Analyzing the Quality of Life in Individuals with Fragile X Syndrome in Relation to Sleep and Mental Health.

The purpose of this paper was to examine the physical, emotional, social and school functioning domains of quality of life of individuals with Fragile X Syndrome, in relation to mental health and sleep patterns to gain a better understanding of how these aspects are affected by the disorder. This study included 119 individuals with Fragile X Syndrome who were given different cognitive examinations by a neuropsychologist or by parent-proxy questionnaires. This study focused on the Pediatric Quality of Life Inventory (PedsQoL), the Anxiety, Depression and Mood Scale (ADAMS), the Children's Sleep Habits Questionnaire (CSHQ), but did include other cognitive tests (Vineland Adaptive Behaviour Scales, Nonverbal IQ, Autism Diagnostic Observation Schedule). We identified significant associations between decreases in emotional, social and school domains of PedsQoL and the ADAMS subtests of Generalized Anxiety, Manic/Hyperactivity and Obsessive/Compulsivity, with the subtest of Depressed Mood having associations with lower physical and emotional domains. We also identified a significant impact between CSHQ subtests of Sleep Anxiety, Night Wakings, Daytime Sleepiness, and Parasomnia with the emotional and school domains of PedsQoL. There were associations connecting school functioning with Bedtime Resistance, and additional associations connecting emotional functioning with Sleep Duration and Sleep Onset Delay. Physical functioning was also associated with Sleep Anxiety. Our study shows how mental health and sleep defects impact improper sleep patterns and mental health which leads to decreases in the quality of life for individuals with FXS, and how it is important to screen for these symptoms in order to alleviate issues.

Long-term Memory Testing in Children With Typical Development and Neurodevelopmental Disorders: Remote Web-based Image Task Feasibility Study.

BACKGROUND: Neurodevelopmental disorders (NDD) cause individuals to have difficulty in learning facts, procedures, or social skills. NDD has been linked to several genes, and several animal models have been used to identify potential therapeutic candidates based on specific learning paradigms for long-term and associative memory. In individuals with NDD, however, such testing has not been used so far, resulting in a gap in translating preclinical results to clinical practice. OBJECTIVE: We aim to assess if individuals with NDD could be tested for paired association learning and long-term memory deficit, as shown in previous animal models. METHODS: We developed an image-based paired association task, which can be performed at different time points using remote web-based testing, and evaluated its feasibility in children with typical development (TD), as well as NDD. We included 2 tasks: object recognition as a simpler task and paired association. Learning was tested immediately after training and also the next day for long-term memory. RESULTS: We found that children aged 5-14 years with TD (n=128) and with NDD of different types (n=57) could complete testing using the Memory Game. Children with NDD showed deficits in both recognition and paired association tasks on the first day of learning, in both 5-9-year old (P<.001 and P=.01, respectively) and 10-14-year old groups (P=.001 and P<.001, respectively). The reaction times to stimuli showed no significant difference between individuals with TD or NDD. Children with NDD exhibited a faster 24-hour memory decay for the recognition task than those with TD in the 5-9-year old group. This trend is reversed for the paired association task. Interestingly, we found that children with NDD had their retention for recognition improved and matched with typically developing individuals by 10-14 years of age. The NDD group also showed improved retention deficits in the paired association task at 10-14 years of age compared to the TD group. CONCLUSIONS: We showed that web-based learning testing using simple picture association is feasible for children with TD, as well as with NDD. We showed how web-based testing allows us to train children to learn the association between pictures, as shown in immediate test results and those completed 1 day after. This is important as many models for learning deficits in NDD target both short- and long-term memory for therapeutic intervention. We also demonstrated that despite potential confounding factors, such as self-reported diagnosis bias, technical issues, and varied participation, the Memory Game shows significant differences between typically developing children and those with NDD. Future experiments will leverage this potential of web-based testing for larger cohorts and cross-validation with other clinical or preclinical cognitive tasks.

Identifying Potential Gamification Elements for A New Chatbot for Families With Neurodevelopmental Disorders: User-Centered Design Approach.

