Search

Finding optimal bipartite matchings-e.g., matching medical students to hospitals for residency, items to buyers in an auction, or papers to reviewers for peer review-is a fundamental combinatorial optimization problem. We found a distributed algorithm for computing matchings by studying the development of the neuromuscular circuit. The neuromuscular circuit can be viewed as a bipartite graph formed between motor neurons and muscle fibers. In newborn animals, neurons and fibers are densely connected, but after development, each fiber is typically matched (i.e., connected) to exactly one neuron. We cast this synaptic pruning process as a distributed matching (or assignment) algorithm, where motor neurons "compete" with each other to "win" muscle fibers. We show that this algorithm is simple to implement, theoretically sound, and effective in practice when evaluated on real-world bipartite matching problems. Thus, insights from the development of neural circuits can inform the design of algorithms for fundamental computational problems., Competing Interests: Competing interests statement:The authors declare no competing interest.

Temporal interference (TI) stimulation is a popular non-invasive neurostimulation technique that utilizes the following salient neural behavior: pure sinusoid (generated in off-target brain regions) appears to cause no stimulation, whereas modulated sinusoid (generated in target brain regions) does. To understand its effects and mechanisms, we examine responses of different cell types, excitatory pyramidal (Pyr) and inhibitory parvalbumin-expressing (PV) neurons, to pure and modulated sinusoids, in intact network as well as in isolation. In intact network, we present data showing that PV neurons are much less likely than Pyr neurons to exhibit TI stimulation. Remarkably, in isolation, our data shows that almost all Pyr neurons stop exhibiting TI stimulation. We conclude that TI stimulation is largely a network phenomenon. Indeed, PV neurons actively inhibit Pyr neurons in the off-target regions due to pure sinusoids (in off-target regions) generating much higher PV firing rates than modulated sinusoids in the target regions. Additionally, we use computational studies to support and extend our experimental observations., (© 2024. The Author(s).)

Using delay differential equations to study mathematical models of Parkinson's disease and Huntington's disease is important to show how important it is for synchronization between basal ganglia loops to work together. We used the delay circuit RLC (resistor, inductor, capacitor) model to show how the direct pathway and the indirect pathway in the basal ganglia excite and inhibit the motor cortex, respectively. A term has been added to the mathematical model without time delay in the case of the hyperdirect pathway. It is proposed to add a non-linear term to adjust the synchronization. We studied Hopf bifurcation conditions for the proposed models. The desynchronization of response times between the direct pathway and the indirect pathway leads to different symptoms of Parkinson's disease. Tremor appears when the response time in the indirect pathway increases at rest. The simulation confirmed that tremor occurs and the motor cortex is in an inhibited state. The direct pathway can increase the time delay in the dopaminergic pathway, which significantly increases the activity of the motor cortex. The hyperdirect pathway regulates the activity of the motor cortex. The simulation showed bradykinesia occurs when we switch from one movement to another that is less exciting for the motor cortex. A decrease of GABA in the striatum or delayed excitation of the substantia nigra from the subthalamus may be a major cause of Parkinson's disease. An increase in the response time delay in one of the pathways results in the chaotic movement characteristic of Huntington's disease., (© 2024. Prof. Dr. Jan van der Hoeven stichting voor theoretische biologie.)

In this study, we develop an in silico model of a neuron's behaviour under demyelination caused by a cytokine storm to investigate the effects of viral infections in the brain. We use a comprehensive model to measure how cytokine-induced demyelination affects the propagation of action potential (AP) signals within a neuron. We analysed the effects of neuron-neuron communications by applying information and communication theory at different levels of demyelination. Our simulations demonstrate that virus-induced degeneration can play a role in the signal power and spiking rate, which compromise the propagation and processing of information between neurons. We propose a transfer function to model the weakening effects on the AP. Our results show that demyelination induced by a cytokine storm not only degrades the signal but also impairs its propagation within the axon. Our proposed in silico model can analyse virus-induced neurodegeneration and enhance our understanding of virus-induced demyelination.

Carrying out any everyday task, be it driving in traffic, conversing with friends or playing basketball, requires rapid selection, integration and segregation of stimuli from different sensory modalities. At present, even the most advanced artificial intelligence-based systems are unable to replicate the multisensory processes that the human brain routinely performs, but how neural circuits in the brain carry out these processes is still not well understood. In this Perspective, we discuss recent findings that shed fresh light on the oscillatory neural mechanisms that mediate multisensory integration (MI), including power modulations, phase resetting, phase-amplitude coupling and dynamic functional connectivity. We then consider studies that also suggest multi-timescale dynamics in intrinsic ongoing neural activity and during stimulus-driven bottom-up and cognitive top-down neural network processing in the context of MI. We propose a new concept of MI that emphasizes the critical role of neural dynamics at multiple timescales within and across brain networks, enabling the simultaneous integration, segregation, hierarchical structuring and selection of information in different time windows. To highlight predictions from our multi-timescale concept of MI, real-world scenarios in which multi-timescale processes may coordinate MI in a flexible and adaptive manner are considered., (© 2024. Springer Nature Limited.)

