Dark Tetrad personality traits, paraphilic interests, and the role of impulsivity: an EEG-study using a Go/No-Go paradigm.

Maladaptive personality traits, such as 'dark personalities' are found to result in a diverse set of negative outcomes, including paraphilic interests and associated (illegal) behaviors. It is however unclear how these are exactly related, and if related, if then only those individuals higher on dark personality traits and higher impulsivity engage in paraphilic behaviors. In the current study, 50 participants were recruited to investigate the relationship between Dark Tetrad personality traits (i.e., narcissism, psychopathy, Machiavellianism and everyday sadism), paraphilic interests (arousal and behavior) and the moderating role of impulsivity. Personality and paraphilic interests were investigated through self-report questionnaires. Impulsivity was measured both through self-reported dysfunctional impulsivity and the P3 event related potential using electroencephalography during the Go/No-Go task (i.e. response inhibition). The results showed that there was a positive association between psychopathy, sadism and paraphilic interests. Whereas everyday sadism was associated with paraphilic (self-reported) arousal, psychopathy was associated with paraphilic behavior. Although P3 amplitude was not associated with paraphilic interests, self-reported dysfunctional impulsivity was associated with paraphilic behavior specifically. However, there was no moderating role of dysfunctional impulsivity and response inhibition (P3) in the relationship between psychopathy and paraphilic behavior. Findings indicate that the relation between specific dark personalities and paraphilic interests may be more complex than initially thought. Nevertheless, risk assessment and intervention approaches for paraphilia and related behavior both may benefit from incorporating Dark Tetrad and impulsivity measurements.

Tai Chi Chuan evidence related to impulsivity and impulse related disorders: A scoping review.

BACKGROUND: The purpose of this study was to review the evidence for the potential of Tai Chi Chuan (TCC) as a model of meditative movement in benefiting people with impulsivity related disorders and provide guidance for future research. METHODS: A scoping review of the literature was conducted in five databases. Eligibility criteria were original articles reporting TCC based interventions or included TCC techniques and provided any assessment on impulsivity or related measures, impulse control disorders, or other psychiatric disorders related to impulsivity (e.g., addictive disorders, ADHD, and other conduct disorders). Twenty-eight out of 304 studies initially retrieved were reviewed. The reports concentrated mostly on neurodegenerative conditions, cognitive decline, and substance use disorders (SUD). RESULTS: TCC had several positive effects in cognitive domains resulting in improvements in memory, executive functions, inhibitory control, attention, and verbal fluency. These improvements in memory, executive function, including inhibitory control and attention, and verbal fluency were associated with changes in the brain plasticity, resting activity, and other neurobiological markers. CONCLUSION: Albeit no study was found on the use of TCC in impulse control disorders or impulse related conditions, other than SUD, the findings suggest that considering the behavioral impact of TCC, especially the improvement of executive functions, it could be a valuable therapeutic tool for approaching impulse control related disorders.

Autoshaped impulsivity: Some explorations with a neural network model.

This study evaluated the effect of delay and magnitude of reinforcement in Pavlovian contingencies, extending the understanding of the phenomenon of autoshaped impulsivity as described in Alcalá's thesis (2017) and Burgos and García-Leal (2015). The effects of adding a trace interval were analyzed on the maintained responses of impulsive choice, seen as the preference of a small and immediate reinforcer over a larger and delayed one, and the role of the contextual unit, as well as the inhibitory units according to the Diffuse Discrepancy Model. In the Simulation, the model with inhibitory units was used, trained in two signals with different delays and reinforcement magnitudes, and subsequently presented concurrently in choice tasks without reinforcement nor learning, using an ABA within-subject design. In general, the DD model successfully simulated the phenomenon of autoshaped impulsivity, consistent with studies from Alcalá's thesis (2017), Burgos and García-Leal (2015), and Picker and Poling (1982). It also predicted the elimination of this effect (autoshaped impulsivity) after introducing a trace interval. The observed results and their implications are discussed, as well as possible future studies with animals and humans.

Association of impulsive behavior and cerebrospinal fluid/plasma oxidation and antioxidation ratio in Chinese men.

