The Effect of a Global, Subject, and Device-Specific Model on a Noninvasive Glucose Monitoring Multisensor System.

BACKGROUND: We study here the influence of different patients and the influence of different devices with the same patients on the signals and modeling of data from measurements from a noninvasive Multisensor glucose monitoring system in patients with type 1 diabetes. The Multisensor includes several sensors for biophysical monitoring of skin and underlying tissue integrated on a single substrate. METHOD: Two Multisensors were worn simultaneously, 1 on the upper left and 1 on the upper right arm by 4 patients during 16 study visits. Glucose was administered orally to induce 2 consecutive hyperglycemic excursions. For the analysis, global (valid for a population of patients), personal (tailored to a specific patient), and device-specific multiple linear regression models were derived. RESULTS: We find that adjustments of the model to the patients improves the performance of the glucose estimation with an MARD of 17.8% for personalized model versus a MARD of 21.1% for the global model. At the same time the effect of the measurement side is negligible. The device can equally well measure on the left or right arm. We also see that devices are equal in the linear modeling. Thus hardware calibration of the sensors is seen to be sufficient to eliminate interdevice differences in the measured signals. CONCLUSIONS: We demonstrate that the hardware of the 2 devices worn on the left and right arms are consistent yielding similar measured signals and thus glucose estimation results with a global model. The 2 devices also return similar values of glucose errors. These errors are mainly due to nonstationarities in the measured signals that are not solved by the linear model, thus suggesting for more sophisticated modeling approaches.

Data processing for noninvasive continuous glucose monitoring with a multisensor device.

BACKGROUND: Impedance spectroscopy has been shown to be a candidate for noninvasive continuous glucose monitoring in humans. However, in addition to glucose, other factors also have effects on impedance characteristics of the skin and underlying tissue. METHOD: Impedance spectra were summarized through a principal component analysis and relevant variables were identified with Akaike's information criterion. In order to model blood glucose, a linear least-squares model was used. A Monte Carlo simulation was applied to examine the effects of personalizing models. RESULTS: The principal component analysis was able to identify two major effects in the impedance spectra: a blood glucose-related process and an equilibration process related to moisturization of the skin and underlying tissue. With a global linear least-squares model, a coefficient of determination (R²) of 0.60 was achieved, whereas the personalized model reached an R² of 0.71. The Monte Carlo simulation proved a significant advantage of personalized models over global models. CONCLUSION: A principal component analysis is useful for extracting glucose-related effects in the impedance spectra of human skin. A linear global model based on Solianis Multisensor data yields a good predictive power for blood glucose estimation. However, a personalized linear model still has greater predictive power.

Estimating interdependences in networks of weakly coupled deterministic systems.

The extraction of information from measured data about the interactions taking place in a network of systems is a key topic in modern applied sciences. This topic has been traditionally addressed by considering bivariate time series, providing methods which are sometimes difficult to extend to multivariate data, the limiting factor being the computational complexity. Here, we present a computationally viable method based on black-box modeling which, while theoretically applicable only when a deterministic hypothesis about the processes behind the recordings is plausible, proves to work also when this assumption is severely affected. Conceptually, the method is very simple and is composed of three independent steps: in the first step a state-space reconstruction is performed separately on each measured signal; in the second step, a local model, i.e., a nonlinear dynamical system, is fitted separately on each (reconstructed) measured signal; afterward, a linear model of the dynamical interactions is obtained by cross-relating the (reconstructed) measured variables to the dynamics unexplained by the local models. The method is successfully validated on numerically generated data. An assessment of its sensitivity to data length and modeling and measurement noise intensity, and of its applicability to large-scale systems, is also provided.

A novel interhemispheric interaction: modulation of neuronal cooperativity in the visual areas.

BACKGROUND: The cortical representation of the visual field is split along the vertical midline, with the left and the right hemi-fields projecting to separate hemispheres. Connections between the visual areas of the two hemispheres are abundant near the representation of the visual midline. It was suggested that they re-establish the functional continuity of the visual field by controlling the dynamics of the responses in the two hemispheres. METHODS/PRINCIPAL FINDINGS: To understand if and how the interactions between the two hemispheres participate in processing visual stimuli, the synchronization of responses to identical or different moving gratings in the two hemi-fields were studied in anesthetized ferrets. The responses were recorded by multiple electrodes in the primary visual areas and the synchronization of local field potentials across the electrodes were analyzed with a recent method derived from dynamical system theory. Inactivating the visual areas of one hemisphere modulated the synchronization of the stimulus-driven activity in the other hemisphere. The modulation was stimulus-specific and was consistent with the fine morphology of callosal axons in particular with the spatio-temporal pattern of activity that axonal geometry can generate. CONCLUSIONS/SIGNIFICANCE: These findings describe a new kind of interaction between the cerebral hemispheres and highlight the role of axonal geometry in modulating aspects of cortical dynamics responsible for stimulus detection and/or categorization.

