Non-invasively measured brain activity and radiological progression in diffuse glioma

Numan, Tianne; Kulik, S. D.; Moraal, Bastiaan; Reijneveld, Jaap C.; Stam, C.J.; Hamer, Philip C. De Witt; Derks, Jolanda; Bruynzeel, A.; Linde, Myra E. van; Wesseling, Pieter; Kouwenhoven, Mathilde C.M.; Klein, Martin; Würdinger, Thomas; Barkhof, Frederik; Geurts, Jeroen J. G.; Hillebrand, Arjan; Douw, Linda

doi:10.1038/s41598-021-97818-y

Cited by 17 publications

(11 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We previously reported higher relative inhibitory activity (lower E/I balance) in glioma patients in the regions around the tumor, both as compared to healthy controls and as compared to the contralateral hemishere. 8 The E/I balance at individual tumor locations may therefore be a relevant factor to further investigate from a clinical perspective, particularly since perampanel, an AMPA inhibitor, has been shown to inhibit tumor growth in vitro. 1 Future work may investigate how intrinsic E/I values at the tumor location relate to pathological decreases in this balance measured at diagnosis, together potentially impacting KPS and perhaps more fine-grained measures of performance, such as cognitive functioning.…”

Section: Discussionmentioning

confidence: 99%

“…Three measures of brain activity were then calculated using these epochs: (1) broadband power of the power spectrum, (2) offset, and (3) slope of the aperiodic component of the power spectrum, as described before. 8 Broadband power reflects the spectral density or area under the curve of the total spectral signal measured with MEG, and reflects the spiking rates of the underlying neuronal populations. 39,40 The offset is related to broadband power, but filters out frequency-specific variations in signals to establish a potentially more specific measure of neuronal spiking.…”

Section: Intrinsic Regional Brain Activitymentioning

confidence: 99%

“…2 Similar results have also been observed when using broadband power measured non-invasively with magnetoencephalography (MEG) and electroencephalography (EEG) as a proxy of neuronal activity. 8 Furthermore, there are indications that healthy and pathological activity in the (peri)tumoral region are interdigitated during cognitive performance in these patients. 9 This complex bidirectional interaction between the brain and glioma that informs both tumor and patient behavior has sparked the relatively new field of 'cancer neuroscience', aiming to elucidate how this crosstalk may inform understanding and treatment of glioma.…”

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

Regional healthy brain activity, glioma occurrence and symptomatology

Numan

Breedt

Maciel

et al. 2022

Preprint

View full text Add to dashboard Cite

It is unclear why exactly gliomas show preferential occurrence in certain brain areas. Increased spiking activity around gliomas leads to faster tumor growth in animal models, while higher non-invasively measured brain activity is related to shorter survival in patients. However, it is unknown how regional intrinsic brain activity, as measured in healthy controls, relates to glioma occurrence. We first investigated whether gliomas occur more frequently in regions with intrinsically higher brain activity. Secondly, we explored whether intrinsic cortical activity at individual patients tumor locations relates to tumor and patient characteristics. Across three cohorts, 306 patients with different tumor subtypes were included. Tumor masks were created for each patient. Intrinsic regional brain activity was assessed through resting-state magnetoencephalography (MEG) acquired in healthy controls, which was then source-localized to 210 cortical brain regions according to the Brainnetome atlas. Brain activity was operationalized as (1) broadband power and (2) offset of the aperiodic component of the power spectrum, which both reflect neuronal spiking of the underlying neuronal population. We additionally assessed (3) the slope of the aperiodic component of the power spectrum, which is thought to reflect the neuronal excitation/inhibition (E/I) balance. First, correlation coefficients were calculated between group-level regional glioma occurrence, as obtained by concatenating tumor masks across patients, and group-averaged regional intrinsic brain activity. Second, intrinsic brain activity at specific tumor locations was calculated by overlaying patients individual tumor masks with regional intrinsic brain activity of the controls and was associated with tumor and patient characteristics. As hypothesized, more malignant glioma preferentially occurred in brain regions characterized by higher intrinsic brain activity in controls as reflected by higher offset. Secondly, intrinsic brain activity at patients individual tumor locations differed according to glioma subtype and performance status: the most malignant IDH-wildtype glioblastoma patients had the lowest E/I balance at their individual tumor locations, while lower E/I balance weakly related to poorer Karnofsky performance status, independent of glioma subtype. In conclusion, malignant gliomas more frequently occur in cortical brain regions with intrinsically higher activity levels, suggesting that more active regions are more vulnerable to glioma development. Moreover, indices of healthy, intrinsic E/I balance at patients individual tumor locations may capture both tumor biology and patients performance status. These findings contribute to our understanding of the complex and bidirectional relationship between normal brain functioning and glioma growth, which is at the core of the relatively new field of cancer neuroscience.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Intrinsic Regional Brain Activitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

