Cerebellar and Prefrontal Cortical Alterations in PTSD: Structural and Functional Evidence

• Main Authors: Sophie E. Holmes, Dustin Scheinost, Nicole DellaGioia, Margaret T. Davis, David Matuskey, Robert H. Pietrzak, Michelle Hampson, John H. Krystal, Irina Esterlis
• Format: Article
• Language: English
• Published: SAGE Publishing 2018-07-01
• Series: Chronic Stress
• Online Access: https://doi.org/10.1177/2470547018786390

Background Neuroimaging studies have revealed that disturbances in network organization of key brain regions may underlie cognitive and emotional dysfunction in posttraumatic stress disorder (PTSD). Examining both brain structure and function in the same population may further our understanding of network alterations in PTSD. Methods We used tensor-based morphometry and intrinsic connectivity distribution to identify regions of altered volume and functional connectivity in unmedicated individuals with PTSD ( n  = 21) and healthy comparison participants ( n  = 18). These regions were then used as seeds for follow-up anatomical covariance and functional connectivity analyses. Results Smaller volume in the cerebellum and weaker structural covariance between the cerebellum seed and the middle temporal gyrus were observed in the PTSD group. Individuals with PTSD also exhibited lower whole-brain connectivity in the cerebellum, dorsolateral prefrontal cortex (dlPFC) and medial prefrontal cortex. Functional connectivity in the cerebellum and grey matter volume in the dlPFC were negatively correlated with PTSD severity as measured by the DSM-5 PTSD Checklist (PCL-5; r  = −.0.77, r  = − 0.79). Finally, seed connectivity revealed weaker connectivity within nodes of the central executive network (right and left dlPFC), and between nodes of the default mode network (medial prefrontal cortex and cerebellum) and the supramarginal gyrus, in the PTSD group. Conclusion We demonstrate structural and functional alterations in PTSD converging on the PFC and cerebellum. Whilst PFC alterations are relatively well established in PTSD, the cerebellum has not generally been considered a key region in PTSD. Our findings add to a growing evidence base implicating cerebellar involvement in the pathophysiology of PTSD.