Computational Principles of Supervised Learning in the Cerebellum.

Supervised learning plays a key role in the operation of many biological and artificial neural networks. Analysis of the computations underlying supervised learning is facilitated by the relatively simple and uniform architecture of the cerebellum, a brain area that supports numerous motor, sensory, and cognitive functions. We highlight recent discoveries indicating that the cerebellum implements supervised learning using the following organizational principles: ( a) extensive preprocessing of input representations (i.e., feature engineering), ( b) massively recurrent circuit architecture, ( c) linear input-output computations, ( d) sophisticated instructive signals that can be regulated and are predictive, ( e) adaptive mechanisms of plasticity with multiple timescales, and ( f) task-specific hardware specializations. The principles emerging from studies of the cerebellum have striking parallels with those in other brain areas and in artificial neural networks, as well as some notable differences, which can inform future research on supervised learning and inspire next-generation machine-based algorithms.

Parents' Empathic Accuracy: Associations With Type 1 Diabetes Management and Familism.

OBJECTIVE: To (1) test associations between parents' empathic accuracy for their adolescents' positive and negative emotions and adolescents' physical and mental health (HbA1c, diabetes self-care, and depressive symptoms) in a predominantly Latinx sample of adolescents with type 1 diabetes and their parents, and (2) explore how familism values were associated with parent empathic accuracy and adolescent physical and mental health in this population. METHODS: Parents and adolescents engaged in a discussion about a topic of frequent conflict related to the adolescents' diabetes management. Parents and adolescents subsequently completed a video recall task in which they rated their own and their partner's emotions once per minute; parents' empathic accuracy was calculated from an average discrepancy between parent and adolescent ratings of the adolescent's emotions. Adolescents reported on their depressive symptoms and both parents and adolescents reported on adolescents' diabetes self-care and their own familism values; HbA1c was obtained from medical records. RESULTS: Results from structural equation modeling revealed that parents' empathic accuracy for adolescents' negative (but not positive) emotions was uniquely associated with adolescents' HbA1c, self-care, and depressive symptoms. There was limited evidence that familism was related to parent empathic accuracy or adolescent physical and mental health. CONCLUSIONS: Promoting parents' empathic accuracy for adolescents' negative emotions in the context of type 1 diabetes management may have important implications for adolescents' mental and physical health.

Challenges and Opportunities in Using Telehealth for Diabetes Care.

The ongoing coronavirus pandemic led to a rapid and dramatic increase in the use of telehealth for diabetes care. In the wake of this transition, we examine new opportunities and ongoing challenges for using telehealth within diabetes management, based on data and experiences from the pre-pandemic and pandemic time frames.

Equity in Medical Care for People Living With Diabetes.

Disparities and inequities exist for individuals with diabetes in marginalized communities of color, especially among people with low socioeconomic status. Although these barriers are apparent, only a few care models have been designed for and examined in racially and ethnically diverse individuals. This article reviews models that have been developed and examined in a variety of different populations and focuses on how to implement elements from these programs in clinical practice. Health equity-promoting ideas and approaches that can be applied throughout the life span (children to seniors) are also included. As diabetes health care providers, researchers, educators, policymakers, and advocates, we must now combine our efforts and focus on historically excluded populations to bridge the gap to essential diabetes care.

Follow-Up Mental Health Care in Youth and Young Adults With Type 1 Diabetes After Positive Depression Screen and/or Suicidal Ideation.

Individuals with type 1 diabetes have higher rates of depression and suicidal ideation than the general population, and symptoms of depression are often associated with higher A1C levels and complications. This study evaluated mental health follow-up rates in youth and young adults with type 1 diabetes who screened positive for depressive symptoms or suicidal ideation and identified differences between those who obtained follow-up mental health care and those who did not. Specifically, males were less likely to obtain follow-up, and those who had mental health follow-up had decreasing A1C over the following year. These findings suggest increased assistance and monitoring are needed to ensure follow-up mental health care is obtained.

Population calcium responses of Purkinje cells in the oculomotor cerebellum driven by nonvisual input.

