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. Author manuscript; available in PMC: 2021 Dec 1.
Published in final edited form as: J Affect Disord Rep. 2021 Jul 10;6:100190. doi: 10.1016/j.jadr.2021.100190

Figure 2.

Figure 2.

Diagram of the baseline study protocol. PTSD patients underwent three days of stress, one day (Day 1) with neutral scripts (NS) and personalized traumatic scripts (TS), and two days (Days 2 and 3) with mental stress (MS) involving public speaking and mental arithmetic tasks. Participants underwent randomized, double-blind assignment to tcVNS or sham stimulation which was paired with stress tasks (or no task) on Days 1, 2 and 3. On Day 1 neutral and traumatic scripts lasted about one minute and occurred in pairs with 10 minutes in between. Stress tasks were paired with stimulation with tcVNS or sham which began immediately after termination of the task and continued for two minutes followed by a blood draw (purple/blue boxes signify pairing of task/stimulation/blood draw but blood draw actually occurred at the termination of stimulation). On Day 1 participants also underwent stimulation with tcVNS or sham for two minutes in the absence of a task (N) repeated twice with 10 minutes in between followed by a blood draw. Neutral and traumatic script pairs were repeated followed by a 60 minute rest and lunch break, with a repeat of neutral and traumatic script pairs in the afternoon each paired with blood draws. The neutral scripts tasks #11 and #12 were followed by a blood draw (which was about 110 minutes after the first trauma script pairs at tasks #3 and #4) and the trauma scripts tasks #13 and #14 paired with tcVNS or sham were followed by the final blood draw at 210 minutes into Day 1 (Traumatic Stress). On Day 2 after a baseline blood draw at rest (task #15) participants underwent mental stress (MS) involving five minutes of public speaking (task #16) with tcVNS or sham at the end, followed by an eight minute rest period, and another five minutes of mental arithmetic (task #17) followed by tcVNS or sham. After a 90 minute rest period participants underwent a blood draw at rest (task#18). This was repeated for Day 3 with baseline (task #19, public speaking (task #20), mental arithmetic (task #21) and a blood draw post-task at rest (task #22). The blood draws for all three days were timed to coincide with the roughly 90 minute time course of interleukin-6 (IL-6) response to stress based on prior studies. Patients then underwent three months of tcVNS/sham followed by a repeat of Day 1 only.