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Article ; Online: Biophysical modulation and robustness of itinerant complexity in neuronal networks.

Venkadesh, Siva / Shaikh, Asmir / Shakeri, Heman / Barreto, Ernest / Van Horn, John Darrell

Frontiers in network physiology

2024 Volume 4, Page(s) 1302499

Abstract: Transient synchronization of bursting activity in neuronal networks, which occurs in patterns of metastable itinerant phase relationships between neurons, is a notable feature of network dynamics ... ...

Abstract	Transient synchronization of bursting activity in neuronal networks, which occurs in patterns of metastable itinerant phase relationships between neurons, is a notable feature of network dynamics observed
Language	English
Publishing date	2024-03-07
Publishing country	Switzerland
Document type	Journal Article
ISSN	2674-0109
ISSN (online)	2674-0109
DOI	10.3389/fnetp.2024.1302499
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Article: Integrative Models of Brain Structure and Dynamics: Concepts, Challenges, and Methods.

Venkadesh, Siva / Van Horn, John Darrell

Frontiers in neuroscience

2021 Volume 15, Page(s) 752332

Abstract: The anatomical architecture of the brain constrains the dynamics of interactions between various regions. On a microscopic scale, neural plasticity regulates the connections between individual neurons. This microstructural adaptation facilitates ... ...

Abstract	The anatomical architecture of the brain constrains the dynamics of interactions between various regions. On a microscopic scale, neural plasticity regulates the connections between individual neurons. This microstructural adaptation facilitates coordinated dynamics of populations of neurons (mesoscopic scale) and brain regions (macroscopic scale). However, the mechanisms acting on multiple timescales that govern the reciprocal relationship between neural network structure and its intrinsic dynamics are not well understood. Studies empirically investigating such relationships on the whole-brain level rely on macroscopic measurements of structural and functional connectivity estimated from various neuroimaging modalities such as Diffusion-weighted Magnetic Resonance Imaging (dMRI), Electroencephalography (EEG), Magnetoencephalography (MEG), and functional Magnetic Resonance Imaging (fMRI). dMRI measures the anisotropy of water diffusion along axonal fibers, from which structural connections are estimated. EEG and MEG signals measure electrical activity and magnetic fields induced by the electrical activity, respectively, from various brain regions with a high temporal resolution (but limited spatial coverage), whereas fMRI measures regional activations indirectly via blood oxygen level-dependent (BOLD) signals with a high spatial resolution (but limited temporal resolution). There are several studies in the neuroimaging literature reporting statistical associations between macroscopic structural and functional connectivity. On the other hand, models of large-scale oscillatory dynamics conditioned on network structure (such as the one estimated from dMRI connectivity) provide a platform to probe into the structure-dynamics relationship at the mesoscopic level. Such investigations promise to uncover the theoretical underpinnings of the interplay between network structure and dynamics and could be complementary to the macroscopic level inquiries. In this article, we review theoretical and empirical studies that attempt to elucidate the coupling between brain structure and dynamics. Special attention is given to various clinically relevant dimensions of brain connectivity such as the topological features and neural synchronization, and their applicability for a given modality, spatial or temporal scale of analysis is discussed. Our review provides a summary of the progress made along this line of research and identifies challenges and promising future directions for multi-modal neuroimaging analyses.
Language	English
Publishing date	2021-10-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2021.752332
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Article ; Online: Combinatorial quantification of distinct neural projections from retrograde tracing.

Venkadesh, Siva / Santarelli, Anthony / Boesen, Tyler / Dong, Hong-Wei / Ascoli, Giorgio A

Nature communications

2023 Volume 14, Issue 1, Page(s) 7271

Abstract: Comprehensive quantification of neuronal architectures underlying anatomical brain connectivity remains challenging. We introduce a method to identify distinct axonal projection patterns from a source to a set of target regions and the count of neurons ... ...

Abstract	Comprehensive quantification of neuronal architectures underlying anatomical brain connectivity remains challenging. We introduce a method to identify distinct axonal projection patterns from a source to a set of target regions and the count of neurons with each pattern. A source region projecting to n targets could have 2
MeSH term(s)	Mice ; Male ; Animals ; Neural Pathways/physiology ; Reproducibility of Results ; Neurons/physiology ; Axons ; Brain ; Somatosensory Cortex
Language	English
Publishing date	2023-11-10
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-43124-2
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Article: Combinatorial quantification of distinct neural projections from retrograde tracing.

Venkadesh, Siva / Santarelli, Anthony / Boesen, Tyler / Dong, Hongwei / Ascoli, Giorgio A

Research square

2023

Abstract: Comprehensive quantification of neuronal architectures underlying anatomical brain connectivity remains challenging. We introduce a method to identify the distinct axonal projection patterns from a source to a set of target regions and the count of ... ...

