Biology subjects

Duzel, E.

Publications and source records attributed to Duzel, E..

9 recordsLinked to original sources

bioRxiv2026

Entorhinal grid coding as a functional link between tau accumulation and episodic memory in human aging

Episodic memory decline is a common feature of cognitively normal aging, but its extent varies markedly across individuals. Although entorhinal tau pathology is thought to be a key contributor to episodic memory impairment, the neural mechanisms linking early tau accumulation to memory differences remain unclear. Grid-cell computations in the entorhinal cortex, which provide scaffolds for organizing experiences into episodic memories, offer one candidate mechanism. Here, we combined virtual-reality functional MRI, multivariate analysis, tau PET, and delayed word-list recall in cognitively normal older adults to test whether tau-related alterations in entorhinal coding are associated with worse episodic memory. Weaker left entorhinal grid-cell-like signal was associated with poorer memory performance, and individuals with higher left entorhinal tau burden showed weaker grid-cell-like signal. This association was specific to the canonical six-fold signal and was not explained by entorhinal volume, mean diffusivity, or intracortical myelination. A cross-sectional Bayesian mediation analysis further demonstrated that bilateral medial temporal tau burden is related to memory indirectly through left entorhinal grid-cell-like signal. Together, these findings provide evidence that entorhinal grid codes may constitute a functional pathway linking tau accumulation to memory variability in normal aging.

neuroscience↗

bioRxiv2026

Characterization and Validation of Compressed Sensing for Time-of-Flight MRI Angiography of the Human Brain at 3T and 7T

BackgroundCerebral vasculature is a key biomarker of brain health, and time-of-flight (TOF) magnetic resonance angiography (MRA) provides noninvasive assessment of vascular anatomy. However, conventional TOF-MRA requires long scan times, increasing patient burden and susceptibility to motion artifacts. Compressed sensing (CS) offers a feasible acceleration strategy. PurposeTo quantitatively evaluate CS acceleration in TOF-MRA at 3T and 7T using automated whole-FOV vascular segmentation and semi-automatic segmentation of representative vessels. Study typeProspective Population23 healthy human participants (3T) and 8 healthy human participants (7T). Field Strength/SequenceCS TOF-MRA (CS factors 4 and 8 at 3T; 8 at 7T) was compared against non-accelerated (CS0) TOF-MRA. AssessmentVisual comparison and vascular segmentation were performed using automated whole-FOV methods and semi-automatic segmentation of the posterior cerebral artery and anterior choroidal artery. Statistical TestsContrast-to-noise ratio (CNR), voxel count, and vessel diameter were assessed using two-tailed paired t-tests. ResultsWhole-FOV CNR differed significantly across CS factors at 3T (CS0 > CS4: p < 0.001, d = 0.77; CS0 < CS8: p = 0.008, d = 0.36; CS4 < CS8: p < 0.001, d = 1.11) and 7T (CS0 < CS8: p = 0.002, d = 0.54), with semi-automatic segmentation yielding consistent findings (p < 0.01 for all comparisons). The diameter measurements for segmented vessels are also higher with high CS-factors (PCA 7T: left: p = 0.006, d = 0.93, right: p = 0.045, d = 0.43; AChA 7T: left: p < 0.001, d = 0.66, right: p = 0.009, d = 1.06; PCA 3T: p < 0.001 for all comparison dLeft = 0.52 (CS0 vs. CS4), 0.56 (CS4 vs. CS8), 1.11 (CS0 vs. CS8) and dRight = 0.78 (CS0 vs. CS4), 0.57 (CS4 vs. CS8), 1.17 (CS0 vs. CS8)). Data ConclusionCS shows promise for enhancing clinical applicability of TOF-MRA, with advantages most pronounced at 7T.

