Reasons for non-participation of children and adolescents in a large-scale school-based mental health project.

Background: Non-participation in mental health studies is an under-explored but very important topic. Investigating reasons for non-participation holds promise for the planning of future study designs and recruitment strategies. This study aimed at investigating reasons for children and adolescents (C&A) not participating in a school-based mental health research project. Methods: Data collection took place within the school-based recruitment of a large-scale multi-site project ("ProHEAD-Promoting Help-seeking using E-technology for Adolescents") in Germany. Participants were N = 534 C&A aged ≥ 12 years attending secondary schools. The present cross-sectional study analyzed anonymous survey data of C&A who themselves or whose parents, respectively, did not provide written consent to participate in the mental health research project. The questionnaire consisted of 14 items covering potential reasons for non-participation, and four free text fields. Besides descriptive statistics, free text field answers were analyzed using qualitative content analysis. Results: Students indicated an average of M = 2.94 (SD = 1.75) reasons for their non-participation in the project. In the descriptive analysis of indicated items, the three most frequently reported reasons for non-participation included students reporting to not be concerned by the topic "mental health" (n = 290, 54.3%), not having returned the consent form to the teacher (n = 175, 32.8%), and not having time for participation (n = 149, 27.9%). In the qualitative content analysis, the most frequently assigned categories were organizational reasons (n = 216, 57.1%), general disinterest in study participation (n = 139, 36.8%), and personal attitudes toward the topic "mental health" (n = 84, 22.2%), such as not being concerned with the topic "mental health" (n = 23, 6.1%) or being too concerned with the topic "mental health" (n = 16, 4.2%). Conclusion: The study provides unique insights into reasons for C&A and their caregivers not participating in a large federally funded mental health research project. The results suggest that in order to increase participation rates, stigma should be reduced, parents as well as teachers should be involved where possible, and the use of incentives might be helpful. The study highlights the importance of assessing reasons for non-participation, especially in online intervention studies on mental health.

Growth hormone treatment in the pre-transplant period is associated with superior outcome after pediatric kidney transplantation.

BACKGROUND: Recombinant human growth hormone (rhGH) is frequently used for treatment of short stature in children with chronic kidney disease (CKD) prior to kidney transplantation (KT). To what extent this influences growth and transplant function after KT is yet unknown. METHODS: Post-transplant growth (height, sitting height, leg length) and clinical parameters of 146 CKD patients undergoing KT before the age of 8 years, from two German pediatric nephrology centers, were prospectively investigated with a mean follow-up of 5.56 years. Outcome in patients with (rhGH group) and without (non-prior rhGH group) prior rhGH treatment was assessed by the use of linear mixed-effects models. RESULTS: Patients in the rhGH group spent longer time on dialysis and less frequently underwent living related KT compared to the non-prior rhGH group but showed similar height z-scores at the time of KT. After KT, steroid exposure was lower and increments in anthropometric z-scores were significantly higher in the rhGH group compared to those in the non-prior rhGH group, although 18% of patients in the latter group were started on rhGH after KT. Non-prior rhGH treatment was associated with a faster decline in transplant function, lower hemoglobin, and higher C-reactive protein levels (CRP). After adjustment for these confounders, growth outcome did statistically differ for sitting height z-scores only. CONCLUSIONS: Treatment with rhGH prior to KT was associated with superior growth outcome in prepubertal kidney transplant recipients, which was related to better transplant function, lower CRP, less anemia, lower steroid exposure, and earlier maturation after KT. A higher resolution version of the Graphical abstract is available as Supplementary information.

Attitudes toward the pandemic and COVID-19 vaccination intention among German university students and the general population: Results from two cross-sectional surveys.

