Oud-beijerland, Netherlands

Study of Neuro-Cognitive Correlates of Pediatric Anxiety Disorders

Study Description: This study examines relations between neurocognitive and clinical features of pediatric anxiety disorders. The study uses neurocognitive tasks, functional magnetic resonance imaging (fMRI), as well as magneto- and electro-encephalography (M/EEG). Patients will be studied over one year, before and after receiving either one of two standard-of-care treatments: cognitive behavioral therapy (CBT) or fluoxetine, a serotonin reuptake inhibitor (SSRI). Healthy comparisons will be studied at comparable time points. Primary Objectives: -To compare healthy youth and symptomatic, medication-free pediatric patients studied prior to receipt of treatment. The study seeks to detect relations between clinical features of anxiety disorders at baseline and a wide range of neurocognitive features associated with attention, memory, and response to motivational stimuli. Secondary Objectives: - To document relations between baseline neurocognitive features and response to Cognitive Behavioral Therapy (CBT) or fluoxetine, as defined by the Pediatric Anxiety Rating Scale (PARS) and Clinical Global Improvement (CGI) Scale. - To document relations between post-treatment changes in neurocognitive features and anxiety symptoms on the PARS following treatment with Cognitive Behavioral Therapy (CBT) or fluoxetine. - To document relations among broad arrays of clinical, cognitive, and neural measures Primary Endpoints: -Indices of percent-signal change in hypothesized brain regions, comprising amygdala, striatum, and prefrontal cortex (PFC) for each fMRI and MEG paradigm. Secondary Endpoints: - Treatment-response as defined by a continuous measure, the Pediatric Anxiety Rating Scale score (PARS), and a categorial measure, the Clinical Global Improvement (CGI) score. - Levels of symptoms and behaviors evoked by tasks that engage attention, memory, and elicit responses to motivational stimuli.

The Psychobiology of Childhood Temperament

Objectives: The goal of this proposal is to study temperament and risk-taking as vulnerability factors for anxiety. Studies have documented that behaviorally inhibited (BI) children are at risk for anxiety disorders. This vulnerability may be associated with neural circuits underlying behavioral tendencies, such as components of the prefrontal cortex (PFC), striatum, and amygdala. Regarding risk-taking behavior, certain high risktaking adolescents also carry enhanced vulnerability to anxiety. We use fMRI, EEG, and MEG to examine activity in PFC, cingulate, amygdala, and striatum, and functional connectivity with resting state methodology in two cohorts, one probing temperament and the other one risk-taking. Study Population: A total of 1410 individuals/ infants (0-40 yo) will be studied. Subjects must be between the ages of 2 months to 14 months, or between the ages of 7 years and 60 years old at the time of enrollment, as the measures we are utilizing are designed for subjects who are in those age ranges. This sample comprises 2 sets of study groups. First, the BI group includes individuals with (1) high motor arousal/high negative affect in early infancy to novelty and sustained BI (BI), (2) high motor arousal/high positive affect to novelty and sustained temperamental exuberance (exuberant), (3) average levels of both reactivity/affect from infancy to childhood (controls), or (4) high or low levels of parent-reported BI based on scores on the Behavioral Inhibition Questionnaire. Second, the risk-taking group includes 4 subgroups representing the interaction of two levels of anxiety (low, high) and two levels of risk-taking (low, high). Finally, a group of healthy individuals will be recruited as controls. Participants will be studied through the age of 60 because both the risk for and expressions of psychopathology continue to change throughout early adulthood. Design: Assessments will include psychiatric, behavioral, and neuropsychological batteries. The protocol uses fMRI and MEG/EEG paradigms targeting different emotional, social, cognitive, motivational, and learning processes during activation studies, as well as the intrinsic function of the brain measured during a resting state. Outcome Measures and Predictions: The main outcome measures are fMRI BOLD signal changes, physiological, neuropsychological and behavioral variables. The proposed fMRI studies will test 2 sets of hypotheses. The first refers to the BI cohort. BI subjects will exhibit (1) enhanced amygdala activation to mild threats (e.g., angry facial), (2) PFC perturbations in associative learning, (3) abnormal fronto-amygdala connectivity, (4) heightened striatal and inferior PFC activation to reward stimuli, (5) unique neural patterns of attention bias and social challenges, (6) differential changes with age as a function of BI status (7) infants of differing temperaments will exhibit structural and functional differences in brain regions associated with salience and ventral attention networks. The second set of hypotheses pertains to the risk-taking cohort. (1) anxious adolescents will activate striatal regions in response to reward more strongly than non-anxious adolescents; (2) risk-takers will also activate striatal regions in response to reward more strongly than non-risk takers; (3) we expect an interaction between risk-taking and anxiety-related factors, such as a potentiation of striatal

