Psychiatric Status Rating Scales

Research Papers

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Real-time fMRI neurofeedback in adolescents with attention deficit hyperactivity disorder

Alegria, Analucia A., Wulff, Melanie, Brinson, Helen, Barker, Gareth J., Norman, Luke J., Brandeis, Daniel, Stahl, Daniel, David, Anthony S., Taylor, Eric, Giampietro, Vincent, Rubia, Katya (2017) · Human Brain Mapping

Attention Deficit Hyperactivity Disorder (ADHD) is associated with poor self-control, underpinned by inferior fronto-striatal deficits. Real-time functional magnetic resonance neurofeedback (rtfMRI-NF) allows participants to gain self-control over dysregulated brain regions. Despite evidence for beneficial effects of electrophysiological-NF on ADHD symptoms, no study has applied the spatially superior rtfMRI-NF neurotherapy to ADHD. A randomized controlled trial tested the efficacy of rtfMRI-NF of right inferior prefrontal cortex (rIFG), a key region that is compromised in ADHD and upregulated with psychostimulants, on improvement of ADHD symptoms, cognition, and inhibitory fMRI activation. To control for region-specificity, an active control group received rtfMRI-NF of the left parahippocampal gyrus (lPHG). Thirty-one ADHD boys were randomly allocated and had to learn to upregulate their target brain region in an average of 11 rtfMRI-NF runs over 2 weeks. Feedback was provided through a video-clip of a rocket that had to be moved up into space. A transfer session without feedback tested learning retention as a proximal measure of transfer to everyday life. Both NF groups showed significant linear activation increases with increasing number of runs in their respective target regions and significant reduction in ADHD symptoms after neurotherapy and at 11-month follow-up. Only the group targeting rIFG, however, showed a transfer effect, which correlated with ADHD symptom reductions, improved at trend level in sustained attention, and showed increased IFG activation during an inhibitory fMRI task. This proof-of-concept study demonstrates for the first time feasibility, safety, and shorter- and longer-term efficacy of rtfMRI-NF of rIFG in adolescents with ADHD. Hum Brain Mapp 38:3190-3209, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

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Real-Time Functional Magnetic Resonance Imaging Amygdala Neurofeedback Changes Positive Information Processing in Major Depressive Disorder

Young, Kymberly D., Misaki, Masaya, Harmer, Catherine J., Victor, Teresa, Zotev, Vadim, Phillips, Raquel, Siegle, Greg J., Drevets, Wayne C., Bodurka, Jerzy (2017) · Biological Psychiatry

BACKGROUND: In participants with major depressive disorder who are trained to upregulate their amygdalar hemodynamic responses during positive autobiographical memory recall with real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) training, depressive symptoms diminish. This study tested whether amygdalar rtfMRI-nf also changes emotional processing of positive and negative stimuli in a variety of behavioral and imaging tasks. METHODS: Patients with major depressive disorder completed two rtfMRI-nf sessions (18 received amygdalar rtfMRI-nf, 16 received control parietal rtfMRI-nf). One week before and following rtfMRI-nf training, participants performed tasks measuring responses to emotionally valenced stimuli including a backward-masking task, which measures the amygdalar hemodynamic response to emotional faces presented for traditionally subliminal duration and followed by a mask, and the Emotional Test Battery in which reaction times and performance accuracy are measured during tasks involving emotional faces and words. RESULTS: During the backward-masking task, amygdalar responses increased while viewing masked happy faces but decreased to masked sad faces in the experimental versus control group following rtfMRI-nf. During the Emotional Test Battery, reaction times decreased to identification of positive faces and during self-identification with positive words and vigilance scores increased to positive faces and decreased to negative faces during the faces dot-probe task in the experimental versus control group following rtfMRI-nf. CONCLUSIONS: rtfMRI-nf training to increase the amygdalar hemodynamic response to positive memories was associated with changes in amygdalar responses to happy and sad faces and improved processing of positive stimuli during performance of the Emotional Test Battery. These results may suggest that amygdalar rtfMRI-nf training alters responses to emotional stimuli in a manner similar to antidepressant pharmacotherapy.

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Correlation between amygdala BOLD activity and frontal EEG asymmetry during real-time fMRI neurofeedback training in patients with depression

Zotev, Vadim, Yuan, Han, Misaki, Masaya, Phillips, Raquel, Young, Kymberly D., Feldner, Matthew T., Bodurka, Jerzy (2016) · NeuroImage. Clinical

Real-time fMRI neurofeedback (rtfMRI-nf) is an emerging approach for studies and novel treatments of major depressive disorder (MDD). EEG performed simultaneously with an rtfMRI-nf procedure allows an independent evaluation of rtfMRI-nf brain modulation effects. Frontal EEG asymmetry in the alpha band is a widely used measure of emotion and motivation that shows profound changes in depression. However, it has never been directly related to simultaneously acquired fMRI data. We report the first study investigating electrophysiological correlates of the rtfMRI-nf procedure, by combining the rtfMRI-nf with simultaneous and passive EEG recordings. In this pilot study, MDD patients in the experimental group (n = 13) learned to upregulate BOLD activity of the left amygdala using an rtfMRI-nf during a happy emotion induction task. MDD patients in the control group (n = 11) were provided with a sham rtfMRI-nf. Correlations between frontal EEG asymmetry in the upper alpha band and BOLD activity across the brain were examined. Average individual changes in frontal EEG asymmetry during the rtfMRI-nf task for the experimental group showed a significant positive correlation with the MDD patients' depression severity ratings, consistent with an inverse correlation between the depression severity and frontal EEG asymmetry at rest. The average asymmetry changes also significantly correlated with the amygdala BOLD laterality. Temporal correlations between frontal EEG asymmetry and BOLD activity were significantly enhanced, during the rtfMRI-nf task, for the amygdala and many regions associated with emotion regulation. Our findings demonstrate an important link between amygdala BOLD activity and frontal EEG asymmetry during emotion regulation. Our EEG asymmetry results indicate that the rtfMRI-nf training targeting the amygdala is beneficial to MDD patients. They further suggest that EEG-nf based on frontal EEG asymmetry in the alpha band would be compatible with the amygdala-based rtfMRI-nf. Combination of the two could enhance emotion regulation training and benefit MDD patients.

