Race-Based Differences in the Response to a Mindfulness Based Integrative Medical Group Visit Intervention for Chronic Pain.

Background: Chronic pain is one of the most common drivers of healthcare utilization and a marked domain for health disparities, as African American/Black populations experience high rates of chronic pain. Integrative Medical Group Visits (IMGV) combine mindfulness techniques, evidence-based integrative medicine, and medical group visits. In a parent randomized controlled trial, this approach was tested as an adjunct treatment in a diverse, medically underserved population with chronic pain and depression. Objective: To determine race-based heterogeneity in the effects of a mindfulness based treatment for chronic pain. Methods: This secondary analysis of the parent trial assessed heterogeneity of treatment effects along racialized identity in terms of primary patient-reported pain outcomes in a racially diverse sample suffering from chronic pain and depression. The analytic approach examined comorbidities and sociodemographics between racialized groups. RMANOVAs examined trajectories in pain outcomes (average pain, pain severity, and pain interference) over three timepoints (baseline, 9, and 21 weeks) between participants identifying as African American/Black (n = 90) vs White (n = 29) across both intervention and control conditions. Results: At baseline, African American/Black participants had higher pain severity and had significantly different age, work status, and comorbidity profiles. RMANOVA models also identified significant race-based differences in the response to the parent IMGV intervention. There was reduced pain severity in African American/Black subjects in the IMGV condition from baseline to 9 weeks. This change was not observed in White participants over this time period. However, there was a reduction in pain severity in White participants over the subsequent interval from 9 to 21 week where IMGV had no significant effect in African American/Black subjects during this latter time period. Conclusion: Interactions between pain and racialization require further investigation to understand how race-based heterogeneity in the response to integrative medicine treatments for chronic pain contribute to the broader landscape of health inequity.

Effects of the Mindfulness-Based Blood Pressure Reduction (MB-BP) program on depression and neural structural connectivity.

BACKGROUND: Hypertension-related illnesses are a leading cause of disability and death in the United States, where hypertension prevalence in adults is 46%, with only half of those afflicted having it under control. Due to the significant challenges in long-term efficacy and adverse effects associated with pharmacological interventions, there is an eminent need for complimentary approaches for treating hypertension. Although initial studies of the Mindfulness-Based Blood Pressure Reduction program (MB-BP) indicate that this novel 8-week intervention is effective at inducing lasting decreases in blood pressure, the neural correlates are unknown. METHODS: The objectives of this study were to identify structural neural correlates of MB-BP using diffusion tensor magnetic resonance imaging (DTI) and assess potential correlations with key clinical outcomes. RESULTS: In a subset of participants (14 MB-BP, 22 controls) from a larger stage IIa randomized controlled trial, MB-BP participants exhibited increased interoception and decreased depressive symptoms compared to controls. Analyses of DTI data revealed significant group differences in multiple white matter neural tracts associated with the limbic system and/or blood pressure. Specific changes in neural structural connectivity were significantly associated with measures of interoception and depression. LIMITATIONS: Limitations include small sample size (leading to insufficient power in the analysis of blood pressure) and the study duration (3 months). The main MRI limitation is suboptimal resolution in areas of extensive neural tract crossings. CONCLUSIONS: It is concluded that MB-BP induces alterations in brain structural connectivity which could mediate beneficial changes in depression and interoceptive awareness in individuals with hypertension.

Introduction to the special issue on evaluator education.

After years in preparation, we are pleased to introduce this special issue of Evaluation and Program Planning that focuses on evaluator education, a topic that we believe is of considerable importance to the field's future. Before describing the issue's content, let us ground the articles in two ways: by examining the larger context within which evaluator education finds itself, and by briefly explaining who we are and describing how the issue came into being.

Depression Predicts Chronic Pain Interference in Racially Diverse, Income-Disadvantaged Patients.

