Graviceptive Neglect treatment in acute stroke using transcranial Electrical stimulation clinical trial (GravNegElect): rationale, objectives, and design

Abstract Background: Stroke is one of the leading causes of disability globally and is often related to poor functional recovery and a high risk of falling. These outcomes correlate closely with an impaired perception of visual verticality (VV), a frequent condition referred to as visual graviceptive neglect (V-GN). Our prior findings indicate that post-stroke VV is most frequently rotated away from the lesioned hemisphere in the roll plane. Furthermore, we demonstrated that a focal transcranial direct current stimulation (tDCS) montage (known as high-definition tDCS; HD-tDCS) can induce a remarkable and sustained rotation away from the stimulated hemisphere when positioned over the temporo-parietal junction (TPJ), a key integrative cortical hub for VV. Therefore, we hypothesize that stimulating the contralesional TPJ in sub-acute stroke individuals will correct their V-GN. Methods: This phase IIa, randomised, double-blind, sham-controlled clinical trial aims to determine whether HD-tDCS can safely correct V-GN in individuals who have experienced a stroke affecting either hemisphere. Ancillary aims are to investigate whether HD-tDCS influences ocular torsion; explore neuroanatomical characteristics related to V-GN; investigate the relationship between EEG functional connectivity and V-GN; and determine the cerebrovascular reactivity effects of HD-tDCS. A total of 28 individuals diagnosed with acute or early sub-acute unihemispheric ischemic stroke (50% with right hemisphere lesions) will be randomized to receive six 20-minute sessions (conducted within 2 days) of either 2mA cathode-centre HD-tDCS or sham stimulation over the contralesional TPJ. VV will be assessed using the bucket method. The primary outcome is the change in VV from baseline to immediately after the intervention protocol, while the secondary outcome is VV assessed at 1 month post-intervention. Fundus photography (ocular torsion), vascular reactivity using transcranial Doppler, and resting state EEG (functional connectivity) will be assessed at the same time-points as VV. Structural and resting state functional MRI will be performed 2-15 days after stroke onset. Fractional anisotropy within the V-GN network regions-of-interest (ROIs) and transcallosal TPJ tract will be correlated with baseline VV and V-GN response to intervention. Discussion: This trial has the potential for a significant public health impact by providing foundational clinical and physiological evidence to develop future clinical interventions for V-GN. Trial registration: ClinicalTrials.gov NCT06747676. Registered on 12 December 2024. Version 2.