All Publications

  • Daily vibrotactile stimulation from a wearable device exhibits equal or greater spasticity relief than botulinum toxin in stroke. Archives of physical medicine and rehabilitation Seim, C., Chen, B., Han, C., Vacek, D., Lowber, A., Lansberg, M., Okamura, A. M. 2023


    OBJECTIVE: To test the feasibility and efficacy of the VibroTactile Stimulation (VTS) Glove, a wearable device that provides vibrotactile stimulation to the impaired limb to reduce spastic hypertonia.DESIGN: Prospective two-arm intervention study - including one group of patients who use Botulinum toxin (BTX-A) for spasticity and one group of patients who do not use BTX-A.SETTING: Participants were recruited through rehabilitation and neurology clinics.PARTICIPANTS: Patients with chronic stroke (N=20; mean age=54 years, mean time since stroke=6.9 years). Patients who were previously receiving the standard of care (BTX-A injection) were eligible to participate, and started the intervention 12 weeks after their last injection.INTERVENTION: Participants were instructed to use the VTS Glove for three hours daily, at home or during everyday activities, for 8 weeks.MAIN OUTCOME MEASURES: Spasticity was assessed with the Modified Ashworth Scale and the Modified Tardieu Scale at baseline and then at 2-week intervals for 12 weeks. Primary outcomes were the difference from baseline and at week 8 (end of VTS Glove use) and week 12 (four weeks after stopping VTS Glove use). Patients who were receiving BTX-A were also assessed during the 12 weeks preceding the start of VTS Glove use to monitor the effect of BTX-A on spastic hypertonia. Range of motion and participant feedback were also studied.RESULTS: A clinically meaningful difference in spastic hypertonia was found during and after daily VTS Glove use. Modified Ashworth and Modified Tardieu scores were reduced by an average of 0.9 (p=0.0014) and 0.7 (p=0.0003), respectively, at week 8 of daily VTS Glove use, and by 1.1 (p=0.00025) and 0.9 (p=0.0001), respectively, one month after stopping VTS Glove use. For participants who used BTX-A, 6 out of 11 showed greater change in Modified Ashworth ratings during VTS Glove use (Mean=-1.8 vs. Mean=-1.6 with BTX-A) and 8 out of 11 showed their lowest level of symptoms during VTS Glove use (vs. BTX-A).CONCLUSIONS: Daily stimulation from the VTS Glove provides relief of spasticity and hypertonia. For more than half of participants who had regularly used BTX-A, the VTS Glove provided equal or greater symptom relief.

    View details for DOI 10.1016/j.apmr.2023.03.031

    View details for PubMedID 37149017

  • Relief of post-stroke spasticity with acute vibrotactile stimulation: controlled crossover study of muscle and skin stimulus methods. Frontiers in human neuroscience Seim, C., Chen, B., Han, C., Vacek, D., Wu, L. S., Lansberg, M., Okamura, A. 2023; 17: 1206027


    Background: Prior work suggests that vibratory stimulation can reduce spasticity and hypertonia. It is unknown which of three predominant approaches (stimulation of the spastic muscle, antagonist muscle, or cutaneous regions) most reduces these symptoms.Objective: Determine which vibrotactile stimulation approach is most effective at reducing spastic hypertonia among post-stroke patients.Methods: Sham-controlled crossover study with random assignment of condition order in fourteen patients with post-stroke hand spasticity. All patients were studied in four conditions over four visits: three stimulation conditions and a sham control. The primary outcome measure was the Modified Ashworth Scale, and the secondary outcome measure was the Modified Tardieu Scale measured manually and using 3D motion capture. For each condition, measures of spastic hypertonia were taken at four time points: baseline, during stimulation, after stimulation was removed, and after a gripping exercise.Results: A clinically meaningful difference in spastic hypertonia was found during and after cutaneous stimulation of the hand. Modified Ashworth and Modified Tardieu scores were reduced by a median of 1.1 (SD = 0.84, p = 0.001) and 0.75 (SD = 0.65, p = 0.003), respectively, during cutaneous stimulation, and by 1.25 (SD = 0.94, p = 0.001) and 0.71 (SD = 0.67, p = 0.003), respectively, at 15 min after cutaneous stimulation. Symptom reductions with spastic muscle stimulation and antagonist muscle stimulation were non-zero but not significant. There was no change with sham stimulation.Conclusions: Cutaneous vibrotactile stimulation of the hand provides significant reductions in spastic hypertonia, compared to muscle stimulation.Clinical trial registration:, identifier: NCT03814889.

