research theme Clinical Neuropsychology

Clinical Neuropsychology

The research projects within the theme ‘Clinical Neuropsychology’ are focused on the cause, development, prediction and treatment of cognitive dysfunctions in a variety of patient populations.

Within this research theme, we use cognitive tests, neuroimaging and data science methods to improve our insights into the behavioral predictors and neural bases of diverse cognitive dysfunctions. The ultimate goal is to prevent cognitive dysfunctions in patients, to enhance the diagnostics and treatment of existing cognitive dysfunctions and to minimize the impact of the cognitive dysfunction on both patient and society.

AMICUS: AI in Medical Imaging for novel Cancer User Support

Medical imaging is the cornerstone of screening, detection, diagnosis, staging, treatment and follow-up in almost every cancer patient. This is without a doubt Big Data. However, the processing and interpretation of images is still mainly a human task. With AMICUS we will develop technology that supports radiologists & oncologists and other stakeholders including the patient in extracting relevant information from images. The technology used for extracting information from images in AMICUS is deep learning, a form of artificial intelligence which has proven to be a breakthrough in the field, but which requires large volumes of imaging data to be successful. However, getting access to imaging data is a problem as it is dispersed across hospitals and is very privacy sensitive. In AMICUS we will develop technology that allows deep learning from these distributed imaging datasets without the need for these data to leave the hospital. As a partner, Tilburg University is responsible for creating and demonstrating the value of the AMICUS technology by implementing compelling solutions for patients to improve cancer outcomes.

Project duration: 4 years: June 2020 – May 2023

Funded by: KWF Kankerbestrijding and NWO Domain AES, as part of their joint strategic research programme: Technology for Oncology II

Collaborating partners: Maastricht University, University of Twente, University of Groningen

Involved team members

Development of clinical tools to map higher cognitive functions in the peritumoral brain

Brain tumor treatment, such as surgery, radiotherapy and chemotherapy, can alleviate neurological and cognitive deficits by decreasing tumor burden, but can also induce or increase deficits by damaging brain structures. Treatment therefore strives for an optimal balance between maximizing of tumor reduction to increase survival and minimizing of long-term functional deficits to preserve cognitive skills, socio-professional functioning and quality of life. Aim of this project is to reduce the negative effects of brain tumor surgery on cognition (e.g. working memory or cognitive control). We will develop and build tools for use both prior to surgery, as well as during surgery.

For the preoperative tool, we will build personalized brain network models (using MRI-based connectomics and functional MRI) to simulate the cognitive effects of tumor removal. This information, visualized through a risk map, can be used to guide the neurosurgeon in setting safe boundaries during surgery. For the intraoperative tool, we will develop new test protocols to identify and monitor cognitive functions during awake surgery. Protocols will be standardized across hospitals, and studies will then be initiated to address to what extent cognitive testing during awake surgery has clinical benefit.

Project duration: 4 years: October 2020 – September 2023

Funded by: ZonMW (as part of the Topspecialistische Zorg en Onderzoek (TZO) project “A personalized care path for brain tumor patients”)

Collaborating partners: Elisabeth-TweeSteden Hospital Tilburg, Lariboisiere Hospital, Paris, University Medical Center Utrecht, Technical University Eindhoven


Brains in sync: Identifying the effects of mother’s anxiety during pregnancy on mother-infant neural synchrony

The mother-infant relationship is foundational for children’s socio-emotional and cognitive development. However, not all mothers are able to provide warm and functional interactions. Approximately, 18-25% of mothers display anxiety symptoms during pregnancy, which could lead to the development of negative mother and infant characteristics, such as maternal hypervigilance and difficult infant temperament. These characteristics are likely to interact, leading to a vicious cycle that is hard to break. This way, disturbances in the mother-infant relationship can result in poorer child outcomes later in life. Early prevention is needed, yet the biological underpinnings and pathways to disturbance are poorly understood, obstructing identification of targets for prevention.

By combining new advances from social neuroscience with developmental psychology, the overarching goal of this proposal is to identify the behavioral predictors and neural bases of mother-infant interaction in the context of maternal prenatal anxiety. To do so, we compare the interaction patterns and brain functioning of anxious and well-functioning mother-infant pairs by employing innovative techniques such as dual-EEG measurement and experience sampling method (ESM). This research line is likely to transform the way we understand how mothers and infants are connected on a biological level and may lead to the identification of a novel brain-to-brain synchrony biomarker for identifying at-risk mother-infant dyads. Importantly, results of this project will not only elucidate how maternal prenatal anxiety can leave long-lasting biological traces on mothers, infants, and dyads, but also provide unique knowledge on how to get mother and infant back on the same wavelength, both figuratively and literally, which will help children get the best start possible.

