Multivariate mapping of low-resilient neurocognitive systems within and around low-grade gliomas

Abstract

Accumulating evidence suggests that the brain exhibits a remarkable capacity for functional compensation in response to neurological damage, a resilience potential that is deeply rooted in the malleable features of its underlying anatomo-functional architecture. This propensity is particularly exemplified by diffuse low-grade gliomas (DLGGs), a subtype of primary brain tumour. However, functional plasticity is not boundless, and surgical resections directed at structures with limited neuroplasticity may lead to incapacitating impairments. Yet, maximizing DLGG resections offers substantial oncological benefits, especially when the resection extends beyond the tumour margins (i.e., supra-tumour or supra-total resection). In this context, the primary objective of this study was to identify which cerebral structures were associated with less favourable cognitive outcomes after surgery, while accounting for intra-tumour and supra-tumour features of the surgical resections. To reach this objective, we leveraged a unique cohort of 400 DLGG patients who underwent surgery with awake cognitive mapping. Patients benefited from a neuropsychological assessment consisting of 18 subtests administered before and 3 months post-surgery. We analysed changes in performance and applied topography-focused and disconnection-focused multivariate lesion-symptom mapping (LSM) using support vector regressions with an attempt to capture resected cortico-subcortical structures less amenable to full cognitive compensations. The observed changes in performance were of a limited magnitude suggesting an overall recovery (13/18 tasks fully recovered despite a mean resection extent of 92.4%). Nevertheless, LSM analyses revealed that a lack of recovery in picture naming was linked to damage in the left inferior temporal gyrus and inferior longitudinal fasciculus. Similarly, for semantic fluency abilities, an association was established with damage to the left precuneus/posterior cingulate. For phonologic fluency abilities, the left dorso-medial frontal cortex and the frontal aslant tract were implicated. Moreover, difficulties in spatial exploration were associated with injury to the right dorsomedial prefrontal cortex and its underlying connectivity. An exploratory analysis suggested that supra-tumoral resections were associated with a less pronounced recovery following specific resection patterns, such as supra-tumour resections of the left uncinate fasciculus (picture naming), the left corticostriatal tract and the anterior corpus callosum (phonologic fluency), the hippocampus and para-hippocampus (episodic memory), and the right frontal-mesial areas (visuospatial exploration). Collectively, these patterns of results shed new light on both low-resilient neural systems and the prediction of cognitive recovery following glioma surgery. Furthermore, they indicate that supra-tumour resections were only occasionally less well-tolerated from a cognitive viewpoint. In doing so, they have deep implications for surgical planning and rehabilitation strategies.

Keywords: awake surgery; cognition; low-grade glioma; plasticity; supratotal resection.