Functional Mapping before and after Low-Grade Glioma Surgery: A New Way to Decipher Various Spatiotemporal Patterns of Individual Neuroplastic Potential in Brain Tumor Patients

Abstract

Intraoperative direct electrostimulation mapping (DEM) is currently the gold-standard for glioma surgery, since functional-based resection allows an optimization of the onco-functional balance (increased resection with preserved quality of life). Besides intrasurgical awake mapping of conation, cognition, and behavior, preoperative mapping by means of functional neuroimaging (FNI) and transcranial magnetic stimulation (TMS) has increasingly been utilized for surgical selection and planning. However, because these techniques suffer from several limitations, particularly for direct functional mapping of subcortical white matter pathways, DEM remains crucial to map neural connectivity. On the other hand, non-invasive FNI and TMS can be repeated before and after surgical resection(s), enabling longitudinal investigation of brain reorganization, especially in slow-growing tumors like low-grade gliomas. Indeed, these neoplasms generate neuroplastic phenomena in patients with usually no or only slight neurological deficits at diagnosis, despite gliomas involving the so-called "eloquent" structures. Here, data gained from perioperative FNI/TMS mapping methods are reviewed, in order to decipher mechanisms underpinning functional cerebral reshaping induced by the tumor and its possible relapse, (re)operation(s), and postoperative rehabilitation. Heterogeneous spatiotemporal patterns of rearrangement across patients and in a single patient over time have been evidenced, with structural changes as well as modifications of intra-hemispheric (in the ipsi-lesional and/or contra-lesional hemisphere) and inter-hemispheric functional connectivity. Such various fingerprints of neural reconfiguration were correlated to different levels of cognitive compensation. Serial multimodal studies exploring neuroplasticity might lead to new management strategies based upon multistage therapeutic approaches adapted to the individual profile of functional reallocation.

Keywords: awake mapping; direct electrostimulation; functional neuroimaging; human connectome; neural networks; neuroplasticity; transcranial magnetic stimulation.

Figure 1

Serial fMRI before and after LGG resection (A): perioperative motor reorganization (from [106]). Left: Preoperative FLAIR-weighted MRI (left column), immediate postoperative diffusion-weighted MRI (center column) and delayed postoperative FLAIR-weighted MRI in 6 patients who underwent resection for an LGG involving the SMA. Right: Evolution of correlation maps within the resting-state sensorimotor network. Correlation coefficients between the sensorimotor network nodes, at both intra-hemispheric (left column) and inter-hemispheric (right column) levels, in the preoperative period (top), in the immediate postoperative period (center), and at 3 months’ follow-up (bottom). In both hemispheres, network nodes include the precentral region, the postcentral region, and the SMA; the SMA was resected on the lesional side and is therefore absent postoperatively. Lower: Longitudinal evolution plot of inter- and intra-hemispheric correlations in the sensorimotor network. The time course of all intra-hemispheric (dashed lines) and inter-hemispheric (continuous lines) correlation coefficients within the sensorimotor network are presented, showing a temporary decrease. (B): perioperative language reorganization (from [107]). Upper: Tumor locations in 32 patients who underwent awake DEM surgery for a left LGG. The sum of all tumor masks in pre-operative condition is displayed. The value in each voxel corresponds to the number of tumors in this specific location (range (0–12)). Lower: Schematic description of the main FC results. The three conditions are displayed: control subjects and patients in pre-and post-operative conditions. Green and red dots correspond respectively to LPH and LLG. Solid lines highlight evidence of FC. Dashed lines show slight FC close to significance or identified using one to one comparison. The FC of the LLG in pre-operative condition is similar to the one in control subjects. The LPH is connected to RPCG in controls and still slightly connected pre-operatively. In the post-operative condition, LPH loses all FC while LLG modifies its connectivity to connect to RPCG as LPH in controls. Abbreviations: RPCG = Right Precentral Gyrus; RLG = Right Lingual Gyrus; LPT = Left Planum Temporale; LPH = Left Parahippocampal gyrus; LLG = Left Lingual Gyrus. (C). (from [108]) FC variations in 82 patients who underwent awake DEM surgery for an LGG. Patients were scanned using rsfMRI successively before surgery (MRI-1), immediately after surgery, within 36 h following surgery (MRI-2), and three months after surgery (MRI-3). Comparison of MRI-1 and MRI-2 (a, axial section) (b, 3-D superior view) show a functional homotopy decrease (yellow to red lines). Comparison of MRI-2 and MRI-3 (c, axial section) (d, 3-D superior view) show a functional homotopy increase (blue lines).

Figure 2

Illustration of remapping in the same patient demonstrated by serial FNI and DEM mappings. (A) Preoperative language fMRI in a patient without deficit, bearing an LGG within the left premotor area: language activation is near the posterior part of the glioma, within the precentral sulcus (white arrow). (B) Intrasurgical views before (left) and after (right) glioma resection, delineated by letter tags. DEM shows a reshaping of the functional maps, with a recruitment of perilesional language sites, enabling a subtotal resection with nevertheless a posterior residue due to the involvement of critical areas (number tags). The yellow arrow shows the precentral sulcus, demonstrating that it was not possible to remove the portion of the LGG involving the precentral gyrus. (C) Immediate postoperative enhanced T1-weighted MRI showing the tumoral residue (small arrow), in front of the precentral gyrus. (D) Postoperative language fMRI 4 years after the first fMRI, revealing a recruitment of the contra-lateral hemisphere (green arrows), and a posterior displacement of a left activation previously located within the precentral sulcus, which now shifted within the central sulcus (white arrow). (E) Intraoperative view during the second surgery, confirming the functional remapping, and making possible a more extensive glioma resection posteriorly, with no permanent deficit. Again, the yellow arrow shows the precentral sulcus, demonstrating that, this time, it was possible to remove a part of the glioma involving the precentral gyrus. (F) Immediate postsurgical axial FLAIR-weighted MRI (3 h after operation) confirming the increase of the extent of resection within the left precentral gyrus, thanks to functional reshaping (the green arrow shows the central sulcus). The patient resumed a normal social and professional life 3 months after reoperation, with no adjuvant oncological treatment. (The images are modified from [19,126])