The impact of yohimbine-induced arousal on facets of behavioural impulsivity

Rationale State-dependent changes in physiological arousal may influence impulsive behaviours. Objectives To examine the relationship between arousal and impulsivity, we assessed the effects of yohimbine (an α2-adrenergic receptor antagonist, which increases physiological arousal via noradrenaline release) on performance on established laboratory-based impulsivity measures in healthy volunteers. Methods Forty-three participants received a single dose of either yohimbine hydrochloride or placebo before completing a battery of impulsivity measures. Blood pressure and heart rate were monitored throughout the study. Results Participants in the yohimbine group showed higher blood pressure and better response inhibition in the Stop Signal Task, relative to the placebo group. Additionally, individual changes in blood pressure were associated with performance on Delay Discounting and Information Sampling tasks: raised blood pressure following drug ingestion was associated with more far-sighted decisions in the Delay Discounting Task (lower temporal impulsivity) yet reduced information gathering in the Information Sampling Task (increased reflection impulsivity). Conclusions These results support the notion that impulsive behaviour is dependent upon state physiological arousal; however, distinct facets of impulsivity are differentially affected by physiological changes

The role of emotions and physiological arousal in modulating impulsive behaviour

Impulsivity refers to both a stable personality trait and a set of behaviours which undergo momentary changes depending on the current circumstances. Impulsivity plays a vital role in daily life as well as clinical practice as it is associated with drug misuse and certain neuropsychiatric conditions. Because of its great health and well-being importance, it is crucial to understand factors which modulate impulsive behaviours. The current studies investigated the role of emotions and physiological arousal as modulators of impulsive actions and decisions in healthy individuals. A set of experiments was conducted using a variety of methods including behavioural testing, physiological recordings, psychopharmacology and neuroimaging. Studies 1 and 2 clarified the influence of emotional states on distinct dimensions of impulsive behaviours. Study 3 investigated the neural correlates behind the impact of emotions on impulsive actions. Finally, studies 4 and 5 focused on the relationship between physiological arousal and behavioural and trait impulsivity. Our findings demonstrate that a degree to which one’s internal (emotional or physiological) state changes, is associated with behavioural impulsivity level. Importantly, distinct dimensions of impulsivity are differentially sensitive to those changes. Namely, increased state level of physiological arousal is associated with decreased motor ‘stopping’ impulsivity, enhanced subjective ratings and objective measurements of arousal are also related to decreased temporal impulsivity. Increased ratings of stress and increased physiological arousal, however, are associated with higher reflection impulsivity. At the neural level, successful response inhibition requires enhanced activation of prefrontal and parietal areas in impulsive individuals, particularly in negative emotional context, suggesting that behavioural control might be more effortful for highly impulsive individuals. In conclusion, changes in internal bodily state are related to behavioural impulsivity level. Staying more attuned to those changes and finding adaptive ways to adjust behaviour according to bodily needs might be vital to reducing impulsivity levels

Electrophysiological Signatures of Fear Conditioning: From Methodological Considerations to Catecholaminergic Mechanisms and Translational Perspectives

Fear conditioning describes a learning mechanism during which a specific stimulus gets associated with an aversive event (i.e., an unconditioned stimulus; US). Thereby, this initially neutral or arbitrary stimulus becomes a so-called “conditioned” stimulus (CS), which elicits a conditioned threat response. Fear extinction refers to the decrease in conditioned threat responses as soon as the CS is repeatedly presented in the absence of the US. While fear conditioning is an important learning model for understanding the etiology and maintenance of anxiety and fear-related disorders, extinction learning is considered to reflect the most important learning process of exposure therapy. Neurophysiological signatures of fear conditioning have been widely studied in rodents, leading to the development of groundbreaking neurobiological models, including brain regions such as the amygdala, insula, and prefrontal areas. These models aim to explain neural mechanisms of threat processing, with the ultimate goal to improve treatment strategies for pathological fear. Recording intracranial electrical activity of single units in animals offers the opportunity to uncover neural processes involved in threat processing with excellent spatial and temporal resolution. A large body of functional magnetic resonance imaging (fMRI) studies have helped to translate this knowledge about the anatomy of fear conditioning into the human realm. fMRI is an imaging technique with a high spatial resolution that is well suited to study slower brain processes. However, the temporal resolution of fMRI is relatively poor. By contrast, electroencephalography (EEG) is a neuroscientific method to capture fast and transient cortical processes. While EEG offers promising opportunities to unravel the speed of neural threat processing, it also provides the possibility to study oscillatory brain activity (e.g., prefrontal theta oscillations). The present thesis contains six research manuscripts, describing fear conditioning studies that mainly applied EEG methods in combination with other central (fMRI) and peripheral (skin conductance, heart rate, and fear-potentiated startle) measures. A special focus of this thesis lies in methodological considerations for EEG fear conditioning research. In addition, catecholaminergic mechanisms are studied, with the ultimate goal of opening up new translational perspectives. Taken together, the present thesis addresses several methodological challenges for neuroscientific (in particular, EEG) fear conditioning research (e.g., appropriate US types and experimental designs, signal-to-noise ratio, simultaneous EEG-fMRI). Furthermore, this thesis gives critical insight into catecholaminergic (noradrenaline and dopamine) mechanisms. A variety of neuroscientific methods (e.g., EEG, fMRI, peripheral physiology, pharmacological manipulation, genetic associations) have been combined, an approach that allowed us (a) to translate knowledge from animal studies to human research, and (b) to stimulate novel clinical directions