    View details for DOI 10.3389/fnhum.2023.1206027

    View details for PubMedID 37706171

  • Fly Cell Atlas: A single-nucleus transcriptomic atlas of the adult fruit fly. Science (New York, N.Y.) Li, H., Janssens, J., De Waegeneer, M., Kolluru, S. S., Davie, K., Gardeux, V., Saelens, W., David, F. P., Brbic, M., Spanier, K., Leskovec, J., McLaughlin, C. N., Xie, Q., Jones, R. C., Brueckner, K., Shim, J., Tattikota, S. G., Schnorrer, F., Rust, K., Nystul, T. G., Carvalho-Santos, Z., Ribeiro, C., Pal, S., Mahadevaraju, S., Przytycka, T. M., Allen, A. M., Goodwin, S. F., Berry, C. W., Fuller, M. T., White-Cooper, H., Matunis, E. L., DiNardo, S., Galenza, A., O'Brien, L. E., Dow, J. A., FCA Consortium, Jasper, H., Oliver, B., Perrimon, N., Deplancke, B., Quake, S. R., Luo, L., Aerts, S., Agarwal, D., Ahmed-Braimah, Y., Arbeitman, M., Ariss, M. M., Augsburger, J., Ayush, K., Baker, C. C., Banisch, T., Birker, K., Bodmer, R., Bolival, B., Brantley, S. E., Brill, J. A., Brown, N. C., Buehner, N. A., Cai, X. T., Cardoso-Figueiredo, R., Casares, F., Chang, A., Clandinin, T. R., Crasta, S., Desplan, C., Detweiler, A. M., Dhakan, D. B., Dona, E., Engert, S., Floc'hlay, S., George, N., Gonzalez-Segarra, A. J., Groves, A. K., Gumbin, S., Guo, Y., Harris, D. E., Heifetz, Y., Holtz, S. L., Horns, F., Hudry, B., Hung, R., Jan, Y. N., Jaszczak, J. S., Jefferis, G. S., Karkanias, J., Karr, T. L., Katheder, N. S., Kezos, J., Kim, A. A., Kim, S. K., Kockel, L., Konstantinides, N., Kornberg, T. B., Krause, H. M., Labott, A. T., Laturney, M., Lehmann, R., Leinwand, S., Li, J., Li, J. S., Li, K., Li, K., Li, L., Li, T., Litovchenko, M., Liu, H., Liu, Y., Lu, T., Manning, J., Mase, A., Matera-Vatnick, M., Matias, N. R., McDonough-Goldstein, C. E., McGeever, A., McLachlan, A. D., Moreno-Roman, P., Neff, N., Neville, M., Ngo, S., Nielsen, T., O'Brien, C. E., Osumi-Sutherland, D., Ozel, M. N., Papatheodorou, I., Petkovic, M., Pilgrim, C., Pisco, A. O., Reisenman, C., Sanders, E. N., Dos Santos, G., Scott, K., Sherlekar, A., Shiu, P., Sims, D., Sit, R. V., Slaidina, M., Smith, H. E., Sterne, G., Su, Y., Sutton, D., Tamayo, M., Tan, M., Tastekin, I., Treiber, C., Vacek, D., Vogler, G., Waddell, S., Wang, W., Wilson, R. I., Wolfner, M. F., Wong, Y. E., Xie, A., Xu, J., Yamamoto, S., Yan, J., Yao, Z., Yoda, K., Zhu, R., Zinzen, R. P. 2022; 375 (6584): eabk2432


    For more than 100 years, the fruit fly Drosophila melanogaster has been one of the most studied model organisms. Here, we present a single-cell atlas of the adult fly, Tabula Drosophilae, that includes 580,000 nuclei from 15 individually dissected sexed tissues as well as the entire head and body, annotated to >250 distinct cell types. We provide an in-depth analysis of cell type-related gene signatures and transcription factor markers, as well as sexual dimorphism, across the whole animal. Analysis of common cell types between tissues, such as blood and muscle cells, reveals rare cell types and tissue-specific subtypes. This atlas provides a valuable resource for the Drosophila community and serves as a reference to study genetic perturbations and disease models at single-cell resolution.