Background: Understanding the pathophysiological dynamics that underline Interictal Epileptiform Events (IEEs) such as epileptic spikes, spike-and-waves or High-Frequency Oscillations (HFOs) is of major importance in the context of neocortical refractory epilepsy, as it paves the way for the development of novel therapies. Typically, these events are detected in Local Field Potential (LFP) recordings obtained through depth electrodes during pre-surgical investigations. Although essential, the underlying pathophysiological mechanisms for the generation of these epileptic neuromarkers remain unclear. The aim of this paper is to propose a novel neurophysiologically relevant reconstruction of the neocortical microcircuitry in the context of epilepsy. This reconstruction intends to facilitate the analysis of a comprehensive set of parameters encompassing physiological, morphological, and biophysical aspects that directly impact the generation and recording of different IEEs., Method: a novel microscale computational model of an epileptic neocortical column was introduced. This model incorporates the intricate multilayered structure of the cortex and allows for the simulation of realistic interictal epileptic signals. The proposed model was validated through comparisons with real IEEs recorded using intracranial stereo-electroencephalography (SEEG) signals from both humans and animals. Using the model, the user can recreate epileptiform patterns observed in different species (human, rodent, and mouse) and study the intracellular activity associated with these patterns., Results: Our model allowed us to unravel the relationship between glutamatergic and GABAergic synaptic transmission of the epileptic neural network and the type of generated IEE. Moreover, sensitivity analyses allowed for the exploration of the pathophysiological parameters responsible for the transitions between these events. Finally, the presented modeling framework also provides an Electrode Tissue Model (ETI) that adds realism to the simulated signals and offers the possibility of studying their sensitivity to the electrode characteristics., Conclusion: The model (NeoCoMM) presented in this work can be of great use in different applications since it offers an in silico framework for sensitivity analysis and hypothesis testing. It can also be used as a starting point for more complex studies., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: If brain effective connectivity network modelling (ECN) could be accurately achieved, early diagnosis of neurodegenerative diseases would be possible. It has been observed in the literature that Dynamic Bayesian Network (DBN) based methods are more successful than others. However, DBNs have not been applied easily and tested much due to computational complexity problems in structure learning., New Method: This study introduces an advanced method for modelling brain ECNs using improved discrete DBN (Improved- dDBN) which addresses the computational challenges previously limiting DBN application, offering solutions that enable accurate and fast structure modelling., Results: The practical data and prior sizes needed for the convergence to the globally correct network structure are proved to be much smaller than the theoretical ones using simulated dDBN data. Besides, Hill Climbing is shown to converge to the true structure at a reasonable iteration step size when the appropriate data and prior sizes are used. Finally, importance of data quantization methods are analysed., Comparison With Existing Methods: The Improved-dDBN method performs better and robust, when compared to the existing methods for realistic scenarios such as varying graph complexity, various input conditions, noise cases and non-stationary connections. The data used in these tests is the simulated fMRI BOLD time series proposed in the literature., Conclusions: Improved-dDBN is a good candidate to be used on real datasets to accelerate developments in brain ECN modelling and neuroscience. Appropriate data and prior sizes can be identified based on the approach proposed in this study for global and fast convergence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We develop a mathematical approach to formally proving that certain neural computations and representations exist based on patterns observed in an organism's behaviour. To illustrate, we provide a simple set of conditions under which an ant's ability to determine how far it is from its nest would logically imply neural structures isomorphic to the natural numbers ℕ . We generalise these results to arbitrary behaviours and representations and show what mathematical characterisation of neural computation and representation is simplest while being maximally predictive of behaviour. We develop this framework in detail using a path integration example, where an organism's ability to search for its nest in the correct location implies representational structures isomorphic to two-dimensional coordinates under addition. We also study a system for processing a n b n strings common in comparative work. Our approach provides an objective way to determine what theory of a physical system is best, addressing a fundamental challenge in neuroscientific inference. These results motivate considering which neurobiological structures have the requisite formal structure and are otherwise physically plausible given relevant physical considerations such as generalisability, information density, thermodynamic stability and energetic cost., (© 2024 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: Depression is a global mental disorder, and traditional diagnostic methods mainly rely on scales and subjective evaluations by doctors, which cannot effectively identify symptoms and even carry the risk of misdiagnosis. Brain-Computer Interfaces inspired deep learning-assisted diagnosis based on physiological signals holds promise for improving traditional methods lacking physiological basis and leads next generation neuro-technologies. However, traditional deep learning methods rely on immense computational power and mostly involve end-to-end network learning. These learning methods also lack physiological interpretability, limiting their clinical application in assisted diagnosis., Methodology: A brain-like learning model for diagnosing depression using electroencephalogram (EEG) is proposed. The study collects EEG data using 128-channel electrodes, producing a 128×128 brain adjacency matrix. Given the assumption of undirected connectivity, the upper half of the 128×128 matrix is chosen in order to minimise the input parameter size, producing 8,128-dimensional data. After eliminating 28 components derived from irrelevant or reference electrodes, a 90×90 matrix is produced, which can be used as an input for a single-channel brain-computer interface image., Result: At the functional level, a spiking neural network is constructed to classify individuals with depression and healthy individuals, achieving an accuracy exceeding 97.5 %., Comparison With Existing Methods: Compared to deep convolutional methods, the spiking method reduces energy consumption., Conclusion: At the structural level, complex networks are utilized to establish spatial topology of brain connections and analyse their graph features, identifying potential abnormal brain functional connections in individuals with depression., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Parkinson's disease (PD) is a common neurodegenerative disease. Transcranial magnetoacoustic stimulation (TMAS) is a new therapy that combines a transcranial focused acoustic pressure field with a magnetic field to excite or inhibit neurons in targeted area, which suppresses the abnormally elevated beta band amplitude in PD states, with high spatial resolution and non-invasively., Objective: To study the effective stimulation parameters of TMAS mononuclear and multinuclear stimulation for the treatment of PD with reduced beta band energy, improved abnormal synchronization, and no thermal damage., Methods: The TMAS model is constructed based on the volunteer's computed tomography, 128 arrays of phase-controlled transducers, and permanent magnets. A basal ganglia-thalamic (BG-Th) neural network model of the PD state was constructed on the basis of the Izhikevich model and the acoustic model. An ultrasound stimulation neuron model is constructed based on the Hodgkin-Huxley model. Numerical simulations of transcranial focused acoustic pressure field, temperature field and induced electric field at single and dual targets were performed using the locations of STN, GPi, and GPe in the human brain as the main stimulation target areas. And the acoustic and electric parameters at the focus were extracted to stimulate mononuclear and multinuclear in the BG-Th neural network., Results: When the stimulating effect of ultrasound is ignored, TMAS-STN simultaneously inhibits the beta-band amplitude of the GPi nucleus, whereas TMAS-GPi fails to simultaneously have an inhibitory effect on the STN. TMAS-STN&GPi can reduce the beta band amplitude. TMAS-STN&GPi&GPe suppressed the PD pathologic beta band amplitude of each nucleus to a greater extent. When considering the stimulatory effect of ultrasound, lower sound pressures of ultrasound do not affect the neuronal firing state, but higher sound pressures may promote or inhibit the stimulatory effect of induced currents., Conclusions: At 9 T static magnetic field, 0.5-1.5 MPa and 1.5-2.0 MPa ultrasound had synergistic effects on individual STN and GPi neurons. TMAS multinuclear stimulation with appropriate ultrasound intensity was the most effective in suppressing the amplitude of pathological beta oscillations in PD and may be clinically useful., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The circuitry and pathways in the brains of humans and other species have long inspired researchers and system designers to develop accurate and efficient systems capable of solving real-world problems and responding in real-time. We propose the Syllable-Specific Temporal Encoding (SSTE) to learn vocal sequences in a reservoir of Izhikevich neurons, by forming associations between exclusive input activities and their corresponding syllables in the sequence. Our model converts the audio signals to cochleograms using the CAR-FAC model to simulate a brain-like auditory learning and memorization process. The reservoir is trained using a hardware-friendly approach to FORCE learning. Reservoir computing could yield associative memory dynamics with far less computational complexity compared to RNNs. The SSTE-based learning enables competent accuracy and stable recall of spatiotemporal sequences with fewer reservoir inputs compared with existing encodings in the literature for similar purpose, offering resource savings. The encoding points to syllable onsets and allows recalling from a desired point in the sequence, making it particularly suitable for recalling subsets of long vocal sequences. The SSTE demonstrates the capability of learning new signals without forgetting previously memorized sequences and displays robustness against occasional noise, a characteristic of real-world scenarios. The components of this model are configured to improve resource consumption and computational intensity, addressing some of the cost-efficiency issues that might arise in future implementations aiming for compactness and real-time, low-power operation. Overall, this model proposes a brain-inspired pattern generation network for vocal sequences that can be extended with other bio-inspired computations to explore their potentials for brain-like auditory perception. Future designs could inspire from this model to implement embedded devices that learn vocal sequences and recall them as needed in real-time. Such systems could acquire language and speech, operate as artificial assistants, and transcribe text to speech, in the presence of natural noise and corruption on audio data., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Parkinsonism is presented as a motor syndrome characterized by rigidity, tremors, and bradykinesia, with Parkinson's disease (PD) being the predominant cause. The discovery that those motor symptoms result from the death of dopaminergic cells in the substantia nigra led to focus most of parkinsonism research on the basal ganglia (BG). However, recent findings point to an active involvement of the cerebellum in this motor syndrome. Here, we have developed a multiscale computational model of the rodent brain's BG-cerebellar network. Simulations showed that a direct effect of dopamine depletion on the cerebellum must be taken into account to reproduce the alterations of neural activity in parkinsonism, particularly the increased beta oscillations widely reported in PD patients. Moreover, dopamine depletion indirectly impacted spike-time-dependent plasticity at the parallel fiber-Purkinje cell synapses, degrading associative motor learning as observed in parkinsonism. Overall, these results suggest a relevant involvement of cerebellum in parkinsonism associative motor symptoms.

