Interplay of neuronal processes during response inhibition: results from a combined event-related potentials (ERPs)/transcranial magnetic stimulation (TMS) study on methylphenidate.

The neuronal processes underlying response inhibition are often studied using either event-related potentials (ERPs) or by applying transcranial magnetic stimulation (TMS) to investigate excitatory and inhibitory processes in the motor system. We performed a more refined analysis of response inhibition by combining both approaches with the aim of identifying an interplay between ERPs and TMS parameters. During a go/nogo task, motor system excitability was measured using TMS single and double pulses and brain electrical activity was recorded in healthy adults (n=14). Each participant completed two testing sessions, once on placebo and once on methylphenidate (double-blind, crossover design). Studying the effects of methylphenidate served as an example application for this combined approach. Developing regression models, inhibition-related TMS measures (e.g., short intracortical inhibition) and the contingent negative variation explained about 85% of the variance of the nogo-P3 under both MPH and placebo medication. The smaller the inhibitory effect in the motor system, the more terminal response control was required and the more resources were allocated for the evaluation of the inhibitory process, respectively, as indicated by a larger P3. Thus, an interplay between processes in the motor system (cortex) and control processes with sources in the prefrontal cortex and the anterior cingulate cortex (ACC) may take place, acting complementarily to facilitate a correct nogo-response. While ERPs rather represent initiation and monitoring of inhibitory processes and response control, motor inhibition may be best analyzed using TMS. A combined ERP/TMS analysis may allow for the development of distinct models concerning the interplay of processes involved in response inhibition.

[1]  C. Marsden,et al.  Corticocortical inhibition in human motor cortex. , 1993, The Journal of physiology.

[2]  H. Sackeim,et al.  Magnetoelectric brain stimulation in the assessment of brain physiology and pathophysiology , 2000, Clinical Neurophysiology.

[3]  R. Cooper,et al.  Brain slow potential and ERP changes associated with operator load in a visual tracking task. , 1988, Electroencephalography and clinical neurophysiology.

[4]  K. Rubia,et al.  Impaired response inhibition in obsessive compulsive disorder , 2007, European Psychiatry.

[5]  W. Walter,et al.  Contingent Negative Variation : An Electric Sign of Sensori-Motor Association and Expectancy in the Human Brain , 1964, Nature.

[6]  J. Rothwell,et al.  Magnetic transcranial stimulation at intensities below active motor threshold activates intracortical inhibitory circuits , 1998, Experimental Brain Research.

[7]  R. Ryan,et al.  Effect of methylphenidate on young adult's vigilance and event-related potentials. , 1981, Electroencephalography and clinical neurophysiology.

[8]  J. Kenemans,et al.  Electrophysiological correlates of attention, inhibition, sensitivity and bias in a continuous performance task , 2004, Clinical Neurophysiology.

[9]  R. Benecke,et al.  Modulation of transcallosally mediated motor inhibition in children with attention deficit hyperactivity disorder (ADHD) by medication with methylphenidate (MPH) , 2006, Neuroscience Letters.

[10]  D Brandeis,et al.  Neuroelectric mapping reveals precursor of stop failures in children with attention deficits , 1998, Behavioural Brain Research.

[11]  M. Falkenstein,et al.  Effects of stimulus–response compatibility on inhibitory processes in Parkinson’s disease , 2009, The European journal of neuroscience.

[12]  L. Cardon,et al.  Genetic etiology of comorbid reading difficulties and ADHD. , 2003 .

[13]  H. Heinrich,et al.  Methylphenidate and intracortical excitability: opposite effects in healthy subjects and attention‐deficit hyperactivity disorder , 2003, Acta psychiatrica Scandinavica.

[14]  J. Ford,et al.  ERPs to response production and inhibition. , 1985, Electroencephalography and clinical neurophysiology.

[15]  M. Spronk,et al.  Response inhibition and attention processing in 5- to 7-year-old children with and without symptoms of ADHD: An ERP study , 2008, Clinical Neurophysiology.

[16]  M. Hallett,et al.  Event-related desynchronization in reaction time paradigms: a comparison with event-related potentials and corticospinal excitability , 2001, Clinical Neurophysiology.

[17]  J C Rothwell,et al.  Releasing the brakes before pressing the gas pedal , 1999, Neurology.

[18]  E Donchin,et al.  A new method for off-line removal of ocular artifact. , 1983, Electroencephalography and clinical neurophysiology.

[19]  R Kakigi,et al.  Temporal changes of pyramidal tract activities after decision of movement: a study using transcranial magnetic stimulation of the motor cortex in humans. , 1997, Electroencephalography and clinical neurophysiology.

[20]  K. R. Ridderinkhof,et al.  The effect of speed-accuracy strategy on response interference control in Parkinson's disease , 2009, Neuropsychologia.