Abstract	Comprehensive quantification of neuronal architectures underlying anatomical brain connectivity remains challenging. We introduce a method to identify the distinct axonal projection patterns from a source to a set of target regions and the count of neurons with each pattern. For a source region projecting to
Language	English
Publishing date	2023-01-09
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-2454289/v1
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Article ; Online: Itinerant complexity in networks of intrinsically bursting neurons.

Venkadesh, Siva / Barreto, Ernest / Ascoli, Giorgio A

Chaos (Woodbury, N.Y.)

2020 Volume 30, Issue 6, Page(s) 61106

Abstract: Active neurons can be broadly classified by their intrinsic oscillation patterns into two classes characterized by spiking or bursting. Here, we show that networks of identical bursting neurons with inhibitory pulsatory coupling exhibit itinerant ... ...

Abstract	Active neurons can be broadly classified by their intrinsic oscillation patterns into two classes characterized by spiking or bursting. Here, we show that networks of identical bursting neurons with inhibitory pulsatory coupling exhibit itinerant dynamics. Using the relative phases of bursts between neurons, we numerically demonstrate that the network exhibits endogenous transitions between multiple modes of transient synchrony. This is true even for bursts consisting of two spikes. In contrast, our simulations reveal that networks of identical singlet-spiking neurons do not exhibit such complexity. These results suggest a role for bursting dynamics in realizing itinerant complexity in neural circuits.
MeSH term(s)	Action Potentials ; Animals ; Models, Neurological ; Nerve Net ; Neurons/physiology
Language	English
Publishing date	2020-07-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1472677-4
ISSN	1089-7682 ; 1054-1500
ISSN (online)	1089-7682
ISSN	1054-1500
DOI	10.1063/5.0010334
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Article: Conduction Velocity, G-ratio, and Extracellular Water as Microstructural Characteristics of Autism Spectrum Disorder.

Newman, Benjamin T / Jacokes, Zachary / Venkadesh, Siva / Webb, Sara J / Kleinhans, Natalia M / McPartland, James C / Druzgal, T Jason / Pelphrey, Kevin A / Van Horn, John Darrell

bioRxiv : the preprint server for biology

2024

Abstract: The neuronal differences contributing to the etiology of autism spectrum disorder (ASD) are still not well defined. Previous studies have suggested that myelin and axons are disrupted during development in ASD. By combining structural and diffusion MRI ... ...

Abstract	The neuronal differences contributing to the etiology of autism spectrum disorder (ASD) are still not well defined. Previous studies have suggested that myelin and axons are disrupted during development in ASD. By combining structural and diffusion MRI techniques, myelin and axons can be assessed using extracellular water, aggregate g-ratio, and a novel metric termed aggregate conduction velocity, which is related to the capacity of the axon to carry information. In this study, several innovative cellular microstructural methods, as measured from magnetic resonance imaging (MRI), are combined to characterize differences between ASD and typically developing adolescent participants in a large cohort. We first examine the relationship between each metric, including microstructural measurements of axonal and intracellular diffusion and the T1w/T2w ratio. We then demonstrate the sensitivity of these metrics by characterizing differences between ASD and neurotypical participants, finding widespread increases in extracellular water in the cortex and decreases in aggregate g-ratio and aggregate conduction velocity throughout the cortex, subcortex, and white matter skeleton. We finally provide evidence that these microstructural differences are associated with higher scores on the Social Communication Questionnaire (SCQ) a commonly used diagnostic tool to assess ASD. This study is the first to reveal that ASD involves MRI-measurable
Language	English
Publishing date	2024-02-14
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.07.23.550166
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Article ; Online: Conduction velocity, G-ratio, and extracellular water as microstructural characteristics of autism spectrum disorder.

Newman, Benjamin T / Jacokes, Zachary / Venkadesh, Siva / Webb, Sara J / Kleinhans, Natalia M / McPartland, James C / Druzgal, T Jason / Pelphrey, Kevin A / Van Horn, John Darrell

