Quantitative Biology

Small dorsal root ganglion (DRG) neurons are primary nociceptors which are responsible for sensing pain. Elucidation of their dynamics is essential for understanding and controlling pain. To this end, we present a numerical bifurcation analysis of a small DRG neuron model in this paper. The model is of Hodgkin-Huxley type and has 9 state variables. It consists of a Na v 1.7 and a Na v 1.8 sodium channel, a leak channel, a delayed rectifier potassium and an A-type transient potassium channel. The dynamics of this model strongly depends on the maximal conductances of the voltage-gated ion channels and the external current, which can be adjusted experimentally. We show that the neuron dynamics are most sensitive to the Na v 1.8 channel maximal conductance ( g ¯ 1.8 ). Numerical bifurcation analysis shows that depending on g ¯ 1.8 and the external current, different parameter regions can be identified with stable steady states, periodic firing of action potentials, mixed-mode oscillations (MMOs), and bistability between stable steady states and stable periodic firing of action potentials. We illustrate and discuss the transitions between these different regimes. We further analyze the behavior of MMOs. Within this region, bifurcation analysis shows a sequence of isolated periodic solution branches with one large action potential and a number of small amplitude peaks per period. A closer inspection reveals more complex concatenated MMOs in between these periodic MMOs branches, forming Farey sequences. Lastly, we also find small solution windows with aperiodic oscillations, which seem to be chaotic. The dynamical patterns found here as a function of different parameters contain information of translational importance as their relation to pain sensation and its intensity is a potential source of insight into controlling pain.

The electric activities of cortical pyramidal neurons are supported by structurally stable, morphologically complex axo-dendritic trees. Anatomical differences between axons and dendrites in regard to their length or caliber reflect the underlying functional specializations, for input or output of neural information, respectively. For a proper assessment of the computational capacity of pyramidal neurons, we have analyzed an extensive dataset of three-dimensional digital reconstructions from the this http URL database, and quantified basic dendritic or axonal morphometric measures in different regions and layers of the mouse, rat or human cerebral cortex. Physical estimates of the total number and type of ions involved in neuronal electric spiking based on the obtained morphometric data, combined with energetics of neurotransmitter release and signaling fueled by glucose consumed by the active brain, support highly efficient cerebral computation performed at the thermodynamically allowed Landauer limit for implementation of irreversible logical operations. Individual proton tunneling events in voltage-sensing S4 protein α -helices of Na + , K + or Ca 2+ ion channels are ideally suited to serve as single Landauer elementary logical operations that are then amplified by selective ionic currents traversing the open channel pores. This miniaturization of computational gating allows the execution of over 1.2 zetta logical operations per second in the human cerebral cortex without combusting the brain by the released heat.

Computational models lie at the intersection of basic neuroscience and healthcare applications because they allow researchers to test hypotheses \textit{in silico} and predict the outcome of experiments and interactions that are very hard to test in reality. Yet, what is meant by "computational model" is understood in many different ways by researchers in different fields of neuroscience and psychology, hindering communication and collaboration. In this review, we point out the state of the art of computational modeling in Electroencephalography (EEG) and outline how these models can be used to integrate findings from electrophysiology, network-level models, and behavior. On the one hand, computational models serve to investigate the mechanisms that generate brain activity, for example measured with EEG, such as the transient emergence of oscillations at different frequency bands and/or with different spatial topographies. On the other hand, computational models serve to design experiments and test hypotheses \emph{in silico}. The final purpose of computational models of EEG is to obtain a comprehensive understanding of the mechanisms that underlie the EEG signal. This is crucial for an accurate interpretation of EEG measurements that may ultimately serve in the development of novel clinical applications.

Dementia is a collection of symptoms associated with impaired cognition and impedes everyday normal functioning. Dementia, with Alzheimer's disease constituting its most common type, is highly complex in terms of etiology and pathophysiology. A more quantitative or computational attitude towards dementia research, or more generally in neurology, is becoming necessary - Computational Neurology. We provide a focused review of some computational approaches that have been developed and applied to the study of dementia, particularly Alzheimer's disease. Both mechanistic modeling and data-drive, including AI or machine learning, approaches are discussed. Linkage to clinical decision support systems for dementia diagnosis will also be discussed.

