Synchronized Auditory Gamma Response to Frontal Transcranial Direct Current Stimulation (tDCS) and its Inter-Individual Variation in Healthy Humans.

In schizophrenia, a disorder associated with N-methyl-D-aspartate receptor (NMDAR) hypofunction, auditory cortical plasticity deficits have been indexed by the synchronized electroencephalographic (EEG) auditory steady-state gamma-band (40-Hz) response (ASSR) and the early auditory evoked gamma-band response (aeGBR), both considered to be target engagement biomarkers for NMDAR function, and potentially amenable to treatment by NMDAR modulators. As transcranial direct current stimulation (tDCS) is likely dependent on NMDAR neurotransmission, this preliminary study, conducted in 30 healthy volunteers, assessed the off-line effects of prefrontal anodal tDCS and sham (placebo) treatment on 40-Hz ASSR and aeGBR. Anodal tDCS failed to alter aeGBR but increased both 40-Hz ASSR power, as measured by event-related spectral perturbations (ERSP), and phase locking, as measured by inter-trial phase consistency (ITPC). Inter-individual differences in tDCS-induced increases in ERSP were negatively related to baseline ERSPs. These findings provide tentative support for further study of tDCS as a potential NMDAR neuromodulatory intervention for synchronized auditory gamma response deficits.

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). Together with preliminary evidence of modest positive associations between impaired gating and dissociative symptoms elicited by ketamine, tentatively support a model of NMDAR hypofunction underlying disturbances in auditory SG in schizophrenia.

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.

The acute dose and baseline amplitude-dependent effects of CDP-choline on deviance detection (MMN) in chronic schizophrenia: A pilot study.

The detection of deviant auditory features is empirically supported as impaired in schizophrenia and has been shown to associate with functional outcome. Modulated by glutamate neurotransmission, this sensory process has also been shown to relate to the α7 nicotinic acetylcholine receptor (nAChR) system, a prioritized molecular target for the development of novel cognition targeted pharmacological treatments. This pilot study assessed the acute effects of CDP-Choline, a choline supplement with α7 nAChR agonist properties, on the mismatch negativity (MMN), an event-related potential index of the detection of an acoustic change, in a sample of individuals diagnosed with chronic schizophrenia. Utilizing a randomized, placebo-controlled, double-blind design, the dose-dependent (500 mg, 1,000 mg, 2,000 mg), baseline amplitude-dependent (low vs. high), and deviant feature-dependent effects of CDP-Choline on the MMN were examined. CDP-choline's effects interacted with dosage, deviance feature, and baseline amplitude with low baseline amplitude patients demonstrating enhanced MMNs, and high baseline amplitude patients demonstrating suppressed MMNs in response to CDP-Choline. These findings offer tentative support for the involvement of the α7 nAChR system in auditory MMN abnormalities in schizophrenia and supports further research assessing the effects of long-term treatment with CDP-Choline in the personalized treatment of auditory deviance processing impairments. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

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. Increases in dissociation symptoms were negatively correlated with ketamine-induced P3b changes, at sensor-level and source-level, in both salience and central executive networks. These P3a alterations during novelty processing, and the symptom-related P3b changes during target processing support a model of NMDAR hypofunction underlying disrupted auditory attention in schizophrenia.

Acute separate and combined effects of cannabinoid and nicotinic receptor agonists on MMN-indexed auditory deviance detection in healthy humans.

The high prevalence of concomitant cannabis and nicotine use has implications for sensory and cognitive processing. While nicotine tends to enhance function in these domains, cannabis use has been associated with both sensory and cognitive impairments, though the underlying mechanisms are unclear. Additionally, the interaction of the nicotinic (nAChR) and cannabinoid (CB1) receptor systems has received limited study in terms of sensory/cognitive processes. This study involving healthy volunteers assessed the acute separate and combined effects of nabilone (a CB1 agonist) and nicotine on sensory processing as assessed by auditory deviance detection and indexed by the mismatch negativity (MMN) event-related potential. It was hypothesized that nabilone would impair auditory discriminability as shown by diminished MMN amplitudes, but not when administered in combination with nicotine. 20 male non-smokers and non-cannabis-users were assessed using a 5-stimulus 'optimal' multi-feature MMN paradigm within a randomized, placebo controlled design (placebo; nabilone [0.5 mg]; nicotine [6 mg]; and nicotine + nabilone). Treatment effects were region- and deviant-dependent. At the temporal regions (mastoid sites), MMN was reduced by nabilone and nicotine separately, whereas co-administration resulted in no impairment. At the frontal region, MMN was enhanced by co-administration of nicotine and nabilone, with no MMN effects being found with separate treatment. These neural effects have relevance for sensory/cognitive processes influenced by separate and simultaneous use of cannabis and tobacco and may have treatment implications for disorders associated with sensory dysfunction and impairments in endocannabinoid and nicotinic cholinergic neurotransmission.

