Manipulating placebo analgesia and nocebo hyperalgesia by changing brain excitability.

Harnessing placebo and nocebo effects has significant implications for research and medical practice. Placebo analgesia and nocebo hyperalgesia, the most well-studied placebo and nocebo effects, are thought to initiate from the dorsal lateral prefrontal cortex (DLPFC) and then trigger the brain's descending pain modulatory system and other pain regulation pathways. Combining repeated transcranial direct current stimulation (tDCS), an expectancy manipulation model, and functional MRI, we investigated the modulatory effects of anodal and cathodal tDCS at the right DLPFC on placebo analgesia and nocebo hyperalgesia using a randomized, double-blind and sham-controlled design. We found that compared with sham tDCS, active tDCS could 1) boost placebo and blunt nocebo effects and 2) modulate brain activity and connectivity associated with placebo analgesia and nocebo hyperalgesia. These results provide a basis for mechanistic manipulation of placebo and nocebo effects and may lead to improved clinical outcomes in medical practice.

How expectations of pain elicited by consciously and unconsciously perceived cues unfold over time.

Expectation can shape the perception of pain within a fraction of time, but little is known about how perceived expectation unfolds over time and modulates pain perception. Here, we combine magnetoencephalography (MEG) and machine learning approaches to track the neural dynamics of expectations of pain in healthy participants with both sexes. We found that the expectation of pain, as conditioned by facial cues, can be decoded from MEG as early as 150 ms and up to 1100 ms after cue onset, but decoding expectation elicited by unconsciously perceived cues requires more time and decays faster compared to consciously perceived ones. Also, results from temporal generalization suggest that neural dynamics of decoding cue-based expectation were predominately sustained during cue presentation but transient after cue presentation. Finally, although decoding expectation elicited by consciously perceived cues were based on a series of time-restricted brain regions during cue presentation, decoding relied on the medial prefrontal cortex and anterior cingulate cortex after cue presentation for both consciously and unconsciously perceived cues. These findings reveal the conscious and unconscious processing of expectation during pain anticipation and may shed light on enhancing clinical care by demonstrating the impact of expectation cues.

Modulatory Effects of Actual and Imagined Acupuncture on the Functional Connectivity of the Periaqueductal Gray and Ventral Tegmental Area.

OBJECTIVE: Both acupuncture and guided imagery hold promise for treating pain. The mechanisms underlying these alternative interventions remain unclear. The reported study aimed to comparatively investigate the modulation effect of actual and imagined acupuncture on the functional connectivity of descending pain modulation system and reward network. METHODS: Twenty-four healthy participants (mean [standard error], 25.21 [0.77] years of age; 66.67% female) completed a crossover study that included five sessions, a training session and four intervention sessions administered in randomized order. We investigated the modulation effect of real acupuncture, sham acupuncture, video-guided acupuncture imagery treatment (VGAIT) and VGAIT control on the resting-state functional connectivity (rsFC) of periaqueductal gray (PAG) and ventral tegmental area (VTA). These are key regions of the descending pain modulatory system and dopaminergic reward system, respectively. RESULTS: Compared with sham acupuncture, real acupuncture produced decreased PAG-precuneus (Pcu) rsFC and increased VTA-amygdala/hippocampus rsFC. Heat pain threshold changes applied on the contralateral forearm were significantly associated with the decreased PAG-Pcu (r = 0.49, p = .016) and increased VTA-hippocampus rsFC (r = -0.77, p < .001). Compared with VGAIT control, VGAIT produced decreased PAG-paracentral lobule/posterior cingulate cortex/Pcu, middle cingulate cortex (MCC), and medial prefrontal cortex rsFC, and decreased VTA-caudate and MCC rsFC. Direct comparison between real acupuncture and VGAIT showed that VGAIT decreased rsFC in PAG-paracentral lobule/MCC, VTA-caudate/anterior cingulate cortex/nucleus accumbens, and VTA-MCC. CONCLUSIONS: Results suggest that both actual and imagined acupuncture can modulate key regions in the descending pain modulatory system and reward networks, but through different pathways. Identification of different pain relief mechanisms may facilitate the development of new pain management methods.

