Evaluation of GC-MS for identification and characterization of pneumococcal serotype 24A, 24B, and 24F capsular polysaccharide.

Analysis of pneumococcal polysaccharides (PnPs) has been an arduous task, especially in similar serotypes. Pneumococci invades the host immune response by modulating capsule structure with small genetic changes making them indistinguishable from similar serotypes by conventional modes of analysis. The new serotype 24F causing invasive pneumococcal-resistant infection is an analytical challenge for its analysis as related serotypes 24A and 24B Ps share a common backbone. The difference in the branched chain which contains arabinitol and ribitol in 24F and 24B respectively are stereoisomers making their identification even more challenging. The composition analysis by GC-MS revealed distinct peaks for arabinitol in 24F and 24A Ps and ribitol in Pn 24B serotype polysaccharide. The mass spectral analysis confirmed their identification along with a heterologous cross-reactivity which confirmed anti-Pn-24F mAb reactive to Pn 24B than Pn 24A. The quantitative analysis of pneumococcal 24A, 24B and 24F using GC-MS showed sensitive analysis over the concentration range 3.125-200 µg/mL with regression coefficient >0.99 making ideal modality for the characterization, identification, and quantitation of pneumococcal 24A, 24B and 24F similar serotypes.

Associations between pain catastrophizing and resting-state functional brain connectivity: Ethnic/race group differences in persons with chronic knee pain.

Chronic pain is a significant public health problem, and the prevalence and societal impact continues to worsen annually. Multiple cognitive and emotional factors are known to modulate pain, including pain catastrophizing, which contributes to pain facilitation and is associated with altered resting-state functional connectivity in pain-related cortical and subcortical circuitry. Pain and catastrophizing levels are reported to be higher in non-Hispanic black (NHB) compared with non-Hispanic White (NHW) individuals. The current study, a substudy of a larger ongoing observational cohort investigation, investigated the pathways by which ethnicity/race influences the relationship between pain catastrophizing, clinical pain, and resting-state functional connectivity between anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (dlPFC), insula, and primary somatosensory cortex (S1). Participants included 136 (66 NHBs and 70 NHWs) community-dwelling adults with knee osteoarthritis. Participants completed the Coping Strategies Questionnaire-Revised Pain Catastrophizing subscale and Western Ontario and McMaster Universities Osteoarthritis Index. Magnetic resonance imaging data were obtained, and resting-state functional connectivity was analyzed. Relative to NHW, the NHB participants were younger, reported lower income, were less likely to be married, and self-reported greater clinical pain and pain catastrophizing (ps < 0.05). Ethnicity/race moderated the mediation effects of catastrophizing on the relationship between clinical pain and resting-state functional connectivity between the ACC, dlPFC, insula, and S1. These results indicate the NHB and NHW groups demonstrated different relationships between pain, catastrophizing, and functional connectivity. These results provide evidence for a potentially important role of ethnicity/race in the interrelationships among pain, catastrophizing, and resting-state functional connectivity.

Executive Function Brain Network Activation Predicts Driving Hazard Detection in ADHD.

Drivers with neurodevelopmental disorders (NDDs), such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are at increased risk of experiencing driving difficulties. An important aspect of driving safety and skill involves hazard detection. This functional magnetic resonance imaging study examined the neural responses associated with driving hazard detection in drivers with ASD, ADHD, and typically developing (TD) drivers. Forty participants (12 ASD, 15 ADHD, 13 TD) ages 16-30 years completed a driving simulator task in which they encountered social and nonsocial hazards; reaction time (RT) for responding to hazards was measured. Participants then completed a similar hazard detection task in the MRI scanner so that neural response to hazards could be measured. Activation of regions of interest considered part of the executive function (EF) and theory of mind (ToM) networks were examined and related to driving simulator behavior. Results showed that stronger activation of the EF network during social hazard processing, including the bilateral dorsolateral prefrontal cortex and posterior parietal cortex, was associated with faster RT to social hazards among drivers with ADHD, but not among drivers with ASD. This provides the first evidence of a relationship between EF network brain activation and driving skills in ADHD and suggests that alterations in this network may underlie driving behavior. In comparison, the current study did not observe a relationship between ToM network activation and RT to social hazards in any group. This study lays the groundwork for relating neural activation to driving behavior among individuals with NDDs.

