Real-time fMRI neurofeedback training of the amygdala activity with simultaneous EEG in veterans with combat-related PTSD

Zotev, Vadim; Phillips, Raquel; Misaki, Masaya; Wong, Chung Ki; Wurfel, Brent E.; Krueger, Frank; Feldner, Matthew T.; Bodurka, Jerzy

doi:10.1016/j.nicl.2018.04.010

Cited by 103 publications

(146 citation statements)

References 56 publications

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“…Two-way repeated-measures ANOVA with the factors training (EXP vs. SHC) and time (run 1 + run 2 vs. run 3 + run 4) and connectivity strengths of the target pathway as dependent variable [31, 52] revealed a significant training × time interaction effect ( F 1, 21 = 4.47, p = 0.047). Post hoc comparisons demonstrated that connectivity in the target pathway increased over the course of the EXP training (run 3 + run 4 > run 1 + run 2, t 22 = 2.81, p = 0.010, Cohen’s d = 0.79, paired t test, two-tailed).…”

Section: Resultsmentioning

confidence: 99%

“…To this end visual analog scales (VAS, anxiety levels from 0 to 100) were administered before and after each training session. VAS scales were chosen based on previous studies demonstrating a high sensitivity of these scales to capture the functional relevance of rtfMRI trainings [32, 52] and studies reporting a direct association between self-reported anxiety and amygdala-prefrontal crosstalk [53]. To control confounding effects of pretraining mood and anxiety states, these were assessed additionally immediately before each training and maintenance session.…”

Section: Methodsmentioning

confidence: 99%

“…22) by means of repeated-measure ANOVAs (analysis of variance) and Bonferroni-corrected post hoc tests. In line with previous studies evaluating the functional and clinical relevance of rt-fMRI NFTs [31, 52] training success was assessed by comparing changes in connectivity strengths between the early stages of learning (first 2 runs) and later stages of the training during which successful control has been implemented (run 3 + run 4 > run 1 + run 2). Training-induced changes in subjective anxiety levels as assessed by the VAS administered before and after each training session served as the primary behavioral outcome.…”

Section: Methodsmentioning

confidence: 99%

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Real-Time Functional Connectivity-Informed Neurofeedback of Amygdala-Frontal Pathways Reduces Anxiety

Zhao

Yao

et al. 2019

Psychother Psychosom

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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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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Real-Time Functional Connectivity-Informed Neurofeedback of Amygdala-Frontal Pathways Reduces Anxiety

Zhao

Yao

et al. 2019

Psychother Psychosom

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“…Many previous studies have suggested that depressive disorders occur frequently during adolescence and adolescent‐onset depressive disorders are related to greater physical health problems, psychosocial impairments and psychiatric comorbidity than adult‐onset depressive disorders (Wilson, Hicks, Foster, McGue, & Iacono, ). Thus, studying the neural substrates of perceived stress and their relations to depressive symptoms in this period is extremely important, as the findings may help to identify distinct biomarkers related to perceived stress, which can be used by clinical and educational experts to develop corresponding intervening programs (e.g., neurofeedback training, Zotev et al, ) to decrease the occurrence of depression in adolescents.…”

Section: Introductionmentioning

confidence: 99%

Stress and the brain: Perceived stress mediates the impact of the superior frontal gyrus spontaneous activity on depressive symptoms in late adolescence