The climbing fiber input to the cerebellum conveys instructive signals that can induce synaptic plasticity and learning by triggering complex spikes accompanied by large calcium transients in Purkinje cells. In the cerebellar flocculus, which supports oculomotor learning, complex spikes are driven by image motion on the retina, which could indicate an oculomotor error. In the same neurons, complex spikes also can be driven by nonvisual signals. It has been shown that the calcium transients accompanying each complex spike can vary in amplitude, even within a given cell, therefore, we compared the calcium responses associated with the visual and nonvisual inputs to floccular Purkinje cells. The calcium indicator GCaMP6f was selectively expressed in Purkinje cells, and fiber photometry was used to record the calcium responses from a population of Purkinje cells in the flocculus of awake behaving mice. During visual (optokinetic) stimuli and pairing of vestibular and visual stimuli, the calcium level increased during contraversive retinal image motion. During performance of the vestibulo-ocular reflex in the dark, calcium increased during contraversive head rotation and the associated ipsiverse eye movements. The amplitude of this nonvisual calcium response was comparable to that during conditions with retinal image motion present that induce oculomotor learning. Thus, population calcium responses of Purkinje cells in the cerebellar flocculus to visual and nonvisual input are similar to what has been reported previously for complex spikes, suggesting that multimodal instructive signals control the synaptic plasticity supporting oculomotor learning.NEW & NOTEWORTHY It was long known that the climbing fiber input to Purkinje cells in the cerebellar flocculus conveys visual feedback about the accuracy of image-stabilizing oculomotor reflexes. More recently, the same climbing fibers were reported to carry nonvisual signals. Here, we report that both visual and nonvisual inputs can elicit robust calcium responses in the Purkinje cells, suggesting that the instructive signals guiding oculomotor plasticity are multimodal.

Psychosocial outcomes in young adolescents with type 1 diabetes participating in shared medical appointments.

For youth with type 1 diabetes (T1D), the early adolescent period is associated with worsening diabetes management and high rates of negative psychosocial issues, including depressive symptoms and family conflict. Alternative clinical models may help improve both diabetes and psychosocial outcomes. Our study aims to investigate whether Team Clinic, a shared medical appointment model developed specifically for adolescents with T1D, will improve psychosocial outcomes for middle school-aged youth. Youth with T1D, 11-13 years of age, and their caregivers, participated in a randomized controlled trial comparing Team Clinic to traditional clinic visits (control group). Diabetes characteristics were obtained at every visit. Participants and caregivers completed depression screening and family conflict questionnaires at baseline and end of study. Changes in mean scores on clinical and psychosocial outcomes from baseline to end of study were compared between groups using linear mixed-effects models. Eighty-six youth (51% female; 74% White; 10% Hispanic) completed at least one visit during the 12-month study period. At the end of the study, control group participants reported increases in Emotional Problems compared to Team Clinic participants, including higher levels of Negative Mood/Physical Symptoms (p = 0.02). Team Clinic participants reported reduced family conflict surrounding diabetes at study end, compared to control group participants (p = 0.03). Caregivers did not report change in depressive symptoms or family conflict during the study. Hemoglobin A1C levels did not change over time in either group. Participation in Team Clinic was associated with improved psychosocial outcomes in middle school-aged participants with T1D.

Telehealth for Young Adults With Diabetes: Addressing Social Determinants of Health.

Type 1 diabetes is a challenging chronic condition and can lead to diabetes-related distress and disengagement. Historically disadvantaged, racially and ethnically diverse young adults (YAs) with type 1 diabetes experience higher blood glucose levels and encounter more barriers to care than their White counterparts. Current research shows that telehealth may provide a route for improving psychosocial issues and diabetes care among YAs.

Glycemic control in youth-onset type 2 diabetes correlates with weight loss.

OBJECTIVE: To identify risk factors for glycemic failure in youth with type 2 diabetes (T2D). METHODS: A retrospective review of HbA1c, anthropomorphic measures, medication records, and laboratory studies was performed using registry data from a dedicated pediatric T2D clinic. Latent profile analysis (LPA) was performed to model longitudinal trajectory of HbA1c over 5 years. RESULTS: The registry includes 229 youth with T2D, of whom 80% self-identify as Latinx. The odds ratio (OR) for uncontrolled diabetes 5 years after diagnosis correlated with diagnostic HbA1c, with OR of 2.41 if HbA1c at diagnosis >8.5% (sensitivity 68%, specificity 54%, P = .015). LPA modeling identified three HbA1c profiles: (a) mean HbA1c <8% throughout the 5 years, (b) persistent elevation of mean HbA1c >9%, and (c) mean HbA1c of 12% at diagnosis, rapid decline to 6.4% by 4 to 6 months, and increase to 11% by 18 months. Our analysis of medication regimen showed that, amongst patients treated with metformin, the addition of multiple daily injections (MDI) did not improve HbA1c compared to those on basal insulin. Finally, weight loss over the 1 year after diagnosis correlated with improvement in HbA1c in both subjects prescribed metformin monotherapy, as well as insulin-containing regimen. CONCLUSION: Youth with T2D exhibit distinct HbA1c profiles. Patients with diagnostic HbA1c >8.5% are at high risk for glycemic failure, irrespective of short-term improvement in HbA1c. Weight management has the potential to improve short-term HbA1c outcome in youth with T2D. Additional studies are needed to determine the role of medication adherence on glycemic control.

