NIRS-based neurofeedback training in a virtual reality classroom for children with attention-deficit/hyperactivity disorder: study protocol for a randomized controlled trial

Friederike Blume, Justin Hudak, Thomas Dresler, Ann-Christine Ehlis, Jan Kühnhausen, Tobias J Renner, Caterina Gawrilow, Friederike Blume, Justin Hudak, Thomas Dresler, Ann-Christine Ehlis, Jan Kühnhausen, Tobias J Renner, Caterina Gawrilow

Abstract

Background: Children with attention-deficit/hyperactivity disorder (ADHD) suffer from attention deficits, motor hyperactivity, and impulsive behaviour. These impairments are experienced at home, at school, and with friends. Functional imaging studies show that ADHD behaviour and impairments in executive functions (EFs) are mirrored by aberrant neurophysiological functioning. Moreover, several studies show that ADHD behaviour, impairments in EFs, and a lack of self-control contribute to poor school performance. Non-pharmacological interventions such as neurofeedback training (NFT), for instance, aim at improving neurophysiological and neuropsychological functioning as well as behaviour. Consequently, NFT is expected to improve school performance, EFs, and self-control in children with ADHD. Generalization of acquired self-regulation skills from laboratory to real life is crucial for a transfer to everyday situations and is hypothesized to be facilitated via training using virtual reality (VR) environments. Consequently, experiencing NFT in VR is expected to yield greater effects than training in two dimensions (2D).

Methods/design: Ninety children with a clinical diagnosis of ADHD will be included in the study. Participants may be medicated or unmedicated. After random assignation to one of three conditions, all participants receive 15 training sessions of either near-infrared spectroscopy (NIRS)-based NFT in VR, NIRS-based NFT in 2D, or electromyogram-based biofeedback training in VR. ADHD symptoms, self-control, EF, health-related quality of life, school performance, and motor activity measured via parent, teacher, and child reports or objectively will be assessed before and after the intervention and at a 6 months follow-up. Furthermore, we are interested in parents' expectations about the training's effects.

Discussion: This is, to our knowledge, the first study investigating the efficacy of NFT for children with ADHD in a VR compared to a 2D environment. Furthermore, this study will contribute to the discussion about the efficacy and specific and unspecific effects of NFTs in children with ADHD. In addition to commonly assessed variables such as ADHD symptoms, NIRS and behavioural data obtained in EF measures, health-related quality of life, and parents' expectations about the intervention's effects, this study will investigate the effects on self-control, school performance, and motor activity.

Trial registration: ClinicalTrials.gov, NCT02572180 . Registered on 19 November 2015.

Keywords: Attention-deficit/hyperactivity disorder; Biofeedback; Electromyography; Near-infrared spectroscopy; Neurofeedback; Randomized controlled trial; School performance; Virtual reality.

Figures

Fig. 1
Fig. 1
2D and VR classroom
Fig. 2
Fig. 2
Flow chart showing the course of the study
Fig. 3
Fig. 3
Alignment of the NIRS channels on the cortex surface. The eight channels from which the feedback signal is computed are marked in red
Fig. 4
Fig. 4
SPIRIT figure presenting an overview of the tests, questionnaires, and other methods employed at different time points in the study. 1If participants are assigned to one of the conditions receiving a NIRS-based NF training. 2If participants are assigned to the condition receiving an EMG-based BF training. 3These tests/questionnaires were developed in the departments of the authors of this study. *Data collection requires medication washout

