I completed my undergraduate degree at the University of Toronto, and my PhD at the University of Cambridge. My work explores the neural mechanisms supporting episodic memory, and how these are affected by aging and Alzheimer's disease. I am currently leading the Stanford Aging and Memory Study, a large-scale longitudinal project examining individual differences in episodic memory in older adults. My research combines structural and functional MRI, PET imaging, and analysis of molecular and genetic risk factors for Alzheimer's disease.
Bachelor of Science, University of Toronto (2012)
Doctor of Philosophy, University of Cambridge (2016)
Association of CSF Biomarkers with Hippocampal-dependent Memory in Preclinical Alzheimer Disease.
To determine if memory tasks with demonstrated sensitivity to hippocampal function can detect variance related to preclinical Alzheimer's disease (AD) biomarkers, we examined associations between performance in three memory tasks and CSF Aβ42/Aβ40 and p-tau181 in cognitively unimpaired older adults (CU).CU enrolled in the Stanford Aging and Memory Study (N=153; age 68.78 ± 5.81 yrs; 94 female) completed a lumbar puncture and memory assessments. CSF Aβ42, Aβ40, and phosopho-tau181 (p-tau181) were measured with the automated Lumipulse G system in a single-batch analysis. Episodic memory was assayed using a standardized delayed recall composite, paired associate (word-picture) cued recall, and a mnemonic discrimination task that involves discrimination between studied 'target' objects, novel 'foil' objects, and perceptually similar 'lure' objects. Analyses examined cross-sectional relationships between memory performance, age, and CSF measures, controlling for sex and education.Age and lower Aβ42/Aβ40 were independently associated with elevated p-tau181. Age, Aβ42/Aβ40, and p-tau181 were each associated with a) poorer associative memory and b) diminished improvement in mnemonic discrimination performance across levels of decreased task difficulty (i.e., target-lure similarity). P-tau mediated the effect of Aβ42/Aβ40 on memory. Relationships between CSF proteins and delayed recall were similar but non-significant. CSF Aβ42 was not significantly associated with p-tau181 or memory.Tests designed to tax hippocampal function are sensitive to subtle individual differences in memory among CU, and correlate with early AD-associated biomarker changes in CSF. These tests may offer utility for identifying cognitively unimpaired older adults with preclinical AD pathology.
View details for DOI 10.1212/WNL.0000000000011477
View details for PubMedID 33408146
Executive function and high ambiguity perceptual discrimination contribute to individual differences in mnemonic discrimination in older adults.
2021; 209: 104556
Mnemonic discrimination deficits, or impaired ability to discriminate between similar events in memory, is a hallmark of cognitive aging, characterised by a stark age-related increase in false recognition. While individual differences in mnemonic discrimination have gained attention due to potential relevance for early detection of Alzheimer's disease, our understanding of the component processes that contribute to variability in task performance across older adults remains limited. The present investigation explores the roles of representational quality, indexed by perceptual discrimination of objects and scenes with overlapping features, and strategic retrieval ability, indexed by standardised tests of executive function, to mnemonic discrimination in a large cohort of older adults (N=124). We took an individual differences approach and characterised the contributions of these factors to performance under Forced Choice (FC) and Yes/No (YN) recognition memory formats, which place different demands on strategic retrieval. Performance in both test formats declined with age. Accounting for age, individual differences in FC memory performance were best explained by perceptual discrimination score, whereas YN memory performance was best explained by executive functions. A linear mixed model and dominance analyses confirmed the relatively greater importance of perceptual discrimination over executive functioning for FC performance, while the opposite was true for YN. These findings highlight parallels between perceptual and mnemonic discrimination in aging, the importance of considering demands on executive functions in the context of mnemonic discrimination, and the relevance of test format for modulating the impact of these factors on performance in older adults.
View details for DOI 10.1016/j.cognition.2020.104556
View details for PubMedID 33450438
Hippocampal and cortical mechanisms at retrieval explain variability in episodic remembering in older adults.
Age-related episodic memory decline is characterized by striking heterogeneity across individuals. Hippocampal pattern completion is a fundamental process supporting episodic memory. Yet, the degree to which this mechanism is impaired with age, and contributes to variability in episodic memory, remains unclear. We combine univariate and multivariate analyses of fMRI data from a large cohort of cognitively normal older adults (N=100) to measure hippocampal activity and cortical reinstatement during retrieval of trial-unique associations. Trial-wise analyses revealed that (a) hippocampal activity scaled with reinstatement strength, (b) cortical reinstatement partially mediated the relationship between hippocampal activity and associative retrieval, (c) older age weakened cortical reinstatement and its relationship to memory behaviour. Moreover, individual differences in the strength of hippocampal activity and cortical reinstatement explained unique variance in performance across multiple assays of episodic memory. These results indicate that fMRI indices of hippocampal pattern completion explain within- and across-individual memory variability in older adults.
