At the macroscale, the brain operates as a network of interconnected neuronal populations, which display rhythmic dynamics that support interareal communication. Understanding how stimulation of a particular brain area impacts such concerted activity is important for gaining basic insights into brain function and for developing neuromodulation as a therapeutic tool. However, it remains difficult to predict the downstream effects of focal stimulation. Specifically, little is known about how the collective oscillatory regime of network activity may affect the outcomes of regional perturbations on cooperative dynamics. Here, we combine connectome data and biophysical modeling to begin filling these gaps. By tuning parameters that control the collective dynamics of the network, we identify distinct states of simulated brain activity, and investigate how the distributed effects of stimulation manifest in different states. When baseline oscillations are weak, the stimulated area exhibits enhanced power and frequency, and due to network interactions, nearby regions develop phase locked activity in the excited frequency band. Importantly, we find that focal stimulation also causes more distributed modifications to network coherence at regions' baseline oscillation frequencies, and that these effects are better predicted by functional rather than structural connectivity. In contrast, when the network operates in a regime of stronger endogenous oscillations, stimulation causes only slight shifts in power and frequency, and network averaged changes in coherence are more homogenous across the choice of the stimulated area. In sum, this work builds upon and extends previous computational studies investigating the impacts of stimulation, and highlights that both the stimulation site, and, crucially, the regime of brain network dynamics, can influence the network wide responses to local perturbations.
Targeted electrical stimulation of the brain perturbs neural networks and modulates their rhythmic activity both at the site of stimulation and at remote brain regions. Understanding, or even predicting, this neuromodulatory effect is crucial for any therapeutic use of brain stimulation. To this end, we analyzed the stimulation responses in 131 stimulation sessions across 66 patients with focal epilepsy recorded through intracranial EEG (iEEG). We considered functional and structural connectivity features as predictors of the response at every iEEG contact. Taking advantage of multiple recordi…
Migraine patients with aura show a peculiar pattern of visual reactivity compared with those of migraine patients without aura: an increased effective connectivity, connected to a reduced synchronization among EEG channels, for frequencies in the beta band. The effective connectivity is evaluated in terms of the Granger causality. This anomalous response to visual stimuli may play a crucial role in the progression of spreading depression and clinical evidences of aura symptoms.
Imaging studies suggest that the functional connectivity patterns of resting state networks (RS-networks) reflect underlying structural connectivity (SC). If the connectome constrains how brain areas are functionally connected, the stimulation of specific brain areas should produce a characteristic wave of activity ultimately resolving into RS-networks. To systematically test this hypothesis, we use a connectome-based network model of the human brain with detailed realistic SC. We systematically activate all possible thalamic and cortical areas with focal stimulation patterns and confirm that …
Stimulation-based control of dynamic brain networks
University of Pennsylvania（宾夕法尼亚大学）；US Army Research Laboratory（美国陆军研究实验室）；University at Buffalo, SUNY（纽约州立大学布法罗分校）；University of California, Riverside（加州大学河滨分校）；University of California, Santa Barbara（加州大学圣塔芭芭拉分校）
Global brain activity self-organizes into discrete patterns characterized by distinct behavioral observables and modes of information processing. The human thalamocortical system is a densely connected network where local neural activation reciprocally influences coordinated collective dynamics. We introduce a semi-empirical model to investigate the relationship between regional activation and long-range functional connectivity in the different brain states visited during the natural wake-sleep cycle. Our model combines functional magnetic resonance imaging (fMRI) data, in vivo estimates of st…
A major challenge in neuroimaging is understanding the mapping of neurophysiological dynamics onto cognitive functions. Traditionally, these maps have been constructed by examining changes in the activity magnitude of regions related to task performance. Recently, network neuroscience has produced methods to map connectivity patterns among many regions to certain cognitive functions by drawing on tools from network science and graph theory. However, these two different views are rarely addressed simultaneously, largely because few tools exist that account for patterns between nodes while simul…
One of the primary goals of systems neuroscience is to relate the structure of neural circuits to their function, yet patterns of connectivity are difficult to establish when recording from large populations in behaving organisms. Many previous approaches have attempted to estimate functional connectivity between neurons using statistical modeling of observational data, but these approaches rely heavily on parametric assumptions and are purely correlational. Recently, however, holographic photostimulation techniques have made it possible to precisely target selected ensembles of neurons, offer…
The human brain exhibits a relatively stable spatiotemporal organization that supports brain function and can be manipulated via local brain stimulation. Such perturbations to local cortical dynamics are globally integrated by distinct neural systems. However, it remains unclear how and why local changes in neural activity affect large-scale system dynamics. Here, we briefly review empirical and computational studies addressing how localized perturbations affect brain activity. We then systematically analyze a model of large-scale brain dynamics, assessing how localized changes in brain activi…
