Drug-Coated Balloon Angioplasty for Thoracic Great Vessel Stenosis Due to Takayasu Arteritis With 1-Year Follow-up.

PURPOSE: Takayasu arteritis is a large-vessel vasculitis in women of childbearing age that affects large vessels including the aorta and its main branches. Inflammation of arteries can produce lesions that lead to occlusion, stenosis, or aneurysms which can lead to complications. If signs of organ dysfunction are present, vascular intervention may be necessary. CASE REPORT: In this article, we present a case of Takayasu arteritis with high-grade stenosis of all the great vessels of the thoracic aorta treated with drug-coated balloon (DCB) angioplasty and stenting requiring multiple follow-up interventions over a 1-year follow-up. CONCLUSION: The DCB angioplasty is a potential endovascular treatment for thoracic great artery stenosis in Takayasu arteritis that could be further explored.

Examining reaction time variability on the stop-signal task in the ABCD study.

OBJECTIVE: Reaction time variability (RTV) has been estimated using Gaussian, ex-Gaussian, and diffusion model (DM) indices. Rarely have studies examined interrelationships among these performance indices in childhood, and the use of reaction time (RT) computational models has been slow to take hold in the developmental psychopathology literature. Here, we extend prior work in adults by examining the interrelationships among different model parameters in the ABCD sample and demonstrate how computational models of RT can clarify mechanisms of time-on-task effects and sex differences in RTs. METHOD: This study utilized trial-level data from the stop signal task from 8916 children (9-10 years old) to examine Gaussian, ex-Gaussian, and DM indicators of RTV. In addition to describing RTV patterns, we examined interrelations among these indicators, temporal patterns, and sex differences. RESULTS: There was no one-to-one correspondence between DM and ex-Gaussian parameters. Nonetheless, drift rate was most strongly associated with standard deviation of RT and tau, while nondecisional processes were most strongly associated with RT, mu, and sigma. Performance worsened across time with changes driven primarily by decreasing drift rate. Boys were faster and less variable than girls, likely attributable to girls' wide boundary separation. CONCLUSIONS: Intercorrelations among model parameters are similar in children as has been observed in adults. Computational approaches play a crucial role in understanding performance changes over time and can also clarify mechanisms of group differences. For example, standard RT models may incorrectly suggest slowed processing speed in girls that is actually attributable to other factors.

DeepLiverNet: a deep transfer learning model for classifying liver stiffness using clinical and T2-weighted magnetic resonance imaging data in children and young adults.

BACKGROUND: Although MR elastography allows for quantitative evaluation of liver stiffness to assess chronic liver diseases, it has associated drawbacks related to additional scanning time, patient discomfort, and added costs. OBJECTIVE: To develop a machine learning model that can categorically classify the severity of liver stiffness using both anatomical T2-weighted MRI and clinical data for children and young adults with known or suspected pediatric chronic liver diseases. MATERIALS AND METHODS: We included 273 subjects with known or suspected chronic liver disease. We extracted data including axial T2-weighted fast spin-echo fat-suppressed images, clinical data (e.g., demographic/anthropomorphic data, particular medical diagnoses, laboratory values) and MR elastography liver stiffness measurements. We propose DeepLiverNet (a deep transfer learning model) to classify patients into one of two groups: no/mild liver stiffening (<3 kPa) or moderate/severe liver stiffening (≥3 kPa). We conducted internal cross-validation using 178 subjects, and external validation using an independent cohort of 95 subjects. We assessed diagnostic performance using accuracy, sensitivity, specificity and area under the receiver operating characteristic curve (AuROC). RESULTS: In the internal cross-validation experiment, the combination of clinical and imaging data produced the best performance (AuROC=0.86) compared to clinical (AuROC=0.83) or imaging (AuROC=0.80) data alone. Using both clinical and imaging data, the DeepLiverNet correctly classified patients with accuracy of 88.0%, sensitivity of 74.3% and specificity of 94.6%. In our external validation experiment, this same deep learning model achieved an accuracy of 80.0%, sensitivity of 61.1%, specificity of 91.5% and AuROC of 0.79. CONCLUSION: A deep learning model that incorporates clinical data and anatomical T2-weighted MR images might provide a means of risk-stratifying liver stiffness and directing the use of MR elastography.

