Hippocampal storage and recall of neocortical "What"-"Where" representations.

A key question for understanding the function of the hippocampus in memory is how information is recalled from the hippocampus to the neocortex. This was investigated in a neuronal network model of the hippocampal system in which "What" and "Where" neuronal firing rate vectors were applied to separate neocortical modules, which then activated entorhinal cortex "What" and "Where" modules, then the dentate gyrus, then CA3, then CA1, then the entorhinal cortex, and then the backprojections to the neocortex. A rate model showed that the whole system could be trained to recall "Where" in the neocortex from "What" applied as a retrieval cue to the neocortex, and could in principle be trained up towards the theoretical capacity determined largely by the number of synapses onto any one neuron divided by the sparseness of the representation. The trained synaptic weights were then imported into an integrate-and-fire simulation of the same architecture, which showed that the time from presenting a retrieval cue to a neocortex module to recall the whole memory in the neocortex is approximately 100 ms. This is sufficiently fast for the backprojection synapses to be trained onto the still active neocortical neurons during storage of the episodic memory, and this is needed for recall to operate correctly to the neocortex. These simulations also showed that the long loop neocortex-hippocampus-neocortex that operates continuously in time may contribute to complete recall in the neocortex; but that this positive feedback long loop makes the whole dynamical system inherently liable to a pathological increase in neuronal activity. Important factors that contributed to stability included increased inhibition in CA3 and CA1 to keep the firing rates low; and temporal adaptation of the neuronal firing and of active synapses, which are proposed to make an important contribution to stabilizing runaway excitation in cortical circuits in the brain.

Stress Drives Soccer Athletes' Wellness and Movement: Using Convergent Cross-Mapping to Identify Causal Relationships in a Dynamic Environment.

PURPOSE: Prediction of athlete wellness is difficult-or, many sports-medicine practitioners and scientists would argue, impossible. Instead, one settles for correlational relationships of variables gathered at fixed moments in time. The issue may be an inherent mismatch between usual methods of data collection and analysis and the complex nature of the variables governing athlete wellness. Variables such as external load, stress, muscle soreness, and sleep quality may affect each other and wellness in a dynamic, nonlinear, way over time. In such an environment, traditional data-collection methods and statistics will fail to capture causal effects. If we are to move this area of sport science forward, a different approach is required. METHODS: We analyzed data from 2 different soccer teams that showed no significance between player load and wellness or among individual measures of wellness. Our analysis used methods of attractor reconstruction to examine possible causal relationships between GPS/accelerometer-measured external training load and wellness variables. RESULTS: Our analysis showed that player self-rated stress, a component of wellness, seems a fundamental driving variable. The influence of stress is so great that stress can predict other components of athlete wellness, and, in turn, self-rated stress can be predicted by observing a player's load data. CONCLUSION: We demonstrate the ability of nonlinear methods to identify interactions between and among variables to predict future athlete stress. These relationships are indicative of the causal relationships playing out in athlete wellness over the course of a soccer season.

Two sub-annual timescales and coupling modes for terrestrial water and carbon cycles.

To bridge the knowledge gap between (a) our (instantaneous-to-seasonal-scale) process understanding of plants and water and (b) our projections of long-term coupled feedbacks between the terrestrial water and carbon cycles, we must uncover what the dominant dynamics are linking fluxes of water and carbon. This study uses the simplest empirical dynamical systems models-two-dimensional linear models-and observation-based data from satellites, eddy covariance towers, weather stations, and machine-learning-derived products to determine the dominant sub-annual timescales coupling carbon uptake and (normalized) evaporation fluxes. We find two dominant modes across the Contiguous United States: (1) a negative correlation timescale on the order of a few days during which landscapes dry after precipitation and plants increase their carbon uptake through photosynthetic upregulation. (2) A slow, seasonal-scale positive covariation through which landscape drying leads to decreased growth and carbon uptake. The slow (positively correlated) process dominates the joint distribution of local water and carbon variables, leading to similar behaviors across space, biomes, and climate regions. We propose that vegetation cover/leaf area variables link this behavior across space, leading to strong emergent spatial patterns of water/carbon coupling in the mean. The spatial pattern of local temporal dynamics-positively sloped tangent lines to a convex long-term mean-state curve-is surprisingly strong, and can serve as a benchmark for coupled Earth System Models. We show that many such models do not represent this emergent mean-state pattern, and hypothesize that this may be due to lack of water-carbon feedbacks at daily scales.