bioengineering↗

bioRxiv2024

Increased recognition memory precision with decreased neural discrimination

Mnemonic discrimination (MD), the ability to distinguish between similar experiences in memory, is essential for memory precision. We hypothesized that training mnemonic discrimination should improve memory precision by increasing the neural activity differences between a new experience and a similar familiar experience (repeat). Participants performed a 2-week, web-based training program. For group 1, memory similarity was adapted to performance. Group 2 trained non-adaptively and group 3 served as active control. Adaptivity improved training gain and led to transfer to other memory tasks. Surprisingly, training reduced neural activity differences between new (lure) and similar familiar (repeat) experiences. Thus, instead of enhancing neural activity to lures and decreasing neural activity to repeats, training led to increased activity to repeats. In several brain regions this pattern was associated with improved MD. These findings highlight an unexpected neural mechanism underpinning improved memory precision in recognition memory.

neuroscience↗

bioRxiv2023

Cognitive Reserve Against Alzheimer's Pathology Is Linked to Brain Activity During Memory Formation

The cognitive reserve (CR) hypothesis posits that individuals can differ in how their brain function is disrupted by pathology associated with aging and neurodegeneration. Here, we tested this hypothesis in the Alzheimers disease continuum using longitudinal data from 490 participants of the DELCODE multicentric observational study. Brain function was measured using task fMRI of visual memory encoding. Using a multivariate moderation analysis we identified a CR-related activity pattern underlying successful memory encoding that moderated the detrimental effect of AD pathological load on cognitive performance. CR was mainly represented by a more pronounced expression of the task-active network encompassing the default mode network (DMN), anterior cingulate cortex (ACC) and inferior temporal regions including the fusiform gyrus. We devised personalized fMRI-based CR scores that moderated the impact of AD pathology on cognitive performance and were positively associated with years of education. Furthermore, higher CR scores were associated with slower cognitive decline over time. Our findings suggest maintenance of core cognitive circuits including the DMN and ACC as the primary mechanism of CR. Individual brain activity levels of these areas during memory encoding have prognostic value for future cognitive decline.

neuroscience↗

bioRxiv2021

Functional connectivity and information pathways in the human entorhinal-hippocampal circuitry

AO_SCPLOWBSTRACTC_SCPLOWCortical processing streams for item and contextual information come together in the entorhinal-hippocampal circuitry. Various evidence suggest that information-specific pathways organize the cortical - entorhinal interaction and the circuitrys inner communication along the transversal axis. Here, we leveraged ultra-high field functional imaging and advance Maass, Berron et al. (2015) who report two functional routes segregating the entorhinal cortex (EC) and subiculum. Our data show specific scene processing in the functionally connected posterior-medial EC and distal subiculum. The regions of another route, that connects the anterior-lateral EC and a newly identified retrosplenial-based anterior-medial EC subregion with the CA1/subiculum border, process object and scene information similarly. Our results support topographical information flow in human entorhinal-hippocampal subregions with organized convergence of cortical processing streams and a unique route for contextual information. They characterize the functional organization of the circuitry and underpin its central role in memory function and pathological decline.

neuroscience↗

bioRxiv2021

Lifelong musical activity is associated with multi-domain cognitive and brain benefits in older adults

1AO_SCPLOWBSTRACTC_SCPLOWRegular musical activity as a highly-stimulating lifestyle activity is proposed to be protective against age-related cognitive decline and Alzheimers disease (AD). This study investigated associations between lifelong regular musical instrument playing, late-life cognitive abilities and brain morphology in older adults. We show that musical activity over the life course is associated with better global cognition, working memory, executive functions, language, and visuospatial abilities accounting for reserve proxies. Playing music is not significantly associated with gray matter volume in regions most affected by aging and AD. Selectively in the musically active participants, multi-domain cognitive abilities were enhanced with preserved gray matter volume in frontal and temporal regions. Our correlational findings suggest that playing a musical instrument may improve the recruitment of existing brain resources to facilitate late-life cognitive capacities. We propose that engaging in regular musical activity could serve as a low-threshold multimodal enrichment strategy that may promote cognitive resilience in advanced age.

