Naturalistic Bladder Filling Reveals Subtypes in Overactive Bladder Syndrome That Differentially Engages Urinary Urgency-Related Brain Circuits: Results From the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN).

PURPOSE: Overactive bladder (OAB) may be attributed to dysfunction in supraspinal brain circuits. Overactive bladder participants enrolled in the LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) study reported sensations of urinary urgency during a bladder-filling paradigm while undergoing brain functional MRI to map supraspinal dysfunction. MATERIALS AND METHODS: OAB participants and controls (CONs) completed 2 resting-state functional MRI scans following consumption of 350 mL water. Scans were conducted at fuller and emptier bladder states, interleaved with voiding. Urgency ratings (0-10) were assessed. Patterns of urgency during bladder filling were investigated using latent class trajectory models. Clusters of participants encompassing each pattern (ie, subtype) were derived from aggregated groups of OAB and CON independent of diagnosis. RESULTS: Two distinct patterns of urgency trajectories were revealed: first subtype with OAB and CON who were unresponsive to bladder filling (OAB-1 and CON-1) and second highly responsive subtype predominantly containing OAB (OAB-2). OAB-2 participants scored significantly higher on urinary symptoms but not pain or psychosocial measures. Neuroimaging analyses showed change in urgency due to both bladder filling and voided volume related to multiple loci of brain network connectivity in OAB-2, and in some cases, different than OAB-1 and/or CON-1. Sensorimotor to dorsomedial/dorsolateral prefrontal connectivity mediated the relationship between stimulus (voided volume) and percept (urgency) in OAB-2. CONCLUSIONS: Our results reveal different OAB subtypes with latent class trajectory models of urgency ratings during natural bladder filling. Functional MRI revealed differences in pathophysiology between subtypes, namely sensorimotor-prefrontal connectivity is a key locus in OAB patients with higher urinary symptoms.

Neurobiology and long-term impact of bladder-filling pain in humans: a Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) research network study.

ABSTRACT: Pain with bladder filling remains an unexplained clinical presentation with limited treatment options. Here, we aim to establish the clinical significance of bladder filling pain using a standardized test and the associated neural signature. We studied individuals diagnosed with urologic chronic pelvic pain syndrome (UCPPS) recruited as part of the multidisciplinary approach to the study of chronic pelvic pain (MAPP) study. Patients with urologic chronic pelvic pain syndrome (N = 429) and pain-free controls (N = 72) underwent a test in which they consumed 350 mL of water and then reported pain across an hour-long period at baseline and 6 months. We used latent class trajectory models of these pain ratings to define UCPPS subtypes at both baseline and 6 months. Magnetic resonance imaging of the brain postconsumption was used to examine neurobiologic differences between the subtypes. Healthcare utilization and symptom flare-ups were assessed over the following 18 months. Two distinct UCPPS subtypes were identified, one showing substantial pain related to bladder filling and another with little to no pain throughout the test. These distinct subtypes were seen at both baseline and 6 month timepoints. The UCPPS subtype with bladder-filling pain (BFP+) had altered morphology and increased functional activity in brain areas involved in sensory and pain processing. Bladder-filling pain positive status predicted increased symptom flare-ups and healthcare utilization over the subsequent 18 months when controlling for symptom severity and a self-reported history of bladder-filling pain. These results both highlight the importance of assessing bladder filling pain in heterogeneous populations and demonstrate that persistent bladder-filling pain profoundly affects the brain.

Reproducible Microstructural Changes in the Brain Associated With the Presence and Severity of Urologic Chronic Pelvic Pain Syndrome (UCPPS): A 3-Year Longitudinal Diffusion Tensor Imaging Study From the MAPP Network.

