Transcranial magnetic stimulation and neuroplasticity

Abstract

We review past results and present novel data to illustrate different ways in which TMS can be used to study neural plasticity. Procedural learning during the serial reaction time task (SRTT) is used as a model of neural plasticity to illustrate the applications of TMS. These different applications of TMS represent principles of use that we believe are applicable to studies of cognitive neuroscience in general and exemplify the great potential of TMS in the study of brain and behavior. We review the use of TMS for (1) cortical output mapping using focal, single-pulse TMS; (2) identification of the mechanisms underlying neuroplasticity using paired-pulse TMS techniques; (3) enhancement of the information of other neuroimaging techniques by transient disruption of cortical function using repetitive TMS; and finally (4) modulation of cortical function with repetitive TMS to influence behavior and guide plasticity.

Introduction

A growing body of evidence from animal models and neurophysiologic and neuroimaging studies in humans, supports the notion that the central nervous system is capable of change and adaptation throughout life (for recent reviews see 4, 16. While the developing nervous system seems more capable of modification, dynamic, plastic changes can be documented in the adult nervous system as well. Unmasking of existing connections, shifting synaptic weighting, even sprouting of new dendritic connections and formation of new synapses seem possible [16]. The central nervous system is a rapidly adapting, dynamically changing system in which modification is driven by afferent input, efferent demand, environmental and behavioral influences, and functional significance. Plastic changes seem to underlay the acquisition of new skills, the adaptation to new contexts and the recovery of function after injury. However, if plasticity is indeed a fundamental property of the central nervous system throughout life, then plastic changes may not necessarily represent a behavioral benefit for a given subject and our challenge is to modulate neural plasticity for the optimal behavioral gain. The picture of the nervous system that is emerging is rather close to the intuitions of Santiago Ramón y Cajal who in 1904, in the Textura del sistema nervioso del hombre y de los vertebrados wrote:. . . the work of a pianist . . . is inaccessible for the untrained human, as the acquisition of new abilities requires many years of mental and physical practice. In order to fully understand this complicated phenomenon it is necessary to admit, in addition to the strengthening of pre-established organic pathways, the establishment of new ones, through ramification and progressive growth of dendritic arborizations and nervous terminals . . . Such a development takes place in response to exercise, while it stops and may be reversed in brain spheres that are not cultivated.fn2 Transcranial magnetic stimulation (TMS) can be used in different ways for studies of neuroplasticity 4, 11, 12, 13, 21, 30. These different applications relate to four principal types of studies: (1) demonstration of plastic changes; (2) elucidation of mechanisms underlying plasticity; (3) providing functional information to findings of neuroplasticity with other neuroimaging techniques; and (4) modulating neuroplasticity to enhance it or reduce it in order to influence behavioral consequences. TMS can be applied in single, focal pulses to different scalp positions over the motor cortex while recording motor evoked potentials or force pulses 11, 39. This methodology allows the generation of cortical output maps serially in the same subject and the correlation with measures of functional capacity. This can be used to demonstrate the reorganization of cortical motor outputs following transient immobilization, acquisition of new motor skills, amputation, or recovery from CNS injury 4, 18, 22, 26, 27. Short trains of repetitive TMS (rTMS) at frequencies of up to 25 Hz can be used to disrupt naming or speech output, generate maps of language function and determine hemispheric language dominance 6, 20. Applied to stroke patients, this technique might be useful to demonstrate patterns of recovery from aphasia. Similarly, rTMS can be used to study plastic reorganization in other cortical areas following injury, such as the functional re-organization of the occipital cortex following peripheral blindness [14]. Paired-pulse TMS techniques [17]can be used to study intracortical excitability and the level of activity of different cortico-cortical connections and neurotransmitter systems. Such studies can illuminate the mechanisms of modulation of motor cortical representation during the acquisition of new skills or transient deafferentation [44]. Repetitive TMS can be used to transiently disrupt areas of activation on neuroimaging studies in order to establish their functional significance. For example, early blind subjects show activation of the occipital cortex in PET and fMRI during tactile Braille reading [34]. This finding suggests cross-modal plasticity. Transient disruption of the occipital cortex with rTMS results in profound worsening of the Braille reading skill, thus providing a true functional insight to the neuroimaging findings [5]. This combination of TMS with other neuroimaging modalities promises to enhance the information from PET, fMRI, or EEG mapping studies as it may provide causal information between a pattern of brain activation and a given behavior (see Paus in this issue). Finally, rTMS can enhance or decrease cortical excitability and thus potentiate or reduce neuroplastic processes [29]. This application of rTMS might be capable of speeding up recovery from stroke, reducing the consequences of immobilization, or enhancing acquisition of new skills. In the present paper we will use studies on the neural substrates of implicit motor learning in the serial reaction time task (SRTT) to illustrate these different applications of TMS in the study of neuroplasticity.