Daily Caffeine Consumption Does Not Influence Acupuncture Analgesia in Healthy Individuals: A Preliminary Study.

Animal studies suggest that caffeine may interfere with acupuncture analgesia. This study investigated the modulation effect of daily caffeine intake on acupuncture analgesia in 27 healthy subjects using a crossover design. We found that real acupuncture increased pain thresholds compared to sham acupuncture. Further, there was no association between caffeine intake measurements of daily caffeine use, duration of caffeine consumption, or their interaction and preacupuncture and postacupuncture pain threshold changes. Our findings suggest that daily caffeine intake may not influence acupuncture analgesia in the cohort of healthy subjects who participated in study.

Characterizing the analgesic effects of real and imagined acupuncture using functional and structure MRI.

Acupuncture and imagery interventions for pain management have a long history. The present study comparatively investigated whether acupuncture and video-guided acupuncture imagery treatment (VGAIT, watching a video of acupuncture on the participant's own body while imagining it being applied) could modulate brain regional connectivity to produce analgesic effects. The study also examined whether pre-intervention brain functional and structural features could be used to predict the magnitude of analgesic effects. Twenty-four healthy participants were recruited and received four different interventions (real acupuncture, sham acupuncture, VGAIT, and VGAIT control) in random order using a cross-over design. Pain thresholds and magnetic resonance imaging (MRI) data were collected before and after each intervention. We first compared the modulatory effects of real acupuncture and VGAIT on intra- and inter-regional intrinsic brain connectivity and found that real acupuncture decreased regional homogeneity (ReHo) and functional connectivity (FC) in sensorimotor areas, whereas VGAIT increased ReHo in basal ganglia (BG) (i.e., putamen) and FC between the BG subcortical network and default mode network. The altered ReHo and FC were associated with changes in pain threshold after real acupuncture and VGAIT, respectively. A multimodality fusion approach with pre-intervention ReHo and gray matter volume (GMV) as features was used to explore the brain profiles underlying individual variability of pain threshold changes by real acupuncture and VGAIT. Variability in acupuncture responses was associated with ReHo and GMV in BG, whereas VGAIT responses were associated with ReHo and GMV in the anterior insula. These results suggest that, through different pathways, both real acupuncture and VGAIT can modulate brain systems to produce analgesic effects.

Impaired mesocorticolimbic connectivity underlies increased pain sensitivity in chronic low back pain.

Chronic low back pain (cLBP) is a prevalent disorder. A growing body of evidence linking the pathology of the reward network to chronic pain suggests that pain sensitization may contribute to cLBP chronification via disruptions of mesocortical and mesolimbic circuits in the reward system. Resting-state (RS) functional magnetic resonance imaging (fMRI) data was acquired from 90 patients with cLBP and 74 matched pain-free controls (HCs) at baseline and after a manipulation for back pain intensification. The ventral tegmental area (VTA) was chosen as a seed region to perform RS functional connectivity (FC) analysis. Baseline rsFC of both the mesocortical (between the VTA and bilateral rostral anterior cingulate cortex (rACC)/and medial prefrontal cortex (mPFC)) and mesolimbic (between the VTA and bilateral hippocampus/parahippocampus) pathways was reduced in patients with cLBP (vs. HCs). In addition, patients exhibiting higher back pain intensity (compared to the relatively lower back pain intensity condition) also showed increases in both mesocortical and mesolimbic connectivity, implicating these pathways in pain downregulation in cLBP. Mediation analysis further isolated the mesolimbic (VTA-hippocampus/parahippocampus) dysconnectivity as a neural mechanism mediating the association between mechanical pain sensitivity (indexed by P40 pressure) and cLBP severity. In sum, the current study demonstrates deficient mesocorticolimbic connectivity in cLBP, with mesolimbic dysconnectivity potentially mediating the contribution of pain sensitization to pain chronification. These reward network dysfunctions and purportedly, dopaminergic dysregulations, may help us to identify key brain targets of neuromodulation in the treatment of cLBP.

