Using FMRI and TMS to probe the functional connectivity of prefrontal cortex and amygdala in top-down regulation of emotion

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According to the World Health Organization, emotional disorders such as depression and anxiety have become the leading causes of disability in the UK and other western countries, and are estimated to become the second greatest cause of disability worldwide by 2020. Efforts to understand the causes of these conditions and potential avenues for treatment are therefore of enormous importance to the general population. This task, however, has proved difficult. One topic of great relevance to depression is the brain mechanisms that allow us to regulate our emotions. Although it's normal and healthy for people to have negative emotions in certain circumstances, one of the features of emotional disorders is that sufferers can't pull themselves out of those negative emotional moods. How do the brains of people with emotional disorders differ from those of healthy individuals, and can such differences explain their inability to regulate emotions? Recent brain imaging studies in healthy individuals have identified specific parts of the frontal lobe of the brain that appear to be involved in regulating emotions. However, although brain imaging can indicate what parts of the brain are active when we regulate our emotions, it cannot tell us whether those parts of the brain are actually responsible for emotion regulation. They could, for example, merely be indicators that our emotions are being regulated, and not play an active role in the regulation itself. Nor can brain imaging tell us how different parts of the brain exert control over our emotions. Research with animals provides some evidence, but human emotions are likely distinct in many ways. The proposed research will combine novel and cutting edge techniques in brain stimulation and brain imaging to provide new insights into the role of parts of the brain's frontal lobes in regulating our emotions. Transcranial magnetic stimulation (TMS), a method that allows parts of the brain to be temporarily perturbed, will be used to directly test the role the frontal lobes play in regulating human emotions. The effects of TMS on activity in other parts of the brain that play a role in human emotions, such as the amygdala, will be measured. In addition, the downstream effects on emotional responses will also be assessed. Another state of the art technique, magnetic resonance spectroscopy (MRS), will be used to measure concentrations of a neurotransmitter called GABA in the amygdala, which is thought to be important in allowing the frontal lobes to exert control over emotional responses. The long term goal of the proposed research is to develop a better understanding of basic emotion processes that can be applied to the study of clinical populations with depression and anxiety disorders. In this way, we aim to develop new ways of diagnosing and treating such debilitating conditions, or preventing them from occurring in the first place.