One-shot entorhinal maps enable flexible navigation in novel environments.

Animals must navigate changing environments to find food, shelter or mates. In mammals, grid cells in the medial entorhinal cortex construct a neural spatial map of the external environment1-5. However, how grid cell firing patterns rapidly adapt to novel or changing environmental features on a timescale relevant to behaviour remains unknown. Here, by recording over 15,000 grid cells in mice navigating virtual environments, we tracked the real-time state of the grid cell network. This allowed us to observe and predict how altering environmental features influenced grid cell firing patterns on a nearly instantaneous timescale. We found evidence that visual landmarks provide inputs to fixed points in the grid cell network. This resulted in stable grid cell firing patterns in novel and altered environments after a single exposure. Fixed visual landmark inputs also influenced the grid cell network such that altering landmarks induced distortions in grid cell firing patterns. Such distortions could be predicted by a computational model with a fixed landmark to grid cell network architecture. Finally, a medial entorhinal cortex-dependent task revealed that although grid cell firing patterns are distorted by landmark changes, behaviour can adapt via a downstream region implementing behavioural timescale synaptic plasticity6. Overall, our findings reveal how the navigational system of the brain constructs spatial maps that balance rapidity and accuracy. Fixed connections between landmarks and grid cells enable the brain to quickly generate stable spatial maps, essential for navigation in novel or changing environments. Conversely, plasticity in regions downstream from grid cells allows the spatial maps of the brain to more accurately mirror the external spatial environment. More generally, these findings raise the possibility of a broader neural principle: by allocating fixed and plastic connectivity across different networks, the brain can solve problems requiring both rapidity and representational accuracy.

Baby food pouches and Baby-Led Weaning: Associations with energy intake, eating behaviour and infant weight status.

Although concern is frequently expressed regarding the potential impact of baby food pouch use and Baby-Led Weaning (BLW) on infant health, research is scarce. Data on pouch use, BLW, energy intake, eating behaviour and body mass index (BMI) were obtained for 625 infants aged 7-10 months in the First Foods New Zealand study. Frequent pouch use was defined as ≥5 times/week during the past month. Traditional spoon-feeding (TSF), "partial" BLW and "full" BLW referred to the relative proportions of spoon-feeding versus infant self-feeding, assessed at 6 months (retrospectively) and current age. Daily energy intake was determined using two 24-h dietary recalls, and caregivers reported on a variety of eating behaviours. Researchers measured infant length and weight, and BMI z-scores were calculated (World Health Organization Child Growth Standards). In total, 28% of infants consumed food from pouches frequently. Frequent pouch use was not significantly related to BMI z-score (mean difference, 0.09; 95% CI -0.09, 0.27) or energy intake (92 kJ/day; -19, 202), but was associated with greater food responsiveness (standardised mean difference, 0.3; 95% CI 0.1, 0.4), food fussiness (0.3; 0.1, 0.4) and selective/restrictive eating (0.3; 0.2, 0.5). Compared to TSF, full BLW was associated with greater daily energy intake (BLW at 6 months: mean difference 150 kJ/day; 95% CI 4, 297; BLW at current age: 180 kJ/day; 62, 299) and with a range of eating behaviours, including greater satiety responsiveness, but not BMI z-score (6 months: 0.06 (-0.18, 0.30); current age: 0.06 (-0.13, 0.26)). In conclusion, neither feeding approach was associated with weight in infants, despite BLW being associated with greater energy intake compared with TSF. However, infants who consumed pouches frequently displayed higher food fussiness and more selective eating.

Household food insecurity and novel complementary feeding methods in New Zealand families.

