Assessment of spinal cord injury using ultrasound elastography in a rabbit model in vivo.

The effect of the mechanical micro-environment on spinal cord injury (SCI) and treatment effectiveness remains unclear. Currently, there are limited imaging methods that can directly assess the localized mechanical behavior of spinal cords in vivo. In this study, we apply new ultrasound elastography (USE) techniques to assess SCI in vivo at the site of the injury and at the time of one week post injury, in a rabbit animal model. Eleven rabbits underwent laminectomy procedures. Among them, spinal cords of five rabbits were injured during the procedure. The other six rabbits were used as control. Two neurological statuses were achieved: non-paralysis and paralysis. Ultrasound data were collected one week post-surgery and processed to compute strain ratios. Histologic analysis, mechanical testing, magnetic resonance imaging (MRI), computerized tomography and MRI diffusion tensor imaging (DTI) were performed to validate USE results. Strain ratios computed via USE were found to be significantly different in paralyzed versus non-paralyzed rabbits. The myelomalacia histologic score and spinal cord Young's modulus evaluated in selected animals were in good qualitative agreement with USE assessment. It is feasible to use USE to assess changes in the spinal cord of the presented animal model. In the future, with more experimental data available, USE may provide new quantitative tools for improving SCI diagnosis and prognosis.

The effect of oral medications on fMRI brain activation: A randomized, double blind, controlled pilot trial of older women with overactive bladder.

INTRODUCTION AND AIM: Observational studies have associated oral anticholinergic medications for overactive bladder (OAB) with cognitive impairment. This is the first pilot trial to compare the effects of two classes of OAB medications on brain activity in women. We evaluated the effect of anticholinergic versus non-anticholinergic (Non-Ach) interventions on regional brain activation during a cognitive task. METHODS: Twelve cognitively normal women seeking OAB therapy were recruited to a randomized, double-blind, parallel, controlled pilot trial. Whole-brain regional activity at baseline and 29 ± 1 days postintervention was assessed with functional magnetic resonance imaging during a working memory task. Average activation strength by region was compared after anticholinergic, beta-3 agonist, or placebo. Two-way ANOVA compared effects of group and time on average activation strength in anticholinergic versus Non-Ach (beta-3 agonists or placebo) groups. RESULTS: The mean (SD) age and body mass index of 12 women were 61 (7) years and 36 (7) kg/m2. Baseline depression and learning scores differed in the anticholinergic group (n = 3) versus the Non-Ach group (n = 9). Right mamillary body activation postintervention was higher after Non-Ach exposure (F 4.9, p < 0.04). In the full sample of participants at follow-up, there was less activation of the right middle frontal gyrus (p = 0.02), superior frontal gyrus (p < 0.01), and supramarginal (p < 0.01) gyrus. CONCLUSION: Activation strength in brain regions underlying working memory was lower over time, and recognition scores improved. A powered trial is needed to adequately evaluate for differential effects of OAB oral medications on regional brain activation.

Predictors for outcomes of noninvasive, individualized transcranial magnetic neuromodulation in multiple sclerosis women with neurogenic voiding dysfunction.

Purpose: Multiple sclerosis (MS) is a multifocal demyelinating disease that affects the central nervous system (CNS) and commonly leads to neurogenic lower urinary tract dysfunction (NLUTD). Proper storage and release of urine relies on synchronized activity of the LUT, which is meticulously regulated by supraspinal circuits, making it vulnerable to diseases such as MS. NLUTD, characterized by voiding dysfunction (VD), storage issues, or a combination of both is a common occurrence in MS. Unfortunately, there are limited treatment options for NLUTD, making the search for alternative treatments such as transcranial rotating permanent magnet stimulation (TRPMS) of utmost importance. To assess effectiveness of treatment we also need to understand underlying factors that may affect outcomes, which we addressed here. Methods: Ten MS subjects with VD and median age of 54.5 years received daily TRPMS sessions for two weeks. Five pre-determined regions of interest (ROIs) known to be involved in the micturition cycle were modulated (stimulated or inhibited) using TRPMS. Clinical data (non-instrumented uroflow and urodynamics parameters, PVR, bladder symptom questionnaires) and neuro-imaging data were collected at baseline and following TRPMS via 7-Tesla Siemens MAGNETOM Terra magnetic resonance imaging (MRI) scanner. Each participant underwent functional MRI (fMRI) concurrently with a repeated urodynamic study (UDS). Baseline data of each arm was evaluated to determine any indicators of successful response to treatment.

