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Common pharmacological treatments for attention-deficit hyperactivity disorder (ADHD) are central nervous system stimulants acting as norepinephrine-dopamine reuptake inhibitors. The noradrenergic and dopaminergic systems have been shown to impact performance on tasks assessing creativity. Some previous studies suggest higher performance on creativity tasks in ADHD. Stimulant medication has been shown to differentially impact creativity in those without ADHD. However, the full range of effects of stimulant medication on creativity in those with ADHD is not known. This study examined the effects of stimulants on convergent and divergent tasks associated with creativity in adults with ADHD. Seventeen adults diagnosed with ADHD who were prescribed stimulant medication attended two counterbalanced sessions: one after taking their prescribed stimulant dose and one after the dose was withheld. Participants completed convergent problem-solving (anagrams, Compound Remote Associates) and divergent generative (letter/semantic fluency, Torrance Test for Creative Thinking (TTCT)-Verbal) tasks. There was a significant increase in words generated on the semantic fluency task for the stimulant session. Additionally, significant increases were found in the stimulant session for originality, flexibility, and fluency scores on the TTCT. Stimulant medication did not have an effect on any of the problem-solving tasks. Stimulant medication enhanced verbal fluency in adults with ADHD but had no effect on convergent abilities. Furthermore, stimulants enhanced fluency, flexibility, and originality scores on the TTCT. Therefore, stimulants appear to have positive effects on divergent task performance in adults with ADHD, but not convergent tasks. This finding warrants further studies into the specific roles of norepinephrine and dopamine in this effect.

The parent-report Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2) is a widely used pediatric neuropsychological measure. Unfortunately, despite meaningful changes from its predecessor, few studies have examined its internal factor structure (now with Behavioral Regulation [BRI], Emotion Regulation [ERI], and Cognitive Regulation [CRI]), and no available literature has investigated higher order models for the BRIEF-2. This study sought to address this shortcoming in the literature by investigating and reporting on the dimensionality of the parent-report BRIEF-2 in a clinical sample. Two hundred and two (202) pediatric neuropsychology examinees (

Many youth with autism spectrum disorder (ASD) experience co-occurring conditions, such as gastrointestinal (GI) problems and internalizing symptoms. However, the relationship among these co-occurring problems is not well-understood. We analyzed parent reports of GI problems and internalizing symptoms of 621 youth with ASD using path models in a structural equation modeling framework. The best-fitting model was a bidirectional model wherein internalizing symptoms, including withdrawn and anxious behavior, were correlated with GI problems, including constipation, diarrhea, nausea, and stomach pain. This study provides a better understanding of the relationship among co-occurring conditions in youth with ASD and should encourage clinicians to consider treatment of underlying internalizing symptoms or GI problems when providing services for individuals with ASD.

Evaluating general cognitive ability (i.e., intelligence) is common in neuropsychological practice, and identifying abbreviated assessments of intelligence is often advantageous. Despite the Wechsler Intelligence Scale for Children, Fifth Edition's (WISC-V) widespread contemporary use, limited research has identified clinically useful short form (SF) full scale IQ (FSIQ) estimations in clinical samples. This study sought to address this gap in the literature. Two hundred sixty-eight pediatric participants (M age = 9.79; 69% male; 88% Caucasian/White) who underwent psychological/neuropsychological evaluation were included. Mean scores for WISC-V scores fell in the low average-to-average ranges, consistent with the clinical nature of this sample (e.g., M FSIQ = 85.3). Ten unique SF combinations with five (pentad) and four (tetrad) subtests, each intentionally selected to represent a breadth of domains subsumed by WISC-V FSIQ, were described by summing subtest age-corrected scaled scores. Regression-based and prorated FSIQ estimates were calculated, and mean differences suggested some prorated estimates should be arithmetically adjusted. Both regression-based and prorated/adjusted methods provided FSIQ estimates that were accurate within five Standard Score points of true FSIQ for approximately 81-92% (pentad) and 65-76% (tetrads) of participants. Prorated/adjusted estimates appeared to provide somewhat better accuracy than regression-based estimates. Relationships between SFs and true FSIQ did not appear to be moderated by participant age, gender, nor how many WISC-V subtests were administered to participants within this archival sample (i.e., 7 vs. 10). Implications of these findings, including benefits, detriments, and other considerations of each SF combination, in addition to limitations of this study, are discussed in detail.

