Definition: To what extent does the study allow us to draw conclusions about a causal effect between two or more constructs? Issues: Selection, maturation, history, mortality, testing, regression towrd the mean, selection by maturation, treatment by mortality, treatment by testing, measured treatment variables Increase: Eliminate the threats, above all do experimental manipulations, random assignment, and counterbalancing.

Reliability and validity

Glioblastoma (GBM) is the most common and lethal tumor of the central nervous system. The natural history of treated GBM remains very poor with 5-year survival rates of 5 %. Survival has not significantly improved over the last decades. Currently, the best that can be offered is a modest 14-month overall median survival in patients undergoing maximum safe resection plus adjuvant chemoradiotherapy. Prognostic factors involved in survival include age, performance status, grade, specific markers (MGMT methylation, mutation of IDH1, IDH2 or TERT, 1p19q codeletion, overexpression of EGFR, etc.) and, likely, the extent of resection. Certain adjuncts to surgery, especially cortical mapping and 5-ALA fluorescence, favor higher rates of gross total resection with apparent positive impact on survival. Recurrent tumors can be offered re-intervention, participation in clinical trials, anti-angiogenic agent or local electric field therapy, without an evident impact on survival. Molecular-targeted therapies, immunotherapy and gene therapy are promising tools currently under research.

Survival in glioblastoma: a review on the impact of treatment modalities.

Test-retest reliability.

At present, direct electrical stimulation (DES) is the only technique that allows directin vivomapping of white matter tracts in humans. In this Review, Hugues Duffau discusses the insights into functional connectivity that have been gained from DES during awake surgery for brain lesions. In addition, the author considers the clinical implications of a paradigmatic shift from a localizationist model to a hodotopical model of cerebral processing. Despite advances in the new science of connectomics, which aims to comprehensively map neural connections at both structural and functional levels, techniques to directly study the function of white matter tracts in vivo in humans have proved elusive. Direct electrical stimulation (DES) mapping of the subcortical fibres offers a unique opportunity to investigate the functional connectivity of the brain. This original method permits real-time anatomo-functional correlations, especially with regard to neural pathways, in awake patients undergoing brain surgery. In this article, the goal is to review new insights, gained from axonal DES, into the functional connectivity underlying the sensorimotor, visuospatial, language and sociocognitive systems. Interactions between these neural networks and multimodal systems, such as working memory, attention, executive functions and consciousness, can also be investigated by axonal stimulation. In this networking model of conation and cognition, brain processing is not conceived as the sum of several subfunctions, but results from the integration and potentiation of parallel—though partially overlapping—subnetworks. This hodotopical account, supported by axonal DES, improves our understanding of neuroplasticity and its limitations. The clinical implications of this paradigmatic shift from localizationism to hodotopy, in the context of brain surgery, neurology, neurorehabilitation and psychiatry, are discussed.

Stimulation mapping of white matter tracts to study brain functional connectivity

This manuscript discusses the current surgical management of glioblastoma. This paper highlights the common pathophysiology attributes of glioblastoma, surgical options for diagnosis/treatment, current thoughts of extent of resection (EOR) of tumor, and post-operative (neo)adjuvant treatment. Glioblastoma is not a disease that can be cured with surgery alone, however safely performed maximal surgical resection is shown to significantly increase progression free and overall survival while maximizing quality of life. Upon invariable tumor recurrence, re-resection also is shown to impact survival in a select group of patients. As adjuvant therapy continues to improve survival, the role of surgical resection in the treatment of glioblastoma looks to be further defined.

Current trends in the surgical management and treatment of adult glioblastoma.

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Could upfront temozolomide chemotherapy postpone the need for radiotherapy in young patients with high-risk low-grade gliomas?

The protection of language function is one of the major challenges of brain surgery. Over the past century, neurosurgeons have attempted to seek the optimal strategy for the preoperative and intraoperative identification of language-related brain regions. Neurosurgeons have investigated the neural mechanism of language, developed neurolinguistics theory, and provided unique evidence to further understand the neural basis of language functions by using intraoperative cortical and subcortical electrical stimulation. With the emergence of modern neuroscience techniques and dramatic advances in language models over the last 25 years, novel language mapping methods have been applied in the neurosurgical practice to help neurosurgeons protect the brain and reduce morbidity. The rapid advancements in brain-computer interface have provided the perfect platform for the combination of neurosurgery and neurolinguistics. In this review, the history of neurolinguistics models, advancements in modern technology, role of neurosurgery in language mapping, and modern language mapping methods (including noninvasive neuroimaging techniques and invasive cortical electroencephalogram) are presented.

Junfeng Lu

Papers

Could upfront temozolomide chemotherapy postpone the need for radiotherapy in young patients with high-risk low-grade gliomas?

Clinical applications of neurolinguistics in neurosurgery