicts equivalent hippocampal involvement in all relational tasks within both semantic and episodic memory. The fMRI results provided partial support for all three theories, though none of them fit the data perfectly. We observed hippocampal activation during all relational tasks, with increased activation for spatial compared to nonspatial relations, and for episodic compared to semantic relations. The placement of activation along the anterior-posterior axis of the hippocampus also differentiated the conditions. We suggest a view of hippocampal function in memory that incorporates aspects of all three theories.
• Ryan, T., Hoscheidt, S. M., Nadel, L., Payne, J., & Ryan, T. L. (2010). Hippocampal activation during retrieval of spatial context from episodic and semantic memory. Behavioural brain research, 212(2).
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  The hippocampus, a region implicated in the processing of spatial information and episodic memory, is central to the debate concerning the relationship between episodic and semantic memory. Studies of medial temporal lobe amnesic patients provide evidence that the hippocampus is critical for the retrieval of episodic but not semantic memory. On the other hand, recent neuroimaging studies of intact individuals report hippocampal activation during retrieval of both autobiographical memories and semantic information that includes historical facts, famous faces, and categorical information, suggesting that episodic and semantic memory may engage the hippocampus during memory retrieval in similar ways. Few studies have matched episodic and semantic tasks for the degree to which they include spatial content, even though spatial content may be what drives hippocampal activation during semantic retrieval. To examine this issue, we conducted a functional magnetic resonance imaging (fMRI) study in which retrieval of spatial and nonspatial information was compared during an episodic and semantic recognition task. Results show that the hippocampus (1) participates preferentially in the retrieval of episodic memories; (2) is also engaged by retrieval of semantic memories, particularly those that include spatial information. These data suggest that sharp dissociations between episodic and semantic memory may be overly simplistic and that the hippocampus plays a role in the retrieval of spatial content whether drawn from a memory of one's own life experiences or real-world semantic knowledge.
• Ryan, T., Walther, K., Birdsill, A. C., Glisky, E. L., & Ryan, T. L. (2010). Structural brain differences and cognitive functioning related to body mass index in older females. Human brain mapping, 31(7).
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  Little is known about the effect of obesity on brain structures and cognition in healthy older adults. This study examined the association between body mass index (BMI), regional volume differences in gray and white matter measured by magnetic resonance imaging (MRI), and cognitive functioning in older females. Participants included 95 community-dwelling older females (ages 52-92 years) who underwent extensive neuropsychological testing and high-resolution MRI scanning. Optimized voxel-based morphometry techniques were employed to determine the correlation between BMI and regional gray and white matter volumes. Volumes of significant regions were then correlated with cognitive functioning. Higher BMI was associated with decreased gray matter volumes in the left orbitofrontal, right inferior frontal, and right precentral gyri, a right posterior region including the parahippocampal, fusiform, and lingual gyri, and right cerebellar regions, as well as increased volumes of white matter in the frontal, temporal, and parietal lobes, even when hypertension was considered. Compared to normal weight women, obese women performed poorer on tests of executive functioning. Smaller gray matter volume in the left orbitofrontal region was associated with lower executive functioning. Additionally, despite the lack of significant group differences in memory and visuomotor speed, gray and white matter volumes predicted performance on these measures. The results provide additional evidence for a negative link between increased body fat and brain functioning in older females.
• Greenberg, D. L., Keane, M. M., Ryan, L., & Verfaellie, M. (2009). Impaired category fluency in medial temporal lobe amnesia: The role of episodic memory. Journal of Neuroscience, 29(35), 10900-10908.
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  PMID: 19726648;PMCID: PMC2761020;Abstract: Memory tasks are often classified as semantic or episodic, but recent research shows that these types of memory are highly interactive. Category fluency, for example, is generally considered to reflect retrieval from semantic memory, but behavioral evidence suggests that episodic memory is also involved: participants frequently draw on autobiographical experiences while generating exemplars of certain categories. Neuroimaging studies accordingly have reported increased medial temporal lobe (MTL) activation during exemplar generation. Studies of fluency in MTL amnesics have yielded mixed results but were not designed to determine the precise contributions of episodic memory. We addressed this issue by asking MTL amnesics and controls to generate exemplars of three types of categories. One type tended to elicit autobiographical and spatial retrieval strategies (AS). Another type elicited strategies that were autobiographical but nonspatial (AN). The third type elicited neither autobiographical nor spatial strategies (N). Amnesic patients and control participants generated exemplars for eight categories of each type. Patients were impaired on all category types but were more impaired on AS and AN categories. After covarying for phonemic fluency (total FAS score), the N category impairment was not significant, but the impairment on AS and AN categories remained. The same results were obtained for patients with lesions restricted to the MTL and those with more extensive lesions. We conclude that patients' episodic memory impairment hindered their performance on this putatively semantic task. This interaction between episodic and semantic memory might partially account for fluency deficits seen in aging, mild cognitive impairment, and Alzheimer's disease. Copyright © 2009 Society for Neuroscience.
• Ryan, L., Glisky, E. L., Walther, K., Ryan, L., Glisky, E. L., & Birdsill, A. (2009). Relationship between Body Mass Index, Regional Brain Volume, and Gender in Healthy Older Adults - a Voxel Based Morphometry Study. NeuroImage, 47, S152. doi:10.1016/s1053-8119(09)71577-0
• Ryan, L., Hoscheidt, S. M., Ryan, L., Nadel, L., & Hoscheidt, S. M. (2008). Chapter 1.1 Perspectives on episodic and semantic memory retrieval. Handbook of Behavioral Neuroscience, 18, 5-616. doi:10.1016/s1569-7339(08)00201-4
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  Abstract Episodic or autobiographical recollection involves re-experiencing a past event that is specific in time and place, while semantic recollection is concerned with facts and general knowledge about the world. Several prominent memory theories posit that the hippocampus differentiates between these two types of memories, mediating episodic, but not semantic, retrieval. In this chapter we explore a different view of hippocampus, one that emphasizes a singular response of the hippocampus during memory encoding and retrieval of both episodic and semantic memories, based on an amalgam of two existing theories of hippocampal function, multiple trace theory (MTT; Nadel & Moscovitch, 1997), and cognitive map theory (O'Keefe & Nadel, 1978). We review neuropsychological and neuroimaging literature suggesting that both semantic and episodic memory retrieval engages the hippocampus, at least within the normally functioning brain. We then describe an updated version of MTT that incorporates these new findings. Finally, we explore the notion that differences in the role the hippocampus plays in these forms of memory reflect two critical factors - the nature of the information being retrieved, and the requirements of the retrieval task.
• Ryan, L., Ryan, L., Nadel, L., Hayes, S. M., & Cox, C. (2008). Hippocampal activation during episodic and semantic memory retrieval: comparing category production and category cued recall.. Neuropsychologia, 46(8), 2109-21. doi:10.1016/j.neuropsychologia.2008.02.030
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  Whether or not the hippocampus participates in semantic memory retrieval has been the focus of much debate in the literature. However, few neuroimaging studies have directly compared hippocampal activation during semantic and episodic retrieval tasks that are well matched in all respects other than the source of the retrieved information. In Experiment 1, we compared hippocampal fMRI activation during a classic semantic memory task, category production, and an episodic version of the same task, category cued recall. Left hippocampal activation was observed in both episodic and semantic conditions, although other regions of the brain clearly distinguished the two tasks. Interestingly, participants reported using retrieval strategies during the semantic retrieval task that relied on autobiographical and spatial information; for example, visualizing themselves in their kitchen while producing items for the category kitchen utensils. In Experiment 2, we considered whether the use of these spatial and autobiographical retrieval strategies could have accounted for the hippocampal activation observed in Experiment 1. Categories were presented that elicited one of three retrieval strategy types, autobiographical and spatial, autobiographical and nonspatial, and neither autobiographical nor spatial. Once again, similar hippocampal activation was observed for all three category types, regardless of the inclusion of spatial or autobiographical content. We conclude that the distinction between semantic and episodic memory is more complex than classic memory models suggest.
