The Effects of Methylphenidate and Non-invasive Brain Stimulation on Inhibitory Control in Children With ADHD

NCT04964427 | Completed DMC

• 1 other identifier: 2185_2020_OPBG
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is comparing the effects of non-pharmacological intervention (transcranial Direct Current Stimulation, tDCS) with those of drug (methylphenidate, MPH) administration in children and adolescents with ADHD. The investigators hypothesized that tDCS would improve inhibitory control and visuo-spatial working memory as well as MPH.

Conditions

Attention Deficit Hyperactivity Disorder

Keywords

methylphenidate; executive functions; working memory; tDCS; inhibitory control

Outcome Measures

Primary Outcomes (1)

• evaluate the change in response inhibition measures

  Compare Stop Signal Reaction Times in patients with ADHD following the administration of a single anodal tDCS session, a single sham tDCS session and a single dose of MPH

  immediately after the interventions

Secondary Outcomes (2)

• evaluate the change in other response inhibition measures

  immediately after the interventions

• evaluate the change in visuo-spatial working memory measure

  immediately after the interventions

Study Arms (6)

anodal tDCS- sham tDCS- MPH

EXPERIMENTAL

(A) anodal tDCS at t1 (B) sham tDCS at t2 (C) MPH at t3

Drug: Methylphenidate; Device: anodal tDCS; Device: sham tDCS

anodal tDCS- MPH- sham tDCS

EXPERIMENTAL

(A) anodal tDCS at t1 (C) MPH at t2 (B) sham tDCS at t3

Drug: Methylphenidate; Device: anodal tDCS; Device: sham tDCS

sham tDCS- anodal tDCS- MPH

EXPERIMENTAL

(B) sham tDCS at t1 (A) anodal tDCS at t2 (C) MPH at t3

Drug: Methylphenidate; Device: anodal tDCS; Device: sham tDCS

sham tDCS- MPH- anodal tDCS

EXPERIMENTAL

(B) sham tDCS at t1 (C) MPH at t2 (A) anodal tDCS at t3

Drug: Methylphenidate; Device: anodal tDCS; Device: sham tDCS

MPH- anodal tDCS- sham tDCS

EXPERIMENTAL

(C) MPH at t1 (A) anodal tDCS at t2 (B) sham tDCS at t3

Drug: Methylphenidate; Device: anodal tDCS; Device: sham tDCS

MPH- sham tDCS- anodal tDCS

EXPERIMENTAL

(C) MPH at t1 (B) sham tDCS at t2 (A) anodal tDCS at t3

Drug: Methylphenidate; Device: anodal tDCS; Device: sham tDCS

Interventions

Methylphenidate DRUG

A single dose of 5-10 mg of immediate release MPH (Ritalin®) will be administered in line with NICE and AIFA (Agenzia Italiana del Farmaco) guidelines for ADHD treatment.

Also known as: Ritalin

MPH- anodal tDCS- sham tDCS; MPH- sham tDCS- anodal tDCS; anodal tDCS- MPH- sham tDCS; anodal tDCS- sham tDCS- MPH; sham tDCS- MPH- anodal tDCS; sham tDCS- anodal tDCS- MPH

anodal tDCS DEVICE

Anodal electrode will be positioned over the left dlPFC, according to the 10-20 EEG on the sites corresponding F3, whereas the reference electrode will be placed above the contralateral supraorbital area, corresponding to Fp2. In the active tDCS condition, the current will increase slowly during the first 30 seconds to 1 mA (ramp-up) and, at the end of the stimulation, the current will decrease slowly to 0 mA during the last 30 seconds (ramp-down). Between the ramp-up and ramp-down constant current will be delivered for 20 minutes, with a density of 0.04 mA/cm2.

MPH- anodal tDCS- sham tDCS; MPH- sham tDCS- anodal tDCS; anodal tDCS- MPH- sham tDCS; anodal tDCS- sham tDCS- MPH; sham tDCS- MPH- anodal tDCS; sham tDCS- anodal tDCS- MPH

sham tDCS DEVICE

In the sham tDCS condition, the stimulation will be delivered by using the same active tDCS montage, respectively left-anodal dlPFC and right-reference electrode over Fp2. Stimulation intensity will be set at 1 mA, but the current will be applied for 30 seconds and will be ramped down without the participants' awareness.

MPH- anodal tDCS- sham tDCS; MPH- sham tDCS- anodal tDCS; anodal tDCS- MPH- sham tDCS; anodal tDCS- sham tDCS- MPH; sham tDCS- MPH- anodal tDCS; sham tDCS- anodal tDCS- MPH

Eligibility Criteria

• Age: 8 Years - 13 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Patients must receive a Diagnostic and Statistical Manual of Mental Disorders (DSM-5) oriented diagnosis of ADHD and need drug treatment for the severity of symptoms;
• Intelligent Quotient (IQ) \> 85;

You may not qualify if:

• Presence of Autism Spectrum Disorders;
• Presence of Mood Disorders;
• Previous/current diagnosis of neurological conditions (i.e. epilepsy, neurodegenerative diseases);
• Presence of Genetic Syndromes;
• Presence of basal medical conditions (i.e. heart, kidney or liver diseases) which may exclude the possibility to administer MPH.

Sponsors & Collaborators

• Bambino Gesù Hospital and Research Institute: lead

Study Sites (1)

Bambino Gesù Hospital and Research Institute

Roma, 00165, Italy

Location

Related Publications (110)

• Adamo N, Hodsoll J, Asherson P, Buitelaar JK, Kuntsi J. Ex-Gaussian, Frequency and Reward Analyses Reveal Specificity of Reaction Time Fluctuations to ADHD and Not Autism Traits. J Abnorm Child Psychol. 2019 Mar;47(3):557-567. doi: 10.1007/s10802-018-0457-z.

