Dysfunctional visual word form processing in progressive alexia - PubMed
Case Reports
. 2013 Apr;136(Pt 4):1260-73.
doi: 10.1093/brain/awt034. Epub 2013 Mar 7.
Affiliations
- PMID: 23471694
- PMCID: PMC3613714
- DOI: 10.1093/brain/awt034
Case Reports
Dysfunctional visual word form processing in progressive alexia
Stephen M Wilson et al. Brain. 2013 Apr.
Abstract
Progressive alexia is an acquired reading deficit caused by degeneration of brain regions that are essential for written word processing. Functional imaging studies have shown that early processing of the visual word form depends on a hierarchical posterior-to-anterior processing stream in occipito-temporal cortex, whereby successive areas code increasingly larger and more complex perceptual attributes of the letter string. A region located in the left lateral occipito-temporal sulcus and adjacent fusiform gyrus shows maximal selectivity for words and has been dubbed the 'visual word form area'. We studied two patients with progressive alexia in order to determine whether their reading deficits were associated with structural and/or functional abnormalities in this visual word form system. Voxel-based morphometry showed left-lateralized occipito-temporal atrophy in both patients, very mild in one, but moderate to severe in the other. The two patients, along with 10 control subjects, were scanned with functional magnetic resonance imaging as they viewed rapidly presented words, false font strings, or a fixation crosshair. This paradigm was optimized to reliably map brain regions involved in orthographic processing in individual subjects. All 10 control subjects showed a posterior-to-anterior gradient of selectivity for words, and all 10 showed a functionally defined visual word form area in the left hemisphere that was activated for words relative to false font strings. In contrast, neither of the two patients with progressive alexia showed any evidence for a selectivity gradient or for word-specific activation of the visual word form area. The patient with mild atrophy showed normal responses to both words and false font strings in the posterior part of the visual word form system, but a failure to develop selectivity for words in the more anterior part of the system. In contrast, the patient with moderate to severe atrophy showed minimal activation of any part of the visual word form system for either words or false font strings. Our results suggest that progressive alexia is associated with a dysfunctional visual word form system, with or without substantial cortical atrophy. Furthermore, these findings demonstrate that functional MRI has the potential to reveal the neural bases of cognitive deficits in neurodegenerative patients at very early stages, in some cases before the development of extensive atrophy.
Figures

Preserved figure copy and delayed copy in the two patients with progressive alexia. (A) The modified Rey-Osterrieth figure (Possin et al., 2011). (B) Patient J’s copy of the figure. (C) Patient J’s delayed copy of the figure after 10 min. (D) Patient B’s copy of the figure. (E) Patient B’s delayed copy of the figure after 10 min.

Reading time increased as a function of word length in Patient J, a pattern that is characteristic of letter-by-letter reading.

Structural images of the two progressive alexic patients. Regions of tissue loss as revealed by voxel-based morphometry (voxel-wise P < 0.005, minimum cluster extent = 1500 mm3) are shown with red outlines (white in printed version). (A) Patient J showed mild atrophy of the left posterior inferior temporal gyrus. (B) Patient B showed much more extensive atrophy of left temporal cortex. VBM = voxel-based morphometry.

Functional identification of the visual word form area. (A, B and C) In three typical control subjects, viewing words or false font strings relative to fixation activated bilateral occipital and posterior temporal regions (voxel-wise P < 0.0001). The contrast of words versus false font strings (voxel-wise P < 0.05) masked by the contrast of words versus rest (voxel-wise P < 0.0001) revealed the VWFA in each of the 10 control participants. (D) Patient J showed typical bilateral occipito-temporal activation for words or false font strings relative to fixation, however there were no regions activated for words versus false font strings. (E) Patient B showed weak right-lateralized activation for words or false font strings relative to fixation, and no regions activated for words versus false font strings.

The visual word form area in control subjects and patients. (A) In the control group, the contrast of words versus false font strings (voxel-wise P < 0.005, corrected for multiple comparisons at P < 0.05) revealed the visual word form area. (B) Activation for this contrast was reduced in the patients relative to the control subjects (voxel-wise P < 0.005, corrected for multiple comparisons at P < 0.05).

The typical anterior-posterior gradient of selectivity for words in occipito-temporal cortex was abnormal in the two patients with progressive alexia. (A–J) In all control subjects, posterior occipito-temporal cortex responded as much for false font strings as for words, whereas more anterior regions showed greater responses to words than false font strings. This pattern was also apparent (arrowheads) when plotting mean occipito-temporal responses in each hemisphere to words and false font strings as a function of y coordinate, as shown in the line graphs below each image. (K and L) This selectivity gradient for words was not apparent in either of the two progressive alexic patients. Additional slices are shown to demonstrate that both patients showed small regions that were selectively responsive to words more dorsally in the right hemisphere. The black outlines show regions that responded more to words than false font strings (voxel-wise P < 0.05) and more to words than fixation (voxel-wise P < 0.0001). The red outlines show regions in the two patients that VBM showed to be atrophic (voxel-wise P < 0.005, minimum cluster extent = 1500 mm3). F = female; M = male.
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