Microstructural alterations have been reported in patients with urologic chronic pelvic pain syndrome (UCPPS). However, it isn't clear whether these alterations are reproducible within 6 months or whether long-term symptom improvement is associated with specific microstructural changes. Using data from the MAPP-II Research Network, the current study performed population-based voxel-wise DTI and probabilistic tractography in a large sample of participants from the multicenter cohort with UCPPS (N = 364) and healthy controls (HCs, N = 61) over 36 months. While fractional anisotropy (FA) differences between UCPPS patients and HCs were observed to be unique at baseline and 6-month follow-up visits, consistent aberrations in mean diffusivity (MD) were observed between UCPPS and HCs at baseline and repeated at 6 months. Additionally, compared to HCs, UCPPS patients showed stronger structural connectivity (SC) between the left postcentral gyrus and the left precuneus, and weaker SC from the left cuneus to the left lateral occipital cortex and the isthmus of the left cingulate cortex at baseline and 6-month. By 36 months, reduced FA and MD aberrations in these same regions were associated with symptom improvement in UCPPS. Together, results suggest changes in white matter microstructure may play a role in the persistent pain symptoms in UCPPS. PERSPECTIVE: This longitudinal study identified reproducible, "disease-associated" patterns in altered mean diffusivity and abnormal microstructural connectivity in UCPPS comparing to HCs over 6 months. These differences were found in regions involved in sensory processing and integration and pain modulation, making it potentially amenable for clinical interventions that target synaptic and/or neuronal reorganization.

Effects of a 12-Week Periodized Resistance Training Program on Resting Brain Activity and Cerebrovascular Function: A Nonrandomized Pilot Trial.

Resistance training is a promising strategy to promote healthy cognitive aging; however, the brain mechanisms by which resistance training benefits cognition have yet to be determined. Here, we examined the effects of a 12-week resistance training program on resting brain activity and cerebrovascular function in 20 healthy older adults (14 females, mean age 69.1 years). In this single group clinical trial, multimodal 3 T magnetic resonance imaging was performed at 3 time points: baseline (preceding a 12-week control period), pre-intervention, and post-intervention. Along with significant improvements in fluid cognition (d = 1.27), 4 significant voxelwise clusters were identified for decreases in resting brain activity after the intervention (Cerebellum, Right Middle Temporal Gyrus, Left Inferior Parietal Lobule, and Right Inferior Parietal Lobule), but none were identified for changes in resting cerebral blood flow. Using a separate region of interest approach, we provide estimates for improved cerebral blood flow, compared with declines over the initial control period, in regions associated with cognitive impairment, such as hippocampal blood flow (d = 0.40), and posterior cingulate blood flow (d = 0.61). Finally, resistance training had a small countermeasure effect on the age-related progression of white matter lesion volume (rank-biserial = -0.22), a biomarker of cerebrovascular disease. These proof-of-concept data support larger trials to determine whether resistance training can attenuate or even reverse salient neurodegenerative processes.

Paired associative stimulation applied to the cortex can increase resting-state functional connectivity: A proof of principle study.

INTRODUCTION: There is emerging evidence that high Beta coherence (hBc) between prefrontal and motor corticies, measured with resting-state electroencephalography (rs-EEG), can be an accurate predictor of motor skill learning and stroke recovery. However, it remains unknown whether and how intracortical connectivity may be influenced using neuromodulation. Therefore, a cortico-cortico PAS (ccPAS) paradigm may be used to increase resting-state intracortical connectivity (rs-IC) within a targeted neural circuit. PURPOSE: Our purpose is to demonstrate proof of principle that ccPAS can be used to increase rs-IC between a prefrontal and motor cortical region. METHODS: Eleven non-disabled adults were recruited (mean age 26.4, sd 5.6, 5 female). Each participant underwent a double baseline measurement, followed by a real and control ccPAS condition, counter-balanced for order. Control and ccPAS conditions were performed over electrodes of the right prefrontal and motor cortex. Both ccPAS conditions were identical apart from the inter-stimulus interval (i.e ISI 5 ms: real ccPAS and 500 ms: control ccPAS). Whole brain rs-EEG of high Beta coherence (hBc) was acquired before and after each ccPAS condition and then analyzed for changes in rs-IC along the targeted circuit. RESULTS: Compared to ccPAS500 and baseline, ccPAS5 induced a significant increase in rs-IC, measured as coherence between electrodes over right prefrontal and motor cortex, (p <.05). CONCLUSION: These findings demonstrate proof of principle that ccPAS with an STDP derived ISI, can effectively increase hBc along a targeted circuit.

Impaired Ability to Relax Pelvic Floor Muscles in Men With Chronic Prostatitis/Chronic Pelvic Pain Syndrome.

