Neuromodulation Through Multisensory Stimulation for Visual Field Deficits in the Subacute Stage of Disease

Overview

Homonymous visual field defects (HVFDs) after acquired brain injuries affect daily life by impairing reading, navigation, and social activities, often impacting anxiety and depression. Spontaneous recovery is rare. Rehabilitation approaches include restorative treatments, which aim to expand the visual field through the stimulation of the so-called transition zone, and compensatory strategies, such as audio-visual training (AVT), which combines eye movement exercises with synchronized visual and auditory cues to train oculomotor scanning and overcome the visual field loss. Combining AVT with non-invasive brain stimulation, such as transcranial direct current stimulation (tDCS), may enhance recovery by promoting brain plasticity. Early evidence suggests that tDCS applied to the lesioned visual cortex during AVT can speed and stabilize improvements, potentially also restoring parts of the visual field. However, most studies on AVT have focused on chronic patients, whereas several clinical trials and international guidelines indicate that early treatment of HVFDs in the subacute phase can optimally exploit the window of maximal neural plasticity and prevent secondary degenerative processes, thereby maximizing visual recovery. In the present randomized clinical trial, we assess the efficacy of a multisensory audio-visual training (AVT) combined with tDCS in patients with subacute HVFDs after stroke (\<3 months post-lesion). Participants are randomly assigned to two groups: AVT combined with real anodal tDCS applied to the lesioned occipital cortex (Group 1), or AVT combined with sham tDCS (Group 2). The AVT requires participants to orient their gaze toward spatio-temporally congruent, cross-modal audio-visual stimuli (starting from a central fixation) and press a button as quickly as possible upon detecting the visual target. All stimuli are presented on 2mx2m panel embedded with 40 LEDs and loudspeakers (Diana, Casati, Melzi, Marzoli, et al., 2024). The training will be administered for 90 minutes daily over 10 consecutive days. All participants underwent a neuro-ophthalmological evaluation and neuropsychological assessment of visuospatial functions before the beginning of the training (t0), at the end of the training (t1), at 2 months (t2) and after 1 year (t3).

Interventions

• Device tDCS
  Anodal or sham tDCS (see "Arms") is applied during the execution of an audio-visual training.
• Behavioral Audio-visual training
  90 min/day x 10 days. Participants are seated in front of a 2 m × 2 m training board, at a distance of 1.2 m, in a dimly lit room. The board features 48 red light-emitting diodes (LED, diameter 1 cm, luminance 90 cd m2), distributed in six horizontal rows (eight lights per row). Forty-eight piezoelectric loudspeakers (0.4 W, 8Ω) are located above each light, producing a white-noise (80 dB, duration 100 ms). Spatio-temporally congruent, cross-modal, audio-visual stimuli are presented at one out

Primary outcome measures

• Change from baseline in Humphrey Visual Field perimetry [Time frame: At baseline (at the beginning of the treatment), at the end of the treatment, at 2- and 12-month follow-ups]

Secondary outcome measures (6)

• Change from baseline in Accuracy and reaction time on the EF Task [Time frame: At baseline (at the beginning of the treatment), at the end of the treatment, at 2- and 12-month follow-ups]
• Change from baseline in Accuracy and Reaction times on the Triangle Task [Time frame: At baseline (at the beginning of the treatment), at the end of the treatment, at 2- and 12-month follow-ups]
• Change from baseline in Accuracy and RTs on the Visual Detection Task [Time frame: At baseline (at the beginning of the treatment), at the end of the treatment, at 2- and 12-month follow-ups]
• Change in retinal layers thickness assessed with Spectral Domain Optical Coherence Tomography [Time frame: At baseline (at the beginning of the treatment), at 2- and 12-month follow-ups]
• Change in Visual Evoked Potential amplitude [Time frame: At baseline (at the beginning of the treatment), at the end of the treatment and at 12-month follow-ups]
• Change from baseline in the functional scale assessing the impact of vision loss in everyday life activities [Time frame: At baseline (at the beginning of the treatment), at the end of the treatment, at 12-month follow-ups]

Eligibility criteria

Inclusion criteria

\- Presence of subacute acquired brain injury (< 3 months) with HVFD according to Neurophthalmological evaluation

Exclusion criteria

• Presence of hemispatial neglect (indexed by pathological asymmetries on paper-and-pencil tests)
• Disorders of conjugated eye movements
• Other neurological disorders (e.g., dementia)
• Exclusion criteria for brain stimulation (i.e., epilepsy or family history of epilepsy; implanted electrodes, stimulators, pacemakers, infusion pumps, or any implanted metal device; pregnancy)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Italy · 1 center

• Istituto Auxologico Italiano IRCCS — Milan

Identifiers

NCT: NCT07358832 · 25C504

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