Enhancing Task fMRI Preprocessing via Individualized Model-Based Filtering of Intrinsic Activity Dynamics

10.1101/2020.12.10.420273 ◽

2020 ◽

Author(s):

Matthew F. Singh ◽

Anxu Wang ◽

Michael Cole ◽

ShiNung Ching ◽

Todd S. Braver

Keyword(s):

Statistical Power ◽

Brain Activity ◽

Intrinsic Activity ◽

Bold Signal ◽

Group Level ◽

Temporal Precision ◽

Brain Responses ◽

Evoked Activity ◽

Activity Dynamics ◽

Do So

AbstractBrain responses recorded during fMRI are thought to reflect both rapid, stimulus-evoked activity and the propagation of spontaneous activity through brain networks. In the current work we describe a method to improve the estimation of task-evoked brain activity by first “filtering-out” the intrinsic propagation of pre-event activity from the BOLD signal. We do so using Mesoscale Individualized NeuroDynamic (MINDy; [1]) models built from individualized resting-state data (MINDy-based Filtering). After filtering, time-series are analyzed using conventional techniques. Results demonstrate that this simple operation significantly improves the statistical power and temporal precision of estimated group-level effects. Moreover, estimates based upon our technique better generalize between tasks measuring the same construct (cognitive control) and better predict individual differences in behavior. Thus, by subtracting the propagation of previous activity, we obtain better estimates of task-related neural activity.

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Pathway-Based Analysis of the Liver Response to Intravenous Methylprednisolone Administration in Rats: Acute Versus Chronic Dosing

Gene Regulation and Systems Biology ◽

10.1177/1177625019840282 ◽

2019 ◽

Vol 13 ◽

pp. 117762501984028 ◽

Cited By ~ 2

Author(s):

Alison Acevedo ◽

Ana Berthel ◽

Debra DuBois ◽

Richard R Almon ◽

William J Jusko ◽

...

Keyword(s):

Metabolic Pathways ◽

Time Series Data ◽

Meta Analysis ◽

Drug Effects ◽

Intrinsic Activity ◽

Series Data ◽

Decomposition Approach ◽

Model Based ◽

Single Response

Pharmacological time-series data, from comparative dosing studies, are critical to characterizing drug effects. Reconciling the data from multiple studies is inevitably difficult; multiple in vivo high-throughput -omics studies are necessary to capture the global and temporal effects of the drug, but these experiments, though analogous, differ in (microarray or other) platforms, time-scales, and dosing regimens and thus cannot be directly combined or compared. This investigation addresses this reconciliation issue with a meta-analysis technique aimed at assessing the intrinsic activity at the pathway level. The purpose of this is to characterize the dosing effects of methylprednisolone (MPL), a widely used anti-inflammatory and immunosuppressive corticosteroid (CS), within the liver. A multivariate decomposition approach is applied to analyze acute and chronic MPL dosing in male adrenalectomized rats and characterize the dosing-dependent differences in the dynamic response of MPL-responsive signaling and metabolic pathways. We demonstrate how to deconstruct signaling and metabolic pathways into their constituent pathway activities, activities which are scored for intrinsic pathway activity. Dosing-induced changes in the dynamics of pathway activities are compared using a model-based assessment of pathway dynamics, extending the principles of pharmacokinetics/pharmacodynamics (PKPD) to describe pathway activities. The model-based approach enabled us to hypothesize on the likely emergence (or disappearance) of indirect dosing-dependent regulatory interactions, pointing to likely mechanistic implications of dosing of MPL transcriptional regulation. Both acute and chronic MPL administration induced a strong core of activity within pathway families including the following: lipid metabolism, amino acid metabolism, carbohydrate metabolism, metabolism of cofactors and vitamins, regulation of essential organelles, and xenobiotic metabolism pathway families. Pathway activities alter between acute and chronic dosing, indicating that MPL response is dosing dependent. Furthermore, because multiple pathway activities are dominant within a single pathway, we observe that pathways cannot be defined by a single response. Instead, pathways are defined by multiple, complex, and temporally related activities corresponding to different subgroups of genes within each pathway.

