Urinary incontinence-related effects on functional connectivity circuits in persons with Parkinson's disease.

INTRODUCTION: Urinary incontinence (UI) is a common and disruptive symptom of Parkinson's disease (PD). This study aimed to identify neural correlates associated with UI among PD patients with UI (UI-PD) compared to those PD patients without UI (nonUI-PD) with the expectation of demonstrating increased functional connectivity (FC) between areas in the striatum and limbic system and decreased FC in executive areas. METHODS: rsfMRI and T1w data (n = 119) were retrieved from the Parkinson's Progression Markers Initiative (PPMI). Resting-state FC analyses assessed temporal covariance with anterior cingulate gyrus, precuneus, and putamen seed regions. RESULTS: The UI-PD group (n = 32, 16 females) showed significantly greater positive FC between the bilateral putamen seed and the right caudate and right thalamus (p < 0.01), relative to individuals with PD but who did not have UI (n = 87, 18 females). The UI-PD group showed greater negative FC between the anterior cingulate seed and right angular gyrus (p < 0.01) relative to nonUI-PD. CONCLUSION: Individuals with PD and UI display stronger FC within neural circuits likely affected by PD such as between the putamen and caudate, as well as within those associated with brain bladder control, compared to persons with PD and without UI. Clinical application based on this study's results can provide greater discernment of treatment strategies for UI-PD patients.

Graded Intensity Aerobic Exercise to Improve Cerebrovascular Function and Performance in Older Veterans: Protocol for a Randomized Controlled Trial.

BACKGROUND: Growing health care challenges resulting from a rapidly expanding aging population necessitate examining effective rehabilitation techniques that mitigate age-related comorbidity and improve quality of life. To date, exercise is one of a few proven interventions known to attenuate age-related declines in cognitive and sensorimotor functions critical to sustained independence. OBJECTIVE: This work aims to implement a multimodal imaging approach to better understand the mechanistic underpinnings of the beneficial exercise-induced adaptations to sedentary older adults' brains and behaviors. Due to the complex cerebral and vascular dynamics that encompass neuroplastic change with aging and exercise, we propose an imaging protocol that will model exercise-induced changes to cerebral perfusion, cerebral vascular reactivity (CVR), and cognitive and sensorimotor task-dependent functional magnetic resonance imaging (fMRI) after prescribed exercise. METHODS: Sedentary older adults (aged 65-80 years) were randomly assigned to either a 12-week aerobic-based interval-based cycling intervention or a 12-week balance and stretching intervention. Assessments of cardiovascular fitness used the YMCA submaximal VO2 test, basal cerebral perfusion using arterial spin labeling (ASL), CVR using hypercapnic fMRI, and cortical activation using fMRI during verbal fluency and motor tapping tasks. A battery of cognitive-executive and motor function tasks outside the scanning environment will be performed before and after the interventions. RESULTS: Our studies and others show that improved cardiovascular fitness in older adults results in improved outcomes related to physical and cognitive health as well as quality of life. A consistent but unexplained finding in many of these studies is a change in cortical activation patterns during task-based fMRI, which corresponds with improved task performance (cognitive-executive and motor). We hypothesize that the 12-week aerobic exercise intervention will increase basal perfusion and improve CVR through a greater magnitude of reactivity in brain areas susceptible to neural and vascular decline (inferior frontal and motor cortices) in previously sedentary older adults. To differentiate between neural and vascular adaptations in these regions, we will map changes in basal perfusion and CVR over the inferior frontal and the motor cortices-regions we have previously shown to be beneficially altered during fMRI BOLD (blood oxygen level dependent), such as verbal fluency and motor tapping, through improved cardiovascular fitness. CONCLUSIONS: Exercise is one of the most impactful interventions for improving physical and cognitive health in aging. This study aims to better understand the mechanistic underpinnings of improved health and function of the cerebrovascular system. If our hypothesis of improved perfusion and cerebrovascular reactivity following a 12-week aerobic exercise intervention is supported, it would add critically important insights into the potential of exercise to improve brain health in aging and could inform exercise prescription for older adults at risk for neurodegenerative disease brought on by cerebrovascular dysfunction. TRIAL REGISTRATION: ClinicalTrials.gov NCT05932069; https://clinicaltrials.gov/study/NCT05932069. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/58316.

