Alex Williams PhD Student
Computational/Theoretical Neuroscience

About

I'm a PhD student in Neuroscience at Stanford University interested in a broad class of theoretical problems related to biology. I work in Surya Ganguli's group, and am funded through the DOE Computational Science Graduate Fellowship Program.

I previously worked at the Salk Institute (with Terry Sejnowski) and Brandeis University (with Eve Marder and Tim O'Leary). I was an undergraduate at Bowdoin College, where I worked with Patsy Dickinson.

Projects

  • Unsupervised Learning Techniques for Large-Scale, Multi-Trial Neural Data
  • An increasingly common paradigm in neuroscience is to simultaneously record the activity of many neurons over repeated experimental trials (e.g., multiple presentations of a sensory stimulus, or a repeated motor action). The resulting datasets can be very large, potentially containing recordings from thousands of neurons over thousands of experimental trials. I'm interested in finding general statistical approaches for understanding datasets of this form.
    • Tensor Decomposition of Neural Data — Commonly used methods for dimensionality reduction (such as PCA) identify low-dimensional features of within-trial neural dynamics, but do not model changes in neural activity across trials. To better understand processes like learning and trial-to-trial variability, I'm exploring tensor decomposition methods to find reduced representations of multi-trial datasets.
    • Sequence Extraction — Many animal behaviors are built as a sequence of motor primitives or decisions. The neurons that support these (and other) behaviors can also fire in repeatable sequences. Yet, statistical methods for identifying neural sequences in an unbiased manner (without pre-conceived reference to animal behavior) are not widely used. I am interested in using convolutive matrix factorization methods to address this problem.
    • Time warping — Analysis of neural data often relies on manual alignment of neural activity to a stimulus or behavioral event on each trial. However, alignment to external events is not always possible (e.g., in cases where neural activity is locked to internal cognitive states or decisions). I'm working to develop automatic alignment methods for these cases, enabling discovery of otherwise hidden neural coding patterns.


  • Theoretical Molecular Neurobiology
  • Biology computes with both electrical and biochemical signals. I'm interested in modeling the interface of these two substrates of computation.
    • Homeostatic Plasticity — Neurons alter ion channel and synaptic receptor expression/activity to maintain activity levels in physiologically stable regimes. This can be modeled from a control theoretic perspective, which provides perspectives on how noisy molecular processes can nevertheless support reliable physiological behaviors.
    • Microtubular Transport in Complex Dendritic Trees — Neurons are remarkably complex cells. Given this, it seems an almost insurmountable challenge to transport molecular cargo reliably. I've studied a few simple models of how reliable transport can be accomplished.
    • PyNeuronToolbox — A package I wrote to enable better NEURON simulations in Jupyter notebooks.


  • Code
  • Open-sourced research code.


Publications

( = personal favorite)

Papers

  • Unsupervised discovery of temporal sequences in high-dimensional datasets, with applications to neuroscience
  • Mackevicius EL, Bahle AH, Williams AH, Gu S, Denissenko NI, Goldman MS, Fee MS (2018). bioRxiv preprint.
  • Unsupervised discovery of demixed, low-dimensional neural dynamics across multiple timescales through tensor components analysis
  • Williams AH, Kim TH, Wang F, Vyas S, Ryu SI, Shenoy KV, Schnitzer M, Kolda TG, Ganguli S (2018). Neuron. 98(6):1099–1115.e8
  • Dendritic trafficking faces physiologically critical speed-precision tradeoffs
  • Williams AH, O’Donnell C, Sejnowski T, O’Leary T (2016). eLife. 5:e20556
  • Distinct or shared actions of peptide family isoforms: II. Multiple pyrokinins exert similar effects in the lobster stomatogastric nervous system.
  • Dickinson PS, Kurland SC, Qu X, Parker BO, Sreekrishnan A, Kwiatkowski MA, Williams AH, Ysasi AB, Christie AE (2015). J Exp Biol. 218:2905-17
  • Summary of the DREAM8 parameter estimation challenge: Toward parameter identification for whole-cell models.
  • Karr JR, Williams AH, Zucker JD, Raue A, Steiert B, Timmer J, Kreutz C, DREAM8 Parameter Estimation Challenge Consortium, Wilkinson S, Allgood BA, Bot BM, Hoff BR, Kellen MR, Covert MW, Stolovitzky GA, Meyer P (2015). PLoS Comput Biol. 11(5):e1004096
  • Cell types, network homeostasis and pathological compensation from a biologically plausible ion channel expression model.
  • O’Leary T, Williams AH, Franci A, Marder E (2014). Neuron. 82(4):809-21
  • Many parameter sets in a multicompartment model oscillator are robust to temperature perturbations.
  • Caplan JS, Williams AH, Marder E (2014). J Neurosci. 34(14):4963-75
  • The neuromuscular transform of the lobster cardiac system explains the opposing effects of a neuromodulator on muscle output.
  • Williams AH, Calkins A, O’Leary T, Symonds R, Marder E, Dickinson PS (2013). J Neurosci. 33(42):16565-75
  • Correlations in ion channel expression emerge from homeostatic regulation mechanisms.
  • O’Leary T, Williams AH, Caplan JS, Marder E (2013). Proc Natl Acad Sci USA. 110(28):E2645-54
  • Animal-to-animal variability in the phasing of the crustacean cardiac motor pattern: an experimental and computational analysis.
  • Williams AH, Kwiatkoswki MA, Mortimer AL, Marder E, Zeeman ML, Dickinson PS (2013). (2013). J Neurophysiol. 109:2451-65.

Reviews

  • Neuromodulation in Small Networks.
  • Williams AH, Hamood AW, Marder E (2015). Springer Encyclopedia of Computational Neuroscience.
  • Homeostatic Regulation of Neuronal Excitability.
  • Williams AH, O’Leary T, Marder E (2015). Scholarpedia. 8(1):1656