Sign-tracking and goal-tracking in humans: Utilising eye-tracking in clinical and non-clinical populations.

BACKGROUND: In Pavlovian conditioning, learned behaviour varies according to the perceived value of environmental cues. For goal-trackers (GT), the cue merely predicts a reward, whilst for sign-trackers (ST), the cue holds incentive value. The sign-tracking/goal-tracking model is well-validated in animals, but translational work is lacking. Despite the model's relevance to several conditions, including attention deficit hyperactivity disorder (ADHD), we are unaware of any studies that have examined the model in clinical populations. METHODS: The current study used an eye-tracking Pavlovian conditioning paradigm to identify ST and GT in non-clinical (N = 54) and ADHD (N = 57) participants. Eye movements were recorded whilst performing the task. Dwell time was measured for two areas of interest: sign (i.e., cue) and goal (i.e., reward), and an eye-gaze index (EGI) was computed based on the dwell time sign-to-goal ratio. Higher EGI values indicate sign-tracking behaviour. ST and GT were determined using median and tertiary split approaches in both samples. RESULTS: Despite greater propensity for sign-tracking in those with ADHD, there was no significant difference between groups. The oculomotor conditioned response was reward-specific (CS+) and present, at least partly, from the start of the task indicating dispositional and learned components. There were no differences in externalising behaviours between ST and GT for either sample. CONCLUSIONS: Sign-tracking is associated with CS+ trials only. There may be both dispositional and learned components to sign-tracking, potentially more common in those with ADHD. This holds translational potential for understanding individual differences in reward-learning.

Role of the basal ganglia in innate and learned behavioural sequences.

Integrating individual actions into coherent, organised behavioural units, a process called chunking, is a fundamental, evolutionarily conserved process that renders actions automatic. In vertebrates, evidence points to the basal ganglia - a complex network believed to be involved in action selection - as a key component of action sequence encoding, although the underlying mechanisms are only just beginning to be understood. Central pattern generators control many innate automatic behavioural sequences that form some of the most basic behaviours in an animal's repertoire, and in vertebrates, brainstem and spinal pattern generators are under the control of higher order structures such as the basal ganglia. Evidence suggests that the basal ganglia play a crucial role in the concatenation of simpler behaviours into more complex chunks, in the context of innate behavioural sequences such as chain grooming in rats, as well as sequences in which innate capabilities and learning interact such as birdsong, and sequences that are learned from scratch, such as lever press sequences in operant behaviour. It has been proposed that the role of the striatum, the largest input structure of the basal ganglia, might lie in selecting and allowing the relevant central pattern generators to gain access to the motor system in the correct order, while inhibiting other behaviours. As behaviours become more complex and flexible, the pattern generators seem to become more dependent on descending signals. Indeed, during learning, the striatum itself may adopt the functional characteristics of a higher order pattern generator, facilitated at the microcircuit level by striatal neuropeptides.

The effects of tryptophan loading on Attention Deficit Hyperactivity in adults: A remote double blind randomised controlled trial.

BACKGROUND: Despite the impact and prevalence of Attention Deficit Hyperactivity Disorder (ADHD), current treatment options remain limited and there is a drive for alternative approaches, including those building on evidence of a role for tryptophan (TRP) and serotonin (5-HT). This study aimed to evaluate the effect of acute TRP loading on attention and impulsivity in adults with ADHD. TRIAL DESIGN AND METHODS: We conducted a remote double blind randomised controlled trial (RCT) using TRP loading to examine the effects of a balanced amino acid load in comparison to low and high TRP loading in individuals with ADHD (medicated, N = 48, and unmedicated, N = 46) and controls (N = 50). Participants were randomised into one of three TRP treatment groups using stratified randomisation considering participant group and gender using a 1:1:1 ratio. Baseline testing of attention and impulsivity using the Test of Variables of Attention Task, Delay Discounting Task, and Iowa Gambling Task was followed by consumption of a protein drink (BAL, LOW, or HIGH TRP) before repeated testing. RESULTS AND CONCLUSIONS: No effects of TRP were observed for any of the measures. In the present study, TRP loading did not impact on any measure of attention or impulsivity in those with ADHD or Controls. The findings need to be confirmed in another trial with a larger number of patients that also considers additional measures of dietary protein, plasma TRP and aggression. (Registration ID ISRCTN15119603).

