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01-02-2010 | Biological Psychiatry - Original Article

Modulation of motorcortical excitability by methylphenidate in adult voluntary test persons performing a go/nogo task

Authors: Johannes Buchmann, A. Dueck, W. Gierow, H. Zamorski, S. Heinicke, H. Heinrich, J. Hoeppner, T. Klauer, O. Reis, F. Haessler

Published in: Journal of Neural Transmission | Issue 2/2010

Abstract

This study investigated the interaction between motorcortical excitability (short interval cortical inhibition, intracortical facilitation and long interval cortical inhibition), different requirement conditions [choice reaction test (CRT), attention/go/nogo], and their pharmacological modulation by methylphenidate (MPH) in normal healthy adults (n = 31) using a transcranial magnetic stimulation paradigm. MPH was administered in a dosage of 1 mg/kg body weight, maximum 60 mg. Additionally, serum level and clearance of MPH were controlled. The statistical analysis of variance revealed a significant three-way interaction of 2 (MPH) × 3 (CRT) × 6 (ISI) predicting motor evoked potential amplitudes (P = 0.032, MPH none and full dose, n = 31). In order to compare effects of dosage an additional between-subjects factor (half vs. full MPH dose) was introduced. None of the interactions involving this between-subject factor reached statistical significance. Exploring interactions with MPH only, a 3 (MPH none, half and full dose) × 3 (CRT) × 6 (ISI) analysis of variance revealed significant two-way interactions for MPH × ISI (P = 0.040) and condition × ISI (P < 0.001, n = 18). Effects observed for MPH were strongest on facilitatory processes, weaker for intracortical inhibition. In sum, MPH seems to interact via striato–thalamo–cortical pathways with original motorcortical processes (ISI), to a lesser extent with task-dependent or behavioral parameters (CRT).

Arnsten AF, Dudley AG (2005) Methylphenidate improves prefrontal cortical cognitive function through alpha2 adrenoceptor and dopamine D1 receptor actions: relevance to therapeutic effects in Attention Deficit Hyperactivity Disorder. Behav Brain Funct 1:2CrossRefPubMed

Arnsten AF, Li BM (2005) Neurobiology of executive functions: catecholamine influences on prefrontal cortical functions. Biol Psychiatry 57:1377–1384CrossRefPubMed

Brickenkamp R (2002) Aufmerksamkeits-Belastungs-Test d2. Hogrefe, Göttingen

Buchmann J, Wolters A, Haessler F, Bohne S, Nordbeck R, Kunesch E (2003) Disturbed transcallosally mediated motor inhibition in children with attention deficit hyperactivity disorder (ADHD). Clin Neurophysiol 114:2036–2042CrossRefPubMed

Buchmann J, Gierow W, Weber S, Hoeppner J, Klauer T, Wittstock M, Benecke R, Haessler F, Wolters A (2006) Modulation of transcallosally mediated motor inhibition in children with attention deficit hyperactivity disorder (ADHD) by medication with methylphenidate (MPH). Neurosci Lett 405(1–2):14–18CrossRefPubMed

Buchmann J, Gierow W, Weber S, Hoeppner J, Klauer T, Benecke R, Haessler F, Wolters A (2007) Restoration of disturbed intracortical motor inhibition and facilitation in attention deficit hyperactivity disorder children by methylphenidate. Biol Psychiatry 62:963–969CrossRefPubMed

Challman TD, Lipsky JJ (2000) Methylphenidate: its pharmacology and uses. Mayo Clin Proc 75:711–721CrossRefPubMed

Chen R (2004) Interactions between inhibitory and excitatory circuits in the human motor cortex. Exp Brain Res 154:1–10CrossRefPubMed

Conte A, Belvisi D, Iezzi E, Mari F, Inghilleri M, Berardelli A (2008) Effects of attention on inhibitory and facilitatory phenomena elicited by paired-pulse transcranial magnetic stimulation in healthy subjects. Exp Brain Res 186:393–399CrossRefPubMed

