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Abnormal corticostriatal resting-state functional connectivity (rsFC) has been implicated in the neuropathology of multiple sclerosis. The striatum, a component of the basal ganglia, is involved in diverse functions including movement, cognition, emotion, and limbic information processing. However, the brain circuits of the striatal subregions contributing to the changes in rsFC in relapsing–remitting multiple sclerosis (RRMS) patients remain unknown. We used six subdivisions of the striatum in each hemisphere as seeds to investigate the rsFC of striatal subregions between RRMS patients and matched healthy controls (HCs). In addition, we also scanned a subcohort of RRMS patients after an average of 7 months to test the reliability of our findings. Compared to HCs, we found significantly increased dorsal caudal putamen (DCP) connectivity with the premotor area, dorsal lateral prefrontal cortex (DLPFC), insula, precuneus, and superior parietal lobule, and significantly increased connectivity between the superior ventral striatum and posterior cingulate cortex (PCC) in RRMS patients following both scans. Furthermore, we found significant associations between the Expanded Disability Status Scale and the rsFC of the left DCP with the DLPFC and parietal areas in RRMS patients. Our results suggest that the DCP may be a critical striatal subregion in the pathophysiology of RRMS.

Background: Subthreshold depression (StD) is associated with substantial functional impairments due to depressive symptoms that do not fully meet the diagnosis of major depressive disorder (MDD). Its high incidence in the general population and debilitating symptoms has recently put it at the forefront of mood disorder research. Aim In this study we investigated common volumetric brain changes in both young and middle-aged StD patients. Methods: Two cohorts of StD patients, young and middle-aged, (n = 57) and matched controls (n = 76) underwent voxel-based morphometry (VBM). Results: VBM analysis found that: 1) compared with healthy controls, StD patients showed decreased gray matter volume (GMV) in the bilateral globus pallidus and precentral gyrus, as well as increased GMV in the left thalamus and right rostral anterior cingulate cortex/medial prefrontal cortex; 2) there is a significant association between Center for Epidemiological Studies Depression Scale scores and the bilateral globus pallidus (negative) and left thalamus (positive); 3) there is no interaction between age (young vs. middle-age) and group (StD vs. controls). Conclusions: Our findings indicate significant VBM brain changes in both young and middle-aged individuals with StD. Individuals with StD, regardless of age, may share common neural characteristics.

Take-all disease is caused by Gaeumannomyces graminis, (Sacc.) Arx & D. Olivier, a soil-borne fungus, which colonizes the root and crown tissue of many members of the Poaceae plant family. This fungus is able to grow along the surface of roots as darkly pigmented runner hyphae, which has the ability to penetrate the root. Here, we describe a genetic transformation of G. graminis var. graminis by using polyethylene glycol (PEG)-based protoplast transformation. Fungus cells were transformed with a plasmid, pHPG, containing the gusA reporter gene that codes for β-glucuronidase (GUS) and the hph gene for hygromycin resistance as the selectable marker. A de novo transformant selection assay was developed to identify the putative transformants that were expressing the hph gene. In addition, the transformed cells maintained the ability to infect the plant tissues. The GUS-expressing fungus can be used to study fungal infection processes including fungal penetration, colonization and the role(s) of melanin during pathogenesis. Thus, this study is the first report of G. graminis var. graminis transformed with a visibly detectable reporter gene that provides a useful tool to a better understanding of host- Gaeumannomyces interactions. [ABSTRACT FROM AUTHOR]

An all solid-state electromechanical device has been developed which produces short-wavelength traveling surface waves. The active wall was nominally designed for the cancellation of TollmienSchlichting waves in a laminar boundary layer in water. The primary purpose of the device was determination of traveling surface wave characteristics which are important for drag reduction with compliant coatings. Wave form, wave speed, frequency, and amplitude are independently selectable. Sinusoidal wall motion, measured in air with an electro-optical displacement sensor, ranged from 0.6-13 µm over a frequency span of 10-150 Hz. Roll-off frequency at the -3 dB point was 120 Hz, while the maximum phase speed was 166 cm/s. The electronic subsystem is a hybrid analog/digital device, and the active wall employs piezoelectric ceramic elements to produce surface motion. [ABSTRACT FROM AUTHOR]