Navigating climate complexity and its control via hyperchaotic dynamics in a 4D Caputo fractional model.

This interdisciplinary study critically analyzes current research, establishing a profound connection between sea water, sea ice, sea temperature, and surface temperature through a 4D hyperchaotic Caputo fractional differential equation. Emphasizing the collective impact on climate, focusing on challenges from anthropogenic global warming, the study scrutinizes theoretical aspects, including existence and uniqueness. Two sliding mode controllers manage chaos in this 4D fractional system, assessed amid uncertainties and disruptions. The global stability of these controlled systems is also confirmed, considering both commensurate and non-commensurate 4D fractional order. To demonstrate the intricate chaotic motion within the system, we employ the Lyapunov exponent and Poincare sections. Numerical simulations are conducted by using the predictor-corrector method. The effects of surface temperature on chaotic dynamics are discussed. The crucial role of sea ice reflection in climate stability is highlighted in two scenarios. Correlation graphs, comparing model and observational data using the predictor-corrector method, enhance the proposed 4D hyperchaotic model's credibility. Subsequently, numerical simulations validate theoretical assertions about the controllers' influence. These controllers indicate which variable significantly contributes to controlling the chaos.

A line attractor encoding a persistent internal state requires neuropeptide signaling.

Internal states drive survival behaviors, but their neural implementation is poorly understood. Recently, we identified a line attractor in the ventromedial hypothalamus (VMH) that represents a state of aggressiveness. Line attractors can be implemented by recurrent connectivity or neuromodulatory signaling, but evidence for the latter is scant. Here, we demonstrate that neuropeptidergic signaling is necessary for line attractor dynamics in this system by using cell-type-specific CRISPR-Cas9-based gene editing combined with single-cell calcium imaging. Co-disruption of receptors for oxytocin and vasopressin in adult VMH Esr1+ neurons that control aggression diminished attack, reduced persistent neural activity, and eliminated line attractor dynamics while only slightly reducing overall neural activity and sex- or behavior-specific tuning. These data identify a requisite role for neuropeptidergic signaling in implementing a behaviorally relevant line attractor in mammals. Our approach should facilitate mechanistic studies in neuroscience that bridge different levels of biological function and abstraction.

Intrinsic Bipolar Head-Direction Cells in the Medial Entorhinal Cortex.

Head-direction (HD) cells are a fundamental component in the hippocampal-entorhinal circuit for spatial navigation and help maintain an internal sense of direction to anchor the orientation in space. A classical HD cell robustly increases its firing rate when the head is oriented toward a specific direction, with each cell tuned to only one direction. Although unidirectional HD cells are reported broadly across multiple brain regions, computation modelling has predicted the existence of multiple equilibrium states of HD network, which has yet to be proven. In this study, a novel HD variant of bipolar HD cells in the medial entorhinal cortex (MEC) are identified that exhibit stable double-peaked directional tuning properties. The bipolar patterns remain stable in the darkness and across environments of distinct geometric shapes. Moreover, bipolar HD cells co-rotate coherently with unipolar HD cells to anchor the external visual cue. The discovery reveals a new spatial cell type of bipolar HD cells, whose unique activity patterns may comprise a potential building block for a sophisticated local neural circuit configuration for the internal representation of direction. These findings may contribute to the understanding of how the brain processes spatial information by shedding light on the role of bipolar HD cells in this process.

A periodic split attractor reconstruction method facilitates cardiovascular signal diagnoses and obstructive sleep apnea syndrome monitoring.

