Biology subjects

Hämmerer, D.

Publications and source records attributed to Hämmerer, D..

5 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↗

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↗

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↗