Machine Learning Prediction of Liver Stiffness Using Clinical and T2-Weighted MRI Radiomic Data.

OBJECTIVE. The purpose of this study is to develop a machine learning model to categorically classify MR elastography (MRE)-derived liver stiffness using clinical and nonelastographic MRI radiomic features in pediatric and young adult patients with known or suspected liver disease. MATERIALS AND METHODS. Clinical data (27 demographic, anthropomorphic, medical history, and laboratory features), MRI presence of liver fat and chemical shift-encoded fat fraction, and MRE mean liver stiffness measurements were retrieved from electronic medical records. MRI radiomic data (105 features) were extracted from T2-weighted fast spin-echo images. Patients were categorized by mean liver stiffness (< 3 vs ≥ 3 kPa). Support vector machine (SVM) models were used to perform two-class classification using clinical features, radiomic features, and both clinical and radiomic features. Our proposed model was internally evaluated in 225 patients (mean age, 14.1 years) and externally evaluated in an independent cohort of 84 patients (mean age, 13.7 years). Diagnostic performance was assessed using ROC AUC values. RESULTS. In our internal cross-validation model, the combination of clinical and radiomic features produced the best performance (AUC = 0.84), compared with clinical (AUC = 0.77) or radiomic (AUC = 0.70) features alone. Using both clinical and radiomic features, the SVM model was able to correctly classify patients with accuracy of 81.8%, sensitivity of 72.2%, and specificity of 87.0%. In our external validation experiment, this SVM model achieved an accuracy of 75.0%, sensitivity of 63.6%, specificity of 82.4%, and AUC of 0.80. CONCLUSION. An SVM learning model incorporating clinical and T2-weighted radiomic features has fair-to-good diagnostic performance for categorically classifying liver stiffness.

Myo-inositol mediates the effects of traffic-related air pollution on generalized anxiety symptoms at age 12 years.

BACKGROUND: Exposure to traffic-related air pollution (TRAP) has been linked to childhood anxiety symptoms. Neuroimaging in patients with anxiety disorders indicate altered neurochemistry. OBJECTIVES: Evaluate the impact of TRAP on brain metabolism and its relation to childhood anxiety symptoms in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS). METHODS: Adolescents (n = 145) underwent magnetic resonance spectroscopy. Brain metabolites, including myo-inositol, N-acetylaspartate, creatine, choline, glutamate, glutamate plus glutamine, and glutathione were measured in the anterior cingulate cortex. Anxiety symptoms were assessed using the Spence Children's Anxiety Scale. TRAP exposure in early-life, averaged over childhood, and during the 12 months prior to imaging was estimated using a validated land use regression model. Associations between TRAP exposure, brain metabolism, and anxiety symptoms were estimated using linear regression and a bootstrapping approach for testing mediation by brain metabolite levels. RESULTS: Recent exposure to high levels of TRAP was associated with significant increases in myo-inositol (ß = 0.26; 95%CI 0.01, 0.51) compared to low TRAP exposure. Recent elevated TRAP exposure (ß = 4.71; 95% CI 0.95, 8.45) and increased myo-inositol levels (ß = 2.98; 95% CI 0.43, 5.52) were also significantly associated with increased generalized anxiety symptoms with 12% of the total effect between TRAP and generalized anxiety symptoms being mediated by myo-inositol levels. CONCLUSIONS: This is the first study of children to utilize neuroimaging to link TRAP exposure, metabolite dysregulation in the brain, and generalized anxiety symptoms among otherwise healthy children. TRAP may elicit atypical excitatory neurotransmission and glial inflammatory responses leading to increased metabolite levels and subsequent anxiety symptoms.