MILD® Percutaneous Image-Guided Lumbar Decompression: A Medicare Claims Study

In this study the treatment group will include all patients receiving MILD, and the control group will include all patients receiving IPD for the treatment of LSS during the enrollment period. Reoperation and harms data will be studied for the MILD and IPD procedures for a 24-month follow-up period after the index procedure using Medicare claims data. This study is exempt from IRB oversight (Department of Health and Human Services regulations 45 CFR 46) and does not require prior enrollment nor patient consent. The inclusion of the study's NCT number on MILD Medicare claims is required and results in enrollment.

An Assessment of Cognitive Improvement Training Among Mid-life Individuals

Many health-relevant decisions involve intertemporal (now vs. later) tradeoffs, where unhealthy choices involve immediate benefits and delayed costs, compared to healthy choices with immediate costs and delayed benefits. Reinforcement for unhealthy behaviors are immediate, while the reinforcement for healthier alternatives are delayed. Thus individuals who continue to engage in these types of unhealthy behaviors despite awareness of the health consequences are exhibiting an inability to delay gratification. Delay discounting (DD) is quantified in human studies by determining the rate at which an individual discounts a delayed reward, typically assessed by having subjects choose between a rewards available immediately and a larger reward available following a delay. For the purpose of this study, the investigators define executive function (EF) as the set of cognitive processes that are responsible for helping individuals manage life tasks and achieve goals (e.g., planning, working memory). The approach of targeting preference for immediate rewards (exhibited by elevated DD) is highly innovative. Multiple studies provide compelling evidence that strengthening EF may decrease DD. Extensive literature indicates that many negative health and financial consequences suffered in mid-life are linked to adversity and disadvantage during early developmental periods of life. By targeting a mechanism of various negative aging-related outcomes (elevated DD), the proposed research may have the novel impact on broadly remediating the health and wellness of mid-life individuals at increased risk for poor consequences due to early-life disadvantage. This research will attempt to reduce Delay Discounting via Executive Functioning training in a population of mid-life individuals with risk factors established during early-life disadvantage. DD, EF, and associated health behaviors/outcomes will be assessed at baseline, following training, and at 3- and 6-month follow-up. Participants will receive Active EF training, or Control training. Given the established effect of Active training in reducing DD in stimulant-dependent individuals, the study team expect reductions in DD, improvements in EF, and improvements in associated health behaviors/outcomes following Active training and at follow-up, with no improvements in the Control group.

Mirror Neuron Network Dysfunction as an Early Biomarker of Neurodevelopmental Disorder

