Functional connectivity of the vigilant-attention network in children and adolescents with attention-deficit/hyperactivity disorder.

The ability to maintain attention to simple tasks (i.e., vigilant attention, VA) is often impaired in attention-deficit/hyperactivity disorder (ADHD), but the underlying pathophysiological mechanisms at the brain network level are not clear yet. We therefore investigated ADHD-related differences in resting-state functional connectivity within a meta-analytically defined brain network of 14 distinct regions subserving VA (comprising 91 connections in total), as well as the association of connectivity with markers of behavioural dysfunction in 17 children (age range: 9-14 years) with a diagnosis of ADHD and 21 age-matched neurotypical controls. Our analyses revealed selective, rather than global, differences in the intrinsic coupling between nodes of the VA-related brain network in children with ADHD, relative to controls. In particular, ADHD patients showed substantially diminished intrinsic coupling for 7 connections and increased coupling for 4 connections, with many differences involving connectivity with the anterior insula. Moreover, connectivity strength of several aberrant connections was found to be associated with core aspects of ADHD symptomatology, such as poor attention, difficulties with social functioning, and impaired cognitive control, attesting to the behavioural relevance of specific connectivity differences observed in the resting state.

Effects of Dietary Acute Tryptophan Depletion (ATD) on NPY Serum Levels in Healthy Adult Humans Whilst Controlling for Methionine Supply-A Pilot Study.

Central nervous serotonin (5-HT) can influence behaviour and neuropsychiatric disorders. Evidence from animal models suggest that lowered levels of neuropeptide Y (NPY) may have similar effects, although it is currently unknown whether decreased central nervous 5-HT impact NPY concentrations. Given that the production of NPY is dependent on the essential amino acid methionine (MET), it is imperative to account for the presence of MET in such investigations. Hence, this study sought to examine the effects of acute tryptophan depletion (ATD; a dietary procedure that temporarily lowers central nervous 5-HT synthesis) on serum concentrations of NPY, whilst using the potential renal acid load indicator (PRAL) to control for levels of MET. In a double-blind repeated measures design, 24 adult humans randomly received an AA-load lacking in TRP (ATD) on one occasion, and a balanced control mixture with TRP (BAL) on a second occasion, both with a PRAL of nearly 47.3 mEq of MET. Blood samples were obtained at 90, 180, and 240 min after each of the AA challenges. ATD, and therefore, diminished substrate availability for brain 5-HT synthesis did not lead to significant changes in serum NPY concentrations over time, compared to BAL, under an acute acidotic stimulus.

Effects of a structured 20-session slow-cortical-potential-based neurofeedback program on attentional performance in children and adolescents with attention-deficit hyperactivity disorder: retrospective analysis of an open-label pilot-approach and 6-month follow-up.

OBJECTIVE: The aim of this approach was to conduct a structured electroencephalography-based neurofeedback training program for children and adolescents with attention-deficit hyperactivity disorder (ADHD) using slow cortical potentials with an intensive first (almost daily sessions) and second phase of training (two sessions per week) and to assess aspects of attentional performance. PATIENTS AND METHODS: A total of 24 young patients with ADHD participated in the 20-session training program. During phase I of training (2 weeks, 10 sessions), participants were trained on weekdays. During phase II, neurofeedback training occurred twice per week (5 weeks). The patients' inattention problems were measured at three assessment time points before (pre, T0) and after (post, T1) the training and at a 6-month follow-up (T2); the assessments included neuropsychological tests (Alertness and Divided Attention subtests of the Test for Attentional Performance; Sustained Attention Dots and Shifting Attentional Set subtests of the Amsterdam Neuropsychological Test) and questionnaire data (inattention subscales of the so-called Fremdbeurteilungsbogen für Hyperkinetische Störungen and Child Behavior Checklist/4-18 [CBCL/4-18]). All data were analyzed retrospectively. RESULTS: The mean auditive reaction time in a Divided Attention task decreased significantly from T0 to T1 (medium effect), which was persistent over time and also found for a T0-T2 comparison (larger effects). In the Sustained Attention Dots task, the mean reaction time was reduced from T0-T1 and T1-T2 (small effects), whereas in the Shifting Attentional Set task, patients were able to increase the number of trials from T1-T2 and significantly diminished the number of errors (T1-T2 & T0-T2, large effects). CONCLUSION: First positive but very small effects and preliminary results regarding different parameters of attentional performance were detected in young individuals with ADHD. The limitations of the obtained preliminary data are the rather small sample size, the lack of a control group/a placebo condition and the open-label approach because of the clinical setting and retrospective analysis. The value of the current approach lies in providing pilot data for future studies involving larger samples.

Studying the effects of dietary body weight-adjusted acute tryptophan depletion on punishment-related behavioral inhibition.

