PET Study of Light and Transcorneal Electrical Stimulation in Humans

Abstract

Purpose: : The ability to measure visual cortex activity in retinal degenerative subjects (RDs) can objectively demonstrate which cortical areas respond when the retina is electrically stimulated. Here we use positron emission tomography (PET) and 18F-fluorodeoxyglucose (FDG) to evaluate brain activation under light stimulation and transcorneal electrical stimulation (TcES) conditions in normal-sighted controls (NCs) and RDs.

Methods: : 3 quantitative FDG PET studies were performed on each of 5 NCs (34.3±10 yrs) and 5 RDs (43.7±10.5 yrs, >10 yrs of light-perception-only best visual acuity). All subjects were right-handed and underwent 30-min dark adaptation prior to each study. For baseline study, subjects were blindfolded during the 30-min FDG uptake. For light stimulation study, subjects’ OD was exposed to a light stimulus for 30 min. The stimulus, which subtended central 10° field of view, was a repeating sequence (30-sec duration) of flashing white square with temporal frequency increasing incrementally from 2 to 30 Hz. For TcES study, a clinical grade neurostimulator (DS7A, Digitimer, LTD) was connected to an ERG-Jet contact lens corneal electrode (Fabrinal SA) that was placed on the subjects’ OD. A continuous train of rectangular, alternating monophasic electrical pulses (2Hz, 2msec pulse width, 1.5× phosphene threshold current amplitude) was delivered to the electrode during the 30-minute FDG uptake. Each PET scan was acquired for 20 min. Converted metabolic images were analyzed using SPM5 to identify changes in cortical activity.

Results: : Each stimulation condition was compared to baseline using SPM with p<0.05 as threshold significance level. Both light stimulation and TcES resulted in activation of primary (BA 17) and secondary visual cortex (BA 18, 19) in NCs and RDs. Both NCs and RDs reported consistent phosphene sensation in the peripheral temporal visual field of the right eye, and this led to retinotopically matched primary visual cortex activation in both groups. TcES modeling corroborated the phosphene sensation by demonstrating preferential neuronal stimulation along the peripheral nasal hemiretina in the right eye.

Conclusions: : The study demonstrates electrical stimulation of the retina can activate visual cortex and lead to visual perception in RDs and establishes a basis for assessing retinal prosthesis functionality in vivo.

Keywords: imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • visual cortex • retinitis