Locations for noninvasive brain stimulation in treating depressive disorders: A combination of meta-analysis and resting-state functional connectivity analysis.

OBJECTIVE: Many noninvasive brain stimulation techniques have been applied to treat depressive disorders. However, the target brain region in most noninvasive brain stimulation studies is the dorsolateral prefrontal cortex. Exploring new stimulation locations may improve the efficacy of noninvasive brain stimulation for depressive disorders. We aimed to explore potential noninvasive brain stimulation locations for depressive disorders through a meta-analysis and a functional connectivity approach. METHODS: We conducted a meta-analysis of 395 functional magnetic resonance imaging studies to identify depressive disorder-associated brain regions as regions of interest. Then, we ran resting-state functional connectivity analysis with three different pipelines in 40 depression patients to find brain surface regions correlated with these regions of interest. The 10-20 system coordinates corresponding to these brain surface regions were considered as potential locations for noninvasive brain stimulation. RESULTS: The 10-20 system coordinates corresponding to the bilateral dorsolateral prefrontal cortex, bilateral inferior frontal gyrus, medial prefrontal cortex, supplementary motor area, bilateral supramarginal gyrus, bilateral primary motor cortex, bilateral operculum, left angular gyrus and right middle temporal gyrus were identified as potential locations for noninvasive brain stimulation in depressive disorders. The coordinates were: posterior to F3, posterior to F4, superior to F3, posterior to F7, anterior to C4, P3, midpoint of F7-T3, posterior to F8, anterior to C3, midpoint of Fz-Cz, midpoint of Fz-Fp1, anterior to T4, midpoint of C3-P3, and anterior to C4. CONCLUSION: Our study identified several potential noninvasive brain stimulation locations for depressive disorders, which may serve as a basis for future clinical investigations.

Imagined and Actual Acupuncture Effects on Chronic Low Back Pain: A Preliminary Study.

Background: Research suggests that imagined experiences can produce brain responses similar to those produced by actual experiences. Shared brain responses that support both imagination and perception may underlie the functional nature of mental imagery. In a previous study, we combined acupuncture and imagery to develop a new treatment method, video-guided acupuncture imagery treatment (VGAIT). We found that VGAIT significantly increased pain thresholds in healthy subjects. The aim of this study is to extend our previous finding by investigating whether VGAIT can relieve symptoms in patients with chronic low back pain. Methods: We first performed a single-arm study in which we administered video-guided acupuncture imagery treatment (VGAIT) on patients with chronic low back pain (cLBP) (Study 1, n = 18, 12 females). We then compared our findings to those from a recently published study in which real or sham acupuncture treatment was applied on patients with cLBP (Study 2, n = 50, 31 females) using a similar protocol. All patients in Studies 1 and 2 received 6 treatments over 4 weeks. Results: All three treatments (VGAIT, real, and sham acupuncture) significantly reduced pain severity as measured by a low back pain bothersomeness score. VGAIT produced similar effects to real acupuncture (p = 0.97) and nonsignificantly greater pain bothersomeness relief compared to sham acupuncture (p = 0.14). Additional analysis showed that there was no significant difference on the sensations evoked by different treatment modalities. Conclusion: These findings support VGAIT as a promising method for pain management.

Identifying inter-individual differences in pain threshold using brain connectome: a test-retest reproducible study.

Individuals are unique in terms of brain and behavior. Some are very sensitive to pain, while others have a high tolerance. However, how inter-individual intrinsic differences in the brain are related to pain is unknown. Here, we performed longitudinal test-retest analyses to investigate pain threshold variability among individuals using a resting-state fMRI brain connectome. Twenty-four healthy subjects who received four MRI sessions separated by at least 7 days were included in the data analysis. Subjects' pain thresholds were measured using two modalities of experimental pain (heat and pressure) on two different locations (heat pain: leg and arm; pressure pain: leg and thumbnail). Behavioral results showed strong inter-individual variability and strong within-individual stability in pain threshold. Resting state fMRI data analyses showed that functional connectivity profiles can accurately identify subjects across four sessions, indicating that an individual's connectivity profile may be intrinsic and unique. By using multivariate pattern analyses, we found that connectivity profiles could be used to predict an individual's pain threshold at both within-session and between-session levels, with the most predictive contribution from medial-frontal and frontal-parietal networks. These results demonstrate the potential of using a resting-state fMRI brain connectome to build a 'neural trait' for characterizing an individual's pain-related behavior, and such a 'neural trait' may eventually be used to personalize clinical assessments.

