Alcohol-related context modulates neural correlates of inhibitory control in alcohol dependent patients: Preliminary data from an fMRI study using an alcohol-related Go/NoGo-task.

Alcohol use disorder (AUD) is characterized by both impaired inhibitory control and heightened cue reactivity, including enhanced craving and drinking urges in response to alcohol-related stimuli. The interaction between these two mechanisms is thought to be crucial in the maintenance of addiction and relapse. The present study used a newly developed alcohol-related Go/NoGo-task to investigate how exposure to alcohol-related cues affects neural processing of inhibitory control in subjects with AUD. Functional magnetic resonance imaging (fMRI) was recorded during performance of a Go/NoGo task, which incorporated alcohol-related and neutral stimuli as Go and NoGo trials in abstinent AUD patients and healthy controls (HC). AUD patients exhibited increased activation of a fronto-striatal-parietal network during successful response inhibition relative to HC. Within the AUD group, activation for alcohol-related (relative to neutral) inhibition was enhanced in regions including bilateral anterior cingulate cortex (ACC), right medial frontal and precentral gyri, and right putamen. Activation differences in the right ACC increased with subjective craving. These preliminary findings suggest that AUD patients need to recruit enhanced neuronal resources for successful inhibition. In parts of the inhibitory network, this hyperactivation is enhanced when inhibition takes place in an alcohol-related context. Activation in the ACC increased stronger in patients experiencing high craving, possibly because of an enhanced conflict. The task introduced here thus allows to investigate neural processing of alcohol-related inhibition in an AUD sample. The preliminary results suggest that exposure to alcohol-related cues intensifies the demand on an already challenged inhibitory system in recently abstinent patients with AUD.

Neurofeedback-Based Enhancement of Single-Trial Auditory Evoked Potentials: Treatment of Auditory Verbal Hallucinations in Schizophrenia.

Auditory verbal hallucinations depend on a broad neurobiological network ranging from the auditory system to language as well as memory-related processes. As part of this, the auditory N100 event-related potential (ERP) component is attenuated in patients with schizophrenia, with stronger attenuation occurring during auditory verbal hallucinations. Changes in the N100 component assumingly reflect disturbed responsiveness of the auditory system toward external stimuli in schizophrenia. With this premise, we investigated the therapeutic utility of neurofeedback training to modulate the auditory-evoked N100 component in patients with schizophrenia and associated auditory verbal hallucinations. Ten patients completed electroencephalography neurofeedback training for modulation of N100 (treatment condition) or another unrelated component, P200 (control condition). On a behavioral level, only the control group showed a tendency for symptom improvement in the Positive and Negative Syndrome Scale total score in a pre-/postcomparison ( t(4) = 2.71, P = .054); however, no significant differences were found in specific hallucination related symptoms ( t(7) = -0.53, P = .62). There was no significant overall effect of neurofeedback training on ERP components in our paradigm; however, we were able to identify different learning patterns, and found a correlation between learning and improvement in auditory verbal hallucination symptoms across training sessions ( r = 0.664, n = 9, P = .05). This effect results, with cautious interpretation due to the small sample size, primarily from the treatment group ( r = 0.97, n = 4, P = .03). In particular, a within-session learning parameter showed utility for predicting symptom improvement with neurofeedback training. In conclusion, patients with schizophrenia and associated auditory verbal hallucinations who exhibit a learning pattern more characterized by within-session aptitude may benefit from electroencephalography neurofeedback. Furthermore, independent of the training group, a significant spatial pre-post difference was found in the event-related component P200 ( P = .04).

Neurofeedback-Based Enhancement of Single Trial Auditory Evoked Potentials: Feasibility in Healthy Subjects.

