LIVIVO - Search results -

Search results

Result 1 - 10 of total 12

Search options

Article: Thalamic stimulation induced changes in effective connectivity.

Gregg, Nicholas M / Valencia, Gabriela Ojeda / Huang, Harvey / Lundstrom, Brian N / Van Gompel, Jamie J / Miller, Kai J / Worrell, Gregory A / Hermes, Dora

medRxiv : the preprint server for health sciences

2024

Abstract: Deep brain stimulation (DBS) is a viable treatment for a variety of neurological conditions, however, the mechanisms through which DBS modulates large-scale brain networks are unresolved. Clinical effects of DBS are observed over multiple timescales. In ... ...

Abstract	Deep brain stimulation (DBS) is a viable treatment for a variety of neurological conditions, however, the mechanisms through which DBS modulates large-scale brain networks are unresolved. Clinical effects of DBS are observed over multiple timescales. In some conditions, such as Parkinson's disease and essential tremor, clinical improvement is observed within seconds. In many other conditions, such as epilepsy, central pain, dystonia, neuropsychiatric conditions or Tourette syndrome, the DBS related effects are believed to require neuroplasticity or reorganization and often take hours to months to observe. To optimize DBS parameters, it is therefore essential to develop electrophysiological biomarkers that characterize whether DBS settings are successfully engaging and modulating the network involved in the disease of interest. In this study, 10 individuals with drug resistant epilepsy undergoing intracranial stereotactic EEG including a thalamus electrode underwent a trial of repetitive thalamic stimulation. We evaluated thalamocortical effective connectivity using single pulse electrical stimulation, both at baseline and following a 145 Hz stimulation treatment trial. We found that when high frequency stimulation was delivered for >1.5 hours, the evoked potentials measured from remote regions were significantly reduced in amplitude and the degree of modulation was proportional to the strength of baseline connectivity. When stimulation was delivered for shorter time periods, results were more variable. These findings suggest that changes in effective connectivity in the network targeted with DBS accumulate over hours of DBS. Stimulation evoked potentials provide an electrophysiological biomarker that allows for efficient data-driven characterization of neuromodulation effects, which could enable new objective approaches for individualized DBS optimization.
Language	English
Publishing date	2024-03-04
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.03.03.24303480
Database	MEDical Literature Analysis and Retrieval System OnLINE

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾

Article ; Online: CARLA: Adjusted common average referencing for cortico-cortical evoked potential data.

Huang, Harvey / Ojeda Valencia, Gabriela / Gregg, Nicholas M / Osman, Gamaleldin M / Montoya, Morgan N / Worrell, Gregory A / Miller, Kai J / Hermes, Dora

Journal of neuroscience methods

2024 Volume 407, Page(s) 110153

Abstract: Human brain connectivity can be mapped by single pulse electrical stimulation during intracranial EEG measurements. The raw cortico-cortical evoked potentials (CCEP) are often contaminated by noise. Common average referencing (CAR) removes common noise ... ...

Abstract	Human brain connectivity can be mapped by single pulse electrical stimulation during intracranial EEG measurements. The raw cortico-cortical evoked potentials (CCEP) are often contaminated by noise. Common average referencing (CAR) removes common noise and preserves response shapes but can introduce bias from responsive channels. We address this issue with an adjusted, adaptive CAR algorithm termed "CAR by Least Anticorrelation (CARLA)". CARLA was tested on simulated CCEP data and real CCEP data collected from four human participants. In CARLA, the channels are ordered by increasing mean cross-trial covariance, and iteratively added to the common average until anticorrelation between any single channel and all re-referenced channels reaches a minimum, as a measure of shared noise. We simulated CCEP data with true responses in 0-45 of 50 total channels. We quantified CARLA's error and found that it erroneously included 0 (median) truly responsive channels in the common average with ≤42 responsive channels, and erroneously excluded ≤2.5 (median) unresponsive channels at all responsiveness levels. On real CCEP data, signal quality was quantified with the mean R
Language	English
Publishing date	2024-05-04
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	282721-9
ISSN	1872-678X ; 0165-0270
ISSN (online)	1872-678X
ISSN	0165-0270
DOI	10.1016/j.jneumeth.2024.110153
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1486: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾

Article ; Online: A canonical visualization tool for SEEG electrodes.

