Modulation of the cortical processing of novel and target stimuli by drugs affecting glutamate and GABA neurotransmission

Abstract

In this double-blind, placebo-controlled study, we examined the effects of subanesthetic doses of ketamine (an NMDA glutamate receptor antagonist) and thiopental (a GABA-A receptor agonist) on the event-related potential (ERP) correlates of deviant stimulus processing in 24 healthy adults. Participants completed three separate pharmacologic challenge sessions (ketamine, thiopental, saline) in a counterbalanced order. EEG data were recorded both before and during each challenge while participants performed a visual “oddball” task consisting of infrequent “target” and “novel” stimuli intermixed with frequent “standard” stimuli. We examined drug effects on the amplitude and latency of the P3(00) component of the ERP elicited by target (P3b) and novel stimuli (P3a), as well as the N2(00) and P2(00) components elicited by both targets and novels. Relative to placebo, both drugs reduced the amplitude of parietal P3b, and also tended to attenuate Target N2. Their effects on novelty processing were more differentiated. While both drugs reduced parietal P3a, this effect was greater for thiopental. Relative to placebo, ketamine also increased frontal P3a amplitude, shortened P3a latency, reduced N2, and enhanced P2 to novel stimuli.

Effects of Acute Ketamine Infusion on Visual Working Memory: Event-Related Potentials

“…This finding is consistent with previous studies in the auditory and visual domains (47)(48)(49)(50)(51)(52)(53)86) although we observed a strong effect only in the encoding phase with the retrieval significance reduced to a trend. We also found a trend for correlation between P300 and cognitive performance under ketamine for both encoding and retrieval conditions.…”

“…Studies so far have focused on auditory oddball paradigms and reported reductions in P300 as well as a marker of automatic WM update, mismatch negativity (47)(48)(49)(50). Visual experiments have focused exclusively on later ERP components, reporting an attenuation of the P300 component (51)(52)(53).…”

GABA Deficits Enhance the Psychotomimetic Effects of Δ9-THC

“…Reductions in P300 amplitude and increased latencies have been observed in a number of other neuropsychiatric disorders including schizophrenia (reviewed in Bramon et al, 2004;Jeon and Polich, 2003). Both GABAergic and glutamatergic systems have been strongly implicated in contributing to the P300 (Watson et al, 2009). In fact, it is now recognized that ERPs such as the P300 are generated by inhibitory and excitatory postsynaptic potentials, which are primarily driven by the release of glutamate and GABA (Luck et al, 2011).…”

Subjective Duration as a Signature of Coding Efficiency: Emerging Links Among Stimulus Repetition, Predictive Coding, and Cortical GABA Levels

“…Specifically, the magnitude of the hemodynamic response of the fMRI-BOLD signal in the visual cortex was reduced in individuals with larger GABA levels in this region, possibly through an effect on local circulation or glutamate levels (Muthukumaraswamy et al, 2009). Pharmacological studies complement this finding by showing that GABA agonists reduce perceptual awareness (van Loon et al, 2012) and visual discrimination (Giersch & Herzog, 2004), and attenuate the neurophysiological response to visual oddball stimuli (P3 event-related brain potential component; Watson et al, 2009). Further studies showed that GABA agonists also impair temporal discrimination of auditory intervals (Rammsayer, 1992(Rammsayer, , 1999.…”