Connectivity precedes function in the development of the visual word form area

Abstract

What determines the cortical location at which a given functionally specific region will arise in development? We tested the hypothesis that functionally specific regions develop in their characteristic locations because of pre-existing differences in the extrinsic connectivity of that region to the rest of the brain. We exploited the visual word form area (VWFA) as a test case, scanning children with diffusion and functional imaging at age 5, before they learned to read, and at age 8, after they learned to read. We found the VWFA developed functionally in this interval and that its location in a particular child at age 8 could be predicted from that child's connectivity fingerprints (but not functional responses) at age 5. These results suggest that early connectivity instructs the functional development of the VWFA, possibly reflecting a general mechanism of cortical development.

Figure 1

Percent signal change (PSC) for each fROI. Left: inflated surface of an example subject, showing each of their fROIs defined from age 8 data (lFFA in yellow, VWFA in magenta, lPFS in cyan). Top: mean PSCs at age 5 in fROIs defined on age 8 data (registered to 5-year-old brain). Before a child is able to read, there is no selectivity to letters, letter-like stimuli (false fonts) or faces in the region that later becomes the VWFA, while lFFA shows clear selectivity for faces even at this age. Bottom: mean PSCs at age 8. We find clear selectivity for faces in lFFA and clear selectivity for words in the VWFA at age 8 in data not used to define the fROI. Error bars denote standard error. Horizontal bars reflect significant post-hoc paired t-tests (P < 0.05, N=14).

Figure 2

Percent signal change in the VWFA as a function of fROI volume. To further test whether there was any selectivity for orthography at age 5, we performed a “binned” analysis where we used one run of age 5 data to define the Nth percentile of letter-selective voxels anywhere within the larger VWFA parcel (i.e. constraint region in Supplementary Figure 1 based on independent data in adults); we then measured the PSC to each condition in the other run of age 5 fMRI data in those same voxels. Children who were not able to read at age 5 did not show selectivity for letters as compared to faces or false fonts (top). The analogous analysis of the age 8 data in the same children (bottom) found strong selectivity for words. Error bars reflect standard error of the mean for N = 14 subjects.

Figure 3

Actual vs. predicted fMRI activation for Words > Objects on the ventral surface of an example subject. Heatmap reflects word selectivity and white outline indicates the boundaries of the left occipitotemporal anatomical parcel. AU = arbitrary units. (a) Actual fMRI activation for Words > Objects at age 8. (b) Activation that is predicted from the same individual’s DWI data at age 5. (c) Activation that is predicted from the same individual’s fMRI data at age 8, from independent, left-out fMRI runs from (a). This split-half reliability illustrates the best possible predictions that one could make about an individual’s word selectivity. The predicted activation from DWI matches the actual activation pattern, capturing loci that are accurately predicted from left-out data. Note that all images (actual, predicted from DWI, and predicted from left-out data) are based on (or trained on) an equal number of fMRI runs.

Figure 4

Correlations of actual word-selectivity at age 8 with predicted word selectivity. Predictions of age 8 word-selectivity from age 5 DWI data were compared to predictions from the age 8 fMRI data of all other subjects (group average) and to predictions from each other subject’s age 8 data. DWI predictions outperformed both of these types of predictions, demonstrating that the prediction of functional activation patterns from connectivity at age 5 is spatially precise enough to predict individual differences in functional activation patterns. Horizontal bars reflect significant differences (paired t-tests, each P < 0.05 × 10⁻⁴, N = 11); error bars reflect standard error of the mean.

Figure 5

Left-lateralized regions that are preferentially connected with the VWFA vs. lFFA or lPFS at age 5. Color bar reflects T-values from the VWFA vs. lFFA comparison (post-hoc paired t-tests, p < 0.05). Connectivity (of the region that will become the VWFA) to these regions is already elevated (compared to nearby cortex) at age 5, even when no evidence of functional differentiation exists in the VWFA at that age.