ABSTRACT
Seeking for the mechanisms by which methylphenidate (MPH) improves behavior has demonstrated that MPH modulates excitability in the primary motor cortex. However, little is known about the influence of MPH on top-down controlled mechanisms in the sensory domain. The present study explored the effects of MPH on the activation of visual cortices in healthy adults who performed a cued visuo-motor task in a double-blind placebo-controlled crossover design. Two distinct measures, posterior alpha power and occipital slow cortical potentials (SCPs), were used to reflect raise in excitability and attention-based activation of visual cortical areas. According to the results, performance parameters (reaction time, response variance and error rate) were not affected by MPH. At the neurophysiologic level reflected by reduced alpha power, MPH increased the overall excitability of the occipital cortex, but not the parietal cortex. Before the cued response, MPH reduced alpha power and increased SCPs only before right hand responses, mostly at the right occipital location. It can be concluded that in visuo-motor tasks, MPH has the potency of adjusting the background excitation/inhibition balance of visual areas. Additionally, MPH may raise the attention controlled activation of visual cortical regions, especially during increased response control.
Subject(s)
Central Nervous System Stimulants/pharmacology , Cues , Evoked Potentials, Visual/drug effects , Methylphenidate/pharmacology , Psychomotor Performance/drug effects , Visual Cortex/drug effects , Adult , Analysis of Variance , Double-Blind Method , Electroencephalography , Female , Functional Laterality , Humans , Male , Neuropsychological Tests , Photic Stimulation , Psychomotor Performance/physiology , Reaction Time/drug effects , Visual Cortex/physiology , Young AdultABSTRACT
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.
Subject(s)
Central Nervous System Stimulants/pharmacology , Contingent Negative Variation/drug effects , Evoked Potentials, Motor/drug effects , Methylphenidate/pharmacology , Motor Cortex/drug effects , Neural Inhibition/drug effects , Adult , Analysis of Variance , Contingent Negative Variation/physiology , Cross-Over Studies , Double-Blind Method , Electroencephalography/methods , Electromyography/methods , Evoked Potentials, Motor/physiology , Female , Humans , Male , Neural Inhibition/physiology , Neuropsychological Tests , Numerical Analysis, Computer-Assisted , Reaction Time/drug effects , Transcranial Magnetic Stimulation/methods , Young AdultABSTRACT
The objective of the study was to investigate neuronal processing during the encoding, retention and retrieval phases of a serial visual working memory task. Particularly, we were interested in how these phases are affected by working memory load and how processing is modulated by methylphenidate. Healthy adults were asked to memorize the order of four, five or six pictures under methylphenidate (20mg) and under placebo while brain electrical activity was recorded. On the performance level, the number of correct responses decreased with increasing working memory load. Concerning brain electrical activity, in the encoding phase P3 amplitudes increased at midline electrodes with increasing memory load while load had no effect in the retention and retrieval phase. Medication neither influenced performance nor the different processing stages significantly. Our data provide evidence that during the encoding phase more attentional resources are allocated in trials with higher load as reflected by larger P3 amplitudes.
Subject(s)
Adrenergic Uptake Inhibitors/pharmacology , Dopamine Uptake Inhibitors/pharmacology , Evoked Potentials, Visual/drug effects , Memory, Short-Term/drug effects , Methylphenidate/pharmacology , Serial Learning/drug effects , Visual Perception/drug effects , Adult , Brain/drug effects , Brain/physiology , Electroencephalography , Female , Humans , Male , Mental Recall/drug effects , Retention, Psychology/drug effectsABSTRACT
BACKGROUND: Motor system excitability is based on a complex interaction of excitatory and inhibitory processes, which in turn are modulated by internal (e.g., volitional inhibition) and external (e.g., drugs) factors. A well proven tool to investigate motor system excitability in vivo is the transcranial magnetic stimulation (TMS). In this study, we used TMS to investigate the effects of methylphenidate (MPH) on the temporal dynamics of motor system excitability during a go/nogo task. METHODS: Using a double-blind, placebo-controlled, crossover design, 14 healthy adults (8 male, 6 female; aged 20-40 yrs) performed a spatial go/nogo task (S1-S2 paradigm) either under dl-methylphenidate (MPH, 20 mg) or placebo. TMS single and double-pulses (interstimulus interval: 3 ms) were delivered either at 120, 230 or 350 ms after the S2 stimulus (control, go and nogo trials). RESULTS: At the performance level, faster reaction times and a trend towards less impulsivity errors under MPH vs. placebo were observed.In nogo trials, i.e., when a prepared response had to be inhibited, motor evoked potentials (MEPs) had a smaller amplitude at an interval of 230 ms compared to 120 and 350 ms. The short-interval intracortical inhibition (SICI) increased over time.Under MPH, SICI in nogo trials was larger compared to placebo. With the interval between S2 and the TMS-pulse increasing, MEP amplitudes increased under MPH in nogo trials but an early inhibitory effect (at 120 ms) could also be observed. CONCLUSION: Our results show a distinct pattern of excitatory and inhibitory phenomena in a go/nogo task. MPH appears to significantly alter the dynamics of motor system excitability. Our findings suggest that a single dose of 20 mg MPH provides some fine-tuning of the motor system in healthy adults.