Wang

Zhao

Zhang

et al. 2019

Human Brain Mapping

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Identifying factors for the prediction of depression is a long‐standing research topic in psychiatry and psychology. Perceived stress, which reflects the tendency to appraise one's life situations as stressful and overwhelming, has emerged as a stable predictor for depressive symptoms. However, the neurobiological bases of perceived stress and how perceived stress influences depressive symptoms in the healthy brain remain largely unknown. Here, we investigated these issues in 217 healthy adolescents by estimating the fractional amplitude of low‐frequency fluctuations (fALFFs) via resting‐state functional magnetic resonance imaging. A whole‐brain correlation analysis showed that higher levels of perceived stress were associated with greater fALFF in the left superior frontal gyrus (SFG), which is a core brain region for cognitive control and emotion regulation‐related processes. Mediation analysis further indicated that perceived stress mediated the link between the fALFF in the left SFG and depressive symptoms. Importantly, our results remained significant even when excluding the influences of head motion, anxiety, SFG gray matter structure, and school environment. Altogether, our findings suggested that the fALFF in the left SFG is a neurofunctional marker of perceived stress in adolescents and revealed a potential indirect effect of perceived stress on the association between the SFG spontaneous activity and depressive symptoms.

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“…Details regarding the neurofeedback procedure and the effects of the procedure on brain activation during the task have been described in a prior report (Zotev et al, 2018). Participants were trained to increase the feedback signal from the left amygdala by recalling a positive autobiographical memory.…”

Section: Introductionmentioning

confidence: 99%

Real-time fMRI amygdala neurofeedback positive emotional training normalized resting-state functional connectivity in combat veterans with and without PTSD: a connectome-wide investigation

Misaki

Phillips

Zotev

et al. 2018

NeuroImage: Clinical

Self Cite

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Self-regulation of brain activation using real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) is an emerging approach for treating mood and anxiety disorders. The effect of neurofeedback training on resting-state functional connectivity warrants investigation as changes in spontaneous brain activation could reflect the association between sustained symptom relief and brain alteration. We investigated the effect of amygdala-focused rtfMRI-nf training on resting-state functional connectivity in combat veterans with and without posttraumatic stress disorder (PTSD) who were trained to increase a feedback signal reflecting left amygdala activity while recalling positive autobiographical memories (Zotev et al., 2018). The analysis was performed in three stages: i) first, we investigated the connectivity in the left amygdala region; ii) next, we focused on the abnormal resting-state functional connectivity identified in our previous analysis of this data (Misaki et al., 2018); and iii) finally, we performed a novel data-driven longitudinal connectome-wide analysis. We introduced a longitudinal multivariate distance matrix regression (MDMR) analysis to comprehensively examine neurofeedback training effects beyond those associated with abnormal baseline connectivity.These comprehensive exploratory analyses suggested that abnormal resting-state connectivity for combat veterans with PTSD was partly normalized after the training. This included hypoconnectivities between the left amygdala and the left ventrolateral prefrontal cortex (vlPFC) and between the supplementary motor area (SMA) and the dorsal anterior cingulate cortex (dACC). The increase of SMA-dACC connectivity was associated with PTSD symptom reduction. Longitudinal MDMR analysis found a connectivity change between the precuneus and the left superior frontal cortex. The connectivity increase was associated with a decrease in hyperarousal symptoms. The abnormal connectivity for combat veterans without PTSD - such as hypoconnectivity in the precuneus with a superior frontal region and hyperconnectivity in the posterior insula with several regions - could also be normalized after the training. These results suggested that the rtfMRI-nf training effect was not limited to a feedback target region and symptom relief could be mediated by brain modulation in several regions other than in a feedback target area. While further confirmatory research is needed, the results may provide valuable insight into treatment effects on the whole brain resting-state connectivity.

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Real-time fMRI neurofeedback training of the amygdala activity with simultaneous EEG in veterans with combat-related PTSD

Cited by 103 publications

References 56 publications

Real-Time Functional Connectivity-Informed Neurofeedback of Amygdala-Frontal Pathways Reduces Anxiety

Real-Time Functional Connectivity-Informed Neurofeedback of Amygdala-Frontal Pathways Reduces Anxiety

Stress and the brain: Perceived stress mediates the impact of the superior frontal gyrus spontaneous activity on depressive symptoms in late adolescence

Real-time fMRI amygdala neurofeedback positive emotional training normalized resting-state functional connectivity in combat veterans with and without PTSD: a connectome-wide investigation

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