Large language models encode clinical knowledge.

Large language models (LLMs) have demonstrated impressive capabilities, but the bar for clinical applications is high. Attempts to assess the clinical knowledge of models typically rely on automated evaluations based on limited benchmarks. Here, to address these limitations, we present MultiMedQA, a benchmark combining six existing medical question answering datasets spanning professional medicine, research and consumer queries and a new dataset of medical questions searched online, HealthSearchQA. We propose a human evaluation framework for model answers along multiple axes including factuality, comprehension, reasoning, possible harm and bias. In addition, we evaluate Pathways Language Model1 (PaLM, a 540-billion parameter LLM) and its instruction-tuned variant, Flan-PaLM2 on MultiMedQA. Using a combination of prompting strategies, Flan-PaLM achieves state-of-the-art accuracy on every MultiMedQA multiple-choice dataset (MedQA3, MedMCQA4, PubMedQA5 and Measuring Massive Multitask Language Understanding (MMLU) clinical topics6), including 67.6% accuracy on MedQA (US Medical Licensing Exam-style questions), surpassing the prior state of the art by more than 17%. However, human evaluation reveals key gaps. To resolve this, we introduce instruction prompt tuning, a parameter-efficient approach for aligning LLMs to new domains using a few exemplars. The resulting model, Med-PaLM, performs encouragingly, but remains inferior to clinicians. We show that comprehension, knowledge recall and reasoning improve with model scale and instruction prompt tuning, suggesting the potential utility of LLMs in medicine. Our human evaluations reveal limitations of today's models, reinforcing the importance of both evaluation frameworks and method development in creating safe, helpful LLMs for clinical applications.

Recommendations for Responsible Development and Application of Neurotechnologies.

Advancements in novel neurotechnologies, such as brain computer interfaces (BCI) and neuromodulatory devices such as deep brain stimulators (DBS), will have profound implications for society and human rights. While these technologies are improving the diagnosis and treatment of mental and neurological diseases, they can also alter individual agency and estrange those using neurotechnologies from their sense of self, challenging basic notions of what it means to be human. As an international coalition of interdisciplinary scholars and practitioners, we examine these challenges and make recommendations to mitigate negative consequences that could arise from the unregulated development or application of novel neurotechnologies. We explore potential ethical challenges in four key areas: identity and agency, privacy, bias, and enhancement. To address them, we propose (1) democratic and inclusive summits to establish globally-coordinated ethical and societal guidelines for neurotechnology development and application, (2) new measures, including "Neurorights," for data privacy, security, and consent to empower neurotechnology users' control over their data, (3) new methods of identifying and preventing bias, and (4) the adoption of public guidelines for safe and equitable distribution of neurotechnological devices.

Single neuron computation: from dynamical system to feature detector.

White noise methods are a powerful tool for characterizing the computation performed by neural systems. These methods allow one to identify the feature or features that a neural system extracts from a complex input and to determine how these features are combined to drive the system's spiking response. These methods have also been applied to characterize the input-output relations of single neurons driven by synaptic inputs, simulated by direct current injection. To interpret the results of white noise analysis of single neurons, we would like to understand how the obtained feature space of a single neuron maps onto the biophysical properties of the membrane, in particular, the dynamics of ion channels. Here, through analysis of a simple dynamical model neuron, we draw explicit connections between the output of a white noise analysis and the underlying dynamical system. We find that under certain assumptions, the form of the relevant features is well defined by the parameters of the dynamical system. Further, we show that under some conditions, the feature space is spanned by the spike-triggered average and its successive order time derivatives.

Computation in a single neuron: Hodgkin and Huxley revisited.

A spiking neuron "computes" by transforming a complex dynamical input into a train of action potentials, or spikes. The computation performed by the neuron can be formulated as dimensional reduction, or feature detection, followed by a nonlinear decision function over the low-dimensional space. Generalizations of the reverse correlation technique with white noise input provide a numerical strategy for extracting the relevant low-dimensional features from experimental data, and information theory can be used to evaluate the quality of the low-dimensional approximation. We apply these methods to analyze the simplest biophysically realistic model neuron, the Hodgkin-Huxley (HH) model, using this system to illustrate the general methodological issues. We focus on the features in the stimulus that trigger a spike, explicitly eliminating the effects of interactions between spikes. One can approximate this triggering "feature space" as a two-dimensional linear subspace in the high-dimensional space of input histories, capturing in this way a substantial fraction of the mutual information between inputs and spike time. We find that an even better approximation, however, is to describe the relevant subspace as two dimensional but curved; in this way, we can capture 90% of the mutual information even at high time resolution. Our analysis provides a new understanding of the computational properties of the HH model. While it is common to approximate neural behavior as "integrate and fire," the HH model is not an integrator nor is it well described by a single threshold.

What causes a neuron to spike?

The computation performed by a neuron can be formulated as a combination of dimensional reduction in stimulus space and the nonlinearity inherent in a spiking output. White noise stimulus and reverse correlation (the spike-triggered average and spike-triggered covariance) are often used in experimental neuroscience to "ask" neurons which dimensions in stimulus space they are sensitive to and to characterize the nonlinearity of the response. In this article, we apply reverse correlation to the simplest model neuron with temporal dynamics-the leaky integrate-and-fire model-and find that for even this simple case, standard techniques do not recover the known neural computation. To overcome this, we develop novel reverse-correlation techniques by selectively analyzing only "isolated" spikes and taking explicit account of the extended silences that precede these isolated spikes. We discuss the implications of our methods to the characterization of neural adaptation. Although these methods are developed in the context of the leaky integrate-and-fire model, our findings are relevant for the analysis of spike trains from real neurons.