• Ryan, L., Winocur, G., Ryan, L., Nadel, L., & Moscovitch, M. (2008). Chapter 3.1 Functional neuroanatomy of remote, episodic memory. Handbook of Behavioral Neuroscience, 18, 239-269. doi:10.1016/s1569-7339(08)00214-2
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  Abstract We examine theories of remote episodic memory with special emphasis on functional neuroanatomy. The chapter highlights the debate between proponents of the standard consolidation model, which considers the hippocampus as a temporary memory structure needed only until memories are consolidated elsewhere, and proponents of multiple trace theory (MTT) who hold that the hippocampus always is needed to retain and recover detailed episodic memories. The theories are evaluated on evidence from behavioral, lesion, and functional neuroimaging studies in humans and other organisms, and in light of theories of anterograde memory function. The contribution of other neocortical structures to remote episodic memory is also reviewed in regard to these theories. Though the evidence is inconclusive with respect to some issues, we conclude that on balance it favors MTT. In the final sections of the chapter, we consider new directions in which the field is moving, with special emphasis on the relation between remote memory and other functions such as sematic memory, planning for the future, problem solving, theory of mind, and imagination.
• Ryan, L., & Schnyer, D. (2007). Regional specificity of format-specific priming effects in mirror word reading using functional magnetic resonance imaging. Cerebral Cortex, 17(4), 982-992.
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  PMID: 16754652;Abstract: The speed and accuracy with which subjects can read words is enhanced or "primed" by a prior presentation of the same words. Moreover, priming effects are generally larger when the physical form of the words is maintained from the first to the second presentation. We investigated the neural basis of format-specific priming in a mirror word-reading task using event-related functional magnetic resonance imaging (fMRI). Participants read words that were presented either in mirror-image (M) orientation or in normal (N) orientation and were repeated either in the same or the alternate orientation, creating 4 study-test conditions, N-N, M-N, N-M, and M-M. Priming of N words resulted in reductions in fMRI signal in multiple brain regions, even though reading times (RTs) were unchanged. Priming of M words showed a pattern of RTs consistent with format-specific priming, with greater reductions when the prime matched the form of the test word. Priming-related reductions in fMRI activity were evident in all regions involved in mirror-image reading, regardless of the orientation of the prime. Importantly, reductions in several posterior regions, including fusiform, superior parietal, and superior temporal regions were also format specific. That is, signal reductions in these regions were greatest when the visual form of the prime and target matched (M-M compared with N-M). The results indicate that, although there are global neural priming effects due to stimulus repetition, it is also possible to identify regional brain changes that are sensitive to the specific perceptual overlap of primes and targets. © The Author 2006. Published by Oxford University Press. All rights reserved.
• Ryan, L., Hoscheidt, S. M., Ryan, L., Payne, J. D., Nadel, L., Jacobs, W. J., Jackson, E. D., & Hoscheidt, S. M. (2007). Stress administered prior to encoding impairs neutral but enhances emotional long-term episodic memories.. Learning & memory (Cold Spring Harbor, N.Y.), 14(12), 861-8. doi:10.1101/lm.743507
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  Stressful events frequently comprise both neutral and emotionally arousing information, yet the impact of stress on emotional and neutral events is still not fully understood. The hippocampus and frontal cortex have dense concentrations of receptors for stress hormones, such as cortisol, which at high levels can impair performance on hippocampally dependent memory tasks. Yet, the same stress hormones can facilitate memory for emotional information, which involves interactions between the hippocampus and amygdala. Here, we induced psychosocial stress prior to encoding and examined its long-term effects on memory for emotional and neutral episodes. The stress manipulation disrupted long-term memory for a neutral episode, but facilitated long-term memory for an equivalent emotional episode compared with a control condition. The stress manipulation also increased salivary cortisol, catecholamines as indicated by the presence of alpha-amylase, heart rate, and subjectively reported stress. Stressed subjects reported more false memories than nonstressed control subjects, and these false memories correlated positively with cortisol levels, providing evidence for a relationship between stress and false memory formation. Our results demonstrate that stress, when administered prior to encoding, produces different patterns of long-term remembering for neutral and emotional episodes. These differences likely emerge from differential actions of stress hormones on memory-relevant regions of the brain.
• Ryan, L., Ryan, L., Ryan, L., Ryan, L., Nadel, L., Nadel, L., Hayes, S. M., & Hayes, S. M. (2007). The effect of scene context on episodic object recognition: parahippocampal cortex mediates memory encoding and retrieval success.. Hippocampus, 17(9), 873-89. doi:10.1002/hipo.20319
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  Previous research has investigated intentional retrieval of contextual information and contextual influences on object identification and word recognition, yet few studies have investigated context effects in episodic memory for objects. To address this issue, unique objects embedded in a visually rich scene or on a white background were presented to participants. At test, objects were presented either in the original scene or on a white background. A series of behavioral studies with young adults demonstrated a context shift decrement (CSD)-decreased recognition performance when context is changed between encoding and retrieval. The CSD was not attenuated by encoding or retrieval manipulations, suggesting that binding of object and context may be automatic. A final experiment explored the neural correlates of the CSD, using functional Magnetic Resonance Imaging. Parahippocampal cortex (PHC) activation (right greater than left) during incidental encoding was associated with subsequent memory of objects in the context shift condition. Greater activity in right PHC was also observed during successful recognition of objects previously presented in a scene. Finally, a subset of regions activated during scene encoding, such as bilateral PHC, was reactivated when the object was presented on a white background at retrieval. Although participants were not required to intentionally retrieve contextual information, the results suggest that PHC may reinstate visual context to mediate successful episodic memory retrieval. The CSD is attributed to automatic and obligatory binding of object and context. The results suggest that PHC is important not only for processing of scene information, but also plays a role in successful episodic memory encoding and retrieval. These findings are consistent with the view that spatial information is stored in the hippocampal complex, one of the central tenets of Multiple Trace Theory.
• Ryan, L., Winocur, G., Ryan, L., Nadel, L., & Moscovitch, M. (2007). Systems consolidation and hippocampus: two views. Debates in Neuroscience, 1(2), 55-66. doi:10.1007/s11559-007-9003-9
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  Two approaches to systems-level memory consolidation are contrasted. The standard model and multiple trace theory are spelled out, their implications are outlined, and their fit to the data from a number of approaches is evaluated. We conclude that the data from neuroimaging studies strongly support multiple trace theory, that data from neuropsychological studies favor but does not conclusively support multiple trace theory, while evidence from a new approach, the study of prospective memory, also supporting multiple trace theory, offers a promising new way to distinguish between these two theories. Work with animals is largely consistent with this conclusion. We suggest that the hippocampal and neocortical systems are critical for different forms of memory, and that the shift of memory from dependence on hippocampus to dependence on neocortex during consolidation is a reflection of the fact that memory often is transformed with time, becoming more generic in nature. Insofar as detailed episodic recollections are retained, the data show that they are dependent on the hippocampal system, much as multiple trace theory postulated.
