ECT is a neuromodulation-based treatment approach for mental ailment that elicits dramatic clinical improvement. It was developed on the premise that Epilepsy and Psychosis were alternating and individuals exhibited opposite features while one of the symptoms dominated. Thus, it was thought that seizures were essential to curb symptoms of psychosis. However, the effectiveness of ECT has not been conclusively linked with presence of convulsions. Rather even the duration of seizure after ECT has not been associated with the clinical response. On the other hand, animal studies have shown that electrical brain stimulation can induce antidepressant-like effects without inducing seizures. In human beings, historical evidence does suggest that reports from the 1940s and 1950s that "sub-convulsive" and "non-convulsive" electrotherapies were effective for some patients without adverse cognitive effects. Moreover, the recent neuromodulation techniques like repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) does not induce seizures and still have been shown to be effective in improving symptoms of mental disorders particularly depression. And there is even report that sub-convulsive electrical stimulation while determining seizure threshold during a course of ECT does not have acute effects on cognition. There are different explanations for the effectiveness of sub-convulsive stimulus of ECT but there are limited studies of it in humans. The studies on response of patients to sub-convulsive stimulus are also lacking. Since the cognitive side effects are also less with sub-convulsive ECT, which is a major drawback for usual ECT, our aim is to study the response of sub-convulsive stimulus of ECT in individuals with treatment resistant depression (TRD).

Studies on functional neuroimaging show that treatment is capable of normalizing brain activations in patients. But these studies are conducted majorly using fMRI or PET techniques. The heavy cost and time consumption of these techniques make them user unfriendly. Newer technique as fNIRS scan can perform the similar task of evaluating cortical hemodynamic activation pattern with ease of use. Studies on electrical cortical activities using qEEG have generated a plethora of data reporting abnormalities in patients and have been associated to treatment response. Studies have also suggested that BDNF might be a potential biomarker for mental illnesses representing neuronal integrity. There are studies suggesting potential role of BDNF as biomarker in ECT.

Significant changes in serum BDNF levels, cerebral Hb changes and event related potentials over time after receiving ECT will shed light over the potential mechanisms of treatment effectiveness in this illness. The correlation analysis to illness severity scale scores will reflect their association with treatment response pattern. It can pave way towards elaboration of the understanding by which such techniques generate effects in patients with TRD. This would increase the effectiveness of the treatment program as biomarkers can serve as objective indicators of health status. The difference in these parameters among the individuals with depressive disorder will further strengthen the association of the biomarkers (singularly or in combination) to a specific disorder