  PMID: 30027330 RESULT

• Adams ZW, Roberts WM, Milich R, Fillmore MT. Does response variability predict distractibility among adults with attention-deficit/hyperactivity disorder? Psychol Assess. 2011 Jun;23(2):427-36. doi: 10.1037/a0022112.

  PMID: 21443365 RESULT

• Andreou P, Neale BM, Chen W, Christiansen H, Gabriels I, Heise A, Meidad S, Muller UC, Uebel H, Banaschewski T, Manor I, Oades R, Roeyers H, Rothenberger A, Sham P, Steinhausen HC, Asherson P, Kuntsi J. Reaction time performance in ADHD: improvement under fast-incentive condition and familial effects. Psychol Med. 2007 Dec;37(12):1703-15. doi: 10.1017/S0033291707000815. Epub 2007 May 31.

  PMID: 17537284 RESULT

• Aron AR, Dowson JH, Sahakian BJ, Robbins TW. Methylphenidate improves response inhibition in adults with attention-deficit/hyperactivity disorder. Biol Psychiatry. 2003 Dec 15;54(12):1465-8. doi: 10.1016/s0006-3223(03)00609-7.

  PMID: 14675812 RESULT

• Arul-Anandam AP, Loo C, Sachdev P. Transcranial direct current stimulation - what is the evidence for its efficacy and safety? F1000 Med Rep. 2009 Jul 27;1:58. doi: 10.3410/M1-58.

  PMID: 20948722 RESULT

• Banaschewski T, Coghill D, Santosh P, Zuddas A, Asherson P, Buitelaar J, Danckaerts M, Dopfner M, Faraone SV, Rothenberger A, Sergeant J, Steinhausen HC, Sonuga-Barke EJ, Taylor E. Long-acting medications for the hyperkinetic disorders. A systematic review and European treatment guideline. Eur Child Adolesc Psychiatry. 2006 Dec;15(8):476-95. doi: 10.1007/s00787-006-0549-0. Epub 2006 May 5.

  PMID: 16680409 RESULT

• Barkley RA, Fischer M, Smallish L, Fletcher K. Young adult outcome of hyperactive children: adaptive functioning in major life activities. J Am Acad Child Adolesc Psychiatry. 2006 Feb;45(2):192-202. doi: 10.1097/01.chi.0000189134.97436.e2.

  PMID: 16429090 RESULT

• Bedard AC, Martinussen R, Ickowicz A, Tannock R. Methylphenidate improves visual-spatial memory in children with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2004 Mar;43(3):260-8. doi: 10.1097/00004583-200403000-00006.

  PMID: 15076258 RESULT

• Bellgrove MA, Hester R, Garavan H. The functional neuroanatomical correlates of response variability: evidence from a response inhibition task. Neuropsychologia. 2004;42(14):1910-6. doi: 10.1016/j.neuropsychologia.2004.05.007.

  PMID: 15381021 RESULT

• Biederman J, Spencer T. Attention-deficit/hyperactivity disorder (ADHD) as a noradrenergic disorder. Biol Psychiatry. 1999 Nov 1;46(9):1234-42. doi: 10.1016/s0006-3223(99)00192-4.

  PMID: 10560028 RESULT

• BINDMAN LJ, LIPPOLD OC, REDFEARN JW. THE ACTION OF BRIEF POLARIZING CURRENTS ON THE CEREBRAL CORTEX OF THE RAT (1) DURING CURRENT FLOW AND (2) IN THE PRODUCTION OF LONG-LASTING AFTER-EFFECTS. J Physiol. 1964 Aug;172(3):369-82. doi: 10.1113/jphysiol.1964.sp007425. No abstract available.

  PMID: 14199369 RESULT

• Boggio PS, Ferrucci R, Mameli F, Martins D, Martins O, Vergari M, Tadini L, Scarpini E, Fregni F, Priori A. Prolonged visual memory enhancement after direct current stimulation in Alzheimer's disease. Brain Stimul. 2012 Jul;5(3):223-230. doi: 10.1016/j.brs.2011.06.006. Epub 2011 Jul 27.

  PMID: 21840288 RESULT

• Boonstra AM, Kooij JJ, Oosterlaan J, Sergeant JA, Buitelaar JK. Does methylphenidate improve inhibition and other cognitive abilities in adults with childhood-onset ADHD? J Clin Exp Neuropsychol. 2005 Apr;27(3):278-98. doi: 10.1080/13803390490515757.

  PMID: 15969353 RESULT

• Brunoni AR, Amadera J, Berbel B, Volz MS, Rizzerio BG, Fregni F. A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. Int J Neuropsychopharmacol. 2011 Sep;14(8):1133-45. doi: 10.1017/S1461145710001690. Epub 2011 Feb 15.

  PMID: 21320389 RESULT

• Buzy WM, Medoff DR, Schweitzer JB. Intra-individual variability among children with ADHD on a working memory task: an ex-Gaussian approach. Child Neuropsychol. 2009 Sep;15(5):441-59. doi: 10.1080/09297040802646991.

  PMID: 19184779 RESULT

• Cachoeira CT, Leffa DT, Mittelstadt SD, Mendes LST, Brunoni AR, Pinto JV, Blazius V, Machado V, Bau CHD, Rohde LA, Grevet EH, Schestatsky P. Positive effects of transcranial direct current stimulation in adult patients with attention-deficit/hyperactivity disorder - A pilot randomized controlled study. Psychiatry Res. 2017 Jan;247:28-32. doi: 10.1016/j.psychres.2016.11.009. Epub 2016 Nov 10.

  PMID: 27863315 RESULT

• Castellanos FX, Sonuga-Barke EJ, Scheres A, Di Martino A, Hyde C, Walters JR. Varieties of attention-deficit/hyperactivity disorder-related intra-individual variability. Biol Psychiatry. 2005 Jun 1;57(11):1416-23. doi: 10.1016/j.biopsych.2004.12.005. Epub 2005 Jan 28.