Coxon JP, Stinear CM, Byblow WD (2007) Selective inhibition of movement. J Neurophysiol 97:2480–2489CrossRefPubMed

Coxon JP, Stinear CM, Byblow WD (2009) Stop and go: the neural basis of selective movement prevention. J Cogn Neurosci 21:1193–1203CrossRefPubMed

Di Lazzaro V, Restuccia D, Oliviero A, Profice P, Ferrara L, Insola A, Mazzone P, Tonali P, Rothwell JC (1998) Magnetic transcranial stimulation at intensities below active motor threshold activates intracortical inhibitory circuits. Exp Brain Res 119:265–268CrossRefPubMed

Federici M, Geracitano R, Bernardi G, Mercuri NB (2005) Actions of methylphenidate on dopaminergic neurons of the ventral midbrain. Biol Psychiatry 57:361–365CrossRefPubMed

Fisher RJ, Nakamura Y, Bestmann S, Rothwell JC, Bostock H (2002) Two phases of intracortical inhibition revealed by transcranial magnetic threshold tracking. Exp Brain Res 143:240–248CrossRefPubMed

Florian J, Muller-Dahlhaus M, Liu Y, Ziemann U (2008) Inhibitory circuits and the nature of their interactions in the human motor cortex a pharmacological TMS study. J Physiol 586:495–514CrossRefPubMed

Gainetdinov RR, Wetsel WC, Jones SR, Levin ED, Jaber M, Caron MG (1999) Role of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity. Science 283:397–401CrossRefPubMed

Gao WJ, Goldman-Rakic PS (2003) Selective modulation of excitatory and inhibitory microcircuits by dopamine. Proc Natl Acad Sci USA 100:2836–2841CrossRefPubMed

Gao WJ, Krimer LS, Goldman-Rakic PS (2001) Presynaptic regulation of recurrent excitation by D1 receptors in prefrontal circuits. Proc Natl Acad Sci USA 98:295–300CrossRefPubMed

Garattini S, Mennini T (1988) Critical notes on the specificity of drugs in the study of metabolism and functions of brain monoamines. Int Rev Neurobiol 29:259–280CrossRefPubMed

Gilbert DL, Sallee FR, Zhang J, Lipps TD, Wassermann EM (2005) Transcranial magnetic stimulation-evoked cortical inhibition: a consistent marker of attention-deficit/hyperactivity disorder scores in tourette syndrome. Biol Psychiatry 57:1597–1600CrossRefPubMed

Gilbert DL, Ridel KR, Sallee FR, Zhang J, Lipps TD, Wassermann EM (2006) Comparison of the inhibitory and excitatory effects of ADHD medications methylphenidate and atomoxetine on motor cortex. Neuropsychopharmacology 31:442–449CrossRefPubMed

Hoeppner J, Neumeyer M, Wandschneider R, Herpertz SC, Gierow W, Haessler F, Buchmann J (2008a) Intracortical motor inhibition and facilitation in adults with attention deficit/hyperactivity disorder. J Neural Transm 115:1701–1707CrossRefPubMed

Hoeppner J, Wandschneider R, Neumeyer M, Gierow W, Haessler F, Herpertz SC, Buchmann J (2008b) Impaired transcallosally mediated motor inhibition in adults with attention-deficit/hyperactivity disorder is modulated by methylphenidate. J Neural Transm 115:777–785CrossRefPubMed

Hwa GG, Avoli M (1992) Excitatory postsynaptic potentials recorded from regular-spiking cells in layers II/III of rat sensorimotor cortex. J Neurophysiol 67:728–737PubMed

Ilic TV, Meintzschel F, Cleff U, Ruge D, Kessler KR, Ziemann U (2002) Short-interval paired-pulse inhibition and facilitation of human motor cortex: the dimension of stimulus intensity. J Physiol 545:153–167CrossRefPubMed