BACKGROUND: Alterations in serotonergic (5-HT) neurotransmission are thought to play a decisive role in affective disorders and impulse control. OBJECTIVE: This study aims to reproduce and extend previous findings on the effects of acute tryptophan depletion (ATD) and subsequently diminished central 5-HT synthesis in a reinforced categorization task using a refined body weight-adjusted depletion protocol. DESIGN: Twenty-four young healthy adults (12 females, mean age [SD]=25.3 [2.1] years) were subjected to a double-blind within-subject crossover design. Each subject was administered both an ATD challenge and a balanced amino acid load (BAL) in two separate sessions in randomized order. Punishment-related behavioral inhibition was assessed using a forced choice go/no-go task that incorporated a variable payoff schedule. RESULTS: Administration of ATD resulted in significant reductions in TRP measured in peripheral blood samples, indicating reductions of TRP influx across the blood-brain barrier and related brain 5-HT synthesis. Overall accuracy and response time performance were improved after ATD administration. The ability to adjust behavioral responses to aversive outcome magnitudes and behavioral adjustments following error contingent punishment remained intact after decreased brain 5-HT synthesis. A previously observed dissociation effect of ATD on punishment-induced inhibition was not observed. CONCLUSIONS: Our results suggest that neurodietary challenges with ATD Moja-De have no detrimental effects on task performance and punishment-related inhibition in healthy adults.

Effects of dietary tryptophan and phenylalanine-tyrosine depletion on phasic alertness in healthy adults - A pilot study.

BACKGROUND: The synthesis of the neurotransmitters serotonin (5-HT) and dopamine (DA) in the brain can be directly altered by dietary manipulation of their relevant precursor amino acids (AA). There is evidence that altered serotonergic and dopaminergic neurotransmission are both associated with impaired attentional control. Specifically, phasic alertness is one specific aspect of attention that has been linked to changes in 5-HT and DA availability in different neurocircuitries related to attentional processes. The present study investigated the impact of short-term reductions in central nervous system 5-HT and DA synthesis, which was achieved by dietary depletion of the relevant precursor AA, on phasic alertness in healthy adult volunteers; body weight-adapted dietary tryptophan and phenylalanine-tyrosine depletion (PTD) techniques were used. METHODS: The study employed a double-blind between-subject design. Fifty healthy male and female subjects were allocated to three groups in a randomized and counterbalanced manner and received three different dietary challenge conditions: acute tryptophan depletion (ATD, for the depletion of 5-HT; N=16), PTD (for the depletion of DA; N=17), and a balanced AA load (BAL; N=17), which served as a control condition. Three hours after challenge intake (ATD/PTD/BAL), phasic alertness was assessed using a standardized test battery for attentional performance (TAP). Blood samples for AA level analyses were obtained at baseline and 360 min after the challenge intake. RESULTS: Overall, there were no significant differences in phasic alertness for the different challenge conditions. Regarding PTD administration, a positive correlation between the reaction times and the DA-related depletion magnitude was detected via the lower plasma tyrosine levels and the slow reaction times of the first run of the task. In contrast, higher tryptophan concentrations were associated with slower reaction times in the fourth run of the task in the same challenge group. CONCLUSION: The present study is the first to demonstrate preliminary data that support an association between decreased central nervous system DA synthesis, which was achieved by dietary depletion strategies, and slower reaction times in specific runs of a task designed to assess phasic alertness in healthy adult volunteers; these findings are consistent with previous evidence that links phasic alertness with dopaminergic neurotransmission. A lack of significant differences between the three groups could be due to compensatory mechanisms and the limited sample size, as well as the dietary challenge procedures administered to healthy participants and the strict exclusion criteria used. The potential underlying neurochemical processes related to phasic alertness should be the subject of further investigations.

Reduced Responsiveness to Social Provocation in Autism Spectrum Disorder.

Deficits in emotion processing and social interaction are prominent symptoms of autism spectrum disorder (ASD). ASD has also been associated with aggressive tendencies towards self and others. The prevalence of aggressive behavior in this disorder, its etiology and its impact on social life are still unclear. This study investigated behavioral and physiological effects of social provocation in patients with ASD and healthy controls. We used a modified Taylor Aggression Paradigm in 24 high-functioning patients with ASD and 24 healthy controls. Participants were instructed to play against a fictitious human opponent. Money withdrawals toward the participant represented provocation and money deduction by the participant denoted aggressive behavior. Throughout the measurement, electrodermal activity (EDA) was recorded. Healthy controls showed higher aggressive responses to high provocation compared to low provocation, which demonstrated the effectiveness of the used procedure in eliciting aggression. Patients' responses were not influenced by the level of social provocation, although in both groups aggression was higher after lost compared to won trials. Physiologically, controls showed fewer but higher EDA amplitudes when responding aggressively, whereas patients displayed the opposite pattern of more but lower EDA amplitudes. The modified Taylor Aggression Paradigm successfully elicited aggression and revealed different behavioral and neurophysiological responses in patients and healthy controls. Patients' aggressive behavior as well as their physiological responses were less modulated by level of provocation compared to controls. Therapeutic attempts for patients might concentrate on improving empathic abilities and the understanding of social situations, including provocation and aggressive behavior.