  PMID: 15950016 RESULT

• Castells X, Ramos-Quiroga JA, Rigau D, Bosch R, Nogueira M, Vidal X, Casas M. Efficacy of methylphenidate for adults with attention-deficit hyperactivity disorder: a meta-regression analysis. CNS Drugs. 2011 Feb;25(2):157-69. doi: 10.2165/11539440-000000000-00000.

  PMID: 21254791 RESULT

• Chabot RJ, Orgill AA, Crawford G, Harris MJ, Serfontein G. Behavioral and electrophysiologic predictors of treatment response to stimulants in children with attention disorders. J Child Neurol. 1999 Jun;14(6):343-51. doi: 10.1177/088307389901400601.

  PMID: 10385840 RESULT

• Cheng J, Xiong Z, Duffney LJ, Wei J, Liu A, Liu S, Chen GJ, Yan Z. Methylphenidate exerts dose-dependent effects on glutamate receptors and behaviors. Biol Psychiatry. 2014 Dec 15;76(12):953-62. doi: 10.1016/j.biopsych.2014.04.003. Epub 2014 Apr 12.

  PMID: 24832867 RESULT

• Cherma MD, Josefsson M, Rydberg I, Woxler P, Trygg T, Hollertz O, Gustafsson PA. Methylphenidate for Treating ADHD: A Naturalistic Clinical Study of Methylphenidate Blood Concentrations in Children and Adults With Optimized Dosage. Eur J Drug Metab Pharmacokinet. 2017 Apr;42(2):295-307. doi: 10.1007/s13318-016-0346-1.

  PMID: 27220743 RESULT

• Clarke AR, Barry RJ, McCarthy R, Selikowitz M, Croft RJ. EEG differences between good and poor responders to methylphenidate in boys with the inattentive type of attention-deficit/hyperactivity disorder. Clin Neurophysiol. 2002 Aug;113(8):1191-8. doi: 10.1016/s1388-2457(02)00147-5.

  PMID: 12139997 RESULT

• Clavenna A, Bonati M. Safety of medicines used for ADHD in children: a review of published prospective clinical trials. Arch Dis Child. 2014 Sep;99(9):866-72. doi: 10.1136/archdischild-2013-304170. Epub 2014 Apr 19.

  PMID: 24748641 RESULT

• Coghill DR, Seth S, Pedroso S, Usala T, Currie J, Gagliano A. Effects of methylphenidate on cognitive functions in children and adolescents with attention-deficit/hyperactivity disorder: evidence from a systematic review and a meta-analysis. Biol Psychiatry. 2014 Oct 15;76(8):603-15. doi: 10.1016/j.biopsych.2013.10.005. Epub 2013 Oct 12.

  PMID: 24231201 RESULT

• Cortese S, Adamo N, Del Giovane C, Mohr-Jensen C, Hayes AJ, Carucci S, Atkinson LZ, Tessari L, Banaschewski T, Coghill D, Hollis C, Simonoff E, Zuddas A, Barbui C, Purgato M, Steinhausen HC, Shokraneh F, Xia J, Cipriani A. Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis. Lancet Psychiatry. 2018 Sep;5(9):727-738. doi: 10.1016/S2215-0366(18)30269-4. Epub 2018 Aug 7.

  PMID: 30097390 RESULT

• Depue BE, Burgess GC, Willcutt EG, Ruzic L, Banich MT. Inhibitory control of memory retrieval and motor processing associated with the right lateral prefrontal cortex: evidence from deficits in individuals with ADHD. Neuropsychologia. 2010 Nov;48(13):3909-17. doi: 10.1016/j.neuropsychologia.2010.09.013. Epub 2010 Sep 21.

  PMID: 20863843 RESULT

• Desman C, Petermann F, Hampel P. Deficit in response inhibition in children with attention deficit/hyperactivity disorder (ADHD): impact of motivation? Child Neuropsychol. 2008 Nov;14(6):483-503. doi: 10.1080/09297040701625831.

  PMID: 18982507 RESULT

• Dhar M, Been PH, Minderaa RB, Althaus M. Information processing differences and similarities in adults with dyslexia and adults with Attention Deficit Hyperactivity Disorder during a Continuous Performance Test: a study of cortical potentials. Neuropsychologia. 2010 Aug;48(10):3045-56. doi: 10.1016/j.neuropsychologia.2010.06.014. Epub 2010 Jun 17.

  PMID: 20600194 RESULT

• Douglas VI, Barr RG, Amin K, O'Neill ME, Britton BG. Dosage effects and individual responsivity to methylphenidate in attention deficit disorder. J Child Psychol Psychiatry. 1988 Jul;29(4):453-75. doi: 10.1111/j.1469-7610.1988.tb00737.x.

  PMID: 3063718 RESULT

• Epstein JN, Conners CK, Hervey AS, Tonev ST, Arnold LE, Abikoff HB, Elliott G, Greenhill LL, Hechtman L, Hoagwood K, Hinshaw SP, Hoza B, Jensen PS, March JS, Newcorn JH, Pelham WE, Severe JB, Swanson JM, Wells K, Vitiello B, Wigal T; MTA Cooperative Study Group. Assessing medication effects in the MTA study using neuropsychological outcomes. J Child Psychol Psychiatry. 2006 May;47(5):446-56. doi: 10.1111/j.1469-7610.2005.01469.x.

  PMID: 16671928 RESULT

• Epstein JN, Langberg JM, Rosen PJ, Graham A, Narad ME, Antonini TN, Brinkman WB, Froehlich T, Simon JO, Altaye M. Evidence for higher reaction time variability for children with ADHD on a range of cognitive tasks including reward and event rate manipulations. Neuropsychology. 2011 Jul;25(4):427-441. doi: 10.1037/a0022155.