White Matter Integrity in Men With Benign Prostatic Hyperplasia and Bladder Outlet Obstruction and Its Contribution to Lower Urinary Tract Symptoms.

PURPOSE: Lower urinary tract symptoms (LUTS) associated with bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH) can negatively impact quality of life. We evaluated the structural connectivity of the brain in men with BPH with chronic BOO using diffusion tensor imaging (DTI). METHODS: Ambulatory male patients aged ≥45 years with BPH and BOO were recruited. LUTS was defined as an International Prostate Symptom Score (IPSS) ≥12 and a maximum urinary flow rate ≤15 mL/sec. Upon recruitment, uroflowmetry and validated questionnaires regarding bladder status were collected. DTI images from each subject were aligned with the ICBM-DTI-81 atlas, defining 50 white matter tracts (WMTs). The mean values of DTI parameters-fractional anisotropy and mean diffusivity-for each WMT were extracted. These measures were then utilized to compute Pearson correlation coefficients with clinical parameters. Objective clinical parameters included uroflowmetry parameters, postvoid residual (PVR) volume, and bladder capacity. Subjective clinical parameters were assessed using validated questionnaires: the IPSS, Incontinence Symptom Index, and Sexual Health Inventory for Men. RESULTS: The correlation analysis revealed 15 WMTs that showed statistically significant associations (P<0.05) with objective and subjective clinical parameters. Eight tracts were associated with uroflowmetry parameters: maximum flow rate (Qmax), mean flow rate (Qmean), and PVR. Among these tracts, the middle cerebellar peduncles and left medial lemniscus were associated with Qmax; the genu of the corpus callosum, left superior corona radiata, corticospinal tract, right medial lemniscus, posterior corona radiata with Qmean; and the left posterior corona radiata with PVR. Seven tracts also demonstrated significant associations with the IPSS. CONCLUSION: Our results suggest correlations between the preserved white matter integrity of specific WMTs and the severity of LUTS based on objective and subjective clinical parameters, leading us to believe that a distinct pathology of the central nervous system might exist.

Transcutaneous spinal stimulation alters cortical and subcortical activation patterns during mimicked-standing: A proof-of-concept fMRI study.

Transcutaneous spinal stimulation (TSS) is a non-invasive neuromodulation technique that has been used to facilitate the performance of voluntary motor functions such as trunk control and self-assisted standing in individuals with spinal cord injury. Although it is hypothesized that TSS amplifies signals from supraspinal motor control networks, the effect of TSS on supraspinal activation patterns is presently unknown. The purpose of this study was to investigate TSS-induced activity in supraspinal sensorimotor regions during a lower-limb motor task. Functional magnetic resonance imaging (fMRI) was used to assess changes in neural activation patterns as eleven participants performed mimicked-standing movements in the scanner. Movements were performed without stimulation, as well as in the presence of (1) TSS, (2) stimulation applied to the back muscle, (3) paresthesia stimulation, and (4) neuromuscular electrical stimulation. TSS was associated with greater activation in subcortical and cortical sensorimotor regions involved in relay and processing of movement-related somatosensory information (e.g., thalamus, caudate, pallidum, putamen), as compared to the other stimulation paradigms. TSS also resulted in deactivation in both nucleus accumbens and posterior parietal cortex, suggesting a shift toward somatosensory feedback-based mechanisms and more reflexive motor control. Together, these findings demonstrate that spinal stimulation can alter the activity within supraspinal sensorimotor networks and promote the use of somatosensory feedback, thus providing a plausible neural mechanism for the stimulation-induced improvements of sensorimotor function observed in participants with neurological injuries and disorders.

A Novel Approach to Estimating the Cortical Sources of Sleep Spindles Using Simultaneous EEG/MEG.