• Ryan, T., Bendlin, B. B., Trouard, T. P., & Ryan, T. L. (2007). Caffeine attenuates practice effects in word stem completion as measured by fMRI BOLD signal. Human brain mapping, 28(7).
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  Caffeine ingestion results in increased brain cell metabolism (Nehlig et al. [1992] Brain Res Brain Res Rev 17:139-170) and decreased cerebral blood flow (Field et al. [2003] Radiology 227:129-135; Mulderink et al. [2002] Neuroimage 15:37-44). The current study investigated the effect of caffeine in a word stem completion task using only novel word stems (no repeated stimuli). Resting perfusion was measured with arterial spin labeled perfusion MRI, along with blood oxygenation level-dependent (BOLD) signal before and after ingestion of regular coffee, decaffeinated coffee, and water. Based on previous research (Laurienti et al. [2002] Neuroimage 17:751-757; Mulderink et al. [2002] Neuroimage 15:37-44), we hypothesized that caffeine would result in increased BOLD signal intensity and extent of BOLD activation. As expected, caffeine resulted in a significant decrease in cerebral perfusion. However, both the control and caffeine groups showed an increase in BOLD signal amplitude across two sets of novel word stems. Additionally, the control group showed a 50% reduction in the extent of BOLD activation, while the caffeine group showed no change in activation extent. Neither group showed changes in BOLD baseline signal over time, which had been suggested to mediate caffeine-related BOLD signal changes. The results suggest that caffeine may attenuate general task practice effects that have been described in recent functional MRI studies of word stem completion (Buckner et al. [2000] Brain 123:620-640).
• Ryan, T., Lin, C., & Ryan, T. L. (2007). Repetition priming without identification of the primes: evidence for a component process view of priming. NeuroImage, 38(3).
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  The aim of the present study was to examine whether priming can occur due to recent perceptual processing of the same stimulus with minimal influence from conceptual process and also to investigate its underlying neural mechanisms using fMRI. Words were presented in mirror orientation in a word identification priming task. The presentation durations of the primes were titrated individually so that each participant could only identify approximately half of the primes, while the remainder disappeared before participants could identify the meaning of the word. A substantial behavioral priming effect was found when these unidentified primes were repeated later, suggesting that recent exposure to the perceptual processes without accessing the meaning is sufficient to prime later identical processes of the same repeated stimuli. Imaging data showed significant repetition suppression in several brain regions mediating perceptual, but not semantic or conceptual, processes. Together, our findings are consistent with the general predictions of transfer appropriate processing (TAP) and the component process view of priming, positing that priming is a function of more efficient cognitive processes that are repeated from study to test, and this increased efficiency is reflected in repetition suppression effects evident on fMRI.
• Ryan, T., Nadel, L., Campbell, J., & Ryan, T. L. (2007). Autobiographical memory retrieval and hippocampal activation as a function of repetition and the passage of time. Neural plasticity, 2007.
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  Multiple trace theory (MTT) predicts that hippocampal memory traces expand and strengthen as a function of repeated memory retrievals. We tested this hypothesis utilizing fMRI, comparing the effect of memory retrieval versus the mere passage of time on hippocampal activation. While undergoing fMRI scanning, participants retrieved remote autobiographical memories that had been previously retrieved either one month earlier, two days earlier, or multiple times during the preceding month. Behavioral analyses revealed that the number and consistency of memory details retrieved increased with multiple retrievals but not with the passage of time. While all three retrieval conditions activated a similar set of brain regions normally associated with autobiographical memory retrieval including medial temporal lobe structures, hippocampal activation did not change as a function of either multiple retrievals or the passage of time. However, activation in other brain regions, including the precuneus, lateral prefrontal cortex, parietal cortex, lateral temporal lobe, and perirhinal cortex increased after multiple retrievals, but was not influenced by the passage of time. These results have important implications for existing theories of long-term memory consolidation.
• Ryan, L., Hoscheidt, S. M., Ryan, L., Payne, J. D., Nadel, L., Jacobs, W. J., Jacobs, J. W., Jackson, E. D., & Hoscheidt, S. M. (2006). The impact of stress on neutral and emotional aspects of episodic memory.. Memory (Hove, England), 14(1), 1-16. doi:10.1080/09658210500139176
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  The present experiment demonstrates that exposure to a significant psychological stressor (administered before watching a slide show) preserves or even enhances memory for emotional aspects of an event, and simultaneously disrupts memory for non-emotional aspects of the same event. Stress exposure also disrupted memory for information that was visually and thematically central to the event depicted in the slide show. Memory for peripheral information, on the other hand, was unaffected by stress. These results are consistent with theories invoking differential effects of stress on brain systems responsible for encoding and retrieving emotional memories (the amygdala) and non-emotional memories (e.g., the hippocampal formation), and inconsistent with the view that memories formed under high levels of stress are qualitatively the same as those formed under ordinary emotional circumstances. These data, which are also consistent with results obtained in a number of studies using animals and humans, have implications for the traumatic memory debate and theories regarding human memory.
• Ryan, L. (2005). Past imperfect. New Scientist, 188(2522), 54-.
• Glisky, E. L., Ryan, L., Ryan, L., Reminger, S. L., Hupbach, A., Hayes, S. M., Hardt, O., & Glisky, E. L. (2004). A case of psychogenic fugue: I understand, aber ich verstehe nichts.. Neuropsychologia, 42(8), 1132-47. doi:10.1016/j.neuropsychologia.2003.08.016
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  Psychogenic fugue is a disorder of memory that occurs following emotional or psychological trauma and results in a loss of one's personal past including personal identity. This paper reports a case of psychogenic fugue in which the individual lost access not only to his autobiographical memories but also to his native German language. A series of experiments compared his performance on a variety of memory and language tests to several groups of control participants including German-English bilinguals who performed the tasks normally or simulated amnesia for the German language. Neuropsychological, behavioral, electrophysiological and functional neuroimaging tests converged on the conclusion that this individual suffered an episode of psychogenic fugue, during which he lost explicit knowledge of his personal past and his native language. At the same time, he appeared to retain implicit knowledge of autobiographical facts and of the semantic or associative structure of the German language. The patient's poor performance on tests of executive control and reduced activation of frontal compared to parietal brain regions during lexical decision were suggestive of reduced frontal function, consistent with models of psychogenic fugue proposed by Kopelman and Markovitsch.
• Kaszniak, A. W., Ryan, L., Ryan, L., Reminger, S. L., Littrell, L. D., Labiner, D. M., Kaszniak, A. W., Kaemingk, K. L., Herring, A. M., & David, B. T. (2004). Bilateral hippocampal volume predicts verbal memory function in temporal lobe epilepsy.. Epilepsy & behavior : E&B, 5(5), 687-95. doi:10.1016/j.yebeh.2004.06.006
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  The present study used quantitative volume estimates of the hippocampus based on structural magnetic resonance imaging (MRI) to predict memory performance of individuals with epilepsy of temporal lobe origin (TLE). Twenty individuals with TLE completed standardized neuropsychological tests and a quality of life inventory, and participated in a brain MRI protocol designed to obtain high-resolution images of the hippocampus. The combined volume of the left and right hippocampi was found to be the best predictor of objective verbal memory performance. This finding is consistent with the functional adequacy model of hippocampal function. In contrast, the asymmetry between right and left hippocampal volume was the best predictor of subjective ratings of cognitive functioning, which is consistent with the functional reserve model. The collective and complementary functions of the left and right hippocampi merit further exploration in prospective studies of memory function and TLE.