OBJECTIVES: Impulsive behavior is the precursor of many psychiatric and neurological conditions. High levels of impulsive behavior will increase health risk behavior and related injuries. Impulsive behavior is produced and regulated by central and peripheral biological factors, and oxidative stress (OS) can aggravate it. However, previous studies only showed that impulsive behavior was related to the level of the peripheral OS. Therefore, this study aims to clarify the relationship between OS and impulsive behavior in the brain and peripheral blood. METHODS: We recruited 64 Chinese men. We measured superoxide dismutase (SOD) (including copper, zinc and manganese) and nitric oxide synthase (NOS) (including total, inducible and constitutive) in cerebrospinal fluid (CSF) and plasma. The Barratt Impulsiveness Scale version 11 (BIS-11) was used to evaluate impulsive behavior. The relationship between OS and impulsive behavior was evaluated by partial correlation analysis and stepwise multiple regression analysis. RESULTS: Partial correlation analysis showed that the ratio of total NOS-to-MnSOD and iNOS-to-MnSOD in CSF were negatively correlated with the BIS-11 motor scores (r = -0.431, p = -0.001; r = -0.434, p = -0.001). Stepwise multiple regression analysis showed that the ratio of CSF iNOS-to-MnSOD was the most influential variable on the BIS-11 motor scores(ß = -0.434, t = -3.433, 95 %CI(-0.374, -0.098), p = 0.001). CONCLUSIONS AND RELEVANCE: The imbalance of central oxidation and antioxidation is related to impulsive behavior, which broadens our understanding of the correlation between impulsive behavior and OS.

Is impulsivity related to attentional bias in cigarette smokers? An exploration across levels of nicotine dependency and deprivation.

Research has largely focused on how attentional bias to smoking-related cues and impulsivity independently influence the development and maintenance of cigarette smoking, with limited exploration of the relationship between these mechanisms. The current experiments systematically assessed relationships between multiple dimensions of impulsivity and attentional bias, at different stages of attention, in smokers varying in nicotine dependency and deprivation. Nonsmokers (NS; n  = 26), light-satiated smokers (LS; n  = 25), heavy-satiated smokers (HS; n  = 23) and heavy 12-hour nicotine-deprived smokers (HD; n  = 30) completed the Barratt Impulsivity Scale, delayed discounting task, stop-signal task, information sampling task and a visual dot-probe assessing initial orientation (200 ms) and sustained attention (2000 ms) toward smoking-related cues. Sustained attention to smoking-related cues was present in both HS and LS, while initial orientation bias was only evident in HS. HS and LS also had greater levels of trait motor and nonplanning impulsivity and heightened impulsive choice on the delay discounting task compared with NS, while heightened trait attentional impulsivity was only found in HS. In contrast, in HD, nicotine withdrawal was associated with no attentional bias but heightened reflection impulsivity, poorer inhibitory control and significantly lower levels of impulsive choice relative to satiated smokers. Trait and behavioral impulsivity were not related to the extent of attentional bias to smoking-related cues at any stage of attention, level of nicotine dependency or state of deprivation. Findings have both clinical and theoretical implications, highlighting the unique and independent roles impulsivity and attentional bias may play at different stages of the nicotine addiction cycle.

EEG complexity in emotion conflict task in individuals with psychiatric disorders.

Analyzing EEG complexity may help to elucidate complex brain dynamics in individuals with psychiatric disorders and provide insight into neural connectivity and its relationship with deficits such as emotion-related impulsivity. EEG complexity was calculated through multiscale entropy and compared between a heterogeneous psychiatric patient group and a healthy control group during the emotion conflict resolution task. Twenty-eight healthy adults and ten psychiatric patients were recruited and compared on the multiscale entropy of EEG acquired in the task. Our results revealed a lower multiscale entropy in the psychiatric patient group compared to the healthy group during the task. This decrease in multiscale entropy suggests reduced long-range interaction between the left frontal region and other brain regions during the emotion conflict resolution task among psychiatric patients. Notably, a positive correlation was observed between multiscale entropy and impulsivity measures in the psychiatric patient group, where the higher the EEG complexity during the emotion regulation task, the higher the level of self-reported impulsivity in the psychiatric patients. Such impulsivity was evident in both healthy individuals and psychiatric patients, with healthy individuals showing shorter reaction times on incongruent conditions compared to congruent conditions and psychiatric patients displaying similar reaction times in both conditions, This study highlights the significance of investigating EEG complexity and its potential applications in the transdiagnostic exploration of impulsivity in psychiatric disorders.