OBJECTIVE: Excessive pelvic floor muscle activity has been suggested as a source of pain in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Our objective was to determine whether men with CP/CPPS have changes in neural drive that impair their ability to relax pelvic floor muscles. METHODS: We recruited 90 men (42 with CP/CPPS and 48 in the control group [without a history of pelvic pain]). All completed the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). We quantified the ability to relax by comparing resting pelvic floor muscle activity under 2 conditions: a "rest-only" condition, in which participants were instructed to simply relax, and a "rest-between-contraction" condition, in which participants were instructed to rest for several seconds between voluntary pelvic floor muscle contractions. We used multivariate mixed-effects models to examine differences between the groups (men with CP/CPPS and men in the control group) as well as the effect of 6 symptoms captured by the NIH-CPSI: pain related to location (perineum, testicles, penis, suprapubic region) and activity (urination, ejaculation). RESULTS: Men with CP/CPPS were significantly different from men in the control group; men with CP/CPPS had higher resting activity in the rest-between-contraction condition than in the rest-only condition, whereas men in the control group had similar resting activities in both conditions. This effect was strongest in men who reported ejaculation-related pain, which was 70% of the CP/CPPS group. CONCLUSION: Men without a history of pelvic pain were able to relax their pelvic floor muscles back to baseline after performing voluntary pelvic floor muscle contractions. In contrast, men with CP/CPPS, particularly those with ejaculation-related pain, had an impaired ability to relax their pelvic floor muscles. IMPACT: This study may support the investigation of more personalized physical therapist approaches for CP/CPPS that enhance the ability to relax pelvic floor muscles as a mechanism for pain reduction.

Analytic consistency and neural correlates of peak alpha frequency in the study of pain.

BACKGROUND: Several studies have found evidence of reduced resting-state peak alpha frequency (PAF) in populations with pain. However, the stability of PAF from different analytic pipelines used to study pain has not been determined and underlying neural correlates of PAF have not been validated in humans. NEW METHOD: For the first time we compare analytic pipelines and the relationship of PAF to activity in the whole brain and thalamus, a hypothesized generator of PAF. We collected resting-state functional magnetic resonance imaging (rs-fMRI) data and subsequently 64 channel resting-state electroencephalographic (EEG) from 47 healthy men, controls from an ongoing study of chronic prostatitis (a pain condition affecting men). We identified important variations in EEG processing for PAF from a review of 17 papers investigating the relationship between pain and PAF. We tested three progressively complex pre-processing pipelines and varied four postprocessing variables (epoch length, alpha band, calculation method, and region-of-interest [ROI]) that were inconsistent across the literature. RESULTS: We found a single principal component, well-represented by the average PAF across all electrodes (grand-average PAF), explained > 95% of the variance across participants. We also found the grand-average PAF was highly correlated among the pre-processing pipelines and primarily impacted by calculation method and ROI. Across methods, interindividual differences in PAF were correlated with rs-fMRI-estimated activity in the thalamus, insula, cingulate, and sensory cortices. CONCLUSIONS: These results suggest PAF is a relatively stable marker with respect to common pre and post-processing methods used in pain research and reflects interindividual differences in thalamic and salience network function.

Evidence for increased neuromuscular drive following spinal manipulation in individuals with subacromial pain syndrome.

BACKGROUND: Thoracic spinal manipulation can improve pain and function in individuals with shoulder pain; however, the mechanisms underlying these benefits remain unclear. Here, we evaluated the effects of thoracic spinal manipulation on muscle activity, as alteration in muscle activity is a key impairment for those with shoulder pain. We also evaluated the relationship between changes in muscle activity and clinical outcomes, to characterize the meaningful context of a change in neuromuscular drive. METHODS: Participants with shoulder pain related to subacromial pain syndrome (n = 28) received thoracic manipulation of low amplitude high velocity thrusts to the lower, middle and upper thoracic spine. Electromyographic muscle activity (trapezius-upper, middle, lower; serratus anterior; deltoid; infraspinatus) and shoulder pain (11-point scale) was collected pre and post-manipulation during arm elevation, and normalized to a reference contraction. Clinical benefits were assessed using the Pennsylvania Shoulder Score (Penn) at baseline and 2-3 days post-intervention. FINDINGS: A significant increase in muscle activity was observed during arm ascent (p = 0.002). Using backward stepwise regression analysis, a specific increase in the serratus anterior muscle activity during arm elevation explained improved Penn scores following post-manipulation (p < 0.05). INTERPRETATION: Thoracic spinal manipulation immediately increases neuromuscular drive. In addition, increased serratus anterior muscle activity, a key muscle for scapular motion, is associated with short-term improvements in shoulder clinical outcomes.