  PMID: 21463041 RESULT

• Evans SW, Owens JS, Bunford N. Evidence-based psychosocial treatments for children and adolescents with attention-deficit/hyperactivity disorder. J Clin Child Adolesc Psychol. 2014;43(4):527-51. doi: 10.1080/15374416.2013.850700. Epub 2013 Nov 18.

  PMID: 24245813 RESULT

• Faraone SV, Buitelaar J. Comparing the efficacy of stimulants for ADHD in children and adolescents using meta-analysis. Eur Child Adolesc Psychiatry. 2010 Apr;19(4):353-64. doi: 10.1007/s00787-009-0054-3. Epub 2009 Sep 10.

  PMID: 19763664 RESULT

• Fayyad J, De Graaf R, Kessler R, Alonso J, Angermeyer M, Demyttenaere K, De Girolamo G, Haro JM, Karam EG, Lara C, Lepine JP, Ormel J, Posada-Villa J, Zaslavsky AM, Jin R. Cross-national prevalence and correlates of adult attention-deficit hyperactivity disorder. Br J Psychiatry. 2007 May;190:402-9. doi: 10.1192/bjp.bp.106.034389.

  PMID: 17470954 RESULT

• Fredriksen M, Egeland J, Haavik J, Fasmer OB. Individual Variability in Reaction Time and Prediction of Clinical Response to Methylphenidate in Adult ADHD: A Prospective Open Label Study Using Conners' Continuous Performance Test II. J Atten Disord. 2021 Mar;25(5):657-671. doi: 10.1177/1087054719829822. Epub 2019 Feb 14.

  PMID: 30762452 RESULT

• Friehs MA, Frings C. Pimping inhibition: Anodal tDCS enhances stop-signal reaction time. J Exp Psychol Hum Percept Perform. 2018 Dec;44(12):1933-1945. doi: 10.1037/xhp0000579. Epub 2018 Oct 8.

  PMID: 30299126 RESULT

• Friehs MA, Frings C. Cathodal tDCS increases stop-signal reaction time. Cogn Affect Behav Neurosci. 2019 Oct;19(5):1129-1142. doi: 10.3758/s13415-019-00740-0.

  PMID: 31313248 RESULT

• Fonteneau C, Redoute J, Haesebaert F, Le Bars D, Costes N, Suaud-Chagny MF, Brunelin J. Frontal Transcranial Direct Current Stimulation Induces Dopamine Release in the Ventral Striatum in Human. Cereb Cortex. 2018 Jul 1;28(7):2636-2646. doi: 10.1093/cercor/bhy093.

  PMID: 29688276 RESULT

• Fukai M, Bunai T, Hirosawa T, Kikuchi M, Ito S, Minabe Y, Ouchi Y. Endogenous dopamine release under transcranial direct-current stimulation governs enhanced attention: a study with positron emission tomography. Transl Psychiatry. 2019 Mar 15;9(1):115. doi: 10.1038/s41398-019-0443-4.

  PMID: 30877269 RESULT

• Gajria K, Lu M, Sikirica V, Greven P, Zhong Y, Qin P, Xie J. Adherence, persistence, and medication discontinuation in patients with attention-deficit/hyperactivity disorder - a systematic literature review. Neuropsychiatr Dis Treat. 2014 Aug 22;10:1543-69. doi: 10.2147/NDT.S65721. eCollection 2014.

  PMID: 25187718 RESULT

• Guven A, Altinkaynak M, Dolu N, Demirci E, Ozmen S, Izzetoglu M, Pektas F. Effects of Methylphenidate on Reaction Time in Children with Attention Deficit / Hyperactivity Disorder. Noro Psikiyatr Ars. 2019 Mar;56(1):27-31. doi: 10.29399/npa.22873. Epub 2018 Apr 20.

  PMID: 30911234 RESULT

• Hervey AS, Epstein JN, Curry JF, Tonev S, Eugene Arnold L, Keith Conners C, Hinshaw SP, Swanson JM, Hechtman L. Reaction time distribution analysis of neuropsychological performance in an ADHD sample. Child Neuropsychol. 2006 Apr;12(2):125-40. doi: 10.1080/09297040500499081.

  PMID: 16754533 RESULT

• Hughes ME, Budd TW, Fulham WR, Lancaster S, Woods W, Rossell SL, Michie PT. Sustained brain activation supporting stop-signal task performance. Eur J Neurosci. 2014 Apr;39(8):1363-9. doi: 10.1111/ejn.12497. Epub 2014 Feb 16.

  PMID: 24528168 RESULT

• Huss M, Duhan P, Gandhi P, Chen CW, Spannhuth C, Kumar V. Methylphenidate dose optimization for ADHD treatment: review of safety, efficacy, and clinical necessity. Neuropsychiatr Dis Treat. 2017 Jul 4;13:1741-1751. doi: 10.2147/NDT.S130444. eCollection 2017.

  PMID: 28740389 RESULT

• Hood J, Baird G, Rankin PM, Isaacs E. Immediate effects of methylphenidate on cognitive attention skills of children with attention-deficit-hyperactivity disorder. Dev Med Child Neurol. 2005 Jun;47(6):408-14. doi: 10.1017/s0012162205000794.

  PMID: 15934489 RESULT

• Inglis SK, Carucci S, Garas P, Hage A, Banaschewski T, Buitelaar JK, Dittmann RW, Falissard B, Hollis C, Kovshoff H, Liddle E, McCarthy S, Nagy P, Neubert A, Rosenthal E, Sonuga-Barke E, Wong I, Zuddas A, Coghill DC; ADDUCE Consortium. Prospective observational study protocol to investigate long-term adverse effects of methylphenidate in children and adolescents with ADHD: the Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) study. BMJ Open. 2016 Apr 26;6(4):e010433. doi: 10.1136/bmjopen-2015-010433.

  PMID: 27118284 RESULT

• Iyer MB, Mattu U, Grafman J, Lomarev M, Sato S, Wassermann EM. Safety and cognitive effect of frontal DC brain polarization in healthy individuals. Neurology. 2005 Mar 8;64(5):872-5. doi: 10.1212/01.WNL.0000152986.07469.E9.