Adult ADHD and pathological narcissism: A retrospective-analysis.

Adult attention deficit hyperactivity disorder (ADHD) is often associated with personality pathology. However, only few studies have been conducted on the link between ADHD and pathological narcissism (PN), with or without a diagnosis of narcissistic personality disorder (NPD). In order to fill this gap, PN and NPD were assessed in 164 subjects suffering from ADHD, with several other measures including ADHD severity, quality of life, depression, anxiety, impulsivity, and emotion dysregulation (ED). We found that a significant proportion of ADHD patients suffered from NPD, and that both narcissistic grandiosity and vulnerability were associated with ADHD hyperactivity and impulsivity symptoms, but not with inattentive symptoms. These two dimensions seemed to be negatively associated with well-being and positively associated with most of the other studied psychiatric dimensions except ED, the latter being only associated with vulnerability, even after adjustment on borderline symptoms. Overall, despite important limitations that limit the generalizability of our findings to the overall ADHD population (notably linked to selection bias), we believe that this exploratory study sheds light on the potential clinical relevance of narcissistic pathology in adult ADHD patients.

Differences in Discounting Behavior and Brain Responses for Food and Money Reward.

Most neuroeconomic research seeks to understand how value influences decision-making. The influence of reward type is less well understood. We used functional magnetic resonance imaging (fMRI) to investigate delay discounting of primary (i.e., food) and secondary rewards (i.e., money) in 28 healthy, normal-weighted participants (mean age = 26.77; 18 females). To decipher differences in discounting behavior between reward types, we compared how well-different option-based statistical models (exponential, hyperbolic discounting) and attribute-wise heuristic choice models (intertemporal choice heuristic, dual reasoning and implicit framework theory, trade-off model) captured the reward-specific discounting behavior. Contrary to our hypothesis of different strategies for different rewards, we observed comparable discounting behavior for money and food (i.e., exponential discounting). Higher k values for food discounting suggest that individuals decide more impulsive if confronted with food. The fMRI revealed that money discounting was associated with enhanced activity in the right dorsolateral prefrontal cortex, involved in executive control; the right dorsal striatum, associated with reward processing; and the left hippocampus, involved in memory encoding/retrieval. Food discounting, instead, was associated with higher activity in the left temporoparietal junction suggesting social reinforcement of food decisions. Although our findings do not confirm our hypothesis of different discounting strategies for different reward types, they are in line with the notion that reward types have a significant influence on impulsivity with primary rewards leading to more impulsive choices.

Vulnerable at rest? A resting-state EEG study and psychosocial factors of young adult offspring of alcohol-dependent parents.

BACKGROUND: Offspring of parents with alcohol use disorder (AUD) are more susceptible to developing AUD, with an estimated heritability of around 50%. Vulnerability to AUD in first-degree relatives is influenced by biological factors, such as spontaneous brain activity, and high-risk psychosocial characteristics. However, existing resting-state EEG studies in AUD offspring have shown inconsistent findings regarding theta, alpha, and beta band frequencies. Additionally, research consistently demonstrates an increased risk of internalizing and externalizing disorders, self-regulation difficulties, and interpersonal issues among AUD offspring. METHODS: This study aimed to investigate the absolute power of theta, alpha, and beta frequencies in young adult offspring with a family history of AUD compared to individuals without family history. The psychosocial profiles of the offspring were also examined in relation to individuals without a family history of AUD. Furthermore, the study sought to explore the potential association between differences in frequency bands and psychosocial variables. Resting-state EEG recordings were obtained from 31 young adult healthy offspring of alcohol-dependent individuals and 43 participants with no family history of AUD (age range: 16-25 years). Participants also completed self-report questionnaires assessing anxiety and depressive symptoms, impulsivity, emotion regulation, and social involvement. RESULTS: The results revealed no significant differences in spontaneous brain activity between the offspring and participants without a family history of AUD. However, in terms of psychosocial factors, the offspring exhibited significantly lower social involvement than the control group. CONCLUSIONS: This study does not provide evidence suggesting vulnerability in offspring based on differences in spontaneous brain activity. Moreover, this investigation highlights the importance of interventions aimed at enhancing social connections in offspring. Such interventions can not only reduce the risk of developing AUD, given its strong association with increased feelings of loneliness but also improve the overall well-being of the offspring.

