Neural Networks Mediating High-Level Mentalizing in Patients With Right Cerebral Hemispheric Gliomas

Abstract

Mentalizing is the ability to understand others' mental state through external cues. It consists of two networks, namely low-level and high-level metalizing. Although it is an essential function in our daily social life, surgical resection of right cerebral hemisphere disturbs mentalizing processing with high possibility. In the past, little was known about the white matter related to high-level mentalizing, and the conservation of high-level mentalizing during surgery has not been a focus of attention. Therefore, the main purpose of this study was to examine the neural networks underlying high-level mentalizing and then, secondarily, investigate the usefulness of awake surgery in preserving the mentalizing network. A total of 20 patients with glioma localized in the right hemisphere who underwent awake surgery participated in this study. All patients were assigned to two groups: with or without intraoperative assessment of high-level mentalizing. Their high-level mentalizing abilities were assessed before surgery and 1 week and 3 months after surgery. At 3 months after surgery, only patients who received the intraoperative high-level mentalizing test showed the same score as normal healthy volunteers. The tract-based lesion symptom analysis was performed to confirm the severity of damage of associated fibers and high-level mentalizing accuracy. This analysis revealed the superior longitudinal fascicles (SLF) III and fronto-striatal tract (FST) to be associated with high-level mentalizing processing. Moreover, the voxel-based lesion symptom analysis demonstrated that resection of orbito-frontal cortex (OFC) causes persistent mentalizing dysfunction. Our study indicates that damage of the OFC and structural connectivity of the SLF and FST causes the disorder of mentalizing after surgery, and assessing high-level mentalizing during surgery may be useful to preserve these pathways.

Keywords: awake surgery; fronto-striatal tract; glioma; mentalizing; superior longitudinal fascicle.

Figure 1

Time series of Wechsler Adult Intelligence Scale (WAIS) picture arrangement (PA) score of all patients. Bar-graph shows mean ± standard deviations of time course of patients group and healthy volunteers group. A Steel analysis (non-parametric multiple comparison analysis) was performed. Scores of all patients at preoperative and postoperative 1 week were significantly lower than those of healthy volunteers, while there was no difference between groups at postoperative 3 months.

Figure 2

Overlap map of resected region. Overlap map of resection cavities shows that the right prefrontal cortex was the region with the greatest overlap. As for subcortical level, the greatest overlap region was equivalent to the course of the frontal-aslant tract (FAT) and fronto-striatal tract (FST).

Figure 3

Results of the voxel-based lesion-symptom (VLSM) analysis. The VLSM analysis of high-level mentalizing accuracy was performed using resection cavity maps. Only voxels surviving on a FDR-controlled threshold (p = 0.05; z = 1.70) are shown.

Figure 4

Results of intraoperative findings with the voxel-based lesion-symptom (VLSM) and tract-based lesion-symptom (TBLS) analyses. Overlapped intraoperative findings on the VLSM results (A). Positive mapping sites (yellow circles) were located on the inferior frontal orbital and deep in the inferior frontal gyrus, which matched results of the VLSM analysis (red region). Numeral tags on intraoperative photographs represent results of mapping as follows; Case 15: Tag 1, motor; Tag 3 and 5, high-level mentalizing; Tag 4, visuospatial cognition, Case 5: Tag 1, dysarthria; Tag 2, high-level mentalizing. Cyan region, resection cavity. Intraoperative findings and the TBLS results (B). Left column: positive mapping site (Tag 9) was found in the superior frontal gyrus, which was on the origin of the fronto-striatal tract (FST) (pink). Tag 2, 3, 4, 5 and 6, dysarthria; Tag 7 and 8, involuntary movement; Tag 9, high-level mentalizing; Tag 11, 12 and 13, positive findings using motor evoked potential. Right column: Spatial location of temporal disconnection of white matter induced by direct electrical stimulation (DES; yellow to orange region) was located along the superior longitudinal fascicles (SLF) III (green). Percentage of disconnection: yellow region, 100%; red region, 50%.