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.

Assessing the acute effects of CDP-choline on sensory gating in schizophrenia: A pilot study.

Deficient sensory gating (SG) in schizophrenia is associated with functional outcome and offers a therapeutic target as it is linked to the altered function/expression of the α7 nicotinic acetylcholine receptors (nAChRs). This study analyzed the effects of citicoline (CDP-choline), a supplement with α7 nAChRs agonist properties, on SG in a sample of schizophrenia (SZ) patients. Using a randomized, placebo-controlled, double-blind design the dose-dependent (500 mg, 1000 mg, 2000 mg) and baseline-dependent (deficient versus normal suppressors) effects of CDP-choline on SG were examined using the P50 event-related potential (ERP) index of SG. Overall analysis failed to demonstrate treatment effects but CDP-choline improved SG (500 mg) in the deficient SZ subgroup by increasing suppression of the S2 P50 amplitude. These findings tentatively support α7 nAChR dysfunction in the expression of SG deficits and suggest further trials to assess the effects of sustained α7 nAChR activation on SG with low doses of CDP-choline.

Effects of transcranial direct current stimulation on the auditory mismatch negativity response and working memory performance in schizophrenia: a pilot study.

Cognitive impairment has been proposed to be the core feature of schizophrenia (Sz). Transcranial direct current stimulation (tDCS) is a non-invasive form of brain stimulation which can improve cognitive function in healthy participants and in psychiatric patients with cognitive deficits. tDCS has been shown to improve cognition and hallucination symptoms in Sz, a disorder also associated with marked sensory processing deficits. Recent findings in healthy controls demonstrate that anodal tDCS increases auditory deviance detection, as measured by the brain-based event-related potential, mismatch negativity (MMN), which is a putative biomarker of Sz that has been proposed as a target for treatment of Sz cognition. This pilot study conducted a randomized, double-blind assessment of the effects of pre- and post-tDCS on MMN-indexed auditory discrimination in 12 Sz patients, moderated by auditory hallucination (AH) presence, as well as working memory performance. Assessments were conducted in three sessions involving temporal and frontal lobe anodal stimulation (to transiently excite local brain activity), and one control session involving 'sham' stimulation (meaning with the device turned off, i.e., no stimulation). Results demonstrated a trend for pitch MMN amplitude to increase with anodal temporal tDCS, which was significant in a subgroup of Sz individuals with AHs. Anodal frontal tDCS significantly increased WM performance on the 2-back task, which was found to positively correlate with MMN-tDCS effects. The findings contribute to our understanding of tDCS effects for sensory processing deficits and working memory performance in Sz and may have implications for psychiatric disorders with sensory deficits.

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.

Neurocognitive effects of acute choline supplementation in low, medium and high performer healthy volunteers.

Novel pharmacological treatments targeting alpha 7 nicotinic acetylcholine receptor (α7 nAChR) hypofunction in schizophrenia have shown mixed success in ameliorating cognitive impairments associated with this disorder. Choline, a selective agonist at α7 receptors is increased with oral administration of cytidine 5'-diphosphocholine (CDP-choline), the cognitive effects of which were assessed in healthy volunteers. Using the CogState test battery, behavioral performance in schizophrenia-relevant cognitive domains was assessed in 24 male participants following a single low (500mg) and moderate (1000mg) dose of CDP-choline. Relative to placebo, CDP-choline improved processing speed, working memory, verbal learning, verbal memory, and executive function in low baseline performers, while exerting no effects in medium baseline performers, and diminishing cognition in high baseline performers. Dose effects varied with cognitive domain but were evident with both the 500mg and 1000mg doses. These preliminary findings of cognitive enhancement in relatively impaired performers are consistent with the α7 receptor mechanism and support further trials with CDP-choline as a potential pro-cognitive strategy for cognitive impairment in schizophrenia.

A review of fMRI studies during visual emotive processing in major depressive disorder.

