Faculty Bibliography

Interval timing, the ability to encode and retrieve the memory of intervals from seconds to minutes, guides fundamental animal behaviors across the phylogenetic tree. In Pavlovian fear conditioning, an initially neutral stimulus (conditioned stimulus, CS) predicts the arrival of an aversive unconditioned stimulus (US, generally a mild foot-shock) at a fixed time interval. Although some studies showed that temporal relations between CS and US events are learned from the outset of conditioning, the question of the memory of time and its underlying neural network in fear conditioning is still poorly understood. The aim of the present study was to investigate the role of the dorsal striatum in timing intervals in odor fear conditioning in male rats. To assess the animal's interval timing ability in this paradigm, we used the respiratory frequency. This enabled us to detect the emergence of temporal patterns related to the odor-shock time interval from the early stage of learning, confirming that rats are able to encode the odor-shock time interval after few training trials. We carried out reversible inactivation of the dorsal striatum before the acquisition session and before a shift in the learned time interval, and measured the effects of this treatment on the temporal pattern of the respiratory rate. In addition, using intracerebral microdialysis, we monitored extracellular dopamine level in the dorsal striatum throughout odor-shock conditioning and in response to a shift of the odor-shock time interval. Contrary to our initial predictions based on the existing literature on interval timing, we found evidence suggesting that transient inactivation of the dorsal striatum may favor a more precocious buildup of the respiratory frequency's temporal pattern during the odor-shock interval in a manner that reflected the duration of the interval. Our data further suggest that the conditioning and the learning of a novel time interval were associated with a decrease in dopamine level in the dorsal striatum, but not in the nucleus accumbens. These findings prompt a reassessment of the role of the striatum and striatal dopamine in interval timing, at least when considering Pavlovian aversive conditioning.

We rapidly classify odors as pleasant or aversive, but the brain circuits underlying how odors motivate approach and avoidance responses are largely unknown. New research describes a direct path from the olfactory bulb to ventral striatum driving odor-mediated reward.

CLINICAL TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov identifier: NCT03583541.

LAY ABSTRACT/UNASSIGNED:Smoking prevention, especially in pregnancy planning, may decrease autism spectrum disorder risk in offspring.

OBJECTIVE:This study aimed to describe informant discrepancies between mother and father reports of child vulnerability in youth with spina bifida (SB) and examine variables that were associated with these discrepancies. METHODS:Ninety-two parent dyads, with a child with SB (ages 8-15 years), were recruited as a part of a longitudinal study. Mothers and fathers completed questionnaires assessing parental perception of child vulnerability (PPCV), as well as medical and demographic information, behavioral aspects of the couple relationship, parenting stress, mental health of the parent, and child behavioral adjustment. The degree to which there was a parenting alliance was assessed with observational data. Mother-father discrepancies were calculated at the item level. RESULTS:Findings revealed that greater father mental health symptoms, parenting stress, and child behavior problems were associated with "father high and mother low" discrepancies in PPCV. There were also lower scores on observed parenting alliance when there were higher rates of "father high and mother low" discrepancies in PPCV. CONCLUSIONS:For families of youth with SB, discrepancies in PPCV where fathers perceive high vulnerability and mothers perceive low vulnerability may be a "red flag" for the presence of other parental and child adjustment difficulties. Findings are discussed in terms of the Attribution Bias Context Model and underscore the importance of including fathers in research on families who have children with chronic health conditions.

Individuals with Autism Spectrum Disorder (ASD) without intellectual disability (ID) represent approximately two-thirds of the ASD population. Here we focused on prospective research assessing different areas of functioning of children with ASD, without ID, until adolescence. Based on a pre-registered protocol (PROSPERO CRD42020189029), a systematic review of prospective studies (published between 01.01.2010 and 01.01.2020) was conducted. Twenty-eight studies met eligibility criteria. Findings indicated that ASD diagnosis and the Intelligence Quotient were highly stable over time across studies. Executive Functioning, Theory of Mind and Central Coherence processes tended to improve, although deficits remained when compared to typically developed controls. Adaptive difficulties and psychiatric comorbidity were relatively stable over time. We discuss potential implications of the findings for clinicians and educators and suggest recommendations for future research.

To synthesize current knowledge of the impact of pediatric neuropsychological evaluations on child functioning, we conducted a systematic review of the literature on parents' overall satisfaction with their child's evaluation and perceptions of how helpful the evaluation was for understanding their child's abilities and how useful the evaluation was for providing actionable information to elicit change. Parent satisfaction is important in this context because studies on healthcare consumption indicate a substantial relationship between patient satisfaction with services and implementation of recommendations and follow-up care. We followed PRISMA guidelines to conduct a systematic review of the literature on parent perception of pediatric neuropsychological evaluations for children aged 3-21 years. Using a set of predefined search terms, we identified 1,163 abstracts across PubMed, PsycINFO, Cochrane Library, and Web of Science electronic databases and included 12 studies in our qualitative synthesis. In general, parents reported high levels of satisfaction with their child's evaluation. Feedback from the evaluation was helpful for understanding their child's pattern of strengths and weaknesses and included useful information for obtaining support. Although parents did report improvement in their child's functional participation in home, school, and community settings, they tended to rate the usefulness of the evaluation for eliciting change lower than their overall satisfaction with the evaluation or how helpful the evaluation was for understanding their child's abilities. Additional effort appears to be needed for pediatric neuropsychological evaluations recommendations to result in durable, meaningful change in child functioning.