Investigating the Role of Upward Comparisons and Self-compassion on Stigma in People With Acne: Cross-sectional Study.

BACKGROUND: The use of image-laden social media is hypothesized as being implicated in psychological distress in individuals with conditions affecting their appearance. However, relatively little is known about the mechanisms involved in this relationship. OBJECTIVE: This cross-sectional study examined the relationship between photo-orientated social media use and feelings of stigmatization in adults with acne, and tested whether upward skin comparisons mediate and self-compassion moderates this relationship. METHODS: Adults (N=650) with acne symptoms completed web-based measures of social media use (daily Facebook or Instagram use, Facebook function use), self-compassion, skin appearance comparisons, and internalized stigmatization. RESULTS: Moderated-mediation and mediation analyses indicated that there was a significant indirect effect of Facebook photo use on stigmatization, mediated by upward appearance comparisons (estimation of indirect effect 11.03, SE 5.11, 95% CI 1.19-21.12). There was no significant relationship between Instagram use and feelings of stigmatization (estimation of indirect effect 0.0002, SE 0.005, 95% CI -0.011 to 0.009), yet upward appearance comparisons predicted feelings of stigmatization (B=0.99, P<.001). Self-compassion did not moderate the indirect or direct relationships between photo-orientated social media use and stigma. However, self-compassion was negatively correlated with upward appearance comparisons and feelings of stigmatization in both Facebook and Instagram users. CONCLUSIONS: The way that individuals engage with social media, and in particular make appearance comparisons, should be considered when working with individuals with skin-related distress. Interventions aimed at boosting self-compassion and reducing appearance comparisons may provide avenues for protecting against feelings of stigma.

Sensory Reinforced Corticostriatal Plasticity.

BACKGROUND: Regional changes in corticostriatal transmission induced by phasic dopaminergic signals are an essential feature of the neural network responsible for instrumental reinforcement during discovery of an action. However, the timing of signals that are thought to contribute to the induction of corticostriatal plasticity is difficult to reconcile within the framework of behavioural reinforcement learning, because the reinforcer is normally delayed relative to the selection and execution of causally-related actions. OBJECTIVE: While recent studies have started to address the relevance of delayed reinforcement signals and their impact on corticostriatal processing, our objective was to establish a model in which a sensory reinforcer triggers appropriately delayed reinforcement signals relayed to the striatum via intact neuronal pathways and to investigate the effects on corticostriatal plasticity. METHODS: We measured corticostriatal plasticity with electrophysiological recordings using a light flash as a natural sensory reinforcer, and pharmacological manipulations were applied in an in vivo anesthetized rat model preparation. RESULTS: We demonstrate that the spiking of striatal neurons evoked by single-pulse stimulation of the motor cortex can be potentiated by a natural sensory reinforcer, operating through intact afferent pathways, with signal timing approximating that required for behavioural reinforcement. The pharmacological blockade of dopamine receptors attenuated the observed potentiation of corticostriatal neurotransmission. CONCLUSION: This novel in vivo model of corticostriatal plasticity offers a behaviourally relevant framework to address the physiological, anatomical, cellular, and molecular bases of instrumental reinforcement learning.

Separation of Channels Subserving Approach and Avoidance/Escape at the Level of the Basal Ganglia and Related Brainstem Structures.

The basal ganglia have the key function of directing our behavior in the context of events from our environment and/or our internal state. This function relies on afferents targeting the main input structures of the basal ganglia, entering bids for action selection at the level of the striatum or sig- nals for behavioral interruption at the level of the subthalamic nucleus, with behavioral reselection facilitated by dopamine signaling. Numerous experiments have studied action selection in relation to inputs from the cerebral cortex. However, less is known about the anatomical and functional link between the basal ganglia and the brainstem. In this review, we describe how brainstem structures also project to the main input structures of the basal ganglia, namely the striatum, the subthalamic nucleus and midbrain dopaminergic neurons, in the context of approach and avoidance (including escape from threat), two fundamental, mutually exclusive behavioral choices in an animal's repertoire in which the brainstem is strongly involved. We focus on three particularly well-described loci involved in approach and avoidance, namely the superior colliculus, the parabrachial nucleus and the periaqueductal grey nucleus. We consider what is known about how these structures are related to the basal ganglia, focusing on their projections toward the striatum, dopaminergic neurons and subthalamic nucleus, and explore the functional consequences of those interactions.

