Consolidation of Human Motor Cortical Neuroplasticity by D-Cycloserine

Nitsche, Michael A.; Jaussi, Wiebke; Liebetanz, David; Lang, N.; Tergau, Frithjof; Paulus, Walter

doi:10.1038/sj.npp.1300517

Cited by 340 publications

(207 citation statements)

References 39 publications

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“…In the current study, participants who received DCS showed greater potentiation of the VEP following HFvS compared with participants who received placebo. This is consistent with prior findings that DCS augmented increases in motor cortex excitability following anodal transcranial direct-current stimulation in humans (37) and augmented LTP in rat hippocampus following high-frequency electrical stimulation (38,39). Our finding is also consistent with preclinical studies demonstrating that potentiation of the VEP following HFvS is NMDAR dependent (8).…”

Section: Discussionsupporting

confidence: 93%

Augmenting NMDA receptor signaling boosts experience-dependent neuroplasticity in the adult human brain

Forsyth

Bachman

Mathalon

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Experience-dependent plasticity is a fundamental property of the brain. It is critical for everyday function, is impaired in a range of neurological and psychiatric disorders, and frequently depends on long-term potentiation (LTP). Preclinical studies suggest that augmenting N-methyl-D-aspartate receptor (NMDAR) signaling may promote experience-dependent plasticity; however, a lack of noninvasive methods has limited our ability to test this idea in humans until recently. We examined the effects of enhancing NMDAR signaling using D-cycloserine (DCS) on a recently developed LTP EEG paradigm that uses high-frequency visual stimulation (HFvS) to induce neural potentiation in visual cortex neurons, as well as on three cognitive tasks: a weather prediction task (WPT), an information integration task (IIT), and a n-back task. The WPT and IIT are learning tasks that require practice with feedback to reach optimal performance. The n-back assesses working memory. Healthy adults were randomized to receive DCS (100 mg; n = 32) or placebo (n = 33); groups were similar in IQ and demographic characteristics. Participants who received DCS showed enhanced potentiation of neural responses following repetitive HFvS, as well as enhanced performance on the WPT and IIT. Groups did not differ on the n-back. Augmenting NMDAR signaling using DCS therefore enhanced activitydependent plasticity in human adults, as demonstrated by lasting enhancement of neural potentiation following repetitive HFvS and accelerated acquisition of two learning tasks. Results highlight the utility of considering cellular mechanisms underlying distinct cognitive functions when investigating potential cognitive enhancers.D-cycloserine | NMDA receptor | neuroplasticity | long-term potentiation | learning E xperience-dependent neuroplasticity is the capacity of the brain to change in response to environmental input, learning, and use. It is a fundamental property of the brain and is critical for everyday functioning. It allows us to learn and remember patterns, predict and obtain reward, and refine and accelerate response selection for adaptive behavior (1). During development, experience-dependent plasticity interacts with genetic programming to organize neurons into the structurally and functionally connected circuits that characterize a mature brain. Although this basic circuitry is established by early adulthood, experience-dependent plasticity continues to shape connectivity within these circuits such that important inputs and action outputs are represented by larger and more coordinated populations of neurons. Given that these changes are the primary means through which the adult brain enables new behavior and that such plasticity is impaired in a range of neurological and psychiatric disorders (2), identifying manipulations that can harness experiencedependent plasticity offers exciting possibilities. Here, we tested whether augmenting N-methyl-D-aspartate receptor (NMDAR) activity could enhance experience-dependent plasticity in the adult human brain.The ...

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Section: Discussionsupporting

confidence: 93%

Augmenting NMDA receptor signaling boosts experience-dependent neuroplasticity in the adult human brain

Forsyth

Bachman

Mathalon

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Whereas the effects of brief stimulation lasting for a few seconds seem to be solely based on membrane potential changes, longer-lasting stimulation for a few minutes induces lasting changes in cortical excitability, which can be stable for about one hour or even longer. These neuroplastic after-effects are assumed to be caused by a change in the strength of glutamatergic synapses, are calcium-dependent [19,20] , and thus share some similarities with long-term potentiation and depression, as found in animal studies [21] .…”

Section: Physiology Of Transcranial Electrical Stimulationmentioning

confidence: 99%

Exploring prefrontal cortex functions in healthy humans by transcranial electrical stimulation

Kuo

Nitsche²

2015

Neurosci. Bull.