Ilic TV, Korchounov A, Ziemann U (2003) Methylphenidate facilitates and disinhibits the motor cortex in intact humans. Neuroreport 14:773–776CrossRefPubMed

Kinoshita H, Yahagi S, Kasai T (2007) Preparatory suppression of the human primary motor cortex induced by repetition of simple and choice reaction time tasks: a transcranial magnetic stimulation study. Brain Res 1184:132–140CrossRefPubMed

Kirschner J, Moll GH, Fietzek UM, Heinrich H, Mall V, Berweck S, Heinen F, Rothenberger A (2003) Methylphenidate enhances both intracortical inhibition and facilitation in healthy adults. Pharmacopsychiatry 36:79–82CrossRefPubMed

Kratz O, Diruf MS, Studer P, Gierow W, Buchmann J, Moll GH, Heinrich H (2009) Effects of methylphenidate on motor system excitability in a response inhibition task. Behav Brain Funct 5:12CrossRefPubMed

Kujirai T, Caramia MD, Rothwell JC, Day BL, Thompson PD, Ferbert A, Wroe S, Asselman P, Marsden CD (1993) Corticocortical inhibition in human motor cortex. J Physiol 471:501–519PubMed

Leocani L, Cohen LG, Wassermann EM, Ikoma K, Hallett M (2000) Human corticospinal excitability evaluated with transcranial magnetic stimulation during different reaction time paradigms. Brain 123(Pt 6):1161–1173CrossRefPubMed

Liepert J, Schwenkreis P, Tegenthoff M, Malin JP (1997) The glutamate antagonist riluzole suppresses intracortical facilitation. J Neural Transm 104:1207–1214CrossRefPubMed

Maffei C, Fossati A, Agostoni I, Barraco A, Bagnato M, Deborah D, Namia C, Novella L, Petrachi M (1997) Interrater reliability and internal consistency of the structured clinical interview for DSM-IV axis II personality disorders (SCID-II), version 2.0. J Pers Disord 11:279–284PubMed

Mall V, Berweck S, Fietzek UM, Glocker FX, Oberhuber U, Walther M, Schessl J, Schulte-Monting J, Korinthenberg R, Heinen F (2004) Low level of intracortical inhibition in children shown by transcranial magnetic stimulation. Neuropediatrics 35:120–125CrossRefPubMed

McDonnell MN, Orekhov Y, Ziemann U (2006) The role of GABA(B) receptors in intracortical inhibition in the human motor cortex. Exp Brain Res 173:86–93CrossRefPubMed

Mink JW (1996) The basal ganglia: focused selection and inhibition of competing motor programs. Prog Neurobiol 50:381–425CrossRefPubMed

Moll GH, Heinrich H, Wischer S, Tergau F, Paulus W, Rothenberger A (1999) Motor system excitability in healthy children: developmental aspects from transcranial magnetic stimulation. Electroencephalogr Clin Neurophysiol Suppl 51:243–249PubMed

Moll GH, Heinrich H, Trott G, Wirth S, Rothenberger A (2000) Deficient intracortical inhibition in drug-naive children with attention-deficit hyperactivity disorder is enhanced by methylphenidate. Neurosci Lett 284:121–125CrossRefPubMed

Moll GH, Heinrich H, Rothenberger A (2003) Methylphenidate and intracortical excitability: opposite effects in healthy subjects and attention-deficit hyperactivity disorder. Acta Psychiatr Scand 107:69–72CrossRefPubMed

Nakamura H, Kitagawa H, Kawaguchi Y, Tsuji H (1997) Intracortical facilitation and inhibition after transcranial magnetic stimulation in conscious humans. J Physiol (Lond) 498:817–823

Nakata H, Inui K, Wasaka T, Tamura Y, Akatsuka K, Kida T, Kakigi R (2006) Higher anticipated force required a stronger inhibitory process in go/nogo tasks. Clin Neurophysiol 117:1669–1676CrossRefPubMed

