Abstract
Deficient neuroplasticity has been implicated in schizophrenia and can be examined with non-invasive methods in humans. High frequency visual stimulation (HFS) induces neuroplastic changes in visual evoked potential (VEP) components, similar to the tetanizing electrical stimulation that induces synaptic long-term potentiation (LTP). While visual HFS paradigms have been used in schizophrenia, the use of a single visual stimulus has precluded demonstration of whether the plasticity effects are specific to the stimulus presented during HFS (i.e., input specific). Additionally, test-retest reliability of VEP plasticity effects, an important consideration for applications of HFS paradigms in schizophrenia clinical trials, remains unknown. Accordingly, we administered a visual HFS paradigm to 38 schizophrenia patients and 27 healthy controls at baseline and two-weeks later. VEPs were elicited by horizontal and vertical line gratings before and after HFS; only one orientation was tetanized with HFS. Using a mass univariate permutation approach, we identified an input-specific cluster across groups that was broadly distributed over parietal-occipital areas between 108 and 183 ms. However, the groups did not differ in terms of the strength of plasticity effect. The test-retest reliability of the input-specific plasticity effect was modest over two weeks, suggesting that this HFS paradigm requires further development before it could be used to track plasticity change in clinical trials. Moreover, while the current HFS paradigm induced significant input-specific neuroplasticity, it did not replicate prior studies showing deficient neuroplasticity in schizophrenia. Accordingly, demonstration of deficient visual LTP-like neuroplasticity in schizophrenia may depend on paradigm parameters that remain to be fully elucidated.