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NeuroImage Oct 2023Is there a way improve our ability to understand the minds of others? Towards addressing this question, here, we conducted a single-arm, proof-of-concept study to...
Is there a way improve our ability to understand the minds of others? Towards addressing this question, here, we conducted a single-arm, proof-of-concept study to evaluate whether real-time fMRI neurofeedback (rtfMRI-NF) from the temporo-parietal junction (TPJ) leads to volitional control of the neural network subserving theory of mind (ToM; the process by which we attribute and reason about the mental states of others). As additional aims, we evaluated the strategies used to self-regulate the network and whether volitional control of the ToM network was moderated by participant characteristics and associated with improved performance on behavioral measures. Sixteen participants underwent fMRI while completing a task designed to individually-localize the TPJ, and then three separate rtfMRI-NF scans during which they completed multiple runs of a training task while receiving intermittent, activation-based feedback from the TPJ, and one run of a transfer task in which no neurofeedback was provided. Region-of-interest analyses demonstrated volitional control in most regions during the training tasks and during the transfer task, although the effects were smaller in magnitude and not observed in one of the neurofeedback targets for the transfer task. Text analysis demonstrated that volitional control was most strongly associated with thinking about prior social experiences when up-regulating the neural signal. Analysis of behavioral performance and brain-behavior associations largely did not reveal behavior changes except for a positive association between volitional control in RTPJ and changes in performance on one ToM task. Exploratory analysis suggested neurofeedback-related learning occurred, although some degree of volitional control appeared to be conferred with the initial self-regulation strategy provided to participants (i.e., without the neurofeedback signal). Critical study limitations include the lack of a control group and pre-rtfMRI transfer scan, which prevents a more direct assessment of neurofeedback-induced volitional control, and a small sample size, which may have led to an overestimate and/or unreliable estimate of study effects. Nonetheless, together, this study demonstrates the feasibility of training volitional control of a social cognitive brain network, which may have important clinical applications. Given the study's limitations, findings from this study should be replicated with more robust experimental designs.
Topics: Humans; Magnetic Resonance Imaging; Theory of Mind; Learning; Control Groups; Brain
PubMed: 37591479
DOI: 10.1016/j.neuroimage.2023.120334 -
Journal of Assisted Reproduction and... May 2023The objective of this study was to investigate the key glycolysis-related genes linked to immune cell infiltration in endometriosis and to develop a new endometriosis...
PURPOSE
The objective of this study was to investigate the key glycolysis-related genes linked to immune cell infiltration in endometriosis and to develop a new endometriosis (EMS) predictive model.
METHODS
A training set and a test set were created from the Gene Expression Omnibus (GEO) public database. We identified five glycolysis-related genes using least absolute shrinkage and selection operator (LASSO) regression and the random forest method. Then, we developed and tested a prediction model for EMS diagnosis. The CIBERSORT method was used to compare the infiltration of 22 different immune cells. We examined the relationship between key glycolysis-related genes and immune factors in the eutopic endometrium of women with endometriosis. In addition, Gene Ontology (GO)-based semantic similarity and logistic regression model analyses were used to investigate core genes. Reverse real-time quantitative PCR (RT-qPCR) of 5 target genes was analysed.
RESULTS
The five glycolysis-related hub genes (CHPF, CITED2, GPC3, PDK3, ADH6) were used to establish a predictive model for EMS. In the training and test sets, the area under the curve (AUC) of the receiver operating characteristic curve (ROC) prediction model was 0.777, 0.824, and 0.774. Additionally, there was a remarkable difference in the immune environment between the EMS and control groups. Eventually, the five target genes were verified by RT-qPCR.
CONCLUSION
The glycolysis-immune-based predictive model was established to forecast EMS patients' diagnosis, and a detailed comprehension of the interactions between endometriosis, glycolysis, and the immune system may be vital for the recognition of potential novel therapeutic approaches and targets for EMS patients.
Topics: Humans; Female; Endometriosis; Machine Learning; Area Under Curve; Control Groups; Glycolysis; Glypicans; Repressor Proteins; Trans-Activators
PubMed: 36930359
DOI: 10.1007/s10815-023-02769-0 -
Clinical Trials (London, England) Aug 2021Although several COVID-19 vaccines have been found to be effective in rigorous evaluation and have emerging availability in parts of the world, their supply will be...