Dysconnection topography in schizophrenia revealed with state-space analysis of EEG.

BACKGROUND: The dysconnection hypothesis has been proposed to account for pathophysiological mechanisms underlying schizophrenia. Widespread structural changes suggesting abnormal connectivity in schizophrenia have been imaged. A functional counterpart of the structural maps would be the EEG synchronization maps. However, due to the limits of currently used bivariate methods, functional correlates of dysconnection are limited to the isolated measurements of synchronization between preselected pairs of EEG signals. METHODS/RESULTS: To reveal a whole-head synchronization topography in schizophrenia, we applied a new method of multivariate synchronization analysis called S-estimator to the resting dense-array (128 channels) EEG obtained from 14 patients and 14 controls. This method determines synchronization from the embedding dimension in a state-space domain based on the theoretical consequence of the cooperative behavior of simultaneous time series-the shrinking of the state-space embedding dimension. The S-estimator imaging revealed a specific synchronization landscape in schizophrenia patients. Its main features included bilaterally increased synchronization over temporal brain regions and decreased synchronization over the postcentral/parietal region neighboring the midline. The synchronization topography was stable over the course of several months and correlated with the severity of schizophrenia symptoms. In particular, direct correlations linked positive, negative, and general psychopathological symptoms to the hyper-synchronized temporal clusters over both hemispheres. Along with these correlations, general psychopathological symptoms inversely correlated within the hypo-synchronized postcentral midline region. While being similar to the structural maps of cortical changes in schizophrenia, the S-maps go beyond the topography limits, demonstrating a novel aspect of the abnormalities of functional cooperation: namely, regionally reduced or enhanced connectivity. CONCLUSION/SIGNIFICANCE: The new method of multivariate synchronization significantly boosts the potential of EEG as an imaging technique compatible with other imaging modalities. Its application to schizophrenia research shows that schizophrenia can be explained within the concept of neural dysconnection across and within large-scale brain networks.

On the complexity of periodic and nonperiodic behaviors of a hysteresis-based electronic oscillator.

We investigate the families of periodic and nonperiodic behaviors admitted by a hysteresis-based circuit oscillator. The analysis is carried out by combining brute-force simulations with continuation methods. As a result of the analysis, it is shown that the existence of many different periodic solutions and of the chaotic behaviors associated with them is organized by few codimension-2 bifurcation points. This implies the possibility of switching between different periodic solutions by controlling only two bifurcation parameters, which makes the oscillator a possible generator of nontrivial periodic solutions suitable, for instance for actual radiofrequency identification systems applications.

A method for determining neural connectivity and inferring the underlying network dynamics using extracellular spike recordings.

In the present paper we propose a novel method for the identification and modeling of neural networks using extracellular spike recordings. We create a deterministic model of the effective network, whose dynamic behavior fits experimental data. The network obtained by our method includes explicit mathematical models of each of the spiking neurons and a description of the effective connectivity between them. Such a model allows us to study the properties of the neuron ensemble independently from the original data. It also permits to infer properties of the ensemble that cannot be directly obtained from the observed spike trains. The performance of the method is tested with spike trains artificially generated by a number of different neural networks.

Assessment of EEG synchronization based on state-space analysis.

Cortical computation involves the formation of cooperative neuronal assemblies characterized by synchronous oscillatory activity. A traditional method for the identification of synchronous neuronal assemblies has been the coherence analysis of EEG signals. Here, we suggest a new method called S estimator, whereby cortical synchrony is defined from the embedding dimension in a state-space. We first validated the method on clusters of chaotic coupled oscillators and compared its performance to that of other methods for assessing synchronization. Then nine adult subjects were studied with high-density EEG recordings, while they viewed in the two hemifields (hence with separate hemispheres) identical sinusoidal gratings either arranged collinearly and moving together, or orthogonally oriented and moving at 90 degrees . The estimated synchronization increased with the collinear gratings over a cluster of occipital electrodes spanning both hemispheres, whereas over temporo-parietal regions of both hemispheres, it decreased with the same stimulus and it increased with the orthogonal gratings. Separate calculations for different EEG frequencies showed that the occipital clusters involved synchronization in the beta band and the temporal clusters in the alpha band. The gamma band appeared to be insensitive to stimulus diversity. Different stimulus configurations, therefore, appear to cause a complex rearrangement of synchronous neuronal assemblies distributed over the cortex, in particular over the visual cortex.

Self-emergence of chaos in the identification of irregular periodic behavior.

Various forms of chaotic synchronization have been proposed as ways of realizing associative memories and/or pattern recognizers. To exploit this kind of synchronization phenomena in temporal pattern recognition, a chaotic dynamical system representing the class of signals that are to be recognized must be established. This system can be determined by means of identification techniques. The fulfillment of the chaotic condition could be imposed as a constraint. However, it is shown here that, even for a very simple identification algorithm, chaos emerges by itself, allowing us to model the diversity of nearly periodic signals.