Simultaneous EEG + fMRI study of brain activity during an emotional Stroop task in individuals in remission from depression.

Individuals in remission from depression (MDDR) tend to experience lingering cognitive and emotional processing alterations. However, little is known about the neural profiles underlying these features. Using simultaneous EEG+fMRI, we assessed neural profiles during the emotional word Stroop task (eStroop) in people with MDDR and healthy volunteers (HVs). Event-related potentials (ERPs) were extracted (N450, N2 & P3). Assessments of brain activation, as modulated by ERPs, were carried out, as were fMRI-informed ERP analyses. A trend for greater P3 amplitudes in MDDR versus HV groups existed. HV versus MDDR groups had greater brain activation to emotional versus neutral words in various regions, including the left amygdala, inferior frontal gyrus (IFG); this appeared to be driven by elevated activity to neutral words in the MDDR group (neutral > emotional). HVs showed greater activation (emotional > neutral) modulated by N450 amplitude in various regions, while MDDRs showed greater neutral > emotional activation modulated by N450 amplitude in the left IFG and left precuneus. Our EEG+fMRI findings indicate that people with MDDR appear to have blunted neural differentiation to emotional versus neutral stimuli or elevated neural responses to neutral information processing. This might represent altered neuronal processing (i.e., underlying attention and conflict processing) during a cognitive task with an emotional component in individuals remitted from depression, or elevated neural responses to ambiguous or neutral information. In sum, subtle lingering neuronal features not accompanied by performance differences appear to exist in people with MDDR.

Sensory gating in tobacco-naïve cannabis users is unaffected by acute nicotine administration.

OBJECTIVES: Long-term cannabis use has been associated with the appearance of psychotic symptoms and schizophrenia-like cognitive impairments; however these studies may be confounded by concomitant use of tobacco by cannabis users. We aimed to determine if previously observed cannabis-associated deficits in sensory gating would be seen in cannabis users with no history of tobacco use, as evidenced by changes in the P50, N100, and P200 event-related potentials. A secondary objective of this study was to examine the effects of acute nicotine administration on cannabis users with no tobacco use history. METHODS: Three components (P50, N100, P200) of the mid-latency auditory-evoked response (MLAER) were elicited by a paired-stimulus paradigm in 43 healthy, non-tobacco smoking male volunteers between the ages of 18-30. Cannabis users (CU, n = 20) were administered nicotine (6 mg) and placebo gum within a randomized, double-blind design. Non-cannabis users (NU, n = 23) did not receive nicotine. RESULTS: Between-group sensory gating effects were only observed for the N100, with CUs exhibiting a smaller N100 to S1 of the paired stimulus paradigm, in addition to reduced dN100 (indicating poorer gating). Results revealed no significant sensory gating differences with acute administration of nicotine compared to placebo cannabis conditions. CONCLUSIONS: These findings suggest a relationship between gating impairment and cannabis use; however, acute nicotine administration nicotine does not appear to impact sensory gating function.

Alterations of Resting EEG in Hallucinating and Nonhallucinating Schizophrenia Patients.

Auditory hallucinations (AHs) are a common symptom of schizophrenia and contribute significantly to disease burden. Research on schizophrenia and AHs is limited and fails to adequately address the effect of AHs on resting EEG in patients with schizophrenia. This study assessed changes in frequency bands (delta, theta, alpha, beta) of resting EEG taken from hallucinating patients (n = 12), nonhallucinating patients (n = 11), and healthy controls (n = 12). Delta and theta activity were unaffected by AHs but differed between patients with schizophrenia and healthy controls. Alpha activity was affected by AHs: nonhallucinators had more alpha activity than hallucinators and healthy controls. Additionally, beta activity was inversely related to trait measures of AHs. These findings contribute to the literature of resting eyes closed EEG recordings of schizophrenia and AHs, and indicate the role of delta, theta, alpha, and beta as markers for schizophrenia and auditory hallucinations.

