Towards a Pseudo-Labeling Workflow for Celltype-Classification from Explanted Brain Slice Recordings
Authors: Cora Jostock, Jonas Ort, Henner Koch, Gregor Schiele, Andreas Erbslöh
Abstract
This paper proposes an unsupervised workflow to pseudo-label extracellular spikes from human brain slice MEA recordings into two putative cell types: pyramidal cells and interneurons. Here, the raw data from the data acquisition system is used and processed. The pipeline for pre-processing includes bandpass filtering, threshold--based spike detection, frame alignment and normalization. In the ML workflow, dimensionality reduction (PCA, t-SNE, UMAP), clustering (GMM, k-means). To achieve an online system, template matching and OSort under varying curation strictness is also considered. All pipelines are evaluated by different cluster quality with within-cluster Pearson correlation, Silhouette score, and Calinski-Harabasz index. Applying stricter curation improves separation at some cost to inclusivity.
Establishing large-scale, high-resolution neural connectivity maps is fundamental to elucidating the structural basis of brain function. However, when processing terabyte- or petabyte-scale electron microscopy data, over-segmentation inherent in automated reconstruction algorithms remains a critical bottleneck, requiring extensive manual proofreading spanning person-years. To alleviate the heavy reliance on annotated data and the limited flexibility of conventional tracing methods, we propose a training-free, targeted neuron tracing framework. Specifically, we introduce a skeleton-guided Heuristic Spatial Search paradigm that leverages geometric priors to iteratively reconstruct neuronal morphologies through a probing-verification cycle. To achieve robust zero-shot semantic verification, we further develop a Dimension-Aware Semantic Verification strategy built upon the foundation model NeuroSAM 2. This strategy resolves intra-slice splits via Planar Ensemble Consensus and inter-slice splits via Axial Spatio-Temporal Propagation. Notably, we integrate the proposed workflow into the Neuroglancer visualization platform, enabling an interactive human-in-the-loop proofreading system. Experimental results demonstrate that the proposed method outperforms supervised baselines and reduces manual proofreading time by 33.4%. The source code is publicly available at https://github.com/HeadLiuYun/Probe-EM.
Robust and accurate neural decoders are integral to neurotechnologies such as brain-computer interfaces and closed-loop experiments. Recent work has shown that tokenizing neural data at the spike level facilitates multi-session pretraining and delivers state-of-the-art decoding performance. However, current spike-based models are restricted to supervised learning (SL), limiting training to datasets with paired behavioural labels. To address this limitation, we introduce MOJO (Masked autOencoder-based JOint training), a training framework for spike-tokenizing models that jointly leverages self-supervised learning (SSL) via masked autoencoding and SL objectives. We evaluate MOJO on three spiking datasets spanning monkey motor cortex during reaching tasks and multi-regional mouse recordings during vision and decision making tasks, demonstrating superior performance over purely SL-trained models. This improvement is especially pronounced when training with limited labelled data, particularly in few-shot finetuning, where only a small amount of labelled data from a new session is available. Incorporating SSL also yields more interpretable neuronal representations, improving performance on brain region classification and spike-statistics prediction without explicit optimization for these tasks. We further show that MOJO generalizes beyond spiking data to human electrocorticography during speech, where it continues to outperform purely SL-trained models and achieves performance comparable to neuro-foundation models (NFMs) designed specifically for continuous signals. Overall, augmenting spike-tokenizing models with SSL improves performance in label-impoverished settings and enables the use of unlabelled data across various tasks and species, while generalizing to other neural modalities. These results suggest a path towards more flexible and scalable data usage when training NFMs.
Ximeng Mao, Nanda H. Krishna, Avery Hee-Woon Ryoo +2
Event identification in continuous neural recordings is a critical task in neuroscience. Decoding in EEG is dominated by classifying windows aligned to known event onsets. However, while available in controlled experiments, such onsets are absent in continuous real-world monitoring. Here, we introduce DANCE, a deep learning pipeline that frames neural decoding as a set-prediction problem and jointly detects and classifies events directly from raw, unaligned signals. Evaluated separately on ten datasets curated from the literature with a wide variety of event types (ranging from milliseconds to minutes in duration), our model outperforms existing methods on a broad range of cognitive, clinical and BCI tasks. This single architecture establishes a new state of the art in the competitive task of seizure monitoring and matches the accuracy of onset-informed models for BCI tasks. Overall, our method marks a step towards end-to-end asynchronous neural decoding models