Precuneal gliomas promote behaviorally relevant remodeling of the functional connectome

J Neurosurg 138:1531–1541, 2023

The precuneus hosts one of the most complex patterns of functional connectivity in the human brain. However, due to the extreme rarity of neurological lesions specifically targeting this structure, it remains unknown how focal damage to the precuneus may impact resting-state functional connectivity (rsFC) at the brainwide level. The aim of this study was to investigate glioma-induced rsFC modulations and to identify patterns of rsFC remodeling that accounted for the maintenance of cognitive performance after awake-guided surgical excision.

METHODS In a unique series of patients with IDH1-mutated low-grade gliomas (LGGs) infiltrating the precuneus who were treated at a single neurosurgical center (Montpellier University Medical Center, 2014–2021), the authors gauged the dynamic modulations induced by tumors on rsFC in comparison with healthy participants. All patients received a preoperative resting-state functional MRI and underwent operation guided by awake cognitive mapping. Connectome multivariate pattern analysis (MVPA), seed-network analysis, and graph theoretical analysis were conducted and correlated to executive neurocognitive scores (i.e., phonological and semantic fluencies, Trail-Making Test [TMT] parts A and B) obtained 3 months after surgery.

RESULTS Seventeen patients with focal precuneal infiltration were selected (mean age 38.1 ± 11.2 years) and matched to 17 healthy participants (mean age 40.5 ± 10.4 years) for rsFC analyses. All patients underwent awake cognitive mapping, allowing total resection (n = 3) or subtotal resection (n = 14), with a mean extent of resection of 90.6% ± 7.3%. Using MVPA (cluster threshold: p–false discovery rate corrected < 0.05, voxel threshold: p-uncorrected < 0.001), remote hotspots with significant rsFC changes were identified, including both insulas, the anterior cingulate cortex, superior sensorimotor cortices, and both frontal eye fields. Further seed-network analyses captured 2 patterns of between-network redistribution especially involving hyperconnectivity between the salience, visual, and dorsal attentional networks. Finally, the global efficiency of the salience-visual-dorsal attentional networks was strongly and positively correlated to 3-month postsurgical scores (n = 15) for phonological fluency (r 15 = 0.74, p = 0.0027); TMT-A (r 15 = 0.65, p = 0.012); TMTB (r 15 = 0.70, p = 0.005); and TMT-B-A (r 15 = 0.62, p = 0.018).

CONCLUSIONS In patients with LGGs infiltrating the precuneus, remote and distributed functional connectivity modulations in the preoperative setting are associated with better maintenance of cognitive performance after surgery. These findings provide a new vision of the mechanistic principles underlying neural plasticity and cognitive compensation in patients with LGGs.

Extending the multistage surgical strategy for recurrent initially low-grade gliomas: functional and oncological outcomes in 31 consecutive patients who underwent a third resection under awake mapping

J Neurosurg 136:1035–1044, 2022

Maximal safe resection is the first treatment in diffuse low-grade glioma (DLGG). Due to frequent tumor recurrence, a second surgery has already been reported, with favorable results. This study assesses the feasibility and functional and oncological outcomes of a third surgery in recurrent DLGG.

METHODS Patients with DLGG who underwent a third functional-based resection using awake mapping were consecutively selected. They were classified into group 1 in cases of slow tumor regrowth or group 2 if a radiological enhancement occurred during follow-up. All data regarding clinicoradiological features, histomolecular results, oncological treatment, and survival were collected.

RESULTS Thirty-one patients were included, with a median age of 32 years. There were 20 astrocytomas and 11 oligodendrogliomas in these patients. Twenty-one patients had medical oncological treatment before the third surgery, consisting of chemotherapy in 19 cases and radiotherapy in 8 cases. No neurological deficit persisted after the third resection except mild missing words in 1 patient, with 84.6% of the patients returning to work. The median follow-up duration was 13.1 ± 3.4 years since diagnosis, and 3.1 ± 2.9 years since the third surgery. The survival rates at 7 and 10 years were 100% and 89.7%, respectively, with an estimated median overall survival of 17.8 years since diagnosis. A comparison between the groups showed that the Karnofsky Performance Scale score dropped below 80 earlier in group 2 (14.3 vs 17.1 years, p = 0.01). Median residual tumor volume at the third surgery was smaller (2.8 vs 14.4 cm 3 , p = 0.003) with a greater extent of resection (89% vs 70%, p = 0.003) in group 1.