Electrocardiogram (ECG) is a powerful tool to detect cardiovascular diseases (CVDs) and health conditions. We proposed a new method for evaluating ECG for efficient medical diagnosis in daily life. By splitting the signal according to the cardiac activity cycle, the periodic split attractor reconstruction (PSAR) method is proposed with time embedding, including three types of splitting methods to show its chaotic domain characteristics. We merged the CVDs dataset and the obstructive sleep apnea syndrome (OSAS) first-lead ECG signal dataset to validate the performance of PSAR for diagnosis and health monitoring using PSAR density maps as SE-ResNet input features. PSAR under 3 split methods showed different sensitivities for different CVDs. While in OSAS monitoring, PSAR showed good ability to recognize sleep abnormalities.

Attractors for Hopfield lattice model in weighted spaces.

The investigation into the dynamic behavior of infinite lattice systems holds paramount significance in the realm of physical phenomena, particularly in mechanics. This intricate domain has captivated the attention of both mathematicians and physicists. In acknowledgment of the inherent noise prevalent in real-world environments, our study embraces this aspect by introducing a random term into our model. This deliberate inclusion of stochasticity engenders a novel perspective, giving rise to a stochastic lattice differential equation. This model proves to be a versatile tool for accurately characterizing spatial structures characterized by discrete components and the associated uncertainties that pervade them. This research elucidates the intricate interplay between lattice dynamics and environmental noise, shedding light on the complex behavior of such systems in a realistic context. Our result generalizes many results in three directions: extending the connections between the terms to non-linear, extending the connection neighborhood from 3 (as in most cases) to arbitrary value n, and extending the results that are in ℓ2 to ℓρ2.

The synaptic correlates of serial position effects in sequential working memory.

Sequential working memory (SWM), referring to the temporary storage and manipulation of information in order, plays a fundamental role in brain cognitive functions. The serial position effect refers to the phenomena that recall accuracy of an item is associated to the order of the item being presented. The neural mechanism underpinning the serial position effect remains unclear. The synaptic mechanism of working memory proposes that information is stored as hidden states in the form of facilitated neuronal synapse connections. Here, we build a continuous attractor neural network with synaptic short-term plasticity (STP) to explore the neural mechanism of the serial position effect. Using a delay recall task, our model reproduces the the experimental finding that as the maintenance period extends, the serial position effect transitions from the primacy to the recency effect. Using both numerical simulation and theoretical analysis, we show that the transition moment is determined by the parameters of STP and the interval between presented stimulus items. Our results highlight the pivotal role of STP in processing the order information in SWM.

A Computational Framework for Memory Engrams.

Memory engrams in mice brains are potentially related to groups of concept cells in human brains. A single concept cell in human hippocampus responds, for example, not only to different images of the same object or person but also to its name written down in characters. Importantly, a single mental concept (object or person) is represented by several concept cells and each concept cell can respond to more than one concept. Computational work shows how mental concepts can be embedded in recurrent artificial neural networks as memory engrams and how neurons that are shared between different engrams can lead to associations between concepts. Therefore, observations at the level of neurons can be linked to cognitive notions of memory recall and association chains between memory items.

Toward quantitative characterization of simulated earthquake-cycle complexities.

Earthquake cycle simulations based on the rate-and-state friction formulation are evolutions of nonlinear dynamical systems (NDS). The term "cycle" implies an overall stable structure that is a phase-space attractor naturally traced out by trajectories of NDS as it evolves. Quantitatively characterizing these attractors should be a basis for measuring complexities of the simulated earthquake cycles, i.e. to determine if and how regular or chaotic they are. I first revisit the textbook-standard quasi-dynamic spring-slider system from an NDS perspective, explicitly showing the attractors, their relationship with the parameters of the NDS, and how they can be characterized taken advantage of their low-dimensionality while aiming to extend the analysis to high-dimensionality. I evaluate two approaches, computing the Lyapunov exponents (LEs) and measuring correlation dimensions, with the simple spring-slider and earthquake-cycle examples whose phase-space attractors can be visually verified. I conclude LEs are too inconvenient and computationally expensive to use whereas measuring correlation dimensions is an easy and effective approach even with highly non-uniform time sampling present in all simulations. For earthquake-cycle simulations, an attractor reconstruction is performed based on Taken's theorem to corroborate my correlation-dimension results. The current method is limited in its ability to detect chaos in a dichotomous manner, which illuminates the direction for future study. An improving ability to quantitatively characterize earthquake-cycle simulations as an overall stable structure offers new opportunities to understand exotic seismic observations such as slow-slip events and enables more informative comparison with real data, particularly from paleoseismology, which could have far-reaching implications in earthquake forecasting.