Frontal lobe-related cognition in the context of self-disgust.

Self- disgust is an adverse self-conscious emotion that plays an important role in psychopathology and well-being. However, self-disgust has received little attention in the emotion literature, therefore our understanding of the processes underlying the experience of self-disgust is relatively scarce, although neuropsychological and neuroimaging studies support the idea that this emotion may heavily rely on frontal lobe-related cognition. To test this hypothesis, in two studies we investigated the relationship between state and trait levels of self-disgust, cognition and emotion regulation in healthy adults. Specifically, in Study 1 we tested the hypothesis that emotion regulation strategies (avoidance, suppression, and cognitive reappraisal) mediate the relationship between inhibition ability and state and trait levels of self-disgust. In Study 2, we followed a more comprehensive approach to test the hypothesis that frontal lobe-related cognitive processes (updating, Theory of Mind-ToM-, and self-attention) are closely related to the experience of self-disgust in healthy adults. Overall, across these studies, we found evidence to support the idea that inhibition ability and ToM may play a role in the experience of state and trait self-disgust, respectively. However, we did not find consistent evidence across the two studies to support the notion held in the literature that the experience of self- conscious emotions, in this case self-disgust, is heavily dependent on frontal lobe-related cognition.

Altered parabrachial nucleus nociceptive processing may underlie central pain in Parkinson's disease.

The presence of central neuropathic pain in Parkinson's disease suggests that the brain circuits that allow us to process pain could be dysfunctional in the disorder. However, there is to date no clear pathophysiological mechanism to explain these symptoms. In this work, we present evidence that the dysfunction of the subthalamic nucleus and/or substantia nigra pars reticulata may impact nociceptive processing in the parabrachial nucleus (PBN), a low level primary nociceptive structure in the brainstem, and induce a cellular and molecular neuro-adaptation in this structure. In rat models of Parkinson's disease with a partial dopaminergic lesion in the substantia nigra compacta, we found that the substantia nigra reticulata showed enhanced nociceptive responses. Such responses were less impacted in the subthalamic nucleus. A total dopaminergic lesion produced an increase in the nociceptive responses as well as an increase of the firing rate in both structures. In the PBN, inhibited nociceptive responses and increased expression of GABAA receptors were found following a total dopaminergic lesion. However, neuro-adaptations at the level of dendritic spine density and post-synaptic density were found in both dopaminergic lesion groups. These results suggest that the molecular changes within the PBN following a larger dopaminergic lesion, such as increased GABAA expression, is a key mechanism to produce nociceptive processing impairment, whilst other changes may protect function after smaller dopaminergic lesions. We also propose that these neuro-adaptations follow increased inhibitory tone from the substantia nigra pars reticulata and may represent the mechanism generating central neuropathic pain in Parkinson's disease.

The NK1 antagonist L-733,060 facilitates sequence learning.

BACKGROUND: Although several brain regions and electrophysiological patterns have been related to sequence learning, less attention has been paid to the role that different neuromodulators play. AIMS: Here we sought to investigate the role of substance P (SP) in sequence learning in an operant conditioning preparation, supported by a reinforcement learning model. METHODS: Two experiments were performed to test the effects of an NK1 receptor (at which SP primarily acts) antagonist on learning and performing action sequences. In experiment 1, rats were trained to perform an action sequence until stable performance was achieved, and then, in phase 2, they were switched to perform the reverse sequence. In experiment 2, rats were trained to perform an action sequence, and in phase 2, they continued to do the same sequence. In both experiments in the first 3 days of phase 2, rats were injected with an NK1 receptor antagonist (L-733,060, i.p.) or with vehicle. Additionally, we developed a reinforcement learning model which allowed the in silico replication of our experimental tasks. RESULTS: We found that administering an NK1 receptor antagonist weakened the stable retention of a well-learned sequence, allowing the faster acquisition of a new sequence, without impairing the continued performance of a crystallized sequence. Using our reinforcement learning model, we suggest that SP could be acting through the state value learning rate, modulating the effects of the reward prediction error. CONCLUSIONS: Our results suggest that SP could be involved in the consolidation of a sequence representation through a modulatory effect on the reward prediction error.