Sleep spindles, defining oscillations of stage II non-rapid eye movement sleep (N2), mediate sleep-dependent memory consolidation. Spindles are disrupted in several neurodevelopmental, neuropsychiatric, and neurodegenerative disorders characterized by cognitive impairment. Increasing spindles can improve memory suggesting spindles as a promising physiological target for the development of cognitive enhancing therapies. This effort would benefit from more comprehensive and spatially precise methods to characterize spindles. Spindles, as detected with electroencephalography (EEG), are often widespread across electrodes. Available evidence, however, suggests that they act locally to enhance cortical plasticity in the service of memory consolidation. Here, we present a novel method to enhance the spatial specificity of cortical source estimates of spindles using combined EEG and magnetoencephalography (MEG) data constrained to the cortex based on structural MRI. To illustrate this method, we used simultaneous EEG and MEG recordings from 25 healthy adults during a daytime nap. We first validated source space spindle detection using only EEG data by demonstrating strong temporal correspondence with sensor space EEG spindle detection (gold standard). We then demonstrated that spindle source estimates using EEG alone, MEG alone and combined EEG/MEG are stable across nap sessions. EEG detected more source space spindles than MEG and each modality detected non-overlapping spindles that had distinct cortical source distributions. Source space EEG was more sensitive to spindles in medial frontal and lateral prefrontal cortex, while MEG was more sensitive to spindles in somatosensory and motor cortices. By combining EEG and MEG data this method leverages the differential spatial sensitivities of the two modalities to obtain a more comprehensive and spatially specific source estimation of spindles than possible with either modality alone.

Supraspinal Neural Changes in Men With Benign Prostatic Hyperplasia Undergoing Bladder Outlet Procedures: A Pilot Functional MRI Study.

OBJECTIVE: To explore brain activation patterns on functional MRI (fMRI) in men with BPH and BOO before and after outlet obstruction procedures. METHODS: Men age ≥45 who failed conservative BPH therapy planning to undergo BOO procedures were recruited. Eligible men underwent a concurrent fMRI/urodynamics testing before and 6 months after BOO procedure. fMRI images were obtained via 3 Tesla MRI. Significant blood-oxygen-level-dependent (BOLD) signal activated voxels (P <.05) were identified at strong desire to void and (attempt at) voiding initiation pre- and post-BOO procedure. RESULTS: Eleven men were enrolled, of which 7 men completed the baseline scan, and 4 men completed the 6-month follow-up scan. Baseline decreased BOLD activity was observed in right inferior frontal gyrus (IFG), bilateral insula, inferior frontal gyrus (IFG) and thalamus. Significant changes in BOLD signal activity following BOO procedures were observed in the insula, IFG, and cingulate cortices. CONCLUSIONS: This represents a pilot study evaluating cortical activity in men with BPH and BOO. Despite limitations we found important changes in supraspinal activity in men with BPH and BOO during filling and emptying phases at baseline and following BOO procedure, with the potential to improve our understanding of neuroplasticity secondary to BPH and BOO. This preliminary data may serve as the foundation for larger future trials.

Altered bladder-related brain network in multiple sclerosis women with voiding dysfunction.

OBJECTIVES: A number of neurourology imaging studies have mainly focused on investigating the brain activations during micturition in healthy and neuropathic patients. It is, however, also necessary to study brain functional connectivity (FC) within bladder-related regions to understand the brain organization during the execution of bladder function. This study aims to identify the altered brain network associated with bladder function in multiple sclerosis (MS) women with voiding dysfunction through comparisons with healthy subjects via concurrent urodynamic study (UDS)/functional magnetic resonance imaging (fMRI). MATERIALS AND METHODS: Ten healthy adult women and nine adult ambulatory women with clinically stable MS for ≥6 months and symptomatic voiding phase neurogenic lower urinary tract dysfunction (NLUTD) underwent UDS/fMRI evaluation with a task of bladder filling/emptying that was repeated three to five times. We quantitatively compared their FC within 17 bladder-related brain regions during two UDS phases: "strong desire to void" and "(attempt at) voiding initiation." RESULTS: At "strong desire to void," the healthy group showed significantly stronger FC in regions involved in bladder filling and suppression of voiding compared to the patient group. These regions included the bilateral anterior cingulate cortex, right supplementary motor area, and right middle frontal gyrus. During "(attempt at) voiding initiation," healthy subjects exhibited stronger FC in the right inferior frontal gyrus compared to MS patients. CONCLUSION: Our study offers a new way to identify alterations in the neural mechanisms underlying NLUTD and provides potential targets for clinical interventions (such as cortical neuromodulation) aimed at restoring bladder functions in MS patients.

