Dissociable roles for the striatal cholinergic system in different flexibility contexts.

The production of behavioural flexibility requires the coordination and integration of information from across the brain, by the dorsal striatum. In particular, the striatal cholinergic system is thought to be important for the modulation of striatal activity. Research from animal literature has shown that chemical inactivation of the dorsal striatum leads to impairments in reversal learning. Furthermore, proton magnetic resonance spectroscopy work has shown that the striatal cholinergic system is also important for reversal learning in humans. Here, we aim to assess whether the state of the dorsal striatal cholinergic system at rest is related to flexible behaviour in reversal learning. We provide preliminary results showing that variability in choline in the dorsal striatum is significantly related to both the number perseverative and regressive errors that participants make, and their rate of learning from positive and negative prediction errors. These findings, in line with previous work, suggest the resting state of dorsal striatal cholinergic system has important implications for producing flexible behaviour. However, these results also suggest the system may have heterogeneous functionality across different types of tasks measuring behavioural flexibility. These findings provide a starting point for further interrogation into understanding the functional role of the striatal cholinergic system in flexibility.

The Effects of Diverse Exercise on Cognition and Mental Health of Children Aged 5–6 Years: A Controlled Trial

The rate of learning and cognitive development is at its highest level in preschool-aged children, making this stage a critical period. Exercise has received increasing attention for its beneficial physical and mental health effects on the development of preschool children. This study investigated the effects of diverse exercise on the cognition of preschool children. Two classes were randomly selected from kindergarten classes of children aged 5–6 years, and designated as the experimental and control classes. Each class contained 20 children (10 boys and 10 girls) according to the kindergarten class system. The experimental class completed exercises according to the designed curriculum, while control class carried out exercises according to the regular teaching plan, for a study period of 12 weeks. The Wechsler Preschool and Primary Scale of Intelligence (WPPSI) and the Mental Health Questionnaire for Children were used to assess outcomes, both at the beginning and end of study. After 12 weeks, the experimental class has improved in the “Object Assembly,” “Block Design,” “Picture Completion,” and “Coding” (14.70 ± 2.14, p < 0.01; 14.54 ± 1.56, p < 0.01; 9.62 ± 2.06, p < 0.05; 15.92 ± 2.72, p < 0.05) in performance test, and showed improvements in the “Movement,” “Cognitive Ability,” “Sociality” and “Living Habits” (5.65 ± 0.59, p < 0.01; 11.20 ± 1.91, p < 0.05; 9.05 ± 1.72, p < 0.05; 7.10 ± 1.45, p < 0.05) in mental health outcomes. Diverse exercise has a significantly beneficial role in promoting the cognitive development of children aged 5–6 years, as well as a beneficial, albeit insignificant, role in their mental health.

Relating Neurochemical Changes Associated with THC Use to Learning and Memory in Adolescent Rats

<p>Cannabis is the most widely used illicit drug. Adolescents may be especially vulnerable to the effects of cannabis, and alarmingly, adolescence is also a period of heavy cannabis use. However, few studies have investigated the cognitive effects of cannabis use in adolescents specifically. Furthermore, the neurochemical correlates of cognitive impairment associated with cannabis use at any age have received very little experimental attention. This research project sought to address these shortcomings in the literature using THC, the major psychoactive component of cannabis, and a rat model of adolescence. The rate of learning was slower in THC-treated animals, and this was attributable to deficits in the cognitive function of 'chunking', a process by which the information capacity of short-term memory is enlarged. Impairment of chunking by cannabinoids has not been previously reported. Behavioural impairment by THC was associated with impaired hippocampal plasticity, including changes in synaptic activity and architecture, as well as changes in neurogenesis. The attenuation of structural and functional plasticity in the hippocampus in response to training in a learning task was more pronounced than the subtle effects of THC-treatment on the survival and early development of newborn neurons. Importantly, no effects of THC were seen in animals not trained in the maze. Thus, plasticity is more sensitive to the effects of THC during times of learning, and this greater sensitivity likely accounts for the behavioural impairment associated with cannabis use. The data presented in this thesis add significantly to the existing literature by identifying novel behavioural and neurochemical processes by which cannabis use may impair learning and memory. Whether these impairments represent a greater sensitivity of adolescents to THC remains to be determined.</p>

Relating Neurochemical Changes Associated with THC Use to Learning and Memory in Adolescent Rats