Trait impulsivity influences behavioural and physiological responses to threat in a virtual environment.

Trait impulsivity represents a tendency to take action without forethought or consideration of consequences. This trait is multifaceted and can be decomposed into attentional, motor and non-planning subtypes of impulsivity. The purpose of the current study was to investigate how subtypes of trait impulsivity responded to different degrees of threat within room-scale virtual reality (VR) with respect to behaviour and level of physiological activation. Thirty-four participants were required to negotiate a virtual environment (VE) where they walked at height with the continuous threat of a virtual 'fall.' Behavioural measures related to the speed of movement, interaction frequency and risk were collected. Participants also wore ambulatory sensors to collect data from electrocardiogram (ECG) and electrodermal activity (EDA). Our results indicated that participants who scored highly on non-planning impulsivity exhibited riskier behaviour and higher skin conductance level (SCL). Participants with higher motor impulsivity interacted with more objects in the VE when threat was high, they also exhibited contradictory indicators of physiological activation. Attentional impulsivity was associated with a greater number of falls across the VE. The results demonstrate that subtypes of trait impulsivity respond to threats via different patterns of behaviour and levels of physiological activation, reinforcing the multifaceted nature of the trait.

Brain-based graph-theoretical predictive modeling to map the trajectory of anhedonia, impulsivity, and hypomania from the human functional connectome.

Clinical assessments often fail to discriminate between unipolar and bipolar depression and identify individuals who will develop future (hypo)manic episodes. To address this challenge, we developed a brain-based graph-theoretical predictive model (GPM) to prospectively map symptoms of anhedonia, impulsivity, and (hypo)mania. Individuals seeking treatment for mood disorders (n = 80) underwent an fMRI scan, including (i) resting-state and (ii) a reinforcement-learning (RL) task. Symptoms were assessed at baseline as well as at 3- and 6-month follow-ups. A whole-brain functional connectome was computed for each fMRI task, and the GPM was applied for symptom prediction using cross-validation. Prediction performance was evaluated by comparing the GPM to a corresponding null model. In addition, the GPM was compared to the connectome-based predictive modeling (CPM). Cross-sectionally, the GPM predicted anhedonia from the global efficiency (a graph theory metric that quantifies information transfer across the connectome) during the RL task, and impulsivity from the centrality (a metric that captures the importance of a region) of the left anterior cingulate cortex during resting-state. At 6-month follow-up, the GPM predicted (hypo)manic symptoms from the local efficiency of the left nucleus accumbens during the RL task and anhedonia from the centrality of the left caudate during resting-state. Notably, the GPM outperformed the CPM, and GPM derived from individuals with unipolar disorders predicted anhedonia and impulsivity symptoms for individuals with bipolar disorders. Importantly, the generalizability of cross-sectional models was demonstrated in an external validation sample. Taken together, across DSM mood diagnoses, efficiency and centrality of the reward circuit predicted symptoms of anhedonia, impulsivity, and (hypo)mania, cross-sectionally and prospectively. The GPM is an innovative modeling approach that may ultimately inform clinical prediction at the individual level.

Choice impulsivity after repeated social stress is associated with increased perineuronal nets in the medial prefrontal cortex.

