Surgical white matter disruption leads to downstream atrophy in the non-resected human brain

Abstract Resective neurosurgery is a cornerstone treatment for many neurological conditions. Although traditionally viewed as localised procedure, increasing evidence from advanced magnetic resonance imaging (MRI) shows that also non-resected anatomy can degenerate following surgery. The relationship between local tissue removal and these postoperative changes remains thus far speculative. Here, we investigate the hypothesis that degenerative changes to surgically preserved grey and white matter are mediated by transneuronal degeneration, a deterioration of intact neuronal populations due to lost axonal input. Using a robust diffusion-weighted and T1-weighted MRI framework specifically tailored for longitudinal analysis of surgical image data, we evaluated evidence to support this mechanism in a series of patients undergoing resective surgery for epilepsy; namely anterior temporal lobectomy (ATL, n=31) or selective amygdalohippocampectomy (SAHE, n=28). We mapped three key aspects of transneuronal degeneration for anatomical regions: 1) loss of surgically resected white matter; 2) longitudinal change in cortical thickness; 3) longitudinal atrophy of non-resected white matter. Using mixed effects models, we explored the evidence in support of a sequential progression of degeneration, where loss of resected white matter leads to downstream atrophy of connected grey matter and the white matter connections thereof. Both ATL and SAHE resulted in extensive resection-related white matter losses, predominately connecting to ipsilateral regions close to resection. We also found pronounced cortical thickness decreases in these regions, as well as extensive white matter atrophy across the ipsilateral hemisphere. These postsurgical alterations were closely associated with resection-related white matter losses, with every 10-fold loss of connections leading to a 3.4% decrease in cortical thickness and a 7.2% decrease in density of downstream pathways. Beyond degenerative effects, we also demonstrate how failure to properly tailor longitudinal image processing to such data can yield misleading evidence for extensive structural network reorganisation, with our more robust approach indicating limited capacity for macroscale plasticity post-resection.