Interaction of Background Noise and Auditory Hallucinations on Phonemic Mismatch Negativity (MMN) and P3a Processing in Schizophrenia.

Auditory hallucinations (AHs) are among the cardinal symptoms of schizophrenia (SZ). During the presence of AHs aberrant activity of auditory cortices have been observed, including hyperactivation during AHs alone and hypoactivation when AHs are accompanied by a concurrent external auditory competitor. Mismatch negativity (MMN) and P3a are common ERPs of interest within the study of SZ as they are robustly reduced in the chronic phase of the illness. The present study aimed to explore whether background noise altered the auditory MMN and P3a in those with SZ and treatment-resistant AHs. METHODS: MMN and P3a were assessed in 12 hallucinating patients (HPs), 11 non-hallucinating patients (NPs) and 9 healthy controls (HCs) within an auditory oddball paradigm. Standard (P = 0.85) and deviant (P = 0.15) stimuli were presented during three noise conditions: silence (SL), traffic noise (TN), and wide-band white noise (WN). RESULTS: HPs showed significantly greater deficits in MMN amplitude relative to NPs in all background noise conditions, though predominantly at central electrodes. Conversely, both NPs and HPs exhibited significant deficits in P3a amplitude relative to HCs under the SL condition only. SIGNIFICANCE: These findings suggest that the presence of AHs may specifically impair the MMN, while the P3a appears to be more generally impaired in SZ. That MMN amplitudes are specifically reduced for HPs during background noise conditions suggests HPs may have a harder time detecting changes in phonemic sounds during situations with external traffic or "real-world" noise compared to NPs.

Mismatch negativity-indexed auditory change detection of speech sounds in early and chronic schizophrenia.

Auditory change detection, as indexed by the EEG-derived mismatch negativity, has been demonstrated to be dysfunctional in chronic schizophrenia using both pure-tone and speech (phoneme) sounds. It is unclear, however, whether reduced MMN amplitudes to speech sound deviants are observed within the first 5 years of the illness. The present study investigated MMNs elicited by across-vowel (phoneme) change in early schizophrenia (ESZ; Experiment 1) as well as chronic schizophrenia (CSZ; Experiment 2). In both experiments, clinical and control participants were presented the Finnish phoneme /e/ (standard; P = .90) and the Finnish phoneme /ö/ (deviant; P = .10) within an oddball paradigm. In experiment 2 we report significantly reduced MMN amplitudes in CSZ relative to HCs, but no differences were found when comparing ESZ and HC in experiment 1. Additionally, in our clinical samples, MMN amplitudes were correlated with symptom scores. These findings suggest that early detection of phonetic change may be impaired in chronic schizophrenia, but not early in the progression of the illness. As MMN reductions only emerged in patients with a longer course of illness, and appeared to change with symptom severity, this suggests a dynamic change in the early auditory processing of language over time in schizophrenia.

Mismatch negativity in tobacco-naïve cannabis users and its alteration with acute nicotine administration.

Chronic cannabis use may interact with factors, such as age of onset of cannabis use, family history, and genetic factors, to elicit schizophrenia (SZ)-like symptoms, including sensory and cognitive deficits. However, evidence of a relationship between cannabis use and cognitive impairment is confounded by concomitant use of tobacco. The objective of this study was to compare tobacco-naïve cannabis users with individuals without a history of tobacco/cannabis use on the auditory mismatch negativity (MMN) event-related potential (ERP), a neural measure of auditory deviance detection which is diminished in SZ. An exploratory arm of the study, conducted within a randomized, double-blind, placebo controlled design, examined the acute effects of nicotine gum (6mg) on MMN in cannabis users. MMN was recorded in response to 5 deviant stimuli within an optimal MMN paradigm in 44 healthy, non-tobacco smoking volunteers aged 18-26. Cannabis users (n=21) started smoking cannabis prior to age 17, at least 1 joint per month. To examine the effects of chronicity, users were grouped into relatively heavy long-term (HLT; n=11) users and light short-term (LST; n=10) users. Impaired deviance detection was shown in cannabis users vs. nonusers as reflected by a smaller MMN to duration deviants. Chronicity of use was also associated with MMN alterations, as HLTs displayed a reduced duration and gap MMN vs. LSTs. Compared with placebo, nicotine treatment enhanced select MMN deviants in cannabis user subgroups. As deficits associated with early and persistent cannabis use are similar to those seen in SZ, these dose-dependant disturbances in early sensory processing with cannabis use may be one cognitive pathway which mediates an increased risk for SZ in vulnerable youth, and be influenced by concurrent cigarette smoking behavior.

