Role of Anterior Cingulate Cortex in Saccade Control

Cognitive control is referred to the guidance of behavior based on internal goals rather than external stimuli. It has been postulated that prefrontal cortex is mainly involved in higher order cognitive functions. Specifically, anterior cingulate cortex (ACC), which is part of the prefrontal cortex, is suggested to be involved in performance monitoring and conflict monitoring that are considered to be cognitive control functions. Saccades are the fast eye movements that align the fovea on the objects of interest in the environment. In this thesis, I have explored the role of ACC in control of saccadic eye movements. First, I performed a resting-state fMRI study to identify areas within the ACC that are functionally connected to the frontal eye fields (FEF). It has been shown that FEF is involved in saccade generation. Therefore, the ACC areas that are functionally connected to FEF could be hypothesized to have a role in saccade control. Then, I performed simultaneous electrophysiological recordings in the ACC and FEF. Furthermore, I explored whether ACC exerts control over FEF. My results show that ACC is involved in cognitive control of saccades. Furthermore, the ACC and FEF neurons communicate through synchronized theta and beta band activity in these areas. The results of this thesis shine light on the mechanisms by which these brain areas communicate. Moreover, my findings support the notion that ACC and FEF have a unique oscillatory property, and more specifically ACC has a prominent theta band, and to a lesser extent beta band activity

Bilateral sequential theta burst stimulation for multiple-therapy-resistant depression: A naturalistic observation study

Depression is a significant health issue with treatment resistance reported in about one third of patients. Treatment resistance results in significant disability, impaired quality of life, and increased healthcare costs. Repetitive transcranial magnetic stimulation (rTMS) is a treatment option for treatment resistant depression (TRD) with response and remission rates in open-label studies being as high as 58% and 37% respectively. Theta-burst is a faster and novel rTMS paradigm that has shown promise as a treatment for TRD in some preliminary studies. In a naturalistic design, we evaluated the response, remission and tolerability of bilateral sequential (right then left) prefrontal theta-burst rTMS (bsTBS) in 50 patients with TRD (600 pulses/session, 20 sessions, 100% of resting motor threshold (80% if intolerant to 100%, n = 2), F4/F3 of 10-20-20 EEG localization). Data was collected over 36 months from a specialized academic TMS clinic. Patients had multiple-treatment resistance with at least two failed trials of different antidepressants with 20% also having failed electroconvulsive therapy and 66% having received professional therapy. We found a 28% remission rate (HAMD-17 score of ≤7) and a 52% response rate (≥50% reduction in HAMD-17) with a 42% reduction in average HAMD-17 score. The treatment was well tolerated, with muscle contractions, mild pain or discomfort, headache, scalp irritation, and changes to vitals being captured as occasional adverse events with two instances of syncope (0.22% of treatments). This naturalistic study shows that bsTBS is a promising paradigm for a multiple-TRD patient population with approximately one-third of treatments achieving remission and over half achieving significant response