Search bioRxivSearch

bioRxiv · 10.1101/297259

Hierarchical Cognition causes Task Related Deactivations but not just in Default Mode Regions

Abstract

AbstractThe well-known deactivation of the Default Mode Network (DMN) during external tasks is usually thought to reflect the suppression of internally directed mental activity during external attention. In 3 experiments with human participants we organized sequences of task events identical in their attentional and control demands into larger task episodes. We found that DMN deactivation across such sequential events was never constant, but was maximum at the beginning of the episode, then decreased gradually across the episode, reaching baseline towards episode completion, with the final event of the episode eliciting an activation. Crucially, this pattern of activity was not limited to a fixed set of DMN regions but, across experiments, was shown by a variable set of regions expected to be uninvolved in processing the ongoing task. This change in deactivation across sequential but identical events showed that the deactivation cannot be related to attentional/control demands which were constant across the episode, instead it has to be related to some episode related load that was maximal at the beginning and then decreased gradually as parts of the episode got executed. We argue that this load resulted from cognitive programs through which the entire episode was hierarchically executed as one unit. At the beginning of task episodes, programs related to their entire duration is assembled, causing maximal deactivation. As execution proceeds, elements within the program related to the completed parts of the episode dismantle, thereby decreasing the program load and causing a decrease in deactivation.\n\nSignificance StatementWe prepare breakfasts and write emails, and not individually execute their many component acts. The current study suggests that cognitive entities that enable such hierarchical execution of goal-directed behavior may cause the ubiquitously seen deactivation during external task execution. Further, while this deactivation has previously been associated with a defined set of the so called default mode regions, current study demonstrates that deactivation is shown by any region not currently involved in task execution, and in certain task episodes can even include attention related fronto-parietal regions as well as primary sensory and motor regions.

Source connections

Explore related subjects

Keep this discovery

BibTeXRIS

Farooqui, A. A., Duncan, J., Manly, T.. 2018-04-07. Hierarchical Cognition causes Task Related Deactivations but not just in Default Mode Regions. https://doi.org/10.1101/297259

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