Down-regulation of amygdala activation with real-time fMRI neurofeedback in a healthy female sample

Christian Paret, Rosemarie Kluetsch, Matthias Ruf, Traute Demirakca, Steffen Hoesterey, Gabriele Ende, Christian Schmahl, Christian Paret, Rosemarie Kluetsch, Matthias Ruf, Traute Demirakca, Steffen Hoesterey, Gabriele Ende, Christian Schmahl

Abstract

Psychiatric conditions of emotion dysregulation are often characterized by difficulties in regulating the activity of limbic regions such as the amygdala. Real-time functional magnetic resonance imaging (rt-fMRI) allows to feedback brain activation and opens the possibility to establish a neurofeedback (NF) training of amygdala activation, e.g., for subjects suffering from emotion dysregulation. As a first step, we investigated whether feedback of the amygdala response to aversive scenes can improve down-regulation of amygdala activation. One group of healthy female participants received amygdala feedback (N = 16) and a control group was presented with feedback from a control region located in the basal ganglia [N(sum) = 32]. Subjects completed a one-session rt-fMRI-NF training where they viewed aversive pictures and received continuous visual feedback on brain activation (REGULATE condition). In a control condition, subjects were advised to respond naturally to aversive pictures (VIEW), and a neutral condition served as the non-affective control (NEUTRAL). In an adjacent run, subjects were presented with aversive pictures without feedback to test for transfer effects of learning. In a region of interest (ROI) analysis, the VIEW and the REGULATE conditions were contrasted to estimate brain regulation success. The ROI analysis was complemented by an exploratory analysis of activations at the whole-brain level. Both groups showed down-regulation of the amygdala response during training. Feedback from the amygdala but not from the control region was associated with down-regulation of the right amygdala in the transfer test. The whole-brain analysis did not detect significant group interactions. Results of the group whole-brain analyses are discussed. We present a proof-of-concept study using rt-fMRI-NF for amygdala down-regulation in the presence of aversive scenes. Results are in line with a potential benefit of NF training for amygdala regulation.

Keywords: affective disorders; affective symptoms; amygdala; emotion regulation; emotions; instrumental learning; mPFC; real-time fMRI neurofeedback.

Figures

Figure 1
Figure 1
Experimental design. (A) Trial structure. A trial started with a 2 s instruction slide indicating trial type (REGULATE, VIEW, NEUTRAL). In the following block, participants either saw an aversive or a scrambled picture with a thermometer at both sides. The thermometer displayed the change in brain activation and was updated every 2 s. After 24 s, the screen changed to gray with a white fixation cross (ITI), and 10 s later, the next trial started. (B) Flow Chart of experimental procedure. Results from resting state data are published elsewhere.
Figure 2
Figure 2
Regions of interest (ROIs) for the extraction of the neurofeedback signal during training. The amygdala mask was prepared using the Talairach Daemon (Lancaster et al., 2000) and included voxels which were exclusively assigned to the amygdala by the online tool. The mask delineating the control region was the same size and shape as the amygdala mask, but was located in another part of the brain, comprising parts of rostral basal ganglia, and white matter.
Figure 3
Figure 3
Results of the region-of-interest analysis of the neurofeedback training. Negative values indicate a decrease of the BOLD signal amplitude in the regulate condition (REGULATE) compared to natural responding toward aversive pictures (VIEW). White box plots: participants receiving feedback from the amygdala during training (experimental group). Gray box plots: participants receiving feedback from a standardized control region during training (control group). Orange dots: participants who had received feedback from a non-standardized control region during training due to a technical error (N = 3). P-values indicate probability of the findings for each group and mask under the null-hypothesis. T-tests were not significant when correcting for multiple comparisons. A.u., artificial units.
Figure 4
Figure 4
Results of the region-of-interest analysis of the transfer run. Negative values indicate a decrease of the BOLD signal amplitude in the regulate condition (REGULATE) compared to natural responding toward aversive pictures (VIEW). White box plots: participants receiving feedback from the amygdala during training (experimental group). Gray box plots: participants receiving feedback from a standardized control region during training (control group). Orange dots: participants who had received feedback from a non-standardized control region during training due to a technical error (N = 3). P-values indicate probability of the findings for each group and mask under the null-hypothesis. Tests were not significant when correcting for multiple comparisons. Black circle: outlier value (3 standard deviations > group mean). A.u., artificial units.
Figure 5
Figure 5
The experimental group down-regulated the right amygdala response in the transfer run. (A) Voxels were found activated at p < 0.05 (family-wise error corrected for multiple comparisons) in an anatomical mask of the right amygdala (Tzourio-Mazoyer et al., 2002) for the contrast VIEW>REGULATE in the experimental group. Crosshairs indicate location of the peak voxel at [24, −7, −14], Montreal Neurological Institute coordinate space. Activation is displayed on a coronal view of the SPM8 canonical standard template. Left is left. Scale indicates t-values of the parameter estimate. (B) Mean parameter estimate of all voxels within the right amygdala mask of the REGULATE>NEUTRAL and VIEW>NEUTRAL contrast, taken from the transfer run. White bars: experimental group (N = 16), gray bars: control group (N = 16). Error bars indicate standard error of mean. A.u., artificial units.
Figure 6
Figure 6
Results of the region-of-interest analysis of the anterior insula. Mean parameter estimate of all voxels within the anterior insula masks of the REGULATE>NEUTRAL and VIEW>NEUTRAL contrast. Error bars indicate standard error of mean. A.u., artificial units. (A) Neurofeedback training (mean over all runs). (B) Transfer run.

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