Subthalamic deep brain stimulation (DBS) robustly generates high-frequency oscillations known as evoked resonant neural activity (ERNA). Recently the importance of ERNA has been demonstrated through its ability to predict the optimal DBS contact in the subthalamic nucleus in patients with Parkinson's disease. However, the underlying mechanisms of ERNA are not well understood, and previous modelling efforts have not managed to reproduce the wealth of published data describing the dynamics of ERNA. Here, we aim to present a minimal model capable of reproducing the characteristics of the slow ERNA dynamics published to date. We make biophysically-motivated modifications to the Kuramoto model and fit its parameters to the slow dynamics of ERNA obtained from data. Our results demonstrate that it is possible to reproduce the slow dynamics of ERNA (over hundreds of seconds) with a single neuronal population, and, crucially, with vesicle depletion as one of the key mechanisms behind the ERNA frequency decay in our model. We further validate the proposed model against experimental data from Parkinson's disease patients, where it captures the variations in ERNA frequency and amplitude in response to variable stimulation frequency, amplitude, and to stimulation pulse bursting. We provide a series of predictions from the model that could be the subject of future studies for further validation., Competing Interests: Declaration of competing interest TD is a founder, director, and shareholder of Amber Therapeutics, Ltd., which also has a controlling interest in Bioinduction Ltd. and Finetech Medical Ltd., the respective designers and manufacturers of the Picostim DyNeuMo system. TD is also an advisor for Synchron and Cortec Neuro., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

With the adoption of smart systems, artificial neural networks (ANNs) have become ubiquitous. Conventional ANN implementations have high energy consumption, limiting their use in embedded and mobile applications. Spiking neural networks (SNNs) mimic the dynamics of biological neural networks by distributing information over time through binary spikes. Neuromorphic hardware has emerged to leverage the characteristics of SNNs, such as asynchronous processing and high activation sparsity. Therefore, SNNs have recently gained interest in the machine learning community as a brain-inspired alternative to ANNs for low-power applications. However, the discrete representation of the information makes the training of SNNs by backpropagation-based techniques challenging. In this survey, we review training strategies for deep SNNs targeting deep learning applications such as image processing. We start with methods based on the conversion from an ANN to an SNN and compare these with backpropagation-based techniques. We propose a new taxonomy of spiking backpropagation algorithms into three categories, namely, spatial, spatiotemporal, and single-spike approaches. In addition, we analyze different strategies to improve accuracy, latency, and sparsity, such as regularization methods, training hybridization, and tuning of the parameters specific to the SNN neuron model. We highlight the impact of input encoding, network architecture, and training strategy on the accuracy-latency tradeoff. Finally, in light of the remaining challenges for accurate and efficient SNN solutions, we emphasize the importance of joint hardware-software codevelopment.

To overcome the energy efficiency bottleneck of the von Neumann architecture and scaling limit of silicon transistors, an emerging but promising solution is neuromorphic computing, a new computing paradigm inspired by how biological neural networks handle the massive amount of information in a parallel and efficient way. Recently, there is a surge of interest in the nematode worm Caenorhabditis elegans (C. elegans), an ideal model organism to probe the mechanisms of biological neural networks. In this article, we propose a neuron model for C. elegans with leaky integrate-and-fire (LIF) dynamics and adjustable integration time. We utilize these neurons to build the C. elegans neural network according to their neural physiology, which comprises: 1) sensory modules; 2) interneuron modules; and 3) motoneuron modules. Leveraging these block designs, we develop a serpentine robot system, which mimics the locomotion behavior of C. elegans upon external stimulus. Moreover, experimental results of C. elegans neurons presented in this article reveals the robustness (1% error w.r.t. 10% random noise) and flexibility of our design in term of parameter setting. The work paves the way for future intelligent systems by mimicking the C. elegans neural system.

Image super-resolution (ISR) is designed to recover lost detail information from low-resolution images, resulting in high-quality and high-definition high-resolution images. In the existing single ISR (SISR) methods based on convolutional neural networks (CNN), however, most of the models cannot effectively combine global and local information and are also easy to ignore the correlation between different hierarchical feature information. To address these problems, this study proposes a multi-level feature interactive image super-resolution network, which is constructed by the convolutional units inspired by nonlinear spiking mechanism in nonlinear spiking neural P systems, including shallow feature processing, deep feature extraction and fusion, and reconstruction modules. The different omni domain self-attention blocks are introduced to extract global information in the deep feature extraction and fusion stage and formed a feature enhancement module having a Transformer structure using a novel convolutional unit for extracting local information. Furthermore, to adaptively fuse features between different hierarchies, we design a multi-level feature fusion module, which not only can adaptively fuse features between different hierarchies, but also can better interact with contextual information. The proposed model is compared with 16 state-of-the-art or baseline models on five benchmark datasets. The experimental results show that the proposed model not only achieves good reconstruction performance, but also strikes a good balance between model parameters and performance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Peripheral neuromodulation has emerged as a powerful modality for controlling physiological functions and treating a variety of medical conditions including chronic pain and organ dysfunction. The underlying complexity of the nonlinear responses to electrical stimulation make it challenging to design precise and effective neuromodulation protocols. Computational models have thus become indispensable in advancing our understanding and control of neural responses to electrical stimulation. However, existing approaches suffer from computational bottlenecks, rendering them unsuitable for real-time applications, large-scale parameter sweeps, or sophisticated optimization. In this work, we introduce an approach for massively parallel estimation and optimization of neural fiber responses to electrical stimulation using machine learning techniques. By leveraging advances in high-performance computing and parallel programming, we present a surrogate fiber model that generates spatiotemporal responses to a wide variety of cuff-based electrical peripheral nerve stimulation protocols. We used our surrogate fiber model to design stimulation parameters for selective stimulation of pig and human vagus nerves. Our approach yields a several-orders-of-magnitude improvement in computational efficiency while retaining generality and high predictive accuracy, demonstrating its robustness and potential to enhance the design and optimization of peripheral neuromodulation therapies., (© 2024. The Author(s).)