Background: The COVID-19 pandemic has had an impact on nearly all people. Vaccines provide an effective tool to combat the pandemic, however, vaccination hesitancy remains an issue. This study aims to investigate (a) students' attitudes toward the pandemic, (b) potential differences in attitudes between university students and the general population, and (c) to examine predictors of vaccination intention in both samples. Methods: In this cross-sectional study data from two research projects were analyzed and compared. First, attitudes toward the COVID-19 pandemic in German university students were assessed within a cross-sectional anonymous online survey (March-April 2021, N = 5,639) and analyzed quantitatively and also qualitatively (free text field answers examined positive and negative aspects of the pandemic). Second, data from a cross-sectional survey within the COVID-19 Snapshot Monitoring project (COSMO; 29th wave of data collection, December 2020, N = 1,387) in the German general population was analyzed. Both samples, were compared in sharedly used variables, regarding attitudes toward the pandemic and vaccination intention, and factors associated with vaccination (logistic regression analyses). Results: In comparison to the general population, university students were significantly more likely to report being worried about/thinking about the coronavirus and to perceive the coronavirus as overrepresented in the media (all p < 0.001). University students reported a more supportive attitude toward vaccinations in general (students: M = 4.57, SD = 0.85; general population: M = 3.92, SD = 1.27) and a significantly higher vaccination intention (students: n = 4,438, 78.7%; general population: n = 635, 47.7%) than the general population (p < 0.001). Regression analyses revealed that in university students, vaccination intention was significantly predicted by not having children, a supporting attitude toward vaccinations in general, the belief that the coronavirus is overrepresented in the media, and less thinking about/worrying about the coronavirus (all p < 0.05). In the general population, vaccination intention was significantly associated with male gender, higher age, not having children, a supporting attitude toward vaccinations in general, and the belief that the coronavirus is overrepresented in the media (p < 0.05). The qualitative analysis among university students revealed that the most frequently stated positive aspect of the pandemic was to be more flexible due to digitalization (n = 1,301 statements, 22.2%) and the most frequently stated negative aspect was restriction in social life (n = 3,572 statements, 24.2%). Conclusion: The results indicate differences in the attitudes toward the pandemic between university students and the general population. In addition, differences regarding factors associated with vaccination intention were found in both samples. These results could be important to be considered when designing and targeting vaccination campaigns aiming at informing different population or age groups. Study registration: DRKS00022424.

Identifying Shared Brain Networks in Individuals by Decoupling Functional and Anatomical Variability.

The connectivity architecture of the human brain varies across individuals. Mapping functional anatomy at the individual level is challenging, but critical for basic neuroscience research and clinical intervention. Using resting-state functional connectivity, we parcellated functional systems in an "embedding space" based on functional characteristics common across the population, while simultaneously accounting for individual variability in the cortical distribution of functional units. The functional connectivity patterns observed in resting-state data were mapped in the embedding space and the maps were aligned across individuals. A clustering algorithm was performed on the aligned embedding maps and the resulting clusters were transformed back to the unique anatomical space of each individual. This novel approach identified functional systems that were reproducible within subjects, but were distributed across different anatomical locations in different subjects. Using this approach for intersubject alignment improved the predictability of individual differences in language laterality when compared with anatomical alignment alone. Our results further revealed that the strength of association between function and macroanatomy varied across the cortex, which was strong in unimodal sensorimotor networks, but weak in association networks.

Reliability correction for functional connectivity: Theory and implementation.

