Brain correlates of phasic autonomic response to acupuncture stimulation: An event‐related fMRI study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100160/1/hbm22091.pd

Differences in cortical response to acupressure and electroacupuncture stimuli

<p>Abstract</p> <p>Background</p> <p>FMRI studies focus on sub-cortical effects of acupuncture stimuli. The purpose of this study was to assess changes in primary somatosensory (S1) activity over the course of different types of acupuncture stimulation. We used whole head magnetoencephalography (MEG) to map S1 brain response during 15 minutes of electroacupuncture (EA) and acupressure (AP). We further assessed how brain response changed during the course of stimulation.</p> <p>Results</p> <p>Evoked brain response to EA differed from AP in its temporal dynamics by showing clear contralateral M20/M30 peaks while the latter demonstrated temporal dispersion. Both EA and AP demonstrated significantly decreased response amplitudes following five minutes of stimulation. However, the latency of these decreases were earlier in EA (~30 ms post-stimulus) than AP (> 100 ms). Time-frequency responses demonstrated early onset, event related synchronization (ERS), within the gamma band at ~70-130 ms and the theta band at ~50-200 ms post-stimulus. A prolonged event related desynchronization (ERD) of alpha and beta power occurred at ~100-300 ms post-stimulus. There was decreased beta ERD at ~100-300 ms over the course of EA, but not AP.</p> <p>Conclusion</p> <p>Both EA and AP demonstrated conditioning of SI response. In conjunction with their subcortical effects on endogenous pain regulation, these therapies show potential for affecting S1 processing and possibly altering maladaptive neuroplasticity. Thus, further investigation in neuropathic populations is needed.</p

Isolated and Combined Effects of Electroacupuncture and Meditation in Reducing Experimentally Induced Ischemic Pain: A Pilot Study

Acupuncture and meditation are promising treatment options for clinical pain. However, studies investigating the effects of these methods on experimental pain conditions are equivocal. Here, the effects of electroacupuncture (EA) and meditation on the submaximum effort tourniquet technique (SETT), a well-established, opiate-sensitive pain paradigm in experimental placebo research were studied. Ten experienced meditators (6 male subjects) and 13 nonmeditators (6 male subjects) were subjected to SETT (250 mmHG) on one baseline (SETT only) and two treatment days (additional EA contralaterally to the SETT, either at the leg on ST36 and LV3 or at the arm on LI4 and LI10 in randomized order). Numeric Rating Scale (NRS) ratings (scale 0–10) were recorded every 3 min. During baseline, meditation induced significantly greater pain tolerance in meditators when compared with the control group. Both the EA conditions significantly increased pain tolerance and reduced pain ratings in controls. Furthermore, EA diminished the group difference in pain sensitivity, indicating that meditators had no additional benefit from acupuncture. The data suggest that EA as a presumable bottom-up process may be as effective as meditation in controlling experimental SETT pain. However, no combined effect of both the techniques could be observed

Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Development, Safety, Parametric Optimization, and Neurophysiological Effects

Cervically implanted vagus nerve stimulation (VNS) is a FDA-approved treatment for epilepsy and major depressive disorder (MDD). Additionally, VNS is a reemerging area of interest, showing promise in numerous animal studies with significant translatable applications. The cost, surgical risk, and human translation difficulty makes noninvasive VNS a highly-desired alternative. We have developed a transcutaneous auricular vagus nerve stimulation (taVNS) system that electrically stimulates the auricular branch of the vagus nerve (ABVN). We aimed to answer the following questions in this body of work: 1) whether taVNS is safe and feasible 2) if taVNS stimulates the vagus system similarly to implanted VNS 3) if the neurobiological effect of taVNS is similar to implanted VNS. We measured physiological recordings in healthy adults during taVNS to determine whether taVNS has vagus-mediated effects. In our first trial (n=15), we explored the physiological effects of 9 various stimulation parameter combinations (various pulse widths and frequencies) as a broad search of the physiological effect. A second, follow up trial was conducted (n=20) to determine the best candidate parameter that optimally activates the parasympathetic nervous system. Lastly, we developed and conducted a novel concurrent taVNS/fMRI trial (n=17) to determine the neurobiological effect of taVNS and its afferent targets. All three trials consisted of 2 visits each, in a randomized, controlled, crossover design in which taVNS was delivered to either the left tragus (active) or earlobe (control). The first physiological trial revealed relevant, immediate heart rate decreases during taVNS followed by a sympathetic rebound upon termination of stimulation. Of the nine parameters tested, two had the largest effect on heart rate (500µs, 10Hz; 500µs, 25Hz). These two parameters were tested in the follow-up trial, which demonstrated that both parameters decrease heart rate, with 500µs 10Hz having the largest physiologic effect. Lastly, findings from the taVNS/fMRI trial demonstrate the neurobiological effect of taVNS mimics that of cervically implanted VNS and targets several cortical and subcortical vagus afferent pathway targets. taVNS in our paradigms was feasible, safe, and demonstrated neurobiological effects that are similar to implantable VNS. Future trials should conduct parametric optimization using the taVNS/fMRI protocol as it reliably targets vagus nerve afferents as well as further explore optimizing taVNS as a possible therapeutic and research tool