Huang, Harvey / Valencia, Gabriela Ojeda / Hermes, Dora / Miller, Kai J

Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference

2021 Volume 2021, Page(s) 6175–6178

Abstract: Stereoencephalographic (SEEG) electrodes are clinically implanted into the brains of patients with refractory epilepsy to locate foci of seizure onset. They are increasingly used in neurophysiology research to determine focal human brain activity in ... ...

Abstract	Stereoencephalographic (SEEG) electrodes are clinically implanted into the brains of patients with refractory epilepsy to locate foci of seizure onset. They are increasingly used in neurophysiology research to determine focal human brain activity in response to tasks or stimuli. Clear visualization of SEEG electrode location with respect to patient anatomy on magnetic resonance image (MRI) scan is vital to neuroscientific understanding. An intuitive way to accomplish this is to plot brain activity and labels at electrode locations on closest MRI slices along the canonical axial, coronal, and sagittal planes. Therefore, we've developed an open-source software tool in Matlab for visualizing SEEG electrode positions, determined from computed tomography (CT), onto canonical planes of resliced brain MRI. The code and graphical user interface are available at: https://github.com/MultimodalNeuroimagingLab/mnl_seegviewClinical Relevance- This tool enables precise communication of SEEG electrode activity and location by visualization on slices of MRI in canonical axial, coronal, and sagittal planes.
MeSH term(s)	Brain/diagnostic imaging ; Brain Mapping ; Electrodes, Implanted ; Electroencephalography ; Humans ; Magnetic Resonance Imaging
Language	English
Publishing date	2021-12-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2694-0604
ISSN (online)	2694-0604
DOI	10.1109/EMBC46164.2021.9630724
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Canonical Response Parameterization: Quantifying the structure of responses to single-pulse intracranial electrical brain stimulation.

Miller, Kai J / Müller, Klaus-Robert / Valencia, Gabriela Ojeda / Huang, Harvey / Gregg, Nicholas M / Worrell, Gregory A / Hermes, Dora

PLoS computational biology

2023 Volume 19, Issue 5, Page(s) e1011105

Abstract: Single-pulse electrical stimulation in the nervous system, often called cortico-cortical evoked potential (CCEP) measurement, is an important technique to understand how brain regions interact with one another. Voltages are measured from implanted ... ...

Abstract	Single-pulse electrical stimulation in the nervous system, often called cortico-cortical evoked potential (CCEP) measurement, is an important technique to understand how brain regions interact with one another. Voltages are measured from implanted electrodes in one brain area while stimulating another with brief current impulses separated by several seconds. Historically, researchers have tried to understand the significance of evoked voltage polyphasic deflections by visual inspection, but no general-purpose tool has emerged to understand their shapes or describe them mathematically. We describe and illustrate a new technique to parameterize brain stimulation data, where voltage response traces are projected into one another using a semi-normalized dot product. The length of timepoints from stimulation included in the dot product is varied to obtain a temporal profile of structural significance, and the peak of the profile uniquely identifies the duration of the response. Using linear kernel PCA, a canonical response shape is obtained over this duration, and then single-trial traces are parameterized as a projection of this canonical shape with a residual term. Such parameterization allows for dissimilar trace shapes from different brain areas to be directly compared by quantifying cross-projection magnitudes, response duration, canonical shape projection amplitudes, signal-to-noise ratios, explained variance, and statistical significance. Artifactual trials are automatically identified by outliers in sub-distributions of cross-projection magnitude, and rejected. This technique, which we call "Canonical Response Parameterization" (CRP) dramatically simplifies the study of CCEP shapes, and may also be applied in a wide range of other settings involving event-triggered data.
MeSH term(s)	Brain ; Evoked Potentials/physiology ; Brain Mapping/methods ; Electrodes, Implanted ; Electric Stimulation/methods
Language	English
Publishing date	2023-05-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2193340-6
ISSN	1553-7358 ; 1553-734X
ISSN (online)	1553-7358
ISSN	1553-734X
DOI	10.1371/journal.pcbi.1011105
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Electrical Stimulation of Temporal and Limbic Circuitry Produces Distinct Responses in Human Ventral Temporal Cortex.

