Medullary projections to the vagus nerve and posterolateral hypothalamus

Hardy, Sandro

doi:10.1002/ar.1092420215

Cited by 5 publications

(5 citation statements)

References 34 publications

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“…Exposure to traumatic events can produce strongly encoded intrusive memories as well as lasting changes in neurobiology, brain circuits involved in the stress response, and symptoms of PTSD ( Bremner and Pearce, 2016 ; Merz et al., 2016 ). Projections of the vagus through the nucleus tractus solitarius (NTS) extend to the locus coeruleus and hypothalamus, key areas involved in sympathetic hyperarousal in PTSD, as well as brain areas like the amygdala that are involved in the fear response and the medial prefrontal cortex / anterior cingulate, which is involved in both fear extinction and modulation of peripheral neurohormonal responses to stress ( Hardy, 1995 ). tcVNS likely travels through these central pathways to effect changes in peripheral inflammation.…”

Section: Discussionmentioning

confidence: 99%

Transcutaneous vagal nerve stimulation blocks stress-induced activation of Interleukin-6 and interferon-γ in posttraumatic stress disorder: A double-blind, randomized, sham-controlled trial

Bremner

Gurel

Jiao

et al. 2020

Brain, Behavior, & Immunity - Health

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Posttraumatic stress disorder (PTSD) is a highly disabling condition associated with alterations in multiple neurobiological systems, including increases in inflammatory function. Vagus nerve stimulation (VNS) decreases inflammation, however few studies have examined the effects of non-invasive VNS on physiology in human subjects, and no studies in patients with PTSD. The purpose of this study was to assess the effects of transcutaneous cervical VNS (tcVNS) on inflammatory responses to stress. Thirty subjects with a history of exposure to traumatic stress with (N = 10) and without (N = 20) PTSD underwent exposure to stressful tasks immediately followed by active or sham tcVNS and measurement of multiple biomarkers of inflammation (interleukin-(IL)-6, IL-2, IL-1β, Tumor Necrosis Factor alpha (TNFα) and Interferon gamma (IFNγ) over multiple time points. Stressful tasks included exposure to personalized scripts of traumatic events on day 1, and public speech and mental arithmetic (Mental Stress) tasks on days 2 and 3. Traumatic scripts were associated with a pattern of subjective anger measured with Visual Analogue Scales and increased IL-6 and IFNγ in PTSD patients that was blocked by tcVNS (p < .05). Traumatic stress had minimal effects on these biomarkers in non-PTSD subjects and there was no difference between tcVNS or sham. No significant differences were seen between groups in IL-2, IL-1β, or TNFα. These results demonstrate that tcVNS blocks behavioral and inflammatory responses to stress reminders in PTSD.

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Section: Discussionmentioning

confidence: 99%

Transcutaneous vagal nerve stimulation blocks stress-induced activation of Interleukin-6 and interferon-γ in posttraumatic stress disorder: A double-blind, randomized, sham-controlled trial

Bremner

Gurel

Jiao

et al. 2020

Brain, Behavior, & Immunity - Health

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“…The study also included Parkinson's disease patients with a wider range of disease durations, thus a comparison with the current results is challenging, as our cohort was more uniform in that respect. It is noteworthy however, that while the medulla oblongata has projections to the hypothalamus [9,36], hypothalamic outputs to this structure have also been identified [9,37]. Thus, a possibility that remains to be tested in future longitudinal studies is that diffusivity alterations in the medulla oblongata and the hypothalamus emerge at different disease stages [38].…”

Section: Discussionmentioning

confidence: 99%

Altered hypothalamic diffusivity in Parkinsonian autonomic dysfunction

Rousseau

Sklerov

Browner

et al. 2019

Preprint

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The pathophysiological basis of autonomic symptoms in Parkinson's disease remains incompletely understood. The hypothalamus plays a key regulatory role in autonomic function and has been shown to be affected in Parkinson's disease. Here, using diffusion magnetic resonance imaging, we investigated whether microstructural properties of the hypothalamus differ in Parkinson's disease patients with high compared to low autonomic symptom burden.Parkinson's disease patients with low (n=25) and high (n=25) autonomic symptom burden were identified from a larger pool, based on scores from a questionnaire assessing autonomic symptoms in Parkinson's disease (SCOPA-AUT). In each patient, we first segmented the hypothalamus manually, based on anatomical landmarks. Diffusivity measures were then extracted from the hypothalamus. Diffusivity measures calculated in the brainstem and the putamen were used to assess the specificity of the results.Relative to patients with low autonomic symptom burden, patients with high burden showed increased mean, axial, and radial diffusivity in the hypothalamus. In contrast, we did not find significant group differences in any of these measures extracted from the brainstem or the putamen.These results reveal consistent differences in the microstructural properties of the hypothalamus between patients with low and high autonomic symptom burden. Hypothalamic diffusivity properties can thus potentially be used as an imaging marker to assist in the identification of therapeutic targets for autonomic dysfunction in Parkinson's disease.