Repeated stress can predispose to substance abuse. However, behavioral and neurobiological adaptations that link stress to substance abuse remain unclear. This study investigates whether intermittent social defeat (ISD), a stress protocol that promotes drug-seeking behavior, alters intertemporal decision-making and cortical inhibitory function in the medial prefrontal cortex (mPFC). Male long evans rats were trained in a delay discounting task (DDT) where rats make a choice between a fast (1 s) small reward (1 sugar pellet) and a large reward (3 sugar pellets) that comes with a time delay (10 s or 20 s). A decreased preference for delayed rewards was used as an index of choice impulsivity. Rats were exposed to ISD and tested in the DDT 24 h after each stress episode, and one- and two-weeks after the last stress episode. Immunohistochemistry was performed in rat's brains to evaluate perineuronal nets (PNNs) and parvalbumin GABA interneurons (PV) labeling as markers of inhibitory function in mPFC. ISD significantly decreased the preference for delayed large rewards in low impulsive, but not high impulsive, animals. ISD also increased the density of PNNs in the mPFC. These results suggest that increased choice impulsivity and cortical inhibition predispose animals to seek out rewards after stress.

Associations between antipsychotics-induced weight gain and brain networks of impulsivity.

Given the unpredictable rapid onset and ubiquitous consequences of weight gain induced by antipsychotics, there is a pressing need to get insights into the underlying processes at the brain system level that will allow stratification of "at risk" patients. The pathophysiological hypothesis at hand is focused on brain networks governing impulsivity that are modulated by neuro-inflammatory processes. To this aim, we investigated brain anatomy and functional connectivity in patients with early psychosis (median age: 23 years, IQR = 21-27) using anthropometric data and magnetic resonance imaging acquired one month to one year after initiation of AP medication. Our analyses included 19 patients with high and rapid weight gain (i.e., ≥5% from baseline weight after one month) and 23 patients with low weight gain (i.e., <5% from baseline weight after one month). We replicated our analyses in young (26 years, IQR = 22-33, N = 102) and middle-aged (56 years, IQR = 51-62, N = 875) healthy individuals from the general population. In early psychosis patients, higher weight gain was associated with poor impulse control score (ß = 1.35; P = 0.03). Here, the observed brain differences comprised nodes of impulsivity networks - reduced frontal lobe grey matter volume (Pcorrected = 0.007) and higher striatal volume (Pcorrected = 0.048) paralleled by disruption of fronto-striatal functional connectivity (R = -0.32; P = 0.04). Weight gain was associated with the inflammatory biomarker plasminogen activator inhibitor-1 (ß = 4.9, P = 0.002). There was no significant association between increased BMI or weight gain and brain anatomy characteristics in both cohorts of young and middle-aged healthy individuals. Our findings support the notion of weight gain in treated psychotic patients associated with poor impulse control, impulsivity-related brain networks and chronic inflammation.

Prefrontal activity during IOWA Gambling Task in young adult women.

This study aims to investigate the relationships between personality traits of impulsivity, using the UPPS-P Impulsive Behaviour Scales shortened version, and prefrontal cortex (PFC) activity during the IOWA Gambling Task (IGT) in young adult women. The study included a sample of 83 young, healthy females (19.8 ± 1.4 years), who voluntarily took part in the study. Repeated measures analysis during the IGT revealed a significant increase in HbO (all p <.001; ηp2 >.31) and a decrease in Hbr (all p <.003; ηp2 >.08) in all prefrontal quadrants. This increase in oxygenation occurs primarily during the choice period under ambiguity (r =.23; p =.039). Additionally, there was a significant linear decrease in selecting the decks associated with a high frequency of losses (p <.001), while the favorable deck with low losses showed a linear increase (F = 12.96; p <.001). Notably, discrepancies were found between UPPS-P and IGT impulsivity ratings. The Lack of Perseverance and Lack of Premeditation scales from the UPPS-P were identified as significant predictors of HbO levels, mainly in the two quadrants of the left hemisphere's, lateral (adjusted R2 =.23; p <.001; f2 =.34) and rostral (adjusted R2 =.13; p <.002; f2 =.17). These findings suggest that young adult women predominantly adopt a punishment-avoidance strategy during IGT, exhibiting increased activation in the left hemisphere, especially during the task's initial phase characterized by ambiguity.

