Most organisms on Earth anticipate changes between day and night using an internal biological clock. This clock is localized in a small brain area: the suprachiasmatic nucleus (SCN). The SCN... Show moreMost organisms on Earth anticipate changes between day and night using an internal biological clock. This clock is localized in a small brain area: the suprachiasmatic nucleus (SCN). The SCN generates rhythms of approximately 24 hours (circadian) which are synchronized to light. We investigated how light signals reach the SCN and how the effects of light and behavioural activity on the SCN differ between diurnal and nocturnal species. In this thesis, we show that cone photoreceptors, involved in colour vision, contribute to the light responses of the circadian clock. As observed in fMRI experiments, the human SCN was also sensitive to different colours of light. Furthermore, the SCN of diurnal species was partly inhibited by light, whereas the SCN of nocturnal species was mostly excited. Finally, we observed that behavioural activity activates the SCN of diurnal species, whereas in nocturnal species the SCN is inhibited. We concluded that the input pathways to the circadian clock differ between diurnal and nocturnal species and hypothesize that these differences could contribute to the temporal activity profiles. Together, our findings facilitate the translation of circadian research from nocturnal laboratory animals to diurnal humans, for the benefit of biological rhythms and health in general. Show less
The aim of this thesis was to identify functional biomarkers for migraine attack prediction based on neurophysiological readout parameters. The main focus of this work was on the development of... Show moreThe aim of this thesis was to identify functional biomarkers for migraine attack prediction based on neurophysiological readout parameters. The main focus of this work was on the development of methodologies to measure brain excitability over the migraine cycle, with special emphasis on identifying changes in excitability of the visual system and the occipital cortex. Applying such measures over the course of a migraine cycle could help elucidate factors that initiate the migraine attack, and might lead to better (or better timing of) preventive measures. The research described in this thesis is divided into two parts. The first part reports on the development and application of several methodologies to measure excitability of the visual system including the cortex in migraine patients and a migraine mouse model. The second part consists of two studies employing transcranial magnetic stimulation (TMS) in combination with concurrent electroencephalography (EEG) recordings to provide direct measures of cortical excitability in migraine and epilepsy. Show less
Children spend most of their days interacting with their social environment. Emotions form a large part of these interactions and vice versa social emotions become meaningful when interacting... Show moreChildren spend most of their days interacting with their social environment. Emotions form a large part of these interactions and vice versa social emotions become meaningful when interacting with others. Understanding the emotion processes that underlie successful social functioning is important, especially in children that experience difficulties in social-emotional functioning such as children with Autism Spectrum Disorders (ASD). These studies used a unique approach towards understanding the complex mechanisms that are involved in emotion processing, incorporating how emotions are perceived, experienced, regulated, and expressed. Sensitive and direct measures of emotion processing such as eyetracking and physiology revealed for the first time on a neurobiological level that children with ASD have difficulties emotionally resonating with others, use less efficient strategies to regulate their emotions, and provided evidence for a possible discordance between the expression and experience of emotions. The preschool years also presented with a possible window of opportunity; children with ASD do feel emotions when it comes to their own experiences and the development of social attention towards others might be prone to improvements during the preschool years. These findings are important to parents and professional and enhance the understanding of emotion processing during these very early years of life. Show less
Complex regional pain syndrome (CRPS) may occur after trauma, usually to one limb, and is characterised by pain and disturbed blood flow, temperature regulation and motor control. Knowledge on CRPS... Show moreComplex regional pain syndrome (CRPS) may occur after trauma, usually to one limb, and is characterised by pain and disturbed blood flow, temperature regulation and motor control. Knowledge on CRPS and its movement disorders is scarce. Dysfunction in small nerve fiber processing was found in CRPS patients with dystonia. Furthermore, a dominant pattern of fixed dystonia was observed in two thirds of arms and legs: finger flexion, wrist flexion, elbow flexion and/or shoulder adduction; and ankle plantar flexion/inversion, toe flexion, knee flexion and/or hip internal rotation. A modelling study demonstrated that aberrant force feedback from Golgi tendon organs may be a factor. Cerebrospinal fluid findings did not support a role of inflammatory mediators in chronic CRPS-related dystonia. Characteristics of CRPS-related myoclonus were diverse. One intrathecal administration of methylprednisolone was not efficacious in chronic CRPS. Also, continuous intrathecal glycine showed no efficacy in CRPS-related dystonia. However, intrathecal baclofen reduced severity of CRPS-related dystonia, improved quality of life and remained efficacious over a period of one year. The findings lend support to the role of GABA (gamma aminobutyric acid)-ergic mechanisms in this cause of dystonia. The findings stimulate new directions of research on this topic. Show less
Mutations in the CACNA1A gene, encoding neuronal Cav2.1 calcium channels, cause a wide spectrum of human neurological diseases, including familial hemiplegic migraine type 1 (FHM1). The role of... Show moreMutations in the CACNA1A gene, encoding neuronal Cav2.1 calcium channels, cause a wide spectrum of human neurological diseases, including familial hemiplegic migraine type 1 (FHM1). The role of Cav2.1 channels is to mediate neurotransmitter release. Using electrophysiological techniques, this thesis investigates the effects of several CACNA1A mutations on neurotransmitter release at the mouse neuromuscular junction (NMJ). It is concluded that the FHM1 mutations R192Q and S218L increase neurotransmitter release and do not result in compensatory contributions of other types of calcium channels. Furthermore, it is shown that spontaneous neurotransmitter at the mouse NMJ is partly Cav2.1 channel-dependent, whereas evoked release relies entirely on Cav2.1 channels. Studies on the Cav2.1 mouse mutant Rolling Nagoya show that spontaneous and evoked neurotransmitter release are controlled independently. Studies on mouse mutants that lack auxiliary Cav2.1 channel subunits revealed that these subunits are redundant and/or absent at the mouse NMJ. The studies presented in this thesis provide novel insights into the synaptic dysfunction caused by Cav2.1 channel mutations. Synaptic effects on central synapses are likely to share many features with those observed at the mouse NMJ and thought to underlie (some of) the neurological symptoms of human and mouse disorders associated with Cav2.1 channel dysfunction Show less