  PMID: 15753425 RESULT

• Lefaucheur JP, Antal A, Ayache SS, Benninger DH, Brunelin J, Cogiamanian F, Cotelli M, De Ridder D, Ferrucci R, Langguth B, Marangolo P, Mylius V, Nitsche MA, Padberg F, Palm U, Poulet E, Priori A, Rossi S, Schecklmann M, Vanneste S, Ziemann U, Garcia-Larrea L, Paulus W. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS). Clin Neurophysiol. 2017 Jan;128(1):56-92. doi: 10.1016/j.clinph.2016.10.087. Epub 2016 Oct 29.

  PMID: 27866120 RESULT

• Lijffijt M, Kenemans JL, Verbaten MN, van Engeland H. A meta-analytic review of stopping performance in attention-deficit/hyperactivity disorder: deficient inhibitory motor control? J Abnorm Psychol. 2005 May;114(2):216-22. doi: 10.1037/0021-843X.114.2.216.

  PMID: 15869352 RESULT

• Logan GD, Van Zandt T, Verbruggen F, Wagenmakers EJ. On the ability to inhibit thought and action: general and special theories of an act of control. Psychol Rev. 2014 Jan;121(1):66-95. doi: 10.1037/a0035230.

  PMID: 24490789 RESULT

• Lipszyc J, Schachar R. Inhibitory control and psychopathology: a meta-analysis of studies using the stop signal task. J Int Neuropsychol Soc. 2010 Nov;16(6):1064-76. doi: 10.1017/S1355617710000895. Epub 2010 Aug 19.

  PMID: 20719043 RESULT

• Logan GD, Cowan WB, Davis KA. On the ability to inhibit simple and choice reaction time responses: a model and a method. J Exp Psychol Hum Percept Perform. 1984 Apr;10(2):276-91. doi: 10.1037//0096-1523.10.2.276.

  PMID: 6232345 RESULT

• MacDonald SW, Nyberg L, Backman L. Intra-individual variability in behavior: links to brain structure, neurotransmission and neuronal activity. Trends Neurosci. 2006 Aug;29(8):474-80. doi: 10.1016/j.tins.2006.06.011. Epub 2006 Jul 3.

  PMID: 16820224 RESULT

• Mannuzza S, Klein RG, Bessler A, Malloy P, LaPadula M. Adult outcome of hyperactive boys. Educational achievement, occupational rank, and psychiatric status. Arch Gen Psychiatry. 1993 Jul;50(7):565-76. doi: 10.1001/archpsyc.1993.01820190067007.

  PMID: 8317950 RESULT

• Marcos E, Pani P, Brunamonti E, Deco G, Ferraina S, Verschure P. Neural variability in premotor cortex is modulated by trial history and predicts behavioral performance. Neuron. 2013 Apr 24;78(2):249-55. doi: 10.1016/j.neuron.2013.02.006.

  PMID: 23622062 RESULT

• McLaren ME, Nissim NR, Woods AJ. The effects of medication use in transcranial direct current stimulation: A brief review. Brain Stimul. 2018 Jan-Feb;11(1):52-58. doi: 10.1016/j.brs.2017.10.006. Epub 2017 Oct 12.

  PMID: 29066167 RESULT

• Menghini D, Armando M, Calcagni M, Napolitano C, Pasqualetti P, Sergeant JA, Pani P, Vicari S. The influence of Generalized Anxiety Disorder on Executive Functions in children with ADHD. Eur Arch Psychiatry Clin Neurosci. 2018 Jun;268(4):349-357. doi: 10.1007/s00406-017-0831-9. Epub 2017 Aug 1.

  PMID: 28766128 RESULT

• Molina BSG, Hinshaw SP, Swanson JM, Arnold LE, Vitiello B, Jensen PS, Epstein JN, Hoza B, Hechtman L, Abikoff HB, Elliott GR, Greenhill LL, Newcorn JH, Wells KC, Wigal T, Gibbons RD, Hur K, Houck PR; MTA Cooperative Group. The MTA at 8 years: prospective follow-up of children treated for combined-type ADHD in a multisite study. J Am Acad Child Adolesc Psychiatry. 2009 May;48(5):484-500. doi: 10.1097/CHI.0b013e31819c23d0.

  PMID: 19318991 RESULT

• Monte-Silva K, Kuo MF, Hessenthaler S, Fresnoza S, Liebetanz D, Paulus W, Nitsche MA. Induction of late LTP-like plasticity in the human motor cortex by repeated non-invasive brain stimulation. Brain Stimul. 2013 May;6(3):424-32. doi: 10.1016/j.brs.2012.04.011. Epub 2012 Jun 2.

  PMID: 22695026 RESULT

• Nigg JT, Casey BJ. An integrative theory of attention-deficit/ hyperactivity disorder based on the cognitive and affective neurosciences. Dev Psychopathol. 2005 Summer;17(3):785-806. doi: 10.1017/S0954579405050376.

  PMID: 16262992 RESULT

• Nitsche MA, Paulus W. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol. 2000 Sep 15;527 Pt 3(Pt 3):633-9. doi: 10.1111/j.1469-7793.2000.t01-1-00633.x.

  PMID: 10990547 RESULT

• Nitsche MA, Cohen LG, Wassermann EM, Priori A, Lang N, Antal A, Paulus W, Hummel F, Boggio PS, Fregni F, Pascual-Leone A. Transcranial direct current stimulation: State of the art 2008. Brain Stimul. 2008 Jul;1(3):206-23. doi: 10.1016/j.brs.2008.06.004. Epub 2008 Jul 1.

