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This study investigated whether the electric field magnitude (E-field) delivered to the left dorsolateral prefrontal cortex (L-DLPFC) changes resting-state brain activity and the L-DLPFC resting-state functional connectivity (rsFC), given the variability in tDCS response and lack of understanding of how rsFC changes. Twenty-one healthy participants received either 2 mA anodal or sham tDCS targeting the L-DLPFC for 10 min. Brain imaging was conducted before and after stimulation. The fractional amplitude of low-frequency fluctuation (fALFF), reflecting resting brain activity, and the L-DLPFC rsFC were analyzed to investigate the main effect of tDCS, main effect of time, and interaction effects. The E-field was estimated by modeling tDCS-induced individual electric fields and correlated with fALFF and L-DLPFC rsFC. Anodal tDCS increased fALFF in the left rostral middle frontal area and decreased fALFF in the midline frontal area (FWE p < 0.050), whereas sham induced no changes. Overall rsFC decreased after sham (positive and negative connectivity, p = 0.001 and 0.020, respectively), with modest and nonsignificant changes after anodal tDCS (p = 0.063 and 0.069, respectively). No significant differences in local rsFC were observed among the conditions. Correlations were observed between the E-field and rsFC changes in the L-DLPFC (r = 0.385, p = 0.115), left inferior parietal area (r = 0.495, p = 0.037), and right lateral visual area (r = 0.683, p = 0.002). Single-session tDCS induced resting brain activity changes and may help maintain overall rsFC. The E-field in the L-DLPFC is associated with rsFC changes in both proximal and distally connected brain regions to the L-DLPFC.

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BACKGROUND: Stress has become a prevalent public health concern, contributing to the rising prevalence of psychiatric disorders. Understanding stress impact considering critical variables, such as age, sex, and individual differences, is of utmost importance for developing effective intervention strategies. METHODS: Stress effects (daily footshocks for ten days) during adolescence (postnatal day, PND31-40) and adulthood (PND65-74) were investigated on behavioral outcomes and parvalbumin (PV)-expressing GABAergic interneurons and their associated perineuronal nets (PNNs) in the prefrontal cortex (PFC) of male and female mice five weeks post-stress. RESULTS: In adulthood, adolescent stress induced behavioral alterations in male mice, including anxiety-like behaviors, social deficits, cognitive impairments, and altered dopamine system responsivity. Applying integrated behavioral z-score analysis, we identified sex-specific differences in response to adolescent stress, with males displaying greater vulnerability than females. Furthermore, adolescent-stressed male mice showed a decrease PV+ and PNN+ cell numbers and PV+/PNN+ colocalization, while in females, adolescent stress reduced prefrontal PV+/PNN+ colocalization in the PFC. Further analysis identified distinct behavioral clusters, with certain females demonstrating resilience to adolescent stress-induced deficits in sociability and PV+ cell number. Adult stress in male and female mice did not cause long-lasting changes in behavior and PV+ and PNN+ cell number. CONCLUSION: Our findings indicate that the timing of stress, sex and individual variabilities seem to be determinants for the development of behavioral changes associated with psychiatric disorders, particularly in male mice during adolescence.

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BACKGROUND: It has been hypothesised that frailty is the root cause of clinically observed but rarely systematically measured unstable disability among older adults. In this study, we measure the extent of short-term disability fluctuations and estimate their association with frailty using intensive longitudinal data. METHODS: Repeated measurements of disability were collected under a measurement burst design in the FRequent health Assessment In Later life (FRAIL70+) study. A total of 426 community-dwelling older adults (70+) in Austria were interviewed about difficulties with basic, instrumental and mobility-related activities of daily living biweekly up to a total of 14 times in two measurement bursts (2891 and 2192 observations). Baseline frailty was assessed with both physical frailty (FP) and the frailty index (FI). Disability fluctuations were measured with the intra-individual interquartile range (iIQR) and estimated with a two-step generalised mixed regression procedure. RESULTS: Fewer participants were frail at baseline according to FP (11%) than FI (32%). Frail study participants reported not only more severe disability but also had more short-term disability fluctuations (iIQR = 1.0-1.5) compared with their robust counterparts (iIQR = 0). Regression models indicated that baseline frailty was associated with 2-3 times larger short-term disability fluctuations, which were also more prevalent among women, and increased with age and disability severity. CONCLUSION: Compared with those who were robust, frail older adults were characterised by not only more severe but also more unstable disability. Short-term disability fluctuations are closely tied to disability severity. Future studies should assess both stressors that may cause disability fluctuations among frail older adults as well as their potential consequences to inform frailty-centred care.

