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Around 50% of patients undergoing frontal lobe surgery for focal drug-resistant epilepsy become seizure free post-operatively; however, only about 30% of patients remain seizure free in the long-term. Early seizure recurrence is likely to be caused by partial resection of the epileptogenic lesion, whilst delayed seizure recurrence can occur even if the epileptogenic lesion has been completely excised. This suggests a coexistent epileptogenic network facilitating ictogenesis in close or distant dormant epileptic foci. As thalamic and striatal dysregulation can support epileptogenesis and disconnection of cortico-thalamostriatal pathways through hemispherotomy or neuromodulation can improve seizure outcome regardless of focality, we hypothesize that projections from the striatum and the thalamus to the cortex may contribute to this common epileptogenic network. To this end, we retrospectively reviewed a series of 47 consecutive individuals who underwent surgery for drug-resistant frontal lobe epilepsy. We performed voxel-based and tractography disconnectome analyses to investigate shared patterns of disconnection associated with long-term seizure freedom. Seizure freedom after 3 and 5 years was independently associated with disconnection of the anterior thalamic radiation and anterior cortico-striatal projections. This was also confirmed in a subgroup of 29 patients with complete resections, suggesting these pathways may play a critical role in supporting the development of novel epileptic networks. Our study indicates that network dysfunction in frontal lobe epilepsy may extend beyond the resection and putative epileptogenic zone. This may be critical in the pathogenesis of delayed seizure recurrence as thalamic and striatal networks may promote epileptogenesis and disconnection may underpin long-term seizure freedom.

The arcuate fasciculus has been considered a major dorsal fronto-temporal white matter pathway linking frontal language production regions with auditory perception in the superior temporal gyrus, the so-called Wernicke’s area. In line with this tradition, both historical and contemporary models of language function have assigned primacy to superior temporal projections of the arcuate fasciculus. However, classical anatomical descriptions and emerging behavioural data are at odds with this assumption. On one hand, fronto-temporal projections to Wernicke’s area may not be unique to the arcuate fasciculus. On the other hand, dorsal stream language deficits have been reported also for damage to middle, inferior and basal temporal gyri that may be linked to arcuate disconnection. These findings point to a reappraisal of arcuate projections in the temporal lobe. Here, we review anatomical and functional evidence regarding the temporal cortical terminations of the left arcuate fasciculus by incorporating dissection and tractography findings with stimulation data using cortico–cortical evoked potentials and direct electrical stimulation mapping in awake patients. First, we discuss the fibres of the arcuate fasciculus projecting to the superior temporal gyrus and the functional rostro-caudal gradient in this region where both phonological encoding and auditory-motor transformation may be performed. Caudal regions within the temporoparietal junction may be involved in articulation and associated with temporoparietal projections of the third branch of the superior longitudinal fasciculus, while more rostral regions may support encoding of acoustic phonetic features, supported by arcuate fibres. We then move to examine clinical data showing that multimodal phonological encoding is facilitated by projections of the arcuate fasciculus to superior, but also middle, inferior and basal temporal regions. Hence, we discuss how projections of the arcuate fasciculus may contribute to acoustic (middle-posterior superior and middle temporal gyri), visual (posterior inferior temporal/fusiform gyri comprising the visual word form area) and lexical (anterior-middle inferior temporal/fusiform gyri in the basal temporal language area) information in the temporal lobe to be processed, encoded and translated into a dorsal phonological route to the frontal lobe. Finally, we point out surgical implications for this model in terms of the prediction and avoidance of neurological deficit.

Perampanel, a non-competitive antagonist of the post-synaptic a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) receptor, is effective for controlling focal to bilateral tonic-clonic seizures but also known to increase feelings of anger. Using statistical parametric mapping-derived measures of activation and task-modulated functional connectivity (psychophysiologic interaction), we investigated 14 people with focal epilepsy who had verbal fluency fMRI twice, before and after the add-on treatment of perampanel. For comparison, we included 28 people with epilepsy, propensity-matched for clinical characteristics, who had two scans but no change in ASM regime in-between. After commencing perampanel, individuals had higher task-related activations in left orbito-frontal cortex (OFC), less task-related activations in subcortical regions including left thalamus and left caudate, and lower task-related thalamo-caudate and caudate-subtantial nigra connectivity. Decreased task-related connectivity is observed between left OFC and precuneus and left medial frontal lobe. Our results highlight the brain regions associated with the beneficiary therapeutic effects on focal to bilateral tonic-clonic seizures (thalamus and caudate) but also the undesired affective side effects of perampanel with increased anger and aggression (OFC).