BACKGROUND: Chronic pain is one of the most common reason adults seek medical care in the United States, with prevalence estimates ranging from 11% to 40%. Mindfulness meditation has been associated with significant improvements in pain, depression, physical and mental health, sleep, and overall quality of life. Group medical visits are increasingly common and are effective at treating myriad illnesses, including chronic pain. Integrative Medical Group Visits (IMGV) combine mindfulness techniques, evidence based integrative medicine, and medical group visits and can be used as adjuncts to medications, particularly in diverse underserved populations with limited access to non-pharmacological therapies. OBJECTIVE AND DESIGN: The objective of the present study was to use a blended analytical approach of machine learning and regression analyses to evaluate the potential relationship between depression and chronic pain in data from a randomized clinical trial of IMGV in diverse, income-disadvantaged patients suffering from chronic pain and depression. METHODS: The analytical approach used machine learning to assess the predictive relationship between depression and pain and identify and select key mediators, which were then assessed with regression analyses. It was hypothesized that depression would predict the pain outcomes of average pain, pain severity, and pain interference. RESULTS: Our analyses identified and characterized a predictive relationship between depression and chronic pain interference. This prediction was mediated by high perceived stress, low pain self-efficacy, and poor sleep quality, potential targets for attenuating the adverse effects of depression on functional outcomes. CONCLUSIONS: In the context of the associated clinical trial and similar interventions, these insights may inform future treatment optimization, targeting, and application efforts in racialized, income-disadvantaged populations, demographics often neglected in studies of chronic pain.

Latent Factor Decomposition Model: Applications for Questionnaire Data.

The analysis of clinical questionnaire data comes with many inherent challenges. These challenges include the handling of data with missing fields, as well as the overall interpretation of a dataset with many fields of different scales and forms. While numerous methods have been developed to address these challenges, they are often not robust, statistically sound, or easily interpretable. Here, we propose a latent factor modeling framework that extends the principal component analysis for both categorical and quantitative data with missing elements. The model simultaneously provides the principal components (basis) and each patients' projections on these bases in a latent space. We show an application of our modeling framework through Irritable Bowel Syndrome (IBS) symptoms, where we find correlations between these projections and other standardized patient symptom scales. This latent factor model can be easily applied to different clinical questionnaire datasets for clustering analysis and interpretable inference.

Altered neural networks and cognition in a hereditary colon cancer.

Familial Adenomatous Polyposis (FAP) is an autosomal dominant disorder caused by mutation of the APC gene presenting with numerous colorectal adenomatous polyps and a near 100% risk of colon cancer. Preliminary research findings from our group indicate that FAP patients experience significant deficits across many cognitive domains. In the current study, fMRI brain metrics in a FAP population and matched controls were used to further the mechanistic understanding of reported cognitive deficits. This research identified and characterized any possible differences in resting brain networks and associations between neural network changes and cognition from 34 participants (18 FAP patients, 16 healthy controls). Functional connectivity analysis was performed using FSL with independent component analysis (ICA) to identify functional networks. Significant differences between cases and controls were observed in 8 well-established resting state networks. With the addition of an aggregate cognitive measure as a covariate, these differences were virtually non-existent, indicating a strong correlation between cognition and brain activity at the network level. The data indicate robust and pervasive effects on functional neural network activity among FAP patients and these effects are likely involved in cognitive deficits associated with this disease.

Keeping weight off: Mindfulness-Based Stress Reduction alters amygdala functional connectivity during weight loss maintenance in a randomized control trial.

Obesity is associated with significant comorbidities and financial costs. While behavioral interventions produce clinically meaningful weight loss, weight loss maintenance is challenging. The objective was to improve understanding of the neural and psychological mechanisms modified by mindfulness that may predict clinical outcomes. Individuals who intentionally recently lost weight were randomized to Mindfulness-Based Stress Reduction (MBSR) or a control healthy living course. Anthropometric and psychological factors were measured at baseline, 8 weeks and 6 months. Functional connectivity (FC) analysis was performed at baseline and 8 weeks to examine FC changes between regions of interest selected a priori, and independent components identified by independent component analysis. The association of pre-post FC changes with 6-month weight and psychometric outcomes was then analyzed. Significant group x time interaction was found for FC between the amygdala and ventromedial prefrontal cortex, such that FC increased in the MBSR group and decreased in controls. Non-significant changes in weight were observed at 6 months, where the mindfulness group maintained their weight while the controls showed a weight increase of 3.4% in BMI. Change in FC at 8-weeks between ventromedial prefrontal cortex and several ROIs was associated with change in depression symptoms but not weight at 6 months. This pilot study provides preliminary evidence of neural mechanisms that may be involved in MBSR's impact on weight loss maintenance that may be useful for designing future clinical trials and mechanistic studies.