BACKGROUND
Although several COVID-19 vaccines have been found to be effective in rigorous evaluation and have emerging availability in parts of the world, their supply will be inadequate to meet international needs for a considerable period of time. There also will be continued interest in vaccines that are more effective or have improved scalability to facilitate mass vaccination campaigns. Ongoing clinical testing of new vaccines also will be needed as variant strains continue to emerge that may elude some aspects of immunity induced by current vaccines. Randomized clinical trials meaningfully enhance the efficiency and reliability of such clinical testing. In clinical settings with limited or no access to known effective vaccines, placebo-controlled randomized trials of new vaccines remain a preferred approach to maximize the reliability, efficiency and interpretability of results. When emerging availability of licensed vaccines makes it no longer possible to use a placebo control, randomized active comparator non-inferiority trials may enable reliable insights.
METHODS
In this article, "hybrid" methods are proposed to address settings where, during the conduct of a placebo-controlled trial, a judgment is made to replace the placebo arm by a licensed COVID-19 vaccine due to emerging availability of effective vaccines in regions participating in that trial. These hybrid methods are based on proposed statistics that aggregate evidence to formally test as well as to estimate the efficacy of the experimental vaccine, by combining placebo-controlled data during the first period of trial conduct with active-controlled data during the second period.
RESULTS
Application of the proposed methods is illustrated in two important scenarios where the active control vaccine would become available in regions engaging in the experimental vaccine's placebo-controlled trial: in the first, the active comparator's vaccine efficacy would have been established to be 50%-70% for the 4- to 6-month duration of follow-up of its placebo-controlled trial; in the second, the active comparator's vaccine efficacy would have been established to be 90%-95% during that duration. These two scenarios approximate what has been seen with adenovirus vaccines or mRNA vaccines, respectively, assuming the early estimates of vaccine efficacy for those vaccines would hold over longer-term follow-up.
CONCLUSION
The proposed hybrid methods could readily play an important role in the near future in the design, conduct and analysis of randomized clinical trials performed to address the need for multiple additional vaccines reliably established to be safe and have worthwhile efficacy in reducing the risk of symptomatic disease from SARS-CoV-2 infections.
Topics: COVID-19; COVID-19 Vaccines; Control Groups; Humans; Placebos; Randomized Controlled Trials as Topic; SARS-CoV-2
PubMed: 34041932
DOI: 10.1177/17407745211018613 -
Molecular Metabolism Apr 2024There is significant interest in uncovering the mechanisms through which exercise enhances cognition, memory, and mood, and lowers the risk of neurodegenerative...
OBJECTIVES
There is significant interest in uncovering the mechanisms through which exercise enhances cognition, memory, and mood, and lowers the risk of neurodegenerative diseases. In this study, we utilize forced treadmill running and distance-matched voluntary wheel running, coupled with light sheet 3D brain imaging and c-Fos immunohistochemistry, to generate a comprehensive atlas of exercise-induced brain activation in mice.
METHODS
To investigate the effects of exercise on brain activity, we compared whole-brain activation profiles of mice subjected to treadmill running with mice subjected to distance-matched wheel running. Male mice were assigned to one of four groups: a) an acute bout of voluntary wheel running, b) confinement to a cage with a locked running wheel, c) forced treadmill running, or d) placement on an inactive treadmill. Immediately following each exercise or control intervention, blood samples were collected for plasma analysis, and brains were collected for whole-brain c-Fos quantification.
RESULTS
Our dataset reveals 255 brain regions activated by acute exercise in mice, the majority of which have not previously been linked to exercise. We find a broad response of 140 regulated brain regions that are shared between voluntary wheel running and treadmill running, while 32 brain regions are uniquely regulated by wheel running and 83 brain regions uniquely regulated by treadmill running. In contrast to voluntary wheel running, forced treadmill running triggers activity in brain regions associated with stress, fear, and pain.
CONCLUSIONS
Our findings demonstrate a significant overlap in neuronal activation signatures between voluntary wheel running and distance-matched forced treadmill running. However, our analysis also reveals notable differences and subtle nuances between these two widely used paradigms. The comprehensive dataset is accessible online at www.neuropedia.dk, with the aim of enabling future research directed towards unraveling the neurobiological response to exercise.
