Biology subjects

Thapa, B. R.

Publications and source records attributed to Thapa, B. R..

6 recordsLinked to original sources

bioRxiv2026

Healthy-to-Stroke Translation of EEG-Based BMIs: EEG Characterization and Reinforcement Learning-Based Decoder Evaluation

PurposeEEG-based brain-machine interfaces (BMIs) may support assistive technologies for individuals with stroke-related motor impairment by translating neural activity into control commands for external devices. However, post-stroke neural reorganization and interindividual EEG variability challenge reliable decoding. This study characterized motor imagery EEG features in healthy and acute stroke participants and evaluated whether population-trained Q-learning Kernel Temporal Difference (Q-KTD) decoders could improve individual stroke decoding through transfer learning. These analyses assess the feasibility of healthy-to-stroke translation for EEG-based BMI neural decoding. Materials and MethodsPublicly available motor imagery EEG datasets from healthy participants (n = 109) and individuals with acute stroke (n = 50) were analyzed using left- and right-hand motor imagery trials. The datasets were selected because of their relatively large sample sizes and comparable motor imagery tasks. EEG characterization included baseline and motor imagery-period band power, ERD/ERS, hemispheric asymmetry, and time-frequency representations. For Q-learning Kernel Temporal Difference (Q-KTD) decoding, filtered time-domain EEG from 0- 0.5 s after motor imagery onset was used as the neural-state input. A Q-KTD model trained on the healthy population was transferred to individual stroke participants, and repeated Monte Carlo simulations compared decoding performance with and without transfer learning across multiple learning epochs. ResultsHealthy and acute stroke participants showed shared motor imagery-related EEG structure, including post-onset mu-band suppression, while the stroke group exhibited greater interparticipant variability, more diffuse time- frequency modulation, and altered hemispheric asymmetry. No channel-level healthy-stroke differences in windowed band power remained significant after false discovery rate correction. Healthy-source transfer learning improved first-epoch Q-KTD success rates in 29 of 50 stroke participants (58%). Across all participants, mean success rate increased from 49.46% without transfer learning to 51.82% with transfer learning. Among participants showing positive transfer, the mean gain was 7.34% and the maximum gain was 18.75%. However, 21 participants showed negative transfer, demonstrating substantial subject-level variability. ConclusionHealthy-source Q-KTD transfer learning improved first-epoch motor imagery BMI decoding for a majority of acute stroke participants, supporting the offline feasibility of population-informed Q-KTD decoding in stroke. These early performance gains may reduce subject-specific calibration burden, although substantial interparticipant variability and negative transfer indicate the need for individualized transfer-selection or adaptation strategies. Assistive Technology ImplicationsO_LIEEG-based brain-machine interfaces may support assistive technologies for individuals with stroke-related motor impairment by translating motor imagery-related neural activity into control commands for external devices. C_LIO_LIHealthy-to-stroke transfer learning may improve early BMI neural-decoder performance and potentially reduce the amount of subject-specific calibration required. C_LIO_LIThe findings support the offline feasibility of Q-KTD for motor imagery BMI neural decoding in individuals with acute stroke. C_LIO_LISubstantial interparticipant variability and negative transfer suggest that individualized source-model selection or adaptation strategies may be needed for reliable post-stroke BMI implementation. C_LIO_LIPhysiological EEG characteristics, including ERD/ERS and hemispheric asymmetry, may provide candidate markers for future transfer-selection strategies, although their predictive value requires direct validation. C_LI

bioengineering↗

bioRxiv2025

A Large Electroencephalogram Database of Freewill Reaching and Grasping Tasks for Brain Machine Interfaces

Brain machine interfaces (BMIs) offer great potential to improve the quality of life for individuals with neurological disorders or severe motor impairments. Among various neural recording modalities, electroencephalogram (EEG) is particularly favorable for BMIs due to its noninvasive nature, portability, and high temporal resolution. Existing EEG datasets for BMIs are often limited to experimental settings that fail to address subjects freewill in decision making. We present a large EEG dataset, containing a total of 6808 trials, recorded from 23 healthy young adults (8 females and 15 males with an age range from 18 to 24 years) while performing reaching and grasping tasks, where the target object is freely chosen at their desired pace according to their own will. This EEG dataset provides a realistic representation of reaching and grasping movement, making it useful for developing practical BMIs.

neuroscience↗

bioRxiv2024

Targeted pre-conditioning and cell transplantation in the murine lower respiratory tract

Transplantation of airway basal stem cells could achieve a durable cure for genetic diseases of the airway, such as cystic fibrosis and primary ciliary dyskinesia. Recent work demonstrated the potential of primary- and pluripotent stem cell (PSC)-derived basal cells to efficiently engrai into the mouse trachea aier injury. However, there are many hurdles to overcome in translating these approaches to humans including developing safe and efficient methods for delivery in larger animal models. We propose a model which targets preconditioning and cell-delivery to the intrapulmonary airways utilizing a micro- bronchoscope for delivery. The detergent polidocanol was adapted for distal lung pre-conditioning, inducing intrapulmonary airway epithelial denudation by 5 and 24-hours post-delivery. While initial re- epithelialization of airways occurred later than tracheas, complete repair was observed within 7-days. Both PSC-derived and primary basal cells delivered via micro-bronchoscope post-polidocanol injury engraied in tracheas and intrapulmonary airways, respectively. Transplanted cells differentiated into ciliated and secretory lineages while maintaining a population of basal cells. These findings demonstrate the utility of bronchoscopically targeted pre-conditioning and cell delivery to the conducting intra- pulmonary airways, providing an important framework for pre-clinical translation of approaches for engineered airway epithelial regeneration.