Neurons receive thousands of inputs onto their dendritic arbour, where individual synapses undergo activity-dependent plasticity. Long-lasting changes in postsynaptic strengths correlate with changes in spine head volume. The magnitude and direction of such structural plasticity - potentiation (sLTP) and depression (sLTD) - depend upon the number and spatial distribution of stimulated synapses. However, how neurons allocate resources to implement synaptic strength changes across space and time amongst neighbouring synapses remains unclear. Here we combined experimental and modelling approaches to explore the elementary processes underlying multi-spine plasticity. We used glutamate uncaging to induce sLTP at varying number of synapses sharing the same dendritic branch, and we built a model incorporating a dual role Ca 2+ -dependent component that induces spine growth or shrinkage. Our results suggest that competition among spines for molecular resources is a key driver of multi-spine plasticity and that spatial distance between simultaneously stimulated spines impacts the resulting spine dynamics., (© 2024. The Author(s).)

When subjects navigate through spatial environments, grid cells exhibit firing fields that are arranged in a triangular grid pattern. Direct recordings of grid cells from the human brain are rare. Hence, functional magnetic resonance imaging (fMRI) studies proposed an indirect measure of entorhinal grid-cell activity, quantified as hexadirectional modulation of fMRI activity as a function of the subject's movement direction. However, it remains unclear how the activity of a population of grid cells may exhibit hexadirectional modulation. Here, we use numerical simulations and analytical calculations to suggest that this hexadirectional modulation is best explained by head-direction tuning aligned to the grid axes, whereas it is not clearly supported by a bias of grid cells toward a particular phase offset. Firing-rate adaptation can result in hexadirectional modulation, but the available cellular data is insufficient to clearly support or refute this option. The magnitude of hexadirectional modulation furthermore depends considerably on the subject's navigation pattern, indicating that future fMRI studies could be designed to test which hypothesis most likely accounts for the fMRI measure of grid cells. Our findings also underline the importance of quantifying the properties of human grid cells to further elucidate how hexadirectional modulations of fMRI activity may emerge., Competing Interests: IB, ER, NA, LK, RK No competing interests declared, (© 2024, Bin Khalid, Reifenstein et al.)

The brain is understood as an intricate biological system composed of numerous elements. It is susceptible to various physical and chemical influences, including temperature. The literature extensively explores the conditions that influence synapses in the context of cellular communication. However, the understanding of how the brain's global physical conditions can modulate ephaptic communication remains limited due to the poorly understood nature of ephapticity. This study proposes an adaptation of the Hodgkin and Huxley (HH) model to investigate the effects of ephaptic entrainment in response to thermal changes (HH-E). The analysis focuses on two distinct neuronal regimes: subthreshold and suprathreshold. In the subthreshold regime, circular statistics are used to demonstrate the dependence of phase differences with temperature. In the suprathreshold regime, the Inter-Spike Interval are employed to estimate phase preferences and changes in the spiking pattern. Temperature influences the model's ephaptic interactions and can modify its preferences for spiking frequency, with the direction of this change depending on specific model conditions and the temperature range under consideration. Furthermore, temperature enhance the anti-phase differences relationship between spikes and the external ephaptic signal. In the suprathreshold regime, ephaptic entrainment is also influenced by temperature, especially at low frequencies. This study reveals the susceptibility of ephaptic entrainment to temperature variations in both subthreshold and suprathreshold regimes and discusses the importance of ephaptic communication in the contexts where temperature may plays a significant role in neural physiology, such as inflammatory processes, fever, and epileptic seizures., (© 2024. The Author(s).)

Temporal rescaling of sequential neural activity has been observed in multiple brain areas during behaviors involving time estimation and motor execution at variable speeds. Temporally asymmetric Hebbian rules have been used in network models to learn and retrieve sequential activity, with characteristics that are qualitatively consistent with experimental observations. However, in these models sequential activity is retrieved at a fixed speed. Here, we investigate the effects of a heterogeneity of plasticity rules on network dynamics. In a model in which neurons differ by the degree of temporal symmetry of their plasticity rule, we find that retrieval speed can be controlled by varying external inputs to the network. Neurons with temporally symmetric plasticity rules act as brakes and tend to slow down the dynamics, while neurons with temporally asymmetric rules act as accelerators of the dynamics. We also find that such networks can naturally generate separate 'preparatory' and 'execution' activity patterns with appropriate external inputs., Competing Interests: MG, NB No competing interests declared, (© 2023, Gillett and Brunel.)

Recent advances in extracellular electrophysiology now facilitate the recording of spikes from hundreds or thousands of neurons simultaneously. This has necessitated both the development of new computational methods for spike sorting and better methods to determine spike-sorting accuracy. One long-standing method of assessing the false discovery rate (FDR) of spike sorting-the rate at which spikes are assigned to the wrong cluster-has been the rate of interspike interval (ISI) violations. Despite their near ubiquitous usage in spike sorting, our understanding of how exactly ISI violations relate to FDR, as well as best practices for using ISI violations as a quality metric, remains limited. Here, we describe an analytical solution that can be used to predict FDR from the ISI violation rate (ISI v ). We test this model in silico through Monte Carlo simulation and apply it to publicly available spike-sorted electrophysiology datasets. We find that the relationship between ISI v and FDR is highly nonlinear, with additional dependencies on firing frequency, the correlation in activity between neurons, and contaminant neuron count. Predicted median FDRs in public datasets recorded in mice were found to range from 3.1 to 50.0%. We found that stochasticity in the occurrence of ISI violations as well as uncertainty in cluster-specific parameters make it difficult to predict FDR for single clusters with high confidence but that FDR can be estimated accurately across a population of clusters. Our findings will help the growing community of researchers using extracellular electrophysiology assess spike-sorting accuracy in a principled manner., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Vincent and Economo.)

The fluid movement of an arm requires multiple spatiotemporal parameters to be set independently. Recent studies have argued that arm movements are generated by the collective dynamics of neurons in motor cortex. An untested prediction of this hypothesis is that independent parameters of movement must map to independent components of the neural dynamics. Using a task where three male monkeys made a sequence of reaching movements to randomly placed targets, we show that the spatial and temporal parameters of arm movements are independently encoded in the low-dimensional trajectories of population activity in motor cortex: each movement's direction corresponds to a fixed neural trajectory through neural state space and its speed to how quickly that trajectory is traversed. Recurrent neural network models show that this coding allows independent control over the spatial and temporal parameters of movement by separate network parameters. Our results support a key prediction of the dynamical systems view of motor cortex, and also argue that not all parameters of movement are defined by different trajectories of population activity., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Colins Rodriguez et al.)

The numerical sense of animals includes identifying the numerosity of a sequence of events that occur with specific intervals, e.g., notes in a call or bar of music. Across nervous systems, the temporal patterning of spikes can code these events, but how this information is decoded (counted) remains elusive. In the anuran auditory system, temporal information of this type is decoded in the midbrain, where "interval-counting" neurons spike only after at least a threshold number of sound pulses have occurred with specific timing. We show that this decoding process, i.e., interval counting, arises from integrating phasic, onset-type and offset inhibition with excitation that augments across successive intervals, possibly due to a progressive decrease in "shunting" effects of inhibition. Because these physiological properties are ubiquitous within and across central nervous systems, interval counting may be a general mechanism for decoding diverse information coded/encoded in temporal patterns of spikes, including "bursts," and estimating elapsed time., Competing Interests: Competing interests statement:The authors declare no competing interest.