Optimal nutrition during infancy is critical given its influence on lifelong health and wellbeing. Two novel methods of infant complementary feeding, commercial baby food pouch use and baby-led weaning (BLW), are becoming increasingly popular worldwide. Household food insecurity may influence complementary feeding practices adopted by families, but no studies have investigated the use of BLW and baby food pouches in families experiencing food insecurity. The First Foods New Zealand study was a multicentre, observational study in infants 7.0-9.9 months of age. Households (n = 604) were classified into one of three categories of food insecurity (severely food insecure, moderately food insecure, and food secure). The use of complementary feeding practices was assessed via a self-administered questionnaire, both at the current age (mean 8.4 months) and retrospectively at 6 months. Mothers experiencing severe food insecurity had 5.70 times the odds of currently using commercial baby food pouches frequently (≥5 times/week) compared to food secure mothers (95% CI [1.54, 21.01]), reporting that pouches were 'easy to use' (89%) and made it 'easy to get fruits and vegetables in' (64%). In contrast, no evidence of a difference in the prevalence of current BLW was observed among mothers experiencing moderate food insecurity (adjusted OR; 1.28, 95% CI [0.73, 2.24]) or severe food insecurity (adjusted OR; 1.03, 95% CI [0.44, 2.43]) compared to food secure mothers. The high prevalence of frequent commercial baby food pouch use in food insecure households underscores the need for research to determine whether frequent pouch use impacts infant health.

Effects of intervention intensity on skill acquisition and task persistence in children with Down syndrome.

BACKGROUND: Modifying intensity is one approach to tailoring intervention to meet the needs of learners with developmental disabilities. This study examined the effects of varying intensity levels of a behaviour analytic intervention on the efficiency of acquisition and task persistence in young children with Down syndrome. METHODS: Using adapted alternating treatment designs, three children were taught expressive language targets when three aspects of the dose of intervention intensity varied: number of opportunities, spacing of opportunities and session duration. RESULTS: Children acquired targets faster in conditions in which the spacing of opportunities was shorter than conditions in which the spacing was longer. Two children showed greater expression of positive affect in moderate levels of intensity. Children showed idiosyncratic differences in off-task behaviour. DISCUSSION: This research suggests that pacing of opportunities may be an important for understanding acquisition outcomes in a behaviour analytic approach to intervention for communication among young children with Down syndrome.

A community support program for children with autism and their typically developing siblings: Initial investigation.

Siblings are a critical part of lifelong support for individuals with autism spectrum disorder (ASD). But siblings face their own social-emotional adjustment needs. These needs may be addressed through programs that include support groups specifically for the siblings. This study examined the effects of a community program on typical siblings' depression, anxiety, ASD knowledge, and peer network as well as reciprocal interactions between the typical sibling and sibling with ASD. The program provided a sibling support group, a skills intervention for children with ASD, and an inclusive recreation time. Siblings reported significant decreases in depression and physiological anxiety and improvements in their peer network. Autism knowledge increased but only approached significance. Direct observations revealed improvement in reciprocal interactions by most children that did not reach statistical significance. Parents, typical siblings, and interventionists indicated positive reactions to the program and its goals and outcomes. Findings are discussed in terms of the need to continue to explore interventions for siblings of children with ASD.

Functional Analysis of Contextually Inappropriate Social Behavior in Children With Down Syndrome.

BACKGROUND: Children with Down syndrome often engage in contextually inappropriate social behavior, which researchers suggest may function to escape from difficult activities to preferred social interactions. Caregivers may reinforce the behavior, perceiving it only as evidence of the child's social strength, when, in fact, the pattern may also prevent or slow the development of critical skills. Unlike overt forms of challenging behavior, contextually inappropriate social behavior had never been subjected to experimental analysis. AIMS: The purpose of the current study was to identify and demonstrate functional control of contextually inappropriate social behavior to caregiver-informed contingencies. METHOD AND PROCEDURES: We interviewed caregivers and subjected contextually inappropriate social behavior to functional analyses for nine young children with Down syndrome. OUTCOMES AND RESULTS: We found sensitivity to the caregiver-informed contingencies for all nine participants with strong functional control and large effect sizes for most. CONCLUSIONS AND IMPLICATIONS: Caregivers may not perceive contextually inappropriate social behavior as problematic, yet patterns of contextually inappropriate and other problem behaviors suggest decreased engagement and poor task persistence. Assessments that lead to intervention decisions may be more informative when they include questions about social topographies of behavior not typically considered as problematic. Once caregivers are aware of the pattern, they may be better prepared to intervene.

