Investigating Aggression in Epilepsy Patients: Behavioral and Neuroimaging Insights

AbstractObjective: Patients with epilepsy, particularly those under treatment with certain antiseizure medications such as Levetiracetam (LEV), Brivaracetam (BRV), and Perampanel (PER), frequently report increased aggression and emotional difficulties. To date, these side effects have primarily been assessed through self-report measures, limiting insight into the underlying mechanisms. This study aims to investigate behavioral and emotional responses to varying levels of social provocation and the associated neural processes in epilepsy patients, using a modified version of the Taylor Aggression Paradigm (TAP) during functional MRI (fMRI).Methods: We included 38 epilepsy patients and 38 healthy controls with no significant difference in age or gender. All participants completed the modified TAP during fMRI scanning, consisting of three blocks with low, medium, and high provocation level defined by the amount of monetary punishment selected by a fictitious opponent. After each block, participants rated their emotional states and fairness perception. Additionally, they completed standardized psychological questionnaires assessing trait aggression (BPAQ), depressive symptoms (BDI), and impulsivity (BIS). Results: Despite higher self-reported trait aggression in patients, no significant group differences were observed in behavioral aggression. Compared to healthy controls, patients exhibited increased neural activity in regions associated with emotional regulation and cognitive control (e.g. Superior Parietal Lobule, Middle Temporal Gyrus, Superior Frontal Gyrus) in response to low provocation. However, they demonstrated diminished sensitivity to escalating provocation at both neural and emotional levels.Significance: The findings emphasize the need for a broader perspective that addresses the internal burden of emotional regulation and the associated neural mechanisms when being provoked, not just overt behavior. We highlight the importance of minor provocations in distinguishing patients from healthy control. Although no clear mechanism for a specific type of medication could be identified, the results indicate a potential impact of antiseizure medications. Keywords: fMRI; taylor aggression paradigm; provocation; depression; antiseizure medication; adverse effects