We build a double-layer, multiple temporal-resolution classification model for decoding single-trial spatiotemporal patterns of spikes. The model takes spiking activities as input signals and binary behavioral or cognitive variables as output signals and represents the input-output mapping with a double-layer ensemble classifier. In the first layer, to solve the underdetermined problem caused by the small sample size and the very high dimensionality of input signals, B-spline functional expansion and L 1-regularized logistic classifiers are used to reduce dimensionality and yield sparse model estimations. A wide range of temporal resolutions of neural features is included by using a large number of classifiers with different numbers of B-spline knots. Each classifier serves as a base learner to classify spatiotemporal patterns into the probability of the output label with a single temporal resolution. A bootstrap aggregating strategy is used to reduce the estimation variances of these classifiers. In the second layer, another L 1-regularized logistic classifier takes outputs of first-layer classifiers as inputs to generate the final output predictions. This classifier serves as a meta-learner that fuses multiple temporal resolutions to classify spatiotemporal patterns of spikes into binary output labels. We test this decoding model with both synthetic and experimental data recorded from rats and human subjects performing memory-dependent behavioral tasks. Results show that this method can effectively avoid overfitting and yield accurate prediction of output labels with small sample size. The double-layer, multi-resolution classifier consistently outperforms the best single-layer, single-resolution classifier by extracting and utilizing multi-resolution spatiotemporal features of spike patterns in the classification.

This letter proposes a novel method, multi-input, multi-output neuronal mode network (MIMO-NMN), for modeling encoding dynamics and functional connectivity in neural ensembles such as the hippocampus. Compared with conventional approaches such as the Volterra-Wiener model, linear-nonlinear-cascade (LNC) model, and generalized linear model (GLM), the NMN has several advantages in terms of estimation accuracy, model interpretation, and functional connectivity analysis. We point out the limitations of current neural spike modeling methods, especially the estimation biases caused by the imbalanced class problem when the number of zeros is significantly larger than ones in the spike data. We use synthetic data to test the performance of NMN with a comparison of the traditional methods, and the results indicate the NMN approach could reduce the imbalanced class problem and achieve better predictions. Subsequently, we apply the MIMO-NMN method to analyze data from the human hippocampus. The results indicate that the MIMO-NMN method is a promising approach to modeling neural dynamics and analyzing functional connectivity of multi-neuronal data.

A hippocampal prosthesis is a very large scale integration (VLSI) biochip that needs to be implanted in the biological brain to solve a cognitive dysfunction. In this letter, we propose a novel low-complexity, small-area, and low-power programmable hippocampal neural network application-specific integrated circuit (ASIC) for a hippocampal prosthesis. It is based on the nonlinear dynamical model of the hippocampus: namely multi-input, multi-output (MIMO)–generalized Laguerre-Volterra model (GLVM). It can realize the real-time prediction of hippocampal neural activity. New hardware architecture, a storage space configuration scheme, low-power convolution, and gaussian random number generator modules are proposed. The ASIC is fabricated in 40 nm technology with a core area of 0.122 mm 2 and test power of 84.4 μ W. Compared with the design based on the traditional architecture, experimental results show that the core area of the chip is reduced by 84.94% and the core power is reduced by 24.30%.

Neurostimulation is a promising therapy for abating epileptic seizures. However, it is extremely difficult to identify optimal stimulation patterns experimentally. In this study, human recordings are used to develop a functional 24 neuron network statistical model of hippocampal connectivity and dynamics. Spontaneous seizure-like activity is induced in silico in this reconstructed neuronal network. The network is then used as a testbed to design and validate a wide range of neurostimulation patterns. Commonly used periodic trains were not able to permanently abate seizures at any frequency. A simulated annealing global optimization algorithm was then used to identify an optimal stimulation pattern, which successfully abated 92% of seizures. Finally, in a fully responsive, or closed-loop, neurostimulation paradigm, the optimal stimulation successfully prevented the network from entering the seizure state. We propose that the framework presented here for algorithmically identifying patient-specific neurostimulation patterns can greatly increase the efficacy of neurostimulation devices for seizures.

This letter examines the results of input-output (nonparametric) modeling based on the analysis of data generated by a mechanism-based (parametric) model of CA3-CA1 neuronal connections in the hippocampus. The motivation is to obtain biological insight into the interpretation of such input-output (Volterra-equivalent) models estimated from synthetic data. The insights obtained may be subsequently used to interpretat input-output models extracted from actual experimental data. Specifically, we found that a simplified parametric model may serve as a useful tool to study the signal transformations in the hippocampal CA3-CA1 regions. Input-output modeling of model-based synthetic data show that GABAergic interneurons are responsible for regulating neuronal excitation, controlling the precision of spike timing, and maintaining network oscillations, in a manner consistent with previous studies. The input-output model obtained from real data exhibits intriguing similarities with its synthetic-data counterpart, demonstrating the importance of a dynamic resonance in the system/model response around 2 Hz to 3 Hz. Using the input-output model from real data as a guide, we may be able to amend the parametric model by incorporating more mechanisms in order to yield better-matching input-output model. The approach we present can also be applied to the study of other neural systems and pathways.

Characterization of long-term activity-dependent plasticity from behaviorally driven spiking activity is important for understanding the underlying mechanisms of learning and memory. In this letter, we present a computational framework for quantifying spike-timing-dependent plasticity (STDP) during behavior by identifying a functional plasticity rule solely from spiking activity. First, we formulate a flexible point-process spiking neuron model structure with STDP, which includes functions that characterize the stationary and plastic properties of the neuron. The STDP model includes a novel function for prolonged plasticity induction, as well as a more typical function for synaptic weight change based on the relative timing of input-output spike pairs. Consideration for system stability is incorporated with weight-dependent synaptic modification. Next, we formalize an estimation technique using a generalized multilinear model (GMLM) structure with basis function expansion. The weight-dependent synaptic modification adds a nonlinearity to the model, which is addressed with an iterative unconstrained optimization approach. Finally, we demonstrate successful model estimation on simulated spiking data and show that all model functions can be estimated accurately with this method across a variety of simulation parameters, such as number of inputs, output firing rate, input firing type, and simulation time. Since this approach requires only naturally generated spikes, it can be readily applied to behaving animal studies to characterize the underlying mechanisms of learning and memory.