PloS one

2024 Volume 19, Issue 4, Page(s) e0301964

Abstract	The neuronal differences contributing to the etiology of autism spectrum disorder (ASD) are still not well defined. Previous studies have suggested that myelin and axons are disrupted during development in ASD. By combining structural and diffusion MRI techniques, myelin and axons can be assessed using extracellular water, aggregate g-ratio, and a new approach to calculating axonal conduction velocity termed aggregate conduction velocity, which is related to the capacity of the axon to carry information. In this study, several innovative cellular microstructural methods, as measured from magnetic resonance imaging (MRI), are combined to characterize differences between ASD and typically developing adolescent participants in a large cohort. We first examine the relationship between each metric, including microstructural measurements of axonal and intracellular diffusion and the T1w/T2w ratio. We then demonstrate the sensitivity of these metrics by characterizing differences between ASD and neurotypical participants, finding widespread increases in extracellular water in the cortex and decreases in aggregate g-ratio and aggregate conduction velocity throughout the cortex, subcortex, and white matter skeleton. We finally provide evidence that these microstructural differences are associated with higher scores on the Social Communication Questionnaire (SCQ) a commonly used diagnostic tool to assess ASD. This study is the first to reveal that ASD involves MRI-measurable in vivo differences of myelin and axonal development with implications for neuronal and behavioral function. We also introduce a novel formulation for calculating aggregate conduction velocity, that is highly sensitive to these changes. We conclude that ASD may be characterized by otherwise intact structural connectivity but that functional connectivity may be attenuated by network properties affecting neural transmission speed. This effect may explain the putative reliance on local connectivity in contrast to more distal connectivity observed in ASD.
MeSH term(s)	Adolescent ; Humans ; Autism Spectrum Disorder ; Magnetic Resonance Imaging ; Diffusion Magnetic Resonance Imaging/methods ; White Matter/pathology ; Cerebral Cortex ; Brain/pathology
Language	English
Publishing date	2024-04-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0301964
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Article ; Online: Simple models of quantitative firing phenotypes in hippocampal neurons: Comprehensive coverage of intrinsic diversity.

Venkadesh, Siva / Komendantov, Alexander O / Wheeler, Diek W / Hamilton, David J / Ascoli, Giorgio A

PLoS computational biology

2019 Volume 15, Issue 10, Page(s) e1007462

Abstract: Patterns of periodic voltage spikes elicited by a neuron help define its dynamical identity. Experimentally recorded spike trains from various neurons show qualitatively distinguishable features such as delayed spiking, spiking with or without frequency ... ...

Abstract	Patterns of periodic voltage spikes elicited by a neuron help define its dynamical identity. Experimentally recorded spike trains from various neurons show qualitatively distinguishable features such as delayed spiking, spiking with or without frequency adaptation, and intrinsic bursting. Moreover, the input-dependent responses of a neuron not only show different quantitative features, such as higher spike frequency for a stronger input current injection, but can also exhibit qualitatively different responses, such as spiking and bursting under different input conditions, thus forming a complex phenotype of responses. In previous work, the comprehensive knowledge base of hippocampal neuron types Hippocampome.org systematically characterized various spike pattern phenotypes experimentally identified from 120 neuron types/subtypes. In this paper, we present a complete set of simple phenomenological models that quantitatively reproduce the diverse and complex phenotypes of hippocampal neurons. In addition to point-neuron models, we created compact multi-compartment models with up to four compartments, which will allow spatial segregation of synaptic integration in network simulations. Electrotonic compartmentalization observed in our compact multi-compartment models is qualitatively consistent with experimental observations. The models were created using an automated pipeline based on evolutionary algorithms. This work maps 120 neuron types/subtypes in the rodent hippocampus to a low-dimensional model space and adds another dimension to the knowledge accumulated in Hippocampome.org. Computationally efficient representations of intrinsic dynamics, along with other pieces of knowledge available in Hippocampome.org, provide a biologically realistic platform to explore the large-scale interactions of various neuron types at the mesoscopic level.
MeSH term(s)	Action Potentials/physiology ; Animals ; Data Interpretation, Statistical ; Databases, Factual ; Hippocampus/metabolism ; Humans ; Models, Neurological ; Neurons/physiology ; Phenotype
Language	English
Publishing date	2019-10-28
Publishing country	United States
Document type	Journal Article ; 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.1007462
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Article ; Online: Increased perivascular space volume in white matter and basal ganglia is associated with cognition in Parkinson's Disease.

Donahue, Erin Kaye / Foreman, Ryan Patrick / Duran, Jared Joshua / Jakowec, Michael Walter / O'Neill, Joseph / Petkus, Andrew J / Holschneider, Daniel P / Choupan, Jeiran / Van Horn, John Darrell / Venkadesh, Siva / Bayram, Ece / Litvan, Irene / Schiehser, Dawn M / Petzinger, Giselle Maria

Brain imaging and behavior

2023 Volume 18, Issue 1, Page(s) 57–65

Abstract: Perivascular spaces (PVS), fluid-filled compartments surrounding brain vasculature, are an essential component of the glymphatic system responsible for transport of waste and nutrients. Glymphatic system impairment may underlie cognitive deficits in ... ...