Entorhinal cortex represents task-relevant remote locations independent of CA1.

Neurons can collectively represent the current sensory experience while an animal is exploring its environment or remote experiences while the animal is immobile. These remote representations can reflect learned associations1-3 and be required for learning4. Neurons in the medial entorhinal cortex (MEC) reflect the animal's current location during movement5, but little is known about what MEC neurons collectively represent during immobility. Here, we recorded thousands of neurons in superficial MEC and dorsal CA1 as mice learned to associate two pairs of rewarded locations. We found that during immobility, the MEC neural population frequently represented positions far from the animal's location, which we defined as 'non-local coding'. Cells with spatial firing fields at remote locations drove non-local coding, even as cells representing the current position remained active. While MEC non-local coding has been reported during sharp-wave ripples in downstream CA16, we observed non-local coding more often outside of ripples. In fact, CA1 activity was less coordinated with MEC during non-local coding. We further observed that non-local coding was pertinent to the task, as MEC preferentially represented remote task-relevant locations at appropriate times, while rarely representing task-irrelevant locations. Together, this work raises the possibility that MEC non-local coding could strengthen associations between locations independently from CA1.

Waveform-based classification of dentate spikes.

Synchronous excitatory discharges from the entorhinal cortex (EC) to the dentate gyrus (DG) generate fast and prominent patterns in the hilar local field potential (LFP), called dentate spikes (DSs). As sharp-wave ripples in CA1, DSs are more likely to occur in quiet behavioral states, when memory consolidation is thought to take place. However, their functions in mnemonic processes are yet to be elucidated. The classification of DSs into types 1 or 2 is determined by their origin in the lateral or medial EC, as revealed by current source density (CSD) analysis, which requires recordings from linear probes with multiple electrodes spanning the DG layers. To allow the investigation of the functional role of each DS type in recordings obtained from single electrodes and tetrodes, which are abundant in the field, we developed an unsupervised method using Gaussian mixture models to classify such events based on their waveforms. Our classification approach achieved high accuracies (> 80%) when validated in 8 mice with DG laminar profiles. The average CSDs, waveforms, rates, and widths of the DS types obtained through our method closely resembled those derived from the CSD-based classification. As an example of application, we used the technique to analyze single-electrode LFPs from apolipoprotein (apo) E3 and apoE4 knock-in mice. We observed that the latter group, which is a model for Alzheimer's disease, exhibited wider DSs of both types from a young age, with a larger effect size for DS type 2, likely reflecting early pathophysiological alterations in the EC-DG network, such as hyperactivity. In addition to the applicability of the method in expanding the study of DS types, our results show that their waveforms carry information about their origins, suggesting different underlying network dynamics and roles in memory processing.

Frequent Use of Baby Food Pouches in Infants and Young Children and Associations with Energy Intake and BMI: An Observational Study.

OBJECTIVE: Most wet commercial infant foods are now sold in squeezable 'pouches'. While multiple expert groups have expressed concern about their use, it is not known how commonly they are consumed and whether they impact energy intake or body mass index (BMI). The objectives were to describe pouch use, and determine associations with energy intake and BMI, in infants and young children. METHODS: In this observational cross-sectional study of 933 young New Zealand children (6.0 months-3.9 years), pouch use was assessed by a questionnaire ('frequent' use was consuming food from a baby food pouch ≥5 times/week in the past month), usual energy intake using two 24-h recalls, and BMI z-score calculated using World Health Organization standards. RESULTS: The sample broadly represented the wider population (27.1% high socioeconomic deprivation, 22.5% Maori). Frequent pouch use declined with age (infants 27%, toddlers 16%, preschoolers 8%). Few children were both frequent pouch users and regularly used the nozzle (infants 5%, toddlers 13%, preschoolers 8%). Preschoolers who were frequent pouch users consumed significantly less energy than non-users (-580 kJ [-1094, -67]), but infants (115 [-35, 265]) and toddlers (-206 [-789, 378]) did not appear to have a different energy intake than non-users. There were no statistically significant differences in the BMI z-score by pouch use. CONCLUSIONS: These results do not support the strong concerns expressed about their use, particularly given the lack of evidence for higher energy intake or BMI.