Altered Resting State Brain Networks and Cognition in Familial Adenomatous Polyposis.

Familial Adenomatous Polyposis (FAP) is an autosomal dominant disorder caused by mutation of the APC gene presenting with numerous colorectal adenomatous polyps and a near 100% risk of colon cancer. Preliminary research findings from our group indicate that FAP patients experience significant deficits across many cognitive domains. In the current study, fMRI brain metrics in a FAP population and matched controls were used to further the mechanistic understanding of reported cognitive deficits. This research identified and characterized any possible differences in resting brain networks and associations between neural network changes and cognition from 34 participants (18 FAP patients, 16 healthy controls). Functional connectivity analysis was performed using FSL with independent component analysis (ICA) to identify functional networks. Significant differences between cases and controls were observed in 8 well-established resting state networks. With the addition of an aggregate cognitive measure as a covariate, these differences were virtually non-existent, indicating a strong correlation between cognition and brain activity at the network level. The data indicate robust and pervasive effects on functional neural network activity among FAP patients and these effects are likely involved in cognitive deficits associated with this disease.

Robustness of sex-differences in functional connectivity over time in middle-aged marmosets.

Nonhuman primates (NHPs) are an essential research model for gaining a comprehensive understanding of the neural mechanisms of neurocognitive aging in our own species. In the present study, we used resting state functional connectivity (rsFC) to investigate the relationship between prefrontal cortical and striatal neural interactions, and cognitive flexibility, in unanaesthetized common marmosets (Callithrix jacchus) at two time points during late middle age (8 months apart, similar to a span of 5-6 years in humans). Based on our previous findings, we also determine the reproducibility of connectivity measures over the course of 8 months, particularly previously observed sex differences in rsFC. Male marmosets exhibited remarkably similar patterns of stronger functional connectivity relative to females and greater cognitive flexibility between the two imaging time points. Network analysis revealed that the consistent sex differences in connectivity and related cognitive associations were characterized by greater node strength and/or degree values in several prefrontal, premotor and temporal regions, as well as stronger intra PFC connectivity, in males compared to females. The current study supports the existence of robust sex differences in prefrontal and striatal resting state networks that may contribute to differences in cognitive function and offers insight on the neural systems that may be compromised in cognitive aging and age-related conditions such as mild cognitive impairment and Alzheimer's disease.

What do we know about evaluator education? A review of peer-reviewed publications (1978-2018).

This article reviews peer-reviewed writings on evaluator education from 1978 to 2018. Despite the topic's presumed importance, scholars to date have not extensively addressed it in peer-reviewed publications. The article first describes the methods used to select articles and the conceptual framework for their analysis. It then presents the content of 64 articles selected for review, divided into two major categories: research studies, and reflective case narratives. We further divide research studies into program directories and empirical studies; the case narratives provide information on programs, curriculum, and instruction and minimally on students/faculty. The article concludes with thoughts on next steps for research on evaluator education.

Chronic alcohol-induced liver injury correlates with memory deficits: Role for neuroinflammation.

