Alessandra Casarotti

Motor and language DTI Fiber Tracking combined with intraoperative subcortical mapping for surgical removal of gliomas

Preoperative DTI Fiber Tracking (DTI-FT) reconstruction of functional tracts combined with intraoperative subcortical mapping (ISM) is potentially useful to improve surgical procedures in gliomas located in eloquent areas. Aims of the study are: (1) to evaluate the modifications of fiber trajectory induced by the tumor; (2) to validate preoperative DTI-FT results with intraoperative identification of functional subcortical sites through direct subcortical stimulation; (3) to evaluate the impact of preoperative DTI-FT reconstructions in a neuronavigational setup combined with ISM technique on duration and modalities of surgical procedures, and on functional outcome of the patients. Data are available on 64 patients (52 low-grade and 12 high-grade gliomas). DTI-FT was acquired by a 3-T MR scanner with a single-shot EPI sequence (TR/TE 8986/80 ms, b=1000 s/mm) with gradients applied along 32 non-collinear directions. 3D Fast Field Echo (FFE) T1-weighted imaging (TR/TE 8/4 ms) was performed for anatomic guidance. The corticospinal tract (CST), superior longitudinal, inferior fronto-occipital and uncinatus fasciculi were reconstructed. Data were transferred to the neuronavigational system. Functional subcortical sites identified during ISM were correlated with fiber tracts depicted by DTI-FT. In high-grade gliomas, DTI-FT depicted tracts mostly at the tumor periphery; in low-grade gliomas, fibers were frequently located inside the tumor mass. There was a high correlation between DTI-FT and ISM (sensitivity for CST=95%, language tracts=97%). For a proper reconstruction of the tracts, it was necessary to use a low FA threshold of fiber tracking algorithm and to position additional regions of interest (ROIs). The combination of DTI-FT and ISM decreased the duration of surgery, patient fatigue, and intraoperative seizures. Combination of DTI-FT and ISM allows accurate identification of eloquent fiber tracts and enhances surgical performance and safety maintaining a high rate of functional preservation.

What is the role of the uncinate fasciculus? Surgical removal and proper name retrieval

The functional role of the uncinate fasciculus is still a matter of debate. We examined 44 patients submitted to awake surgery for removal of a left frontal or temporal glioma. In 18 patients, the removal included the uncinate fasciculus. We compared patients with or without removal on a series of neuropsychological tasks, performed at different time intervals: pre-surgery, in the first week after surgery and 3 months after surgery. Functional magnetic resonance and diffusion tensor imaging, fibre-tracking techniques were performed before surgery. At the last examination, patients with uncinate removal were significantly impaired in naming of famous faces and objects as compared with patients without removal. We further divided patients according to the site of the tumour (either frontal or temporal). At the follow-up, patients with a temporal glioma who underwent uncinate removal had the worst loss of performance in famous face naming. In addition, on the same task, the group with a frontal glioma that underwent resection of the frontal part of the uncinate performed significantly worse than the group with a frontal glioma but without uncinate removal. In conclusion, the resection of the uncinate fasciculus, in its frontal or temporal part, has long-lasting consequences for famous face naming. We suggest that this fibre tract is part of a circuitry involved in the retrieval of word form for proper names. Retrieval of conceptual knowledge was intact.

Measuring clinical outcomes in neuro-oncology. A battery to evaluate low-grade gliomas (LGG)

We describe how a neuropsychological evaluation in patients with brain tumors should be performed, specifically in the case of low-grade gliomas. Neuropsychological examination is crucial before starting any treatment as well as during the follow-up, since it can improve neurosurgery techniques and reveal potential cognitive effects of chemotherapy and radiotherapy, besides planning rehabilitation. We underline that sensitive and wide-ranging tests are required; specific tasks based on the lesion site should be added. Moreover, some tests can provide additional information about the evolution of the tumor. A careful, thorough examination improves quality of life.

Connectivity constraints on cortical reorganization of neural circuits involved in object naming

The brains plasticity in response to sensory deprivation and other perturbations is well established. While the functional properties of the reorganized areas are under vigorous investigation, the factors that constrain cortical reorganization remain poorly understood. One factor constraining such reorganization may be long-distance subcortical connectivity between relevant cortical regions-reorganization attempts to preserve the functionality of subcortical connections. Here we provide human neurophysiological evidence for the role of the subcortical connections in shaping cortical reorganization of the networks involved in object naming following perturbation of normal function. We used direct electrical stimulation (DES) during surgical removal of gliomas to identify the sites that are involved in naming different categories of objects. The sites that were selectively inhibited in naming either living or non-living objects were displaced relative to those observed with other subject populations, possibly reflecting cortical reorganization due to slowly evolving brain damage. Subcortical DES applied to the white matter underlying these regions also led to category-specific naming deficits. The existence of these subcortical fiber pathways was confirmed using diffusion tensor tractography. These results constitute the first neurophysiological evidence for the critical role of subcortical pathways as part of the neural circuits that are involved in object naming; they also highlight the importance of subcortical connectivity in shaping cortical reorganization following perturbations of normal function.

Cerebral Correlates of Visuospatial Neglect: A Direct Cerebral Stimulation Study

To assess the role of the superior longitudinal fascicle, the inferior fronto‐occipital fascicle, and the posterior parietal lobe in visuospatial attention in humans during awake brain surgery.

