Chou-Ming Cheng

Neuronal correlates in the modulation of placebo analgesia in experimentally-induced esophageal pain: A 3T-fMRI study

&NA; Visceral pain/discomfort is the cardinal complaints and treatment targets for functional gastrointestinal disorders (FGID). However, effective treatment for such pain is limited and often associated with high placebo effects. The mechanisms of placebo effects in visceral pain are unclear. We used functional neuroimaging to study the central representations of the placebo effect and its anticipation during esophageal pain in healthy adults. Fourteen subjects were enrolled. Pain extent, psychophysical inventories [Pain Catastrophizing Scale (PAS), visual analogue scale (VAS) and short‐form McGill questionnaire], and brain activity upon placebo intervention and upon anticipation were assessed in response to esophageal balloon distension. Large reductions of pain extent, VAS rating, short‐form McGill questionnaire scores, and brain activity in the visceral pain matrix [thalamus, somatosensory cortices, insula, prefrontal cortex (PFC), anterior cingulate cortex] were observed upon placebo treatment. The aforementioned brain areas and the bilateral amygdala were significantly correlated with decreased pain extent and VAS in response to placebo. The ventral lateral PFC (VLPFC) was associated with increased activity during anticipation of visceral pain. PAS cannot predict the placebo effect in visceral pain. In conclusion, pronounced placebo analgesia was coupled with prominent changes of brain activity in visceral pain matrix, which are thus likely involved in high placebo efficacy during the treatment of visceral pain in FGID. VLPFC activation during the anticipation of placebo analgesia suggests top‐down control in the modulation of pain experience.

Menstrual pain is associated with rapid structural alterations in the brain

Summary One to 3 days of menstrual pain is associated with rapid gray matter alterations in the brain. ABSTRACT Dysmenorrhea is the most prevalent gynecological disorder in women of child‐bearing age. Dysmenorrhea is associated with central sensitization and functional and structural changes in the brain. Our recent brain morphometry study disclosed that dysmenorrhea is associated with trait‐related abnormal gray matter (GM) changes, even in the absence of menstrual pain, indicating that the adolescent brain is vulnerable to menstrual pain. Here we report rapid state‐related brain morphological changes, ie, between pain and pain‐free states, in dysmenorrhea. We used T1‐weighted anatomic magnetic resonance imaging to investigate regional GM volume changes between menstruation and periovulatory phases in 32 dysmenorrhea subjects and 32 age‐ and menstrual cycle‐matched asymptomatic controls. An optimized voxel‐based morphometry analysis was conducted to disclose the possible state‐related regional GM volume changes across different menstrual phases. A correlation analysis was also conducted between GM differences and the current menstrual pain experience in the dysmenorrhea group. Compared with the periovulatory phase, the dysmenorrhea subjects revealed greater hypertrophic GM changes than controls during the menstruation phase in regions involved in pain modulation, generation of the affective experience, and regulation of endocrine function, whereas atrophic GM changes were found in regions associated with pain transmission. Volume changes in regions involved in the regulation of endocrine function and pain transmission correlated with the menstrual pain experience scores. Our results demonstrated that short‐lasting cyclic menstrual pain is associated not only with trait‐related but also rapid state‐related structural alterations in the brain. Considering the high prevalence rate of menstrual pain, these findings mandate a great demand to revisit dysmenorrhea with regard to its impact on the brain and other clinical pain conditions.

Enhanced affect/cognition-related brain responses during visceral placebo analgesia in irritable bowel syndrome patients.

Summary IBS patients and controls achieve comparable placebo analgesia upon experimentally induced rectal pain. The placebo analgesia during the visceral pain involves enhanced brain activities relating to affect/cognition in IBS patients. ABSTRACT Placebo analgesia is a psychosocial context effect that is rarely studied in visceral pain. Patients with irritable bowel syndrome (IBS) exhibit visceral hyperalgesia and heightened affective/cognitive brain region activation during visceral stimuli. Psychological factors alter the pain and brain activation pattern, and these changes are more pronounced in IBS patients. Expectation constitutes the major neuropsychological mechanism in the placebo effect. This study confirmed the heightened affective/cognitive brain responses in IBS patients during visceral placebo analgesia using a placebo model with expectation, which was enhanced by suggestion and conditioning. Seventeen IBS patients and 17 age‐/sex‐matched controls were enrolled. Psychophysical inventories (Hospital Anxiety and Depression Scale [HADS], visual analogue scale, and short‐form McGill questionnaire) were completed. Brain activity during placebo intervention and anticipation was assessed in response to rectal distension using 3T‐functional magnetic resonance imaging. Suggestion‐/conditioning‐enhanced placebo was used to convince controls/patients of the efficacy of a newly developed intravenous drug (saline, in actuality) for the relief of rectal distension‐induced visceral pain. A comparable visceral placebo analgesia was observed in IBS patients and control subjects. IBS patients demonstrated a higher HADS‐anxiety score, which was predictive of a weak placebo effect. Suggestion‐/conditioning‐enhanced placebo evoked more activity in affective/cognitive brain regions (insula, midcingulate cortex, and ventrolateral prefrontal cortex [VLPFC]) in IBS patients than in healthy controls. VLPFC was also more active during anticipation in IBS patients. In conclusion, IBS patients and control subjects achieved comparable placebo analgesia during experimentally induced rectal pain. The visceral placebo analgesia produced heightened activity in affective/cognitive brain regions in IBS patients.