Huang, Harvey / Gregg, Nicholas M / Ojeda Valencia, Gabriela / Brinkmann, Benjamin H / Lundstrom, Brian N / Worrell, Gregory A / Miller, Kai J / Hermes, Dora

The Journal of neuroscience : the official journal of the Society for Neuroscience

2023 Volume 43, Issue 24, Page(s) 4434–4447

Abstract: The human ventral temporal cortex (VTC) is highly connected to integrate visual perceptual inputs with feedback from cognitive and emotional networks. In this study, we used electrical brain stimulation to understand how different inputs from multiple ... ...

Abstract	The human ventral temporal cortex (VTC) is highly connected to integrate visual perceptual inputs with feedback from cognitive and emotional networks. In this study, we used electrical brain stimulation to understand how different inputs from multiple brain regions drive unique electrophysiological responses in the VTC. We recorded intracranial EEG data in 5 patients (3 female) implanted with intracranial electrodes for epilepsy surgery evaluation. Pairs of electrodes were stimulated with single-pulse electrical stimulation, and corticocortical evoked potential responses were measured at electrodes in the collateral sulcus and lateral occipitotemporal sulcus of the VTC. Using a novel unsupervised machine learning method, we uncovered 2-4 distinct response shapes, termed basis profile curves (BPCs), at each measurement electrode in the 11-500 ms after stimulation interval. Corticocortical evoked potentials of unique shape and high amplitude were elicited following stimulation of several regions and classified into a set of four consensus BPCs across subjects. One of the consensus BPCs was primarily elicited by stimulation of the hippocampus; another by stimulation of the amygdala; a third by stimulation of lateral cortical sites, such as the middle temporal gyrus; and the final one by stimulation of multiple distributed sites. Stimulation also produced sustained high-frequency power decreases and low-frequency power increases that spanned multiple BPC categories. Characterizing distinct shapes in stimulation responses provides a novel description of connectivity to the VTC and reveals significant differences in input from cortical and limbic structures.
MeSH term(s)	Humans ; Female ; Temporal Lobe/physiology ; Cerebral Cortex ; Evoked Potentials/physiology ; Hippocampus ; Brain Mapping/methods ; Electric Stimulation/methods
Language	English
Publishing date	2023-05-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.1325-22.2023
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1668: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Book ; Online: CARLA

Huang, Harvey / Valencia, Gabriela Ojeda / Gregg, Nicholas M. / Osman, Gamaleldin M. / Montoya, Morgan N. / Worrell, Gregory A. / Miller, Kai J. / Hermes, Dora

