Search

It has been suggested that the inferior longitudinal fasciculus (ILF) may play an important role in several aspects of language processing such as visual object recognition, visual memory, lexical retrieval, reading, and specifically, in naming visual stimuli. In particular, the ILF appears to convey visual information from the occipital lobe to the anterior temporal lobe (ATL). However, direct evidence proving the essential role of the ILF in language and semantics remains limited and controversial. The first aim of this study was to prove that patients with a brain glioma damaging the left ILF would be selectively impaired in picture naming of objects; the second aim was to prove that patients with glioma infiltrating the ATL would not be impaired due to functional reorganization of the lexical retrieval network elicited by the tumor. We evaluated 48 right-handed patients with neuropsychological testing and magnetic resonance imaging (MRI) before and after surgery for resection of a glioma infiltrating aspects of the left temporal, occipital, and/or parietal lobes; diffusion tensor imaging (DTI) was acquired preoperatively in all patients. Damage to the ILF, inferior frontal occipital fasciculus (IFOF), uncinate fasciculus (UF), arcuate fasciculus (AF), and associated cortical regions was assessed by means of preoperative tractography and pre-/pos-toperative MRI volumetry. The association of fascicles damage with patients' performance in picture naming and three additional cognitive tasks, namely, verbal fluency (two verbal non-visual tasks) and the Trail Making Test (a visual attentional task), was evaluated. Nine patients were impaired in the naming test before surgery. ILF damage was demonstrated with tractography in six (67%) of these patients. The odds of having an ILF damage was 6.35 (95% CI: 1.27-34.92) times higher among patients with naming deficit than among those without it. The ILF was the only fascicle to be significantly associated with naming deficit when all the fascicles were considered together, achieving an adjusted odds ratio of 15.73 (95% CI: 2.30-178.16, p = .010). Tumor infiltration of temporal and occipital cortices did not contribute to increase the odd of having a naming deficit. ILF damage was found to be selectively associated with picture naming deficit and not with lexical retrieval assessed by means of verbal fluency. Early after surgery, 29 patients were impaired in naming objects. The association of naming deficit with percentage of ILF resection (assessed by 3D-MRI) was confirmed (beta = -56.78 ± 20.34, p = .008) through a robust multiple linear regression model; no significant association was found with damage of IFOF, UF or AF. Crucially, postoperative neuropsychological evaluation showed that naming scores of patients with tumor infiltration of the anterior temporal cortex were not significantly associated with the percentage of ILF damage (rho = .180, p > .999), while such association was significant in patients without ATL infiltration (rho = -.556, p = .004). The ILF is selectively involved in picture naming of objects; however, the naming deficits are less severe in patients with glioma infiltration of the ATL probably due to release of an alternative route that may involve the posterior segment of the AF. The left ILF, connecting the extrastriatal visual cortex to the anterior region of the temporal lobe, is crucial for lexical retrieval on visual stimulus, such as in picture naming. However, when the ATL is also damaged, an alternative route is released and the performance improves., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: The aim of this study was to achieve a consensus on the minimum set of outcome measures and predictors to be used in the neurosurgical practice and on the timing of outcome assessment., Methods: A consensus building approach was employed. All neurosurgical departments in Lombardy (Italy) were invited to participate by the Carlo Besta Neurologic Institute IRCCS Foundation. Three workshops were organized during which a multidisciplinary group called Neurosurgical Outcome Network (NEON) was created and the methodology to select outcome measures, predictors, and timing of outcome assessment was established. Eight working groups were created for the different neurosurgical diseases (neuro-oncological, skull base, vascular, traumatic, spinal, peripheral nervous system, malformation, functional) and 8 workshops were organized to identify the outcome measures and predictors specific for each of the neurosurgical diseases based on the experts' clinical practice and the existing literature., Results: A total of 20 neurosurgical departments participated in this study. Specific outcome measures, predictors and the timing of outcome assessment were identified for each of the 8 neurosurgical diseases. Moreover, a list of variables common to all pathologies were identified by the NEON group as further data to be collected., Conclusions: A consensus on the minimum set of outcome measures and predictors and the timing of outcome assessments for 8 neurosurgical diseases was achieved by a group of neurosurgeons of the Lombardy region, called NEON. These sets could be used in future studies for a more homogeneous data collection and as a starting point to reach further agreement also at national and international level.

