ABSTRACT Affective symptoms are a common feature of neuropsychiatric disorders that reflect dysfunction in a distributed brain network that supports emotion. How aberrant functioning in a single emotion network underlies a wide range of affective symptoms, such as depression and anxiety, is not well understood. Anchored by the anterior cingulate cortex and ventral anterior insula, the emotion network responds to numerous affective stimuli. A more sophisticated understanding of how the emotion network produces emotions—and how atypical emotion network functioning relates to affective symptoms—will be critical for advancing current neuroanatomical models of neuropsychiatric disorders. Intracranial electroencephalography (iEEG) provides direct estimates of neuronal populations and can be used to map the spatiotemporal dynamics of the emotion network at a millisecond-level resolution. Although functional neuroimaging studies have uncovered little evidence for neural differentiation among emotions, these studies lack the spatiotemporal and spectral resolution to determine whether emotions are characterized by unique neural signatures. The overall goals of the proposed project are to elucidate how emotion network dynamics relate to the behavioral, autonomic, and experiential changes that accompany emotions and to investigate how emotion network dysfunction relates to affective symptoms. Anatomically- specific biomarkers of emotion network dysfunction could be used to guide development of novel treatments, monitor symptoms and treatment response, and improve animal models of affective symptoms. We will study 100 patients with intractable epilepsy undergoing surgery for seizure localization. Subjects with iEEG electrodes within the emotion network will undergo continuous neural and video recordings during a multi-day hospital stay. Naturalistic affective behaviors that subjects display spontaneously throughout their hospitalization, emotional reactivity in response to standardized affective stimuli, and emotional reactions following electrical stimulation of emotion network hubs will be quantified. We will examine how activity within emotion network hubs changes during emotions and how emotion network properties make some individuals more vulnerable to affective symptoms than others. We will address three key aims. In Aim 1, we will determine how emotion network activity relates to naturalistic affective behaviors. In Aim 2, we will uncover the unique neural signatures of discrete emotions and their relations to task-based measures of emotional reactivity. In Aim 3, we will probe whether electrical stimulation of emotion network hubs changes network activity and alters emotions, mood, and anxiety. By utilizing a multidisciplinary approach, the proposed project has the potential to ask novel questions about the neural origins of emotions and to advance current models of the neurobiological basis of emotions and affective symptoms.