12 weeks of strength training improves fluid cognition in older adults: A nonrandomized pilot trial.

OBJECTIVES: Resistance training (RT) is a promising strategy to slow or prevent fluid cognitive decline during aging. However, the effects of strength-specific RT programs have received little attention. The purpose of this single-group proof of concept clinical trial was to determine whether a 12-week strength training (ST) program could improve fluid cognition in healthy older adults 60 to 80 years of age, and to explore concomitant physiological and psychological changes. METHODS: Twenty participants (69.1 ± 5.8 years, 14 women) completed this study with no drop-outs or severe adverse events. Baseline assessments were completed before an initial 12-week control period, then participants were re-tested at pre-intervention and after the 12-week ST intervention. The NIH Toolbox Cognition Battery and standard physical and psychological measures were administered at all three time points. During the 36 sessions of periodized ST (3 sessions per week), participants were supervised by an exercise specialist and challenged via autoregulatory load progression. RESULTS: Test-retest reliability over the control period was good for fluid cognition and excellent for crystallized cognition. Fluid composite scores significantly increased from pre- to post-intervention (8.2 ± 6.1%, p < 0.01, d = 1.27), while crystallized composite scores did not (-0.5 ± 2.8%, p = 0.46, d = -0.34). Performance on individual fluid instruments, including executive function, attention, working memory, and processing speed, also significantly improved. Surprisingly, changes in fluid composite scores had small negative correlations with changes in muscular strength and sleep quality, but a small positive correlation with changes in muscular power. CONCLUSIONS: Thus, improvements in fluid cognition can be safely achieved in older adults using a 12-week high-intensity ST program, but further controlled studies are needed to confirm these findings. Furthermore, the relationship with other widespread physiological and psychological benefits remains unclear.

Corticomotor excitability of gluteus maximus and hip extensor strength: The influence of sex.

PURPOSE: To compare hip extensor strength and corticomotor excitability (CME) of gluteus maximus (GM) between males and females. A secondary purpose was to determine if CME of GM is predictive of hip extensor strength. METHOD: Thirty-two healthy individuals participated (15 males and 17 females). CME of GM was assessed using the input-output curve (IOC) procedure acquired from transcranial magnetic stimulation (average slope). Hip extensor strength was measured by a dynamometer during a maximal voluntary isometric contraction. Independent t-tests were used to compare CME of GM and peak hip extensor torque between males and females. Linear regression analysis was used to determine whether peak hip extensor torque was predicted by CME of GM. RESULT: Compared to males, females demonstrate lower peak hip extensor torque (4.42 ± 1.11 vs. 6.15 ± 1.72 Nm/kg/m2, p < 0.01) and lower CME of GM (1.36 ± 1.07 vs. 2.67 ± 1.30, p < 0.01). CME of GM was a significant predictor of peak hip extensor torque for males and females combined (r2 = 0.36, p < 0.001). CONCLUSION: Our findings support the premise that corticomotor excitability plays a role in the ability of a muscle to generate torque.

Individuals with recurrent low back pain exhibit further altered frontal plane trunk control in remission than when in pain.

BACKGROUND: Movement alterations due to low back pain (LBP) could lead to long-term adverse consequences if they do not resolve after symptoms subside. This study aims to determine if altered trunk control associated with recurrent low back pain persists beyond symptom duration. METHODS: Twenty young adults with recurrent LBP were tested once during an LBP episode and once in symptom remission, and twenty matched back-healthy participants served as controls. Participants walked on a treadmill with five prescribed step widths (0.33, 0.67, 1, 1.33, 1.67 × preferred step width). Motion capture and surface electromyography were used to record trunk kinematics and muscle activation. Thorax-pelvis coordination was calculated using vector coding, and longissimus activation and co-activation were analyzed. FINDINGS: Young adults with recurrent LBP exhibited a "looser" trunk control strategy in the frontal plane during gait that was persistent regardless of pain status across multiple step widths compared to controls. The looser trunk control was demonstrated by a greater pelvis-only, less thorax-only coordination pattern, and decreased bilateral longissimus co-activation in individuals with recurrent LBP compared to controls. The looser trunk control strategy was further amplified when individuals were in symptom remission and exhibited greater trunk excursion and reduced in-phase coordination in the frontal plane. INTERPRETATION: The amplification of aberrant movement during symptom remission may suggest that movement patterns or anatomical factors existing prior to the tested painful episode underlie altered trunk control in individuals with recurrent LBP. The symptom remission period of recurrent LBP may be a critical window into clinical evaluation and treatment.