Correlation-based Hebbian plasticity is thought to shape neuronal connectivity during development and learning, whereas homeostatic plasticity would stabilize network activity. Here we investigate another, new aspect of this dichotomy: Can Hebbian associative properties also emerge as a network effect from a plasticity rule based on homeostatic principles on the neuronal level? To address this question, we simulated a recurrent network of leaky integrate-and-fire neurons, in which excitatory connections are subject to a structural plasticity rule based on firing rate homeostasis. We show that …
Running title: Frontoparietal anodal tDCS reduces ketamine-induced oscillopathies.Abstract: During the prodromal phase of schizophrenia with its complex and insidious clinical picture, electroencephalographic recordings detect widespread oscillation disturbances (or oscillopathies). Neural oscillations are electro-biomarkers of the connectivity state within systems. A single systemic administration of ketamine, a non-competitive NMDA glutamate receptor antagonist, transiently reproduces the oscillopathies with a clinical picture reminiscent of the psychosis prodrome. This acute pharmacological…
We present an error-controlled mesh refinement procedure for needle insertion simulation and apply it to the simulation of electrode implantation for deep brain stimulation, including brain shift. Our approach enables to control the error in the computation of the displacement and stress fields around the needle tip and needle shaft by suitably refining the mesh, whilst maintaining a coarser mesh in other parts of the domain. We demonstrate through academic and practical examples that our approach increases the accuracy of the displacement and stress fields around the needle without increasing…
A large body of literature has shown the substantial inter-regional functional connectivity in the mammal brain. One important property remaining un-studied is the cross-time interareal connection. This paper serves to provide a tool to characterize the cross-time functional connectivity. The method is extended from the temporal embedding based brain temporal coherence analysis. Both synthetic data and in-vivo data were used to evaluate the various properties of the cross-time functional connectivity matrix, which is also called the cross-regional temporal coherence matrix.
Whole-brain computational modeling based on structural connectivity has shown great promise in successfully simulating fMRI BOLD signals with temporal co-activation patterns that are highly similar to empirical functional connectivity patterns during resting state. Importantly, previous studies have shown that spontaneous fluctuations in co-activation patterns of distributed brain regions have an inherent dynamic nature with regard to the frequency spectrum of intrinsic brain oscillations. In this modeling study, we introduced frequency dynamics into a system of coupled oscillators, where each…
Magnetoencephalographic (MEG) recordings from a large normative cohort (n = 619) were processed to extract measures of regional neuroelectric activity. The overall objective of the effort was to use these measures to identify normative human neuroelectric brain function. The aims were (a) to identify and measure the values and range of those neuroelectric properties which are common to the cohort, (b) to identify and measure the values and range of those neuroelectric properties which distinguish one individual from another, and (c) to identify relationships of the measures to properties of th…
Small-World Networks (SWNs) represent a fundamental model for the comprehension of many complex man-made and biological networks. In the central nervous system, SWN models have been shown to fit well both anatomical and functional maps at the macroscopic level. However the functional microscopic level, where the nodes of a network are composed of single neurons, is still poorly understood. At this level, although recent evidences suggest that functional connectivity maps exhibit small-world organization, it is not known whether and how these maps, distributed in multiple brain regions, change …
Transcranial magnetic stimulation of visual-motion area V5/MT modulates sensory thalamus responses during visual speech recognition
Dresden University of Technology（德累斯顿工业大学）；Basque Center on Cognition, Brain and Language（巴斯克认知、大脑与语言中心）；Max Planck Institute for Human Cognitive and Brain Sciences（马克斯·普朗克人类认知与脑科学研究所）；Ikerbasque, Basque Foundation for Science（伊卡巴斯科，巴斯克科学基金会）；Universitat Internacional de Catalunya, Faculty of Medicine and Health Sciences（加泰罗尼亚国际大学，医学与健康科学学院）
The relationship between brain structure and function has been probed using a variety of approaches, but how the underlying structural connectivity of the human brain drives behavior is far from understood. To investigate the effect of anatomical brain organization on human task performance, we use a data-driven computational modeling approach and explore the functional effects of naturally occurring structural differences in brain networks. We construct personalized brain network models by combining anatomical connectivity estimated from diffusion spectrum imaging of individual subjects with …
Maintaining upright posture is a complex task governed by the integration of afferent sensorimotor and visual information with compensatory neuromuscular reactions. The objective of this work was to characterize the visual dependency and functional dynamics of cortical activation during postural control. Proprioceptic vibratory stimulation of calf muscles at 85 Hz was performed to evoke postural perturbation in open-eye (OE) and closed-eye (CE) experimental trials, with pseudorandom binary stimulation phases divided into four segments of 16 stimuli. 64-channel EEG was recorded; with perturbati…