Project duration: 3 years

Funded by: NWO – Veni grant (PI: M.I. van den Heuvel)



  • Gholampour, F., Riem, M.M.E., & van den Heuvel, M.I. (in press). Maternal brain in the process of maternal-infant bonding: Review of the Literature. Social Neuroscience.
Connected brains in mother-infant dyads - The role of neural synchrony in intergenerational transmission of trauma: A cross-cultural study

The overall aim of this project is to examine the impact of maternal trauma on mother-infant neural synchrony. This will extend current research on the impact of trauma on individual brains to mother-infant brains. We will study this cross-culturally, in Dutch and Israeli samples, to inform both countries on the impact of trauma on mother-child dyads and to increase our understanding of cultural differences in interbrain synchrony. Importantly, the project will also examine the extent to which various aspects of caregiving (i.e., synchronous, empathic and contained parenting) can moderate intergenerational transmission of trauma.

Project duration: 2 years

Funded by: KNAW – Sara van Dam Project grant (PI: M.I. van den Heuvel)


Personalized Cognitive Diagnostics for Early Detection of Dementia

This project will improve early diagnosis of dementia (including Mild Cognitive Impairment) by using statistical learning methods to develop personalized ‘norms’ for online cognitive tests. By comparing the findings to tests currently used to diagnose dementia in clinical practice the sensitivity of cognitive tests for early detection will be investigated.

Project duration: 4 years: October 2020-September 2023

Funded by: Herbert Simon Research Institute (Cross-Cutting Theme PhD position); We Care (collaboration between Tilburg University and ETZ, Tilburg); Universiteitfonds


The MoCIS study (Motor and Cognitive Impairment in Stroke)

Research into the relationship between subjective experience and objective disorders in motor and cognitive functioning after a stroke. This is a 2 year, prospective follow-up study.



Innovate Dementia 2.0: a user-driven living lab for assistive technology to support people living at home with dementia.

The overall aim of Innovate Dementia (ID) 2.0 is to facilitate person-centered innovations developed for people with dementia (PWD) and their informal caregivers at all stages as the dementia progresses. This should lead to newly designed concepts which are more able to answer the unmet needs of PWD and their caregivers.

Funded by: Stichting TopKlas, Rino Groep



Longitudinal early markers of Alzheimer’s disease in individuals with Down syndrome (Horizon-21 cohort)

This is an observational, multicenter, longitudinal study across several existing cohorts to validate a selection of tests in adults with DS aged 25 years and older which are believed to be sensitive measures of early cognitive decline and provide early markers for AD neuropathology.


  • Multicenter study involving collaboration with researchers in the Horizon-21 consortium (including: The Radboud University Medical Centre, Nijmegen; King’s College London; The Jérôme Lejeune Institute, Paris; The University of Barcelona and Sant Pau Hospital, Spain; University of Cambridge, England; Klinikum der Universität München; Erasmus University Medical Center, Rotterdam; University College London; Trinity College Dublin; and colleagues in Sweden and Norway)

Publications (many, for example)

  • Nieuwenhuis-Mark, R. E. (2009). Diagnosing Alzheimer's dementia in Down syndrome: problems and possible solutions. Research in Developmental Disabilities, 30(5), 827-838. 
  • Strydom, A., Coppus, A., Blesa, R., Danek, A., Fortea, J., Hardy, J., . . . Ritchie, C. (2018). Alzheimer's disease in Down syndrome: An overlooked population for prevention trials. Alzheimer's & Dementia: Translational Research & Clinical Interventions, 4, 703-713. 
Monitoring and Predicting outcomes in patients who visit the neurosurgical clinic

A substantial number of patients who visit the neurosurgical clinic already have cognitive deficits, psychological complaints and fatigue prior to surgical treatment. Additional functional problems in these areas may occur after surgery and even persist for a prolonged period. These problems may also have a negative impact on personal and social life, daily functioning and return to work. At the same time, factors such as cognitive performance or depressive complaints have been prognostic of tumor recurrence or survival after surgery in patients with brain tumors.

This study aims to evaluate functional outcomes, and predictors thereof, in patients with brain tumors (e.g., meningiomas, adenomas, or gliomas), and cerebrovascular disorders (e.g., vascular compression syndromes such as trigeminal neuralgia) who visit the neurosurgical department of the Elisabeth-TweeSteden hospital Tilburg and who undergo standard care neuropsychological assessments and/or structural and functional MR imaging before and/or after surgery. With this study, we aim to evaluate and improve clinical neurosurgical care and contribute to the knowledge on the predictors of outcomes in individual neurosurgical patients. This information is relevant for adequately informing patients and the clinical team during early on decision making in clinical treatment, in which we strive for an optimal balance between maximizing treatment effects, and minimizing long-term functional deficits.

