A randomized controlled clinical trial of real-time functional magnetic resonance imaging neurofeedback for adolescents with attention deficit hyperactivity disorder (ADHD)

Event Abstract Back to Event A randomized controlled clinical trial of real-time functional magnetic resonance imaging neurofeedback for adolescents with attention deficit hyperactivity disorder (ADHD) Katya Rubia1*, Analucia Alegria1, Melanie Wulff1, Helen Brinson1, Vincent Giampietro2, Gareth Barker2, Daniel Brandeis3, Daniel Stahl4 and Anthony David5 1 King's College London, Institute of Psychiatry, Psychology & Neuroscience, Child & Adolescent Psychiatry, United Kingdom 2 King's College London, Center for Neuroimaging, United Kingdom 3 Zuerich University, Child & Adolescent Psychiatry, Switzerland 4 King's College London, Biostatistics, United Kingdom 5 Kings College London, Psychosis, United Kingdom Introduction: Right inferior frontal cortex (rIFC) is one of the most consistently underactivated brain regions in ADHD children during cognitive control tasks (Norman et al., 2015, Hart et al., 2012). Furthermore, we found this region to be a disorder-specific neurofunctional biomarker of ADHD relative to other childhood disorders (Rubia, 2011, Norman et al., 2016). rIFC is also the brain region that is most consistently upregulated with psychostimulant medication, which is the benchmark treatment for ADHD as it is effective in 70% of patients (Rubia et al., 2014). However, stimulant medication has side effects and long-term efficacy has not been demonstrated. In this study, we wanted to teach ADHD adolescents to self-upregulate this brain region which is consistently underactivated and most consistently upregulated with stimulant medication using real-time Neurofeedback with functional magnetic resonance imaging (rtfMRI-NF). For this purpose, we conducted a proof of concept randomised controlled trial (RCT) of rtfMRI-NF of rIFC in ADHD adolescents. We hypothesised that rtfMRI-NF would improve clinical symptoms of ADHD, cognitive control functions that are mediated by rIFC (such as sustained attention, inhibition, temporal discounting, time estimation) and the activation of rIFC during a motor inhibition stop task that is typically underactivated. Methods: Thirty-one ADHD boys were randomized in a single-blind RCT (only patients and parents were blind, but not researchers for practical reasons) to rt-fMRI-NF (14 sessions) of the rIFC (active group) or the left parahippocampal gyrus (lPHG, control group). Visual feedback was presented via a video-clip of a rocket that had to be moved from the ground to the space. Main outcome measures were changes in parents' rating of clinical ADHD symptoms which were assessed at pre, post, and on average 11 month follow-up. A computer-based test battery and a fMRI Stop task were also used to assess NF effects on cognition and IFC brain function. Results: Both NF groups showed significantly linearly progressive increased activation with increasing session numbers in their respective target regions relative to the other group. Both groups also showed reduced ADHD symptoms from pre to post with no significant group differences; these changes, furthermore correlated significantly with the brain changes in their respective target regions. Only the active group, however, showed a transfer effect, whereby they showed increased activation in rIFC without the neurofeedback. Also, only the active group maintained the achieved improvements in ADHD symptoms at an average of 11 month follow-up. Furthermore, only the active group improved in intra-subject response variability and (trend-wise) in sustained attention. Lastly, only the active group showed significantly enhanced rIFC activation after the training relative to before the training during a Stop motor inhibition task, relative to the control group, who did not show this effect. The rIFC upregulation effect was similar to the one we have previously observed with stimulant medication (Rubia et al., 2014). Discussion: The proof of concept study shows that ADHD adolescents can learn to self-up-regulate rIFC activation and this is associated with improved ADHD symptoms, cognition and inhibitory rIFC activation. References Hart H, Radua J, Mataix D, Rubia K (2013) Meta-analysis of fMRI studies of inhibition and attention in ADHD: exploring task-specific, stimulant medication and age effects. JAMA Psychiatry 70(2):185-98 Norman, L, Carlisi, C, Lukito S, Hart H, Mataix-Cols, Radua J, D, Rubia, K (2016) A comparative meta-analysis of structural and functional brain abnormalities in ADHD and OCD. JAMA Psychiatry, doi: 10.1001/jamapsychiatry.2016.0700. Epub ahead of print. Rubia K. (2011). "Cool" inferior fronto-cerebellar dysfunction in Attention Deficit Hyperactivity Disorder (ADHD) versus "hot" ventromedial orbitofronto-limbic dysfunction in conduct disorder. Biological Psychiatry, 2011; 69: e69–e87. Rubia K, Alzamora A, Smith ABS, Cubillo A, Brammer M, Radua Q (2014): Effects of stimulants on brain function in ADHD: a systematic review and meta-analysis. Biological Psychiatry, 5;76(8):616-28. Keywords: ADHD, Neurofeedback, fMRI-Neurofeedback, inhibition, adolescents Conference: SAN2016 Meeting, Corfu, Greece, 6 Oct - 9 Oct, 2016. Presentation Type: Oral Presentation in SAN 2016 Conference Topic: Symposium in fMRI and NIRS Neurofeedback Citation: Rubia K, Alegria A, Wulff M, Brinson H, Giampietro V, Barker G, Brandeis D, Stahl D and David A (2016). A randomized controlled clinical trial of real-time functional magnetic resonance imaging neurofeedback for adolescents with attention deficit hyperactivity disorder (ADHD). Conference Abstract: SAN2016 Meeting. doi: 10.3389/conf.fnhum.2016.220.00060 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers' terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Jul 2016; Published Online: 01 Aug 2016. * Correspondence: Prof. Katya Rubia, King's College London, Institute of Psychiatry, Psychology & Neuroscience, Child & Adolescent Psychiatry, London, SE5 8AF, United Kingdom, katya.rubia@kcl.ac.uk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Katya Rubia Analucia Alegria Melanie Wulff Helen Brinson Vincent Giampietro Gareth Barker Daniel Brandeis Daniel Stahl Anthony David Google Katya Rubia Analucia Alegria Melanie Wulff Helen Brinson Vincent Giampietro Gareth Barker Daniel Brandeis Daniel Stahl Anthony David Google Scholar Katya Rubia Analucia Alegria Melanie Wulff Helen Brinson Vincent Giampietro Gareth Barker Daniel Brandeis Daniel Stahl Anthony David PubMed Katya Rubia Analucia Alegria Melanie Wulff Helen Brinson Vincent Giampietro Gareth Barker Daniel Brandeis Daniel Stahl Anthony David Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.