Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/423277

Dissociating refreshing and elaboration by their neural signatures and their effects on memory in young and old adults

Bartsch, L. M.·Loaiza, V. M.·Jäncke, L.·Oberauer, K.·Lewis-Peacock, J.
View original source ↗Export metadata ↓

Abstract

Maintenance of information in working memory (WM) is assumed to rely on refreshing and elaboration, but clear mechanistic descriptions of these cognitive processes are lacking, and it is unclear whether they are simply two labels for the same process. This fMRI study investigated the extent to which refreshing, elaboration, and repeating of items in WM are distinct neural processes with dissociable behavioral outcomes in WM and long-term memory (LTM). Multivariate pattern analyses of fMRI data revealed differentiable neural signatures for these processes, which we also replicated in an independent sample of older adults. In some cases, the degree of neural separation within an individual predicted their memory performance. Elaboration improved LTM, but not WM, and this benefit increased as its neural signature became more distinct from repetition. Refreshing had no impact on LTM, but did improve WM, although the neural discrimination of this process was not predictive of the degree of improvement. These results demonstrate that refreshing and elaboration are separate processes that differently contribute to memory performance.\n\nHighlightsO_LIRepeated reading, refreshing, and elaboration are differentiable in brain activation patterns in both young and older adults.\nC_LIO_LIElaboration selectively improved long-term memory for young adults, and the size of the benefit was related to the neural separability of elaboration from other processes.\nC_LIO_LIOlder adults implemented a sub-optimal form of elaboration, and this may be a factor contributing to age-related deficits in long-term memory.\nC_LI\n\nEthics statementThe study was approved by the ethical review board of the canton of Zurich (BASEC-No. 2017-00190) and all subjects gave informed written consent in accordance with the Declaration of Helsinki.\n\nData and code availability statementAll behavioral data and analysis scripts can be assessed on the Open Science Framework (osf.io/p2h8b/). The fMRI data that support the findings of this study are available on request from the corresponding author, LMB. The fMRI data are not publicly available due to restrictions of the Swiss Ethics Committees on research involving humans regarding data containing information that could compromise the privacy of research participants.

Source connections

Explore related subjects

neurosciencePreprint

Keep this discovery

BibTeXRIS

Bartsch, L. M., Loaiza, V. M., Jäncke, L., Oberauer, K., Lewis-Peacock, J.. 2018-09-21. Dissociating refreshing and elaboration by their neural signatures and their effects on memory in young and old adults. https://doi.org/10.1101/423277

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

The Unreasonable Effectiveness of Cell Types in Describing Neuronal Physiological Features

Single-cell RNA sequencing (scRNA-seq) captures detailed gene expression profiles at scale, while patch-clamp recordings measure intrinsic neuronal electrophysiological properties. Modeling the relations between these two modalities remains a challenge. Here, we compare how well electrophysiological features can be predicted by traditional transcriptomic cell type classification, representations derived from a foundational model (scGPT) pretrained on large-scale scRNA-seq datasets, ion channel-coding genes, and highly variable genes. Using paired transcriptomic and electrophysiological patch-sequencing data from 495 human neurons from neurosurgical tissue, we find that cluster-level cell type representations consistently outperform highly variable gene selection, ion channel gene selection, and context-enriched scGPT embeddings. Notably, performance varies across model architectures and initializations, and the best results are obtained by combining the outputs of separate cell type and scGPT-based models. Together, these findings suggest that traditional discrete cellular classification is highly effective in predicting physiological features. For maximum performance it can be complemented by pretrained transformer models.

neuroscience↗
bioRxiv2026

A nonlinear inhibition pathway underlying cortical responses to tuned holographic optogenetic perturbations

Optogenetics enables causal manipulation of cortical activity. Perturbation responses can be counterintuitive due to network interactions, making theory essential for predicting them. Existing approaches often rely on linear approximations, which fail for many biologically relevant perturbations. Here we develop a nonlinear theory of responses to holographic perturbations in cell-type-specific recurrent networks with structured connectivity. We fit a nonlinear model to mouse V1 data, which shows cotuned-ensemble suppression: perturbing spatially clustered neurons with similar preferred orientations yields markedly stronger short-range suppression than perturbing untuned ensembles. We show that cotuned-ensemble suppression arises from a feature-tuned, nonlinear inhibition pathway implicating somatostatin-positive (SST) interneurons. The theory predicts that cotuned ensembles suppress parvalbumin-positive (PV) neurons but facilitate SST neurons, and links the degree of cotuned-ensemble suppression or facilitation to the variance of the SST response. This framework identifies mechanisms by which nonlinear inhibition sculpts cortical dynamics and establishes a predictive basis for targeted optogenetic interventions.

neuroscience↗
bioRxiv2026

Proteomic signatures of APOE ε4 across human tissues and cell types in Alzheimers disease

The apolipoprotein E {varepsilon}4 (APOE {varepsilon}4) allele is the strongest genetic risk factor for late-onset Alzheimers disease (AD). However, the underlying molecular mechanisms remain unclear. This study included 1691 participants from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), 1226 participants from the Accelerating Medicines Partnership - Alzheimers Disease (AMP-AD) Diverse Cohorts Study, and 735 participants from the Alzheimers Disease Neuroimaging Initiative (ADNI). To characterise APOE {varepsilon}4 molecular effects, we analysed proteomic data from plasma, cerebrospinal fluid (CSF), and induced pluripotent stem cell (iPSC)-derived astrocytes and neurons, as well as transcriptomic and proteomic data from multiple brain regions. The association of APOE {varepsilon}4 with AD neuropathology was also examined. APOE {varepsilon}4 carriers shared a plasma proteomic signature enriched for immune processes, irrespective of AD diagnosis. A machine learning classifier trained on this signature discriminated APOE {varepsilon}4 carriers from non-carriers in an independent cohort using CSF proteomics. APOE {varepsilon}4 carriage was associated with higher Braak stages and Consortium to Establish a Registry for Alzheimers Disease (CERAD) score. However, only limited APOE {varepsilon}4-associated transcriptomic and proteomic changes were observed in bulk brain tissue, with poor cross-layer concordance. Proteomic analyses of iPSC-derived astrocytes and neurons further revealed cell-type-specific APOE {varepsilon}4-associated changes. APOE {varepsilon}4 is associated with a consistent proteomic signature across plasma and CSF. Its molecular effects in the brain differ across cell types, brain regions and molecular layers. These findings support the need for cell-type-resolved multi-omic studies to elucidate how APOE {varepsilon}4 confers AD risk.

neuroscience↗