neuroscience↗

bioRxiv2018

Neural signatures of detours, shortcuts and back-tracking during navigation

Central to the concept of the cognitive map is that it confers behavioural flexibility, allowing animals to take efficient detours, exploit shortcuts and realise the need to back-track rather than persevere on a poorly chosen route. The neural underpinnings of such naturalistic and flexible behaviour remain unclear. During fMRI we tested human subjects on their ability to navigate to a set of goal locations in a virtual desert island riven by lava, which occasionally shifted to block selected paths (necessitating detours) or receded to open new paths (affording shortcuts). We found that during self-initiated back-tracking, activity increased in frontal regions and the dorsal anterior cingulate cortex, while activity in regions associated with the core default-mode network was suppressed. Detours activated a network of frontal regions compared to shortcuts. Activity in right dorsolateral prefrontal cortex specifically increased when participants encountered new plausible shortcuts but which in fact added to the path (false shortcuts). These results help inform current models as to how the brain supports navigation and planning in dynamic environments.\n\nSignificance StatementAdaptation to change is important for survival. Although real-world spatial environments are prone to continual change, little is known about how the brain supports navigation in dynamic environments where flexible adjustments to route plans are needed. Here, we used fMRI to examine the brain activity elicited when humans took forced detours, identified shortcuts and spontaneously back-tracked along their recent path. Both externally and internally generated changes in the route activated the fronto-parietal attention network, whereas only internally generated changes generated increased activity in the dorsal anterior cingulate cortex with a concomitant disengagement in regions associated with the default-mode network. The results provide new insights into how the brain plans and re-plans in the face of a changing environment.

neuroscience↗

bioRxiv2018

Spotting the path that leads nowhere: Modulation of human theta and alpha oscillations induced by trajectory changes during navigation

The capacity to take efficient detours and exploit novel shortcuts during navigation is thought to be supported by a cognitive map of the environment. Despite advances in understanding the neural basis of the cognitive map, little is known about the neural dynamics associated with detours and shortcuts. Here, we recorded magnetoencephalography from humans as they navigated a virtual desert island riven by shifting lava flows. The task probed their ability to take efficient detours and shortcuts to remembered goals. We report modulation in event-related fields and theta power as participants identified real shortcuts and differentiated these from false shortcuts that led along suboptimal paths. Additionally, we found that a decrease in alpha power preceded back-tracking where participants spontaneously turned back along a previous path. These findings help advance our understanding of the fine-grained temporal dynamics of human brain activity during navigation and support the development of models of brain networks that support navigation.

neuroscience↗

bioRxiv2018

Altered cingulate and substantia nigra/ventral tegmental activation to novelty and emotional salience in antipsychotic naive first episode psychosis patients

Abnormal salience processing has been suggested to contribute to the formation of positive psychotic symptoms in schizophrenia and related conditions. Previous research utilising reward learning or anticipation paradigms has demonstrated cortical and subcortical abnormalities in people with psychosis, specifically in the prefrontal cortex, the dopaminergic midbrain and the striatum. In these paradigms, reward prediction errors attribute motivational salience to stimuli. However, little is known about possible abnormalities across different forms of salience processing in psychosis patients, and whether any such abnormalities involve the dopaminergic midbrain. The aim of our study was, therefore, to investigate possible alterations in psychosis in neural activity in response to various forms of salience: novelty, negative emotion, targetness (task-driven salience) and rareness/deviance. We studied 14 antipsychotic naive participants with first episode psychosis, and 37 healthy volunteers. During fMRI scanning, participants performed a visual oddball task containing these four forms of salience. Psychosis patients showed abnormally reduced signalling in the substantia nigra/ventral tegmental area (SN/VTA) for novelty, negative emotional salience and targetness; reduced striatal and occipital (lingual gyrus) signalling to novelty and negative emotional salience, reduced signalling in the amygdala, anterior cingulate cortex and parahippocamal gyrus to negative emotional salience, and reduced cerebellar signalling to novelty and negative emotional salience. Our results indicate alterations of several forms of salience processing in patients with psychosis in the midbrain SN/VTA, with additional subcortical and cortical regions also showing alterations in salience signalling, the exact pattern of alterations depending on the form of salience in question.

neuroscience↗