OBJECTIVE 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 (r15 = 0.74, p = 0.0027); TMT-A (r15 = 0.65, p = 0.012); TMT-B (r15 = 0.70, p = 0.005); and TMT-B-A (r15 = 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.

Predictive and reactive behaviors represent two mutually exclusive strategies for successfully completing a sensorimotor task. It is thought that predictive actions are based on the medial premotor system, in the superior frontal gyrus (SFG) and reactive stimulus-response behaviors rely on a lateral premotor system, in the inferior frontal gyrus (IFG). The frontal aslant tract (FAT), a white matter tract connecting SFG and IFG, is a possible neural substrate of the predictive/reactive interactions. We used diffusion-weighted imaging (DWI) of 17 male and female healthy human volunteers, to dissect 3 sub-bundles of fibers belonging to the left FAT (bundles 1, 2 and 3), arising ventrally from 1) the ventral precentral gyrus, 2) midway between the PCG and pars opercularis (POp) and 3) the POp and terminating dorsally in 3 different parts of the SFG, in a caudal-rostral order. We applied online transcranial magnetic stimulation (TMS) to 6 spots, corresponding to the medial and lateral terminations of bundles 1-3 during the fixed-duration set period of a delayed reaction task, that can be solved using a predictive (anticipatory) strategy or with a reactive strategy. Results showed that TMS changed the frequency of predictive/reactive strategies only when applied over 2 spots, the SFG and IFG terminations of bundle 2. Importantly, the effects of TMS were opposite when applied to the SFG or to the IFG. Our data show that the SFG and the IFG have opposite roles in producing predictive or reactive behavior and that reciprocal integration or competition is probably mediated by the FAT.Significance StatementAs is well-known by athletes at starting blocks, interaction with the world can occur with a predictive strategy (anticipating a GO-signal) or a reactive strategy (waiting for the GO-signal to be manifest) and they are mutually exclusive. Here we showed, by using non-invasive brain stimulation (TMS), that two specific cortical regions in the superior frontal gyrus (SFG) and the inferior frontal gyrus (IFG) have opposite roles in facilitating a predictive or a reactive strategy. Importantly these two very distant regions but with highly interconnected functions are specifically connected by a small white matter bundle, which probably mediates the competition between predictive and reactive strategies. More generally, we show that the implementing anatomical connectivity in TMS studies strongly reduces spatial noise.

Individuals with temporal lobe epilepsy (TLE) may have significant language deficits. Language capabilities may further decline following temporal lobe resections. The language network, comprising dispersed gray matter regions interconnected with white matter fibers, may be atypical in individuals with TLE. This review explores the structural changes to the language network and the functional reorganization of language abilities in TLE. We discuss the importance of detailed reporting of patient's characteristics, such as, left- and right-sided focal epilepsies as well as lesional and nonlesional pathological subtypes. These factors can affect the healthy functioning of gray and/or white matter. Dysfunction of white matter and displacement of gray matter function could concurrently impact their ability, in turn, producing an interactive effect on typical language organization and function. Surgical intervention can result in impairment of function if the resection includes parts of this structure-function network that are critical to language. In addition, impairment may occur if language function has been reorganized and is included in a resection. Conversely, resection of an epileptogenic zone may be associated with recovery of cortical function and thus improvement in language function. We explore the abnormality of functional regions in a clinically applicable framework and highlight the differences in the underlying language network. Avoidance of language decline following surgical intervention may depend on tailored resections to avoid critical areas of gray matter and their white matter connections. Further work is required to elucidate the plasticity of the language network in TLE and to identify sub-types of language representation, both of which will be useful in planning surgery to spare language function.

