Common mechanisms of attractorless oscillatory regimes in radioengineering models of brain thalamocortical network

This work aims to show that long transient processes in mesascale models of thalamocortical brain network can appear in very general case, in particular for different number of elements in the ensemble (different level of detalization) and different initial phase of external driving, with these regimes surviving at small variations of number and structure of couplings. Methods. Thalamocortical brain networks are modelled using electronic circuit realized using computer SPICE eluating software. FitzHugh – Nagumo analog generator is used as a single circuit element. Results. Long quasiregular and nonregular oscillation processes with stationary amplitude were shown to occur in ensembles of 14, 28 and 56 model FitzHug – Nagumo generators. The dependency of transient process length on the external driving initial phase and particular coupling matrix structure was studied. Conclusion. The proposed electronic models of thalamocortical system were proved to reproduce the pathological regimes of brain activity in similar way despite the number of elements in the circuit, connectivity matrix and initial driving phase.

Bedtime to the brain: How infants sleep habits intertwine with sleep neurophysiology

Adequate sleep is critical for development and facilitates the maturation of the neurophysiological circuitries at the basis of cognitive and behavioral function. Observational research has associated sleep problems in early life with worse later cognitive, psychosocial, and somatic health outcomes. Yet, the extent to which day-to-day sleep habits in early life relate to neurophysiology - acutely and long-term - remains to be explored. Here, we report that sleep habits in 32 healthy 6-month-olds assessed with actimetry are linked to fundamental aspects of their neurophysiology measured with high-density electroencephalography (hdEEG). Our study reveals four key findings: First, daytime sleep habits are linked to EEG slow wave activity (SWA). Second, habits of nighttime movement and awakenings from sleep are connected with spindle density. Third, habitual sleep timing is linked to neurophysiological connectivity quantified as Delta-coherence. And lastly, Delta-coherence at age 6 months predicts nighttime sleep duration at age 12 months. These novel findings widen our understanding that infants' sleep habits are closely intertwined with three particular levels of neurophysiology: sleep pressure (determined by SWA), the maturation of the thalamocortical system (spindles), and the maturation of cortical connectivity (coherence). Our companion paper complements this insight in the perspective of later developmental outcomes: early thalamocortical connectivity (spindle density) at age 6 months predicts later behavioural status at 12 and 24 months. The crucial next step is to extend this concept to clinical groups to objectively characterize infants' sleep habits "at risk" that foster later neurodevelopmental problems.

The Temporally-Integrated Causality Landscape: Reconciling Neuroscientific Theories With the Phenomenology of Consciousness

In recent years, there has been a proliferation of neuroscientific theories of consciousness. These include theories which explicitly point to EM fields, notably Operational Architectonics and, more recently, the General Resonance Theory. In phenomenological terms, human consciousness is a unified composition of contents. These contents are specific and meaningful, and they exist from a subjective point of view. Human conscious experience is temporally continuous, limited in content, and coherent. Based upon those phenomenal observations, pre-existing theories of consciousness, and a large body of experimental evidence, I derived the Temporally-Integrated Causality Landscape (TICL). In brief, the TICL proposes that the neural correlate of consciousness is a structure of temporally integrated causality occurring over a large portion of the thalamocortical system. This structure is composed of a large, integrated set of neuronal elements (the System), which contains some subsystems, defined as having a higher level of temporally-integrated causality than the System as a whole. Each Subsystem exists from the point of view of the System, in the form of meaningful content. In this article, I review the TICL and consider the importance of EM forces as a mechanism of neural causality. I compare the fundamentals of TICL to those of several other neuroscientific theories. Using five major characteristics of phenomenal consciousness as a standard, I compare the basic tenets of Integrated Information Theory, Global Neuronal Workspace, General Resonance Theory, Operational Architectonics, and the Temporo-spatial Theory of Consciousness with the framework of the TICL. While the literature concerned with these theories tends to focus on different lines of evidence, there are fundamental areas of agreement. This means that, in time, it may be possible for many of them to converge upon the truth. In this analysis, I conclude that a primary distinction which divides these theories is the feature of spatial and temporal nesting. Interestingly, this distinction does not separate along the fault line between theories explicitly concerned with EM fields and those which are not. I believe that reconciliation is possible, at least in principle, among those theories that recognize the following: just as the contents of consciousness are distinctions within consciousness, the neural correlates of conscious content should be distinguishable from but fall within the spatial and temporal boundaries of the full neural correlates of consciousness.

