Full Length ArticlesfMRI neurofeedback of amygdala response to aversive stimuli enhances prefrontal–limbic brain connectivity
Introduction
Real-time functional magnetic resonance imaging neurofeedback (rtfMRI NF) has attracted increasing interest from basic and clinical scientists. With rtfMRI NF, information on brain activation is fed back to the participant via a brain–computer interface (Weiskopf, 2012). Cumulative evidence is reported for a potential effect of rtfMRI NF on brain self-regulation in domains of high relevance for clinical psychology and psychiatry, such as emotion regulation (e.g. Brühl et al., 2014, Caria et al., 2010, Scheinost et al., 2013, Veit et al., 2012, Zotev et al., 2011), and an improved regulation of disturbed brain circuits supported by neurofeedback training may yield therapeutic benefits (Linden, 2014, Stoeckel et al., 2014).
There is initial evidence for an alteration of amygdala–prefrontal connectivity via amygdala neurofeedback when giving the instruction to upregulate (Yuan et al., 2014, Zotev et al., 2011, Zotev et al., 2013). Though, to date, it is unknown whether amygdala neurofeedback with the instruction to down-regulate involves similar neural mechanisms. This is of eminent interest for advancing rtfMRI NF towards the treatment of mental disorders involving limbic hyperactivation and aberrant prefrontal–limbic connectivity, that might become a therapeutic option in the future.
In a previous study, we recently demonstrated amygdala down-regulation with blood oxygenation level dependent (BOLD) signal feedback from the amygdala in healthy individuals (Paret et al., 2014). We adapted an established emotion regulation paradigm that involved viewing aversive and scrambled ‘neutral’ pictures in an fMRI environment. Participants were instructed to regulate a continuously updated biofeedback signal, obtained from the amygdala and displayed at both sides of the aversive picture (Fig. 1). They significantly decreased amygdala activation when instructed to regulate the feedback signal as compared to the instruction to respond naturally, i.e., to view the picture. In this recent report, however, changes in brain connectivity were not addressed. Hence, the major aim of the present paper is to delineate changes in functional amygdala connectivity with rtfMRI NF and the instruction to down-regulate the amygdala response to aversive pictures. This is not only necessary for advancing the development of the technique towards clinical application. It is also needed to scrutinize the present reports on connectivity with amygdala neurofeedback, which focused on amygdala up-regulation and interpret changes of prefrontal–limbic connectivity in terms of a top-down control model. Data from amygdala down-regulation are suited to test this model and deepen our understanding of the dialectic interplay of prefrontal cortex and amygdala in neurofeedback regulation. Addressing this point in this paper, it is expected, that amygdala neurofeedback compared to control region feedback would enhance functional connectivity of the amygdala with the prefrontal cortex. Functional connectivity is analyzed in the data set described above using psychophysiological interaction (PPI) analysis to identify prefrontal regions communicating with the amygdala in a task-dependent and (amygdala-feedback) specific manner. Connectivity with the ventromedial prefrontal cortex (vmPFC) region detected with this approach is further investigated for causal directionality using dynamic causal modeling (DCM) to inform the interpretation of connectivity changes in terms of top-down and bottom-up processes.
Section snippets
Participants
Thirty-two females aged 24.56 ± 3.91 (M ± SD) who did not report any current or lifetime psychiatric diagnosis participated in the study. Group assignment to the experimental and control group was randomized and blinded. Groups were matched for age, highest educational attainment and sample size (N = 16 per group). Results from the same sample had been published earlier (Paret et al., 2014); more details on sample characteristics can be obtained there. For the purpose of this article, the data were
Amygdala connectivity: group interaction
We analyzed differences in amygdala functional connectivity between a condition where participants were instructed to down-regulate brain activation (‘regulate’) and a condition with the instruction to respond naturally to aversive picture content (‘view’) with the contrast ‘regulate vs. view’. Regions associated with an increase in connectivity with amygdala neurofeedback versus control region feedback were identified with the corresponding group interaction contrast (i.e., ‘experimental group
Discussion
Receiving the instruction to down-regulate amygdala neurofeedback compared to sham region feedback resulted in increased connectivity of the right amygdala most prominently to the vmPFC in healthy participants. Amygdala–vmPFC connectivity was correlated with picture arousal, and an analysis of effective connectivity demonstrated dominant bottom-up information flow from the amygdala to the vmPFC. The results were complemented by a task-dependent functional connectivity increase of the vmPFC with
Conclusions
To conclude, functional connectivity of the amygdala with the vmPFC was altered by amygdala neurofeedback but not by feedback from a control region in healthy participants. Increased connectivity may reflect a boosted bottom-up exchange of emotion information. Changes in brain connectivity are supportive for a potential benefit of neurofeedback training to the treatment of dysregulated neural networks. This should be addressed in further investigations with patients with borderline personality
Acknowledgments
We would like to thank Lydia Robnik for her support in study organization, Rebekka Knies, Kathrin Haeussler and Marie-Luise Zeitler for recruitment and conducting the diagnostic interviews, Steffen Hoesterey and Jenny Zaehringer for their support in data acquisition and analysis, Anja Voigt for her help with the preparation of figures, and Bettina Kirr for assisting in data acquisition. We also thank all the participants who participated in our study. The work was part of the Clinical Research
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Authors contributed equally.