Cerebral Perfusion and Sensory Testing Results Differ in Interstitial Cystitis/Bladder Pain Syndrome Patients with and without Fibromyalgia: A Site-Specific MAPP Network Study.

PURPOSE: Fibromyalgia is a common co-morbidity in patients with interstitial cystitis/bladder pain syndrome. Quantitative sensory testing measures and regional cerebral blood flow measures have been noted to differ from healthy controls in both subjects with fibromyalgia and those with interstitial cystitis when studied independently. The present study examined such measures in subjects with the diagnosis of interstitial cystitis both with and without the co-diagnosis of fibromyalgia to determine whether differences in these measures may be associated with co-morbidity. PATIENTS AND METHODS: Female subjects with the diagnosis of interstitial cystitis with (n = 15) and without (n = 19) the co-diagnosis of fibromyalgia as well as healthy control subjects (n = 41) underwent quantitative sensory testing. A subset of these patients (9 with and 9 without fibromyalgia) underwent brain perfusion studies using arterial spin labeled functional magnetic resonance imaging. An analysis was performed of absolute regional cerebral blood flow of regions-of-interest when experiencing a full bladder compared with an empty bladder. RESULTS: Subjects with both interstitial cystitis and fibromyalgia were more hypersensitive than those without fibromyalgia as well as healthy controls in most sensory measures except heat. Subjects with interstitial cystitis, but no fibromyalgia, differed from healthy controls only in toleration of the ischemic forearm task. Other co-morbidities were more common in those subjects with both interstitial cystitis and fibromyalgia. Bladder fullness was associated with significantly greater whole brain gray matter blood flow in subjects with interstitial cystitis and fibromyalgia when compared with that of subjects with interstitial cystitis without fibromyalgia. Examination of regional cerebral blood flow in individual regions-of-interest demonstrated statistically significant differences between the subjects with interstitial cystitis with and those without fibromyalgia bilaterally in the thalamus, amygdala and hippocampus, as well as the right prefrontal cortex and greater responsiveness to changes in bladder fullness in the insula. CONCLUSION: Quantitative sensory testing and brain perfusion data support that there are two phenotypes of interstitial cystitis patients, which can be differentiated by a co-diagnosis of fibromyalgia. This may affect responsiveness to treatment and suggest the utility of stratifying interstitial cystitis patients according to their co-morbidities.

Natural bladder filling alters resting brain function at multiple spatial scales: a proof-of-concept MAPP Network Neuroimaging Study.

Neural circuitry regulating urine storage in humans has been largely inferred from fMRI during urodynamic studies driven by catheter infusion of fluid into the bladder. However, urodynamic testing may be confounded by artificially filling the bladder repeatedly at a high rate and examining associated time-locked changes in fMRI signals. Here we describe and test a more ecologically-valid paradigm to study the brain response to bladder filling by (1) filling the bladder naturally with oral water ingestion, (2) examining resting state fMRI (rs-fMRI) which is more natural since it is not linked with a specific stimulus, and (3) relating rs-fMRI measures to self-report (urinary urge) and physiologic measures (voided volume). To establish appropriate controls and analyses for future clinical studies, here we analyze data collected from healthy individuals (N = 62) as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. Participants orally ingested approximately 350 mL of water, and had a 10 min "fuller bladder" rs-fMRI scan approximately 1 h later. A second 10 min "empty bladder" rs-fMRI scan was conducted immediately following micturition. We examined multiple spatial scales of brain function, including local activity, circuits, and networks. We found changes in brain function distributed across micturition loci (e.g., subregions of the salience, sensorimotor, and default networks) that were significantly related to the stimulus (volume) and response (urinary urge). Based on our results, this paradigm can be applied in the future to study the neurobiological underpinnings of urologic conditions.

Sensitivity of functional connectivity to periaqueductal gray localization, with implications for identifying disease-related changes in chronic visceral pain: A MAPP Research Network neuroimaging study.