View details for DOI 10.7554/eLife.55335
View details for PubMedID 32469308
Tau PET imaging with 18F-PI-2620 in aging and neurodegenerative diseases.
European journal of nuclear medicine and molecular imaging
In vivo measurement of the spatial distribution of neurofibrillary tangle pathology is critical for early diagnosis and disease monitoring of Alzheimer's disease (AD).Forty-nine participants were scanned with 18F-PI-2620 PET to examine the distribution of this novel PET ligand throughout the course of AD: 36 older healthy controls (HC) (age range 61 to 86), 11 beta-amyloid+ (Aβ+) participants with cognitive impairment (CI; clinical diagnosis of either mild cognitive impairment or AD dementia, age range 57 to 86), and 2 participants with semantic variant primary progressive aphasia (svPPA, age 66 and 78). Group differences in brain regions relevant in AD (medial temporal lobe, posterior cingulate cortex, and lateral parietal cortex) were examined using standardized uptake value ratios (SUVRs) normalized to the inferior gray matter of the cerebellum.SUVRs in target regions were relatively stable 60 to 90 min post-injection, with the exception of very high binders who continued to show increases over time. Robust elevations in 18F-PI-2620 were observed between HC and Aβ+ CI across all AD regions. Within the HC group, older age was associated with subtle elevations in target regions. Mildly elevated focal uptake was observed in the anterior temporal pole in one svPPA patient.Preliminary results suggest strong differences in the medial temporal lobe and cortical regions known to be impacted in AD using 18F-PI-2620 in patients along the AD trajectory. This work confirms that 18F-PI-2620 holds promise as a tool to visualize tau aggregations in AD.
View details for DOI 10.1007/s00259-020-04923-7
View details for PubMedID 32572562
Neural evidence for age-related differences in representational quality and strategic retrieval processes.
Neurobiology of aging
2019; 84: 50–60
Mounting behavioral evidence suggests that declines in both representational quality and controlled retrieval processes contribute to episodic memory decline with age. The present study sought neural evidence for age-related change in these factors by measuring neural differentiation during encoding of paired associates and changes in regional blood oxygenation level-dependent activity and functional connectivity during retrieval conditions that placed low (intact pairs) and high (recombined pairs) demands on controlled retrieval processes. Pattern similarity analysis revealed age-related declines in the differentiation of stimulus representations at encoding, manifesting as both reduced pattern similarity between closely related events and increased pattern similarity between distinct events. During retrieval, both groups increased recruitment of areas within the core recollection network when endorsing studied pairs, including the hippocampus and angular gyrus. In contrast, only younger adults increased recruitment of, and hippocampal connectivity with, lateral prefrontal regions during correct rejections of recombined pairs. These results provide evidence for age-related changes in representational quality and in the neural mechanisms supporting memory retrieval under conditions of high, but not low, control demand.
View details for DOI 10.1016/j.neurobiolaging.2019.07.012
View details for PubMedID 31491595
Dissociable contributions of thalamic nuclei to recognition memory: novel evidence from a case of medial dorsal thalamic damage
LEARNING & MEMORY
2018; 25 (1): 31–44
The thalamic nuclei are thought to play a critical role in recognition memory. Specifically, the anterior thalamic nuclei and medial dorsal nuclei may serve as critical output structures in distinct hippocampal and perirhinal cortex systems, respectively. Existing evidence indicates that damage to the anterior thalamic nuclei leads to impairments in hippocampal-dependent tasks. However, evidence for the opposite pattern following medial dorsal nuclei damage has not yet been identified. In the present study, we investigated recognition memory in NC, a patient with relatively selective medial dorsal nuclei damage, using two object recognition tests with similar foils: a yes/no (YN) test that requires the hippocampus, and a forced choice corresponding test (FCC) that is supported by perirhinal cortex. NC performed normally in the YN test, but was impaired in the FCC test. Critically, FCC performance was impaired only when the study-test delay period was filled with interference. We interpret these results in the context of the representational-hierarchical model, which predicts that memory deficits following damage to the perirhinal system arise due to increased vulnerability to interference. These data provide the first evidence for selective deficits in a task that relies on perirhinal output following damage to the medial dorsal nuclei, providing critical evidence for dissociable thalamic contributions to recognition memory.