Resting-state functional connectivity of subcortical locomotor centers explains variance in walking capacity.

Walking capacity influences the quality of life and disability in normal aging and neurological disease, but the neural correlates remain unclear and subcortical locomotor regions identified in animals have been more challenging to assess in humans. Here we test whether resting-state functional MRI connectivity (rsFC) of midbrain and cerebellar locomotor regions (MLR and CLR) is associated with walking capacity among healthy adults. Using phenotypic and MRI data from the Nathan Kline Institute Rockland Sample (n =119, age 18-85), the association between walking capacity (6-min walk test distance) and rsFC was calculated from subcortical locomotor regions to 81 other gait-related regions of interest across the brain. Additional analyses assessed the independence and specificity of the results. Walking capacity was associated with higher rsFC between the MLR and superior frontal gyrus adjacent to the anterior cingulate cortex, higher rsFC between the MLR and paravermal cerebellum, and lower rsFC between the CLR and primary motor cortex foot area. These rsFC correlates were more strongly associated with walking capacity than phenotypic variables such as age, and together explained 25% of the variance in walking capacity. Results were specific to locomotor regions compared with the other brain regions. The rsFC of locomotor centers correlates with walking capacity among healthy adults. These locomotion-related biomarkers may prove useful in future work aimed at helping patients with reduced walking capacity.

Dysfunction in emotion processing underlies functional (psychogenic) dystonia.

OBJECTIVE: We sought to determine whether abnormalities in emotion processing underlie functional (psychogenic) dystonia, one of the most common functional movement disorders. METHODS: Motor and emotion circuits were examined in 12 participants with functional dystonia, 12 with primary organic dystonia, and 25 healthy controls using functional magnetic resonance imaging at 4T and a finger-tapping task (motor task), a basic emotion-recognition task (emotional faces task), and an intense-emotion stimuli task. RESULTS: There were no differences in motor task activation between groups. In the faces task, when compared with the other groups, functional dystonia patients showed areas of decreased activation in the right middle temporal gyrus and bilateral precuneus and increased activation in the right inferior frontal gyrus, bilateral occipital cortex and fusiform gyrus, and bilateral cerebellum. In the intense-emotion task, when compared with the other groups, functional dystonia patients showed decreased activation in the left insular and left motor cortices (compared to organic dystonia, they showed an additional decrease in activation in the right opercular cortex and right motor cortex) and increased activation in the left fusiform gyrus. CONCLUSIONS: Functional dystonia patients exhibited stimulus-dependent altered activation in networks involved in motor preparation and execution, spatial cognition, and attentional control. These results support the presence of network dysfunction in functional dystonia. © 2017 International Parkinson and Movement Disorder Society.

Socio-economic status and fertility decline: Insights from historical transitions in Europe and North America.

The timings of historical fertility transitions in different regions are well understood by demographers, but much less is known regarding their specific features and causes. In the study reported in this paper, we used longitudinal micro-level data for five local populations in Europe and North America to analyse the relationship between socio-economic status and fertility during the fertility transition. Using comparable analytical models and class schemes for each population, we examined the changing socio-economic differences in marital fertility and related these to common theories on fertility behaviour. Our results do not provide support for the hypothesis of universally high fertility among the upper classes in pre-transitional society, but do support the idea that the upper classes acted as forerunners by reducing their fertility before other groups. Farmers and unskilled workers were the latest to start limiting their fertility. Apart from these similarities, patterns of class differences in fertility varied significantly between populations.

Impact of frequency and lateralization of interictal discharges on neuropsychological and fine motor status in children with benign epilepsy with centrotemporal spikes.

