Pharmacological Modulation of Plasticity in the Human Motor Cortex

Ziemann, Ulf; Meintzschel, Frank; Korchounov, Alexei; Ilić, Tihomir V.

doi:10.1177/1545968306287154

Cited by 94 publications

(60 citation statements)

References 101 publications

(123 reference statements)

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“…This contradiction of GABA-A receptor expression in early and adult brain damage is not surprising since the motor cortex of congenital hemiplegia patients has shown increased metabolism (28) whereas decreased glucose metabolism has been shown in adults damaged by stroke (29). It is well known that cortical disinhibition promotes neural plasticity, especially practice-dependent plasticity (30). Ischemic conditions in the mature brain cause transient downregulation of GABA-A receptors in the affected periinfarct viable neurons or contralateral hemisphere because of extracellular liberation of excessive GABA, thereby prompting practicedependent plasticity in the motor cortex (31).…”

Section: Discussionmentioning

confidence: 99%

Increased GABA-A Receptor Binding and Reduced Connectivity at the Motor Cortex in Children with Hemiplegic Cerebral Palsy: A Multimodal Investigation Using ¹⁸F-Fluoroflumazenil PET, Immunohistochemistry, and MR Imaging

Kim

Park

et al. 2013

J Nucl Med

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Section: Discussionmentioning

confidence: 99%

Increased GABA-A Receptor Binding and Reduced Connectivity at the Motor Cortex in Children with Hemiplegic Cerebral Palsy: A Multimodal Investigation Using ¹⁸F-Fluoroflumazenil PET, Immunohistochemistry, and MR Imaging

Kim

Park

et al. 2013

J Nucl Med

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“…Both explanations are compatible with the observation that SICI is also reduced in patients with cortical lesions not affecting the primary motor cortex (38). Because reduced SICI enhances plasticity and the capacity for motor learning (43), disinhibition could be interpreted as a prerequisite for use-dependent plasticity within the affected hemisphere. Alternatively, or in addition, reduced SICI may compensate for the lesion-induced reduction of cortical excitatory potentials, maintaining an appropriate corticospinal output to the paretic hand.…”

Section: Discussionmentioning

confidence: 99%

Abnormal Motor Cortex Excitability in Congenital Stroke

et al. 2008

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ABSTRACT:The aim of the present study was to investigate corticospinal and intracortical excitability in patients with congenital stroke. In adults, stroke sequelae reduce corticospinal excitability, as indicated by an elevated threshold for motor evoked potentials (MEP), and increase intracortical excitability, as indicated by reduced intracortical inhibition. Ten patients with pre-or perinatally acquired, unilateral cortico-subcortical infarctions in the middle cerebral artery territory were studied with single pulse transcranial magnetic stimulation (TMS) to measure motor threshold (MT) and with paired pulse TMS to study short interval intracortical inhibition (SICI) and intracortical facilitation (ICF). Eight healthy, age-matched subjects served as controls. MT over the affected hemisphere of patients compared with the dominant hemisphere of controls was significantly elevated, reflecting reduced corticospinal excitability, and SICI was significantly reduced, reflecting increased intracortical excitability. No such differences were found for ICF. Findings in patients with congenital stroke were comparable with adulthood stroke. Thus, similar assumptions can be made: reduced corticospinal excitability is probably a consequence of neuronal damage. Reduced intracortical inhibition might represent deficient inhibitory cortical properties or might reflect a compensational mechanism, dispositioning for use-dependent plasticity. T he human brain is capable of reorganization (1-3). In patients with congenital stroke, reorganization is determined by the maturational state of the brain at the time of the insult (4). Early studies using transcranial magnetic stimulation (TMS) focused on corticospinal connectivity and revealed in some patients preserved ipsilateral motor pathways from the undamaged motor cortex to the hemiplegic hand (5-9). Subsequent studies combining TMS with structural and functional magnetic resonance imaging (MRI) revealed that the type of corticospinal reorganization as well as the compensatory recruitment of areas within the contralesional hemisphere depend on the extent of the underlying brain lesion (10). Furthermore, location and timing period affect the type and efficacy of reorganization, with significant impact on clinical outcome (11).Until now, studies investigating intracortical excitability by transcranial magnetic paired pulse stimulation have been conducted only in patients with adulthood stroke (12-15). This technique allows us to study changes in the excitability of both inhibitory and excitatory intracortical circuits, a mechanism credited to be involved in reorganization of the brain (16 -19). In adulthood, cortical stroke intracortical excitability is increased, as indicated by a reduced intracortical inhibition with a heightened amplitude of the conditioned motor evoked potential (MEP) (12-15). There is evidence from developmental studies that corticospinal excitability as well as intracortical excitability are age dependent and are not fully established up to several years post...

