Linda Douw

Linda Douw
Amsterdam University Medical Center | VUmc · Department of Anatomy and Neurosciences

PhD

About

177
Publications
17,390
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4,256
Citations
Additional affiliations
September 2011 - present
Massachusetts General Hospital / Harvard Medical School
Position
  • Researcher

Publications

Publications (177)
Article
Background Glioma is associated with pathologically high neuronal activity around the tumor, which associates with faster tumor progression in patients. Concurrently, patients with glioma have local and widespread disturbances of the functional brain network as measured with magnetoencephalography (MEG) such as higher network clustering (the extent...
Article
Background Protocols for assessment of (neuro)psychological outcomes in lower-grade glioma patients vary between hospitals. This potentially complicates generalization of these outcomes. We compared standardized scores on tests of two frequently impaired cognitive domains (attention and executive functioning (EF)), and two relevant patient-reported...
Article
Background Glioma patients often experience cognitive problems, which are associated with decreased functional independence and health-related quality of life. However, the prevalence and nature of cognitive impairment in these patients is relatively underreported, particularly during stable disease. In this study we determine the prevalence of cog...
Article
Background Many patients with glioma suffer from deficits in executive functioning (EF), regardless of tumor location and size. While some patients experience improving EF after tumor resection, others deteriorate over time. This variability in cognitive trajectories is still poorly understood, but neuroscientific approaches that view the brain as...
Article
Background While patients with diffuse low-grade glioma (LGG) often survive for years, there is a risk of tumour progression which may impact on patients’ long-term health-related quality of life (HRQOL) and neurocognitive functioning (NCF). We present a follow-up of LGG patients and their informal caregivers (T3) who took part in our previous HRQO...
Preprint
Background Even though fatigue is one of the most prevalent and burdensome symptoms in patients with glioma, its etiology and determinants are still poorly understood. We aimed to identify which demographic, tumor- and treatment-related characteristics and patient-reported outcome measures (PROMs) are associated with or are predictors of fatigue in...
Preprint
Many patients with glioma, primary brain tumors, suffer from poorly understood executive functioning deficits before and/or after tumor resection. We aimed to test whether frontoparietal network centrality of multilayer networks, which allow for integration across multiple frequencies, relates to and predicts executive functioning in glioma patient...
Article
Full-text available
Background: Cannabinoids have been suggested to alleviate frequently experienced symptoms of reduced mental well-being such as anxiety and depression. Mental well-being is an important subdomain of health-related quality of life (HRQoL). Reducing symptoms and maintaining HRQoL are particularly important in malignant primary brain tumor patients, as...
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Background Fatigue is the most frequent and burdensome symptom of patients with diffuse glioma. It is closely linked to decreased health-related quality of life and symptoms such as depression and sleep disturbances. Currently, there is no evidence-based treatment that targets severe fatigue in patients with brain tumours. Cognitive behavioural the...
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Prior studies suggest that methylphenidate, the primary pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD), alters functional brain connectivity. As the neurotransmitter systems targeted by methylphenidate undergo significant alterations throughout development, the effects of methylphenidate on functional connectivity may...
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Many women with breast cancer suffer from a decline in memory and executive function, particularly after treatment with chemotherapy. Recent neuroimaging studies suggest that changes in network dynamics are fundamental in decline in these cognitive functions. This has, however, not yet been investigated in breast cancer patients. Using resting stat...
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There is an ongoing need for novel biomarkers in clinical neuroscience, as diagnosis of neurological and psychiatric disorders is hampered by the pronounced overlap of behavioral symptoms and other pathophysiological characteristics. The question that this Focus Feature puts center stage is whether network-based biomarkers may provide a viable tool...
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Cognitive impairment is common in people with multiple sclerosis and strongly affects their daily functioning. Reports have linked disturbed cognitive functioning in multiple sclerosis to changes in the organization of the functional network. In the healthy brain, communication between brain regions and which network a region belongs to is continuo...
Article
Full-text available
The brain is an extraordinarily complex system that facilitates the optimal integration of information from different regions to execute its functions. With the recent advances in technology, researchers can now collect enormous amounts of data from the brain using neuroimaging at different scales and from numerous modalities. With that comes the n...