Baby Food Pouches, Baby-Led Weaning, and Iron Status in New Zealand Infants: An Observational Study.

Iron deficiency in infants can impact development, and there are concerns that the use of baby food pouches and baby-led weaning may impair iron status. First Foods New Zealand (FFNZ) was an observational study of 625 New Zealand infants aged 6.9 to 10.1 months. Feeding methods were defined based on parental reports of infant feeding at "around 6 months of age": "frequent" baby food pouch use (five+ times per week) and "full baby-led weaning" (the infant primarily self-feeds). Iron status was assessed using a venepuncture blood sample. The estimated prevalence of suboptimal iron status was 23%, but neither feeding method significantly predicted body iron concentrations nor the odds of iron sufficiency after controlling for potential confounding factors including infant formula intake. Adjusted ORs for iron sufficiency were 1.50 (95% CI: 0.67-3.39) for frequent pouch users compared to non-pouch users and 0.91 (95% CI: 0.45-1.87) for baby-led weaning compared to traditional spoon-feeding. Contrary to concerns, there was no evidence that baby food pouch use or baby-led weaning, as currently practiced in New Zealand, were associated with poorer iron status in this age group. However, notable levels of suboptimal iron status, regardless of the feeding method, emphasise the ongoing need for paying attention to infant iron nutrition.

Teaching the Skill of Chewing From a Behavior Analytic Approach: A Systematic Review.

Relatively few empirical studies of pediatric chewing interventions have been published in the psychology literature. The purpose of this paper was to systematically review chewing interventions within the applied behavior analysis literature. We identified a small, but growing, behavior analytic literature demonstrating the effectiveness of various multicomponent treatment packages to teach and improve chewing skills. Future researchers should consider a range of participant characteristics, including results of oral motor assessments, explore a more extensive definition of chewing to target the complex nature of chewing as well as component skills, and examine the necessary and sufficient components of chewing interventions along with the potential benefits of multidisciplinary interventions.

Neural ensembles in navigation: From single cells to population codes.

The brain can represent behaviorally relevant information through the firing of individual neurons as well as the coordinated firing of ensembles of neurons. Neurons in the hippocampus and associated cortical regions participate in a variety of types of ensembles to support navigation. These ensemble types include single cell codes, population codes, time-compressed sequences, behavioral sequences, and engrams. We present the physiological basis and behavioral relevance of ensemble firing. We discuss how these traditional definitions of ensembles can constrain or expand potential analyses due to the underlying assumptions and abstractions made. We highlight how coding can change at the ensemble level while underlying single cell codes remain intact. Finally, we present how ensemble definitions could be broadened to better understand the full complexity of the brain.

What If You Can't Ask Them? Psychometric Properties of a Behavioral Assessment of Sibling Relationship Quality.

Building on studies of preferences for social interaction in children with autism spectrum disorder (ASD) we sought to provide a way for siblings with ASD to express their perspective about the quality of their sibling relationships. We developed a behavioral assessment of sibling relationship preference (Sibling Relationship Assessment [SRA]) and examined the psychometric properties of test-retest reliability, inter-rater reliability, and convergent validity. The SRA was feasible to administer and revealed expected differences between sibling dyads with one sibling with ASD compared to typically-developing sibling dyads. We found strong positive correlations for inter-rater reliability and test-retest reliability and convergent validity. The SRA provides a way to assess the perspective of the sibling with ASD that taps one characteristic, preference for spending time with one's sibling, of the quality of sibling relationships.

