N-methyl-D-aspartate receptor antagonism impairs sensory gating in the auditory cortex in response to speech stimuli.

Deficits in early auditory sensory processing in schizophrenia have been linked to N-methyl-D-aspartate receptor (NMDAR) hypofunction, but the role of NMDARs in aberrant auditory sensory gating (SG) in this disorder is unclear. This study, conducted in 22 healthy humans, examined the acute effects of a subanesthetic dose of the NMDAR antagonist ketamine on SG as measured electrophysiologically by suppression of the P50 event-related potential (ERP) to the second (S2) relative to the first (S1) of two closely paired (500 ms) identical speech stimuli. Ketamine induced impairment in SG indices at sensor (scalp)-level and at source-level in the auditory cortex (as assessed with eLORETA).

N-methyl-d-aspartate receptor antagonism modulates P300 event-related potentials and associated activity in salience and central executive networks.

Impairments in auditory information processing in schizophrenia as indexed electrophysiologically by P300 deficits during novelty (P3a) and target (P3b) processing are linked to N -methyl- D -aspartate receptor (NMDAR) dysfunction. This study in 14 healthy volunteers examined the effects of a subanesthetic dose of the NMDAR antagonist ketamine on P300 and their relationship to psychomimetic symptoms and cortical source activity (with eLORETA). Ketamine reduced early (e- P3a) and late (l-P3a) novelty P300 at sensor (scalp)-level and at source-level in the salience network.

Resting-state functional EEG connectivity in salience and default mode networks and their relationship to dissociative symptoms during NMDA receptor antagonism.

N-methyl-d-aspartate receptor (NMDAR) antagonists administered to healthy humans results in schizophrenia-like symptoms, which are thought in part to be related to glutamatergically altered electrophysiological connectivity in large-scale intrinsic functional brain networks. Here, we examine resting-state source electroencephalographic (EEG) connectivity within and between the default mode (DMN: for self-related cognitive activity) and salience networks (SN: for detection of salient stimuli in internal and external environments) in 21 healthy volunteers administered a subanesthetic dose of the dissociative anesthetic and NMDAR antagonist, ketamine. In addition to provoking symptoms of dissociation, which are thought to originate from an altered sense of self that is common to schizophrenia, ketamine induces frequency-dependent increases and decreases in connectivity within and between DMN and SN.

NMDA Receptor Antagonist Effects on Speech-Related Mismatch Negativity and Its Underlying Oscillatory and Source Activity in Healthy Humans.

Unlabelled: Previous studies in schizophrenia have consistently shown that deficits in the generation of the auditory mismatch negativity (MMN) - a pre-attentive, event-related potential (ERP) typically elicited by changes to simple sound features - are linked to -methyl-D-aspartate (NMDA) receptor hypofunction. Concomitant with extensive language dysfunction in schizophrenia, patients also exhibit MMN deficits to changes in speech but their relationship to NMDA-mediated neurotransmission is not clear. Accordingly, our study aimed to investigate speech MMNs in healthy humans and their underlying electrophysiological mechanisms in response to NMDA antagonist treatment.

Effects of Ketamine on Resting-State EEG Activity and Their Relationship to Perceptual/Dissociative Symptoms in Healthy Humans.

-methyl-D-aspartate (NMDA) receptor antagonists administered to healthy humans results in schizophrenia-like symptoms, which preclinical research suggests are due to glutamatergically altered brain oscillations. Here, we examined resting-state electroencephalographic activity in 21 healthy volunteers assessed in a placebo-controlled, double-blind, randomized study involving administration of either a saline infusion or a sub-anesthetic dose of ketamine, an NMDA receptor antagonist. Frequency-specific current source density (CSD) was assessed at sensor-level and source-level using eLORETA within regions of interest of a triple network model of schizophrenia (this model posits a dysfunctional switching between large-scale Default Mode and Central Executive networks by the monitor-controlling Salience Network).