Background. The prognostic factors for surgically removed spinal hemangioblastomas, the impact of VHL disease on outcome, and the role of intraoperative neuromonitoring are still not completely clear. The aim of this study was to review our experience with spinal hemangioblastomas in order to assess potential predictors of neurological outcome after surgery.Methods. All cases of spinal hemangioblastomas removed at two Italian academic institutions from 1985 to 2020 were reviewed. Data about clinical presentation and symptoms duration, diagnosis of VHL, surgical approach, use of IONM, duration of hospital stay, follow up, McCormick grade before and after surgery were extracted.Results. Sixty-one patients (31 F, 30 M) underwent 69 surgeries to remove 74 spinal hemangioblastomas (37 cervical, 32 thoracic, 5 lumbar). Improvement was found in 32.3% of cases, neurological condition remained stable in 51.6% of cases, and deteriorated in 16.1% of patients.A worsening trend in VHL patients and an improvement trend in non-VHL patients were detected, despite the lack of statistical significance. Laminotomy and use of IONM were found to be associated with better outcome, although no association was found between surgery without IOM and worse outcome.Conclusion. In most cases, patients affected by spinal hemangioblastomas can expect a good long-term outcome. In our experience, laminotomy seems to be associated with better outcome compared to laminectomy. While its absence is not associated with worse outcome, IONM seems to be associated with a better neurological outcome. Our study suggests that the more impaired the preoperative neurological condition, the worse the outcome.

BackgroundCortico-cortical evoked potentials (CCEPs) recorded by stereo-electroencephalography (SEEG) are a valuable clinical tool to investigate brain reactivity and effective connectivity. However, these invasive recordings are spatially sparse since they depend on clinical needs. This sparsity hampers systematic comparisons across-subjects, the detection of the whole-brain spatiotemporal properties of CCEPs, as well as their relationships with classic sensory evoked potentials.ObjectiveTo demonstrate that CCEPs recorded by high-density electroencephalography (hd-EEG) are sensitive to changes in stimulation parameters and compensate for the limitations typical of invasive recordings.MethodsSEEG and hd-EEG activities were simultaneously recorded during SPES in drug-resistant epileptic patients (N=36). Changes in stimulation parameters encompassed physical (pulse intensity and width), geometrical (angle and position with respect to white/grey matter) and topological (stimulated cortical area) properties. Differences were assessed by measuring the overall responses and the amplitude of N1 and N2 components of the CCEPs, and by their spectral profiles.ResultsWhile invasive and non-invasive CCEPs were generally correlated, differences in pulse duration, angle and stimulated cortical area were better captured by hd-EEG. Further, hd-EEG responses to SPES reproduced basic features of responses to transcranial magnetic stimulation and showed a much larger amplitude as compared to typical sensory evoked potentials.ConclusionsThe present results show that macroscale hd-EEG recordings are exquisitely sensitive to variations in SPES parameters, including local changes in physical and geometrical stimulus properties, while providing valuable information about whole-brain dynamics. Moreover, the common reference space across subjects represented by hd-EEG may facilitate the construction of a perturbational atlas of effective connectivity.HighlightsCCEPs recorded with hd-EEG and SEEG are correlated.hd-EEG recording is highly sensitive to changes in stimulation parameters.hd-EEG responses show higher amplitude responses with respect to non-invasive ones.Simultaneous recordings provide a fixed observation point across subjects.

Background In jargonaphasia, speech is fluent but meaningless. While neuropsychological evaluation may distinguish a neologistic component characterised by non-word production and a semantic component where pronounced words are real but speech is senseless, how this relates to the underlying white matter anatomy is debated. Objective To identify white matter pathways causally involved in jargonaphasia. Methods We retrospectively screened the intraoperative brain mapping data of 571 awake oncological resections using direct cortico-subcortical electrostimulation. Jargonaphasia was induced in 17 patients (19 sites) during a naming task. Stimulation sites were normalized to the Montreal Neurological Institute template space and used to generate individual disconnectome maps. Non-parametric voxelwise one and two sample t-tests were performed to identify the underlying white matter anatomy. Results Jargonaphasia was induced only during stimulation of the left hemisphere. No cortical stimulation generated jargonaphasia. Subcortical sites causally associated with jargonaphasia clustered in 3 regions: in the temporal lobe (middle to inferior temporal gyri; n = 12), in the parietal lobe (supramarginal gyrus; n = 3) and in the temporal stem (n = 4). Disconnectome analysis indicated the inferior-fronto-occipital fasciculus (IFOF) was damaged in both neologistic and semantic jargonaphasia, while the involvement of the arcuate fasciculus was specific to neologistic jargonaphasia. Conclusion For the first time, we show that jargonaphasia is induced by white matter stimulation, hinting at disconnection. As IFOF disconnection unites both variants, these may represent a continuum of disorders distinguished by semantic impairment. Conversely, damage to the arcuate fasciculus in addition to the IFOF is specific to neologistic jargonaphasia, thus suggesting a dual-disconnection syndrome.

