Bilateral brainstem activation by thermal stimulation of the face in healthy volunteers

Abstract

Contralateral sensory deficits in Wallenberg's lateral medullary syndrome suggest bilateral processing of trigeminal afferent input in the human brainstem. On the basis of experiments in rodents and clinical data, the present study addresses the hypothesis of bilateral projection of facial nociceptive input onto the spinal trigeminal nucleus (STN) in healthy humans. Nociceptive processing in the brainstem was investigated by functional magnetic resonance imaging (fMRI) in 18 healthy volunteers. Heat stimuli (39, 43, 46 degrees C) were applied by a Peltier type thermode to the left forehead (V1) and the left mental region (V3). Analyses of fMRI data were performed with SPM2 and BrainVoyager software. A region-of-interest approach analyzed local activation in the STN. Heat evoked significant bilateral activation in the STN (P < 0.01, T > 2.8). Contralateral activation was more frequent during stimulation of the V1 than of the V3 region. Whereas activation by V1 stimulation was located in caudal STN, V3 stimulation induced activity in more rostral parts of the STN. Functional MRI data in humans suggest bilateral brainstem activation when heat is applied to the face. Contralateral brainstem activity is more pronounced by stimulation of V1 as compared to V3. The results indicate similar nociceptive processing in humans and rodents and may explain clinical findings.

Temporal Sequencing of Brain Activations During Naturally Occurring Thermoregulatory Events

“…Recent evidence suggests that the application of thermal stimulation results in responses in several regions we assessed, including the brain stem ( particularly regions closer to the spinal cord (Kubina et al 2010;Summers et al 2010). Thus, application of noxious thermal stimulation (as opposed to innocuous stimulation) to the face or the hand generates a measurable difference in the fMRI response in regions of the brainstem and the spinal cord.…”

Simultaneous cortical, subcortical, and brainstem mapping of sensory activation

“…While a limited number of studies have probed subcortical activity during non-painful sensory stimuli, these challenges have so far precluded a full systems study of the cortical, subcortical, and brainstem regions involved in sensory processing. Existing techniques to address the challenges of brainstem fMRI include using a restricted field of view (DaSilva et al 2002; Pattinson, Mitsis, et al 2009; Kubina et al 2010; Faull et al 2015; Matt et al 2019), moving from 3T to 7T MRI (Hahn et al 2013; Faull et al 2015; Priovoulos et al 2018; Sclocco et al 2018), and implementing physiological denoising strategies like RETROICOR (Glover et al 2000; Limbrick-Oldfield et al 2012; Brooks et al 2013; Sclocco et al 2020; Oliva et al 2021). While restricted field-of-view studies can enable greater spatial resolution, they limit the scope of brain systems-level investigation.…”

In vivo correlates of thermoregulatory defense in humans: Temporal course of sub‐cortical and cortical responses assessed with fMRI

“…For example, during endogenous heat challenges, such as in menopausal hot flashes [Diwadkar et al, 2014], brain stem responses are closely associated with the onset of hot flashes. As such, interoceptive responses are general, resulting not only from endogenous thermal events such as hot flashes but also during the application of exogenously applied temperature sensation, including heat [Davis et al, 1998;Kubina et al, 2010;Kwan et al, 2000] and cold [Kwan et al, 2000;McAllen et al, 2006]. These latter interoceptive responses appear to reflect neural responses to changes in physiological states [Craig, 2002].…”

“…These latter interoceptive responses appear to reflect neural responses to changes in physiological states [Craig, 2002]. As such, interoceptive responses are general, resulting not only from endogenous thermal events such as hot flashes but also during the application of exogenously applied temperature sensation, including heat [Davis et al, 1998;Kubina et al, 2010;Kwan et al, 2000] and cold [Kwan et al, 2000;McAllen et al, 2006]. Processes associated with whole body skin cooling engage thermoregulatory defense mechanisms, associated with both responses to cooling and responses to (relatively) prolonged exposure to cold; however, these have rarely been studied with fMRI.…”