Resilience, pain, and the brain: Relationships differ by sociodemographics.

Chronic musculoskeletal (MSK) pain is disabling to individuals and burdensome to society. A relationship between telomere length and resilience was reported in individuals with consideration for chronic pain intensity. While chronic pain associates with brain changes, little is known regarding the neurobiological interface of resilience. In a group of individuals with chronic MSK pain, we examined the relationships between a previously investigated resilience index, clinical pain and functioning measures, and pain-related brain structures, with consideration for sex and ethnicity/race. A cross-sectional analysis of 166 non-Hispanic Black and non-Hispanic White adults, 45-85 years of age with pain ≥ 1 body site (s) over the past 3 months was completed. Measures of clinical pain and functioning, biobehavioral and psychosocial resilience, and structural MRI were completed. Our findings indicate higher levels of resilience associate with lower levels of clinical pain and functional limitations. Significant associations between resilience, ethnicity/race, and/or sex, and pain-related brain gray matter structure were demonstrated in the right amygdaloid complex, bilateral thalamus, and postcentral gyrus. Our findings provide compelling evidence that in order to decipher the neurobiological code of chronic pain and related protective factors, it will be important to improve how chronic pain is phenotyped; to include an equal representation of females in studies including analyses stratifying by sex, and to consider other sociodemographic factors.

A method for pre-operative single-subject thalamic segmentation based on probabilistic tractography for essential tremor deep brain stimulation.

PURPOSE: Deep brain stimulation is a common treatment for medication-refractory essential tremor. Current coordinate-based targeting methods result in variable outcomes due to variation in thalamic structure and the optimal patient-specific functional location. The purpose of this study was to compare the coordinate-based pre-operative targets to patient-specific thalamic segmentation utilizing a probabilistic tractography methodology. METHODS: Using available diffusion MRI of 32 subjects from the Human Connectome Project database, probabilistic tractography was performed. Each thalamic voxel was coded based on one of six predefined cortical targets. The segmentation results were analyzed and compared to a 2-mm spherical target centered at the coordinate-based location of the ventral intermediate thalamic nucleus. RESULTS: The traditional coordinate-based target had maximal overlap with the junction of the region most connected to primary motor cortex (M1) (36.6 ± 25.7% of voxels on left; 58.1 ± 28.5% on right) and the area connected to the supplementary motor area/premotor cortex (SMA/PMC) (44.9 ± 21.7% of voxels on left; 28.9 ± 22.2% on right). There was a within-subject coefficient of variation from right-to-left of 69.4 and 63.1% in the volume of overlap with the SMA/PMC and M1 regions, respectively. CONCLUSION: Thalamic segmentation based on structural connectivity measures is a promising technique that may enhance traditional targeting methods by generating reproducible, patient-specific pre-operative functional targets. Our results highlight the problematic intra- and inter-subject variability of indirect, coordinate-based targets. Future prospective clinical studies will be needed to validate this targeting methodology in essential tremor patients.

Longitudinal multiple sclerosis lesion segmentation: Resource and challenge.

In conjunction with the ISBI 2015 conference, we organized a longitudinal lesion segmentation challenge providing training and test data to registered participants. The training data consisted of five subjects with a mean of 4.4 time-points, and test data of fourteen subjects with a mean of 4.4 time-points. All 82 data sets had the white matter lesions associated with multiple sclerosis delineated by two human expert raters. Eleven teams submitted results using state-of-the-art lesion segmentation algorithms to the challenge, with ten teams presenting their results at the conference. We present a quantitative evaluation comparing the consistency of the two raters as well as exploring the performance of the eleven submitted results in addition to three other lesion segmentation algorithms. The challenge presented three unique opportunities: (1) the sharing of a rich data set; (2) collaboration and comparison of the various avenues of research being pursued in the community; and (3) a review and refinement of the evaluation metrics currently in use. We report on the performance of the challenge participants, as well as the construction and evaluation of a consensus delineation. The image data and manual delineations will continue to be available for download, through an evaluation website2 as a resource for future researchers in the area. This data resource provides a platform to compare existing methods in a fair and consistent manner to each other and multiple manual raters.

