Spatiotemporal Integrity and Spontaneous Nonlinear Dynamic Properties of the Salience Network Revealed by Human Intracranial Electrophysiology: A Multicohort Replication

Abstract The salience network (SN) plays a critical role in cognitive control and adaptive human behaviors, but its electrophysiological foundations and millisecond timescale dynamic temporal properties are poorly understood. Here, we use invasive intracranial EEG (iEEG) from multiple cohorts to investigate the neurophysiological underpinnings of the SN and identify dynamic temporal properties that distinguish it from the default mode network (DMN) and dorsolateral frontal–parietal network (FPN), two other large-scale brain networks that play important roles in human cognition. iEEG analysis of network interactions revealed that the anterior insula and anterior cingulate cortex, which together anchor the SN, had stronger intranetwork interactions with each other than cross-network interactions with the DMN and FPN. Analysis of directionality of information flow between the SN, DMN, and FPN revealed causal outflow hubs in the SN consistent with its role in fast temporal switching of network interactions. Analysis of regional iEEG temporal fluctuations revealed faster temporal dynamics and higher entropy of neural activity within the SN, compared to the DMN and FPN. Critically, these results were replicated across multiple cohorts. Our findings provide new insights into the neurophysiological basis of the SN, and more broadly, foundational mechanisms underlying the large-scale functional organization of the human brain.

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Nonlinear visuoauditory integration in the mouse superior colliculus

10.1101/2021.01.26.428325 ◽

2021 ◽

Author(s):

Shinya Ito ◽

Yufei Si ◽

Alan M. Litke ◽

David A. Feldheim

Keyword(s):

Superior Colliculus ◽

Sensory Integration ◽

Large Scale ◽

Temporal Dynamics ◽

Critical Role ◽

Sensory Information ◽

Population Level ◽

Object Identification ◽

Response Properties ◽

The Individual

AbstractSensory information from different modalities is processed in parallel, and then integrated in associative brain areas to improve object identification and the interpretation of sensory experiences. The Superior Colliculus (SC) is a midbrain structure that plays a critical role in integrating visual, auditory, and somatosensory input to assess saliency and promote action. Although the response properties of the individual SC neurons to visuoauditory stimuli have been characterized, little is known about the spatial and temporal dynamics of the integration at the population level. Here we recorded the response properties of SC neurons to spatially restricted visual and auditory stimuli using large-scale electrophysiology. We then created a general, population-level model that explains the spatial, temporal, and intensity requirements of stimuli needed for sensory integration. We found that the mouse SC contains topographically organized visual and auditory neurons that exhibit nonlinear multisensory integration. We show that nonlinear integration depends on properties of auditory but not visual stimuli. We also find that a heuristically derived nonlinear modulation function reveals conditions required for sensory integration that are consistent with previously proposed models of sensory integration such as spatial matching and the principle of inverse effectiveness.

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Altered Resting-State Electroencephalography Microstates in Idiopathic Generalized Epilepsy: A Prospective Case-Control Study

Frontiers in Neurology ◽

10.3389/fneur.2021.710952 ◽

2021 ◽

Vol 12 ◽

Author(s):

YuBao Jiang ◽

MingYu Zhu ◽

Ying Hu ◽

Kai Wang

Keyword(s):

Resting State ◽

Large Scale ◽

Temporal Dynamics ◽

The Other ◽

Salience Network ◽

Idiopathic Generalized Epilepsy ◽

Class A ◽

Class C ◽

Microstate Analysis ◽

Generalized Epilepsy

Objective: Idiopathic generalized epilepsy (IGE) involves aberrant organization and functioning of large-scale brain networks. This study aims to investigate whether the resting-state EEG microstate analysis could provide novel insights into the abnormal temporal and spatial properties of intrinsic brain activities in patients with IGE.Methods: Three groups of participants were chosen for this study (namely IGE-Seizure, IGE-Seizure Free, and Healthy Controls). EEG microstate analysis on the resting-state EEG datasets was conducted for all participants. The average duration (“Duration”), the average number of microstates per second (“Frequency”), as well as the percentage of total analysis time occupied in that state (“Coverage”) of the EEG microstate were compared among the three groups.Results: For microstate classes B and D, the differences in Duration, Frequency, and Coverage among the three groups were not statistically significant. Both Frequency and Coverage of microstate class A were statistically significantly larger in the IGE-Seizure group than in the other two groups. The Duration and Coverage of microstate class C were statistically significantly smaller in the IGE-Seizure group than those in the other two groups.Conclusions: The Microstate class A was regarded as a sensorimotor network and Microstate class C was mainly related to the salience network, this study indicated an altered sensorimotor and salience network in patients with IGE, especially in those who had experienced seizures in the past 2 years, while the visual and attention networks seemed to be intact.Significance: The temporal dynamics of resting-state networks were studied through EEG microstate analysis in patients with IGE, which is expected to generate indices that could be utilized in clinical researches of epilepsy.