References

    1. American Psychiatric Association . DSM-5 Attention Deficit/Hyperactivity Disorder Fact Sheet. Arlington: American Psychiatric Association; 2013.
    1. Barkley RA. Behavioral inhibition, sustained attention, and executive functions: Constructing a unifying theory of ADHD. Psychol Bull. 1997;121:65–94. doi: 10.1037/0033-2909.121.1.65.
    1. Barkley RA. ADHD and the nature of self-control. New York: Guildford Press; 1997.
    1. Sonuga-Barke EJS. Psychological heterogeneity in AD/HD—a dual pathway model of behaviour and cognition. Behav Brain Res. 2002;130:29–36. doi: 10.1016/S0166-4328(01)00432-6.
    1. Faraone SV, Asherson P, Banaschewski T, Biederman J, Buitelaar JK, Ramos-Quiroga JA, Rohde LA, Sonuga-Barke EJS, Tannock R, Franke B. Attention-deficit/hyperactivity disorder. Nat Rev. 2015;1:1–23.
    1. Daley D, Birchwood J. ADHD and academic performance: why does ADHD impact on academic performance and what can be done to support ADHD children in the classroom? Child Care Health Dev. 2010;36:455–464. doi: 10.1111/j.1365-2214.2009.01046.x.
    1. Loe IM, Feldman HM. Academic and educational outcomes of children with ADHD. J Pediatr Psychol. 2007;32:643–654. doi: 10.1093/jpepsy/jsl054.
    1. Frazier TW, Youngstrom EA, Glutting JJ, Watkins MW. ADHD and achievement: meta-analysis of the child, adolescent, and adult literatures and a concomitant study with college students. J Learn Disabil. 2007;40:49–65. doi: 10.1177/00222194070400010401.
    1. Rodriguez A, Jarvelin M-R, Obel C, Taanila A, Miettunen J, Moilanen I, Henriksen T, Pietilainen K, Ebeling H, Kotimaa A, Linnet K, Olsen J. Do inattention and hyperactivity symptoms equal scholastic impairment? Evidence from three European cohorts. BMC Public Health. 2007;7:327. doi: 10.1186/1471-2458-7-327.
    1. Miller AC, Keenan JM, Betjemann RS, Willcutt EG, Pennington BF, Olson RK. Reading comprehension in children with ADHD: cognitive underpinnings of the centrality deficit. J Abnorm Child Psychol. 2013;41:473–483. doi: 10.1007/s10802-012-9686-8.
    1. Sciberras E, Mueller KL, Efron D, Bisset M, Anderson V, Schilpzand EJ, Jongeling B, Nicholson JM. Language problems in children with ADHD: a community-based study. Pediatrics. 2014;133:793–800. doi: 10.1542/peds.2013-3355.
    1. Sowerby P, Seal S, Tripp G. Working memory deficits in ADHD: the contribution of age, learning/language difficulties, and task parameters. J Atten Disord. 2011;15:461–472. doi: 10.1177/1087054710370674.
    1. Willcutt EG, Doyle AE, Nigg JT, Faraone SV, Pennington BF. Validity of the executive function theory of attention-deficit/hyperactivity disorder: a meta-analytic review. Biol Psychiatry. 2005;57:1336–1346. doi: 10.1016/j.biopsych.2005.02.006.
    1. Barry RJ, Johnstone SJ, Clarke AR. A review of electrophysiology in attention-deficit/hyperactivity disorder: II. Event-related potentials. Clin Neurophysiol. 2003;114:184–198. doi: 10.1016/S1388-2457(02)00363-2.
    1. Negoro H, Sawada M, Iida J, Ota T, Tanaka S, Kishimoto T. Prefrontal dysfunction in attention-deficit/hyperactivity disorder as measured by near-infrared spectroscopy. Child Psychiatry Hum Dev. 2010;41:193–203. doi: 10.1007/s10578-009-0160-y.
    1. Ehlis A-C, Bähne CG, Jacob CP, Herrmann MJ, Fallgatter AJ. Reduced lateral prefrontal activation in adult patients with attention-deficit/hyperactivity disorder (ADHD) during a working memory task: a functional near-infrared spectroscopy (fNIRS) study. J Psychiatr Res. 2008;42:1060–1067. doi: 10.1016/j.jpsychires.2007.11.011.
