Transorbital alternating current stimulation modifies BOLD activity in healthy subjects and in a stroke patient with hemianopia: A 7 Tesla fMRI feasibility study

Background: Modifying brain activity using non-invasive, low intensity transcranial electrical brain stimulation (TES) has rapidly increased during the past 20 years. Alternating current stimulation (ACS), for example, has been shown to alter brain rhythm activities and modify neuronal functioning in the visual system. Daily application of transorbital ACS to patients with optic nerve damage induces functional connectivity reorganization, and partially restores vision. While ACS is thought to mainly modify neuronal mechanisms, e.g. changes in brain oscillations that can be detected by EEG, it is still an open question, whether and how it may alter BOLD activity. Objective: We evaluated whether transorbital ACS modulates BOLD activity in early visual cortex using high-resolution 7 Tesla functional magnetic resonance imaging (fMRI). Methods: In this feasibility study transorbital ACS in the alpha range and sham ACS was applied in a random block design in five healthy subjects for 20 min at 1 mA. Brain activation in the visual areas V1, V2 and V3 were measured using 7 Tesla fMRI-based retinotopic mapping at the time points before (baseline) and after stimulation. In addition, we collected data from one hemianopic stroke patient with visual cortex damage after ten daily sessions with 25-50 min stimulation duration. Results: In healthy subjects transorbital ACS increased the activated cortical surface area, decreased the fMRI response amplitude and increased coherence in the visual cortex, which was most prominent in the full field task. In the patient, stimulation improved contrast sensitivity in the central visual field. BOLD amplitudes and coherence values were increased in most early visual areas in both hemispheres, with the most pronounced activation detected during eccentricity testing in retinotopic mapping. Conclusions: This feasibility study showed that transorbital ACS modifies BOLD activity to visual stimulation, which outlasts the duration of the AC stimulation. This is in line with earlier neurophysiological findings of increased power in EEG recordings and functional connectivity reorganization in patients with impaired vision. Accordingly, the larger BOLD response area after stimulation can be explained by more coherent activation and lower variability in the activation. Alternatively, increased neuronal activity can also be taken into account. Controlled trials are needed to systematically evaluate the potential of repetitive transorbital ACS to improve visual function after visual pathway stroke and to determine the cause-effect relationship between neural and BOLD activity changes.