The Mirror Neuron System and The Strange Case of Broca's Area

Mirror neurons, originally described in the monkey premotor area F5, are embedded in a frontoparietal network for action execution and observation. A similar Mirror Neuron System (MNS) exists in humans, including precentral gyrus, inferior parietal lobule, and superior temporal sulcus. Controversial is the inclusion of Brocas area, as homologous to F5, a relevant issue in light of the mirror hypothesis of language evolution, which postulates a key role of Brocas area in action/speech perception/production. We assess “mirror” properties of this area by combining neuroimaging and intraoperative neurophysiological techniques. Our results show that Brocas area is minimally involved in action observation and has no motor output on hand or phonoarticulatory muscles, challenging its inclusion in the MNS. The presence of these functions in premotor BA6 makes this area the likely homologue of F5 suggesting that the MNS may be involved in the representation of articulatory rather than semantic components of speech. Hum Brain Mapp 36:1010–1027, 2015.

Specific disgust processing in the left insula: New evidence from direct electrical stimulation

Neuropsychological and neuroimaging studies yielded controversial results concerning the specific role of the insula in recognizing the facial expression of disgust. To verify whether the insula has a selective role in facial disgust processing, emotion recognition was studied in thirteen patients during intraoperative stimulation of the insula in awake surgery performed for removal of a glioma close to this structure. Direct electrical stimulation of the left insula produced a general decrease in emotion recognition but only in the case of disgust there was a statistically significant detrimental effect (p=0.004). Happiness and anger were the best and the worst recognized emotion, respectively. The worst baseline performance with anger and, partly, fear could be explained with the involvement of the left temporal regions, striatum, and the connection between the striatum and the frontal lobe, as suggested in previous studies. Therefore, upon these intra-operative evidences, we argue for a selective role of the left insula in disgust recognition, although a (non significant) decrease in the recognition of other negative emotions was found. However, additional networks can develop, as demonstrated by the fact that disgust recognition was not impaired after surgery even in patients with insular resection in the current as in previous studies.

Decision-making abilities in patients with frontal low-grade glioma

Decisions in daily life are often quite complex, especially when one has to decide about his/her own health, as it is the case for patients with brain tumours. The integrity of the prefrontal cortex (and of the orbito-frontal in particular) is crucial in humans for practical decision-making. We investigated decision-making in 22 right-handed patients with a left frontal low-grade glioma, by means of a more complex, computerized version of the Iowa gambling task and we compared their performance with that of 26 neurologically-unimpaired subjects. After the experiment, we also administered a questionnaire to evaluate subjects’ conscious comprehension level of the task and two self-report scales to verify potential effects of individual personality differences. Patients chose significantly less cards than controls from the advantageous deck, without modifying their behaviour over time, and this correlated with abstract reasoning abilities. In both groups, level of comprehension, significantly affected performance. An improvement was found post-surgery. In conclusion, the performance in the Gambling Task suggests that patients with left frontal low-grade gliomas can be impaired in decision-making, apparently requiring more time to understand the task: therefore, a particular attention and care should be taken to explain risks and consequences of his/her illness and treatment in order to obtain an informed decision from the patient.

Mapping the brain network of the phonological loop

The cortical and subcortical neural correlates underlying item and order information in verbal short‐term memory (STM) were investigated by means of digit span in 29 patients with direct electrical stimulation during awake surgery for removal of a neoplastic lesion. Stimulation of left Brocas area interfered with span, producing significantly more item than order errors, as compared to the stimulation of the supramarginal/angular gyrus, which also interfered with span but, conversely, produced more order than item errors. Similarly, stimulation of the third segment of the left superior longitudinal fasciculus (SLF‐III), also known as anterior segment of the arcuate fascicle (AF), produced more order than item errors. Therefore, we obtained two crucial results: first, we were able to distinguish between content and order information storage. Second, we demonstrated that the SLF‐III is involved in transferring order information from Geschwinds area to Brocas area. In a few patients, we demonstrated that also order information of nonverbal material was disrupted by left supramarginal gyrus stimulation. Order information is thus likely stored in the supramarginal gyrus, possibly independently from the nature of the material. Hum Brain Mapp 38:3011–3024, 2017.

Monopolar high-frequency language mapping: can it help in the surgical management of gliomas? A comparative clinical study

OBJECT Intraoperative language mapping is traditionally performed with low-frequency bipolar stimulation (LFBS). High-frequency train-of-five stimulation delivered by a monopolar probe (HFMS) is an alternative technique for motor mapping, with a lower reported seizure incidence. The application of HFMS in language mapping is still limited. Authors of this study assessed the efficacy and safety of HFMS for language mapping during awake surgery, exploring its clinical impact compared with that of LFBS. METHODS Fifty-nine patients underwent awake surgery with neuropsychological testing, and LFBS and HFMS were compared. Frequency, type, and site of evoked interference were recorded. Language was scored preoperatively and 1 week and 3 months after surgery. Extent of resection was calculated as well. RESULTS High-frequency monopolar stimulation induced a language disturbance when the repetition rate was set at 3 Hz. Interference with counting (p = 0.17) and naming (p = 0.228) did not vary between HFMS and LFBS. These results held true when preoperative tumor volume, lesion site, histology, and recurrent surgery were considered. Intraoperative responses (1603) in all patients were compared. The error rate for both modalities differed from baseline values (p < 0.001) but not with one another (p = 0.06). Low-frequency bipolar stimulation sensitivity (0.458) and precision (0.665) were slightly higher than the HFMS counterparts (0.367 and 0.582, respectively). The error rate across the 3 types of language errors (articulatory, anomia, paraphasia) did not differ between the 2 stimulation methods (p = 0.279). CONCLUSIONS With proper setting adjustments, HFMS is a safe and effective technique for language mapping.