Modeling Flow Diverters Using a Porous Medium Approach: A Fast Alternative to Virtual Flow Diverter Deployment.

BACKGROUND: The Tubridge flow diverter (FD) (MicroPort Medical Co. Ltd., Shanghai, China) is a novel device aimed at reconstructing the parent artery and eliminating the aneurysm. Numerical simulations based on virtual FD deployment allow the assessment of the complex nature of aneurismal flow changes before the actual intervention but are demanding on computational resources. Here, we evaluate an alternative strategy of modeling FD effects for the Tubridge system using a porous medium. The goal of this study is to reduce demands on time and complexity of the simulation procedure for applications in clinical research. METHODS: Ten patient-specific aneurysm models were reconstructed from retrospectively collected diagnostic 3-dimensional digital subtraction angiographic images. Virtual FDs were deployed (SolidWorks, Dassault Systems, Concord, Massachusetts, USA; Meshmixer, Autodesk, San Rafael, California, USA) and corresponding porous medium patches were constructed at the ostium with a research computational fluid dynamics prototype (Siemens Healthineers, Forchheim, Germany). Hemodynamic conditions were simulated in 2 approaches. RESULTS: Hemodynamics inside the aneurysm based on these 2 approaches were compared. Both approaches yielded similar results. Mean wall shear stress and mean pressure of the aneurysmal wall correlated significantly (r = 0.8, r = 1.0, P < 0.05) as did mean velocity and mean pressure at a region inside the aneurysm, at the ostium and at a cross section containing the main vertex (for velocities r = 0.9; for pressures r = 1.0, P < 0.05). The use of porous medium patches reduced the preparation and simulation time together by approximately 50%. CONCLUSIONS: Using a porous medium approach yields comparable mean values for hemodynamic alterations compared to direct virtual FD simulations. Additionally, the porous medium approach greatly reduced the modeling complexity and computation time.

Alterations in brain activation patterns in women with functional defecatory disorder: A novel fMRI rectal balloon expulsion study.

BACKGROUND: Functional defecatory disorders (FDD) are common among women. Despite the extensive research on peripheral mechanisms involved in FDD, the central-neural contribution to its pathophysiology remains poorly understood. We aimed to delineate specific supra-spinal regions involved in defecation and examine whether their activity, as measured by blood-oxygen-level-dependent (BOLD) signals, is different in FDD. METHODS: We performed functional MRI (fMRI) with concurrent rectal manometry in 15 controls and 18 females with ROME III diagnosis of FDD. A block design was used and brain activation maps based on BOLD effect employing the generalized linear model were calculated for each subject. Statistical significance between groups was assessed by a Student t-test with cluster-based multiple comparisons correction (corrected p < 0.01). KEY RESULTS: Simulated defecation was associated with activation of regions of primary and supplementary motor (SMA) and somatosensory cortices, homeostatic afferent (thalamus, mid-cingulate cortex, and insula), and emotional arousal networks (hippocampus and prefrontal cortex), occipital and cerebellum along with deactivation of right anterior cingulate cortex (ACC) in controls. Women with FDD had fewer regions engaged in defecation and BOLD activation was much decreased is areas related to executive-cognitive function (insula, parietal, and prefrontal cortices). Patients unlike controls showed activation in right ACC and otherwise had similar brain activation patterns during anal squeeze. CONCLUSIONS & INFERENCES: Our results provide evidence that distinct differences exist in supra-spinal control of defecation in key regions of motivational-affective regulation and executive-cognitive function, in patients with FDD as compared to controls.