Different exercise modalities relieve pain syndrome in patients with knee osteoarthritis and modulate the dorsolateral prefrontal cortex: A multiple mode MRI study.

OBJECTIVES: Knee osteoarthritis (KOA) is a common degenerative joint disease with no satisfactory intervention. Recently, both physical and mindfulness exercises have received considerable attention for their implications in KOA pain management, and the dorsolateral prefrontal cortex (DLPFC) has displayed a critical role in pain modulation. This study aimed to comparatively investigate the modulation effects of different exercises using multidisciplinary measurements. METHODS: 140 KOA patients were randomized into Tai Chi, Baduanjin, stationary cycling, or health education control groups for 12 weeks. Knee Injury and Osteoarthritis Outcome Score (KOOS), resting state functional magnetic resonance imaging (fMRI), structural MRI, and serum biomarkers were measured at baseline and at the end of the study. RESULTS: We found: 1) increased KOOS pain subscores (pain reduction) and serum programmed cell death protein 1 (PD-1) levels in the three exercise groups compared to the control group; 2) decreased resting state functional connectivity (rsFC) of the DLPFC-supplementary motor area (SMA) and increased rsFC between the DLPFC and anterior cingulate cortex in all exercise groups compared to the control group; 3) significant associations between DLPFC-SMA rsFC with KOOS pain subscores and serum PD-1 levels at baseline; 4) significantly increased grey matter volume in the SMA in the Tai Chi and stationary cycling groups, and a trend toward significant increase in the Baduanjin group compared to the control group; 5) significant DLPFC rsFC differences among different exercise groups; and 6) that baseline DLPFC-SMA rsFC can predict the effect of mind-body exercise on pain improvement in KOA. CONCLUSION: Our results suggest that different exercises can modulate both common and unique DLPFC (cognitive control) pathways, and altered DLPFC-SMA rsFC is associated with serum biomarker levels. Our findings also highlight the potentials of neuroimaging biomarkers in predicting the therapeutic effect of mind-body exercises on KOA pain.

Modulatory effects of different exercise modalities on the functional connectivity of the periaqueductal grey and ventral tegmental area in patients with knee osteoarthritis: a randomised multimodal magnetic resonance imaging study.

BACKGROUND: Knee osteoarthritis is a prevalent disorder with unsatisfactory treatment options. Both physical and mindful exercises may be able to relieve its pain symptoms. We compared the modulatory effects of different exercise modalities on the periaqueductal grey (PAG) and ventral tegmental area (VTA), which play important roles in descending opioidergic pathways and reward/motivation systems in patients with knee osteoarthritis. METHODS: We recruited and randomised 140 patients into Tai Chi, Baduanjin, stationary cycling, and health education control groups for 12 weeks. Knee injury and Osteoarthritis Outcome Score (KOOS), functional and structural MRI, and blood biomarkers were measured at the beginning and end of the experiment. We used the PAG and VTA as seeds in resting-state functional connectivity (rsFC) analysis. RESULTS: Compared with the control group: (i) all exercises significantly increased KOOS pain sub-scores (pain reduction) and serum programmed death 1 (PD-1) concentrations; (ii) all exercises decreased right PAG rsFC with the medial orbital prefrontal cortex, and the decreased rsFC was associated with improvements in knee pain; and (iii) grey matter volume in the medial orbital prefrontal cortex was significantly increased in all exercise groups. There was also significantly decreased rsFC between the left VTA and the medial orbital prefrontal cortex in the Tai Chi and Baduanjin groups. CONCLUSIONS: Exercise can simultaneously modulate the rsFC of the descending opioidergic pathway and reward/motivation system and blood inflammation markers. Elucidating the shared and unique mechanisms of different exercise modalities may facilitate the development of exercise-based interventions for chronic pain. CLINICAL TRIAL REGISTRATION: ChiCTR-IOR-16009308.

