Timothy A. Machado, PhD

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Presidential Assistant Professor
Department: Neuroscience
Graduate Group Affiliations

Contact information
Department of Neuroscience
3450 Hamilton Walk
Stemmler Hall, Room G10
Philadelphia, PA 19104
Lab: (215) 573-8815
BS (Cognitive Science, specialization in Neuroscience)
University of California, San Diego, 2008.
PhD (Neurobiology and Behavior)
Columbia University, 2015.
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Description of Research Expertise

How do motor command pathways interact to generate specific movements?

Complex movements arise from the concerted action of many neural circuits distributed across the brain that combine sensory information, memories of past experiences, and internal state. In contrast, simpler reflexive actions can be driven by short neural pathways that reside entirely in the brainstem or spinal cord. In between these two extremes of behavioral complexity are actions that may be driven by different neural pathways in different contexts. My laboratory uses a combination of new multiregion neural recording techniques, tissue clearing methods, and computational data analysis to study how motor command pathways are recruited during these kinds of behaviors. The results from our work will lead to a better understanding of how neural computation produces behavior—and will inform new approaches for treating neurological conditions and for building brain machine interfaces.

Past studies have shown that many parallel pathways that arise in different regions across the brain are each involved in driving specific movements. But until recently, it was difficult to study how these parallel pathways interact with each other on a moment-to-moment basis to produce behavior. This is because it was not straightforward to simultaneously record from large numbers of neurons in distinct regions. Thanks to recent advances in neural recording technology, we are now able to simultaneously measure the commands sent by different brain areas during different kinds of movements. This lets us study how motor command syntax might change as a function of changing brain state (e.g. with thirst or arousal), or as a consequence of neurodegenerative disease.

Prior to starting my laboratory, I was a postdoctoral working in the Deisseroth Lab at Stanford. Before that, I started a company called CTRL-labs that used ideas related to my doctoral work to build non-invasive technologies for decoding motor intention. I went to graduate school at Columbia where I studied spinal motor circuits.

Selected Publications

Machado TA*, Kauvar IV*, Deisseroth K.: Multiregion neuronal activity: the forest and the trees. Nat Rev Neurosci Oct 2022 Notes: * Denotes equal author contribution.

Chandrashekhar V, Tward DJ, Crowley D, Crow AK, Wright MA, Hsueh BY, Gore F, Machado TA, Branch A, Rosenblum JS, Deisseroth K, Vogelstein JT.: CloudReg: automatic terabyte-scale cross-modal brain volume registration. Nature Methods 18: 845-846, 2021.

Kauvar IV*, Machado TA*, Yuen E, Kochalka J, Choi M, Allen WE, Wetzstein G, Deisseroth K.: Cortical Observation by Synchronous Multifocal Optical Sampling Reveals Widespread Population Encoding of Actions. Neuron 107: 351-367, Jul 2020 Notes: * Denotes equal author contribution.

Marshel JH*, Kim YS*, Machado TA*, Quirin S*, Benson B, Kadmon J, Raja C, Chibukhchyan A, Ramakrishnan C, Inoue M, Shane JC, McKnight DJ, Yoshizawa S, Kato HE, Ganguli S, Deisseroth K.: Cortical layer-specific critical dynamics triggering perception. Science 365: eaaw5202, Aug 2019 Notes: * Denotes equal author contribution.

Berens P, Freeman J, Deneux T, Chenkov N, McColgan T, Speiser A, Macke JH, Turaga SC, Mineault P, Rupprecht P, Gerhard S, Friedrich RW, Friedrich J, Paninski L, Pachitariu M, Harris KD, Bolte B, Machado TA, Ringach D, Stone J, Rogerson LE, Sofroniew NJ, Reimer J, Froudarakis E, Euler T, Román Rosón M, Theis L, Tolias AS, Bethge M.: Community-based benchmarking improves spike rate inference from two-photon calcium imaging data. PLoS Computational Biology 14: e1006157, May 2018.

Rad KR, Machado TA, Paninski L: Robust and scalable Bayesian analysis of spatial neural tuning function data. Annals of Applied Statistics 11(2): 598-637, 2017.

Bikoff JB, Gabitto MI, Rivard AF, Drobac E, Machado TA, Miri A, Brenner-Morton S, Famojure E, Diaz C, Alvarez FJ, Mentis GZ, Jessell TM.: Spinal inhibitory interneuron diversity delineates variant motor microcircuits. Cell 165: 207-219, Mar 2016.

Pnevmatikakis EA, Soudry D, Gao Y, Machado TA, Merel J, Pfau D, Reardon T, Mu Y, Lacefield C, Yang W, Ahrens M, Bruno R, Jessell TM, Peterka DS, Yuste R, Paninski L.: Simultaneous denoising, deconvolution, and demixing of calcium imaging data. Neuron 89: 285-99, Jan 2016.

Machado TA, Pnevmatikakis E, Paninski L, Jessell TM, Miri A.: Primacy of flexor locomotor pattern revealed by ancestral reversion of motor neuron identity. Cell 162: 338-350, Jul 2015.

Buesing L, Machado TA, Cunningham JP, Paninski L: Clustered factor analysis of multineuronal spike data. Advances in Neural Information Processing Systems Page: 3500-3508, 2014.

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Last updated: 03/24/2023
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