“The Wandering Nerve Linking Heart and Mind” – The Complementary Role of Transcutaneous Vagus Nerve Stimulation in Modulating Neuro-Cardiovascular and Cognitive Performance
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Abstract
The vagus nerve is the longest nerve in the human body, providing afferent information
about visceral sensation, integrity and somatic sensations to the CNS
via brainstem nuclei to subcortical and cortical structures. Its efferent arm influences
GI motility and secretion, cardiac ionotropy, chonotropy and heart rate variability,
blood pressure responses, bronchoconstriction and modulates gag and cough responses
via palatine and pharyngeal innervation. Vagus nerve stimulation has been utilized as
a successful treatment for intractable epilepsy and treatment-resistant depression,
and new non-invasive transcutaneous (t-VNS) devices offer equivalent therapeutic potential
as invasive devices without the surgical risks. t-VNS offers exciting potential as
a therapeutic intervention in cognitive decline and aging populations, classically
affected by reduced cerebral perfusion by modulating both limbic and frontal cortical
structures, regulating cerebral perfusion and improving parasympathetic modulation
of the cardiovascular system. In this narrative review we summarize the research to
date investigating the cognitive effects of VNS therapy, and its effects on neurocardiovascular
stability.
Healthy biological systems exhibit complex patterns of variability that can be described by mathematical chaos. Heart rate variability (HRV) consists of changes in the time intervals between consecutive heartbeats called interbeat intervals (IBIs). A healthy heart is not a metronome. The oscillations of a healthy heart are complex and constantly changing, which allow the cardiovascular system to rapidly adjust to sudden physical and psychological challenges to homeostasis. This article briefly reviews current perspectives on the mechanisms that generate 24 h, short-term (~5 min), and ultra-short-term (<5 min) HRV, the importance of HRV, and its implications for health and performance. The authors provide an overview of widely-used HRV time-domain, frequency-domain, and non-linear metrics. Time-domain indices quantify the amount of HRV observed during monitoring periods that may range from ~2 min to 24 h. Frequency-domain values calculate the absolute or relative amount of signal energy within component bands. Non-linear measurements quantify the unpredictability and complexity of a series of IBIs. The authors survey published normative values for clinical, healthy, and optimal performance populations. They stress the importance of measurement context, including recording period length, subject age, and sex, on baseline HRV values. They caution that 24 h, short-term, and ultra-short-term normative values are not interchangeable. They encourage professionals to supplement published norms with findings from their own specialized populations. Finally, the authors provide an overview of HRV assessment strategies for clinical and optimal performance interventions.
Background Given the projected trends in population ageing and population growth, the number of people with dementia is expected to increase. In addition, strong evidence has emerged supporting the importance of potentially modifiable risk factors for dementia. Characterising the distribution and magnitude of anticipated growth is crucial for public health planning and resource prioritisation. This study aimed to improve on previous forecasts of dementia prevalence by producing country-level estimates and incorporating information on selected risk factors. Methods We forecasted the prevalence of dementia attributable to the three dementia risk factors included in the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 (high body-mass index, high fasting plasma glucose, and smoking) from 2019 to 2050, using relative risks and forecasted risk factor prevalence to predict GBD risk-attributable prevalence in 2050 globally and by world region and country. Using linear regression models with education included as an additional predictor, we then forecasted the prevalence of dementia not attributable to GBD risks. To assess the relative contribution of future trends in GBD risk factors, education, population growth, and population ageing, we did a decomposition analysis. Findings We estimated that the number of people with dementia would increase from 57·4 (95% uncertainty interval 50·4–65·1) million cases globally in 2019 to 152·8 (130·8–175·9) million cases in 2050. Despite large increases in the projected number of people living with dementia, age-standardised both-sex prevalence remained stable between 2019 and 2050 (global percentage change of 0·1% [–7·5 to 10·8]). We estimated that there were more women with dementia than men with dementia globally in 2019 (female-to-male ratio of 1·69 [1·64–1·73]), and we expect this pattern to continue to 2050 (female-to-male ratio of 1·67 [1·52–1·85]). There was geographical heterogeneity in the projected increases across countries and regions, with the smallest percentage changes in the number of projected dementia cases in high-income Asia Pacific (53% [41–67]) and western Europe (74% [58–90]), and the largest in north Africa and the Middle East (367% [329–403]) and eastern sub-Saharan Africa (357% [323–395]). Projected increases in cases could largely be attributed to population growth and population ageing, although their relative importance varied by world region, with population growth contributing most to the increases in sub-Saharan Africa and population ageing contributing most to the increases in east Asia. Interpretation Growth in the number of individuals living with dementia underscores the need for public health planning efforts and policy to address the needs of this group. Country-level estimates can be used to inform national planning efforts and decisions. Multifaceted approaches, including scaling up interventions to address modifiable risk factors and investing in research on biological mechanisms, will be key in addressing the expected increases in the number of individuals affected by dementia. Funding Bill & Melinda Gates Foundation and Gates Ventures.
Historically, the locus coeruleus-norepinephrine (LC-NE) system has been implicated in arousal, but recent findings suggest that this system plays a more complex and specific role in the control of behavior than investigators previously thought. We review neurophysiological and modeling studies in monkey that support a new theory of LC-NE function. LC neurons exhibit two modes of activity, phasic and tonic. Phasic LC activation is driven by the outcome of task-related decision processes and is proposed to facilitate ensuing behaviors and to help optimize task performance (exploitation). When utility in the task wanes, LC neurons exhibit a tonic activity mode, associated with disengagement from the current task and a search for alternative behaviors (exploration). Monkey LC receives prominent, direct inputs from the anterior cingulate (ACC) and orbitofrontal cortices (OFC), both of which are thought to monitor task-related utility. We propose that these frontal areas produce the above patterns of LC activity to optimize utility on both short and long timescales.
[1]1Department of Age-Related Healthcare, Tallaght University Hospital , Dublin, Ireland
[2]2Department of Medical Gerontology, School of Medicine, Trinity College Dublin , Dublin, Ireland
[3]3Department of Medical Physics, St James’s Hospital , Dublin, Ireland
[4]4Department of Psychology, Maynooth University , Maynooth, Ireland
Author notes
Edited by: Knut Asbjorn Hestad, Hedmark University of Applied Sciences, Norway
Reviewed by: Lin Sørensen, University of Bergen, Norway; Guillaume T. Vallet, UMR
6024 Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), France
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