Pretraining neural and neuropsychological measures of executive functioning are associated with response to working memory training in Veterans with PTSD.

Although there are several evidence-based treatments for post-traumatic stress disorder (PTSD), up to half of patients do not experience significant symptom relief. Executive functioning (EF) impairment is believed to impede PTSD recovery and diminish treatment response, but is not directly targeted by traditional treatments. Cognitive training for EF has emerged as a promising treatment alternative for PTSD, but may only benefit certain patients. The present study aimed to identify, validate, and characterize the subgroup of patients with PTSD who respond to an EF training program. Veterans with PTSD (N = 79) completed neuropsychological tests and a working memory task during functional magnetic resonance imaging scanning, followed by 16 sessions of an EF training program (working memory training [WMT]). Growth mixture modeling identified subgroups based on session-by-session working memory changes. Mixed-effects models then evaluated differences in spatial working memory and PTSD symptom improvement among these subgroups. Finally, the subgroups were compared on baseline neuropsychological performance and neural activity. Three subgroups were extracted, with one subgroup (labeled low-WM/steep improvement subgroup) exhibiting steeper working memory improvement across training and greater spatial working memory and PTSD symptom improvement following training. The low-WM/steep improvement subgroup was uniquely characterized by a combination of lower EF task performance and lower working memory-related neural activity at baseline. WMT may be a promising alternative PTSD treatment for Veterans with EF impairments. Patients likely to benefit from WMT could be identified using a combination of neuropsychological and neuroimaging assessments, but further research is needed to confirm these indicators.