Optimising transcranial electrical stimulation for the treatment of depression

摘要

Transcranial electrical stimulation (tES) refers to a group of neuromodulatory techniques where a mild electric current is applied to the brain through electrodes placed on the scalp. TES can produce changes in the brain that outlast the period of stimulation and repeated sessions result in lasting cumulative changes. Studies over the last decade suggest tES is a promising novel treatment for depression. However the optimal stimulation for therapeutic efficacy remains unknown. This thesis presents four studies that investigate two critical aspects of stimulation technique: stimulation parameters and electrode montage. Two proof-of-concept studies examined optimal stimulation parameters in healthy participants. Motor cortical excitability, as measured through motor evoked potentials elicited through transcranial magnetic stimulation, provided an objective and quantitative measure of changes that resulted from tES. Study 1 examined transcranial direct current stimulation (tDCS) and transcranial random noise stimulation (tRNS), and found that forms of stimulation with a direct current component and net transfer of charge (e.g. tDCS, tRNS with a direct current offset) were more likely to result in cortical excitability increases. Study 2 analysed data from seven studies of anodal tDCS that examined the effect of current intensity and electrode size across single and repeated sessions of stimulation. The results showed greater increases in motor cortical excitability when larger electrodes were used. Two studies examined electrode montages in pilot studies of novel electrode placements in depressed patients. Clinical outcomes were assessed and compared with brain simulation maps derived from computational modelling. Study 3 examined two novel electrode placements designed to stimulate central and deep brain structures postulated as key targets in the treatment of depression. Clinical outcomes suggest that a fronto-occipital, but not a fronto-cerebellar, montage may have promising antidepressant potential. Study 4 examined a bitemporal electrode montage, adapted from the bitemporal montage used in electroconvulsive therapy. Results suggest that bitemporal tDCS may have clinically meaningful efficacy though computational modelling showed lower activation of postulated key brain regions. In summary this thesis presents a series of studies that contribute to the existing understanding of tES and how it can be optimised, particularly for the treatment of depression.