    1. Barry RJ, Clarke AR, Johnstone SJ. A review of electrophysiology in attention-deficit/hyperactivity disorder: I. Qualitative and quantitative electroencephalography. Clin Neurophysiol. 2003;114:171–183. doi: 10.1016/S1388-2457(02)00362-0.
    1. Hinterberger T, Veit R, Strehl U, Trevorrow T, Erb M, Kotchoubey B, Flor H, Birbaumer N. Brain areas activated in fMRI during self-regulation of slow cortical potentials (SCPs) Exp Brain Res. 2003;152:113–122. doi: 10.1007/s00221-003-1515-4.
    1. Hennighausen K, Schulte-Körne G, Warnke A, Remschmidt H. Contingent negative variation (CNV) in children with hyperkinetic syndrome—an experimental study using the Continuous Performance Test (CPT) Z Kinder Jugendpsychiatr Psychother. 2000;28:239–246. doi: 10.1024//1422-4917.28.4.239.
    1. Chabot RJ, Serfontein G. Quantitative electroencephalographic profiles of children with attention deficit disorder. Biol Psychiatry. 1996;40:951–963. doi: 10.1016/0006-3223(95)00576-5.
    1. Loo SK, Barkley RA. Clinical utility of EEG in attention deficit hyperactivity disorder. Appl Neuropsychol. 2005;12:64–76. doi: 10.1207/s15324826an1202_2.
    1. Gevensleben H, Moll GH, Rothenberger A, Heinrich H. Neurofeedback in attention-deficit/hyperactivity disorder — Different models, different ways of application. Front Hum Neurosci. 2014;8:1–10.
    1. Drechsler R, Straub M, Doehnert M, Heinrich H, Steinhausen H-C, Brandeis D. Controlled evaluation of a neurofeedback training of slow cortical potentials in children with Attention deficit/hyperactivity disorder (ADHD) Behav Brain Funct. 2007;3:35. doi: 10.1186/1744-9081-3-35.
    1. Holtmann M, Sonuga-Barke E, Cortese S, Brandeis D. Neurofeedback for attention-deficit/hyperactivity disorder. Child Adolesc Psychiatr Clin N Am. 2014;23:789–806. doi: 10.1016/j.chc.2014.05.006.
    1. Cortese S, Ferrin M, Brandeis D, Holtmann M, Aggensteiner P, Daley D, Santosh P, Simonoff E, Stevenson J, Stringaris A, Sonuga-Barke EJS. Neurofeedback for attention-deficit/hyperactivity disorder: meta-analysis of clinical and neuropsychological outcomes from randomized controlled trials. J Am Acad Child Adolesc Psychiatry. 2016;55:444–455. doi: 10.1016/j.jaac.2016.03.007.
    1. Arns M, de Ridder S, Strehl U, Breteler M, Coenen A. Efficacy of neurofeedback treatment in ADHD: the effects on inattention, impulsivity and hyperactivity: a meta-analysis. Clin EEG Neurosci. 2009;40:180–189. doi: 10.1177/155005940904000311.
    1. Marx A-M, Ehlis A-C, Furdea A, Holtmann M, Banaschewski T, Brandeis D, Rothenberger A, Gevensleben H, Freitag CM, Fuchsenberger Y, Fallgatter AJ, Strehl U. Near-infrared spectroscopy (NIRS) neurofeedback as a treatment for children with attention deficit hyperactivity disorder (ADHD) — a pilot study. Front Hum Neurosci. 2015. .
    1. Meisel V, Servera M, Garcia-Banda G, Cardo E, Moreno I. Neurofeedback and standard pharmacological intervention in ADHD: a randomized controlled trial with six-month follow-up. Biol Psychol. 2013;94:12–21. doi: 10.1016/j.biopsycho.2013.04.015.
    1. Raggi V, Chronis A. Interventions to address the academic impairment of children and adolescents with ADHD. Clin Child Fam Psychol Rev. 2006;9:85–111. doi: 10.1007/s10567-006-0006-0.
