Induction of interhemispheric visual plasticity by paired associative stimulation

Unveiling the plastic mechanisms of the primary visual cortex (V1) is crucial for understanding how visual processing can change and adapt, ultimately informing interventions to promote functional recovery following visual system damage. Paired associative stimulation (PAS) protocols can induce associative plasticity within the human V1. However, previous paradigms used full-field visual stimulation, engaging both hemispheres simultaneously, leaving unclear whether plasticity can be selectively targeted to a single visual pathway and whether it can modulate the non-stimulated hemisphere. Across three experiments in healthy participants, we investigated the neurophysiological, behavioural, and interhemispheric outcomes of a novel lateralized visual PAS protocol (vPAS). Pattern-reversal checkerboards were presented in a single visual hemifield and time-locked to transcranial magnetic stimulation (TMS) pulses delivered over the contralateral V1. Experiment 1 assessed neurophysiological effects by recording hemifield-lateralized visual-evoked potentials (VEPs) and testing three inter-stimulus intervals (ISIs: 75, 100, and 125 ms) between vPAS-paired stimuli. Experiment 2 evaluated perceptual changes in contrast detection, while Experiment 3 examined vPAS hemispheric specificity and aftereffects on interhemispheric visuomotor transfer. Only the 75-ms ISI consistently modulated visual processing in the non-conditioned hemisphere, reducing N75 amplitude and improving contrast detection for visual stimuli presented contralateral to the TMS side. Longer ISIs were not effective. Furthermore, this protocol altered interhemispheric transfer exclusively when the left, but not the right, V1 was targeted during vPAS. In conclusion, lateralized vPAS induces timing-dependent changes beyond the stimulated cortex, suggesting that associative plasticity can engage contralateral visual circuits and modulate visual processing.