cell biology↗

bioRxiv2023

Generation of human alveolar epithelial type I cells from pluripotent stem cells

In the distal lung, alveolar epithelial type I cells (AT1s) comprise the vast majority of alveolar surface area and are uniquely flattened to allow the diffusion of oxygen into the capillaries. This structure along with a quiescent, terminally differentiated phenotype has made AT1s particularly challenging to isolate or maintain in cell culture. As a result, there is a lack of established models for the study of human AT1 biology, and in contrast to alveolar epithelial type II cells (AT2s), little is known about the mechanisms regulating their differentiation. Here we engineer a human in vitro AT1 model system through the directed differentiation of induced pluripotent stem cells (iPSC). We first define the global transcriptomes of primary adult human AT1s, suggesting gene-set benchmarks and pathways, such as Hippo-LATS-YAP/TAZ signaling, that are enriched in these cells. Next, we generate iPSC-derived AT2s (iAT2s) and find that activating nuclear YAP signaling is sufficient to promote a broad transcriptomic shift from AT2 to AT1 gene programs. The resulting cells express a molecular, morphologic, and functional phenotype reminiscent of human AT1 cells, including the capacity to form a flat epithelial barrier which produces characteristic extracellular matrix molecules and secreted ligands. Our results indicate a role for Hippo-LATS-YAP signaling in the differentiation of human AT1s and demonstrate the generation of viable AT1-like cells from iAT2s, providing an in vitro model of human alveolar epithelial differentiation and a potential source of human AT1s that until now have been challenging to viably obtain from patients.

cell biology↗

bioRxiv2022

Directed differentiation of mouse pluripotent stem cells into functional lung-specific mesenchyme

The successful generation of endodermal, ectodermal, and most mesodermal lineages from pluripotent stem cells has resulted in basic discoveries and regenerative medicine clinical trials of cell-based therapies. In contrast, the derivation of tissue-specific mesenchyme via directed differentiation in vitro has markedly lagged, due in part to a limited understanding of the signaling pathways regulating in vivo mesenchymal development and a lack of specific markers or reporters able to purify such lineages. The derivation of lung-specific mesenchyme is a particularly important goal since this tissue plays important roles in lung development and respiratory disease pathogenesis. Here we generate a mouse induced pluripotent stem cell (iPSC) line carrying a lung-specific mesenchymal reporter/lineage tracer facilitating the tracking and purification of engineered lung-specific mesenchyme. We identify the key signaling pathways (RA and Shh) necessary to specify lung mesenchyme from lateral plate mesodermal precursors and find that mouse iPSC-derived lung mesenchyme (iLM) expresses the molecular and functional phenotypes of primary developing lung mesenchyme. Purified iLM can be recombined with separately engineered lung epithelial progenitors, self-organizing into 3-dimensional organoids featuring significantly augmented structural complexity and lineage purity, including interacting juxtaposed layers of epithelium and mesenchyme. Co-culture with iLM increases the yield of lung epithelial progenitors and impacts epithelial and mesenchymal differentiation programs, suggesting functional epithelial-mesenchymal crosstalk. Our iPSC-derived population thus expresses key features of developing lung mesenchyme, providing an inexhaustible source of cells for studying lung development, modeling diseases, and developing therapeutics.

developmental biology↗

bioRxiv2022

Durable alveolar engraftment of PSC-derived lung epithelial cells into immunocompetent mice

Durable reconstitution of the injured distal lung epithelium with pluripotent stem cell (PSC) derivatives, if realized, would represent a promising potential therapy for diseases that result from alveolar damage. Here we differentiate murine PSCs in vitro into self-renewing lung epithelial progenitors able to engraft into the injured distal lung epithelium of immunocompetent, syngeneic mouse recipients. Emulating the roadmap of the developing embryo, we generate transplantable PSC-derived Nkx2-1+/Sox9+ lung epithelial progenitors that are highly similar to cultured primary embryonic distal lung bud tip progenitors. These cells display a stable phenotype after frozen archiving or extensive expansion in culture, providing a nearly inexhaustible source of cells that can be engrafted into syngeneic injured mouse lungs without the need for immunosuppression. After transplantation PSC-derived tip-like progenitors downregulate Sox9 and mature in the distal lung, upregulating alveolar type 2 cell markers or assuming the flat morphology and molecular phenotype of terminally differentiated alveolar type 1 cells. After months in vivo, donor-derived cells retain their alveolar epithelial type 2-like and type 1-like phenotypes, as characterized by single cell RNA sequencing, ultrastructural analyses, in vivo histologic profiling, and ex vivo organoid assays that demonstrate continued capacity of the engrafted cells to proliferate and differentiate. These results indicate durable reconstitution of the distal lungs facultative progenitor and differentiated epithelial cell compartments in vivo with PSC-derived cells, thus establishing a novel model for pulmonary cell therapy which can be utilized to better understand the mechanisms and utility of engraftment prior to future clinical studies.

cell biology↗