Occlusion therapy improves phase-alignment of the cortical response in amblyopia

Abstract

The visual evoked potential (VEP) generated by the amblyopic visual system demonstrates reduced amplitude, prolonged latency, and increased variation in response timing (phase-misalignment). This study examined VEPs before and after occlusion therapy (OT) and whether phase-misalignment can account for the amblyopic VEP deficits. VEPs were recorded to 0.5-4cycles/degree gratings in 10 amblyopic children (2-6years age) before and after OT. Phase-misalignment was measured by Fourier analysis across a limited bandwidth. Signal-to-noise ratios (SNRs) were estimated from amplitude and phase synchrony in the Fourier domain. Responses were compared to VEPs corrected for phase-misalignment (individual epochs shifted in time to correct for the misalignment). Before OT, amblyopic eyes (AE) had significantly more phase-misalignment, latency prolongation, and lower SNR relative to the fellow eye. Phase-misalignment contributed significantly to low SNR but less so to latency delay in the AE. After OT, phase-alignment improved, SNR improved and latency shortened in the AE. Raw averaged waveforms from the AE improved after OT, primarily at higher spatial frequencies. Correcting for phase-misalignment in the AE sharpened VEP peak responses primarily at low spatial frequencies, but could not account for VEP waveform improvements in the AE after OT at higher spatial frequencies. In summary, VEP abnormalities from the AE are associated with phase-misalignment and reduced SNR possibly related to desynchronization of neuronal activity. The effect of OT on VEP responses is greater than that accounted for by phase-misalignment and SNR alone.

Temporal Ventriloquism Reveals Intact Audiovisual Temporal Integration in Amblyopia

“…[12][13][14] Physiologically, cortical responses driven by stimulation of the amblyopic eye are less synchronized, 17 and their temporal encoding is less reliable. 15,16 Studies of normally sighted people also demonstrate that audition is more temporally precise than vision, 37 and tends to be dominant in processing the temporal dimension of audiovisual events. 23,[38][39][40] Given the normal dominance of audition in temporal audiovisual processing, any amblyopic deficit in auditory temporal resolution would likely have diminished the magnitude of the temporal ventriloquism effect and the sound-induced flash illusion, yet no such diminution was observed in the present study or previously.…”

“…Indeed, increased temporal jitter 15,16 and increased latency 41,42 in cortical signals from the amblyopic eye may alter the perceived timing of a visual event such that the probability distribution for the estimate of visual event timing is widened and shifted toward later onset. Miscalibration of visual temporal reliability, induced by amblyopic visual input and crystallized during development, may therefore provide an explanation for the weaker temporal constraints (i.e., wider temporal window) for audiovisual perceptual binding documented in the present study and in prior work on amblyopic multisensory perception.…”

“…31 In amblyopia, the neural mechanism for cross-modal matching may be miscalibrated in early life under the influence of increased temporal jitter 15,17 and interocular latency differences. 41,42 If audiovisual cross-modal matching is calibrated before the end of the sensitive period for amblyopic visual recovery, 43 then therapy that improves vision, equalizes evoked response latencies, 44,45 and reduces internal temporal noise 16 may not narrow the audiovisual temporal binding window. Such asynchronous sensitive periods for unisensory and multisensory functions may therefore explain how cross-modal matching may be selectively impaired, and why the deficit persists under binocular viewing conditions that provide highfidelity temporal information from the fellow eye.…”

“…14 In agreement with these behavioral deficits in temporal perception, visual evoked responses in humans show increased latency jitter and decreased signal-to-noise ratios. 15,16 Physiological recordings in cats show reduced synchronization among neurons in the striate cortex 17 when driven by stimulation of the amblyopic eye. Beyond vision, amblyopic abnormalities in multisensory processing and integration also are well documented.…”

A window into visual cortex development and recovery of vision: Introduction to the Vision Research special issue on Amblyopia

“…They found that a measure of interocular inhibition was highly accurate in discriminating amblyopic eyes from myopic eyes with or without the presence of refractive correction. With respect to the treatment of amblyopia, Kelly et al (2015) used visually evoked potentials (VEPs) to investigate the effect of occlusion therapy on the cortical response to information from the amblyopic eye. Prior to treatment, amblyopic eye VEPs exhibited a poorer signal-to-noise ratio, a longer latency and increased phase misalignment relative to fellow eye VEPs.…”