Background: The standardization of outcome measures is needed for comparing studies and using common measures in clinical practice. We aimed to identify cognitive and patient-reported outcomes and timing of assessment for glioma, meningioma, and vascular surgery., Method: A consensus study was conducted. Participants selected cognitive and patient-reported measures among a list of instruments identified through a literature search., Results: Seventeen cognitive tests for the glioma and meningioma's evaluation, 8 for the vascular diseases, and one questionnaire on quality of life and one on emotional distress were identified. The timing of outcome assessment selected was before surgery, at discharge, and after 3 and 12 months for glioma; before surgery and after 3 months for meningioma; before surgery, at discharge, and after 6 months for vascular diseases., Conclusion: The identification of common outcome measures is the first step toward a shared data collection improving the quality and comparability of future studies., (© 2022. Fondazione Società Italiana di Neurologia.)

Background and Purpose: Standard of care for recurrent high grade glioma (HGG) is missing. Several treatment options have been investigated including re-irradiation (re-RT). Results are promising but provided by retrospective studies. We designed a single arm prospective phase II study aiming to evaluate efficacy, and toxicity of re-irradiation., Materials and Methods: Adults patients with good performance status, HGG diagnosis reclassified according to the new 2021 fifth edition WHO CNS classification, an interval time (IT) from previous RT ≥ 6 months were included. Outcome was evaluated by MRI imaging at 1 month, and every 3 months thereafter. Toxicities were evaluated in terms of radionecrosis occurrence, and neurocognitive status., Results: Ninety recurrent HGG patients were treated, 11 oligodendroglioma grade 3, 18 astrocytoma grade 3 and 4, and 61 glioblastoma grade 4. The median age was 54 years, and majority had KPS 90-100. The median IT between first-RT and re-RT was 24 months. Re-surgery has been performed in 56.6%, and chemotherapy in 53.3%. The median follow up time was 64 months; median overall survival (OS) time,1,2,3-year OS rates were 17 months (95%CI 14-19), 66.7%±4.9, 32.6%±5.0, and 22.2 ± 4.7. Prognostic factors impacting on survival were age (p = 0.0154), IT between first RT and re-RT (p = 0.0051), glioma grade (p = 0.0090), and IDH status (p = 0.0001). Radionecrosis grade 2-3 occurred in 9 (10%) patients; neurocognitive functions remained stable until disease progression., Conclusion: Re-RT proved to be a safe and feasible treatment option with low toxicity. Younger patients with grade 3 IDH mutated gliomas, and a longer IT had the better outcome., Trial Registration Number: NCT02567539., (Published by Elsevier B.V.)

(1) Background: We investigated the role of [11C]-methionine PET in a cohort of newly diagnosed glioblastoma multiforme (GBM) patients to evaluate whether it could modify the extent of surgical resection and improve radiation therapy volume delineation. (2) Methods: Newly diagnosed GBM patients, ages 18-70, with a Karnofsky performance scale (KPS) ≥ 70 with available MRI and [11C]-methionine PET were included. Patients were treated with different amounts of surgical resection followed by radio-chemotherapy. The role of [11C]-methionine PET in surgical and RT planning was analyzed. A threshold of SUVmax was searched. (3) Results: From August 2013 to April 2016, 93 patients were treated and included in this analysis. Residual tumor volume was detected in 63 cases on MRI and in 78 on [11C]-methionine PET, including 15 receiving gross total resection. The location of uptake was mainly observed in FLAIR abnormalities. [11C]-methionine uptake changed RT volume in 11% of patients. The presence of [11C]-methionine uptake in patients receiving GTR proved to influence survival ( p = 0.029). The threshold of the SUVmax conditioning outcome was five. (4) Conclusions: [11C]-methionine PET allowed to detect areas at higher risk of recurrence located in FLAIR abnormalities in patients affected by GBM. A challenging issue is represented by integrating morphological and functional imaging to better define the extent of surgical resection to perform.