• Ryan, L., Schnyer, D. M., Ryan, L., Nadel, L., & Hayes, S. M. (2004). An fMRI study of episodic memory: retrieval of object, spatial, and temporal information.. Behavioral neuroscience, 118(5), 885-96. doi:10.1037/0735-7044.118.5.885
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  Sixteen participants viewed a videotaped tour of 4 houses that highlighted a series of objects and their spatial locations. Participants were tested for memory of object, spatial, and temporal-order information while undergoing functional magnetic resonance imaging. Preferential activation was observed in the right parahippocampal gyrus during the retrieval of spatial-location information. Retrieval of contextual information (spatial location and temporal order) was associated with activation in the right dorsolateral prefrontal cortex. In bilateral posterior parietal regions, greater activation was associated with processing of visual scenes regardless of the memory judgment. These findings support current theories positing roles for frontal and medial temporal regions during episodic retrieval and suggest a specific role for the hippocampal complex in the retrieval of spatial-location information.
• Ryan, L., Gmitro, A. F., Weerd, P. D., Trouard, T. P., Schnyer, D. M., Ryan, L., Reinke, K. S., Perschler, P., Mcisaac, T. L., & Gmitro, A. F. (2003). Cortical mechanisms for acquisition and performance of bimanual motor sequences.. NeuroImage, 19(4), 1405-16. doi:10.1016/s1053-8119(03)00222-2
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  We used functional magnetic resonance imaging to investigate the cortical mechanisms contributing to the acquisition and performance of a complex, bimanual motor sequence. To that aim, five subjects were trained on a difficult, asymmetrical finger opposition task. Their performance rate almost doubled in the course of training and approached the performance rate in an untrained, symmetrical finger opposition task. Before training, performance of the asymmetrical sequence was associated with activity in M1, premotor cortex, supplementary motor cortex, and parietal cortex. After training, performance of the asymmetrical sequence was associated mainly with activity in M1, and little activity outside M1 remained. The latter pattern of cortical activation resembled that observed during the execution of symmetrical sequences, which was unaffected by practice with the asymmetrical sequence. The activation pattern obtained with the symmetrical bimanual sequence was indistinguishable from the combined activation measured in contralateral hemispheres during unimanual control sequences. The data indicate that cortical regions previously implicated in the acquisition of difficult unimanual motor sequences also contribute to the acquisition of asymmetrical bimanual sequences. We found no evidence for an expansion of activity in M1 after acquisition of the asymmetrical sequence (while this has been reported after acquisition of unimanual sequences). In the context of existing literature, the data suggest that the acquisition of unimanual and bimanual motor sequences may rely on similar cortical mechanisms, but that the formation of long-term, procedural memories for the two types of sequences might at least in part depend on different mechanisms.
• Ryan, L., Ryan, L., Nadel, L., Moscovitch, M., Hayes, S. M., & Gilboa, A. (2003). The role of the hippocampal complex in long-term episodic memory. International Congress Series, 1250, 215-234. doi:10.1016/s0531-5131(03)01069-0
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  That the hippocampal complex plays a critical role in memory is no longer in dispute. Several essential questions remain unanswered, however, nearly 50 years after the seminal work of Scoville and Milner [1]. These include: what aspects of memory require hippocampal participation, when hippocampal participation is needed, and how various parts of the hippocampal complex are involved in these memory processes. Though there are provisional answers to each of these questions, vigorous debate continues in each case. To make matters more complicated, these questions are not independent of one another— the role played by various parts of the hippocampal complex may change over time, and with respect to the kind of memory involved. Answers to these questions force a consideration of the interactions between the hippocampal complex and the neocortex, as we will see. We begin with a brief overview of the current status of each of these debates, present some data that bear on them, and finally outline our current approach to these issues. Some definitions, however, are essential at the outset. First, what exactly is meant by the term ‘‘hippocampal complex’’? Starting from the core, the hippocampus consists of the CA fields and the dentate gyrus, the hippocampal formation incorporates the subiculum, and the hippocampal complex further includes the parahippocampal region, which incorporates the entorhinal cortex, the perirhinal cortex, and the parahippocampal gyrus. Second, what is meant by the term ‘‘memory’’? This seemingly innocent question is actually quite tangled in ways that have contributed to some of the debates in the field. The
• Ryan, L., Hatfield, C., & Hofstetter, M. (2002). Caffeine reduces time-of-day effects on memory performance in older adults. Psychological Science, 13(1), 68-71.
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  PMID: 11892781;Abstract: For most older adults, memory performance depends on the time of day, with performance being optimal early in the morning and declining during the late afternoon hours. In the present study, we asked whether this decline could be ameliorated by a simple stimulant, caffeine. Adults over the age of 65 who considered themselves "morning types" were tested twice over an interval of 5 to 11 days, once in the morning and once in the late afternoon. Participants ingested either coffee with caffeine or decaffeinated coffee at both sessions. Participants who ingested decaffeinated coffee showed a significant decline in memory performance from morning to afternoon. In contrast, those who ingested caffeine showed no decline in performance from morning to afternoon. The results suggest that time-of-day effects may be mediated by nonspecific changes in level of arousal. Copyright © 2002 American Psychological Society.
• Ryan, L., Trouard, T. P., Schnyer, D. M., Ryan, L., & Forster, K. I. (2002). Masked word repetition results in increased fMRI signal: a framework for understanding signal changes in priming.. Neuroreport, 13(3), 281-4. doi:10.1097/00001756-200203040-00007
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  Evidence from multiple paradigms has converged on the finding that stimulus repetition most often results in decreases in neural activity. The mechanisms of these decreases, however, are not yet well understood. The current study attempted to determine, through the use of masked word repetition priming, whether decreases in activity levels occur in response to pre- or post-prime identification processes. fMRI was performed while participants engaged in a lexical decision task where words were primed with a briefly presented and masked word. Masked word priming resulted in increased fMRI signal in regions of cortex associated with the perceptual identification of the target words. This finding provides evidence suggesting that the impact of repetition priming on the fMRI signal may depend upon whether or not the prime is identified.
• Bierley, R. A., Drake, A. I., Ahmed, S., Date, E. S., Rosner, M., Warden, D., Salazar, A. M., Schwab, K. A., Tackitt, P. H., McDonough, T. L., Punch, W., Ivins, B., Litvan, I., Lipski, R., Grafman, J. H., Ryan, L., Wilkinson, J., Martin, E. M., Coyle, M., , Cole, R. A., et al. (2001). Biased responding: A case series demonstrating a relationship between somatic symptoms and impaired recognition memory performance for traumatic brain injured individuals. Brain Injury, 15(8), 697-714.
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  PMID: 11485610;Abstract: Biased responding on the Sternberg Recognition Memory Test was observed in four patients with traumatic brain injury. None of these individuals met the Diagnostic and Statistical Manual's (DSM-IV) criteria for malingering. Individual recognition memory scores were high shortly after injury, declined to chance or below at the 6- and 12-month evaluations, and then showed substantial recovery by the 24-month evaluation. Recall memory performance actually declined slightly across this same 2-year period. Recognition memory scores were related to the extent to which the patients endorsed somatic items on the Hamilton Rating Scale for Depression (HAM-D). Poor performance was associated with high somatic scores. The relationship between memory and somatic scores on the HAM-D in this case series suggests that unconscious processes can influence memory performance and, because of this, that clinicians should not use such performance as a primary indicator of malingering. More importantly, biased responding and actual memory deficits may coexist. This is indicated in the current cases by the failure of recall memory to improve during the 2 years these patients were followed.
