What Has Neuroimaging Taught Us on the Neurobiology of Yoga? A Review

Yoga is becoming increasingly popular worldwide, with several implicated physical and mental benefits. Here we provide a comprehensive and critical review of the research generated from the existing neuroimaging literature in studies of yoga practitioners. We reviewed 34 international peer-reviewed neuroimaging studies of yoga using magnetic resonance imaging (MRI), positron emission tomography (PET), or single-photon emission computed tomography (SPECT): 11 morphological and 26 functional studies, including three studies that were classified as both morphological and functional. Consistent findings include increased gray matter volume in the insula and hippocampus, increased activation of prefrontal cortical regions, and functional connectivity changes mainly within the default mode network. There is quite some variability in the neuroimaging findings that partially reflects different yoga styles and approaches, as well as sample size limitations. Direct comparator groups such as physical activity are scarcely used so far. Finally, hypotheses on the underlying neurobiology derived from the imaging findings are discussed in the light of the potential beneficial effects of yoga.status: publishe

Understanding Adoption of Electronic Medical Records: Application of Process Mining for Health Worker Behavior Analysis

In the Philippine Health Insurance Company (PHIC) Advisory 04-2016, Primary Care Providers were given until the end of the year to adopt any of the certified electronic medical record providers for submission of patient profiling and patient consultations. With much emphasis on how electronic medical records can pave the way for better health care, this study presents finding on one year usage of a certified electronic medical record in selected areas in the Philippines. The study uses a novel approach in understanding technology adoption through process mining - technique often used in Business Process Analysis (BPA). A total of 8.8 million system-generated usage logs including: Session ID, Timestamp, URL Visited, URL Source, User ID were extracted as part of the dataset. Pre-processing techniques were performed on the data set prior to process mining. In using process mining to understand user behavior based on system-generated usage logs, one must consider: how to identify a case (i.e. how to group activities together), and how to structure your data in a way that allows the inference of real world activities and processes. Using standard adoption models shows us that adoption of early implementation of EMRs remain at basic usage with only a few users fully embracing the technology. However, use of process mining in understanding user behavior depicts actual workflow and presents adoption at a more advanced level

Long-term Ashtanga yoga practice decreases medial temporal and brainstem glucose metabolism in relation to years of experience

BACKGROUND: Yoga is increasingly popular worldwide with several physical and mental benefits, but the underlying neurobiology remains unclear. Whereas many studies have focused on pure meditational aspects, the triad of yoga includes meditation, postures, and breathing. We conducted a cross-sectional study comparing experienced yoga practitioners to yoga-naive healthy subjects using a multiparametric 2 × 2 design with simultaneous positron emission tomography/magnetic resonance (PET/MR) imaging. METHODS: 18F-FDG PET, morphometric and diffusion tensor imaging, resting state fMRI, and MR spectroscopy were acquired in 10 experienced (4.8 ± 2.3 years of regular yoga experience) yoga practitioners and 15 matched controls in rest and after a single practice (yoga practice and physical exercise, respectively). RESULTS: In rest, decreased regional glucose metabolism in the medial temporal cortex, striatum, and brainstem was observed in yoga practitioners compared to controls (p < 0.0001), with a significant inverse correlation of resting parahippocampal and brainstem metabolism with years of regular yoga practice (ρ < - 0.63, p < 0.05). A single yoga practice resulted in significant hypermetabolism in the cerebellum (p < 0.0001). None of the MR measures differed, both at rest and after intervention. CONCLUSIONS: Experienced yoga practitioners show regional long-term decreases in glucose metabolism related to years of practice. To elucidate a potential causality, a prospective longitudinal study in yoga-naive individuals is warranted.status: publishe

Quantification and discriminative power of 18F-FE-PE2I PET in patients with Parkinson’s disease

