The present research project attempts to address a pressing question in field of affective sciences: can neuroscience offer insights into emotional responding in the human brain? To address this central question, we first adopt a theoretical position of appraisal theory of emotion. This theory postulates that an emotional response arises subsequent to a series of evaluative processes, which appraise the respective information, be it internal or external, in terms of the overall well-being and concerns of the individual. A critical process, according to appraisal theory, is relevance, which refers to the appraisal of the degree to which the information corresponds to the organism's concerns and overall well-being. Within this process, however, there are several sub-processes, which evaluate the information or stimulus for specific areas of relevance. These are novelty, intrinsic pleasantness and concern-relevance. Here, we investigate novelty and concern-relevance. To investigate the neural correlates associated with novelty processing, we first employ coordinate-based meta-analytic techniques to previously published fMRI papers contrasting novel information against non-novel information. This research thus provides insight into the substrates underlying a critical appraisal process likely occurring prior to concern-relevance. To examine concern-relevance in more depth, we employ functional magnetic resonance imaging (fMRI) to investigate how the brain responds to individual concern-relevance. Given the amygdala's theorized role in novelty and relevance, we further assessed amygdala processing via intracerebral encephalographic (iEEG) studies within the amygdala to better delineate the amygdala's role in the two processes of novelty and relevance detection. Finally, we apply the tenets of appraisal theory, with respect to goal-relevance processing, a component of concern-relevance, to social anxiety disorder as a theoretical case study, wherein we highlight social anxiety to be attributed to faulty goal-relevance processing and poor self-structure, in addition to other maladaptive appraisals, such as coping potential.