Anodal high definition transcranial direct current stimulation for neurorehabilitation of chronic stress and depression (PhD)

Abstract

Neurological and psychiatric disorders are recognized as the leading cause of disability adjusted life-years (DALYs) and the second leading cause of deaths. Neurodegeneration conditions or cognitive impairments are one of the serious problems related to the disturbances in the lifestyle of surviving patients and surrounding caregivers. Generally, stress and depression are associated with the neurodegeneration condition, which also leads to cognitive impairment by a decline in the cognitive function skills, including loss of memory trouble in thinking, learning new things, state of confusion and many more. In recent years, non-invasive brain stimulation (NIBS) techniques through transcranial direct current stimulation (tDCS) are a promising and effective tool for neurorehabilitation, as confirmed by the evidence related to the recovery of the surviving patients from neurological disorders. Such stimulation techniques are found to enhance the cognitive functionality skills by modulating the neuronal activity.

In this thesis work, simulation based study has been used, to find out the best multi-electrode anodal high definition transcranial direct current stimulation (HD-tDCS) configuration, and the appropriate amount of weak direct current intensity in terms of enhancement in focality of the targeted surface area. Further, a small sized high definition dual-purpose spiking electrode has been fabricated for sensing EEG signal and stimulating using HDtDCS. The main benefit of these sensing and stimulating fabricated electrodes is to record EEG signals before and after injecting the weak amount of direct current on targeted locations of the brain with the same fabricated electrodes. Two different types of dual-purpose electrodes have been fabricated namely Au/AgCl and Pt/AgCl. The I-V characteristics of both sensing electrodes were providing a good response. Moreover, I-V characteristics in the case of Au/AgCl show a better response than Pt/AgCl. Further, an experimental trial has been carried out to validate the fabricated sensing electrodes for recording EEG signal after required impedance matching, which is less than 50 k The analysis involving current density studies confirms that the electric field provided by the fabricated electrodes can penetrate deep into the cerebral cortex region. These fabricated electrodes can also play a significant role in maintaining high focality of HD-tDCS of the brain. A preclinical validation study of the research work has been carried out after developing chronic stress and depression-like behaviour rat model over a period of 14-days; and the effects of a single anodal HD-tDCS antidepressant dose (2.00 mA 5 minutes) have been validated, which has been done by placing the fabricated Au/AgCl electrode on the region of interest of the rat brain. This study has provided strong positive evidence in terms of improvement in behavioural tests and EEG signal in the treatment group rats after a single anodal HD-tDCS antidepressant dose as compared to the rats with naive and chronic stress or depression-like behaviour. Also, the present study has provided evidence in terms of improvement in the glutamate/GABA (E/I) ratio, both in the cortex and hippocampus regions of the treatment group rats after single anodal HD-tDCS dose, as compared to the rat group with chronic stress or depression-like behaviour, which is also associated with an enhancement in the memory and learning ability of the rats. It is worthy of note that the single anodal HD-tDCS dose has provided strong evidence related to the significant increase in the microglia labelled ionized calcium binding adaptor molecule 1 (Iba1) expression in both cortex and hippocampus region of treatment group rats as compared to the rat group with chronic stress or depression-like behaviour. The study also provides evidence related to the reduction in the count of partially degenerative neurons after a single anodal HDtDCS dose in the treatment group rats as compared to the rat group with chronic stress or depression-like behaviour. Hence, the fabricated electrodes have an ability to provide stimulation through HD-tDCS dose that can penetrate up to the cortex and hippocampus region from the surface of the brain within tolerable and safety limits. Moreover, the single anodal HD-tDCS antidepressant dose (2.00 mA x 5 minutes) has the capability to treat patients suffering from chronic stress and depression. The final outcome of this work is the development of a prototype of an HD-tDCS device, which is also compatible with fabricated dual-purpose electrodes. The prototype of the HD-tDCS device has the capability of providing a weak amount of direct current ranging from 1.00 mA to 4.00 mA with a maximum error of less than 2%. Such type of emerging advancement in the HD-tDCS device can help patients suffering from cognitive disorders without a permanent support from the caregivers.