Myelin dystrophy impairs signal transmission and working memory in a multiscale model of the aging prefrontal cortex.

Normal aging leads to myelin alterations in the rhesus monkey dorsolateral prefrontal cortex (dlPFC), which are positively correlated with degree of cognitive impairment. It is hypothesized that remyelination with shorter and thinner myelin sheaths partially compensates for myelin degradation, but computational modeling has not yet explored these two phenomena together systematically. Here, we used a two-pronged modeling approach to determine how age-related myelin changes affect a core cognitive function: spatial working memory. First, we built a multicompartment pyramidal neuron model fit to monkey dlPFC empirical data, with an axon including myelinated segments having paranodes, juxtaparanodes, internodes, and tight junctions. This model was used to quantify conduction velocity (CV) changes and action potential (AP) failures after demyelination and subsequent remyelination. Next, we incorporated the single neuron results into a spiking neural network model of working memory. While complete remyelination nearly recovered axonal transmission and network function to unperturbed levels, our models predict that biologically plausible levels of myelin dystrophy, if uncompensated by other factors, can account for substantial working memory impairment with aging. The present computational study unites empirical data from ultrastructure up to behavior during normal aging, and has broader implications for many demyelinating conditions, such as multiple sclerosis or schizophrenia.

Detection of contractility changes in the heart from arterial blood pressure data using symmetric Projection Attractor Reconstruction.

The potential for unintended drug induced changes in cardiac contractility is a major concern in medicines development. Whilst direct left ventricular pressure (LVP) measurement is the gold standard for measuring cardiac contractility in vivo, it is resource intensive and poses a welfare burden on research animals. In contrast, arterial blood pressure (BP) measurement has fewer challenges. Symmetric Projection Attractor Reconstruction (SPAR) is a signal processing technique which transforms physiological time-series signals into a corresponding visual image ('attractor'), amplifying morphology changes within physiological waveforms. It was hypothesized that SPAR analysis of BP signals would provide a surrogate measure of cardiac contractility by specifically amplifying the maximum slope of the systolic upstroke. BP (abdominal aorta) signals obtained from beagle dogs, treated with positive and negative inotropes, were retrospectively analysed to identify signal features that correlated with the maximum upslope of the LVP signal from simultaneously acquired LVP recordings. SPAR transformation of BP signals quantified drug induced changes in the maximum slope of the systolic upstroke. We identified key SPAR metrics that provided >0.8 correlation with the LVP maximum upslope, outperforming the BP systolic upstroke alone. This was observed for all 4 different drugs, doses and time points evaluated across studies. Thus, we conclude that the SPAR measures derived from the BP signal could be used as a first pass in vivo screen to flag any risk of drug induced changes in cardiac contractility during the conduct of non-clinical medicines development, potentially reducing or replacing the need to perform direct left ventricular measurements.

Learning sequence attractors in recurrent networks with hidden neurons.

The brain is targeted for processing temporal sequence information. It remains largely unclear how the brain learns to store and retrieve sequence memories. Here, we study how recurrent networks of binary neurons learn sequence attractors to store predefined pattern sequences and retrieve them robustly. We show that to store arbitrary pattern sequences, it is necessary for the network to include hidden neurons even though their role in displaying sequence memories is indirect. We develop a local learning algorithm to learn sequence attractors in the networks with hidden neurons. The algorithm is proven to converge and lead to sequence attractors. We demonstrate that the network model can store and retrieve sequences robustly on synthetic and real-world datasets. We hope that this study provides new insights in understanding sequence memory and temporal information processing in the brain.