    View details for DOI 10.1126/science.abk2432

    View details for PubMedID 35239393

  • Temporal evolution of single-cell transcriptomes of Drosophila olfactory projection neurons. eLife Xie, Q., Brbic, M., Horns, F., Kolluru, S. S., Jones, R. C., Li, J., Reddy, A. R., Xie, A., Kohani, S., Li, Z., McLaughlin, C. N., Li, T., Xu, C., Vacek, D., Luginbuhl, D. J., Leskovec, J., Quake, S. R., Luo, L., Li, H. 2021; 10


    Neurons undergo substantial morphological and functional changes during development to form precise synaptic connections and acquire specific physiological properties. What are the underlying transcriptomic bases? Here, we obtained the single-cell transcriptomes of Drosophila olfactory projection neurons (PNs) at four developmental stages. We decoded the identity of 21 transcriptomic clusters corresponding to 20 PN types and developed methods to match transcriptomic clusters representing the same PN type across development. We discovered that PN transcriptomes reflect unique biological processes unfolding at each stage-neurite growth and pruning during metamorphosis at an early pupal stage; peaked transcriptomic diversity during olfactory circuit assembly at mid-pupal stages; and neuronal signaling in adults. At early developmental stages, PN types with adjacent birth order share similar transcriptomes. Together, our work reveals principles of cellular diversity during brain development and provides a resource for future studies of neural development in PNs and other neuronal types.

    View details for DOI 10.7554/eLife.63450

    View details for PubMedID 33427646

  • Single-cell transcriptomes of developing and adult olfactory receptor neurons in Drosophila. eLife McLaughlin, C. N., Brbić, M. n., Xie, Q. n., Li, T. n., Horns, F. n., Kolluru, S. S., Kebschull, J. M., Vacek, D. n., Xie, A. n., Li, J. n., Jones, R. C., Leskovec, J. n., Quake, S. R., Luo, L. n., Li, H. n. 2021; 10


    Recognition of environmental cues is essential for the survival of all organisms. Transcriptional changes occur to enable the generation and function of the neural circuits underlying sensory perception. To gain insight into these changes, we generated single-cell transcriptomes of Drosophila olfactory- (ORNs), thermo-, and hygro-sensory neurons at an early developmental and adult stage using single-cell and single-nucleus RNA sequencing. We discovered that ORNs maintain expression of the same olfactory receptors across development. Using receptor expression and computational approaches, we matched transcriptomic clusters corresponding to anatomically and physiologically defined neuron types across multiple developmental stages. We found that cell-type-specific transcriptomes partly reflected axon trajectory choices in development and sensory modality in adults. We uncovered stage-specific genes that could regulate the wiring and sensory responses of distinct ORN types. Collectively, our data reveal transcriptomic features of sensory neuron biology and provide a resource for future studies of their development and physiology.

    View details for DOI 10.7554/eLife.63856

    View details for PubMedID 33555999

  • Single-Cell Transcriptomes Reveal Diverse Regulatory Strategies for Olfactory Receptor Expression and Axon Targeting. Current biology : CB Li, H. n., Li, T. n., Horns, F. n., Li, J. n., Xie, Q. n., Xu, C. n., Wu, B. n., Kebschull, J. M., McLaughlin, C. N., Kolluru, S. S., Jones, R. C., Vacek, D. n., Xie, A. n., Luginbuhl, D. J., Quake, S. R., Luo, L. n. 2020


    The regulatory mechanisms by which neurons coordinate their physiology and connectivity are not well understood. The Drosophila olfactory receptor neurons (ORNs) provide an excellent system to investigate this question. Each ORN type expresses a unique olfactory receptor, or a combination thereof, and sends their axons to a stereotyped glomerulus. Using single-cell RNA sequencing, we identified 33 transcriptomic clusters for ORNs and mapped 20 to their glomerular types, demonstrating that transcriptomic clusters correspond well with anatomically and physiologically defined ORN types. Each ORN type expresses hundreds of transcription factors. Transcriptome-instructed genetic analyses revealed that (1) one broadly expressed transcription factor (Acj6) only regulates olfactory receptor expression in one ORN type and only wiring specificity in another type, (2) one type-restricted transcription factor (Forkhead) only regulates receptor expression, and (3) another type-restricted transcription factor (Unplugged) regulates both events. Thus, ORNs utilize diverse strategies and complex regulatory networks to coordinate their physiology and connectivity.

    View details for DOI 10.1016/j.cub.2020.01.049

    View details for PubMedID 32059767