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Complex behavioral sequences such as courtship displays are often multimodal, and coordination between modalities is critically important. In learned and variable behavioral sequences such as songs, individual variability may also extend to multimodal coordination and the associations between modalities. However, individual variability in complex multimodal sequences and in coordination between distinct behaviors remains underexplored. Here, we report that budgerigars, which continuously learn and modify their complex warble songs, exhibit associations between body movements and song notes during courtship. Some associations are unique to individuals, and others are universal across individuals. Additionally, some individuals exhibit more unique associations than others. We also find that birds warbling in the absence of body movements emit all notes with broadly similar odds ratios. Our data suggests a hierarchy of associations, some individual-specific and others common to all individuals, between body movements and songs. We propose that these associations may be learnt and modified through social interactions, resulting in individual variability.

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Small chrysomonads are important bacterivores in aquatic ecosystems with a high molecular diversity compared to low morphological differences observed by light microscopy. The high diversity of these morphologically almost indistinguishable species leads to the question to which extent their functional role in ecosystems differs and how their ecological traits can be defined. The present study investigates the prey size and population growth rate of different chrysomonad species. Eleven phylogenetically well-defined strains representing seven strains of heterotrophic and four strains of mixotrophic chrysomonads were compared. All investigated strains belonged to the same functional group of bacterivorous flagellates, feeding on the same bacteria size range, while population growth rates of chrysomonads depended on nutritional strategy and species-specific differences. We observed a high individual variability of growth rates within a population. Our results point to the necessity to consider not only differences in ecological traits among species but also among specimens within a population.

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BACKGROUND: Exercise is known to provide multiple metabolic benefits such as improved insulin sensitivity and glucose control in individuals with type 2 diabetes mellitus (T2DM) and those at risk. Beyond the traditional exercise dose, exercise timing is perceived as a contemporary hot topic, especially in the field of T2DM; however, the number of intervention studies assessing exercise timing and glucose metabolism is scarce. Our aim is to test the effect of exercise timing (i.e., morning, afternoon, or evening) on the inter-individual response variability in glycemic control and related metabolic health parameters in individuals with T2DM and those at risk during a 12-week intervention. METHODS: A randomized crossover exercise intervention will be conducted involving two groups: group 1, individuals with T2DM; group 2, age-matched older adults with overweight/obesity. The intervention will consist of three 2-week blocks of supervised post-prandial exercise using high-intensity interval training (HIIT). Between each training block, a 2-week washout period, where participants avoid structured exercise, will take place. Assessments will be conducted in both groups before and after each exercise block. The primary outcomes include the 24-h area under the curve continuous glucose monitoring-based glucose. The secondary outcomes include body composition, resting energy expenditure, insulin response to a meal tolerance test, maximal aerobic capacity, peak power output, physical activity, sleep quality, and insulin and glucose levels. All primary and secondary outcomes will be measured at each assessment point. DISCUSSION: Outcomes from this trial will provide us additional insight into the role of exercise timing on the inter-individual response variability in glycemic control and other related metabolic parameters in two distinct populations, thus contributing to the development of more effective exercise prescription guidelines for individuals with T2DM and those at risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT06136013. Registered on November 18, 2023.