OBJECTIVES: This review synthesized literature on brain activity, indexed by functional magnetic resonance imaging (fMRI), during visual affective information processing in major depressive disorder (MDD). Activation was examined in regions consistently implicated in emotive processing, including the anterior cingulate cortex (ACC), prefrontal cortex (PFC), amygdala, thalamus/basal ganglia and hippocampus. We also reviewed the effects of antidepressant interventions on brain activity during emotive processing. METHODS: Sixty-four fMRI studies investigating neural activity during visual emotive information processing in MDD were included. RESULTS: Evidence indicates increased ventro-rostral ACC activity to emotive stimuli and perhaps decreased dorsal ACC activity in MDD. Findings are inconsistent for the PFC, though medial PFC hyperactivity tends to emerge to emotive information processing in the disorder. Depressed patients display increased amygdala activation to negative and arousing stimuli. MDD may also be associated with increased activity to negative, and decreased activity to positive, stimuli in basal ganglia/thalamic structures. Finally, there may be increased hippocampus activation during negative information processing. Typically, antidepressant interventions normalize these activation patterns. CONCLUSION: In general, depressed patients have increased activation to emotive, especially negative, visual stimuli in regions involved in affective processing, with the exception of certain PFC regions; this pattern tends to normalize with treatment.

CDP-choline: effects of the procholine supplement on sensory gating and executive function in healthy volunteers stratified for low, medium and high P50 suppression.

Diminished auditory sensory gating and associated neurocognitive deficits in schizophrenia have been linked to altered expression and function of the alpha-7 nicotinic acetycholinergic receptor (α7 nAChR), the targeting of which may have treatment potential. Choline is a selective α7 nAChR agonist and the aim of this study was to determine whether cytidine 5'-diphosphocholine (CDP-choline), or citicoline, a dietary source of choline, increases sensory gating and cognition in healthy volunteers stratified for gating level. In a randomized, placebo-controlled, double-blind design involving acute administration of low, moderate doses (500 mg, 1000 mg) of CDP-choline, 24 healthy volunteers were assessed for auditory gating as indexed by suppression of the P50 event-related potential (ERP) in a paired-stimulus (S1, S2) paradigm, and for executive function as measured by the Groton Maze Learning Task (GMLT) of the CogState Schizophrenia Battery. CDP-choline improved gating (1000 mg) and suppression of the S2 P50 response (500 mg, 1000 mg), with the effects being selective for individuals with low gating (suppression) levels. Tentative support was also shown for increased GMLT performance (500 mg) in low suppressors. These preliminary findings with CDP-choline in a healthy, schizophrenia-like surrogate sample are consistent with a α7 nAChR mechanism and support further trials with choline as a pro-cognitive strategy.

Modulation of auditory deviance detection by acute nicotine is baseline and deviant dependent in healthy nonsmokers: a mismatch negativity study.

OBJECTIVE: Cognitive enhancement resulting from nicotinic acetylcholine receptor stimulation may be evidenced by increased efficiency of the auditory-frontal cortex network of auditory discrimination, which is impaired in schizophrenia, a cognitive disorder associated with excessive tobacco use. Investigating automatic (preattentive) detection of acoustic change with the mismatch negativity (MMN) brain event-related potential in response to nicotine in individuals with varying baseline levels of auditory discrimination may provide useful insight into the cholinergic regulation of this neural network and its potential amelioration with novel nicotinic agents. METHODS: Sixty healthy, non-smoking male volunteers were presented with an 'optimal' multi-feature MMN paradigm in a randomized, placebo controlled double-blind design with 6 mg of nicotine gum. RESULTS: Participants with low, medium, and high baseline amplitudes responded differently to nicotine (vs. placebo), and nicotine response was feature specific. Whereas MMN in individuals with high amplitudes was diminished by nicotine, MMN increased in those with low amplitudes. Nicotine effects were not shown in medium amplitude participants. CONCLUSIONS: These findings provide preliminary support for the role of nicotinic neurotransmission in sensory memory processing of auditory change and suggest that nicotinic receptor modulation can both enhance and diminish change detection, depending on baseline MMN and its eliciting stimulus feature.

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.

Baseline dependency of nicotine's sensory gating actions: similarities and differences in low, medium and high P50 suppressors.