Nicotine, Auditory Sensory Memory, and sustained Attention in a Human Ketamine Model of Schizophrenia: Moderating Influence of a Hallucinatory Trait.

Background: The procognitive actions of the nicotinic acetylcholine receptor (nAChR) agonist nicotine are believed, in part, to motivate the excessive cigarette smoking in schizophrenia, a disorder associated with deficits in multiple cognitive domains, including low-level auditory sensory processes and higher-order attention-dependent operations.

Objectives: As N-methyl-d-aspartate receptor (NMDAR) hypofunction has been shown to contribute to these cognitive impairments, the primary aims of this healthy volunteer study were to: (a) to shed light on the separate and interactive roles of nAChR and NMDAR systems in the modulation of auditory sensory memory (and sustained attention), as indexed by the auditory event-related brain potential - mismatch negativity (MMN), and (b) to examine how these effects are moderated by a predisposition to auditory hallucinations/delusions (HD).

Methods: In a randomized, double-blind, placebo-controlled design involving a low intravenous dose of ketamine (0.

Effects of nicotine on electroencephalography and affect in adolescent females with major depressive disorder: a pilot study.

Background: Given that smoking is typically initiated during adolescence, and that this period in brain development seems to be uniquely sensitive to nicotine, depressed youth may be most susceptible to the neuromodulatory and mood-altering effects of nicotine. Electroencephalographic (EEG) studies suggest that individuals with major depressive disorder (MDD) exhibit left frontal lobe hypoactivation (indexed by increased EEG alpha), a region implicated in positive affect regulation, as well as right parietal hypoactivation. Smoking/nicotine abstinence has been associated with increased left frontal and right parietal alpha activity (reduced activation), which has been correlated with increased depression ratings; nicotine administration seems to normalize this depression-associated asymmetry.

Separate and combined effects of low dose ketamine and nicotine on behavioural and neural correlates of sustained attention.

Given the cognitive-promoting properties of the nicotinic acetylcholinergic receptor (nAChR) agonist, nicotine, the increased prevalence of smoke-inhaled nicotine in schizophrenia has been interpreted as an attempt to self-correct cognitive deficits, which have been particularly pronounced in the attentional domain. As glutamatergic abnormalities have been implicated in these attentional deficiencies, this study attempted to shed light on the separate and interactive roles of the N-methyl-d-aspartate receptor (NMDAR) and nAChR systems in the modulation of attention by investigating, in healthy volunteers, the separate and combined effects of nicotine and the NMDAR antagonist ketamine on neural and behavioural responses in a sustained attention task. In a randomized, double-blind, placebo controlled study, performance and the P300 event-related brain potential (ERP) in a visual information processing (RVIP) task were examined in 20 smokers and 20 non-smokers (both male and female).

Craving-induced EEG reactivity in smokers: effects of mood induction, nicotine dependence and gender.

Background/aims: Cigarette craving is a core symptom of smoking withdrawal, which is more intense and more frequently observed in smokers with depressed mood. Using self-reports and electroencephalographic (EEG) indices of frontal hemispheric asymmetry, which has been shown to be sensitive to mood states, the purpose of this study was to investigate the neural basis of cue-elicited cigarette craving, its variation with experimentally induced depressed mood, and with differences in gender and smoker type.

Methods: Cigarette-cue reactivity was examined in 11 (5 male) regular and 11 (6 male) light smokers in two sessions involving the induction of neutral or depressed mood.

EEG correlates of imagery-induced cigarette craving in male and female smokers.

Functional neuroimaging studies of cue-elicited craving in smokers have identified a distributed system of brain activation which includes the frontal cortex. As electroencephalographic (EEG) activity recorded from frontal brain regions indexes emotive functions, which are believed to play a key role in craving processes, this study examined frontal EEG in 20 cigarette smokers (10 male) exposed to imagery scripts containing positive, negative, or neutral affective content with and without descriptions of smoking urges. Urge scripts increased subjective cravings related to both the rewarding and withdrawal-relief properties of smoking, the latter tending to be greater in female smokers, as were self-reports of frustration.