Objective: To identify and validate an fMRI-based neural marker for migraine without aura (MwoA) and to examine its association with treatment response., Methods: We conducted cross-sectional studies with resting-state fMRI data from 230 participants and machine learning analyses. In studies 1 through 3, we identified, cross-validated, independently validated, and cross-sectionally validated an fMRI-based neural marker for MwoA. In study 4, we assessed the relationship between the neural marker and treatment responses in migraineurs who received a 4-week real or sham acupuncture treatment, or were waitlisted, in a registered clinical trial., Results: In study 1 (n = 116), we identified a neural marker with abnormal functional connectivity within the visual, default mode, sensorimotor, and frontal-parietal networks that could discriminate migraineurs from healthy controls (HCs) with 93% sensitivity and 89% specificity. In study 2 (n = 38), we investigated the generalizability of the marker by applying it to an independent cohort of migraineurs and HCs and achieved 84% sensitivity and specificity. In study 3 (n = 76), we verified the specificity of the marker with new datasets of migraineurs and patients with other chronic pain disorders (chronic low back pain and fibromyalgia) and demonstrated 78% sensitivity and 76% specificity for discriminating migraineurs from nonmigraineurs. In study 4 (n = 116), we found that the changes in the marker responses showed significant correlation with the changes in headache frequency in response to real acupuncture., Conclusion: We identified an fMRI-based neural marker that captures distinct characteristics of MwoA and can link disease pattern changes to brain changes., (© 2020 American Academy of Neurology.)

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the dynamic functional connectivity of thalamocortical networks in interictal migraine patients and whether clinical features are associated with abnormal connectivity., Methods: We investigated dynamic functional network connectivity (dFNC) of the migraine brain in 89 interictal migraine patients and 70 healthy controls. We focused on the temporal properties of thalamocortical connectivity using sliding window cross-correlation, clustering state analysis, and graph-theory methods. Relationships between clinical symptoms and abnormal dFNC were evaluated using a multivariate linear regression model., Results: Five dFNC brain states were identified to characterize and compare dynamic functional connectivity patterns. We demonstrated that migraineurs spent more time in a strongly interconnected between-network state, but they spent less time in a sparsely connected state. Interestingly, we found that abnormal posterior thalamus (pulvinar nucleus) dFNC with the visual cortex and the precuneus were significantly correlated with headache frequency of migraine. Further topologic measures revealed that migraineurs had significantly lower efficiency of information transfer in both global and local dFNC., Conclusion: Our results demonstrated a transient pathologic state with atypical thalamocortical connectivity in migraineurs and extended current findings regarding abnormal thalamocortical networks and dysrhythmia in migraine., (© 2019 American Academy of Neurology.)

Introduction: The influence of sex on the prevalence and clinical manifestations of functional dyspepsia (FD) has recently been a topic of increasing interest. However, brain MRI pathology based on sexual dimorphism in FD has not yet been investigated. The amygdala, which plays a vital role in processing gastrointestinal signals, may be associated with the sex-related pathophysiology of FD., Methods: We investigated the resting-state functional connectivity (rsFC) of amygdala subregions in patients with FD and healthy subjects as well as the sex differences between male and female FD patients., Results: The results showed that FD patients manifested altered rsFC in the basolateral amygdala (BLA) and centromedial amygdala subregions compared with HS and that female FD patients showed increased BLA rsFC with the insula (INS) and decreased BLA rsFC with the medial prefrontal cortex and dorsal lateral prefrontal cortex compared with male FD patients and female HS., Discussion: Our findings suggest that FD females tend to have more severe dysfunction of cognitive-affective processing among the brain regions associated with the salience network, central executive network, and default mode network.