Effectiveness of social media (Facebook), targeted mailing, and in-person solicitation for the recruitment of young adult in a diabetes self-management clinical trial.

BACKGROUND/AIMS: Research is needed to identify promising recruitment strategies to reach and engage diverse young adults in diabetes clinical research. The aim of this study was to examine the relative strengths and weaknesses of three recruitment strategies used in a diabetes self-management clinical trial: social media advertising (Facebook), targeted mailing, and in-person solicitation of clinic patients. METHODS: Strategies were compared in terms of (1) cost-effectiveness (i.e. cost of recruitment/number of enrolled participants), (2) ability to yield participants who would not otherwise be reached by alternative strategies, and (3) likelihood of participants recruited through each strategy to adhere to study procedures. We further explored the appeal (overall and among age and gender subgroups) of social media advertisement features. RESULTS: In-person recruitment of clinic patients was overall the most cost-effective strategy. However, differences in demographic, clinical, and psychosocial characteristics of participants recruited via different strategies suggest that the combination of these approaches yielded a more diverse sample than would any one strategy alone. Once successfully enrolled, there was no difference in study completion and intervention adherence between individuals recruited by the three recruitment strategies. CONCLUSIONS: Ultimately, the utility of a recruitment strategy is defined by its ability to effectively attract people representative of the target population who are willing to enroll in and complete the study. Leveraging a variety of recruitment strategies appears to produce a more representative sample of young adults, including those who are less engaged in diabetes care.

Prevalence, characteristics, and diabetes management in children with comorbid autism spectrum disorder and type 1 diabetes.

OBJECTIVE: To determine autism spectrum disorder (ASD) prevalence within our pediatric type 1 diabetes (T1D) clinic population and determine clinical characteristics and technology used by individuals with both ASD and T1D compared to matched controls with T1D alone and compared to our overall pediatric T1D clinic. METHODS: Medical chart review showed 30 individuals with both ASD and type 1 diabetes (ASD + T1D). Controls (n = 90) were matched for age, sex, race/ethnicity, and T1D duration. ASD + T1D was compared to both matched controls and the pediatric T1D clinical population. RESULTS: ASD prevalence in the pediatric T1D population was 1.16% (CI 0.96-1.26). Compared to the T1D clinic, ASD + T1D had more males (93% vs 52%; P < 0.0001), lower hemoglobin A1c (HbA1c) (8.2% vs 8.9%; 66 vs 74 mmol/mol; P = 0.006), and lower insulin pump (CSII) use (37% vs 56%; P < 0.0001). No differences were found between ASD + T1D and matched controls in HbA1c or blood glucose checks per day. The ASD + T1D group was less likely to use CSII than matched controls (37% vs 61%; P = 0.03). HbA1c did not change after CSII initiation in ASD + T1D, but increased for matched controls. CONCLUSIONS: Prevalence of ASD in the pediatric T1D population is comparable to the general population in Colorado. Individuals with ASD may experience barriers limiting CSII use, but achieve equivalent glycemic control compared to those without ASD. CSII may be more effective in maintaining lower HbA1c over time in those with ASD than in those without ASD.

Depressed by Learning-Heterogeneity of the Plasticity Rules at Parallel Fiber Synapses onto Purkinje Cells.

Climbing fiber-driven long-term depression (LTD) of parallel fiber synapses onto cerebellar Purkinje cells has long been investigated as a putative mechanism of motor learning. We recently discovered that the rules governing the induction of LTD at these synapses vary across different regions of the cerebellum. Here, we discuss the design of LTD induction protocols in light of this heterogeneity in plasticity rules. The analytical advantages of the cerebellum provide an opportunity to develop a deeper understanding of how the specific plasticity rules at synapses support the implementation of learning.