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A large-scale analysis of task switching practice effects across the lifespan

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1906788116 ◽

2019 ◽

Vol 116 (36) ◽

pp. 17735-17740 ◽

Cited By ~ 4

Author(s):

Mark Steyvers ◽

Guy E. Hawkins ◽

Frini Karayanidis ◽

Scott D. Brown

Keyword(s):

Task Switching ◽

Large Scale ◽

Temporal Dynamics ◽

Age Groups ◽

Relevant Information ◽

Human Cognition ◽

Older Individuals ◽

Adult Lifespan ◽

Task Practice ◽

Task Irrelevant

An important feature of human cognition is the ability to flexibly and efficiently adapt behavior in response to continuously changing contextual demands. We leverage a large-scale dataset from Lumosity, an online cognitive-training platform, to investigate how cognitive processes involved in cued switching between tasks are affected by level of task practice across the adult lifespan. We develop a computational account of task switching that specifies the temporal dynamics of activating task-relevant representations and inhibiting task-irrelevant representations and how they vary with extended task practice across a number of age groups. Practice modulates the level of activation of the task-relevant representation and improves the rate at which this information becomes available, but has little effect on the task-irrelevant representation. While long-term practice improves performance across all age groups, it has a greater effect on older adults. Indeed, extensive task practice can make older individuals functionally similar to less-practiced younger individuals, especially for cognitive measures that focus on the rate at which task-relevant information becomes available.

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Salience network atrophy links neuron type-specific pathobiology to loss of empathy in frontotemporal dementia

10.1101/691212 ◽

2019 ◽

Author(s):

Lorenzo Pasquini ◽

Alissa L. Nana ◽

Gianina Toller ◽

Jesse Brown ◽

Jersey Deng ◽

...

Keyword(s):

Frontotemporal Dementia ◽

Large Scale ◽

Anterior Cingulate ◽

Projection Neurons ◽

Salience Network ◽

Neuron Type ◽

Social Emotional ◽

Emotional Empathy ◽

Emotional Function ◽

Fork Cells

AbstractEach neurodegenerative syndrome reflects a stereotyped pattern of cellular, regional, and large-scale brain network degeneration. In behavioral variant frontotemporal dementia (bvFTD), a disorder of social-emotional function, von Economo neurons (VENs) and fork cells are among the initial neuronal targets. These large layer 5 projection neurons are concentrated in the anterior cingulate and frontoinsular (FI) cortices, regions that anchor the salience network, a large-scale system linked to social-emotional function. Here, we studied patients with bvFTD, amyotrophic lateral sclerosis (ALS), or both, given that these syndromes share common pathobiological and genetic factors. Our goal was to determine how neuron type-specific TAR DNA-binding protein of 43 kDa (TDP-43) pathobiology relates to atrophy in specific brain structures and to loss of emotional empathy, a cardinal feature of bvFTD. We combined questionnaire-based empathy assessments, in vivo structural MR imaging, and quantitative histopathological data from 16 patients across the bvFTD/ALS spectrum. We show that TDP-43 pathobiology within right FI VENs and fork cells is associated with salience network atrophy spanning insular, medial frontal, and thalamic regions. Gray matter degeneration within these structures mediated loss of emotional empathy, suggesting a chain of influence linking the cellular, regional/network, and behavioral levels in producing signature bvFTD clinical features.

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Early alterations of large-scale brain networks temporal dynamics in young children with autism

10.1101/2020.09.24.311423 ◽

2020 ◽

Author(s):

Aurélie Bochet ◽

Holger Franz Sperdin ◽

Tonia Anahi Rihs ◽

Nada Kojovic ◽

Martina Franchini ◽

...

Keyword(s):

Large Scale ◽

Developmental Stages ◽

Temporal Dynamics ◽

Brain Networks ◽

Autism Spectrum ◽

Compensatory Mechanism ◽

Temporal Properties ◽

Early Developmental Stages ◽

Spatio Temporal ◽

Early Developmental

ABSTRACTDisruption of large-scale brain networks is associated with autism spectrum disorders (ASD). Recently, we found that directed functional connectivity alterations of social brain networks are a core component of atypical brain development at early developmental stages in ASD (Sperdin et al., 2018). Here, we investigated the spatio-temporal dynamics of whole-brain neuronal networks at a subsecond scale in 90 toddlers and preschoolers (47 with ASD) using an EEG microstate approach. Results revealed the presence of five microstate classes that best described the entire dataset (labeled as microstate classes A-E). Microstate class C related to the Default Mode Network (DMN) occurred less in children with ASD. Analysis of brain-behavioural relationships within the ASD group suggested that a compensatory mechanism from microstate C was associated with less severe symptoms and better adaptive skills. These results demonstrate that the temporal properties of some specific EEG microstates are altered in ASD at early developmental stages.