Rodent Somatosensory Thalamocortical Circuitry: Neurons, Synapses, and Connectivity

As our understanding of the thalamocortical system deepens, the questions we face become more complex. Their investigation requires the adoption of novel experimental approaches complemented with increasingly sophisticated computational modeling. In this review, we take stock of current data and knowledge about the circuitry of the somatosensory thalamocortical loop in rodents, discussing common principles across modalities and species whenever appropriate. We review the different levels of organization, including the cells, synapses, neuroanatomy, and network connectivity. We provide a complete overview of this system that should be accessible for newcomers to this field while nevertheless being comprehensive enough to serve as a reference for seasoned neuroscientists and computational modelers studying the thalamocortical system. We further highlight key gaps in data and knowledge that constitute pressing targets for future experimental work. Filling these gaps would provide invaluable information for systematically unveiling how this system supports behavioral and cognitive processes.

The generation and propagation of the human alpha rhythm

The alpha rhythm is the longest-studied brain oscillation and has been theorized to play a key role in cognition. Still, its physiology is poorly understood. In this study, we used microelectrodes and macroelectrodes in surgical epilepsy patients to measure the intracortical and thalamic generators of the alpha rhythm during quiet wakefulness. We first found that alpha in both visual and somatosensory cortex propagates from higher-order to lower-order areas. In posterior cortex, alpha propagates from higher-order anterosuperior areas toward the occipital pole, whereas alpha in somatosensory cortex propagates from associative regions toward primary cortex. Several analyses suggest that this cortical alpha leads pulvinar alpha, complicating prevailing theories of a thalamic pacemaker. Finally, alpha is dominated by currents and firing in supragranular cortical layers. Together, these results suggest that the alpha rhythm likely reflects short-range supragranular feedback, which propagates from higher- to lower-order cortex and cortex to thalamus. These physiological insights suggest how alpha could mediate feedback throughout the thalamocortical system.

Community-informed connectomics of the thalamocortical system in generalized epilepsy

ObjectiveTo study the intrinsic organization of the thalamocortical circuitry in patients with generalized epilepsy with tonic-clonic seizures (GTCS) via resting-state fMRI (rs-fMRI) connectome analysis and to evaluate its relation to drug response.MethodsIn a prospectively followed-up sample of 41 patients and 27 healthy controls, we obtained rs-fMRI and structural MRI. After 1 year of follow-up, 27 patients were classified as seizure-free and 14 as drug-resistant. We examined connectivity within and between resting-state communities in cortical and thalamic subregions. In addition to comparing patients to controls, we examined associations with seizure control. We assessed reproducibility in an independent cohort of 21 patients.ResultsCompared to controls, patients showed a more constrained network embedding of the thalamus, while frontocentral neocortical regions expressed increased functional diversity. Findings remained significant after regressing out thalamic volume and cortical thickness, suggesting independence from structural alterations. We observed more marked network imbalances in drug-resistant compared to seizure-free patients. Findings were similar in the reproducibility dataset.ConclusionsOur findings suggest a pathoconnectomic mechanism of generalized epilepsy centered on diverging changes in cortical and thalamic connectivity. More restricted thalamic connectivity could reflect the tendency to engage in recursive thalamocortical loops, which may contribute to hyperexcitability. Conversely, increased connectional diversity of frontocentral networks may relay abnormal activity to an extended bilateral territory. Network imbalances were observed shortly after diagnosis and related to future drug response, suggesting clinical utility.