Previous studies showed a global reduction of the event-related potential component N100 in patients with schizophrenia, a phenomenon that is even more pronounced during auditory verbal hallucinations. This reduction assumingly results from dysfunctional activation of the primary auditory cortex by inner speech, which reduces its responsiveness to external stimuli. With this study, we tested the feasibility of enhancing the responsiveness of the primary auditory cortex to external stimuli with an upregulation of the event-related potential component N100 in healthy control subjects. A total of 15 healthy subjects performed 8 double-sessions of EEG-neurofeedback training over 2 weeks. The results of the used linear mixed effect model showed a significant active learning effect within sessions ( t = 5.99, P < .001) against an unspecific habituation effect that lowered the N100 amplitude over time. Across sessions, a significant increase in the passive condition ( t = 2.42, P = .03), named as carry-over effect, was observed. Given that the carry-over effect is one of the ultimate aims of neurofeedback, it seems reasonable to apply this neurofeedback training protocol to influence the N100 amplitude in patients with schizophrenia. This intervention could provide an alternative treatment option for auditory verbal hallucinations in these patients.

Low Motivational Incongruence Predicts Successful EEG Resting-state Neurofeedback Performance in Healthy Adults.

Neurofeedback is becoming increasingly sophisticated and widespread, although predictors of successful performance still remain scarce. Here, we explored the possible predictive value of psychological factors and report the results obtained from a neurofeedback training study designed to enhance the self-regulation of spontaneous EEG microstates of a particular type (microstate class D). Specifically, we were interested in life satisfaction (including motivational incongruence), body awareness, personality and trait anxiety. These variables were quantified with questionnaires before neurofeedback. Individual neurofeedback success was established by means of linear mixed models that accounted for the amount of observed target state (microstate class D contribution) as a function of time and training condition: baseline, training and transfer (results shown in Diaz Hernandez et al.). We found a series of significant negative correlations between motivational incongruence and mean percentage increase of microstate D during the condition transfer, across-sessions (36% of common variance) and mean percentage increase of microstate D during the condition training, within-session (42% of common variance). There were no significant correlations related to other questionnaires, besides a trend in a sub-scale of the Life Satisfaction questionnaire. We conclude that motivational incongruence may be a potential predictor for neurofeedback success, at least in the current protocol. The finding may be explained by the interfering effect on neurofeedback performance produced by incompatible simultaneously active psychological processes, which are indirectly measured by the Motivational Incongruence questionnaire.

Corrigendum: Inefficient Preparatory fMRI-BOLD Network Activations Predict Working Memory Dysfunctions in Patients with Schizophrenia.

[This corrects the article on p. 29 in vol. 7, PMID: 27047395.].

Inefficient Preparatory fMRI-BOLD Network Activations Predict Working Memory Dysfunctions in Patients with Schizophrenia.

Patients with schizophrenia show abnormal dynamics and structure of temporally -coherent networks (TCNs) assessed using fMRI, which undergo adaptive shifts in preparation for a cognitively demanding task. During working memory (WM) tasks, patients with schizophrenia show persistent deficits in TCNs as well as EEG indices of WM. Studying their temporal relationship during WM tasks might provide novel insights into WM performance deficits seen in schizophrenia. Simultaneous EEG-fMRI data were acquired during the performance of a verbal Sternberg WM task with two load levels (load 2 and load 5) in 17 patients with schizophrenia and 17 matched healthy controls. Using covariance mapping, we investigated the relationship of the activity in the TCNs before the memoranda were encoded and EEG spectral power during the retention interval. We assessed four TCNs - default mode network (DMN), dorsal attention network (dAN), left and right working memory networks (WMNs) - and three EEG bands - theta, alpha, and beta. In healthy controls, there was a load-dependent inverse relation between DMN and frontal midline theta power and an anti-correlation between DMN and dAN. Both effects were not significantly detectable in patients. In addition, healthy controls showed a left-lateralized load-dependent recruitment of the WMNs. Activation of the WMNs was bilateral in patients, suggesting more resources were recruited for successful performance on the WM task. Our findings support the notion of schizophrenia patients showing deviations in their neurophysiological responses before the retention of relevant information in a verbal WM task. Thus, treatment strategies as neurofeedback -targeting prestates could be beneficial as task performance relies on the preparatory state of the brain.

