Mapping of cognitive function in diffuse low grade glioma surgery

• Research type

  Research Study

• Full title

  Intraoperative mapping of cognitive function in patients undergoing brain surgery for diffuse low grade glioma

• IRAS ID

  179868

• Contact name

  Thomas Santarius

• Contact email

  thomas.santarius@addenbrookes.nhs.uk

• Sponsor organisation

  Cambridge University Hospitals NHS Foundation Trust

• Duration of Study in the UK

  5 years, 0 months, 1 days

• Research summary

  Research Summary
  Diffuse low grade gliomas (DLGGs) are slow-growing and infiltrative tumours arising from the brain. Radical resection (surgical removal of as much of the tumour as possible) improves overall survival of patients. Thus the aim of surgery is to maximise the amount of tumour removed while preserving brain function to maintain quality of life.

  During surgery, mapping of sensory and motor function using direct brain electrical stimulation is performed to minimize the risk of damage to these functions. In some patients, mapping of the brain involved in speech and language is required. Patients are awakened during surgery and are asked to speak and name pictures while electrical stimulation is applied on different parts of the exposed brain. Stimulation that leads to impairment in speech production implies the involvement of this region in language. This information is used by the neurosurgeon to decide whether to remove this tissue or not.

  We aim to develop advanced techniques for this procedure to further improve its safety and efficiency. We will expand the currently used procedure by:
  (1) Developing more efficient tasks for language functional mapping.
  (2) Extending mapping to executive functions, which serve as the basis for daily life structured goal-directed behaviour.
  (3) Using multiple techniques for functional mapping during surgery, including electrical stimulation and neurophysiological assessment during task performance.
  (4) Using neurocognitive tests before and after surgery to gain better understanding of how the cognitive function relates to intraoperative functional mapping and resected tissue.

  The overall aim is to allow better planning of surgery, reduced use of electrical stimulation during surgery (therefore reduced risks associated with stimulation such as seizures), and more radical resections with less functional impairment. Additional research-related aims are to better understand how brain networks relate to cognitive function and how cognitive function post-surgery relates to the resected brain regions.

  Summary of Results
  The main results of the study include::

  1. Patients with low grade glioma often have remarkably few neuropsychological impairments at presentation despite often large tumours in eloquent brain regions. Nevertheless, in most participants at least one neuropsychological domain has a degree of impairment that often worsens in the immediate perioperative period before re-establishing its baseline performance.

  2. Novel interactive neuropsychological assessments offer advantages over traditional formal neuropsychological testing including improved replicability, insights into higher cognitive function domains such as executive dysfunction.

  3. Brain networks derived from resting-state functional MRI correspond to the function of a variety of higher cognitive processes at the individual level, providing a non-invasive biomarker of neuropsychological function and post-operative recovery.

  4. Higher order cognitive processes (e.g. executive function) can be mapped during awake neurosurgical procedures using a combination of neurophysiology and network analyses. Areas in the frontal cortex are a key hub for executive function and show divergent activity in different frequency bands and in different regions. This serves as a proof of principle of how awake brain surgery and recordings directly from the surface of the brain using electrocorticography (ECOG) can be used to map complex brain function.

  5. The peri-tumoural region demonstrates a complex response to surgery. Pre-operatively there is a reduction in neurite (axon & dendrite) density that results in low connectivity with the rest of the brain. Following surgery this same region increases its neurite density and overall connectivity. This response may underlie the fatigue commonly associated with the post-operative period, as well as adding to our body of evidence highlighting non-local effects of focal tumours.

  6. Some functionality related to higher cognitive function is preserved on tumour tissue as measured during surgery with electrocorticography during surgery. Such functional preservation is also linked to increased connectivity larger scale brain networks associated with these functions as measures with resting-state functional MRI. At the methodological level this funding demonstrates the importance of converging evidence across neuroimaging modalities for better understanding of the effects of tumours on cognitive function.

  7. Overlap of the tumour with specific higher cognitive function resting state networks predicts specific post-operative deficits beyond that which can be appreciated on standard structural imaging.
  Has the registry been updated to include summary results?: No
  If yes - please enter the URL to summary results:
  If no – why not?: The study is not a clinical trial and is not registered.
  Did you follow your dissemination plan submitted in the IRAS application form (Q A51)?: Yes
  If yes, describe or provide URLs to disseminated materials: The results have been disseminated via multiple channels, both scientific and to the public. The results were published in several publications in scientific journals, with additional manuscripts in preparation. The results were presented in multiple national and international conferences. The study was covered by the BBC television and was broadcasted nationally and internationally (views on YouTube >450,00). The results were shared and presented to the participating patients in a special Patients Day.

