| Popis: |
Gliomas are a rare form of primary brain tumor, and the rate of morbidity and mortality is very high (Ho et al., 2014). Glioma patients often suffer from cognitive deficits, particularly in Executive Functioning (EF), which can decrease their quality of life (Caramanna et al., 2021; van Kessel et al., 2017; Weyer-Jamora et al., 2021). EF refers to a set of cognitive processes that are important in the cognitive control of behaviors such as attention, decision-making and working memory. EF deficits exist before surgery, and although studies have shown that tumor resection may be helpful in alleviating such problems, research has demonstrated varying trajectories in EF changes in patients that have undergone tumor resection, with some noting improving as well as deteriorating EF after surgery (Lemaitre et al., 2021; Ng et al., 2019; Noll et al., 2021; Sinha et al., 2020; Talacchi et al., 2011). Research has shown that gliomas are often localized in the frontal regions of the brain, residing in the white matter under the frontal cortices (Larjavaara et al., 2007, Wang et al., 2020). These brain regions have been shown to play an important role in the regulation of EF. Importantly, gliomas seem to directly integrate into their neural environment. The area in the vicinity of the tumor, the peritumoral area, has been shown to be hyperactive (Venkatesh et al., 2019, Numan et al., 2021). Investigations into the relationship between gliomas and neuronal activity in rodents, have revealed a direct link between the two, whereby synaptic and electric integration of gliomas into the neuronal networks occurs, which in turn promotes glioma progression (Buckingham et al., 2011; Campbell et al., 2012; Gibson et al., 2014; Venkatesh et al., 2015; Venkatesh et al., 2017; Venkatesh et al., 2019). Studies in rodents have further revealed that increased neuronal activity promotes glioma proliferation and growth (Gibson et al., 2014; Venkatesh et al., 2015). Various molecular mechanisms underlying this phenomenon have been researched, with some studies focusing on neuroligin-3 (NLGN3), whereby stimulation of neurons causes the cleavage and secretion of NLGN3, stimulating glioma growth (Venkatesh et al., 2015; Venkatesh et al., 2017). Other studies have shown similar mechanisms to occur through the secretion of brain derived neurotrophic factor (BDNF), glutamate and dopamine, all of which seem to promote tumor growth (Xiong et al., 2013; Dolma et al., 2016; Ishiuchi et al., 2002; Ishiuchi et al., 2007). Conversely, gliomas are also able to stimulate neuronal activity by forming synapses with healthy neurons through glutamate release (Buckingham et al., 2011; Campbell et al., 2012). Overall, such studies have shown an intricate bidirectional relationship between neurons and gliomas which impacts tumor growth. Further studies, in glioma patients, have also linked tumor progression and brain activity, as measured with magnetoencephalography (MEG), which may contribute to the progression of the disease. In patients, it has been shown that activity, as measured with magnetoencephalography (MEG), is pathologically heightened in comparison to healthy controls (HCs), not only around the tumor but throughout the entire brain (Numan et al., 2022; Zimmermann et al., 2023) Lower levels of oscillatory brain activity were correlated with lower levels of NLGN3 and with longer progression free survival (PFS) in glioma patients (Derks et al., 2018). Similarly, higher levels of broadband power, a proxy for neural activity, postoperatively, predicted shorter PFS and overall survival (OS) in this patient group and were shown to serve as an additional prognostic marker (Belgers et al., 2020). Further supporting the concept of glioma induced neuronal circuits remodeling, are studies that have observed altered electrophysiological properties throughout the brain of patients with glioma, when comparing to HCs. Distinct electrophysiological patterns have been detected, characterized by an increase in slow wavelengths such as higher delta band activity in comparison to HCs (Aabedi et al., 2022; Baayen et al., 2003; Bosma et al., 2008; De Jongh et al., 2003; Oshino et al., 2007). Such alterations have also been correlated with differences in cognition, such as language (Wolthuis et al., 2022). Moreover, recent studies using magnetoencephalography (MEG) demonstrated differences in network clustering (Derks et al., 2021) and connectivity in the brain as compared to HCs (Bartolomei et al., 2006a; Bartolomei et al., 2006b). These findings in turn have been associated with cognitive functioning (Bosma et al., 2008; Bosma et al., 2009; van Dellen et al., 2012; Derks et al., 2019). A recent study by van Lingen et al., (2023) investigated the link between alterations in multilayer network topology in the frontoparietal network (FPN), a network that plays an important role in facilitating EF, and changes in EF in glioma patients from the pre-operative state to a one-year follow up (FU). Results showed that lower set shifting correlated with a decrease in integration. Although studies, such as the previously mentioned one, have investigated how gliomas may affect cognitive functioning in patients, most of the current research has focused on linking alterations in neuronal networks and EF. However, neuronal activity has yet to be investigated with regard to its relationship to cognitive functioning in glioma patients. This is of particular interest due to the previously illustrated findings that demonstrated the integration of the tumor into its neural surroundings and the finding that activity is heightened throughout the brain in these patients in comparison to controls (Numan et al., 2021; Zimmermann et al., 2023). Additionally, it is unknown how activity changes from pre- to post-tumor resection in such patients. This study will therefore aim to bridge these gaps of knowledge by building upon previous work conducted by van Lingen et al., (2023). In addition to analyzing the relationship between activity and EF in patients, this study aims to explore the same in healthy individuals. Patient studies have found that greater brain activity in the default mode network (DMN) is associated with better cognitive flexibility (Sambataro et al., 2010). Furthermore, Zou et al. (2012) discovered that intrinsic resting-state brain activity was significantly correlated with working memory task performance. In addition to such research, brain stimulation, through techniques such as transcranial alternating current stimulation (tACS) and transcranial random noise stimulation (TRNS), have been shown to enhance long-term memory and other cognitive functions (Grover et al., 2022; Qi et al., 2021; Snowball et al., 2023). Although these findings suggest that activity may be related to cognitive performance, the association between EF and activity in the FPN in healthy individuals is unknown. This study therefore intends to investigate the relationship between activity in the FPN and EF in glioma patients and HCs. As brain activity has been shown to impact various aspects of glioma pathology, the question remains how this may relate to cognition. |