Bladder Distension Increases Blood Flow in Pain Related Brain Structures in Subjects with Interstitial Cystitis.

PURPOSE: In healthy control subjects certain brain regions of interest demonstrate increased regional cerebral blood flow in response to painful stimuli. We examined the effect of bladder distension on arterial spin label functional magnetic resonance imaging measures of regional cerebral blood flow in regions of interest in subjects with interstitial cystitis. MATERIALS AND METHODS: A total of 11 female subjects with interstitial cystitis and 11 healthy controls underwent 3 brain perfusion scan studies using arterial spin label functional magnetic resonance imaging, including 1) with a full bladder, 2) with an empty bladder and 3) while experiencing heat pain. Regional cerebral blood flow was calculated using custom software and individual scans were spatially normalized to the MNI (Montreal Neurological Institute) template. Region of interest based, absolute regional cerebral blood flow was determined for each condition and for the within group/within subject regional cerebral blood flow distribution changes induced by each condition. RESULTS: Bladder distension was associated with robust increases in regional cerebral blood flow in subjects with interstitial cystitis. The increases were greater than those in healthy controls in multiple regions of interest, including the supplemental motor area (mainly Brodmann area 6), the motor and sensory cortex, the insula bilaterally, the hippocampal structures bilaterally, and the middle and posterior cingulate areas bilaterally. During heat pain healthy controls had more robust regional cerebral blood flow increases in the amygdala bilaterally. At baseline with an empty bladder there was lower regional cerebral blood flow in the insula, and the mid and posterior cingulate cortex bilaterally in subjects with interstitial cystitis. CONCLUSIONS: Compared to healthy controls, subjects with interstitial cystitis have limited differences in regional cerebral blood flow in baseline (empty bladder) conditions as well as during heat pain. However, they had robust regional cerebral blood flow increases in the full bladder state in regions of interest typically associated with pain, emotion and/or motor control, indicating altered processing of bladder related sensations.

Environmental and sociocultural factors are associated with pain-related brain structure among diverse individuals with chronic musculoskeletal pain: intersectional considerations.

Chronic musculoskeletal pain including knee osteoarthritis (OA) is a leading cause of disability worldwide. Previous research indicates ethnic-race groups differ in the pain and functional limitations experienced with knee OA. However, when socioenvironmental factors are included in analyses, group differences in pain and function wane. Pain-related brain structures are another area where ethnic-race group differences have been observed. Environmental and sociocultural factors e.g., income, education, experiences of discrimination, and social support influence brain structures. We investigate if environmental and sociocultural factors reduce previously observed ethnic-race group differences in pain-related brain structures. Data were analyzed from 147 self-identified non-Hispanic black (NHB) and non-Hispanic white (NHW), middle and older aged adults with knee pain in the past month. Information collected included health and pain history, environmental and sociocultural resources, and brain imaging. The NHB adults were younger and reported lower income and education compared to their NHW peers. In hierarchical multiple regression models, sociocultural and environmental factors explained 6-37% of the variance in pain-related brain regions. Self-identified ethnicity-race provided an additional 4-13% of explanatory value in the amygdala, hippocampus, insula, bilateral primary somatosensory cortex, and thalamus. In the rostral/caudal anterior cingulate and dorsolateral prefrontal cortex, self-identified ethnicity-race was not a predictor after accounting for environmental, sociocultural, and demographic factors. Findings help to disentangle and identify some of the factors contributing to ethnic-race group disparities in pain-related brain structures. Numerous arrays of environmental and sociocultural factors remain to be investigated. Further, the differing sociodemographic representation of our NHB and NHW participants highlights the role for intersectional considerations in future research.

Environmental and sociocultural factors are associated with pain-related brain structure among diverse individuals with chronic musculoskeletal pain.