Objective: This investigation has two main objectives: 1) combine two child-friendly brain imaging techniques and stochastic modeling to determine the neural basis for the development of imitation and mimicry in human infants and 2) use machine learning to identify brain activation patterns that predict impairment in imitation and mimicry in infants at risk for social communication disorders. Study Population: This study will focus on two groups of infants. The first group includes 60 typically developing infants, who will complete the imitation and neuroimaging paradigm between the ages of 9-12 months (+/- 2 weeks) and again at 12 months of age (+/- 2 weeks). The second group includes 60 infants at increased risk for social communication disorders, including those with motor delay, language delay, preterm birth, or a sibling with an autism spectrum disorder. These infants will complete the imitation and neuroimaging paradigm at 12 months of age (+/- 1 month) as well as a follow up evaluation of social communication skills and developmental status at 24 months of age (+/- 1 month). Design: We propose to conduct longitudinal studies of changes in EEG and fNIRS correlates of mirror neuron network activity in typical development and infants at risk for social communication delay. We will measure both EEG mu suppression and hemodynamic change over the motor cortex during an established infant action/observation paradigm. At all study visits, infants will also complete developmental assessments that measure abilities in cognitive, motor, language, and social domains. Outcome measures: Both neuroimaging measures and developmental status will serve as outcomes for this study. For the typically developing infants, change in the neuroimaging metrics (i.e., percent mu suppression, percent oxyhemoglobin change) will be used to characterize development of the mirror neuron system, while the relation between neuroimaging variables, their trajectories, and developmental ability will be used to develop hypotheses about the role of the mirror neuron network in development of social communication skills. For the infants at risk for social communication disorders, the main outcome will be developmental status, with neuroimaging metrics used as predictors.

Testing the Capability of the Smart Underwear Device to Detect Increased Microbiome Activity Following Lactose Consumption

Nature IDEAS Study: an RCT to Increase Time Spent in Nature Among University Students

America faces a syndemic of youth 'nature deficit disorder' and poor mental health. These conditions can be improved by nature contact, but the outdoors is not equally accessible, particularly for students of color. This study leverages the NatureDose™ app to identify racial/ethnic inequities in nature opportunities, belonging, and benefits and conduct an RCT to improve mental health and address disparities by getting university students outdoors into nature. The investigators will test 3 over-arching questions: 1. Are there differences in nature opportunities and/or belongingness for White versus students of color? 2. Does more time in nature correlate with greater feelings of nature connectedness, belongingness, and better mental health? 3. Is a nature-based intervention that leverages NatureDoseTM a cost-effective way to improve mental health, particularly for students of color? This project has two stages. 1) We will determine nature opportunities at each institution using park and sports field mapping, remote sensing, and tree canopy assessment within 30 miles of campuses to identify disparities. 2) As Fall semester starts, we will recruit 160 students/site for a randomized controlled trial (N=1,440 total, giving 80% power to detect effects down to Cohen's d=0.2 even with attrition). Students will complete baseline surveys on nature connectedness (NR-6), nature belongingness (validated scale for university students), mental health (distress, worry, positive/negative affect), and demographics. Next, students will download the NatureDose™ app, which uses 30+ datasets and machine learning models to quantify nature. The app calculates how much nature is near users whenever they are outdoors, and weekly minutes in nature. App data will be collected over a 2-week baseline period, after which students will be randomized to receive 1) standard information about the health benefits of nature (50%) (Active Control) or 2) standard health information, a request to increase weekly minutes in nature, eligibility for a prize, and peer performance comparison. After 2 weeks, students will repeat baseline surveys.

Gut Microbial Metabolites of Apple Polyphenols

This is a randomized, cross-over controlled feeding trial. Thirty healthy adult volunteers will be selected to participate on the basis of urinary screening results measuring a gut bacterial metabolite that is produced following consumption of a soy food: 15 O-desmethylangolensin (ODMA) producers and 15 age and gender-matched ODMA non-producers will be included. Participants will be assigned to consume two diets in random order: an apple catechin diet that provides a controlled amount of catechins in apple juice, and a nutritionally-matched low catechin diet. Both diet phases will last 3 days, with a 10 day washout period in between the two diet phases.

Longitudinal Investigation of Sleep, Memory, and Brain Development Across the Nap Transition

