Presurgical Executive Functioning in Low-Grade Glioma Patients Cannot Be Topographically Mapped

Simple Summary This study investigated the role of the superior longitudinal fasciculus and frontotemporoparietal network in executive functions. The results demonstrated that neither structural and network overlap nor network disconnection predictors explained executive dysfunction in 156 presurgical IDH-mutated low-grade glioma patients. We specifically looked for features that explain executive dysfunction prior to surgery, both at the level of the individual branches of the superior longitudinal fasciculus (distance to glioma; integrity of tracts) as well as at the network level (via disconnection analyses) with data pooled from two neurosurgical centers. Contrary to our expectations, no predictors were found. We believe it is important to share these null results. It is of interest to neurologists, neurosurgeons, and clinical neuroscientists to know that there is no straightforward topographical explanation of executive dysfunction in presurgical low-grade glioma patients and that we need to develop novel methods to unveil the complex underlying mechanisms. We extensively discuss possible explanations for our findings and suggest how to proceed from here. Executive dysfunctions have a high prevalence in low-grade glioma patients and may be the result of structural disconnections of particular subcortical tracts and/or networks. However, little research has focused on preoperative low-grade glioma patients. The frontotemporoparietal network has been closely linked to executive functions and is substantiated by the superior longitudinal fasciculus. The aim of this study was to investigate their role in executive functions in low-grade glioma patients. Patients from two neurological centers were included with IDH-mutated low-grade gliomas. The sets of preoperative predictors were (i) distance between the tumor and superior longitudinal fasciculus, (ii) structural integrity of the superior longitudinal fasciculus, (iii) overlap between tumor and cortical networks, and (iv) white matter disconnection of the same networks. Linear regression and random forest analyses were performed. The group of 156 patients demonstrated significantly lower performance than normative samples and had a higher prevalence of executive impairments. However, both regression and random forest analyses did not demonstrate significant results, meaning that neither structural, cortical network overlap, nor network disconnection predictors explained executive performance. Overall, our null results indicate that there is no straightforward topographical explanation of executive performance in low-grade glioma patients. We extensively discuss possible explanations, including plasticity-induced network-level equipotentiality. Finally, we stress the need for the development of novel methods to unveil the complex and interacting mechanisms that cause executive deficits in low-grade glioma patients.

Automated summary

This study investigated the role of the superior longitudinal fasciculus and frontotemporoparietal network in executive functions in 156 presurgical IDH-mutated low-grade glioma patients. However, the results showed that neither structural and network overlap nor network disconnection predictors explained executive dysfunction in these patients. The study highlights the need for developing new methods to understand the complex mechanisms behind executive deficits in low-grade glioma patients.