• Heyes, M. P., Ellis, R. J., Ryan, L., Childers, M. E., Grant, I., Wolfson, T., Archibald, S., Jernigan, T. L., Atkinson, J. H., McCutchan, J. A., Marcotte, T. D., Wallace, M. R., Letendre, S., Schier, R., Heaton, R. K., Cherner, M., Rippeth, J., Hesselink, J., Masliah, E., , Masys, D. R., et al. (2001). Elevated cerebrospinal fluid quinolinic acid levels are associated with region-specific cerebral volume loss in HIV infection. Brain, 124(5), 1033-1042.
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  PMID: 11335705;Abstract: Neuronal injury, dendritic loss and brain atrophy are frequent complications of infection with human immunodeficiency virus (HIV) type 1. Activated brain macrophages and microglia can release quinolinic acid, a neurotoxin and NMDA (N-methyl-D-aspartate) receptor agonist, which we hypothesize contributes to neuronal injury and cerebral volume loss. In the present cross-sectional study of 94 HIV-1-infected patients, elevated CSF quinolinic acid concentrations correlated with worsening brain atrophy, quantified by MRI, in regions vulnerable to excitotoxic injury (the striatum and limbic cortex) but not in regions relatively resistant to excitotoxicity (the non-limbic cortex, thalamus and white matter). Increased CSF quinolinic acid concentrations also correlated with higher CSF HIV-1 RNA levels. In support of the specificity of these associations, blood levels of quinolinic acid were unrelated to striatal and limbic volumes, and CSF levels of β2-microglobulin, a non-specific and non-excitotoxic marker of immune activation, were unrelated to regional brain volume loss. These results are consistent with the hypothesis that quinolinic acid accumulation in brain tissue contributes to atrophy in vulnerable brain regions in HIV infection and that virus replication is a significant driver of local quinolinic acid biosynthesis.
• Ryan, L., & Johnson, J. L. (2001). Search and selection processes in WSC revisited: correcting response time in event-related item analyses. NeuroImage, 13(6), 689. doi:10.1016/s1053-8119(01)92032-4
• Ryan, L., Lane, R. D., Trouard, T. P., Ryan, L., Lane, R. D., Johnson, S. C., & Fort, C. L. (2001). Dissociable representations of emotional state in dorsal and ventral medial prefrontal cortex. NeuroImage, 13(6), 437. doi:10.1016/s1053-8119(01)91780-x
• Ryan, L., Ostergaard, A., Norton, L., & Johnson, J. (2001). Search and selection processes in implicit and explicit word-stem completion performance in young, middle-aged, and older adults. Memory and Cognition, 29(5), 678-690.
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  PMID: 11531223;Abstract: In the present investigation, we sought to (1) replicate previous reports of impaired word-stem completion (WSC) priming and cued recall performance in older adults, (2) gain a better understanding of the differential roles of search and selection processes in implicit and explicit WSC, and (3) determine the particular aspects of WSC performance that are influenced by age. Experiment 1 demonstrated that older adults primed and recalled fewer items on a WSC task than middle-aged adults did, who in turn primed and recalled fewer itmes than young adults did. A series of item analyses indicated that choice of a stem completion is influenced by two independent sources of information: the familiarity of the completion reflected by word frequency and the cue-specific match between the stem and the completion word based on the common pronunciation of the stem. Experiment 2 demonstrated that older adults utilized cue-specific matching to the same degree as young and middle-aged adults. However, the impact of target familiarity changed across the lifespan. Older adults produced and recalled high-frequency targets as well as young adults but produced and recalled fewer low-frequency targets than did young participants. The results are consistent with the view that older adults rely on familiarity to a greater degree than do young adults.
• Ryan, L., Ryan, L., & Nadel, L. (2001). A direct comparison of hippocampal activation during semantic and episodic retrieval. NeuroImage, 13(6), 733. doi:10.1016/s1053-8119(01)92075-0
• Ryan, L., Ryan, L., Trouard, T. P., Trouard, T. P., Schnyer, D. M., Schnyer, D. M., Ryan, L., Ryan, L., Putnam, K., Putnam, K., Nadel, L., Nadel, L., Moscovitch, M., Moscovitch, M., Keil, K., & Keil, K. (2001). Hippocampal complex and retrieval of recent and very remote autobiographical memories: evidence from functional magnetic resonance imaging in neurologically intact people.. Hippocampus, 11(6), 707-14. doi:10.1002/hipo.1086
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  It has been argued that the role of the hippocampus in memory is time-limited: during a period of memory consolidation, other brain regions such as the neocortex are said to acquire the ability to support memory retention and retrieval on their own. An alternative view is that retention and retrieval of memory for autobiographical episodes depend on the hippocampal complex, regardless of the age of the memory. We examined the participation of the hippocampal complex in a functional magnetic resonance imaging (fMRI) study in which participants were asked to recollect autobiographical events that occurred either within the last 4 years or more than 20 years ago. We found equivalent levels of hippocampal activation in both conditions in all participants (N = 10). In addition, activation in neocortical regions did not differ as a function of the age of the memory, even though most of the recent memories recalled were less than 2 years old and the remote memories more than 35 years old. The results support the notion that the hippocampal complex participates in retention and recovery of even very old autobiographical memories, and place boundary conditions on theories of memory consolidation.
• Ryan, L., Trouard, T. P., Ryan, L., & Johnson, J. L. (2001). Age-related differences in BOLD hemodynamic response: Evidence from event-related fMRI. NeuroImage, 13(6), 40. doi:10.1016/s1053-8119(01)91383-7
• Ryan, L., Trouard, T. P., Smith, V. L., Ryan, L., Mccabe, K., & Houser, D. (2001). A functional imaging study of cooperation in two-person reciprocal exchange.. Proceedings of the National Academy of Sciences of the United States of America, 98(20), 11832-5. doi:10.1073/pnas.211415698
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  Cooperation between individuals requires the ability to infer each other's mental states to form shared expectations over mutual gains and make cooperative choices that realize these gains. From evidence that the ability for mental state attribution involves the use of prefrontal cortex, we hypothesize that this area is involved in integrating theory-of-mind processing with cooperative actions. We report data from a functional MRI experiment designed to test this hypothesis. Subjects in a scanner played standard two-person "trust and reciprocity" games with both human and computer counterparts for cash rewards. Behavioral data shows that seven subjects consistently attempted cooperation with their human counterpart. Within this group prefrontal regions are more active when subjects are playing a human than when they are playing a computer following a fixed (and known) probabilistic strategy. Within the group of five noncooperators, there are no significant differences in prefrontal activation between computer and human conditions.