    1. Holtmann M, Pniewski B, Wachtlin D, Wörz S, Strehl U. Neurofeedback in children with attention-deficit/hyperactivity disorder (ADHD)—a controlled multicenter study of a non-pharmacological treatment approach. BMC Pediatr. 2014;14:202. doi: 10.1186/1471-2431-14-202.
    1. Birbaumer N, Elbert T, Brigitte R, Daum I, Wolf P, Canavan A. Clinical-psychological treatment of epileptic seizures: a controlled study. New York: Plenum Press; 1991. pp. 81–96.
    1. Albrecht B, Uebel-von Sandersleben H, Gevensleben H, Rothenberger A. Pathophysiology of ADHD and associated problems — starting points for neurofeedback interventions? Front Hum Neurosci. 2015;9:359. doi: 10.3389/fnhum.2015.00359.
    1. Gevensleben H, Rothenberger A, Moll GH, Heinrich H. Neurofeedback in children with ADHD: validation and challenges. Expert Rev Neurother. 2012;12:447–460. doi: 10.1586/ern.12.22.
    1. Bohil CJ, Alicea B, Biocca FA. Virtual reality in neuroscience research and therapy. Nat Rev Neurosci. 2011;12:752–762.
    1. Keshavan MS, Vinogradov S, Rumsey J, Sherrill J, Wagner A. Cognitive training in mental disorders: update and future directions. Am J Psychiatry. 2014;171:510–522. doi: 10.1176/appi.ajp.2013.13081075.
    1. Käthner I, Ruf CA, Pasqualotto E, Braun C, Birbaumer N, Halder S. A portable auditory P300 brain-computer interface with directional cues. Clin Neurophysiol. 2013;124:327–338. doi: 10.1016/j.clinph.2012.08.006.
    1. Kouneiher F, Charron S, Koechlin E. Motivation and cognitive control in the human prefrontal cortex. Nat Neurosci. 2009;12:939–945. doi: 10.1038/nn.2321.
    1. Subramaniam K, Kounios J, Parrish TB, Jung-Beeman M. Brain mechanism for facilitation of insight by positive affect. J Cogn Neurosci. 2009;21:415–432. doi: 10.1162/jocn.2009.21057.
    1. Chan A-W, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krleža-Jerić K, Hróbjartsson A, Mann H, Dickersin K, Berlin JA, Doré CJ, Parulekar WR, Summerskill WSM, Groves T, Schulz KF, Sox HC, Rockhold FW, Rennie D, Moher D. SPIRIT 2013 Statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013;2013(158):200–207. doi: 10.7326/0003-4819-158-3-201302050-00583.
    1. Chan A-W, Tetzlaff JM, Gøtzsche PC, Altman DG, Mann H, Berlin JA, Dickersin K, Hróbjartsson A, Schulz KF, Parulekar WR, Krleža-Jerić K, Laupacis A, Moher D. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013;346.
    1. Falkai P, Wittchen H-U. Diagnostisches und Statistisches Manual Psychischer Störungen DSM-5. 1. Göttingen: Hogrefe; 2014.
    1. Lidzba K, Christiansen H, Drechsler R. Conners Skalen zu Aufmerksamkeit und Verhalten-3. Deutschsprachige Adaption der Conners 3rd Edition von Keith Conners. Bern: Huber; 2013.
    1. Goodman R. The Strengths and Difficulties Questionnaire. A research note. J Child Psychol Psychiatry. 1997;38:581–586. doi: 10.1111/j.1469-7610.1997.tb01545.x.
    1. Strehl U. Lerntheoretische Grundlagen und Überlegungen zum Neurofeedback. In: Strehl U, editor. Neurofeedback. 1. Stuttgart: Verlag W. Kohlhammer; 2013. pp. 13–30.
    1. Strehl U, Leins U, Goth G, Klinger C, Hinterberger T, Birbaumer N. Self-regulation of slow cortical potentials: a new treatment for children with attention-deficit/hyperactivity disorder. Pediatrics. 2006;118:e1530–e1540. doi: 10.1542/peds.2005-2478.
    1. Villringer A, Planck J, Hock C, Schleinkofer L, Dirnagl U. Near infrared spectroscopy (NIRS): a new tool to study hemodynamic changes during activation of brain function in human adults. Neurosci Lett. 1993;154:101–104. doi: 10.1016/0304-3940(93)90181-J.