Acute nicotine fails to alter event-related potential or behavioral performance indices of auditory distraction in cigarette smokers.

Behavioral studies have shown that nicotine enhances performance in sustained attention tasks, but they have not shown convincing support for the effects of nicotine on tasks requiring selective attention or attentional control under conditions of distraction. We investigated distractibility in 14 smokers (7 females) with event-related brain potentials (ERPs) and behavioral performance measures extracted from an auditory discrimination task requiring a choice reaction time response to short- and long-duration tones, both with and without embedded deviants. Nicotine gum (4 mg), administered in a randomized, double-blind, placebo-controlled crossover design, failed to counter deviant-elicited behavioral distraction (i.

Neural effects of nicotine during auditory selective attention in smokers: an event-related potential study.

Acute nicotine has been found to improve task performance in smokers after smoking abstinence, but the attentional processes mediating these improvements are unclear. Since scalp-recorded event-related potentials (ERPs) have been shown to be sensitive indicators of selective attention, the effects of acutely administered nicotine were examined on ERPs and concomitant behavioural performance measures in an auditory selective attention task. Ten (6 males) overnight smoking-abstinent cigarette smokers received nicotine gum (4 mg) in a randomized, double-blind, placebo-controlled, crossover design.

Clonidine pre-treatment fails to block acute smoking-induced EEG arousal/mood in cigarette smokers.

Given the arousal eliciting actions of smoking and nicotine, and the contributing role of noradrenaline in brain arousal systems, this study examined the neuroelectric and affective correlates of cigarette smoking following acute pre-treatment with the alpha 2-noradrenergic auto-receptor agonist, clonidine. In a double-blind placebo-controlled crossover design, quantitative electroencephalography (EEG), mood, and smoking withdrawal symptoms were assessed in 12 overnight smoking abstinence smokers, before and after sham and cigarette smoking. Orally administered clonidine (0.

Anticipatory cues differentially provoke in vivo peptidergic and monoaminergic release at the medial prefrontal cortex.

Like primary reinforcers, the anticipation of reward ought to affect neurochemical release in brain regions, such as the medial prefrontal cortex (mPFC), which are associated with appraisal processes. To assess the neurochemical changes associated with anticipation, rats were exposed to the pairing of auditory (60-dB white noise), visual, and olfactory cues with the daily presentation of a palatable snack (Cue Relevant group). Rats of a second group were similarly trained, but for a 2-week period, the snack was no longer provided following cue presentation (Extinction group).

Anxiety in rats selectively bred for Fast and Slow kindling rates: situation-specific outcomes.

Rats selectively bred for amygdala excitability, realized by fast or slow kindling epileptogenesis, were previously reported to exhibit differential levels of anxiety. Although the Slow kindling rats generally appeared more anxious in several behavioral tests, under certain test conditions the Fast kindling rats displayed greater anxiety or stressor reactivity. The present investigation confirmed that in a test of anxiety comprising suppression of consumption of a palatable snack in an unfamiliar environment, the Slow kindling rats exhibited greater anxiety and that this effect was attenuated by diazepam.

Differential involvement of amygdaloid CRH system(s) in the salience and valence of the stimuli.

Anxiety is a heterogeneous term encompassing not only state or trait characteristics but also a wide range of pathologies such as generalized anxiety disorders, phobias, panic and obsessive-compulsive disorders, acute stress disorder, and posttraumatic stress disorder. Given that diverse forms of anxiety exist, numerous animal models have been developed, which are considered to be useful in identifying mechanisms underlying anxiety states. Examples of such animal models include paradigms that assess the behavioral response to neurogenic (or painful stimuli) or psychogenic stressors or to cues that had previously been associated with painful stimuli.