The Effects of Different Exercise Approaches on Attention Deficit Hyperactivity Disorder in Adults: A Randomised Controlled Trial.

Attention deficit hyperactivity disorder (ADHD) results in significant functional impairment. Current treatments, particularly for adults, are limited. Previous research indicates that exercise may offer an alternative approach to managing ADHD, but research into different types of exercise and adult populations is limited. The aim of this study was to examine the effects of acute exercise (aerobic cycling vs mind-body yoga exercises) on symptoms of ADHD in adults. Adults with ADHD (N = 82) and controls (N = 77) were randomly allocated to 10 min of aerobic (cycling) or mind-body (Hatha yoga) exercise. Immediately before and after exercise, participants completed the Test of Variables of Attention task, Delay Discounting Task, and Iowa Gambling Task to measure attention and impulsivity. Actigraphy measured movement frequency and intensity. Both groups showed improved temporal impulsivity post-exercise, with cycling beneficial to all, whilst yoga only benefited those with ADHD. There were no effects of exercise on attention, cognitive or motor impulsivity, or movement in those with ADHD. Exercise reduced attention and increased movement in controls. Exercise can improve temporal impulsivity in adult ADHD but did not improve other symptoms and worsened some aspects of performance in controls. Exercise interventions should be further investigated.

The Subthalamic Nucleus: A Hub for Sensory Control via Short Three- Lateral Loop Connections with the Brainstem?

The subthalamic nucleus (STN) is classically subdivided into sensori-motor, associative and limbic regions, which is consistent with the involvement of this structure in not only motor control, but also in cognitive and emotional tasks. However, the function of the sensory inputs to the STN's sensori-motor territory is comparatively less well explored, although sensory responses have been reported in this structure. There is still a paucity of information regarding the characteristics of that subdivision and its potential functional role in basal ganglia processing and more widely in associated networks. In this perspective paper, we summarize the type of sensory stimuli that have been reported to activate the STN, and describe the complex sensory properties of the STN and its anatomical link to a sensory network involving the brainstem, characterized in our recent work. Analyzing the sensory input to the STN led us to suggest the existence of previously unreported threelateral subcortical loops between the basal ganglia and the brainstem which do not involve the cortex. Anatomically, these loops closely link the STN, the substantia nigra pars reticulata and various structures from the brainstem such as the superior colliculus and the parabrachial nucleus. We also discuss the potential role of the STN in the control of sensory activity in the brainstem and its possible contribution to favoring sensory habituation or sensitization over brainstem structures to optimize the best selection of action at a given time.

Schizophrenia decreases guilt and increases self-disgust: Potential role of altered executive function.

Our knowledge of how the more complex self-conscious emotions (SCEs) are affected in schizophrenia is sparse. SCEs, unlike basic emotions, involve sophisticated frontal-lobe-related cognition, impairment of which characterizes the neurocognitive profile of schizophrenia. We investigated, in a cross-sectional study, whether SCEs (shame, guilt and self-disgust) are affected in schizophrenia, and the relationship between changes in SCEs and executive (dys)function. Twenty-nine Greek and thirty Arabic patients with schizophrenia were recruited alongside twenty-two Greek and thirty Arabic matched controls. Participants were administered the Self-Disgust Scale (TOSCA for shame and guilt was also administered to the Greek sample), and the Trail Making and Verbal Fluency Tests to measure executive function (EF). Trait levels of self-disgust and guilt were found to be higher and lower, respectively, in patients with schizophrenia relative to control participants; and poorer EF was related with higher trait levels of SD, but lower trait levels of guilt. The pattern of findings was largely unaffected when controlling for anxiety and depression. Given that altered levels of SCEs are closely related to poorer EF, we suggest that the link between EF and emotion regulation, widely established in basic emotions but under-studied in SCEs, may explain the current findings.

A brief online writing intervention improves positive body image in adults living with dermatological conditions.

