Posttraumatic stress disorder (PTSD) is an anxiety disorder that can develop after trauma and is characterized by experiencing intrusive memories, flashbacks, hypervigilance, nightmares, social avoidance, and social dysfunctions (144). It has a lifetime prevalence of 8.3% using the definition for DSM-5 (145). The symptoms of PTSD can be classified into four clusters: intrusion symptoms, avoidance behavior, cognitive and affective alterations, and changes in arousal and reactivity (146). People who suffer from PTSD tend to live as though under a permanent threat. They exhibit fight and flight behavior or a perpetual behavioral shutdown and dissociation, with no possibility of reaching a calm state and developing positive social interactions. Over time, these maladaptive autonomic responses lead to the development of an increased risk for psychiatric comorbidities, such as addiction and cardiovascular diseases (147).
Posttraumatic stress disorder symptoms are partly mediated by the vagus nerve. There is evidence for diminished parasympathetic activity in PTSD, indicating an autonomic imbalance (148). The vagal control of heart rate via the myelinated vagal fibers varies with respiration. Thus, the vagal influence on the heart can be evaluated by quantifying the amplitude of rhythmic fluctuations in heart rate—respiratory sinus arrhythmia (RSA). A recent study has demonstrated a reduced resting RSA in veterans with PTSD (149). Further, patients with PTSD have been shown to have lower high-frequency heart rate variability than healthy controls (150).
Continuous expression of emotional symptoms to conditioned cues despite the absence of additional trauma is one of the many hallmarks of PTSD. Behavioral therapies employed to treat PTSD rely on helping the patient to gradually reduce her/his fear of this cue over time. Thus, exposure-based therapies are considered the gold standard of treatment for PTSD (151). The goal of exposure-based therapies is to replace conditioned associations of the trauma with new, more appropriate associations which compete with fearful associations. Studies have shown that PTSD patients exhibit deficient extinction recall along with dysfunctional activation of the fear extinction network (152, 153). This network includes the vmPFC, the amygdala, and the hippocampus. It is highly important for the contextual retrieval of fear memories after extinction (154).
Posttraumatic stress disorder symptom severity and structural abnormalities in the anterior hippocampus and centromedial amygdala have been associated (155). There is evidence for increased activation of the amygdala in humans and rodents during conditioned fear (156). The amygdala and the vmPFC have reciprocal synaptic connections (157). Indeed, under conditions of uncertainty and threat, the PFC can become hypoactive leading to a failure to inhibit overactivity of the amygdala with emergence of PTSD symptoms, such as hyperarousal and re-experiencing (158). Further, in response to stressful stimuli as fearful faces, patients with PTSD showed a higher activation of the basolateral amygdala during unconscious face processing compared to healthy controls as well as patients with panic disorder and generalized anxiety disorder (159).
The hippocampus is also a crucial component of the fear circuit and implicated in the pathophysiology of PTSD. Patients with PTSD show a reduced hippocampal volume that is associated with symptom severity (160). The hippocampus is a key structure in episodic memory and spatial context encoding. Hippocampal damage leads to deficits in context encoding in humans as well as rodents. The neural circuit consisting of the hippocampus, amygdala, and vmPFC is highly important for the contextual retrieval of fear memories after extinction (154). Impairment of hippocampal functioning, resulting dysfunctional context generalization in patients with PTSD, might cause patients to re-experience trauma-related symptoms (161).
VNS in PTSD
Vagus nerve stimulation has shown promise as therapeutic option in treatment-resistant anxiety disorders, including PTSD (8). Chronic VNS has been shown to reduce anxiety in rats (96) and improve scores on the Hamilton Anxiety Scale in patients suffering from treatment-resistant depression (8). When stimulated, the vagus nerve sends signals to the NTS (162) and the NTS sends direct projections to the amygdala and the hypothalamus. Further, VNS increases the release of NE in basolateral amygdala (163) as well as the hippocampus and cortex (93). NE infusion in the amygdala results in better extinction learning (164). Thus, VNS could be a good tool to increase extinction retention. For example, in rats, extinction paired with VNS treatment can lead to remission of fear and improvements in PTSD-like symptoms (151). Further, VNS paired with extinction learning facilitates the plasticity between the infralimbic medial prefrontal cortex and the basolateral complex of the amygdala to facilitate extinction of conditioned fear responses (165). Additionally, VNS may also enhance extinction by inhibiting activity of the sympathetic nervous system (119). It is possible that an immediate VNS-induced reduction in anxiety contributes to VNS-driven extinction by interfering with the sympathetic response to the CS, thus breaking the association of the CS with fear. However, there is need for randomized controlled trials to approve these observations.