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by atypical social communication and repetitive behaviors. In this study, we applied a multimodal approach to investigate brain structural connectivity, resting state activity, and surface area, as well as their associations with the core symptoms of ASD. Data from forty boys with ASD (mean age, 11.5 years; age range, 5.5-19.5) and forty boys with typical development (TD) (mean age, 12.3; age range, 5.8-19.7) were extracted from the Autism Brain Imaging Data Exchange II (ABIDE II) for data analysis. We found significantly decreased structural connectivity, resting state brain activity, and surface area at the occipital cortex in boys with ASD compared to boys with TD. In addition, we found that resting state brain activity and surface area in the lateral occipital cortex was negatively correlated with communication scores in boys with ASD. Our results suggest that decreased structural connectivity and resting-state brain activity in the occipital cortex may impair the integration of verbal and non-verbal communication cues in boys with ASD, thereby impacting their social development., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Classical theories suggest placebo analgesia and nocebo hyperalgesia are based on expectation and conditioned experience. Whereas the neural mechanism of how expectation modulates placebo and nocebo effects during pain anticipation have been extensively studied, little is known about how experience may change brain networks to produce placebo and nocebo responses. We investigated the neural pathways of direct and observational conditioning for conscious and nonconscious conditioned placebo/nocebo effects using magnetoencephalography and a face visual cue conditioning model. We found that both direct and observational conditioning produced conscious conditioned placebo and nocebo effects and a nonconscious conditioned nocebo effect. Alpha band brain connectivity changes before and after conditioning could predict the magnitude of conditioned placebo and nocebo effects. Particularly, the connectivity between the rostral anterior cingulate cortex and middle temporal gyrus was an important indicator for the manipulation of placebo and nocebo effects. Our study suggests that conditioning can mediate our pain experience by encoding experience and modulating brain networks., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Eye tracking (ET) holds potential for the early detection of autism spectrum disorder (ASD). To overcome the difficulties of working with young children, developing a short and informative paradigm is crucial for ET. We investigated the fixation times of 37 ASD and 37 typically developing (TD) children ages 4-6 watching a 10-second video of a female speaking. ASD children showed significant reductions in fixation time at six areas of interest. Furthermore, discriminant analysis revealed fixation times at the mouth and body could significantly discriminate ASD from TD with a classification accuracy of 85.1%, sensitivity of 86.5%, and specificity of 83.8%. Our study suggests that a short video clip may provide enough information to distinguish ASD from TD children.

Transcutaneous vagus nerve stimulation (tVNS) may be a promising treatment for major depressive disorder (MDD). In this exploratory study, fMRI scans were acquired during continuous real or sham tVNS from 41 MDD patients. Then, all patients received real or sham tVNS treatment for four weeks. We investigated the functional connectivity (FC) of the nucleus accumbens (NAc) at different frequency bands during real and sham tVNS and explored their associations with depressive symptom changes after one month of treatment. The results revealed: 1) significant positive FCs between the NAc and surrounding areas including the putamen, caudate, and distinct areas of the medial prefrontal cortex (MPFC) and the anterior cingulate cortex (ACC) during continuous real and sham tVNS; 2) compared with sham tVNS, real tVNS increased the FC between the left NAc and bilateral MPFC/rACC in the slow-5 band (0.008-0.027) and between the right NAc and left insula, occipital gyrus, and right lingual/fusiform gyrum in the typical low band (0.008-0.09); and 3) the FC of the NAc-MPFC/rACC during real tVNS showed a negative association with Hamilton Depression Rating Scale (HAMD) score changes in the real tVNS group after one month of treatment, but not in the sham group. Our findings demonstrate that tVNS can modulate low frequency intrinsic FC among key brain regions involved in reward and motivation processing and provide insights into the brain mechanism underlying tVNS treatment of MDD., (Copyright © 2017. Published by Elsevier Ltd.)