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While overweight or obesity are thought to affect over 70% of the US population, the effects of adiposity on neurocognitive efficiency and stability remain unclear. Intra-individual variability or trial-to-trial variability (IIV) could provide insights into the influence of adiposity on neurophysiological stability. However, previous work examining the association between adiposity and IIV of cognitive outcomes is limited. Thus, this study examined the association between whole-body fat (%BF) and central tendency and IIV metrics of behavioral performance and event-related potentials. Adults (n = 320; 19-64 yrs) completed the Flanker task to assess attentional inhibition with concurrent electroencephalogram recordings to examine the N2 and P3b components. In addition to central tendency outcomes typically reported (i.e., mean accuracy and reaction time [RT]), dispersion outcomes (e.g., standard deviation [SD] of RT, P3b latency, N2 latency, etc.) were also extracted. Upon controlling for age and sex, %BF was inversely associated with (congruent: ß = -.18, p = .016; incongruent: ß = -.23, p < .001) accuracy. Increasing %BF was related to greater RT SD (congruent: ß = .13, p = .032; incongruent: ß = .23, p < .001). Furthermore, increased %BF was associated with slower P3b latencies (congruent: ß = .21, p = .003; incongruent: ß = .18, p = .010), and greater incongruent N2 (ß = .16, p = .017) and P3b (ß = .16, p = .025) latency SD. These findings suggest adiposity exerts a generalized negative influence on attentional inhibition for both measures of central tendency and dispersion across behavioral and neuroelectric indices.

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Numerous neuroimaging studies have identified significant individual variability in intertemporal choice, often attributed to three neural mechanisms: (1) increased reward circuit activity, (2) decreased cognitive control, and (3) prospection ability. These mechanisms that explain impulsivity, however, have been primarily studied in the gain domain. This study extends this investigation to the loss domain. We employed a hierarchical Bayesian drift-diffusion model (DDM) and the inter-subject representational similarity approach (IS-RSA) to investigate the potential computational neural substrates underlying impulsivity in loss domain across two experiments (n = 155). These experiments utilized a revised intertemporal task that independently manipulated the amounts of immediate and delayed-loss options. Behavioral results demonstrated positive correlations between the drift rate, measured by the DDM, and the impulsivity index K in Exp. 1 (n = 97) and were replicated in Exp. 2 (n = 58). Imaging analyses further revealed that the drift rate significantly mediated the relations between brain properties (e.g., prefrontal cortex activations and gray matter volume in the orbitofrontal cortex and precuneus) and K in Exp. 1. IS-RSA analyses indicated that variability in the drift rate also mediated the associations between inter-subject variations in activation patterns and individual differences in K. These findings suggest that individuals with similar impulsivity levels are likely to exhibit similar value processing patterns, providing a potential explanation for individual differences in impulsivity within a loss framework.

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BACKGROUND: Lung function is a key outcome used in the evaluation of disease progression in cystic fibrosis. The variability of individual lung function measurements over time (within-individual variability) has been shown to predict subsequent lung function changes. Nevertheless, the association between within-individual lung function variability and demographic and genetic covariates has not been quantified. METHODS: We performed a longitudinal analysis of data from a cohort of 7099 adults with cystic fibrosis (between 18 and 49 years old) from the UK cystic fibrosis registry, containing annual review data between 1996 and 2020. A mixed-effects location-scale model is used to quantify mean FEV1 (forced expiratory volume in 1 s) trajectories and FEV1 within-individual variability as a function of sex, age at annual review, diagnosis after first year of life, homozygous F508 genotype and birth cohort. RESULTS: Mean FEV1 decreased with age and lung function variability showed a near-quadratic trend by age. Males showed higher FEV1 mean and variability than females across the whole age range. Earlier diagnosis and homozygous F508 genotype were also associated with higher FEV1 mean and variability. Individuals who died during follow-up showed on average higher lung function variability than those who survived. CONCLUSIONS: Key variables known to be linked with mean lung function in cystic fibrosis are also associated with an individual's lung function variability. This work opens new avenues to understand the role played by lung function variability in disease progression and its utility in predicting key outcomes such as mortality.

