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Düzel, E.

Publications and source records attributed to Düzel, E..

11 recordsLinked to original sources
bioRxiv2025

Different dopaminergic circuits defined by D2/D3 receptor availablity patterns show structure-specific links to memory in ageing

Cognitive ageing is marked by progressive decline in episodic memory and dopaminergic function, yet the extent to which individual differences in dopaminergic system integrity influence memory under motivational contexts remains unclear. In this study, we investigated how baseline D2/D3 receptor availability (BPND0) in key dopaminergic pathways relates to reward-modulated memory performance in healthy older adults. Thirty-three healthy seniors (aged 64-85) underwent two session concurrent MR-PET imaging with [1F]fallypride involving scene categorisation task with high- and low-motivational contexts. We quantified BPND0 across nine dopaminergic regions of interest and examined their relationships with recognition memory performance at short ([~]15m) and long ([~]24h) delays. Baseline D2/D3 receptor availability showed high test-retest reliability and regionally distinct profiles, suggesting it reflects a stable neurochemical characteristic in healthy ageing, and principal axis factor analysis revealed two partially independent dopaminergic subsystems (dorsal striatal vs mesolimbic) based on interindividual patterns in receptor densities. Region-specific associations further linked D2/D3 receptor availability to distinct memory outcomes. Higher caudate D2/D3 receptor availability was associated with a liberal response bias (increased hits and false alarms both), whereas higher putamen D2/D3 predicted more durable long-term memory retention. Greater thalamic D2/D3 receptor availability correlated with fewer short-term false memories, while greater D2/D3 receptor availability in the amygdala was associated with better recognition at longer delays. In contrast, higher midbrain (substantia nigra and ventral tegmental area) D2/D3 availability which was linked to poorer reward-related memory performance. These findings suggest several complementary dopaminergic circuits supporting episodic memory. Our results highlight dopaminergic neuromodulation as a key factor in cognitive ageing and a potential target for interventions to bolster memory in late life. Patient consent and ethics approvalAll subjects who were included in this study have provided their consent prior to their participation, following the guidelines of the ethics committee at University Hospital Magdeburg in Magdeburg, Germany.

neuroscience↗
bioRxiv2025

Pupil dilation as a marker of attention/effort in aging and mild cognitive impairment

Pupil dilation (PD) can be easily measured and reflects responses to subjectively salient or cognitively demanding events. It therefore holds promise as a cognitive marker especially for individuals with mild cognitive impairment (MCI) or other neurodegenerative conditions with restricted abilities to respond in cognitive assessments. We assessed PD during two tasks, an oddball task for investigating attentional allocation and a Simon task which additionally allows for investigating cognitive effort in younger adults (YAs), older adults (OAs), and patients with MCI. PD is a useful marker for investigating attention and cognitive effort in MCI, as suggested by elevated PD to salient stimuli in particular of individuals with better attentional control in MCI patients, as well as YAs and OAs. Measurement of PD may serve as an easy-to-administer measure to assess changes in cognitive function in healthy aging and MCI.

neuroscience↗
bioRxiv2025

Disrupted Forward Connectivity in Parieto-temporal Network Impairs Memory Performance in Alzheimer's Disease

Alzheimers disease (AD) is characterised by the accumulation of beta-amyloid (A{beta}) and tau proteins, leading to neurodegeneration and cognitive decline. While A{beta} and tau are known to disrupt synaptic function, the mechanisms linking these molecular pathologies to network-level dysfunction and memory impairment remain poorly understood. Here we investigated the effects of A{beta} and tau pathology (CSF A{beta}42/40 ratio and tau phosphorylated at position 181, p-tau-181, respectively) on effective connectivity (EC) related to memory encoding, which may constitute a link between synaptic pathology and cognitive outcomes. Functional magnetic resonance imaging (fMRI) during visual memory encoding was acquired from participants of the multicentric DZNE Longitudinal Cognitive Impairment and Dementia Study (DELCODE), including 203 cognitively normal older participants (CN) as well as individuals with subjective cognitive decline (SCD; N = 204), mild cognitive impairment (MCI; N = 65), and early dementia due to AD (DAT; N = 21). EC was assessed by applying Dynamic causal modelling (DCM) to the fMRI data, using brain regions previously implicated in memory-encoding: the parahippocampal place area (PPA), the hippocampus (HC) and the precuneus (PCU). Disruptions in forward connectivity from the PPA to the HC and PCU were associated with both memory impairment and indices of AD pathology. Specifically, reduced excitatory EC from the PPA to the HC was associated with higher p-tau-181 levels and correlated with poorer memory performance. Diminished inhibitory EC from the PPA to the PCU was driven by both tau and amyloid pathology and was likewise linked to memory decline. Our findings suggest that disrupted forward connectivity within the temporo-parietal memory network constitutes a candidate mechanism mediating the relationship between molecular pathology and cognitive dysfunction.