Reduced suppression of the P50 auditory event-related potential in schizophrenia patients relative to normal controls is indicative of a sensory gating deficit and is one of the most robust findings reported for functional brain abnormalities in this disorder. However, there is considerable gating variability in patients and controls and there is little understanding as to how inter-individual differences moderate gating responses to drugs and nicotinic agonists in particular, which have shown potential to reverse gating deficits. In this study the effects of acutely administered nicotine (gum, 6 mg) on sensory gating in a paired (S1-S2) auditory stimulus paradigm were investigated in 57 healthy, non-smoking volunteers stratified as low (n = 19), medium (n = 19) and high (n = 19) P50 suppressors on the basis of three separate baseline derived gating indices, P50 ratios, P50 difference scores, and gating difference waveforms. Relative to placebo, nicotine consistently improved gating in low suppressors as stratified with all three gating indices, exerted no effects in medium suppressors and reduced gating in high suppressors. Analysis of individual stimulus (S2, S2) amplitudes showed distinctly different mechanisms of action underlying nicotine effects in individuals with low and high baseline suppression. The results parallel similar findings of baseline-dependency in the gating effects of several antipsychotic drugs in healthy volunteers and support the use of group segmentation as a translational model in novel cognitive drug development for schizophrenia.

Auditory P3 in antidepressant pharmacotherapy treatment responders, non-responders and controls.

Event-related potentials (ERPs), derived from electroencephalographic (EEG) recordings, can index electrocortical activity related to cognitive operations. The fronto-central P3a ERP is involved in involuntary processing of novel auditory information, whereas the parietal P3b indexes controlled attention processing. The amplitude of the auditory P3b has been found to be decreased in major depressive disorder (MDD). However, few studies have examined the relations between the P3b, the related P3a, and antidepressant treatment response. We tested 53 unmedicated individuals (25 females) with MDD, as well as 43 non-depressed controls (23 females) on the novelty oddball task, wherein infrequent deviant (target) and frequent standard (non-target) tones were presented, along with infrequent novel (non-target/distractor) sounds. The P3a and P3b ERPs were assessed to novel and target sounds, respectively, as were their accompanying behavioral performance measures. Depression ratings and the antidepressant response status were assessed following 12 weeks of pharmacotherapy with three different regimens. Antidepressant treatment non-responders had smaller baseline P3a/b amplitudes than responders and healthy controls. Baseline P3b amplitude also weakly predicted the extent of depression rating changes by week 12. Females exhibited larger P3a/b amplitudes than males. With respect to task performance, controls had more target hits than treatment non-responders. ERP measures correlated with clinical changes in males and with behavioral measures in females. These results suggest that greater (or control-like) baseline P3a/b amplitudes are associated with a positive antidepressant response, and that gender differences characterize the P3 and, by extension, basic attentive processes.

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.

Response prediction to antidepressants using scalp and source-localized loudness dependence of auditory evoked potential (LDAEP) slopes.

The loudness-dependence of the auditory evoked potential (LDAEP) slope may be inversely related to serotonin (5-HT) neurotransmission. Thus, steep LDAEPs tend to predict a positive response to selective serotonin reuptake inhibitor (SSRI) antidepressants, which augment 5-HT. However, LDAEPs also predict outcome to antidepressants indirectly altering 5-HT (e.g. bupropion). Hence, the LDAEP's predicative specificity and sensitivity to antidepressant response/outcome remains elusive. Scalp N1, P2 and N1/P2 LDAEP slopes and standardized low resolution brain electromagnetic tomography (sLORETA)-localized N1 and P2 LDAEP slopes were assessed in depressed individuals (N=51) at baseline, 1 and 12 weeks post-treatment with one of three antidepressant regimens [escitalopram (ESC)+bupropion (BUP), ESC or BUP]. Clinical response was greatest with ESC+BUP at week 1. Treatment responders had steep N1 sLORETA-LDAEP baseline slopes while non-responders had shallow ones. P2 sLORETA-LDAEP slope increases at 1 week existed in responders; decreases were noted in non-responders. Exploratory analyses indicated that more BUP and ESC responders versus non-responders had steep baseline N1 sLORETA-LDAEP slopes. Additionally, slight decreases in scalp P2 LDAEP by week 1 existed for ESC treatment, while slope increases existed with ESC+BUP treatment. Only baseline N1 sLORETA-LDAEP discriminated treatment responders/non-responders. This work confirms that certain LDAEP measures are associated with treatment outcome and appear to be differentially modulated with varying antidepressant drug regimens, though this should be confirmed using larger samples.

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.