Our research uses neuroimaging, neurocognitive, and psychopharmacological methods to better understand ADHD and related child psychiatric disorders as well as normal brain development from childhood to adulthood. Furthermore, we use neurotherapeutics such as fMRI-Neurofeedback and brain stimulation to develop novel brain-based treatment for these disorders.
Brain abnormalities in ADHD and related disorders
The main goal of our research is to understand how brain structure and function in ADHD and related childhood disorders differs from normal brain development, and how they differ between each other. We think that a better understanding of the disorder-relevant and disorder-specific underlying brain deficits will ultimately lead to more targeted treatment development, be it pharmacological or non-pharmacological.
Most of our neuroimaging research is in ADHD, where we assess abnormal brain structure and function in children and adults with ADHD using mostly structural and functional MRI but also EEG and PET methods. Hereby we also use multivariate pattern recognition analyses to test whether we can predict individual diagnostic status of ADHD based on their brain imaging patterns.
Other childhood disorders
We use structural and functional MRI to investigate the underlying brain abnormalities in paediatric obsessive-compulsive disorder, autism, conduct disorder, post-traumatic stress disorder, childhood abuse and others related disorders.
Specificity of brain deficits
A key interest of our research is to understand what is specific in the underlying neurobiological abnormalities in different childhood disorders. For this purpose, we compare different child psychiatric disorders in structural and functional MRI to understand disorder-specific neurobiological abnormalities.
Understanding the abnormalities and the specificity of brain abnormalities in the different disorders is important to develop tailored treatments that are targeted to the different disorders.
Normal brain function development
We consider it fundamental to understand normal brain development in order to understand the brain abnormalities in developmental disorders and how they relate to normal brain development. Therefore, part of our research is dedicated to understanding the underlying brain function maturation of late developing higher cognitive functions that are typically impaired in psychiatric disorders such as inhibitory self-control, attention and timing. We investigate the neuroimaging correlates of these cognitive functions between childhood and adulthood.
Our psychopharmacological fMRI research tries to understand the effects of neurotransmitter manipulations (i.e. essential fatty acids, dietary manipulations such as Tryptophan depletion) and the mechanisms of action of existing pharmacological treatment on the brain function of ADHD and related disorders. The aim of pharmacological imaging research is to help us to better understand the biochemical imbalance that is underlying childhood disorders and the mechanisms of action of existing drugs such as stimulant and non-stimulant medications on the brain function of patients. A better understanding of the underlying neurotransmitter abnormalities and mechanisms of action of medications may ultimately lead to more targeted pharmacological treatment development. We also use positron emission tomography (PET) to understand the mechanisms of action of psychostimulant treatment in ADHD adults.
We are interested in both positive and negative effects on brain plasticity. For the domain of ‘negative’ neuroplasticity, we investigate environmental effects like the effects of childhood physical abuse on brain structure and function development. For positive brain plasticity we have several collaborations where we investigate the effects of meditation on the structure, function and connectivity of the brain and the effects of music on the structural and function brain plasticity and cognition of normal schoolchildren.
Our translational neuroscience studies use modern safe, non-invasive and nonpharmacological technologies such as fMRI-Neurofeedback and brain stimulation to modify the activation of brain regions which we found to be under-activated in ADHD in the last two decades of neuroimaging studies.
- a)fMRI-Neurofeedback: In fMRI-Neurofeedback, the child with ADHD learns to self-control his own brain activation via a computer game that is connected to his brain activity. We provide feedback on the brain activation in an fMRI scanner and reward the child when it upregulates specific brain areas that we know are abnormal in ADHD. With this technique we aim to improve the brain activation of problematic brain areas in ADHD patients. Theultimate goal is that the upregulation of brain areas that are underlying the disorder will lead to an improvement of the behavioural symptoms and cognitive deficits.
- b) Brain stimulation using transcranial direct current stimulation (tDCS). The new treatment applies non-invasive stimulation of aparticular brainregion of attention and self-control in the frontal cortex that we found to be under-activated in ADHD. The children will play an adaptive computer game that trains attention and self-control skills while at the same time stimulating the relevant brain region with tDCS. Pilot studies have shown that children with ADHD can improve in their symptoms and in their cognitive skills if they receive brain stimulation over frontal regions. Brain stimulation combined with cognitive training, however, can boost the cognitive training effects and the brain stimulation effects. We therefore expect that brain stimulation over frontal regions together with cognitive training of skills that are mediated by the frontal cortex may result in better skills of attention and self-control and improve ADHD symptoms. TDCS has been shown to be perfectly safe and has minimal side effects like temporary itching over the scalp in a small number of people.
- c) Brain stimulation using external Trigeminal Nerve Stimulation (TNS). The NIHR funded multicenter trial will test a new brain therapy for ADHD. TNS has been approved by the FDA and in Europe as the first medical device based treatment for ADHD based on findings of improvement of ADHD symptoms in a US study in 62 subjects. TNS will be applied every night for 8 hours for 4 weeks to children and adolescents with ADHD and compared to sham TNS. TNS stimulates the trigeminal nerve which is connected to the brain stem and can lead to activation of frontal and other parts of the brain. We will test whether TNS can improve ADHD symptoms, other clinical behaviours that are typical for ADHD, performance on cognitive tests and we will test how it works on the brain with fMRI. If we find that TNS can improve ADHD symptoms in this large multicenter study, then this provide the path for a novel non-pharmacological treatment for ADHD.
We have designed a neuropsychological task battery, the MARS (Maudsley Attention and Response Suppression task battery), that assesses neurocognitive functions that mature late in childhood and adolescence and are important for mature adult behaviour such as inhibitory control, attention, timing, motivation control and reward-related decision making. These functions are typically impaired in disorders of impulsiveness such as ADHD but are also relevant to other related externalising and internalising childhood and adult disorders. A main aim is to understand which neurocognitive functions are specifically impaired in ADHD and other childhood or adult disorders.