<p>Cannabis is the most widely used illicit drug. Adolescents may be especially vulnerable to the effects of cannabis, and alarmingly, adolescence is also a period of heavy cannabis use. However, few studies have investigated the cognitive effects of cannabis use in adolescents specifically. Furthermore, the neurochemical correlates of cognitive impairment associated with cannabis use at any age have received very little experimental attention. This research project sought to address these shortcomings in the literature using THC, the major psychoactive component of cannabis, and a rat model of adolescence. The rate of learning was slower in THC-treated animals, and this was attributable to deficits in the cognitive function of 'chunking', a process by which the information capacity of short-term memory is enlarged. Impairment of chunking by cannabinoids has not been previously reported. Behavioural impairment by THC was associated with impaired hippocampal plasticity, including changes in synaptic activity and architecture, as well as changes in neurogenesis. The attenuation of structural and functional plasticity in the hippocampus in response to training in a learning task was more pronounced than the subtle effects of THC-treatment on the survival and early development of newborn neurons. Importantly, no effects of THC were seen in animals not trained in the maze. Thus, plasticity is more sensitive to the effects of THC during times of learning, and this greater sensitivity likely accounts for the behavioural impairment associated with cannabis use. The data presented in this thesis add significantly to the existing literature by identifying novel behavioural and neurochemical processes by which cannabis use may impair learning and memory. Whether these impairments represent a greater sensitivity of adolescents to THC remains to be determined.</p>

Disrupted state transition learning as a computational marker of compulsivity

Background Disorders involving compulsivity, fear, and anxiety are linked to beliefs that the world is less predictable. We lack a mechanistic explanation for how such beliefs arise. Here, we test a hypothesis that in people with compulsivity, fear, and anxiety, learning a probabilistic mapping between actions and environmental states is compromised. Methods In Study 1 (n = 174), we designed a novel online task that isolated state transition learning from other facets of learning and planning. To determine whether this impairment is due to learning that is too fast or too slow, we estimated state transition learning rates by fitting computational models to two independent datasets, which tested learning in environments in which state transitions were either stable (Study 2: n = 1413) or changing (Study 3: n = 192). Results Study 1 established that individuals with higher levels of compulsivity are more likely to demonstrate an impairment in state transition learning. Preliminary evidence here linked this impairment to a common factor comprising compulsivity and fear. Studies 2 and 3 showed that compulsivity is associated with learning that is too fast when it should be slow (i.e. when state transition are stable) and too slow when it should be fast (i.e. when state transitions change). Conclusions Together, these findings indicate that compulsivity is associated with a dysregulation of state transition learning, wherein the rate of learning is not well adapted to the task environment. Thus, dysregulated state transition learning might provide a key target for therapeutic intervention in compulsivity.

Cannabidiol Exposure During the Mouse Adolescent Period Is Without Harmful Behavioral Effects on Locomotor Activity, Anxiety, and Spatial Memory

Cannabidiol (CBD) is a non-intoxicating phytocannabinoid whose purported therapeutic benefits and impression of a high safety profile has promoted its increasing popularity. CBD’s popularity is also increasing among children and adolescents who are being administered CBD, off label, for the treatment of numerous symptoms associated with autism spectrum disorder, attention deficit hyperactivity disorder, anxiety, and depression. The relative recency of its use in the adolescent population has precluded investigation of its impact on the developing brain and the potential consequences that may present in adulthood. Therefore, there’s an urgency to identify whether prolonged adolescent CBD exposure has substantive impacts on the developing brain that impact behavioral and cognitive processes in adulthood. Here, we tested the effect of twice-daily intraperitoneal administrations of CBD (20 mg/kg) in male and female C57BL/6J mice during the adolescent period of 25–45 days on weight gain, and assays for locomotor behavior, anxiety, and spatial memory. Prolonged adolescent CBD exposure had no detrimental effects on locomotor activity in the open field, anxiety behavior on the elevated plus maze, or spatial memory in the Barnes Maze compared to vehicle-treated mice. Interestingly, CBD-treated mice had a faster rate of learning in the Barnes Maze. However, CBD-treated females had reduced weight gain during the exposure period. We conclude that prolonged adolescent CBD exposure in mice does not have substantive negative impacts on a range of behaviors in adulthood, may improve the rate of learning under certain conditions, and impacts weight gain in a sex-specific manner.