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The prefrontal cortex is involved in a multitude of cognitive, emotional, motivational, and social processes, so exploring its specifi c functions is crucial for understanding human experience and behavior. Functional imaging approaches have largely contributed to the enhancement of our understanding, but might have limitations in establishing causal relationships between physiology and the related psychological and behavioral processes. Non-invasive electrical stimulation with direct or alternating currents can help to enhance our understanding with regard to specific processes, and might provide future protocols able to improve them in case of malfunctions. We review the current state of the fi eld, and provide an outlook for future developments.

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“…tDCS induces plasticity by a tonic modulation of resting membrane potentials Paulus, 2000, 2001;Nitsche et al, 2003aNitsche et al, , 2008. The aftereffects of tDCS, like those of PAS, depend on NMDA receptor and calcium channel activity (Nitsche et al, 2003b(Nitsche et al, , 2004. However, contrary to PAS, which is thought to induce plasticity at somatosensory-motor cortical synapses activated by both peripheral nerve and transcranial magnetic stimulation of the motor cortex, plasticity induction by tDCS is thought not to be restricted to specific synaptic subgroups because of the completely different stimulation protocol: in tDCS, the relatively large stimulation electrodes, which deliver a continuous current flow for some minutes, are thought to affect the majority of neurons beneath the electrodes (Nitsche et al, 2007, Purpura andMcMurtry, 1965) and thus the effects are much less restricted or focal.…”

Section: Proposed Mechanisms Of Actionmentioning

confidence: 99%

Dose-Dependent Nonlinear Effect of l-DOPA on Paired Associative Stimulation-Induced Neuroplasticity in Humans

Thirugnanasambandam

Grundey²,

Paulus³

et al. 2011

J. Neurosci.

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Dopamine is one of the major neuromodulators in the CNS, which is involved in learning and memory processes. A nonlinear, inverted U-shaped dose-response curve of its effects on cognition has been observed in animal studies. The basis for this nonlinear effect might be a similar effect of dopamine on neuroplasticity. Whereas it has been shown that dopamine affects paired associative stimulation (PAS)-induced plasticity, which might reflect learning-related processes to a larger degree than other noninvasive plasticity induction protocols in the human motor cortex in principle, its dose-dependency has not been explored previously. We studied the effect of different dosages of the dopamine precursor L-DOPA on motor cortex plasticity induced by facilitatory and inhibitory PAS of the motor cortex in 12 healthy humans. They received 25, 100, or 200 mg of L-DOPA or placebo medication combined with either excitability-enhancing or -diminishing PAS. Cortical excitability level was monitored before and for up to 2 d after plasticity induction by assessment of transcranial magnetic stimulation-induced motor-evoked potentials. Low-dose L-DOPA abolished the aftereffects of PAS and medium-dose L-DOPA prolonged facilitatory plasticity. High-dose L-DOPA reversed the excitability enhancement accomplished by facilitatory PAS to diminution. Thus, the results show a clear nonlinear effect of L-DOPA dosage on associative plasticity, different from that on nonfocal plasticity. This might help to explain dopaminergic effect on cognition and could be relevant for understanding the pathophysiology and treatment of neuropsychiatric diseases accompanied by alterations of the dopaminergic system.

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Consolidation of Human Motor Cortical Neuroplasticity by D-Cycloserine

Cited by 340 publications

References 39 publications

Augmenting NMDA receptor signaling boosts experience-dependent neuroplasticity in the adult human brain

Augmenting NMDA receptor signaling boosts experience-dependent neuroplasticity in the adult human brain

Exploring prefrontal cortex functions in healthy humans by transcranial electrical stimulation

Dose-Dependent Nonlinear Effect of l-DOPA on Paired Associative Stimulation-Induced Neuroplasticity in Humans

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