Welcome

Tuesday, June 12, 2012: 1:30 PM  - 3:30 PM

Room: Plenary Hall, Level 4

¹Children`s Hospital of Philadelphia, Philadelphia, United States, <sup>2</sup>Children`s Hospital of Philadelphia, Philadelphia, PA, ³Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA

Manzar Ashtari
Children`s Hospital of Philadelphia
Philadelphia, United States

Our visual system not only mediates information about the visual environment but is capable of generating nonexistent patterns and lights called phosphenes (1,2). Phosphenes can be points, spots, bars or chaotic structures of colorless or colored light (2) and are caused by excitation (mechanical, electrical, or magnetic) of visual cells as well as random firing of cells (3). Phosphenes may occur in a variety of retinal diseases such as Leber congenital amaurosis (LCA). LCA is a group of hereditary retinal dystrophies characterized by profound impairment in retinal and visual function in infancy and early childhood followed by progressive deterioration and loss of retinal cells We performed fMRI on a group of LCA patients with a common form of LCA, LCA2, which is due to a mutation in RPE654. Cortical activations were recorded in the presence and absence of phosphenes in several patients who reported experiencing them. Although LCA2 patients undergo rigorous clinical testing, none of the clinical tests revealed the existence of phosphenes.

All data were acquired on a Siemens 3T Verio system at CHOP using a 32 channel head coil. Functional data were acquired using the BOLD technique. Isotropic 3D structural high-resolution T1 images of the whole brain were obtained for visual activation locations and generation of inflated hemispheres. MRI compatible goggles were used to present the stimuli and the paradigm was programmed in E-Prime. Checkerboard patterns with a constant light intensity were used in a block design, with three levels of contrast: high (100%), medium (34%), and low (10%). Fig-1 shows a schematic diagram of the checkerboard paradigm. Data was analyzed in BrainVoyagerQX using the GLM model. Each condition (high, medium, low contrast) was analyzed by specifying a design matrix defined as active versus rest the condition followed by application of the hemodynamic response function and corrected for the false discovery rate (fdr).

fMRI results from one LCA2 subject during and in the absence of phosphenes are presented in Figs-2&3, respectively. Results from a control subject matched in age and sex is presented in Fig-4. Comparison shows similar cortical patterns for the LCA2 and control while performing the checkerboard paradigm. However, as shown in Fig-2, the pattern and extent of activity is dramatically enhanced for the LCA2 subject performing the task while experiencing phosphenes.

This study, for the first time, reveals the cortical activation pattern of phosphenes with retinal origin in LCA2 patients. Our results clearly indicate that the presence of phosphenes creates activity throughout the entire occipital cortex of both hemispheres and activation patterns are no longer due to the stimulus presented to the subject. In the absence of phosphenes, activation in the same subject is comparable to those seen in the matched control. Although the experience of phosphenes in LCA2 patients may not be surprising, there are no clinical tests to confirm the experience of phosphenes unless the patient voluntarily reports it. We speculate that the phosphenes reported by the LCA2 patients are symptoms of the degenerative disease initiated by the abnormalities of retinal cells. A recent study (5) suggests that retinal phosphenes may be due to overproduction of the ultraweak spontaneous photons (biophotons) that are constantly emitted by retinal rod cells and photoreceptors without any external excitation. If these biophoton emissions exceed a certain threshold, it can appear as phosphene lights to our brain. fMRI plays an important role in identifying patients with and without phosphenes. Such identification may provide additional information regarding interpretation of other visual function tasks and may focus further attention on searching for structural abnormalities or retinal degenerative disease.