• Lane, R. D., Ryan, L., Trouard, T. P., Ryan, L., Lane, R. D., & Fort, C. L. (2000). Activation of medial prefrontal cortex during selective attention to subjective emotional responses. NeuroImage, 11(5), S926. doi:10.1016/s1053-8119(00)91854-8
• Ryan, L., Ryan, L., Samsonovich, A. V., Samsonovich, A. V., Ryan, L., Ryan, L., Nadel, L., Nadel, L., Moscovitch, M., & Moscovitch, M. (2000). Multiple trace theory of human memory: computational, neuroimaging, and neuropsychological results.. Hippocampus, 10(4), 352-68. doi:10.1002/1098-1063(2000)10:4<352::aid-hipo2>3.0.co;2-d
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  Hippocampal-neocortical interactions in memory have typically been characterized within the "standard model" of memory consolidation. In this view, memory storage initially requires hippocampal linking of dispersed neocortical storage sites, but over time this need dissipates, and the hippocampal component is rendered unnecessary. This change in function over time is held to account for the retrograde amnesia (RA) gradients often seen in patients with hippocampal damage. Recent evidence, however, calls this standard model into question, and we have recently proposed a new approach, the "multiple memory trace" (MMT) theory. In this view, hippocampal ensembles are always involved in storage and retrieval of episodic information, but semantic (gist) information can be established in neocortex, and will survive damage to the hippocampal system if enough time has elapsed. This approach accounts more readily for the very long RA gradients often observed in amnesia. We report the results of analytic and connectionist simulations that demonstrate the feasibility of MMT. We also report a neuroimaging study showing that retrieval of very remote (25-year-old) memories elicits as much activation in hippocampus as retrieval of quite recent memories. Finally, we report new data from the study of patients with temporal lobe damage, using more sensitive measures than previously the case, showing that deficits in both episodic and spatial detail can be observed even for very remote memories. Overall, these findings indicate that the standard model of memory consolidation, which views the hippocampus as having only a temporary role in memory, is wrong. Instead, the data support the view that for episodic and spatial detail the hippocampal system is always necessary.
• Ryan, L., Thomas, K. G., Ryan, L., Nadel, L., Jacobs, W. J., & Hsu, M. (2000). Functional neuroimaging of place learning in a computer-generated space. NeuroImage, 11(5), S441. doi:10.1016/s1053-8119(00)91372-7
• Ryan, L., Trouad, T., Jackson, T., & Johnson, J. L. (2000). Event related FMRI study of search and selection processes during word stem completion. NeuroImage, 11(5), S442. doi:10.1016/s1053-8119(00)91373-9
• Ryan, L., Trouard, T. P., Schnyer, D. M., & Ryan, L. (2000). An event-related fMRI examination of format specific word priming. NeuroImage, 11(5), S428. doi:10.1016/s1053-8119(00)91359-4
• Ryan, L., Trouard, T. P., Schnyer, D. M., Ryan, L., & Forster, K. I. (2000). An event-related fMRI examination of masked word priming: Are signal reductions related to conscious experience of the prime?. NeuroImage, 11(5), S445. doi:10.1016/s1053-8119(00)91376-4
• Ryan, L., Trouard, T. P., Schnyer, D. M., Ryan, L., & Moscovitch, M. (2000). Is right frontal activation related to retrieval mode or post-retrieval monitoring and evaluation? A new methodology using event related fMRI. NeuroImage, 11(5), S430. doi:10.1016/s1053-8119(00)91361-2
• Ryan, L., Trouard, T. P., Schnyer, D. M., Ryan, L., Putnam, K., Nadel, L., Moscovitch, M., & Keil, T. (2000). Hippocampal activation during retrieval of remote memories. NeuroImage, 11(5), S396. doi:10.1016/s1053-8119(00)91327-2
• Ryan, L., Trouard, T. P., Smith, V. L., Ryan, L., Mccabe, K., Houser, D., & Coricelli, G. (2000). Frontal lobe function in two person exchange. NeuroImage, 11(5), S101. doi:10.1016/s1053-8119(00)91034-6
• Ryan, L., Weerd, P. D., Trouard, T. P., Schnyer, D. M., Ryan, L., Reinke, K. S., Johnson, J. L., & Fuglevand, A. J. (2000). Activation of motor areas during bimanual finger tapping: An FMRI study. NeuroImage, 11(5), S813. doi:10.1016/s1053-8119(00)91741-5
• Ryan, L., Ryan, L., Putnam, K., Nadel, L., & Keil, K. (1999). Episodic memory: It's about time (and space). Behavioral and Brain Sciences, 22(3), 463-464. doi:10.1017/s0140525x99402031
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  Aggleton & Brown rightly point out the shortcomings of the medial temporal lobe hypothesis as an approach to anterograde amnesia. Their broader perspective is a necessary corrective, and one hopes it will be taken very seriously. Although they correctly note the dangers of conflating recognition and recall, they themselves make a similar mistake in discussing familiarity; we suggest an alternative approach. We also discuss implications of their view for an analysis of retrograde amnesia. The notion that there are two routes by which the hippocampus can reactivate neuronal ensembles in the neocortex could help us understand some currently puzzling facts about the dynamics of memory consolidation.
• White, D. A., Taylor, M. J., Mack, C., Salmon, D. P., Peavy, G., Ryan, L., Heaton, R. K., Atkinson, J. H., Chandler, J. L., Grant, I., Kelly, M., Wallace, M. R., McCutchan, J. A., Spector, S. A., Thal, L., Hesselink, J., Jernigan, T., Masliah, E., Wiley, C. A., , Abramson, I., et al. (1997). Memory for verbal information in individuals with HIV-associated dementia complex. Journal of Clinical and Experimental Neuropsychology, 19(3), 357-366.
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  PMID: 9268810;Abstract: Patterns of memory performance were examined for 9 participants with HIV-associated dementia (HAD), 15 HIV-seropositive participants without dementia, and 15 HIV-seronegative controls. Episodic and semantic memory were assessed using the California Verbal Learning Test, the Boston Naming Test, and Verbal Fluency tests. The HAD group showed deficits in episodic memory, with relative sparing of semantic memory. In addition, results suggest a retrieval deficit in HAD rather than a deficit in retention of information. This pattern is consistent with the presence of a subcortical dementing process and supports findings from previous neuropathological, neuroimaging, and neuropsychological studies suggesting that subcortical brain dysfunction is frequently associated with HIV disease (e.g., Navia, Jordan, and Price, 1986).
• Ryan, L., Clark, C. M., Klonoff, H., David, L. i., & Paty, D. (1996). Patterns of cognitive impairment in relapsing-remitting multiple sclerosis and their relationship to neuropathology on magnetic resonance images. Neuropsychology, 10(2), 176-193.
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  Abstract: Several reviews (J. M. Peyser and C. M. Poser, 1986; S. M. Rao, 1986) have suggested that multiple sclerosis (MS) results in cognitive impairment in learning and memory, abstract reasoning, information-processing efficiency, and often visual-spatial ability. MS patients may undergo idiosyncratic cognitive changes dependent on the site of white matter lesions. In the present study, researchers used cluster analysis on the neuropsychological data from a group of mildly disabled relapsing-remitting MS patients (n = 177) and a well-matched control group (n = 89). In those MS patients identified with unequivocal cognitive impairment, the majority clustered into groups with a specific deficit in 1 or 2 areas of cognitive functioning, with normal performance in others. On magnetic resonance imaging, an association Was obtained between 2 lesion sites and 2 cognitive tests. Impairment in visual-spatial ability, as assessed by the Benton Visual Retention Test, was associated with lesions in the genu of the corpus callosum (CC) and with more lesions throughout the CC. Impaired performance on Paired Associates, a test of learning and memory, was associated with a lesion in the deep white matter of the left parietal lobe. The findings support the hypothesis that MS results in multiple patterns of cognitive impairment that depend on the individual placement of white matter lesions.