Introduction: Dermatological conditions can affect how individuals feel about their bodies. This research therefore seeks to evaluate the potential for a brief writing intervention, focused on body functionality, to improve body image in adults living with a range of dermatological conditions. Methods: As part of a parallel Randomised Controlled Trial, 451 adults living with a dermatological condition were randomized to either three functionality-based writing tasks or three creative writing tasks (control). Of these, 155 participants completed pre- and post-intervention measures of body appreciation, functionality appreciation, appearance anxiety, skin-related shame, and skin-related quality-of-life. Results: For participants with relatively low or mid-range scores on baseline body appreciation and functionality appreciation, there were medium-to-large positive effects of the intervention. Effects were smaller, with all but-one remaining significant, at 1-month follow up and in intention-to-treat analyses. No between-group effects of the intervention were found for measures of appearance anxiety, skin-related shame, and skin-related quality-of-life. Discussion: These findings suggest that a 1-week writing intervention has the potential to improve positive aspects of body image, but not appearance- and skin-related distress in adults living with a dermatological condition. Clinical trial registration: [https://clinicaltrials.gov/ct2/history/NCT044459 74?V_3=View], identifier [NCT04445974].

Higher Trait Levels of Guilt may Protect Against Gambling, Whereas Higher State Levels Lead to Riskier Behaviour.

Research on the role of affect in problem gambling remains scarce to date, although it has been proposed that trait-levels of negative self-conscious emotions (SCEs) could be potential risk factors. We report two studies investigating the relationship between negative SCEs, gambling, and risky behavior. In the first study, we investigated shame, guilt and self-disgust in a group of problem-gamblers and control non-gamblers. In the second study, we investigated if experimentally manipulating state levels of guilt, using a narration-induction paradigm, in students with different levels of gambling behavior, would influence their behavior in the Balloon Analog Risk Task. We found that problem gamblers had significantly lower trait-levels of guilt when we adjusted for the influence of depression and anxiety symptoms (p = .008). Problem gamblers also exhibited lower levels of shame, but this difference seemed to be driven by guilt. Lower levels of guilt were significantly associated with higher levels of trait impulsivity (p = .004). In the second study, gamblers had higher state levels of guilt than non-gamblers at the outset, and the narration paradigm successfully induced guilt (p = .001). After the guilt induction, the group of gamblers had significantly less risky behaviour (lower number of pumps) than the group of non-gamblers (p = .021). However, this was primarily driven by an increase in risky behaviour in the non-gamblers (p = .006). Thus, overall our findings suggest that higher trait levels of guilt may act as a protective factor for gambling, whereas high state levels of guilt lead to riskier behaviour but only in people who are not gamblers.

Autonomic factors do not underlie the elevated self-disgust levels in Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) is manifested along with non-motor symptoms such as impairments in basic emotion regulation, recognition and expression. Yet, self-conscious emotion (SCEs) such as self-disgust, guilt and shame are under-investigated. Our previous research indicated that Parkinson patients have elevated levels of self-reported and induced self-disgust. However, the cause of that elevation-whether lower level biophysiological factors, or higher level cognitive factors, is unknown. METHODS: To explore the former, we analysed Skin Conductance Response (SCR, measuring sympathetic activity) amplitude and high frequency Heart Rate Variability (HRV, measuring parasympathetic activity) across two emotion induction paradigms, one involving narrations of personal experiences of self-disgust, shame and guilt, and one targeting self-disgust selectively via images of the self. Both paradigms had a neutral condition. RESULTS: Photo paradigm elicited significant changes in physiological responses in patients relative to controls-higher percentages of HRV in the high frequency range but lower SCR amplitudes, with patients to present lower responses compared to controls. In the narration paradigm, only guilt condition elicited significant SCR differences between groups. CONCLUSIONS: Consequently, lower level biophysiological factors are unlikely to cause elevated self-disgust levels in Parkinson's disease, which by implication suggests that higher level cognitive factors may be responsible.

Blocking NK1 receptors disrupts the sequential and temporal organization of chain grooming in rats.