BACKGROUND: Chatbots have been increasingly considered for applications in the health care field. However, it remains unclear how a chatbot can assist users with complex health needs, such as parents of children with neurodevelopmental disorders (NDDs) who need ongoing support. Often, this population must deal with complex and overwhelming health information, which can make parents less likely to use a software that may be very helpful. An approach to enhance user engagement is incorporating game elements in nongame contexts, known as gamification. Gamification needs to be tailored to users; however, there has been no previous assessment of gamification use in chatbots for NDDs. OBJECTIVE: We sought to examine how gamification elements are perceived and whether their implementation in chatbots will be well received among parents of children with NDDs. We have discussed some elements in detail as the initial step of the project. METHODS: We performed a narrative literature review of gamification elements, specifically those used in health and education. Among the elements identified in the literature, our health and social science experts in NDDs prioritized five elements for in-depth discussion: goal setting, customization, rewards, social networking, and unlockable content. We used a qualitative approach, which included focus groups and interviews with parents of children with NDDs (N=21), to assess the acceptability of the potential implementation of these elements in an NDD-focused chatbot. Parents were asked about their opinions on the 5 elements and to rate them. Video and audio recordings were transcribed and summarized for emerging themes, using deductive and inductive thematic approaches. RESULTS: From the responses obtained from 21 participants, we identified three main themes: parents of children with NDDs were familiar with and had positive experiences with gamification; a specific element (goal setting) was important to all parents, whereas others (customization, rewards, and unlockable content) received mixed opinions; and the social networking element received positive feedback, but concerns about information accuracy were raised. CONCLUSIONS: We showed for the first time that parents of children with NDDs support gamification use in a chatbot for NDDs. Our study illustrates the need for a user-centered design in the medical domain and provides a foundation for researchers interested in developing chatbots for populations that are medically vulnerable. Future studies exploring wide range of gamification elements with large number of potential users are needed to understand the impact of gamification elements in enhancing knowledge mobilization.

Receptor dependence of BDNF actions in superficial dorsal horn: relation to central sensitization and actions of macrophage colony stimulating factor 1.

Peripheral nerve injury elicits an enduring increase in the excitability of the spinal dorsal horn. This change, which contributes to the development of neuropathic pain, is a consequence of release and prolonged exposure of dorsal horn neurons to various neurotrophins and cytokines. We have shown in rats that nerve injury increases excitatory synaptic drive to excitatory neurons but decreases drive to inhibitory neurons. Both effects, which contribute to an increase in dorsal horn excitability, appear to be mediated by microglia-derived BDNF. We have used multiphoton Ca2+ imaging and whole cell recording of spontaneous excitatory postsynaptic currents in defined-medium organotypic cultures of GAD67-GFP+ mice spinal cord to determine the receptor dependence of these opposing actions of BDNF. In mice, as in rats, BDNF enhances excitatory transmission onto excitatory neurons. This is mediated via presynaptic TrkB and p75 neurotrophin receptors and exclusively by postsynaptic TrkB. By contrast with findings from rats, in mice BDNF does not decrease excitation of inhibitory neurons. The cytokine macrophage colony-stimulating factor 1 (CSF-1) has also been implicated in the onset of neuropathic pain. Nerve injury provokes its de novo synthesis in primary afferents, its release in spinal cord, and activation of microglia. We now show that CSF-1 increases excitatory drive to excitatory neurons via a BDNF-dependent mechanism and decreases excitatory drive to inhibitory neurons via BDNF-independent processes. Our findings complete missing steps in the cascade of events whereby peripheral nerve injury instigates increased dorsal horn excitability in the context of central sensitization and the onset of neuropathic pain. NEW & NOTEWORTHY Nerve injury provokes synthesis of macrophage colony-stimulating factor 1 (CSF-1) in primary afferents and its release in the dorsal horn. We show that CSF-1 increases excitatory drive to excitatory dorsal horn neurons via BDNF activation of postsynaptic TrkB and presynaptic TrkB and p75 neurotrophin receptors. CSF-1 decreases excitatory drive to inhibitory neurons via a BDNF-independent processes. This completes missing steps in understanding how peripheral injury instigates central sensitization and the onset of neuropathic pain.