Ketamine evoked disruption of entorhinal and hippocampal spatial maps.

Ketamine, a rapid-acting anesthetic and acute antidepressant, carries undesirable spatial cognition side effects including out-of-body experiences and spatial memory impairments. The neural substrates that underlie these alterations in spatial cognition however, remain incompletely understood. Here, we used electrophysiology and calcium imaging to examine ketamine's impacts on the medial entorhinal cortex and hippocampus, which contain neurons that encode an animal's spatial position, as mice navigated virtual reality and real world environments. Ketamine acutely increased firing rates, degraded cell-pair temporal firing-rate relationships, and altered oscillations, leading to longer-term remapping of spatial representations. In the reciprocally connected hippocampus, the activity of neurons that encode the position of the animal was suppressed after ketamine administration. Together, these findings demonstrate ketamine-induced dysfunction of the MEC-hippocampal circuit at the single cell, local-circuit population, and network levels, connecting previously demonstrated physiological effects of ketamine on spatial cognition to alterations in the spatial navigation circuit.

Ketamine evoked disruption of entorhinal and hippocampal spatial maps.

Ketamine, a rapid-acting anesthetic and acute antidepressant, carries undesirable spatial cognition side effects including out-of-body experiences and spatial memory impairments. The neural substrates that underlie these alterations in spatial cognition however, remain incompletely understood. Here, we used electrophysiology and calcium imaging to examine ketamine's impacts on the medial entorhinal cortex and hippocampus, which contain neurons that encode an animal's spatial position, as mice navigated virtual reality and real world environments. Ketamine induced an acute disruption and long-term re-organization of entorhinal spatial representations. This acute ketamine-induced disruption reflected increased excitatory neuron firing rates and degradation of cell-pair temporal firing rate relationships. In the reciprocally connected hippocampus, the activity of neurons that encode the position of the animal was suppressed after ketamine administration. Together, these findings point to disruption in the spatial coding properties of the entorhinal-hippocampal circuit as a potential neural substrate for ketamine-induced changes in spatial cognition.

An Evaluation of a Telehealth Caregiver Training Package to Treat Food Selectivity.

Telehealth behavioral interventions are increasingly necessary when in-person services are not accessible (e.g., due to geographic location, time, cost, and health and safety restrictions). There is a growing evidence-base for the effectiveness of telehealth interventions but few demonstrations of telehealth interventions for pediatric feeding disorders. The purpose of this study was to evaluate a telehealth caregiver training package to teach caregivers to implement a feeding intervention, in their home as primary interventionists, to treat their children's food selectivity. To address some previously documented caregiver concerns regarding some intervention procedures (e.g., nonremoval of the spoon or escape extinction) and ensure caregivers could safely/feasibility implement intervention, the intervention included differential reinforcement of bites consumed within a 3-minute opportunity. All three caregivers demonstrated high levels of correct performance following training and all children demonstrated increases in the number of bites consumed and decreases in disruptive behaviors. Findings suggest training caregivers via telehealth may be a viable option to treat some children's food selectivity without first requiring in-person services.

Waveform-based classification of dentate spikes.