Introduction: Verbs and nouns can be selectively impaired, suggesting that they are processed, at least in part, by distinct neural structures. While several tests of object naming are available, tasks involving action verb naming with normative data are lacking. We report the construction and standardization of a new test for the assessment of picture naming of actions., Material and Methods: The test includes 50 stimuli, strictly controlled for several confounding variables. Normative data on 290 Italian subjects pooled across homogenous subgroups for age, sex, and education are reported., Results: Multiple regression analyses revealed that age and education significantly correlated with the subject's score. In particular, increasing age negatively affected performance, while the performance increased with a higher education., Conclusions: In the clinical practice, the availability of equivalent scores will help the comparison with performance in the picture naming of objects. This test allows investigating action naming deficits in aphasic patients, in Parkinson's disease patients and in further neurodegenerative disorders, in which a specific impairment of action verbs is expected, filling a gap in the clinical neuropsychological assessment.

Background: MR Tractography enables non-invasive preoperative depiction of language subcortical tracts, which is crucial for the presurgical work-up of brain tumors; however, it cannot evaluate the exact function of the fibers., Purpose: A systematic pipeline was developed to combine tractography reconstruction of language fiber bundles, based on anatomical landmarks (Anatomical-T), with language fMRI cortical activations. A fMRI-targeted Tractography (fMRI-T) was thus obtained, depicting the subsets of the anatomical tracts whose endpoints are located inside a fMRI activation. We hypothesized that fMRI-T could provide additional functional information regarding the subcortical structures, better reflecting the eloquent white matter structures identified intraoperatively., Methods: Both Anatomical-T and fMRI-T of language fiber tracts were performed on 16 controls and preoperatively on 16 patients with left-hemisphere brain tumors, using a q -ball residual bootstrap algorithm based on High Angular Resolution Diffusion Imaging (HARDI) datasets ( b = 3000 s/mm 2 ; 60 directions); fMRI ROIs were obtained using picture naming, verbal fluency, and auditory verb generation tasks. In healthy controls, normalized MNI atlases of fMRI-T and Anatomical-T were obtained. In patients, the surgical resection of the tumor was pursued by identifying eloquent structures with intraoperative direct electrical stimulation mapping and extending surgery to the functional boundaries. Post-surgical MRI allowed to identify Anatomical-T and fMRI-T non-eloquent portions removed during the procedure., Results: MNI Atlases showed that fMRI-T is a subset of Anatomical-T, and that different task-specific fMRI-T involve both shared subsets and task-specific subsets - e.g., verbal fluency fMRI-T strongly involves dorsal frontal tracts, consistently with the phonogical-articulatory features of this task. A quantitative analysis in patients revealed that Anatomical-T removed portions of AF-SLF and IFOF were significantly greater than verbal fluency fMRI-T ones, suggesting that fMRI-T is a more specific approach. In addition, qualitative analyses showed that fMRI-T AF-SLF and IFOF predict the exact functional limits of resection with increased specificity when compared to Anatomical-T counterparts, especially the superior frontal portion of IFOF, in a subcohort of patients., Conclusion: These results suggest that performing fMRI-T in addition to the 'classic' Anatomical-T may be useful in a preoperative setting to identify the 'high-risk subsets' that should be spared during the surgical procedure., (Copyright © 2020 Sanvito, Caverzasi, Riva, Jordan, Blasi, Scifo, Iadanza, Crespi, Cirillo, Casarotti, Leonetti, Puglisi, Grimaldi, Bello, Gorno-Tempini, Henry, Falini and Castellano.)

The relationship between verbal-auditory short-term memory (STM) and language is an open area of debate and contrasting hypotheses have been proposed, suggesting either that STM would strongly rely on language-related processes, or that it depends on a dedicated system related to language, but independent from it. In this study we examined 103 patients undergoing surgery for glioma resection in the left or right hemisphere, and we conducted a VLSM analysis on their behavioral performance on auditory-verbal STM, as well as on more general verbal and nonverbal tasks. The aim was to investigate whether the anatomical correlates of auditory-verbal STM were part of the language system or they were spatially segregated from it. VLSM results showed that digit span scores were linked to lesions in both the left supramarginal gyrus and superior-posterior temporal areas, as reported in the literature on patients with a selective deficit of auditory-verbal STM. Conversely, other verbal tasks involved areas only partly overlapping with those found for digit span, with repetition being affected by lesions in more anterior regions in the parietal, temporal, and frontal lobes, and word comprehension by lesions in a network including cortical and subcortical pathways in the temporal lobe. The present results, thus, show that auditory-verbal STM neural correlates are only partially overlapping with those supporting comprehension and production: while the left posterior-superior temporal cortex, involved in speech perception, takes part in both functions, the left supramarginal gyrus has a consistent and specific role only in STM, supporting the hypothesis of interacting but segregated networks.