  PMID: 20633386 RESULT

• Nitsche MA, Boggio PS, Fregni F, Pascual-Leone A. Treatment of depression with transcranial direct current stimulation (tDCS): a review. Exp Neurol. 2009 Sep;219(1):14-9. doi: 10.1016/j.expneurol.2009.03.038. Epub 2009 Apr 5.

  PMID: 19348793 RESULT

• Oosterlaan J, Logan GD, Sergeant JA. Response inhibition in AD/HD, CD, comorbid AD/HD + CD, anxious, and control children: a meta-analysis of studies with the stop task. J Child Psychol Psychiatry. 1998 Mar;39(3):411-25.

  PMID: 9670096 RESULT

• Johnson KA, Kelly SP, Bellgrove MA, Barry E, Cox M, Gill M, Robertson IH. Response variability in attention deficit hyperactivity disorder: evidence for neuropsychological heterogeneity. Neuropsychologia. 2007 Mar 2;45(4):630-8. doi: 10.1016/j.neuropsychologia.2006.03.034. Epub 2006 Dec 8.

  PMID: 17157885 RESULT

• Kim S, Stephenson MC, Morris PG, Jackson SR. tDCS-induced alterations in GABA concentration within primary motor cortex predict motor learning and motor memory: a 7 T magnetic resonance spectroscopy study. Neuroimage. 2014 Oct 1;99:237-43. doi: 10.1016/j.neuroimage.2014.05.070. Epub 2014 Jun 3.

  PMID: 24904994 RESULT

• KIRCHNER WK. Age differences in short-term retention of rapidly changing information. J Exp Psychol. 1958 Apr;55(4):352-8. doi: 10.1037/h0043688. No abstract available.

  PMID: 13539317 RESULT

• Klein RM, Castel AD, Pratt J. The effects of memory load on the time course of inhibition of return. Psychon Bull Rev. 2006 Apr;13(2):294-9. doi: 10.3758/bf03193846.

  PMID: 16892997 RESULT

• Klorman R, Brumaghim JT, Fitzpatrick PA, Borgstedt AD. Methylphenidate reduces abnormalities of stimulus classification in adolescents with attention deficit disorder. J Abnorm Psychol. 1992 Feb;101(1):130-8. doi: 10.1037//0021-843x.101.1.130.

  PMID: 1537959 RESULT

• Klorman R, Brumaghim JT, Salzman LF, Strauss J, Borgstedt AD, McBride MC, Loeb S. Effects of methylphenidate on processing negativities in patients with attention-deficit hyperactivity disorder. Psychophysiology. 1990 May;27(3):328-37. doi: 10.1111/j.1469-8986.1990.tb00391.x.

  PMID: 2236435 RESULT

• Klotz JM, Johnson MD, Wu SW, Isaacs KM, Gilbert DL. Relationship between reaction time variability and motor skill development in ADHD. Child Neuropsychol. 2012;18(6):576-85. doi: 10.1080/09297049.2011.625356. Epub 2011 Nov 24.

  PMID: 22111593 RESULT

• Kofler MJ, Rapport MD, Sarver DE, Raiker JS, Orban SA, Friedman LM, Kolomeyer EG. Reaction time variability in ADHD: a meta-analytic review of 319 studies. Clin Psychol Rev. 2013 Aug;33(6):795-811. doi: 10.1016/j.cpr.2013.06.001. Epub 2013 Jun 13.

  PMID: 23872284 RESULT

• Konrad K, Gunther T, Heinzel-Gutenbrunner M, Herpertz-Dahlmann B. Clinical evaluation of subjective and objective changes in motor activity and attention in children with attention-deficit/hyperactivity disorder in a double-blind methylphenidate trial. J Child Adolesc Psychopharmacol. 2005 Apr;15(2):180-90. doi: 10.1089/cap.2005.15.180.

  PMID: 15910203 RESULT

• Krishnan C, Santos L, Peterson MD, Ehinger M. Safety of noninvasive brain stimulation in children and adolescents. Brain Stimul. 2015 Jan-Feb;8(1):76-87. doi: 10.1016/j.brs.2014.10.012. Epub 2014 Oct 28.

  PMID: 25499471 RESULT

• Kuntsi J, Klein C. Intraindividual variability in ADHD and its implications for research of causal links. Curr Top Behav Neurosci. 2012;9:67-91. doi: 10.1007/7854_2011_145.

  PMID: 21769722 RESULT

• Kuo MF, Paulus W, Nitsche MA. Boosting focally-induced brain plasticity by dopamine. Cereb Cortex. 2008 Mar;18(3):648-51. doi: 10.1093/cercor/bhm098. Epub 2007 Jun 24.

  PMID: 17591596 RESULT

• Kuo MF, Paulus W, Nitsche MA. Therapeutic effects of non-invasive brain stimulation with direct currents (tDCS) in neuropsychiatric diseases. Neuroimage. 2014 Jan 15;85 Pt 3:948-60. doi: 10.1016/j.neuroimage.2013.05.117. Epub 2013 Jun 4.

  PMID: 23747962 RESULT

• Palm U, Keeser D, Schiller C, Fintescu Z, Nitsche M, Reisinger E, Padberg F. Skin lesions after treatment with transcranial direct current stimulation (tDCS). Brain Stimul. 2008 Oct;1(4):386-7. doi: 10.1016/j.brs.2008.04.003. Epub 2008 Jun 20. No abstract available.

  PMID: 20633396 RESULT

• Pani P, Menghini D, Napolitano C, Calcagni M, Armando M, Sergeant JA, Vicari S. Proactive and reactive control of movement are differently affected in Attention Deficit Hyperactivity Disorder children. Res Dev Disabil. 2013 Oct;34(10):3104-11. doi: 10.1016/j.ridd.2013.06.032. Epub 2013 Jul 22.

  PMID: 23886755 RESULT

• Pauls AM, O'Daly OG, Rubia K, Riedel WJ, Williams SC, Mehta MA. Methylphenidate effects on prefrontal functioning during attentional-capture and response inhibition. Biol Psychiatry. 2012 Jul 15;72(2):142-9. doi: 10.1016/j.biopsych.2012.03.028. Epub 2012 May 1.

