ABSTRACTABSTRACT

Purpose.Purpose. To expand the behavioral Ocular Motor System (OMS) model for Infantile Nystagmus To expand the behavioral Ocular Motor System (OMS) model for Infantile Nystagmus Syndrome (INS) by incorporating the variation of IN amplitude with gaze angle.Syndrome (INS) by incorporating the variation of IN amplitude with gaze angle.Methods.Methods. In a previous study, gaze-angle effects in Fusion Maldevelopment Nystagmus In a previous study, gaze-angle effects in Fusion Maldevelopment Nystagmus Syndrome (i.e., foveating and defoveating fast-phase alternation) waveforms were simulated, Syndrome (i.e., foveating and defoveating fast-phase alternation) waveforms were simulated, guided by Alexander’s law input. Alexander’s law describes the increase in the amplitude of guided by Alexander’s law input. Alexander’s law describes the increase in the amplitude of nystagmus as the eye is moved in the direction of the fast phase. In the current study, fixation nystagmus as the eye is moved in the direction of the fast phase. In the current study, fixation data from INS subjects at various gaze angles were examined and used as templates for the data from INS subjects at various gaze angles were examined and used as templates for the simulations. All simulations were performed in the MATLAB Simulink environment. The original simulations. All simulations were performed in the MATLAB Simulink environment. The original OMS model is available online at OMS model is available online at http://www.omlab.org.. Results.Results. The Alexander’s law functional block in the internal monitor of the OMS model is based The Alexander’s law functional block in the internal monitor of the OMS model is based on a tonic imbalance signal and efference copy of eye position signal. In INS, the “null” position on a tonic imbalance signal and efference copy of eye position signal. In INS, the “null” position and sharpness could be approximated by the two Alexander’s law relationships (one for each and sharpness could be approximated by the two Alexander’s law relationships (one for each direction), with their intersection indicating the “null” position and the slopes of the curves direction), with their intersection indicating the “null” position and the slopes of the curves controlling the broadness of the “null.” At various gaze angles, these Alexander’s law controlling the broadness of the “null.” At various gaze angles, these Alexander’s law relationships influenced the slow-phase amplitude of IN waveforms differently, thus mimicking relationships influenced the slow-phase amplitude of IN waveforms differently, thus mimicking the same gaze-angle effects as we observed in INS patients.the same gaze-angle effects as we observed in INS patients. Conclusions.Conclusions. The behavioral output of the OMS model demonstrated the effectiveness of using The behavioral output of the OMS model demonstrated the effectiveness of using Alexander’s law input to simulate the variation of IN waveforms across the whole visual domain. Alexander’s law input to simulate the variation of IN waveforms across the whole visual domain. This improvement in the OMS model adds another step in the implementation of a complete and This improvement in the OMS model adds another step in the implementation of a complete and idiosyncratic OMS model that can simulate normal as well as pathological (i.e., INS) behaviors.idiosyncratic OMS model that can simulate normal as well as pathological (i.e., INS) behaviors.

Nothing to Disclose.Nothing to Disclose.

OMS MODEL: INSOMS MODEL: INSFoundations/Requirements (based on recorded data): Foundations/Requirements (based on recorded data): • Simulate normal saccadic and pursuit responsesSimulate normal saccadic and pursuit responses• Contain ALL necessary functional OMS blocksContain ALL necessary functional OMS blocks• IN waveforms are independent of prior saccadesIN waveforms are independent of prior saccades• ALL saccades within waveforms are correctiveALL saccades within waveforms are corrective• IN waveforms must contain foveation periods ON IN waveforms must contain foveation periods ON

TARGETTARGET• NO OSCILLOPSIA (i.e., the model has stable signals NO OSCILLOPSIA (i.e., the model has stable signals

representing reconstructed target position and velocity)representing reconstructed target position and velocity)

Models of INS Models of Foveation PeriodsModels of INS Models of Foveation Periods