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: 19.6 ± 1.6 years; 28 females) participated. Functional magnetic resonance imaging was carried out while participants performed letter and category fluency tasks. These tasks were interposed with the Montreal Imaging Stress Test to induce stress or a no-stress control task. Buccal swabs collected were used to genotype for the presence of polymorphisms on the SLC6A4 gene known to contribute to atypical stress responses. Significant variations in strength of FC were noted between several ROIs, including left inferior frontal gyrus and left middle temporal gyrus. Overall, males showed regional increases in FC strength over long and short distances during task under stress. Additionally, variability in effects of stress on task performance was associated with effects of stress on FC. Results suggest that long distance FC may be strengthened to compensate for additional cognitive load of the stressor but that specific short distance functional connections may be strengthened in a gender specific manner. Additionally, FC may serve as a marker for effects of stress on performance. This is the first study exploring stress effects on language tasks with imaging markers. Future studies will need to explore stress susceptible populations and establish the role of FC as a marker, with implications for targeted therapeutic interventions.

Beta-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. In this preliminary investigation, we examined whether the benefits of propranolol are associated with functional properties in the brain. Adolescents/adults (mean age = 22.54 years) with (n = 13) and without autism spectrum disorder (n = 13) attended three sessions in which propranolol, nadolol ( beta-adrenergic antagonist that does not cross the blood–brain barrier), or placebo was administered before a semantic fluency task during functional magnetic resonance imaging. Autonomic nervous system measures and functional connectivity between language/associative processing regions and within the fronto-parietal control, dorsal attention, and default mode networks were examined. Propranolol was associated with improved semantic fluency performance, which was correlated with the baseline resting heart rate. Propranolol also altered network efficiency of regions associated with semantic processing and in an exploratory analysis reduced functional differences in the fronto-parietal control network in individuals with autism spectrum disorder. Thus, the cognitive benefits from beta-adrenergic antagonism may be generally associated with improved information processing in the brain in domain-specific networks, but individuals with autism spectrum disorder may also benefit from additional improvements in domain-general networks. The benefits from propranolol may also be able to be predicted from baseline autonomic nervous system measures, which warrants further investigation.

Autism spectrum disorder (ASD) is often accompanied by gastrointestinal disturbances, which also may impact behavior. Alterations in autonomic nervous system functioning are also frequently observed in ASD. The relationship between these findings in ASD is not known. We examined the relationship between gastrointestinal symptomatology, examining upper and lower gastrointestinal tract symptomatology separately, and autonomic nervous system functioning, as assessed by heart rate variability and skin conductance level, in a sample of 120 individuals with ASD. Relationships with co-occurring medical and psychiatric symptoms were also examined. While the number of participants with significant upper gastrointestinal tract problems was small in this sample, 42.5% of participants met criteria for functional constipation, a disorder of the lower gastrointestinal tract. Heart rate variability, a measure of parasympathetic modulation of cardiac activity, was found to be positively associated with lower gastrointestinal tract symptomatology at baseline. This relationship was particularly strong for participants with co-occurring diagnoses of anxiety disorder and for those with a history of regressive ASD or loss of previously acquired skills. These findings suggest that autonomic function and gastrointestinal problems are intertwined in children with ASD; although it is not possible to assess causality in this data set. Future work should examine the impact of treatment of gastrointestinal problems on autonomic function and anxiety, as well as the impact of anxiety treatment on gastrointestinal problems. Clinicians should be aware that gastrointestinal problems, anxiety, and autonomic dysfunction may cluster in children with ASD and should be addressed in a multidisciplinary treatment plan. Autism Res 2017, 10: 276-288. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

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: 19.6 ​± ​1.6 years; 28 females) were recruited to be a part of this study and genotyped to determine the presence or absence of at least one copy of the short (S) allele of the serotonin transporter gene, which is associated with greater susceptibility to stress. The participants underwent functional magnetic resonance imaging in two separate sessions (stress and no stress control). One session utilized a modified version of the Montreal Imaging Stress Test (MIST) to induce stress while the other session consisted of a no stress control task. The MIST and control tasks were interleaved with task blocks during which the participants performed the compound remote associates task, a convergent task that engages divergent thinking, which is a critical component of creativity. We examined the relationship between stress effects on performance and effects on connectivity of language processing regions activated during this task. Results There was no main effect of stress on functional connectivity for individual ROI pairs. However, in the examination of whether stress effects on performance related to effects on connectivity, changes in middle temporal gyrus connectivity with stress correlated positively with changes in solution latency for individuals with the S allele, but anti-correlated for those with only the L allele. A trend towards a gene ​× ​stress interaction on solution latency was also observed. Discussion Results from the study suggest that genetic susceptibility to stress, such as the presence of the S allele, affects neural correlates of performance on tasks related to verbal problem solving, as indicated by connectivity of the middle temporal gyrus. Future work will need to determine whether connectivity of the middle temporal gyrus serves as a marker for the effect of stress susceptibility on cognition, extending into stress susceptible patient populations.