15 Years of Microstate Research in Schizophrenia - Where Are We? A Meta-Analysis.

Schizophrenia patients show abnormalities in a broad range of task demands. Therefore, an explanation common to all these abnormalities has to be sought independently of any particular task, ideally in the brain dynamics before a task takes place or during resting state. For the neurobiological investigation of such baseline states, EEG microstate analysis is particularly well suited, because it identifies subsecond global states of stable connectivity patterns directly related to the recruitment of different types of information processing modes (e.g., integration of top-down and bottom-up information). Meanwhile, there is an accumulation of evidence that particular microstate networks are selectively affected in schizophrenia. To obtain an overall estimate of the effect size of these microstate abnormalities, we present a systematic meta-analysis over all studies available to date relating EEG microstates to schizophrenia. Results showed medium size effects for two classes of microstates, namely, a class labeled C that was found to be more frequent in schizophrenia and a class labeled D that was found to be shortened. These abnormalities may correspond to core symptoms of schizophrenia, e.g., insufficient reality testing and self-monitoring as during auditory verbal hallucinations. As interventional studies have shown that these microstate features may be systematically affected using antipsychotic drugs or neurofeedback interventions, these findings may help introducing novel diagnostic and treatment options.

Towards Using Microstate-Neurofeedback for the Treatment of Psychotic Symptoms in Schizophrenia. A Feasibility Study in Healthy Participants.

Spontaneous EEG signal can be parsed into sub-second periods of stable functional states (microstates) that assumingly correspond to brief large scale synchronization events. In schizophrenia, a specific class of microstate (class "D") has been found to be shorter than in healthy controls and to be correlated with positive symptoms. To explore potential new treatment options in schizophrenia, we tested in healthy controls if neurofeedback training to self-regulate microstate D presence is feasible and what learning patterns are observed. Twenty subjects underwent EEG-neurofeedback training to up-regulate microstate D presence. The protocol included 20 training sessions, consisting of baseline trials (resting state), regulation trials with auditory feedback contingent on microstate D presence, and a transfer trial. Response to neurofeedback was assessed with mixed effects modelling. All participants increased the percentage of time spent producing microstate D in at least one of the three conditions (p < 0.05). Significant between-subjects across-sessions results showed an increase of 0.42 % of time spent producing microstate D in baseline (reflecting a sustained change in the resting state), 1.93 % of increase during regulation and 1.83 % during transfer. Within-session analysis (performed in baseline and regulation trials only) showed a significant 1.65 % increase in baseline and 0.53 % increase in regulation. These values are in a range that is expected to have an impact upon psychotic experiences. Additionally, we found a negative correlation between alpha power and microstate D contribution during neurofeedback training. Given that microstate D has been related to attentional processes, this result provides further evidence that the training was to some degree specific for the attentional network. We conclude that microstate-neurofeedback training proved feasible in healthy subjects. The implementation of the same protocol in schizophrenia patients may promote skills useful to reduce positive symptoms by means of EEG-neurofeedback.

Remotely Versus Locally Facilitated Simulation-based Training in Management of the Deteriorating Patient by Newly Graduated Health Professionals: A Controlled Trial.

INTRODUCTION: This study evaluated delivery of immersive simulation-based training (SBT) by distance education. Newly graduated health professionals' experience of and learning outcomes from videoconference-enabled remotely facilitated (RF) were prospectively compared with a locally facilitated (LF) format within a course addressing management of the deteriorating patient. METHODS: Participants were exposed to both RF and LF formats in an intervention course (IC). The primary outcome measure was a questionnaire detailing participants' experience of 1 RF scenario and 1 LF scenario. The 16-item questionnaire measured perceived learning, comfort, interaction with other learners and instructor, as well as quality of instruction, factors that are considered essential in both SBT and distance education. As a secondary outcome measure, learning outcomes, measured as precourse and postcourse scores and pass rates in multiple-choice question tests, were also measured and compared with those of participants completing control courses, in which only the LF format was used. RESULTS: The study was conducted between April 2013 and April 2014. Among the 155 participants who participated in ICs, questionnaire results revealed a small, significantly higher median total score (25-75 interquartile range) for LF versus RF format scenarios [78 (72-80) vs. 76 (68-80), P = 0.01]. Multiple-choice question test scores compared between 155 IC and 150 control course participants showed no significant differences. CONCLUSIONS: Participants' experience of SBT using the RF format was slightly less positive than the LF format; however, it had no measured impact on knowledge. The impact of RF-SBT on more complex training applications remains poorly understood. Instructors could potentially optimize learner comfort and engagement by improving their interactive skills.