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BACKGROUND: Children's cognitive performance fluctuates across multiple timescales. However, fluctuations have often been neglected in favour of research into average cognitive performance, limiting the unique insights into cognitive abilities and development that cognitive variability may afford. Preliminary evidence suggests that greater variability is associated with increased symptoms of neurodevelopmental disorders, and differences in behavioural and neural functioning. The relative dearth of empirical work on variability, historically limited due to a lack of suitable data and quantitative methodology, has left crucial questions unanswered, which the CODEC (COgnitive Dynamics in Early Childhood) study aims to address. METHOD: The CODEC cohort is an accelerated 3-year longitudinal study which encompasses 600 7-to-10-year-old children. Each year includes a 'burst' week (3 times per day, 5 days per week) of cognitive measurements on five cognitive domains (reasoning, working memory, processing speed, vocabulary, exploration), conducted both in classrooms and at home through experience sampling assessments. We also measure academic outcomes and external factors hypothesised to predict cognitive variability, including sleep, mood, motivation and background noise. A subset of 200 children (CODEC-MRI) are invited for two deep phenotyping sessions (in year 1 and year 3 of the study), including structural and functional magnetic resonance imaging, eye-tracking, parental measurements and questionnaire-based demographic and psychosocial measures. We will quantify developmental differences and changes in variability using Dynamic Structural Equation Modelling, allowing us to simultaneously capture variability and the multilevel structure of trials nested in sessions, days, children and classrooms. DISCUSSION: CODEC's unique design allows us to measure variability across a range of different cognitive domains, ages, and temporal resolutions. The deep-phenotyping arm allows us to test hypotheses concerning variability, including the role of mind wandering, strategy exploration, mood, sleep, and brain structure. Due to CODEC's longitudinal nature, we are able to quantify which measures of variability at baseline predict long-term outcomes. In summary, the CODEC study is a unique longitudinal study combining experience sampling, an accelerated longitudinal 'burst' design, deep phenotyping, and cutting-edge statistical methodologies to better understand the nature, causes, and consequences of cognitive variability in children. TRIAL REGISTRATION: ClinicalTrials.gov - NCT06330090.

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Cefaclor is a substrate of human-peptide-transporter-1 (PEPT1), and the impact of inter-individual pharmacokinetic variation due to genetic polymorphisms of solute-carrier-family-15-member-1 (SLC15A1) has been a topic of great debate. The main objective of this study was to analyze and interpret cefaclor pharmacokinetic variations according to genetic polymorphisms in SLC15A1 exons 5 and 16. The previous cefaclor bioequivalence results were integrated with additional SLC15A1 exons 5 and 16 genotyping results. An analysis of the structure-based functional impact of SLC15A1 exons 5 and 16 genetic polymorphisms was recently performed using a PEPT1 molecular modeling approach. In cefaclor pharmacokinetic analysis results according to SLC15A1 exons 5 and 16 genetic polymorphisms, no significant differences were identified between genotype groups. Furthermore, in the population pharmacokinetic modeling, genetic polymorphisms in SLC15A1 exons 5 and 16 were not established as effective covariates. PEPT1 molecular modeling results also confirmed that SLC15A1 exons 5 and 16 genetic polymorphisms did not have a significant effect on substrate interaction with cefaclor and did not have a major effect in terms of structural stability. This was determined by comprehensively considering the insignificant change in energy values related to cefaclor docking due to point mutations in SLC15A1 exons 5 and 16, the structural change in conformations confirmed to be less than 0.05 Å, and the relative stabilization of molecular dynamic simulation energy values. As a result, molecular structure-based analysis recently suggested that SLC15A1 exons 5 and 16 genetic polymorphisms of PEPT1 were limited to being the main focus in interpreting the pharmacokinetic diversity of cefaclor.

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Transdermal drug delivery is suitable for low-molecular-weight drugs with specific lipophilicity, like fentanyl, which is widely used for cancer-induced pain management. However, fentanyl's transdermal therapy displays high intra-individual variability. Factors like skin characteristics at application sites and ambient temperature contribute to this variation. In this study, we developed a physics-based digital twin of the human body to cope with this variability and propose better adapted setups. This twin includes an in-silico skin model for drug penetration, a pharmacokinetic model, and a pharmacodynamic model. Based on the results of our simulations, applying the patch on the flank (side abdominal area) showed a 15.3 % higher maximum fentanyl concentration in the plasma than on the chest. Additionally, the time to reach this maximum concentration when delivered through the flank was 19.8 h, which was 10.3 h earlier than via the upper arm. Finally, this variation led to an 18 % lower minimum pain intensity for delivery via the flank than the chest. Moreover, the impact of seasonal changes on ambient temperature and skin temperature by considering the activity level was investigated. Based on our result, the fentanyl uptake flux by capillaries increased by up to 11.8 % from an inactive state in winter to an active state in summer. We also evaluated the effect of controlling fentanyl delivery by adjusting the temperature of the patch to alleviate the pain to reach a mild pain intensity (rated three on the VAS scale). By implementing this strategy, the average pain intensity decreased by 1.1 points, and the standard deviation for fentanyl concentration in plasma and average pain intensity reduced by 37.5 % and 33.3 %, respectively. Therefore, our digital twin demonstrated the efficacy of controlled drug release through temperature regulation, ensuring the therapy toward the intended target outcome and reducing therapy outcome variability. This holds promise as a potentially useful tool for physicians.