Objective We examined the feasibility of using cortico-cortical evoked potentials (CCEPs) to monitor the major cortical white matter tract involved in language, the arcuate fasciculus (AF), during surgery under general anaesthesia. Methods We prospectively recruited nine patients undergoing surgery for lesions in the left peri-sylvian cortex, for whom awake surgery was not indicated. High angular resolution diffusion imaging (HARDI) tractography was used to localise frontal and temporal AF terminations, which guided intraoperative cortical strip placement. Results CCEPs were successfully evoked in 5/9 patients, showing a positive potential (P1) at 12 ms and a negative component (N1) at 21 ms when stimulating from the frontal lobe and recording in the temporal lobe. CCEP responses peaked in the posterior middle temporal gyrus. No CCEPs were evoked when stimulating temporal sites and recording from frontal contacts. Conclusion For the first time, we show that CCEPs can be evoked from the peri-sylvian cortices also in adult patients who are not candidates for awake procedures. Our results are akin to those described in the awake setting and suggest the recorded activity is conveyed by the arcuate fasciculus. Significance This intraoperative approach may have promising implications in reducing deficits in patients that require surgery in language areas under general anesthesia.

Muscle motor-evoked potentials are commonly monitored during brain tumour surgery in motor areas, as these are assumed to reflect the integrity of descending motor pathways, including the corticospinal tract. However, while the loss of muscle motor-evoked potentials at the end of surgery is associated with long-term motor deficits (muscle motor-evoked potential-related deficits), there is increasing evidence that motor deficit can occur despite no change in muscle motor-evoked potentials (muscle motor-evoked potential-unrelated deficits), particularly after surgery of non-primary regions involved in motor control. In this study, we aimed to investigate the incidence of muscle motor-evoked potential-unrelated deficits and to identify the associated brain regions. We retrospectively reviewed 125 consecutive patients who underwent surgery for peri-Rolandic lesions using intra-operative neurophysiological monitoring. Intraoperative changes in muscle motor-evoked potentials were correlated with motor outcome, assessed by the Medical Research Council scale. We performed voxel–lesion–symptom mapping to identify which resected regions were associated with short- and long-term muscle motor-evoked potential-associated motor deficits. Muscle motor-evoked potentials reductions significantly predicted long-term motor deficits. However, in more than half of the patients who experienced long-term deficits (12/22 patients), no muscle motor-evoked potential reduction was reported during surgery. Lesion analysis showed that muscle motor-evoked potential-related long-term motor deficits were associated with direct or ischaemic damage to the corticospinal tract, whereas muscle motor-evoked potential-unrelated deficits occurred when supplementary motor areas were resected in conjunction with dorsal premotor regions and the anterior cingulate. Our results indicate that long-term motor deficits unrelated to the corticospinal tract can occur more often than currently reported. As these deficits cannot be predicted by muscle motor-evoked potentials, a combination of awake and/or novel asleep techniques other than muscle motor-evoked potentials monitoring should be implemented., Graphical Abstract Graphical Abstract

Background Cerebellar mutism can occur in a third of children undergoing cerebellar resections. Recent evidence proposes it may arise from uni- or bilateral damage of cerebellar efferents to the cortex along the cerebello-dento-thalamo-cortical pathway. At present, no neurophysiological procedure is available to monitor this pathway intraoperatively. Here, we specifically aimed at filling this gap. Methods We assessed 10 patients undergoing posterior fossa surgery using a conditioning-test stimulus paradigm. Electrical conditioning stimuli (cStim) were delivered to the exposed cerebellar cortex at interstimulus intervals (ISIs) of 8–24 ms prior to transcranial electric stimulation of the motor cortex, which served as test stimulus (tStim). The variation of motor-evoked potentials (MEP) to cStim + tStim compared with tStim alone was taken as a measure of cerebello-cortical connectivity. Results cStim alone did not produce any MEP. cStim preceding tStim produced a significant inhibition at 8 ms (p < 0.0001) compared with other ISIs when applied to the lobules IV-V-VI in the anterior cerebellum and the lobule VIIB in the posterior cerebellum. Mixed effects of decrease and increase in MEP amplitude were observed in these areas for longer ISIs. Conclusions The inhibition exerted by cStim at 8 ms on the motor cortex excitability is likely to be the product of activity along the cerebello-dento-thalamo-cortical pathway. We show that monitoring efferent cerebellar pathways to the motor cortex is feasible in intraoperative settings. This study has promising implications for pediatric posterior fossa surgery with the aim to preserve the cerebello-cortical pathways and thus prevent cerebellar mutism.