Emotion processing impairments are common in patients undergoing brain surgery for fronto-temporal tumour resection, with potential consequences on social interactions. However, evidence is controversial concerning side and site of lesions causing such deficits. This study investigates visual and auditory emotion recognition in brain tumour patients with the aim of clarifying which lesion sites are related to impairments in emotion processing from different modalities. Thirty-four patients were evaluated, before and after surgery, on facial expression and emotional prosody recognition; voxel-based lesion-symptom mapping (VLSM) analyses were performed on patients' post-surgery MRI images. Results showed that patients' performance decreased after surgery in both visual and auditory modalities, but, in general, recovered 3 months after surgery. In facial expression recognition, left brain-damaged patients showed greater post-surgery deterioration than right brain-damaged ones, whose performance specifically decreased for sadness and fear. VLSM analysis revealed two segregated areas in the left hemisphere accounting for post-surgery scores for happy (fronto-temporo-insular region) and surprised (middle frontal gyrus and inferior fronto-occipital fasciculus) facial expressions. Our findings demonstrate that surgical removal of tumours in the fronto-temporal region produces impairment in facial emotion recognition with an overall recovery at 3 months, suggesting a partially different representation of positive and negative emotions in the left and right hemispheres for visually - but not auditory - presented emotions; moreover, we show that deficits in specific expression recognition are associated with discrete lesion locations., (© 2017 The British Psychological Society.)

OBJECTIVEApraxia is a cognitive-motor deficit affecting the execution of skilled movements, termed praxis gestures, in the absence of primary sensory or motor disorders. In patients affected by stroke, apraxia is associated with lesions of the lateral parietofrontal stream, connecting the posterior parietal areas with the ventrolateral premotor area and subserving sensory-motor integration for the hand movements. In the neurosurgical literature to date, there are few reports regarding the incidence of apraxia after glioma surgery. A retrospective analysis of patients who harbored a glioma around the central sulcus and close to the parietofrontal circuits in depth showed a high incidence of long-term postoperative hand apraxia, impairing the patients' quality of life. To avoid the occurrence of postoperative apraxia, the authors sought to develop an innovative intraoperative hand manipulation task (HMt) that can be used in association with the brain mapping technique to identify and preserve the cortical and subcortical structures belonging to the praxis network.METHODSThe intraoperative efficacy of the HMt was investigated by comparing the incidence of postoperative ideomotor apraxia between patients undergoing mapping with (n = 79) and without (n = 41) the HMt. Patient groups were balanced for all demographic and clinical features.RESULTSIn patients with lesions in the dominant hemisphere, the HMt dramatically reduced the incidence of apraxia, with a higher sensitivity for the ideomotor than for the constructional abilities; patients with lesions in the nondominant hemisphere benefitted from the HMt for both ideomotor and constructional abilities. The administration of the test did not reduce the extent of resection.CONCLUSIONSThe HMt is a safe and feasible intraoperative tool that allowed surgeons to prevent the occurrence of long-term hand apraxia while attaining resection goals for the surgical treatment of glioma.

