Tumour-infiltrated cortex participates in large-scale cognitive circuits.

The extent to which tumour-infiltrated brain tissue contributes to cognitive function remains unclear. We tested the hypothesis that cortical tissue infiltrated by diffuse gliomas participates in large-scale cognitive circuits using a unique combination of intracranial electrocorticography (ECoG) and resting-state functional magnetic resonance (fMRI) imaging in four patients. We also assessed the relationship between functional connectivity with tumour-infiltrated tissue and long-term cognitive outcomes in a larger, overlapping cohort of 17 patients. We observed significant task-related high gamma (70-250 Hz) power modulations in tumour-infiltrated cortex in response to increased cognitive effort (i.e., switch counting compared to simple counting), implying preserved functionality of neoplastic tissue for complex tasks probing executive function. We found that tumour locations corresponding to task-responsive electrodes exhibited functional connectivity patterns that significantly co-localised with canonical brain networks implicated in executive function. Specifically, we discovered that tumour-infiltrated cortex with larger task-related high gamma power modulations tended to be more functionally connected to the dorsal attention network (DAN). Finally, we demonstrated that tumour-DAN connectivity is evident across a larger cohort of patients with gliomas and that it relates to long-term postsurgical outcomes in goal-directed attention. Overall, this study contributes convergent fMRI-ECoG evidence that tumour-infiltrated cortex participates in large-scale neurocognitive circuits that support executive function in health. These findings underscore the potential clinical utility of mapping large-scale connectivity of tumour-infiltrated tissue in the care of patients with diffuse gliomas.

A Prospective Study of Longitudinal Risks of Cognitive Deficit for People Undergoing Glioblastoma Surgery Using a Tablet Computer Cognition Testing Battery: Towards Personalized Understanding of Risks to Cognitive Function.

Glioblastoma and the surgery to remove it pose high risks to the cognitive function of patients. Little reliable data exist about these risks, especially postoperatively before radiotherapy. We hypothesized that cognitive deficit risks detected before surgery will be exacerbated by surgery in patients with glioblastoma undergoing maximal treatment regimens. We used longitudinal electronic cognitive testing perioperatively to perform a prospective, longitudinal, observational study of 49 participants with glioblastoma undergoing surgery. Before surgery (A1), the participant risk of deficit in 5/6 cognitive domains was increased compared to normative data. Of these, the risks to Attention (OR = 31.19), Memory (OR = 97.38), and Perception (OR = 213.75) were markedly increased. These risks significantly increased in the early period after surgery (A2) when patients were discharged home or seen in the clinic to discuss histology results. For participants tested at 4-6 weeks after surgery (A3) before starting radiotherapy, there was evidence of risk reduction towards A1. The observed risks of cognitive deficit were independent of patient-specific, tumour-specific, and surgery-specific co-variates. These results reveal a timeframe of natural recovery in the first 4-6 weeks after surgery based on personalized deficit profiles for each participant. Future research in this period could investigate personalized rehabilitation tools to aid the recovery process found.

High gamma activity distinguishes frontal cognitive control regions from adjacent cortical networks.

Though the lateral frontal cortex is broadly implicated in cognitive control, functional MRI (fMRI) studies suggest fine-grained distinctions within this region. To examine this question electrophysiologically, we placed electrodes on the lateral frontal cortex in patients undergoing awake craniotomy for tumor resection. Patients performed verbal tasks with a manipulation of attentional switching, a canonical control demand. Power in the high gamma range (70-250 Hz) distinguished electrodes based on their location within a high-resolution fMRI network parcellation of the frontal lobe. Electrodes within the canonical fronto-parietal control network showed increased power in the switching condition, a result absent in electrodes within default mode, language and somato-motor networks. High gamma results contrasted with spatially distributed power decreases in the beta range (12-30 Hz). These results confirm the importance of fine-scale functional distinctions within the human frontal lobe, and pave the way for increased precision of functional mapping in tumor surgeries.

Intraoperative mapping of executive function using electrocorticography for patients with low-grade gliomas.