Electrocorticography (ECoG) provides direct measurements of synchronized postsynaptic potentials at the exposed cortical surface. Patterns of signal covariance across ECoG sensors have been associated with diverse cognitive functions and remain a critical marker of seizure onset, progression, and termination. Yet, a systems level understanding of these patterns (or networks) has remained elusive, in part due to variable electrode placement and sparse cortical coverage. Here, we address these challenges by constructing inter-regional ECoG networks from multi-subject recordings, demonstrate simi…
Neurostimulation is a promising therapy for abating epileptic seizures. However, it is extremely difficult to identify optimal stimulation patterns experimentally. In this study human recordings are used to develop a functional 24 neuron network statistical model of hippocampal connectivity and dynamics. Spontaneous seizure-like activity is induced in-silico in this reconstructed neuronal network. The network is then used as a testbed to design and validate a wide range of neurostimulation patterns. Commonly used periodic trains were not able to permanently abate seizures at any frequency. A s…
How spiking activity reverberates through neuronal networks, how evoked and spontaneous activity interact and blend, and how the combined activities represent external stimulation are pivotal questions in neuroscience. We simulated minimal models of unstructured spiking networks in silico, asking whether and how gentle external stimulation might be subsequently reflected in spontaneous activity fluctuations. Consistent with earlier findings in silico and in vitro, we observe a privileged sub-population of 'pioneer neurons' that, by their firing order, reliably encode previous external stimulat…
Experiments show that spike-triggered stimulation performed with Bidirectional Brain-Computer-Interfaces (BBCI) can artificially strengthen connections between separate neural sites in motor cortex (MC). What are the neuronal mechanisms responsible for these changes and how does targeted stimulation by a BBCI shape population-level synaptic connectivity? The present work describes a recurrent neural network model with probabilistic spiking mechanisms and plastic synapses capable of capturing both neural and synaptic activity statistics relevant to BBCI conditioning protocols. When spikes from …
Synthetic reverberating activity patterns are experimentally generated by stimulation of a subset of neurons embedded in a spontaneously active network of cortical cells in-vitro. The neurons are artificially connected by means of conditional stimulation matrix, forming a synthetic local circuit with a predefined programmable connectivity and time-delays. Possible uses of this experimental design are demonstrated, analyzing the sensitivity of these deterministic activity patterns to transmission delays and to the nature of ongoing network dynamics.
Neurons in the primary visual cortex are more or less selective for the orientation of a light bar used for stimulation. A broad distribution of individual grades of orientation selectivity has in fact been reported in all species. A possible reason for emergence of broad distributions is the recurrent network within which the stimulus is being processed. Here we compute the distribution of orientation selectivity in randomly connected model networks that are equipped with different spatial patterns of connectivity. We show that, for a wide variety of connectivity patterns, a linear theory bas…
Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) is widely used to study the reactivity and connectivity of brain regions for clinical or research purposes. The electromagnetic pulse of the TMS device generates at the instant of administration an artifact of large amplitude and a duration up to tens of milliseconds that overlaps with brain activity. Methods for TMS artifact correction have been developed to remove the artifact and recover the underlying, immediate response of the cerebral cortex to the magnetic stimulus. In this study, three such algorithms are …
We study neural connectivity in cultures of rat hippocampal neurons. We measure the neurons' response to an electric stimulation for gradual lower connectivity, and characterize the size of the giant cluster in the network. The connectivity undergoes a percolation transition described by the critical exponent $β\simeq 0.65$. We use a theoretic approach based on bond.percolation on a graph to describe the process of disintegration of the network and extract its statistical properties. Together with numerical simulations we show that the connectivity in the neural culture is local, characterized…
In this paper, we develop an approach to modeling high-dimensional networks with a large number of nodes arranged in a hierarchical and modular structure. We propose a novel multi-scale factor analysis (MSFA) model which partitions the massive spatio-temporal data defined over the complex networks into a finite set of regional clusters. To achieve further dimension reduction, we represent the signals in each cluster by a small number of latent factors. The correlation matrix for all nodes in the network are approximated by lower-dimensional sub-structures derived from the cluster-specific fact…
The experimental study of neural networks requires simultaneous measurements of a massive number of neurons, while monitoring properties of the connectivity, synaptic strengths and delays. Current technological barriers make such a mission unachievable. In addition, as a result of the enormous number of required measurements, the estimated network parameters would differ from the original ones. Here we present a versatile experimental technique, which enables the study of recurrent neural networks activity while being capable of dictating the network connectivity and synaptic strengths. This m…
The most studies on functional connectivity have been done by analyzing the brain's hemodynamic response to a stimulation. On the other hand, the low-frequency spontaneous fluctuations in the blood oxygen level dependent (BOLD) signals of functional MRI have been observed in the resting state. However, the BOLD signals in resting state are significantly corrupted by huge noises arising from cardiac pulsation, respiration, subject motion, scanner, and so forth. Especially, the noise compounds are stronger in the rat brain than in the human brain. To overcome such an artifact, we assumed that fr…
