Neuronal responses in visual area V2 (V2) of macaque monkeys with strabismic amblyopia

Abstract

Amblyopia, a developmental disorder of spatial vision, is thought to result from a cascade of cortical deficits over several processing stages beginning at the primary visual cortex (V1). However, beyond V1, little is known about how cortical development limits the visual performance of amblyopic primates. We quantitatively analyzed the monocular and binocular responses of V1 and V2 neurons in a group of strabismic monkeys exhibiting varying depths of amblyopia. Unlike in V1, the relative effectiveness of the affected eye to drive V2 neurons was drastically reduced in the amblyopic monkeys. The spatial resolution and the orientation bias of V2, but not V1, neurons were subnormal for the affected eyes. Binocular suppression was robust in both cortical areas, and the magnitude of suppression in individual monkeys was correlated with the depth of their amblyopia. These results suggest that the reduced functional connections beyond V1 and the subnormal spatial filter properties of V2 neurons might have substantially limited the sensitivity of the amblyopic eyes and that interocular suppression was likely to have played a key role in the observed alterations of V2 responses and the emergence of amblyopia.

Figure 1.

Spatial contrast sensitivity functions of 3 normal (top row) and experimental monkeys with the onset age of 3 weeks (second row), 6 weeks (third row) and 6 months (bottom row). For the monkey (MK-292) that exhibited “bilateral amblyopia,” AI values are shown for an interocular comparison and the comparison between the operated eye (filled symbols) and the average function of the 3 normal monkeys (dotted line).

Figure 2.

(A) Effects of refractive errors of individual monkeys during early development (measured at 90 days of age) on the depth of amblyopia (AI). Open circles show data for the operated eyes and filled circles the fellow eyes. Triangles show comparable data for age-matched normal infant monkeys. (B) Relationships between the mean ocular deviation and the depth of amblyopia (AI) for individual strabismic monkeys. (C) Effects of the onset age of strabismus on the depth of amblyopia. The square symbols in all panels indicate an additional data point for MK-292 (bilateral amblyope) when comparisons were made between the function for the operated eye and the average function of the 3 normal monkeys. Triangles show the data points for normal monkeys.

Figure 3.

(A) Ocular dominance distribution of V1 (top) and V2 neurons (bottom) for normal monkeys (left), monkeys with mild amblyopia (AI < 0.5) (middle), and monkeys with severe amblyopia (AI > 0.5) (right). ROII, relative ocular dominance imbalance (see the text for details). A, amblyopic eye; NA, fellow “nonamblyopic” eye; R, right eye; L, left eye. Open histograms show the prevalence of “binocularly balanced cells” and filled histograms show binocularly imbalanced/monocular cells. AI values and ROII values are also illustrated in each panel. (B) ROII of individual monkeys as a function of their AI. Dotted open circles show data from the “late-onset” (6 months) group and square symbols indicate data from normal monkeys.

Figure 4.

Examples of orientation tuning functions (A) and spatial frequency tuning functions (B) of a V2 neuron from a severely amblyopic monkey. Orientation bandwidth (half-width at half height) was 10.9 degree for the fellow eye and 24.5 degree for the amblyopic eye while orientation bias was 0.76 for the fellow eye and 0.46 for the affected eye. The optimal spatial frequency was 6.0 c/d for the fellow eye and 3.7 c/d for the amblyopic eye while spatial resolution for the fellow eye was 14.6 c/d and 10.2 c/d for the affected eye.

Figure 5.

Histograms illustrating the distribution of the optimal spatial frequencies of V1 (top) and V2 neurons (bottom) for normal monkeys (left), monkeys with mild amblyopia (AI < 0.5) (middle), and monkeys with severe amblyopia (AI > 0.5) (right). Open histograms show the data for the amblyopic eye and filled histograms illustrate the distributions for the fellow eye. Triangles show geometric means. Mean (±standard error) for the affected eye (A) and the fellow eye (F) is shown on top.

Figure 6.

Histograms illustrating the distribution of the spatial resolutions of V1 (top) and V2 neurons (bottom) for normal monkeys (left), monkeys with mild amblyopia (AI < 0.5) (middle), and monkeys with severe amblyopia (AI > 0.5) (right). Open histograms show the data for the amblyopic eye and filled histograms illustrate the distributions for the fellow eye. Triangles show geometric means. Mean (±standard error) for the affected eye (A) and the fellow eye (F) is shown on top.

Figure 7.

Histograms illustrating the distribution of orientation bandwidths of V1 (top) and V2 neurons (bottom) for normal monkeys (left), monkeys with mild amblyopia (AI < 0.5) (middle), and monkeys with severe amblyopia (AI > 0.5) (right). Open histograms show the data for the amblyopic eye and filled histograms illustrate the distributions for the fellow eye. Triangles show geometric means. Mean (±standard error) for the affected eye (A) and the fellow eye (F) is shown on top.

Figure 8.

Histograms illustrating the distribution of orientation biases of V1 (top) and V2 neurons (bottom) for normal monkeys (left), monkeys with mild amblyopia (AI < 0.5) (middle), and monkeys with severe amblyopia (AI > 0.5) (right). Open histograms show the data for the amblyopic eye and filled histograms illustrate the distributions for the fellow eye. Triangles show geometric means values. Mean (±standard error) for the affected eye (A) and the fellow eye (F) is shown on top.

Figure 9.

Relationships between the peak firing rates and the spatial resolutions (A) and the orientation biases (B) of individual V2 units from severely amblyopic monkeys. Open circles indicate the tuning for the affected eyes and filled circles show the tuning for the fellow eyes.

Figure 10.

(A) An example of a spatial phase disparity tuning function of a V2 neuron from a normal monkey exhibiting facilitatory binocular interactions (Peak B/M = 5.47 db) and high sensitivity to spatial phase disparity (BII = 0.78). (B) An example of a spatial phase disparity tuning function of a V2 neuron from an amblyopic monkey exhibiting a robust binocular suppression (Peak B/M = -1.84 db) and no disparity sensitivity (BII = 0.06). DM, monocular response for the dominant eye; NDM, monocular response for the nondominant eye; N, spontaneous activity.

Figure 11.

(A) Histograms illustrating the distribution of binocular interaction index (BII) values for V1 (top) and V2 (bottom) neurons in normal (left), mildly amblyopic (middle) and severely amblyopic monkeys (right). (B) Relationships between the average BIIs of V1 (left) and V2 (right) neurons for individual monkeys and the depth of their amblyopia (AI). Square symbols indicate the mean BII of normal monkeys.

Figure 12.

(A) Distribution histograms of peak binocular/Monocular response ratios (db) for V1 (top) and V2 (bottom) neurons in normal (left), mildly amblyopic (middle), and severely amblyopic monkeys (right). Bars on the left side of the dashed line represent binocularly suppressive units (Peak B/M < 0.0 db). Mean values (±standard error) are shown with triangles. (B) Relationships between the average Peak B/M of V1 (top) and V2 (bottom) neurons in individual monkeys and the depth of their amblyopia (AI) (left columns). Relationships between the proportion of binocularly suppressive V1 (top) and V2 (bottom) neurons of individual monkeys and the depth of their amblyopia (AI) (right columns).

Figure 13.

Comparisons of the relative magnitude of V2 deficits with the depth of amblyopia (AI). The proportions of binocularly suppressive unit, the ocular dominance imbalance (ROII), the average spatial resolution, and the average orientation bias of V2 neurons in individual monkeys were first normalized to the respective maximum value and then were fit to obtain a regression line for each V2 deficit. The slope (±standard error of the mean) is given for each function.