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1.  Frontal Dysfunctions of Impulse Control – A Systematic Review in Borderline Personality Disorder and Attention-Deficit/Hyperactivity Disorder 
Disorders such as borderline personality disorder (BPD) or attention-deficit/hyperactivity disorder (ADHD) are characterized by impulsive behaviors. Impulsivity as used in clinical terms is very broadly defined and entails different categories including personality traits as well as different cognitive functions such as emotion regulation or interference resolution and impulse control. Impulse control as an executive function, however, is neither cognitively nor neurobehaviorally a unitary function. Recent findings from behavioral and cognitive neuroscience studies suggest related but dissociable components of impulse control along functional domains like selective attention, response selection, motivational control, and behavioral inhibition. In addition, behavioral and neural dissociations are seen for proactive vs. reactive inhibitory motor control. The prefrontal cortex with its sub-regions is the central structure in executing these impulse control functions. Based on these concepts of impulse control, neurobehavioral findings of studies in BPD and ADHD were reviewed and systematically compared. Overall, patients with BPD exhibited prefrontal dysfunctions across impulse control components rather in orbitofrontal, dorsomedial, and dorsolateral prefrontal regions, whereas patients with ADHD displayed disturbed activity mainly in ventrolateral and medial prefrontal regions. Prefrontal dysfunctions, however, varied depending on the impulse control component and from disorder to disorder. This suggests a dissociation of impulse control related frontal dysfunctions in BPD and ADHD, although only few studies are hitherto available to assess frontal dysfunctions along different impulse control components in direct comparison of these disorders. Yet, these findings might serve as a hypothesis for the future systematic assessment of impulse control components to understand differences and commonalities of prefrontal cortex dysfunction in impulsive disorders.
doi:10.3389/fnhum.2014.00698
PMCID: PMC4153044  PMID: 25232313
impulsivity; response inhibition; borderline personality disorder; attention-deficit/hyperactivity disorder, fMRI
2.  Effects of smoking abstinence on impulsive behavior among smokers high and low in ADHD-like symptoms 
Psychopharmacology  2011;219(2):537-547.
Rationale
Impulsivity, a multifaceted construct that includes inhibitory control and heightened preference for immediate reward, is central to models of drug use and abuse. Within a self-medication framework, abstinence from smoking may lead to an increase in impulsive behavior and the likelihood of relapse, particularly among persons with disorders (e.g., attention-deficit/hyperactivity disorder, ADHD) and personality traits (e.g., impulsivity) linked to impulsive behavior.
Objectives
This study aimed to examine the effects of smoking abstinence on multiple measures of impulsivity among a non-clinical sample of adult smokers selected for high and low levels of ADHD symptoms.
Methods
In a within-subjects design, participants selected for high or low levels of self-reported ADHD symptoms (N=56) completed sessions following overnight abstinence and when smoking as usual (order counterbalanced). Measures of impulsive behavior included response inhibition (i.e., stop signal task), interference control (i.e., attentional modification of prepulse inhibition (PPI) of startle), and impulsive choice (i.e., hypothetical delay discounting).
Results
As hypothesized, abstinence decreased response inhibition and PPI. Although ADHD symptoms moderated abstinence effects on impulsive choice and response inhibition, the pattern was opposite to our predictions: the low-ADHD group responded more impulsively when abstinent, whereas the high-ADHD group was relatively unaffected by abstinence.
Conclusions
These findings highlight the importance of utilizing multiple laboratory measures to examine a multifactorial construct such as impulsive behavior and raise questions about how best to assess symptoms of ADHD and impulsivity among non-abstinent smokers.
doi:10.1007/s00213-011-2324-2
PMCID: PMC3184469  PMID: 21559802
Smoking; Abstinence; Impulsivity; Attention-deficit/hyperactivity disorder; Individual differences; Stop task; Delay discounting; Prepulse inhibition; Inhibitory control
3.  Tourette-like behaviors in the normal population are associated with hyperactive/impulsive ADHD-like behaviors but do not relate to deficits in conditioned inhibition or response inhibition 
Attention-Deficit Hyperactivity Disorder (ADHD) and Tourette Syndrome (TS) present as distinct conditions clinically; however, comorbidity and inhibitory control deficits have been proposed for both. Whilst such deficits have been studied widely within clinical populations, findings are mixed—partly due to comorbidity and/or medication effects—and studies have rarely distinguished between subtypes of the disorders. Studies in the general population are sparse. Using a continuity approach, the present study examined (i) the relationships between inattentive and hyperactive/impulsive aspects of ADHD and TS-like behaviors in the general population, and (ii) their unique associations with automatic and executive inhibitory control, as well as (iii) yawning (a proposed behavioral model of TS). One hundred and thirty-eight participants completed self-report measures for ADHD and TS-like behaviors as well as yawning, and a conditioned inhibition task to assess automatic inhibition. A sub-sample of fifty-four participants completed three executive inhibition tasks. An exploratory factor analysis of the TS behavior checklist supported a distinction between phonic and motor like pure TS behaviors. Whilst hyperactive/impulsive aspects of ADHD were associated with increased pure and compulsive TS-like behaviors, inattention in isolation was related to reduced obsessive-compulsive TS-like behaviors. TS-like behaviors were associated with yawning during situations of inactivity, and specifically motor TS was related to yawning during stress. Phonic TS and inattention aspects of ADHD were associated with yawning during concentration/activity. Whilst executive interference control deficits were linked to hyperactive/impulsive ADHD-like behaviors, this was not the case for inattentive ADHD or TS-like behaviors, which instead related to increased performance on some measures. No associations were observed for automatic conditioned inhibition.
doi:10.3389/fpsyg.2014.00946
PMCID: PMC4151087  PMID: 25228890
Attention-Deficit/Hyperactivity Disorder; Tourette Syndrome; conditioned inhibition; automatic inhibition; executive inhibition
4.  Intraindividual Variability in Inhibitory Function in Adults with ADHD – An Ex-Gaussian Approach 
PLoS ONE  2014;9(12):e112298.
Objective
Attention deficit disorder (ADHD) is commonly associated with inhibitory dysfunction contributing to typical behavioral symptoms like impulsivity or hyperactivity. However, some studies analyzing intraindividual variability (IIV) of reaction times in children with ADHD (cADHD) question a predominance of inhibitory deficits. IIV is a measure of the stability of information processing and provides evidence that longer reaction times (RT) in inhibitory tasks in cADHD are due to only a few prolonged responses which may indicate deficits in sustained attention rather than inhibitory dysfunction. We wanted to find out, whether a slowing in inhibitory functioning in adults with ADHD (aADHD) is due to isolated slow responses.
Methods
Computing classical RT measures (mean RT, SD), ex-Gaussian parameters of IIV (which allow a better separation of reaction time (mu), variability (sigma) and abnormally slow responses (tau) than classical measures) as well as errors of omission and commission, we examined response inhibition in a well-established GoNogo task in a sample of aADHD subjects without medication and healthy controls matched for age, gender and education.
Results
We did not find higher numbers of commission errors in aADHD, while the number of omissions was significantly increased compared with controls. In contrast to increased mean RT, the distributional parameter mu did not document a significant slowing in aADHD. However, subjects with aADHD were characterized by increased IIV throughout the entire RT distribution as indicated by the parameters sigma and tau as well as the SD of reaction time. Moreover, we found a significant correlation between tau and the number of omission errors.
Conclusions
Our findings question a primacy of inhibitory deficits in aADHD and provide evidence for attentional dysfunction. The present findings may have theoretical implications for etiological models of ADHD as well as more practical implications for neuropsychological testing in aADHD.
doi:10.1371/journal.pone.0112298
PMCID: PMC4257533  PMID: 25479234
5.  Reward circuit connectivity relates to delay discounting in children with attention-deficit/hyperactivity disorder 
Attention-deficit/hyperactivity disorder (ADHD) is a prevalent psychiatric disorder that has poor long-term outcomes and remains a major public health concern. Recent theories have proposed that ADHD arises from alterations in multiple neural pathways. Alterations in reward circuits are hypothesized as one core dysfunction, leading to altered processing of anticipated rewards. The nucleus accumbens (NAcc) is particularly important for reward processes; task-based fMRI studies have found atypical activation of this region while the participants performed a reward task. Understanding how reward circuits are involved with ADHD may be further enhanced by considering how the NAcc interacts with other brain regions. Here we used the technique of resting-state functional connectivity MRI (rs-fcMRI) to examine the alterations in the NAcc interactions and how they relate to impulsive decision making in ADHD. Using rs-fcMRI, this study: examined differences in functional connectivity of the NAcc between children with ADHD and control children; correlated the functional connectivity of NAcc with impulsivity, as measured by a delay discounting task; and combined these two initial segments to identify the atypical NAcc connections that were associated with impulsive decision making in ADHD. We found that functional connectivity of NAcc was atypical in children with ADHD and the ADHD-related increased connectivity between NAcc and the prefrontal cortex was associated with greater impulsivity (steeper delayed-reward discounting). These findings are consistent with the hypothesis that atypical signaling of the NAcc to the prefrontal cortex in ADHD may lead to excessive approach and failure in estimating future consequences; thus, leading to impulsive behavior.
doi:10.1016/j.euroneuro.2012.10.015
PMCID: PMC3581744  PMID: 23206930
Attention Deficit Hyperactivity Disorder; reward; nucleus accumbens; fMRI; delay discounting; functional connectivity
6.  Different Neural Patterns Are Associated With Trials Preceding Inhibitory Errors in Children With and Without Attention-Deficit/Hyperactivity Disorder 
Objective
Attention-deficit/hyperactivity disorder (ADHD) is associated with difficulty inhibiting impulsive, hyperactive, and off-task behavior. However, no studies have examined whether a distinct pattern of brain activity precedes inhibitory errors in typically developing (TD) children and children with ADHD. In healthy adults, increased activity in the default mode network, a set of brain regions more active during resting or internally focused states, predicts commission errors, suggesting that momentary lapses of attention are related to inhibitory failures.
Method
Event-related functional magnetic resonance imaging and a go/no-go paradigm were used to explore brain activity preceding errors in 13 children with ADHD and 17 TD controls.
Results
Comparing pre-error with pre-correct trials, TD children showed activation in the precuneus/posterior cingulate cortex and parahippocampal and middle frontal gyri. In contrast, children with ADHD demonstrated activation in the cerebellum, dorsolateral prefrontal cortex (DLPFC), and basal ganglia. Between-group comparison for the pre-error versus pre-correct contrast showed that children with ADHD showed greater activity in the cerebellum, DLPFC, and ventrolateral PFC compared with TD controls. Results of region-of-interest analysis confirmed that the precuneus/posterior cingulate cortex are more active in TD children compared with children with ADHD.
Conclusions
These preliminary data suggest that brain activation patterns immediately preceding errors differ between children with ADHD and TD children. In TD children, momentary lapses of attention precede errors, whereas pre-error activity in children with ADHD may be mediated by different circuits, such as those involved in response selection and control.
