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Abstract
Disorders of consciousness (DoC) are the hallmark of severe acquired brain injuries characterized by abnormal activity in important brain areas and disruption within and between brain networks. As DoC's therapeutic arsenal is limited, new potential therapies such as transcutaneous auricular vagal nerve stimulation (taVNS) have recently been explored. The potential of taVNS in the process of consciousness recovery has been highlighted in recent studies with DoC patients. However, it is not clear how taVNS plays a role in the recovery of consciousness. In this article, we first describe the neural correlates of consciousness, the vagus nerve anatomy and functions, along with the results of functional magnetic resonance imaging studies using taVNS. Based on consciousness recovery and taVNS mechanisms, we propose the Vagal Cortical Pathways model. This model highlights four consecutive pathways (A. Lower brainstem activation, B. Upper brainstem activation, C. Norepinephrine pathway, and D. Serotonin pathway) likely to have an impact on patients with a brain injury and DoC. Additionally, we suggest six different mechanisms of action: (1) Activation of the ascending reticular activating system; (2) Activation of the thalamus; (3) Re-establishment of the cortico-striatal-thalamic-cortical loop; (4) Promotion of negative connectivity between external and default mode networks by the activation of the salience network; (5) Increase in activity and connectivity within the external network through the norepinephrine pathway; and (6) Increase in activity within the default mode network through the serotonin pathway. This model aims to explain the potential therapeutic effects that taVNS has on brain activity in the process of consciousness recovery.
Highlights
Acquired brain injury is an umbrella term for any brain damage that occurs after birth and that is not hereditary, congenital, degenerative, or induced by birth trauma [1]
Advanced technologies and analytic approaches, such as high-density electroencephalography (EEG), functional magnetic resonance imaging, and positron emission tomography (PET), represent tools used to measure the level of consciousness in patients with disorders of consciousness (DoC) [7], but none of them are able to ascertain the level of consciousness
To challenge the Vagal Cortical Pathways model, we looked at the transcutaneous auricular vagal nerve stimulation (taVNS) functional magnetic resonance imaging (fMRI) studies mentioned in Table 1 and used their results to corroborate each of the four pathways of the proposed model
Summary
Acquired brain injury is an umbrella term for any brain damage that occurs after birth and that is not hereditary, congenital, degenerative, or induced by birth trauma [1]. The posterior cingulate cortex (PCC) is located in the medial part of the inferior parietal lobe and lies within the posteromedial cortex, which includes the precuneal and retrosplenial cortices [28] This group of structures has been reported as the most metabolically active measured with fluorodeoxyglucose (FDG) PET-scan [29] during resting state (i.e., not performing any task) in healthy persons. The fMRI results revealed higher signals in the nucleus of the tractus solitarius and the locus coeruleus and confirmed that the first two stimulation sites were associated to the vagus nerve This activation pattern was not demonstrated after the stimulation of the infero-posterior wall neither at the ear lobe [87]. Frangos et al [82] Yakunina et al [83] Badran et al [84] Sclocco et al [85] Sclocco et al [86]
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