Causal evidence for cholinergic stabilization of attractor landscape dynamics.

There is substantial evidence that neuromodulatory systems critically influence brain state dynamics; however, most work has been purely descriptive. Here, we quantify, using data combining local inactivation of the basal forebrain with simultaneous measurement of resting-state fMRI activity in the macaque, the causal role of long-range cholinergic input to the stabilization of brain states in the cerebral cortex. Local inactivation of the nucleus basalis of Meynert (nbM) leads to a decrease in the energy barriers required for an fMRI state transition in cortical ongoing activity. Moreover, the inactivation of particular nbM sub-regions predominantly affects information transfer in cortical regions known to receive direct anatomical projections. We demonstrate these results in a simple neurodynamical model of cholinergic impact on neuronal firing rates and slow hyperpolarizing adaptation currents. We conclude that the cholinergic system plays a critical role in stabilizing macroscale brain state dynamics.

Mechanisms of Action of TMS in the Treatment of Depression.

Transcranial magnetic stimulation (TMS) is entering increasingly widespread use in treating depression. The most common stimulation target, in the dorsolateral prefrontal cortex (DLPFC), emerged from early neuroimaging studies in depression. Recently, more rigorous casual methods have revealed whole-brain target networks and anti-networks based on the effects of focal brain lesions and focal brain stimulation on depression symptoms. Symptom improvement during therapeutic DLPFC-TMS appears to involve directional changes in signaling between the DLPFC, subgenual and dorsal anterior cingulate cortex, and salience-network regions. However, different networks may be involved in the therapeutic mechanisms for other TMS targets in depression, such as dorsomedial prefrontal cortex or orbitofrontal cortex. The durability of therapeutic effects for TMS involves synaptic neuroplasticity, and specifically may depend upon dopamine acting at the D1 receptor family, as well as NMDA-receptor-dependent synaptic plasticity mechanisms. Although TMS protocols are classically considered 'excitatory' or 'inhibitory', the actual effects in individuals appear quite variable, and might be better understood at the level of populations of synapses rather than individual synapses. Synaptic meta-plasticity may provide a built-in protective mechanism to avoid runaway facilitation or inhibition during treatment, and may account for the relatively small number of patients who worsen rather than improve with TMS. From an ethological perspective, the antidepressant effects of TMS may involve promoting a whole-brain attractor state associated with foraging/hunting behaviors, centered on the rostrolateral periaqueductal gray and salience network, and suppressing an attractor state associated with passive threat defense, centered on the ventrolateral periaqueductal gray and default-mode network.

From a false sense of safety to resilience under uncertainty.

Understanding and acting upon risk is notably challenging, and navigating complexity with understandings developed for stable environments may inadvertently build a false sense of safety. Neglecting the potential for non-linear change or "black swan" events - highly impactful but uncommon occurrences - may lead to naive optimisation under assumed stability, exposing systems to extreme risks. For instance, loss aversion is seen as a cognitive bias in stable environments, but it can be an evolutionarily advantageous heuristic when complete destruction is possible. This paper advocates for better accounting of non-linear change in decision-making by leveraging insights from complex systems and psychological sciences, which help to identify blindspots in conventional decision-making and to develop risk mitigation plans that are interpreted contextually. In particular, we propose a framework using attractor landscapes to visualize and interpret complex system dynamics. In this context, attractors are states toward which systems naturally evolve, while tipping points - critical thresholds between attractors - can lead to profound, unexpected changes impacting a system's resilience and well-being. We present four generic attractor landscape types that provide a novel lens for viewing risks and opportunities, and serve as decision-making contexts. The main practical contribution is clarifying when to emphasize particular strategies - optimisation, risk mitigation, exploration, or stabilization - within this framework. Context-appropriate decision making should enhance system resilience and mitigate extreme risks.

A theory of hippocampal function: New developments.

