Effect of Retinitis Pigmentosa Blindness on Functional Brain Network Measures.

Our brain undergoes significant alteration in response to blindness. Understanding these neuroplastic changes and finding reliable methods for quantification of such reorganization is consequential for devising optimum sight restoration therapies and clinical rehabilitation. In recent years, graph theory measures have been applied to brain connectivity, but few studies have examined blindness-induced cortical alterations using these methods. In this study, we investigated alterations in key global and local measures of functional plasticity in the brain network after visual deprivation. Four resting-state functional MRI runs from 10 sighted and 10 blind subjects, with severe retinitis pigmentosa, provided data for our analysis. The whole-brain ROI-ROI resting-state functional connectivity (rsFC) matrices were created for all subjects. Using the resulting rsFC matrices, the global density and efficiency were extracted for the whole brain and the visual system. Additionally, weighted degree, as a local metric, was investigated for all the nodes in the functional brain network. Our results revealed a statistically significant decrease in global density and efficiency of the visual system and weighted degree for lower visual areas, following visual deprivation in the blind group. The explored network measures can serve as tools to gauge functional neuroplasticity following blindness, as a complement to the behavioral indices. Future investigation with a larger number of test subjects for this rare condition can enable correlation analysis with patients' characteristics and further verify the application of these metrics as biomarkers of brain reorganization following vision loss.

Sight restoration reverses blindness-induced cross-modal functional connectivity changes between the visual and somatosensory cortex at rest.

Resting-state functional connectivity (rsFC) has been used to assess the effect of vision loss on brain plasticity. With the emergence of vision restoration therapies, rsFC analysis provides a means to assess the functional changes following sight restoration. Our study demonstrates a partial reversal of blindness-induced rsFC changes in Argus II retinal prosthesis patients compared to those with severe retinitis pigmentosa (RP). For 10 healthy control (HC), 10 RP, and 7 Argus II subjects, four runs of resting-state functional magnetic resonance imaging (fMRI) per subject were included in our study. rsFC maps were created with the primary visual cortex (V1) as the seed. The rsFC group contrast maps for RP > HC, Argus II > RP, and Argus II > HC revealed regions in the post-central gyrus (PostCG) with significant reduction, significant enhancement, and no significant changes in rsFC to V1 for the three contrasts, respectively. These findings were also confirmed by the respective V1-PostCG ROI-ROI analyses between test groups. Finally, the extent of significant rsFC to V1 in the PostCG region was 5,961 in HC, 0 in RP, and 842 mm3 in Argus II groups. Our results showed a reduction of visual-somatosensory rsFC following blindness, consistent with previous findings. This connectivity was enhanced following sight recovery with Argus II, representing a reversal of changes in cross-modal functional plasticity as manifested during rest, despite the rudimentary vision obtained by Argus II patients. Future investigation with a larger number of test subjects into this rare condition can further unveil the profound ability of our brain to reorganize in response to vision restoration.

Inactivation of the Lateral Entorhinal Area Increases the Influence of Visual Cues on Hippocampal Place Cell Activity.

The hippocampus is important for both navigation and associative learning. We previously showed that the hippocampus processes two-dimensional (2D) landmarks and objects differently. Our findings suggested that landmarks are more likely to be used for orientation and navigation, whereas objects are more likely to be used for associative learning. The process by which cues are recognized as relevant for navigation or associative learning, however, is an open question. Presumably both spatial and nonspatial information are necessary for classifying cues as landmarks or objects. The lateral entorhinal area (LEA) is a good candidate for participating in this process as it is implicated in the processing of three-dimensional (3D) objects and object location. Because the LEA is one synapse upstream of the hippocampus and processes both spatial and nonspatial information, it is reasonable to hypothesize that the LEA modulates how the hippocampus uses 2D landmarks and objects. To test this hypothesis, we temporarily inactivated the LEA ipsilateral to the dorsal hippocampal recording site using fluorophore-conjugated muscimol (FCM) 30 min prior to three foraging sessions in which either the 2D landmark or the 2D object was back-projected to the floor of an open field. Prior to the second session we rotated the 2D cue by 90°. Cues were returned to the original configuration for the third session. Compared to the Saline treatment, FCM inactivation increased the percentage of rotation responses to manipulations of the landmark cue, but had no effect on information content of place fields. In contrast, FCM inactivation increased information content of place fields in the presence of the object cue, but had no effect on rotation responses to the object cue. Thus, LEA inactivation increased the influence of visual cues on hippocampal activity, but the impact was qualitatively different for cues that are useful for navigation vs. cues that may not be useful for navigation. FCM inactivation also led to reductions in both frequency and power of hippocampal theta rhythms, indicative of the loss of functionally important LEA inputs to hippocampus. These data provide evidence that the LEA is involved in modulating how the dorsal hippocampus utilizes visual environmental cues.