Noninvasive, Individualized Cortical Modulation Using Transcranial Rotating Permanent Magnet Stimulator for Voiding Dysfunction in Women with Multiple Sclerosis: A Pilot Trial.

PURPOSE: Voiding dysfunction (VD) leading to urinary retention is a common neurogenic lower urinary tract symptom in patients with multiple sclerosis (MS). Currently, the only effective management for patients with MS with VD is catheterization. Transcranial Rotating Permanent Magnet Stimulator (TRPMS) is a noninvasive, portable, multifocal neuromodulator that simultaneously modulates multiple cortical regions and the strength of their functional connections. In this pilot trial (ClinicalTrials.gov Identifier: NCT03574610), we investigated the safety and therapeutic effects of TRPMS in modulating brain regions of interest (ROIs) engaged with voiding initiation to improve VD in MS women. MATERIALS AND METHODS: Ten MS women with VD (having % post-void residual/bladder capacity [%PVR/BC] ≥40% or being in the lower 10th percentile of the Liverpool nomogram) underwent concurrent functional magnetic resonance imaging/urodynamic study (fMRI/UDS) with 3 cycles of bladder filling/emptying, at baseline and post-treatment. Predetermined ROIs and their activations at voiding initiation were identified on patients' baseline fMRI/UDS scans, corresponding to microstimulator placement. Patients received 10 consecutive 40-minute treatment sessions. Brain activation group analysis, noninstrumented uroflow, and validated questionnaires were compared at baseline and post-treatment. RESULTS: No treatment-related adverse effects were reported. Post-treatment, patients showed significantly increased activation in regions known to be involved at voiding initiation in healthy subjects. %PVR/BC significantly decreased. Significant improvement of bladder emptying symptoms were reported by patients via validated questionnaires. CONCLUSIONS: Both neuroimaging and clinical data suggested TRPMS effectively and safely modulated brain regions that are involved in the voiding phase of the micturition cycle, leading to clinical improvements in bladder emptying in patients with MS.

Therapeutic effects of non-invasive, individualized, transcranial neuromodulation treatment for voiding dysfunction in multiple sclerosis patients: study protocol for a pilot clinical trial.

BACKGROUND: Voiding dysfunction (VD) is a common neurogenic lower urinary tract dysfunction (NLUTD) in multiple sclerosis (MS) patients. Currently, the only effective management for VD and urinary retention in MS patients is catheterization, prompting us to look for novel therapeutic options beyond the bladder, such as the brain. Transcranial rotating permanent magnet stimulator (TRPMS) is a non-invasive, portable, multifocal neuromodulator that simultaneously modulates multiple cortical regions, enhancing or attenuating strengths of functional connections between these regions. The objective of this pilot clinical trial is to evaluate the feasibility of a TRPMS trial to address lower urinary tract symptoms in MS patients, through investigating the therapeutic effects of TRPMS in modulating brain regions during voiding initiation and mitigating VD in female MS individuals. METHODS: Ten adult female MS patients with VD (defined as having %post-void residual/bladder capacity (%PVR/BC) ≥ 40% or Liverpool nomogram percentile < 10%) will be recruited for this study. Concurrent urodynamic and functional MRI evaluation with a bladder filling/emptying task repeated three to four times will be performed at baseline and post-treatment. Predetermined regions of interest and their blood-oxygen-level-dependent (BOLD) activation at voiding initiation will be identified on each patient's baseline anatomical and functional MRI scan, corresponding to the microstimulators placement on their individualized TRPMS treatment cap to either stimulate or inhibit these regions. Patients will receive 10 40-min treatment sessions. Non-instrumented uroflow and validated questionnaires will also be collected at baseline and post-treatment to evaluate clinical improvement. DISCUSSION: Despite the crucial role of the central nervous system in urinary control and its sensitivity to MS, there has been no treatment for urinary dysfunction targeting the brain centers that are involved in proper bladder function. This trial, to our knowledge, will be the first of its kind in humans to consider non-invasive and individualized cortical modulation for treating VD in MS patients. Results from this study will provide a better understanding of the brain control of neurogenic bladders and lay the foundation for a potential alternative therapy for VD in MS patients and other NLUTD in a larger neurogenic population in the future. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.Gov ( NCT03574610 , 2 July 2018.) and Houston Methodist Research Institute IRB (PRO00019329).