Disentangling associations between impulsivity, compulsivity, and performance monitoring.

Disorders marked by high levels of impulsivity and compulsivity have been linked to changes in performance monitoring, specifically the error-related negativity (ERN). We investigated the relationship between performance monitoring and individual differences in impulsivity and compulsivity. A total of 142 participants were recruited into four groups, each with different combinations of impulsivity and compulsivity, and they performed a flanker task to assess error-related brain activity. We defined error-related brain activity as ERN amplitude and theta power. Single-trial regression was employed to analyze the amplitude differences between incorrect and correct trials within the ERN time window. The findings revealed that impulsivity, compulsivity, and different measures of response processing exhibited distinct interactions, which were influenced by the configuration of impulsivity and compulsivity, but also depended on the measure of response processing. Specifically, high compulsivity predicted larger ERN amplitudes in individuals with low impulsivity, whereas high impulsivity had no significant effect on ERN amplitude in individuals with low compulsivity. Furthermore, when both impulsivity and compulsivity were high, no significant increase in ERN amplitude was observed; instead, there was a reduced difference between incorrect and correct trials. No significant differences were found for theta power. While the association between error-related brain activity and transdiagnostic markers or psychopathology may be smaller than generally assumed, considering the interaction between different transdiagnostic markers and their facets can enhance our understanding of the complex associations that arise during the investigation of neural correlates of performance monitoring, specifically the ERN.

Urged to feel certain again: The role of emotion-related impulsivity on the relationships between intolerance of uncertainty and OCD symptom severity.

OBJECTIVES: Obsessive-compulsive disorder (OCD) is a debilitating mental disorder characterized by persistent and intrusive thoughts accompanied by repetitive mental or physical acts. While both intolerance of uncertainty and emotion-related impulsivity have been consistently evidenced as cognitive risk factors of OCD, no studies have considered their joint effects. The current study examined the interaction between intolerance of uncertainty and two forms of emotion-related impulsivity-including both a behavioural and cognitive form-in predicting OCD symptoms. DESIGN: Cross-sectional data were collected online from community-based adult participants. METHODS: Participants (N = 673) completed a battery of self-report measures of OCD symptom severity, intolerance of uncertainty, and emotion-related impulsivity. RESULTS: The behavioural form of emotion-related impulsivity positively moderated the relationship between intolerance of uncertainty and OCD symptoms. Elevated levels of both factors predicted the most severe symptoms, particularly checking, washing, and obsessing. This interaction effect was not found for the cognitive form of emotion-related impulsivity, which still emerged as a unique predictor of OCD symptom severity, specifically obsessing symptoms. CONCLUSIONS: Current findings furthered the understanding of the link between intolerance of uncertainty and OCD symptoms by highlighting the role of emotion-related impulsivity. When uncertainty triggers distress in individuals with high intolerance of uncertainty, the urge to behaviourally alleviate this distress could promote the use of maladaptive obsessions and compulsions, leading to greater OCD symptoms. Results also indicated the potentially differential effects from the behavioural versus cognitive forms of emotion-related impulsivity on different symptom domains, and the mechanistic link here is worthy of further investigation.

Pramipexole restores behavioral inhibition in highly impulsive rats through a paradoxical modulation of frontostriatal networks.

