Cortical metabolic activity matches the pattern of visual suppression in strabismus

Abstract

When an eye becomes deviated in early childhood, a person does not experience double vision, although the globes are aimed at different targets. The extra image is prevented from reaching perception in subjects with alternating exotropia by suppression of each eye's peripheral temporal retina. To test the impact of visual suppression on neuronal activity in primary (striate) visual cortex, the pattern of cytochrome oxidase (CO) staining was examined in four macaques raised with exotropia by disinserting the medial rectus muscles shortly following birth. No ocular dominance columns were visible in opercular cortex, where the central visual field is represented, indicating that signals coming from the central retina in each eye were perceived. However, the border strips at the edges of ocular dominance columns appeared pale, reflecting a loss of activity in binocular cells from disruption of fusion. In calcarine cortex, where the peripheral visual field is represented, there were alternating pale and dark bands resembling ocular dominance columns. To interpret the CO staining pattern, [(3)H]proline was injected into the right eye in two monkeys. In the right calcarine cortex, the pale CO columns matched the labeled proline columns of the right eye. In the left calcarine cortex, the pale CO columns overlapped the unlabeled columns of the left eye in the autoradiograph. Therefore, metabolic activity was reduced in the ipsilateral eye's ocular dominance columns which serve peripheral temporal retina, in a fashion consistent with the topographic organization of suppression scotomas in humans with exotropia.

Figure 1.

Schematic diagram showing perception of the visual scene by subjects with exotropia. Here, the right eye is shown looking at a central cross and the left eye is deviated by 16°, causing the image of the cross to land on its temporal retina. When the left eye fixates centrally, the converse occurs. Dashed lines represent the nasal extent of each eye's visual field. Blue and red shading of eyes indicates portions of each retina engaged in perception; gray shading denotes suppressed temporal retina. The smaller the exotropic deviation, the closer temporal suppression extends toward the vertical meridians in each eye. In striate cortex, dark and light CO columns (depicted by blue/gray or red/gray shading) occur in the peripheral visual field representation (from 8° to 64°), reflecting suppression of neuronal activity in ocular dominance columns supplied by the peripheral temporal (ipsilateral gray) retinas. In the central visual field representation (from 0° to 8°), both retinas are active perceptually. Consequently, CO staining density is equal in the cores of the ocular dominance columns, indicated by alternating red and blue shading. It is reduced, however, in binocular border strips (thin white lines) along the edges of ocular dominance columns because fusion is absent.

Figure 2.

CO patterns in striate cortex in exotropia. a, c, Alternating light and dark CO columns (arrows) in layer 4C in the peripheral visual field representation of a monkey with a 20° exotropia induced at age 14 d. The dark columns are 700 μm apart, consistent with the width of a pair of ocular dominance columns. b, d, In the central visual field representation, thin pale strips are present (arrows), spaced about twice as closely as the columns in a and c. Following their trajectory into lighter-staining layer 4B, they emerge in the pale areas between rows of patches, suggesting that they are located at the border of each ocular dominance column.

Figure 3.

Assessment of exotropia. The monkey is fixating on the camera with his right eye. The left eye is deviated outward, causing nasal decentration of its corneal light reflex by 0.5 mm, which corresponds to 7°. The monkey alternated fixation freely, but preferred the right eye.

Figure 4.

Patterns of CO activity in left striate cortex in exotropia. a, Single section from a flatmount shows no ocular dominance columns in layer 4C from the foveal representation to an eccentricity of about 4°. From 4° to the monocular crescent representation, there are alternating light and dark CO columns. b, Boxed area from 1° to 2° in the section above. CO stain reveals extremely faint, pale strips in layer 4C, but no ocular dominance columns. c, Adjacent [³H]proline autoradiograph labeling the ocular dominance columns in layer 4C in the same region. d, Hand tracing of the pale CO strips, superimposed on the image in b. e, Tracing of the pale strips in d transferred onto the autoradiograph in c, showing that the pale strips straddle the borders of the ocular dominance columns.

Figure 5.

Patterns of CO activity in right striate cortex in exotropia. a, Just as in the left cortex (Fig. 4), there are no ocular dominance columns in layer 4C from the foveal representation to 4°, but from 4° to the monocular crescent representation there are alternating light and dark CO columns. b, Boxed area from central field representation of right striate cortex in a, showing subtle, pale border strips in 4C, but no pattern of ocular dominance columns. c, Adjacent autoradiograph of ocular dominance columns. d, Hand tracing of pale strips, superimposed on b. e, Tracing in d, transferred onto c, confirming that pale strips are located at borders of ocular dominance columns.

Figure 6.

Reduced CO activity in ipsilateral eye's columns in cortex representing peripheral visual field. a, Boxed region from the peripheral left cortex in Figure 4, showing alternating light and dark CO columns surrounding the blind spot representation (asterisk), which is not complete because the lower border enters layer 5. Three pale columns are marked with arrows. b, Adjacent autoradiograph in darkfield, with dark columns representing the ocular dominance columns of the unlabeled left eye (arrows). They correspond to the pale CO columns above, indicating that CO activity is reduced in the left eye's columns. c, Boxed region from the peripheral right cortex in Figure 5, showing alternating light and dark CO columns around the blind spot. Three pale columns are marked by arrows. d, Adjacent autoradiograph, showing that bright, labeled columns from the right eye match the pale columns above, indicating that CO activity is reduced in the right eye's columns in this hemisphere. Note solid labeling from the right eye of the left eye's blind spot “representation.”

Figure 7.

Suppression causes loss of CO activity in patches in layer 3. a, CO activity in layer 4C showing three pale columns serving the ipsilateral eye (arrows) in Figure 6c at higher magnification. The asterisk marks the blind spot area, where ocular dominance columns are absent. b, Section through layer 3 from the same region, showing that patches in rows (arrows) aligned with the pale columns in layer 4C are slightly pale and small, compared with patches in intercalated rows serving the contralateral eye. Toward the upper right, in the blind spot area, the pattern of alternating light and dark rows of patches disappears, because only the ipsilateral eye is represented.