Contingent negative variation as a dopaminergic biomarker: evidence from dose-related effects of methylphenidate

Linssen, A.M.W.; Vuurman, E.F.P.M.; Sambeth, Anke; Navé, Stephane; Spooren, Will; Vargas, Gabriel; Santarelli, Luca; Riedel, Wim J.

doi:10.1007/s00213-011-2345-x

Cited by 70 publications

(43 citation statements)

References 41 publications

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“…This is consistent with the notion that MPH speeds up response time in healthy volunteers (Elliott et al, 1997), reflecting response-readiness enhancing effects (Linssen et al, 2011).…”

Section: Speed Of Processingsupporting

confidence: 91%

“…Another component assessed in the studies listed in Table 4 was the Contingent Negative Variation (CNV). MPH was observed to enhance CNV amplitude, reflecting increased response readiness (Coons et al, 1981;Linssen et al, 2011). Event-related desynchronization, measured during a visual search task, was not affected by MPH (Oken et al, 1995).…”

Section: Imaging Studies On Cognitive Performance Under the Influencementioning

confidence: 88%

See 1 more Smart Citation

Cognitive effects of methylphenidate in healthy volunteers: a review of single dose studies

Linssen

Sambeth

Vuurman

et al. 2014

Int. J. Neuropsychopharm.

124

100

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Methylphenidate (MPH), a stimulant drug with dopamine and noradrenaline reuptake inhibition properties, is mainly prescribed in attention deficit hyperactivity disorder, is increasingly used by the general population, intending to enhance their cognitive function. In this literature review, we aim to answer whether this is effective. We present a novel way to determine the extent to which MPH enhances cognitive performance in a certain domain. Namely, we quantify this by a percentage that reflects the number of studies showing performance enhancing effects of MPH. To evaluate whether the dose-response relationship follows an inverted-U-shaped curve, MPH effects on cognition are also quantified for low, medium and high doses, respectively. The studies reviewed here show that single doses of MPH improve cognitive performance in the healthy population in the domains of working memory (65% of included studies) and speed of processing (48%), and to a lesser extent may also improve verbal learning and memory (31%), attention and vigilance (29%) and reasoning and problem solving (18%), but does not have an effect on visual learning and memory. MPH effects are dose-dependent and the dose-response relationship differs between cognitive domains. MPH use is associated with side effects and other adverse consequences, such as potential abuse. Future studies should focus on MPH specifically to adequately asses its benefits in relation to the risks specific to this drug.

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“…This is consistent with the notion that MPH speeds up response time in healthy volunteers (Elliott et al, 1997), reflecting response-readiness enhancing effects (Linssen et al, 2011).…”

Section: Speed Of Processingsupporting

confidence: 91%

Section: Imaging Studies On Cognitive Performance Under the Influencementioning

confidence: 88%

Cognitive effects of methylphenidate in healthy volunteers: a review of single dose studies

Linssen

Sambeth

Vuurman

et al. 2014

Int. J. Neuropsychopharm.

124

100

View full text Add to dashboard Cite

show abstract

“…In a recent study, methylphenidate was found to increase CNV-amplitudes (Linssen et al, 2011). Most of the children with ADHD in the present study received treatment with methylphenidate.…”

Section: Methodological Issuessupporting

confidence: 51%

Cortical inhibition in attention deficit hyperactivity disorder: new insights from the electroencephalographic response to transcranial magnetic stimulation