The capacity to initiate actions endogenously is critical for goal-directed behavior. Spontaneous voluntary actions are typically preceded by slow-ramping activity in medial frontal cortex that begins around two seconds before movement, which may reflect spontaneous fluctuations that influence action timing. However, the mechanisms by which these slow ramping signals emerge from single-neuron and network dynamics remain poorly understood. Here, we developed a spiking neural-network model that produces spontaneous slow ramping activity in single neurons and population activity with onsets ~2 s before threshold crossings. A key prediction of our model is that neurons that ramp together have correlated firing patterns before ramping onset. We confirmed this model-derived hypothesis in a dataset of human single neuron recordings from medial frontal cortex. Our results suggest that slow ramping signals reflect bounded spontaneous fluctuations that emerge from quasi-winner-take-all dynamics in clustered networks that are temporally stabilized by slow-acting synapses., (© 2024. The Author(s).)

The significance of intracellular recording in neurophysiology is emphasized in this article, with considering the functions of neurons, particularly the role of first spike latency in response to external stimuli. The study employs advanced machine learning techniques to predict first spike latency from whole cell patch recording data. Experiments were conducted on Control (Salin) and Experiment (Harmaline) groups, generating a dataset for developing predictive models. Because the dataset has a limited number of samples, we utilized models that are effective with small datasets. Among different groups of regression models (linear, ensemble, and tree models), the ensemble models, specifically the LGB method, can achieve better performance. The results demonstrate accurate prediction of first spike latency, with an average mean squared error of 0.0002 and mean absolute error of 0.01 in 10-fold cross-validation. The research suggests the potential of machine learning in forecasting the first spike latency, allowing reliable estimation without the need for extensive animal testing. This intelligent predictive system facilitates efficient analysis of first spike latency changes in both healthy and unhealthy brain cells, streamlining experimentation and providing more detailed insights into the captured signals.

Knowledge integration based on the relationship between structure and function of the neural substrate is one of the main targets of neuroinformatics and data-driven computational modeling. However, the multiplicity of data sources, the diversity of benchmarks, the mixing of observables of different natures, and the necessity of a long-term, systematic approach make such a task challenging. Here we present a first snapshot of a long-term integrative modeling program designed to address this issue in the domain of the visual system: a comprehensive spiking model of cat primary visual cortex. The presented model satisfies an extensive range of anatomical, statistical and functional constraints under a wide range of visual input statistics. In the presence of physiological levels of tonic stochastic bombardment by spontaneous thalamic activity, the modeled cortical reverberations self-generate a sparse asynchronous ongoing activity that quantitatively matches a range of experimentally measured statistics. When integrating feed-forward drive elicited by a high diversity of visual contexts, the simulated network produces a realistic, quantitatively accurate interplay between visually evoked excitatory and inhibitory conductances; contrast-invariant orientation-tuning width; center surround interactions; and stimulus-dependent changes in the precision of the neural code. This integrative model offers insights into how the studied properties interact, contributing to a better understanding of visual cortical dynamics. It provides a basis for future development towards a comprehensive model of low-level perception., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Antolík et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Every day, hundreds of thousands of people undergo general anesthesia. One hypothesis is that anesthesia disrupts dynamic stability-the ability of the brain to balance excitability with the need to be stable and controllable. To test this hypothesis, we developed a method for quantifying changes in population-level dynamic stability in complex systems: delayed linear analysis for stability estimation (DeLASE). Propofol was used to transition animals between the awake state and anesthetized unconsciousness. DeLASE was applied to macaque cortex local field potentials (LFPs). We found that neural dynamics were more unstable in unconsciousness compared with the awake state. Cortical trajectories mirrored predictions from destabilized linear systems. We mimicked the effect of propofol in simulated neural networks by increasing inhibitory tone. This in turn destabilized the networks, as observed in the neural data. Our results suggest that anesthesia disrupts dynamical stability that is required for consciousness., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Scaling relationships are key in characterizing complex systems at criticality. In the brain, they are evident in neuronal avalanches-scale-invariant cascades of neuronal activity quantified by power laws. Avalanches manifest at the cellular level as cascades of neuronal groups that fire action potentials simultaneously. Such spatiotemporal synchronization is vital to theories on brain function yet avalanche synchronization is often underestimated when only a fraction of neurons is observed. Here, we investigate biases from fractional sampling within a balanced network of excitatory and inhibitory neurons with all-to-all connectivity and critical branching process dynamics. We focus on how mean avalanche size scales with avalanche duration. For parabolic avalanches, this scaling is quadratic, quantified by the scaling exponent, χ = 2, reflecting rapid spatial expansion of simultaneous neuronal firing over short durations. However, in networks sampled fractionally, χ is significantly lower. We demonstrate that applying temporal coarse-graining and increasing a minimum threshold for coincident firing restores χ = 2, even when as few as 0.1% of neurons are sampled. This correction crucially depends on the network being critical and fails for near sub- and supercritical branching dynamics. Using cellular 2-photon imaging, our approach robustly identifies χ = 2 over a wide parameter regime in ongoing neuronal activity from frontal cortex of awake mice. In contrast, the common 'crackling noise' approach fails to determine χ under similar sampling conditions at criticality. Our findings overcome scaling bias from fractional sampling and demonstrate rapid, spatiotemporal synchronization of neuronal assemblies consistent with scale-invariant, parabolic avalanches at criticality., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Schizophrenia phenotypes are suggestive of impaired cortical plasticity in the disease, but the mechanisms of these deficits are unknown. Genomic association studies have implicated a large number of genes that regulate neuromodulation and plasticity, indicating that the plasticity deficits have a genetic origin. Here, we used biochemically detailed computational modeling of postsynaptic plasticity to investigate how schizophrenia-associated genes regulate long-term potentiation (LTP) and depression (LTD). We combined our model with data from postmortem RNA expression studies (CommonMind gene-expression datasets) to assess the consequences of altered expression of plasticity-regulating genes for the amplitude of LTP and LTD. Our results show that the expression alterations observed post mortem, especially those in the anterior cingulate cortex, lead to impaired protein kinase A (PKA)-pathway-mediated LTP in synapses containing GluR1 receptors. We validated these findings using a genotyped electroencephalogram (EEG) dataset where polygenic risk scores for synaptic and ion channel-encoding genes as well as modulation of visual evoked potentials were determined for 286 healthy controls. Our results provide a possible genetic mechanism for plasticity impairments in schizophrenia, which can lead to improved understanding and, ultimately, treatment of the disorder., Competing Interests: Competing interests statement:O.A.A. is a consultant to Cortechs.ai and has received speakers honorarium from Lundbeck, Sunovion, Otsuka and Jansen. T.E. is a consultant to Cumulus and Sumitomo Pharma America and received speaker’s honoraria from Lundbeck and Janssen Cilag.