In preoperative planning for neurosurgery, both anatomical (diffusion imaging tractography) and functional tools (MR-navigated transcranial magnetic stimulation) are increasingly used to identify and preserve eloquent language structures specific to individuals. Using these tools in healthy adults shows that speech production errors occur mainly in perisylvian cortical sites that correspond to subject-specific terminations of the major language pathway, the arcuate fasciculus. It is not clear whether this correspondence remains in oncological patients with altered tissue. We studied a heterogeneous cohort of 30 patients (fourteen male, mean age 44), undergoing a first or second surgery for a left hemisphere brain tumour in a language-eloquent region, to test whether speech production errors induced by preoperative transcranial magnetic stimulation had consistent anatomical correspondence to the arcuate fasciculus. We used navigated repetitive transcranial magnetic stimulation during picture naming and recorded different perisylvian sites where transient interference to speech production occurred. Spherical deconvolution diffusion imaging tractography was performed to map the direct fronto-temporal and indirect (fronto-parietal and parieto-temporal) segments of the arcuate fasciculus in each patient. Speech production errors were reported in all patients when stimulating the frontal lobe, and in over 90% of patients in the parietal lobe. Errors were less frequent in the temporal lobe (54%). In all patients, at least one error site corresponded to a termination of the arcuate fasciculus, particularly in the frontal and parietal lobes, despite distorted anatomy due to a lesion and/or previous resection. Our results indicate that there is strong correspondence between terminations of the arcuate fasciculus and speech errors. This indicates that white matter anatomy may be a robust marker for identifying functionally eloquent cortex, particularly in the frontal and parietal lobe. This knowledge may improve targets for preoperative mapping of language in the neurosurgical setting., Navigated transcranial magnetic stimulation for mapping language areas is increasingly used in presurgical planning for personalized brain tumour treatment. Giampiccolo et al. use tractography to show arcuate fasciculus terminations match speech-eloquent cortex, even in patients with distorted anatomy., Graphical Abstract Graphical Abstract

Background The function of the primate’s posterior parietal cortex (PPC) in sensorimotor transformations is well-established, though in humans its complexity is still challenging. Well-established models indicate that the posterior parietal cortex influences motor output indirectly, by means of connections to the premotor cortex, which in turn is directly connected to the motor cortex. Objective The possibility that the PPC could be at the origin of direct afferents to M1 has been suggested in humans but has never been confirmed directly. We aim to do so in the present study by using the novel technique of paired intraoperative cortical stimulation. Methods In the present cross-sectional study, we assessed during intraoperative monitoring of the corticospinal tract in brain tumour patients the existence of short-latency effects of parietal stimulation on corticospinal excitability to the upper limb. MEPs were evoked by test stimuli over the motor cortex, which were preceded in some trials by conditioning stimuli on the PPC. Results We identified two active cortical loci. One in the inferior parietal lobule exerted short-latency excitatory effects and one in the superior parietal lobule that drove short-latency inhibitory effects on cortical motor output. All active foci were distributed in the rostral portion of the PPC and on the postcentral sulcus. Conclusions For the first time in humans, the present data show direct evidence in favour of a distributed system of connections from the posterior parietal cortex to the ipsilateral primary motor cortex. In addition, we show that dual cortical stimulation is a novel and efficient technique to investigate intraoperative brain connectivity in the anaesthetized patient.