Objective: The goal of surgery for gliomas is maximal tumor removal while preserving the patient's full functional integrity. At present during frontal tumor removal, this goal is mostly achieved, although the risk of impairing the executive functions (EFs), and thus the quality of life, remains significant. The authors investigated the accuracy of an intraoperative version of the Stroop task (iST), adapted for intraoperative mapping, to detect EF-related brain sites by evaluating the impact of the iST brain mapping on preserving functional integrity following a maximal tumor resection., Methods: Forty-five patients with nondominant frontal gliomas underwent awake surgery; brain mapping was used to establish the functional boundaries for the resection. In 18 patients language, praxis, and motor functions, but not EFs (control group), were mapped intraoperatively at the cortical-subcortical level. In 27 patients, in addition to language, praxis, and motor functions, EFs were mapped with the iST at the cortical-subcortical level (Stroop group). In both groups the EF performance was evaluated preoperatively, at 7 days and 3 months after surgery., Results: The iST was successfully administered in all patients. Consistent interferences, such as color-word inversion/latency, were obtained by stimulating precise white matter sites below the inferior and middle frontal gyri, anterior to the insula and over the putamen, and these were used to establish the posterior functional limit of the resection. Procedures implemented with iST dramatically reduced the EF deficits at 3 months. The EOR was similar in Stroop and control groups., Conclusions: Brain mapping with the iST allows identification and preservation of the frontal lobe structures involved in inhibition of automatic responses, reducing the incidence of postoperative EF deficits and enhancing the further posterior and inferior margin of tumor resection.

Twenty-nine patients who underwent surgery for a temporal glioma, either in the left (16 patients) or right (13 patients) hemisphere, were administered standardized tests of unknown voice discrimination (UVD) and of famous voice recognition (VO-REC), which included tasks of familiarity evaluation, semantic identification and naming of famous voices. The UVD consisted of twenty stimuli, in which two audio files were consecutively presented; the subject was requested to judge whether the voices belonged to the same or different persons. In the VO-REC, patients were requested to recognize the voices of 40 very well known people; these voices were intermingled with the voices of 20 unknown people for a familiarity check, followed by identification and naming of persons recognized as familiar. We aimed at verifying the effect of laterality and intra-temporal site of lesion on familiarity assessment, false alarms, identification and naming of familiar people. As for the effect of lesion side, our results showed that patients with right temporal gliomas were significantly more impaired in voices discrimination and produced more false alarms than patients with a left glioma, who, in turn, were significantly more impaired in name retrieval than patients with a right temporal glioma. The high number of false alarms in patients with a right temporal glioma suggests that familiarity judgment was impaired. Regarding the neuroanatomical correlates of these different patterns of impairment, MRI data suggested that: (a) UVD disorders are due to lesions involving the whole right anterior temporal lobe and extending to lateral portions of the temporal and frontal lobes; (b) familiarity judgments (testified by an increased number of false alarms) are impaired in lesions restricted to the right anterior temporal lobe; (c) name retrieval deficits are found only in patients with left temporal lesions. UVD disorders were interpreted, at least in part, as due to an impairment of executive functions, resulting from a disconnection of the right temporal lobe from the frontal lobe control. A partly unexpected finding was that some patients with a right temporal tumour had a normal performance in famous voice recognition and identification, in spite of having severe voice discrimination disturbances. These unexpected results, in agreement with previous observation made in the visual (face) modality, are inconsistent with strictly hierarchical models of voice processing., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Data concerning the neural basis of noun and verb processing are inconsistent. Some authors assume that action-verb processing is based on frontal areas while nouns processing relies on temporal regions; others argue that the circuits processing verbs and nouns are closely interconnected in a predominantly left-lateralized fronto-temporal-parietal network; yet, other researchers consider that the primary motor cortex plays a crucial role in processing action verbs. In the present study, one hundred and two patients with a tumour either in the right or left hemisphere were submitted to picture naming of objects and actions before and after surgery. To test the effect of specific brain regions in object and action naming, patients' lesions were mapped and voxel-lesion-symptom mapping (VLSM) was computed. Behavioural results showed that left-brain damaged patients were significantly more impaired than right brain-damaged patients. The VLSM showed that these two grammatical classes are segregated in the left hemisphere. In particular, scores in naming of objects correlated with damage to the anterior temporal region, while scores in naming of actions correlated with lesions in the parietal areas and in the posterior temporal cortex. In addition, VLSM analyses carried out on non-linguistic tasks were not significant, confirming that the regions associated with deficits in object and action naming were not generally engaged in all cognitive tasks. Finally, the involvement of subcortical pathways was investigated and the inferior longitudinal fasciculus proved to play a role in object naming, while no specific bundle was identified for actions.