Chronic musculoskeletal pain is a leading cause of disability worldwide. Previous research indicates ethnic/race groups are disproportionately affected by chronic pain conditions. However, when considering socioenvironmental factors these disparities are no longer observed. Ethnic/race group differences have also been reported in pain-related brain structure. Given that environmental and sociocultural factors influence biology and health outcomes, this study aimed to investigate possible environmental and sociocultural contributions to structural differences in pain-related brain regions. A total of 147 non-Hispanic black and non-Hispanic white, middle and older aged adults with knee pain in the past month and a brain MRI are included in the analyses. Individuals also provided information specific to health and pain history and environmental and sociocultural resources. In hierarchical multiple regression models, sociocultural and environmental factors explained 6%-37% of the variance in thickness of pain-related brain regions, with seven of the eight brain regions being statistically significant. In the amygdala, hippocampus, insula, bilateral primary somatosensory cortex, and thalamus, ethnicity/race provided an additional 4%-13% of explanatory value. In the rostral/caudal anterior cingulate and dorsolateral prefrontal cortex, ethnicity/race was not a predictor after accounting for environmental, sociocultural, and other demographic measures. Findings inform health disparities research by elucidating the complexity of factors contributing to previously reported ethnicity/race group differences.

Greater socioenvironmental risk factors and higher chronic pain stage are associated with thinner bilateral temporal lobes.

INTRODUCTION: Previous research indicates ethnic/race group differences in pain and neurodegenerative diseases. Accounting for socioenvironmental factors reduces ethnic/race group differences in clinical and experimental pain. In the current study sample, we previously reported that in individuals with knee pain, ethnic/race group differences were observed in bilateral temporal lobe thickness, areas of the brain associated with risk for Alzheimer's disease, and related dementias. The purpose of the study was to determine if socioenvironmental factors reduce or account for previously observed ethnic/race group differences and explore if a combined effect of socioenvironmental risk and chronic pain severity on temporal lobe cortices is evident. METHODS: Consistent with the prior study, the sample was comprised of 147 adults (95 women, 52 men), 45-85 years of age, who self-identified as non-Hispanic Black (n = 72) and non-Hispanic White (n = 75), with knee pain with/at risk for osteoarthritis. Measures included demographics, health history, pain questionnaires, cognitive screening, body mass index, individual- and community-level socioenvironmental factors (education, income, household size, marital and insurance status, and area deprivation index), and brain imaging. We computed a summative socioenvironmental risk index. RESULTS: Regression analyses showed that with the inclusion of socioenvironmental factors, the model was significant (p < .001), and sociodemographic (ethnic/race) group differences were not significant (p = .118). Additionally, findings revealed an additive stress load pattern indicating thinner temporal lobe cortices with greater socioenvironmental risk and chronic pain severity (p = .048). IMPLICATIONS: Although individual socioenvironmental factors were not independent predictors, when collectively combined in models, ethnic/race group differences in bilateral temporal lobe structures were not replicated. Further, combined socioenvironmental risk factors and higher chronic pain severity were associated with thinner bilateral temporal lobes.

Quantitative changes in regional cerebral blood flow induced by cold, heat and ischemic pain: a continuous arterial spin labeling study.

BACKGROUND: The development of arterial spin labeling methods has allowed measuring regional cerebral blood flow (rCBF) quantitatively and to show the pattern of cerebral activity associated with any state such as a sustained pain state or changes due to a neurotropic drug. METHODS: The authors studied the differential effects of three pain conditions in 10 healthy subjects on a 3 Tesla scanner during resting baseline, heat, cold, and ischemic pain using continuous arterial spin labeling. RESULTS: Cold pain showed the greatest absolute rCBF increases in left anterior cingulate cortex, left amygdala, left angular gyrus, and Brodmann area 6, and a significant rCBF decrease in the cerebellum. Changes in rCBF were characteristic of the type of pain condition: cold and heat pain showed increases, whereas the ischemic condition showed a reduction in mean absolute gray matter flow compared with rest. An association of subjects' pain tolerance and cerebral blood flow was noted. CONCLUSIONS: The observation that quantitative rCBF changes are characteristic of the pain task used and that there is a consistent rCBF change in Brodman area 6, an area responsible for the integration of a motor response to pain, should provide extremely useful information in the quest to develop an imaging biomarker of pain. Conceivably, response in BA6 may serve as an objective measure of analgesic efficacy.