Preprint
Introduction Computational models are often used to assess how functional connectivity (FC) patterns emerge from neuronal population dynamics and anatomical connections in the brain. However, group averaged data is often used in this context and it remains unclear whether individual predictions of FC patterns using this approach can be made. Here,...
Preprint
Prior studies suggest that methylphenidate, the primary pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD), alters functional brain connectivity. As the neurotransmitter systems targeted by methylphenidate undergo significant alterations throughout development, the effects of methylphenidate on functional connectivity may...
Preprint
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 h...
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Full-text available
Multiple sclerosis (MS) features extensive connectivity changes, but how structural and functional connectivity relate, and whether this relation could be a useful biomarker for cognitive impairment in MS is unclear. This study included 79 MS patients and 40 healthy controls (HCs). Patients were classified as cognitively impaired (CI) or cognitivel...
Preprint
Background: Glioma patients experience a multitude of symptoms, impacting health-related quality of life. We aimed to assess frequency and burden of patient-reported symptoms in glioma patients with stable disease and whether patients would consider treatment. We also explored how symptoms co-occur and interact within a network.Methods: Patients ra...
Article
BACKGROUND Patients with low-grade gliomas (LGGs) often survive for many years, yet little is known about patients’ health-related quality of life (HRQOL) in long-term survivorship. We previously investigated HRQOL in LGG patients diagnosed on average 6 years prior to assessment (T1, N=195) with a follow-up in stable patients on average 12 years af...
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Purpose This longitudinal study aimed to disentangle the impact of chemotherapy on fatigue and hypothetically associated functional brain network alterations. Methods In total, 34 breast cancer patients treated with chemotherapy (BCC +), 32 patients not treated with chemotherapy (BCC −), and 35 non-cancer controls (NC) were included. Fatigue was a...
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Temporal lobe epilepsy (TLE) patients are at risk of memory deficits, which have been linked to functional network disturbances, particularly of integration of the default mode network (DMN). However, the cellular substrates of functional network integration are unknown. We leverage a unique cross-scale dataset of drug-resistant TLE patients (n = 3...
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The success of epilepsy surgery in patients with refractory epilepsy depends upon correct identification of the epileptogenic zone (EZ) and an optimal choice of the resection area. In this study we developed individualized computational models based upon structural brain networks to explore the impact of different virtual resections on the propagat...
Article
Full-text available
Non-invasively measured brain activity is related to progression-free survival in glioma patients, suggesting its potential as a marker of glioma progression. We therefore assessed the relationship between brain activity and increasing tumor volumes on routine clinical magnetic resonance imaging (MRI) in glioma patients. Postoperative magnetoenceph...
Article
BACKGROUND Patients with diffuse glioma experience many tumor- and treatment-related symptoms, including fatigue, cognitive deficits, and anxiety. It remains unclear how the frequency and burden of these symptoms change over time and specifically which symptoms patients experience during the stable phase of the disease. We assessed the frequency an...
Article
BACKGROUND Many patients with low-grade gliomas (LGGs) continue to survive for many years, yet little is known about patients’ health-related quality of life (HRQOL) in long-term survivorship. We previously investigated HRQOL in LGG patients diagnosed on average 6 years prior to assessment (T1, N=195) with a follow-up in stable patients on average...
Article
BACKGROUND Glioma patients experience a high symptom burden contributing to poorer quality of life. Symptoms include depression, cognitive impairment, and fatigue and vary throughout the disease. These symptoms are rarely studied from a comprehensive perspective, while their interdependence may be relevant for their development, perpetuation, and u...
Article
BACKGROUND Gliomas are primary brain tumors with a dismal prognosis. Reducing symptoms and maintaining quality of life (QoL) are main treatment aims in glioma patients. Mental well-being is an important subdomain of QoL. Cannabinoids have been suggested to alleviate frequently experienced symptoms of reduced mental well-being such as anxiety or dep...
Chapter
Network neuroscience investigates brain functioning through the prism of connectivity, and graph theory has been the main framework to understand brain networks. Recently, an alternative framework has gained attention: topological data analysis. It provides a set of metrics that go beyond pairwise connections and offer improved robustness against n...
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In recent years, there has been an increase in applications of network science in many different fields. In clinical neuroscience and psychopathology, the developments and applications of network science have occurred mostly simultaneously, but without much collaboration between the two fields. The promise of integrating these network applications...