Description and Level of Difficulty in Learning Hematology for Medical Laboratory Technology (MLT) Students during One Year of the COVID-19 Pandemic

This research aims (1) to determine the description of learning difficulties and the percentage of supporting and inhibiting factors for learning hematology in the COVID-19 pandemic era, (2) to determine the success rate of learning hematology in the COVID-19 pandemic era. This research is a qualitative descriptive type, with research subjects from D4 Analyst students at the Universitas Muhammadiyah Semarang who study hematology. This data collection was carried out from February to March 2021. Data were collected from a questionnaire via Google Form. Based on the results of the study, the following findings were obtained: 1) description and percentage of supporting and inhibiting factors for hematology learning difficulties as follows: (1) health factors (53.33%), (2) cognitive factors (60%), (3) interest factors (50%). The average internal factor of hematology learning difficulties is 54,44% in the medium category. While the percentage of external factors of learning difficulties in hematology are as follows: (1) family factors (46.67%), (2) living place conditions (46.67%), (3) facilities (48.89%), (4) learning materials (54%). The average external factor of hematology learning difficulties is 49.06% in the medium category, 2) the success rate of learning hematology in the COVID-19 pandemic era with an average of 61.73 (medium). The study results can contribute in the form of information on the description of the factors of learning difficulties in the Hematology course in the COVID-19 pandemic era as a basis for finding solutions.

A “Talent Agency” refers children for research: A case study

Objective Ethical standards state research participation must be voluntary and free of coercion and undue influence, but what if a third party appears to engage in research-relevant coercion, without the researchers’ knowledge? This case study describes this type of situation and its resolution. Methods We are engaged in a randomized clinical trial evaluating pedestrian safety with 7- and 8- years old. Depending on children's rate of learning, families receive up to $1275 for their time. We recently learned a third-party “talent agency,” a firm placing children in modeling and acting jobs, was referring families to our research with the expectation that families would share 20% of study reimbursements. Results We sensed clear impropriety, but identified no ethical violations on our part as researchers. Once paid a study reimbursement, participants can spend funds how they wish. We were concerned, however, that the third-party was exploitatively coercing families to participate. Conclusions We pursued four avenues to resolve the issue. First, we documented the situation to our university Institutional Review Board. Second, we contacted the talent agency and requested they stop referring families to our research. They agreed. Third, we retained children engaged in our study who were referred from the talent agency; removing them partway through the clinical trial could impact study results. In doing so, we explained that we were unaware of the talent agency referral and that they were not obligated by us to offer a portion of the study reimbursement to the talent agency. Last, we asked newly enrolled families about their referral source.

Dopaminergic signaling supports auditory social learning

Explicit rewards are commonly used to reinforce a behavior, a form of learning that engages the dopaminergic neuromodulatory system. In contrast, skill acquisition can display dramatic improvements from a social learning experience, even though the observer receives no explicit reward. Here, we test whether a dopaminergic signal contributes to social learning in naïve gerbils that are exposed to, and learn from, a skilled demonstrator performing an auditory discrimination task. Following five exposure sessions, naïve observer gerbils were allowed to practice the auditory task and their performance was assessed across days. We first tested the effect of an explicit food reward in the observer’s compartment that was yoked to the demonstrator’s performance during exposure sessions. Naïve observer gerbils with the yoked reward learned the discrimination task significantly faster, as compared to unrewarded observers. The effect of this explicit reward was abolished by administration of a D1/D5 dopamine receptor antagonist during the exposure sessions. Similarly, the D1/D5 antagonist reduced the rate of learning in unrewarded observers. To test whether a dopaminergic signal was sufficient to enhance social learning, we administered a D1/D5 receptor agonist during the exposure sessions in which no reward was present and found that the rate of learning occurred significantly faster. Finally, a quantitative analysis of vocalizations during the exposure sessions suggests one behavioral strategy that contributes to social learning. Together, these results are consistent with a dopamine-dependent reward signal during social learning.

Human click-based echolocation: Effects of blindness and age, and real-life implications in a 10-week training program

Understanding the factors that determine if a person can successfully learn a novel sensory skill is essential for understanding how the brain adapts to change, and for providing rehabilitative support for people with sensory loss. We report a training study investigating the effects of blindness and age on the learning of a complex auditory skill: click-based echolocation. Blind and sighted participants of various ages (21–79 yrs; median blind: 45 yrs; median sighted: 26 yrs) trained in 20 sessions over the course of 10 weeks in various practical and virtual navigation tasks. Blind participants also took part in a 3-month follow up survey assessing the effects of the training on their daily life. We found that both sighted and blind people improved considerably on all measures, and in some cases performed comparatively to expert echolocators at the end of training. Somewhat surprisingly, sighted people performed better than those who were blind in some cases, although our analyses suggest that this might be better explained by the younger age (or superior binaural hearing) of the sighted group. Importantly, however, neither age nor blindness was a limiting factor in participants’ rate of learning (i.e. their difference in performance from the first to the final session) or in their ability to apply their echolocation skills to novel, untrained tasks. Furthermore, in the follow up survey, all participants who were blind reported improved mobility, and 83% reported better independence and wellbeing. Overall, our results suggest that the ability to learn click-based echolocation is not strongly limited by age or level of vision. This has positive implications for the rehabilitation of people with vision loss or in the early stages of progressive vision loss.