Synchronous excitatory discharges from the entorhinal cortex (EC) to the dentate gyrus (DG) generate fast and prominent patterns in the hilar local field potential (LFP), called dentate spikes (DSs). As sharp-wave ripples in CA1, DSs are more likely to occur in quiet behavioral states, when memory consolidation is thought to take place. However, their functions in mnemonic processes are yet to be elucidated. The classification of DSs into types 1 or 2 is determined by their origin in the lateral or medial EC, as revealed by current source density (CSD) analysis, which requires recordings from linear probes with multiple electrodes spanning the DG layers. To allow the investigation of the functional role of each DS type in recordings obtained from single electrodes and tetrodes, which are abundant in the field, we developed an unsupervised method using Gaussian mixture models to classify such events based on their waveforms. Our classification approach achieved high accuracies (> 80%) when validated in 8 mice with DG laminar profiles. The average CSDs, waveforms, rates, and widths of the DS types obtained through our method closely resembled those derived from the CSD-based classification. As an example of application, we used the technique to analyze single-electrode LFPs from apolipoprotein (apo) E3 and apoE4 knock-in mice. We observed that the latter group, which is a model for Alzheimer's disease, exhibited wider DSs of both types from a young age, with a larger effect size for DS type 2, likely reflecting early pathophysiological alterations in the EC-DG network, such as hyperactivity. In addition to the applicability of the method in expanding the study of DS types, our results show that their waveforms carry information about their origins, suggesting different underlying network dynamics and roles in memory processing.

Sensory Phenotypes in Autism: Making a Case for the Inclusion of Sensory Integration Functions.

Sensory features are part of the diagnostic criteria for autism and include sensory hypo/hyper reactivity and unusual sensory interest; however, additional sensory differences, namely differences in sensory integration, have not been routinely explored. This study characterized sensory integration differences in a cohort of children (n = 93) with a confirmed diagnosis of autism (5-9 years) using a standardized, norm-referenced battery. Mean z scores, autism diagnostic scores, and IQ are reported. Participants showed substantial deficits in tactile perception, praxis, balance, visual perception, and visual-motor skills. Relationship with autism diagnostic test scores were weak or absent. Findings suggest additional sensory difficulties that are not typically assessed or considered when characterizing sensory features in autism. These data have implications for a greater understanding of the sensory features in the autism phenotype and the development of personalized treatments.

Quality of the sibling relationship when one sibling has autism spectrum disorder: A randomized controlled trial of a sibling support group.

LAY ABSTRACT: The sibling relationship can be negatively impacted when one child has autism spectrum disorder. One way to improve the quality of that relationship is through typically developing sibling participation in a support group in which they learn about autism spectrum disorder and coping skills, develop a peer network, and discuss their feelings. Compared to participating in a similar group without a focus on autism spectrum disorder, siblings in the support group showed improvements in the quality of the sibling relationship. Findings suggest that sibling support groups can be a valuable resource to improve sibling relationship quality when one sibling has autism spectrum disorder.

Notes from an epicenter: navigating behavioral clinical trials on autism spectrum disorder amid the COVID-19 pandemic in the Bronx.

BACKGROUND: The COVID-19 pandemic impacted nearly all facets of our daily lives, and clinical research was no exception. Here, we discuss the impact of the pandemic on our ongoing, three-arm randomized controlled trial (RCT) Sensory Integration Therapy (SIT) in Autism: Mechanisms and Effectiveness (NCT02536365), which investigates the immediate and sustained utility of SIT to strengthen functional daily-living skills and minimize the presence of maladaptive sensory behaviors in autistic children. MAIN TEXT: In this text, we detail how we navigated the unique challenges that the pandemic brought forth between the years 2020 and 2021, including the need to rapidly adjust our study protocol, recruitment strategy, and in-person assessment battery to allow for virtual recruitment and data collection. We further detail how we triaged participants and allocated limited resources to best preserve our primary outcome measures while prioritizing the safety of our participants and study team. We specifically note the importance of open and consistent communication with all participating families throughout the pandemic in ensuring all our protocol adjustments were successfully implemented. CONCLUSIONS: Though the COVID-19 pandemic resulted in an unprecedented interruption to in-person clinical research, clinical trials have always been and will continue to be at risk for unforeseen interruptions, whether from world events or participants' personal circumstances. By presenting our steps to preserving this RCT throughout the pandemic, we offer suggestions for successfully managing unexpected interruptions to research. Ideally, by taking these into account, future RCTs may be increasingly prepared to minimize the impact of these potential interruptions to research.