OMS MODELOMS MODELEmergent Behavior:Emergent Behavior:

• VoluntaryVoluntary saccade amplitudes saccade amplitudes werewere modulated modulated by the INby the IN• Normal saccadic system Normal saccadic system shiftedshifted IN waveforms to allow IN waveforms to allow target foveationtarget foveation• Occasional Occasional missed braking saccadesmissed braking saccades resulted in larger IN; i.e., braking resulted in larger IN; i.e., braking

saccades saccades dampeddamped the IN the IN• Spontaneous Spontaneous bias reversalsbias reversals were automatically caused by were automatically caused by small voluntary small voluntary

saccadessaccades correcting accumulated position error correcting accumulated position error• IN IN slow phasesslow phases could could suppresssuppress required corrective saccades following required corrective saccades following

hypometric saccades and accomplish hypometric saccades and accomplish target acquisitiontarget acquisition• Foveating Foveating saccade-magnitude variabilitysaccade-magnitude variability reflected minor reflected minor motor-command motor-command

variabilityvariability• Braking and foveating Braking and foveating saccade magnitudessaccade magnitudes were affected by were affected by slow-phase slow-phase

velocityvelocity• Initial Initial catch-up saccadescatch-up saccades during ramp and step-ramp pursuit were during ramp and step-ramp pursuit were

diminisheddiminished by IN slow phases by IN slow phases

Emergent Behavior Support for Hypothetical MechanismsEmergent Behavior Support for Hypothetical Mechanisms

QUESTIONSQUESTIONS

What causes the What causes the variationvariation of INS with of INS with gaze anglegaze angle? ?

Is it related to the Is it related to the Alexander’s lawAlexander’s law variation of variation of vestibular and fusion maldevelopment nystagmus?vestibular and fusion maldevelopment nystagmus?

Can the Can the positionposition and and sharpnesssharpness of NAFX of NAFX peakspeaks (INS (INS ““nullsnulls”) be determined by the ”) be determined by the intersection intersection and and slopesslopes of the of the Alexander’s lawAlexander’s law line for each direction ? line for each direction ?

HYPOTHESESHYPOTHESES

Improper Improper calibrationcalibration of the of the Alexander’s lawAlexander’s law control of control of vestibular nystagmus affects the vestibular nystagmus affects the amplitudeamplitude of INS as of INS as gaze anglegaze angle is changed. is changed.

The The intersectionintersection and and slopesslopes of the linear of the linear Alexander’s lawAlexander’s law relationships for nystagmus in each direction determine relationships for nystagmus in each direction determine the the positionposition and and sharpnesssharpness of NAFX of NAFX peakspeaks. .

METHODSMETHODS

Ocular motor simulations using a Ocular motor simulations using a behavioral OMS modelbehavioral OMS model were performed in MATLAB Simulink.were performed in MATLAB Simulink.

Simulations of different types of INS variation with gaze Simulations of different types of INS variation with gaze angle were based on eye-movement data that were angle were based on eye-movement data that were calibrated using the calibrated using the foveation periodsfoveation periods of the of the fixatingfixating eye. eye.

INS Block DiagramINS Block Diagram

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INS ModelINS Model

AL Gain Modulation in PMC+ BlockAL Gain Modulation in PMC+ Block

Internal MonitorInternal Monitor

METHODSMETHODS

Alexander’s law Alexander’s law outputoutput used in the used in the PMC+ blockPMC+ block to alter the to alter the gaingain of the INS oscillation. of the INS oscillation.

Alexander’s law Alexander’s law slopesslopes and and intersectionsintersections set to simulate set to simulate different different INS vs. gaze angleINS vs. gaze angle characteristics. characteristics.

Model run with Model run with positivepositive and and negativenegative step-changes in target step-changes in target position during both position during both PfsPfs and and PPfsPPfs INS waveforms. INS waveforms.