Network properties can be estimated using functional connectivity MRI (fcMRI). However, regional variation of the fMRI signal causes systematic biases in network estimates including correlation attenuation in regions of low measurement reliability. Here we computed the spatial distribution of fcMRI reliability using longitudinal fcMRI datasets and demonstrated how pre-estimated reliability maps can correct for correlation attenuation. As a test case of reliability-based attenuation correction we estimated properties of the default network, where reliability was significantly lower than average in the medial temporal lobe and higher in the posterior medial cortex, heterogeneity that impacts estimation of the network. Accounting for this bias using attenuation correction revealed that the medial temporal lobe's contribution to the default network is typically underestimated. To render this approach useful to a greater number of datasets, we demonstrate that test-retest reliability maps derived from repeated runs within a single scanning session can be used as a surrogate for multi-session reliability mapping. Using data segments with different scan lengths between 1 and 30 min, we found that test-retest reliability of connectivity estimates increases with scan length while the spatial distribution of reliability is relatively stable even at short scan lengths. Finally, analyses of tertiary data revealed that reliability distribution is influenced by age, neuropsychiatric status and scanner type, suggesting that reliability correction may be especially important when studying between-group differences. Collectively, these results illustrate that reliability-based attenuation correction is an easily implemented strategy that mitigates certain features of fMRI signal nonuniformity.

Sex differences in brain plasticity: a new hypothesis for sex ratio bias in autism.

Several observations support the hypothesis that differences in synaptic and regional cerebral plasticity between the sexes account for the high ratio of males to females in autism. First, males are more susceptible than females to perturbations in genes involved in synaptic plasticity. Second, sex-related differences in non-autistic brain structure and function are observed in highly variable regions, namely, the heteromodal associative cortices, and overlap with structural particularities and enhanced activity of perceptual associative regions in autistic individuals. Finally, functional cortical reallocations following brain lesions in non-autistic adults (for example, traumatic brain injury, multiple sclerosis) are sex-dependent. Interactions between genetic sex and hormones may therefore result in higher synaptic and consecutively regional plasticity in perceptual brain areas in males than in females. The onset of autism may largely involve mutations altering synaptic plasticity that create a plastic reaction affecting the most variable and sexually dimorphic brain regions. The sex ratio bias in autism may arise because males have a lower threshold than females for the development of this plastic reaction following a genetic or environmental event.

Abnormalities in hemispheric specialization of caudate nucleus connectivity in schizophrenia.

IMPORTANCE: Hemispheric specialization of the human brain is a marker of successful neurodevelopment. Altered brain asymmetry that has been repeatedly reported in schizophrenia may represent consequences of disrupted neurodevelopment in the disorder. However, a complete picture of functional specialization in the schizophrenic brain and its connectional substrates is yet to be unveiled. OBJECTIVES: To quantify intrinsic hemispheric specialization at cortical and subcortical levels and to reveal potential disease effects in schizophrenia. DESIGN, SETTING, AND PARTICIPANTS: Resting-state functional connectivity magnetic resonance imaging has been previously used to quantitatively measure hemispheric specialization in healthy individuals in a reliable manner. We quantified the intrinsic hemispheric specialization at the whole brain level in 31 patients with schizophrenia and 37 demographically matched healthy controls from November 28, 2007, through June 29, 2010, using resting-state functional magnetic resonance imaging. RESULTS: The caudate nucleus and cortical regions with connections to the caudate nucleus had markedly abnormal hemispheric specialization in schizophrenia. Compared with healthy controls, patients exhibited weaker specialization in the left, but the opposite pattern in the right, caudate nucleus (P < .001). Patients with schizophrenia also had a disruption of the interhemispheric coordination among the cortical regions with connections to the caudate nucleus. A linear classifier based on the specialization of the caudate nucleus distinguished patients from controls with a classification accuracy of 74% (with a sensitivity of 68% and a specificity of 78%). CONCLUSIONS AND RELEVANCE: These data suggest that hemispheric specialization could serve as a potential imaging biomarker of schizophrenia that, compared with task-based functional magnetic resonance imaging measures, is less prone to the confounding effects of variation in task compliance, cognitive ability, and command of language.

Opposing brain differences in 16p11.2 deletion and duplication carriers.