Attenuation of mismatch negativity (MMN) and novelty P300 in schizophrenia patients with auditory hallucinations experiencing acute exacerbation of illness.

This study examined measures of early auditory feature analysis, including the mismatch negativity (MMN) and novelty P300 (NP3) in schizophrenia patients (SZ) with persistent auditory hallucinations (AH) during an acute psychotic episode requiring hospitalisation. Neuroelectric activity was recorded in 10 SZ patients and 13 healthy controls (HC) during a passive auditory oddball task including novel environmental sounds. MMN/NP3 amplitudes and latencies were compared between groups and were correlated with trait (PSYRATS) and state measures of AH severity as well as clinical symptom ratings in SZs.SZ patients (vs. HCs) exhibited reduced MMN amplitudes to both rare deviant and novel stimuli, as well as reduced NP3 amplitudes. Additionally, while novelty MMN amplitudes were correlated with measures of hallucinatory trait, NP3 amplitudes were correlated with measures of hallucinatory state. Therefore, in acutely ill SZ patients, individual components of the auditory novelty detection mechanism may be differentially sensitive to varying aspects of AHs.

Auditory verbal hallucinations in schizophrenia correlate with P50 gating.

OBJECTIVE: While auditory verbal hallucinations (AVHs) are a common symptom of schizophrenia, the underlying mechanisms behind these perceptual anomalies and their effects on auditory processing are not fully understood. Patients suffering from schizophrenia have been shown to exhibit impaired sensory gating of acoustic stimuli, evidenced by a failure to inhibit the auditory P50 scalp recorded middle latency evoked potential response to the second of two paired auditory "clicks" (S1-S2). METHODS: Because abnormal activation of auditory pathways is associated with a general AVH trait of schizophrenia patients, this study correlated the hallucinatory trait subscale of the Psychotic Symptoms Ratings Scale (PSYRATS) scores of 16 actively hallucinating patients with their P50 responses to S1 and S2 as well as sensory gating indices. P50 gating in patients was also compared to twenty one healthy controls. RESULTS: Control S1 amplitudes were significantly greater than those of patients. There was a negative correlation between PSYRATS scores and gating difference score as well as with S1 amplitude, and a positive correlation with gating ratio, indicating the global trait of hallucinating schizophrenia patients may be associated with deficiencies in the processing of auditory stimuli. No significant correlation was found when the same analysis was applied to a state-dependent hallucination ratings scale. SIGNIFICANCE: Results suggest the relationship between auditory hallucinations and auditory processing dysfunction measured by P50 response is more trait than state dependent in schizophrenia.

Effects of nicotine on electroencephalographic (EEG) and behavioural measures of visual working memory in non-smokers during a dual-task paradigm.

Research in smokers has shown that nicotine may have the ability to improve certain aspects of cognitive performance, including working memory and attention, processes which implicate frontal and frontal-parietal brain networks. There is limited research on the cognitive effects of nicotine and their associated neural underpinnings in non-smokers. This study examined the effects of acute nicotine on a working memory task alone or combined with a visual detection task (single- and dual-task conditions) using electroencephalographic (EEG) recordings and behavioural performance measures. Twenty non-smokers (13 females; 7 males) received nicotine gum (6 mg) in a double-blind, randomized, placebo-controlled, repeated measures design. Spectral EEG, together with response speed and accuracy measures, were obtained while participants completed a series of N-Back tasks under single- and dual-task conditions. Nicotine failed to exert any significant effects on performance measures, however, EEG changes were observed, primarily in frontal recordings, which varied with memory load, task condition and hemisphere. These findings, discussed in relation to previous studies in smokers, support the notion that nicotine may modulate central executive systems and contribute to smoking behaviour.