BACKGROUND: Intraoperative functional mapping with direct electrical stimulation during awake surgery for patients with diffuse low-grade glioma has been used in recent years to optimize the balance between surgical resection and quality of life following surgery. Mapping of executive functions is particularly challenging because of their complex nature, with only a handful of reports published so far. Here, we propose the recording of neural activity directly from the surface of the brain using electrocorticography to map executive functions and demonstrate its feasibility and potential utility. METHODS: To track a neural signature of executive function, we recorded neural activity using electrocorticography during awake surgery from the frontal cortex of three patients judged to have an appearance of diffuse low-grade glioma. Based on existing functional magnetic resonance imaging (fMRI) evidence from healthy participants for the recruitment of areas associated with executive function with increased task demands, we employed a task difficulty manipulation in two counting tasks performed intraoperatively. Following surgery, the data were extracted and analyzed offline to identify increases in broadband high-gamma power with increased task difficulty, equivalent to fMRI findings, as a signature of activity related to executive function. RESULTS: All three patients performed the tasks well. Data were recorded from five electrode strips, resulting in data from 15 channels overall. Eleven out of the 15 channels (73.3%) showed significant increases in high-gamma power with increased task difficulty, 26.6% of the channels (4/15) showed no change in power, and none of the channels showed power decrease. High-gamma power increases with increased task difficulty were more likely in areas that are within the canonical frontoparietal network template. CONCLUSIONS: These results are the first step toward developing electrocorticography as a tool for mapping of executive function complementarily to direct electrical stimulation to guide resection. Further studies are required to establish this approach for clinical use.

Practical Application of Networks in Neurosurgery: Combined 3-Dimensional Printing, Neuronavigation, and Preoperative Surgical Planning.

BACKGROUND: A plethora of cutting-edge neuroimaging analyses have been developed and published, yet they have not hitherto been realized as improvements in neurosurgical outcomes. In this paper we propose a novel interface between neuroimaging and neurosurgery for aiding translational research. Our objective is to create a method for applying advanced neuroimaging and network analysis findings to neurosurgery and illustrate its application through the presentation of 2 detailed case vignettes. METHODS: This interface comprises a combination of network visualization, 3-dimensional printing, and ex-vivo neuronavigation to enable preoperative planning according to functional neuroanatomy. Clinical cases were selected from a prospective cohort study. RESULTS: The first case vignette describes a low-grade glioma with potential language and executive function network involvement that underwent a successful complete resection of the lesion with preservation of network features. The second case describes a low-grade glioma in an apparently noneloquent location that underwent a subtotal resection but demonstrated unexpected and significant impairment in executive function postoperatively that subsequently abated during follow-up. In both examples the neuroimaging and network data highlight the complexity of the surrounding functional neuroanatomy at the individual level, beyond that which can be perceived on standard structural sequences. CONCLUSIONS: The described interface has widespread applications for translational research including preoperative planning, neurosurgical training, and detailed patient counseling. A protocol for assessing its effectiveness and safety is proposed. Finally, recommendations for effective translation of findings from neuroimaging to neurosurgery are discussed, with the aim of making clinically meaningful improvements to neurosurgical practice.

An unusual anatomic and geographic location of primary germinoma of the fourth ventricle.

Intracranial germinoma is most commonly found in the pineal and suprasellar regions. The medulla oblongata and fourth ventricle are rare sites of primary germinoma, with only 12 previous patients reported, all from the Far East. To our knowledge, we report the first patient from Europe. A 25-year-old female of Afro-Caribbean origin presented with several weeks of worsening migraines, dizziness, tachycardia and veering to the right whilst walking. MRI revealed a lesion in the fourth ventricle, which was treated with surgical debulking and post operative radiotherapy. Two months following completion of radiotherapy, MRI showed almost complete resolution of the enhancing disease within the primary tumour area and no intraspinal pathological enhancement. This patient highlights the importance of considering germinoma in the differential diagnosis of all medullary masses with extension into the fourth ventricle irrespective of geographic location.