Diabetes management mediating effects between diabetes symptoms and health-related quality of life in adolescents and young adults with type 1 diabetes.

OBJECTIVES: The primary objective was to investigate the mediating effects of diabetes management in the relationship between diabetes symptoms and generic health-related quality of life (HRQOL) in adolescents and young adults (AYAs) with type 1 diabetes. The secondary objective explored patient health communication and perceived treatment adherence barriers as mediators in a serial multiple mediator model. METHODS: The PedsQL 3.2 Diabetes Module 15-item diabetes symptoms summary score, 18-item diabetes management summary score, and PedsQL 4.0 generic core scales were completed in a 10-site national field test study by 418 AYA aged 13 to 25 years with type 1 diabetes. Diabetes symptoms and diabetes management were tested for bivariate and multivariate linear associations with overall generic HRQOL. Mediational analyses were conducted to test the hypothesized mediating effects of diabetes management as an intervening variable between diabetes symptoms and generic HRQOL. RESULTS: The predictive effects of diabetes symptoms on HRQOL were mediated in part by diabetes management. In predictive analytics models utilizing multiple regression analyses, demographic and clinical covariates, diabetes symptoms, and diabetes management significantly accounted for 53% of the variance in generic HRQOL (P < 0.001), demonstrating a large effect size. Patient health communication and perceived treatment adherence barriers were significant mediators in an exploratory serial multiple mediator model. CONCLUSIONS: Diabetes management explains in part the effects of diabetes symptoms on HRQOL in AYA with type 1 diabetes. Patient health communication to healthcare providers and perceived treatment adherence barriers further explain the mechanism in the relationship between diabetes symptoms and overall HRQOL.

AIDS-Affected Orphans in Sub-Saharan Africa: A Scoping Review on Outcome Differences in Rural and Urban Environments.

Currently, there are more than 11 million AIDS-affected orphans that suffer from various adverse effects, most of whom reside in sub-Saharan Africa. The difference between whether a child resides in a rural or urban environment can have a significant role in a child's education, health status and access to healthcare, and social or family relationships. A scoping review was conducted in order to understand any possible environment-based differences on orphans directly affected by HIV/AIDS in sub-Saharan Africa. There were 233 sources used for this review; however, 164 manuscripts focused more so on a general review of orphans within a rural or urban environment. Thus, after eliminating for various factors, 69 manuscripts were removed, which focused primarily on the social aspect of orphans due to HIV/AIDS. Rural environments provided more family support, while urban environments generally had more resources available to orphans (e.g. school fees). Unfortunately, both rural and urban environments were found to be fairly non-supportive of orphans and their development. This scoping review found, in general, that orphans in both urban and rural environments continue to suffer from the consequential effects of low parental support due to AIDS mortality. These conclusions suggest that specific support to orphans through school and social relationships encourage better development outcomes in sub-Saharan Africa.

Diabetes symptoms predictors of health-related quality of life in adolescents and young adults with type 1 or type 2 diabetes.

OBJECTIVES: The objective was to investigate the patient-reported diabetes symptoms predictors of generic health-related quality of life (HRQOL) in adolescents and young adults (AYA) with type 1 or type 2 diabetes. METHODS: The 15-item PedsQL™ 3.2 Diabetes Module Diabetes Symptoms Summary Score and PedsQL™ 4.0 Generic Core Scales were completed in a 10-site national field test study by 513 AYA ages 13-25 years with type 1 (n = 424) or type 2 (n = 89) diabetes. Diabetes symptoms were tested for bivariate and multivariate linear associations with generic HRQOL. RESULTS: Diabetes symptoms were associated with decreased HRQOL in bivariate analyses. In predictive analytics models utilizing hierarchical multiple regression analyses controlling for relevant demographic and clinical covariates, diabetes symptoms accounted for 38 and 39% of the variance in patient-reported generic HRQOL for type 1 and type 2 diabetes, respectively, reflecting large effect sizes. The diabetes symptoms facets hyperglycemia symptoms, hypoglycemia symptoms, and nonspecific diabetes symptoms individually accounted for a significant percentage of the variance in separate exploratory predictive analytics models after controlling for demographic and clinical covariates, with small-to-large effect sizes. CONCLUSIONS: Diabetes symptoms are potentially modifiable predictors of generic HRQOL in AYA with diabetes. Identifying specific diabetes symptoms or symptoms facets that are the most important predictors from the patient perspective facilitates a patient-centered approach in clinical research, clinical trials, and practice designed to enhance overall generic HRQOL in AYA with diabetes.