The basal ganglia are a group of sub-cortical structures believed to play a critical role in action selection and sequencing. The striatum is the largest input structure of the basal ganglia and contains the neuropeptide substance P in abundance. Recent computational work has suggested that substance P could play a critical role in action sequence performance and acquisition, but this has not been tested experimentally before. The aim of the present study was to test how blocking substance P's main NK1-type receptors affected the sequential and temporal organization of spontaneous behavioral patterns. We did this in rats by focusing on the grooming chain, an innate and highly stereotyped ordered sequence. We performed an open field experiment in which the NK1 receptor antagonist L-733,060 was injected intraperitoneally in rats at two doses (2 and 4 mg/kg/ml), in a within-subject counterbalanced design. We used first order transition probabilities, Variable Length Markov Models, entropy metrics and T-pattern analysis to evaluate the effects of L-733,060 on sequential and temporal aspects of spontaneously ordered behavioral sequences. Our results suggest that blocking NK1 receptors made the transitions between the grooming chain elements significantly more variable, the transition structure of the grooming bouts simpler, and it increased the probability of transitioning from active to inactive states. Overall, this suggest that blocking substance P receptors led to a general break down in the fluency of spontaneous behavioral sequences, suggesting that substance P could be playing a key role in the implementation of sequential patterns.

Self-Disgust Is Associated With Loneliness, Mental Health Difficulties, and Eye-Gaze Avoidance in War Veterans With PTSD.

In the present study, we examined, for the first time, the association between self-disgust, loneliness, and mental health difficulties in war veterans diagnosed with PTSD. For this purpose, we used a mixed methods design, incorporating surveys and a novel eye-tracking paradigm, and compared the findings from the PTSD veteran group (n = 19) to those from a general population group (n = 22). Our results showed that the PTSD veteran group reported almost three times higher scores in self-disgust, and significantly higher scores in loneliness and mental health difficulties (anxiety and depression), compared to the general population. Furthermore, self-disgust mediated the association between loneliness and anxiety symptoms in both groups. The results from the eye-tracking paradigm further showed that veterans with PTSD displayed a self-avoidance gaze pattern, by looking significantly more toward pictures of faces of unknown others and away from their own face-a pattern that was not replicated in the general population group. Higher self-disgust scores were significantly associated with longer total gaze to the pictures of others (vs. the self). Our findings have implications for the role of self-disgust in the mental health of war veterans.

The relationship between sensory processing sensitivity and attention deficit hyperactivity disorder traits: A spectrum approach.

The aim of the present study was to examine the relationship between sensory processing sensitivity (SPS) and symptoms of Attention Deficit Hyperactivity Disorder (ADHD) in adults. The Highly Sensitive Person Scale (HSPS) scale and the Adult ADHD Self-Report Scale (ASRS) were administered to a non-clinical group of 274 participants recruited from a university volunteers list. We found a highly significant positive correlation between number of self-reported ADHD traits and sensory sensitivity. Furthermore, ADHD traits and age were predictors of SPS and exploratory factor analysis revealed a factor that combined ADHD traits and items from the HSPS. The psychometric properties of the HSPS were also examined supporting the unidimensional nature of the concept. To our knowledge, this is the first study to identify a positive relationship between HSPS and ADHD traits in the general population. Our results further support recent findings suggesting abnormal sensory processing in ADHD.

The neuropathological basis of anxiety in Parkinson's disease.

Evidence suggests that 24.5%-46.7% (mean 31%) of patients with Parkinson's disease experience an anxiety disorder, a much higher prevalence than in controls. Anxiety does not appear to be a consequence of diagnosis or the motoric symptoms of the disorder and can manifest as Generalised Anxiety Disorder, phobias or panic attacks. At present, the neural underpinnings of anxiety disorders in Parkinson's disease is unknown. Here, we make the novel proposal that the superior colliculus (SC), one component of a rapid, reflexive threat detection system in the brain, consisting of the colliculus, pulvinar and amygdala, becomes hyper-responsive to sensory stimuli following dopamine denervation of the striatum in Parkinson's disease. This in turn leads to heightened responses to existing threat-related stimuli (giving rise to phobias and panic attacks), and heightened responses to anticipated threats (giving rise to Generalised Anxiety Disorder). This proposal is supported by a range of evidence, in particular elevated visual responses in the SC in an animal model of Parkinson's disease and in Parkinson's disease itself. Also facilitated saccadic eye movements (prosaccades, express saccades and fixational saccades) and increased distractibility in Parkinson's disease, both of which involve the SC. Identifying one potential locus of change in the brain in Parkinson's disease relevant to anxiety gives a potential target for interventions to combat a non-motor symptom that has a substantial negative effect on quality of life in the disorder.