Abstract
In the human brain, aging is characterized by progressive neuronal loss, leading to disruption of synapses and to a degree of failure in neurotransmission. However, there is increasing evidence to support the notion that the aged brain has a remarkable ability to reorganize itself, with the aim of preserving its physiological activity. It is important to develop objective markers able to characterize the biological processes underlying brain aging in the intact human, and to distinguish them from brain degeneration associated with many neurological diseases. Transcranial magnetic stimulation (TMS), coupled with electromyography or electroencephalography (EEG), is particularly suited to this aim, due to the functional nature of the information provided, and thanks to the ease with which it can be integrated with behavioral manipulation. In this review, we aimed to provide up to date information about the role of TMS and TMS-EEG in the investigation of brain aging. In particular, we focused on data about cortical excitability, connectivity and plasticity, obtained by using readouts such as motor evoked potentials and transcranial evoked potentials. Overall, findings in the literature support an important potential contribution of TMS to the understanding of the mechanisms underlying normal brain aging. Further studies are needed to expand the current body of information and to assess the applicability of TMS findings in the clinical setting.
Highlights
Physiological aging is a finely controlled process which entails biological alterations at different dimensional scales, from molecules, to cells and integrated systems [1,2]. Some of these changes likely represent the undesirable outcome of exposure to stressors [3], whereas others are physiological and might subtend the attempt of the organism to maintain its function. The latter is true for the central nervous system, whose functional remodeling during aging supports the preservation of activity performance in daily tasks [4]
Short interval intracortical facilitation (SICF) can be elicited by a suprathreshold first stimulus followed by a second stimulus at about resting motor threshold (RMT) [65,66], by an interstimulus interval (ISI) compatible with I-waves period (i.e., 1.3–1.5 ms)
transcranial magnetic stimulation (TMS) research have further explored this phenomenon and found that LIHI from the contralateral M1 to iM1 decreased during motor tasks in older compared to young participants, suggesting a reduced inhibitory drive from cM1 to iM1 with aging [121,128]
Summary
Physiological aging is a finely controlled process which entails biological alterations at different dimensional scales, from molecules, to cells and integrated systems [1,2] Some of these changes likely represent the undesirable outcome of exposure to stressors [3], whereas others are physiological and might subtend the attempt of the organism to maintain its function. Neurophysiological techniques, in particular transcranial magnetic stimulation (TMS) and TMS-electroencephalography (EEG) coregistration, are very useful to this aim They are able to assess the activity of several brain circuits with a very high-temporal resolution, allowing to identify even subtle changes in the functionality of mechanisms controlling movement, learning and cognitive performances [21,22]. Cortical plastic changes occur throughout the normal lifespan in response to the numerous events that represent everyday experiences, and synaptic plasticity mechanisms, such as long-term potentiation (LTP) and long-term depression (LTD), must be tightly regulated to prevent saturation, which would impair learning and memory [23,24,25,26,27,28]
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