Right amygdala ablation reduces maladaptive negative interpretation bias and symptoms in a patient with...

Negative interpretation bias - the tendency to perceive ambiguous stimuli as threatening - is a core cognitive distortion underlying post-traumatic stress disorder (PTSD). The amygdala, a key structure in fear processing, is implicated in PTSD-related hypervigilance and heightened fear perception, yet direct causal evidence linking amygdala function to negative interpretation bias remains limited. Here, we present a unique prospective case of a male patient with refractory epilepsy and comorbid chronic PTSD, who underwent stereoelectroencephalography-guided radiofrequency ablation (SEEG-guided RFA) targeting the right amygdala. Before ablation, the patient exhibited heightened negative interpretation bias, judging ambiguous faces as more fearful compared to control groups of epilepsy patients without PTSD. Intracranial SEEG recordings revealed that this cognitive bias was associated with increased late-phase event-related potential (L-ERP) differentiation between fearful and happy faces in the right amygdala. Immediately following focal right amygdala ablation, negative interpretation bias and PTSD symptom severity were significantly reduced, while seizure frequency remained unchanged. Notably, reductions in L-ERP amplitude after ablation closely tracked decreases in fear perception, highlighting L-ERP as a potential biomarker of negative interpretation bias and therapeutic response. Our findings provide causal evidence from an n-of-1 study that the right amygdala supports maladaptive negative interpretation bias in a patient with PTSD and that right amygdala ablation can contribute to the relief of PTSD symptomatology.