We develop further here the only quantitative theory of the storage of information in the hippocampal episodic memory system and its recall back to the neocortex. The theory is upgraded to account for a revolution in understanding of spatial representations in the primate, including human, hippocampus, that go beyond the place where the individual is located, to the location being viewed in a scene. This is fundamental to much primate episodic memory and navigation: functions supported in humans by pathways that build 'where' spatial view representations by feature combinations in a ventromedial visual cortical stream, separate from those for 'what' object and face information to the inferior temporal visual cortex, and for reward information from the orbitofrontal cortex. Key new computational developments include the capacity of the CA3 attractor network for storing whole charts of space; how the correlations inherent in self-organizing continuous spatial representations impact the storage capacity; how the CA3 network can combine continuous spatial and discrete object and reward representations; the roles of the rewards that reach the hippocampus in the later consolidation into long-term memory in part via cholinergic pathways from the orbitofrontal cortex; and new ways of analysing neocortical information storage using Potts networks.

Grid codes vs. multi-scale, multi-field place codes for space.

Introduction: Recent work on bats flying over long distances has revealed that single hippocampal cells have multiple place fields of different sizes. At the network level, a multi-scale, multi-field place cell code outperforms classical single-scale, single-field place codes, yet the performance boundaries of such a code remain an open question. In particular, it is unknown how general multi-field codes compare to a highly regular grid code, in which cells form distinct modules with different scales. Methods: In this work, we address the coding properties of theoretical spatial coding models with rigorous analyses of comprehensive simulations. Starting from a multi-scale, multi-field network, we performed evolutionary optimization. The resulting multi-field networks sometimes retained the multi-scale property at the single-cell level but most often converged to a single scale, with all place fields in a given cell having the same size. We compared the results against a single-scale single-field code and a one-dimensional grid code, focusing on two main characteristics: the performance of the code itself and the dynamics of the network generating it. Results: Our simulation experiments revealed that, under normal conditions, a regular grid code outperforms all other codes with respect to decoding accuracy, achieving a given precision with fewer neurons and fields. In contrast, multi-field codes are more robust against noise and lesions, such as random drop-out of neurons, given that the significantly higher number of fields provides redundancy. Contrary to our expectations, the network dynamics of all models, from the original multi-scale models before optimization to the multi-field models that resulted from optimization, did not maintain activity bumps at their original locations when a position-specific external input was removed. Discussion: Optimized multi-field codes appear to strike a compromise between a place code and a grid code that reflects a trade-off between accurate positional encoding and robustness. Surprisingly, the recurrent neural network models we implemented and optimized for either multi- or single-scale, multi-field codes did not intrinsically produce a persistent "memory" of attractor states. These models, therefore, were not continuous attractor networks.

Explaining empirical dynamic modelling using verbal, graphical and mathematical approaches.

Empirical dynamic modelling (EDM) is becoming an increasingly popular method for understanding the dynamics of ecosystems. It has been applied to laboratory, terrestrial, freshwater and marine systems, used to forecast natural populations and has addressed fundamental ecological questions. Despite its increasing use, we have not found full explanations of EDM in the ecological literature, limiting understanding and reproducibility. Here we expand upon existing work by providing a detailed introduction to EDM. We use three progressively more complex approaches. A short verbal explanation of EDM is then explicitly demonstrated by graphically working through a simple example. We then introduce a full mathematical description of the steps involved. Conceptually, EDM translates a time series of data into a path through a multi-dimensional space, whose axes are lagged values of the time series. A time step is chosen from which to make a prediction. The state of the system at that time step corresponds to a 'focal point' in the multi-dimensional space. The set (called the library) of candidate nearest neighbours to the focal point is constructed, to determine the nearest neighbours that are then used to make the prediction. Our mathematical explanation explicitly documents which points in the multi-dimensional space should not be considered as focal points. We suggest a new option for excluding points from the library that may be useful for short-term time series that are often found in ecology. We focus on the core simplex and S-map algorithms of EDM. Our new R package, pbsEDM, enhances understanding (by outputting intermediate calculations), reproduces our results and can be applied to new data. Our work improves the clarity of the inner workings of EDM, a prerequisite for EDM to reach its full potential in ecology and have wide uptake in the provision of advice to managers of natural resources.