Alterations of mismatch negativity (MMN) in schizophrenia patients with auditory hallucinations experiencing acute exacerbation of illness.

Auditory verbal hallucinations (AHs), or hearing 'voices', are one of the hallmark symptoms of patients with schizophrenia. The primary objective of this study was to compare hallucinating schizophrenia patients with respect to differences in deviance detection, as indexed by the auditory mismatch negativity (MMN). Patients were recruited during an acute psychotic episode requiring hospitalization, during which time symptoms of psychosis, including auditory hallucinations, are likely to be at their most severe. MMNs to duration, frequency, gap, intensity and location deviants (as elicited by the 'optimal' multi-feature paradigm) were recorded in 12 acutely ill schizophrenia patients (SZ) with persistent AHs and 15 matched healthy controls (HC). Electrical activity was recorded from 32 scalp electrodes. MMN amplitudes and latencies for each deviant were compared between groups and were correlated with trait (PSYRATS) and state measures of AH severity and Positive and Negative Syndrome Scale (PANSS) ratings in SZs. There were significant group differences for duration, gap, intensity and location MMN amplitudes, such that SZs exhibited reduced MMNs compared to HCs. Additionally, gap MMN amplitudes were correlated with measures of hallucinatory state and frequency of AHs, while location MMN was correlated with perceived location of AHs. In summary, this study corroborates previous research reporting a robust duration MMN deficit in schizophrenia, as well as reporting gap, intensity and location MMN deficits in acutely ill schizophrenia patients with persistent AHs. Additionally, MMN amplitudes were correlated with state and trait measures of AHs. These findings offer further support to previous work suggesting that the presence of auditory hallucinations may make a significant contribution to the widely reported MMN deficits in schizophrenia.

Nicotine and the hallucinating brain: effects on mismatch negativity (MMN) in schizophrenia.

Elevated smoking rates have been noted in schizophrenia, and it has been hypothetically attributed to nicotine's ameliorating abnormal brain processes in this illness. There is some preliminary evidence that nicotine may alter pre-attentive auditory change detection, as indexed by the EEG-derived mismatch negativity (MMN), but no previous study has examined what role auditory verbal hallucinations (AVH) may have on these effects. The objective of this study was to examine MMN-indexed acoustic change detection in schizophrenia (SZ) following nicotine administration and elucidate its association with AVH. Using a modified multi-feature paradigm, MMNs to duration, frequency and intensity deviants were recorded in 12 schizophrenia outpatients (SZ) with persistent AVHs following nicotine (6mg) and placebo administration. Electrical activity was recorded from 32 scalp electrodes; MMN amplitudes and latencies for each deviant were compared between treatments and were correlated with trait (PSYRATS) and state measures of AVH severity and Positive and Negative Syndrome Scale (PANSS) ratings. Nicotine administration resulted in a shortened latency for intensity MMN. Additionally, nicotine-related change in MMN amplitude was correlated with nicotine-related change in subjective measures of hallucinatory state. In summary, nicotine did not affect MMN amplitudes in schizophrenia patients with persistent AVHs, however this study reports accelerated auditory change detection to intensity deviants with nicotine in this group. Additionally, nicotine appeared to induce a generalized activation of the auditory cortex in schizophrenia, resulting in a concurrent increase in intensity MMN amplitude and subjective clarity of AVHs.

Effects of acute nicotine administration on behavioral and neural (EEG) correlates of working memory in non-smokers.