The Catechol-O-Methyltransferase (COMT) val158met Polymorphism Affects Brain Responses to Repeated Painful Stimuli

Despite the explosion of interest in the genetic underpinnings of individual differences in pain sensitivity, conflicting findings have emerged for most of the identified "pain genes". Perhaps the prime example of this inconsistency is represented by catechol-O-methyltransferase (COMT), as its substantial association to pain sensitivity has been reported in various studies, but rejected in several others. In line with findings from behavioral studies, we hypothesized that the effect of COMT on pain processing would become apparent only when the pain system was adequately challenged (i.e., after repeated pain stimulation). In the present study, we used functional Magnetic Resonance Imaging (fMRI) to investigate the brain response to heat pain stimuli in 54 subjects genotyped for the common COMT val158met polymorphism (val/val = n 22, val/met = n 20, met/met = n 12). Met/met subjects exhibited stronger pain-related fMRI signals than val/val in several brain structures, including the periaqueductal gray matter, lingual gyrus, cerebellum, hippocampal formation and precuneus. These effects were observed only for high intensity pain stimuli after repeated administration. In spite of our relatively small sample size, our results suggest that COMT appears to affect pain processing. Our data demonstrate that the effect of COMT on pain processing can be detected in presence of 1) a sufficiently robust challenge to the pain system to detect a genotype effect, and/or 2) the recruitment of pain-dampening compensatory mechanisms by the putatively more pain sensitive met homozygotes. These findings may help explain the inconsistencies in reported findings of the impact of COMT in pain regulation.United States. National Institutes of Health (R01AT005280)United States. National Institutes of Health (R21AT00949)United States. National Institutes of Health (KO1AT003883)United States. National Institutes of Health (R21AT004497)National Center for Complementary and Alternative Medicine (U.S.) (PO1-AT002048)United States. National Institutes of Health (M01-RR-01066)United States. National Institutes of Health (UL1 RR025758-01)United States. National Institutes of Health (P41RR14075)United States. National Institutes of Health (DE-FG03-99ER62764)Swedish Society for Medical Researc

Differences in cortical response to acupressure and electroacupuncture stimuli

Background FMRI studies focus on sub-cortical effects of acupuncture stimuli. The purpose of this study was to assess changes in primary somatosensory (S1) activity over the course of different types of acupuncture stimulation. We used whole head magnetoencephalography (MEG) to map S1 brain response during 15 minutes of electroacupuncture (EA) and acupressure (AP). We further assessed how brain response changed during the course of stimulation. Results Evoked brain response to EA differed from AP in its temporal dynamics by showing clear contralateral M20/M30 peaks while the latter demonstrated temporal dispersion. Both EA and AP demonstrated significantly decreased response amplitudes following five minutes of stimulation. However, the latency of these decreases were earlier in EA (~30 ms post-stimulus) than AP (> 100 ms). Time-frequency responses demonstrated early onset, event related synchronization (ERS), within the gamma band at ~70-130 ms and the theta band at ~50-200 ms post-stimulus. A prolonged event related desynchronization (ERD) of alpha and beta power occurred at ~100-300 ms post-stimulus. There was decreased beta ERD at ~100-300 ms over the course of EA, but not AP. Conclusion Both EA and AP demonstrated conditioning of SI response. In conjunction with their subcortical effects on endogenous pain regulation, these therapies show potential for affecting S1 processing and possibly altering maladaptive neuroplasticity. Thus, further investigation in neuropathic populations is needed

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 runtime 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