Methods to Compare Predicted and Observed Phosphene Experience in tACS Subjects

Abstract

Background Phosphene generation is an objective physical measure of potential transcranial alternating current stimulation (tACS) biological side effects. Interpretations from phosphene analysis can serve as a first step in understanding underlying mechanisms of tACS in healthy human subjects and assist validation of computational models. Objective/Hypothesis This preliminary study introduces and tests methods to analyze predicted phosphene occurrence using computational head models constructed from tACS recipients against verbal testimonies of phosphene sensations. Predicted current densities in the eyes and the occipital lobe were also verified against previously published threshold values for phosphenes. Methods Six healthy subjects underwent 10 Hz tACS while being imaged in an MRI scanner. Two different electrode montages, T7-T8 and Fpz-Oz, were used. Subject ratings of phosphene experience were collected during tACS and compared against current density distributions predicted in eye and occipital lobe regions of interest (ROIs) determined for each subject. Calculated median current densities in each ROI were compared to minimum thresholds for phosphene generation. Main Results All subjects reported phosphenes, and predicted median current densities in ROIs exceeded minimum thresholds for phosphenes found in the literature. Higher current densities in the eyes were consistently associated with decreased phosphene generation for the Fpz-Oz montage. There was an overall positive association between phosphene perceptions and current densities in the occipital lobe. Conclusions These methods may have promise for predicting phosphene generation using data collected during in-scanner tACS sessions and may enable better understanding of phosphene origin. Additional empirical data in a larger cohort is required to fully test the robustness of the proposed methods. Future studies should include additional montages that could dissociate retinal and occipital stimulation.

Amplitude modulating frequency overrides carrier frequency in tACS‐induced phosphene percept

“…This result implies that the leaking current to the eye during occipital stimulation with its least intensity was strong enough to elicit a retinal response, which is in line with previous findings (Evans et al, 2019 ; Schwiedrzik, 2009 ; Paulus, 2010 ; Vöröslakos et al, 2018 ) to support retina as the phosphene generator of occipital tACS. Indahlastari and colleagues (Indahlastari et al, 2018 ) estimated the current density in occipital cortex and eye using Fpz‐Oz and T7‐T8 montages. Their result revealed a higher current density in the eye than in the visual cortex, also, the current density in the eye predicted participants' phosphene rating better than which in the visual cortex.…”

“…Nevertheless, the cortical contribution during tACS‐induced phosphene cannot be excluded completely for the following reasons. Firstly, the conventional large rubber electrodes usually elicit a wide‐range current distribution that inevitably affects the retina (Indahlastari et al, 2018 ; Mehta et al, 2015 ; Vöröslakos et al, 2018 ). This causes difficulty in dissociating phosphene that is generated from the cortex or the retina (Paulus, 2010 ; Schutter & Hortensius, 2010 ).…”

Review of individualized current flow modeling studies for transcranial electrical stimulation

“…Caulfield et al (2020) found a positive correlation between the motor threshold of tES and the estimated stimulation intensity to reach an electric field intensity of 1 V/m in the cortex underneath the anode. In the eye, as a distinct target subsystem, studies comparing current flow modeling results and phosphene perception indicated good agreement of current density intensity in the retina and perceived phosphenes for transcranial stimulation at electrode positions T7–T8 (Indahlastari et al, 2018) and transorbital stimulation (Sabel et al, 2021), indicating simulated current flow as a marker for physiological stimulation effects. The study by Indahlastari and colleagues indicated a significant correlation between simulated current density and functional connectivity in a cohort of healthy elderly participating in a working memory task (Indahlastari et al, 2021).…”

Noninvasive Brain Stimulation for Neurorehabilitation in Post-Stroke Patients

“…It has also been suggested that the optimal tACS parameters may not be fixed. Combining tACS with techniques such as EEG and fMRI can provide individualized and adaptive stimulation parameters using feedback from the electrophysiological brain signals, which may help to improve the effectiveness of tACS and advance the application of tACS in clinical practice [ 81 , 82 , 83 ].…”