Quantitation of endotoxin by gas chromatography-mass spectrometry in Neisseria meningitidis serogroups A, C, W, Y and X during polysaccharide purification used in conjugate vaccine.

Bacterial lipopolysaccharide (LPS) responsible for endotoxin effect induces inflammatory reactions. The endotoxins are difficult to separate from the gram-negative polysaccharide (PS) during polysaccharide purification. The most common method to quantify LPS is the limulus amebocyte lysate (LAL) test which interferes with the agents used during PS purification. The gas chromatography-mass spectrometry (GC-MS) provides a suitable alternative by estimating lipid-A chain anchored 3-hydroxy fatty acid methyl ester (FAME) to estimate LPS however, there are no reports of its application in natural polysaccharides used for vaccine preparation. The transesterification of LPS and meningococcal PS yielded primary target 3-O-acetylated myristic acid which was detected by GC-MS and provided quantitative estimation of endotoxin. The GC-MS method was found in agreement with the LAL values showing lower endotoxin content< 10Eu/µg in meningococcal C and Y serogroup polysaccharides in comparison to higher endotoxin 177-523 Eu/µg in meningococcal A, W and X serogroups. The high endotoxin content in purified polysaccharide was attributed to it being detected in its intermediate stage by GC-MS unlike the LAL test. Thus GC-MS serves as a valuable method for endotoxin monitoring and quantitation in gram-negative meningococcal intermediate and purified PS during vaccine preparation.

Chronic Pain Severity and Sociodemographics: An Evaluation of the Neurobiological Interface.

Chronic pain is variably associated with brain structure. Phenotyping based on pain severity may address inconsistencies. Sociodemographic groups also differ in the experience of chronic pain severity. Whether differences by chronic pain severity and/or sociodemographic groups are indicated in pain-related areas of the brain is unknown. Relations between 2 measures of chronic pain severity and brain structure via T1-weighted MRI were investigated and sociodemographic group differences explored. The observational study included 142 community-dwelling (68 non-Hispanic Black [NHB] and 74 non-Hispanic White [NHW]) adults with/at risk for knee osteoarthritis. Relationships between chronic pain severity, sociodemographic groups, and a priori selected brain structures (postcentral gyrus, insula, medial orbitofrontal, anterior cingulate, rostral middle frontal gyrus, hippocampus, amygdala, thalamus) were explored. Chronic pain severity associated with cortical thickness. NHB participants reported lower sociodemographic protective factors and greater clinical pain compared to NHWs who reported higher sociodemographic protective factors and lower clinical pain. Greater chronic pain severity was associated with smaller amygdala volumes in the NHB group and larger amygdala volumes in the NHW group. Brain structure by chronic pain stage differed between and within sociodemographic groups. Overall, chronic pain severity and sociodemographic factors are associated with pain-related brain structures. Our findings highlight the importance of further investigating social and environmental contributions in the experience of chronic pain to unravel the complex array of factors contributing to disparities. PERSPECTIVE: The study presents data demonstrating structural brain relationships with clinical pain severity, characteristic pain intensity and chronic pain stage, differ by sociodemographic groups. Findings yield insights into potential sources of previous inconsistent pain-brain relationships and highlights the need for future investigations to address social and environmental factors in chronic pain disparities research.

Differences in resting cerebellar and prefrontal cortical blood flow in spinal cord injury-related neuropathic pain: A brief report.