Background: Major depression is the fourth leading cause of disability worldwide and poses a socioeconomic burden worldwide. Transcutaneous vagus nerve stimulation (tVNS) is a promising noninvasive clinical device that may reduce the severity of major depression. However, the neural mechanism underlying continuous tVNS has not yet been elucidated., Objective: We aimed to explore the effect of hypothalamic subregion functional connectivity (FC) changes during continuous tVNS treatment on major depressive disorder (MDD) patients and to identify the potential biomarkers for treatment outcomes., Methods: Forty-one mild to moderate MDD patients were recruited and received either real or sham tVNS treatment for 4 weeks. We used a seed-to-whole brain approach to estimate the FC changes of hypothalamic subregions and their surrounding control areas during continuous tVNS treatment and explored their association with clinical outcome changes after 4 weeks of treatment., Results: Of the thirty-six patients that completed the study, those in the tVNS group had significantly lower scores on the 24-item Hamilton Depression (HAM-D) Rating Scale compared to the sham tVNS group after 4 weeks of treatment. The FC between the bilateral medial hypothalamus (MH) and rostral anterior cingulate cortex (rACC) was significantly decreased during tVNS but not during sham tVNS. The strength of this FC was significantly correlated with HAM-D improvements after 4 weeks of tVNS., Conclusion: The FC between the bilateral MH and rACC may serve as a potential biomarker for the tVNS state and predict treatment responses. Our results provide insights into the neural modulation mechanisms of continuous tVNS and reveal a potential therapeutic target for MDD patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The amygdala is a key region in emotion processing, and studies have suggested that amygdala-frontal functional connectivity deficits could be modulated by antidepressants in major depressive disorder (MDD). Transcutaneous vagus nerve stimulation (tVNS), a non-invasive, peripheral neuromodulation method at the ear, has shown promising results in treating major depressive disorder (MDD) in several pilot studies. However, the neural mechanism underlying tVNS treatment of depression has not been fully investigated. In this study, we investigated how tVNS can modulate the amygdala-lateral prefrontal network resting state functional connectivity (rsFC) in mild or moderate major depressive disorder (MDD) patients., Methods: Forty-nine MDD patients were recruited and received tVNS or sham tVNS (stVNS) treatments for four weeks. Resting state fMRI scans were applied before and after treatments., Results: After 1 month of tVNS treatment, the 24-item Hamilton Depression Rating Scale (HAMD) scores were reduced significantly in the tVNS group as compared with the sham tVNS group. The rsFC in the tVNS group between the right amygdala and left dorsolateral prefrontal cortex was increased compared with sham tVNS. All the rsFC increases were also associated with HAMD reduction as well as reductions in the anxiety and retardation HAMD subscales., Conclusions: tVNS can significantly modulate the amygdala-lateral prefrontal rsFC of MDD patients; our results provide insights into the brain mechanism of tVNS treatment for MDD patients., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Depression presents a significant burden to both patients and society. One treatment that has emerged is vagus nerve stimulation (VNS), an FDA-approved physical treatment for depressive disorders. However, the application of this intervention has been limited by the involvement of surgery and potential side effects. The aim of this study is to explore the effectiveness of stimulating the superficial branches of the vagus nerve as a solo treatment for MDD., Methods: This is a nonrandomized, controlled study. The first cohort of patients (n=91) only received transcutaneous auricular VNS (taVNS) for 12 weeks. In the second cohort (n=69), patients first received 4 weeks of sham taVNS followed by 8 weeks of taVNS. All treatments were self-administered by the patients at home after they received training from the hospitals. The primary outcome measurement was the 24-item Hamilton Depression Rating Scale measured at weeks 0, 4, 8, and 12. Data analysis included a timelag analysis comparing (1) real and sham taVNS groups at week 4; (2) the real taVNS group at week 4 vs the sham taVNS group at week 8 (fourth week of real taVNS following 4 weeks of sham); and (3) the real taVNS group at week 8 vs the sham taVNS group at week 12 (eighth week of real taVNS following sham)., Results: After four weeks of treatment, MDD patients in the taVNS group showed greater improvement than patients in the sham taVNS group as indicated by Hamilton score changes as well as response and remission rates at week four. In addition, we also found that the clinical improvements continued until week 12 during taVNS., Limitations: Patients were not randomized in this study., Conclusions: Our results suggest that taVNS is a promising, safe, and cost-effective therapeutic method for mild and moderate MDD., (Copyright © 2016 Elsevier B.V. All rights reserved.)