BackgroundTraumatic brain injury (TBI) with post-traumatic stress disorder (PTSD) is treatment-resistant, with conventional psychotherapy showing limited efficacy due to neurocognitive impairments.Case SummaryWe report two patients with severe TBI and psychiatric comorbidities treated with Prism neurofeedback.Case 144-year-old female, 35 years post-childhood TBI, with agoraphobia and hyperacusis, achieved 42% PTSD reduction and substantial functional gains (social reintegration, independent driving) sustained through 4-month follow-up.Case 240-year-old male, 3.5 years post-adult TBI with bipolar II disorder and severe PTSD (PCL-5 = 62), achieved 90% PTSD reduction with complete remission sustained at 1-month follow-up, enabling return to work and family system transformation. Both patients developed personalized regulatory strategies and maintained gains without relapse.ConclusionsPrism neurofeedback demonstrates clinically meaningful outcomes in severe TBI-PTSD where traditional psychotherapy shows limited efficacy. The intervention’s circumvention of cognitive processing demands may explain the favorable outcomes. Controlled trials are warranted.

