Abnormal left prefrontal N100 and its relationship with fronto-limbic metabolism in major depressive disorder.

Major depressive disorder (MDD) is a highly prevalent and disabling psychiatric illness affecting approximately 5% of the world’s population. It is expected to be the leading cause of disability by 2030 []. Despite the increased availability of treatment options in recent decades, treatment-resistant depression (TRD) patients who rarely respond to currently available antidepressant regimens continue to account for a significant proportion []. This underscores the importance of gaining a precise understanding of the pathophysiology of MDD. Neuroimaging studies have reported variations in brain structure and functional connectivity among patients with MDD [], and revealed potential mechanisms contributing to abnormalities in cognitive processing [], mood regulation [], impulsive behavior [], and motivational function []. The inhibitory GABAergic systems are thought to play a crucial role in MDD pathogenesis, as evidenced by the promising antidepressant effects of ketamine []. These systems are also considered one of the key underlying mechanisms of Theta-burst stimulation (TBS) treatment []. TMS-evoked potentials (TEPs), assessed by concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG), are significantly associated with GABA receptor activity and may be consistently quantified from the prefrontal cortex (PFC) []. Furthermore, hypoactivity of the PFC, a crucial component of the fronto-limbic network, has been identified in MDD patients, and both treatment refractoriness and severity of symptoms were connected with the degree of PFC dysfunction [, ]. N100, a substantial negative deflection around 100 ms following a TMS pulse, is one of the most commonly studied TMS-EEG markers. It mostly represents inhibitory neuronal processes mediated by GABA-B receptors []. Several studies have reported that N100 is a possible predictor of antidepressant response and suicidal ideation in treatment-resistant patients, as well as being associated with symptom severity [, ]. Additionally, N100 has a high test-retest reliability and is less affected by signal decay and muscle artifacts [, ]. Collectively, these findings support the utility of the N100 as a promising biomarker for neurophysiological research in MDD.