Successful use of closed-loop allostatic neurotechnology for post-traumatic stress symptoms in military personnel: self-reported and autonomic improvements

Advanced understanding and treatment for post-traumatic stress disorder (PTSD) will require a paradigm that appreciates its complexity and holds a promising solution for its extensive burden of suffering. Conventionally, PTSD is classified and treated as a behavioral disturbance that can follow a traumatic event, and its main symptom clusters pertain to re-experiencing the trauma, avoidance and generalized numbing, negative cognitions and mood, and heightened arousal [1]. However, while military service members with PTSD are beset with increased psychosocial risks, including compromised role functions [2], substance abuse [3], and suicidality [4], studies also show an increased risk for cardiovascular and metabolic diseases [5, 6] as well as all-cause mortality [7]. Care for individuals with traumatic stress symptomatology should thus entail attention to both behavioral and physical health status. Moreover, although therapies based on re-exposure to trauma have been designated as evidence-based treatments [8], there is concern about high dropout rates associated with this approach [9], as well as a lack of impact on sleep disturbances [10]. In addition, despite the undeniable suffering of American veterans of the Vietnam War, which contributed to recognition of PTSD as a Diagnostic and Statistical Manual of Mental Disorders (DSM) clinical disorder, there are also concerns that the medicalization of combat-related stress can lead to unhelpful consequences related to stigmatization [11, 12].

To improve modeling of PTSD (or post-traumatic stress, PTS, more broadly), a promising starting point may be the recognition of the brain as the organ of central command. The physiological paradigm of allostasis (stability through change) notes that the brain directs set points for biological function on the basis of perceived needs for organism-level survival [13, 14]. Stated another way, it is the brain that lets environmental stressors “get under the skin” [15]. Within the allostasis paradigm, the sympathetic and parasympathetic divisions of the autonomic nervous system serve as principal pathways for bidirectional communication and coordination between the brain and peripheral physiology. For example, in the setting of an acute threat, the brain orchestrates these divisions to affect an instantaneous redirection of metabolic resources away from the anabolic process of digestion toward the catabolic process of mobilization. Allostasis thus fully predicts that over time, exposure to traumatic stresses is likely to entail both behavioral and physical health disturbances. For therapeutics, allostasis points to the potential for multi-system symptom reduction through interventions that are expressly designed to facilitate the brain’s role as the organ of central command [16]. Moreover, through its emphasis on context-dependent heightened stress responsivity, the allostasis paradigm supports destigmatization of PTS-related phenomenology. There is no single normal mode of brain function; rather, there are ranges for set points [17] that are subject to modification based on neuroplasticity. The functional set point for a given capacity—vigilance, for example—may or may not be adaptive (“pathological”), depending on the environment.

Given its crucial and distributed role for connecting the brain, body, and behavior, the autonomic nervous system merits special attention in the allostasis paradigm. Autonomic regulation of the cardiovascular system can be characterized by measuring heart rate variability (HRV) and baroreflex sensitivity (BRS). HRV and BRS indicate the physiological capacity to produce dynamically varied responses to the changing needs of an environment, and prospective studies show that decreased HRV is a risk factor for incident cardiovascular disease [18] and all-cause mortality [19]. Furthermore, depressed HRV is seen generally across behavioral disorders [20], specifically in military personnel and veterans with diagnosed PTSD [21–25], and as a pre-deployment predictor of new post-deployment PTSD diagnoses or symptom severity [26, 27].

An open question in studies of PTS and autonomic dysregulation pertains to how or why HRV is depressed in persons who have been exposed to traumatic stress. An epigenetic and neural oscillatory explanation is provided by the bihemispheric autonomic model (BHAM) [28]. The BHAM begins by recognizing that there is hemispheric lateralization in the management of the autonomic nervous system, with the right and left sides having primary responsibility for the sympathetic and parasympathetic divisions, respectively. The BHAM proposes that trauma-related sympathetic hyperarousal may be an expression of maladaptive right temporal lobe activity, whereas the avoidant and dissociative features of the traumatic stress response may be indicators of a parasympathetic “freeze” response that is significantly driven by the left temporal lobe. An implication of the BHAM is that a successful allostatic (i.e., brain-based, top-down) intervention may facilitate the reduction of symptom clusters associated with autonomic disturbances through the mitigation of maladaptive asymmetries.

