Differing Connectivity of Exner's Area for Numbers and Letters

Abstract

There is a growing body of evidence indicating a crucial role of Exner's area in (hand-) writing symbolic codes such as letters and words. However, a recent study reported a patient with a lesion affecting Broca's and Exner's area, who suffered from severe peripheral agraphia for letters but not for Arabic digits. The authors suggested a speculative account postulating differential connectivity of Exner's area for numbers and letters in order to explain this dissociation. In the present study, we evaluated this account, employing atlas-based tractography for the patient's anatomy, deterministic fiber-tracking as well as an automated toolkit to investigate the connectivity of Exner's area in healthy adults. In particular, fiber pathways connecting Exner's area with areas associated with language processing (e.g., the arcuate fascicle, ventral pathways encompassing the external/extreme capsule system) reached the inferior part of Exner's area, while fronto-parietal fibers (e.g., the superior longitudinal fascicle) connected the upper part of Exner's area with the intraparietal sulcus typically involved in number processing. Our results substantiated the differential connectivity account for Exner's area by identifying the neural connections between fiber tracts and cortex areas of interest. Our data strongly suggest that white matter connectivity should be taken into account when investigating the neural underpinnings of impaired and intact human cognition.

Keywords: Exner’s area; atlas-based tractography; connectivity; dissociation between numbers and letters; fiber tractography.

Figure 1

Patient CU’s anatomy in standard Montreal Neurological Institute (MNI) space on transverse slices. (A) Depicts a high-resolution T1-weighted structural MRI, while (B) shows a fluid-attenuated inversion recovery (FLAIR) scan. In most cases, T2-weighted images such as FLAIR scans show more extensive injury (e.g., gliosis) that is difficult to detect on T1-weighted scans. While large parts of Exner’s area and the ventral pathway are replaced by a pseudocyst following a colliquative necrosis, parts of the superior longitudinal fascicle (SLF II), might be affected by some gliosis (white tissue).

Figure 2

(A) Patient CU’s anatomy in standard MNI space on transverse slices of a high-resolution T1-weighted structural fMRI scan. The lesion affects Broca’s area and extends into Exner’s area due to a left-hemispheric MCA stroke after ACI dissection. (B) Overlay of CU’s brain with the arcuate fascicle, which connects Broca’s area (BA 44 and BA 45) with Wernicke’s area. As can be taken from the figure, the fibers of the arcuate fascicle overlap to a considerable extent with patient CU’s lesion, especially in the upper part of Broca’s as well as in the lower part of Exner’s area. (C) Overlay of CU’s anatomy with the inferior-fronto-occipital fascicle (IFOF), which in the temporal lobe encompasses ventrally the external/extreme capsule (EC/EmC) system, thereby connecting language areas ventrally with inferior frontal areas such as Broca’s area. As can be taken from the figure, the lesion in Broca’s area fully overlaps with the IFOF, so there is no ventral connection to Exner’s area via Broca’s area. Furthermore, it can be seen that the IFOF does not have contact with Exner’s area. (D) Overlay of patient CU’s anatomy with the SLF II. As can be seen clearly, the SLF II reaches into the upper part of Exner’s area connecting Exner’s area with parietal cortex.

Figure 3

Example of typical fiber tracking results within healthy participants. (A) Depicts the sagittal view of both fiber trackings: (i) the connections between Exner’s area (blue sphere) to the intraparietal cortex (green sphere) via the SLF II (green fibers), (ii) the connections between Exner’s area (blue) and the superior temporal gyrus (upper red sphere) given in blue fibers (AF, longitudinal segment), and (iii) the connections between Exner’s area (blue) and the middle temporal gyrus (lower red sphere) given in yellow fibers. As can be seen, the blue fibers connect these two areas, both, dorsally (via the arcuate fascicle) as well as ventrally via the external/extreme capsule (EC/EmC) system. Importantly, both, the ventral connection as well as the dorsal arcuate fascicle reach Exner’s area considerably inferior to the SLF II. Therefore, in case the lower part of Exner’s area is affected by a lesion, there may be a dorsal fronto-parietal connection left, nevertheless. (B,C) Illustrate the same findings from a perspective a bit more superior and tilted towards the reader, providing also the coronal and transversal slices. (B) This view is given with the seed regions used, while in (C) only the fibers within the brain context are depicted. Note that the following (Jones et al., 2002) DTI analyses were based on data averaged across all participants, whereas segmented fibers of a representative participant are shown here for illustration purposes.

Figure 4

Disconnectome maps as provided by BCBtoolkit. The SLF II seemed to be intact, while both, the anterior segment of the AF as well as ventral fibers seemed to be affected by the lesion.