A Randomized, Sham-Controlled Trial of Cranial Electrical Stimulation for Fibromyalgia Pain and Physical Function, Using Brain Imaging Biomarkers.

Fibromyalgia is a chronic pain syndrome that presents with a constellation of broad symptoms, including decreased physical function, fatigue, cognitive disturbances, and other somatic complaints. Available therapies are often insufficient in treating symptoms, with inadequate pain control commonly leading to opioid usage for attempted management. Cranial electrical stimulation (CES) is a promising non-pharmacologic treatment option for pain conditions that uses pulsed electrical current stimulation to modify brain function via transcutaneous electrodes. These neural mechanisms and the applications of CES in fibromyalgia symptom relief require further exploration. A total of 50 participants from the Atlanta Veterans Affairs Healthcare System (VAHCS) diagnosed with fibromyalgia were enrolled and then block-randomized into either a placebo plus standard therapy or active CES plus standard therapy group. Baseline assessments were obtained prior to the start of treatment. Both interventions occurred over 12 weeks, and participants were assessed at 6 weeks and 12 weeks after treatment initiation. The primary outcome investigated whether pain and functional improvements occur with the application of CES. Additionally, baseline and follow-up resting state functional connectivity magnetic resonance imaging (rs-fcMRI) were obtained at the 6-week and 12-week time points to assess for clinical applications of neural connectivity biomarkers and the underlying neural associations related to treatment effects. This is a randomized, placebo-controlled trial to determine the efficacy of CES for improving pain and function in fibromyalgia and further develop rs-fcMRI as a clinical tool to assess the neural correlates and mechanisms of chronic pain and analgesic response.

Percutaneous electric nerve field stimulation alters cortical thickness in a pilot study of veterans with fibromyalgia.

Objective: To evaluate changes in cortical thickness and right posterior insula (r-pIns) gamma-aminobutyric acid (GABA) concentrations in veterans with fibromyalgia treated with auricular percutaneous electric nerve field stimulation (PENFS). Materials & methods: This was a randomized, controlled, open label investigation conducted in a government hospital. Twenty-one veterans with fibromyalgia were randomized to receive either standard therapy (ST; i.e., 4 weekly visits with a pain practitioner) or ST with auricular PENFS (ST + PENFS). Neuroimaging data was collected at baseline (i.e. before the first treatment session) and again within 2 weeks post-treatment.​ Clinical pain and physical function were also assessed at these timepoints. Single-voxel magnetic resonance spectroscopy was carried out in r-pIns to assess changes in r-pIns GABA concentrations and high-resolution T1-weighted images were collected to assess changes in regional gray matter volume using cortical thickness. Results: Both the ST + PENFS and ST groups reported a decrease in pain with treatment. Volumetric: Cortical thickness significantly decreased in the left middle posterior cingulate (p = 0.018) and increased in the left cuneus (p = 0.014) following ST + PENFS treatment. These findings were significant following FDR correction for multiple comparisons. ST group right hemisphere insula cortical thickness increased post-treatment and was significantly (p = 0.02) inversely correlated with pain scores. ST + PENFS group right hemisphere posterior dorsal cingulate size significantly (p = 0.044) positively correlated with pain scores. GABA: There were no significant correlations with GABA, though a trend was noted towards increased GABA following treatment in both groups (p = 0.083) using a linear mixed effects model. Conclusions: Results suggest a novel effect of PENFS reflected by differential volumetric changes compared to ST. The changes in GABA that occur in both groups are more likely related to ST. Insular GABA and cortical thickness in key regions of interest may be developed as potential biomarkers for evaluating chronic pain pathology and treatment outcomes.

Defect transitions in nematic liquid-crystal capillary bridges.

We use experiment and computational modeling to understand the defect structure and director configuration in a nematic liquid crystal capillary bridge confined between two parallel plates. We find that tuning of the aspect ratio of the bridge drives a transition between a ring defect and a point defect. This transition exhibits hysteresis, due to the metastability of the point-defect structure. In addition, we see that the shape of the capillary-bridge surface determines whether the defect is hyperbolic or radial, with waistlike bridges containing hyperbolic defects and barrel-like bridges containing radial defects.