Nambu A, Tokuno H, Takada M (2002) Functional significance of the cortico–subthalamo–pallidal ‘hyperdirect’ pathway. Neurosci Res 43:111–117CrossRefPubMed

Patrick KS, Caldwell RW, Ferris RM, Breese GR (1987) Pharmacology of the enantiomers of threo-methylphenidate. J Pharmacol Exp Ther 241:152–158PubMed

Paulus W, Classen J, Cohen LG, Large DH, DiLazarro V, Nitsche M, Pascual-Leone A, Rosenow F, Rothwell JC, Ziemann U (2008) State of the art: Pharmacologic effects on cortical excitability measures tested by transcranial magnetic stimulation. Brain Stimulat 1:151–163CrossRef

Peurala SH, Muller-Dahlhaus JF, Arai N, Ziemann U (2008) Interference of short-interval intracortical inhibition (SICI) and short-interval intracortical facilitation (SICF). Clin Neurophysiol 119:2291–2297CrossRefPubMed

Porrino LJ, Lucignani G (1987) Different patterns of local brain energy metabolism associated with high and low doses of methylphenidate. Relevance to its action in hyperactive children. Biol Psychiatry 22:126–138CrossRefPubMed

Reis J, Swayne OB, Vandermeeren Y, Camus M, Dimyan MA, Harris-Love M, Perez MA, Ragert P, Rothwell JC, Cohen LG (2008) Contribution of transcranial magnetic stimulation to the understanding of cortical mechanisms involved in motor control. J Physiol 586:325–351CrossRefPubMed

Richter MM, Ehlis AC, Jacob CP, Fallgatter AJ (2007) Cortical excitability in adult patients with attention-deficit/hyperactivity disorder (ADHD). Neurosci Lett 419:137–141CrossRefPubMed

Roshan L, Paradiso GO, Chen R (2003) Two phases of short-interval intracortical inhibition. Exp Brain Res 151:330–337CrossRefPubMed

Rossini PM, Barker AT, Berardelli A, Caramia MD, Caruso G, Cracco RQ, Dimitrijevic MR, Hallett M, Katayama Y, Lucking CH et al (1994) Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application. Report of an IFCN committee. Electroencephalogr Clin Neurophysiol 91:79–92CrossRef

Rothwell JC, Hallett M, Berardelli A, Eisen A, Rossini P, Paulus W (1999) Magnetic stimulation: motor evoked potentials. The International Federation of Clinical Neurophysiology. Electroencephalogr Clin Neurophysiol Suppl 52:97–103PubMed

Sanger TD, Garg RR, Chen R (2001) Interactions between two different inhibitory systems in the human motor cortex. J Physiol 530:307–317CrossRefPubMed

Sohn YH, Wiltz K, Hallett M (2002) Effect of volitional inhibition on cortical inhibitory mechanisms. J Neurophysiol 88:333–338PubMed

Sohn YH, Dang N, Hallett M (2003) Suppression of corticospinal excitability during negative motor imagery. J Neurophysiol 90:2303–2309CrossRefPubMed

Sonuga-Barke EJ (2005) Causal models of attention-deficit/hyperactivity disorder: from common simple deficits to multiple developmental pathways. Biol Psychiatry 57:1231–1238CrossRefPubMed

Spitzer RL, Williams JB, Gibbon M, First MB (1992) The structured clinical interview for DSM-III-R (SCID). I: history, rationale, and description. Arch Gen Psychiatry 49:624–629PubMed

Srinivas NR, Hubbard JW, Quinn D, Midha KK (1992) Enantioselective pharmacokinetics and pharmacodynamics of dl-threo-methylphenidate in children with attention deficit hyperactivity disorder. Clin Pharmacol Ther 52:561–568PubMed

Srinivas NR, Hubbard JW, Korchinski ED, Midha KK (1993) Enantioselective pharmacokinetics of dl-threo-methylphenidate in humans. Pharm Res 10:14–21CrossRefPubMed