Despite a positive prognosis for seizure remission, children with benign epilepsy with centrotemporal spikes (BECTS) have been reported to exhibit subtle neuropsychological difficulties. We examined the relationship between patterns of centrotemporal spikes (the typical electroencephalography [EEG] finding in BECTS) and neuropsychological and motor outcomes in children with new-onset BECTS. Thirty-four patients with new-onset BECTS (not taking antiepileptic medication) and 48 typically developing children participated in the study. In BECTS patients, centrotemporal spikes (CTS) were evaluated in the first hour awake and first 2 h of sleep in a 24-h EEG recording and left or right-sided origin was noted. General intellectual function, language, visuospatial skill, processing speed, and fine motor skill were assessed in all participants. We found no significant difference between BECTS patients and controls on measures of general intellectual function, or visuospatial or language testing. There were significant differences in processing speed index and nondominant hand fine motor scores between groups. Significant negative relationships were observed between rates of left-sided CTS and right hand fine motor scores. This suggests that psychomotor and fine motor speed are affected in BECTS, but the extent of affected domains may be more limited than previously suggested, especially in untreated patients early in the course of their epilepsy.

Cognitive and behavioral outcomes in benign childhood epilepsy with centrotemporal spikes.

We review the evidence that BECTS may be associated with cognitive dysfunction and behavioral problems, the extent to which these problems may be associated with patterns of EEG abnormalities in BECTS, and the impact of antiepileptic medication on cognition and behavior in BECTS. A growing literature examining cognitive and behavioral outcomes suggests that children with BECTS perform below the level of their peers. Consistent with this, neuroimaging studies reveal that BECTS has an impact on structural and functional brain development, but the potential influence of frequency and lateralization of centrotemporal spikes (CTS) on cognition and behavior is not well understood. Treatment with AEDs is an option in BECTS, but existing studies have not clearly shown a clear relationship between elimination of CTS and improved cognitive or behavioral outcomes.

Occupation and fertility on the frontier: Evidence from the state of Utah.

BACKGROUND: Most of what we know about fertility decline in the United States comes from aggregate (often state or county level) data sources. It is difficult to identify variation in fertility change across socio-economic classes in such data, although understanding such variation would provide deeper insight into the history of the fertility transition. OBJECTIVE: We use rich micro-level data to examine differences across occupational classes in fertility levels and in the timing and pace of change in fertility in the US state of Utah in the late 19th and early 20th centuries. METHODS: Our evidence comes from the Utah Population Database, which contains several generations of linked family histories, including information on residents of Utah from the mid-1800s to the present. We use standard linear regression models to identify variation in fertility across birth cohorts and occupational classes as well as cohort-occupation interaction effects (to identify differences across classes in the pace of change over time). RESULTS: Families of white collar workers led changes in many fertility-related behaviors, particularly those tied to the start of family life (marriage age and first birth interval). Farm families had high fertility levels and added children into late ages, although they also experienced declining fertility. CONCLUSIONS: Examination of detailed micro-level data on fertility change identifies important differences in the patterns of change which may be tied to variation in relevant economic circumstances - for instance, the length of education and training required for particular occupations, or the need for family-based labor on the farm.

Diffusion Tensor Imaging Along Perivascular Spaces (DTI-ALPS) to Assess Effects of Age, Sex, and Head Size on Interstitial Fluid Dynamics in Healthy Subjects.

Diffusion tensor imaging along perivascular spaces (DTI-ALPS) is a novel MRI method for assessing brain interstitial fluid dynamics, potentially indexing glymphatic function. Failed glymphatic clearance is implicated in Alzheimer's disease (AD) pathophysiology. We assessed the contribution of age and female sex (strong AD risk factors) to DTI-ALPS index in healthy subjects. We also for the first time assessed the effect of head size. In accord with prior studies, we show reduced DTI-ALPS index with aging, and in men compared to women. However, head size may be a major contributing factor to this counterintuitive sex difference.

Reduction in Constitutively Activated Auditory Brainstem Microglia in Aging and Alzheimer's Disease.