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“…Mostly afferent projections of myelinated A fibers of the vagus, relay sensory activity of the visceral organs to the brain through the Nucleus Tractus Solitarius (NTS) in the medulla oblongata. Efferent branches of mostly unmyelinated C fibers of the vagus nerve modulate autonomic and inflammatory function [152] through peripheral anti-sympathetic, pro-parasympathetic, and anti-inflammatory effects [185][186][187]. These effects may benefit patients with OUD [147,188].…”

Section: Physiological Correlates Of Vagal Nerve Stimulationmentioning

confidence: 99%

“…The effects of nVNS, however, are likely mediated through the brain [189]. Projections of the vagus to the brain through the Nucleus Tractus Solitarius (NTS) extend to the locus ceoruleus and hypothalamus [187], key areas involved in sympathetic hyperarousal during opioid withdrawal, as well as to brain areas such as the amygdala and anterior cingulate that mediate emotion and anxiety [187]. Afferent vagal nerve fibers travel through the carotid sheath in the neck (cervical) just medial to the sternocleidomastoid muscle [190] as well as in the ear (auricular), and devices have been developed to non-invasively stimulate the vagus nerve at either branch.…”

Section: Physiological Correlates Of Vagal Nerve Stimulationmentioning

confidence: 99%

“…VNS has effects on a number of neurotransmitters that mediate symptoms of mental disorders including OUD [191]. The NTS has direct projections to the Locus Coeruleus (LC), which is located in the pons and is the major site of Norepinephrine (NE) cell bodies in the brain [187]. One of the primary effects of VNS on the brain is activation of norepinephrine in the LC.…”

Section: Physiological Correlates Of Vagal Nerve Stimulationmentioning

confidence: 99%

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Noninvasive Vagal Nerve Stimulation for Opioid Use Disorder

Douglas Bremner

2023

anndepressanxiety

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Background: Opioid Use Disorder (OUD) is an escalating public health problem with over 100,000 drug overdose-related deaths last year most of them related to opioid overdose, yet treatment options remain limited. Non-invasive Vagal Nerve Stimulation (nVNS) can be delivered via the ear or the neck and is a non-medication alternative to treatment of opioid withdrawal and OUD with potentially widespread applications. Methods: This paper reviews the neurobiology of opioid withdrawal and OUD and the emerging literature of nVNS for the application of OUD. Literature databases for Pubmed, Psychinfo, and Medline were queried for these topics for 1982-present. Results: Opioid withdrawal in the context of OUD is associated with activation of peripheral sympathetic and inflammatory systems as well as alterations in central brain regions including anterior cingulate, basal ganglia, and amygdala. NVNS has the potential to reduce sympathetic and inflammatory activation and counter the effects of opioid withdrawal in initial pilot studies. Preliminary studies show that it is potentially effective at acting through sympathetic pathways to reduce the effects of opioid withdrawal, in addition to reducing pain and distress. Conclusions: NVNS shows promise as a non-medication approach to OUD, both in terms of its known effect on neurobiology as well as pilot data showing a reduction in withdrawal symptoms as well as physiological manifestations of opioid withdrawal.

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Medullary projections to the vagus nerve and posterolateral hypothalamus

Cited by 5 publications

References 34 publications

Transcutaneous vagal nerve stimulation blocks stress-induced activation of Interleukin-6 and interferon-γ in posttraumatic stress disorder: A double-blind, randomized, sham-controlled trial

Transcutaneous vagal nerve stimulation blocks stress-induced activation of Interleukin-6 and interferon-γ in posttraumatic stress disorder: A double-blind, randomized, sham-controlled trial

Altered hypothalamic diffusivity in Parkinsonian autonomic dysfunction

Noninvasive Vagal Nerve Stimulation for Opioid Use Disorder

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