Alcohol use disorder (AUD) affects over 15 million adults over age 18 in the United States, with estimated costs of 220 billion dollars annually - mainly due to poor quality of life and lost productivity, which in turn is intricately linked to cognitive dysfunction. AUD-induced neuroinflammation in the brain, notably the hippocampus, is likely to contribute to cognitive impairments. The neuroinflammatory mechanisms mediating the impact of chronic alcohol on the central nervous system, specifically cognition, require further study. We hypothesized that chronic alcohol consumption impairs memory and increases the inflammatory cytokines TNFα, IL6, MCP1, and IL1ß in the hippocampus and prefrontal cortex regions in the brain. Using the chronic-binge Gao-NIAAA alcohol mouse model of liver disease, representative of the drinking pattern common to human alcoholics, we investigated behavioral and neuroinflammatory parameters. Our data show that chronic alcohol intake elevated peripheral and brain alcohol levels, induced serum alanine aminotransferase (ALT, a marker of liver injury), impaired memory and sensorimotor coordination, and increased inflammatory gene expression in the hippocampus and prefrontal cortex. Interestingly, serum ALT and hippocampal IL6 correlated with memory impairment, suggesting an intrinsic relationship between neuroinflammation, cognitive decline, and liver disease. Overall, our results point to a likely liver-brain functional partnership and suggest that future strategies to alleviate hepatic and/or neuroinflammatory impacts of chronic AUD may result in improved cognitive outcomes.

Putting evaluation capacity building in context: Reflections on the Ontario Brain Institute's Evaluation Support Program.

This article, in three parts, reflects on the content of the six articles included in the forum. It begins with a description of the Evaluation Support Program, emphasizing its key attributes. Next, it raises two points regarding ECB theory: (1) the need to become clearer about the concepts and terms used to describe and study this phenomenon, and (2) the potential value of social science theory to understand ECB and improve its practice. The article concludes with practical ideas for improving ECB: (1) framing it as an educative act, which assigns the evaluator the critical role of evaluation teacher/coach; and (2) the importance of never assuming that an ECB effort begins in unchartered territory, but rather that it builds on people's knowledge, skills, attitudes, and previous experiences.

The current state of evaluator education: A situation analysis and call to action.

Education is critically important for the maintenance and growth of programme evaluation and its emergence as a profession. This position paper presents evaluator education as an initiative and provides a foundation for its evaluation. In it, the authors use Stufflebeam's Context, Input, Process, and Product (CIPP) model to frame a review of the literature and practice. We follow this analysis of the current state of evaluator education in formal settings, with discussion of its implications, and directions for future research and action. Our analysis suggests that there is much work to be done to understand the needs for evaluator education, to delineate standards for quality in both education and practice, to identify the inputs and processes most effective for addressing those needs, and to document its ultimate impacts. The paper provides a call to action for improving the quality, consistency, and integrity of this important work.

Promoting evaluation capacity building in a complex adaptive system.

This study provides results from an NSF funded, four year, case study about evaluation capacity building in a complex adaptive system, the Nanoscale Informal Science Education Network (NISE Net). The results of the Complex Adaptive Systems as a Model for Network Evaluations (CASNET) project indicate that complex adaptive system concepts help to explain evaluation capacity building in a network. The NISE Network was found to be a complex learning system that was supportive of evaluation capacity building through feedback loops that provided for information sharing and interaction. Participants in the system had different levels of and sources of evaluation knowledge. To be successful at building capacity, the system needed to have a balance between both centralized and decentralized control, coherence, redundancy, and diversity. Embeddedness of individuals within the system also provided support and moved the capacity of the system forward. Finally, success depended on attention being paid to the control of resources. Implications of these findings are discussed.

Early life social stress and resting state functional connectivity in postpartum rat anterior cingulate circuits.

