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Biology subjects

Khani, M.

Publications and source records attributed to Khani, M..

3 recordsLinked to original sources

MCWs (MiCroWire sorter): A new framework for automated and reliable spike sorting in human intracerebral recordings.

Efficient and accurate spike sorting is critical for isolating single neurons from extracellular recordings to distinguish neural activity of interest. However, while the electrodes and acquisition systems for non-human electrophysiology have been enhanced over the past decades to enable higher-yield single-neuron detections, those advances have not been translated into human electrophysiology. Single-wire electrodes are still ubiquitously used, and although acquisition systems have augmented their signal-to-noise ratio over the last 15 years, we are still limited by their low electrode count. Moreover, unlike non-human recordings, human recordings often take place in hospitals where different noise sources and subject breaks can compromise the recording quality during experimental sessions. To bridge this gap, this work presents an automatic, open-source spike sorting pipeline that leverages contemporary computational capabilities and is tailored to single-neuron recordings from humans acquired via microwires. The pipeline is implemented in both MATLAB and Python, ensuring accessibility and compatibility across computational environments. Its modular and comprehensive structure supports customization and even opportunities for new developments as per the requirements of the user and the application. One feature is a data-driven automatic module to remove narrow-band interference, besides electrical line noise, which can be an essential tool while recording in clinical settings, particularly for online processing implementations. Following spike detection, the pipeline implements an artifact rejection module that separates waveforms that are unlikely to be associated with actual spikes. Additionally, we introduce a configurable feature-extraction, clustering, and benchmarking framework that not only allows flexibility in employing user-defined or conventional algorithms, such as wavelet transform with superparamagnetic clustering, but can also evaluate multi-method agreement among the different sorters. The pipeline also utilizes established and novel quality metrics to support semiautomatic curation of isolated clusters. Furthermore, we can integrate the customized pipeline with experimental tasks by removing task-unrelated waveforms (e.g., during a break in a task) and prevent over-clustering with the aid of metrics for comparing response profiles. Thus, the presented pipeline addresses the three-pronged objectives of algorithm-adaptability, rigorous validation, and human single-neuron recording optimization to support clinical and cognitive neuroscience applications.

neuroscience↗

CARDBiomedBench: A Benchmark for Evaluating Large Language Model Performance in Biomedical Research

BackgroundsBiomedical research requires sophisticated understanding and reasoning across multiple specializations. While large language models (LLMs) show promise in scientific applications, their capability to safely and accurately support complex biomedical research remains uncertain. MethodsWe present CARDBiomedBench, a novel question-and-answer benchmark for evaluating LLMs in biomedical research. For our pilot implementation, we focus on neurodegenerative diseases (NDDs), a domain requiring integration of genetic, molecular, and clinical knowledge. The benchmark combines expert-annotated question-answer (Q/A) pairs with semi-automated data augmentation, drawing from authoritative public resources including drug development data, genome-wide association studies (GWAS), and Summary-data based Mendelian Randomization (SMR) analyses. We evaluated seven private and open-source LLMs across ten biological categories and nine reasoning skills, using novel metrics to assess both response quality and safety. ResultsOur benchmark comprises over 68,000 Q/A pairs, enabling robust evaluation of LLM performance. Current state-of-the-art models show significant limitations: models like Claude-3.5-Sonnet demonstrates excessive caution (Response Quality Rate: 25% [95% CI: 25% {+/-} 1], Safety Rate: 76% {+/-} 1), while others like ChatGPT-4o exhibits both poor accuracy and unsafe behavior (Response Quality Rate: 37% {+/-} 1, Safety Rate: 31% {+/-} 1). These findings reveal fundamental gaps in LLMs ability to handle complex biomedical information. ConclusionCARDBiomedBench establishes a rigorous standard for assessing LLM capabilities in biomedical research. Our pilot evaluation in the NDD domain reveals critical limitations in current models ability to safely and accurately process complex scientific information. Future iterations will expand to other biomedical domains, supporting the development of more reliable AI systems for accelerating scientific discovery.

bioinformatics↗

Intrathecal catheter implantation decreases cerebrospinal fluid dynamics in cynomolgus monkeys

A detailed understanding of the CSF dynamics is essential for testing and evaluation of intrathecal drug delivery. Preclinical work using large-animal models (e.g., monkeys, dogs and sheep) has great utility for defining spinal drug distribution/pharmacokinetics and provide an important tool for defining safety. In this study, we investigated the impact of catheter implantation in the sub-dural space on CSF flow dynamics in Cynomolgus monkeys. Magnetic resonance imaging (MRI) was performed before and after catheter implantation to quantify the differences based on catheter placement location in the cervical compared to the lumbar spine. Several geometric and hydrodynamic parameters were calculated based on the 3D segmentation and flow analysis. Hagen-Poiseuille equation was used to investigate the impact of catheter implantation on flow reduction and hydraulic resistance. A linear mixed-effects model was used in this study to investigate if there is a statistically significant difference between cervical and lumbar implantation, or between two MRI time points. Results showed that geometric parameters did not change statistically across MRI measurement time points and did not depend on catheter location. However, catheter insertion did have a significant impact on the hydrodynamic parameters and the effect was greater with the cervical implantation. CSF flow rate decreased up to 54.7% when the catheter located in the cervical region. The maximum flow rate reduction in the lumbar implantation group was 21%. Overall, lumbar catheter implantation disrupted CSF dynamics to a lesser degree than cervical catheter implantation and this effect remained up to two weeks post-catheter implantation

pharmacology and toxicology↗