Elsevier

Clinical Neurophysiology

Volume 126, Issue 10, October 2015, Pages 1847-1868
Clinical Neurophysiology

Review
TMS and drugs revisited 2014

https://doi.org/10.1016/j.clinph.2014.08.028Get rights and content

Highlights

  • Pharmaco-TMS improved our understanding of the effects of TMS on the human brain.

  • Pharmaco-TMS-EEG is a new research field to measure directly drug effects on brain excitability and connectivity.

  • Pharmaco-TMS can monitor and possibly predict drug responses in neurological and psychiatric patients.

Abstract

The combination of pharmacology and transcranial magnetic stimulation to study the effects of drugs on TMS-evoked EMG responses (pharmaco-TMS-EMG) has considerably improved our understanding of the effects of TMS on the human brain. Ten years have elapsed since an influential review on this topic has been published in this journal (Ziemann, 2004). Since then, several major developments have taken place: TMS has been combined with EEG to measure TMS evoked responses directly from brain activity rather than by motor evoked potentials in a muscle, and pharmacological characterization of the TMS-evoked EEG potentials, although still in its infancy, has started (pharmaco-TMS-EEG). Furthermore, the knowledge from pharmaco-TMS-EMG that has been primarily obtained in healthy subjects is now applied to clinical settings, for instance, to monitor or even predict clinical drug responses in neurological or psychiatric patients. Finally, pharmaco-TMS-EMG has been applied to understand the effects of CNS active drugs on non-invasive brain stimulation induced long-term potentiation-like and long-term depression-like plasticity. This is a new field that may help to develop rationales of pharmacological treatment for enhancement of recovery and re-learning after CNS lesions.

This up-dated review will highlight important knowledge and recent advances in the contribution of pharmaco-TMS-EMG and pharmaco-TMS-EEG to our understanding of normal and dysfunctional excitability, connectivity and plasticity of the human brain.

Section snippets

Effects of CNS active drugs with incompletely known or multiple modes of action on TMS-EMG measures of corticospinal and motor cortical excitability

Using TMS, drugs with a clear mode of action have shown typical electrophysiological signatures of their underlying mechanism in the human M1 (see Section 1). Such a signature may result from direct or remote effects of the drug on the cortical system. Moreover, the physiological correlates of particular TMS measures have been studied intensively in humans (Hallett, 2007, Reis et al., 2008), and less frequently in animals (Hsieh et al., 2014, Luft et al., 2001, Rotenberg et al., 2010). As a

Effects of anesthetics and analgesics on TMS-EMG measures of corticospinal and motor cortical excitability

Most data concerning the effects of anesthetics and analgesics on TMS measures of corticospinal and motor cortical excitability result from studies in patients undergoing surgery of brainstem or spinal cord. Although MEP recordings after TMS are regularly employed to monitor corticospinal tract integrity in this intraoperative setting, transcranial electrical stimulation (TES) is more often used than TMS for practical reasons. However, it appeared that the sensitivity of TES and TMS to detect

TMS-EEG to measure key parameters of cortical functioning in humans

Despite a highly static structure, the human brain generates a large repertoire of behavioral and psychological phenomena spanning from simple motor acts to cognition and consciousness. This ability relies on the activation of highly specialized thalamic and cortical structures that interact on a subsecond timescale by means of long-range bundles of fibers (Park and Friston, 2013, Sporns, 2013). Hence, the electrical reactivity of the cerebral cortex to a direct, local stimulation (cortical

TMS/RTMS induced changes in endogenous neurotransmitters and neuromodulators

Dopamine (DA) plays an important role in learning, reward, motor control, emotion and executive functions. Thanks to the development of neuroimaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), it is now possible to quantify dopaminergic activity in the living human brain. The combination of these technologies with rTMS offers great potential in that it is capable of tackling questions regarding region-specific/function-specific

Effects of CNS active drugs on TMS-EMG measures of motor cortical excitability in epilepsy

The TMS studies concerned with the effects of CNS active drugs on measures of cortical excitability reviewed in the previous sections were all performed on healthy subjects to whom drugs were administered. Therefore, none of the observed drug effects can be ascribed to brain pathology. In those studies, cortical excitability was measured immediately before the administration of a single dose of the study drug (baseline). Thereafter, repeat measurements were performed at delays adjusted to the

Conflict of interest

All authors state that they have no conflicts of interest. There was no external funding.

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