Child participants will be recruited from databases maintained at each university (see Human Subjects). Initially, parent-report will determine whether the child qualifies as a habitual napper, which will later be confirmed by actigraphy. In each wave, participants will then complete 3 sessions, 3-7 days apart. The first two sessions will consist of nap or wake promotion (counter-balanced, separated by one week) and memory assessments. The third session will consist of a visit to the university for the MRI scan. All of the participants will also have overnight sleep and overnight sleep-dependent memory consolidation assessed on the evenings following the nap/wake sessions. An Actiwatch watch will be given to the participant at the beginning of the first wave. Instructions will be included describing how to put the watch on the child and that the watch should be worn as often as possible. Nap and wake sessions will begin 30 mins prior to the child's typical nap time (if habitual nappers) or approximately 12:30 pm (non-habitual nappers). First, children will complete the encoding and immediate retrieval phases of the mnemonic similarity task. Subsequently, children will either be nap- or wake-promoted. Polysomnography (PSG) will be applied in the nap condition, but timing will be equated in the wake condition. Thirty-minutes following wake (or approximately 3:30 pm for those in the wake group), children will complete the delayed retrieval phase of the mnemonic similarity task. Participants at both testing sites will also have overnight sleep and memory assessed after the nap and wake sessions. Experimenters will arrive at the participant's house about 30 mins prior the child's typical bedtime. The child will encode a new set of stimuli and complete the immediate retrieval phase of the mnemonic discrimination task. Subsequently, the child will be fitted with PSG. Parents are given instructions on placement of the PSG amplifier during the night and how to remove in the electrodes in the morning. Experimenters will return in the morning to retrieve the equipment and obtain the delayed retrieval phase of the mnemonic similarity task. Approximately 3-7 days after the second visit, children will complete the MRI session. The researchers will attempt to obtain MRI scans in the morning to avoid confounds with nap status. The Actiwatch will also be collected in this session. Children will then be fitted with the Fitbit to wear as often as possible between testing waves. These procedures will be repeated every 6 months for 2-3 waves.

Neurocognitive Mechanisms of Sentence Production Impairment in Aphasia

Post-stroke agrammatic aphasia (PSA-G) is characterized by a cluster of symptoms (fragmented sentences, errors in functional morphology, a dearth of verbs, and slow speech rate), yet extant theories and language interventions focus on individual symptoms. This single-symptom theoretical and intervention focus results in limited gains in functional communication. The long-term goal of this research is to improve the clinical effectiveness of interventions for PSA-G. As a first step towards this goal, this project's objective is to advance the theoretical framework of PSA-G by addressing two critical gaps. The first gap is in the mechanistic understanding of how lexical, grammatical, motoric, and cognitive processes work together to enable fluent sentence production and how this breaks down in PSA-G. The second gap is in the understanding of neural mechanisms underlying how sentence production planning normally unfolds over time and what crucial spatiotemporal alterations give rise to PSA-G versus other variants of post-stroke aphasia with predominantly lexico-semantic deficits (PSA-LS). The central hypothesis is that agrammatic language production results from spatiotemporal alterations in the neural dynamics of morphosyntactic and phonomotor processes, causing a cumulative processing bottleneck at the point of articulatory planning. This Synergistic Processing Bottleneck Model of Agrammatism will be tested with two specific aims. Specific Aim 1 will elucidate the relative contribution of syntactic and non-syntactic processes towards sentence production in aphasia by using speed metrics and a path modeling framework. The expected outcomes of this aim are an improved understanding of the extent to which delays in different linguistic processes underlying the agrammatic symptom cluster impair fluent sentence production in aphasia generally, and in PSA-G versus PSA-LS more specifically. Specific Aim 2 will determine the neural mechanisms underlying sentence production across language deficit profiles. Magnetoencephalography (MEG) will be used to compare alterations in timecourse and functional connectivity of key perilesional and contralesional syntactic hubs across increasingly demanding morphosyntactic production tasks. The expected outcome of this aim is a spatiotemporally specified neural model of sentence production in neurotypical, PSA-G, and PSA-LS speakers. The significance this research is that it will forward an empirically established multidimensional model of sentence production, which will lay the foundation for developing more targeted and effective language interventions for agrammatic aphasia. It will also contribute to a better understanding of agrammatism in neurodegenerative aphasias. The innovative aspects of this project include: a novel multidimensional theoretical framework that incorporates non-syntactic dimensions of phonomotor planning, processing capacity and speed, and neurophysiological dynamics; direct comparisons between PSA-G and PSA-LS groups; and MEG analysis of spoken language with simultaneous electromyographic measurement.