bioRxiv Science⌕ Search

bioRxiv · 10.1101/2025.07.22.666182

Elucidating directed neural dynamics of scene construction across memory and imagination

Abstract

Autobiographical memory (AM) and imagination both rely on the brains ability to construct vivid, coherent mental representations of past or imagined experiences. A central cognitive process underlying these functions is scene construction--the mental generation of spatially organized, imagery-rich representations of environments. Using ultra-high field 7T fMRI combined with Dynamic Causal Modeling (DCM), we examined directed effective connectivity among key nodes of the default mode network: the ventromedial prefrontal cortex (vmPFC), hippocampus, and precuneus during object imagery, single-scene construction, and AM retrieval. Our results revealed distinct patterns of network dynamics depending on task demands. During AM retrieval, effective connectivity was characterized by vmPFC-driven top-down modulation primarily targeting the precuneus, supporting the temporal and self-relevant structuring of episodic memory. In contrast, extended scenario imagination engaged hippocampal bidirectional influences with both vmPFC and precuneus, reflecting the dynamic simulation and integration of unfolding events. Single Scene construction shifted network leadership to the precuneus, which exerted modulatory effects on both vmPFC and hippocampus, consistent with its pivotal role in spatial integration and the generation of coherent mental scenes. Object imagery showed minimal stable connectivity within this network, suggesting limited engagement of the hippocampal-default mode circuit during simpler visual representations. Together, our findings highlight a flexible, task-dependent reorganization of effective connectivity within the vmPFC- hippocampus-precuneus network during the construction of rich mental experiences. Scene construction emerges as a unifying mechanism linking memory and imagination, with the direction and strength of neural interactions adapting according to whether temporal or spatial demands predominate. HighlightsO_LIAutobiographical memory is reflected by vmPFC-driven effective connectivity C_LIO_LIEffective connectivity varies flexibly amongst vmPFC, hippocampus and precuneus C_LIO_LIScene construction emerges as a core process across memory and imagination C_LI

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Kindler, C., Taube, J., Leelaarporn, P., Stirnberg, R., McCormick, C.. 2025-07-24. Elucidating directed neural dynamics of scene construction across memory and imagination. https://doi.org/10.1101/2025.07.22.666182

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

KEEP EXPLORING

Related preprints

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↗

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↗

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↗