Preprint
Executive functioning is a higher-order cognitive process that is thought to depend on a brain network organization facilitating network integration across specialized subnetworks. The frontoparietal network (FPN), a subnetwork that has diverse connections to other brain modules, seems pivotal to this integration, and a more central role of regions...
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Stress is a major risk factor for the development of almost all psychiatric disorders. Next to the acute stress response, an efficient recovery in the aftermath of stress is important for optimal resilience. Increased stress vulnerability across psychiatric disorders may therefore be related to altered trajectories during the recovery phase followi...
Article
Introduction: Glioma patients show increased global brain network clustering relating to poorer cognition and epilepsy. However, it is unclear whether this increase is spatially widespread, localized in the (peri)tumor region only, or decreases with distance from the tumor. Materials and methods: Weighted global and local brain network clusterin...
Preprint
Full-text available
Background The success of epilepsy surgery in patients with refractory epilepsy depends upon correct identification of the epileptogenic zone (EZ) and an optimal choice of the resection area. In this study we developed individualized computational models based upon structural brain networks to explore the impact of different virtual resections on t...
Article
Full-text available
Background The impact of cerebellar damage and (dys)function on cognition remains understudied in multiple sclerosis. Objective To assess the cognitive relevance of cerebellar structural damage and functional connectivity (FC) in relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS). Methods This study...
Preprint
Full-text available
The brain is an extraordinarily complex system that facilitates the efficient integration of information from different regions to execute its functions. With the recent advances in technology, researchers can now collect enormous amounts of data from the brain using neuroimaging at different scales and from numerous modalities. With that comes the...
Preprint
Non-invasively measured brain activity is related to progression-free survival in glioma patients, suggesting its potential as a marker of glioma progression. We therefore assessed the relationship between brain activity and increasing tumor volumes on routine clinical magnetic resonance imaging (MRI) in glioma patients. Postoperative magnetoenceph...
Preprint
Full-text available
Temporal lobe epilepsy patients are heterogeneous regarding cognitive functioning, with predominant risk of memory deficits. Despite major advances within cellular neuroscience, neuroimaging, and neuropsychology, it remains challenging to integrate memory performance with cellular characteristics and brain network topology. In a unique dataset, we...
Article
Full-text available
Background More than 80% of multiple sclerosis (MS) patients experience symptoms of fatigue. MS-related fatigue is only partly explained by structural (lesions and atrophy) and functional (brain activation and conventional static functional connectivity) brain properties. Objectives To investigate the relationship of dynamic functional connectivit...
Article
Full-text available
Background Cognitive decline remains difficult to predict as structural brain damage cannot fully explain the extensive heterogeneity found between MS patients. Objective To investigate whether functional brain network organization measured with magnetoencephalography (MEG) predicts cognitive decline in MS patients after 5 years and to explore its...
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It has long been understood that a multitude of biological systems, from genetics, to brain networks, to psychological factors, all play a role in personality. Understanding how these systems interact with each other to form both relatively stable patterns of behaviour, cognition and emotion, but also vast individual differences and psychiatric dis...
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Objective To investigate the association between β-amyloid (Aβ) load and postmortem structural network topology in decedents without dementia. Methods Fourteen decedents (mean age at death 72.6 ± 7.2 years) without known clinical diagnosis of neurodegenerative disease and meeting pathology criteria only for no or low Alzheimer disease (AD) patholo...
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Repetitive transcranial magnetic stimulation (rTMS) is used to investigate normal brain function in healthy participants and as a treatment for brain disorders. Various subject factors can influence individual response to rTMS, including brain network properties. A previous study by our group showed that “virtually lesioning” the left dorsolateral...
Article
Background Migraine is a common disorder with high social and medical impact. Patients with migraine have a much higher chance of experiencing headache attacks as compared to the general population. Recent neuroimaging studies have confirmed that pathophysiology in the brain is not limited to the moment of the attack but is also present in between...
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Functional brain networks are shaped and constrained by the underlying structural network. However, functional networks are not merely a one-to-one reflection of the structural network. Several theories have been put forward to understand the relationship between structural and functional networks. However, it remains unclear how these theories can...