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

Diaz Hernandez, Laura, Rieger, Kathryn, Baenninger, Anja, Brandeis, Daniel, Koenig, Thomas (2016) · Brain Topography

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.

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Resting-state functional connectivity modulation and sustained changes after real-time functional magnetic resonance imaging neurofeedback training in depression

Yuan, Han, Young, Kymberly D., Phillips, Raquel, Zotev, Vadim, Misaki, Masaya, Bodurka, Jerzy (2014) · Brain Connectivity

Amygdala hemodynamic responses to positive stimuli are attenuated in major depressive disorder (MDD) and normalize with remission. Real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) training with the goal of upregulating amygdala activity during recall of happy autobiographical memories (AMs) has been suggested, and recently explored, as a novel therapeutic approach that resulted in improvement in self-reported mood in depressed subjects. In this study, we assessed the possibility of sustained brain changes as well as the neuromodulatory effects of rtfMRI-nf training of the amygdala during recall of positive AMs in MDD and matched healthy subjects. MDD and healthy subjects went through one visit of rtfMRI-nf training. Subjects were assigned to receive active neurofeedback from the left amygdale (LA) or from a control region putatively not modulated by AM recall or emotion regulation, that is, the left horizontal segment of the intraparietal sulcus. To assess lasting effects of neurofeedback in MDD, the resting-state functional connectivity before and after rtfMRI-nf in 27 depressed subjects, as well as in 27 matched healthy subjects before rtfMRI-nf was measured. Results show that abnormal hypo-connectivity with LA in MDD is reversed after rtfMRI-nf training by recalling positive AMs. Although such neuromodulatory changes are observed in both MDD groups receiving feedback from respective active and control brain regions, only in the active group are larger decreases of depression severity associated with larger increases of amygdala connectivity and a significant, positive correlation is found between the connectivity changes and the days after neurofeedback. In addition, active neurofeedback training of the amygdala enhances connectivity with temporal cortical regions, including the hippocampus. These results demonstrate lasting brain changes induced by amygdala rtfMRI-nf training and suggest the importance of reinforcement learning in rehabilitating emotion regulation in depression.

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The effect of EEG biofeedback on reducing postcancer cognitive impairment

Alvarez, Jean, Meyer, Fremonta L., Granoff, David L., Lundy, Allan (2013) · Integrative Cancer Therapies

BACKGROUND AND HYPOTHESES: Postcancer cognitive impairment (PCCI) is observed in a substantial number of breast cancer survivors, persisting for as long as 20 years in some subgroups. Although compensatory strategies are frequently suggested, no restorative interventions have yet been identified. This study examined the feasibility of EEG biofeedback ("neurofeedback") and its potential effectiveness in reducing PCCI as well as the fatigue, sleep disturbance, and psychological symptoms that frequently accompany PCCI. STUDY DESIGN: This was a 6-month prospective study with a waitlist control period followed by an active intervention. Participants were female breast cancer survivors (n = 23), 6 to 60 months postchemotherapy, with self-reported cognitive impairment. METHODS: Four self-report outcome measures (Functional Assessment of Cancer Therapy-Cognitive Function [FACT-Cog], Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue], Pittsburgh Sleep Quality Index [PSQI], and Brief Symptom Inventory [BSI]-18) were administered 3 times during a 10-week waitlist control period, 3 times during a 10-week (20-session) neurofeedback training regimen, and once at 4 weeks postneurofeedback. RESULTS: All 23 participants completed the study, demonstrating the feasibility of EEG biofeedback in this population. Initially, the sample demonstrated significant dysfunction on all measures compared with general population norms. Repeated-measures ANOVAs revealed strongly significant improvements (P < .001) on all 4 cognitive measures (perceived cognitive impairment, comments from others, perceived cognitive abilities, and impact on quality of life [QOL]), the fatigue scale, and the 4 psychological scales (somatization, depression, anxiety and global severity index) as well as on 3 of 8 sleep scales (quality, daytime dysfunction, and global). Two of the other sleep scales (latency and disturbance) were significant at P < .01, and 1 (use of medication) at P < .05; 2 were not significant. Improvements were generally linear across the course of training, and were maintained at the follow-up testing. At the follow-up testing, the sample no longer differed significantly from normative populations on 3 of the 4 FACT-Cog measures (impairment, impact on QOL, and comments), FACIT-Fatigue, PSQI sleep quality and habitual efficiency, or any of the BSI-18 measures of psychological disturbance. CONCLUSIONS: Data from this limited study suggest that EEG biofeedback has potential for reducing the negative cognitive and emotional sequelae of cancer treatment as well as improving fatigue and sleep patterns.

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