Rationale Dopamine transporter (DAT) imaging is an important adjunct in the diagnostic workup of patients with Parkinsonism. F-18-FE-PE2I is a suitable PET radioligand for DAT quantification and imaging with good pharmacokinetics. The aim of this study was to determine a clinical optimal simplified reference tissue-based image acquisition protocol and to compare the discriminatory value and effect size for F-18-FE-PE2I to that for I-123-FP-CIT scan currently used in clinical practice. Methods Nine patients with early Parkinson's disease (PD, 64.3 +/- 6.8 years, 3M), who had previously undergone a I-123-FP-CIT scan as part of their diagnostic workup, and 34 healthy volunteers (HV, 47.7 +/- 16.8 years, 13M) underwent a 60-min dynamic F-18-FE-PE2I PET-MR scan on a GE Signa 3T PET-MR. Based on dynamic data and MR-based VOI delineation, BPND, semi-quantitative uptake ratio and SUVR[t1-t2] images were calculated using either occipital cortex or cerebellum as reference region. For start-and-end time of the SUVR interval, three time frames [t(1)-t(2)] were investigated: [15-40] min, [40-60] min, and [50-60] min postinjection. Data for putamen (PUT) and caudate nucleus-putamen ratio (CPR) were compared in terms of quantification bias versus BPND and discriminative power. Results Using occipital cortex as reference region resulted in smaller bias of SUVR with respect to BPND + 1 and higher correlation between SUVR and BPND + 1 compared with using cerebellum, irrespective of SUVR [t(1)-t(2)] interval. Smallest bias was observed with the [15-40]-min time window, in accordance with previous literature. The correlation between BPND + 1 and SUVR was slightly better for the late time windows. Discriminant analysis between PD and HV using both PUT and CPR SUVRs showed an accuracy of >= 90%, for both reference regions and all studied time windows. Semi-quantitative I-123-FP-CIT and F-18-FE-PE2I values and relative decrease in the striatum for patients were highly correlated, with a higher effect size for F-18-FE-PE2I for PUT and CPR SUVR. Conclusion F-18-FE-PE2I is a suitable radioligand for in vivo DAT imaging with high discriminative power between early PD and healthy controls. Whereas a [15-40]-min window has lowest bias with respect to BPND, a [50-60]-min time window at pseudoequilibrium can be advocated in terms of clinical feasibility with optimal discriminative power. The occipital cortex may be slightly preferable as reference region because of the higher time stability, stronger correlation of SUVR with BPND + 1, and lower bias. Moreover, the data suggest that the diagnostic accuracy of a 10-min static F-18-FE-PE2I scan is non-inferior compared with I-123-FP-CIT scan used in standard clinical practice

Development of CliniPup, a Serious Game Aimed at Reducing Perioperative Anxiety and Pain in Children: Mixed Methods Study

BACKGROUND: An increasing number of children undergo ambulatory surgery each year, and a significant proportion experience substantial preoperative anxiety and postoperative pain. The management of perioperative anxiety and pain remains challenging in children and is inadequate, which negatively impacts the physical, psychosocial, and economic outcomes. Existing nonpharmacological interventions are costly, time consuming, vary in availability, and lack benefits. Therefore, there is a need for an evidence-based, accessible, nonpharmacological intervention as an adjunct to existing pharmacological alternatives to reduce perioperative anxiety and pain in children undergoing ambulatory surgery. Technology-enabled interventions have been proposed as a method to address the unmet need in this setting. In particular, serious games hold a unique potential to change health beliefs and behaviors in children. OBJECTIVE: The objective of this research was to describe the rationale, scientific evidence, design aspects, and features of CliniPup, a serious game aimed at reducing perioperative anxiety and pain in children undergoing ambulatory surgery. METHODS: The SERES Framework for serious game development was used to create the serious game, CliniPup. In particular, we used a mixed methods approach that consisted of a structured literature review supplemented with ethnographic research, such as expert interviews and a time-motion exercise. The resulting scientific evidence base was leveraged to ensure that the resulting serious game was relevant, realistic, and theory driven. A participatory design approach was applied, wherein clinical experts qualitatively reviewed several versions of the serious game, and an iterative creative process was used to integrate the applicable feedback. RESULTS: CliniPup, a serious game, was developed to incorporate a scientific evidence base from a structured literature review, realistic content collected during ethnographic research such as expert interviews, explicit pedagogical objectives from scientific literature, and game mechanics and user interface design that address key aspects of the evidence. CONCLUSIONS: This report details the systematic development of CliniPup, a serious game aimed at reducing perioperative anxiety and pain in children undergoing ambulatory surgery. Clinical experts validated CliniPup's underlying scientific evidence base and design foundations, suggesting that it was well designed for preliminary evaluation in the target population. An evaluation plan is proposed and briefly described.status: publishe