Topics: Mice; Male; Animals; Motor Activity; Brain; Physical Conditioning, Animal; Cognition
PubMed: 38428817
DOI: 10.1016/j.molmet.2024.101907 -
Progress in Brain Research 1997Motor control is defined as the process of restricting the output of the motor nervous system so that meaningful and coordinated behavior ensues. The high dimensionality... (Review)
Review
Motor control is defined as the process of restricting the output of the motor nervous system so that meaningful and coordinated behavior ensues. The high dimensionality of the computation underlying motor control is presented and a simplifying framework is outlined. Evidence that movements are performed non-continuously is reviewed as is the construct of the 'motor synergy' as a fundamental unit of control. It is proposed that the pulsatile nature of movement and the tendency of muscle collectives to be activated as synergies reflect processes that the nervous system has evolved to reduce the dimensionality of motor control. We propose that the inferior olive simplifies the computation underlying motor control by biasing the activities of spinal and cranial motor systems so that discrete collectives of muscles are predisposed to contract at specific times during movement. The well-characterized oscillatory activity of olivary neurons is postulated to provide a pacemaking signal and to restrict the control process to particular moments in time while the process of electrotonic coupling and uncoupling of assemblies of olivary neurons is proposed to underlie the spatial distribution of synergic muscle activations. It is proposed that the olivocerebellar contribution to the control process is to allow movements to be executed rapidly in a feedforward manner, so that the need for sensory guidance and feedback is minimized.
Topics: Animals; Cerebellum; Humans; Models, Neurological; Motor Activity; Movement; Muscle, Skeletal; Olivary Nucleus; Spinal Cord
PubMed: 9193160
DOI: 10.1016/s0079-6123(08)63380-4 -
Research in Nursing & Health Dec 2019Researchers trialing behavioral interventions often use attention control groups, but few publish details on attention control activities or perceived benefit. Attention... (Randomized Controlled Trial)
Randomized Controlled Trial
Researchers trialing behavioral interventions often use attention control groups, but few publish details on attention control activities or perceived benefit. Attention control groups receive the same dose of interpersonal interaction as intervention participants but no other elements of the intervention, to control for the benefits of attention that may come from behavioral interventions. Because intervention success is analyzed compared to control conditions, it is useful to examine attention control content and outcomes. The purpose of this study is to report on attention control visit activities and their perceived benefit in a randomized control trial. The trial tested an aging-in-place intervention comprised of a series of participant goal-directed visits facilitated by an occupational therapist, nurse, and handyman. The attention control group participants received visits from a lay person. We report on the number and length of visits received, types of visit activities that participants chose, and how much visit time was spent on each activity, based on the attention visitor's records. We report on participant perceptions of benefit based on a 10-item Likert-scale survey. The attention control group participants (n = 148) were cognitively intact, at least 65 years old, with at least one Instrumental Activities of Daily Living. Attention control group participants most often chose conversation (20.1% of visit time), and playing games (18.7%), as visit activities. The majority of attention control group participants (63.4%) reported "a great deal" of perceived benefit. Attention control group visits may be an appropriate comparison in studies of behavioral interventions for community-dwelling older adults.
Topics: Aged; Attention; Behavior Therapy; Control Groups; Female; Humans; Independent Living; Male; Quality of Life
PubMed: 31647125
DOI: 10.1002/nur.21992 -
Experimental Physiology Nov 2017What is the central question of this study? In the present study, a reproducible model of maternal voluntary physical activity was developed to evaluate the adaptive...
What is the central question of this study? In the present study, a reproducible model of maternal voluntary physical activity was developed to evaluate the adaptive response of physical activity by attenuating the effects of maternal undernutrition on physical features, reflex ontogeny and growth trajectory of offspring during development. What is the main finding and its importance? Maternal physical activity may induce neuronal maturation of sensorimotor connections impacting on the patterns of locomotor activity in malnourished offspring. Thus, physical activity should be considered as a therapeutic means of countering the effects of maternal undernutrition, by providing a useful strategy for enhancing the neuronal activity of children born to mothers who experience a restricted diet during pregnancy. This study evaluated the effects of maternal voluntary physical activity during pregnancy and lactation on somatic growth (SG), reflex ontogeny (RO) and locomotor activity (LA) of rats whose mothers were protein restricted. Virgin female Wistar rats were divided into the following six groups: control, normal protein (C-NP, n = 4); control, low protein (C-LP, n = 4); inactive, normal protein (I-NP, n = 8); inactive, low protein (I-LP, n = 7); very active, normal protein (VA-NP, n = 8); and very active, low protein (VA-LP, n = 6). Voluntary physical activity was recorded daily in dams. The LP groups were fed an 8% casein diet, whereas control groups were fed a 17% casein diet during pregnancy and lactation. Offspring were evaluated in terms of SG (body weight and length, latero-lateral skull axis and anteroposterior head axis) and RO (palmar grasp, righting, free-fall righting, negative geotaxis, cliff avoidance, auditory startle response and vibrissa placing). The LA was evaluated at 23, 45 and 60 days old in the open field. Voluntary physical activity was reduced during pregnancy and lactation independent of the maternal diet. Pups from LP dams showed delayed SG, reflex maturation and patterns of LA when compared with control pups. The C-LP and I-LP pups showed a delayed SG, RO and LA. Pups from VA-LP mothers showed no delay in SG and RO and presented a faster development of patterns of LA. Maternal voluntary physical activity attenuated the effects of LP diet on indicators of neurodevelopment and patterns of LA of offspring.
