Memory recovery is related to default mode network impairment and neurite density during brain tumours treatment

Objective The aim of this study is to test brain tumour interactions with brain networks thereby identifying protective features and risk factors for memory recovery after surgical resection. Methods Seventeen patients with diffuse non-enhancing glioma (aged 22-56 years) were longitudinally MRI-scanned before and after surgery, and during a 12-months recovery period (47 MRI in total after exclusion). After each scanning session, a battery of memory tests was performed using a tablet-based screening tool, including free verbal memory, overall verbal memory, episodic memory, orientation, forward digit span and backwards digit span. Using structural MRI and Neurite Orientation Dispersion and Density Imaging (NODDI) derived from diffusion-weighted images, we respectively estimated lesion overlap and Neurite Density with brain networks derived from normative data in healthy participants (somato-motor, dorsal attention, ventral attention, fronto-parietal and Default Mode Network -DMN-). Linear Mixed Models (LMMs) that regressed out the effect of age, gender, tumour grade, type of treatment, total lesion volume and total neurite density were used to test the potential longitudinal associations between imaging markers and memory recovery. Results Memory recovery was not significantly associated with tumour location based on traditional lobe classification nor with the type of treatment received by patients ( i . e . surgery alone or surgery with adjuvant chemoradiotherapy). Non-local effects of tumours were evident on Neurite Density, which was reduced not only within the tumour, but also beyond the tumour boundary. In contrast, high preoperative Neurite Density outside the tumour, but within the DMN, was associated with better memory recovery (LMM, P fdr <10−3). Furthermore, postoperative and follow-up Neurite Density within the DMN and fronto-parietal network were also associated with memory recovery (LMM, Pfdr =0.014 and Pfdr =0.001, respectively). Preoperative tumour, and post-operative lesion, overlap with the DMN showed a significant negative association with memory recovery (LMM, Pfdr =0.002 and Pfdr <10−4, respectively). Conclusion Imaging biomarkers of cognitive recovery and decline can be identified using NODDI and resting-state networks. Brain tumours and their corresponding treatment affecting brain networks that are fundamental for memory functioning such as the DMN can have a major impact on patient’s memory recovery. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was supported by The Brain Tumour Charity, the Guarantors of Brain (RG91650) and the Cambridge Philosophical Society. ### Author Declarations All relevant ethical guidelines have been followed and any necessary IRB and/or ethics committee approvals have been obtained. Yes All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes Any clinical trials involved have been registered with an ICMJE-approved registry such as ClinicalTrials.gov and the trial ID is included in the manuscript. Not Applicable I have followed all appropriate research reporting guidelines and uploaded the relevant Equator, ICMJE or other checklist(s) as supplementary files, if applicable. Yes Data is not currently available