neuroscience↗
bioRxiv2024

Fully Automated MRI-based Analysis of the Locus Coeruleus in Aging and Alzheimer's Disease Dementia using ELSI-Net

INTRODUCTIONThe Locus Coeruleus (LC) is linked to the development and pathophysiology of neurodegenerative diseases such as Alzheimers Disease (AD). Magnetic Resonance Imaging based LC features have shown potential to assess LC integrity in vivo. METHODSWe present a Deep Learning based LC segmentation and feature extraction method: ELSI-Net and apply it to healthy aging and AD dementia datasets. Agreement to expert raters and previously published LC atlases were assessed. We aimed to reproduce previously reported differences in LC integrity in aging and AD dementia and correlate extracted features to cerebrospinal fluid (CSF) biomarkers of AD pathology. RESULTSELSI-Net demonstrated high agreement to expert raters and published atlases. Previously reported group differences in LC integrity were detected and correlations to CSF biomarkers were found. DISCUSSIONAlthough we found excellent performance, further evaluations on more diverse datasets from clinical cohorts are required for a conclusive assessment of ELSI-Nets general applicability. HighlightsO_LIthorough evaluation of a fully automatic LC segmentation method termed ELSI-Net in aging and AD dementia C_LIO_LIELSI-Net outperforms previous work and shows high agreement with manual ratings and previously published LC atlases C_LIO_LIELSI-Net replicates previously shown LC group differences in aging and AD C_LIO_LIELSI-Nets LC volume correlates with CSF biomarkers of AD pathology C_LI RESEARCH IN CONTEXTO_LISystematic Review: The authors reviewed the literature using traditional sources (e.g. Pubmed, Google Scholar). Although there are several publications introducing semi-automatic methods for LC segmentation, the application of Deep Learning methods is underexplored. To the best of our knowledge, this is the first paper using a Deep Learning based approach for automated LC segmentation in AD dementia. C_LIO_LIInterpretation: Our work introduces and evaluates an improved automatic, Deep Learning based LC segmentation and analysis approach. The results suggest a very high potential for practical applicability, e.g. in large-scale clinical studies for neurodegenerative diseases. C_LIO_LIFuture Directions: ELSI-Net can be used to assess LC integrity on large- or small-scale studies in Alzheimers Disease dementia. To ensure robust performance, ELSI-Net should be further evaluated in larger, more diverse datasets comprising varying LC MRI protocols and clinical populations. C_LI

bioinformatics↗
bioRxiv2024

Decoding Salience: A Functional Magnetic Resonance Imaging Investigation of Reward and Contextual Unexpectedness in Memory Encoding and Retrieval

The present study investigated the neuromodulatory substrates of salience processing and its impact on memory encoding and behaviour, with a specific focus on two distinct types of salience: reward and contextual unexpectedness. 46 participants performed a novel task paradigm modulating these two aspects independently and allowing for investigating their distinct and interactive effects on memory encoding while undergoing high resolution fMRI. By using advanced image processing techniques tailored to examine midbrain and brainstem nuclei with high precision, our study additionally aimed to elucidate differential activation patterns in subcortical nuclei in response to reward-associated and contextually unexpected stimuli, including distinct pathways involving in particular dopaminergic modulation. We observed a differential involvement of the ventral striatum, substantia nigra and caudate nucleus, as well as a functional specialisation within the subregions of the cingulate cortex for the two salience types. Moreover, distinct subregions within the substantia nigra in processing salience could be identified. Dorsal areas preferentially processed salience related to stimulus processing (of both reward and contextual unexpectedness) versus ventral areas were involved in salience-related memory encoding (for contextual unexpectedness only). These functional specialisations within SN are in line with different projection patterns of dorsal and ventral SN to brain areas supporting attention and memory, respectively. By disentangling stimulus processing and memory encoding related to two salience types, we hope to further consolidate our understanding of neuromodulatory structures differential as well as interactive roles in modulating behavioural responses to salient events.