A Web-Based Serious Game for Health to Reduce Perioperative Anxiety and Pain in Children (CliniPup): Pilot Randomized Controlled Trial

BACKGROUND: As pediatric ambulatory surgeries are rising and existing methods to reduce perioperative anxiety and pain are lacking in this population, a serious game for health (SGH), CliniPup, was developed to address this unmet need. CliniPup was generated using the SERES framework for serious game development. OBJECTIVE: The goal of the research was to clinically evaluate CliniPup as an adjunct therapy to existing pharmacological interventions aimed at reducing perioperative anxiety and pain in children undergoing ambulatory surgery. METHODS: CliniPup was evaluated in a prospective randomized controlled pilot trial in 20 children aged 6 to 10 years who underwent elective surgery and their parents. Study participants were randomly assigned to the test (n=12) or control group (n=8). Children in the test group played CliniPup 2 days prior to surgery, and children in the control group received standard of care. On the day of surgery, pediatric anxiety was measured with the modified Yale Preoperative Anxiety Scale and parental anxiety was assessed with the State-Trait Anxiety Inventory. Pediatric postoperative pain was assessed by the Wong-Baker Faces Pain Rating Scale. Child and parent user experience and satisfaction were also evaluated in the test group using structured questionnaires. RESULTS: Despite the small sample, preoperative anxiety scores were significantly lower (P=.01) in children who played CliniPup prior to surgery compared to controls. Parental preoperative anxiety scores were also lower in the test group (P=.10) but did not reach significance. No significant differences were observed in postoperative pain scores between groups (P=.54). The evaluation of user experience and satisfaction revealed that both children and parents were satisfied with CliniPup and would recommend the game to peers. CONCLUSIONS: Results of the pilot trial introduce CliniPup as a potentially effective and attractive adjunct therapy to reduce preoperative anxiety in children undergoing ambulatory surgery with a trend toward positive impact on parental preoperative anxiety. These results support the use of the SERES framework to generate an evidence-based SGH that results in positive health outcomes for patients. Based on these preliminary findings, we propose a research agenda to further develop and investigate this tool. TRIAL REGISTRATION: ClinicalTrials.gov NCT03874442; https://clinicaltrials.gov/ct2/show/NCT03874442 (Archived by WebCite at http://www.webcitation.org/78KZab8qc).status: publishe

Age-related GABAergic differences in the primary sensorimotor cortex: A multimodal approach combining PET, MRS and TMS.

Healthy aging is associated with mechanistic changes in gamma-aminobutyric acid (GABA), the most abundant inhibitory neurotransmitter in the human brain. While previous work mainly focused on magnetic resonance spectroscopy (MRS)-based GABA+ levels and transcranial magnetic stimulation (TMS)-based GABAA receptor (GABAAR) activity in the primary sensorimotor (SM1) cortex, the aim of the current study was to identify age-related differences in positron emission tomography (PET)-based GABAAR availability and its relationship with GABA+ levels (i.e. GABA with the contribution of macromolecules) and GABAAR activity. For this purpose, fifteen young (aged 20-28 years) and fifteen older (aged 65-80 years) participants were recruited. PET and MRS images were acquired using simultaneous time-of-flight PET/MR to evaluate age-related differences in GABAAR availability (distribution volume ratio with pons as reference region) and GABA+ levels. TMS was applied to identify age-related differences in GABAAR activity by measuring short-interval intracortical inhibition (SICI). Whereas GABAAR availability was significantly higher in the SM cortex of older as compared to young adults (18.5%), there were neither age-related differences in GABA+ levels nor SICI. A correlation analysis revealed no significant associations between GABAAR availability, GABAAR activity and GABA+ levels. Although the exact mechanisms need to be further elucidated, it is possible that a higher GABAAR availability in older adults is a compensatory mechanism to ensure optimal inhibitory functionality during the aging process.status: Published onlin

Quantifying SV2A density and drug occupancy in the human brain using [C-11]UCB-J PET imaging and subcortical white matter as reference tissue