  Coverage by the BBC:
  https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Furl6570.hra.nhs.uk%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbdiL34lSpLgGqo-2BEXB-2F6Tn5TQEqclbvH1YKVQe3wks9z5qkCGLDh-2FvgnVe9Pnnc2AA-3D-3DbV7w_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YJlrsnTdmFPl88bcU7gnSjPzJQ9i-2F-2Buf99gyQVljBSdRbLXbMOw0AWS82iQwWut3KaM8W7-2Bgjks-2FMtTXCx4IWF6vWjwKgxx2ard-2FExAjPTHqM9E8mVMbrMS9rykV1KWoo4FuVlw-2F0KmKLkP32i70-2Bz-2F1zuweM3UN8QW-2BzI3KutZmOEL1opXN3JqJ1BAKKZBW8Q-3D&data=04%7C01%7Capprovals%40hra.nhs.uk%7C2cc6bb27e30b4e37a1b808d9914f7284%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637700592669605887%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C1000&sdata=Z6TXwz%2FPbK6jL39cmpsk%2FgKhKTjfyRDmvuGP7yRhdpQ%3D&reserved=0
  https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Furl6570.hra.nhs.uk%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbUerPtN23GaUCba3rzolc-2FghCDj4dOV10cjDVLa-2BX4ZLguK3ktPngUp2qJxZ8FN7vA-3D-3Dlt60_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YJlrsnTdmFPl88bcU7gnSjPN-2BYcW3HDtBs-2BE5AivHcS-2BmjO0Q1SjIeD053rajCgcYlicnYa-2F287SeIT-2B1npwrtARaH9qOrSRcXnOoWf2tdNuhNBuX20foKBVWD0Mp0KedqdmgDIYxtV1omKfv2NyZUAx2kzKcXSBP22LSZGT-2BNpLCZBGoxfcYzBJwSIS3Lim1U-3D&data=04%7C01%7Capprovals%40hra.nhs.uk%7C2cc6bb27e30b4e37a1b808d9914f7284%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637700592669605887%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C1000&sdata=72ojH1jjoaSGEwkd1wLuSdrayH2p%2BrypCaOL9XEnbX4%3D&reserved=0

  Journal peer-reviewed articles:

  Romero-Garcia R.*, Suckling J.*, Owen M., Assem M., Sinha R. Coelho P., Woodberry E., Price S.J., Burke G.A.A., Santarius T., Erez Y. & Hart M.G. (2021). Memory recovery is related to default mode network impairment and neurite density during brain tumours treatment. Journal of Neurosurgery, In press. doi: 10.3171/2021.1.JNS203959. (* equal contribution)
  Preprint: https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Furl6570.hra.nhs.uk%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbVDknLRlk3r9Y0tfvaGiBUDbwiDpf99N0bvwWSj9y-2FJiePRjP-2B6MlAZfLLlMLNZiCw-3D-3D4rBu_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YJlrsnTdmFPl88bcU7gnSjPjkKF7a904TbMyeVEAieTzv8F1BhDgOPMDP6KsrHxmftA7ltq5uNXMQY-2FwIcd6lj2UF-2F-2BBrX5izOELM7cQS2wBnjVkt-2FbzHKUJ-2B9MuI9aDHZnPoRa5II-2B-2FW39yOh4BqA6-2F9Q3cr-2FrSB0Oo9-2FZzrNZzFFtjF8Hx6bJgRb76X1rhXM-3D&data=04%7C01%7Capprovals%40hra.nhs.uk%7C2cc6bb27e30b4e37a1b808d9914f7284%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637700592669605887%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C1000&sdata=lzNXHh4e%2BcciYKHOzl41EbKqNZaq4BUXryP7Q3aw368%3D&reserved=0

  Romero-Garcia R., Hart M. G., Bethlehem R., Owen M, Mandal A., Assem M., Crespo-Facorro B., Gorriz J. M., Woodberry E, Burke G. A. A., Price S. J., Santarius T., Erez Y. & Suckling J. (2021). BOLD coupling between lesioned and healthy brain is associated with glioma patients’ recovery. Cancers, 13(19), 5008. doi: 10.3390/cancers13195008.

  Erez Y., Assem M., Coelho P., Romero-Garcia R., Owen M., McDonald A., Woodberry E., Morris R.C., Price S.J., Suckling J., Duncan J., Hart M.G. & Santarius T. (2021). Intraoperative mapping of executive function using electrocorticography for patients with low grade gliomas. Acta Neurochirurgica 163(5), 1299-1309. doi: 10.1007/s00701-020-04646-6.
  Preprint: https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Furl6570.hra.nhs.uk%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbdwd1X4i-2BJ96f9yOqdDkHNA-3D8ehz_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YJlrsnTdmFPl88bcU7gnSjPQ0Fhgx1djNYCY39ozIexC83GtNQuW8W9aVTt9db4VT-2FmOFlWhty8yhYQZLv9R5flTi-2FNz7v-2FIsOJsA9WrwhsgMlDZHPelXaZ-2BFnY1OsOA0uw4wKQe0AMDhjOlfh29mAvF455sBYFe-2FCIlaq8bFBW-2ByJq2Qjwf8bOAToJ-2BKeUpCQ-3D&data=04%7C01%7Capprovals%40hra.nhs.uk%7C2cc6bb27e30b4e37a1b808d9914f7284%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637700592669605887%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C1000&sdata=8J6AefctLY2RKGy4WSm%2FUEmpV8mXRYEDxQzL6gD%2FtXk%3D&reserved=0

