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Effects of L-theanine-caffeine combination on sustained attention and inhibitory control among children with ADHD: a proof-of-concept neuroimaging RCT.

ABSTRACT: We examined the acute effects of L-theanine, caffeine and their combination on sustained attention, inhibitory control and overall cognition in boys with attention deficit hyperactivity disorder (ADHD). L-Theanine (2.5 mg/kg), caffeine (2.0 mg/kg), their combination and a placebo were administered in a randomized four-way repeated-measures crossover with washout, to five boys (8-15 years) with ADHD. Functional magnetic resonance imaging (fMRI) was performed during a Go/NoGo task and a Stop-signal task?~?1 h post-dose. NIH Cognition Toolbox was administered?~?2 h post-dose. Treatment vs. placebo effects were examined in multi-level mixed-effects models. L-Theanine improved total cognition composite in NIH Cognition Toolbox (p?=?0.040) vs. placebo. Caffeine worsened and L-theanine had a trend of worsening inhibitory control (i.e. increased Stop-signal reaction time; p?=?0.031 and p?=?0.053 respectively). L-Theanine-caffeine combination improved total cognition composite (p?=?0.041), d-prime in the Go/NoGo task (p?=?0.033) and showed a trend of improvement of inhibitory control (p?=?0.080). L-Theanine-caffeine combination was associated with decreased task-related reactivity of a brain network associated with mind wandering (i.e. default mode network). L-Theanine-caffeine combination may be a potential therapeutic option for ADHD-associated impairments in sustained attention, inhibitory control and overall cognitive performance.

SUBMITTER: Kahathuduwa CN

PROVIDER: S-EPMC7403383 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Effects of L-theanine-caffeine combination on sustained attention and inhibitory control among children with ADHD: a proof-of-concept neuroimaging RCT.

Kahathuduwa Chanaka N CN Wakefield Sarah S West Blake D BD Blume Jessica J Dassanayake Tharaka L TL Weerasinghe Vajira S VS Mastergeorge Ann A

Scientific reports 20200804 1

We examined the acute effects of L-theanine, caffeine and their combination on sustained attention, inhibitory control and overall cognition in boys with attention deficit hyperactivity disorder (ADHD). L-Theanine (2.5 mg/kg), caffeine (2.0 mg/kg), their combination and a placebo were administered in a randomized four-way repeated-measures crossover with washout, to five boys (8-15 years) with ADHD. Functional magnetic resonance imaging (fMRI) was performed during a Go/NoGo task and a Stop-signa ...[more]

PMID: 32753637

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Project description:BackgroundMultiple pathway models of ADHD suggest that multiple, separable biological pathways may lead to symptoms of the disorder. If this is the case, it should be possible to identify subgroups of children with ADHD based on distinct patterns of brain activity. Previous studies have used latent class analysis (LCA) to define subgroups at the behavioral and cognitive level and to then test whether they differ at the neurobiological level. In this proof of concept study, we took a reverse approach. We applied LCA to functional imaging data from two previously published studies to explore whether we could identify subgroups of children with ADHD symptoms at the neurobiological level with a meaningful relation to behavior or neuropsychology.MethodsFifty-six children with symptoms of ADHD (27 children with ADHD and 29 children with ASD and ADHD symptoms) and 31 typically developing children performed two neuropsychological tasks assessing reward sensitivity and temporal expectancy during functional magnetic resonance imaging. LCA was used to identify subgroups with similar patterns of brain activity separately for children with ADHD-symptoms and typically developing children. Behavioral and neuropsychological differences between subgroups were subsequently investigated.ResultsFor typically developing children, a one-subgroup model gave the most parsimonious fit, whereas for children with ADHD-symptoms a two-subgroup model best fits the data. The first ADHD subgroup (n = 49) showed attenuated brain activity compared to the second subgroup (n = 7) and to typically developing children (n = 31). Notably, the ADHD subgroup with attenuated brain activity showed less behavioral problems in everyday life.ConclusionsIn this proof of concept study, we showed that we could identify distinct subgroups of children with ADHD-symptoms based on their brain activity profiles. Generalizability was limited due to the small sample size, but ultimately such neurobiological profiles could improve insight in individual prognosis and treatment options.

Project description:BackgroundADHD is currently defined as a cognitive/behavioral developmental disorder where all clinical criteria are behavioral. Overactivity, impulsiveness, and inattentiveness are presently regarded as the main clinical symptoms. There is no biological marker, but there is considerable evidence to suggest that ADHD behavior is associated with poor dopaminergic and noradrenergic modulation of neuronal circuits that involve the frontal lobes. The best validated animal model of ADHD, the Spontaneously Hypertensive Rat (SHR), shows pronounced overactivity, impulsiveness, and deficient sustained attention. While dopamine release is decreased in SHR, norepinephrine concentrations are elevated. The primary objective of the present research was to test effects of a range of doses of the catecholamine agonists d- and l-amphetamine on ADHD-like symptoms in SHR.MethodsThe present study tested behavioral effects of 0.64 to 1.91 mg/kg d-amphetamine; and 1.27 to 3.81 mg/kg l-amphetamine base/kg i.p. in male SHRs and their controls, the Wistar Kyoto rat (WKY). ADHD-like behavior was tested with a visual discrimination task measuring overactivity, impulsiveness and inattentiveness.ResultsThe striking impulsiveness, overactivity, and poorer sustained attention during baseline conditions in the SHR were improved by treatment with the amphetamine isomers. The dose-response curves were, however, different for the different behaviors. Most significantly, d-amphetamine reduced overactivity and impulsiveness more efficiently than comparable doses of l-amphetamine. The lowest dose of d-amphetamine and low-to-medium doses of l-amphetamine improved sustained attention. The highest dose of d-amphetamine used interfered with SHR behavior. A second study showed that the impaired sustained attention (percent correct lever choice) in the SHR was not due to impaired visual functions or poorer working memory.DiscussionThe present results indicate that overactivity and impulsiveness may to some extent be associated with imbalances in neural circuits that differ from those causing poor sustained attention and that the two amphetamine isomers may affect the different neuromodulators differently. While d-amphetamine improved SHR overactivity, impulsiveness as well as sustained attention, the behavioral effects of l-amphetamine were relatively more specific for improving sustained attention than for the other 2 symptoms. Thus, while d- and l-amphetamine affect similar neuronal systems their relative potencies may be different.

Dataset Information

Effects of L-theanine-caffeine combination on sustained attention and inhibitory control among children with ADHD: a proof-of-concept neuroimaging RCT.

Publications

Effects of L-theanine-caffeine combination on sustained attention and inhibitory control among children with ADHD: a proof-of-concept neuroimaging RCT.

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