Objective . Brain–computer interfaces (BCIs) can enable individuals with tetraplegia to communicate and control external devices. Though much progress has been made in improving the speed and robustness of neural control provided by intracortical BCIs, little research has been devoted to minimizing the amount of time spent on decoder calibration. Approach . We investigated the amount of time users needed to calibrate decoders and achieve performance saturation using two markedly different decoding algorithms: the steady-state Kalman filter, and a novel technique using Gaussian process regression (GP-DKF). Main results . Three people with tetraplegia gained rapid closed-loop neural cursor control and peak, plateaued decoder performance within 3 min of initializing calibration. We also show that a BCI-naïve user (T5) was able to rapidly attain closed-loop neural cursor control with the GP-DKF using self-selected movement imagery on his first-ever day of closed-loop BCI use, acquiring a target 37 s after initiating calibration. Significance . These results demonstrate the potential for an intracortical BCI to be used immediately after deployment by people with paralysis, without the need for user learning or extensive system calibration.

Introduction: Artificial intelligence (AI) and neuroimaging offer new opportunities for diagnosis and prognosis of dementia.Methods: We systematically reviewed studies reporting AI for neuroimaging in diagnosis and/or prognosis of cognitive neurodegenerative diseases.Results: A total of 255 studies were identified. Most studies relied on the Alzheimer's Disease Neuroimaging Initiative dataset. Algorithmic classifiers were the most commonly used AI method (48%) and discriminative models performed best for differentiating Alzheimer's disease from controls. The accuracy of algorithms varied with the patient cohort, imaging modalities, and stratifiers used. Few studies performed validation in an independent cohort.Discussion: The literature has several methodological limitations including lack of sufficient algorithm development descriptions and standard definitions. We make recommendations to improve model validation including addressing key clinical questions, providing sufficient description of AI methods and validating findings in independent datasets. Collaborative approaches between experts in AI and medicine will help achieve the promising potential of AI tools in practice.Highlights: There has been a rapid expansion in the use of machine learning for diagnosis and prognosis in neurodegenerative disease Most studies (71%) relied on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset with no other individual dataset used more than five times There has been a recent rise in the use of more complex discriminative models (e.g., neural networks) that performed better than other classifiers for classification of AD vs healthy controls We make recommendations to address methodological considerations, addressing key clinical questions, and validation We also make recommendations for the field more broadly to standardize outcome measures, address gaps in the literature, and monitor sources of bias

Predicting dementia early has major implications for clinical management and patient outcomes. Yet, we still lack sensitive tools for stratifying patients early, resulting in patients being undiagnosed or wrongly diagnosed. Despite rapid expansion in machine learning models for dementia prediction, limited model interpretability and generalizability impede translation to the clinic. We build a robust and interpretable predictive prognostic model (PPM) and validate its clinical utility using real-world, routinely-collected, non-invasive, and low-cost (cognitive tests, structural MRI) patient data. To enhance scalability and generalizability to the clinic, we: 1) train the PPM with clinically-relevant predictors (cognitive tests, grey matter atrophy) that are common across research and clinical cohorts, 2) test PPM predictions with independent multicenter real-world data from memory clinics across countries (UK, Singapore). PPM robustly predicts (accuracy: 81.66%, AUC: 0.84, sensitivity: 82.38%, specificity: 80.94%) whether patients at early disease stages (MCI) will remain stable or progress to Alzheimer's Disease (AD). PPM generalizes from research to real-world patient data across memory clinics and its predictions are validated against longitudinal clinical outcomes. PPM allows us to derive an individualized AI-guided multimodal marker (i.e. predictive prognostic index) that predicts progression to AD more precisely than standard clinical markers (grey matter atrophy, cognitive scores; PPM-derived marker: hazard ratio = 3.42, p = 0.01) or clinical diagnosis (PPM-derived marker: hazard ratio = 2.84, p < 0.01), reducing misdiagnosis. Our results provide evidence for a robust and explainable clinical AI-guided marker for early dementia prediction that is validated against longitudinal, multicenter patient data across countries, and has strong potential for adoption in clinical practice. Wellcome Trust, Royal Society, Alzheimer's Research UK, Alzheimer's Drug Discovery Foundation Diagnostics Accelerator, Alan Turing Institute.

The Kalman filter provides a simple and efficient algorithm to compute the posterior distribution for state-space models where both the latent state and measurement models are linear and gaussian. Extensions to the Kalman filter, including the extended and unscented Kalman filters, incorporate linearizations for models where the observation model $p(observation|state)$ is nonlinear. We argue that in many cases, a model for $p(state|observation)$ proves both easier to learn and more accurate for latent state estimation. Approximating $p(state|observation)$ as gaussian leads to a new filtering algorithm, the discriminative Kalman filter (DKF), which can perform well even when $p(observation|state)$ is highly nonlinear and/or nongaussian. The approximation, motivated by the Bernstein–von Mises theorem, improves as the dimensionality of the observations increases. The DKF has computational complexity similar to the Kalman filter, allowing it in some cases to perform much faster than particle filters with similar precision, while better accounting for nonlinear and nongaussian observation models than Kalman-based extensions. When the observation model must be learned from training data prior to filtering, off-the-shelf nonlinear and nonparametric regression techniques can provide a gaussian model for $p(observation|state)$ that cleanly integrates with the DKF. As part of the BrainGate2 clinical trial, we successfully implemented gaussian process regression with the DKF framework in a brain-computer interface to provide real-time, closed-loop cursor control to a person with a complete spinal cord injury. In this letter, we explore the theory underlying the DKF, exhibit some illustrative examples, and outline potential extensions.

Intracortical brain computer interfaces can enable individuals with paralysis to control external devices through voluntarily modulated brain activity. Decoding quality has been previously shown to degrade with signal nonstationarities—specifically, the changes in the statistics of the data between training and testing data sets. This includes changes to the neural tuning profiles and baseline shifts in firing rates of recorded neurons, as well as nonphysiological noise. While progress has been made toward providing long-term user control via decoder recalibration, relatively little work has been dedicated to making the decoding algorithm more resilient to signal nonstationarities. Here, we describe how principled kernel selection with gaussian process regression can be used within a Bayesian filtering framework to mitigate the effects of commonly encountered nonstationarities. Given a supervised training set of (neural features, intention to move in a direction)-pairs, we use gaussian process regression to predict the intention given the neural data. We apply kernel embedding for each neural feature with the standard radial basis function. The multiple kernels are then summed together across each neural dimension, which allows the kernel to effectively ignore large differences that occur only in a single feature. The summed kernel is used for real-time predictions of the posterior mean and variance under a gaussian process framework. The predictions are then filtered using the discriminative Kalman filter to produce an estimate of the neural intention given the history of neural data. We refer to the multiple kernel approach combined with the discriminative Kalman filter as the MK-DKF. We found that the MK-DKF decoder was more resilient to nonstationarities frequently encountered in-real world settings yet provided similar performance to the currently used Kalman decoder. These results demonstrate a method by which neural decoding can be made more resistant to nonstationarities.