Noninvasive vagus nerve stimulation alters neural response and physiological autonomic tone to noxious thermal challenge.

The mechanisms by which noninvasive vagal nerve stimulation (nVNS) affect central and peripheral neural circuits that subserve pain and autonomic physiology are not clear, and thus remain an area of intense investigation. Effects of nVNS vs sham stimulation on subject responses to five noxious thermal stimuli (applied to left lower extremity), were measured in 30 healthy subjects (n = 15 sham and n = 15 nVNS), with fMRI and physiological galvanic skin response (GSR). With repeated noxious thermal stimuli a group × time analysis showed a significantly (p < .001) decreased response with nVNS in bilateral primary and secondary somatosensory cortices (SI and SII), left dorsoposterior insular cortex, bilateral paracentral lobule, bilateral medial dorsal thalamus, right anterior cingulate cortex, and right orbitofrontal cortex. A group × time × GSR analysis showed a significantly decreased response in the nVNS group (p < .0005) bilaterally in SI, lower and mid medullary brainstem, and inferior occipital cortex. Finally, nVNS treatment showed decreased activity in pronociceptive brainstem nuclei (e.g. the reticular nucleus and rostral ventromedial medulla) and key autonomic integration nuclei (e.g. the rostroventrolateral medulla, nucleus ambiguous, and dorsal motor nucleus of the vagus nerve). In aggregate, noninvasive vagal nerve stimulation reduced the physiological response to noxious thermal stimuli and impacted neural circuits important for pain processing and autonomic output

Following one's heart: cardiac rhythms gate central initiation of sympathetic reflexes

Central nervous processing of environmental stimuli requires integration of sensory information with ongoing autonomic control of cardiovascular function. Rhythmic feedback of cardiac and baroreceptor activity contributes dynamically to homeostatic autonomic control. We examined how the processing of brief somatosensory stimuli is altered across the cardiac cycle to evoke differential changes in bodily state. Using functional magnetic resonance imaging of brain and noninvasive beat-to-beat cardiovascular monitoring, we show that stimuli presented before and during early cardiac systole elicited differential changes in neural activity within amygdala, anterior insula and pons, and engendered different effects on blood pressure. Stimulation delivered during early systole inhibited blood pressure increases. Individual differences in heart rate variability predicted magnitude of differential cardiac timing responses within periaqueductal gray, amygdala and insula. Our findings highlight integration of somatosensory and phasic baroreceptor information at cortical, limbic and brainstem levels, with relevance to mechanisms underlying pain control, hypertension and anxiety

Beyond Patient Reported Pain: Perfusion Magnetic Resonance Imaging Demonstrates Reproducible Cerebral Representation of Ongoing Post-Surgical Pain

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Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee

These guidelines provide an up-date of previous IFCN report on "Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application" (Rossini et al., 1994). A new Committee, composed of international experts, some of whom were in the panel of the 1994 "Report", was selected to produce a current state-of-the-art review of non-invasive stimulation both for clinical application and research in neuroscience. Since 1994, the international scientific community has seen a rapid increase in non-invasive brain stimulation in studying cognition, brain-behavior relationship and pathophysiology of various neurologic and psychiatric disorders. New paradigms of stimulation and new techniques have been developed. Furthermore, a large number of studies and clinical trials have demonstrated potential therapeutic applications of non-invasive brain stimulation, especially for TMS. Recent guidelines can be found in the literature covering specific aspects of non-invasive brain stimulation, such as safety (Rossi et al., 2009), methodology (Groppa et al., 2012) and therapeutic applications (Lefaucheur et al., 2014). This up-dated review covers theoretical, physiological and practical aspects of non-invasive stimulation of brain, spinal cord, nerve roots and peripheral nerves in the light of more updated knowledge, and include some recent extensions and developments

Localization of pain-related brain activation: A meta-analysis of neuroimaging data

A meta-analysis of 140 neuroimaging studies was performed using the activation-likelihood-estimate (ALE) method to explore the location and extent of activation in the brain in response to noxious stimuli in healthy volunteers. The first analysis involved the creation of a likelihood map illustrating brain activation common across studies using noxious stimuli. The left thalamus, right anterior cingulate cortex (ACC), bilateral anterior insulae, and left dorsal posterior insula had the highest likelihood of being activated. The second analysis contrasted noxious cold with noxious heat stimulation and revealed higher likelihood of activation to noxious cold in the subgenual ACC and the amygdala. The third analysis assessed the implications of using either a warm stimulus or a resting baseline as the control condition to reveal activation attributed to noxious heat. Comparing noxious heat to warm stimulation led to peak ALE values that were restricted to cortical regions with known nociceptive input. The fourth analysis tested for a hemispheric dominance in pain processing and showed the importance of the right hemisphere, with the strongest ALE peaks and clusters found in the right insula and ACC. The fifth analysis compared noxious muscle with cutaneous stimuli and the former type was more likely to evoke activation in the posterior and anterior cingulate cortices, precuneus, dorsolateral prefrontal cortex, and cerebellum. In general, results indicate that some brain regions such as the thalamus, insula and ACC have a significant likelihood of activation regardless of the type of noxious stimuli, while other brain regions show a stimulus-specific likelihood of being activated. © 2011 Wiley Periodicals, Inc