Background: Alzheimer's disease (AD) pathology is considered to begin in the brainstem, and cerebral microglia are known to play a critical role in AD pathogenesis, yet little is known about brainstem microglia in AD. Translocator protein (TSPO) PET, sensitive to activated microglia, shows high signal in dorsal brainstem in humans, but the precise location and clinical correlates of this signal are unknown. Objective: To define age and AD associations of brainstem TSPO PET signal in humans. Methods: We applied new probabilistic maps of brainstem nuclei to quantify PET-measured TSPO expression over the whole brain including brainstem in 71 subjects (43 controls scanned using 11C-PK11195; 20 controls and 8 AD subjects scanned using 11C-PBR28). We focused on inferior colliculi (IC) because of visually-obvious high signal in this region, and potential relevance to auditory dysfunction in AD. We also assessed bilateral cortex. Results: TSPO expression was normally high in IC and other brainstem regions. IC TSPO was decreased with aging (p = 0.001) and in AD subjects versus controls (p = 0.004). In cortex, TSPO expression was increased with aging (p = 0.030) and AD (p = 0.033). Conclusions: Decreased IC TSPO expression with aging and AD-an opposite pattern than in cortex-highlights underappreciated regional heterogeneity in microglia phenotype, and implicates IC in a biological explanation for strong links between hearing loss and AD. Unlike in cerebrum, where TSPO expression is considered pathological, activated microglia in IC and other brainstem nuclei may play a beneficial, homeostatic role. Additional study of brainstem microglia in aging and AD is needed.

Oral methylphenidate normalizes cingulate activity in cocaine addiction during a salient cognitive task.

Anterior cingulate cortex (ACC) hypoactivations during cognitive demand are a hallmark deficit in drug addiction. Methylphenidate (MPH) normalizes cortical function, enhancing task salience and improving associated cognitive abilities, in other frontal lobe pathologies; however, in clinical trials, MPH did not improve treatment outcome in cocaine addiction. We hypothesized that oral MPH will attenuate ACC hypoactivations and improve associated performance during a salient cognitive task in individuals with cocaine-use disorders (CUD). In the current functional MRI study, we used a rewarded drug cue-reactivity task previously shown to be associated with hypoactivations in both major ACC subdivisions (implicated in default brain function) in CUD compared with healthy controls. The task was performed by 13 CUD and 14 matched healthy controls on 2 d: after ingesting a single dose of oral MPH (20 mg) or placebo (lactose) in a counterbalanced fashion. Results show that oral MPH increased responses to this salient cognitive task in both major ACC subdivisions (including the caudal-dorsal ACC and rostroventromedial ACC extending to the medial orbitofrontal cortex) in the CUD. These functional MRI results were associated with reduced errors of commission (a common impulsivity measure) and improved task accuracy, especially during the drug (vs. neutral) cue-reactivity condition in all subjects. The clinical application of such MPH-induced brain-behavior enhancements remains to be tested.

The evolution of economic and political inequality: minding the gap.

The extent of economic and political inequality, their change over time, and the forces shaping them have profound implications for the sustainability of a society and the well-being of its members. Here we review the evolution of economic and political inequality broadly, though with particular attention to Europe and the USA. We describe legal/institutional, technological and social forces that have shaped this evolution. We highlight the cumulative effects of inequality across generations as channelled through wealth and inheritance but also through other intergenerational connections. We also review the state of research on the effects of inequality on economic growth, health and societal cohesion. This article is part of the theme issue 'Evolutionary ecology of inequality'.

Association of Hoover's Sign with Maximal Expiratory-to-Inspiratory Pressure Ratio in Patients with COPD.

