Western University Scholarship@Western Electronic Thesis and Dissertation Repository 9-21-2016 12:00 AM Role of Anterior Cingulate Cortex in Saccade Control Sahand Babapoor-Farrokhran The University of Western Ontario Supervisor Dr. Stefan Everling The University of Western Ontario Graduate Program in Neuroscience A thesis submitted in partial fulfillment of the equirr ements for the degree in Doctor of Philosophy © Sahand Babapoor-Farrokhran 2016 Follow this and additional works at: https://ir.lib.uwo.ca/etd Part of the Cognitive Neuroscience Commons, Other Neuroscience and Neurobiology Commons, Systems and Integrative Physiology Commons, and the Systems Neuroscience Commons Recommended Citation Babapoor-Farrokhran, Sahand, "Role of Anterior Cingulate Cortex in Saccade Control" (2016). Electronic Thesis and Dissertation Repository. 4150. https://ir.lib.uwo.ca/etd/4150 This Dissertation/Thesis is brought to you for free and open access by Scholarship@Western. It has been accepted for inclusion in Electronic Thesis and Dissertation Repository by an authorized administrator of Scholarship@Western. For more information, please contact [email protected]. ABSTRACT: Cognitive control is referred to the guidance of behavior based on internal goals rather than external stimuli. The brain areas involved in implementing cognitive control are more developed and have larger proportional spatial extent in humans and non-human primates compared to other species. Studying the mechanisms by which cognitive control is implemented has recently gained more attention. 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. Saccade system is one of the most studied motor systems in the brain. This is mainly due to the simplicity of the saccade system and amenability of saccade- related brain areas to electrophysiological recordings. This makes the saccadic system an ideal candidate to study the cognitive control functions. 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 to investigate the mechanisms by which information is transmitted between these areas. Furthermore, I explored whether ACC exerts control over FEF. In the first chapter, I have shown that ACC has functional connectivity with the FEF. Furthermore, I observed differential functional connectivity of medial and lateral FEF with other brain areas. In the second chapter, I have shown that theta and beta bands are involved in information transmission between FEF and ACC. Finally, using Granger causality analysis, I have shown that ACC exerts control over FEF when monkeys perform saccade-related tasks. These findings 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. Keywords: Cognitive control, anterior cingulate cortex (ACC), frontal eye field (FEF), resting-state fMRI, functional connectivity, working memory, memory-guided saccade task, pro-/anti- saccade task, local field potentials (LFP), multi-unit recording, brain oscillations, theta band, beta band, spectral power, field-field coherence, spike-field coherence. iii TABLE OF CONTENTS: ABSTRACT: ..................................................................................................................... ii TABLE OF CONTENTS: ............................................................................................... iv CO-AUTHORSHIP STATEMENT: ............................................................................. vii EPIGRAPH: ................................................................................................................... viii DEDICATION: ................................................................................................................ ix ACKNOWLEDGEMENTS: ............................................................................................ x LIST OF TABLES: .......................................................................................................... xi LIST OF FIGURES: ....................................................................................................... xii LIST OF ABBREVIATIONS: ...................................................................................... xxi CHAPTER 1: ..................................................................................................................... 1 1. GENERAL INTRODUCTION: .................................................................................. 1 1.1. ANTERIOR CINGULATE CORTEX (ACC): ................................................... 1 1.1.1. History: ............................................................................................................. 1 1.1.2. ACC subdivisions: ............................................................................................ 2 1.1.3. ACC connectivity: ............................................................................................ 3 1.1.4. ACC functions: ................................................................................................. 4 1.1.4.1. ACC and motor functions: ......................................................................... 7 1.1.4.2. ACC and the limbic system: ...................................................................... 8 1.1.4.3. ACC and conflict monitoring: ................................................................... 9 1.1.4.4. ACC and performance monitoring: ......................................................... 11 1.2. SACCADES AND THE OCULOMOTOR SYSTEM: ..................................... 14 1.2.1. Frontal eye fields: ........................................................................................... 15 1.2.2. Frontal eye fields and visual functions: .......................................................... 18 1.2.3. Memory-guided saccade task: ......................................................................... 20 1.2.4. Pro-/Anti-saccade task: ................................................................................... 21 1.2.5. Cingulo-Frontal (ACC-FEF) interaction in saccade tasks: ............................. 24 1.2.5.1 Resting-state connectivity of the ACC: .................................................... 25 1.2.5.2. Resting-state fMRI: .................................................................................. 27 1.2.5.3. Analytic approaches for resting-state fMRI: ............................................ 30 1.2.5.4. Resting-state fMRI and clinical applications: .......................................... 31 1.3. BRAIN RHYTHMS: ............................................................................................ 34 1.3.1. Communication through coherence (CTC): .................................................... 35 1.3.2. Theta band: ...................................................................................................... 37 1.3.3. Beta band: ....................................................................................................... 40 1.4. OBJECTIVES: ..................................................................................................... 42 1.4.1. Obtain the functional connectivity map of the FEF: ....................................... 42 1.4.2. Evaluate whether the functionally connected ACC and FEF areas display synchronized neuronal activity: ................................................................................ 43 1.4.3. Examine the direction of information flow between ACC and FEF: ............. 43 iv 1.5. REFERENCES: ................................................................................................... 44 CHAPTER 2: ................................................................................................................... 56 2. Functional connectivity patterns of medial and lateral macaque frontal eye fields reveal distinct visuomotor networks ............................................................................. 56 2.1. ABSTRACT: ........................................................................................................ 56 2.2. INTRODUCTION: .............................................................................................. 57 2.3. MATERIALS AND METHODS: ....................................................................... 59 2.3.1. Data acquisition: ............................................................................................. 59 2.3.2. Image preprocessing: .....................................................................................