Neuroimaging studies have identified brain structural and functional alterations of type 2 diabetes mellitus (T2DM) patients; however, there is no systematic information on the relations between abnormalities in these two domains. We conducted a multimodal meta-analysis of voxel-based morphometry and regional resting-state functional MRI studies in T2DM, including fifteen structural datasets (693 patients and 684 controls) and sixteen functional datasets (378 patients and 358 controls). We found, in patients with T2DM compared to controls, conjoint decreased regional gray matter volume (GMV) and altered intrinsic activity mainly in the default mode network including bilateral superior temporal gyrus/Rolandic operculum, left middle and inferior temporal gyrus, and left supramarginal gyrus; decreased GMV alone in the limbic system; and functional abnormalities alone in the cerebellum, insula, and visual cortex. This meta-analysis identified complicated patterns of conjoint and dissociated brain alterations in T2DM patients, which may help provide new insight into the neuropathology of T2DM.

OBJECTIVES/OBJECTIVE:The COVID-19 related lockdowns and distancing measures have presented families with unprecedented challenges. A UK-wide cohort study tracking changes in families' mental health since early lockdown (Co-SPACE) found a significant rise in primary school-aged children's behaviour problems and associated family-related stress. Three-quarters of parents in Co-SPACE also reported wanting extra support. In SPARKLE, we will examine whether providing Co-SPACE families with a smartphone application delivering information and parenting support, Parent Positive, can reverse the negative effects of the pandemic on children and parents. The efficacy on child and parent outcomes and cost-effectiveness of Parent Positive will be examined. We will also test whether the effects are moderated by pre-existing levels of child conduct problems and usage of Parent Positive. Exploratory analyses will examine whether other baseline characteristics or lockdown circumstances moderate the effects of Parent Positive. TRIAL DESIGN/METHODS:SPARKLE is a two-arm superiority parallel group randomised controlled trial embedded in an existing large UK-wide self-selected community cohort - Co-SPACE. Those who consent to SPARKLE will be randomised 1:1 to either Parent Positive or Follow-up As Usual (FAU). PARTICIPANTS/METHODS:Co-SPACE (a UK-wide longitudinal cohort study) parents aged ≥18 who have children aged 4-10 years will be eligible for SPARKLE. INTERVENTION AND COMPARATOR/UNASSIGNED:Parent Positive: is a digital public health intervention that can be delivered rapidly at scale to support parents in managing their children's behaviour to reduce conduct problems and levels of family conflict, which were exacerbated during the first lockdown, and which may increase further in future months as families need to cope with continuous uncertainty and further disruption to their daily lives. Co-designed with parents and based on decades of parenting research, Parent Positive consists of three elements: (i) Parenting Boosters: where advice, delivered in the form of narrated animations, videos, graphics and text is provided to help parents with eight common parenting challenges; (ii) Parenting Exchange: a facilitated parent-to-parent communication and peer support platform and; (iii) Parent Resources: giving access to carefully selected high-quality, evidence-based online parenting resources. Follow-up as Usual: FAU was selected as a comparator because the public health nature meant that an active comparator was not appropriate due to the pragmatic, rapid implementation of the trial. Individuals randomised to FAU will receive no intervention for the first two months while the data for baseline (T1), T2 and T3 are collected. They will then be given full access to the app until 30th November 2021. MAIN OUTCOMES/RESULTS:Outcome measures will be collected remotely through Qualtrics according to the Co-SPACE schedule at baseline (T1), which will be the Co-SPACE survey data obtained immediately prior to randomisation, and then at one month (T2) and two months (T3) post-randomisation. Measures will be collected to assess group differences in child and parent outcomes, costs and service utilisation, and adverse events. Usage of Parent Positive will also be tracked. The primary outcome is parent-reported child conduct problems at one-month post-randomisation measured using the Strengths and Difficulties Questionnaire conduct problems subscale. RANDOMISATION/UNASSIGNED:Enrolled participants will be allocated to Parent Positive or FAU at the ratio of 1:1 by simple randomisation using the Randomizer function within the Qualtrics programme. Neither blocking nor stratification will be used. BLINDING (MASKING)/UNASSIGNED:It is not possible to blind parents enrolled in the study and Qualtrics will automatically inform parents of their group allocation. Blinded members of the research team and the senior statistician will not be given access to the Qualtrics system or the data in order to remain blinded until after the analysis is complete. We do not anticipate any serious harms associated with taking part in the intervention, therefore there will be no need to unblind any blinded staff during the study. The junior statistician will be unblinded throughout. NUMBERS TO BE RANDOMISED (SAMPLE SIZE)/UNASSIGNED:A total of 616 will be recruited into the trial with 308 consenting parents randomised to each treatment arm. TRIAL STATUS/UNASSIGNED:July 2021. TRIAL REGISTRATION/BACKGROUND:Clinicaltrial.gov: NCT04786080 . The trial was prospectively registered on 8 March 2021. FULL PROTOCOL/UNASSIGNED:The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).