Identifying brain regions associated with the neuropathology of chronic low back pain: a resting-state amplitude of low-frequency fluctuation study.

BACKGROUND: Previous studies have found widespread pain processing alterations in the brain in chronic low back pain (cLBP) patients. We aimed to (1) identify brain regions showing altered amplitude of low-frequency fluctuations (ALFF) using MRI and use these regions to discriminate cLBP patients from healthy controls (HCs) and (2) identify brain regions that are sensitive to cLBP pain intensity changes. METHODS: We compared ALFF differences by MRI between cLBP subjects (90) and HCs (74), conducted a discriminative analysis to validate the results, and explored structural changes in key brain regions of cLBP. We also compared ALFF changes in cLBP patients after pain-exacerbating manoeuvres. RESULTS: ALFF was increased in the post-/precentral gyrus (PoG/PrG), paracentral lobule (PCL)/supplementary motor area (SMA), and anterior cingulate cortex (ACC), and grey matter volume was increased in the left ACC in cLBP patients. PCL/SMA ALFF reliably discriminated cLBP patients from HCs in an independent cohort. cLBP patients showed increased ALFF in the insula, amygdala, hippocampal/parahippocampal gyrus, and thalamus and decreased ALFF in the default mode network (DMN) when their spontaneous low back pain intensity increased after the pain-exacerbating manoeuvre. CONCLUSIONS: Brain low-frequency oscillations in the PCL, SMA, PoG, PrG, and ACC may be associated with the neuropathology of cLBP. Low-frequency oscillations in the insula, amygdala, hippocampal/parahippocampal gyrus, thalamus, and DMN are sensitive to manoeuvre-induced spontaneous back pain intensity changes.

Teleneurology service provided via tablet technology: 3-year outcomes and physician satisfaction.

INTRODUCTION: This study aimed to demonstrate that teleneurology consultations conducted via tablet technology are an efficient and cost-effective means of managing acute neurologic emergencies at community-based hospitals and that utilizing such technology yields high community physician satisfaction. METHOD: During a 39-month period, Vanderbilt University Medical Center in Tennessee USA, provided teleneurology services to 10 community-based hospitals that lacked adequate neurology coverage. Hospitalists at one community-based hospital were not comfortable treating any patient with a neurologic symptom, resulting in 100% of those patients being transferred. This facility now retains more than 60% of neurology patients. For less than US$1200, these hospitals were able to meet the only capital expenditure required to launch this service: the purchase of handheld tablet computers. Real-time teleneurology consultations were conducted via tablet using two-way video conferencing, radiologic image sharing, and medical record documentation. Community physicians were regularly surveyed to assess satisfaction. RESULTS: From February 2014 to May 2017, 3626 teleneurology consultations were conducted. Community physicians, in partnership with neurologists, successfully managed 87% of patients at the community-based hospital. Only 13% of patients required transfer to another facility for a higher level of care. The most common diagnoses included stroke (34%), seizure (11%), and headache/migraine (6%). The average time for the neurologist to answer a request for consultation page and connect with the community physician was 10.6 minutes. Ninety-one percent of community physicians were satisfied or somewhat satisfied with the overall service. CONCLUSION: In the assessment of neurology patients, tablets are a more cost-effective alternative to traditional telehealth technologies. The devices promote efficiency in consultations through ease of use and low transfer rates, and survey results indicate community physician satisfaction.

Magneto-optical trapping in a near-suface borehole.