Elevated whole blood serotonin levels are observed in more than 25 % of children with autism spectrum disorder (ASD). Co-occurring gastrointestinal (GI) symptoms are also common in ASD but have not previously been examined in relationship with hyperserotonemia, despite the synthesis of serotonin in the gut. In 82 children and adolescents with ASD, we observed a correlation between a quantitative measure of lower GI symptoms and whole blood serotonin levels. No significant association was seen between functional constipation diagnosis and serotonin levels in the hyperserotonemia range, suggesting that this correlation is not driven by a single subgroup. More specific assessment of gut function, including the microbiome, will be necessary to evaluate the contribution of gut physiology to serotonin levels in ASD.

The most frequently used measures of executive functioning are either sensitive to left frontal lobe functioning or bilateral frontal functioning. Relatively little is known about right frontal lobe contributions to executive functioning given the paucity of measures sensitive to right frontal functioning. The present investigation reports the development and initial validation of a new measure designed to be sensitive to right frontal lobe functioning, the Figure Trail Making Test (FTMT). The FTMT, the classic Trial Making Test, and the Ruff Figural Fluency Test (RFFT) were administered to 42 right-handed men. The results indicated a significant relationship between the FTMT and both the TMT and the RFFT. Performance on the FTMT was also related to high beta EEG over the right frontal lobe. Thus, the FTMT appears to be an equivalent measure of executive functioning that may be sensitive to right frontal lobe functioning. Applications for use in frontotemporal dementia, Alzheimer’s disease, and other patient populations are discussed.

Based upon checklist data from the Autism Speaks Autism Treatment Network, we hypothesized that functional constipation (FC) would be associated with rigid-compulsive behavior in children with autism spectrum disorder (ASD). We used the Questionnaire on Pediatric Gastrointestinal Symptoms - Rome III to assess FC symptoms in 108 children with ASD. As hypothesized, FC was associated with parent ratings on the Repetitive Behavior Scales – Revised (RBS-R) Compulsive, Ritualistic, and Sameness subscales in the overall population. Of note, FC was less common in children who were not taking medications that target behavior or treat FC. In the medication-free children, rigid-compulsive behavior was not significantly associated with FC. More research is needed to understand the mechanisms underlying these associations.

Autism spectrum disorder (ASD) is characterized by impairments in social communication as well as restricted, repetitive behaviors. Evidence suggests that some individuals with ASD have cognitive impairments related to weak central coherence and hyperrestricted processing. Reducing noradrenergic activity may improve aspects of network processing and thus improve cognitive abilities, such as verbal problem solving, in individuals with ASD. The present pilot study explores the effects of acute administration of the beta-adrenergic antagonist propranolol on verbal problem solving in adults and adolescents with ASD. In a within-subject crossover-design, 20 participants with ASD received a single dose of propranolol or placebo on one of two sessions in a double-blinded, counterbalanced manner. Verbal problem solving was assessed via an anagram task. Baseline measurements of autonomic nervous system functioning were obtained, and anxiety was assessed at baseline and following drug administration. Participants solved the anagrams more quickly in the propranolol condition, as compared to the placebo condition, suggesting a potential cognitive benefit of this agent. Additionally, we observed a negative linear relationship between response to propranolol on the anagram task and two measures of baseline autonomic activity, as well as a positive linear relationship between drug response and baseline anxiety. These relationships propose potential markers for treatment response, as propranolol influences both autonomic functioning and anxiety. Further investigation is needed to expand on the present single-dose psychopharmacological challenge and explore the observed effects of propranolol in a serial-dose setting.

The beta-adrenergic antagonist propranolol benefits some social and communication domains affected in autism spectrum disorder (ASD), and these benefits appear to be associated with increased functional connectivity (FC) in the brain during task performance. FC is implicated in ASD, with the majority of studies suggesting long distance hypo-connectivity combined with regionally specific local hyper-connectivity. The objective in the current investigation was to examine the effect of propranolol on FC at rest and determine whether ASD-specific effects exist. Participants with and without ASD attended three sessions in which propranolol, nadolol (a beta-adrenergic antagonist that does not cross the blood-brain barrier), or placebo were administered. Resting-state fMRI data were acquired, and graph theory techniques were utilized to assess additional aspects of FC. Compared to placebo, propranolol administration was associated with decreased FC in the dorsal medial prefrontal cortex subnetwork of the default mode network and increased FC in the medial temporal lobe subnetwork, regardless of diagnosis. These effects were not seen with nadolol suggesting that the alterations in FC following propranolol administration were not exclusively due to peripheral cardiovascular effects. Thus, beta-adrenergic antagonism can up- or down- regulate FC, depending on the network, and alter coordinated functional activation in the brain. These changes in information processing, as demonstrated by FC, may mediate some of the clinical and behavioral effects of beta-adrenergic antagonism previously reported in patients with ASD.

