The effect of age on relational encoding as revealed by hippocampal functional connectivity

The neural processes mediating cognition occur in networks distributed throughout the brain. The encoding and retrieval of relational memories, memories for multiple items or multifeatural events, is supported by a network of brain regions, particularly the hippocampus. The hippocampal coupling hypothesis suggests that the hippocampus is functionally connected with the default mode network (DMN) during retrieval, but during encoding, decouples from the DMN. Based on prior research suggesting that older adults are less able to modulate between brain network states, we tested the hypothesis that older adults’ hippocampus would show functional connectivity with the DMN during relational encoding. The results suggest that, while the hippocampus is functionally connected to some regions of the DMN during relational encoding in both younger and older adults, older adults show additional DMN connectivity. Such age-related changes in network modulation appear not to be mediated by compensatory processes, but rather to reflect a form of neural inefficiency, most likely due to reduced inhibition

Hippocampus at 25

The journal Hippocampus has passed the milestone of 25 years of publications on the topic of a highly studied brain structure, and its closely associated brain areas. In a recent celebration of this event, a Boston memory group invited 16 speakers to address the question of progress in understanding the hippocampus that has been achieved. Here we present a summary of these talks organized as progress on four main themes: (1) Understanding the hippocampus in terms of its interactions with multiple cortical areas within the medial temporal lobe memory system, (2) understanding the relationship between memory and spatial information processing functions of the hippocampal region, (3) understanding the role of temporal organization in spatial and memory processing by the hippocampus, and (4) understanding how the hippocampus integrates related events into networks of memories

Understanding User Cognition: From Spatial Ability to Code Writing and Review

Understanding how developers carry out different computer science activities with objective measures can help to improve productivity and guide the use and development of supporting tools in software engineering. In this thesis, we present three research components using three different objective measures including neuroimaging (functional magnetic resonance imaging (fMRI) and functional near-infrared spectroscopy (fNIRS)) and eye tracking. We evaluate on over 140 human subjects to explore multiple computing activities, including data structure manipulations, code writing and code review. This thesis presents a systematic framework and shows that it is possible to conduct studies that acquire objective data in a natural setting to provide an understanding of users' underlying cognitive processes in software engineering tasks. We also provide basic principles and guidelines to adapt multiple psycho-physiological measures to software engineering.PHDComputer Science & EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/169678/1/yhhy_1.pd

TheRelationship between brain network organization and variability in episodic memory outcomes and abilities:

Thesis advisor: Maureen RitcheyThesis advisor: Elizabeth KensingerOur brains afford us the remarkable ability to remember past events from our lives, to travel back in time in our minds' eye and relive our memories anew. What are the brain processes that support this ability? In this thesis I investigated this question across three experiments. In Chapter 1, I examined how the brain regions previously linked to episodic cognition (i.e., the hippocampus, parahippocampal cortex, retrosplenial cortex, posterior cingulate cortex, precuneus, angular gyrus, and medial prefrontal cortex) support recollection by building a model that incorporates both region-specific and network-level contributions. I found that these brain regions form ventral and dorsal subnetworks and that their contributions to recollection outcomes are largely explained by subnetwork-level rather than region-specific engagement. In Chapter 2, I used an openly available MRI dataset to test whether individual differences in functional connectivity were related to individual differences in memory ability, finding that network connectivity outside of the classic episodic networks supports individual differences in our ability to remember. In Chapter 3, I tested a neuroscience inspired hypothesis that individuals would have different capacities to bind their memories around social-emotional and visual-spatial content, ultimately finding inconclusive evidence for or against my hypothesis. Together, these results help to solidify our understanding of the brain as an interconnected network of brain regions and shed new light on how these networks support individual differences in memory.Thesis (PhD) — Boston College, 2023.Submitted to: Boston College. Graduate School of Arts and Sciences.Discipline: Psychology

Individual Differences in Memory Functions and Their Relation to Hippocampal Connectivity