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Accumulating world knowledge is a major task of development and education. The productive process of self-derivation through memory integration seemingly is a valid model of the process. To test the model, we examined relations between generation and retention of new factual knowledge via self-derivation through integration and world knowledge as measured by standardised assessments. We also tested whether the productive process of self-derivation predicted world knowledge even when a measure of learning through direct instruction also was considered. Participants were 162 children ages 8-12 years (53% female; 15% Black, 6% Asian, 1% Arab, 66% White, 5% mixed race, 7% unreported; 1% Latinx). Age accounted for a maximum of 4% of variance in self-derivation and retention. In contrast, substantial individual variability related to general knowledge and content knowledge in several domains, explaining 20-40% variance. In each domain for which self-derivation performance was a unique predictor, it explained a nominally greater share of the variance than the measure of learning through direct instruction. The findings imply that individual variability in self-derivation has functional consequences for accumulation of semantic knowledge across the elementary-school years.

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Background: Traumatic events can cause long-lasting and uncontrollable fear and anxiety. Posttraumatic stress disorder is an intractable mental disorder, and neurobiological mechanisms using animal models are expected to help development of posttraumatic stress disorder treatment. In this study, we combined multiple stress (MS) and longitudinal in vivo magnetic resonance imaging to reveal the effects of long-lasting anxiety-like behaviors on adult male rat brains. Methods: Twelve male Wistar rats (8 weeks old) were exposed to the MS of 1-mA footshocks and forced swimming, while 12 control rats were placed in a plastic cage. Contextual fear conditioning with 0.1-mA footshocks in a context different from the MS was conducted 15 days after the MS for both groups. Three retention tests were administered after 24 hours and 9 and 16 days. Two magnetic resonance imaging scans were conducted, one on the day before MS induction and one the day after the third retention test, with a 32-day interval. Results: The MS group showed greater freezing responses than the control group in all retention tests. Whole-brain voxel-based morphometry analyses revealed reduced gray matter volume in the anterior amygdalohippocampal area in MS group rats compared with control rats. These volume changes were negatively associated with freezing time in the third retention test in the MS group. Conclusions: These results suggest that individual variability in the amygdalohippocampal area may be related to long-lasting fear responses after severe stress.

Traumatic events can cause long-lasting and uncontrollable fear and anxiety. In this study, we combined multiple stress (MS) and longitudinal in vivo magnetic resonance imaging to reveal the effects of long-lasting anxiety-like behaviors on adult male rat brains. The MS group showed greater freezing responses than the control group in all retention tests. Brain morphometry analyses revealed reduced gray matter volume in the anterior amygdalohippocampal area in MS group rats compared with control rats. These results suggest that individual variability in the amygdalohippocampal area may be related to long-lasting fear responses after severe stress.