[21]  K. J. Bruin,et al.  Response priming in a go/nogo task: do we have to explain the go/nogo N2 effect in terms of response activation instead of inhibition? , 2001, Clinical Neurophysiology.

[22]  H. Heinrich,et al.  Methylphenidate enhances both intracortical inhibition and facilitation in healthy adults. , 2003, Pharmacopsychiatry.

[23]  G. Band,et al.  Inhibitory motor control in stop paradigms: review and reinterpretation of neural mechanisms. , 1999, Acta psychologica.

[24]  J. Nigg,et al.  Is ADHD a disinhibitory disorder? , 2001, Psychological bulletin.

[25]  A. Barker,et al.  NON-INVASIVE MAGNETIC STIMULATION OF HUMAN MOTOR CORTEX , 1985, The Lancet.

[26]  J. Hohnsbein,et al.  ERP components in Go/Nogo tasks and their relation to inhibition. , 1999, Acta psychologica.

[27]  Stewart H. Mostofsky,et al.  Response Inhibition and Response Selection: Two Sides of the Same Coin , 2008, Journal of Cognitive Neuroscience.

[28]  A. Fallgatter,et al.  The NoGo-anteriorization as a neurophysiological standard-index for cognitive response control. , 1999, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[29]  D. Dietrich,et al.  Effects of methylphenidate in ADHD adults on target evaluation processing reflected by event-related potentials , 2007, Neuroscience Letters.

[30]  Borís Burle,et al.  Mechanisms and Dynamics of Cortical Motor Inhibition in the Stop-signal Paradigm: A TMS Study , 2010, Journal of Cognitive Neuroscience.

[31]  Babak Boroojerdi,et al.  Pharmacologic Influences on TMS Effects , 2002, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[32]  R. C. Oldfield The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[33]  M Hallett,et al.  Human corticospinal excitability evaluated with transcranial magnetic stimulation during different reaction time paradigms. , 2000, Brain : a journal of neurology.

[34]  Patrick Ragert,et al.  Contribution of transcranial magnetic stimulation to the understanding of cortical mechanisms involved in motor control , 2008, The Journal of physiology.

[35]  W. Byblow,et al.  Intracortical inhibition during volitional inhibition of prepared action. , 2006, Journal of neurophysiology.

[36]  H. Heinrich,et al.  Effects of methylphenidate on motor system excitability in a response inhibition task , 2009, Behavioral and Brain Functions.

[37]  H. Heinrich,et al.  Transcranial magnetic stimulation in child psychiatry: disturbed motor system excitability in hypermotoric syndromes , 2002 .

[38]  Mark Hallett,et al.  Effect of volitional inhibition on cortical inhibitory mechanisms. , 2002, Journal of neurophysiology.

[39]  G. Logan,et al.  Response inhibition in the stop-signal paradigm , 2008, Trends in Cognitive Sciences.

[40]  J. Kenemans,et al.  Methylphenidate Restores Link Between Stop-Signal Sensory Impact and Successful Stopping in Adults with Attention-Deficit/Hyperactivity Disorder , 2009, Biological Psychiatry.

[41]  H. Heinrich,et al.  Deficient intracortical inhibition in drug-naive children with attention-deficit hyperactivity disorder is enhanced by methylphenidate , 2000, Neuroscience Letters.

[42]  M. Rieger,et al.  Inhibition of ongoing responses in patients with Parkinson’s disease , 2004, Journal of Neurology, Neurosurgery & Psychiatry.

[43]  John J. Foxe,et al.  Changing plans: a high density electrical mapping study of cortical control. , 2003, Cerebral cortex.

[44]  Carlo Miniussi,et al.  TMS-EEG co-registration: On TMS-induced artifact , 2009, Clinical Neurophysiology.

[45]  Winston D. Byblow,et al.  Primary motor cortex and movement prevention: Where Stop meets Go , 2009, Neuroscience & Biobehavioral Reviews.

[46]  B. Kopp,et al.  N2, P3 and the lateralized readiness potential in a nogo task involving selective response priming. , 1996, Electroencephalography and clinical neurophysiology.

[47]  R. Benecke,et al.  Restoration of Disturbed Intracortical Motor Inhibition and Facilitation in Attention Deficit Hyperactivity Disorder Children by Methylphenidate , 2007, Biological Psychiatry.

[48]  J. Rothwell,et al.  Cortical potentials related to the nogo decision , 2000, Experimental Brain Research.

[49]  F. Earls,et al.  Psychometric properties of impulsivity measures: temporal stability, validity and factor structure. , 1995, Journal of child psychology and psychiatry, and allied disciplines.

[50]  Tobias Banaschewski,et al.  Annotation: what electrical brain activity tells us about brain function that other techniques cannot tell us - a child psychiatric perspective. , 2007, Journal of child psychology and psychiatry, and allied disciplines.