Characterizing brain cortical plasticity and network dynamics across the age-span in health and disease with TMS-EEG and TMS-fMRI

Abstract

Brain plasticity can be conceptualized as nature's invention to overcome limitations of the genome and adapt to a rapidly changing environment. As such, plasticity is an intrinsic property of the brain across the lifespan. However, mechanisms of plasticity may vary with age. The combination of transcranial magnetic stimulation (TMS) with electroencephalography (EEG) or functional magnetic resonance imaging (fMRI) enables clinicians and researchers to directly study local and network cortical plasticity, in humans in vivo, and characterize their changes across the age-span. Parallel, translational studies in animals can provide mechanistic insights. Here, we argue that, for each individual, the efficiency of neuronal plasticity declines throughout the age-span and may do so more or less prominently depending on variable 'starting-points' and different 'slopes of change' defined by genetic, biological, and environmental factors. Furthermore, aberrant, excessive, insufficient, or mistimed plasticity may represent the proximal pathogenic cause of neurodevelopmental and neurodegenerative disorders such as autism spectrum disorders or Alzheimer's disease.

Figures

Fig. 1

Schematic representation of the concept of plasticity. Brain plasticity allows for rapid adaptation to environmental changes that occur quicker than genetic or epigenetic response times

Fig. 2

A bell-curve response to plasticity levels suggests that both too little and too much plastic response can hinder cognitive performance and overall brain health. “Optimal amounts of plasticity” will necessarily be different for different individuals, varying across brain regions and networks and changing across the lifespan

Fig. 3

Schematic representation of individual plasticity across the lifespan. Although mechanisms of plasticity show a downward trend over the course of a typical lifetime, this trend will manifest differently according to initial “baseline” levels, genetic factors, and environmental influences. Therefore, one may conceptualize each individual has a unique “slope of plasticity” across the lifespan

Fig. 4

TMS-based measures of cortical reactivity and plasticity. As recorded using either electromyography (EMG) or electroencephalography (EEG), brain responses to TMS can be measured as motor evoked potentials (when TMS is applied to motor cortex) or localized evoked field potentials. Such responses reflect cortical or corticospinal reactivity. These measures can be obtained before and following a given intervention, for example controlled modulation of cortical excitability by repetitive TMS in the form of theta burst stimulation (TBS). The TBS-induced change in EMG or EEG responses to TMS provides a measure of local cortical plasticity. An example of TMS-EEG measures before and after continuous TBS illustrates the measurement of LTD-like plasticity

Fig. 5

Modified from Freitas et al. (2011a, b). Correlation between age and duration of the modulation of cortico-spinal responses to TMS after cTBS in cognitively intact, healthy adults ranging in age from 19 to 81 years. This measure of plasticity shows a significant decrease with age

Fig. 6

Schematic representation of the influence of genetic or environmental impacts on brain plasticity. Alteration of local plasticity will trigger secondary adaptive responses across diffuse neural networks that may prove ultimately adaptive or maladaptive for the individual. Depending upon the amount and scope of such secondary responses, initial insult effects may be alleviated or heightened

Fig. 7

Alterations of TMS-based measures of plasticity in nervous system pathology exemplified by autism spectrum disorder (ASD; a) and Alzheimer’s diseases (AD; b). a As compared with age-, gender- and IQ-matched controls, subjects with ASD show stronger and longer-lasting modulatory responses to continuous theta burst stimulation suggesting abnormal, hyper-plastic mechanisms. This is true for both, LTP- and LTD-like plasticity. b As compared with age-, gender- and IQ-matched controls, subjects with mild AD show weaker and shorter-lasting modulatory responses to continuous theta burst stimulation suggesting abnormal, hypo-plastic mechanisms

Fig. 8

Schematic representation of the hypothesized balance between local and network plasticity, its change across the lifespan, and its alterations by pathology