Signal Processing and Analysis of Noisy Eye Position Sensor Data

TITLE: Signal Processing and Analysis of Noisy Eye Position Sensor Data

INVESTIGATORS:

Jennifer Raymond (1)

Brian Angeles (1)

Sriram Jayabal (1)

  1. Department of Neurobiology

DATE: Wednesday, 17 May 2023

TIME: 1:30–3:00 PM

LOCATION: Conference Room X399, Medical School Office Building, 1265 Welch Road, Stanford, CA

ABSTRACT

The Data Studio Workshop brings together a biomedical investigator with a group of experts for an in-depth session to solicit advice about statistical and study design issues that arise while planning or conducting a research project. This week, the investigator(s) will discuss the following project with the group.

INTRODUCTION

Our lab measures eye velocity responses to visual and vestibular stimuli and their modification by learning, and the neural underpinnings thereof.

BACKGROUND

A key function of the brain is to learn about the statistical relationships between events in the world. A mechanism of this learning is associative neural plasticity, controlled by the timing between neural events. Here, we show that experience can dramatically alter the timing rules governing associative plasticity to match the constraints of a particular circuit and behavior, thereby improving learning. In normal mice, the timing requirements for associative plasticity in the oculomotor cerebellum are precisely matched to the 120 ms delay for visual feedback about behavioral errors. This task-specific specialization of the timing rules for plasticity is acquired through experience; in dark-reared mice that had never experienced visual feedback about oculomotor errors, plasticity defaulted to a coincidence-based rule. Computational modeling suggests two broad strategies for implementing this Adaptive Tuning of the Timing Rules for Associative Plasticity (ATTRAP), which tune plasticity to different features of the statistics of neural activity. The modeling predicts a critical role of this process in optimizing the accuracy of temporal credit assignment during learning; consistent with this, behavioral experiments revealed a delay in the timing of learned eye movements in mice lacking experience-dependent tuning of the timing rules for plasticity. ATTRAP provides a powerful mechanism for matching the timing contingencies for associative plasticity to the functional requirements of a particular circuit and learning task, thereby providing a candidate neural mechanism for meta-learning.

METHODOLOGY

We have previously collected eye position data at a sampling rate of 1 kHz. The data corresponds to the eye movement of an animal either being sinusoidally rotated 180 degrees clockwise and counterclockwise at a rate of 1 Hz. Particular training protocols are conducted to either increase or decrease the magnitude of the eye’s sinusoidal motion. We then differentiate our eye position signals to extract the corresponding velocity traces, and using the stimulus signal data as a reference, we would like to compute the average eye velocity trace over a single 1 Hz period of the stimulus oscillation.

STATISTICAL ISSUES

  1. Is there a better and more principled way to characterize the timing of the eye movement response to sinusoidal stimuli? In much of our previous work, we have fit the eye velocity responses with a sinusoid and reported the amplitude and phase of the fit. But now we are seeing interesting timing effects that are not captured by the sinusoidal fits. In bottom of Fig 2H of the bioRxiv preprint, we just plotted the time (ms) of the absolute peak of the learned eye movement trace for each mouse (calculated by average eye velocity response across ~40 stimulus repetitions post-training minus avg of pre-training eye velocity response).
  2. Unfortunately, our processed and filtered data is still quite noisy, and differentiating the noisy data only makes it worse. We typically apply a lowpass Butterworth filter on our positional data, use a windowed Savitzky-Golay filter to get the corresponding velocity trace, and then apply a custom saccade detection/removal algorithm. We now would like to explore other possible methods to get a cleaner velocity trace from our noisy positional data that has minimal effect on the temporal and amplitude information within the data.
  3. As time allows, we would also appreciate advice about several aspects of the pre-processing steps used to compute eye velocity.
    1. methods for digital differentiation and filtering of raw eye position-related signals to obtain eye velocity
    2. identification of eye saccades (brief, discrete high velocity/acceleration eye movement events, which we exclude from the analysis) vs. lower frequency continuous “smooth” eye movements and noise
    3. elimination of very high frequency noise, which appears in the raw data as a single, occasional wayward 1ms sample in an otherwise smoother raw trace of eye position as a function of time.

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Signal Processing and Analysis of Noisy Eye Position Sensor Data

TITLE: Signal Processing and Analysis of Noisy Eye Position Sensor Data

INVESTIGATORS:

Jennifer Raymond (1)

Brian Angeles (1)

Sriram Jayabal (1)

Department of Neurobiology

TIME: 1:30–3:00 PM

LOCATION: Conference Room X399, Medical School Office Building, 1265 Welch Road, Stanford, CA

ABSTRACT

The Data Studio Workshop brings together a biomedical investigator with a group of experts for an in-depth session to solicit advice about statistical and study design issues that arise while planning or conducting a research project. This week, the investigator(s) will discuss the following project with the group.

INTRODUCTION

Our lab measures eye velocity responses to visual and vestibular stimuli, their modification via training and learning, and the neural underpinnings thereof. There were great ideas (at the previous workshop) regarding methods to characterize the timing of our eye velocity cycle averages. Unfortunately, time constraints prevented us from presenting our questions and challenges regarding the pre-processing of the eye position data to handle noise and artifacts in the eye position recordings and differentiate to obtain eye velocity.

BACKGROUND

Our lab is interested in understanding the algorithms that the brain uses to learn. To do so, we use oculomotor learning (learned changes in the eye movement responses to visual and vestibular sensory stimuli) as an experimental behavioral model owing to its simplicity, experimental and analytical tractability. We collect eye position data from mice using a magnetic sensing method developed in the lab, as they track a moving visual stimulus or counter-rotate their eyes during head rotation (a vestibular stimulus). We can train the mice to alter the amplitude or timing of the eye movement responses.  We would like to optimize the methods we use to pre-process the raw eye position data and the amplitude and timing of the eye movement responses.