INTRODUCTION: Continued development and refinement of resting state functional connectivity (RSFC) fMRI techniques in both animal and clinical studies has enhanced our comprehension of the adverse effects of stress on psychiatric health. The objective of the current study was to assess both maternal behavior and resting state functional connectivity (RSFC) changes in these animals when they were dams caring for their own young. It was hypothesized that ECSS exposed dams would express depressed maternal care and exhibit similar (same networks), yet different specific changes in RSFC (different individual nuclei) than reported when they were adult females. METHODS: We have developed an ethologically relevant transgenerational model of the role of chronic social stress (CSS) in the etiology of postpartum depression and anxiety. Initial fMRI investigation of the CSS model indicates that early life exposure to CSS (ECSS) induces long term changes in functional connectivity in adult nulliparous female F1 offspring. RESULTS: ECSS in F1 dams resulted in depressed maternal care specifically during early lactation, consistent with previous CSS studies, and induced changes in functional connectivity in regions associated with sensory processing, maternal and emotional responsiveness, memory, and the reward pathway, with robust changes in anterior cingulate circuits. LIMITATIONS: The sample sizes for the fMRI groups were low, limiting statistical power. CONCLUSION: This behavioral and functional neuroanatomical foundation can now be used to enhance our understanding of the neural etiology of early life stress associated disorders and test preventative measures and treatments for stress related disorders.

Glutamine/glutamate (Glx) concentration in prefrontal cortex predicts reversal learning performance in the marmoset.

This study used Magnetic Resonance Spectroscopy (MRS) to identify potential neurometabolitic markers of cognitive performance in male (n = 7) and female (n = 8) middle-aged (∼5 years old) common marmosets (Callithrix jacchus). Anesthetized marmosets were scanned with a 4.7 T/40 cm horizontal magnet equipped with 450 mT/m magnetic field gradients and a 20 G/cm magnetic field gradient insert, within 3 months of completing the CANTAB serial Reversal Learning task. Neurometabolite concentrations of N-Acetyl Asparate, Myo-Inositol, Choline, Phosphocreatine + creatine, Glutamate and Glutamine were acquired from a 3 mm3 voxel positioned in the Prefrontal Cortex (PFC). Males acquired the reversals (but not simple discriminations) faster than the females. Higher PFC Glx (glutamate + glutamine) concentration was associated with faster acquisition of the reversals. Interestingly, the correlation between cognitive performance and Glx was significant in males, but not in females. These results suggest that MRS is a useful tool to identify biochemical markers of cognitive performance in the healthy nonhuman primate brain and that biological sex modulates the relationship between neurochemical composition and cognition.

Menthol enhances nicotine-induced locomotor sensitization and in vivo functional connectivity in adolescence.

Mentholated cigarettes capture a quarter of the US market, and are disproportionately smoked by adolescents. Menthol allosterically modulates nicotinic acetylcholine receptor function, but its effects on the brain and nicotine addiction are unclear. To determine if menthol is psychoactive, we assessed locomotor sensitization and brain functional connectivity. Adolescent male Sprague Dawley rats were administered nicotine (0.4 mg/kg) daily with or without menthol (0.05 mg/kg or 5.38 mg/kg) for nine days. Following each injection, distance traveled in an open field was recorded. One day after the sensitization experiment, functional connectivity was assessed in awake animals before and after drug administration using magnetic resonance imaging. Menthol (5.38 mg/kg) augmented nicotine-induced locomotor sensitization. Functional connectivity was compared in animals that had received nicotine with or without the 5.38 mg/kg dosage of menthol. Twenty-four hours into withdrawal after the last drug administration, increased functional connectivity was observed for ventral tegmental area and retrosplenial cortex with nicotine+menthol compared to nicotine-only exposure. Upon drug re-administration, the nicotine-only, but not the menthol groups, exhibited altered functional connectivity of the dorsal striatum with the amygdala. Menthol, when administered with nicotine, showed evidence of psychoactive properties by affecting brain activity and behavior compared to nicotine administration alone.

Evidence of Altered Brain Responses to Nicotine in an Animal Model of Attention Deficit/Hyperactivity Disorder.