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IntroductionProgression-free survival (PFS) in glioma patients varies widely, even when stratifying for known predictors (i.e. age, molecular tumor subtype, presence of epilepsy, tumor grade and Karnofsky performance status). Neuronal activity has been shown to accelerate tumor growth in an animal model, suggesting that brain activity may be valuab...
Article
Background Although most patients with medically refractory temporal lobe epilepsy (TLE) experience seizure freedom after anterior temporal lobectomy, approximately 40% may continue to have seizures. Functional network integration, as measured with preoperative resting-state functional MRI, may help stratify patients who are more likely to experien...
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Full-text available
Deficits in cognitive functioning are a common yet poorly understood symptom in Parkinson’s disease (PD). Recent studies have highlighted the importance of (dynamic) interactions between resting-state networks for cognition, which remains understudied in PD. We investigated how altered (dynamic) functional interactions between brain networks relate...
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Full-text available
The brain is a complex, multiscale dynamical system composed of many interacting regions. Knowledge of the spatiotemporal organization of these interactions is critical for establishing a solid understanding of the brain’s functional architecture and the relationship between neural dynamics and cognition in health and disease. The possibility of st...
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Full-text available
An efficient network such as the human brain features a combination of global integration of information, driven by long-range connections, and local processing involving short-range connections. Whether these connections are equally damaged in multiple sclerosis is unknown, as is their relevance for cognitive impairment and brain function. Therefo...
Article
BACKGROUND Our previous study among 195 low-grade glioma (LGG) patients six years after initial diagnosis, showed that high radiation doses (>2 Gy) were associated with neurocognitive disability. Follow-up at 12 years in 64 LGG patients showed patients without radiotherapy to have stable neurocognitive and radiological status while attentional func...
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Full-text available
Background: Cognitive deficits affect up to 70% of all patients with Multiple Sclerosis (MS) and have a significant impact on quality of life. Cognitive assessments need to be performed by a neuropsychologist and are often time-consuming, hampering timely identification and adequate monitoring of cognitive decline in MS. Objective: To develop a...
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Full-text available
Functional brain networks are often constructed by quantifying correlations between time series of activity of brain regions. Their topological structure includes nodes, edges, triangles, and even higher-dimensional objects. Topological data analysis (TDA) is the emerging framework to process data sets under this perspective. In parallel, topology...
Article
Introduction Functional brain networks in glioma patients are characterized by higher global clustering than healthy controls, indicating stronger connectivity in triads of brain regions when averaging across the entire brain. However, this could be due to either primary increased local clustering of (peri)tumor regions or higher local clustering t...
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Full-text available
Introduction: Patients with diffuse glioma often experience neurocognitive impairment already prior to surgery. Pertinent information on whether damage to a specific brain region due to tumor activity results in neurocognitive impairment or not, is relevant in clinical decision-making, and at the same time renders unique information on brain lesio...
Article
Research on the association between non-motor symptoms (NMS) of Parkinson's disease (PD) and patients' quality of life (QoL) has given insight into the burden of NMS. Most studies investigate NMS by assessing the contribution of individual symptoms to QoL. However, symptoms could also have an interactive relationship, which might not be fully taken...
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Full-text available
Clinical network neuroscience, the study of brain network topology in neurological and psychiatric diseases, has become a mainstay field within clinical neuroscience. Being a multidisciplinary group of clinical network neuroscience experts based in The Netherlands, we often discuss the current state of the art and possible avenues for future invest...
Article
Background Previous studies have demonstrated extensive functional network disturbances in patients with multiple sclerosis (MS), showing a less efficient brain network. Recent studies indicate that the dynamic properties of the brain network show a strong correlation with cognitive function. Purpose To investigate network dynamics on functional MR...
Preprint
Full-text available
Structural network analysis of diffusion imaging is increasingly used to study neurological disease, its pathophysiology and symptoms. We therefore evaluate structural hub connectivity in glioma patients and its association with molecular subtype and clinical status. Using retrospective diffusion imaging, structural connectivity was investigated in...
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Full-text available
Introduction Cognitive deficits occur frequently in diffuse glioma patients, but are limitedly understood. An important marker for survival in these patients is isocitrate dehydrogenase (IDH) mutation (IDH‐mut). Patients with IDH‐mut glioma have a better prognosis but more often suffer from epilepsy than patients with IDH‐wildtype (IDH‐wt) glioma,...