A Neural Basis for Developmental Topographic Disorientation

Abstract

Developmental topographic disorientation (DTD) is a life-long condition in which affected individuals are severely impaired in navigating around their environment. Individuals with DTD have no apparent structural brain damage on conventional imaging and the neural mechanisms underlying DTD are currently unknown. Using functional and diffusion tensor imaging, we present a comprehensive neuroimaging study of an individual, J.N., with well defined DTD. J.N. has intact scene-selective responses in the parahippocampal place area (PPA), transverse occipital sulcus, and retrosplenial cortex (RSC), key regions associated with scene perception and navigation. However, detailed fMRI studies probing selective tuning properties of these regions, as well as functional connectivity, suggest that J.N.'s RSC has an atypical response profile and an atypical functional coupling to PPA compared with human controls. This deviant functional profile of RSC is not due to compromised structural connectivity. This comprehensive examination suggests that the RSC may play a key role in navigation-related processing and that an alteration of the RSC's functional properties may serve as the neural basis for DTD.

Significance statement: Individuals with developmental topographic disorientation (DTD) have a life-long impairment in spatial navigation in the absence of brain damage, neurological conditions, or basic perceptual or memory deficits. Although progress has been made in identifying brain regions that subserve normal navigation, the neural basis of DTD is unknown. Using functional and structural neuroimaging and detailed statistical analyses, we investigated the brain regions typically involved in navigation and scene processing in a representative DTD individual, J.N. Although scene-selective regions were identified, closer scrutiny indicated that these areas, specifically the retrosplenial cortex (RSC), were functionally disrupted in J.N. This comprehensive examination of a representative DTD individual provides insight into the neural basis of DTD and the role of the RSC in navigation-related processing.

Keywords: developmental topographic disorientation; navigation; parahippocampal place area; retrosplenial cortex; scene perception; transverse occipital sulcus.

Figure 1.

Sample stimuli used for functional localizers: scene and topographic ROIs in J.N. and control subject C1. A, Sample stimuli used for functional localizers. B, Scene-selective RSC, PPA, and TOS in J.N. and C1. C, Topographically organized ROIs in visual cortex including V1, V2, V3, V4, MT, V3a, and V3b are shown on flattened surface reconstructions in J.N. and C1. Retinotopic mapping revealed patterns of topographic organization in both hemispheres in J.N. that were similar to controls.

Figure 2.

Category-selective responses, ROI sizes, and cortical thickness in J.N. and controls. Scene-selective responses in J.N.'s PPA, TOS, and RSC were not reliably different from control subjects in both hemispheres. Similarly, object-selective responses in J.N.'s LOC and face-selective responses in J.N.'s FFA were not reliably different from that in controls. None of the ROIs examined were different in size or cortical thickness between J.N. and controls. Error bars indicate SD.

Figure 3.

Sample stimuli, presentation sequence, and time course results for the adaptation experiment. A, Sample scenes used for the adaptation experiments. The familiar and unfamiliar scenes shown are those that were familiar and unfamiliar to J.N. B, Presentation sequence of the adaptation experiments. During scene and fixation blocks, subjects were instructed to detect a fixation color change. C, Time courses of responses from PPA, TOS, and RSC from the familiar/unfamiliar adaptation experiment are shown for J.N., C1, and averaged controls. Blue lines indicate new scenes and red lines indicate repeated scenes. Solid lines indicate scenes that were familiar and dotted lines scenes that were unfamiliar.

Figure 4.

AI and effect of scene types. A, Across all scene ROIs and experiments, controls showed reliable adaptation effects (asterisks above blue bars, ***p < 0.001). Error bars indicate SEM to assess the reliability of adaptation effects (AI > 0). J.N.'s AIs were not reliably different from controls in PPA and TOS. However, for both experiments, J.N.'s RSC did not show adaptation effects (asterisks comparing J.N. vs controls, *p < 0.05). B, AIs are shown separately for each hemisphere in both experiments. Compared with controls, J.N.'s RSC in both hemispheres consistently showed reduced AIs for both familiar/unfamiliar scenes and indoor/outdoor scenes. C, Both controls and J.N. showed a reliable familiarity effect (familiar > unfamiliar, **p < 0.01) in PPA, TOS, and RSC. None of the ROIs showed an effect for indoor versus outdoor scenes.

Figure 5.

Functional connectivity. A, Temporal correlation matrix for J.N., C1, and averaged controls. B, The connectivity scores shown for individual (C1–C13) and averaged controls and J.N. across different seed and target ROIs. When RSC is seeded, J.N.'s PPA resulted in a significantly lower correlation than controls' (***p < 0.0001). When PPA was seeded, J.N.'s RSC and TOS resulted in lower connectivity scores compared with controls' (†p = 0.06). C, Hierarchical clustering results show that J.N.'s RSC is not clustered with PPA.

Figure 6.

Functional connectivity results for left and right hemispheres and adaptation experiments. A, The ranked connectivity scores for each control subject (C1–C13), averaged controls, and J.N. are shown for the left and right hemispheres with RSC as the seed and PPA as the target ROI using the resting-state data. B, Bilateral functional connectivity scores using the adaptation experiments data. J.N.'s RSC–PPA connectivity scores were significantly reduced compared with that of controls in all analyses (**p < 0.01, ***p < 0.001).

Figure 7.

Visualization of whole-brain connectivity with PPA and RSC as seeds. A, Whole-brain connectivity results in J.N. and C1 when the right PPA is seeded. The green crosshairs denote the center of each subject's respective right RSC. Unlike C1, there were no voxels near RSC showing correlation to PPA responses in J.N. B, Similarly, the correlation results in J.N. and C1 are shown when the right RSC is seeded. The green crosshairs denote the centers of J.N. and C1's respective right PPA. Again, unlike C1, there were no voxels near J.N.'s PPA showing correlation to RSC responses.

Figure 8.

Overall functional connectivity for each seed ROI to the rest of the target ROIs. For each seed ROI (e.g., V1), the mean connectivity value (i.e., averaged Pearson's r) was computed to determine the extent of the connectivity between this seed ROI and the other 12 target ROIs. J.N.'s FFA, PPA, RSC, and HIP were significantly less correlated with the rest of the ROIs than the ROI connectivity values of the controls. (***p ≤ 0.001, **p < 0.01, *p < 0.05).

Figure 9.

Structural connectivity, functional connectivity, and navigability. A, WM tracts connecting RSC and PPA that were consistent across at least 50% of the controls displayed in MNI space. B, Yellow voxels denote the overlap between J.N.'s RSC–PPA path result and controls' from A. J.N.'s RSC is shown in blue and PPA in green. C, D, FA and MD values extracted from the RSC–PPA tracks among J.N., C1, and averaged controls. E, Pattern of the structural connectivity between RSC and the rest of the ROIs were highly similar across J.N. and controls. F, Controls' structural and functional connectivity patterns of RSC were positively correlated. Blue dots denote individual target ROI's (averaged across controls) connectivity to RSC. G, J.N.'s functional and structural connectivity patterns of RSC were not correlated. H, Structural and functional coupling of RSC's connectivity to other ROIs correlated positively with navigation ability, as assessed by SBSDS. Values plotted in F–H are z-scores.