High spatial correlation in brain connectivity between micturition and resting states within bladder-related networks using 7 T MRI in multiple sclerosis women with voiding dysfunction.

BACKGROUND: Several studies have reported brain activations and functional connectivity (FC) during micturition using functional magnetic resonance imaging (fMRI) and concurrent urodynamics (UDS) testing. However, due to the invasive nature of UDS procedure, non-invasive resting-state fMRI is being explored as a potential alternative. The purpose of this study is to evaluate the feasibility of utilizing resting states as a non-invasive alternative for investigating the bladder-related networks in the brain. METHODS: We quantitatively compared FC in brain regions belonging to the bladder-related network during the following states: 'strong desire to void', 'voiding initiation (or attempt at voiding initiation)', and 'voiding (or continued attempt of voiding)' with FC during rest in nine multiple sclerosis women with voiding dysfunction using fMRI data acquired at 7 T and 3 T. RESULTS: The inter-subject correlation analysis showed that voiding (or continued attempt of voiding) is achieved through similar network connections in all subjects. The task-based bladder-related network closely resembles the resting-state intrinsic network only during voiding (or continued attempt of voiding) process but not at other states. CONCLUSION: Resting states fMRI can be potentially utilized to accurately reflect the voiding (or continued attempt of voiding) network. Concurrent UDS testing is still necessary for studying the effects of strong desire to void and initiation of voiding (or attempt at initiation of voiding).

Protocol for a multicenter randomized, double blind, controlled pilot trial of higher neural function in overactive bladder patients after anticholinergic, beta-3 adrenergic agonist, or placebo.

INTRODUCTION: Overactive bladder (OAB) syndrome has a negative impact on quality of life and prevalence increases with advanced age. Anticholinergics (AC) and beta-3 adrenergic agonists (ß3a) are commonly prescribed medications for treatment of OAB. AC medication has been associated with dementia in population studies and with cortical atrophy in imaging studies. Higher neural effects of both classes of OAB medications have not been evaluated with functional neuroimaging. Longitudinal clinical assessments of cognition after OAB therapy with AC has produced conflicting results. ß3a medication is has not been associated with dementia in clinical studies; however, higher neural effects are unknown.Our multicenter, double blind, randomized, placebo-controlled trial uses functional magnetic resonance imaging (fMRI) and cognitive testing to evaluate the effects of AC and ß3a on brain functional connectivity in females with non-neurogenic OAB. METHODS AND ANALYSIS: and analysis: Female patients with OAB symptoms ages 50-90 years old without baseline cognitive impairment, moderate to severe depression or anxiety, neurologic disorders, or significant incomplete bladder emptying are invited to participate. Subjects are randomized to one of three interventions for 29 ± 1 day: AC (Solifenacin succinate, Teva), ß3a (Mirabegron, Myrbetriq, Astellas), or placebo. Functional neuroimaging data at baseline and post-intervention will be analyzed accordingly. Clinical cognitive assessments will be compared from baseline to post-intervention. ETHICS: All qualifying patients are properly consented before enrolling in this study that has been approved by the Institutional Review Board of participating institutions.

A pilot study using a machine-learning approach of morphological and hemodynamic parameters for predicting aneurysms enhancement.

