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.

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 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.

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.

Comparison of endothelial cell phenotypic markers of late-outgrowth endothelial progenitor cells isolated from patients with coronary artery disease and healthy volunteers.

The lack of easily isolated autologous endothelial cell (EC) sources is one of the major challenges with vascular tissue engineering interventions. This article examines the isolation and expansion of late-outgrowth endothelial progenitor cells (EPCs) from 50-mL samples of peripheral blood drawn from patients with significant coronary artery disease (CAD) and healthy young adult volunteers. In cases in which late-outgrowth EPCs were successfully isolated, the cells were assayed in vitro for their expression of EC markers, proliferation potential and ability to endothelialize synthetic materials, form new blood vessels, and produce nitric oxide. Late-outgrowth EPCs from patients with CAD and healthy volunteers exhibited critical EC markers and morphological characteristics that were analogous to a control population of human aortic ECs. To our knowledge, this is the first study to examine the suitability of late-outgrowth EPCs from patients with CAD for autologous endothelialization applications.