Abstract
purpose. By 6 weeks of age, neurons in the monkey’s primary visual cortex
acquire qualitatively adult-like binocular response properties and
behaviorally stereopsis emerges. In this study, it was
determined whether the onset of strabismus has a more severe impact on
cortical binocularity before or after this critical developmental age.
methods. Infant monkeys were fit with a light-weight helmet which held a total
of 27 diopters of base-in prisms in front of their two eyes for a fixed
period of two weeks. For one group of infant monkeys, prism-rearing
began at 2 weeks of age and for a second group, the onset was at 6
weeks of age. Immediately after the rearing period, i.e., at 4 weeks
and 8 weeks of age, respectively, extracellular single-unit recording
methods were used to determine the nature and severity of alterations
in the binocular response properties of V1 neurons. Dichoptic
sinewave gratings were used as visual stimuli.
results. In comparison to normal age-matched infants, V1 neurons in both
strabismic groups exhibited reductions in sensitivity to interocular
spatial phase disparities (disparity sensitivity) and a higher
prevalence of binocular inhibitory interactions (binocular
suppression). However, the reduction in disparity sensitivity and the
magnitude of binocular suppression were much greater in the late (6–8
weeks) than the early (2–4 weeks) onset group.
conclusions. Discordant binocular signals due to brief periods of early strabismus
have more serious effects on the development of binocular properties of
V1 neurons if they occur shortly after rather than before the emergence
of stereopsis (i.e., when the binocular connections are relatively more
mature but the visual cortex still shows a high degree of
plasticity).
Early onset strabismus is known to severely disrupt vision
development in a substantial proportion of human infants.
1 One of the most commonly debated issues concerning the management of
infants with congenital strabismus is how early (at what age) proper
eye alignment needs to be restored to preserve stereoscopic vision and
to prevent the emergence of amblyopia. There appears to be very little
disagreement with the view that surgical alignment should be performed
before 2 years of age.
2 3 4 However, it has become a matter
of debate whether earlier surgery (e.g., before 6 months of age) is of
significant benefit for preserving “normal” binocular sensory
functions.
5 6 7 8 9 10 11
To gain insight into this critical issue of vision development, we have
been investigating how the binocular response properties of neurons in
the primary visual cortex (V1) mature in normal monkeys and how
binocularly conflicting signals early in life alter their postnatal
development. As early as 6 days of age, an adult-like proportion of
neurons is sensitive to interocular spatial phase disparities in normal
infant monkeys.
12 Over the next 3 to 4 postnatal weeks
both binocular and monocular response properties of V1 neurons rapidly
mature.
12 13 Consequently, V1 neurons exhibit
qualitatively adult-like properties by 4 to 6 weeks of age (equivalent
to 4 to 6 months in humans), a critical age during normal development
(Fig. 1) . This rapid cortical maturation just precedes the age when stereopsis,
a sensitive measure of the status of binocular visual functions,
normally emerges in monkeys.
14
Although early strabismus is known to disrupt binocular vision
development, it is not clear whether misalignment before or after the
emergence of stereopsis causes more serious disruptions in binocular
sensory development. In the present study, we investigated this issue
by examining the development of binocular response properties of V1
neurons in infant monkeys that were subjected to brief periods of
early strabismus.
Tungsten-in-glass microelectrodes were used to isolate activity
from individual cortical neurons. Action potentials were
extracellularly recorded and amplified using conventional technology.
For each isolated neuron, the receptive fields for both eyes were
mapped, and ocular dominance was determined using handheld stimuli. For
the quantitative analyses of monocular tuning and binocular signal
interactions, the receptive fields were projected onto the centers of
two matched cathode ray tube (CRT) screens (P-31 phosphores). The CRTs
had a space average luminance of 56 cd/m2. The
visual stimuli were drifting sinewave gratings. The neuron’s responses
were sampled at a rate of 100 Hz (10 msec bin widths) by a laboratory
computer and compiled into peristimulus time histograms that were equal
in duration to, and synchronized with, the temporal cycle of the
sinewave grating. The amplitudes and phases of the temporal response
components in the peristimulus time histograms were determined by
Fourier analysis. Responses to drifting sinusoidal gratings (TF =
3.1 Hz, contrast = 35%–45%) were measured to determine the
orientation tuning, spatial frequency tuning, and direction selectivity
of individual units. Cells were classified as simple or complex based
on the temporal characteristics of their responses to a drifting
sinewave grating of the optimal spatial frequency and orientation.
To determine the strength and nature of binocular interactions,
responses were collected for dichoptic sinewave gratings of the optimal
spatial frequency and orientation as a function of the relative
interocular spatial phase disparity of the grating pair
(Fig. 2) .
12 17 18 In addition, monocular stimuli for each eye and
one zero-contrast control were included in each stimulus parameter
file. For descriptive and analytical purposes, a single cycle of a
sinewave was fit to each neuron’s phase tuning function. The amplitude
of the fitted sinewave was used to calculate the degree of binocular
interaction (binocular interaction index [BII] = amplitude of the
fitted sinewave/the average response amplitude). Operationally, a unit
was considered as “disparity tuned” if its BII value was equal to
or greater than 0.3.
12 17 18 19
To determine whether binocular signal interactions were excitatory or
inhibitory in nature, the binocular response amplitude/dominant
monocular amplitude ratios were calculated for each unit. Depending on
a cell’s disparity sensitivity, two different criteria were used in
determining whether a unit was binocularly suppressive. Specifically,
if a cell was disparity tuned (i.e., BII ≥ 0.3), we took the
ratio of the peak binocular response amplitude over the
dominant monocular response amplitude. For those cells that were
non-disparity tuned (BII < 0.3), the mean binocular
amplitude was compared with the dominant monocular amplitude. If the
ratio of the binocular response amplitudes over the cell’s dominant
monocular response amplitude was less than 1.0 (B/M < 1.0), the
cell was considered to exhibit binocular suppression.