Overview

Methods: computational modeling and empirical research

Models have many functions in science, but two of the most important ones are that they synthesize what is known, and that they allow researchers to derive new predictions. Both functions have been central themes in my research to date. My work is built around computational models of brain and behaviour. In these models, I integrate anatomical and physiological knowledge with detailed behavioural analyses. I apply the models to get at the central question of how the brain produces behaviour, and also to get insights into abnormal states of the brain: the damaged brain, the brain in psychiatric disorders, and under psychoactive medication.

Computational modelling is not an independent branch of science – its goal is not solely to build beautiful theories but to derive new hypotheses for empirical scientists to test. In my own work, this means that I strive to create models that produce precise predictions at the behavioural, pharmacological, neuropsychological, and neurophysiological level. This makes my models a platform of multidisciplinary integration. To test model predictions, I have set up my own lines of empirical research, and have developed collaborations centred on behavioural research, patient research, neurophysiology, neuroimaging, and pharmacological research in humans and animals.

Memory loss after brain damage

In my PhD research with Jaap Murre (UvA), I focused on the loss of remote memories after brain damage. Theoretically, such loss is interesting because it suggests where remote memories reside in the brain. Moreover, the work led me to start an ongoing collaborative investigation with Walter van den Broek (Erasmus University Rotterdam) into electroconvulsive therapy (ECT). ECT is often successful in combating severe depressions, but is highly controversial because it is thought to erase large parts of a patient’s remote memory. With mathematical models of forgetting and memory tests developed in my PhD work, we attempt to quantify such loss, whereas previous studies were only able to conclude that the loss of memories was statistically significant.

Memory

Since my PhD, I have focused on two central functions of the mind: memory and attention. One main line of work on memory, funded by a VENI grant from the Dutch funding agency NWO, involves modelling neuromodulation in the hippocampus. This is an area in the middle of the brain that is known to be crucial for our everyday memory. The hippocampus is heavily innervated by neuromodulatory systems, and these systems are in turn the main targets of psychoactive drugs. My goal is to generate, from the physiological effects of these drugs, predictions on how they will affect memory. One motivation for this work is that it will one day allow the development of drugs with fewer cognitive side effects. A first set of predictions, involving antidepressants working on serotonergic receptors, were confirmed in a collaborative study with Wim Riedel (University of Maastricht). This work led to a new hypothesis on why memory is degraded in patients suffering from depression. 

Another line, in close collaboration with Lucia Talamini (UvA), involves memory deficits in schizophrenia. Our idea is that these deficits are primarily the result of abnormalities in the parahippocampal gyrus (the area next to the hippocampus). This brain area, next to the hippocampus, integrates input from all areas of the brain and sends it on to the hippocampus. In patients with schizophrenia, this integration does not work as well as in other people. 

Visual attention

My work on visual attention grew out of a postdocship with Jan Theeuwes (VU Univ Amsterdam). I have done behavioural and electrophysiological studies on priming in visual attention. This theme is gaining prominence because it suggests that cognitive control not a wholly free agent (i.e., a homunculus who decides what you do), but is partly the slave of recent experience. In addition, I co-supervised the PhD project of Stefan vd Stigchel centred on the control of eye movements. We built a low-level model of the eye movement system in the primate brain, and systematically explored saccade trajectories as a way to uncover the processing that occurs during a saccade. With Chris Olivers (VU) I created the model Boost and Bounce model of access to working memory. This model undercuts the received view of the attentional blink, a much-investigated effect in which consciousness seems to ‘blink’ for half a second after detection of a target. 

Bringing animal and human psychology together

A third main line of research combines the two above. It grew out of the realisation that since most neuroscientific data come from experiments with nonhuman animals, it is essential to understand how paradigms used in neuroscience compare to those used in psychology; making such links explicit is a task often ignored by both fields. With Mark Gluck and Catherine Myers (Rutgers Univ., Newark), I worked on a model in which the rodent classical conditioning literature is reinterpreted in the light of our knowledge on primate and human episodic memory. In work with the Honda Research institute (Offenbach, Germany), this model was extended to rodent instrumental conditioning paradigms. An extension of that model to orienting towards novel stimuli inspired a whole new project on novelty, since it led me to realise that our understanding of how the brain deals with novel stimuli is far from complete. This has strong repercussions for our understanding of memory and learning and of the orienting of attention. The gaps in our knowledge also have the potential to undermine the widespread use of the orienting response as an index of cognitive abilities of human infants and of rodents.