The primary motor cortex does not uniquely or directly produce alpha motoneurone (α-MN) drive to muscles during voluntary movement. Rather, α-MN drive emerges from the synthesis and competition among excitatory and inhibitory inputs from multiple descending tracts, spinal interneurons, sensory inputs, and proprioceptive afferents. One such fundamental input is velocity-dependent stretch reflexes in lengthening muscles, which should be inhibited to enable voluntary movement. It remains an open question, however, the extent to which unmodulated stretch reflexes disrupt voluntary movement, and whether and how they are inhibited in limbs with numerous multiarticular muscles. We used a computational model of a Rhesus Macaque arm to simulate movements with feedforward α-MN commands only, and with added velocity-dependent stretch reflex feedback. We found that velocity-dependent stretch reflex caused movement-specific, typically large and variable disruptions to arm movements. These disruptions were greatly reduced when modulating velocity-dependent stretch reflex feedback (i) as per the commonly proposed (but yet to be clarified) idealized alpha-gamma (α-γ) coactivation or (ii) an alternative α-MN collateral projection to homonymous γ-MNs. We conclude that such α-MN collaterals are a physiologically tenable propriospinal circuit in the mammalian fusimotor system. These collaterals could still collaborate with α-γ coactivation, and the few skeletofusimotor fibers (β-MNs) in mammals, to create a flexible fusimotor ecosystem to enable voluntary movement. By locally and automatically regulating the highly nonlinear neuro-musculo-skeletal mechanics of the limb, these collaterals could be a critical low-level enabler of learning, adaptation, and performance via higher-level brainstem, cerebellar, and cortical mechanisms., Competing Interests: Competing interests statement:The authors declare no competing interests.

Modern neurophysiological recordings are performed using multichannel sensor arrays that are able to record activity in an increasingly high number of channels numbering in the 100s to 1000s. Often, underlying lower-dimensional patterns of activity are responsible for the observed dynamics, but these representations are difficult to reliably identify using existing methods that attempt to summarize multivariate relationships in a post hoc manner from univariate analyses or using current blind source separation methods. While such methods can reveal appealing patterns of activity, determining the number of components to include, assessing their statistical significance, and interpreting them requires extensive manual intervention and subjective judgment in practice. These difficulties with component selection and interpretation occur in large part because these methods lack a generative model for the underlying spatio-temporal dynamics. Here, we describe a novel component analysis method anchored by a generative model where each source is described by a bio-physically inspired state-space representation. The parameters governing this representation readily capture the oscillatory temporal dynamics of the components, so we refer to it as oscillation component analysis. These parameters - the oscillatory properties, the component mixing weights at the sensors, and the number of oscillations - all are inferred in a data-driven fashion within a Bayesian framework employing an instance of the expectation maximization algorithm. We analyze high-dimensional electroencephalography and magnetoencephalography recordings from human studies to illustrate the potential utility of this method for neuroscience data., Competing Interests: PD, MH, PP No competing interests declared, (© 2024, Das et al.)

The central complex of insects contains cells, organised as a ring attractor, that encode head direction. The 'bump' of activity in the ring can be updated by idiothetic cues and external sensory information. Plasticity at the synapses between these cells and the ring neurons, that are responsible for bringing sensory information into the central complex, has been proposed to form a mapping between visual cues and the heading estimate which allows for more accurate tracking of the current heading, than if only idiothetic information were used. In Drosophila, ring neurons have well characterised non-linear receptive fields. In this work we produce synthetic versions of these visual receptive fields using a combination of excitatory inputs and mutual inhibition between ring neurons. We use these receptive fields to bring visual information into a spiking neural network model of the insect central complex based on the recently published Drosophila connectome. Previous modelling work has focused on how this circuit functions as a ring attractor using the same type of simple visual cues commonly used experimentally. While we initially test the model on these simple stimuli, we then go on to apply the model to complex natural scenes containing multiple conflicting cues. We show that this simple visual filtering provided by the ring neurons is sufficient to form a mapping between heading and visual features and maintain the heading estimate in the absence of angular velocity input. The network is successful at tracking heading even when presented with videos of natural scenes containing conflicting information from environmental changes and translation of the camera., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Stentiford et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

During reaching, neurons in motor cortex exhibit complex, time-varying activity patterns. Though single-neuron activity correlates with movement parameters, movement correlations explain neural activity only partially. Neural responses also reflect population-level dynamics thought to generate outputs. These dynamics have previously been described as "rotational," such that activity orbits in neural state space. Here, we reanalyze reaching datasets from male Rhesus macaques and find two essential features that cannot be accounted for with standard dynamics models. First, the planes in which rotations occur differ for different reaches. Second, this variation in planes reflects the overall location of activity in neural state space. Our "location-dependent rotations" model fits nearly all motor cortex activity during reaching, and high-quality decoding of reach kinematics reveals a quasilinear relationship with spiking. Varying rotational planes allows motor cortex to produce richer outputs than possible under previous models. Finally, our model links representational and dynamical ideas: representation is present in the state space location, which dynamics then convert into time-varying command signals., (© 2024. The Author(s).)

Resting-state functional magnetic resonance imaging (fMRI) provides an efficient way to analyze the functional connectivity between brain regions. A comprehensive understanding of brain functionality requires a unified description of multi-scale layers of neural structure. However, existing brain network modeling methods often simplify this property by averaging Blood oxygen level dependent (BOLD) signals at the brain region level for fMRI-based analysis with the assumption that BOLD signals are homogeneous within each brain region, which ignores the heterogeneity of voxels within each Region of Interest (ROI). This study introduces a novel multi-stage self-supervised learning framework for multiscale brain network analysis, which effectively delineates brain functionality from voxel to ROIs and up to sample level. A Contrastive Voxel Clustering (CVC) module is proposed to simultaneously learn the voxel-level features and clustering assignments, which ensures the retention of informative clustering features at the finest voxel-level and concurrently preserves functional connectivity characteristics. Additionally, based on the extracted features and clustering assignments at the voxel level by CVC, a Brain ROI-based Graph Neural Network (BR-GNN) is built to extract functional connectivity features at the brain ROI-level and used for sample-level prediction, which integrates the functional clustering maps with the pre-established structural ROI maps and creates a more comprehensive and effective analytical tool. Experiments are performed on two datasets, which illustrate the effectiveness and generalization ability of the proposed method by analyzing voxel-level clustering results and brain ROIs-level functional characteristics. The proposed method provides a multiscale modeling framework for brain functional connectivity analysis, which will be further used for other brain disease identification. Code is available at https://github.com/yanliugroup/fmri-cvc., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

It is increasingly clear that unconscious information impairs the performance of the corresponding action when the instruction to act is delayed. However, whether this impairment occurs at the response level or at the perceptual level remains controversial. This study used fMRI and a computational model with a pre-post design to address this elusive issue. The fMRI results showed that when the unconscious information containing strong stimulus-response associations was irrelevant to subsequent stimuli, the precuneus in the parietal lobe, which is thought to be involved in sensorimotor processing, was activated. In contrast, when the unconscious information was relevant to subsequent stimuli, regardless of the strength of the stimulus-response associations, some regions in the occipital and temporal cortices, which are thought to be involved in visual perceptual processing, were activated. In addition, the percent signal change in the regions of interest associated with motor inhibition was modulated by compatibility in the irrelevant but not in the relevant stimuli conditions. Modeling of behavioral data further supported that the irrelevant and relevant stimuli conditions involved fundamentally different mechanisms. Our finding reconciles the debate about the mechanism by which unconscious information impairs action performance and has important implications for understanding of unconscious cognition., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

A large-scale biophysical network model for the isolated striatal body is developed to optimise potential intrastriatal deep brain stimulation applied to, e.g. obsessive-compulsive disorder. The model is based on modified Hodgkin-Huxley equations with small-world connectivity, while the spatial information about the positions of the neurons is taken from a detailed human atlas. The model produces neuronal spatiotemporal activity patterns segregating healthy from pathological conditions. Three biomarkers were used for the optimisation of stimulation protocols regarding stimulation frequency, amplitude and localisation: the mean activity of the entire network, the frequency spectrum of the entire network (rhythmicity) and a combination of the above two. By minimising the deviation of the aforementioned biomarkers from the normal state, we compute the optimal deep brain stimulation parameters, regarding position, amplitude and frequency. Our results suggest that in the DBS optimisation process, there is a clear trade-off between frequency synchronisation and overall network activity, which has also been observed during in vivo studies., (© 2024. The Author(s).)