neuroscience↗
bioRxiv2022

Plasma concentrations of anti-inflammatory cytokine TGF-β are associated with hippocampal structure related to explicit memory performance in older adults

Human cognitive abilities, and particularly hippocampus-dependent memory performance typically decline with increasing age. Immunosenescence, the age-related disintegration of the immune system, is increasingly coming into the focus of research as a considerable factor contributing to cognitive decline. In the present study, we investigated potential associations between plasma levels of pro- and anti-inflammatory cytokines and learning and memory performance as well as hippocampal anatomy in young and older adults. Plasma concentrations of the inflammation marker CRP as well as the pro-inflammatory cytokines IL-6 and TNF- and the anti-inflammatory cytokine TGF-{beta}1 were measured in 142 healthy adults (57 young, 24.47 {+/-} 4.48 years; 85 older, 63.66 {+/-} 7.32 years) who performed tests of explicit memory (Verbal Learning and Memory Test, VLMT; Wechsler Memory Scale, Logical Memory, WMS) with an additional delayed recall test after 24 hours. Hippocampal volumetry and hippocampal subfield segmentation were performed using FreeSurfer, based on T1-weighted and high-resolution T2-weighted MR images. When investigating the relationship between memory performance, hippocampal structure, and plasma cytokine levels, we found that TGF- {beta}1 concentrations were positively correlated with the volumes of the hippocampal CA4-dentate gyrus region in older adults. These volumes were in turn positively associated with better performance in the WMS, particularly in the delayed memory test. Our results support the notion that endogenous anti-inflammatory mechanisms may act as protective factors in neurocognitive aging.

neuroscience↗
bioRxiv2022

Structural and functional MRI data differentially predict chronological age and behavioral memory performance

Human cognitive abilities decline with increasing chronological age, with decreased explicit memory performance being most strongly affected. However, some older adults show "successful aging", that is, relatively preserved cognitive ability in old age. One explanation for this could be higher brain structural integrity in these individuals. Alternatively, the brain might recruit existing resources more efficiently or employ compensatory cognitive strategies. Here, we approached this question by testing multiple candidate variables from structural and functional neuroimaging for their ability to predict chronological age and memory performance, respectively. Prediction was performed using support vector machine (SVM) classification and regression across and within two samples of young (N = 106) and older (N = 153) adults. The candidate variables were (i) behavioral response frequencies in an episodic memory test, (ii) recently described fMRI scores reflecting preservation of functional memory networks, (iii) whole-brain fMRI contrasts for novelty processing and subsequent memory, (iv) resting-state fMRI maps quantifying voxel-wise signal fluctuation and (v) gray matter volume estimated from structural MR images. While age group could be reliably decoded from all variables, chronological age within young and older subjects was best predicted from gray matter volume. In contrast, memory performance was best predicted from task-based fMRI contrasts and particularly single-value fMRI scores, whereas gray matter volume has no predictive power with respect to memory performance in healthy adults. Our results suggest that superior memory performance in healthy older adults is better explained by efficient recruitment of memory networks rather than by preserved brain structure.

neuroscience↗
bioRxiv2022

Summary statistics of memory-related fMRI activity reflect dissociable neuropsychological and anatomical signatures of neurocognitive aging

Memory-related functional magnetic resonance imaging (fMRI) activations show age-related differences across multiple brain regions that can be captured in summary statistics like single-value scores. Recently, we described two single-value scores reflecting deviations from prototypical whole-brain fMRI activity of young adults during novelty processing and successful encoding. Here, we investigate the brain-behavior associations of these scores with age-related neurocognitive changes in 153 healthy older adults. All scores were associated with episodic recall performance. The memory network scores, but not the novelty network scores, additionally correlated with medial temporal gray matter and a composite measure comprising pro-active inhibition, episodic memory, tonic alertness, flexibility, and working memory. Our results thus suggest that novelty-network-based fMRI scores show high brain-behavior associations with episodic memory and that encoding-network-based fMRI scores additionally capture individual differences in global cognitive function. More generally, our results suggest that single-value scores of memory-related fMRI provide a comprehensive measure of individual differences in network dysfunction that may contribute to age-related cognitive decline.