Bruckmann

Hauk

Roessner

et al. 2012

Brain

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Attention deficit hyperactivity disorder is one of the most frequent neuropsychiatric disorders in childhood. Transcranial magnetic stimulation studies based on muscle responses (motor-evoked potentials) suggested that reduced motor inhibition contributes to hyperactivity, a core symptom of the disease. Here we employed the N100 component of the electroencephalographic response to transcranial magnetic stimulation as a novel marker for a direct assessment of cortical inhibitory processes, which has not been examined in attention deficit hyperactivity disorder so far. We further investigated to what extent affected children were able to regulate motor cortical inhibition, and whether effects of age on the electroencephalographic response to transcranial magnetic stimulation were compatible with either a delay in brain maturation or a qualitatively different development. N100 amplitude evoked by transcranial magnetic stimulation and its age-dependent development were assessed in 20 children with attention deficit hyperactivity disorder and 19 healthy control children (8-14 years) by 64-channel electroencephalography. Amplitude and latency of the N100 component were compared at rest, during response preparation in a forewarned motor reaction time task and during movement execution. The amplitude of the N100 component at rest was significantly lower and its latency tended to be shorter in children with attention deficit hyperactivity disorder. Only in controls, N100 amplitude to transcranial magnetic stimulation was reduced by response preparation. During movement execution, N100 amplitude decreased while motor evoked potential amplitudes showed facilitation, indicating that the electroencephalographic response to transcranial magnetic stimulation provides further information on cortical excitability independent of motor evoked potential amplitudes and spinal influences. Children with attention deficit hyperactivity disorder showed a smaller N100 amplitude reduction during movement execution compared with control children. The N100 amplitude evoked by transcranial magnetic stimulation decreased with increasing age in both groups. The N100 reduction in children with attention deficit hyperactivity disorder at all ages suggests a qualitative difference rather than delayed development of cortical inhibition in this disease. Findings further suggest that top-down control of motor cortical inhibition is reduced in children with attention deficit hyperactivity disorder. We conclude that evoked potentials in response to transcranial magnetic stimulation are a promising new marker of cortical inhibition in attention deficit hyperactivity disorder during childhood.

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“…Patient research and studies with healthy individuals have indicated that the CNV might be related to the dopaminergic system (e.g., Amabile et al, 1986; Gerschlager et al, 1999; Linssen et al, 2011). Consequently, the observed interaction between task difficulty and reward in this component appears to be consistent with the results of the previous fMRI study of Krebs et al (2012) showing a very similar interaction pattern in the dopaminergic midbrain with highest activation levels in respond to cues that predicted both reward and high difficulty.…”

Section: Discussionmentioning

confidence: 99%

Task preparation processes related to reward prediction precede those related to task-difficulty expectation

et al. 2014

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Recently, attempts have been made to disentangle the neural underpinnings of preparatory processes related to reward and attention. Functional magnetic resonance imaging (fMRI) research showed that neural activity related to the anticipation of reward and to attentional demands invokes neural activity patterns featuring large-scale overlap, along with some differences and interactions. Due to the limited temporal resolution of fMRI, however, the temporal dynamics of these processes remain unclear. Here, we report an event-related potentials (ERP) study in which cued attentional demands and reward prospect were combined in a factorial design. Results showed that reward prediction dominated early cue processing, as well as the early and later parts of the contingent negative variation (CNV) slow-wave ERP component that has been associated with task-preparation processes. Moreover these reward-related electrophysiological effects correlated across participants with response-time speeding on reward-prospect trials. In contrast, cued attentional demands affected only the later part of the CNV, with the highest amplitudes following cues predicting high-difficulty potential-reward targets, thus suggesting maximal task preparation when the task requires it and entails reward prospect. Consequently, we suggest that task-preparation processes triggered by reward can arise earlier, and potentially more directly, than strategic top-down aspects of preparation based on attentional demands.

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Contingent negative variation as a dopaminergic biomarker: evidence from dose-related effects of methylphenidate

Cited by 70 publications

References 41 publications

Cognitive effects of methylphenidate in healthy volunteers: a review of single dose studies

Cognitive effects of methylphenidate in healthy volunteers: a review of single dose studies

Cortical inhibition in attention deficit hyperactivity disorder: new insights from the electroencephalographic response to transcranial magnetic stimulation

Task preparation processes related to reward prediction precede those related to task-difficulty expectation

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