    1. Inman VT, Ralston HJ, De CM Saunders JB, Bertram Feinstein MB, Wright EW. Relation of human electromyogram to muscular tension. Electroencephalogr Clin Neurophysiol. 1952;4:187–194. doi: 10.1016/0013-4694(52)90008-4.
    1. Weiß RH, Osterland J. CFT 1-R. Grundintelligenztest Skala 1 - Revision. Göttingen: Hogrefe Verlag; 2013.
    1. Weiß RH, Weiß B. CFT 20-R. Grundintelligenztest Skala 2 - Revision. Göttingen: Hogrefe Verlag; 2006.
    1. Woerner W, Becker A, Friedrich C, Rothenberger A, Klasen H, Goodman R. Normierung und Evaluation der deutschen Elternversion des Strengths and Difficulties Questionnaire (SDQ): Ergebnisse einer repräsentativen Felderhebung. Z Kinder Jugendpsychiatr Psychother. 2002;30:105–112. doi: 10.1024//1422-4917.30.2.105.
    1. Goodman R. Psychometric properties of the Strengths and Difficulties Questionnaire. J Am Acad Child Adolesc Psychiatry. 2001;40:1337–1345. doi: 10.1097/00004583-200111000-00015.
    1. Ravens-Sieberer U, Ellert U, Erhart M. Health-related quality of life of children and adolescents in Germany. Norm Data from the German Health Interview and Examination Survey (KiGGS) Bundesgesundheitsblatt - Gesundheitsforsch - Gesundheitsschutz. 2007;50:810–818. doi: 10.1007/s00103-007-0244-4.
    1. Rauch WA, Gawrilow C, Schermelleh-Engel K, Schmitt K. Dispositionelle Selbstkontrollkapazität bei Kindern. Diagnostica. 2014;60:61–72. doi: 10.1026/0012-1924/a000099.
    1. Schwarzer R, Jerusalem M. Skalen zur Erfassung von Lehrer- und Schülermerkmalen. Berlin: Dokumentation der psychometrischen Verfahren im Rahmen der wissenschaftlichen Begleitung des Modellversuchs selbstwirksame Schulen. Berlin: Freie Universität Berlin; 1999.
    1. Juang LP, Silbereisen RK. The relationship between adolescent academic capability beliefs, parenting and school grades. J Adolesc. 2002;25:3–18. doi: 10.1006/jado.2001.0445.
    1. Drechsler R, Steinhausen H-C. BRIEF. Verhaltensinventar zur Beurteilung exekutiver Funktionen. Göttingen: Hogrefe Verlag; 2013.
    1. Vollmann K, Hautzinger M, Strehl U. Entwicklung und Überprüfung eines Fragebogens zur Erfassung relevanter Therapiebedingungen (FERT) [dissertation] 2009.
    1. Verbruggen F, Logan GD, Stevens MA. STOP-IT. 2013.
    1. Soreni N, Crosbie J, Ickowicz A, Schachar R. Stop Signal and Conners’ Continuous Performance Tasks Test—Retest reliability of two inhibition measures in ADHD children. J Atten Disord. 2009;13:137–143. doi: 10.1177/1087054708326110.
    1. Corsi PM. Human memory and the medial temporal region of the brain. Diss Abstr Int. 1972;34:891.
    1. Mueller ST, Piper BJ. The Psychology Experiment Building Language (PEBL) and PEBL test battery. J Neurosci Methods. 2014;222:250–259. doi: 10.1016/j.jneumeth.2013.10.024.
    1. Mueller ST. The PEBL The PEBL. 2011.
    1. Schellig D. Block-Tapping-Test (BTT). Manual. Frankfurt: Pearson Assessment; 1997.
    1. Petermann F, Petermann U. Wechsler Intelligence Scale for Children - Fourth Edition Deutsche Bearbeitung. Frankfurt: Pearson; 2011.
    1. Aschenbrenner S, Tucha O, Lange KW. Regensburger Wortflüssigkeits-Test (RWT) Göttingen: Hogrefe; 2001.
    1. Schecklmann M, Ehlis A-C, Plichta MM, Fallgatter AJ. Functional near-infrared spectroscopy: a long-term reliable tool for measuring brain activity during verbal fluency. Neuroimage. 2008;43:147–155. doi: 10.1016/j.neuroimage.2008.06.032.