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Nonlinear visuoauditory integration in the mouse superior colliculus

PLoS Computational Biology ◽

10.1371/journal.pcbi.1009181 ◽

2021 ◽

Vol 17 (11) ◽

pp. e1009181

Author(s):

Shinya Ito ◽

Yufei Si ◽

Alan M. Litke ◽

David A. Feldheim

Keyword(s):

Superior Colliculus ◽

Sensory Integration ◽

Large Scale ◽

Temporal Dynamics ◽

Critical Role ◽

Sensory Information ◽

Population Level ◽

Object Identification ◽

Response Properties ◽

The Individual

Sensory information from different modalities is processed in parallel, and then integrated in associative brain areas to improve object identification and the interpretation of sensory experiences. The Superior Colliculus (SC) is a midbrain structure that plays a critical role in integrating visual, auditory, and somatosensory input to assess saliency and promote action. Although the response properties of the individual SC neurons to visuoauditory stimuli have been characterized, little is known about the spatial and temporal dynamics of the integration at the population level. Here we recorded the response properties of SC neurons to spatially restricted visual and auditory stimuli using large-scale electrophysiology. We then created a general, population-level model that explains the spatial, temporal, and intensity requirements of stimuli needed for sensory integration. We found that the mouse SC contains topographically organized visual and auditory neurons that exhibit nonlinear multisensory integration. We show that nonlinear integration depends on properties of auditory but not visual stimuli. We also find that a heuristically derived nonlinear modulation function reveals conditions required for sensory integration that are consistent with previously proposed models of sensory integration such as spatial matching and the principle of inverse effectiveness.

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Cerebral cartography and connectomics

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2014.0173 ◽

2015 ◽

Vol 370 (1668) ◽

pp. 20140173 ◽

Cited By ~ 39

Author(s):

Olaf Sporns

Keyword(s):

Large Scale ◽

Computational Models ◽

Network Science ◽

Temporal Dynamics ◽

Functional Organization ◽

Brain Connectivity ◽

Hierarchical Organization ◽

Large Scale Networks ◽

Definition Of ◽

The Brain

Cerebral cartography and connectomics pursue similar goals in attempting to create maps that can inform our understanding of the structural and functional organization of the cortex. Connectome maps explicitly aim at representing the brain as a complex network, a collection of nodes and their interconnecting edges. This article reflects on some of the challenges that currently arise in the intersection of cerebral cartography and connectomics. Principal challenges concern the temporal dynamics of functional brain connectivity, the definition of areal parcellations and their hierarchical organization into large-scale networks, the extension of whole-brain connectivity to cellular-scale networks, and the mapping of structure/function relations in empirical recordings and computational models. Successfully addressing these challenges will require extensions of methods and tools from network science to the mapping and analysis of human brain connectivity data. The emerging view that the brain is more than a collection of areas, but is fundamentally operating as a complex networked system, will continue to drive the creation of ever more detailed and multi-modal network maps as tools for on-going exploration and discovery in human connectomics.

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Anatomical and functional connectivity support the existence of a salience network node within the caudal ventrolateral prefrontal cortex

10.1101/2021.10.01.462813 ◽

2021 ◽

Author(s):

Lucas R. Trambaiolli ◽

Xiaolong Peng ◽

Julia F. Lehman ◽

Hesheng Liu ◽

Suzanne N. Haber

Keyword(s):

