The brain circuitry underlying the temporal evolution of nausea in humans.

Nausea is a universal human experience. It evolves slowly over time, and brain mechanisms underlying this evolution are not well understood. Our functional magnetic resonance imaging (fMRI) approach evaluated brain activity contributing to and arising from increasing motion sickness. Subjects rated transitions to increasing nausea, produced by visually induced vection within the fMRI environment. We evaluated parametrically increasing brain activity 1) precipitating increasing nausea and 2) following transition to stronger nausea. All subjects demonstrated visual stimulus-associated activation (P < 0.01) in primary and extrastriate visual cortices. In subjects experiencing motion sickness, increasing phasic activity preceding nausea was found in amygdala, putamen, and dorsal pons/locus ceruleus. Increasing sustained response following increased nausea was found in a broader network including insular, anterior cingulate, orbitofrontal, somatosensory and prefrontal cortices. Moreover, sustained anterior insula activation to strong nausea was correlated with midcingulate activation (r = 0.87), suggesting a closer linkage between these specific regions within the brain circuitry subserving nausea perception. Thus, while phasic activation in fear conditioning and noradrenergic brainstem regions precipitates transition to strong nausea, sustained activation following this transition occurs in a broader interoceptive, limbic, somatosensory, and cognitive network, reflecting the multiple dimensions of this aversive commonly occurring symptom.

Static and dynamic autonomic response with increasing nausea perception.

BACKGROUND: Nausea is a commonly occurring symptom typified by epigastric discomfort with urge to vomit. The relationship between autonomic nervous system (ANS) outflow and increasing nausea perception is not fully understood. METHODS: Our study employed a nauseogenic visual stimulus (horizontally translating stripes) while 17 female subjects freely rated transitions in nausea level and autonomic outflow was measured (heart rate, HR; heart rate variability, HRV; skin conductance response, SCR; respiratory rate). We also adopted a recent approach to continuous high-frequency (HF) HRV estimation to evaluate dynamic cardiovagal modulation. RESULTS: HR increased from baseline for all increasing nausea transitions, especially transition to strong nausea (15.0 +/- 11.4 bpm), but decreased (-6.6 +/- 4.6 bpm) once the visual stimulus ceased. SCR also increased for all increasing nausea transitions, especially transition to strong nausea (1.76 +/- 1.68 microS), but continued to increase (0.52 +/- 0.65 microS) once visual stimulation ceased. LF/HF HRV increased following transition to moderate (1.54 +/- 2.11 a.u.) and strong (2.57 +/- 3.49 a.u.) nausea, suggesting a sympathetic shift in sympathovagal balance. However, dynamic HF HRV suggested that bursts of cardiovagal modulation precede transitions to higher nausea, perhaps influencing subjects to rate higher levels of nausea. No significant change in respiration rate was found. CONCLUSIONS: Our results suggest that increasing nausea perception is associated with both increased sympathetic and decreased parasympathetic ANS modulation. These findings corroborate past ANS studies of nausea, applying perception-linked analyses and dynamic estimation of cardiovagal modulation in response to nausea.

Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity.

OBJECTIVE: Fibromyalgia (FM) is considered to be the prototypical central chronic pain syndrome and is associated with widespread pain that fluctuates spontaneously. Multiple studies have demonstrated altered brain activity in these patients. The objective of this study was to investigate the degree of connectivity between multiple brain networks in patients with FM, as well as how activity in these networks correlates with the level of spontaneous pain. METHODS: Resting-state functional magnetic resonance imaging (FMRI) data from 18 patients with FM and 18 age-matched healthy control subjects were analyzed using dual-regression independent components analysis, which is a data-driven approach for the identification of independent brain networks. Intrinsic, or resting-state, connectivity was evaluated in multiple brain networks: the default mode network (DMN), the executive attention network (EAN), and the medial visual network (MVN), with the MVN serving as a negative control. Spontaneous pain levels were also analyzed for covariance with intrinsic connectivity. RESULTS: Patients with FM had greater connectivity within the DMN and right EAN (corrected P [P(corr)] < 0.05 versus controls), and greater connectivity between the DMN and the insular cortex, which is a brain region known to process evoked pain. Furthermore, greater intensity of spontaneous pain at the time of the FMRI scan correlated with greater intrinsic connectivity between the insula and both the DMN and right EAN (P(corr) < 0.05). CONCLUSION: These findings indicate that resting brain activity within multiple networks is associated with spontaneous clinical pain in patients with FM. These findings may also have broader implications for how subjective experiences such as pain arise from a complex interplay among multiple brain networks.

Monitoring acupuncture effects on human brain by FMRI.

Functional MRI is used to study the effects of acupuncture on the BOLD response and the functional connectivity of the human brain. Results demonstrate that acupuncture mobilizes a limbic-paralimbic-neocortical network and its anti-correlated sensorimotor/paralimbic network at multiple levels of the brain and that the hemodynamic response is influenced by the psychophysical response. Physiological monitoring may be performed to explore the peripheral response of the autonomic nerve function. This video describes the studies performed at LI4 (hegu), ST36 (zusanli) and LV3 (taichong), classical acupoints that are commonly used for modulatory and pain-reducing actions. Some issues that require attention in the applications of fMRI to acupuncture investigation are noted.

Brain encoding of acupuncture sensation--coupling on-line rating with fMRI.

Acupuncture-induced sensations have historically been associated with clinical efficacy. These sensations are atypical, arising from sub-dermal receptors, and their neural encoding is not well known. In this fMRI study, subjects were stimulated at acupoint PC-6, while rating sensation with a custom-built, MR-compatible potentiometer. Separate runs included real (ACUP) and sham (SHAM) acupuncture, the latter characterized by non-insertive, cutaneous stimulation. FMRI data analysis was guided by the on-line rating timeseries, thereby localizing brain correlates of acupuncture sensation. Sensation ratings correlated with stimulation more (p<0.001) for SHAM (r=0.63) than for ACUP (r=0.32). ACUP induced stronger and more varied sensations with significant persistence into no-stimulation blocks, leading to more run-time spent rating low and moderate sensations compared to SHAM. ACUP sensation correlated with activation in regions associated with sensorimotor (SII, insula) and cognitive (dorsomedial prefrontal cortex (dmPFC)) processing, and deactivation in default-mode network (DMN) regions (posterior cingulate, precuneus). Compared to SHAM, ACUP yielded greater activity in both anterior and posterior dmPFC and dlPFC. In contrast, SHAM produced greater activation in sensorimotor (SI, SII, insula) and greater deactivation in DMN regions. Thus, brain encoding of ACUP sensation (more persistent and varied, leading to increased cognitive load) demonstrated greater activity in both cognitive/evaluative (posterior dmPFC) and emotional/interoceptive (anterior dmPFC) cortical regions. Increased cognitive load and dmPFC activity may be a salient component of acupuncture analgesia--sensations focus attention and accentuate bodily awareness, contributing to enhanced top-down modulation of any nociceptive afference and central pain networks. Hence, acupuncture may function as a somatosensory-guided mind-body therapy.