ICA-based spatiotemporal approach for single-trial analysis of postmovement MEG beta synchronization☆

The extraction of event-related oscillatory neuromagnetic activities from single-trial measurement is challenging due to the non-phase-locked nature and variability from trial to trial. The present study presents a method based on independent component analysis (ICA) and the use of a template-based correlation approach to extract Rolandic beta rhythm from magnetoencephalographic (MEG) measurements of right finger lifting. A single trial recording was decomposed into a set of coupled temporal independent components and corresponding spatial maps using ICA and the reactive beta frequency band for each trial identified using a two-spectrum comparison between the postmovement interval and a reference period. Task-related components survived dual criteria of high correlation with both the temporal and the spatial templates with an acceptance rate of about 80%. Phase and amplitude information for noise-free MEG beta activities were preserved not only for optimal calculation of beta rebound (event-related synchronization) but also for profound penetration into subtle dynamics across trials. Given the high signal-to-noise ratio (SNR) of this method, various methods of source estimation were used on reconstructed single-trial data and the source loci coherently anchored in the vicinity of the primary motor area. This method promises the possibility of a window into the intricate brain dynamics of motor control mechanisms and the cortical pathophysiology of movement disorder on a trial-by-trial basis.

Neural Network of Body Representation Differs between Transsexuals and Cissexuals

Body image is the internal representation of an individual’s own physical appearance. Individuals with gender identity disorder (GID), commonly referred to as transsexuals (TXs), are unable to form a satisfactory body image due to the dissonance between their biological sex and gender identity. We reasoned that changes in the resting-state functional connectivity (rsFC) network would neurologically reflect such experiential incongruence in TXs. Using graph theory-based network analysis, we investigated the regional changes of the degree centrality of the rsFC network. The degree centrality is an index of the functional importance of a node in a neural network. We hypothesized that three key regions of the body representation network, i.e., the primary somatosensory cortex, the superior parietal lobule and the insula, would show a higher degree centrality in TXs. Twenty-three pre-treatment TXs (11 male-to-female and 12 female-to-male TXs) as one psychosocial group and 23 age-matched healthy cissexual control subjects (CISs, 11 males and 12 females) were recruited. Resting-state functional magnetic resonance imaging was performed, and binarized rsFC networks were constructed. The TXs demonstrated a significantly higher degree centrality in the bilateral superior parietal lobule and the primary somatosensory cortex. In addition, the connectivity between the right insula and the bilateral primary somatosensory cortices was negatively correlated with the selfness rating of their desired genders. These data indicate that the key components of body representation manifest in TXs as critical function hubs in the rsFC network. The negative association may imply a coping mechanism that dissociates bodily emotion from body image. The changes in the functional connectome may serve as representational markers for the dysphoric bodily self of TXs.

Dynamic Changes of Functional Pain Connectome in Women with Primary Dysmenorrhea.

Primary dysmenorrhea (PDM) is the most prevalent gynecological problem. Many key brain systems are engaged in pain processing. In light of dynamic communication within and between systems (or networks) in shaping pain experience and behavior, the intra-regional functional connectivity (FC) in the hub regions of the systems may be altered and the functional interactions in terms of inter-regional FCs among the networks may be reorganized to cope with the repeated stress of menstrual pain in PDM. Forty-six otherwise healthy PDM subjects and 49 age-matched, healthy female control subjects were enrolled. Intra- and inter-regional FC were assessed using regional homogeneity (ReHo) and ReHo-seeded FC analyses, respectively. PDM women exhibited a trait-related ReHo reduction in the ventromedial prefrontal cortex, part of the default mode network (DMN), during the periovulatory phase. The trait-related hypoconnectivity of DMN-salience network and hyperconnectivity of DMN-executive control network across the menstrual cycle featured a dynamic transition from affective processing of pain salience to cognitive modulation. The altered DMN-sensorimotor network may be an ongoing representation of cumulative menstrual pain. The findings indicate that women with long-term PDM may develop adaptive neuroplasticity and functional reorganization with a network shift from affective processing of salience to the cognitive modulation of pain.

Brain signature characterizing the body-brain-mind axis of transsexuals.