Adjusted common average referencing for cortico-cortical evoked potential data

2023

Abstract	Human brain connectivity can be mapped by single pulse electrical stimulation during intracranial EEG measurements. The raw cortico-cortical evoked potentials (CCEP) are often contaminated by noise. Common average referencing (CAR) removes common noise and preserves response shapes but can introduce bias from responsive channels. We address this issue with an adjusted, adaptive CAR algorithm termed "CAR by Least Anticorrelation (CARLA)". CARLA was tested on simulated CCEP data and real CCEP data collected from four human participants. In CARLA, the channels are ordered by increasing mean cross-trial covariance, and iteratively added to the common average until anticorrelation between any single channel and all re-referenced channels reaches a minimum, as a measure of shared noise. We simulated CCEP data with true responses in 0 to 45 of 50 total channels. We quantified CARLA's error and found that it erroneously included 0 (median) truly responsive channels in the common average with less than or equal to 42 responsive channels, and erroneously excluded less than or equal to 2.5 (median) unresponsive channels at all responsiveness levels. On real CCEP data, signal quality was quantified with the mean R-squared between all pairs of channels, which represents inter-channel dependency and is low for well-referenced data. CARLA re-referencing produced significantly lower mean R-squared than standard CAR, CAR using a fixed bottom quartile of channels by covariance, and no re-referencing. CARLA minimizes bias in re-referenced CCEP data by adaptively selecting the optimal subset of non-responsive channels. It showed high specificity and sensitivity on simulated CCEP data and lowered inter-channel dependency compared to CAR on real CCEP data. Comment: 29 pages, 8 main figures, 3 supplemental figures. For associated code, see https://github.com/hharveygit/CARLA_JNM
Keywords	Quantitative Biology - Quantitative Methods
Subject code	003
Publishing date	2023-09-29
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: A motor association area in the depths of the central sulcus.

Jensen, Michael A / Huang, Harvey / Valencia, Gabriela Ojeda / Klassen, Bryan T / van den Boom, Max A / Kaufmann, Timothy J / Schalk, Gerwin / Brunner, Peter / Worrell, Gregory A / Hermes, Dora / Miller, Kai J

Nature neuroscience

2023 Volume 26, Issue 7, Page(s) 1165–1169

Abstract: Cells in the precentral gyrus directly send signals to the periphery to generate movement and are principally organized as a topological map of the body. We find that movement-induced electrophysiological responses from depth electrodes extend this map ... ...

Abstract	Cells in the precentral gyrus directly send signals to the periphery to generate movement and are principally organized as a topological map of the body. We find that movement-induced electrophysiological responses from depth electrodes extend this map three-dimensionally throughout the gyrus. Unexpectedly, this organization is interrupted by a previously undescribed motor association area in the depths of the midlateral aspect of the central sulcus. This 'Rolandic motor association' (RMA) area is active during movements of different body parts from both sides of the body and may be important for coordinating complex behaviors.
MeSH term(s)	Motor Cortex/physiology ; Movement ; Brain Mapping/methods
Language	English
Publishing date	2023-05-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1420596-8
ISSN	1546-1726 ; 1097-6256
ISSN (online)	1546-1726
ISSN	1097-6256
DOI	10.1038/s41593-023-01346-z
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4891: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 67: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Plasma metabolomic profiling in patients with rheumatoid arthritis identifies biochemical features predictive of quantitative disease activity.

Hur, Benjamin / Gupta, Vinod K / Huang, Harvey / Wright, Kerry A / Warrington, Kenneth J / Taneja, Veena / Davis, John M / Sung, Jaeyun

Arthritis research & therapy

2021 Volume 23, Issue 1, Page(s) 164

Abstract: Background: Rheumatoid arthritis (RA) is a chronic, autoimmune disorder characterized by joint inflammation and pain. In patients with RA, metabolomic approaches, i.e., high-throughput profiling of small-molecule metabolites, on plasma or serum has thus ...

