Cognitive Fluctuations in a Rare Disease Population: Leveraging Cognitive and Speech Ecological Momentary Assessment in Individuals with Phenylketonuria.

Background: Phenylketonuria (PKU) is a rare, hereditary disease that causes disruption in phenylalanine (Phe) metabolism. Despite early intervention, individuals with PKU may have difficulty in several different cognitive domains, including verbal fluency, processing speed, and executive functioning.

Objective: The overarching goal of the Evaluating Fluctuations in Cognitive and Speech Characteristics in Phenylketonuria study (CSP Study) is to characterize the relationships among cognition, speech, mood, and blood-based biomarkers (Phe, Tyr) in individuals with early treated PKU.

Visual Working Memory in Adolescents with Autism Spectrum Disorder.

Previous research suggests that individuals with autism spectrum disorder (ASD) may experience working memory (WM) problems, but the nature of the underlying disruption remains unknown. A recent study (Bodner et al. 2019) found that young adults with ASD experienced intact WM capacity but disruptions in their ability to efficiently filter and allocate attention.

Initial results from the PHEFREE longitudinal natural history study: Cross-sectional observations in a cohort of individuals with phenylalanine hydroxylase (PAH) deficiency.

Over fifty years have passed since the last large scale longitudinal study of individuals with PAH deficiency in the U.S. Since then, there have been significant changes in terms of treatment recommendations as well as treatment options.

The relationship between working memory and anxiety in individuals with early treated phenylketonuria (PKU).

Objective: Although early diagnosis and treatment prevent the severe impairments associated with untreated phenylketonuria (PKU), individuals with early treated PKU (ETPKU) nonetheless experience significant neurocognitive and psychological sequelae, including difficulties in working memory (WM) and increased risk of anxiety. The primary objective of the present study was to examine the extent to which anxiety may moderate the relationship between ETPKU and WM performance.

Method: A sample of 40 adults with ETPKU and a demographically comparable sample of 40 healthy adults without PKU completed a comprehensive assessment of WM performance and anxiety symptomatology.

Exposure to written content eliciting weight stigmatization: Neural responses in appetitive and food reward regions.

Objective: Neural activity in food reward- and appetite-related regions was examined in response to high-calorie (HC), low-calorie, and non-food pictures after exposure to written weight stigma (WS) content. Relationships with eating behavior (by Three-Factor Eating Questionnaire [TFEQ]), blood glucose, and subjective appetite were also explored.

Methods: Adults with overweight and obesity were randomized to read either a WS (n = 20) or control (n = 20) article and subsequently underwent brain scans while they rated pleasantness of food pictures.

Total choline intake and working memory performance in adults with phenylketonuria.

Background: Despite early diagnosis and compliance with phenylalanine (Phe)-restricted diets, many individuals with phenylketonuria (PKU) still exhibit neurological changes and experience deficits in working memory and other executive functions. Suboptimal choline intake may contribute to these impairments, but this relationship has not been previously investigated in PKU. The objective of this study was to determine if choline intake is correlated with working memory performance, and if this relationship is modified by diagnosis and metabolic control.

Neuropsychological assessment of adults with phenylketonuria using the NIH toolbox.

Among researchers and clinicians, there is a call for the development and validation of new measures to better assess and characterize neurocognitive difficulties associated with early-treated phenylketonuria (ETPKU) and other metabolic disorders. The NIH Toolbox represents a relatively new computer-administered assessment tool and provides a sampling of performance across multiple cognitive domains, several of which (e.g.

Inhibitory Control in Male and Female Adolescents with Autism Spectrum Disorder (ASD).

The present study examined potential sex- and age-related differences in inhibitory control in adolescents with and without ASD. A computerized flanker visual filtering task and a go/no-go task were used to assess the ability to resist interference from visual distractors (RIVD) and prepotent response inhibition, respectively. Overall, the ASD and non-ASD groups performed comparably on both tasks and no sex-related differences or interactions (group-by-sex) were apparent.

The relationship between metabolic control and basal ganglia morphometry and function in individuals with early-treated phenylketonuria.

Abnormalities of the cortical white matter are the most prominent and widely-reported neurological findings in individuals with early-treated phenylketonuria (ETPKU). Much less is known regarding the effects of ETPKU on gray matter structures in the brain such as the basal ganglia. Previous findings on basal ganglia in ETPKU have been mixed.

A comprehensive assessment of neurocognitive and psychological functioning in adults with early-treated phenylketonuria.

Objective: Relative to youth with early-treated phenylketonuria (ETPKU), much less is known regarding the cognitive profile of adults with ETPKU. The present study aimed to address this gap by providing a comprehensive assessment of neuropsychological functioning among adults with ETPKU.

Method: A sample of 40 adults with ETPKU (ages 18 - 36) and a demographically matched group of 32 healthy individuals without PKU participated.

Management of early treated adolescents and young adults with phenylketonuria: Development of international consensus recommendations using a modified Delphi approach.

Background: Early treated patients with phenylketonuria (PKU) often become lost to follow-up from adolescence onwards due to the historical focus of PKU care on the pediatric population and lack of programs facilitating the transition to adulthood. As a result, evidence on the management of adolescents and young adults with PKU is limited.

Methods: Two meetings were held with a multidisciplinary international panel of 25 experts in PKU and comorbidities frequently experienced by patients with PKU.