  PMID: 22552046 RESULT

• Polanczyk GV, Willcutt EG, Salum GA, Kieling C, Rohde LA. ADHD prevalence estimates across three decades: an updated systematic review and meta-regression analysis. Int J Epidemiol. 2014 Apr;43(2):434-42. doi: 10.1093/ije/dyt261. Epub 2014 Jan 24.

  PMID: 24464188 RESULT

• Poreisz C, Boros K, Antal A, Paulus W. Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients. Brain Res Bull. 2007 May 30;72(4-6):208-14. doi: 10.1016/j.brainresbull.2007.01.004. Epub 2007 Jan 24.

  PMID: 17452283 RESULT

• Rapport MD, DuPaul GJ, Kelly KL. Attention deficit hyperactivity disorder and methylphenidate: the relationship between gross body weight and drug response in children. Psychopharmacol Bull. 1989;25(2):285-90. No abstract available.

  PMID: 2602521 RESULT

• Rosch KS, Fosco WD, Pelham WE Jr, Waxmonsky JG, Bubnik MG, Hawk LW Jr. Reinforcement and Stimulant Medication Ameliorate Deficient Response Inhibition in Children with Attention-Deficit/Hyperactivity Disorder. J Abnorm Child Psychol. 2016 Feb;44(2):309-21. doi: 10.1007/s10802-015-0031-x.

  PMID: 25985978 RESULT

• Rubia K, Halari R, Cubillo A, Mohammad AM, Brammer M, Taylor E. Methylphenidate normalises activation and functional connectivity deficits in attention and motivation networks in medication-naive children with ADHD during a rewarded continuous performance task. Neuropharmacology. 2009 Dec;57(7-8):640-52. doi: 10.1016/j.neuropharm.2009.08.013. Epub 2009 Aug 26.

  PMID: 19715709 RESULT

• Russell VA, Oades RD, Tannock R, Killeen PR, Auerbach JG, Johansen EB, Sagvolden T. Response variability in Attention-Deficit/Hyperactivity Disorder: a neuronal and glial energetics hypothesis. Behav Brain Funct. 2006 Aug 23;2:30. doi: 10.1186/1744-9081-2-30.

  PMID: 16925830 RESULT

• Simon V, Czobor P, Balint S, Meszaros A, Bitter I. Prevalence and correlates of adult attention-deficit hyperactivity disorder: meta-analysis. Br J Psychiatry. 2009 Mar;194(3):204-11. doi: 10.1192/bjp.bp.107.048827.

  PMID: 19252145 RESULT

• Salehinejad MA, Wischnewski M, Nejati V, Vicario CM, Nitsche MA. Transcranial direct current stimulation in attention-deficit hyperactivity disorder: A meta-analysis of neuropsychological deficits. PLoS One. 2019 Apr 12;14(4):e0215095. doi: 10.1371/journal.pone.0215095. eCollection 2019.

  PMID: 30978259 RESULT

• Schachar R, Ickowicz A, Crosbie J, Donnelly GA, Reiz JL, Miceli PC, Harsanyi Z, Darke AC. Cognitive and behavioral effects of multilayer-release methylphenidate in the treatment of children with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2008 Feb;18(1):11-24. doi: 10.1089/cap.2007.0039.

  PMID: 18294084 RESULT

• Soltaninejad Z, Nejati V, Ekhtiari H. Effect of Anodal and Cathodal Transcranial Direct Current Stimulation on DLPFC on Modulation of Inhibitory Control in ADHD. J Atten Disord. 2019 Feb;23(4):325-332. doi: 10.1177/1087054715618792. Epub 2015 Dec 20.

  PMID: 26689935 RESULT

• Soff C, Sotnikova A, Christiansen H, Becker K, Siniatchkin M. Transcranial direct current stimulation improves clinical symptoms in adolescents with attention deficit hyperactivity disorder. J Neural Transm (Vienna). 2017 Jan;124(1):133-144. doi: 10.1007/s00702-016-1646-y. Epub 2016 Nov 16.

  PMID: 27853926 RESULT

• Solanto MV. Behavioral effects of low-dose methylphenidate in childhood attention deficit disorder: implications for a mechanism of stimulant drug action. J Am Acad Child Psychiatry. 1986 Jan;25(1):96-101. doi: 10.1016/s0002-7138(09)60604-x. No abstract available.

  PMID: 3950273 RESULT

• Solanto MV. Dopamine dysfunction in AD/HD: integrating clinical and basic neuroscience research. Behav Brain Res. 2002 Mar 10;130(1-2):65-71. doi: 10.1016/s0166-4328(01)00431-4.

  PMID: 11864719 RESULT

• Sonuga-Barke EJ, Sergeant JA, Nigg J, Willcutt E. Executive dysfunction and delay aversion in attention deficit hyperactivity disorder: nosologic and diagnostic implications. Child Adolesc Psychiatr Clin N Am. 2008 Apr;17(2):367-84, ix. doi: 10.1016/j.chc.2007.11.008.

  PMID: 18295151 RESULT

• Spencer SV, Hawk LW Jr, Richards JB, Shiels K, Pelham WE Jr, Waxmonsky JG. Stimulant treatment reduces lapses in attention among children with ADHD: the effects of methylphenidate on intra-individual response time distributions. J Abnorm Child Psychol. 2009 Aug;37(6):805-16. doi: 10.1007/s10802-009-9316-2.

  PMID: 19291387 RESULT

• Stein MA, Sarampote CS, Waldman ID, Robb AS, Conlon C, Pearl PL, Black DO, Seymour KE, Newcorn JH. A dose-response study of OROS methylphenidate in children with attention-deficit/hyperactivity disorder. Pediatrics. 2003 Nov;112(5):e404. doi: 10.1542/peds.112.5.e404.