Background: Cardiac troponin [cTn (I or T)] is the preferred biomarker for the diagnosis of myocardial infarction (MI)., Aim: We studied the analytical performance of the POCT AQT90 FLEX cTnI assay and its diagnostic accuracy, in comparison to the Dimension Vista cTnI method, in patients presenting to the Emergency Department (ED) with suspect of acute coronary syndrome (ACS)., Methods: 786 consecutive patients were enrolled. cTnI was measured at admission to the ED and about 3 and 6 hours later. The imprecision study was carried out using different lots of quality controls (QCs). ROC curve analysis was conducted using discharge diagnoses in order to verify the global diagnostic accuracy., Results: The concentrations measured in the QCs ranging from 0.033 to 1.26μg/L show CVs% ranging from 2.81 to 7.56%, comparable to those declared by the manufacturer. Passing-Bablok and linear regression analysis show a high significant correlation (R 2 =0.90, p<0.0001); Bland-Altman test describes a statistically significant negative bias (Bias=-0.2336; 95%CI=-0.4217/-0.0456, p=0.0150). ROC curves obtained using Dimension Vista and AQT90 FLEX cTnI assays displayed similar clinical performance being not statistically significant the difference of the corresponding AUC. Comparing sensitivity and specificity of cTnI concentrations obtained from the ROC curve analysis using AQT90 FLEX, we found a "best cut-off" (0.014μg/L) lower than that declared from the manufacturer (0.023μg/L)., Conclusions: The comparison of two different assays of cTnI against a diagnosis of acute MI (AMI) shows that both assays behave equally well with a high degree of sensitivity and specificity. The resulting "best cut-off" suggests that this AQT90 FLEX cTnI concentration could be evaluated as the potentially new "clinically usable" cut-off for AMI/myocardial necrosis diagnoses., (Copyright © 2017. Published by Elsevier Inc.)

Background: The current standard of care for newly diagnosed glioblastoma (GBM) is surgical resection, followed by radiation therapy (RT) with concurrent and adjuvant temozolomide chemotherapy (TMZ-CHT). The patients outcome is still poor. In this study we evaluated hypofractionated radiation therapy (HFRT), instead of standard fractionated radiation therapy, with concomitant and adjuvant TMZ chemotherapy, in terms of safety and effectiveness., Methods: Patients with newly diagnosed GBM, Karnofsky performance scale (KPS) ≥70, and tumor up to 10 cm underwent maximal feasible surgical resection were treated. HFRT consisted of 60 Gy, in daily fractions of 4 Gy given 5 days per week for 3 weeks. The primary endpoints were overall survival (OS), progression free survival (PFS), and incidence of radiation induced brain toxicity. Secondary endpoint was the evaluation of neurocognitive function., Results: A total of 97 patients were included in this phase II study. The median age was 60.5 years (range 23-77 years). Debulking surgery was performed in 83.5% of patients, HFRT was completed in all 97 patients, concurrent and adjuvant TMZ in 93 (95.9%). The median number of TMZ cycles was six (range 1-12 cycles). No severe toxicity occurred and the neuropsychological evaluation remained stable. At a median follow up time of 15.2 months the median OS time, 1,2-year OS rate were 15.9 months (95% CI 14-18), 72.2% (95% CI 62.1-80) and 30.4% (95% CI 20.8-40.6). Age, KPS, MGMT methylation status, and extent of surgical resection were significant factors influencing the outcome., Conclusion: HFRT with concomitant and adjuvant TMZ chemotherapy is an effective and safe treatment., Competing Interests: CONFLICTS OF INTEREST L. Cozzi acts as Scientific Advisor to Varian Medical Systems and is Clinical Research Scientist at Humanitas Cancer Center. All other co-authors have no conflicts of interest

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 Broca's 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 Geschwind's area to Broca's 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. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Background: Music is one of the most sophisticated and fascinating functions of the brain. Yet, how music is instantiated within the brain is not fully characterized. Singing is a peculiar aspect of music, in which both musical and linguistic skills are required to provide a merged vocal output. Identifying the neural correlates of this process is relevant for both clinical and research purposes., Case Description: An adult white man with a presumed left temporal glioma was studied. He is a professional opera singer. A tailored music evaluation, the Montreal Battery of Evaluation of Amusia, was performed preoperatively and postoperatively, with long-term follow-up. Intraoperative stimulation mapping (ISM) with awake surgery with a specific music evaluation battery was used to identify and preserve the cortical and subcortical structures subserving music, along with standard motor-sensory and language mapping. A total resection of a grade I glioma was achieved. The Montreal Battery of Evaluation of Amusia reported an improvement in musical scores after the surgery. ISM consistently elicited several types of errors in the superior temporal gyrus and, to a lesser extent, in the inferior frontal operculum. Most errors occurred during score reading; fewer errors were elicited during the assessment of rhythm. No spontaneous errors were recorded. These areas did not overlap with eloquent sites for counting or naming., Conclusions: ISM and a tailored music battery enabled better characterization of a specific network within the brain subserving score reading independently from speech with long-term clinical impact., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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.

