Transcranial direct current stimulation: the effects on excitability and pain perception in healthy adults

Painful stimuli are processed in a network called the pain neuromatrix (PNM) which comprises both the cortical and subcortical areas of the brain. The primary motor cortex (M1), primary sensory cortex (S1), and dorsolateral prefrontal cortex (DLPFC) are the cortical sites of the PNM. Literature indicates that modulatory changes occur in the excitability of these cortical sites during pain processing. These changes coincide with behavioral modulations such as sensory (STh) and pain (PTh) thresholds, and pain level (PL) changes. Transcranial direct current stimulation (tDCS) of cortical sites provides supportive evidence for the modulation of these cortical and behavioral changes. tDCS is a non-invasive neuromodulatory technique with a polarity dependent manner. The application of an anode over the target cortical sites (a-tDCS) increases corticospinal excitability (CSE), and the application of a cathode over the target (c-tDCS) decreases the CSE. Although there is an upward trend using a- and c-tDCS over M1, S1, and DLPFC for increasing STh and/or PTh, there is no consensus on the superiority of different tDCS modes and stimulation sites on the aforementioned effects. Therefore, the broad aim of the present study was to investigate the effects of tDCS modes and stimulation sites on CSE and STh/PTh modulation. Prior to the experimental studies, two systematic review and meta-analyses (Studies 1-2) were conducted to verify the effect of a-tDCS and c-tDCS on different cortical sites of the PNM on STh and PTh in healthy individuals and patients with chronic pain. These reviews confirmed that these stimulation effects are site specific in both healthy and patient groups following a- and c-tDCS. A reliability study was then conducted to test the intra- and intersession reliability of elicited MEPs and to fine-tune the set-up for application of TMS as an assessment tool (Study 3). The reliability study was a necessary step before conduction of the other experimental studies in this thesis. In Studies 4 and 5, we investigated how single-site a-tDCS and c-tDCS of functionally connected cortical sites of the PNM affect the level of M1 and S1 excitability. The result of Study 4 showed that a-tDCS of M1 and DLPFC are the best cortical sites for induction of greater CSE. This site specificity was not found for STh/PTh changes and a-tDCS of these three cortical sites increased STh/PTh in healthy adults. The results of Study 5 showed that c-tDCS of M1, S1, and DLPFC reduce M1 and S1 excitability, while it had opposite effects on STh/PTh. In fact, no site specificity was found following c-tDCS of these cortical sites in healthy adults. Studies 6 and 7 compared the effects of single-site (conventional) tDCS and a novel tDCS technique termed unihemispheric concurrent dual-site tDCS (tDCSUHCDS) on M1 CSE, short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF). In this technique two unihemispheric functionally connected sites of the PNM were concurrently stimulated to intensify tDCS-induced CSE changes. Study 6 indicated that a-tDCSUHCDS of M1-DLPFC induces larger M1 CSE with day-long lasting effects, compared to M1 a-tDCS. This increase was mainly associated with an ICF increase. Study 7 showed that the application of c-tDCSUHCDS on cortical sites of the PNM not only failed to induce inhibitory effects, but even induced excitatory changes in some experimental conditions. These changes were associated with an ICF increase and a SICI decrease. Overall, in these two studies, we concluded that tDCSUHCDS is a more effective technique for induction of CSE changes compared to single-site tDCS. In Study 8, this novel technique is used to explore the effect of both a- and c-tDCSUHCDS of cortical sites of the PNM on STh/PTh. The results in this concluding chapter revealed that, compared to single-site tDCS and c-tDCSUHCDS, a-tDCSUHCDS of M1-DLPFC is the most efficient technique to enhance STh and PTh with day-long lasting effects.