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4 recordsLinked to original sources
PubMed2025

New insights into multistability and complex resonances driven by subthreshold periodic signals in a neuronal model.

Understanding how neurons respond to weak external signals is crucial for accurate signal transmission and processing in both individual nerve cells and interconnected neuronal networks. One mechanism for the detection of these responses is through resonances. In this paper, we numerically investigate the firing patterns induced in a silent Huber-Braun neuron by a sinusoidal external force. We observe complex resonance patterns, including a sequence of frequency-locking exhibited in a Devil's Staircase structure. Furthermore, we also explore the emergence of multistability induced by the nonlinear resonance. This multistability manifests as the coexistence of three attractors, such as periodic spiking, chaotic spiking, and subthreshold oscillations. The dynamical behaviors are comprehensively analyzed using time series, bifurcation diagrams, phase portraits, and the basin of attraction. In addition, we compute the maximum Lyapunov exponent to verify chaotic regimes, and estimate the fractal dimension of basin boundaries using the uncertainty exponent. We also analyze the energy consumption of resonance-induced firing patterns and coexisting attractors. The results presented in this paper have important implications for understanding the detection of subthreshold signals and the encoding of stimulus information within a neuron's firing patterns.

Basins of attraction↗
PubMed2026

Genetic heterogeneity affects the risk of incident depression, comorbidity, and response to environment: A prospective trajectory study.

BACKGROUND: Depression exhibits significant heterogeneity in its genetic underpinnings. The role of genetic components in the development of depression and its comorbidities remains insufficiently explored. METHODS: First, depression risk loci from a large-scale genome-wide meta-analysis were annotated to Gene Ontology (GO) terms by functional enrichment. GO-based polygenic risk scores (GO-PRS) were then calculated for individuals in the UK Biobank. Principal component analysis (PCA) was applied for dimensionality reduction, followed by cluster analysis to identify genetic subtypes of depression. Multistate models were applied to assess the impact of genetic patterns on the trajectory from healthy status to incident depression, and depression to 26 subsequent diseases, as well as the associations between environmental factors and disease trajectories across genetic subtypes. RESULTS: Participants were categorized into three genetic subtypes: immune-dominant, neuro-dominant, and comprehensive-risk. Significant differences in risk of depression and subsequent diseases, and susceptibility to environmental factors were observed across subtypes. Comprehensive-risk subtype showed higher risks of depression compared to immune-dominant (HR: 1.10, 95% CI: 1.05-1.15) and neuro-dominant subtype (HR: 1.12, 95% CI: 1.08-1.16). Comprehensive-risk subtype exhibited higher risks of transition from depression to subsequent diseases, such as anemia compared to immune-dominant subtype, and diseases of the digestive system compared to neuro-dominant subtype. Environmental factors were more strongly associated with the transition from depression to subsequent diseases in immune-dominant and comprehensive-risk subtypes, including cardiovascular, respiratory, and metabolic diseases. CONCLUSIONS: Our findings highlight the genetic heterogeneity of depression and comorbidities, and shed light on how genetic components modulate responses to environmental factors.

Humans↗
PubMed2026

Mining Stored-Specimen Studies for Information about Cancer Natural History.

The advent of new multicancer early detection tests and publication of early diagnostic results have generated expectations of clinical benefit from multicancer screening. The clinical benefit of a cancer screening test depends critically on disease natural history, which is typically learned from prospective screening studies. Retrospective studies of stored blood specimens are important in learning about a test's preclinical diagnostic performance but have rarely been used to infer natural history. The extent to which these studies might be harnessed to also learn natural history is discussed in the context of an article in this issue that infers the combined natural history of a range of cancers targeted by a multicancer early detection test using a case-control subsample of specimens from a large cohort study. The critical question concerns the identifiability of key transition rates in multistate models of natural history alongside state-specific sensitivities. The article suggests that these parameters are estimable within a Bayesian framework that leverages prior information about test sensitivity from diagnostic studies. We offer a heuristic discussion of identifiability in this setting and encourage formal study to determine the extent to which models with varying degrees of complexity may be learned from stored-specimen studies. See related article by Dai et al., p. 1535.

Humans↗
PubMed2025

Balanced state of networks of winner-take-all units.

Irregularly timed action potentials, or spikes, are pervasively observed in the brain activity of awake mammals. However, the role of this temporal irregularity in neural computation is still not well understood. In canonical network models irregular spiking emerges via balanced, fluctuating input currents, leading to collective responses that track inputs linearly. How networks characterized by irregular spiking could support flexible nonlinear dynamics needed for general-purpose computation remains under ongoing debate. Here we characterize the dynamics of networks whose elementary unit is not a single neuron but a small group of neurons, with distinct tunings, that compete at each timestep via a winner-take-all (WTA) interaction. While WTA has long been proposed as an elementary functional motif in the brain and represents a powerful computational primitive, how large networks of such units behave has received less investigation. We show that these networks, like classic excitatory-inhibitory balanced networks, exhibit a chaotic fluctuation-driven regime characterized by sustained irregular activity resembling realistic cortical spiking, which we interpret as a multidimensional balance spread over several competing neural populations with different tunings. We develop a mean-field theory for the network, which shows how irregular spiking sustained by time-varying input fluctuations can support flexible nonlinear collective dynamics. Using the theory we predict and verify network regimes in which input fluctuations alone yield multistability, stable sequence generation, or complex heterogeneous firing rate dynamics-three core dynamical primitives thought to underlie memory-dependent neural computation-via consistent Poisson-like spiking produced through chaos. Thus, networks of WTA units support a chaotic fluctuation-driven regime characterized by irregular spiking that can power complex nonlinear collective dynamics. This represents a new model of brain activity capable of simultaneously reproducing realistic spike trains and diverse nonlinear firing rate patterns well posed for flexible computation, and which can be trained or fit to data.

Models, Neurological↗