Unifying integration and segregation in the brain has been a fundamental puzzle in neuroscience ever since the conception of the "binding problem." Here, we introduce a framework that places integration and segregation within a continuum based on a fundamental property of the brain-its structural connectivity graph Laplacian harmonics and a new feature we term the gap-spectrum. This framework organizes harmonics into three regimes-integrative, segregative, and degenerate-that together account for various group-level properties. Integrative and segregative harmonics occupy the ends of the continuum, and they share properties such as reproducibility across individuals, stability to perturbation, and involve "bottom-up" sensory networks. Degenerate harmonics are in the middle of the continuum, and they are subject-specific, flexible, and involve "top-down" networks. The proposed framework accommodates inter-subject variation, sensitivity to changes, and structure-function coupling in ways that offer promising avenues for studying cognition and consciousness in the brain., (© 2024. The Author(s).)

Objective. Implanted neural microelectrodes are an important tool for recording from and stimulating the cerebral cortex. The performance of chronically implanted devices, however, is often hindered by the development of a reactive tissue response. Previous computational models have investigated brain strain from micromotions of neural electrodes after they have been inserted, to investigate design parameters that might minimize triggers to the reactive tissue response. However, these models ignore tissue damage created during device insertion, an important contributing factor to the severity of inflammation. The objective of this study was to evaluate the effect of electrode geometry, insertion speed, and surface friction on brain tissue strain during insertion. Approach . Using a coupled Eulerian-Lagrangian approach, we developed a 3D finite element model (FEM) that simulates the dynamic insertion of a neural microelectrode in brain tissue. Geometry was varied to investigate tip bluntness, cross-sectional shape, and shank thickness. Insertion velocities were varied from 1 to 8 m s -1 . Friction was varied from frictionless to 0.4. Tissue strain and potential microvasculature hemorrhage radius were evaluated for brain regions along the electrode shank and near its tip. Main results . Sharper tips resulted in higher mean max principal strains near the tip except for the bluntest tip on the square cross-section electrode, which exhibited high compressive strain values due to stress concentrations at the corners. The potential vascular damage radius around the electrode was primarily a function of the shank diameter, with smaller shank diameters resulting in smaller distributions of radial strain around the electrode. However, the square shank interaction with the tip taper length caused unique strain distributions that increased the damage radius in some cases. Faster insertion velocities created more strain near the tip but less strain along the shank. Increased friction between the brain and electrode created more strain near the electrode tip and along the shank, but frictionless interactions resulted in increased tearing of brain tissue near the tip. Significance . These results demonstrate the first dynamic FEM study of neural electrode insertion, identifying design factors that can reduce tissue strain and potentially mitigate initial reactive tissue responses due to traumatic microelectrode array insertion., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

The ability to make accurate and timely decisions, such as judging when it is safe to cross the road, is the foundation of adaptive behavior. While the computational and neural processes supporting simple decisions on isolated stimuli have been well characterized, decision-making in the real world often requires integration of discrete sensory events over time and space. Most previous experimental work on perceptual decision-making has focused on tasks that involve only a single, task-relevant source of sensory input. It remains unclear, therefore, how such integrative decisions are regulated computationally. Here we used psychophysics, electroencephalography, and computational modeling to understand how the human brain combines visual motion signals across space in the service of a single, integrated decision. To that purpose, we presented two random-dot kinematograms in the left and the right visual hemifields. Coherent motion signals were shown briefly and concurrently in each location, and healthy adult human participants of both sexes reported the average of the two motion signals. We directly tested competing predictions arising from influential serial and parallel accounts of visual processing. Using a biologically plausible model of motion filtering, we found evidence in favor of parallel integration as the fundamental computational mechanism regulating integrated perceptual decisions., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Epilepsy is defined by the abrupt emergence of harmful seizures, but the nature of these regime shifts remains enigmatic. From the perspective of dynamical systems theory, such critical transitions occur upon inconspicuous perturbations in highly interconnected systems and can be modeled as mathematical bifurcations between alternative regimes. The predictability of critical transitions represents a major challenge, but the theory predicts the appearance of subtle dynamical signatures on the verge of instability. Whether such dynamical signatures can be measured before impending seizures remains uncertain. Here, we verified that predictions on bifurcations applied to the onset of hippocampal seizures, providing concordant results from in silico modeling, optogenetics experiments in male mice and intracranial EEG recordings in human patients with epilepsy. Leveraging pharmacological control over neural excitability, we showed that the boundary between physiological excitability and seizures can be inferred from dynamical signatures passively recorded or actively probed in hippocampal circuits. Of importance for the design of future neurotechnologies, active probing surpassed passive recording to decode underlying levels of neural excitability, notably when assessed from a network of propagating neural responses. Our findings provide a promising approach for predicting and preventing seizures, based on a sound understanding of their dynamics., (© 2024. The Author(s).)

When multiple visual stimuli are presented simultaneously in the receptive field, the neural response is suppressed compared to presenting the same stimuli sequentially. The prevailing hypothesis suggests that this suppression is due to competition among multiple stimuli for limited resources within receptive fields, governed by task demands. However, it is unknown how stimulus-driven computations may give rise to simultaneous suppression. Using fMRI, we find simultaneous suppression in single voxels, which varies with both stimulus size and timing, and progressively increases up the visual hierarchy. Using population receptive field (pRF) models, we find that compressive spatiotemporal summation rather than compressive spatial summation predicts simultaneous suppression, and that increased simultaneous suppression is linked to larger pRF sizes and stronger compressive nonlinearities. These results necessitate a rethinking of simultaneous suppression as the outcome of stimulus-driven compressive spatiotemporal computations within pRFs, and open new opportunities to study visual processing capacity across space and time., (© 2024. The Author(s).)

In tactile sensing, decoding the journey from afferent tactile signals to efferent motor commands is a significant challenge primarily due to the difficulty in capturing population-level afferent nerve signals during active touch. This study integrates a finite element hand model with a neural dynamic model by using microneurography data to predict neural responses based on contact biomechanics and membrane transduction dynamics. This research focuses specifically on tactile sensation and its direct translation into motor actions. Evaluations of muscle synergy during in -vivo experiments revealed transduction functions linking tactile signals and muscle activation. These functions suggest similar sensorimotor strategies for grasping influenced by object size and weight. The decoded transduction mechanism was validated by restoring human-like sensorimotor performance on a tendon-driven biomimetic hand. This research advances our understanding of translating tactile sensation into motor actions, offering valuable insights into prosthetic design, robotics, and the development of next-generation prosthetics with neuromorphic tactile feedback., (© 2024. The Author(s).)