Abstract	Perivascular spaces (PVS), fluid-filled compartments surrounding brain vasculature, are an essential component of the glymphatic system responsible for transport of waste and nutrients. Glymphatic system impairment may underlie cognitive deficits in Parkinson's disease (PD). Studies have focused on the role of basal ganglia PVS with cognition in PD, but the role of white matter PVS is unknown. This study examined the relationship of white matter and basal ganglia PVS with domain-specific and global cognition in individuals with PD. Fifty individuals with PD underwent 3T T1w magnetic resonance imaging (MRI) to determine PVS volume fraction, defined as PVS volume normalized to total regional volume, within (i) centrum semiovale, (ii) prefrontal white matter (medial orbitofrontal, rostral middle frontal, superior frontal), and (iii) basal ganglia. A neuropsychological battery included assessment of global cognitive function (Montreal Cognitive Assessment, and global cognitive composite score), and cognitive-specific domains (executive function, memory, visuospatial function, attention, and language). Higher white matter rostral middle frontal PVS was associated with lower scores in both global cognitive and visuospatial function. In the basal ganglia higher PVS was associated with lower scores for memory with a trend towards lower global cognitive composite score. While previous reports have shown that greater amount of PVS in the basal ganglia is associated with decline in global cognition in PD, our findings suggest that increased white matter PVS volume may also underlie changes in cognition.
MeSH term(s)	Humans ; Parkinson Disease/complications ; White Matter/pathology ; Glymphatic System/diagnostic imaging ; Glymphatic System/pathology ; Magnetic Resonance Imaging/methods ; Cognition ; Basal Ganglia/diagnostic imaging
Language	English
Publishing date	2023-10-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2377165-3
ISSN	1931-7565 ; 1931-7557
ISSN (online)	1931-7565
ISSN	1931-7557
DOI	10.1007/s11682-023-00811-4
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Article ; Online: Magnetic resonance spectroscopy shows associations between neurometabolite levels and perivascular space volume in Parkinson's disease: a pilot and feasibility study.

Donahue, Erin K / Bui, Vy / Foreman, Ryan P / Duran, Jared J / Venkadesh, Siva / Choupan, Jeiran / Van Horn, John D / Alger, Jeffry R / Jakowec, Michael W / Petzinger, Giselle M / O'Neill, Joseph

Neuroreport

2022 Volume 33, Issue 7, Page(s) 291–296

Abstract: Objective: Higher volume fraction of perivascular space (PVS) has recently been reported in Parkinson's disease (PD) and related disorders. Both elevated PVS and altered levels of neurometabolites, assayed by proton magnetic resonance spectroscopy (MRS), ...

Abstract	Objective: Higher volume fraction of perivascular space (PVS) has recently been reported in Parkinson's disease (PD) and related disorders. Both elevated PVS and altered levels of neurometabolites, assayed by proton magnetic resonance spectroscopy (MRS), are suspected indicators of neuroinflammation, but no published reports have concurrently examined PVS and MRS neurometabolites. Methods: In an exploratory pilot study, we acquired multivoxel 3-T MRS using a semi-Localization by Adiabatic SElective Refocusing (sLASER) pulse-sequence (repetition time/echo time = 2810/60 ms, voxels 10 × 10 × 10 mm3) from a 2D slab sampling bilateral frontal white matter (FWM) and anterior middle cingulate cortex (aMCC). PVS maps obtained from high-resolution (0.8 × 0.8 × 0.8 mm3) T1-weighted MRI were co-registered with MRS. In each MRS voxel, PVS volume and neurometabolite levels were measured. Results: Linear regression accounting for age, sex, and BMI found greater PVS volume for higher levels of choline-containing compounds (Cho; P = 0.047) in FWM and lower PVS volume for higher levels of N-acetyl compounds (NAA; P = 0.012) in aMCC. Since (putatively) higher Cho is associated with inflammation while NAA has anti-inflammatory properties, these observations add to evidence that higher PVS load is a sign of inflammation. Additionally, lower Montreal Cognitive Assessment scores were associated with lower NAA in aMCC (P = 0.002), suggesting that local neuronal dysfunction and inflammation contribute to cognitive impairment in PD. Conclusion: These exploratory findings indicate that co-analysis of PVS and MRS is feasible and may help elucidate the cellular and metabolic substrates of glymphatic and inflammatory processes in PD.
MeSH term(s)	Aspartic Acid/metabolism ; Brain/diagnostic imaging ; Brain/metabolism ; Creatine/metabolism ; Feasibility Studies ; Humans ; Inflammation/metabolism ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy/methods ; Parkinson Disease/metabolism ; Pilot Projects
Chemical Substances	Aspartic Acid (30KYC7MIAI) ; Creatine (MU72812GK0)
Language	English
Publishing date	2022-04-08
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	1049746-8
ISSN	1473-558X ; 0959-4965
ISSN (online)	1473-558X
ISSN	0959-4965
DOI	10.1097/WNR.0000000000001781
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