Dopamine, decision-making, and aging : neural and behavioural correlates

On any given day, we make tons of decisions. These can be as simple as deciding how to dress or what to eat, or more complex, such as whether to spend or invest money. Good decision-making involves being able to select the best alternative from a range of options, and adjust one’s preferences based on what is happening in the environment. As humans get older, their ability to do this changes. Age-related changes in decision-making ability result from changes in brain structure and function, such as the deterioration of the brain’s dopaminergic system in old age. In this thesis, we used a sample of 30 older and 30 younger participants to investigate age-related differences in neural and behavioural correlates of value-based decision-making, which involves making decisions that can result in rewards and punishments. Such decisions are known to rely on dopaminergic functioning. In the brain, we have looked at neural activity reflecting value and reward prediction errors (RPEs), the availability of dopamine D1 receptors, and integrity of white matter microstructure. For the behavioural data, we have used computational modelling to disentangle motivational biases and other parameters reflecting parts of the learning process that underlies successful decision-making. In study 1, we investigated whether performance on a value-based decision-making task differed between the two age groups. We also looked at whether performance differences could be explained by differential neural processing of RPEs and expected value in the striatum and prefrontal cortex (PFC). We used a novel computational model to estimate expected value, decision uncertainty and confidence. We found that older adults earned fewer rewards on the task. The number of rewards earned could be predicted by the strength of the neural signal reflecting expected value in the ventromedial PFC (vmPFC), which was attenuated in older adults. Beyond age, the strength of this neural signal could be predicted by dopamine D1 receptor (D1-R) availability in the nucleus accumbens (NAcc). In study 2, we showed that integrity of white matter microstructure in the pathway between the NAcc and vmPFC also predicted the neural value signal in the vmPFC, independently of age and D1-R availability in the NAcc. In study 3 and 4, we focused on dissociating the effects of action and valence on neural and behavioural correlates of decision-making. In study 3, we used com-putational modelling to characterize faster learning to act in response to rewards, and abstaining from acting in response to punishments, as being the result of biased instrumental learning. Study 3 also showed that variability in dopamine D1-R availability could be divided into cortical, dorsal striatal and ventral striatal components. Regardless of age, dopamine D1-R availability in the dorsal striatal component was related to biased learning from rewarded actions. In study 4 we investigated anticipatory value signals after learning had reached an asymptote. We observed no differences between age groups in anticipatory neural responses to action and valence, and no relationship between anticipatory neural signals and dopamine D1-R availability. Older adults did show an attenuated punishment prediction error signal in the insula, compared with younger adults. The strength of differentiation between reward- and punishment prediction error signals in the insula was related to dopamine D1-R availability in the cortex. These studies have demonstrated that the existing theoretical framework sur-rounding the role of dopamine system in decision-making and aging fits with dopamine D1-R availability data and behavioural data in older and younger adults, and partly explain why older adults show behavioural differences in value-based decision-making tasks. Collectively, the studies in this thesis provide important multimodal evidence that increases our understanding of the neural correlates that underlie value-based decision-making and how they are affected in healthy aging

Variability in Action Selection Relates to Striatal Dopamine 2/3 Receptor Availability in Humans: A PET Neuroimaging Study Using Reinforcement Learning and Active Inference Models

Choosing actions that result in advantageous outcomes is a fundamental function of nervous systems. All computational decision-making models contain a mechanism that controls the variability of (or confidence in) action selection, but its neural implementation is unclear-especially in humans. We investigated this mechanism using two influential decision-making frameworks: active inference (AI) and reinforcement learning (RL). In AI, the precision (inverse variance) of beliefs about policies controls action selection variability-similar to decision 'noise' parameters in RL-and is thought to be encoded by striatal dopamine signaling. We tested this hypothesis by administering a 'go/no-go' task to 75 healthy participants, and measuring striatal dopamine 2/3 receptor (D2/3R) availability in a subset (n = 25) using [11C]-(+)-PHNO positron emission tomography. In behavioral model comparison, RL performed best across the whole group but AI performed best in participants performing above chance levels. Limbic striatal D2/3R availability had linear relationships with AI policy precision (P = 0.029) as well as with RL irreducible decision 'noise' (P = 0.020), and this relationship with D2/3R availability was confirmed with a 'decision stochasticity' factor that aggregated across both models (P = 0.0006). These findings are consistent with occupancy of inhibitory striatal D2/3Rs decreasing the variability of action selection in humans

Investigating the use of comprehensive motion monitoring for intrafraction 3D drift assessment of hypofractionated prostate cancer patients on a 1.5T magnetic resonance imaging radiotherapy system