Enhancements in working memory (WM) performance have been previously reported following acute smoking/nicotine. Neuroimaging and behavioral assessments of nicotine's effects on WM have yielded inconsistent findings. Few studies, however, have examined the effects of nicotine on WM-related neural activity in non-smokers. The present study examined the effect of acute nicotine gum administration (6 mg) on electroencephalographic (EEG) activity (alpha(1), alpha(2) and theta bands) and performance on the parametrically manipulated N-back task of WM in 20 non-smoking adults. EEG activity varied with WM load (e.g. alpha(1) decreasing and theta increasing). Performance on the N-back was also load-sensitive, with slower reaction times and decreased accuracy associated with increasing memory load. Neither response speed nor accuracy measures were affected by nicotine but EEG was, with the effects varying by load and brain region. Nicotine-induced increases in alpha(2) and theta were observed under lower (0-, 1-back) memory load conditions Additionally, nicotine significantly reduced signal detection sensitivity values and altered response bias toward being more conservative at all levels of the N-back. Taken together, these findings suggest that while nicotine may boost WM neural processes at lower levels of WM load in non-smokers, it also may activate concurrent behavioral inhibition networks that negate any effects on behavioral performance. Additionally, nicotine appears to have no impact, or perhaps a negative impact, on these processes under more demanding (2-back, 3-back) conditions in non-smokers.

Effects of acute nicotine administration on resting EEG in nonsmokers.

Smoking/nicotine has been shown to increase brain arousal states, yet previous studies have failed to distinguish between absolute improvements due to nicotine versus relief from withdrawal symptoms in smokers. This study examined the electrocortical response to nicotine in a nonsmoking population, in order to negate potential withdrawal symptoms. Twenty right-handed, nonsmoking participants were administered nicotine (6 mg) or placebo gum within a double-blind, repeated-measures design. In each session, EEG was recorded during a 2-min, resting, eyes-open condition. Nicotine administration (vs. placebo) resulted in significantly greater frontal (specifically left-frontal) alpha2 power. Similar to previous findings in smokers. The absence of slow-wave changes following nicotine in nonsmokers suggest that these previous results in smokers may be related to withdrawal state.

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). Assessment involved intravenous injection of a low subperceptual bolus dose (.04mg/kg) of ketamine or placebo, which was accompanied by acute treatment with nicotine (4mg) or placebo gum. Nicotine-enhanced attentional processing was most evident in nonsmokers, with both performance accuracy and P300 amplitude measures. Ketamine's detrimental effects on these behavioural and electrophysiologic measures were negatively moderated by acute nicotine, the synergistic effects being expressed differently in smokers and nonsmokers. These findings support the view that acute alterations and individual differences in nAChR function can moderate even subtle glutamatergic-driven cognitive deficiencies in schizophrenia and can be important therapeutic targets for treating cognitive impairments in schizophrenia.

Effects of auditory hallucinations on the mismatch negativity (MMN) in schizophrenia as measured by a modified 'optimal' multi-feature paradigm.

UNLABELLED: The recently developed Optimal-3 multi-feature MMN paradigm, a shortened version of the 'optimal' multi-feature MMN paradigm, allows for the focused recording of the most widely reported MMN deviants (frequency, duration, intensity) within an efficient and time-saving paradigm. The objective of this study was to examine MMN acoustic change detection in schizophrenia (SZ), and elucidate its association with auditory verbal hallucinations (AH), using the Optimal-3. METHODS: MMN to duration, frequency and intensity deviants were recorded in 12 SZ outpatients (SZs) with persistent AHs and 12 matched healthy controls (HC). Electrical activity was recorded from 32 scalp electrodes; MMN amplitudes and latencies for each deviant were compared between groups and were correlated with trait (PSYRATS) and state measures of AH severity and Positive and Negative Syndrome Scale (PANSS) ratings in SZs. RESULTS: SZs showed a significantly smaller duration MMN compared to HCs. Furthermore, in SZs attenuated duration MMN amplitudes were correlated with increased PSYRATS scores, as well as increased PANSS positive symptom, hallucination item and general psychoticism ratings, while attenuated intensity MMN amplitudes were correlated with increased PSYRATS scores. CONCLUSIONS: This is the first study to examine MMN in SZ within the modified (Optimal-3) multi-feature MMN paradigm. This study corroborates previous research reporting a robust duration MMN deficit in SZ and supports previous findings suggesting that AHs may contribute to MMN deficits in SZ.