    1. Conners KC, Epstein JN, Angold A, Klaric J. Continuous performance test performance in a normative epidemiological sample. J Abnorm Child Psychol. 2003;31:555–562. doi: 10.1023/A:1025457300409.
    1. Strathmann AM, Klauer KJ. LVD-M 2–4 Lernverlaufsdiagnostik für zweite bis vierte Klassen. Göttingen: Hogrefe; 2012.
    1. Krajewski K, Küspert P, Schneider W, Visé M. DEMAT 1+. Deutscher Mathematiktest für erste Klassen. Göttingen: Beltz; 2004.
    1. Krajewski K, Liehm S, Schneider W. DEMAT 2+. Deutscher Mathematiktest für zweite Klassen. Göttingen: Beltz; 2004.
    1. Gölitz D, Marx H, Schneider W. DEMAT 4. Deutscher Mathematiktest für vierte Klassen. Göttingen: Beltz; 2004.
    1. Obrig H, Wenzel R, Kohl M, Horst S, Wobst P, Steinbrink J, Thomas F, Villringer A. Near-infrared spectroscopy: does it function in functional activation studies of the adult brain? Int J Psychophysiol. 2000;35:125–142. doi: 10.1016/S0167-8760(99)00048-3.
    1. Alderliesten T, De Vis JB, Lemmers PMA, van Bel F, Benders MJNL, Hendrikse J, Petersen ET. Simultaneous quantitative assessment of cerebral physiology using respiratory-calibrated MRI and near-infrared spectroscopy in healthy adults. Neuroimage. 2014;85:255–263. doi: 10.1016/j.neuroimage.2013.07.015.
    1. Steinbrink J, Villringer A, Kempf F, Haux D, Boden S, Obrig H. Illuminating the BOLD signal: combined fMRI–fNIRS studies. Magn Reson Imaging. 2006;24:495–505. doi: 10.1016/j.mri.2005.12.034.
    1. Jasper H. Report of the committee on methods of clinical examination in electroencephalography. Electroencephalogr Clin Neurophysiol. 1958;10:370–375. doi: 10.1016/0013-4694(58)90053-1.
    1. Cutini S, Scatturin P, Zorzi M. A new method based on ICBM152 head surface for probe placement in multichannel fNIRS. Neuroimage. 2011;54:919–927. doi: 10.1016/j.neuroimage.2010.09.030.
    1. Wilke M, Holland SK, Altaye M, Gaser C. Template-O-Matic: a toolbox for creating customized pediatric templates. Neuroimage. 2008;41:903–913. doi: 10.1016/j.neuroimage.2008.02.056.
    1. NeuroConn . BrainsightTM. 2012.
    1. Moll K, Landerl K. Lese- und Rechtschreibtest (SLRT-II). Weiterentwicklung des Salzburger Lese- und Rechtschreibtests (SLRT). 2, korrig. Bern: Verlag Hans Huber; 2014.
    1. Verbruggen F, Logan GD, Stevens MA. STOP-IT: Windows executable software for the stop-signal paradigm. Behav Res Methods. 2008;40:479–483. doi: 10.3758/BRM.40.2.479.
    1. Gevensleben H, Holl B, Albrecht B, Schlamp D, Kratz O, Studer P, Wangler S, Rothernberger A, Moll GH, Heinrich H. Distinct EEG effects related to neurofeedback training in children with ADHD: a randomized controlled trial. Int J Psychophysiol. 2009;74:149–157. doi: 10.1016/j.ijpsycho.2009.08.005.
    1. Baumeister RF, Vohs KD, Tice DM. The strength model of self-control. Curr Dir Psychol Sci. 2007;16:351–355. doi: 10.1111/j.1467-8721.2007.00534.x.
    1. Bakhshayesh AR, Hänsch S, Wyschkon A, Rezai MJ, Esser G. Neurofeedback in ADHD: a single-blind randomized controlled trial. Eur Child Adolesc Psychiatry. 2011;20:481–491. doi: 10.1007/s00787-011-0208-y.
    1. Arns M, Conners CK, Kraemer HC. A decade of EEG theta/beta ratio research in ADHD: a meta-analysis. J Atten Disord. 2013;17:374–383. doi: 10.1177/1087054712460087.

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