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Representation, abstraction, and simple-minded sophisticates

Behavioral and Brain Sciences ◽

10.1017/s0140525x19002942 ◽

2020 ◽

Vol 43 ◽

Author(s):

Peter Dayan

Keyword(s):

Decision Theory ◽

Predictive Coding ◽

Bayesian Decision Theory ◽

Bayesian Decision ◽

Model Based ◽

Model Free

Abstract Bayesian decision theory provides a simple formal elucidation of some of the ways that representation and representational abstraction are involved with, and exploit, both prediction and its rather distant cousin, predictive coding. Both model-free and model-based methods are involved.

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Quantitative Model-Based Image Analysis of NuMa Distribution Links Nuclear Organization with Cell Phenotype

Microscopy and Microanalysis ◽

10.1017/s1431927600028968 ◽

2001 ◽

Vol 7 (S2) ◽

pp. 578-579

Author(s):

David W. Knowles ◽

Sophie A. Lelièvre ◽

Carlos Ortiz de Solόrzano ◽

Stephen J. Lockett ◽

Mina J. Bissell ◽

...

Keyword(s):

Image Analysis ◽

Mammary Epithelial Cells ◽

Nuclear Organization ◽

Critical Role ◽

Quantitative Model ◽

Mammary Epithelial ◽

Cell Phenotype ◽

Proliferating Cells ◽

Mitotic Apparatus ◽

Model Based

The extracellular matrix (ECM) plays a critical role in directing cell behaviour and morphogenesis by regulating gene expression and nuclear organization. Using non-malignant (S1) human mammary epithelial cells (HMECs), it was previously shown that ECM-induced morphogenesis is accompanied by the redistribution of nuclear mitotic apparatus (NuMA) protein from a diffuse pattern in proliferating cells, to a multi-focal pattern as HMECs growth arrested and completed morphogenesis . A process taking 10 to 14 days.To further investigate the link between NuMA distribution and the growth stage of HMECs, we have investigated the distribution of NuMA in non-malignant S1 cells and their malignant, T4, counter-part using a novel model-based image analysis technique. This technique, based on a multi-scale Gaussian blur analysis (Figure 1), quantifies the size of punctate features in an image. Cells were cultured in the presence and absence of a reconstituted basement membrane (rBM) and imaged in 3D using confocal microscopy, for fluorescently labeled monoclonal antibodies to NuMA (fαNuMA) and fluorescently labeled total DNA.

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Substrate specificity and inducibility of TACE (tumour necrosis factor α-converting enzyme) revisited: the Ala-Val preference, and induced intrinsic activity

Biochemical Society Symposium ◽

10.1042/bss0700039 ◽

2003 ◽

Vol 70 ◽

pp. 39-52 ◽

Cited By ~ 54

Author(s):

Roy A. Black ◽

John R. Doedens ◽

Rajeev Mahimkar ◽

Richard Johnson ◽

Lin Guo ◽

...

Keyword(s):

Substrate Specificity ◽

Recent Work ◽

Tumour Necrosis Factor ◽

Tumour Necrosis ◽

Transforming Growth Factor ◽

Intrinsic Activity ◽

Converting Enzyme ◽

Tumour Necrosis Factor Α ◽

Factor Α ◽

Necrosis Factor

Tumour necrosis factor α (TNFα)-converting enzyme (TACE/ADAM-17, where ADAM stands for a disintegrin and metalloproteinase) releases from the cell surface the extracellular domains of TNF and several other proteins. Previous studies have found that, while purified TACE preferentially cleaves peptides representing the processing sites in TNF and transforming growth factor α, the cellular enzyme nonetheless also sheds proteins with divergent cleavage sites very efficiently. More recent work, identifying the cleavage site in the p75 TNF receptor, quantifying the susceptibility of additional peptides to cleavage by TACE and identifying additional protein substrates, underlines the complexity of TACE-substrate interactions. In addition to substrate specificity, the mechanism underlying the increased rate of shedding caused by agents that activate cells remains poorly understood. Recent work in this area, utilizing a peptide substrate as a probe for cellular TACE activity, indicates that the intrinsic activity of the enzyme is somehow increased.

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