Impulse control disorders (ICDs), a wide spectrum of maladaptive behaviors which includes pathological gambling, hypersexuality and compulsive buying, have been recently suggested to be triggered or aggravated by treatments with dopamine D2/3 receptor agonists, such as pramipexole (PPX). Despite evidence showing that impulsivity is associated with functional alterations in corticostriatal networks, the neural basis of the exacerbation of impulsivity by PPX has not been elucidated. Here we used a hotspot analysis to assess the functional recruitment of several corticostriatal structures by PPX in male rats identified as highly (HI), moderately impulsive (MI) or with low levels of impulsivity (LI) in the 5-choice serial reaction time task (5-CSRTT). PPX dramatically reduced impulsivity in HI rats. Assessment of the expression pattern of the two immediate early genes C-fos and Zif268 by in situ hybridization subsequently revealed that PPX resulted in a decrease in Zif268 mRNA levels in different striatal regions of both LI and HI rats accompanied by a high impulsivity specific reduction of Zif268 mRNA levels in prelimbic and cingulate cortices. PPX also decreased C-fos mRNA levels in all striatal regions of LI rats, but only in the dorsolateral striatum and nucleus accumbens core (NAc Core) of HI rats. Structural equation modeling further suggested that the anti-impulsive effect of PPX was mainly attributable to the specific downregulation of Zif268 mRNA in the NAc Core. Altogether, our results show that PPX restores impulse control in highly impulsive rats by modulation of limbic frontostriatal circuits.

Anatomical correlates of apathy and impulsivity co-occurrence in early Parkinson's disease.

BACKGROUND: Although apathy and impulse control disorders (ICDs) are considered to represent opposite extremes of a continuum of motivated behavior (i.e., hypo- and hyperdopaminergic behaviors), they may also co-occur in Parkinson's disease (PD). OBJECTIVES: We aimed to explore the co-occurrence of ICDs and apathy and its neural correlates analyzing gray matter (GM) changes in early untreated PD patients. Moreover, we aimed to investigate the possible longitudinal relationship between ICDs and apathy and their putative impact on cognition during the first five years of PD. METHODS: We used the Parkinson's Progression Markers Initiative (PPMI) database to identify the co-occurrence of apathy and ICDs in 423 early drug-naïve PD patients at baseline and at 5-year follow-up. Baseline MRI volumes and gray matter changes were analyzed between groups using voxel-based morphometry. Multi-level models assessed the longitudinal relationship (across five years) between apathy and ICDs and cognitive functioning. RESULTS: At baseline, co-occurrence of apathy and ICDs was observed in 23 patients (5.4%). This finding was related to anatomical GM reduction along the cortical regions involved in the limbic circuit and cognitive control systems. Longitudinal analyses indicated that apathy and ICDs were related to each other as well as to the combined use of levodopa and dopamine agonists. Worse apathetic and ICDs states were associated with poorer executive functions. CONCLUSIONS: Apathy and ICDs are joint non-exclusive neuropsychiatric disorders also in the early stages of PD and their co-occurrence was associated with GM decrease in several cortical regions of the limbic circuit and cognitive control systems.

Noradrenergic regulation of cue-guided decision making and impulsivity is doubly dissociable across frontal brain regions.

RATIONALE: Win-paired stimuli can promote risk taking in experimental gambling paradigms in both rats and humans. We previously demonstrated that atomoxetine, a noradrenaline reuptake inhibitor, and guanfacine, a selective α2A adrenergic receptor agonist, reduced risk taking on the cued rat gambling task (crGT), a rodent assay of risky choice in which wins are accompanied by salient cues. Both compounds also decreased impulsive premature responding. OBJECTIVE: The key neural loci mediating these effects were unknown. The lateral orbitofrontal cortex (lOFC) and the medial prefrontal cortex (mPFC), which are highly implicated in risk assessment, action selection, and impulse control, receive dense noradrenergic innervation. We therefore infused atomoxetine and guanfacine directly into either the lOFC or prelimbic (PrL) mPFC prior to task performance. RESULTS: When infused into the lOFC, atomoxetine improved decision making score and adaptive lose-shift behaviour in males, but not in females, without altering motor impulsivity. Conversely, intra-PrL atomoxetine improved impulse control in risk preferring animals of both sexes, but did not alter decision making. Guanfacine administered into the PrL, but not lOFC, also altered motor impulsivity in all subjects, though in the opposite direction to atomoxetine. CONCLUSIONS: These data highlight a double dissociation between the behavioural effects of noradrenergic signaling across frontal regions with respect to risky choice and impulsive action. Given that the influence of noradrenergic manipulations on motor impulsivity could depend on baseline risk preference, these data also suggest that the noradrenaline system may function differently in subjects that are susceptible to the risk-promoting lure of win-associated cues.