Preclinical findings suggest that transcranial infrared laser stimulation (TILS) improves fear extinction learning and cognitive function by enhancing prefrontal cortex (PFC) oxygen metabolism. These findings prompted our investigation of treating pathological fear using this non-invasive stimulation approach either alone to the dorsolateral PFC (dlPFC), or to the ventromedial PFC (vmPFC) in combination with exposure therapy.

Volunteers with pathological fear of either enclosed spaces, contamination, public speaking, or anxiety-related bodily sensations were recruited for this randomized, single-blind, sham-controlled trial with four arms: (a) Exposure + TILS_vmPFC (n = 29), (b) Exposure + sham TILS_vmPFC (n = 29), (c) TILS_dlPFC alone (n = 26), or (d) Sham TILS _dlPFC alone (n = 28). Post-treatment assessments occurred immediately following treatment. Follow-up assessments occurred 2 weeks after treatment.

A total of 112 participants were randomized [age range: 18–63 years; 96 females (85.71%)]. Significant interactions of Group × Time and Group × Context indicated differential treatment effects on retention (i.e. between time-points, averaged across contexts) and on generalization (i.e. between contexts, averaged across time-points), respectively. Among the monotherapies, TILS_dlPFC outperformed SHAM_dlPFC in the initial context, b = −13.44, 95% CI (−25.73 to −1.15), p = 0.03. Among the combined treatments, differences between EX + TILS_vmPFC and EX + SHAM_vmPFC were non-significant across all contrasts.

TILS to the dlPFC, one of the PFC regions implicated in emotion regulation, resulted in a context-specific benefit as a monotherapy for reducing fear. Contrary to prediction, TILS to the vmPFC, a region implicated in fear extinction memory consolidation, did not enhance exposure therapy outcome.

临床前研究结果表明，经颅红外激光刺激 (TILS) 通过增强前额叶皮层 (PFC) 氧代谢来改善恐惧消退学习和认知功能。这些发现促使我们研究使用这种非侵入性刺激方法单独治疗背外侧 PFC (dlPFC) 或结合暴露疗法治疗腹内侧 PFC (vmPFC) 的病理性恐惧。

招募了对封闭空间、污染、公开演讲或与焦虑相关的身体感觉有病态恐惧的志愿者进行这项随机、单盲、假对照试验，有四组：(a) 暴露 + TILS_vmPFC（n = 29 ）， (b) 曝光 + 假 TILS_vmPFC ( n = 29)，(c) 仅 TILS_dlPFC ( n = 26)，或 (d) 仅假 TILS_dlPFC ( n = 28)。治疗后立即进行治疗后评估。治疗后 2 周进行随访评估。

共有 112 名参与者被随机分配 [年龄范围：18-63 岁；96 名女性 (85.71%)]。Group × Time 和 Group × Context 的显着相互作用表明分别对保留（即时间点之间，跨上下文平均）和泛化（即上下文之间，跨时间点平均）的不同处理效果。在单一疗法中，TILS_dlPFC 在初始情况下优于 SHAM_dlPFC，b = −13.44, 95% CI（−25.73 至 −1.15），p = 0.03。在联合治疗中，EX + TILS_vmPFC 和 EX + SHAM_vmPFC 之间的差异在所有对比中均不显着。

dlPFC 的 TILS 是涉及情绪调节的 PFC 区域之一，作为一种减少恐惧的单一疗法，它产生了特定情境的益处。与预测相反，对 vmPFC（与恐惧消退记忆巩固有关的区域）的 TILS 并没有增强暴露疗法的结果。