Context: Little is understood about differences in resting neural activity among those with spinal cord injury (SCI)-related neuropathic pain. The purpose of this pilot study was to determine resting cerebral blood flow differences in persons with SCI-related neuropathic pain compared to healthy, pain-free able-bodied controls.Methods: Five persons with paraplegia and ten able-bodied participants were included in this study. Resting blood flow, as measured by a continuous arterial spin labeling (ASL) method of fMRI, was analyzed via statistical parametric mapping.Results: Persons with SCI-related neuropathic pain had significantly lower resting blood flow in the cerebellum (Crus I/II), rostral ventromedial medulla and left insular cortex. In contrast, greater resting blood flow occurred in the medial orbitofrontal cortex among those with SCI-related neuropathic pain compared to controls.Conclusion: Differences in resting blood flow were observed among those with SCI-related pain, particularly in regions that may be involved in affective-motivational and cognitive-evaluative aspects of pain. Larger ASL studies in addition to functional connectivity studies using fMRI are needed to clarify unique neural patterns in this complex and often intractable form of pain.

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.

Clear and Consistent Imaging of Hippocampal Internal Architecture With High Resolution Multiple Image Co-registration and Averaging (HR-MICRA).

Magnetic resonance imaging of hippocampal internal architecture (HIA) at 3T is challenging. HIA is defined by layers of gray and white matter that are less than 1 mm thick in the coronal plane. To visualize HIA, conventional MRI approaches have relied on sequences with high in-plane resolution (≤0.5 mm) but comparatively thick slices (2-5 mm). However, thicker slices are prone to volume averaging effects that result in loss of HIA clarity and blurring of the borders of the hippocampal subfields in up to 61% of slices as has been reported. In this work we describe an approach to hippocampal imaging that provides consistently high HIA clarity using a commonly available sequence and post-processing techniques that is flexible and may be applicable to any MRI platform. We refer to this approach as High Resolution Multiple Image Co-registration and Averaging (HR-MICRA). This approach uses a variable flip angle turbo spin echo sequence to repeatedly acquire a whole brain T2w image volume with high resolution in three dimensions in a relatively short amount of time, and then co-register the volumes to correct for movement and average the repeated scans to improve SNR. We compared the averages of 4, 9, and 16 individual scans in 20 healthy controls using a published HIA clarity rating scale. In the body of the hippocampus, the proportion of slices with good or excellent HIA clarity was 90%, 83%, and 67% for the 16x, 9x, and 4x HR-MICRA images, respectively. Using the 4x HR-MICRA images as a baseline, the 9x HR-MICRA images were 2.6 times and 16x HR-MICRA images were 3.2 times more likely to have high HIA ratings (p < 0.001) across all hippocampal segments (head, body, and tail). The thin slices of the HR-MICRA images allow reformatting in any plane with clear visualization of hippocampal dentation in the sagittal plane. Clear and consistent visualization of HIA will allow application of this technique to future hippocampal structure research, as well as more precise manual or automated segmentation.

Relationships Between Chronic Pain Stage, Cognition, Temporal Lobe Cortex, and Sociodemographic Variables.

BACKGROUND: Non-Hispanic black (NHB) individuals have increased risk of Alzheimer's disease (AD) relative to non-Hispanic whites (NHW). Ethnicity/race can serve as a proxy sociodemographic variable for a complex representation of sociocultural and environmental factors. Chronic pain is a form of stress with high prevalence and sociodemographic disparities. Chronic pain is linked to lower cognition and accelerated biological aging. OBJECTIVE: The purpose of this study is to seek understanding of potential cognitive and temporal lobe structural brain AD vulnerabilities based on chronic pain stage and ethnicity/race. METHODS: Participants included 147 community dwelling NHB and NHW adults without dementia between 45-85 years old who had or were at risk of knee osteoarthritis. All participants received an MRI (3T Philips), the Montreal Cognitive Assessment (MoCA), and assessment of clinical knee pain stage. RESULTS: There were ethnic/race group differences in MoCA scores but no relationships with chronic knee pain stage. Ethnicity/race moderated the relationship between AD-related temporal lobe thickness and chronic pain stage with quadratic patterns suggesting thinner cortex in high chronic pain stage NHB adults. CONCLUSION: There appear to be complex relationships between chronic knee pain stage, temporal lobe cortex, and sociodemographic variables. Specifically, NHB participants without dementia but with high chronic knee pain stage appeared to have thinner temporal cortex in areas associated with AD. Understanding the effects of sociocultural and socioeconomic factors on health outcomes is the first step to challenging the disparities in healthcare that now appear to link disease conditions to neurodegenerative processes.

