Cross-Over Studies
Research Papers
Magnetoencephalographic neurofeedback training decreasesβ-low-γphase-amplitude coupling of the motor cortex of healthy adults: a double-blinded randomized crossover feasibility study
Objective.The coupling between the beta (13-30 Hz) phase and low gamma (50-100 Hz) amplitude in the motor cortex is thought to regulate motor performance. Abnormal phase-amplitude coupling (PAC) of beta-low gamma (β-low-γPAC) is associated with motor symptoms of Parkinson's disease. However, the causal relationship betweenβ-low-γPAC and motor performance in healthy subjects is unknown. We hypothesized that healthy subjects could change the strength of theβ-low-γPAC in the resting state by neurofeedback training (NFT) to control theβ-low-γPAC, such that the motor performance changes in accordance with the changes inβ-low-γPAC in the resting state.Approach.We developed an NFT to control the strength of theβ-low-γPAC in the motor cortex, which was evaluated by magnetoencephalography (MEG) using a current source estimation technique. Twenty subjects were enrolled in a double-blind randomized crossover trial to test the feasibility of the MEG NFT. In the NFT for 2 d, the subjects were instructed to reduce the size of a black circle whose radius was proportional (down-training) or inversely proportional (up-training) to the strength of theβ-low-γPAC. The reaction times (RTs) to press a button according to some cues were evaluated before and after training. This study was registered at ClinicalTrials.gov (NCT03837548) and UMIN-CTR (UMIN000032937).Main results.Theβ-low-γPAC during the resting state was significantly decreased after down-training, although not significantly after up-training. RTs tended to decrease after both trainings, however the differences were not statistically significant. There was no significant correlation between the changes inβ-low-γPAC during rest and RTs.Significance.The proposed MEG NFT was demonstrated to change theβ-low-γPAC of the motor cortex in healthy subjects. However, a relationship between PAC and RT has not yet been demonstrated.
View Full Paper →Randomized, Sham-Controlled Trial of Real-Time Functional Magnetic Resonance Imaging Neurofeedback for Tics in Adolescents With Tourette Syndrome
BACKGROUND: Activity in the supplementary motor area (SMA) has been associated with tics in Tourette syndrome (TS). The aim of this study was to test a novel intervention-real-time functional magnetic resonance imaging neurofeedback from the SMA-for reduction of tics in adolescents with TS. METHODS: Twenty-one adolescents with TS were enrolled in a double-blind, randomized, sham-controlled, crossover study involving two sessions of neurofeedback from their SMA. The primary outcome measure of tic severity was the Yale Global Tic Severity Scale administered by an independent evaluator before and after each arm. The secondary outcome was control over the SMA assessed in neuroimaging scans, in which subjects were cued to increase/decrease activity in SMA without receiving feedback. RESULTS: All 21 subjects completed both arms of the study and all assessments. Participants had significantly greater reduction of tics on the Yale Global Tic Severity Scale after real neurofeedback as compared with the sham control (p < .05). Mean Yale Global Tic Severity Scale Total Tic score decreased from 25.2 ± 4.6 at baseline to 19.9 ± 5.7 at end point in the neurofeedback condition and from 24.8 ± 8.1 to 23.3 ± 8.5 in the sham control condition. The 3.8-point difference is clinically meaningful and corresponds to an effect size of 0.59. However, there were no differences in changes on the secondary measure of control over the SMA. CONCLUSIONS: This first randomized controlled trial of real-time functional magnetic resonance imaging neurofeedback in adolescents with TS suggests that this neurofeedback intervention may be helpful for improving tic symptoms. However, no effects were found in terms of change in control over the SMA, the hypothesized mechanism of action.