INTRODUCTION: Individuals with attention deficit/hyperactivity disorder (ADHD) are susceptible to earlier and more severe nicotine addiction. To shed light on the relationship between nicotine and ADHD, we examined nicotine's effects on functional brain networks in an animal model of ADHD. METHODS: Awake magnetic resonance imaging was used to compare functional connectivity in adolescent (post-natal day 44 ± 2) males of the spontaneously hypertensive rat (SHR) strain and two control strains, Wistar-Kyoto and Sprague-Dawley (n = 16 each). We analyzed functional connectivity immediately before and after nicotine exposure (0.4 mg/kg base) in naïve animals, using a region-of-interest approach focussing on 16 regions previously implicated in reward and addiction. RESULTS: Relative to the control groups, the SHR strain demonstrated increased functional connectivity between the ventral tegmental area (VTA) and retrosplenial cortex in response to nicotine, suggesting an aberrant response to nicotine. In contrast, increased VTA-substantia nigra connectivity in response to a saline injection in the SHR was absent following a nicotine injection, suggesting that nicotine normalized function in this circuit. CONCLUSIONS: In the SHR, nicotine triggered an atypical response in one VTA circuit while normalizing activity in another. The VTA has been widely implicated in drug reward. Our data suggest that increased susceptibility to nicotine addiction in individuals with ADHD may involve altered responses to nicotine involving VTA circuits. IMPLICATIONS: Nicotine addiction is more common among individuals with ADHD. We found that two circuits involving the VTA responded differently to nicotine in animals that model ADHD in comparison to two control strains. In one circuit, nicotine normalized activity that was abnormal in the ADHD animals, while in the other circuit nicotine caused an atypical brain response in the ADHD animals. The VTA has been implicated in drug reward. Our results would be consistent with an interpretation that nicotine may normalize abnormal brain activity in ADHD, and that nicotine may be more rewarding for individuals with ADHD.

Relationship of mindful awareness to neural processing of angry faces and impact of mindfulness training: A pilot investigation.

Mindfulness is paying attention, non-judgmentally, to experience in the moment. Mindfulness training reduces depression and anxiety and influences neural processes in midline self-referential and lateralized somatosensory and executive networks. Although mindfulness benefits emotion regulation, less is known about its relationship to anger and the corresponding neural correlates. This study examined the relationship of mindful awareness and brain hemodynamics of angry face processing, and the impact of mindfulness training. Eighteen healthy volunteers completed an angry face processing fMRI paradigm and measurement of mindfulness and anger traits. Ten of these participants were recruited from a Mindfulness-Based Stress Reduction (MBSR) class and also completed imaging and other assessments post-training. Self-reported mindful awareness increased after MBSR, but trait anger did not change. Baseline mindful awareness was negatively related to left inferior parietal lobule activation to angry faces; trait anger was positively related to right middle frontal gyrus and bilateral angular gyrus. No significant pre-post changes in angry face processing were found, but changes in trait mindful awareness and anger were associated with sub-threshold differences in paralimbic activation. These preliminary and hypothesis-generating findings, suggest the analysis of possible impact of mindfulness training on anger may begin with individual differences in angry face processing.

Altered neural connectivity in adult female rats exposed to early life social stress.

The use of a variety of neuroanatomical techniques has led to a greater understanding of the adverse effects of stress on psychiatric health. One recent advance that has been particularly valuable is the development of resting state functional connectivity (RSFC) in clinical studies. The current study investigates changes in RSFC in F1 adult female rats exposed to the early life chronic social stress (ECSS) of the daily introduction of a novel male intruder to the cage of their F0 mothers while the F1 pups are in the cage. This ECSS for the F1 animals consists of depressed maternal care from their F0 mothers and exposure to conflict between their F0 mothers and intruder males. Analyses of the functional connectivity data in ECSS exposed adult females versus control females reveal broad changes in the limbic and reward systems, the salience and introspective socioaffective networks, and several additional stress and social behavior associated nuclei. Substantial changes in connectivity were found in the prefrontal cortex, nucleus accumbens, hippocampus, and somatosensory cortex. The current rodent RSFC data support the hypothesis that the exposure to early life social stress has long term effects on neural connectivity in numerous social behavior, stress, and depression relevant brain nuclei. Future conscious rodent RSFC studies can build on the wealth of data generated from previous neuroanatomical studies of early life stress and enhance translational connectivity between animal and human fMRI studies in the development of novel preventative measures and treatments.