International IEEE/EMBS Conference on Neural Engineering : [proceedings]. International IEEE EMBS Conference on Neural Engineering最新文献

Surgical neuromodulation through implantable devices allows for stimulation delivery to subcortical regions, crucial for symptom control in many debilitating neurological conditions. Novel closed-loop algorithms deliver therapy tailor-made to endogenous physiological activity, however rely on precise sensing of signals such as subcortical oscillations. The frequency of such intrinsic activity can vary depending on subcortical target nucleus, while factors such as regional anatomy may also contribute to variability in sensing signals. While artefact parameters have been explored in more 'standard' and commonly used targets (such as the basal ganglia, which are implanted in movement disorders), characterisation in novel candidate nuclei is still under investigation. One such important area is the brainstem, which contains nuclei crucial for arousal and autonomic regulation. The brainstem provides additional implantation targets for treatment indications in disorders of consciousness and sleep, yet poses distinct anatomical challenges compared to central subcortical targets. Here we investigate the region-specific artefacts encountered during activity and rest while streaming data from brainstem implants with a cranially-mounted device in two patients. Such artefacts result from this complex anatomical environment and its interactions with physiological parameters such as head movement and cardiac functions. The implications of the micromotion-induced artefacts, and potential mitigation, are then considered for future closed-loop stimulation methods.

Application of closed-loop approaches in systems neuroscience and brain-computer interfaces holds great promise for revolutionizing our understanding of the brain and for developing novel neuromodulation strategies to restore lost function. The anterior forebrain mesocircuit (AFM) of the mammalian brain is hypothesized to underlie arousal regulation of the cortex and striatum, and support cognitive functions during wakefulness. Dysfunction of arousal regulation is hypothesized to contribute to cognitive dysfunctions in various neurological disorders, and most prominently in patients following traumatic brain injury (TBI). Several clinical studies have explored the use of daily central thalamic deep brain stimulation (CT-DBS) within the AFM to restore consciousness and executive attention in TBI patients. In this study, we explored the use of closed-loop CT-DBS in order to episodically regulate arousal of the AFM of a healthy non-human primate (NHP) with the goal of restoring behavioral performance. We used pupillometry and near real-time analysis of ECoG signals to episodically initiate closed-loop CT-DBS and here we report on our ability to enhance arousal and restore the animal's performance. The initial computer based approach was then experimentally validated using a customized clinical-grade DBS device, the DyNeuMo-X, a bi-directional research platform used for rapidly testing closed-loop DBS. The successful implementation of the DyNeuMo-X in a healthy NHP supports ongoing clinical trials employing the internal DyNeuMo system (NCT05437393, NCT05197816) and our goal of developing and accelerating the deployment of novel neuromodulation approaches to treat cognitive dysfunction in patients with structural brain injuries and other etiologies.

Learning in the mammalian lateral amygdala (LA) during auditory fear conditioning (tone - foot shock pairing), one form of associative learning, requires N-methyl-D-aspartate (NMDA) receptor-dependent plasticity. Despite this fact being known for more than two decades, the biophysical details related to signal flow and the involvement of the coincidence detector, NMDAR, in this learning, remain unclear. Here we use a 4000-neuron computational model of the LA (containing two types of pyramidal cells, types A and C, and two types of interneurons, fast spiking FSI and low-threshold spiking LTS) to reverse engineer changes in information flow in the amygdala that underpin such learning; with a specific focus on the role of the coincidence detector NMDAR. The model also included a Ca^2s based learning rule for synaptic plasticity. The physiologically constrained model provides insights into the underlying mechanisms that implement habituation to the tone, including the role of NMDARs in generating network activity which engenders synaptic plasticity in specific afferent synapses. Specifically, model runs revealed that NMDARs in tone-FSI synapses were more important during the spontaneous state, although LTS cells also played a role. Training trails with tone only also suggested long term depression in tone-PN as well as tone-FSI synapses, providing possible hypothesis related to underlying mechanisms that might implement the phenomenon of habituation.

Human behavior is incredibly complex and the factors that drive decision making-from instinct, to strategy, to biases between individuals-often vary over multiple timescales. In this paper, we design a predictive framework that learns representations to encode an individual's 'behavioral style', i.e. long-term behavioral trends, while simultaneously predicting future actions and choices. The model explicitly separates representations into three latent spaces: the recent past space, the short-term space, and the long-term space where we hope to capture individual differences. To simultaneously extract both global and local variables from complex human behavior, our method combines a multi-scale temporal convolutional network with latent prediction tasks, where we encourage embeddings across the entire sequence, as well as subsets of the sequence, to be mapped to similar points in the latent space. We develop and apply our method to a large-scale behavioral dataset from 1,000 humans playing a 3-armed bandit task, and analyze what our model's resulting embeddings reveal about the human decision making process. In addition to predicting future choices, we show that our model can learn rich representations of human behavior over multiple timescales and provide signatures of differences in individuals.

In recent years, tractography based on diffusion magnetic resonance imaging (dMRI) has become a popular tool for studying microstructural changes resulting from brain diseases like Parkinson's Disease (PD). Quantitative anisotropy (QA) is a parameter that is used in deterministic fiber tracking as a measure of connection between brain regions. It remains unclear, however, if microstructural changes caused by lesioning the median forebrain bundle (MFB) to create a Parkinsonian rat model can be resolved using tractography based on ex-vivo diffusion MRI. This study aims to fill this gap and enable future mechanistic research on structural changes of the whole brain network rodent models of PD. Specifically, it evaluated the ability of correlational tractography to detect structural changes in the MFB of 6-hydroxydopamine (6-OHDA) lesioned rats. The findings reveal that correlational tractography can detect structural changes in lesioned MFB and differentiate between the 6-OHDA and control groups. Imaging results are supported by behavioral and histological evidence demonstrating that 6-OHDA lesioned rats were indeed Parkinsonian. The results suggest that QA and correlational tractography is appropriate to examine local structural changes in rodent models of neurodegenerative disease. More broadly, we expect that similar techniques may provide insight on how disease alters structure throughout the brain, and as a tool to optimize therapeutic interventions.