  PMID: 14595084 RESULT

• Tamm L, Narad ME, Antonini TN, O'Brien KM, Hawk LW Jr, Epstein JN. Reaction time variability in ADHD: a review. Neurotherapeutics. 2012 Jul;9(3):500-8. doi: 10.1007/s13311-012-0138-5.

  PMID: 22930417 RESULT

• Tannock R, Ickowicz A, Schachar R. Differential effects of methylphenidate on working memory in ADHD children with and without comorbid anxiety. J Am Acad Child Adolesc Psychiatry. 1995 Jul;34(7):886-96. doi: 10.1097/00004583-199507000-00012.

  PMID: 7649959 RESULT

• Vaurio RG, Simmonds DJ, Mostofsky SH. Increased intra-individual reaction time variability in attention-deficit/hyperactivity disorder across response inhibition tasks with different cognitive demands. Neuropsychologia. 2009 Oct;47(12):2389-96. doi: 10.1016/j.neuropsychologia.2009.01.022. Epub 2009 Jan 22.

  PMID: 19552927 RESULT

• Volkow ND, Wang GJ, Fowler JS, Gatley SJ, Logan J, Ding YS, Hitzemann R, Pappas N. Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. Am J Psychiatry. 1998 Oct;155(10):1325-31. doi: 10.1176/ajp.155.10.1325.

  PMID: 9766762 RESULT

• Wigal SB, Nordbrock E, Adjei AL, Childress A, Kupper RJ, Greenhill L. Efficacy of Methylphenidate Hydrochloride Extended-Release Capsules (Aptensio XR) in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Phase III, Randomized, Double-Blind Study. CNS Drugs. 2015 Apr;29(4):331-40. doi: 10.1007/s40263-015-0241-3.

  PMID: 25877989 RESULT

• 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 Jun 1;57(11):1336-46. doi: 10.1016/j.biopsych.2005.02.006.

  PMID: 15950006 RESULT

• Williams BR, Ponesse JS, Schachar RJ, Logan GD, Tannock R. Development of inhibitory control across the life span. Dev Psychol. 1999 Jan;35(1):205-13. doi: 10.1037//0012-1649.35.1.205.

  PMID: 9923475 RESULT

• Costanzo F, Menghini D, Casula L, Amendola A, Mazzone L, Valeri G, Vicari S. Transcranial Direct Current Stimulation Treatment in an Adolescent with Autism and Drug-Resistant Catatonia. Brain Stimul. 2015 Nov-Dec;8(6):1233-5. doi: 10.1016/j.brs.2015.08.009. Epub 2015 Aug 24. No abstract available.

  PMID: 26590479 RESULT

• Costanzo F, Varuzza C, Rossi S, Sdoia S, Varvara P, Oliveri M, Koch G, Vicari S, Menghini D. Reading changes in children and adolescents with dyslexia after transcranial direct current stimulation. Neuroreport. 2016 Mar 23;27(5):295-300. doi: 10.1097/WNR.0000000000000536.

  PMID: 26848997 RESULT

• Costanzo F, Varuzza C, Rossi S, Sdoia S, Varvara P, Oliveri M, Giacomo K, Vicari S, Menghini D. Evidence for reading improvement following tDCS treatment in children and adolescents with Dyslexia. Restor Neurol Neurosci. 2016;34(2):215-26. doi: 10.3233/RNN-150561.

  PMID: 26890096 RESULT

• Costanzo F, Rossi S, Varuzza C, Varvara P, Vicari S, Menghini D. Long-lasting improvement following tDCS treatment combined with a training for reading in children and adolescents with dyslexia. Neuropsychologia. 2019 Jul;130:38-43. doi: 10.1016/j.neuropsychologia.2018.03.016. Epub 2018 Mar 14.

  PMID: 29550525 RESULT

• Costanzo F, Menghini D, Maritato A, Castiglioni MC, Mereu A, Varuzza C, Zanna V, Vicari S. New Treatment Perspectives in Adolescents With Anorexia Nervosa: The Efficacy of Non-invasive Brain-Directed Treatment. Front Behav Neurosci. 2018 Jul 20;12:133. doi: 10.3389/fnbeh.2018.00133. eCollection 2018.

  PMID: 30083095 RESULT

• Lazzaro G, Bertoni S, Menghini D, Costanzo F, Franceschini S, Varuzza C, Ronconi L, Battisti A, Gori S, Facoetti A, Vicari S. Beyond Reading Modulation: Temporo-Parietal tDCS Alters Visuo-Spatial Attention and Motion Perception in Dyslexia. Brain Sci. 2021 Feb 19;11(2):263. doi: 10.3390/brainsci11020263.

  PMID: 33669651 RESULT

• Lazzaro G, Costanzo F, Varuzza C, Rossi S, Vicari S, Menghini D. Effects of a short, intensive, multi-session tDCS treatment in developmental dyslexia: Preliminary results of a sham-controlled randomized clinical trial. Prog Brain Res. 2021;264:191-210. doi: 10.1016/bs.pbr.2021.01.015.

  PMID: 34167656 RESULT

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Interventions

Methylphenidate; Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Study participants will receive the three conditions in random order: * a single dose of immediate release MPH (Ritalin®) administered according to the AIFA and NICE guidelines for ADHD; * a single 1 mA anodal tDCS session over the DLPFC for 20 min * a single session of sham tDCS over the DLPFC for 30s at the beginning and end of the tDCS session. The order of administration of the conditions will be counterbalanced between the participants and the conditions will be spaced apart from an interval of 24 hours.

Study Record Dates

• First Submitted: July 1, 2021
• First Posted: July 16, 2021
• Study Start: February 8, 2021
• Primary Completion: October 2, 2022
• Study Completion: November 2, 2022
• Last Updated: February 8, 2023

Record last verified: 2023-02

Locations

IT (1)