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., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

A previous study reporting on 44 patients who underwent awake surgery for a left frontal or temporal glioma resection demonstrated the removal of the uncinate fasciculus to have consequences on language 3 months post-surgery. At this time-point, patients with a temporal glioma who had undergone uncinate removal showed the worst overall performance with a significant impairment in naming of famous faces and objects compared to patients without removal. Also, verbal fluency was mildly impaired. We report a longer-term follow-up (9-12 months) in a selected group of 17 patients (six female, age range 27-64) who did not suffer any tumour recurrence in this timeframe. MRI and DTI were performed before and after surgery. While verbal fluency on categorical cue and object naming recovered to the same level as before surgery, proper naming remained significantly impaired even after 12 months (P = 0.032) in patients with uncinate removal, demonstrating this structure to be crucial for that function and supporting the hypothesis that subcortical connectivity is relevant to allow plasticity. We thus argued that the left frontal and temporal poles connected by means of the uncinate fasciculus constitute a dedicated circuit for naming of unique entities.

The aim of this study was to evaluate the measurement of C-peptide, insulin, sex hormone binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAS), tests of specific clinical value that are not frequently measured in routine clinical laboratories, carried out using an automated system, AIA 2000 (Tosoh). The obtained data demonstrated that the evaluated system, characterized by fluorescence system detector provides satisfactory analytical performance comparable to those of different instrument that use the well known and widely diffused chemiluminescent principle (Immulite 2000). These characteristics allow an excellent comparability between methods for the measurement of same specific hormones not frequently used in clinical practice., (Copyright © 2015. Published by Elsevier Inc.)

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 Broca's area, as homologous to F5, a relevant issue in light of the mirror hypothesis of language evolution, which postulates a key role of Broca's area in action/speech perception/production. We assess "mirror" properties of this area by combining neuroimaging and intraoperative neurophysiological techniques. Our results show that Broca's 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., (© 2014 Wiley Periodicals, Inc.)

Semantic verbal fluency test is frequently used in clinical practice to assess lexical retrieval and production in neurological and psychiatric diseases. Semantic category is a crucial variable to consider in patients with language disorders. Norms for this task were collected from a population of 290 Italian healthy participants with age ranging from 18 to 98 years. The aim was to provide normative data both for the global score and for each semantic category (animals, fruits, brands of cars). Multiple regression analysis revealed that age and education significantly correlated with the global score and with single semantic categories. In particular, increasing age negatively affected performance, whereas the performance increased with a higher education. Statistically significant differences between men and women were found only for brands of cars. The availability of equivalent scores for the single semantic categories will prove useful in clinical practice since it allows the comparison of single semantic categories in patients with language disorders.

Data for copying and delayed recall (after a 15-min delay) of the Modified Taylor Complex Figure (MTCF), an alternative form of the Rey-Osterrieth Complex Figure (ROCF), were collected from 290 healthy participants. Normative data are provided. Age and education were significantly correlated with MTCF scores and must be corrected for to interpret results accurately. More specifically, increasing age adversely affected performance, whereas a higher education resulted in a better performance. Twenty-five participants were tested with both complex figures (MTCF and ROCF) in two separate sessions to assess correlation, which proved to be high. The collected data allow using the MTCF as a valid alternative material for testing visual long-term memory avoiding implicit learning that can occur when the same version of the ROCF is used for repeated testing sessions., (© 2013 The British Psychological Society.)