Borehole gravity sensing can be used in a number of applications to measure features around a well, including rock-type change mapping and determination of reservoir porosity. Quantum technology gravity sensors, based on atom interferometry, have the ability to offer increased survey speeds and reduced need for calibration. While surface sensors have been demonstrated in real world environments, significant improvements in robustness and reductions to radial size, weight, and power consumption are required for such devices to be deployed in boreholes. To realise the first step towards the deployment of cold atom-based sensors down boreholes, we demonstrate a borehole-deployable magneto-optical trap, the core package of many cold atom-based systems. The enclosure containing the magneto-optical trap itself had an outer radius of (60 ± 0.1) mm at its widest point and a length of (890 ± 5) mm. This system was used to generate atom clouds at 1 m intervals in a 14 cm wide, 50 m deep borehole, to simulate how in-borehole gravity surveys are performed. During the survey, the system generated, on average, clouds of (3.0 ± 0.1) × 105 87Rb atoms with the standard deviation in atom number across the survey observed to be as low as 8.9 × 104.

Abnormal Anatomical and Functional Connectivity of the Thalamo-sensorimotor Circuit in Chronic Low Back Pain: Resting-state Functional Magnetic Resonance Imaging and Diffusion Tensor Imaging Study.

Thalamocortical dysfunction is thought to underlie the pathophysiology of chronic pain revealed by electroencephalographic studies. The thalamus serves as a primary relay center to transmit sensory information and motor impulses via dense connections with the somatosensory and motor cortex. In this study, diffusion tensor imaging (DTI) (probabilistic tractography) and resting-state functional magnetic resonance imaging (functional connectivity) were used to characterize the anatomical and functional integrity of the thalamo-sensorimotor pathway in chronic low back pain (cLBP). Fifty-four patients with cLBP and 54 healthy controls were included. The results suggested significantly increased anatomical connectivity of the left thalamo-motor pathway characterized by probabilistic tractography in patients with cLBP. Moreover, there was significantly altered resting-state functional connectivity (rsFC) of bilateral thalamo-motor/somatosensory pathways in patients with cLBP as compared to healthy controls. We also detected a significant correlation between pain intensity during the MRI scan and rsFC of the right thalamo-somatosensory pathway in cLBP. Our findings highlight the involvement of the thalamo-sensorimotor circuit in the pathophysiology of cLBP.

A thematic analysis of smokers' and non-smokers' accounts of E-cigarettes.

This study explored smokers' and non-smokers' accounts of E-cigarettes. A total of 51 UK-based participants, 20 men and 31 women, responded to open-ended questions online. Inductive thematic analysis identified that the factors that influence E-cigarette behaviour and opinion in adult smokers and non-smokers are related to social context, informative sources, practical aspects and health implications. Participants presented varying accounts of E-cigarettes, suggesting that individual narratives regarding E-cigarettes are multi-faceted. This is important information for health professionals and policy makers tasked with advising on E-cigarette use.

An investigation of factors encouraging and deterring EC use: a thematic analysis of accounts from UK adults.

OBJECTIVE: This study aimed to explore E-cigarette (EC) accounts from a small sample of UK adults with varied smoking/EC experiences. This was to contribute to existing knowledge of adult perceptions and understand the factors that encourage or deter use to inform health messaging aimed at professionals, policy makers and the general public. DESIGN: Twelve participants, five men and seven women aged 23-55 years (mean age 32.43) with mixed smoking/EC backgrounds took part in face-to-face interviews, analysed using semantic-level inductive thematic analysis. RESULTS: The analysis identified three key themes. Social influence (1) relates to the understanding of the social representations of ECs. Representation and knowledge (2) captures the impact of varied EC related communication on perception. Aspects of addiction (3) conveys aspects of nicotine addiction and how this influences EC use. CONCLUSION: ECs were generally perceived as more socially acceptable than cigarettes by non-smokers, although there were varying levels of acceptability depending on the type of EC device used. There was also unanimity concerning uncertainty surrounding the devices. Behavioural/sensory elements and personal enjoyment of ECs were consistent elements that encouraged or deterred use. Although non-smokers/vapers did not use the devices, they expressed similar apprehensions to those who did.

Different Eye Tracking Patterns in Autism Spectrum Disorder in Toddler and Preschool Children.

