Tieme W. P. Janssen

Neural correlates of response inhibition in children with attention-deficit/hyperactivity disorder: A controlled version of the stop-signal task

The stop-signal task has been used extensively to investigate the neural correlates of inhibition deficits in children with ADHD. However, previous findings of atypical brain activation during the stop-signal task in children with ADHD may be confounded with attentional processes, precluding strong conclusions on the nature of these deficits. In addition, there are recent concerns on the construct validity of the SSRT metric. The aim of this study was to control for confounding factors and improve the specificity of the stop-signal task to investigate inhibition mechanisms in children with ADHD. FMRI was used to measure inhibition related brain activation in 17 typically developing children (TD) and 21 children with ADHD, using a highly controlled version of the stop-signal task. Successful inhibition trials were contrasted with control trials that were comparable in frequency, visual presentation and absence of motor response. We found reduced brain activation in children with ADHD in key inhibition areas, including the right inferior frontal gyrus/insula, and anterior cingulate/dorsal medial prefrontal cortex. Using a more stringent controlled design, this study replicated and specified previous findings of atypical brain activation in ADHD during motor response inhibition.

Alterations in the ventral attention network during the stop-signal task in children with ADHD: an event-related potential source imaging study

Objective: Deficits in response inhibition figure prominently in models of ADHD; however, attentional deficiencies may better explain previous findings of impaired response inhibition in ADHD. We tested this hypothesis at the neurophysiological level. Method: Dense array ERPs (event-related potentials) were obtained for 46 children with ADHD and 51 controls using the stop-signal task (SST). Early and late components were compared between groups. N2 and P3 components were localized with LAURA distributed linear inverse solution. Results: A success-related N1 modulation was only apparent in the ADHD group. N2 and P3 amplitudes were reduced in ADHD. During the successful inhibition N2, the ADHD group showed reduced activation in right inferior frontal gyrus (rIFG), supplementary motor area (SMA), and right temporoparietal junction (rTPJ), and during failed inhibition in the rIFG. During the successful inhibition P3, reduced activation was found in anterior cingulate cortex (ACC) and SMA. Conclusion: Impairments in the ventral attention network contribute to the psychopathology of ADHD and challenge the dominant view that ADHD is underpinned by impaired inhibitory control.

Behavioral Effects of Neurofeedback Compared to Stimulants and Physical Activity in Attention-Deficit/Hyperactivity Disorder: A Randomized Controlled Trial

OBJECTIVE The efficacy of neurofeedback as a treatment for attention-deficit/hyperactivity disorder (ADHD), and whether neurofeedback is a viable alternative for stimulant medication, is still an intensely debated subject. The current randomized controlled trial compared neurofeedback to (1) optimally titrated methylphenidate and (2) a semi-active control intervention, physical activity, to account for nonspecific effects. METHODS A multicenter 3-way parallel-group study with balanced randomization was conducted. Children with a DSM-IV-TR diagnosis of ADHD, aged 7-13 years, were randomly allocated to receive neurofeedback (n = 39), methylphenidate (n = 36), or physical activity (n = 37) over a period of 10-12 weeks. Neurofeedback comprised theta/beta training on the vertex (Cz). Physical activity consisted of moderate to vigorous intensity exercises. Neurofeedback and physical activity were balanced in terms of number (~30) and duration of sessions. A double-blind pseudorandomized placebo-controlled crossover titration procedure was used to determine an optimal dose in the methylphenidate intervention. Parent and teacher ratings on the Strengths and Difficulties Questionnaire (SDQ) and Strengths and Weaknesses of ADHD Symptoms and Normal Behavior (SWAN) were used to assess intervention outcomes. Data collection took place between September 2010 and March 2014. RESULTS Intention-to-treat analyses revealed an improvement in parent-reported behavior on the SDQ and the SWAN Hyperactivity/Impulsivity scale, irrespective of received intervention (ηp² = 0.21-0.22, P ≤ .001), whereas the SWAN Inattention scale revealed more improvement in children who received methylphenidate than neurofeedback and physical activity (ηp² = 0.13, P ≤ .001). Teachers reported a decrease of ADHD symptoms on all measures for methylphenidate, but not for neurofeedback or physical activity (range of ηp² = 0.14-0.29, P < .001). CONCLUSIONS The current study found that optimally titrated methylphenidate is superior to neurofeedback and physical activity in decreasing ADHD symptoms in children with ADHD. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01363544.

