Patterns of Individual Variation in Visual Pathway Structure and Function in the Sighted and Blind

Abstract

Many structural and functional brain alterations accompany blindness, with substantial individual variation in these effects. In normally sighted people, there is correlated individual variation in some visual pathway structures. Here we examined if the changes in brain anatomy produced by blindness alter the patterns of anatomical variation found in the sighted. We derived eight measures of central visual pathway anatomy from a structural image of the brain from 59 sighted and 53 blind people. These measures showed highly significant differences in mean size between the sighted and blind cohorts. When we examined the measurements across individuals within each group we found three clusters of correlated variation, with V1 surface area and pericalcarine volume linked, and independent of the thickness of V1 cortex. These two clusters were in turn relatively independent of the volumes of the optic chiasm and lateral geniculate nucleus. This same pattern of variation in visual pathway anatomy was found in the sighted and the blind. Anatomical changes within these clusters were graded by the timing of onset of blindness, with those subjects with a post-natal onset of blindness having alterations in brain anatomy that were intermediate to those seen in the sighted and congenitally blind. Many of the blind and sighted subjects also contributed functional MRI measures of cross-modal responses within visual cortex, and a diffusion tensor imaging measure of fractional anisotropy within the optic radiations and the splenium of the corpus callosum. We again found group differences between the blind and sighted in these measures. The previously identified clusters of anatomical variation were also found to be differentially related to these additional measures: across subjects, V1 cortical thickness was related to cross-modal activation, and the volume of the optic chiasm and lateral geniculate was related to fractional anisotropy in the visual pathway. Our findings show that several of the structural and functional effects of blindness may be reduced to a smaller set of dimensions. It also seems that the changes in the brain that accompany blindness are on a continuum with normal variation found in the sighted.

Fig 1. Patterns of shared variation in visual pathway anatomy.

A: The eight measures of visual pathway anatomy are illustrated on an axial schematic of the human brain. The groupings of the measures are to assist subsequent interpretation of the data. B: The Euclidean distance matrix and dendrogram for the 8 measures across the sighted population. Left. The square-root, sum-squared difference in values between two measures across subjects provides a measure of Euclidean distance. Darker shades indicate pairings of measures that have similar variation across subjects, and thus lower distance values. Right. The distance matrix was subjected to hierarchical clustering, yielding a dendrogram. The length of each branch reflects the distance between the paired measures. The three primary clusters of anatomical variation are colored green, blue, and red. C: Left. The distance matrix across the 8 measures for the blind population. A similar overall structure is seen as compared to the sighted. Right. The dendrogram derived from measures from the blind subjects. The same overall cluster structure is seen. Note that there is some rearrangement in the measurements assigned to cluster #2 in the blind as compared to the sighted.

Fig 2. Group differences in anatomy, organized by cluster.

Each anatomical size measurement was transformed to a mean-centered z-score and then averaged within a cluster. The sign of values in cluster #1 was reversed, so that positive values represent thinner V1 cortex. Anatomical scores within each cluster were then averaged within subject groups, corresponding to the normally sighted, postnatally blind, and congenitally blind. Across all three clusters, a graded change in the anatomical scores is seen for these subject groupings, although the difference between postnatally and congenitally blind is not significant for cortical thinness (cluster #1).

Fig 3. Relation of clustered anatomical variation to cross-modal response and fractional anisotropy.

A: For each of 52 subjects (blind and sighted), we obtained the BOLD fMRI response in V1 while subjects listened to auditory sentences played forwards and in reverse, as compared to white noise. We modeled the ability of individual variation in the three anatomical clusters to account for variation in cross-modal BOLD fMRI response. For each subject, the x-axis gives the prediction of the model for BOLD fMRI response, and the y-axis the observed response. There was a significant model fit (p = 0.00051). B: Model weights for the fit to the cross-modal response data. Shown are the mean and standard error of weights upon each of the clusters of anatomical variation in their prediction of V1 BOLD fMRI response. Only the first cluster of anatomical variation (V1 cortical thinness) had a fitting weight significantly different from zero. The loading on this weight is negative, indicating that thicker V1 cortex predicts greater cross-modal responses. C: For each of 59 subjects, we measured fractional anisotropy within the optic radiations and splenium of the corpus callosum. We modeled the ability of individual variation in the three anatomical clusters to account for variation in FA. For each subject, the x-axis gives the prediction of the model for FA, and the y-axis the observed measure. The entire model fits the data above chance (p = 0.016). D: Model weights for the fit to the FA data. Shown are the mean and standard error of weights upon each of the clusters of anatomical variation in their prediction of the FA measure. Only the third cluster of anatomical variation (chiasm and LGN volume) had a fitting weight significantly different from zero.