One of the most consistent neurophysiological effects of VNS is decreasing the hippocampal activity, possibly through enhancement of GABAergic signaling (166). As described above, the hippocampus is a crucial component of the fear circuit, since it is a key structure in episodic memory and spatial context encoding. Decreased hippocampal activity after VNS has been reported in a number of other studies in other conditions such as depression (77, 167) or schizophrenia (168).
.Positive influence of meditation and yoga on PTSD
There is clinical evidence for the efficacy of mindfulness-based stress reduction (MBSR) in the treatment of PTSD (176–178). During MBSR, slow breathing and long exhalation phases lead to an increase in parasympathetic tone (179). In addition, clinical studies have demonstrated the effectiveness of yoga as a therapeutic intervention for PTSD and dissociation through a downregulation of the stress response (180–182). Yoga practices also decreased symptoms in PSTD after natural disasters (183, 184). Yoga-responsive anxiety disorders, including PTSD, go together with low HRV and low GABA activity (139). The interactions of the PFC, hippocampus, and amygdala in conjunction with inputs from the autonomous nervous system and GABA system provide a network through which yoga-based practices may decrease symptoms (185). There are indications that impaired extinction of conditioned fear in PTSD is associated with decreased vmPFC control over amygdala activity (157). PFC activation associated with increased parasympathetic activity during yoga could improve inhibitory control over the amygdala via PFC GABA projections, decreasing amygdala overactivity, and reducing PTSD symptoms.
Positive influence of neurofeedback on PTSD
Neurofeedback (NFB) positively influences PTSD by retraining the brain to modulate abnormal brainwave patterns, leading to significant reductions in symptoms like hyperarousal, anxiety, and intrusive memories. It enhances top-down emotional control and improves brain connectivity in regions like the amygdala and prefrontal cortex. NFB acts as a non-invasive, effective, and often long-lasting complement to traditional therapy.
Key Positive Influences and Mechanisms:
- Significant Symptom Reduction: Studies and meta-analyses confirm that NFB reduces core PTSD symptoms, with one study showing a high, 79.3% remission rate in NFB groups compared to 24.4% in control groups.
- Normalized Brain Activity: NFB helps normalize overactive brain regions associated with fear and trauma (e.g., the Salience Network) and strengthens the Default Mode Network, which is often dysfunctional in PTSD.
- Improved Emotional Regulation: By targeting specific brain regions, NFB helps patients better manage emotional triggers and reduces the intensity of flashbacks and nightmares.
- Reduced Hyperarousal: NFB effectively lowers excessive beta-wave activity associated with anxiety, hypervigilance, and insomnia.
- Targeting Deep Brain Structures: NFB is effective in reaching deeper, earlier-developing brain structures (like the limbic system) that are often challenging to address through verbal, top-down therapies.
- Complementary Treatment: NFB is safely used in conjunction with other treatments like EMDR therapy to enhance overall therapeutic outcomes.
These improvements often lead to better daily functioning, increased calmness, and enhanced cognitive control in both veterans and civilian populations with trauma.
This article is part of the Research Topic: Nutritional Psychiatry: How do Brain – Gut Interactions Work?
Sigrid Breit1† Aleksandra Kupferberg1† Gerhard Rogler2Gregor Hasler1* 1Division of Molecular Psychiatry, Translational Research Center, University Hospital of Psychiatry, University of Bern, Bern, Switzerland 2Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
This work was supported by the University of Bern. For full reference list see https://www.frontiersin.org/articles/10.3389/fpsyt.2018.00044/full The authors gratefully acknowledge Sarah Steinau for her contributions to this article.
Oksana Pueschel 