Deletions and duplications of the recurrent ~600 kb chromosomal BP4-BP5 region of 16p11.2 are associated with a broad variety of neurodevelopmental outcomes including autism spectrum disorder. A clue to the pathogenesis of the copy number variant (CNV)'s effect on the brain is that the deletion is associated with a head size increase, whereas the duplication is associated with a decrease. Here we analyzed brain structure in a clinically ascertained group of human deletion (N = 25) and duplication (N = 17) carriers from the Simons Variation in Individuals Project compared with age-matched controls (N = 29 and 33, respectively). Multiple brain measures showed increased size in deletion carriers and reduced size in duplication carriers. The effects spanned global measures of intracranial volume, brain size, compartmental measures of gray matter and white matter, subcortical structures, and the cerebellum. Quantitatively, the largest effect was on the thalamus, but the collective results suggest a pervasive rather than a selective effect on the brain. Detailed analysis of cortical gray matter revealed that cortical surface area displays a strong dose-dependent effect of CNV (deletion > control > duplication), whereas average cortical thickness is less affected. These results suggest that the CNV may exert its opposing influences through mechanisms that influence early stages of embryonic brain development.

The effects of methylphenidate on whole brain intrinsic functional connectivity.

Methylphenidate (MPH) is an indirect dopaminergic and noradrenergic agonist that is used to treat attention deficit hyperactivity disorder and that has shown therapeutic potential in neuropsychiatric diseases such as depression, dementia, and Parkinson's disease. While effects of MPH on task-induced brain activation have been investigated, little is known about how MPH influences the resting brain. To investigate the effects of 40 mg of oral MPH on intrinsic functional connectivity, we used resting state fMRI in 54 healthy male subjects in a double-blind, randomized, placebo-controlled study. Functional connectivity analysis employing ICA revealed seven resting state networks (RSN) of interest. Connectivity strength between the dorsal attention network and the thalamus was increased after MPH intake. Other RSN located in association cortex areas, such as the left and right frontoparietal networks and the executive control network, showed MPH-induced connectivity increase to sensory-motor and visual cortex regions and connectivity decrease to cortical and subcortical components of cortico-striato-thalamo-cortical circuits (CST). RSN located in sensory-motor cortex areas showed the opposite pattern with MPH-induced connectivity increase to CST components and connectivity decrease to sensory-motor and visual cortex regions. Our results provide evidence that MPH does not only alter intrinsic connectivity between brain areas involved in sustained attention, but that it also induces significant changes in the cortico-cortical and cortico-subcortical connectivity of many other cognitive and sensory-motor RSN.

Convergent Findings of Altered Functional and Structural Brain Connectivity in Individuals with High Functioning Autism: A Multimodal MRI Study.

Brain tissue changes in autism spectrum disorders seem to be rather subtle and widespread than anatomically distinct. Therefore a multimodal, whole brain imaging technique appears to be an appropriate approach to investigate whether alterations in white and gray matter integrity relate to consistent changes in functional resting state connectivity in individuals with high functioning autism (HFA). We applied diffusion tensor imaging (DTI), voxel-based morphometry (VBM) and resting state functional connectivity magnetic resonance imaging (fcMRI) to assess differences in brain structure and function between 12 individuals with HFA (mean age 35.5, SD 11.4, 9 male) and 12 healthy controls (mean age 33.3, SD 9.0, 8 male). Psychological measures of empathy and emotionality were obtained and correlated with the most significant DTI, VBM and fcMRI findings. We found three regions of convergent structural and functional differences between HFA participants and controls. The right temporo-parietal junction area and the left frontal lobe showed decreased fractional anisotropy (FA) values along with decreased functional connectivity and a trend towards decreased gray matter volume. The bilateral superior temporal gyrus displayed significantly decreased functional connectivity that was accompanied by the strongest trend of gray matter volume decrease in the temporal lobe of HFA individuals. FA decrease in the right temporo-parietal region was correlated with psychological measurements of decreased emotionality. In conclusion, our results indicate common sites of structural and functional alterations in higher order association cortex areas and may therefore provide multimodal imaging support to the long-standing hypothesis of autism as a disorder of impaired higher-order multisensory integration.

Individual variability in functional connectivity architecture of the human brain.