Project duration: 2010-…

Funded by: CZ Fonds, Elisabeth-TweeSteden Hospital Tilburg, ZonMw

Collaborating partners: Elisabeth-TweeSteden Hospital Tilburg, Department of Neurosurgery



Better informed shared decision-making for patients with brain tumors using personal goal identification and artificial intelligence prediction

In brain tumor treatment, we strive for an optimal balance between maximizing tumor reduction to increase survival, and minimizing long-term functional deficits to preserve cognitive skills, socio-professional functioning and quality of life. There are large inter-individual differences in functional outcome of patients with brain tumors after treatment that we are currently not able to explain. In addition, treatment options may have varying effects of on patients’ personal life goals. Doctors are often not aware of patients’ personal goals and, consequently, refrain from discussing how these might be affected by any given treatment option.

This project therefore aims to improve pre-treatment shared decision-making and subsequent quality of life in patients with meningioma and glioma based on:

  1. Artificial Intelligence (AI) analyses in our large and unique database to develop individual predictions of the patients’ cognitive functioning after neurosurgery, creating visualizations thereof and utilizing these visualized predictions in shared decision-making.
  2. Identifying individual patients’ personal life goals with an eHealth app (Goings-On) and sharing these goals in a shared decision-making setting.

This project will make information that is vital for patient functioning and life goal attainment, yet currently largely absent, available in a for patient and clinical team usable eHealth dashboard. Making more accurate information available both from individualized predictions and on patient personal goals may better enable balancing and personalizing the gains and losses in terms of functional outcome.

Project duration: 4 years: October 2020 – September 2023

Funded by: WeCare & ZonMW (as part of the Topspecialistische Zorg en Onderzoek (TZO) project “A personalized care path for brain tumor patients”)

Collaborating partners: Elisabeth-TweeSteden Hospital Tilburg, Department of Neurosurgery; TiU, Department of Cognitive Science and Artificial Intelligence



CAR-studies A and B: Evaluation of cognitive outcomes after Stereotactic Radiosurgery and Whole Brain Radiation Therapy in patients with multiple brain metastases

Many patients with brain metastases (BM) experience cognitive impairments that may be caused by several factors, including the brain metastases itself, medication use, the primary cancer, or side effects. Stereotactic radiosurgery (SRS) is increasingly used to treat patients with multiple BM. Historically, the standard of care for patients with multiple (>3) BM was whole brain radiation therapy (WBRT). However, its use has decreased in recent years due to advances in radiation technology and growing concerns regarding the late adverse effects of WBRT on cognition (e.g., memory, attention and concentration difficulties).

In the Elisabeth-TweeSteden Hospital, Gamma Knife Radiosurgery (GKRS) has been successfully applied in patients with up to 10 BM and occasionally up to 20. GKRS is expected to cause fewer cognitive side effects than WBRT, but scientific evidence is lacking. This research line includes two projects:

In CAR-Study A, cognitive functions (e.g., memory and concentration) of patients with 1-10 brain metastases are assessed over a longer period of time after GKRS. Cognitive functions are measured using neuropsychological tests. Patients are assessed before treatment, and at 3, 6, 9, 12, 15 and 21 months after treatment.

​CAR-Study B is a prospective randomized multicenter study. The aim of this study is to compare cognitive decline after treatment with either GKRS or WBRT in patients with 11 to 20 BM at time of treatment initiation. Cognitive functions are measured using neuropsychological tests. Patients are assessed before treatment, and at 3, 6, 9, 12, and 15 months after treatment.

Ultimately, the purpose of this research is to inform doctors and individual patients with BM more precisely about the (long-term) cognitive effects of BM treatment and the benefits and consequences they can expect from treatment with either WBRT or SRS. This will enable patients and doctors to make a better-informed shared treatment decision grounded on scientific evidence.

