The pharmacology of neuroplasticity induced by non‐invasive brain stimulation: building models for the clinical use of CNS active drugs

Abstract

The term neuroplasticity encompasses structural and functional modifications of neuronal connectivity. Abnormal neuroplasticity is involved in various neuropsychiatric diseases, such as dystonia, epilepsy, migraine, Alzheimer's disease, fronto-temporal degeneration, schizophrenia, and post cerebral stroke. Drugs affecting neuroplasticity are increasingly used as therapeutics in these conditions. Neuroplasticity was first discovered and explored in animal experimentation. However, non-invasive brain stimulation (NIBS) has enabled researchers recently to induce and study similar processes in the intact human brain. Plasticity induced by NIBS can be modulated by pharmacological interventions, targeting ion channels, or neurotransmitters. Importantly, abnormalities of plasticity as studied by NIBS are directly related to clinical symptoms in neuropsychiatric diseases. Therefore, a core theme of this review is the hypothesis that NIBS-induced plasticity can explore and potentially predict the therapeutic efficacy of CNS-acting drugs in neuropsychiatric diseases. We will (a) review the basics of neuroplasticity, as explored in animal experimentation, and relate these to our knowledge about neuroplasticity induced in humans by NIBS techniques. We will then (b) discuss pharmacological modulation of plasticity in animals and humans. Finally, we will (c) review abnormalities of plasticity in neuropsychiatric diseases, and discuss how the combination of NIBS with pharmacological intervention may improve our understanding of the pathophysiology of abnormal plasticity in these diseases and their purposeful pharmacological treatment.Ulf Ziemann (far left) is clinical director of the Department of Neurology and Stroke, Hertie Institute for Clinical Brain Research, Eberhard-Karls University of Tübingen, Germany. His expertise is in clinical neurophysiology with focus on motor cortical excitability, plasticity, learning and neurorehabilitation. He has developed the field of pharmaco-TMS, which provides important knowledge on the physiology of TMS measures of excitability and the pharmacological regulation of plasticity in human motor cortex. Florian Müller-Dahlhaus (centre left) is resident at the Department of Neurology, Goethe-University Frankfurt, Germany. He has expertise in cellular electrophysiology and imaging as well as pharmaco-TMS. Research focuses on understanding mechanisms of neural plasticity involved in motor learning to enhance rehabilitation post stroke. Walter Paulus (centre right) is clinical director of the Department of Clinical Neurophysiology, University Medical Centre, Germany. He investigates motor cortex physiology by means of transcranial stimulation, further refined by co-application of CNS-active drugs. He was involved in the development of new stimulation methods for induction of neuroplasticity such as tDCS, tACS and tRNS. His clinical focus encompasses Parkinson's disease, restless legs syndrome, epilepsy and pain. Michael A. Nitsche (far right) is a consultant in the same department. His ...

Neurochemical Modulation in Posteromedial Default-mode Network Cortex Induced by Transcranial Magnetic Stimulation

“…Intracranial recordings [66,67] further confirmed that DMN has a unique pattern of synaptic activity, which has been postulated as one of the several factors modulating the rTMS brain response [68]. However, it should be noted that discrepancies with previous MRS results can be related to other possibilities instead to idiosyncratic DMN characteristics such as differential cito-and neurotransmitter architectonics [69,70], coil orientation interacting with different gyral morphometry [71] or a differential modulating role of other neurotransmitters [72]. After stimulating left IPL with protocols inducing reduced excitability other studies have found increases in the connectivity and coherence in the DMN [31,32] while after stimulating the IPL with high-frequency TMS reductions of DMN connectivity have been observed.…”

TMS and drugs revisited 2014

“…NIBS offers the possibility to study the effects of CNS active drugs on cortical plasticity in humans non-invasively [for review see e.g., (Nitsche et al, 2012)]. This is possible because tDCS and TMS can induce alterations in cortical excitability, which outlast the stimulation period and map onto synaptic plasticity .…”

The Physiological Basis of Brain Stimulation

“…There is a large and increasing number of TMS protocols that allow modulation of cortical excitability. A full review of the use of TMS as a neuromodulatory technique is beyond the scope of this chapter, but readers are referred to Nitsche, Muller-Dahlhaus, Paulus, and Ziemann (2012) for a review.…”