The hippocampus plays an important role in many aspects of learning and memory. It is most known for its role in episodic memory and spatial navigation, though it has also been shown to contribute to other processes like prioritizing memory for motivationally salient information and connecting related memories to form generalized knowledge. How can a single structure support different types of learning? As the hippocampus does not work in isolation to support memory, one proposal is that it may form connections with different brain regions to support different functions of memory. Recent work has shown how stable, trait-like connections can be leveraged to predict individual behavior. Thus, the present dissertation aims to explore 1) how different hippocampal connections relate to different memory processes, and 2) whether intrinsic hippocampal connections can be linked to individual memory performance. In three empirical chapters, I demonstrate how distinct hippocampal connections are associated with different functions of memory, including reward motivated learning, generalization and memory specificity. Moreover, I show how anterior and posterior hippocampus form distinct connections that may further support different aspects of memory. Finally, the dissertation demonstrates how stable, trait-like hippocampal connections can be linked to individual behavior. Together, these findings provide insight into the different functions of hippocampal connectivity and the utility of intrinsic connections in understanding individual memory abilities

The neural architecture of semantic retrieval with and without cues: evidence from neuropsychology and neuroimaging

Everyday situations are conceptually rich, but not all of this knowledge is relevant at a given time. At the heart of adaptive cognition is flexibility, which allows us to focus on particular mental representations in a way that suits the changing context and goals. Previous work has highlighted the importance of semantic control mechanisms in retrieval, which allow cognition to diverge from dominant associations (Lambon Ralph et al., 2016). However, a clear understanding of the cognitive and neural substrates of semantic flexibility is currently lacking. This work collects evidence from different methods and experimental populations to tackle this broad question. We use novel multimodal semantic cues (i.e. affect and spatial locations) to examine the mechanisms that support flexible patterns of retrieval when the context is helpful or unhelpful. The first two empirical chapters examine behavioural effects of cues and miscues in patients with semantic aphasia (Chapter 2) and investigate whether patients with SA show greater benefits of coherent cue combinations compared to minimal levels of cueing (Chapter 3). The third chapter explores the neural bases of cued semantic retrieval, and tests the predictions of another recent framework which situates the default mode network at the top of a cortical hierarchy of abstraction (Margulies et al., 2016). The final chapter investigates whether the intrinsic connectivity of the brain at rest is predictive of the behavioural efficiency in cued semantic retrieval. Our findings provide evidence for the existence of two qualitatively distinct mechanisms for semantic flexibility, one driven by control processes (impaired in SA) and one driven by the integration of contextual information with long-term semantic knowledge (relatively intact in SA). In line with a growing body of work suggesting a role of default mode network in information integration, we show that more coherent patterns of retrieval which are driven by the context recruit this network. In contrast, multiple-demand regions appear to support more executive aspects of cued retrieval required for the maintenance of cue information. Finally, this thesis provide evidence that affect and location cues are both effective at shaping the activation of semantic knowledge. In summary, this thesis suggests that semantic flexibility is a complex and multi-faceted process which requires an interplay of different cognitive and neural components

Impact of APOE genotype and age on large-scale MTL neurocognitive networks

Research on medial temporal lobe (MTL) function converges on the notion that the hippocampus and perirhinal cortex (PRC) are specialised for different types of representational content: scenes and objects. The evolutionary accretion model advances this further, proposing that these MTL structures constitute key nodes within the extended hippocampal navigation and feature networks, respectively. The former network is considered more vulnerable to the impact of age and age-related neurodegenerative disease, including Alzheimer’s disease (AD). Additionally, young carriers of the apolipoprotein E (APOE) ε4 allele – an AD risk factor – have been shown to exhibit alterations within this network, supporting lifespan accounts of cognitive decline. Recently, however, this network-selective vulnerability has been challenged by reports of object-related impairments in ageing and AD risk. This thesis therefore investigated the impact of APOE genotype – especially APOE ε4 – and age on these two neurocognitive networks and their representations. To achieve this, web-based cognitive testing (Chapter 2), magnetic resonance imaging (MRI)-based structural covariance analysis (Chapter 3), and diffusion MRI-based tractography (Chapter 4) were used. In middle-aged and older adults, APOE ε4 and APOE ε2 – a risk-reducing allele – were associated with divergent age trends in perceptual discrimination independent of condition (Chapter 2). Conversely, in a sample spanning the adult lifespan, age and gender/sex – but not APOE ε4 – were associated with the structural covariance of the hippocampus and PRC (Chapter 3). Finally, in younger adults, APOE ε4 impacted the lateralisation of inferior longitudinal fasciculus (ILF) microstructure – a key tract in the feature network (Chapter 4). The findings of this thesis provide evidence that APOE genotype and age impact aspects of these networks and their representations, but it remains challenging to interpret them collectively. Nonetheless, this research addresses pre-existing limitations, and provides a foundation for studies that could aid our understanding of age- and APOE-related impact(s) on the brain and cognition