View details for DOI 10.1101/lm.045484.117
View details for Web of Science ID 000423996900004
View details for PubMedID 29246979
View details for PubMedCentralID PMC5733467
Declines in Representational Quality and Strategic Retrieval Processes Contribute to Age-Related Increases in False Recognition
JOURNAL OF EXPERIMENTAL PSYCHOLOGY-LEARNING MEMORY AND COGNITION
2017; 43 (12): 1883–97
In a Yes/No object recognition memory test with similar lures, older adults typically exhibit elevated rates of false recognition. However, the contributions of impaired retrieval, relative to reduced availability of target details, are difficult to disentangle using such a test. The present investigation sought to decouple these factors by comparing performance on a Yes/No (YN) test to that on a Forced Choice (FC) test, which minimizes demands on strategic retrieval processes, enabling a more direct measure of the availability of object details. Older adults exhibited increased lure false recognition across test formats (Experiment 1), suggesting a decline in the availability of object details contributes to deficits in performance. Manipulating interference by varying the number of objects studied selectively enhanced performance in the FC test, resulting in matched performance across groups, whereas age differences in YN performance persisted (Experiment 2), indicating an additional contribution of impaired strategic retrieval. Consistent with differential sensitivity of test format to strategic retrieval and the quality of stimulus representations among older adults, variability in the quality of object representations, measured using a perceptual discrimination task, was selectively related to FC performance. In contrast, variability in memory control processes, as measured with tests of recall and executive function, was related to performance across test formats. These results suggest that both declines in the availability of object details and impaired retrieval of object details contribute to elevated rates of lure false recognition with age, and highlight the utility of test format for dissociating these factors in memory-impaired populations. (PsycINFO Database Record
View details for DOI 10.1037/xlm0000412
View details for Web of Science ID 000417904300004
View details for PubMedID 28530412
View details for PubMedCentralID PMC5729965
Identifying Age-Invariant and Age-Limited Mechanisms for Enhanced Memory Performance: Insights From Self-Referential Processing in Younger and Older Adults
PSYCHOLOGY AND AGING
2015; 30 (2): 324–33
Self-referential processing has been identified as a possible tool for supporting effective encoding processes in the elderly population. However, the importance of self-reference per se, relative to the increase in meaningful elaboration normally associated with self-reference instructions, remains unclear. The present study sought to explore this issue further by examining self-referential encoding strategies that inherently involve more extensive stimulus elaboration: episodic autobiographical memory (AM) retrieval and semantic AM retrieval. These were compared with an analogous task involving retrieval of general semantic knowledge, as well as traditional binary self-referential and semantic encoding judgments. We found that both AM retrieval and general semantic retrieval at encoding resulted in substantial enhancements to recall and recognition memory of concrete nouns relative to binary encoding judgments across both age groups. Furthermore, older adults exhibited larger benefits from this additional elaboration than did younger adults, leading to elimination of age-related deficits in recognition memory. However, younger adults showed an additional boost to subsequent memory following episodic, relative to semantic, AM retrieval during free recall that was not exhibited by older adults. This may be because of greater demands on frontally mediated control processes and cognitive resources associated with the use of this strategy. Taken together, the results suggest that the mnemonic benefits associated with self-referential processing vary substantially depending on the specific nature of the encoding strategy, and suggest that, under certain conditions, semantic processing and self-referential processing are equally effective in mitigating age-related deficits in memory performance.
View details for DOI 10.1037/a0039116
View details for Web of Science ID 000355839900012
View details for PubMedID 25961877
- Decoding the Role of the Angular Gyrus in the Subjective Experience of Recollection JOURNAL OF NEUROSCIENCE 2014; 34 (43): 14167–69
Hyper-Binding Across Time: Age Differences in the Effect of Temporal Proximity on Paired-Associate Learning
JOURNAL OF EXPERIMENTAL PSYCHOLOGY-LEARNING MEMORY AND COGNITION
2014; 40 (1): 293–99
Older adults show hyper- (or excessive) binding effects for simultaneously and sequentially presented distraction. Here, we addressed the potential role of hyper-binding in paired-associate learning. Older and younger adults learned a list of word pairs and then received an associative recognition task in which rearranged pairs were formed from items that had originally occurred either close together or far apart in the study list. Across 3 experiments, older adults made more false alarms to near re-pairings than to far re-pairings. Younger adults, on the other hand, showed no difference in false alarms to the 2 types of rearranged pairs. These findings may be tied to the greater tendency of older adults to maintain access to recently attended information, inadvertently forming broader associations across time, than is the case for younger adults.
View details for DOI 10.1037/a0034109
View details for Web of Science ID 000329049600021
View details for PubMedID 23937237