Topics: Age Factors; Animal Nutritional Physiological Phenomena; Animals; Behavior, Animal; Disease Models, Animal; Female; Gestational Age; Lactation; Maternal Nutritional Physiological Phenomena; Motor Activity; Nervous System; Neurodevelopmental Disorders; Nutritional Status; Physical Conditioning, Animal; Pregnancy; Prenatal Exposure Delayed Effects; Protein-Energy Malnutrition; Rats, Wistar; Volition
PubMed: 28833822
DOI: 10.1113/EP086400 -
JAMA Network Open Nov 2023Mobile mental health applications (apps) for moderate to severe depression are proliferating, likely owing to their capacity to overcome the limitations of conventional... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Mobile mental health applications (apps) for moderate to severe depression are proliferating, likely owing to their capacity to overcome the limitations of conventional psychotherapy, but research on the potential moderators of treatment efficacy is lacking.
OBJECTIVE
To examine the treatment efficacy associated with mobile app interventions for moderate to severe depression and identify the potential moderators associated with better treatment outcomes.
DATA SOURCES
PubMed, Embase, and PsycINFO were searched from their inception to January 22, 2023.
STUDY SELECTION
Only randomized clinical trials evaluating mobile app treatments in adults with moderate to severe depression that published their results in English were included in the analysis.
DATA EXTRACTION AND SYNTHESIS
Three independent researchers extracted and assessed relevant studies, their risk of bias, the characteristics of the population and study design, and the components of the intervention program following the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines. A fixed-effects model was used for data analysis, and exploratory post hoc meta-regression and subgroup analyses were also conducted. Data were analyzed from February 16 to March 25, 2023.
MAIN OUTCOMES AND MEASURES
The main outcome was changes in depression symptom severity from before to after treatment, measured by standardized depression assessment instruments. Secondary outcomes included study-, intervention-, and patient-level factors associated with app efficacy.
RESULTS
Of 2128 studies identified, 13 studies evaluating 16 intervention apps with 1470 participants with moderate to severe depression were included in the analysis. The overall pooled effect size of mobile app interventions vs both active and inactive control groups was 0.50 (95% CI, 0.40 to 0.61). Interventions with in-app notifications were associated with significantly lower treatment outcomes (standardized mean difference [SMD], 0.45; 95% CI, 0.29-0.60) than interventions without (SMD, 0.71; 95% CI, 0.54-0.87; P = .02). In addition, app interventions delivered for less than 8 weeks were associated with a significantly greater effect size (SMD, 0.77; 95% CI, 0.59-0.96) than interventions delivered for 8 weeks or longer (SMD, 0.43; 95% CI, 0.30-0.57; P = .004).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, the feasibility and efficacy of mobile app interventions were supported in treating moderate and severe depression, and practical implications were also provided for developing effective app-based interventions in clinical practice.
Topics: Adult; Humans; Depression; Depressive Disorder, Major; Mobile Applications; Behavior Therapy; Control Groups
PubMed: 37983028
DOI: 10.1001/jamanetworkopen.2023.44120 -
Quarterly Journal of Experimental... Sep 2021The degree to which executive function (EF) abilities (including working memory [WM], inhibitory control [IC], and cognitive flexibility [CF]) can be enhanced through... (Randomized Controlled Trial)
Randomized Controlled Trial
The degree to which executive function (EF) abilities (including working memory [WM], inhibitory control [IC], and cognitive flexibility [CF]) can be enhanced through training is an important question; however, research in this area is inconsistent. Previous cognitive training studies largely agree that training leads to improvements in the trained task, but the generalisability of this improvement to other related tasks remains controversial. In this article, we present a pre-registered experiment that used an adaptive training procedure to examine whether EFs can be enhanced through cognitive training, and directly compared the efficacy and generalisability across sub-components of EF using training programmes that target WM, IC, or CF versus an active control group. Participants ( = 160) first completed a battery of tasks that assessed EFs, then were randomly assigned to one of the four training groups, and completed an adaptive procedure over 21 days (10 training sessions) that targeted a specific sub-component of EF (or was comparatively engaging and challenging, but did not train a specific EF). At post-test, participants returned to the lab to repeat the battery of EF tasks. Results revealed robust direct training effects (i.e., on trained task), but limited evidence to support near (i.e., same EF, different task) and far (i.e., different EF and task) transfer effects. Where indirect training benefits emerged, the effects were more readily attributable to the overlapping training/assessment task routines, rather than more general enhancements to the underlying cognitive processes or neural circuits.