The fact that people think or behave differently from one another is rooted in individual differences in brain anatomy and connectivity. Here, we used repeated-measurement resting-state functional MRI to explore intersubject variability in connectivity. Individual differences in functional connectivity were heterogeneous across the cortex, with significantly higher variability in heteromodal association cortex and lower variability in unimodal cortices. Intersubject variability in connectivity was significantly correlated with the degree of evolutionary cortical expansion, suggesting a potential evolutionary root of functional variability. The connectivity variability was also related to variability in sulcal depth but not cortical thickness, positively correlated with the degree of long-range connectivity but negatively correlated with local connectivity. A meta-analysis further revealed that regions predicting individual differences in cognitive domains are predominantly located in regions of high connectivity variability. Our findings have potential implications for understanding brain evolution and development, guiding intervention, and interpreting statistical maps in neuroimaging.

Long-term test-retest reliability of resting-state networks in healthy elderly subjects and with amnestic mild cognitive impairment patients.

The investigation of cerebral resting-state networks (RSNs) by functional magnetic resonance imaging (fMRI) is a promising tool for the early diagnosis and follow-up of neuropsychiatric and neurodegenerative disorders like Alzheimer's disease (AD). In this context, the determination of inter-session reliability of these networks is crucial. However, data on network reliability in healthy elderly subjects is rare and does not exist for patients with amnestic mild cognitive impairment (aMCI), a prodromal stage of AD. Therefore, the aim of this study was to investigate the long-term test-retest reliability of RSNs in both groups. Twelve healthy controls (HC) and 13 aMCI patients underwent resting-state fMRI and neuropsychological testing (CERAD test battery) twice, at baseline and after 13-16 months. Resting-state fMRI data was decomposed into independent components using independent component analysis. Inter-session test-retest reliability of the resulting RSNs was determined by calculating voxel-wise intra-class correlation coefficients. Overall test-retest reliability of corresponding RSNs was moderate to high in both groups, but significantly higher in the HC group compared to the aMCI group (p < 0.001), while the cognitive performance within the CERAD test battery remained stable over time in either group. Most reliable RSNs derived from the HC group and were associated with sensory and motor as well as higher order cognitive and the default-mode function. Particularly low reliability was found in basal frontal regions, which are known to be prone to susceptibility-induced noise. We conclude that stable RSNs may represent healthy aging, whereas decreased RSN reliability may indicate progressive neuro-functional alterations before the actual manifestation of clinical symptoms.

Classifying fMRI-derived resting-state connectivity patterns according to their daily rhythmicity.

The vast majority of biological functions express rhythmic fluctuations across the 24-hour day. We investigated the degree of daily modulation across fMRI (functional Magnetic Resonance Imaging) derived resting-state data in 15 subjects by evaluating the time courses of 20 connectivity patterns over 8h (4 sessions). For each subject, we determined the chronotype, which describes the relationship between the individual circadian rhythm and the local time. We could therefore analyze the daily time course of the connectivity patterns controlling for internal time. Furthermore, as the participants' scan times were staggered as a function of their chronotype, we prevented sleep deprivation and kept time awake constant across subjects. Individual functional connectivity within each connectivity pattern was defined at each session as connectivity strength measured by a mean z-value and, in addition, as the spatial extent expressed by the number of activated voxels. Highly rhythmic connectivity patterns included two sub-systems of the Default-Mode Network (DMN) and a network extending over sensori-motor regions. The network characterized as the most stable across the day is mainly associated with processing of executive control. We conclude that the degree of daily modulation largely varies across fMRI derived resting-state connectivity patterns, ranging from highly rhythmic to stable. This finding should be considered when interpreting results from fMRI studies.

Diagnostic power of default mode network resting state fMRI in the detection of Alzheimer's disease.