Purpose: In chronic obstructive pulmonary disease (COPD) some patients develop paradoxical inspiratory rib motion, which is termed Hoover's sign. Our objective was to determine whether Hoover's sign is associated with a difference in the maximal expiratory pressure (MEP), the maximal inspiratory pressure (MIP), the MEP/MIP ratio, and other features on pulmonary function tests (PFTs). Methods: This observational prospective single-center cohort study enrolled patients with an established diagnosis of COPD with Global initiative for chronic Obstructive Lung Disease (GOLD) stage 3 (severe) and 4 (very severe) based on PFTs. Respiratory pressure measurements were also collected. Patients were examined for the presence or absence of Hoover's sign on physical examination by 2 internal medicine resident physicians trained in examining for Hoover's sign by a pulmonologist. Results: A total of 71 patients were examined for the presence of Hoover's sign. Hoover's sign was present in 49.3% of patients. Observer agreement (k statistic) was 0.8 for Hoover's sign. Median MEP/MIP was significantly greater in patients with Hoover's sign than those without Hoover's sign (1.88 versus 1.16, p<0.001). Patients with Hoover's sign also had a significantly lower MIP (39.0 versus 58.0, p<0.001) and higher residual volume (RV) to total lung capacity (TLC) ratio indicating a higher degree of air trapping (65 versus 59.5, p<0.014). Conclusion: The presence of Hoover's sign in patients with COPD is associated with a higher MEP/MIP ratio. This suggests respiratory pressure measurements can predict diaphragm dysfunction in patients with GOLD stage 3 and 4 COPD. Patients with Hoover's sign were also found to have a lower MIP and more air trapping.

Functional Magnetic Resonance Imaging Activation During Unscripted Discourse in People With Poststroke Aphasia.

PURPOSE: The purpose of this project was to determine the feasibility of employing a functional magnetic resonance imaging (fMRI) task that captured activation associated with overt, unscripted (or free) discourse of people with aphasia (PWA), using a continuous scan paradigm. METHOD: Seven participants (six females, ages 48-70 years) with chronic poststroke aphasia underwent two fMRI scanning sessions that included a discourse fMRI paradigm that consisted of five 1-min picture description tasks, using personally relevant photographs, interspersed with two 30-s control periods where participants looked at a fixation cross. Audio during the continuous fMRI scan was collected and marked with speaking times and coded for correct information units. Activation maps from the fMRI data were generated for the contrast between speaking and control conditions. In order to show the effects of the multi-echo data analysis, we compared it to a single-echo analysis by using only the middle echo (echo time of 30 ms). RESULTS: Through the implementation of the free discourse fMRI task, we were able to elicit activation that included bilateral regions in the planum polare, central opercular cortex, precentral gyrus, superior temporal gyrus, middle temporal gyrus, superior temporal gyrus, Crus I of the cerebellum, as well as bilateral occipital regions. CONCLUSIONS: We describe a new tool for assessing discourse recovery in PWA. By demonstrating the feasibility of a natural language paradigm in patients with chronic, poststroke aphasia, we open a new area for future research.

ABCD_Harmonizer: An Open-source Tool for Mapping and Controlling for Scanner Induced Variance in the Adolescent Brain Cognitive Development Study.

Data from multisite magnetic resonance imaging (MRI) studies contain variance attributable to the scanner that can reduce statistical power and potentially bias results if not appropriately managed. The Adolescent Cognitive Brain Development (ABCD) study is an ongoing, longitudinal neuroimaging study acquiring data from over 11,000 children starting at 9-10 years of age. These scans are acquired on 29 different scanners of 5 different model types manufactured by 3 different vendors. Publicly available data from the ABCD study include structural MRI (sMRI) measures such as cortical thickness and diffusion MRI (dMRI) measures such as fractional anisotropy. In this work, we 1) quantify the variance attributable to scanner effects in the sMRI and dMRI datasets, 2) demonstrate the effectiveness of the data harmonization approach called ComBat to address scanner effects, and 3) present a simple, open-source tool for investigators to harmonize image features from the ABCD study. Scanner-induced variance was present in every image feature and varied in magnitude by feature type and brain location. For almost all features, scanner variance exceeded variability attributable to age and sex. ComBat harmonization was shown to effectively remove scanner induced variance from all image features while preserving the biological variability in the data. Moreover, we show that for studies examining relatively small subsamples of the ABCD dataset, the use of ComBat harmonized data provides more accurate estimates of effect sizes compared to controlling for scanner effects using ordinary least squares regression.