Stinear CM, Coxon JP, Byblow WD (2009) Primary motor cortex and movement prevention: where Stop meets Go. Neurosci Biobehav Rev 33:662–673CrossRefPubMed

Strafella AP, Paus T (2001) Cerebral blood-flow changes induced by paired-pulse transcranial magnetic stimulation of the primary motor cortex. J Neurophysiol 85:2624–2629PubMed

Valls-Sole J, Pascual-Leone A, Wassermann EM, Hallett M (1992) Human motor evoked responses to paired transcranial magnetic stimuli. Electroencephalogr Clin Neurophysiol 85:355–364CrossRefPubMed

Volkow ND, Ding YS, Fowler JS, Wang GJ, Logan J, Gatley JS, Dewey S, Ashby C, Liebermann J, Hitzemann R et al (1995) Is methylphenidate like cocaine? Studies on their pharmacokinetics and distribution in the human brain. Arch Gen Psychiatry 52:456–463PubMed

Volkow ND, Wang GJ, Fowler JS, Gatley SJ, Logan J, Ding YS, Hitzemann R, Pappas N (1998) Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. Am J Psychiatry 155:1325–1331PubMed

Volkow ND, Gatley SJ, Fowler JS, Wang GJ, Swanson J (2000) Serotonin and the therapeutic effects of ritalin. Science 288:11CrossRefPubMed

Volkow ND, Wang G, Fowler JS, Logan J, Gerasimov M, Maynard L, Ding Y, Gatley SJ, Gifford A, Franceschi D (2001) Therapeutic doses of oral methylphenidate significantly increase extracellular dopamine in the human brain. J Neurosci 21:RC121PubMed

Volkow ND, Wang GJ, Fowler JS, Logan J, Franceschi D, Maynard L, Ding YS, Gatley SJ, Gifford A, Zhu W, Swanson JM (2002) Relationship between blockade of dopamine transporters by oral methylphenidate and the increases in extracellular dopamine: therapeutic implications. Synapse 43:181–187CrossRefPubMed

Wassermann EM, Samii A, Mercuri B, Ikoma K, Oddo D, Grill SE, Hallett M (1996) Responses to paired transcranial magnetic stimuli in resting, active, and recently activated muscles. Exp Brain Res 109:158–163CrossRefPubMed

Werhahn KJ, Kunesch E, Noachtar S, Benecke R, Classen J (1999) Differential effects on motorcortical inhibition induced by blockade of GABA uptake in humans. J Physiol 517:591–597CrossRefPubMed

Williams JB, Gibbon M, First MB, Spitzer RL, Davies M, Borus J, Howes MJ, Kane J, Pope HG Jr, Rounsaville B et al (1992) The structured clinical interview for DSM-III-R (SCID). II. Multisite test–retest reliability. Arch Gen Psychiatry 49:630–636PubMed

Yamanaka K, Kimura T, Miyazaki M, Kawashima N, Nozaki D, Nakazawa K, Yano H, Yamamoto Y (2002) Human cortical activities during Go/NoGo tasks with opposite motor control paradigms. Exp Brain Res 142:301–307CrossRefPubMed

Ziemann U, Rothwell JC, Ridding MC (1996) Interaction between intracortical inhibition and facilitation in human motor cortex. J Physiol 496:873–881PubMed

Title: Modulation of motorcortical excitability by methylphenidate in adult voluntary test persons performing a go/nogo task
Authors: Johannes Buchmann
A. Dueck
W. Gierow
H. Zamorski
S. Heinicke
H. Heinrich
J. Hoeppner
T. Klauer
O. Reis
F. Haessler
Publication date: 01-02-2010
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 2/2010
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-009-0349-z

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Modulation of motorcortical excitability by methylphenidate in adult voluntary test persons performing a go/nogo task

Abstract

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Abstract

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