The coordinated activity of neural populations underlies myriad brain functions. Manipulating this activity using brain stimulation techniques has great potential for scientific and clinical applications, as they causally influence the nervous system. To improve the accuracy by which one can manipulate neural activity, it is important to (1) take into account the pre-stimulation brain state, which can influence the brain's response to stimulation, and (2) adaptively update stimulation parameters over time to compensate for changes in the brain's response to stimulation. In this work, we propose Online MicroStimulation Optimization (OMiSO), a brain stimulation framework that leverages brain state information to find stimulation parameters that can drive neural population activity toward specified states. OMiSO includes two key advances: i) training a stimulation-response model that leverages the pre-stimulation brain state, and inverting this model to choose the stimulation parameters, and ii) updating this inverse model online using newly-observed responses to stimulation. We tested OMiSO using intracortical microstimulation with a "Utah" array and found that it outperformed competing methods that do not incorporate these advances. Taken together, OMiSO provides greater accuracy in achieving specified activity states, thereby advancing neuromodulation technologies for understanding the brain and for treating brain disorders.

Multi-compartment Hodgkin-Huxley models are biophysical models of how electrical signals propagate throughout a neuron, and they form the basis of our knowledge of neural computation at the cellular level. However, these models have many free parameters that must be estimated for each cell, and existing fitting methods rely on intracellular voltage measurements that are highly challenging to obtain in vivo. Recent advances in neural recording technology with high-density probes and arrays enable dense sampling of extracellular voltage from many sites surrounding a neuron, allowing indirect measurement of many compartments of a cell simultaneously. Here, we propose a method for inferring the underlying membrane voltage, biophysical parameters, and the neuron's position relative to the probe, using extracellular measurements alone. We use an Extended Kalman Filter to infer membrane voltage and channel states using efficient, differentiable simulators. Then, we learn the model parameters by maximizing the marginal likelihood using gradient-based methods. We demonstrate the performance of this approach using simulated data and real neuron morphologies.

This week, I covered the story of Casey Harrell --a man with ALS who is "the first power user" of a brain implant, according to the researchers who worked with him. Harrell is paralyzed and unable to speak coherently without the device. He has now spent almost three years using a brain-computer interface (BCI) that enables him to "speak," surf the web, and perform his job as a climate activist, largely independently. Since Harrell was implanted with the device, in July 2023, a team at the University of California, Davis, has worked with him to adjust and improve its offerings. They've refined its accuracy, for example.

Understanding how the human brain progresses from processing simple linguistic inputs to performing high-level reasoning is a fundamental challenge in neuroscience. While modern large language models (LLMs) are increasingly used to model neural responses to language, their internal representations are highly "entangled," mixing information about lexicon, syntax, meaning, and reasoning. This entanglement biases conventional brain encoding analyses toward linguistically shallow features (e.g., lexicon and syntax), making it difficult to isolate the neural substrates of cognitively deeper processes. Here, we introduce a residual disentanglement method that computationally isolates these components. By first probing an LM to identify feature-specific layers, our method iteratively regresses out lower-level representations to produce four nearly orthogonal embeddings for lexicon, syntax, meaning, and, critically, reasoning. We used these disentangled embeddings to model intracranial (ECoG) brain recordings from neurosurgical patients listening to natural speech. We show that: 1) This isolated reasoning embedding exhibits unique predictive power, accounting for variance in neural activity not explained by other linguistic features and even extending to the recruitment of visual regions beyond classical language areas.

Casey Harrell has had a set of electrodes embedded in his brain for almost three years. Harrell, who has amyotrophic lateral sclerosis (ALS) and is paralyzed, first used his brain-computer interface (BCI) to "speak" sentences with the help of a research team in 2023. Since then, Harrell has clocked thousands of hours of use. He can use the device largely independently, once he's been "plugged in" with the help of a carer. His team has added new features to it, and Harrell also uses it to surf the web and perform his job.

Researchers hope the experiments will pave the way for people with paralysis to explore virtual worlds or more intuitively control electric wheelchairs in this one. Peter Janssen at KU Leuven in Belgium and colleagues implanted three rhesus macaque ( Macaca mulatta) monkeys with BCIs. Crucially, each animal got three implants, each consisting of 96 electrodes, positioned in the primary motor, dorsal and ventral premotor cortex. The first area is commonly used in BCI research and relates to physical movement, but the latter two are thought to be involved in planning movement in a higher, more abstract way. Electrical signals from the implants were then interpreted by an AI model and used to control VR avatars as the monkeys watched a 3D monitor.

New silicon technology is enabling large-scale electrophysiological recordings in vivo from hundreds to thousands of channels. Interpreting these recordings requires scalable and accurate automated methods for spike sorting, which should minimize the time required for manual curation of the results. Here we introduce KiloSort, a new integrated spike sorting framework that uses template matching both during spike detection and during spike clustering. KiloSort models the electrical voltage as a sum of template waveforms triggered on the spike times, which allows overlapping spikes to be identified and resolved. Unlike previous algorithms that compress the data with PCA, KiloSort operates on the raw data which allows it to construct a more accurate model of the waveforms. Processing times are faster than in previous algorithms thanks to batch-based optimization on GPUs. We compare KiloSort to an established algorithm and show favorable performance, at much reduced processing times. A novel post-clustering merging step based on the continuity of the templates further reduced substantially the number of manual operations required on this data, for the neurons with nearzero error rates, paving the way for fully automated spike sorting of multichannel electrode recordings.

Deep learning based neural decoding from stereotactic electroencephalography (sEEG) would likely benefit from scaling up both dataset and model size. To achieve this, combining data across multiple subjects is crucial. However, in sEEG cohorts, each subject has a variable number of electrodes placed at distinct locations in their brain, solely based on clinical needs. Such heterogeneity in electrode number/placement poses a significant challenge for data integration, since there is no clear correspondence of the neural activity recorded at distinct sites between individuals. Here we introduce seegnificant: a training framework and architecture that can be used to decode behavior across subjects using sEEG data.

We present the Brain Treebank, a large-scale dataset of electrophysiological neural responses, recorded from intracranial probes while 10 subjects watched one or more Hollywood movies. Subjects watched on average 2.6 Hollywood movies, for an average viewing time of 4.3 hours, and a total of 43 hours. The audio track for each movie was transcribed with manual corrections. Word onsets were manually annotated on spectrograms of the audio track for each movie. Each transcript was automatically parsed and manually corrected into the universal dependencies (UD) formalism, assigning a part of speech to every word and a dependency parse to every sentence. In total, subjects heard over 38,000 sentences (223,000 words), while they had on average 168 electrodes implanted. This is the largest dataset of intracranial recordings featuring grounded naturalistic language, one of the largest English UD treebanks in general, and one of only a few UD treebanks aligned to multimodal features. We hope that this dataset serves as a bridge between linguistic concepts, perception, and their neural representations. To that end, we present an analysis of which electrodes are sensitive to language features while also mapping out a rough time course of language processing across these electrodes.

The Chinese automaker is racing ahead of global competitors--but don't expect to see those gains in the US anytime soon. Somehow, the whole thing got even faster. Earlier this month, Chinese automaker BYD announced that its Flash Chargers, first rolled out a year ago, can now charge some electric vehicle batteries from around 10 to 70 percent in five minutes, and from 10 to full in about nine. That's more than 600 miles of range in the time it takes to order a cappuccino and leave a nice tip. The new BYD chargers can add miles super quickly because they deliver up to 1,500 kilowatts (kW) per charge.