It has long been assumed that activity patterns persist in neuronal circuits after they are first experienced, as part of the process of information processing and storage by the brain. However, these "reverberations" of current activity have not been directly observed on a single-neuron level in a mammalian system. Here we demonstrate that specific induced activity patterns are retained in mature cultured hippocampal neuronal networks. Neurons within the network are induced to fire at a single frequency or in a more complex pattern containing two distinct frequencies. After the stimulation was stopped, the subsequent neuronal activity of hundreds of neurons in the network was monitored. In the case of single-frequency stimulation, it was observed that many of the neurons continue to fire at the same frequency that they were stimulated to fire at. Using a recurrent neural network trained to detect specific, more complex patterns, we found that the multiple-frequency stimulation patterns were also retained within the neuronal network. Moreover, it appears that the component frequencies of the more complex patterns are stored in different populations of neurons and neuron subtypes., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Niewinski et al.)

The hippocampus receives sequences of sensory inputs from the cortex during exploration and encodes the sequences with millisecond precision. We developed a predictive autoencoder model of the hippocampus including the trisynaptic and monosynaptic circuits from the entorhinal cortex (EC). CA3 was trained as a self-supervised recurrent neural network to predict its next input. We confirmed that CA3 is predicting ahead by analyzing the spike coupling between simultaneously recorded neurons in the dentate gyrus, CA3, and CA1 of the mouse hippocampus. In the model, CA1 neurons signal prediction errors by comparing CA3 predictions to the next direct EC input. The model exhibits the rapid appearance and slow fading of CA1 place cells and displays replay and phase precession from CA3. The model could be learned in a biologically plausible way with error-encoding neurons. Similarities between the hippocampal and thalamocortical circuits suggest that such computation motif could also underlie self-supervised sequence learning in the cortex., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The brain's extraordinary abilities are often attributed to its capacity to learn and adapt. But memory has its limitations, especially when faced with tasks such as retrieving thousands of food items-a common behavior in scatter-hoarding animals. Here, we propose a brain mechanism that may facilitate caching and retrieval behaviors, with a focus on hippocampal spatial cells. Rather than memorizing the locations of their caches, as previously hypothesized, we suggest that cache-hoarding animals employ a static mechanism akin to hash functions commonly used in computing. Our mathematical model aligns with the activity of hippocampal spatial cells, which respond to an animal's positional attention. We know that the region that activates each spatial cell remains consistent across subsequent visits to the same area but not between areas. This remapping, combined with the uniqueness of cognitive maps, produces persistent hash functions that can serve both food caching and retrieval. We present a simple neural network architecture that can generate such a probabilistic hash that is unique to the animal and not sensitive to environmental changes. This mechanism could serve a virtually boundless capacity for the encoding of any structured data., (© 2024. The Author(s).)

Theory predicts that nonlinear summation of synaptic potentials within dendrites allows neurons to perform linearly non-separable computations (LNSCs). Using Boolean analysis approaches, we predicted that both supralinear and sublinear synaptic summation could allow single neurons to implement a type of LNSC, the feature binding problem (FBP), which does not require inhibition contrary to the exclusive-or function (XOR). Notably, sublinear dendritic operations enable LNSCs when scattered synaptic activation generates increased somatic spike output. However, experimental demonstrations of scatter-sensitive neuronal computations have not yet been described. Using glutamate uncaging onto cerebellar molecular layer interneurons, we show that scattered synaptic-like activation of dendrites evoked larger compound EPSPs than clustered synaptic activation, generating a higher output spiking probability. Moreover, we also demonstrate that single interneurons can indeed implement the FBP. Using a biophysical model to explore the conditions in which a neuron might be expected to implement the FBP, we establish that sublinear summation is necessary but not sufficient. Other parameters such as the relative sublinearity, the EPSP size, depolarization amplitude relative to action potential threshold, and voltage fluctuations all influence whether the FBP can be performed. Since sublinear synaptic summation is a property of passive dendrites, we expect that many different neuron types can implement LNSCs., (© 2024. The Author(s).)

Biological synaptic transmission is unreliable, and this unreliability likely degrades neural circuit performance. While there are biophysical mechanisms that can increase reliability, for instance by increasing vesicle release probability, these mechanisms cost energy. We examined four such mechanisms along with the associated scaling of the energetic costs. We then embedded these energetic costs for reliability in artificial neural networks (ANNs) with trainable stochastic synapses, and trained these networks on standard image classification tasks. The resulting networks revealed a tradeoff between circuit performance and the energetic cost of synaptic reliability. Additionally, the optimised networks exhibited two testable predictions consistent with pre-existing experimental data. Specifically, synapses with lower variability tended to have (1) higher input firing rates and (2) lower learning rates. Surprisingly, these predictions also arise when synapse statistics are inferred through Bayesian inference. Indeed, we were able to find a formal, theoretical link between the performance-reliability cost tradeoff and Bayesian inference. This connection suggests two incompatible possibilities: evolution may have chanced upon a scheme for implementing Bayesian inference by optimising energy efficiency, or alternatively, energy-efficient synapses may display signatures of Bayesian inference without actually using Bayes to reason about uncertainty., Competing Interests: JM, CO, CH, LA No competing interests declared, (© 2023, Malkin et al.)

Understanding how neural circuits generate sequential activity is a longstanding challenge. While foundational theoretical models have shown how sequences can be stored as memories in neural networks with Hebbian plasticity rules, these models considered only a narrow range of Hebbian rules. Here, we introduce a model for arbitrary Hebbian plasticity rules, capturing the diversity of spike-timing-dependent synaptic plasticity seen in experiments, and show how the choice of these rules and of neural activity patterns influences sequence memory formation and retrieval. In particular, we derive a general theory that predicts the tempo of sequence replay. This theory lays a foundation for explaining how cortical tutor signals might give rise to motor actions that eventually become "automatic." Our theory also captures the impact of changing the tempo of the tutor signal. Beyond shedding light on biological circuits, this theory has relevance in artificial intelligence by laying a foundation for frameworks whereby slow and computationally expensive deliberation can be stored as memories and eventually replaced by inexpensive recall., Competing Interests: Competing interests statement:The authors declare no competing interest.

Living systems, from single cells to higher vertebrates, receive a continuous stream of non-stationary inputs that they sense, for e.g. via cell surface receptors or sensory organs. By integrating these time-varying, multi-sensory, and often noisy information with memory using complex molecular or neuronal networks, they generate a variety of responses beyond simple stimulus-response association, including avoidance behavior, life-long-learning or social interactions. In a broad sense, these processes can be understood as a type of biological computation. Taking as a basis generic features of biological computations, such as real-time responsiveness or robustness and flexibility of the computation, we highlight the limitations of the current attractor-based framework for understanding computations in biological systems. We argue that frameworks based on transient dynamics away from attractors are better suited for the description of computations performed by neuronal and signaling networks. In particular, we discuss how quasi-stable transient dynamics from ghost states that emerge at criticality have a promising potential for developing an integrated framework of computations, that can help us understand how living system actively process information and learn from their continuously changing environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)