Experimentally-constrained biophysical models of tonic and burst firing modes in thalamocortical neurons

Somatosensory thalamocortical (TC) neurons from the ventrobasal (VB) thalamus are central components in the flow of sensory information between the periphery and the cerebral cortex, and participate in the dynamic regulation of thalamocortical states including wakefulness and sleep. This property is reflected at the cellular level by the ability to generate action potentials in two distinct firing modes, called tonic firing and low-threshold bursting. Although the general properties of TC neurons are known, we still lack a detailed characterization of their morphological and electrical properties in the VB thalamus. The aim of this study was to build biophysically-detailed models of VB TC neurons explicitly constrained with experimental data from rats. We recorded the electrical activity of VB neurons (N = 49) and reconstructed morphologies in 3D (N = 50) by applying standardized protocols. After identifying distinct electrical types, we used a multi-objective optimization to fit single neuron electrical models (e-models), which yielded multiple solutions consistent with the experimental data. The models were tested for generalization using electrical stimuli and neuron morphologies not used during fitting. A local sensitivity analysis revealed that the e-models are robust to small parameter changes and that all the parameters were constrained by one or more features. The e-models, when tested in combination with different morphologies, showed that the electrical behavior is substantially preserved when changing dendritic structure and that the e-models were not overfit to a specific morphology. The models and their analysis show that automatic parameter search can be applied to capture complex firing behavior, such as co-existence of tonic firing and low-threshold bursting over a wide range of parameter sets and in combination with different neuron morphologies.Author summaryThalamocortical neurons are one of the main components of the thalamocortical system, which are implicated in key functions including sensory transmission and the transition between brain states. These functions are reflected at the cellular level by the ability to generate action potentials in two distinct modes, called burst and tonic firing. Biophysically-detailed computational modeling of these cells can provide a tool to understand the role of these neurons within thalamocortical circuitry. We started by collecting single cell experimental data by applying standardized experimental procedures in brain slices of the rat. Prior work has demonstrated that biological constraints can be integrated using multi-objective optimization to build biologically realistic models of neuron. Here, we employ similar techniques as those previously employed, but extend them to capture the multiple firing modes of thalamic neurons. We compared the model results with additional experimental data test their generalization and quantitatively reject those that deviated significantly from the experimental variability. These models can be readily integrated in a data-driven pipeline to reconstruct and simulate circuit activity in the thalamocortical system.

Altered Forebrain Functional Connectivity and Neurotransmission in a Kinase-Inactive Met Mouse Model of Autism

MET, the gene encoding the tyrosine kinase receptor for hepatocyte growth factor, is a susceptibility gene for autism spectrum disorder (ASD). Genetically altered mice with a kinase-inactive Met offer a potential model for understanding neural circuit organization changes in autism. Here, we focus on the somatosensory thalamocortical circuitry because distinct somatosensory sensitivity phenotypes accompany ASD, and this system plays a major role in sensorimotor and social behaviors in mice. We employed resting-state functional magnetic resonance imaging and in vivo high-resolution proton MR spectroscopy to examine neuronal connectivity and neurotransmission of wild-type, heterozygous Met–Emx1, and fully inactive homozygous Met–Emx1 mice. Met–Emx1 brains showed impaired maturation of large-scale somatosensory network connectivity when compared with wild-type controls. Significant sex × genotype interaction in both network features and glutamate/gamma-aminobutyric acid (GABA) balance was observed. Female Met–Emx1 brains showed significant connectivity and glutamate/GABA balance changes in the somatosensory thalamocortical system when compared with wild-type brains. The glutamate/GABA ratio in the thalamus was correlated with the connectivity between the somatosensory cortex and the thalamus in heterozygous Met–Emx1 female brains. The findings support the hypothesis that aberrant functioning of the somatosensory thalamocortical system is at the core of the conspicuous somatosensory behavioral phenotypes observed in Met–Emx1 mice.