Background: Children with autism spectrum disorder (ASD) have been observed to be associated with fixation abnormality as measured eye tracking, but the dynamics behind fixation patterns across age remain unclear. Materials and Methods: In this study, we investigated gaze patterns between toddlers and preschoolers with and without ASD while they viewed video clips and still images (i.e., mouth-moving face, biological motion, mouthing face vs. moving object, still face picture vs. objects, and moving toys). Results: We found that the fixation time percentage of children with ASD showed significant decrease compared with that of TD children in almost all areas of interest (AOI) except for moving toy (helicopter). We also observed a diagnostic group (ASD vs. TD) and chronological age (Toddlers vs. preschooler) interaction for the eye AOI during the mouth-moving video clip. Support vector machine analysis showed that the classifier could discriminate ASD from TD in toddlers with an accuracy of 80% and could discriminate ASD from TD in preschoolers with an accuracy of 71%. Conclusion: Our results suggest that toddlers and preschoolers may be associated with both common and distinct fixation patterns. A combination of eye tracking and machine learning methods has the potential to shed light on the development of new early screening/diagnosis methods for ASD.

Altered functional connectivity between hypothalamus and limbic system in fibromyalgia.

The hypothalamus links the nervous system to the endocrine system and plays a crucial role in maintaining the human body's homeostasis. This study aims to investigate the resting state functional connectivity (rsFC) changes of the hypothalamus in fibromyalgia patients. 24 Fibromyalgia patients and 24 matched healthy controls (HCs) were recruited. Resting state fMRI data were collected from the fibromyalgia patients and HC's. Fibromyalgia patients went through a second scan after 12 weeks of Tai Chi mind-body intervention. Data analysis showed that fibromyalgia patients displayed less medial hypothalamus (MH) rsFC with the thalamus and amygdala when compared to the functional connectivity in the HCs. After the Tai Chi mind-body intervention, fibromyalgia patients showed increased MH rsFC with the thalamus and amygdala accompanied by clinical improvement. Effective connectivity analysis showed disrupted MH and thalamus interaction in the fibromyalgia patients, which was altered by mind-body exercise. Our findings suggest that fibromyalgia is associated with altered functional connectivity within the diencephalon and limbic system. Elucidating the roles of the diencephalon and limbic system in the pathophysiology and development of fibromyalgia may facilitate the development of a new biomarker and effective treatment methods for this prevalent disorder.Trial Registration ClinicalTrials.gov, NCT02407665. Registered: 3 April 2015, https://clinicaltrials.gov/ct2/show/NCT02407665?term=NCT02407665&draw=2&rank=1.

Altered Extended Locus Coeruleus and Ventral Tegmental Area Networks in Boys with Autism Spectrum Disorders: A Resting-State Functional Connectivity Study.

INTRODUCTION: Previous studies have suggested that cerebral projections of the norepinephrine (NE) and dopamine (DA) systems have important etiology and treatment implications for autism spectrum disorder (ASD). METHODS: We used functional magnetic resonance imaging to evaluate spontaneous resting state functional connectivity in boys aged 7-15 years with ASD (n=86) and age-, intelligence quotient-matched typically developing boys (TD, n=118). Specifically, we investigated functional connectivity of the locus coeruleus (LC) and ventral tegmental area (VTA), the main source projection of neurotransmitters NE and DA, respectively. RESULTS: 1) Both the LC and VTA showed reduced connectivity with the postcentral gyrus (PoCG) in boys with ASD, reflecting the potential roles of NE and DA in modulating the function of the somatosensory cortex in boys with ASD. 2) The VTA had increased connectivity with bilateral thalamus in ASD; this alteration was correlated with repetitive and restrictive features. 3) Altered functional connectivity of both the LC and VTA with brain regions such as the angular gyrus (AG), middle temporal gyrus visual area (MT/V5), and occipital face area (OFA) in ASD group. DISCUSSION: Our findings implicate the role of LC-NE and VTA-DA systems from the perspective of functional neuroimaging and may shed light on pharmacological studies targeting NE and DA for the treatment of autism in the future.