Project duration: 2015-2023

Funded by: ZonMw Xperiment TopZorg & Elekta

Collaborating partners: Elisabeth-TweeSteden Hospital Tilburg, Department of Neurosurgery/Gamma Knife Center; TiU, Department of Methodology and Statistics



(eHealth) cognitive rehabilitation for patients with brain tumor patients

Many patients with primary brain tumors suffer from cognitive deficits, which negatively impact patients’ their ability to resume work and family life. Cognitive rehabilitation programs for these patients are scarce. We developed an eHealth cognitive rehabilitation program (‘ReMind’) for brain tumor patients, which was based on our effective face-to-face cognitive rehabilitation program. We evaluated our original program in a randomized controlled trial (RCT) in 140 patients with gliomas from 11 Dutch Hospitals. It successor, the ReMind app, was evaluated in a feasibility study and a pilot RCT in 3 Dutch hospitals. A care pathway for the use of ReMind in clinical practice was designed with input from patients, carers and clinicians. Next steps are to include ReMind in brain tumor treatment guidelines and healthcare contracts. While clinical implementation is ongoing in the Netherlands, further research on the English version of ReMind is being conducted in two studies at the University of California San Francisco, and a French version is to be developed together with Gustave Roussy Cancer Campus, Paris. This project will make an evidence-based digital cognitive rehabilitation program available as part of reimbursed regular care for brain tumor patients, and subsequently, for patients with other diseases, to help them overcome cognitive difficulties in everyday activities at home and at work.

Collaborating partners: University of California San Francisco, Brain Tumor Center, San Francisco, USA; stichting ‘t Hoofdgerecht; Gustave Roussy Cancer Campus, Department of Radiotherapy, Paris, France; Leids Universitair Medisch Centrum, National eHealth Living Lab

Funded by: lower grade glioma research collective (loglio) UCSF, ZonMw, Innovatiefonds Zorgverzekeraars, CbusineZ, stichting ‘t Hoofdgerecht, KWF Kankerbestrijding


  • Karin Gehring (ETZ/TiU)
  • Margriet Sitskoorn
  • Petra Hoogendoorn (LUMC)
  • Sophie van der Linden (ETZ/TiU)
  • Geert-Jan Rutten (ETZ)
  • Frédéric Dhermain (Gustave Roussy)
  • Jennie Taylor (UCSF)
  • Christina Weyer Jamora (UCSF)
  • Shawn Hervey Jumper (UCSF)
  • Javier Villanueva-Meyer (UCSF)
  • Steven Braunstein (UCSF);
  • racy Luks (UCSF)
  • Paige Bracci (UCSF)
  • Jennifer Clarke (UCSF)
  • Nancy Ann Oberheim-Bush (UCSF)
  • Nicholas Butowski (UCSF)
  • Susan Chang (UCSF)


Combined physical and cognitive training for the improvement of cognitive functioning in brain tumor patients

Patients with brain tumors often suffer from cognitive deficits. Physical exercise has been effective in delaying or ameliorating cognitive deficits in older adults and neurological patients. Little is known about the effects of exercise on functioning in patients with brain tumors. First, we explored in a pilot randomized controlled trial (RCT) the feasibility and potential effects of a home-based exercise intervention, designed to improve cognitive functioning in glioma patients, regarding cognitive test performance and patient-reported outcomes.

A next step is to develop a combination of physical training with (simultaneous) cognitive training with immersive gaming elements, which may be more attractive for patients to attend to, and at the same time have stronger cognitive effects. A prototype has been build, which will be further developed and evaluated in scientific research in the next years. This project potentially adds an immersive intervention as a novel tool for rehabilitation of cognitive impairment for use in (brain) cancer patients.

Funded by: Dutch Cancer Society, NWO SPRONG seed money Amsterdam University of Applied Sciences

Collaborating partners: Amsterdam University of Applied Sciences, Faculties of Health (lectorate Functional Recovery from Cancer and its Treatment) & Digital Media Creation and Creative Industry (Master Digital Design); The Netherlands Cancer Institute, Center for Quality of Life & Psychosocial Research and Epidemiology; HU University of Applied Sciences Utrecht, Research Group Innovation of Human Movement Care.



Discovering latent patterns of fatigue in patients with benign and malignant brain tumors - A first step towards personalized monitoring and treatment

Fatigue is one of the most common symptoms of brain tumors that affects patients’ lives across disease stages. A key difficulty in explaining and finding effective interventions for fatigue is the vast heterogeneity in its nature and severity between individual patients. This study investigates latent patterns in previously collected multidimensional data on fatigue of 300 patients with brain tumors before start of treatment, and their relationship with disease and patient characteristics. We aim to better understand the heterogeneity in the manifestation of fatigue in this population. The identification of fatigue profiles, in which the complex nature of the symptom and individual differences and are taken into account, is an essential step towards the personalization of care of fatigued patients.

Funded by: Herbert Simon Research Institute (TiU) seed funding grant

Collaborating partners: Elisabeth-TweeSteden Hospital Tilburg, Department of Neurosurgery/Gamma Knife Center; TiU Department of Cognitive Neuropsychology & Department of Methodology and Statistics