The dopaminergic system is implicated in depressive disorders and research has also shown that dopamine constricts lexical/semantic networks by reducing spreading activation. Hence, depression, which is linked to reductions of dopamine, may be associated with increased spreading activation. However, research has generally found no effects of depression on spreading activation, using semantic priming paradigms. We used a different paradigm to investigate the relationship between depression and spreading activation, one based on word frequencies. Our sample included 97 undergraduates who completed the BDI-II and the Controlled Oral Word Association test as well as the Animal Naming test. The results indicated that the group scoring within the depressed ranged evidenced greater spreading activation as compared to those who scored within the normal range on the BDI-II. The implications of these results as they relate to creativity in depression is discussed.

Objective Interhemispheric and intrahemispheric balance models may be integrated to gain an increased understanding of how cerebral systems are involved in the regulation of heart rate and blood pressure. We sought to examine the relationship between left and right frontal and posterior activity and resting heart rate and blood pressure. Based on this integration, we predicted that lateral (left minus right hemisphere) and longitudinal (frontal minus posterior regions) asymmetry in cerebral activity would be related to resting measures of heart rate and blood pressure. Methods Resting heart rate, blood pressure, and EEG (low and high beta) were obtained in a sample of 42 men. Physiological measures were obtained during an eyes closed resting period. Results Our results provided partial support, finding significant correlations between resting heart rate and not only frontal lobe lateral asymmetry but also frontal–parietal asymmetry. Conclusions These results provide support for the relative differential associations of the left and right frontal and parietal lobes and cardiovascular activity. Significance Previous research has not examined cerebral control of cardiovascular functioning from a functional cerebral systems perspective. The results are discussed as they relate to research on aggression and hostility.

Autism spectrum disorder (ASD) is often accompanied by gastrointestinal disturbances, which also may impact behavior. Alterations in autonomic nervous system functioning are also frequently observed in ASD. The relationship between these findings in ASD is not known. We examined the relationship between gastrointestinal symptomatology, examining upper and lower gastrointestinal tract symptomatology separately, and autonomic nervous system functioning, as assessed by heart rate variability and skin conductance level, in a sample of 120 individuals with ASD. Relationships with co-occurring medical and psychiatric symptoms were also examined. While the number of participants with significant upper gastrointestinal tract problems was small in this sample, 42.5% of participants met criteria for functional constipation, a disorder of the lower gastrointestinal tract. Heart rate variability, a measure of parasympathetic modulation of cardiac activity, was found to be positively associated with lower gastrointestinal tract symptomatology at baseline. This relationship was particularly strong for participants with co-occurring diagnoses of anxiety disorder and for those with a history of regressive ASD or loss of previously acquired skills. These findings suggest that autonomic function and gastrointestinal problems are intertwined in children with ASD; although it is not possible to assess causality in this data set. Future work should examine the impact of treatment of gastrointestinal problems on autonomic function and anxiety, as well as the impact of anxiety treatment on gastrointestinal problems. Clinicians should be aware that gastrointestinal problems, anxiety, and autonomic dysfunction may cluster in children with ASD and should be addressed in a multidisciplinary treatment plan. Autism Res 2017, 10: 276-288. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Pharmacological intervention for autism spectrum disorder (ASD) is an important addition to treatment, yet currently available agents target co-morbid psychiatric concerns, such as aggression and irritability. Propranolol, a beta-adrenergic antagonist with anxiolytic effects, has been shown to improve verbal fluency and working memory in adults and adolescents with ASD in single-dose challenges. The present pilot study explores the acute effects of propranolol on a measure of conversational reciprocity in this population. We also examined whether autonomic activity and anxiety moderate or mediate response to the drug, given relationships between these variables and ASD, as well as the drug’s effects. In a within-subject crossover design, 20 individuals with ASD received a single dose of propranolol or placebo during two sessions in a double-blinded, counterbalanced manner. After drug administration, participants performed a conversational reciprocity task by engaging in a short conversation with the researcher. Measurements of autonomic activity and anxiety were obtained before and after drug administration. Propranolol significantly improved performance on the conversational reciprocity task total [d = 0.40] and nonverbal communication domain scores when compared to the placebo condition. However, neither autonomic activity nor anxiety was significantly associated with drug response. Acute propranolol administration improved conversational reciprocity in ASD. Further exploration of these preliminary findings, as well as other potential treatment response predictors, with serial doses is warranted.

Research has supported hemispheric specialisation in the regulation of cardiovascular functioning, with the left hemisphere being associated with parasympathetic functioning and the right hemisphere with sympathetic functioning. We sought to investigate this relationship further using vibrotactile stimulation applied to the palms. Our prediction was that vibrotactile stimulation applied to the left hand would result in increased heart rate and blood pressure, and that stimulation applied to the right hand would result in decreased heart rate and blood pressure. The results indicated significant differences in heart rate change scores in the predicted direction. No differences were noted for systolic or diastolic blood pressure. Hence the findings provide partial support for the lateralisation of autonomic functions.