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The human brain is organized as a complex, hierarchical network. However, the structural covariance patterns among brain regions and the underlying biological substrates of such covariance networks remain to be clarified. The present study proposed a novel individualized structural covariance network termed voxel-based texture similarity networks (vTSNs) based on 76 refined voxel-based textural features derived from structural magnetic resonance images. Validated in three independent longitudinal healthy cohorts (40, 23, and 60 healthy participants, respectively) with two common brain atlases, we found that the vTSN could robustly resolve inter-subject variability with high test-retest reliability. In contrast to the regional-based texture similarity networks (rTSNs) that calculate radiomic features based on region-of-interest information, vTSNs had higher inter- and intra-subject variability ratios and test-retest reliability in connectivity strength and network topological properties. Moreover, the Spearman correlation indicated a stronger association of the gene expression similarity network (GESN) with vTSNs than with rTSNs (vTSN: r = 0.600, rTSN: r = 0.433, z = 39.784, P < 0.001). Hierarchical clustering identified 3 vTSN subnets with differential association patterns with 13 coexpression modules, 16 neurotransmitters, 7 electrophysiology, 4 metabolism, and 2 large-scale structural and 4 functional organization maps. Moreover, these subnets had unique biological hierarchical organization from the subcortex-limbic system to the ventral neocortex and then to the dorsal neocortex. Based on 424 unrelated, qualified healthy subjects from the Human Connectome Project, we found that vTSNs could sensitively represent sex differences, especially for connections in the subcortex-limbic system and between the subcortex-limbic system and the ventral neocortex. Moreover, a multivariate variance component model revealed that vTSNs could explain a significant proportion of inter-subject behavioral variance in cognition (80.0 %) and motor functions (63.4 %). Finally, using 494 healthy adults (aged 19-80 years old) from the Southwest University Adult Lifespan Dataset, the Spearman correlation identified a significant association between aging and vTSN strength, especially within the subcortex-limbic system and between the subcortex-limbic system and the dorsal neocortex. In summary, our proposed vTSN is robust in uncovering individual variability and neurobiological brain processes, which can serve as biologically plausible measures for linking biological processes and human behavior.

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BACKGROUND: Self-regulation is crucial for children's learning and development. Several studies have explored children's inter-individual differences in self-regulation, but little is known about sources of intra-individual variation. AIMS: This study addressed the variability of children's self-regulation across typical classroom situations and how this might be associated with children's executive functions (EFs). SAMPLE: The study included 148 children (54.7% girls; Mage = 56.73 months). METHODS: Self-regulation was assessed with an observational measure in teacher-led and child-led activities within naturalistic classroom settings. Children's EFs were assessed with direct assessments at the start and end of the school year. RESULTS: Linear mixed-effect models showed that children demonstrated higher levels of self-regulation in child-led in comparison with teacher-led activities. Children with higher levels of EFs at the start of the school year showed less variation across teacher-led and child-led activities in comparison with children with lower levels of EFs. Regarding other aspects of the classroom context, neither the group size in which the activity took place nor which school subject it was focused on were associated with children's self-regulation. However, in teacher-led activities the type of interaction involved in the activity and the type of task influenced children's self-regulation. CONCLUSION: These results suggest that children who start school with higher levels of EFs are more able to adapt to different situations, highlighting the importance of fostering these skills in early childhood. In turn, children with lower levels of EFs may need additional support from teachers to remain self-regulated across different contexts.

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This study aimed to investigate cardiovascular and cardiorespiratory adaptations to exercise intervention among participants who showed higher (responders-RSBFP) and lower (non-responders-NRSBFP) levels of body fat percentage (BFP) responsiveness. Adolescents (42.5% males) participated in a ten-week school-based high-intensity interval training (HIIT), followed by a comparison of BFP, blood pressure (BP), and cardiorespiratory fitness (CRF). RSBFP age of 16.15 ± 0.36 years, body height 170.82 ± 8.16 cm, weight 61.23 ± 12.80 kg, and BMI 20.86 ± 3.29 kg/m2. Meanwhile, NRSBFP age of 16.04 ± 0.36 years, body height 168.17 ± 8.64 cm, weight 57.94 ± 8.62 kg, and BMI 20.47 ± 2.24 kg/m2. HIIT intervention impacted BFP, with a higher decrease in the RSBFP than the NRSBFP (ΔBFPRs = - 2.30 ± 3.51(10.34%) vs. ΔBFPNRs = 1.51 ± 1.54(6.96%) p < 0.001). The primary comparison showed a statistically significant interaction effect in relation to CRF (F(1,71) = 14.12; p < 0.001). Detailed comparisons showed large and significant CRF changes in RSBFP (7.52%; d = 0.86; p < 0.001) but not in NRSBFP (2.01%; d = 0.11; p = 0.576). In addition, RSBFP and NRSBFP benefited equally in SBP (5.49%, d = 0.75; p < 0.001; 4.95%, d = 0.74; p < 0.001, respectively). These findings highlight that exercise benefits on body fat may be mainly related to gains in CRF. Due to substantial intra-individual variability in adaptation, there is a need for personalized intervention tailored for those with different reaction thresholds in body mass components.