neuroscience↗
bioRxiv2021

It is the Locus Coeruleus! Or... is it? : A proposition for analyses and reporting standards for structural and functional magnetic resonance imaging of the noradrenergic Locus Coeruleus

The noradrenergic locus coeruleus (LC) in the brainstem shows early signs of protein pathologies in neurodegenerative diseases such as Alzheimers and Parkinsons disease. As the LCs small size (approximately 2.5 mm in width) presents a challenge for molecular imaging, the past decade has seen a steep rise in structural and functional Magnetic Resonance (MR) studies aiming to characterise the LCs changes in ageing and neurodegeneration. However, given its position in the brainstem and small volume, great care must be taken to yield methodologically reliable MR results as spatial deviations in transformations can greatly reduce the statistical power of the analyses at the group level. Here, we suggest a spatial transformation procedure and a set of quality assessment methods which allow LC researchers to achieve the spatial precision necessary for investigating this small but potentially impactful brain structure. Using a combination of available toolboxes (SPM12, ANTs, FSL, FreeSurfer), individual structural and functional 3T LC scans are transformed into MNI space via a study-specific anatomical template. Following this, the precision of spatial alignment in individual MNI-transformed images is quantified using in-plane distance measures based on slice-specific centroids of structural LC segmentations and based on landmarks of salient anatomical features in mean functional images, respectively. Median in-plane distance of all landmarks on the transformed structural as well as functional LC imaging data were below 2 mm, thereby falling below the typical LC width of 2.5 mm suggested by post-mortem data. With the set of spatial post-processing steps outlined in this paper and available for download, we hope to give readers interested in LC imaging a starting point for a reliable analysis of structural and functional MR data of the LC and to have also taken a first step towards establishing reporting standards of LC imaging data.

neuroscience↗
bioRxiv2021

A comprehensive score reflecting memory-related fMRI activations and deactivations as potential biomarker for neurocognitive aging

Older adults and particularly those at risk for developing dementia typically show a decline in episodic memory performance, which has been associated with altered memory network activity detectable via functional magnetic resonance imaging (fMRI). To quantify the degree of these alterations, a score has been developed as a putative imaging biomarker for successful aging in memory for older adults (Functional Activity Deviations during Encoding, FADE; Duzel et al., 2011). Here, we introduce and validate a more comprehensive version of the FADE score, termed FADE-SAME (Similarity of Activations during Memory Encoding), which differs from the original FADE score by considering not only activations but also deactivations in fMRI contrasts of stimulus novelty and successful encoding, and by taking into account the variance of young adults activations. We computed both scores for novelty and subsequent memory contrasts in a cohort of 217 healthy adults, including 106 young and 111 older participants, as well as a replication cohort of 117 young subjects. We further tested the stability and generalizability of both scores by controlling for different MR scanners and gender, as well as by using different data sets of young adults as reference samples. Both scores showed robust age-group-related differences for the subsequent memory contrast, and the FADE-SAME score additionally exhibited age-group-related differences for the novelty contrast. Furthermore, both scores correlate with behavioral measures of cognitive aging, namely memory performance. Taken together, our results suggest that single-value scores of memory-related fMRI responses may constitute promising biomarkers for quantifying neurocognitive aging.

neuroscience↗
bioRxiv2019

Memorability of photographs in subjective cognitive decline and mild cognitive impairment: implications for cognitive assessment

INTRODUCTIONImpaired long-term memory is a defining feature of Mild Cognitive Impairment (MCI). We tested whether this impairment is item-specific, limited to some memoranda whereas some remain consistently memorable.\n\nMETHODSWe conducted item-based analyses of long-term visual recognition memory. 394 participants (healthy controls (HC), Subjective Cognitive Decline (SCD), and MCI) in the multicentric DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) were tested with images from a pool of 835 photographs.\n\nRESULTSWe observed consistent memorability for images in HCs, SCDs, and MCI, predictable by a neural network trained on another healthy sample. Looking at memorability differences between groups, we identified images that could successfully categorize group membership with higher success and a substantial image reduction than the original image set.\n\nDISCUSSIONIndividuals with SCD and MCI show consistent memorability for specific items, while other items show significant diagnosticity. Certain stimulus features could optimize diagnostic assessment, while others could support memory.

neuroscience↗