Individuals with gender identity disorder (GID), who are commonly referred to as transsexuals (TXs), are afflicted by negative psychosocial stressors. Central to the psychological complex of TXs is the conviction of belonging to the opposite sex. Neuroanatomical and functional brain imaging studies have demonstrated that the GID is associated with brain alterations. In this study, we found that TXs identify, when viewing male-female couples in erotic or non-erotic (“neutral”) interactions, with the couple member of the desired gender in both situations. By means of functional magnetic resonance imaging, we found that the TXs, as opposed to controls (CONs), displayed an increased functional connectivity between the ventral tegmental area, which is associated with dimorphic genital representation, and anterior cingulate cortex subregions, which play a key role in social exclusion, conflict monitoring and punishment adjustment. The neural connectivity pattern suggests a brain signature of the psychosocial distress for the gender-sex incongruity of TXs.

Neuromagnetic index of hemispheric asymmetry predicting long-term outcome in sudden hearing loss.

The neuromagnetic index of hemispheric asymmetry in terms of ipsilateral/contralateral ratio at acute stage was previously revealed to prognosticate the 1-month hearing outcome of acute unilateral idiopathic sudden sensorineural hearing loss (ISSNHL), showing a dynamic relationship between top- and down-levels of auditory pathway. However, the prognostic effect of reorganization pattern for the long-term results remained elusive. This study aimed to probe the prognosticating relevance of hemispheric asymmetry to the hearing at chronic stage of ISSNHL. Using magnetoencephalography (MEG), inter-hemispheric differences in peak dipole of N100m responses to monaural tones were evaluated in 21 controls and 21 ISSNHL patients at initial and final (12 months later) stages. Predictive value of hemispheric asymmetry was assessed by correlating hearing level and ipsilateral/contralateral ratio (I/C) of N100m latency and amplitude. Healthy-side dominance of N100m was observed in ISSNHL initially, and remained in three final prognostic subgroups (complete, partial, and no recovery) of ISSNHL. The initial I/C(amplitude) on affected-ear stimulation strongly correlated with the hearing level of final stage in ISSNHL. However, there was no prognostic effect of hemispheric asymmetry pattern for the 12-month hearing improvement. The heterogeneity between neuromagnetic index and hearing levels possibly echoed different pathogeneses of ISSNHL. Since a restored hearing status did not necessarily lead toward a normal functional organization, the dynamics of hemispheric asymmetry could actually index a central resilient reorganization in the brain for sound processing in ISSNHL. Our finding showed not only a clinically relevant measure to predict final hearing of ISSNHL, but also a linkage between central plasticity and cochlear lesion. This finding suggests a new perspective, and perhaps new interventions, to diagnose and treat unilateral ISSNHL.

Effect of acupuncture ‘dose’ on modulation of the default mode network of the brain

Objective Recent functional MRI (fMRI) studies show that brain activity, including the default mode network (DMN), can be modulated by acupuncture. Conventional means to enhance the neurophysiological ‘dose’ of acupuncture, including an increased number of needles and manual needle manipulation, are expected to enhance its physiological effects. The aim of this study was to compare the effects of both methods on brain activity. Methods 58 healthy volunteers were randomly assigned into four groups that received single needle acupuncture (SNA, n=15) or transcutaneous electrical nerve stimulation (TENS, n=13) as active controls, or enhanced acupuncture by way of three needle acupuncture (TNA, n=17) or SNA plus manual stimulation (SNA+MS, n=13). Treatment-associated sensations were evaluated using a visual analogue scale. Central responses were recorded before, during, and after treatment at LI4 on the left hand using resting state fMRI. Results TNA and SNA+MS induced DMN-insula activity and extensive DMN activity compared to SNA, despite comparable levels of de qi sensation. The TNA and SNA+MS groups exhibited a delayed and enhanced modulation of the DMN, which was not observed followed SNA and TENS. Furthermore, TNA increased precuneus activity and increased the DMN-related activity of the cuneus and left insula, while SNA+MS increased activity in the right insula. Conclusions The results showed that conventional methods to enhance the acupuncture dose induce different DMN modulatory effects. TNA induces the most extensive DMN modulation, compared with other methods. Conventional methods of enhancing the acupuncture dose could potentially be applied as a means of modulating brain activity.

Unaltered intrinsic functional brain architecture in young women with primary dysmenorrhea

Primary dysmenorrhea (PDM), painful menstruation without organic causes, is the most prevalent gynecological problem in women of reproductive age. Dysmenorrhea later in life often co-occurs with many chronic functional pain disorders, and chronic functional pain disorders exhibit altered large-scale connectedness between distributed brain regions. It is unknown whether the young PDM females exhibit alterations in the global and local connectivity properties of brain functional networks. Fifty-seven otherwise healthy young PDM females and 62 age- and education-matched control females participated in the present resting-state functional magnetic resonance imaging study. We used graph theoretical network analysis to investigate the global and regional network metrics and modular structure of the resting-state brain functional networks in young PDM females. The functional network was constructed by the interregional functional connectivity among parcellated brain regions. The global and regional network metrics and modular structure of the resting-state brain functional networks were not altered in young PDM females at our detection threshold (medium to large effect size differences [Cohen’s d ≥ 0.52]). It is plausible that the absence of significant changes in the intrinsic functional brain architecture allows young PDM females to maintain normal psychosocial outcomes during the pain-free follicular phase.