PURPOSE: The development of straightforward classification methods is needed to identify unstable aneurysms and rupture risk for clinical use. In this study, we aim to investigate the relative importance of geometrical, hemodynamic and clinical risk factors represented by the PHASES score for predicting aneurysm wall enhancement using several machine-learning (ML) models. METHODS: Nine different ML models were applied to 65 aneurysm cases with 24 predictor variables. ML models were optimized with the training set using tenfold cross-validation with five repeats with the area under the curve (AUC) as cost parameter. Models were validated using the test set. Accuracy being significantly higher (p < 0.05) than the non-information rate (NIR) was used as measure of performance. The relative importance of the predictor variables was determined from a subset of five ML models in which this information was available. RESULTS: Best-performing ML model was based on gradient boosting (AUC = 0.98). Second best-performing model was based on generalized linear modeling (AUC = 0.80). The size ratio was determined as the dominant predictor for wall enhancement followed by the PHASES score and mean wall shear stress value at the aneurysm wall. Four ML models exhibited a statistically significant higher accuracy (0.79) than the NIR (0.58): random forests, generalized linear modeling, gradient boosting and linear discriminant analysis. CONCLUSIONS: ML models are capable of predicting the relative importance of geometrical, hemodynamic and clinical parameters for aneurysm wall enhancement. Size ratio, PHASES score and mean wall shear stress value at the aneurysm wall are of highest importance when predicting wall enhancement in cerebral aneurysms.

Similarity of individual functional brain connectivity patterns formed by music listening quantified with a data-driven approach.

INTRODUCTION: This study aims to explore the similarities in functional connectivity (FC) patterns in individuals when listening to different music genres and, in comparison, to the spoken word, using a novel data-driven approach. Our model and findings can potentially be utilized for evaluating the neurological effects of therapeutic music interventions. MATERIALS AND METHODS: Twelve healthy volunteers listened to seven different sound tracks while undergoing functional magnetic resonance imaging (fMRI) scans: music of the volunteer's choice with positive emotional attachment, two selections of unfamiliar classical music, one classical piece repeated with visual guidance and three spoken language tracks. FC network graphs were created, and selected graph properties were evaluated toward their commonalities across sound tracks. For comparison, FC patterns represented by the graph adjacency matrices were directly compared for high and low BOLD activation during listening. RESULTS: Graph properties averaged across subjects showed similar values for the same sound track compared to different sound tracks (p < 0.003). For high BOLD activation involving most areas in the auditory cortex, FC patterns for the same sound track correlated highly (0.74 ± 0.11), whereas FC patterns for different sound tracks did not (0.09 ± 0.07; p < 6e-5). For low BOLD activation involving additional brain regions, correlation of FC patterns for the sound tracks was still higher (0.43 ± 0.07) than for different sound tracks (0.09 ± 0.05; p < 8e-6). CONCLUSION: Similar music creates similar functional activation and connectivity patterns in the brain of healthy individuals as does listening to the spoken word. Direct comparison of FC patterns yielded higher correlations than indirect comparisons of graph properties derived from corresponding FC networks.

Higher neural contribution underlying persistent lower urinary tract symptoms in men with Benign Prostatic Hyperplasia undergoing bladder outlet procedures.

INTRODUCTION AND BACKGROUND: Benign Prostatic Hyperplasia (BPH) affects the micturition cycle. Lower urinary tract symptoms (LUTS) refers to storage symptoms such as urinary frequency, urgency, urge urinary incontinence and nocturia. Surgical options for bladder outlet obstruction (BOO) are currently offered for symptomatic improvement. However, 30% of patients report persistent LUTS after BOO procedures. Neuroplasticity induced by BPH and BOO can be contributory in these men, having different brain activation patterns during the micturition cycle. Our multimodal functional Magnetic Resonance Imaging (fMRI) study will identify for the first time, structural and functional brain contributions to LUTS in men with BPH and BOO at baseline and following BOO procedures. We hypothesize that men with symptomatic BPH with persistent LUTS following BOO procedures have a distinct brain activation pattern in regions of interest (ROIs) of the micturition cycle. METHODS: Male patients older than 45 years of age undergoing BOO procedures will be enrolled and categorized in two groups. Group 1: patients with BPH with significant improvement in storage symptoms after BOO procedures. Group 2: patients with BPH with persistent storage symptoms after BOO procedures. Our control group are male patients without LUTS undergoing radical prostatectomy. Patients will complete subjective questionnaires and post void residual at clinic visits. BOLD signals at full urge will be measured at baseline and following BOO procedures. All patients will undergo fMRI studies at baseline and at 6 months. Clinical data will be correlated to BOLD signal changes as well as to structural changes in white matter tracts. ETHICS AND DISSEMINATION: After IRB approval, patients will be recruited and properly consented before enrolling to this study. Results of neural contribution to lower urinary tract symptoms will be presented at national and international meetings and will be published in scholarly journals.