The objective of this report is to document changes in self-reported symptoms, autonomic, and functional measures after use of a closed-loop acoustic stimulation neurotechnology by a series of active duty service members or recent veterans with military-related symptoms of traumatic stress. The neurotechnology strategy (HIRREM®; Brain State Technologies, Scottsdale, Arizona) is aligned with the allostasis paradigm through its brain-focused strategy for the auto-calibration of neural oscillations [16]; through its attention to hemispheric asymmetry, it is also designed to leverage insights described in the BHAM. We hypothesized that use of the neurotechnology would be followed by reductions in self-reported PTSD-related symptomatology as well as improvements in HRV and BRS. For a subset of the initial subjects, we also conducted exploratory analysis of changes in biochemical and epigenetic markers related to stress or inflammation. Changes in brain network connectivity demonstrated through analysis of whole brain, resting-state magnetic resonance imaging (MRI) evaluations are reported elsewhere [29, 30].

This report documents outcomes for a series of active-duty military service members and veterans with symptoms of military-related PTS, predominantly special operations warfighters or support personnel, who participated in the use of a closed-loop, allostatic, acoustic stimulation neurotechnology. On average, there were robust and durable reductions in the symptoms of PTS, insomnia, depressive mood, and anxiety. At the first post-intervention data collection, there were marked increases in HRV and BRS, and there were trends for improvements in physical functional performance and markers of stress or inflammation. There were no adverse events, and all participants completed their course of intervention sessions along with all follow-up data collections.

The present findings are consistent with outcomes reported after the use of closed-loop allostatic neurotechnology by civilians with self-reported PTS, who were mostly women with non-military trauma [45] or athletes with sports-related concussions [46]. Together, these studies concur with the idea that real-time monitoring and modulation of brain activity (closed-loop strategies) can support advanced remediation of neurological and psychiatric disorders, sleep enhancement and, potentially, performance optimization [47–50]. The authors are aware of only two other studies that have reported quantitative HRV effects after the use of any type of intervention by military personnel or veterans with PTSD. HRV decreased with the use of escitalopram [51] and showed no change after the use of mindfulness meditation [52].

Limitations to the generalizability of these findings include the modest sample size and the absence of a control group. Improvements in reaction testing may have been related to practice effects, which have been documented with the drop-stick procedure [53]. The use of numerous types of psychoactive medications, as well as alcohol or recreational drugs, was an exclusion to enrollment, and it is unknown how these co-interventions or influences might affect the outcomes of future studies. Although the improvements demonstrated may have been influenced by subjective expectations, positive social interactions with study personnel, or other “placebo” components, it seems unlikely that these non-specific factors were the fundamental drivers. HRV is an objective physiological measure, and meta-analysis has found that placebo effects in clinical trials tend to be limited to continuous subjective outcomes [54]. In addition, the durability of the symptom score improvements appears inconsistent with the interpretation that changes were due to statistical randomness, regression to the mean, or natural history of disease. Given the protracted duration of symptoms, and numerous other therapies that had been tried previously, spontaneous recovery over a few weeks to months would also be considered unlikely.

Various aspects of the intervention point to its promise as an innovative modality for the remediation of the effects of traumatic stress for active-duty military service members, veterans, and other populations. The reductions in insomnia symptoms are noteworthy given the intractability of sleep complaints in PTSD [55]. Sequelae of TBI can complicate PTSD-specific interventions [56], yet the numerous TBIs reported by the subjects did not appear to hinder their participation, and there was a reduction in TBI-specific symptomatology. The noninvasive methodology is encouraging with respect to safety, feasibility, and scalability considerations. Moreover, support from the US Army Research Office [57] has allowed the development of a self-use configuration of the core technology (Braintellect®-2; Brain State Technologies, Scottsdale, Arizona), with sensor locations at prefrontal and temporal scalp locations only. This device may further facilitate the development of population-based strategies that leverage precision-guided, allostatic neurotechnology, and its standalone use has been proposed as a potential strategy to enable the primary prevention of PTSD through the optimization of sleep quality [58].

A series of active-duty military personnel and veterans with symptoms of military-related traumatic stress used a closed-loop acoustic stimulation methodology to support the auto-calibration of neural oscillations. Subsequently, participants showed robust improvements in autonomic cardiovascular regulation and durable reductions in PTS-related symptomatology, including insomnia, with no adverse events or dropouts. This study is the first to show an increase in both HRV and BRS, which are significant indicators of the capacity of the brain to exert dynamic and adaptive regulation of peripheral physiology, following an intervention provided to military personnel or veterans with PTS. The composite intervention profile points to the promise of allostatic neurotechnology for system-level PTS management. Ongoing investigations are strongly warranted.