Letter: Introducing New Tasks for Intraoperative Mapping in Awake Glioma Surgery: Clearing the Line Between Patient Care and Scientific Research

To the Editor: Over the past two decades, it has been demonstrated that brain mapping in an awake patient is a very reliable tool for brain tumor resection, allowing us to maximize the extent of resection while minimizing the functional risk.1 This methodology is becoming more and more popular, and different teams have introduced many new tasks in their intraoperative battery, for motor functions2 as well as for cognitive functions.3,4 While the aim of preserving functions better and better cannot be blamed, it should be kept in mind that selecting for each case a personalized minimal set of tasks is crucial: the awake surgery team has to find an optimal trade-off between the number of tasks incorporated in the intraoperative battery and the limited amount of time of the awake period (about 2 h, in keeping with the onset of the patient's tiredness, which renders monitoring unreliable). More than that, there is a risk of introducing tasks that would be too sensitive, in the sense that the removal of a positive site would not necessarily lead to a permanent deficit of the function, meaning that brain mapping would restrict the extent of resection for no good reasons. We, thus, would like to highlight in this letter that the introduction of a new task tapping a specific sensorimotor, cognitive, or emotional process should follow a strict scientific plan. First, it needs to be demonstrated in a retrospective series of patients operated on without any intraoperative monitoring of the task that some of them do indeed suffer from a permanent deficit of the cognitive function at hand. By permanent deficit, we mean a score decrease of 1.5 SD or more at 1 yr after surgery, despite patients benefitting from a targeted rehabilitation program in the postoperative period. Time and training are indeed the two parameters underlying an optimal efficiency of brain plasticity implementation. One or both of the conditions were not met in several recent studies. For example, in the study of Martino et al,5 only 50% of patients were entered in a rehabilitation program, potentially contributing to lessen the degree of recovery of verbal short-term memory, and likely explaining the discrepancy with the study of Teixidor et al.6 Another example is given by a recent study about deficits in spatial working memory,7 in which the chronicity was defined at 1 mo postop, which is too early in the process of recovery. Of note, an analysis of intrapatient changes should be preferred to a group-level analysis. For example, this might explain the discrepancy in the study of Herbet et al8 and the one of Nakajima et al9 regarding the long-term deficits in high-level mentalizing. Once it has been established that some patients do suffer permanent deficits, one needs to determine which part of the resected brain and/or which part of the brain still infiltrated by a residual tumor correlates with the persistent impairment. Again, this is important, as using widely the new task for any location could lead to prematurely stop the resection because of the intraoperative response to electrical stimulation, whereas the function would have recovered in the long term, after an acute period of impairment (the so-called “false positives”10). For example, before introducing intraoperatively the Read the Mind in the Eye test for right-sided frontal tumors,11 Herbet et al8 first demonstrated that resections in the right posterior inferior frontal gyrus were associated with long-term deficits in a subset of patients. Finally, definitive evidence should be given by comparing the cognitive scores of 2 consecutive cohorts, one operated on with task monitoring and one without. Very few studies complied with this requirement. This has been done in a recent study looking at executive function testing during right frontal resections: outcomes were much better in the group in which the Stroop task was monitored compared to the control group.12 In the same vein, Mandonnet et al13 first reported a strong deficit in cognitive flexibility after a right parietal glioma resection and determined how this deficit was caused by a wide disconnection within the associative fibers of the cognitive control network. Then, they demonstrated in a second patient-case with a tumor at a similar location that the stimulation of the white matter in the right parieto-temporal junction disrupted intraoperatively the part B of the trail making test, prompting the surgeon to stop the resection and allowing to preserve cognitive flexibility.14 Last but not least, and although this does not constitute a proof by itself, the fact that several teams adopt a new task is a good indicator of its interest and reproducibility. Hence, several groups have confirmed the usefulness of line bisection,15,16 nonverbal semantic association,16-19 or mentalization tasks,9 following the seminal reports introducing these new tasks.20-22 We, thus, advocate to analyze in a systematic manner the level of evidence before introducing a new intraoperative task. This would help better delineate the situations in which mapping is performed for patient care from situations in which mapping is motivated by a scientific quest. For example, additional tasks, such as a 2-back verbal memory task, have been sometimes introduced into the operating theater, with an identification of structures eliciting disturbances of verbal working memory during electrical mapping, and with, nonetheless, a surgical resection of these structures despite a positive mapping23: therefore, the task was useless for the patient, and was tested only for research purposes. Not to say that new tasks should never be tested only for research, but in this latter case, the patient should be clearly informed and should agree with the purely exploratory nature of this new task monitoring. Disclosures The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.