CONCLUSIONS This is the first consecutive series showing evidence that, in select patients with progressive DLGG, a third functional-based surgery can be achieved using awake mapping with low neurological risk and a high rate of total resection, especially when reoperation is performed before malignant transformation.

Intraoperative Cognition Mapping and Monitoring “à la carte” in Brain Tumor Patients

Neurosurgery 88:919–930, 2021

The purpose of surgery for brain tumors involving eloquent neural circuits is to maximize the extent of resection while preserving an optimal quality of life. To this end, especially in diffuse glioma, the goal is to remove the cerebral parenchyma invaded by the neoplasm up to the individual cortico-subcortical networks critical for brain functions.

Intraoperative mapping combined with real-time cognitive monitoring throughout the resection in awake patient is thus highly recommended to resume a normal life. Indeed, beyond avoiding hemiplegia or aphasia, enjoying a familial, social, and professional life implies that motor and language mapping is not sufficient.

Identifying and sparing neural networks that subserve cognition (movement control, visuospatial cognition, executive functions, multimodal semantics, metacognition) andmentalizing (theory ofmind, which plays a key role for social cognition) is essential to preserve an adapted behavior.

Here, the aim is to review when and how to map these critical functions, which have nonetheless been neglected for many decades by neurosurgeons. In fact, the disorders generated by surgical injuries of circuits underpinning nonmotor and nonspeech functions are usually not immediately visible on postoperative standard clinical examination, leading the physician to believe that the patient has no deficit. Yet, cognitive or emotional disturbances may subsequently prevent to resume an active life, as to work full time.

Therefore, a systematic neuropsychological assessment should be performed before, during, and after mapping-guided surgery, regardless of the tumor location, to preserve the functional connectome intraoperatively and to plan a postoperative tailored cognitive rehabilitation according to the patient’s needs.

Brain connectomics applied to oncological neuroscience: from a traditional surgical strategy focusing on glioma topography to a meta-network approach

Acta Neurochirurgica (2021) 163:905–917

The classical way for surgical selection and planning in cerebral glioma mainly focused on tumor topography. The emerging science of connectomics, which aims of mapping brain connectivity, resulted in a paradigmatic shift from a modular account of cerebral organization to a meta-network perspective. Adaptive behavior is actually mediated by constant changes in interactions within and across large-scale delocalized neural systems underlying conation, cognition, and emotion.

Here, to optimize the onco-functional balance of glioma surgery, the purpose is to switch toward a connectome-based resection taking account of both relationships between the tumor and critical distributed circuits (especially subcortical pathways) as well as the perpetual instability of the meta-network. Such dynamic in the neural spatiotemporal integration permits functional reallocation leading to neurological recovery after massive resection in structures traditionally thought as “inoperable.” This better understanding of connectome increases benefit/risk ratio of surgery (i) by selecting resection in areas deemed “eloquent” according to a localizationist dogma; (ii), conversely, by refining intraoperative awake cognitive mapping and monitoring in so-called non-eloquent areas; (iii) by improving preoperative information, enabling an optimal selection of intrasurgical tasks tailored to the patient’s wishes; (iv) by developing an “oncological disconnection surgery”; (v) by defining a personalized multistep surgical strategy adapted to individual brain reshaping potential; and (vi) ultimately by preserving environmentally and socially appropriate behavior, including return to work, while increasing the extent of (possibly repeated) resection(s).

Such a holistic vision of neural processing can enhance reliability of connectomal surgery in oncological neuroscience and may also be applied to restorative neurosurgery.