Neural Changes in Children With Residual Speech Sound Disorder After Ultrasound Biofeedback Speech Therapy.

PURPOSE: Children with residual speech sound disorders (RSSD) have shown differences in neural function for speech production, as compared to their typical peers; however, information about how these differences may change over time and relative to speech therapy is needed. To address this gap, we used functional magnetic resonance imaging (fMRI) to examine functional activation and connectivity on adaptations of the syllable repetition task (SRT-Early Sounds and SRT-Late Sounds) in children with RSSD before and after a speech therapy program. METHOD: Sixteen children with RSSD completed an fMRI experiment before (Time 1) and after (Time 2) a speech therapy program with ultrasound visual feedback for /ɹ/ misarticulation. Progress in therapy was measured via perceptual ratings of productions of untreated /ɹ/ word probes. To control for practice effects and developmental change in patterns of activation and connectivity, 17 children with typical speech development (TD) completed the fMRI at Time 1 and Time 2. Functional activation was analyzed using a region-of-interest approach and functional connectivity was analyzed using a seed-to-voxel approach. RESULTS: Children with RSSD showed a range of responses to therapy. After correcting for multiple comparisons, we did not observe any statistically significant cross-sectional differences or longitudinal changes in functional activation. A negative relationship between therapy effect size and functional activation in the left visual association cortex was on the SRT-Late Sounds after therapy, but it did not survive correction for multiple comparisons. Significant longitudinal changes in functional connectivity were observed for the RSSD group on SRT-Early Sounds and SRT-Late Sounds, as well as for the TD group on the SRT-Early Sounds. RSSD and TD groups showed connectivity differences near the left insula on the SRT-Late Sounds at Time 2. CONCLUSION: RSSD and treatment with ultrasound visual feedback may thus be associated with neural differences in speech motor and visual association processes recruited for speech production.

Augmented pain-evoked primary sensorimotor cortex activation in adolescent girls with juvenile fibromyalgia.

ABSTRACT: Juvenile fibromyalgia (JFM) is a chronic widespread pain condition that primarily affects adolescent girls. Previous studies have found increased sensitivity to noxious pressure in adolescents with JFM. However, the underlying changes in brain systems remain unclear. The aim of this study was to characterize pain-evoked brain responses and identify brain mediators of pain hypersensitivity in adolescent girls with JFM. Thirty-three adolescent girls with JFM and 33 healthy adolescent girls underwent functional magnetic resonance imaging scans involving noxious pressure applied to the left thumbnail at an intensity of 2.5 or 4 kg/cm 2 and rated pain intensity and unpleasantness on a computerized Visual Analogue Scale. We conducted standard general linear model analyses and exploratory whole-brain mediation analyses. The JFM group reported significantly greater pain intensity and unpleasantness than the control group in response to noxious pressure stimuli at both intensities ( P < 0.05). The JFM group showed augmented right primary somatosensory cortex (S1) activation to 4 kg/cm 2 (Z > 3.1, cluster-corrected P < 0.05), and the peak S1 activation magnitudes significantly correlated with the scores on the Widespread Pain Index ( r = 0.35, P = 0.048) with higher activation associated with more widespread pain. We also found that greater primary sensorimotor cortex activation in response to 4 kg/cm 2 mediated the between-group differences in pain intensity ratings ( P < 0.001). In conclusion, we found heightened sensitivity to noxious pressure stimuli and augmented pain-evoked sensorimotor cortex responses in adolescent girls with JFM, which could reflect central sensitization or amplified nociceptive input.