Evaluation of APOE ɛ2/ɛ3/ɛ4 Alleles in a Cohort of Individuals Affected by Developmental Topographical Disorientation.

The three common alleles of the APOE gene, ɛ2/ɛ3/ɛ4, have been linked to human spatial orientation. We investigated the genetic role of APOE in developmental topographical disorientation (DTD), a lifelong condition that results in topographical disorientation. We genotyped the APOE ɛ2/ɛ3/ɛ4 alleles in a cohort of 20 unrelated DTD probands, and found allele frequencies not statistically different from the those seen in the population as a whole. Therefore, we found no evidence that DTD occurs preferentially on a genetic background containing any particular APOE allele, making it unlikely that these APOE alleles are contributing to the development of DTD.

Ventral-Dorsal Functional Contribution of the Posterior Cingulate Cortex in Human Spatial Orientation: A Meta-Analysis.

The retrosplenial cortex has long been implicated in human spatial orientation and navigation. However, neural activity peaks labeled "retrosplenial cortex" in human neuroimaging studies investigating spatial orientation often lie significantly outside of the retrosplenial cortex proper. This has led to a large and anatomically heterogenous region being ascribed numerous roles in spatial orientation and navigation. Here, we performed a meta-analysis of functional Magnetic Resonance Imaging (fMRI) investigations of spatial orientation and navigation and have identified a ventral-dorsal functional specialization within the posterior cingulate for spatial encoding vs. spatial recall. Generally, ventral portions of the posterior cingulate cortex were more likely to be activated by spatial encoding, i.e., passive viewing of scenes or active navigation without a demand to respond, perform a spatial computation, or localize oneself in the environment. Conversely, dorsal portions of the posterior cingulate cortex were more likely to be activated by cognitive demands to recall spatial information or to produce judgments of distance or direction to non-visible locations or landmarks. The greatly varying resting-state functional connectivity profiles of the ventral (centroids at MNI -22, -60, 6 and 20, -56, 6) and dorsal (centroid at MNI 4, -60, 28) posterior cingulate regions identified in the meta-analysis supported the conclusion that these regions, which would commonly be labeled as "retrosplenial cortex," should be more appropriately referred to as distinct subregions of the posterior cingulate cortex. We suggest that future studies investigating the role of the retrosplenial and posterior cingulate cortex in spatial tasks carefully localize activity in the context of these identifiable subregions.

Familial aggregation in developmental topographical disorientation (DTD).

A variety of brain lesions may affect the ability to orient, resulting in what is termed "acquired topographical disorientation". In some individuals, however, topographical disorientation is present from childhood, with no apparent brain abnormalities and otherwise intact general cognitive abilities, a condition referred to as "developmental topographical disorientation" (DTD). Individuals affected by DTD often report relatives experiencing the same lifelong orientation difficulties. Here, we sought to assess the familial aggregation of DTD by investigating its occurrence in the families of DTD probands, and in the families of control probands who did not experience topographical disorientation. We found that DTD appears to cluster in the DTD families, with tested relatives displaying the trait, whereas in the control families we did not detect any individuals with DTD. These findings provide the very first evidence for the familial clustering of DTD and motivate further work investigating the genetic factors producing this clustering.