Biology subjects

Pritchard, A. L.

Publications and source records attributed to Pritchard, A. L..

4 recordsLinked to original sources

bioRxiv2026

A generalizable speech neuroprosthesis

Intracortical brain-computer interfaces (BCIs) can restore communication to people with vocal tract paralysis by decoding cortical activity during attempted speech into text. State-of-the-art systems pairing neural-to-phoneme decoders with phoneme-to-word language models have achieved word error rates (WERs) as low as 1%, but only after collecting thousands of sentences of training data. Shortening the data collection process would facilitate scaling this new technology by reducing the time from device implant to high-accuracy communication. Here we introduce a transformer-based decoder model trained jointly across six intracortical speech BCI participants. For every participant -- regardless of sex, disease etiology, or attempted speaking strategy -- a multi-user model decoded speech more accurately (over 50% lower relative WER on average) than models trained on individual users data. Notably, the multi-user model could be finetuned on fewer than 200 sentences from a held-out user to achieve a WER below 7%. These results reveal how to pool intracortical data across people to yield more accurate, generalizable, and rapidly-deployable decoding models.

bioengineering↗

bioRxiv2025

Encoding of speech modes and loudness in ventral precentral gyrus

The ability to vary the mode and loudness of speech is an important part of the expressive range of human vocal communication. However, the encoding of these behaviors in the ventral precentral gyrus (vPCG) has not been studied at the resolution of neuronal firing rates. We investigated this in two participants who had intracortical microelectrode arrays implanted in their vPCG as part of a speech neuroprosthesis clinical trial. Neuronal firing rates modulated strongly in vPCG as a function of attempted mimed, whispered, normal or loud speech. At the neural ensemble level, mode/loudness and phonemic content were encoded in distinct neural subspaces. Attempted mode/loudness could be decoded from vPCG with an accuracy of 94% and 89% for two participants respectively, and corresponding neural preparatory activity could be detected hundreds of milliseconds before speech onset. We then developed a closed-loop loudness decoder that achieved 94% online accuracy in modulating a brain-to-text speech neuroprosthesis output based on attempted loudness. These findings demonstrate the feasibility of decoding mode and loudness from vPCG, paving the way for speech neuroprostheses capable of synthesizing more expressive speech.

neuroscience↗

bioRxiv2024

A mosaic of whole-body representations in human motor cortex

Understanding how the body is represented in motor cortex is key to understanding how the brain controls movement. The precentral gyrus (PCG) has long been thought to contain largely distinct regions for the arm, leg and face (represented by the "motor homunculus"). However, mounting evidence has begun to reveal a more intermixed, interrelated and broadly tuned motor map. Here, we revisit the motor homunculus using microelectrode array recordings from 20 arrays that broadly sample PCG across 8 individuals, creating a comprehensive map of human motor cortex at single neuron resolution. We found whole-body representations throughout all sampled points of PCG, contradicting traditional leg/arm/face boundaries. We also found two speech-preferential areas with a broadly tuned, orofacial-dominant area in between them, previously unaccounted for by the homunculus. Throughout PCG, movement representations of the four limbs were interlinked, with homologous movements of different limbs (e.g., toe curl and hand close) having correlated representations. Our findings indicate that, while the classic homunculus aligns with each areas preferred body region at a coarse level, at a finer scale, PCG may be better described as a mosaic of functional zones, each with its own whole-body representation.

neuroscience↗

bioRxiv2020

The deacylase SIRT5 supports melanoma viability by regulating chromatin dynamics

Cutaneous melanoma remains the most lethal skin cancer, and ranks third among all malignancies in terms of years of life lost. Despite the advent of immune checkpoint and targeted therapies, only roughly half of patients with advanced melanoma achieves a durable remission. SIRT5 is a member of the sirtuin family of protein deacylases that regulate metabolism and other biological processes. Germline Sirt5 deficiency is associated with mild phenotypes in mice. Here we show that SIRT5 is required for proliferation and survival across all cutaneous melanoma genotypes tested, as well as uveal melanoma, a genetically distinct melanoma subtype that arises in the eye and is incurable once metastatic. Likewise, SIRT5 is required for efficient tumor formation by melanoma xenografts and in an autochthonous mouse Braf;Pten-driven melanoma model. Via metabolite and transcriptomic analyses, we find that SIRT5 is required to maintain histone acetylation and methylation levels in melanoma cells, thereby promoting proper gene expression. SIRT5-dependent genes notably include MITF, a key lineage-specific survival oncogene in melanoma, and the c-MYC proto-oncogene. SIRT5 may represent a novel, druggable genotype-independent addiction in melanoma.

cancer biology↗