Table 1.
Subject demographics.
Figure 1.
Real time fMRI software allows continuous monitoring of subject's cortical response for specific regions of interest (ROIs) placed in the area of interest. In the example above, two ROIs (white and green circles shown with white arrows) are selected in the right and left primary visual cortex (V1) located in the medial aspect of the occipital lobes encompassing the calcarine fissures. Real time fMRI monitoring also allows motion detection in three translational and three rotational orientations depicted in the B and C panels respectively. Experiments are interrupted if no response is detected in panel A or the rotational and translational movements are>0.6.
Figure 2.
fMRI stimuli and paradigm design.
(A) Checkerboard stimuli with a constant light intensity of 5 lux at three levels of contrast: high (H; 100%), medium (M; 34%) and low (L; 10%), were presented in a boxcar block design. (B) The checkerboard paradigm consisted of 15 sec active blocks of contrast reversing (8 Hz) checkerboards interleaved with 15 sec presentations of a blank (black) screen as control blocks (rest period). Three blocks of each contrast were interspersed randomly and interleaved with nine rest blocks.
Table 2.
Cluster information of activated brain regions for LCA2 patients while not experiencing phosphenes.
Table 3.
Cluster information of activated brain regions in LCA2 patients when experiencing phosphenes.
Figure 3.
fMRI results for NP02 left and right eye (treated eye) with and without experiencing phosphenes.
(A) fMRI results from the left eye when presented with the same checkerboard stimuli, when no phosphene was reported, showed significant clusters of activations (fdr<5%, Corrected p<0.004, cca ≥100 mm2) which were primarily distributed on the lateral aspects of visual cortex with minimal spread to the medial surface of the right hemisphere. (C) fMRI results from the right eye (treated eye) when presented with the same checkerboard stimuli while no phosphene reported by the subject (Uncorrected p<. 010, cca>100 mm2). (D) Similar to the left eye, visual cortex showed extraordinary amount of activations in response to the checkerboard stimuli presented to the right eye (treated eye) in the presence of phosphenes. fMRI results showed significant widespread (fdr<3%, Corrected p<0.006, cca ≥1000 mm2) bilateral activations extending and spreading to all visual centers of occipital cortex. (B) fMRI results for the left eye when presented with checkerboard stimuli showed significant widespread (fdr<3%, Corrected p<0.005, cca ≥1000 mm2) activations that were bilaterally distributed to all areas of visual cortex, when NP02 reported experiencing phosphene.
Figure 4.
fMRI results for CH08 left and right eye (treated eye) with and without experiencing phosphenes.
(A) fMRI results from the left eye when presented with the same checkerboard stimuli and no phosphene was reported showed small areas of activations detectable only at a less stringent statistical threshold (not fdr corrected) and much lower extent threshold (Uncorrected p<0.005, cca ≥50 mm2). (C) fMRI results from the right eye (treated eye) when presented with the same checkerboard stimuli and no phosphene reported by the subject. CH08 presented with significant activations for his treated eye (fdr<5%, Corrected p<0.005 cca>100 mm2) as compared to his untreated eye (left). However, although there are noticeably more activations for the treated eye, the magnitude and distribution of cortical activations for the treated eye when experiencing phosphene are significantly greater (D). (B) fMRI results showed significant widespread (fdr<3%, Corrected p<0.004, continuous connected area (cca) ≥1000 mm2) bilateral activations in all areas of visual cortex extending from medial to lateral and posterior to anterior aspects of the occipital cortex after presentation of checkerboard stimuli to his left eye while experiencing phosphene. (D) Similar to the left eye, visual cortex showed remarkable response to the checkerboard stimuli presented to the right eye (treated eye) while under the influence of phosphenes. fMRI results showed significant widespread (fdr<3%, Corrected p<0.004, cca ≥1000 mm2) bilateral activations extending and spreading to all brain visual centers.
Figure 5.
fMRI results for CH11 left and right (treated) eye with and without experiencing phosphenes.
(A) fMRI results from the CH11 left eye, when presented with the same checkerboard stimuli and phosphenes were absent, showed limited areas of activations detectable only at a less stringent statistical threshold (Uncorrected p<0.010, cca ≥100 mm2). (C) fMRI results from the right eye (treated eye) when presented with the same checkerboard stimuli and no phosphene was reported. CH11 presented with significant activations for her treated eye (Uncorrected p<0.01, cca>100 mm2) as compared to her untreated eye (left). However, although there is noticeably more activation for CH11's treated eye, the magnitude and distribution of cortical activations for the treated eye when experiencing phosphene (D) are significantly more. (B) fMRI results showed significant widespread (fdr<3%, Corrected p<0.003, cca ≥1000 mm2) bilateral activations in all areas of visual cortex extending from medial to lateral and posterior to anterior aspects of the occipital cortex after presentation of checkerboard stimuli to the left eye while experiencing phosphene. (D) Similar to the left eye, visual cortex showed significant widespread responses (fdr<3%, Corrected p<0.004, cca ≥1000 mm2) to the checkerboard stimuli presented to the right eye (treated eye) while CH11 reported seeing phosphenes.
Figure 6.
fMRI results for normal controls NC04 and NC05 left and right eye.
(A) Left eye of NC04. (C) Right eye of NC04. (B) Left eye of NC05. (D) Right eye of NC05. Both subjects show a more normal activation pattern associated with the checkerboard stimuli (fdr<5%, Corrected p<0.004, cca>100 mm2). Note that the amount of activations seen in the normal control subjects is noticeably less than that of subjects experiencing phosphene. It is also important to point out that the activation pattern for both NC04 and NC05 in response to the checkerboard stimuli is more medially focused around the calcarine fissure than the more widespread pattern of activations seen in cases of phosphene. As shown here, the cortical activation pattern for the LCA patients, in the absence of phosphene, is drastically different from those of normal controls where activation is more focused in the primary visual cortex and symmetrically distributed between hemispheres for both the left and right eyes.
Table 4.
Cluster information of activated brain areas for sighted controls.