This work investigates the use of a multi-2D cine magnetic resonance imaging-based comprehensive motion monitoring (CMM) system for the assessment of prostate intrafraction 3D drifts. The data of six healthy volunteers were analyzed and the values of a clinically-relevant registration quality factor metric exported by CMM were presented. Additionally, the CMM-derived prostate motion was compared to a 3D-based reference and the 2D-3D tracking agreement was reported. Due to the low quality of SI motion tracking (often >2 mm tracking mismatch between anatomical planes) we conclude that further improvements are desirable prior to clinical introduction of CMM for prostate drift corrections

Geometrical imaging accuracy, image quality and plan quality for prostate cancer treatments on a 1.5 T MRLinac in patients with a unilateral hip implant

Purpose. To assess the feasibility of prostate cancer radiotherapy for patients with a hip implant on an 1.5 T MRI-Linac (MRL) in terms of geometrical image accuracy, image quality, and plan quality. Methods. Pretreatment MRI images on a 1.5 T MRL and 3 T MRI consisting of a T2-weighted 3D delineation scan and main magnetic field homogeneity (B 0) scan were performed in six patients with a unilateral hip implant. System specific geometrical errors due to gradient nonlinearity were determined for the MRL. Within the prostate and skin contour, B 0 inhomogeneity, gradient nonlinearity error and the total geometrical error (vector summation of the prior two) was determined. Image quality was determined by visually scoring the extent of implant-born image artifacts. A treatment planning study was performed on five patients to quantify the impact of the implant on plan quality, in which conventional MRL IMRT plans were created, as well as plans which avoid radiation through the left or right femur. Results. The total maximum geometrical error in the prostate was <1 mm and the skin contour <1.7 mm; in all cases the machine-specific gradient error was most dominant. The B 0 error for the MRlinac MRI could partly be predicted based on the pre-treatment 3 T scan. Image quality for all patients was sufficient at 1.5 T MRL. Plan comparison showed that, even with avoidance of the hips, in all cases sufficient target coverage could be obtained with similar D1cc and D5cc to rectum and bladder, while V28Gy was slightly poorer in only the rectum for femur avoidance. Conclusion. We showed that geometrical accuracy, image quality and plan quality for six prostate patients with a hip implant or hip fixation treated on a 1.5 T MRL did not show relevant deterioration for the used image settings, which allowed safe treatment

Salience-driven overestimation of total somatosensory stimulation

Psychological characterisation of sensory systems often focusses on minimal units of perception, such as thresholds, acuity, selectivity and precision. Research on how these units are aggregated to create integrated, synthetic experiences is rarer. We investigated mechanisms of somatosensory integration by asking volunteers to judge the total intensity of stimuli delivered to two fingers simultaneously. Across four experiments, covering physiological pathways for tactile, cold and warm stimuli, we found that judgements of total intensity were particularly poor when the two simultaneous stimuli had different intensities. Total intensity of discrepant stimuli was systematically overestimated. This bias was absent when the two stimulated digits were on different hands. Taken together, our results showed that the weaker stimulus of a discrepant pair was not extinguished, but contributed less to the perception of the total than the stronger stimulus. Thus, perception of somatosensory totals is biased towards the most salient element. ‘Peak’ biases in human judgements are well-known, particularly in affective experience. We show that a similar mechanism also influences sensory experience

Data Carpentry: Social Sciences

Reproduceerbaar analyseren voor praktijk-gerichte onderzoekers a.d.h.v. The Carpentrie

Superconductivity in CeCu₂Si2 (invited)

The specific heat, dc magnetization, and resistivity have been measured on a number of samples of CeCu2Si2, which was previously found to assume a novel superconducting state below 0.5 K [F. Steglich e t a l., Phys. Rev. Lett. 43, 1892 (1979)]. By comparing the transition temperatures of samples which have undergone different heat treatments, we demonstrate that small fractions of spurious phases hinder the onset of superconductivity but are gradually removed with annealing. With a very pure sample obtained in this way, we have fully confirmed all the characteristics of the superconductingphase transition reported before on less pure samples. However, even after this heat treatment, the samples show clear signs of striking inhomogeneities, manifested by a static Meissner effect of bulk samples representing typically only a few percent of the volume. An increase of this Meissner signal up to 60 vol% is observed after powdering the samples. In addition to measurements in the superconducting state, the intrinsic value of the low‐temperature susceptibility in the normal state was determined by measurements on a pure sample and is discussed in connection with the large electronic specific‐heat coefficient γ