• Stout, J. C., Salmon, D. P., Butters, N., Taylor, M., Peavy, G., Heindel, W. C., Delis, D. C., Ryan, L., Atkinson, J. H., Chandler, J. L., & Grant, I. (1995). Decline in working memory associated with HIV infection. Psychological Medicine, 25(6), 1221-1232.
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  PMID: 8637952;Abstract: HIV infection has been associated with decline in a number of cognitive functions that are components of 'working memory'. Thus, tests of working memory that require the interaction of these components may be particularly sensitive to cognitive dysfunction that arises from HIV infection. To assess this possibility, working memory was examined in 147 HIV-seropositive (HIV+) and 38 HIV-seronegative (HIV-) males using the Reading Span Test and the Digit Span subtest from the Wechsler Memory Scale-Revised (WMS-R). Speed of information processing, a component of some working memory tasks, was assessed with a version of the Sternberg Memory Scanning task. Results indicated that symptomatic HIV+ subjects were impaired relative to HIV- control subjects on the Reading Span and Digit Span tests. Asymptomatic and mildly symptomatic HIV+ groups exhibited a trend toward impairment on these tests, and on the whole, a greater proportion of HIV+ subjects than HIV- subjects were impaired. The groups did not differ significantly in information processing speed. These results indicate that deficits in working memory are apparent in at least a subset of HIV-infected individuals. These deficits are most apparent in symptomatic HIV+ individuals, but the decline may begin during the asymptomatic phase of infection.
• Eich, E., Macaulay, D., & Ryan, L. (1994). Mood Dependent Memory for Events of the Personal Past. Journal of Experimental Psychology: General, 123(2), 201-215.
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  PMID: 8014613;Abstract: Previous research on mood dependent memory (MDM) suggests that the more one must rely on internal resources, rather than on external aids, to generate both the target events and the cues required for their retrieval, the more likely is one's memory for these events to be mood dependent. To instantiate this "do-it-yourself" principle, three experiments were conducted in which Ss experiencing either a pleasant or an unpleasant mood generated autobiographical events in response to neutral nouns. Subsequently, Ss were tested for event free recall while in the same or the alternative mood state. All three studies showed MDM, such that the likelihood of recalling an event generated 2 or 3 days ago was higher when generation and recall moods matched than when they mismatched. Prospects for future research aimed at elucidating and extending these results are discussed.
• Clark, C. M., & Ryan, L. (1993). Implications of statistical tests of variance and means. Journal of Clinical and Experimental Neuropsychology, 15(4), 619-622.
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  PMID: 8354713;Abstract: The primary purpose of this paper is to illustrate that tests for the homogeneity of variance in the statistical analysis of clinical neuropsychological data may provide unique information. Specifically, tests of variance homogeneity are more sensitive to outliers than the more commonly used tests of group means. Moreover, when both a test of means and of variance are done and the results compared, the nature of the deficit within the sample can be interpreted with greater confidence.
• Ryan, L., Clark, C. M., Klonoff, H., & Paty, D. (1993). Models of cognitive deficit and statistical hypotheses: Multiple sclerosis, an example. Journal of Clinical and Experimental Neuropsychology, 15(4), 563-577.
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  PMID: 8354709;Abstract: The purpose of the current study was to describe four models of cognitive deficit and to outline the statistical hypotheses underlying each model. The four models of cognitive deficit were (a) specific deficit; (b) subgroup deficit; (c) a syndrome dissociation model; and (d) a global function dissociation model. Neuropsychological data are analyzed to examine each of these four models in a sample of mild Multiple Sclerosis (MS) patients. The results suggest that for these subjects and tests, the specific deficit model best fits the data. The results are reviewed initially in the context of MS. There follows a consideration of statistical caveats and finally, general applications of the proposed procedures.
• Graf, P., & Ryan, L. (1990). Transfer-Appropriate Processing for Implicit and Explicit Memory. Journal of Experimental Psychology: Learning, Memory, and Cognition, 16(6), 978-992.
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  Abstract: To examine how feature-specific pattern-analyzing processes affect implicit and explicit memory test performance, words were displayed for study and testing in 2 visually distinct formats: upside down vs. normal for Experiment 1, upside down vs. backward for Experiment 2, and in Applesoft pudgy vs. shadow typeface for Experiment 3. Implicit and explicit memory performance was assessed with word identification and recognition tests, respectively. The results showed larger priming effects when the study and test formats were the same rather than different, but only in some experimental conditions. The discussion focuses on how skill and processing strategies contribute to format-specific effects on implicit and explicit memory test performance, and it outlines a theoretical account based on the idea of transfer-appropriate processing.

Proceedings Publications

• Ryan, L., Trouard, T. P., Ryan, L., Pu, L., Huang, C., Bilgin, A., & Altbach, M. I. (2011). Model-based compressive diffusion tensor imaging. In 2011 IEEE International Symposium on Biomedical Imaging: From Nano to Macro, 254-257.
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  Diffusion tensor imaging (DTI) is a Magnetic Resonance Imaging (MRI) technique that can reveal in vivo tissue microstructure by measuring diffusion of water in tissue. DTI has become an important tool in many clinical applications, such as assessment of white matter maturation, locating white matter lesions, and providing anatomical connectivity information. However, DTI usually requires long examination times due to the repetitive nature of the acquisition and is very sensitive to motion. These drawbacks have become the largest obstacles to full utilization of DTI. In this work, we propose to overcome these obstacles by using a model-based compressive imaging approach. Our approach consist of models to efficiently represent diffusion-encoded images and the corresponding recovery schemes based on compressive sensing (CS) principles. Our results indicate that the proposed model-based approach can allow reliable recovery of DTI signal from undersampled measurements and outperforms conventional CS recovery.

Presentations

• Ryan, T. L. (2015, June). Age differences in the interaction between perirhinal cortex and hippocampus during complex object discrimination. Spring Hippocampal Research Conference. Taormina, Sicily: Hippocampus.
• Ryan, T. L., & Cardoza, J. (2013, June). An fMRI Study of Age-Related Differences in Complex Object Discrimination. Annual Meeting of the Canadian Society for Brain, Behaviour and Cognitive Science. Calgary, Alberta, CN: Canadian Society for Brain, Behaviour and Cognitive Science.

Poster Presentations

• Matijevic, S., Elias, M., Huentelman, M. J., & Ryan, T. L. (2019, October). Interactive Effects of Sex and BDNF Val66Met Polymorphism on Cognition in Older Adults. Society for Neuroscience Annual Meeting. Chicago, IL.
• Matijevic, S., Grilli, M. D., & Ryan, T. L. (2019, May). Role of white matter integrity in age-related differences in autobiographical memory. Arizona Alzheimer’s Consortium Annual Meeting. Tempe, AZ.
• Palmer, J. M., Lawrence, A. V., Huentelman, M. J., & Ryan, T. L. (2019, May). Context-dependent memory in cognitively-normal older e4 carriers and non-carriers. Arizona Alzheimer’s Consortium Annual Meeting. Tempe, AZ.
• Matijevic, S., Walther, K., & Ryan, T. L. (2018, May). Relationship between diffusion tensor imaging metrics and white matter hyperintensity volume in aging. Cognitive Aging Conference. Atlanta, GA.