Intracortical brain computer interfaces (iBCIs) decode neural activity from the cortex and enable motor and communication prostheses, such as cursor control, handwriting and speech, for people with paralysis. This paper introduces a new iBCI communication prosthesis using a 3D keyboard interface for typing using continuous, closed loop movement of multiple fingers. A participant-specific BCI keyboard prototype was developed for a BrainGate2 clinical trial participant (T5) using neural recordings from the hand-knob area of the left premotor cortex. We assessed the relative decoding accuracy of flexion/extension movements of individual single fingers (5 degrees of freedom (DOF)) vs. three groups of fingers (thumb, index-middle, and ring-small fingers, 3 DOF). Neural decoding using 3 independent DOF was more accurate (95%) than that using 5 DOF (76%). A virtual keyboard was then developed where each finger group moved along a flexion-extension arc to acquire targets that corresponded to English letters and symbols. The locations of these letter/symbols were optimized using natural language statistics, resulting in an approximately a 2× reduction in distance traveled by fingers on average compared to a random keyboard layout. This keyboard was tested using a simple real-time closed loop decoder enabling T5 to type with 31 symbols at 90% accuracy and approximately 2.3 sec/symbol (excluding a 2 second hold time) on average.

Finding points in time where the distribution of neural responses changes (change points) is an important step in many neural data analysis pipelines. However, in complex and free behaviors, where we see different types of shifts occurring at different rates, it can be difficult to use existing methods for change point (CP) detection because they can't necessarily handle different types of changes that may occur in the underlying neural distribution. Additionally, response changes are often sparse in high dimensional neural recordings, which can make existing methods detect spurious changes. In this work, we introduce a new approach for finding changes in neural population states across diverse activities and arousal states occurring in free behavior. Our model follows a contrastive learning approach: we learn a metric for CP detection based on maximizing the Sinkhorn divergences of neuron firing rates across two sides of a labeled CP. We apply this method to a 12-hour neural recording of a freely behaving mouse to detect changes in sleep stages and behavior. We show that when we learn a metric, we can better detect change points and also yield insights into which neurons and sub-groups are important for detecting certain types of switches that occur in the brain.

We report a computational algorithm that uses an inverse modeling scheme to infer neuron position and morphology of cortical pyramidal neurons using spatio-temporal extracellular action potential recordings.. We first develop a generic pyramidal neuron model with stylized morphology and active channels that could mimic the realistic electrophysiological dynamics of pyramidal cells from different cortical layers. The generic stylized single neuron model has adjustable parameters for soma location, and morphology and orientation of the dendrites. The ranges for the parameters were selected to include morphology of the pyramidal neuron types in the rodent primary motor cortex. We then developed a machine learning approach that uses the local field potential simulated from the stylized model for training a convolutional neural network that predicts the parameters of the stylized neuron model. Preliminary results suggest that the proposed methodology can reliably infer the key position and morphology parameters using the simulated spatio-temporal profile of EAP waveforms. We also provide partial support to validate the inference algorithm using in vivo data. Finally, we highlight the issues involved and ongoing work to develop a pipeline to automate the scheme.

The development of models and approaches for controlling the spreading dynamics of epileptic seizures is an essential step towards new therapies for people with pharmacologically resistant epilepsy. Beyond resective neurosurgery, in which epileptogenic zones (EZs) are the target of surgery, closed-loop control based on intracranial electrical stimulation, applied at the very early stage of seizure evolution, has been the main alternative, e.g. the RNS system from NeuroPace (Mountain View, CA). In this approach the electrical stimulation is delivered to target brain areas after detection of seizure initiation in the EZ. Here, we examined, on model simulations, some of the closed-loop control aspects of the problem. Seizure dynamics and spread are typically modeled with highly nonlinear dynamics on complex brain networks. Despite the nonlinearity and complexity, currently available optimal feedback control approaches are mostly based on linear approximations. Alternative machine learning control approaches might require amounts of data beyond what is commonly available in the intended application. We thus examined how standard linear feedback control approaches perform when applied to nonlinear models of neural dynamics of seizure generation and spread. In particular, we considered patient-specific epileptor network models for seizure onset and spread. The models incorporate network connectivity derived from (diffusion MRI) white-matter tractography, have been shown to capture the qualitative dynamics of epileptic seizures and can be fit to patient data. For control, we considered simple linear quadratic Gaussian (LQG) regulators. The LQG control was based on a discrete-time state-space model derived from the linearization of the patient-specific epileptor network model around a stable fixed point in the regime of preictal dynamics. We show in simulations that LQG regulators acting on the EZ node during the initial seizure period tend to be unstable. The LQG solution for the control law in this case leads to global feedback to the EZ-node actuator. However, if the LQG solution is constrained to depend on only local feedback originating from the EZ node itself, the controller is stable. In this case, we demonstrate that localized LQG can easily terminate the seizure at the early stage and prevent spread. In the context of optimal feedback control based on linear approximations, our results point to the need for investigating in more detail feedback localization and additional relevant control targets beyond epileptogenic zones.