Critical role of glutamatergic and GABAergic neurotransmission in the central mechanisms of theta‐burst stimulation

Li, Cheng Ta; Huang, Yufei; Bai, Ya‐Mei; Tsai, Shih‐Jen; Su, Tung‐Ping; Cheng, Chih‐Ming

doi:10.1002/hbm.24485

Cited by 55 publications

(47 citation statements)

References 65 publications

(165 reference statements)

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“…Importantly, growing consensus suggests the role of inhibitory circuits in regulating human motor cortical plasticity . Therefore, in RTT, defects in cortical inhibitory connectivity might also explain alteration in motor plasticity.…”

Section: Discussionmentioning

confidence: 98%

Neurophysiological Signatures of Motor Impairment in Patients with Rett Syndrome

Bernardo

Cobb

Coppola

et al. 2020

Annals of Neurology

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Objective: Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder due to pathogenic mutations in the MECP2 gene. Motor impairment constitutes the core diagnostic feature of RTT. Preclinical studies have consistently demonstrated alteration of excitation/inhibition (E/I) balance and aberrant synaptic plasticity at the cortical level. We aimed to understand neurobiological mechanisms underlying motor deficit by assessing in vivo synaptic plasticity and E/I balance in the primary motor cortex (M1). Methods: In 14 patients with typical RTT, 9 epilepsy control patients, and 11 healthy controls, we applied paired-pulse transcranial magnetic stimulation (TMS) protocols to evaluate the excitation index, a biomarker reflecting the contribution of inhibitory and facilitatory circuits in M1. Intermittent TMS-theta burst stimulation was used to probe long-term potentiation (LTP)-like plasticity in M1. Motor impairment, assessed by ad hoc clinical scales, was correlated with neurophysiological metrics. Results: RTT patients displayed a significant increase of the excitation index (p = 0.003), as demonstrated by the reduction of short-interval intracortical inhibition and increase of intracortical facilitation, suggesting a shift toward cortical excitation likely due to GABAergic dysfunction. Impairment of inhibitory circuits was also confirmed by the reduction of long-interval intracortical inhibition (p = 0.002). LTP-like plasticity in M1 was abolished (p = 0.008) and scaled with motor disability (all p = 0.003). Interpretation: TMS is a method that can be used to assess cortical motor function in RTT patients. Our findings support the introduction of TMS measures in clinical and research settings to monitor the progression of motor deficit and response to treatment. ANN NEUROL 2020;87:763-773 R ett syndrome (RTT) is the second most common cause of severe intellectual disability in females and is usually the result of dominantly acting mutations in the X-linked gene MECP2, which encodes methyl-CpG-binding protein 2 (MeCP2). 1 MeCP2 is expressed quite widely throughout the body, with notably high expression in postnatal neurons. 2,3 The currently used diagnostic criteria for RTT include an early neurologic regression occurring after an initially normal development that severely affects motor, cognitive, and communication skills. 4 Motor impairment constitutes the core diagnostic features of RTT, such as partial or complete loss of acquired purposeful hand skills and spoken language, the development of gait abnormalities, stereotypic hand movements, and the View this article online at wileyonlinelibrary.com.

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Section: Discussionmentioning

confidence: 98%

Neurophysiological Signatures of Motor Impairment in Patients with Rett Syndrome

Bernardo

Cobb

Coppola

et al. 2020

Annals of Neurology

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“…However, the varying responses to TBS could be related to the difference in the motor function role between hands (mainly fine motor control) and legs (mainly cyclic movement, such as a gait). The different responsibilities in the brain may affect the responsiveness of synaptic plasticity induced by TBS (Li et al, 2019). A study reported that TBS induces significant cortical plasticity in hand muscles, whereas no significant response was observed in arm muscles (Martin et al, 2006).…”