Prefrontal Cortex ◽

Functional Connectivity ◽

Large Scale ◽

Cognitive Networks ◽

Anterior Cingulate ◽

Salience Network ◽

Subcortical Structures ◽

Dorsal Anterior Cingulate Cortex ◽

Ventrolateral Prefrontal Cortex ◽

Caudal Area

AbstractThree large-scale brain networks are considered essential to cognitive flexibility: the ventral and dorsal attention (VAN and DAN) and salience (SN) networks. The ventrolateral prefrontal cortex (vlPFC) is a known component of the VAN and DAN, but its role in the SN is controversial. In this study, we used a translational and multimodal approach to demonstrate the existence of a SN node within the vlPFC. First, we used tract-tracing methods in non-human primates (NHP) to quantify the anatomic connectivity strength between the different vlPFC areas and the frontal and insular cortices. The strongest connections with the dorsal anterior cingulate cortex (dACC) and anterior insula (AI) locations comprising the two main cortical SN nodes were derived from the caudal area 47/12. This location also has strong axonal projections to subcortical structures of the salience network, including the dorsomedial thalamus, hypothalamus, sublenticular extended amygdala, and periaqueductal gray. Second, we used a seed-based functional connectivity analysis in NHP resting-state functional MRI (rsfMRI) data to validate the caudal area 47/12 as an SN node. Third, we used the same approach in human rsfMRI data to identify a homologous structure in caudal area 47/12, also showing strong connections with the SN cortical nodes, thus confirming the caudal area 47/12 as the SN node in the vlPFC. Taken together, the vlPFC contains nodes for all three cognitive networks, the VAN, DAN, and SN. Thus, the vlPFC is in a position to switch between these three cognitive networks, suggesting a key role as an attentional hub. Its tight additional connections to the orbitofrontal, dorsolateral, and ventral premotor cortices, places the vlPFC at the center for switching behaviors based on environmental stimuli, computing value and cognitive control.

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Segregation, integration, and balance of large-scale resting brain networks configure different cognitive abilities

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2022288118 ◽

2021 ◽

Vol 118 (23) ◽

pp. e2022288118

Author(s):

Rong Wang ◽

Mianxin Liu ◽

Xinhong Cheng ◽

Ying Wu ◽

Andrea Hildebrandt ◽

...

Keyword(s):

Cognitive Abilities ◽

Structural Equation ◽

Large Scale ◽

Functional Organization ◽

Diffusion Tensor ◽

Brain Activity ◽

Brain Networks ◽

Deep Understanding ◽

Human Cognition ◽

Equation Modeling

Diverse cognitive processes set different demands on locally segregated and globally integrated brain activity. However, it remains an open question how resting brains configure their functional organization to balance the demands on network segregation and integration to best serve cognition. Here we use an eigenmode-based approach to identify hierarchical modules in functional brain networks and quantify the functional balance between network segregation and integration. In a large sample of healthy young adults (n = 991), we combine the whole-brain resting state functional magnetic resonance imaging (fMRI) data with a mean-filed model on the structural network derived from diffusion tensor imaging and demonstrate that resting brain networks are on average close to a balanced state. This state allows for a balanced time dwelling at segregated and integrated configurations and highly flexible switching between them. Furthermore, we employ structural equation modeling to estimate general and domain-specific cognitive phenotypes from nine tasks and demonstrate that network segregation, integration, and their balance in resting brains predict individual differences in diverse cognitive phenotypes. More specifically, stronger integration is associated with better general cognitive ability, stronger segregation fosters crystallized intelligence and processing speed, and an individual’s tendency toward balance supports better memory. Our findings provide a comprehensive and deep understanding of the brain’s functioning principles in supporting diverse functional demands and cognitive abilities and advance modern network neuroscience theories of human cognition.

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Salience Network Atrophy Links Neuron Type-Specific Pathobiology to Loss of Empathy in Frontotemporal Dementia

Cerebral Cortex ◽

10.1093/cercor/bhaa119 ◽

2020 ◽

Vol 30 (10) ◽

pp. 5387-5399 ◽

Cited By ~ 1

Author(s):

Lorenzo Pasquini ◽

Alissa L Nana ◽

Gianina Toller ◽

Jesse A Brown ◽

Jersey Deng ◽

...

Keyword(s):

Frontotemporal Dementia ◽

Large Scale ◽

Anterior Cingulate ◽

Projection Neurons ◽

Salience Network ◽

Neuron Type ◽

Social Emotional ◽

Emotional Empathy ◽

Emotional Function ◽

Fork Cells

Abstract Each neurodegenerative syndrome reflects a stereotyped pattern of cellular, regional, and large-scale brain network degeneration. In behavioral variant of frontotemporal dementia (bvFTD), a disorder of social-emotional function, von Economo neurons (VENs), and fork cells are among the initial neuronal targets. These large layer 5 projection neurons are concentrated in the anterior cingulate and frontoinsular (FI) cortices, regions that anchor the salience network, a large-scale system linked to social-emotional function. Here, we studied patients with bvFTD, amyotrophic lateral sclerosis (ALS), or both, given that these syndromes share common pathobiological and genetic factors. Our goal was to determine how neuron type-specific TAR DNA-binding protein of 43 kDa (TDP-43) pathobiology relates to atrophy in specific brain structures and to loss of emotional empathy, a cardinal feature of bvFTD. We combined questionnaire-based empathy assessments, in vivo structural MR imaging, and quantitative histopathological data from 16 patients across the bvFTD/ALS spectrum. We show that TDP-43 pathobiology within right FI VENs and fork cells is associated with salience network atrophy spanning insular, medial frontal, and thalamic regions. Gray matter degeneration within these structures mediated loss of emotional empathy, suggesting a chain of influence linking the cellular, regional/network, and behavioral levels in producing signature bvFTD clinical features.

Download Full-text