Previous studies examining the resting-state functional connectivity of the periaqueductal gray (PAG) in chronic visceral pain have localized PAG coordinates derived from BOLD responses to provoked acute pain. These coordinates appear to be several millimeters anterior of the anatomical location of the PAG. Therefore, we aimed to determine whether measures of PAG functional connectivity are sensitive to the localization technique, and if the localization approach has an impact on detecting disease-related differences in chronic visceral pain patients. We examined structural and resting-state functional MRI (rs-fMRI) images from 209 participants in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network study. We applied three different localization techniques to define a region-of-interest (ROI) for the PAG: 1) a ROI previously-published as a Montreal Neurological Institute (MNI) coordinate surrounded by a 3 mm radius sphere (MNI-sphere), 2) a ROI that was hand-traced over the PAG in a MNI template brain (MNI-trace), and 3) a ROI that was hand-drawn over the PAG in structural images from 30 individual participants (participant-trace). We compared the correlation among the rs-fMRI signals from these PAG ROIs, as well as the functional connectivity of these ROIs with the whole brain. First, we found important non-uniformities in brainstem rs-fMRI signals, as rs-fMRI signals from the MNI-trace ROI were significantly more similar to the participant-trace ROI than to the MNI-sphere ROI. We then found that choice of ROI also impacts whole-brain functional connectivity, as measures of PAG functional connectivity throughout the brain were more similar between MNI-trace and participant-trace compared to MNI-sphere and participant-trace. Finally, we found that ROI choice impacts detection of disease-related differences, as functional connectivity differences between pelvic pain patients and healthy controls were much more apparent using the MNI-trace ROI compared to the MNI-sphere ROI. These results indicate that the ROI used to localize the PAG is critical, especially when examining brain functional connectivity changes in chronic visceral pain patients.

The probability of choosing both hands depends on an interaction between motor capacity and limb-specific control in chronic stroke.

A goal of rehabilitation after stroke is to promote pre-stroke levels of arm use for every day, frequently bimanual, functional activities. We reasoned that, after a stroke, the choice to use one or both hands for bimanual tasks might depend not only on residual motor capacity, but also the specialized demands imposed by the task on the paretic hand. To capture spontaneous, task-specific choices, we covertly observed 50 pre-stroke right-handed chronic stroke survivors (25 each of left, LHD, and right-hemisphere damage, RHD) and 11 age-similar control adults and recorded their hand use strategies for two pairs of bimanual tasks with distinct demands: one with greater precision requirements (photo-album tasks), and another with greater stabilization requirements (letter-envelope tasks). The primary outcome was the choice to use one or both hands. Logistic regression was used to test the two hypotheses that the probability of choosing a bimanual strategy would be greater in those with less severe motor impairment and also in those with LHD. When collapsed across the four tasks, we found support for these hypotheses. Notably, however, the influence of these factors on bimanual choice varied based on task demands. For the photo-album pair, the probability of a bimanual strategy was greater for those with LHD compared to RHD, regardless of the degree of motor impairment. For the letter-envelope pair, we found a significant interaction between impairment and side of lesion in determining the likelihood of choosing both hands. Therefore, the manner in which side of lesion moderates the effect of impairment on hand use depends on the task.

Salience network functional connectivity is spatially heterogeneous across sensorimotor cortex in healthy humans.

The salience network is responsive during a range of conditions requiring immediate behavioral responses, including pain processing. Resting-state functional connectivity of the salience network to the sensorimotor cortex is altered in chronic pain. However, little is understood about their fundamental communication in the absence of pain. In this study, we mapped salience network resting-state functional connectivity across sensorimotor cortex in healthy individuals. Using electromyography and task-based functional magnetic resonance imaging (fMRI), we first localized distinct regions-of-interest across sensorimotor cortex in medial (gluteal), intermediate (shoulder), and lateral (hand) areas. We then used resting-state fMRI for two cohorts (primary and replication) of healthy individuals from public repositories to map salience network resting-state functional connectivity across sensorimotor cortex. Both the primary and replication cohorts exhibited significant heterogeneity in salience network resting-state functional connectivity across the sensorimotor regions-of-interest. Using a cortical flatmap to visualize the entire sensorimotor surface, we observed similar heterogeneity in both cohorts. In general, the somatotopic representation of proximal body regions (trunk/face) had higher salience network resting-state functional connectivity compared to distal body regions (upper/lower limbs). We conclude that sensorimotor cortex is spatially heterogeneous in its interaction with the salience network in healthy individuals.

The Multidisciplinary Approach to The Study of Chronic Pelvic Pain (MAPP) Research Network*: Design and implementation of the Symptom Patterns Study (SPS).

