Trackingthe neuroplastic changes associated with transcranial direct current stimulation: a push for multimodal imaging

Abstract

The human brain operates through an intricate balance of excitatory and inhibitory processes. Transcranial direct current stimulation (tDCS) is a non-invasive technique that is generally assumed to work by increasing the level of brain activity near the anode (positive polarity), while decreasing it near the cathode (negative polarity). However, this is based in part on untested assumptions: the exact (cellular and synaptic) inhibitory or excitatory processes that are targeted preferentially using either polarity is still an open area of research. Furthermore, the relationship between electrode polarity and membrane excitability is highly contingent upon stimulation parameters (e.g., montage, intensity, cognitive task, etc.). Although neuroimaging has been utilized to verify these general effects in the brain, further development is needed to advance our understanding of the mechanisms by which tDCS produces changes across different levels of the nervous system. To date, tDCS has produced reliable changes in neurometabolite concentration using magnetic resonance spectroscopy (MRS; Rango et al., 2008; Stagg et al., 2009; Clark et al., 2011); whole-brain functional connectivity using functional magnetic resonance imaging (fMRI; Baudewig et al., 2001; Kwon et al., 2008; Polania et al., 2011a, 2012; Pena-Gomez et al., 2012; Sehm et al., 2012, 2013; Park et al., 2013; see Turi et al., 2012 for review); and neural oscillations and event-related potentials using electroencephalography (EEG; Keeser et al., 2011; Polania et al., 2011b; Jacobson et al., 2012) or magnetocenphalography (MEG; Venkatakrishnan et al., 2011). While each of these imaging techniques provides information at specific levels within the brain's neural architecture, from the micro-scales (e.g., neuro-metabolites) to the macro-scales (e.g., population-level neural synchronization), no study has combined more than one imaging modality with tDCS in order to track neuroplastic changes across these different scales. In this Opinion Article, we briefly summarize the progress made on tracking tDCS-induced neuroplastic changes using single imaging modalities (specifically MRS, fMRI, and EEG). We then demonstrate the need for multimodal imaging, with the goal of establishing a more comprehensive examination of both local and global neuroplastic changes due to tDCS. Such a design would enable measurements of brain chemistry and large-scale functional connectivity within the same subject and tDCS session, thus capturing interactions of these measures that may account for significant variability in cognition and behavior.