Department of Psychiatry and Human Behavior, The Warren Alpert Medical School, Brown University, Providence, RI, USA; VA RR&D Center for Neurorestoration and Neurotechnology, VA Providence Healthcare System, Providence, RI, USA.
Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, MA, USA.
Neuromodulation. 2022 Jun;25(4):588-595. doi: 10.1111/ner.13529. Epub 2022 Feb 3.
Posttraumatic stress disorder (PTSD) is associated with autonomic dysfunction as indicated by deficits in the sympathetic and parasympathetic nervous systems. These abnormalities are expressed as elevated heart rate and reduced heart rate variability (HRV), respectively. Intermittent theta-burst stimulation (iTBS), a form of transcranial magnetic stimulation, has demonstrated effectiveness in PTSD. Nevertheless, it remains unclear whether HRV may be an iTBS biomarker for PTSD and whether iTBS impacts autonomic activity.
Fifty veterans with PTSD participated in a randomized controlled trial, receiving ten daily sessions of sham-controlled iTBS (right dorsolateral prefrontal cortex, 1800 pulses/day, 80% active motor threshold, 9.5 min). With a usable dataset (N = 47), HRV parameters were assessed as predictors of clinical response immediately after stimulation. iTBS effects on autonomic response (mean RR interval, root mean square of successive differences [RMSSD], total power [TP], and low-frequency/high-frequency [LF/HF] ratio) were evaluated using an ultra-short approach.
TP and RMSSD were significant predictors of acute clinical response to iTBS. Individuals with higher TP had better response to iTBS with improved symptoms on the Clinician-Administered PTSD Scale (r = -0.58, p = 0.004), and higher functionality on the Social and Occupational Function Scale (r = 0.43, p = 0.04). Similarly, higher RMSSD was associated with superior outcomes (r = -0.44, p = 0.04). No other significant changes in HRV metrics were observed (p ≥ 0.05).
Our findings indicate that autonomic activity is a potential low-cost and technically simple predictive biomarker of iTBS response in PTSD. Less autonomic dysfunction was associated with superior clinical improvements with iTBS. Future studies might consider HRV acquisition during iTBS, as well as prospective testing of these findings in patients with elevated hyperarousal.
创伤后应激障碍（PTSD）与自主神经系统功能障碍有关，表现为交感神经系统和副交感神经系统功能缺陷。这些异常分别表现为心率升高和心率变异性（HRV）降低。间串刺激（iTBS）是一种经颅磁刺激形式，已被证明对 PTSD 有效。然而，HRV 是否可以作为 PTSD 的 iTBS 生物标志物，以及 iTBS 是否会影响自主活动，仍不清楚。
50 名 PTSD 退伍军人参加了一项随机对照试验，接受了 10 天的假对照 iTBS（右侧背外侧前额叶皮质，每天 1800 个脉冲，80%主动运动阈值，9.5 分钟）。在有可用数据集（N=47）的情况下，HRV 参数被评估为刺激后即刻临床反应的预测因子。使用超短方法评估 iTBS 对自主反应（平均 RR 间期、连续差异的均方根 [RMSSD]、总功率 [TP]和低频/高频 [LF/HF] 比）的影响。
TP 和 RMSSD 是 iTBS 急性临床反应的显著预测因子。TP 较高的个体对 iTBS 的反应更好，创伤后应激障碍量表（r=-0.58，p=0.004）的症状改善，社会和职业功能量表（r=0.43，p=0.04）的功能更高。同样，较高的 RMSSD 与更好的结果相关（r=-0.44，p=0.04）。未观察到 HRV 指标的其他显著变化（p≥0.05）。
我们的研究结果表明，自主活动是 PTSD 中 iTBS 反应的一种潜在低成本、技术简单的预测生物标志物。自主神经功能障碍较少与 iTBS 后临床改善更好相关。未来的研究可能需要在 iTBS 期间进行 HRV 采集，并在有过度警觉症状的患者中前瞻性测试这些发现。