We propose a model for description of activity-dependent evolution and self-wiring between binary neurons. Specifically, this model can be used for investigation of growth of neuronal connectivity in the developing neocortex. By using computational simulations with appropriate training pattern sequences, we show that long-term memory can be encoded in neuronal connectivity and that the external stimulations form part of the functioning neocortical circuit. It is proposed that such binary neuron representations of point-like cortical neurons fail to reproduce cytoarchitectural differences of th…
Functional connectivity (FC) between brain regions tracks symptom severity in many neuropsychiatric disorders. Transcranial magnetic stimulation (TMS) directly alters regional activity and indirectly alters FC. Predicting how FC will change following TMS is difficult, but would allow novel therapies that target FC to improve symptoms. We address this challenge by proposing a predictive model that explains how TMS-induced activation can change the strength of FC. Here, we focus on the FC of the frontoparietal (FPS) and default mode (DMS) systems given the importance of their FC in executive fun…
The brain is an assembly of neuronal populations interconnected by structural pathways. Brain activity is expressed on and constrained by this substrate. Therefore, statistical dependencies between functional signals in directly connected areas can be expected higher. However, the degree to which brain function is bound by the underlying wiring diagram remains a complex question that has been only partially answered. Here, we introduce the structural-decoupling index to quantify the coupling strength between structure and function, and we reveal a macroscale gradient from brain regions more st…
Over one third of the estimated 3 million people with epilepsy in the US are medication resistant. Responsive neurostimulation from chronically implanted electrodes provides a promising treatment option and alternative to resective surgery. However, determining personalized optimal stimulation parameters, including when and where to intervene to guarantee a positive patient outcome, is a major open challenge. Network neuroscience and control theory offer useful tools that may guide improvements in parameter selection for control of anomalous neural activity. Here we use a novel method to chara…
The human brain is a complex dynamical system that gives rise to cognition through spatiotemporal patterns of coherent and incoherent activity between brain regions. As different regions dynamically interact to perform cognitive tasks, variable patterns of partial synchrony can be observed, forming chimera states. We propose that the emergence of such states plays a fundamental role in the cognitive organization of the brain, and present a novel cognitively-informed, chimera-based framework to explore how large-scale brain architecture affects brain dynamics and function. Using personalized br…
First-episode schizophrenia (FES) results in abnormality of brain connectivity at different levels. Despite some successful findings on functional and structural connectivity of FES, relatively few studies have been focused on morphological connectivity, which may provide a potential biomarker for FES. In this study, we aim to investigate cortical morphological connectivity in FES. T1-weighted magnetic resonance image data from 92 FES patients and 106 healthy controls (HCs) are analyzed.We parcellate brain into 68 cortical regions, calculate the averaged thickness and surface area of each regi…
Neuroengineering is faced with unique challenges in repairing or replacing complex neural systems that are composed of many interacting parts. These interactions form intricate patterns over large spatiotemporal scales, and produce emergent behaviors that are difficult to predict from individual elements. Network science provides a particularly appropriate framework in which to study and intervene in such systems, by treating neural elements (cells, volumes) as nodes in a graph and neural interactions (synapses, white matter tracts) as edges in that graph. Here, we review the emerging discipli…
We study living neural networks by measuring the neurons' response to a global electrical stimulation. Neural connectivity is lowered by reducing the synaptic strength, chemically blocking neurotransmitter receptors. We use a graph-theoretic approach to show that the connectivity undergoes a percolation transition. This occurs as the giant component disintegrates, characterized by a power law with critical exponent $β\simeq 0.65$ is independent of the balance between excitatory and inhibitory neurons and indicates that the degree distribution is gaussian rather than scale free
It is currently accepted that cortical maps are dynamic constructions that are altered in response to external input. Experience-dependent structural changes in cortical microcurcuts lead to changes of activity, i.e. to changes in information encoded. Specific patterns of external stimulation can lead to creation of new synaptic connections between neurons. The calcium influxes controlled by neuronal activity regulate the processes of neurotrophic factors released by neurons, growth cones movement and synapse differentiation in developing neural systems. We propose a model for description and …
With an estimated five million new stroke survivors every year and a rapidly aging population suffering from hyperintensities and diseases of presumed vascular origin that affect white matter and contribute to cognitive decline, it is critical that we understand the impact of white matter damage on brain structure and behavior. Current techniques for assessing the impact of lesions consider only location, type, and extent, while ignoring how the affected region was connected to the rest of the brain. Regional brain function is a product of both local structure and its connectivity. Therefore, …