Neural correlates of working memory and its association with metabolic parameters in early-treated adults with phenylketonuria.

Background: Phenylketonuria (PKU) is an inborn error of metabolism affecting the conversion of phenylalanine (Phe) into tyrosine. Previous research has found cognitive and functional brain alterations in individuals with PKU even if treated early. However, little is known about working memory processing and its association with task performance and metabolic parameters.

Motor control and learning in individuals with early-treated phenylketonuria.

Objective: Although past studies have documented motor control impairments in individuals with early-treated phenylketonuria (ETPKU), much less is known regarding motor learning in ETPKU. The goal of the present study was to advance our understanding on this front.

Method: We isolated and examined motor kinematics associated with the learning of a rapid aimed limb movement in a sample of 40 individuals (13-34 years of age) with ETPKU and a matched comparison group of 40 individuals without phenylketonuria (PKU).

Brief Report: A Preliminary Study of the Relationship between Repetitive Behaviors and Concurrent Executive Function Demands in Children with Autism Spectrum Disorder.

The present study evaluated the hypothesis that the strength of the relationship between executive function (EF) and repetitive behaviors and restricted interests (RBRI) symptomatology is moderated by the degree to which concurrent demands are placed on multiple aspects of EF. An eye movement task was used to evaluate inhibition and task switching ability (both together and in isolation) in a sample of 22 children with autism spectrum disorder (ASD). The Repetitive Behavior Scale-Revised (RBS-R) was used to assess the severity of RBRI symptoms.

Inter- and intra-tract analysis of white matter abnormalities in individuals with early-treated phenylketonuria (PKU).

Even with early and continuous treatment, individuals with phenylketonuria (PKU) may exhibit abnormalities of cortical white matter (WM). The present study utilizes a new analysis approach called Automated Fiber-Tract Quantification (AFQ) to advance our understanding of the tract-specific patterns of change in WM abnormalities in individuals with early-treated PKU (ETPKU). Diffusion Tensor Imaging (DTI) data from a sample of 22 individuals with ETPKU and a demographically-matched sample of 21 healthy individuals without PKU was analyzed using AFQ.

A porcine model of phenylketonuria generated by CRISPR/Cas9 genome editing.

Phenylalanine hydroxylase-deficient (PAH-deficient) phenylketonuria (PKU) results in systemic hyperphenylalaninemia, leading to neurotoxicity with severe developmental disabilities. Dietary phenylalanine (Phe) restriction prevents the most deleterious effects of hyperphenylalaninemia, but adherence to diet is poor in adult and adolescent patients, resulting in characteristic neurobehavioral phenotypes. Thus, an urgent need exists for new treatments.

The effects of early-treated phenylketonuria on volumetric measures of the cerebellum.

Past murine studies of phenylketonuria (PKU) have documented significant effects on cerebellum at both the gross and cellular levels. The profile of neurocognitive and motor difficulties associated with early-treated PKU (ETPKU) is also consistent with potential cerebellar involvement. Previous neuroanatomical studies of cerebellum in patients with PKU, however, have yielded mixed results.

Executive function in phenylketonuria (PKU): Insights from the Behavior Rating Inventory of Executive Function (BRIEF) and a large sample of individuals with PKU.

Objective: Previous research has documented executive function (EF) impairments in individuals with early treated phenylketonuria (ETPKU). It remains unclear, however, whether some aspects of EF may be more affected than others. A number of factors, including small sample sizes and variability in EF tasks, have likely contributed to past mixed findings.

Effects of stress on functional connectivity during verbal processing.

Effects of stress on functional connectivity (FC) in specific language processing regions of the brain during verbal fluency tasks were explored. Roles of gender and serotonin transporter gene polymorphisms (5-HTTLPR), associated with stress susceptibility, were also examined to understand their effect. Forty-five healthy volunteers (Mean age: 19.

Effects of stress on functional connectivity during problem solving.

Aim: Our purpose was to examine how stress affects functional connectivity (FC) in language processing regions of the brain during a verbal problem solving task associated with creativity. We additionally explored how gender and the presence of the stress-susceptible short allele of the serotonin transporter gene polymorphism influenced this effect.

Methods: Forty-five healthy participants (Mean age: 19.

Contributions of filtering and attentional allocation to working memory performance in individuals with autism spectrum disorder.

Past findings on working memory (WM) ability in individuals with autism spectrum disorder (ASD) are mixed. The present objective was to assess not only the integrity of WM capacity, but also the potential contribution of filtering ability and attentional selection to WM performance, in individuals with ASD. A sample of 24 participants with ASD ( = 19.

-adrenergic antagonism alters functional connectivity during associative processing in a preliminary study of individuals with and without autism.

adrenergic antagonism (e.g. propranolol) has been associated with cognitive/behavioral benefits following stress-induced impairments and for some cognitive/behavioral domains in individuals with autism spectrum disorder.

Brief Report: Flanker Visual Filtering Ability in Older Adolescents with Autism Spectrum Disorder.

Recent research has documented impaired ability to resist interference from visual distractors in individuals with autism spectrum disorder (ASD) and suggests that this phenomenon may be more pronounced in young versus older children (Christ et al., Neuropsychology 25(6):690-701, 2011). The present study extends previous findings by examining visual filtering inhibitory ability within an older adolescent population.