• Ryan, T. L., & Memel, M. B. (2018, February). Visual integration of objects and scenes results in age-specific changes in HC and PHC contributions to successful memory retrieval. Annual Meeting of the International Neuropsychological Society. Washington DC.
• Stickel, A., McKinnon, A., Ruiz, J., & Ryan, T. L. (2018, March). Memory and processing speed predict functional independence differentially in non-Hispanic and Hispanic White middle aged and older adults. Cognitive Neuroscience Society Annual Meeting. Boston, MA.
• Stickel, A., Meyer, A., & Ryan, T. L. (2018, February). Body mass index and percent body fat differentially predict memory in young old and older old adults. Annual Meeting of the International Neuropsychological Society.. Washington DC.
• Gallegos, N. J., Stickel, A., & Ryan, T. L. (2017, November). The impacts of family history of Alzheimer's disease and education on white matter integrity. Society for Neuroscience Annual Meeting. Washington, DC.
• Memel, M. B., & Ryan, T. L. (2017, February). Contributions of visual integration and frontotemporal white matter integrity on associative memory in older adults. Forty Fifth Annual Meeting of the International Neuropsychological Society. New Orleans, LA.
• Stickel, A., & Ryan, T. L. (2017, November). Associations between cardiovascular risk factors and cognition in aging Hispanics compared to NonHispanic Whites. Society for Neuroscience Annual Meeting. Washington, DC.
• Lawrence, A., & Ryan, T. L. (2016, April). Recognition Memory Context Effects in Aging. Cognitive Neuroscience Society Annual Meeting. New York, New York.
• Lawrence, A., & Ryan, T. L. (2016, November). Familiar context effects on pattern separation in aging. Society for Neuroscience Annual Meeting. San Diego, CA.
• Memel, M., & Ryan, T. L. (2016, November). An fMRI analysis of visual unitization and the age-related associative memory deficit. Society for Neuroscience Annual Meeting. San Diego, CA.
• Stickel, A., Walther, K., Huentelman, M., & Ryan, T. L. (2016, November). FTO gene and BMI interact to predict white matter integrity in late middle age and older adults. Society for Neuroscience Annual Meeting. San Diego, CA.
• Kawa, K., Schmit, M. B., Cardoza, J., Stickel, A., Glisky, E. L., & Ryan, T. L. (2015, October). Age-related differences in networks of brain activation across two executive functioning domains – updating and task-switching. Society for Neuroscience Annual Meeting. Chicago, IL: Society for Neuroscience.
• Schmit, M. B., Kawa, K., Stickel, A., & Ryan, T. L. (2015, October). Fractional anisotropy in the left uncinate fasciculus and the inferior cingulum differentially predict memory and executive functions in older adults. Society for Neuroscience Annual Meeting. Chicago, IL: Society for Neuroscience.
• Singh, P., Stickel, A., Kawa, K., Buller, A., & Ryan, T. L. (2015, March). Age related decrease in white matter and gray matter volumes related to family history of Alzheimer’s disease. Cognitive Neuroscience Society Annual Meeting. San Francisco, CA: Cognitive Neuroscience Society.
• Baena, E., Buckley, T., Myhre, J. W., & Ryan, L. (2014, April). Age related differences in hippocampal response to increasing difficulty in an associative memory retrieval task: An fMRI investigation of functional compensation in a face-name pairs task. Cognitive Aging Conference. Atlanta, GA.
• Cardoza, J., Arnold, W., Flores-Wallentin, J., Barense, M., & Ryan, L. (2014, November). Age-related differences in object discrimination: the effects of familiarity on perirhinal cortex, hippocampus and temporal pole fMRI activation. Society for Neuroscience Annual Meeting. Washington, DC.
• Cardoza, J., Arnold, W., Flores-Wallentin, J., Barense, M., & Ryan, L. (2014, Spring). An fMRI study comparing perirhinal cortex, temporal pole, and hippocampus activation during complex object discrimination. Cognitive Aging Conference. Atlanta, GA.
• Cooke, K. A., Kawa, K., Memel, M. B., & Ryan, L. (2014, April). Differential effects of context shifts on object recognition and source memory in older adults. Cognitive Aging Conference. Atlanta, GA.
• Kawa, K., Cardoza, J., Stickel, A., Schmit, M., Lozano, M., Glisky, E. L., & Ryan, L. (2014, November). Comparing regional activations between older and younger adults on an fMRI task-switching and memory updating paradigm. Society for Neuroscience Annual Meeting. Washington, DC.
• Memel, M., & Ryan, L. (2014, November). Age-related declines in a hippocampal-mediated visual associative memory task: Integration or segmentation?. Society for Neuroscience Annual Meeting. Washington, DC.
• Ryan, L., & Baena, E. (2014, November). fMRI correlates of successful encoding and retrieval in response to increasing difficulty during an episodic memory task. Society for Neuroscience Annual Meeting. Washington, DC.
• Schmit, M. B., Cooke, K. A., & Ryan, L. (2014, April). Familiarity and the context shift decrement in young and older adults. Cognitive Aging Conference. Atlanta, GA.
• Baena, E., & Ryan, T. L. (2013, Spring). Functional compensation in response to increasing task difficulty: Comparing semantic and episodic memory tasks in young and older adults. Annual Conference of the Cognitive Neuroscience Society. San Francisco, CA: Cognitive Neuroscience Society.
• Baena, E., & Ryan, T. L. (2013, Spring). The Effects of Age and Increasing Task Difficulty on the Neural Correlates of Semantic Knowledge and Episodic Memory: An fMRI Investigation of Functional Compensation. 41st Annual Meeting of the International Neuropsychological Society. Waikoloa, HI: International Neuropsychological Society.
• Baena, E., Wohltmann, J., & Ryan, T. L. (2013, November). Age related differences in hippocampal response to increasing difficulty in an associative memory retrieval task: An fMRI investigation of face-name pairs. Society for Neuroscience Annual Meeting. San Diego, CA: Society for Neuroscience.
• Buckley, T., Sherman, S., Baena, E., & Ryan, L. (2013, Spring). The effects of caffeine and exercise on implicit and explicit memory performance in younger adults: an investigation of physiological arousal. Annual Conference of the Cognitive Neuroscience Society. San Francisco, CA: Cognitive Neuroscience Society.
• Cardoza, J., Kawa, K., Arnold, W. A., Wallentin-Flores, J., Barense, M. D., & Ryan, T. L. (2013, November). An fMRI study comparing perirhinal cortex, temporal pole, and hippocampus activation during complex object discrimination in younger adults. Society for Neuroscience Annual Meeting. San Diego, CA: Society for Neuroscience.
• Cooke, K. A., & Ryan, T. L. (2013, November). The differential role of visual context for young and older adults during object item memory and source memory. Society for Neuroscience Annual Meeting. San Diego, CA: Society for Neuroscience.
• Kawa, K., Stickel, A., Walther, K., Glisky, E. L., Hackett, N., Huentelman, M. J., & Ryan, T. L. (2013, November). The effects of KIBRA, APOE, and hypertension status on measures of memory functioning in older adults. Society for Neuroscience Annual Meeting. San Diego, CA: Society for Neuroscience.
• Stickel, A., Kawa, K., & Ryan, T. L. (2013, November). The effects of BMI on executive functioning in young-older adults versus old-older adults. Society for Neuroscience Annual Meeting. San Diego, CA: Society for Neuroscience.