Associations of pain catastrophizing with pain-related brain structure in individuals with or at risk for knee osteoarthritis: Sociodemographic considerations.

Compelling evidence exists that non-Hispanic blacks (NHB) engage in pain catastrophizing (negatively evaluate one's ability to cope with pain) more often than non-Hispanic whites (NHW). Functional neuroimaging studies revealed that individuals with high levels of trait pain catastrophizing show increased cerebral responses to pain in several pain-related brain regions (e.g., insula, primary somatosensory cortex [S1]), but associations between brain structure and catastrophizing remain largely unexplored. The current investigation was conducted at the University of Florida and the University of Alabama at Birmingham. Participants were 129 community-dwelling adults with or at risk of knee osteoarthritis (OA). Participants completed the pain catastrophizing subscale of the Coping Strategies Questionnaire-Revised and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain intensity subscale. Magnetic Resonance Imaging data were obtained. MANOVA and Chi-Square analyses assessed sociodemographic/clinical differences stratified by ethnicity/race. Multivariate regression analyses with insula and somatosensory cortical thickness entered as dependent variables with catastrophizing and the interaction between catastrophizing and ethnicity/race as the independent variables. Covariates include education, body mass index, study site, and WOMAC pain (ethnicity/race was an additional covariate in non-stratified analyses). There were significant interactions between ethnicity/race, pain catastrophizing, and brain structure. Higher pain catastrophizing was associated with thinner S1 bilaterally (ps < .05) in NHW, but not NHB participants with or at risk for knee OA. These results suggest that pain catastrophizing might have differing effects on pain-related central pathways and may contribute to ethnic/race group differences in individuals with or at risk for knee OA.

Pain relief for osteoarthritis through combined treatment (PROACT): Protocol for a randomized controlled trial of mindfulness meditation combined with transcranial direct current stimulation in non-Hispanic black and white adults with knee osteoarthritis.

Knee osteoarthritis (OA) is a leading cause of late life pain and disability, and non-Hispanic black (NHB) adults experience greater OA-related pain and disability than non-Hispanic whites (NHWs). Recent evidence implicates psychosocial stress, cognitive-attentional processes, and altered central pain processing as contributors to greater OA-related pain and disability among NHBs. To address these ethnic/race disparities, this clinical trial will test whether a mindfulness intervention (Breathing and Attention Training, BAT) combined with transcranial direct current stimulation (tDCS) will enhance pain modulatory balance and pain-related brain function, reduce clinical pain, and attenuate ethnic differences therein, among NHBs and NHWs with knee OA. Participants will complete assessments of clinical pain, function, psychosocial measures, and quantitative sensory testing (QST), including mechanical temporal summation and conditioned pain modulation. Neuroimaging will be performed to examine pain-related brain structure and function. Then, participants will be randomized to one of four groups created by crossing two BAT conditions (Real vs. Sham) with two tDCS conditions (Real vs. Sham). Participants will then undergo five treatment sessions during which the assigned BAT and tDCS interventions will be delivered concurrently for 20 min over one week. After the fifth intervention session, participants will undergo assessments of clinical pain and function, QST and neuroimaging identical to the pretreatment measures, and monthly follow-up assessments of pain will be conducted for three months. This will be the first study to determine whether mindfulness and tDCS treatments will show additive or synergistic effects when combined, and whether treatment effects differ across ethnic/race groups.

Ictogenesis during sEEG evaluation after acute intracranial hemorrhage.

We present a unique case of a patient with drug-resistant focal epilepsy undergoing stereoelectroencephalography (sEEG) who developed an acute posttraumatic intracranial hemorrhage during monitoring, first detected by changes on sEEG. Our case demonstrates the evolution of electrographic changes at the time of initial hemorrhage to the development of ictal activity. We conducted spectral analysis of the sEEG data to illustrate the transition from an interictal to ictal state. Initially, delta power increased in the region of acute hemorrhage, followed by sustained regional reduction in frequency variability. Our findings provide further information on the development of epileptiform activity in acute hemorrhage.