View Full Paper →Rt-fMRI neurofeedback-guided cognitive reappraisal training modulates amygdala responsivity in posttraumatic stress disorder
BACKGROUND: Traumatic experiences are associated with neurofunctional dysregulations in key regions of the emotion regulation circuits. In particular, amygdala responsivity to negative stimuli is exaggerated while engagement of prefrontal regulatory control regions is attenuated. Successful application of emotion regulation (ER) strategies may counteract this disbalance, however, application of learned strategies in daily life is hampered in individuals afflicted by posttraumatic stress disorder (PTSD). We hypothesized that a single session of real-time fMRI (rtfMRI) guided upregulation of prefrontal regions during an emotion regulation task enhances self-control during exposure to negative stimuli and facilitates transfer of the learned ER skills to daily life. METHODS: In a cross-over design, individuals with a PTSD diagnosis after a single traumatic event (n = 20) according to DSM-IV-TR criteria and individuals without a formal psychiatric diagnosis (n = 21) underwent a cognitive reappraisal training. In randomized order, all participants completed two rtfMRI neurofeedback (NF) runs targeting the left lateral prefrontal cortex (lPFC) and two control runs without NF (NoNF) while using cognitive reappraisal to reduce their emotional response to negative scenes. During the NoNF runs, two %%-signs were displayed instead of the two-digit feedback (FB) to achieve a comparable visual stimulation. The project aimed at defining the clinical potential of the training according to three success markers: (1) NF induced changes in left lateral prefrontal cortex and bilateral amygdala activity during the regulation of aversive scenes compared to cognitive reappraisal alone (primary registered outcome), (2) associated changes on the symptomatic and behavioral level such as indicated by PTSD symptom severity and affect ratings, (3) clinical utility such as indicated by perceived efficacy, acceptance, and transfer to daily life measured four weeks after the training. RESULTS: In comparison to the reappraisal without feedback, a neurofeedback-specific decrease in the left lateral PFC (d = 0.54) alongside an attenuation of amygdala responses (d = 0.33) emerged. Reduced amygdala responses during NF were associated with symptom improvement (r = -0.42) and less negative affect (r = -0.63) at follow-up. The difference in symptom scores exceeds requirements for a minimal clinically important difference and corresponds to a medium effect size (d = 0.64). Importantly, 75% of individuals with PTSD used the strategies in daily life during a one-month follow-up period and perceived the training as efficient. CONCLUSION: Our findings suggest beneficial effects of the NF training indicated by reduced amygdala responses that were associated with improved symptom severity and affective state four weeks after the NF training as well as patient-centered perceived control during the training, helpfulness and application of strategies in daily life. However, reduced prefrontal involvement was unexpected. The study suggests good tolerability of the training protocol and potential for clinical use in the treatment of PTSD.
View Full Paper →Real-Time Functional Connectivity-Informed Neurofeedback of Amygdala-Frontal Pathways Reduces Anxiety
BACKGROUND: Deficient emotion regulation and exaggerated anxiety represent a major transdiagnostic psychopathological marker. On the neural level these deficits have been closely linked to impaired, yet treatment-sensitive, prefrontal regulatory control over the amygdala. Gaining direct control over these pathways could therefore provide an innovative and promising intervention to regulate exaggerated anxiety. To this end the current proof-of-concept study evaluated the feasibility, functional relevance and maintenance of a novel connectivity-informed real-time fMRI neurofeedback training. METHODS: In a randomized crossover sham-controlled design, 26 healthy subjects with high anxiety underwent real-time fMRI-guided neurofeedback training to enhance connectivity between the ventrolateral prefrontal cortex (vlPFC) and the amygdala (target pathway) during threat exposure. Maintenance of regulatory control was assessed after 3 days and in the absence of feedback. Training-induced changes in functional connectivity of the target pathway and anxiety ratings served as primary outcomes. RESULTS: Training of the target, yet not the sham control, pathway significantly increased amygdala-vlPFC connectivity and decreased levels of anxiety. Stronger connectivity increases were significantly associated with higher anxiety reduction on the group level. At the follow-up, volitional control over the target pathway was maintained in the absence of feedback. CONCLUSIONS: The present results demonstrate for the first time that successful self-regulation of amygdala-prefrontal top-down regulatory circuits may represent a novel intervention to control anxiety. As such, the present findings underscore both the critical contribution of amygdala-prefrontal circuits to emotion regulation and the therapeutic potential of connectivity-informed real-time neurofeedback.
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