While total and even subtotal resection in surgery of brain tumors significantly improves life expectancy, disconnection of essential cerebral networks leads to neurological deficit and impairs quality of life. As classical cortical localization of brain functions has moved toward a hodological perspective, total and “supratotal” resection exceeding tumor borders according to functional margins has been proposed. These functional margins, rather than cortical networks, consist of subcortical white matter tracts. Although awake surgery is often advocated, when operating in situations of poor compliance, such as children or patients with preexisting neurological deficits, there may be a requirement for a different surgical strategy. One such strategy is the use of intraoperative neurophysiological monitoring (ION), enabling functional identification of functionally defined, but anatomically ambiguous, cortico-subcortical structures through mapping and monitoring techniques. Here we review well-established ION practices for preservation of function, with particular focus on motor and visual ability.

OBJECTIVE Motor cortical dysfunction has been shown to be reversible in patients with unilateral atherosclerotic disease after cerebral revascularization. Moyamoya vasculopathy (MMV) is a rare bilateral stenoocclusive cerebrovascular disease. The aim of this study was to analyze the corticospinal excitability and the role of bypass surgery in restoring cortical motor function in patients by using navigated transcranial magnetic stimulation (nTMS). METHODS Patients with bilateral MMV who met the criteria for cerebral revascularization were prospectively included. Corticospinal excitability, cortical representation area, and intracortical inhibition and facilitation were assessed by nTMS for a small hand muscle (first dorsal interosseous) before and after revascularization. The clinically and/or hemodynamically more severely affected hemisphere was operated first as the leading hemisphere. Intra- and interhemispheric differences were analyzed before and after direct or combined revascularization. RESULTS A total of 30 patients with bilateral MMV were examined by nTMS prior to and after revascularization surgery. The corticospinal excitability was higher in the leading hemisphere compared with the non-leading hemisphere prior to revascularization. This hyperexcitability was normalized after revascularization as demonstrated in the resting motor threshold ratio of the hemispheres (preoperative median 0.97 [IQR 0.89–1.08], postoperative median 1.02 [IQR 0.94–1.22]; relative effect = 0.61, p = 0.03). In paired-pulse paradigms, a tendency for a weaker inhibition of the leading hemisphere was observed compared with the non-leading hemisphere. Importantly, the paired paradigm also demonstrated approximation of excitability patterns between the two hemispheres after surgery. CONCLUSIONS The study results suggested that, in the case of a bilateral chronic ischemia, a compensation mechanism between both hemispheres seemed to exist that normalized after revascularization surgery. A potential role of nTMS in predicting the efficacy of revascularization must be further assessed.

the function of the primate’s posterior parietal cortex in sensorimotor transformations is well-established, though in humans its complexity is still challenging. Well-established models indicate that the posterior parietal cortex influences motor output indirectly, by means of connections to the premotor cortex, which in turn is directly connected to the motor cortex. The possibility that the posterior parietal cortex could be at the origin of direct afferents to M1 has been suggested in humans but has never been confirmed directly. In the present work we assessed during intraoperative monitoring of the corticospinal tract in brain tumour patients the existence of short-latency effects of parietal stimulation on corticospinal excitability to the upper limb. We identified several foci within the inferior parietal lobule that drove short-latency influences on cortical motor output. Active foci were distributed along the postcentral gyrus and clustered around the anterior intraparietal area and around the parietal operculum. For the first time in humans, the present data show direct evidence in favour of a distributed system of connections from the posterior parietal cortex to the ipsilateral primary motor cortex.

Glioblastoma is a tumor with widely variable morphology. It may rarely show pseudoepithelial components or true epithelial differentiation. Metastasis to glioblastomas have been previously reported, but were unsupported by immunohistochemical or molecular analyses. Herein we describe a glioblastoma with carcinomatous foci in a patient with no past clinical history of tumors outside the central nervous system. The carcinomatous foci expressed epithelial, but not glial markers. Therefore, whole-body imaging was carried out to verify the presence of carcinoma. A lung mass was biopsied and it resulted as primary lung adenocarcinoma. Carcinomatous foci of glioblastoma and lung adenocarcinoma had the same KRAS mutation which was absent in glial areas of the glioblastoma. Thus, glioblastoma with tumor-to-tumor metastasis was diagnosed. This case demonstrates that, albeit rare, metastases to glioblastoma may occur, and they should be considered in the differential diagnosis of glioblastoma with carcinomatous foci. Even when the past clinical history is negative, the presence of carcinoma should be investigated to rule out glioblastoma with tumor-to-tumor metastasis.