Section: Interindividual Variability In Corticospinal Excitability Chmentioning

confidence: 99%

“…The original TBS article suggests that TBS modulates synaptic plasticity in the circuits under the TMS coil, involving corticospinal excitability for MEPs, inhibitory circuits for SICI, and facilitatory circuits for ICF simultaneously (Huang et al, 2005). Review articles further suggest that both GABAergic and glutamatergic neurotransmission play a crucial in the induction of plasticity by TBS (Suppa et al, 2016;Huang et al, 2017;Li et al, 2019). It is also well-known that SICI is mediated by GABAergic interneurons and ICF could be mediated by glutamatergic interneurons (Ziemann et al, 2015).…”

Section: Relationship Between the Effects Of Tbs And Neurophysiologicmentioning

confidence: 99%

“…To investigate the variability of TBS-induced synaptic plasticity on lower-limb motor cortex, we used three protocols of TBS (iTBS, cTBS, and sham iTBS) to modulate corticospinal and intracortical excitability. Furthermore, inhibitory or facilitatory interneurons play important roles in the TBS-induced plasticity of the cortical excitability of stimulated regions (Suppa et al, 2016;Li et al, 2019). Thus, we hypothesized that the excitability of intracortical inhibition or facilitation before TBS may be associated with the plastic changes in corticospinal excitability induced by TBS.…”

Section: Introductionmentioning

confidence: 99%

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Interindividual Variability of Lower-Limb Motor Cortical Plasticity Induced by Theta Burst Stimulation

et al. 2020

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“…In contrast, conventional rTMS generally takes more than 15 minutes. That the mechanisms of TBS are also dependent on glutamatergic function 4 has been evidenced by the finding that memantine, which is a NMDA receptor antagonist, blocks the aftereffects of cTBS as well as iTBS.…”

Section: Basic Technology and The Neural Mechanisms Underlying Nibsmentioning

confidence: 99%

Non‐invasive brain stimulation and short‐term cortical plasticity

Ogata

2020

Neurology & Clinical Neurosc

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Non‐invasive brain stimulation (NIBS) techniques have been widely used to study central nervous system pathophysiology and have revealed new information about the functional roles of specific brain structures. This review first outlines the basic technologies and neural mechanisms associated with NIBS. Transcranial magnetic stimulation (TMS) was first utilized to obtain motor‐evoked potentials, which reflect corticospinal tract function. Later, studies using repetitive TMS and patterned TMS‐like theta‐burst stimulation reported the presence of aftereffects, which can enhance or inhibit cortical excitability depending on the stimulus frequency or continuous/intermittent stimulation. Over the past two decades, transcranial electrical stimulation has become increasingly popular for neuromodulation, which includes direct current stimulation (tDCS) and alternating current stimulation (tACS). While tDCS modulates cortical excitability depending on the stimulation polarity, tACS exerts its effects in a frequency‐phase–dependent manner. Although entrainment may be an important underlying mechanism, the recorded aftereffects are likely due to spike‐timing–dependent plasticity. Second, recent innovations using NIBS to induce short‐term cortical plasticity are highlighted. State‐dependent or informed open‐loop stimulation can be used to explore the interactions between endogenous cortical oscillations and TMS. Electroencephalographic oscillations prior to TMS stimulation reflect instantaneous cortical excitability depending on the stimulation power and phase, and repetitive TMS at a certain EEG state can enhance cortical excitability. Finally, temporal deafferentation of the peripheral nerve induced by a modified ischemic nerve block can modulate sensorimotor function after tourniquet deflation. Overall, NIBS techniques are promising tools for investigating human brain functions and developing new protocols for neurorehabilitation.

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Critical role of glutamatergic and GABAergic neurotransmission in the central mechanisms of theta‐burst stimulation

Cited by 55 publications

References 65 publications

Neurophysiological Signatures of Motor Impairment in Patients with Rett Syndrome

Neurophysiological Signatures of Motor Impairment in Patients with Rett Syndrome

Interindividual Variability of Lower-Limb Motor Cortical Plasticity Induced by Theta Burst Stimulation

Non‐invasive brain stimulation and short‐term cortical plasticity

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