MMN responsivity to manipulations of frequency and duration deviants in chronic, clozapine-treated schizophrenia patients.

Event-related potential (ERP) probing of abnormal sensory processes in schizophrenia with the mismatch negativity (MMN) has shown impairments in auditory change detection, but knowledge of the acoustic features leading to this deficit is incomplete. Changes in the duration and frequency properties of sound stimuli result in diminished MMNs in schizophrenia but it is unclear as to whether this reduced responsiveness is seen with more subtle changes in sound frequency. In a sample of 19 healthy controls and 21 patients with chronic schizophrenia treated with clozapine, MMN was assessed in response to tone frequency changes of 5%, 10% and 20%, and to tone duration changes. Patients exhibited reduced amplitudes and shorter latencies than controls to all frequency changes, and attenuated amplitudes to tone duration increments and decrements. Clozapine dose was related to MMN, with increasing dose being positively associated with frequency-MMN amplitudes (10% ∆f, 20% ∆f) and negatively associated with the amplitude and latency of duration-MMNs. These data support the well-established findings of auditory sensory abnormality in schizophrenia and underscore the sensitivity of MMN to relatively small auditory change detection deficits that may appear to characterize chronic schizophrenia.

Effects of deviant probability on the 'optimal' multi-feature mismatch negativity (MMN) paradigm.

UNLABELLED: The introduction of the multi-feature 'optimal' mismatch negativity (MMN) paradigm was a significant innovation that allows for the collection of MMNs from five different deviant types in a relatively short period of time. Given the very specific stimulus presentation structure of this paradigm, the deletion of deviants results in an increase in the stimulus probability of each remaining deviant while holding constant the probability of the standard stimulus. The focus of this paper is two-fold: first, to examine the effects of altering deviant probability, but not standard probability, on MMN generation and, secondly, to validate a shorter, 3-stimulus version of the 'optimal' paradigm. METHODS: Twenty-four participants were presented either with the original 5-stimulus 'optimal' multi-feature MMN paradigm (Optimal-5) or a modified, 3-stimulus version containing only duration, frequency and intensity deviants (Optimal-3). MMN amplitudes and latencies to common deviant types were compared between groups. RESULTS: MMN amplitudes elicited by Optimal-3 were significantly smaller than those elicited by Optimal-5 for frequency and intensity deviants. There were no significant differences between MMN amplitudes for duration deviants, nor were there any significant MMN latency differences for any of the three deviant types. CONCLUSIONS: These results support previous suggestions that MMN attenuation following increased deviant presentation probability is due to the development of separate deviant memory traces, not due to a weakening of the standard memory trace. Furthermore, while MMN amplitudes to Optimal-3 were reduced, they were still present; the Optimal-3 paradigm may be a useful tool for eliciting MMNs in populations unable to tolerate long test sessions, such as acute schizophrenia.

Acute nicotine alteration of sensory memory impairment in smokers with schizophrenia.

