No abstract

Several lines of research suggest that impairments in long-term potentiation (LTP)-like synaptic plasticity might be a key pathophysiological mechanism in schizophrenia (SZ) and bipolar disorder type I (BDI) and II (BDII). Using modulations of visually evoked potentials (VEP) of the electroencephalogram, impaired LTP-like visual cortical plasticity has been implicated in patients with BDII, while there has been conflicting evidence in SZ, a lack of research in BDI, and mixed results regarding associations with symptom severity, mood states, and medication. We measured the VEP of patients with SZ spectrum disorders (n = 31), BDI (n = 34), BDII (n = 33), and other BD spectrum disorders (n = 2), and age-matched healthy control (HC) participants (n = 200) before and after prolonged visual stimulation. Compared to HCs, modulation of VEP component N1b, but not C1 or P1, was impaired both in patients within the SZ spectrum (χ 2 = 35.1, P = 3.1 × 10−9) and BD spectrum (χ 2 = 7.0, P = 8.2 × 10−3), including BDI (χ 2 = 6.4, P = .012), but not BDII (χ 2 = 2.2, P = .14). N1b modulation was also more severely impaired in SZ spectrum than BD spectrum patients (χ 2 = 14.2, P = 1.7 × 10−4). N1b modulation was not significantly associated with Positive and Negative Syndrome Scale (PANSS) negative or positive symptoms scores, number of psychotic episodes, Montgomery and Åsberg Depression Rating Scale (MADRS) scores, or Young Mania Rating Scale (YMRS) scores after multiple comparison correction, although a nominal association was observed between N1b modulation and PANSS negative symptoms scores among SZ spectrum patients. These results suggest that LTP-like plasticity is impaired in SZ and BD. Adding to previous genetic, pharmacological, and electrophysiological evidence, these results implicate aberrant synaptic plasticity as a mechanism underlying SZ and BD.

29Experience-dependent modulation of the visual evoked potential (VEP) is a 30 promising proxy measure of synaptic plasticity in the cerebral cortex. However, 31 existing studies are limited by small to moderate sample sizes as well as by 32 considerable variability in how VEP modulation is quantified. In the present study, we 33 used a large sample (n = 415) of healthy volunteers to compare different 34 quantifications of VEP modulation with regards to effect sizes and retention of the 35 modulation effect over time. We observed significant modulation for VEP 36 components C1 (Cohen's d = 0.53), P1 (d = 0.66), N1 (d = -0.27), N1b (d = -0.66), 37 but not P2 (p = 0.1), and in one time-frequency cluster (~30 Hz and ~70 ms post-38 stimulus; d = -0.48), 2-4 minutes after 2 Hz prolonged visual stimulation. For 39 components N1 (d = -0.21) and N1b (d = -0.38), as well for the time-frequency cluster 40 (d = -0.33), this effect was retained after 54-56 minutes. Moderate to high 41 correlations (r = [0.39, 0.69]) between modulation at different postintervention blocks 42 revealed a relatively high temporal stability in the modulation effect for each VEP 43component. However, different VEP components also showed markedly different 44 temporal retention patterns. Finally, P1 modulation correlated positively with age (t = 45 5.26), and was larger for female participants (t = 3.91), with no effects of either age or 46 sex on N1 and N1b potentiation. These results provide strong support for VEP 47 modulation, and especially N1b modulation, as a robust measure of synaptic 48 plasticity, but underscore the need to differentiate between components, and to 49 control for demographic confounders. 50