Impaired Potentiation of Theta Oscillations During a Visual Cortical Plasticity Paradigm in Individuals With Schizophrenia.

Holly K Hamilton,Timothy J Teyler,Wesley C Clapp,Judith M Ford,Idil Cavus,Brian J Roach,Erendiz Tarakci,Daniel H Mathalon,John H Krystal

doi:10.3389/fpsyt.2020.590567

Abstract

Long-term potentiation (LTP) is a form of experience-dependent synaptic plasticity mediated by glutamatergic transmission at N-methyl-D-aspartate receptors (NMDARs). Impaired neuroplasticity has been implicated in the pathophysiology of schizophrenia, possibly due to underlying NMDAR hypofunction. Analogous to the high frequency electrical stimulation used to induce LTP in vitro and in vivo in animal models, repeated high frequency presentation of a visual stimulus in humans in vivo has been shown to induce enduring LTP-like neuroplastic changes in electroencephalography (EEG)-based visual evoked potentials (VEPs) elicited by the stimulus. Using this LTP-like visual plasticity paradigm, we previously showed that visual high-frequency stimulation (VHFS) induced sustained changes in VEP amplitudes in healthy controls, but not in patients with schizophrenia. Here, we extend this prior work by re-analyzing the EEG data underlying the VEPs, focusing on neuroplastic changes in stimulus-evoked EEG oscillatory activity following VHFS. EEG data were recorded from 19 patients with schizophrenia and 21 healthy controls during the visual plasticity paradigm. Event-related EEG oscillations (total power, intertrial phase coherence; ITC) elicited by a standard black and white checkerboard stimulus (~0.83 Hz, several 2-min blocks) were assessed before and after exposure to VHFS with the same stimulus (~8.9 Hz, 2 min). A cluster-based permutation testing approach was applied to time-frequency data to examine LTP-like plasticity effects following VHFS. VHFS enhanced theta band total power and ITC in healthy controls but not in patients with schizophrenia. The magnitude and phase synchrony of theta oscillations in response to a visual stimulus were enhanced for at least 22 min following VHFS, a frequency domain manifestation of LTP-like visual cortical plasticity. These theta oscillation changes are deficient in patients with schizophrenia, consistent with hypothesized NMDA receptor dysfunction.

Highlights

Neural plasticity dysfunction in schizophrenia has been hypothesized to underlie cognitive impairment [1,2,3], which is a core feature of the illness and a major determinant of functional outcomes [4, 5]
Using a cluster-based permutation testing approach [65], we found that the delivery of repetitive high frequency visual stimulation (VHFS) induced Long-term potentiation (LTP)-like visual cortical potentiation in healthy individuals
This was evident as an increase in visual eventrelated EEG theta band total power and phase synchrony (ITC) over posterior scalp electrodes from pre- to post-visual high-frequency stimulation (VHFS), plasticity effects that persisted for at least 22 min post-VHFS

Summary

INTRODUCTION

Neural plasticity dysfunction in schizophrenia has been hypothesized to underlie cognitive impairment [1,2,3], which is a core feature of the illness and a major determinant of functional outcomes [4, 5]. LTP is typically observed following high frequency “tetanizing” electrical stimulation and is identified electrophysiologically as a persistent increase in postsynaptic cellular currents using single-cell or local field recordings Using these methods, LTP has been documented in animals at synapses in regions that include the hippocampus, amygdala, and striatum, as well as visual, auditory, and somatosensory cortices [9, 10, 30]. Neural assemblies show synchronous oscillatory activity across a wide range of frequency bands (e.g., delta, theta, alpha, beta, gamma), observed both in local field potentials as well as in scalp-recorded EEG These oscillations are implicated as a primary mechanism for coordinated communication between local and distant neuronal networks and are involved in the integration of a variety of brain functions including learning and memory as well as other sensory, perceptual, and higherorder cognitive processes. We sought to replicate Clapp et al.’s [61] finding of VHFS-induced alpha ERD enhancement in healthy individuals, and we examined whether patients with schizophrenia showed deficient potentiation of alpha-ERD following VHFS

Participants

RESULTS

DISCUSSION

ETHICS STATEMENT