Intrinsic connectivity network dynamics in PTSD during amygdala downregulation using real-time fMRI neurofeedback: A preliminary analysis

Abstract

Posttraumatic stress disorder (PTSD) has been associated with a disturbance in neural intrinsic connectivity networks (ICN), including the central executive network (CEN), default mode network (DMN), and salience network (SN). Here, we conducted a preliminary investigation examining potential changes in ICN recruitment as a function of real-time fMRI neurofeedback (rt-fMRI-NFB) during symptom provocation where we targeted the downregulation of neural response within the amygdala-a key region-of-interest in PTSD neuropathophysiology. Patients with PTSD (n = 14) completed three sessions of rt-fMRI-NFB with the following conditions: (a) regulate: decrease activation in the amygdala while processing personalized trauma words; (b) view: process trauma words while not attempting to regulate the amygdala; and (c) neutral: process neutral words. We found that recruitment of the left CEN increased over neurofeedback runs during the regulate condition, a finding supported by increased dlPFC activation during the regulate as compared to the view condition. In contrast, DMN task-negative recruitment was stable during neurofeedback runs, albeit was the highest during view conditions and increased (normalized) during rest periods. Critically, SN recruitment was high for both the regulate and the view conditions, a finding potentially indicative of CEN modality switching, adaptive learning, and increasing threat/defense processing in PTSD. In conclusion, this study provides provocative, preliminary evidence that downregulation of the amygdala using rt-fMRI-NFB in PTSD is associated with dynamic changes in ICN, an effect similar to those observed using EEG modalities of neurofeedback.

Keywords: amygdala; brain connectivity; central executive network; default mode network; emotion; fMRI neurofeedback; independent component analysis; intrinsic connectivity networks; posttraumatic stress disorder; salience network.

© 2018 Wiley Periodicals, Inc.

Figures

Figure 1

Real‐time fMRI amygdala neurofeedback experimental design. Patients with PTSD were instructed to downregulate neurofeedback thermometer bars, denoting amygdala activation, on regulate trials only. Personalized trauma words were presented in the scanner for regulate and view conditions, while neutral words were presented for the neutral conditions. During view and neutral conditions, patients with PTSD were instructed to respond naturally to words, while not attempting to regulate their amygdala activation. Our experiment consisted of three consecutive sessions of neurofeedback training, followed by one transfer run without neurofeedback immediately after. Before each condition, there was an initial rest period [Color figure can be viewed at wileyonlinelibrary.com]

Figure 2

(a) Right amygdala parameter estimates corresponding to amygdala activation during neurofeedback training runs for the view (solid green line) and regulate (solid red line) conditions. (b) Left amygdala parameter estimates corresponding to amygdala activation during neurofeedback training runs for the view (solid green line) and regulate (solid red line) conditions. (c) Bilateral amygdala parameter estimates corresponding to activation during the transfer run without neurofeedback for the view (solid green line) and regulate (solid red line) conditions. Shaded red and green regions adjacent to the solid lines indicate standard error of the mean. Statistical thresholds corresponds to a‐priori paired‐sample t‐tests, comparing amygdala activation during view versus regulate across the whole condition. Reg = regulate [Color figure can be viewed at wileyonlinelibrary.com]

Figure 3

Task relatedness of the left central executive network during amygdala downregulating neurofeedback training runs and the transfer run, for the regulate, view, and neutral conditions, as well as the initial rest. Runs 1–3 consist of neurofeedback training runs, and run 4 is the transfer run without neurofeedback. Brain images to the right of the graph indicate areas included within the central executive network component. Slice references are in MNI space. Beta weights denote network task‐relatedness to an experimental condition. Top (a) The main effect of run across neurofeedback conditions for the left central executive network. Significant differences between runs are denoted by a red significance bar. Bottom (b) The interaction between condition and run for the left central executive network. Simple main effects: significant differences between runs within a condition are denoted by the significance bar that is in the same color as the condition in legend. Significant differences between conditions within a specific run are denoted by a red significance bar [Color figure can be viewed at wileyonlinelibrary.com]

Figure 4

Task relatedness of the right central executive network during amygdala downregulating neurofeedback training runs and the transfer run, for the regulate, view, and neutral conditions, as well as for the initial rest. Runs 1–3 consist of neurofeedback training runs, and run 4 is the transfer run without neurofeedback. Brain images to the right of the graph indicate areas included within the right central executive network component. Slice references are in MNI space. Beta weights denote network task‐relatedness to an experimental condition. Top (a) The main effect of condition across neurofeedback runs for the right central executive network. Significant differences between conditions are denoted by a red significance bar. Bottom (b) The interaction between condition and run for the right central executive network. Simple main effects: significant differences between runs within a condition are denoted by the significance bar that is in the same color as the condition in legend. Significant differences between conditions within a specific run are denoted by a red significance bar [Color figure can be viewed at wileyonlinelibrary.com]

Figure 5

Task relatedness of the anterior default mode network across runs during amygdala downregulating neurofeedback for the regulate, view, and neutral conditions, as well as the initial rest. Brain images to the right of the graph indicate areas included within the default mode network component. Slice references are in MNI space. Beta weights denote network task relatedness to an experimental condition. Top (a) The main effect of condition across neurofeedback runs for the default mode network. Significant differences between conditions are denoted by a red significance bar. Bottom (b) The interaction between condition and run for default mode network. Simple main effects: significant differences between runs within a condition are denoted by the significance bar that is in the same color as the condition in legend. Significant differences between conditions within a run are denoted by a red significance bar [Color figure can be viewed at wileyonlinelibrary.com]

Figure 6

Task relatedness of the salience network during amygdala downregulating neurofeedback training runs and the transfer run, for the regulate, view, and neutral conditions, as well as the initial rest. Runs 1–3 consist of neurofeedback training runs, and run 4 is the transfer run without neurofeedback. Displayed is the main effect of condition, and red significance bars indicate differences between conditions averaged across runs. Brain images to the right of the graph indicate areas included within the salience network component. Slice references are in MNI space. Beta weights denote network task relatedness to an experimental condition [Color figure can be viewed at wileyonlinelibrary.com]