PURPOSE: A [11C]UCB-J blocking study was performed in healthy volunteers to validate simplified, non-invasive measures for quantifying presynaptic SV2A expression using subcortical white matter as reference tissue. METHODS: Ninety minutes dynamic [11C]UCB-J PET scanning with arterial blood sampling was performed in 10 healthy volunteers (8 M/2F; age 27.6 ± 10.0 yrs), before and after administration of a novel chemical entity with selective affinity for SV2A. The centrum semi-ovale (SO) was validated as reference region by comparing baseline and post treatment distribution volume (VT). Using SO as reference tissue, Binding Potential (BPSO) using a Simplified Reference Tissue Model (SRTM, down to 60 min acquisition) and Standardized Uptake Value Ratios (60-90 min post injection - SUVRSO,60-90min) were compared with regional distribution volume ratios (DVR). Next, SV2A occupancy values based on SRTM BPSO and SUVRSO,60-90min were compared to occupancy estimates using regional VT values and a Lassen plot. RESULTS: After pretreatment, regional VT values were reduced significantly except for SO. Highly significant correlations were found between DVR, SRTM BPSO and SUVRSO,60-90min. Compared to DVR, baseline SRTM BPSO showed a small bias (≤ 6.1%) with lower precision for shorter acquisition times, while SUVRSO,60-90min showed 3.5% bias with similar precision. Differences between SV2A occupancy values based on SUVRSO,60-90min and occupancy estimates using VT and a Lassen plot were small but significant, while negligible bias was found for SRTM based occupancy estimates (at least 70 min acquisition). CONCLUSION: This [11C]UCB-J blocking study validated SO as a suitable reference region for non-invasive quantification of SV2A availability and drug occupancy in the human brain. Accurate quantification can be achieved by using either SUVRSO,60-90min with a 60-90 min PET acquisition or SRTM BPSOwith at least 70 min dynamic PET acquisition.status: publishe

Use of Multimodal Imaging and Clinical Biomarkers in Presymptomatic Carriers of C9orf72 Repeat Expansion

Importance: During a time with the potential for novel treatment strategies, early detection of disease manifestations at an individual level in presymptomatic carriers of a hexanucleotide repeat expansion in the C9orf72 gene (preSxC9) is becoming increasingly relevant. Objectives: To evaluate changes in glucose metabolism before symptom onset of amyotrophic lateral sclerosis or frontotemporal dementia in preSxC9 using simultaneous fluorine 18-labeled fluorodeoxyglucose ([18F]FDG positron emission tomographic (PET) and magnetic resonance imaging as well as the mutation's association with clinical and fluid biomarkers. Design, Setting, and Participants: A prospective, case-control study enrolled 46 participants from November 30, 2015, until December 11, 2018. The study was conducted at the neuromuscular reference center of the University Hospitals Leuven, Leuven, Belgium. Main Outcomes and Measures: Neuroimaging data were spatially normalized and analyzed at the voxel level at a height threshold of P < .001, cluster-level familywise error-corrected threshold of P < .05, and statistical significance was set at P < .05 for the volume-of-interest level analysis, using Benjamini-Hochberg correction for multiple correction. W-score maps were computed using the individuals serving as controls as a reference to quantify the degree of [18F]FDG PET abnormality. The threshold for abnormality on the W-score maps was designated as an absolute W-score greater than or equal to 1.96. Neurofilament levels and performance on cognitive and neurologic examinations were determined. All hypothesis tests were 1-sided. Results: Of the 42 included participants, there were 17 with the preSxC9 mutation (12 women [71%]; mean [SD] age, 51 [9] years) and 25 healthy controls (12 women [48%]; mean [SD] age, 47 [10] years). Compared with control participants, significant clusters of relative hypometabolism were found in frontotemporal regions, basal ganglia, and thalami of preSxC9 participants and relative hypermetabolism in the peri-Rolandic region, superior frontal gyrus, and precuneus cortex. W-score frequency maps revealed reduced glucose metabolism with local maxima in the insular cortices, central opercular cortex, and thalami in up to 82% of preSxC9 participants and increased glucose metabolism in the precentral gyrus and precuneus cortex in up to 71% of preSxC9 participants. Other findings in the preSxC9 group were upper motor neuron involvement in 10 participants (59%), cognitive abnormalities in 5 participants (29%), and elevated neurofilament levels in 3 of 16 individuals (19%) who underwent lumbar puncture. Conclusions and Relevance: The results suggest that [18F]FDG PET can identify glucose metabolic changes in preSxC9 at an individual level, preceding significantly elevated neurofilament levels and onset of symptoms.status: publishe