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“…We expected significant modulating effects on PAS-induced LTP-like plasticity. These findings are pertinent to the setting of clinical neurorehabilitation, where NMDs may have detrimental or beneficial effects on the long-term outcome of sensorimotor function in stroke patients (Goldstein, 1995;Ziemann et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Neuromodulatory Neurotransmitters Influence LTP-Like Plasticity in Human Cortex: A Pharmaco-TMS Study

Korchounov

Ziemann

2011

Neuropsychopharmacol

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Long-term potentiation (LTP) of synaptic efficacy is considered a fundamental mechanism of learning and memory. At the cellular level a large body of evidence demonstrated that the major neuromodulatory neurotransmitters dopamine (DA), norepinephrine (NE), and acetylcholine (ACh) influence LTP magnitude. Noninvasive brain stimulation protocols provide the opportunity to study LTP-like plasticity at the systems level of human cortex. Here we applied paired associative stimulation (PAS) to induce LTP-like plasticity in the primary motor cortex of eight healthy subjects. In a double-blind, randomized, placebo-controlled, crossover design, the acute effects of a single oral dose of the neuromodulatory drugs cabergoline (DA agonist), haloperidol (DA antagonist), methylphenidate (indirect NE agonist), prazosine (NE antagonist), tacrine (ACh agonist), and biperiden (ACh antagonist) on PAS-induced LTP-like plasticity were examined. The antagonists haloperidol, prazosine, and biperiden depressed significantly the PAS-induced LTP-like plasticity observed under placebo, whereas the agonists cabergoline, methylphenidate, and tacrine had no effect. Findings demonstrate that antagonists in major neuromodulatory neurotransmitter systems suppress LTP-like plasticity at the systems level of human cortex, in accord with evidence of their modulating action of LTP at the cellular level. This provides further supportive evidence for the known detrimental effects of these drugs on LTP-dependent mechanisms such as learning and memory.

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Pharmacological Modulation of Plasticity in the Human Motor Cortex

Cited by 94 publications

References 101 publications

Increased GABA-A Receptor Binding and Reduced Connectivity at the Motor Cortex in Children with Hemiplegic Cerebral Palsy: A Multimodal Investigation Using ¹⁸F-Fluoroflumazenil PET, Immunohistochemistry, and MR Imaging

Increased GABA-A Receptor Binding and Reduced Connectivity at the Motor Cortex in Children with Hemiplegic Cerebral Palsy: A Multimodal Investigation Using ¹⁸F-Fluoroflumazenil PET, Immunohistochemistry, and MR Imaging

Abnormal Motor Cortex Excitability in Congenital Stroke

Neuromodulatory Neurotransmitters Influence LTP-Like Plasticity in Human Cortex: A Pharmaco-TMS Study

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Pharmacological Modulation of Plasticity in the Human Motor Cortex

Cited by 94 publications

References 101 publications

Increased GABA-A Receptor Binding and Reduced Connectivity at the Motor Cortex in Children with Hemiplegic Cerebral Palsy: A Multimodal Investigation Using 18F-Fluoroflumazenil PET, Immunohistochemistry, and MR Imaging

Increased GABA-A Receptor Binding and Reduced Connectivity at the Motor Cortex in Children with Hemiplegic Cerebral Palsy: A Multimodal Investigation Using 18F-Fluoroflumazenil PET, Immunohistochemistry, and MR Imaging

Abnormal Motor Cortex Excitability in Congenital Stroke

Neuromodulatory Neurotransmitters Influence LTP-Like Plasticity in Human Cortex: A Pharmaco-TMS Study

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Increased GABA-A Receptor Binding and Reduced Connectivity at the Motor Cortex in Children with Hemiplegic Cerebral Palsy: A Multimodal Investigation Using ¹⁸F-Fluoroflumazenil PET, Immunohistochemistry, and MR Imaging

Increased GABA-A Receptor Binding and Reduced Connectivity at the Motor Cortex in Children with Hemiplegic Cerebral Palsy: A Multimodal Investigation Using ¹⁸F-Fluoroflumazenil PET, Immunohistochemistry, and MR Imaging