Abstract	Background: Rheumatoid arthritis (RA) is a chronic, autoimmune disorder characterized by joint inflammation and pain. In patients with RA, metabolomic approaches, i.e., high-throughput profiling of small-molecule metabolites, on plasma or serum has thus far enabled the discovery of biomarkers for clinical subgroups, risk factors, and predictors of treatment response. Despite these recent advancements, the identification of blood metabolites that reflect quantitative disease activity remains an important challenge in precision medicine for RA. Herein, we use global plasma metabolomic profiling analyses to detect metabolites associated with, and predictive of, quantitative disease activity in patients with RA. Methods: Ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was performed on a discovery cohort consisting of 128 plasma samples from 64 RA patients and on a validation cohort of 12 samples from 12 patients. The resulting metabolomic profiles were analyzed with two different strategies to find metabolites associated with RA disease activity defined by the Disease Activity Score-28 using C-reactive protein (DAS28-CRP). More specifically, mixed-effects regression models were used to identify metabolites differentially abundant between two disease activity groups ("lower", DAS28-CRP ≤ 3.2; and "higher", DAS28-CRP > 3.2) and to identify metabolites significantly associated with DAS28-CRP scores. A generalized linear model (GLM) was then constructed for estimating DAS28-CRP using plasma metabolite abundances. Finally, for associating metabolites with CRP (an indicator of inflammation), metabolites differentially abundant between two patient groups ("low-CRP", CRP ≤ 3.0 mg/L; "high-CRP", CRP > 3.0 mg/L) were investigated. Results: We identified 33 metabolites differentially abundant between the lower and higher disease activity groups (P < 0.05). Additionally, we identified 51 metabolites associated with DAS28-CRP (P < 0.05). A GLM based upon these 51 metabolites resulted in higher prediction accuracy (mean absolute error [MAE] ± SD: 1.51 ± 1.77) compared to a GLM without feature selection (MAE ± SD: 2.02 ± 2.21). The predictive value of this feature set was further demonstrated on a validation cohort of twelve plasma samples, wherein we observed a stronger correlation between predicted and actual DAS28-CRP (with feature selection: Spearman's ρ = 0.69, 95% CI: [0.18, 0.90]; without feature selection: Spearman's ρ = 0.18, 95% CI: [-0.44, 0.68]). Lastly, among all identified metabolites, the abundances of eight were significantly associated with the CRP patient groups while controlling for potential confounders (P < 0.05). Conclusions: We demonstrate for the first time the prediction of quantitative disease activity in RA using plasma metabolomes. The metabolites identified herein provide insight into circulating pro-/anti-inflammatory metabolic signatures that reflect disease activity and inflammatory status in RA patients.
MeSH term(s)	Arthritis, Rheumatoid ; Biomarkers ; C-Reactive Protein ; Chromatography, Liquid ; Humans ; Metabolomics ; Severity of Illness Index ; Tandem Mass Spectrometry
Chemical Substances	Biomarkers ; C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2021-06-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2107602-9
ISSN	1478-6362 ; 1478-6354
ISSN (online)	1478-6362
ISSN	1478-6354
DOI	10.1186/s13075-021-02537-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5490: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Signatures of Electrical Stimulation Driven Network Interactions in the Human Limbic System.

Ojeda Valencia, Gabriela / Gregg, Nicholas M / Huang, Harvey / Lundstrom, Brian N / Brinkmann, Benjamin H / Pal Attia, Tal / Van Gompel, Jamie J / Bernstein, Matt A / In, Myung-Ho / Huston, John / Worrell, Gregory A / Miller, Kai J / Hermes, Dora

The Journal of neuroscience : the official journal of the Society for Neuroscience

2023 Volume 43, Issue 39, Page(s) 6697–6711

Abstract: Stimulation-evoked signals are starting to be used as biomarkers to indicate the state and health of brain networks. The human limbic network, often targeted for brain stimulation therapy, is involved in emotion and memory processing. Previous anatomic, ... ...