Perspectives on care for young adults with type 1 diabetes transitioning from pediatric to adult health systems: A national survey of pediatric endocrinologists.

BACKGROUND: Healthcare transition from pediatric to adult care for young adults (YA) with type 1 diabetes (T1D) is associated with risk of adverse outcomes. Consensus recommendations exist from US professional societies on transition care for YA with T1D, but it is not known whether they have been widely adopted. We describe experiences, barriers, and provider characteristics associated with transition care in a national sample of pediatric endocrinologists. METHODS: US pediatric endocrinologists identified through the American Medical Association Physician Masterfile were sent an electronic survey. RESULTS: Response rate was 16% (164/1020) representing 32 states. The majority of pediatric endocrinologists (age 44 ± 10; years in practice 12 ± 11) were female (67%) and worked in academic centers (75%). Main reasons for transfer were age (49%) and glycemic control (18%). Barriers to transition included ending long-therapeutic relationships with patients (74%), lack of transition protocols (46%), and perceived deficiencies in adult care (42%). The majority of pediatric endocrinologists reported lack of transition training (68%); those who received training were less likely to have difficulty ending patient relationships [odds ratio (OR) = 0.39, P = .03], more likely to perform patient record transfer to adult systems (OR=1.27, P = .006), and less likely to report patient returns to pediatric care after transfer (OR=0.49, P = .01), independent of endocrinologist gender, years in practice, or practice type. CONCLUSIONS: There is wide variation in transition care for YA with T1D among US pediatric endocrinologists despite consensus recommendations. Dissemination of educational programming on transition care and provision of actionable solutions to overcome local health system and perceived barriers is needed.

Team Clinic: An Innovative Group Care Model for Youth with Type 1 Diabetes-Engaging Patients and Meeting Educational Needs.

The purpose of this pilot was to implement an innovative group care model, "Team Clinic", for adolescents with type 1 diabetes and assess patient and provider perspectives. Ninety-one intervention patients and 87 controls were enrolled. Ninety-six percent of intervention adolescents endorsed increased support and perceived connecting with peers as important. The medical providers and staff also provided positive feedback stating Team Clinic allowed more creativity in education and higher quality of care. Team Clinic may be a promising model to engage adolescents and incorporate education and support into clinic visits in a format valued by patients and providers.

Fear of Hypoglycemia in Children and Adolescents and Their Parents with Type 1 Diabetes.

Hypoglycemia is a frequent occurrence in children and adolescents with type 1 diabetes. A variety of efforts have been made to standardize the definition of hypoglycemia and to define one of its most significant psychosocial consequences-fear of hypoglycemia (FOH). In addition to documenting the experience of FOH in children and adolescents type 1 diabetes and their parents, studies have investigated the relations between FOH and glycemic control and diabetes technology use. This review provides a summary of the recent FOH literature as it applies to pediatric type 1 diabetes.

Cerebellar encoding of multiple candidate error cues in the service of motor learning.

For learning to occur through trial and error, the nervous system must effectively detect and encode performance errors. To examine this process, we designed a set of oculomotor learning tasks with more than one visual object providing potential error cues, as would occur in a natural visual scene. A task-relevant visual target and a task-irrelevant visual background both influenced vestibulo-ocular reflex learning in rhesus monkeys. Thus, motor learning does not identify a single error cue based on behavioral relevance, but can be simultaneously influenced by more than one cue. Moreover, the relative weighting of the different cues could vary. If the speed of the visual target's motion on the retina was low (≪1°/s), background motion dominated learning, but if target speed was high, the effects of the background were suppressed. The target and background motion had similar, nonlinear effects on the putative neural instructive signals carried by cerebellar climbing fibers, but with a stronger influence of the background on the climbing fibers than on learning. In contrast, putative neural instructive signals carried by the simple spikes of Purkinje cells were influenced solely by the motion of the visual target. Because they are influenced by different cues during training, joint control of learning by the climbing fibers and Purkinje cells may expand the learning capacity of the cerebellar circuit.