On the Relationship between MRI and Local Field Potential Measurements of Spatial and Temporal Variations in Functional Connectivity.

Correlations between fluctuations in resting state BOLD fMRI signals are interpreted as measures of functional connectivity (FC), but the neural basis of their origins and their relationships to specific features of underlying electrophysiologic activity, have not been fully established. In particular, the dependence of FC metrics on different frequency bands of local field potentials (LFPs), and the relationship of dynamic changes in BOLD FC to underlying temporal variations of LFP correlations, are not known. We compared the spatial profiles of resting state coherences of different frequency bands of LFP signals, with high resolution resting state BOLD FC measurements. We also compared the probability distributions of temporal variations of connectivity in both modalities using a Markov chain model-based approach. We analyzed data obtained from the primary somatosensory (S1) cortex of monkeys. We found that in areas 3b and 1 of S1 cortex, low frequency LFP signal fluctuations were the main contributions to resting state LFP coherence. Additionally, the dynamic changes of BOLD FC behaved most similarly to the LFP low frequency signal coherence. These results indicate that, within the S1 cortex meso-scale circuit studied, resting state FC measures from BOLD fMRI mainly reflect contributions from low frequency LFP signals and their dynamic changes.

Intrinsic functional architecture of the non-human primate spinal cord derived from fMRI and electrophysiology.

Resting-state functional MRI (rsfMRI) has recently revealed correlated signals in the spinal cord horns of monkeys and humans. However, the interpretation of these rsfMRI correlations as indicators of functional connectivity in the spinal cord remains unclear. Here, we recorded stimulus-evoked and spontaneous spiking activity and local field potentials (LFPs) from monkey spinal cord in order to validate fMRI measures. We found that both BOLD and electrophysiological signals elicited by tactile stimulation co-localized to the ipsilateral dorsal horn. Temporal profiles of stimulus-evoked BOLD signals covaried with LFP and multiunit spiking in a similar way to those observed in the brain. Functional connectivity of dorsal horns exhibited a U-shaped profile along the dorsal-intermediate-ventral axis. Overall, these results suggest that there is an intrinsic functional architecture within the gray matter of a single spinal segment, and that rsfMRI signals at high field directly reflect this underlying spontaneous neuronal activity.

Discrete Modules and Mesoscale Functional Circuits for Thermal Nociception within Primate S1 Cortex.

This study addresses one long-standing question of whether functional separations are preserved for somatosensory modalities of touch, heat, and cold nociception within primate primary somatosensory (S1) cortex. This information is critical for understanding how the nature of pain is represented in the primate brain. Using a combination of submillimeter-resolution fMRI and microelectrode local field potential (LFP) and spike recordings, we identified spatially segregated cortical zones for processing touch and nociceptive heat and cold stimuli in somatotopically appropriate areas 3a, 3b, 1, and 2 of S1 in male monkeys. The distances between zones were comparable (∼3.4 mm) across stimulus modalities (heat, cold, and tactile), indicating the existence of uniform, modality-specific modules. Stimulus-evoked LFP maps validated the fMRI maps in areas 3b and 1. Isolation of heat and cold nociceptive neurons from the fMRI zones confirmed the validity of using fMRI to probe nociceptive regions and circuits. Resting-state fMRI analysis revealed distinct intrinsic functional circuits among functionally related zones. We discovered distinct modular structures and networks for thermal nociception within S1 cortex, a finding that has significant implications for studying chronic pain syndromes and guiding the selection of neuromodulation targets for chronic pain management.SIGNIFICANCE STATEMENT Primate S1 subregions contain discrete heat and cold nociceptive modules. Modules with the same properties exhibit strong functional connection. Nociceptive fMRI response coincides with LFP and spike activities of nociceptive neurons. Functional separation of heat and cold pain is retained within primate S1 cortex.