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.

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Figure 1: Percent signal change (PSC) for each fROI.
Figure 2: PSC in the VWFA as a function of fROI volume.
Figure 3: Actual versus predicted fMRI activation for words > objects on the ventral surface of an example subject.
Figure 4: Correlations of actual word selectivity at age 8 with predicted word selectivity.
Figure 5: Left-lateralized regions that are preferentially connected with the VWFA versus lFFA or lPFS at age 5.

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Acknowledgements

We thank B. Fischl and M. Reuter for their guidance and advice on longitudinal registration, S. Robinson and O. Ozernov-Palchik for assistance with participant coordination and A. Park for technical assistance. We thank the Athinoula A. Martinos Imaging Center at the McGovern Institute for Brain Research at the Massachusetts Institute of Technology and its staff. We also thank our READ Study research testers, school coordinators and principals, and participating families. This work was funded by NICHD/NIH grant F32HD079169 to Z.M.S., NIH/NICHD R01HD067312 to J.D.E.G. and N.G., Ellison Medical Foundation, EY13455 to N.K., and grant 1444913 from McGovern Institute for Brain Research MINT to N.K. and Z.M.S.

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Contributions

Z.M.S., D.E.O. and N.K. designed the experiments. Z.M.S., E.S.N., D.A.Y., S.D.B., N.G., J.D.E.G. and N.K. conducted the experiments or supplied data. Z.M.S., D.E.O., D.A.Y. and J.F. analyzed the data. Z.M.S., D.E.O. and N.K. wrote the manuscript.

Corresponding author

Correspondence to Zeynep M Saygin.

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The authors declare no competing financial interests.

Integrated supplementary information

Supplementary Figure 1 fMRI experiment on 8 year olds.

(a) At age 8, children were shown words, scrambled words, line-drawings of objects, and line-drawings of faces over 6 experimental runs in a blocked design. A grid was overlaid on top of the stimuli so that all stimulus types (not just scrambled words) had edges. Each stimulus was presented for 500ms (ISI=0.193s) and overlaid on a different single-color background. Each run consisted of 18 blocks (4 blocks per stimulus type and 3 fixation blocks per run), and participants performed a one-back task. (b) fROIs were defined in each individual by intersecting that individual’s relevant thresholded activation contrast map with the relevant constraint region (e.g. for the VWFA, words > line-drawings of objects within VWFA constraint region). Constraint regions were defined from fMRI data in a separate group of adult participants as parcels within which most subjects had a significant activation, and were registered to each child’s native anatomy. Constraint regions for the VWFA (magenta), lFFA (yellow), and lPFS (cyan) are shown on an example subject’s inflated cortical surface. Note that while constraint regions are large (to accommodate individual variation) and overlap, the resulting fROIs within an individual are small and do not overlap.

Supplementary Figure 2 Percent signal change (PSC) for each fROI and age in pre-readers and readers.