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A successful adjustment to dynamic changes in one's environment requires contingent adaptive behaviour. Such behaviour is underpinned by cognitive flexibility, which conceptually is part of fluid intelligence. We argue, however, that conventional approaches to measuring fluid intelligence are insufficient in capturing cognitive flexibility. We address the discrepancy between conceptualisation and operationalisation by introducing two newly developed tasks that aim at capturing within-person processes of dealing with novelty. In an exploratory proof-of-concept study, the two flexibility tasks were administered to 307 university students, together with a battery of conventional measures of fluid intelligence. Participants also provided information about their Grade Point Averages obtained in high school and in their first year at university. We tested (1) whether an experimental manipulation of a requirement for cognitive inhibition resulted in systematic differences in difficulty, (2) whether these complexity differences reflect psychometrically differentiable effects, and (3) whether these newly developed flexibility tasks show incremental value in predicting success in the transition from high school to university over conventional operationalisations of fluid intelligence. Our findings support the notion that cognitive flexibility, when conceptualised and operationalised as individual differences in within-person processes of dealing with novelty, more appropriately reflects the dynamics of individuals' behaviour when attempting to cope with changing demands.

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BACKGROUND AND OBJECTIVE: Recent advancements in brain-computer interface (BCI) technology have seen a significant shift towards incorporating complex decoding models such as deep neural networks (DNNs) to enhance performance. These models are particularly crucial for sophisticated tasks such as regression for decoding arbitrary movements. However, these BCI models trained and tested on individual data often face challenges with limited performance and generalizability across different subjects. This limitation is primarily due to a tremendous number of parameters of DNN models. Training complex models demands extensive datasets. Nevertheless, group data from many subjects may not produce sufficient decoding performance because of inherent variability in neural signals both across individuals and over time METHODS: To address these challenges, this study proposed a transfer learning approach that could effectively adapt to subject-specific variability in cortical regions. Our method involved training two separate movement decoding models: one on individual data and another on pooled group data. We then created a salience map for each cortical region from the individual model, which helped us identify the input's contribution variance across subjects. Based on the contribution variance, we combined individual and group models using a modified knowledge distillation framework. This approach allowed the group model to be universally applicable by assigning greater weights to input data, while the individual model was fine-tuned to focus on areas with significant individual variance RESULTS: Our combined model effectively encapsulated individual variability. We validated this approach with nine subjects performing arm-reaching tasks, with our method outperforming (mean correlation coefficient, r = 0.75) both individual (r = 0.70) and group models (r = 0.40) in decoding performance. In particular, there were notable improvements in cases where individual models showed low performances (e.g., r = 0.50 in the individual decoder to r = 0.61 in the proposed decoder) CONCLUSIONS: These results not only demonstrate the potential of our method for robust BCI, but also underscore its ability to generalize individual data for broader applicability.

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Existing knowledge on changes of the haptoglobin (Hp) molecule suggests that it may exist in multiple proteoforms, which obviously exhibit different functions. Using two-dimensional electrophoresis (2DE) in combination with mass spectrometry and immunodetection, we have analyzed blood plasma samples from both healthy donors and patients with primary grade IV glioblastoma (GBM), and obtained a detailed composite 2DE distribution map of ß-chain proteoforms, as well as the full-length form of Hp (zonulin). Although the total level of plasma Hp exceeded normal values in cancer patients (especially patients with GBM), the presence of particuar proteoforms, detected by their position on the 2DE map, was very individual. Variability was found in both zonulin and the Hp ß-chain. The presence of an alkaline form of zonulin in plasma can be considered a conditional, but insufficient, GBM biomarker. In other words, we found that at the level of minor proteoforms of Hp, even in normal conditions, there was a high individual variability. On the one hand, this raises questions about the reasons for such variability, if it is present not only in Hp, but also in other proteins. On the other hand, this may explain the discrepancy between the number of experimentally detected proteoforms and the theoretically possible ones not only in Hp, but also in other proteins.

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