Abstract	Stimulation-evoked signals are starting to be used as biomarkers to indicate the state and health of brain networks. The human limbic network, often targeted for brain stimulation therapy, is involved in emotion and memory processing. Previous anatomic, neurophysiological, and functional studies suggest distinct subsystems within the limbic network (Rolls, 2015). Studies using intracranial electrical stimulation, however, have emphasized the similarities of the evoked waveforms across the limbic network. We test whether these subsystems have distinct stimulation-driven signatures. In eight patients (four male, four female) with drug-resistant epilepsy, we stimulated the limbic system with single-pulse electrical stimulation. Reliable corticocortical evoked potentials (CCEPs) were measured between hippocampus and the posterior cingulate cortex (PCC) and between the amygdala and the anterior cingulate cortex (ACC). However, the CCEP waveform in the PCC after hippocampal stimulation showed a unique and reliable morphology, which we term the "limbic Hippocampus-Anterior nucleus of the thalamus-Posterior cingulate, HAP-wave." This limbic HAP-wave was visually distinct and separately decoded from the CCEP waveform in ACC after amygdala stimulation. Diffusion MRI data show that the measured end points in the PCC overlap with the end points of the parolfactory cingulum bundle rather than the parahippocampal cingulum, suggesting that the limbic HAP-wave may travel through fornix, mammillary bodies, and the anterior nucleus of the thalamus (ANT). This was further confirmed by stimulating the ANT, which evoked the same limbic HAP-wave but with an earlier latency. Limbic subsystems have unique stimulation-evoked signatures that may be used in the future to help network pathology diagnosis.
MeSH term(s)	Humans ; Male ; Female ; Limbic System/physiology ; Electroencephalography ; Evoked Potentials/physiology ; Epilepsy ; Electric Stimulation ; Anterior Thalamic Nuclei
Language	English
Publishing date	2023-08-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.2201-22.2023
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1668: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: A subset of topologically associating domains fold into mesoscale core-periphery networks.

Huang, Harvey / Chen, Sunnia T / Titus, Katelyn R / Emerson, Daniel J / Bassett, Danielle S / Phillips-Cremins, Jennifer E

Scientific reports

2019 Volume 9, Issue 1, Page(s) 9526

Abstract: Mammalian genomes are folded into a hierarchy of compartments, topologically associating domains (TADs), subTADs, and long-range looping interactions. The higher-order folding patterns of chromatin contacts within TADs and how they localize to disease- ... ...

Abstract	Mammalian genomes are folded into a hierarchy of compartments, topologically associating domains (TADs), subTADs, and long-range looping interactions. The higher-order folding patterns of chromatin contacts within TADs and how they localize to disease-associated single nucleotide variants (daSNVs) remains an open area of investigation. Here, we analyze high-resolution Hi-C data with graph theory to understand possible mesoscale network architecture within chromatin domains. We identify a subset of TADs exhibiting strong core-periphery mesoscale structure in embryonic stem cells, neural progenitor cells, and cortical neurons. Hyper-connected core nodes co-localize with genomic segments engaged in multiple looping interactions and enriched for occupancy of the architectural protein CCCTC binding protein (CTCF). CTCF knockdown and in silico deletion of CTCF-bound core nodes disrupts core-periphery structure, whereas in silico mutation of cell type-specific enhancer or gene nodes has a negligible effect. Importantly, neuropsychiatric daSNVs are significantly more likely to localize with TADs folded into core-periphery networks compared to domains devoid of such structure. Together, our results reveal that a subset of TADs encompasses looping interactions connected into a core-periphery mesoscale network. We hypothesize that daSNVs in the periphery of genome folding networks might preserve global nuclear architecture but cause local topological and functional disruptions contributing to human disease. By contrast, daSNVs co-localized with hyper-connected core nodes might cause severe topological and functional disruptions. Overall, these findings shed new light into the mesoscale network structure of fine scale genome folding within chromatin domains and its link to common genetic variants in human disease.
MeSH term(s)	CCCTC-Binding Factor/antagonists & inhibitors ; CCCTC-Binding Factor/genetics ; CCCTC-Binding Factor/metabolism ; Chromatin Assembly and Disassembly ; Chromosomes/chemistry ; Chromosomes/genetics ; Chromosomes/metabolism ; Embryonic Stem Cells/cytology ; Embryonic Stem Cells/metabolism ; Genome ; Humans ; Mental Disorders/genetics ; Mental Disorders/pathology ; Models, Biological ; Neural Stem Cells/cytology ; Neural Stem Cells/metabolism ; Neurons/chemistry ; Neurons/metabolism ; Polymorphism, Single Nucleotide ; RNA Interference
Chemical Substances	CCCTC-Binding Factor
Language	English
Publishing date	2019-07-02
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-45457-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito