Cognitive and motor impulsivity in the healthy brain, and implications for eating disorders and obesity: A coordinate-based meta-analysis and systematic review.

Alterations in the impulse-control balance, and in its neural bases, have been reported in obesity and eating disorders (EDs). Neuroimaging studies suggest a role of fronto-parietal networks in impulsive behaviour, with evaluation and anticipatory processes additionally recruiting meso-limbic regions. However, whether distinct facets of cognitive and motor impulsivity involve common vs. specific neural correlates remains unclear. We addressed this issue through Activation Likelihood Estimation (ALE) meta-analyses of fMRI studies on delay discounting (DD) and go/no-go (GNG) tasks, alongside conjunction and subtraction analyses. We also performed systematic reviews of neuroimaging studies using the same tasks in individuals with obesity or EDs. ALE results showed consistent activations in the striatum, anterior/posterior cingulate cortex, medial/left superior frontal gyrus and left supramarginal gyrus for impulsive choices in DD, while GNG tasks elicited mainly right-lateralized fronto-parietal activations. Conjunction and subtraction analyses showed: i) common bilateral responses in the caudate nucleus; ii) DD-specific responses in the ventral striatum, anterior/posterior cingulate cortex, left supramarginal and medial frontal gyri; iii) GNG-specific activations in the right inferior parietal cortex. Altered fronto-lateral responses to both tasks are suggestive of dysfunctional cortico-striatal balance in obesity and EDs, but these findings are controversial due to the limited number of studies directly comparing patients and controls. Overall, we found evidence for distinctive neural correlates of the motor and cognitive facets of impulsivity: the right inferior parietal lobe underpins action inhibition, whereas fronto-striatal regions and the left supramarginal gyrus are related to impulsive decision-making. While showing that further research on clinical samples is required to better characterize the neural bases of their behavioural changes, these findings help refining neurocognitive model of impulsivity and highlight potential translational implications for EDs and obesity treatment.

Internal Capsule/Nucleus Accumbens Deep Brain Stimulation Increases Impulsive Decision Making in Obsessive-Compulsive Disorder.

BACKGROUND: Deep brain stimulation of the anterior limb of the internal capsule (ALIC)/nucleus accumbens is an effective treatment in patients with obsessive-compulsive disorder but may increase impulsive behavior. We aimed to investigate how active stimulation alters subdomains of impulsive decision making and whether respective effects depend on the location of stimulation sites. METHODS: We assessed 15 participants with obsessive-compulsive disorder performing the Cambridge Gambling Task during active and inactive ALIC/nucleus accumbens deep brain stimulation. Specifically, we determined stimulation-induced changes in risk adjustment and delay aversion. To characterize underlying neural pathways, we computed probabilistic stimulation maps and applied fiber filtering based on normative structural connectivity data to identify "hot" and "cold" spots/fibers related to changes in impulsive decision making. RESULTS: Active stimulation significantly reduced risk adjustment while increasing delay aversion, both implying increased impulsive decision making. Changes in risk adjustment were robustly associated with stimulation sites located in the central ALIC and fibers connecting the thalamus and subthalamic nucleus with the medial and lateral prefrontal cortex. Both hot spots and fibers for changes in risk adjustment were robust to leave-one-out cross-validation. Changes in delay aversion were similarly associated with central ALIC stimulation, but validation hereof was nonsignificant. CONCLUSIONS: Our findings provide experimental evidence that ALIC/nucleus accumbens stimulation increases impulsive decision making in obsessive-compulsive disorder. We show that changes in risk adjustment depend on the location of stimulation volumes and affected fiber bundles. The relationship between impulsive decision making and long-term clinical outcomes requires further investigation.

Contrasting effects of DOM and lisuride on impul-sive decision-making in delay discounting task / 中国药理学与毒理学杂志

OBJECTIVE The 5-HT2A receptor is the major target of classic hallucinogens.Both DOM(2,5-dimethoxy-4-methylamphetamine)and lisuride act at 5-HT2A receptors,and lisuride shares comparable affinity with DOM and acts as a partial agonist at 5-HT2A recep-tors.However,not like DOM,lisuride lacks hallucinogenic properties.Impulsive decision-making refers to the prefer-ence for an immediate small reinforcer(SR)over a delayed large reinforcer(LR).The current study aims to compare the effects of DOM and lisuride on impulsive decision-making and further to investigate the possible receptor mechanisms responsible for the actions of the two drugs.METHODS Impulsive decision-making was evaluated in male Sprague-Dawley rats by the percent-age of choice for the LR in delay discounting task(DDT).Delay to the LR changed in an ascending order(0,4,8,16,and 32 s)across one session.RESULTS DOM(0.3 and 0.5 mg·kg-1)increased impulsive decision-making,and the effects of DOM(0.5 mg·kg-1)was blocked by the 5-HT2A receptor antagonist ketanserin(1.0 mg·kg-1)rather than the 5-HT2C receptor antagonist SB-242084(1.0 mg·kg-1).Contrarily,lisuride(0.1,0.3 and 0.5 mg·kg-1)decreased impulsive decision-making.The effects of lisu-ride(0.3 mg·kg-1)were not antagonized by ketanserin(1.0 mg·kg-1),selective 5-HT1A antagonist WAY-100635(1.0 mg·kg-1)or selective dopamine D4 receptor antagonist L-745870(1.0 mg·kg-1),but were attenuated by the selec-tive dopamine D2/D3 receptor antagonist tiapride(40 mg·kg-1).CONCLUSION DOM and lisuride have contrasting effects on impulsive decision-making via distinct recep-tors.DOM-induced increase of impulsivity is mediated by the 5-HT2A receptor,while lisuride-induced inhibition of impulsivity is regulated by the dopamine D2/D3 receptor.

Contrasting effects of DOI and lisuride on impulsive decision-making in delay discounting task.

RATIONALE: The 5-HT2A receptor is the major target of classic hallucinogens. Both DOI (2,5-dimethoxy-4-iodoamphetamine) and lisuride act at 5-HT2A receptors, and lisuride shares comparable affinity with DOI and acts as a partial agonist at 5-HT2A receptors. However, not like DOI, lisuride lacks hallucinogenic properties. Impulsive decision-making refers to the preference for an immediate small reinforcer (SR) over a delayed large reinforcer (LR). OBJECTIVES: The current study aims to compare the effects of DOI and lisuride on impulsive decision-making and further to investigate the possible receptor mechanisms responsible for the actions of the two drugs. METHODS: Impulsive decision-making was evaluated in male Sprague-Dawley rats by the percentage of choice for the LR in delay discounting task (DDT). Delay to the LR changed in an ascending order (0, 4, 8, 16, and 32 s) across one session. RESULTS: DOI (0.5 and 1.0 mg/kg) increased impulsive decision-making, and the effects of DOI (1.0 mg/kg) were blocked by the 5-HT2A receptor antagonist ketanserin (1.0 mg/kg) rather than the 5-HT2C receptor antagonist SB-242084 (1.0 mg/kg). Contrarily, lisuride (0.1, 0.3, and 0.5 mg/kg) decreased impulsive decision-making. The effects of lisuride (0.3 mg/kg) were not antagonized by ketanserin (1.0 mg/kg), selective 5-HT1A antagonist WAY-100635 (1.0 mg/kg), or selective dopamine D4 receptor antagonist L-745870 (1.0 mg/kg) but were attenuated by the selective dopamine D2/D3 receptor antagonist tiapride (40 mg/kg). CONCLUSIONS: DOI and lisuride have contrasting effects on impulsive decision-making via distinct receptors. DOI-induced increase of impulsivity is mediated by the 5-HT2A receptor, while lisuride-induced inhibition of impulsivity is regulated by the dopamine D2/D3 receptor.

Cognitive Flexibility and Impulsivity Deficits in Suicidal Adolescents.

Although neurocognitive deficits have been documented in adolescents with suicidal ideation (SI) and suicide attempts (SA), it is unclear whether certain impairments differentiate these groups, potentially suggesting heightened risk for SA. Focus on specific facets of impulsivity and cognitive control may indicate distinctions between adolescents with SA vs. SI. The current study examined dimensions of impulsivity and cognitive control in 141 adolescents with SA (n = 41) vs. SI without SA (n = 49) vs. typically-developing controls (TDCs; n = 51). Adolescents completed cross-sectional neurocognitive tasks via the Cambridge Neuropsychological Testing Automated Battery, in addition to demographic and clinical measures. Analyses involved ANOVAs and ANCOVAs. Results indicated that adolescents with SA demonstrated less set shifting/cognitive flexibility (reduced ability to adapt to/disengage from stimuli) and greater impulsive decision making (reduced ability to collect/evaluate information before making decisions) compared to TDCs. In addition, both TDCs and adolescents with SA had greater response inhibition (increased ability to stop motor responses that have begun/become prepotent) than those with SI. Similar results were found when analyzing female adolescents separately. There were no significant differences for male adolescents, potentially due to the small subsample (n = 40). There were no significant findings for spatial planning/problem solving or visuospatial working memory. Findings suggest: 1) less set shifting/cognitive flexibility and greater impulsive decision making for adolescents with SA vs. TDCs; and 2) greater response inhibition for TDCs and adolescents with SA vs. SI. Such information may be useful for improving risk assessments (adding neurocognitive tasks) and targeted treatments (incorporating cognitive remediation) for this impaired population.

Impulsive and risky decision-making in adolescents with attention-deficit/hyperactivity disorder (ADHD): The need for a developmental perspective.

Impulsive and risky decision-making peaks in adolescence, and is consistently associated with the neurodevelopmental disorder Attention-Deficit/Hyperactivity Disorder (ADHD), regardless of age. In this brief review, we demonstrate the similarity of theoretical models explaining impulsive and risky decision-making that originate in two relatively distinct literatures (i.e., on adolescence and on ADHD). We summarize research thus far and conclude that the presence of ADHD during adolescence further exacerbates the tendency that is already present in adolescents to make impulsive and risky decisions. We also conclude that much is still unknown about the developmental trajectories of individuals with ADHD with regard to impulsive and risky decision making, and we therefore provide several hypotheses that warrant further longitudinal research.

The Effects of a Working Memory Load on Delay Discounting in Those with Externalizing Psychopathology.

This study investigated the influence of executive working memory (EWM) capacity on impulsive decision-making in a sample of young adults (n=623) that varied in degree of externalizing psychopathology (EXT) by examining: (i) the effects of WM load on delay discounting rates, and, (ii) the association between EWM capacity and delay discounting rates. EXT was measured as a latent variable indicated by lifetime problems with alcohol, marijuana, other drugs, childhood conduct, and adult antisocial behavior. Results showed that (i) the WM load increased discounting rates throughout the spectrum of EXT, (ii) EXT was associated with higher discounting rates and lower EMW capacity, and (iii) WM capacity was significantly associated with higher discounting rates when controlling for IQ, but only after a WM load. The results are discussed in terms of the role of EWM capacity in impulsive decision making in EXT.

The association between cingulate cortex glutamate concentration and delay discounting is mediated by resting state functional connectivity.

Humans vary in their ability to delay gratification and impulsive decision making is a common feature in various psychiatric disorders. The level of delay discounting is a relatively stable psychological trait, and therefore neural processes implicated in delay discounting are likely to be based on the overall functional organization of the brain (under task-free conditions) in which state-dependent shifts from baseline levels occur. The current study investigated whether delay discounting can be predicted by intrinsic properties of brain functioning. Fourteen healthy male subjects performed a delay discounting task. In addition, resting state functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (¹H MRS) were used to investigate the relationship between individual differences in delay discounting and molecular and regional measures of resting state (baseline) activity of dorsal anterior cingulate cortex (dACC). Results showed that delay discounting was associated with both dACC glutamate concentrations and resting state functional connectivity of the dACC with a midbrain region including ventral tegmental area and substantia nigra. In addition, a neural pathway was established, showing that the effect of glutamate concentrations in the dACC on delay discounting is mediated by functional connectivity of the dACC with the midbrain. The current findings are important to acknowledge because spontaneous intrinsic brain processes have been proposed to be a potential promising biomarker of disease and impulsive decision making is associated with several psychiatric disorders.