CONTEXT: Patients with schizophrenia have a high rate of cigarette smoking and also exhibit profound deficits in sensory processing, which may in part be ameliorated by the acute actions of smoke-inhaled nicotine. The mismatch negativity (MMN), a preattentive event-related potential index of auditory sensory memory, is diminished in schizophrenia. The MMN is increased in healthy controls with acute nicotine. OBJECTIVE: To utilize the MMN to compare auditory sensory memory in minimally tobacco-deprived (3 hours) patients and matched tobacco-deprived smoking controls and to assess the effects of acute nicotine on MMN-indexed sensory memory processing in the patients. DESIGN: Event-related potentials were recorded in 2 auditory oddball paradigms, one involving tone frequency changes (frequency MMN) and one involving tone duration changes (duration MMN). Controls were assessed once under nontreatment conditions, and patients were assessed twice under randomized double-blind treatment conditions involving placebo and nicotine (8 mg) gum. SETTING: Outpatient mental health center. PATIENTS: Twelve smokers with schizophrenia and twelve control smokers. RESULTS: Compared with the controls, the patients showed reduced frequency-MMN (P < 0.001) and duration-MMN (P < 0.04) amplitudes. In addition to prolonging peak latency in duration MMN (P < 0.01), nicotine, relative to placebo, increased the amplitude of the patients' duration MMN (P < 0.01), but not their frequency MMN, to a level comparable with that seen in the controls. CONCLUSIONS: These preliminary findings demonstrate for the first time that acute nicotine can normalize temporal aspects of sensory memory processing in patients with schizophrenia, an effect that may be mediated by activation of α7 nicotinic acetylcholine receptors, the function of which is diminished in schizophrenia. These ameliorating actions of nicotine may have implications for understanding the close relationship between tobacco smoking and schizophrenia and for developing nicotinic pharmacotherapies to alleviate sensory memory impairments in schizophrenia.

Auditory hallucinations and the P3a: attention-switching to speech in schizophrenia.

BACKGROUND: In line with emerging research strategies focusing on specific symptoms rather than global syndromes in psychiatric disorders, we examined the functional neural correlates of auditory verbal hallucinations (AHs) in schizophrenia. Recent neuroimaging and behavioural evidence suggest altered early cognitive processes may be seen in patients with AH as a result of limited processing resources. METHODS: The P3a subcomponent of the P300, an event-related potential (ERP) index of early attention switching, was assessed in 12 hallucinating patients (HP), 12 non-hallucinating patients (NP) and 12 healthy controls (HC) within a passive two-tone auditory oddball paradigm using vowel phonemes. P3a amplitudes and latencies were measured in response to across-phoneme changes. Following P3a acquisition, patients indicated the duration, intensity and clarity of their auditory hallucinations during recording. RESULTS: Hallucinating patients exhibited smaller P3a amplitudes than non-hallucinating patients and healthy controls. In HPs, P3a amplitude was negatively correlated with AH trait scores. SIGNIFICANCE: These findings suggest that AHs are associated with impaired processing of speech as evidenced by altered P3a amplitudes to vowel phonemes. This finding may be due to limited cognitive resources available for incoming external stimuli due to a usurping of finite resources by AHs. The P3a may be a useful non-invasive tool for probing relationships between hallucinatory and neural states within schizophrenia and the manner in which auditory processing is altered in these afflicted patients.

Light up and see: enhancement of the visual mismatch negativity (vMMN) by nicotine.

Both smoking and nicotine can facilitate cognitive efficiency in humans, however the exact mechanism underlying this improvement in cognitive performance is unclear. Nicotine-related improvements in visual task performance may stem from facilitation of the identification and encoding of rare deviant stimuli at early sensory levels. Visual processes at these early levels are thought to be indexed by the visual mismatch negativity (vMMN), an event-related potential (ERP) measure of pre-conscious deviant detection. In order to contribute to our understanding of the neural mechanisms underlying nicotinic modulated cognition, the current study investigated the acute effects of nicotine on vMMN in a non-smoking sample. Twenty-seven volunteers (7 males, 20 females) were treated with nicotine gum (6 mg) in a double-blind randomized, placebo-controlled repeated measures design. ERPs (vMMN; visual N100 and P200) and motor indices of performance were extracted from an intermodal task, requiring participants to attend selectively to auditory targets presented within concurrent, non-overlapping oddball sequences of visual standard and deviant stimuli. Behavioural performance was unaffected by nicotine, however nicotine was found to enhance vMMN and P200 amplitude. The findings are discussed in relation to attentional and neurobiological theories of nicotine dependence and of cognition in general.