METHODOLOGY

Horizontal eye position time-series data is acquired from magnetic sensors at a sampling rate of 1000 Hz, which then undergoes multiple processing steps:

  1. From the raw position data, 1 ms (single sample) transient noise artifact spikes are removed by applying Laplace smoothing (i.e. linearly interpolating the center point of the spike with the average of its nearest neighbors).
  2. A 9th order lowpass (zero-phase) Butterworth filter is applied with a cutoff frequency between 15 and 30 Hz on a mouse-by-mouse basis.
  3. The corresponding eye velocity trace (first derivative) of each block is approximated using a Savitzky-Golay filter over a 30-ms (i.e., 30 sample point) window.
  4. Saccades (brief, discrete high velocity/acceleration eye movement events, which we exclude from the analysis) and other unwanted artifacts in the eye position recordings (caused by electrical noise or body movements/vibrations) are removed by using velocity thresholding; which involves computing the squared differences between the velocity trace and its corresponding 1 Hz sinusoidal fit, and removing the sample points where its corresponding squared difference exceed some set threshold value.
  5. Velocity cycle averages are then computed over a single sinusoidal stimulus cycle.
  6. We typically average the eye velocity responses across stimulus repetitions, and then calculate the differences between velocity averages post- vs pre- behavioral training to calculate the learned change in the eye movement behavior in each session/mouse, and then conduct statistical tests comparing different populations of mice, and/or different kinds of training.

STATISTICAL ISSUES

We would like advice regarding several aspects of the pre-processing steps used to compute eye velocity from noisy positional data.

  1. Recommendations regarding the elimination of the 1ms high frequency transient noise found in our raw position data which we currently remove via interpolation.
  2. Importance of the order of pre-processing steps (e.g., application of a lowpass filter on the raw position signal before or after its differentiation).
  3. Methods for filtering and differentiation of raw eye position-related signals to remove the noise without affecting the eye movement signal.
  4. Best approaches for the detection and removal of eye saccades and unwanted motion artifacts from the eye velocity data.

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Eyelid Elasticity—Molecular Basis and Exploration of Stiffening Techniques

TITLE: Eyelid Elasticity—Molecular Basis and Exploration of Stiffening Techniques

INVESTIGATORS:

Andrea K. M. Ross (1)

Albert Y. Wu (1)

  1. Department of Ophthalmology

DATE: Wednesday, 7 June 2023

TIME: 1:30–3:00 PM

LOCATION: Conference Room X399, Medical School Office Building, 1265 Welch Road, Stanford, CA

ABSTRACT

The Data Studio Workshop brings together a biomedical investigator with a group of experts for an in-depth session to solicit advice about statistical and study design issues that arise while planning or conducting a research project. This week, the investigator(s) will discuss the following project with the group.

INTRODUCTION

Connective tissue disorders of the eyelid such as ectropion, entropion, and Floppy Eyelid Syndrome have a high prevalence in the general population. Patients suffer from chronic eye irritation and inflammation, and corneal scarring is associated with vision loss and the risk of blindness. Eyelid laxity is based on age-related collagen and elastin degradation in the tarsal plate. These conditions are commonly treated with surgery as less invasive therapy options are limited. We aim to characterize the biomechanical properties of the eyelid and its associated connective tissue. Further, we intend to explore alternative and less invasive techniques to stiffen the affected tissues. Riboflavin-based UVA crosslinking therapy is the clinically established standard treatment for halting disease progression of keratoconus and other corneal ectasias. The conventional Dresden protocol was introduced by Wollensak et al. and consists of UVA-light irradiation with a wavelength of 370 nm and a power of 3 mW/cm2 for 30 minutes to the de-epithelialized cornea. First laboratory attempts have shown a promising stiffening effect in other collagenous tissues such as the tarsal plate.

HYPOTHESIS & AIM

We intend to investigate the biomechanical effect of various crosslinking protocols on the tarsal plate ex vivo and subsequently transition the ex vivo crosslinking technique to an in vivo approach. This represents the decisive step towards establishing a new alternative and non-invasive treatment method for eyelid laxity syndromes. Regarding this study question, we additionally aim to analyze different pathways of riboflavin penetration into the tarsal plate. Further, we will study the biomechanical effect of banking/storage of tarsal plate in different media.

PLANNED EXPERIMENTS

The following individual projects will be conducted:

  1. Tarsal Plate Banking
  2. Riboflavin Penetration of Tarsal Plate
  3. Tarsal Plate Crosslinking – ex vivo
    1. Part I (Aim: Determine best protocol based on previous study results in literature)
    2. Part II (Aim: Narrow down intensity intervals to determine best protocol from Part I)
    3. Part III (Aim: Does the Bunsen law of reciprocity apply for tarsal plate crosslinking?)
  4. Tarsal Plate Crosslinking – in vivo

STATISTICAL MODELS

We aim to determine the most effective procedure (banking method, riboflavin penetration, CXL procedure) for all individual experiments. Therefore, we are searching for suitable statistical tests to compare the results between the different study groups. Further, we would like to discuss adequate group sizes in order to calculate the tissues needed in advance.

STATISTICAL QUESTIONS

(1) What are adequate group sizes for each individual project?

(2) How should we perform the statistical evaluation regarding statistical tests (and models)?

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