Functional magnetic resonance imaging (fMRI) of default mode network (DMN) brain activity during resting is recently gaining attention as a potential noninvasive biomarker to diagnose incipient Alzheimer's disease. The aim of this study was to determine which method of data processing provides highest diagnostic power and to define metrics to further optimize the diagnostic value. fMRI was acquired in 21 healthy subjects, 17 subjects with mild cognitive impairment and 15 patients with Alzheimer's disease (AD) and data evaluated both with volumes of interest (VOI)-based signal time course evaluations and independent component analyses (ICA). The first approach determines the amount of DMN region interconnectivity (as expressed with correlation coefficients); the second method determines the magnitude of DMN coactivation. Apolipoprotein E (ApoE) genotyping was available in 41 of the subjects examined. Diagnostic power (expressed as accuracy) of data of a single DMN region in independent component analyses was 64%, that of a single correlation of time courses between 2 DMN regions was 71%, respectively. With multivariate analyses combining both methods of analysis and data from various regions, accuracy could be increased to 97% (sensitivity 100%, specificity 95%). In nondemented subjects, no significant differences in activity within DMN could be detected comparing ApoE ε4 allele carriers and ApoE ε4 allele noncarriers. However, there were some indications that fMRI might yield useful information given a larger sample. Time course correlation analyses seem to outperform independent component analyses in the identification of patients with Alzheimer's disease. However, multivariate analyses combining both methods of analysis by considering the activity of various parts of the DMN as well as the interconnectivity between these regions are required to achieve optimal and clinically acceptable diagnostic power.

Evaluation of effectiveness of instruction and study habits in two consecutive clinical semesters of the medical curriculum Munich (MeCuM) reveals the need for more time for self study and higher frequency of assessment.

BACKGROUND: Seven years after implementing a new curriculum an evaluation was performed to explore possibilities for improvements. PURPOSES: To analyze students' study habits in relation to exam frequency and to evaluate effectiveness of instruction. METHODS: Time spent on self study (TSS) and the quantity of instruction (QI) was assessed during the internal medicine and the surgical semester. Students and faculty members were asked about study habits and their evaluation of the current curriculum. RESULTS: The TSS/QI ratio as a measure of effectiveness of instruction ranges mainly below 1.0 and rises only prior to exams. Students and teachers prefer to have multiple smaller exams over the course of the semester. Furthermore, students wish to have more time for self-guided study. CONCLUSIONS: The TSS/QI ratio is predominantly below the aspired value of 1.0. Furthermore, the TSS/QI ratio is positively related to test frequency. We therefore propose a reduction of compulsory lessons and an increase in test frequency.

Test-retest reproducibility of the default-mode network in healthy individuals.

Independent component analysis (ICA) of functional magnetic resonance imaging (fMRI) time-series reveals distinct coactivation patterns in the resting brain representing spatially coherent spontaneous fluctuations of the fMRI signal. Among these patterns, the so-called default-mode network (DMN) has been attributed to the ongoing mental activity of the brain during wakeful resting state. Studies suggest that many neuropsychiatric diseases disconnect brain areas belonging to the DMN. The potential use of the DMN as functional imaging marker for individuals at risk for these diseases, however, requires that the components of the DMN are reproducible over time in healthy individuals. In this study, we assessed the reproducibility of the DMN components within and between imaging sessions in 18 healthy young subjects (mean age, 27.5 years) who were scanned three times with two resting state scans during each session at 3.0 T field strength. Statistical analysis of fMRI time-series was done using ICA implemented with BrainVoyager QX. At all three sessions the essential components of the DMN could be identified in each individual. Spatial extent of DMN activity and size of overlap within and between sessions were most reproducible for the anterior and posterior cingulate gyrus. The degree of reproducibility of the DMN agrees with the degree of reproducibility found with motor paradigms. We conclude that DMN coactivation patterns are reproducible in healthy young subjects. Therefore, these data can serve as basis to further explore the effects of aging and neuropsychiatric diseases on the DMN of the brain.