Neurofeedback to improve neurocognitive functioning of children treated for a brain tumor: design of a randomized controlled double-blind trial

BackgroundNeurotoxicity caused by treatment for a brain tumor is a major cause of neurocognitive decline in survivors. Studies have shown that neurofeedback may enhance neurocognitive functioning. This paper describes the protocol of the PRISMA study, a randomized controlled trial to investigate the efficacy of neurofeedback to improve neurocognitive functioning in children treated for a brain tumor.Methods/DesignEfficacy of neurofeedback will be compared to placebo training in a randomized controlled double-blind trial. A total of 70 brain tumor survivors in the age range of 8 to 18 years will be recruited. Inclusion also requires caregiver-reported neurocognitive problems and being off treatment for more than two years. A group of 35 healthy siblings will be included as the control group. On the basis of a qEEG patients will be assigned to one of three treatment protocols. Thereafter patients will be randomized to receive either neurofeedback training (n=35) or placebo training (n=35). Neurocognitive tests, and questionnaires administered to the patient, caregivers, and teacher, will be used to evaluate pre- and post-intervention functioning, as well as at 6-month follow-up. Siblings will be administered the same tests and questionnaires once.DiscussionIf neurofeedback proves to be effective for pediatric brain tumor survivors, this can be a valuable addition to the scarce interventions available to improve neurocognitive and psychosocial functioning.Trial registrationClinicalTrials.gov NCT00961922.

An ERP source imaging study of the oddball task in children with Attention Deficit/Hyperactivity Disorder

OBJECTIVE Children with ADHD have difficulties attending to task-relevant events, which has been consistently associated with reductions in the amplitude of the P3b event-related potential (ERP) component. However, the underlying neural networks involved in this P3b reduction remain elusive. Therefore, this study explored source localization of P3b alterations in children with ADHD, aiming at a more detailed account of attentional difficulties. METHODS Dense array ERPs were obtained for 36 children with ADHD and 49 typically developing children (TD) using an auditory oddball task. The P3b component (310-410 ms) was individually localized with the LAURA distributed linear inverse solution method and compared between groups. RESULTS The ADHD group showed reduced P3b amplitudes in response to targets compared to the TD group. Differences were located primarily in frontopolar (cinguloopercular network, BA10) and temporoparietal regions (ventral attention network, BA39 and 19) in the left hemisphere. Reductions in P3b amplitudes were related to more inattention and hyperactivity/impulsivity problems in the ADHD group. CONCLUSIONS The results show alterations in both top-down and bottom-up attention-related brain areas, which may underlie P3b amplitude reductions in children with ADHD. SIGNIFICANCE This study provides novel data on both temporal and spatial aspects of dysfunctional attention processes in ADHD.

1-year follow-up of neurofeedback treatment in adolescents with attention-deficit hyperactivity disorder : Randomised controlled trial

Background Estimates of the effectiveness of neurofeedback as a treatment for attention-deficit hyperactivity disorder (ADHD) are mixed. Aims To investigate the long-term additional effects of neurofeedback (NFB) compared with treatment as usual (TAU) for adolescents with ADHD. Method Using a multicentre parallel-randomised controlled trial design, 60 adolescents with a DSM-IV-TR diagnosis of ADHD receiving NFB+TAU (n=41) or TAU (n=19) were followed up. Neurofeedback treatment consisted of approximately 37 sessions of theta/sensorimotor rhythm (SMR)-training on the vertex (Cz). Outcome measures included behavioural self-reports and neurocognitive measures. Allocation to the conditions was unmasked. Results At 1-year follow-up, inattention as reported by adolescents was decreased (range ηp2=0.23–0.36, P<0.01) and performance on neurocognitive tasks was faster (range ηp2=0.20–0.67, P<0.005) irrespective of treatment group. Conclusions Overall, NFB+TAU was as effective as TAU. Given the absence of robust additional effects of neurofeedback in the current study, results do not support the use of theta/SMR neurofeedback as a treatment for adolescents with ADHD and comorbid disorders in clinical practice. Declaration of interest None. Copyright and usage

Neural network topology in ADHD; evidence for maturational delay and default-mode network alterations

OBJECTIVE Attention-deficit/hyperactivity disorder (ADHD) has been associated with widespread brain abnormalities in white and grey matter, affecting not only local, but global functional networks as well. In this study, we explored these functional networks using source-reconstructed electroencephalography in ADHD and typically developing (TD) children. We expected evidence for maturational delay, with underlying abnormalities in the default mode network. METHODS Electroencephalograms were recorded in ADHD (n=42) and TD (n=43) during rest, and functional connectivity (phase lag index) and graph (minimum spanning tree) parameters were derived. Dependent variables were global and local network metrics in theta, alpha and beta bands. RESULTS We found evidence for a more centralized functional network in ADHD compared to TD children, with decreased diameter in the alpha band (ηp2=0.06) and increased leaf fraction (ηp2=0.11 and 0.08) in the alpha and beta bands, with underlying abnormalities in hub regions of the brain, including default mode network. CONCLUSIONS The finding of a more centralized network is in line with maturational delay models of ADHD and should be replicated in longitudinal designs. SIGNIFICANCE This study contributes to the literature by combining high temporal and spatial resolution to construct EEG network topology, and associates maturational-delay and default-mode interference hypotheses of ADHD.

Stimulus-preceding negativity in ADHD.

Children with ADHD often show disrupted response preparation as indicated by attenuated stimulus-preceding negativity (SPN). This study examined response preparation in a relatively short cue–stimulus interval. No differences in SPN occurred between children with ADHD and their normal peers. A strong positive relationship was found between SPN and mean reaction time in both groups. Children with ADHD are able to mentally prepare themselves for upcoming events in short cue–stimulus intervals.