Measurements of electric potentials from neural activity have played a key role in neuroscience for almost a century, and simulations of neural activity is an important tool for understanding such measurements. Volume conductor (VC) theory is used to compute extracellular electric potentials such as extracellular spikes, MUA, LFP, ECoG and EEG surrounding neurons, and also inversely, to reconstruct neuronal current source distributions from recorded potentials through current source density methods. In this book chapter, we show how VC theory can be derived from a detailed electrodiffusive theory for ion concentration dynamics in the extracellular medium, and show what assumptions that must be introduced to get the VC theory on the simplified form that is commonly used by neuroscientists. Furthermore, we provide examples of how the theory is applied to compute spikes, LFP signals and EEG signals generated by neurons and neuronal populations.

Cue integration, the combination of different sources of information to reduce uncertainty, is a fundamental computational principle of brain function. Starting from a normative model we show that the dynamics of multi-compartment neurons with conductance-based dendrites naturally implement the required probabilistic computations. The associated error-driven plasticity rule allows neurons to learn the relative reliability of different pathways from data samples, approximating Bayes-optimal observers in multisensory integration tasks. Additionally, the model provides a functional interpretation of neural recordings from multisensory integration experiments and makes specific predictions for membrane potential and conductance dynamics of individual neurons.

Epilepsy is a chronic neurological disorder affecting more than 50 million people globally. An epileptic seizure acts like a temporary shock to the neuronal system, disrupting normal electrical activity in the brain. Epilepsy is frequently diagnosed with electroencephalograms (EEGs). Current methods study the time-varying spectra and coherence but do not directly model changes in extreme behavior. Thus, we propose a new approach to characterize brain connectivity based on the joint tail behavior of the EEGs. Our proposed method, the conditional extremal dependence for brain connectivity (Conex-Connect), is a pioneering approach that links the association between extreme values of higher oscillations at a reference channel with the other brain network channels. Using the Conex-Connect method, we discover changes in the extremal dependence driven by the activity at the foci of the epileptic seizure. Our model-based approach reveals that, pre-seizure, the dependence is notably stable for all channels when conditioning on extreme values of the focal seizure area. Post-seizure, by contrast, the dependence between channels is weaker, and dependence patterns are more "chaotic". Moreover, in terms of spectral decomposition, we find that high values of the high-frequency Gamma-band are the most relevant features to explain the conditional extremal dependence of brain connectivity.

Universal Turing Machines [29, 10, 18] are well known in computer science but they are about manual programming for general purposes. Although human children perform conscious learning (i.e., learning while being conscious) from infancy [24, 23, 14, 4], it is unknown that Universal Turing Machiness can facilitate not only our understanding of Autonomous Programming For General Purposes (APFGP) by machines, but also enable early-age conscious learning. This work reports a new kind of AI---conscious learning AI from a machine's "baby" time. Instead of arguing what static tasks a conscious machine should be able to do during its "adulthood", this work suggests that APFGP is a computationally clearer and necessary criterion for us to judge whether a machine is capable of conscious learning so that it can autonomously acquire skills along its "career path". The results here report new concepts and experimental studies for early vision, audition, natural language understanding, and emotion, with conscious learning capabilities that are absent from traditional AI systems.

The integration and transmission of information in the brain are dependent on the interplay between structural and dynamical properties. Implicit in any pursuit aimed at understanding neural dynamics from appropriate sets of mathematically bounded conditions is the notion of an underlying fundamental structure-function constraint imposed by the geometry of the structural networks and the resultant latencies involved with transfer of information. We recently described the construction and theoretical analysis of a framework that models how local structure-function rules give rise to emergent global dynamics on a neural network. An important part of this research program is the requirement for a set of mathematical methods that allow us to catalog, theoretically analyze, and numerically study the rich dynamical patterns that result. One direction we are exploring is an extension of the theory of graphlets. In this paper we introduce an extension of graphlets and associated metric that maps the topological transition of a network from one moment in time to another at the same time that causal relationships are preserved.

We construct embedded functional connectivity networks (FCN) from benchmark resting-state functional magnetic resonance imaging (rsfMRI) data acquired from patients with schizophrenia and healthy controls based on linear and nonlinear manifold learning algorithms, namely, Multidimensional Scaling (MDS), Isometric Feature Mapping (ISOMAP) and Diffusion Maps. Furthermore, based on key global graph-theoretical properties of the embedded FCN, we compare their classification potential using machine learning techniques. We also assess the performance of two metrics that are widely used for the construction of FCN from fMRI, namely the Euclidean distance and the lagged cross-correlation metric. We show that the FCN constructed with Diffusion Maps and the lagged cross-correlation metric outperform the other combinations.