Objective: 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., Experimental Design: Seven patients with hemispheric gliomas (six in the right hemisphere) entered the study. During surgery in asleep/awake anesthesia, guided by Diffusion Tensor Imaging Fiber Tractography, visuospatial neglect was assessed during direct electrical stimulation by computerized line bisection., Principal Observations: A rightward deviation, indicating left visuospatial neglect, was induced in six of seven patients by stimulation of the parietofrontal connections, in a location consistent with the trajectory of the second branch of the superior longitudinal fascicle. Stimulation of the medial and dorsal white matter of the superior parietal lobule (corresponding to the first branch of the superior longitudinal fascicle), of the ventral and lateral white matter of the supramarginal gyrus (corresponding to the third branch of the superior longitudinal fascicle), and of the inferior occipitofrontal fasciculus, was largely ineffective. Stimulation of the superior parietal lobule (Brodmann's area 7) caused a marked rightward deviation in all of the six assessed patients, while stimulation of Brodmann's areas 5 and 19 was ineffective., Conclusions: The parietofrontal connections of the dorso-lateral fibers of the superior longitudinal fascicle (i.e., the second branch of the fascicle), and the posterior superior parietal lobe (Brodmann's area 7) are involved in the orientation of spatial attention. Spatial neglect should be assessed systematically during awake brain surgery, particularly when the right parietal lobe may be involved by the neurosurgical procedure., (Copyright © 2013 Wiley Periodicals, Inc.)

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.

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.

Aim: This work reports the analysis of the relationship between inferior fronto-occipital fasciculus (IFO), neoplastic lesions and surgical resection, in patients operated for gliomas located in the frontal, temporal and insular lobes of the dominant hemisphere. Aim of the study is evaluating the predictive value of inferior fronto-occipital fasciculus DTI-fiber tracking (FT) for determining the extent of resection preoperatively., Methods: We selected 38 cases affected by lesions located in the frontal, temporal and insular lobes of the dominant hemisphere, which were related to the trajectory of the IFO. For each patient preoperative and postoperative MR images and DTI-FT were loaded into the neuronavigation system and merged; volumetric scan analysis was used for establishing tumor location and topography, as well as the volume of the lesion and of the residual tumor. All preoperative fiber tracking datasets were evaluated and the position of the tract (IFO) compared to the tumor was recorded. Postoperative MR scans were then compared with DTI-FT, in order to evaluate the correspondence between the resection boundaries and the trajectory of the fiber tract., Results: Amongst the cases in which the IFO was inside the lesion, we found only incomplete resections (5 subtotal and 6 partial resections), while considering the cases in which the IFO was located outside the tumor, it was possible to perform a relevant (total/subtotal) resection in 18 of them (78%)., Conclusion: FT of the inferior frontal-occipital fasciculus predicts the possibility and the extent of the resection for a frontal, temporal and/or insular lesion of the dominant hemisphere.

The brain's 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., (Copyright © 2011 Elsevier Inc. All rights reserved.)

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.

Low-grade gliomas ([LGGs] WHO Grade II) are slow-growing intrinsic cerebral lesions that diffusely infiltrate the brain parenchyma along white matter tracts and almost invariably show a progression toward malignancy. The treatment of these tumors forces the neurosurgeon to face uncommon difficulties and is still a subject of debate. At the authors' institution, resection is the first option in the treatment of LGGs. It requires the combined efforts of a multidisciplinary team of neurosurgeons, neuroradiologists, neuropsychologists, and neurophysiologists, who together contribute to the definition of the location, extension, and extent of functional involvement that a specific lesion has caused in a particular patient. In fact, each tumor induces specific modifications of the brain functional network, with high interindividual variability. This requires that each treatment plan is tailored to the characteristics of the tumor and of the patient. Consequently, surgery is performed according to functional and anatomical boundaries to achieve the maximal resection with maximal functional preservation. The identification of eloquent cerebral areas, which are involved in motor, language, memory, and visuospatial functions and have to be preserved during surgery, is performed through the intraoperative use of brain mapping techniques. The use of these techniques extends surgical indications and improves the extent of resection, while minimizing the postoperative morbidity and safeguarding the patient's quality of life. In this paper the authors present their paradigm for the surgical treatment of LGGs, focusing on the intraoperative neurophysiological monitoring protocol as well as on the brain mapping technique. They briefly discuss the results that have been obtained at their institution since 2005 as well as the main critical points they have encountered when using this approach.

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.