Topics: Control Groups; Executive Function; Humans; Memory, Short-Term
PubMed: 33656380
DOI: 10.1177/17470218211002509 -
The Cochrane Database of Systematic... Apr 2014Lack of physical stimulation may contribute to metabolic bone disease of preterm infants, resulting in poor bone mineralization and growth. Physical activity programs... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lack of physical stimulation may contribute to metabolic bone disease of preterm infants, resulting in poor bone mineralization and growth. Physical activity programs combined with adequate nutrition might help to promote bone mineralization and growth.
OBJECTIVES
The primary objective was to assess whether physical activity programs in preterm infants improve bone mineralization and growth and reduce the risk of fracture.The secondary objectives included other potential benefits in terms of length of hospital stay, skeletal deformities and neurodevelopmental outcomes, and adverse events.Subgroup analysis:• Given that the smallest infants are most vulnerable for developing osteopenia (Bishop 1999), a subgroup analysis was planned for infants with birth weight < 1000 g.• Calcium and phosphorus intake may affect an infant's ability to increase bone mineral content (Kuschel 2004). Therefore, an additional subgroup analysis was planned for infants receiving different amounts of calcium and phosphorus, along with full enteral feeds as follows. ∘ Below 100 mg/60 mg calcium/phosphorus or equal to/above 100 mg/60 mg calcium/phosphorus per 100 mL milk. ∘ Supplementation of calcium without phosphorus. ∘ Supplementation of phosphorus without calcium.
SEARCH METHODS
The standard search strategy of the Cochrane Neonatal Review Group (CNRG) was used. The search included the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 9), MEDLINE, EMBASE, CINAHL (1966 to March 2013), and cross-references, as well as handsearching of abstracts of the Society for Pediatric Research and the International Journal of Sports Medicine.
SELECTION CRITERIA
Randomized and quasi-randomized controlled trials comparing physical activity programs (extension and flexion, range-of-motion exercises) versus no organized physical activity programs in preterm infants.
DATA COLLECTION AND ANALYSIS
Data collection, study selection, and data analysis were performed according to the methods of the CNRG.
MAIN RESULTS
Eleven trials enrolling 324 preterm infants (gestational age 26 to 34 weeks) were included in this review. All were small (N = 16 to 50) single-center studies that evaluated daily physical activity for three and one-half to eight weeks during initial hospitalization. Methodological quality and reporting of included trials were variable.Four trials demonstrated moderate short-term benefits of physical activity for bone mineralization at completion of the physical activity program. The only trial assessing long-term effects on bone mineralization showed no effect of physical activity administered during initial hospitalization on bone mineralization at 12 months corrected age. Meta-analysis from four trials demonstrated a positive effect of physical activity on daily weight gain (weighted mean difference (WMD) 2.21 g/kg/d, 95% confidence interval (CI) 1.23 to 3.19). Data from four trials showed a positive effect on linear growth (WMD 0.12 cm/wk, 95% CI 0.01 to 0.24) but not on head growth (WMD -0.03 cm/wk, 95% CI -0.14 to 0.08) during the study period. Only one trial reported on fractures (this outcome did not occur in intervention and control groups) and complications of preterm birth (no significant differences between intervention and control groups). None of the trials assessed other outcomes relevant to this review.
AUTHORS' CONCLUSIONS
Some evidence suggests that physical activity programs might promote short-term weight gain and bone mineralization in preterm infants. Data are inadequate to allow assessment of harm or long-term effects. Current evidence does not support the routine use of physical activity programs in preterm infants. Further trials incorporating infants with a high baseline risk of osteopenia are required. These trials should address adverse events, long-term outcomes, and the effects of nutritional intake (calories, protein, calcium, phosphorus).
Topics: Bone Density; Bone Diseases, Metabolic; Calcification, Physiologic; Humans; Infant; Infant, Newborn; Infant, Premature; Motor Activity; Musculoskeletal Manipulations; Randomized Controlled Trials as Topic; Weight Gain
PubMed: 24752440
DOI: 10.1002/14651858.CD005387.pub3