(a) Example stimuli used for the age 5 fMRI experiment. The fMRI experiments at age 5 and age 8 were slightly different e.g. used different scanning protocols and different stimuli. To test whether the age 5 fMRI experiment could detect orthographic selectivity when it is present at age 5, we analyzed another cohort of children who could already read at age 5 (“readers”, right). We performed the same fROI percent signal change analysis that we did for the main cohort of children who could not read at age 5, defining fROIs on the age-8 data and measuring response magnitudes in those fROIs in independent data. (b) Percent signal change in VWFA, lFFA, and lPFS at age 8 (bottom) and age 5 (top) for children who could not read at age 5 (“pre- readers”, left; note that this is the same data as Figure 1 but is included here for comparison to the readers). (c) Percent signal change analysis in the children who could read (“readers") at both age 5 (top) and age 8 (bottom). Like the pre-readers (b), we find clear selectivity for faces in lFFA (F3,21 = 23.52, P = 6.49 x10-7; faces vs. words: P = 2.51 x 10-4; T = 6.81; faces vs. objects: P = 4.77 x 10-5; T = 8.85; faces vs. scrambled words: P = 7.41 x 10-4; T = 5.69) and clear selectivity for words in the VWFA for readers at age 8 (repeated measures ANOVA by condition: F3,21 = 5.92, P = 4.33 x10-3; words vs. objects: P = 2.01 x 10-3; T = 4.78; vs. faces: P = 2.99 x 10-2; T = 2.72; vs. scrambled words: P = 9.82 x 10-3; T = 3.51). However, while pre-readers do not show selectivity to letters in the VWFA at age 5, the readers do show selectivity to letters (bottom bar plots in b and c; repeated measures ANOVA by condition: F2,14 = 4.59, P = 2.93 x10-2; letters vs. faces: P = 3.48 x 10-2; T = 2.61; vs. false fonts: P = 2.07 x 10-2; T = 2.97). The lFFA also showed strong selectivity to faces over letters or false fonts at age 5 (F2,14 = 33.51, P = 4.60 x10-6; faces vs. letters: P = 1.14 x 10-4; T = 7.73; vs. false fonts: P = 8.66 x 10-4; T = 5.54. The response profile of the VWFA was distinct from both the lFFA (fROI x condition repeated measure ANOVA: F2,28 = 21.13, P = 2.55 x10-6) and from the lPFS at age 5 (F2,28 = 9.78, P = 6.01 x10-4) as well as at age 8 (VWFA vs. lFFA same three conditions as age 5, i.e. no objects condition: F2,28 = 18.30, P = 8.26 x10-6 and VWFA vs. lPFS: F2,28 = 5.93, P = 7.12 x10-3). Error bars = SE and horizontal bars reflect individual posthoc tests significant at P < 0.05.

Supplementary Figure 3 Percent signal change in the VWFA as a function of fROI volume in pre-readers and readers.

(a) Children who were not able to read at age 5 (“pre-readers”) did not show selectivity for letters as compared to faces or false fonts (top; for 5th percentile: letters vs. false fonts: P = 0.126; T(13) = 1.63; letters vs. faces: P = 0.711; T(13) = -0.379). We also defined percentiles in exactly the same way from age 8 data (bottom), and found strong selectivity for words (words vs. scrambled words: P = 3.02 x10-2; T(13) = 2.43; words vs. faces: P = 1.38 x10-2; T(13) = 4.05). Note that (a) is the same figure as Figure 2 in main text but also included here for comparison to children who could already read at age 5 (“readers”). (b) Readers do show selectivity for letters as compared to faces or false fonts, even in the most selective bin (top 5%) at age 5 (top; letters vs. false fonts: P = 1.79x10-2; T(7) = 3.08; letters vs. faces: P = 2.04 x 10-3; T(7) = 4.77) as well as at age 8 (bottom; words vs. scrambled words: P = 2.65 x10-2; (t7) = 2.80; words vs. faces: P = 2.19 x10-2; T(7) = 2.93). Error bars = SE.

Supplementary Figure 4 MVPA accuracy on age 5 fMRI data for all voxels within the VWFA parcel.

In children who could not yet read (left), classification accuracy was at chance for discriminating letters (from faces or false fonts; P = 0.30; T(13) = 1.07). In contrast, classification performance was significantly above chance for letters in children who could already read at age 5 (P = 3.10 x10-2; T(7) = 2.70). The region that will later become the VWFA cannot discriminate letters from faces or false fonts before these children can read. Thick lines reflect mean, thin lines reflect SE. Dotted line is chance accuracy.

Supplementary Figure 5 Group average (random effects) map for words > objects for leave-one-subject-out analysis on template brain.

Although the VWFA usually falls within the lateral surface of the occipitotemporal cortex, its precise location varies substantially across individuals13. Thus the group average maps of word-selectivity do not show above threshold activations as illustrated here. Colorbar scale indicates -log(p) values.

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Saygin, Z., Osher, D., Norton, E. et al. Connectivity precedes function in the development of the visual word form area. Nat Neurosci 19, 1250–1255 (2016). https://doi.org/10.1038/nn.4354

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