Regional healthy brain activity, glioma occurrence and symptomatology

Numan

Breedt

Maciel

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Three measures of brain activity were then calculated using these epochs: (i) broadband power of the power spectrum; (ii) offset; and (iii) slope of the aperiodic component of the power spectrum, as described before. 8 Broadband power reflects the spectral density or area under the curve of the total spectral signal measured with MEG, and reflects the spiking rates of the underlying neuronal populations. 41 , 42 The offset is related to broadband power, but filters out frequency-specific variations in signals to establish a potentially more specific measure of neuronal spiking.…”

Section: Methodsmentioning

confidence: 99%

“… 2 Similar results have also been observed when using broadband power measured non-invasively with magnetoencephalography (MEG) and EEG as a proxy of neuronal activity. 8 Furthermore, there are indications that healthy and pathological activity in the (peri)tumoural region are interdigitated during cognitive performance in these patients. 9 This complex bidirectional interaction between the brain and glioma that informs both tumour and patient behaviour has sparked the relatively new field of ‘cancer neuroscience’, aiming to explain how this crosstalk may inform understanding and treatment of glioma.…”

Section: Introductionmentioning

confidence: 98%

Regional healthy brain activity, glioma occurrence and symptomatology

Numan

Breedt

Maciel

et al. 2022

Brain

View full text Add to dashboard Cite

It is unclear why exactly gliomas show preferential occurrence in certain brain areas. Increased spiking activity around gliomas leads to faster tumour growth in animal models, while higher non-invasively measured brain activity is related to shorter survival in patients. However, it is unknown how regional intrinsic brain activity, as measured in healthy controls, relates to glioma occurrence. We first investigated whether gliomas occur more frequently in regions with intrinsically higher brain activity. Second, we explored whether intrinsic cortical activity at individual patients’ tumour locations relates to tumour and patient characteristics. Across three cross-sectional cohorts, 413 patients were included. Individual tumour masks were created. Intrinsic regional brain activity was assessed through resting-state magnetoencephalography acquired in healthy controls and source-localized to 210 cortical brain regions. Brain activity was operationalized as: (i) broadband power; and (ii) offset of the aperiodic component of the power spectrum, which both reflect neuronal spiking of the underlying neuronal population. We additionally assessed (iii) the slope of the aperiodic component of the power spectrum, which is thought to reflect the neuronal excitation/inhibition ratio. First, correlation coefficients were calculated between group-level regional glioma occurrence, as obtained by concatenating tumour masks across patients, and group-averaged regional intrinsic brain activity. Second, intrinsic brain activity at specific tumour locations was calculated by overlaying patients’ individual tumour masks with regional intrinsic brain activity of the controls and was associated with tumour and patient characteristics. As proposed, glioma preferentially occurred in brain regions characterized by higher intrinsic brain activity in controls as reflected by higher offset. Second, intrinsic brain activity at patients’ individual tumour locations differed according to glioma subtype and performance status: the most malignant isocitrate dehydrogenase-wild-type glioblastoma patients had the lowest excitation/inhibition ratio at their individual tumour locations as compared to isocitrate dehydrogenase-mutant, 1p/19q-codeleted glioma patients, while a lower excitation/inhibition ratio related to poorer Karnofsky Performance Status, particularly in codeleted glioma patients. In conclusion, gliomas more frequently occur in cortical brain regions with intrinsically higher activity levels, suggesting that more active regions are more vulnerable to glioma development. Moreover, indices of healthy, intrinsic excitation/inhibition ratio at patients’ individual tumour locations may capture both tumour biology and patients’ performance status. These findings contribute to our understanding of the complex and bidirectional relationship between normal brain functioning and glioma growth, which is at the core of the relatively new field of ‘cancer neuroscience’.

show abstract