  Romero-Garcia R., Erez Y., Owen M., Morris R.C., Price S.J., Santarius T., Suckling J. & Hart M.G. (2020). Practical applications of networks in neurosurgery: combined 3D printing, neuronavigation, and pre-operative surgical planning. World Neurosurgery, 137:e126-e137. doi: 10.1016/j.wneu.2020.01.085.
  Preprint: https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Furl6570.hra.nhs.uk%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbVSBVKHaZQlk6Go6YDZQBWU-3DGroE_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YJlrsnTdmFPl88bcU7gnSjPq-2FHr8Rzoq5LVwR6yBZieHmgwHZDJR7m3vXWxcdbuxEdxOXdRKln3r8DOOzQp3VHOPQ54QZZ7PE-2FY52XAVcAaWIBYh4S4R-2FQ3txVmHYy8sHz3sHd0j5LcKGdgHw0VpeA3FA0pFdrIGJb8F-2BmQtRIdkLjDXh-2BEcmriXG4LOFrzNmM-3D&data=04%7C01%7Capprovals%40hra.nhs.uk%7C2cc6bb27e30b4e37a1b808d9914f7284%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637700592669605887%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C1000&sdata=MSU%2Bth0Kr73NjIL5TrUyicOBnnbsNl4j7GtJeV01Jy0%3D&reserved=0

  Submitted manuscripts:

  Assem M., Hart M.G., Coelho P., Romero-Garcia R., McDonald A., Woodberry E., Morris R.C., Price S.J., Suckling J, Santarius T., Duncan J. & Erez Y. Focal gamma activity in frontal control regions revealed using intraoperative electrocorticography. Preprint: https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Furl6570.hra.nhs.uk%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbVDknLRlk3r9Y0tfvaGiBUDbwiDpf99N0bvwWSj9y-2FJilXKIP5UaVWeO-2Bj13RGPr8iAEg4iW56q-2BNmb0hUHG0gc-3DEtnH_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YJlrsnTdmFPl88bcU7gnSjPno43-2BayMBO99HPG4k1aoA0KaAccEvseUSOpYM0e2PHDVvEWrwXWuoGOgN10BjpS-2BqjdxDNhh7NtmYOJJPhg7U-2FoQJYYLQw5ZRb1b3Q8PUaP7FUJo-2BSRwM-2BSk-2B2Ysx-2FdRyQhTbmw-2F3qqWPvDUcBuCQAGLuWlcqqMLNUYNzOtdycc-3D&data=04%7C01%7Capprovals%40hra.nhs.uk%7C2cc6bb27e30b4e37a1b808d9914f7284%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637700592669605887%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C1000&sdata=ZfKoXHqGSrGObJy6o2VzZy5%2BA1whg8uQB5r%2F7rQYpso%3D&reserved=0

  Owen M., Romero-Garcia R., McDonald A., Woodberry E., Coelho P., Morris R.C., Price S.J., Santarius T., Suckling J., Erez Y. & Hart M.G. Assessment of neuropsychological function during early treatment of diffuse glioma.
  Preprint: https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Furl6570.hra.nhs.uk%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbVDknLRlk3r9Y0tfvaGiBUDbwiDpf99N0bvwWSj9y-2FJisQgDr9jQT9-2FXXvFLe4-2BnV9hX-2FKhgGrQbsFPtoIG74ec-3D1dDQ_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YJlrsnTdmFPl88bcU7gnSjPr04grKaHIw8g2DZKCsMOyXEhAfmfs5jGZl3QfTcv-2FXk-2FoeC939ccKFPzhAjSel-2BDvuVtvUG93U4cxqlzpBdvBPPPBprPjbZ3k-2BS2HIZWZOdmskKWQLjRmHcsqBuiEY6sSW5I5QyLQgzaIIN5fhjde5MKAm38eKKbgFZdL6oIHaI-3D&data=04%7C01%7Capprovals%40hra.nhs.uk%7C2cc6bb27e30b4e37a1b808d9914f7284%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637700592669605887%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C1000&sdata=GGCB233t8CTdTGHMTd9LfKsjNCxJhWje7Z%2FzUrBZLe0%3D&reserved=0

• REC name

  East of England - Cambridge Central Research Ethics Committee

• REC reference

  16/EE/0151

• Date of REC Opinion

  6 Oct 2016

• REC opinion

  Further Information Favourable Opinion