Model outputs plotted on same graph to observe Model outputs plotted on same graph to observe saccadicsaccadic responsesresponses and and INS changesINS changes with gaze angle. with gaze angle.

Alexander’s Law BlockAlexander’s Law Block

MODEL PREDICTIONSMODEL PREDICTIONS

Sharp AL (0° Intersection)

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Sharp AL (10° Intersection)

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MODEL PREDICTIONSMODEL PREDICTIONS

Medium AL (0° Intersection)

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Medium AL (15° Intersection)

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MODEL PREDICTIONSMODEL PREDICTIONS

Broad AL (0° Intersection)

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Broad AL (-15° Intersection)

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MODEL OUTPUTSMODEL OUTPUTS(Pfs, Sharp “Null”)(Pfs, Sharp “Null”)

“Null”

MODEL OUTPUTSMODEL OUTPUTS(Sharp “Nulls”)(Sharp “Nulls”)

“Null”“Null”

MODEL OUTPUTSMODEL OUTPUTS(Medium “Nulls”)(Medium “Nulls”)

“Null” “Null”

MODEL OUTPUTSMODEL OUTPUTS(Broad “Nulls”)(Broad “Nulls”)

“Null”

“Null”

MODEL OUTPUTSMODEL OUTPUTS(PPfs, Sharp “Null”)(PPfs, Sharp “Null”)

“Null”

INS CHARACTERISTICSINS CHARACTERISTICS(NAFX vs Gaze Angle)(NAFX vs Gaze Angle)

Sharp NAFX peak at 0°

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INS CHARACTERISTICSINS CHARACTERISTICS(NAFX vs Gaze Angle)(NAFX vs Gaze Angle)

Medium NAFX peak at 0°

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Medium NAFX peak at 15°

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INS CHARACTERISTICSINS CHARACTERISTICS(NAFX vs Gaze Angle)(NAFX vs Gaze Angle)

Broad NAFX peak at 0°

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NAFX

Broad NAFX peak at -15°

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NAFX

RESULTSRESULTS

The simulated The simulated responsesresponses matchedmatched those measured in INS those measured in INS patients with patients with differentdifferent null null positionspositions and and sharpnesssharpness..

The The positionspositions of the NAFX of the NAFX peakspeaks could be set to could be set to simulatesimulate INS patients with INS patients with differentdifferent null positions. null positions.

The The sharpnesssharpness of the NAFX of the NAFX peakspeaks could be set to could be set to simulatesimulate INS patients with INS patients with differentdifferent null sharpness. null sharpness.

CONCLUSIONSCONCLUSIONS

The The Alexander’s-law Alexander’s-law imbalance (possibly asymmetric) imbalance (possibly asymmetric) produced by produced by improper calibrationimproper calibration of the of the vestibularvestibular system may be the system may be the underlyingunderlying reasonreason for INS variation for INS variation with gaze angle.with gaze angle.

The The positionposition of the NAFX of the NAFX peakpeak may be determined by may be determined by the the intersectionintersection of the two of the two Alexander’s lawAlexander’s law lines. lines.

The The sharpnesssharpness of the NAFX of the NAFX peakpeak may be determined by may be determined by the the slopesslopes of the two of the two Alexander’s lawAlexander’s law lines. lines.

FUTURE WORKFUTURE WORK

The INS The INS amplitudeamplitude variationvariation with gaze angle will be with gaze angle will be applied to applied to jerkjerk waveforms. waveforms.

The The Alexander’s-law Alexander’s-law effects on INS amplitude will be effects on INS amplitude will be used to control the used to control the idiosyncratic transitionsidiosyncratic transitions between between pendularpendular and and jerkjerk waveforms. waveforms.

The effects of The effects of inattentioninattention on INS on INS waveformswaveforms will be will be incorporated into the model.incorporated into the model.

These have been incorporated into Version 1.5These have been incorporated into Version 1.5