AIMS: The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network initiated a second observational cohort study-the Symptom Patterns Study (SPS)-to further investigate the underlying pathophysiology of Urologic Chronic Pelvic Pain Syndrome (UCPPS) and to discover factors associated with longitudinal symptom changes and responses to treatments. METHODS: This multisite cohort study of males and females with UCPPS features a run-in period of four weekly web-based symptom assessments before a baseline visit, followed by quarterly assessments up to 36 months. Controls were also recruited and assessed at baseline and 6 months. Extensive clinical data assessing urological symptoms, nonurological pain, chronic overlapping pain syndromes, and psychosocial factors were collected. Diverse biospecimens for biomarker and microbiome studies, quantitative sensory testing (QST) data under multiple stimuli, and structural and functional neuroimaging scans were obtained under a standardized protocol. RESULTS: Recruitment was initiated (July 2015) and completed (February 2019) at six discovery sites. A total of 620 males and females with UCPPS and 73 Controls were enrolled, including 83 UCPPS participants who re-enrolled from the first MAPP Network cohort study (2009-2012). Baseline neuroimaging scans, QST measures, and biospecimens were obtained on 578 UCPPS participants. The longitudinal follow-up of the cohort is ongoing. CONCLUSIONS: This comprehensive characterization of a large UCPPS cohort with extended follow-up greatly expands upon earlier MAPP Network studies and provides unprecedented opportunities to increase our understanding of UCPPS pathophysiology, factors associated with symptom change, clinically relevant patient phenotypes, and novel targets for future interventions.

When 90% of the variance is not enough: residual EMG from muscle synergy extraction influences task performance.

Muscle synergies are usually identified via dimensionality reduction techniques, such that the identified synergies reconstruct the muscle activity to an accuracy level defined heuristically, often set to 90% of the variance. Here, we question the assumption that the residual muscle activity not explained by the synergies is due to noise. We hypothesize instead that the residual activity is not entirely random and can influence the execution of motor tasks. Young healthy subjects performed an isometric reaching task in which the surface electromyography of 10 arm muscles was mapped onto a two-dimensional force used to control a cursor. Three to five synergies explained 90% of the variance in muscle activity. We altered the muscle-force mapping via "hard" and "easy" virtual surgeries. Whereas in both surgeries the forces associated with synergies spanned the same dimension of the virtual environment, the muscle-force mapping was as close as possible to the initial mapping in the easy surgery; in contrast, it was as far as possible in the hard surgery. This design maximized potential differences in reaching errors attributable to residual activity. Results show that the easy surgery produced smaller directional errors than the hard surgery. Additionally, simulations of surgeries constructed with 1 to 10 synergies show that the errors in the easy and hard surgeries differ significantly for up to 8 synergies, which explains 98% of the variance on average. Our study thus indicates the need for cautious interpretations of results derived from synergy extraction techniques based on heuristics with lenient accuracy levels.NEW & NOTEWORTHY The muscle synergy hypothesis posits that the central nervous system simplifies motor control by grouping muscles into modules. Current techniques use dimensionality reduction, such that the identified synergies reconstruct 90% of the muscle activity. We show that residual muscle activity following such identification can have a large systematic effect on movements, even when the number of synergies approaches the number of muscles. Current synergy extraction techniques must therefore be updated to identify true physiological synergies.

Relationship between Interhemispheric Inhibition and Dexterous Hand Performance in Musicians and Non-musicians.

Interhemispheric inhibition (IHI) is essential for dexterous motor control. Small previous studies have shown differences in IHI in musicians compared to non-musicians, but it is not clear whether these differences are robustly linked to musical performance. In the largest study to date, we examined IHI and comprehensive measures of dexterous bimanual performance in 72 individuals (36 musicians and 36 non-musicians). Dexterous bimanual performance was quantified by speed, accuracy, and evenness derived from a series of hand tasks. As expected, musicians significantly outperformed non-musicians. Surprisingly, these performance differences could not be simply explained by IHI, as IHI did not significantly differ between musicians and non-musicians. However, canonical correlation analysis revealed a significant relationship between combinations of IHI and performance variables in the musician group. Specifically, we identified that IHI may contribute to the maintenance of evenness regardless of speed, a feature of musical performance that may be driven by practice with a metronome. Therefore, while IHI changes by themselves may not be sufficient to explain superior hand dexterity exhibited by musicians, IHI may be a potential neural correlate for specific features of musical performance.