doi:10.1016/j.jaac.2011.03.014
PMCID: PMC3971481  PMID: 21703498
ADHD; children; functional magnetic resonance imaging; commission error; go/no-go task
7.  Rate dependent effects of acute nicotine on risk taking in young adults are not related to ADHD diagnosis 
Beneficial effects of nicotine on cognition and behavioral control are hypothesized to relate to the high rates of cigarette smoking in Attention-Deficit/Hyperactivity Disorder (ADHD). Given that ADHD is associated with both impulsivity and elevated risk taking, we hypothesized that nicotine modulates risk taking, as it does impulsivity. 26 non-smoking young adults (15 controls with normal impulsivity and 11 ADHD with high impulsivity) received 7 mg transdermal nicotine, 20 mg oral mecamylamine, and placebo on separate days, followed by the Balloon Analogue Risk Task (BART). Statistical analyses found no group differences in baseline risk taking. Reexamination of the data using a median split on baseline risk taking, to create high (HRT) and low (LRT) risk taking groups, revealed significant effects of nicotinic drugs that differed by group. Nicotine reduced risk taking in HRT and mecamylamine increased risk taking in LRT. This finding supports the hypothesis that nicotinic receptor function modulates risk taking broadly, beyond those with ADHD, and is consistent with rate dependent cholinergic modulation of other cognitive functions. Further, the results demonstrate that high impulsivity is separable from high risk taking in young adults with ADHD, supporting the utility of these differential behavioral phenotypes for neurobiological studies.
doi:10.1016/j.pbb.2012.11.005
PMCID: PMC3545091  PMID: 23159875
risk taking; Balloon Analog Risk Task; cholinergic; nicotine; mecamylamine; impulsivity; ADHD; acetylcholine
8.  Brain functional domains inform therapeutic interventions in attention-deficit/hyperactivity disorder and pediatric bipolar disorder 
A deeper understanding of how the relationships between impulsivity, reward systems and executive function deficits may be similar or different in attention-deficit/hyperactivity disorder (ADHD) and pediatric bipolar disorder (PBD) is fundamental for better defining phenotypy in these two developmental illnesses, and moving towards improved treatment and intervention. We focus our article on recent neurocognitive and neuroimaging data examining the behavioral and neural aspects of poor behavior regulation, response inhibition and reward systems in ADHD and PBD. In light of recent research evidence, we propose that the common behavioral manifestations of impulsivity in ADHD and PBD may indeed originate from different neural mechanisms mediated by altered reward systems. In order to define and differentiate these mechanisms, unlike previous approaches, our theoretical model examines the interface of the dorsal frontostriatal circuit, involved in behavior regulation, and the ventral frontostriatal circuit, which is involved in reward-related and affect processes. Preliminary evidence suggests that the neural systems involved in impulsivity, reward systems and executive function engage differently in the two illnesses. In PBD, `emotional impulsivity' is predominantly `bottom-up' and emotionally/motivationally driven, and stems from ventral frontostriatal circuitry dysfunction. By contrast, in ADHD `cognitive impulsivity' is predominantly `top-down' and more `cognitively driven', and stems from dorsal frontostriatal dysfunction. We discuss this evidence in view of clinically relevant questions and implications for illness-based intervention. We conclude that the reward-related mechanisms underlying the interactions between executive function, behavior regulation and impulsivity in PBD and ADHD may be differentially compromised, and in accordance differently shape the clinical symptoms of impulsivity and goal-directed behavior.
doi:10.1586/ern.11.71
PMCID: PMC3129632  PMID: 21651336
ADHD; adolescents; affect; behavior regulation; children; executive function; functional MRI; impulsivity; inhibition; neurocognitive; pediatric bipolar disorder; reward
9.  Neural substrates of impaired sensorimotor timing in adult attention-deficit/hyperactivity disorder 
Biological psychiatry  2010;68(4):359-367.
Background
Timing abilities are critical to the successful management of everyday activities and personal safety, and timing abnormalities have been argued to be fundamental to impulsiveness, a core symptom of attention-deficit/hyperactivity disorder (ADHD). Despite substantial evidence of timing deficits in ADHD youth, only two studies have explicitly examined timing in ADHD adults, and only at the supra-second time-scale. Also, the neural substrates of these deficits are largely unknown for both youth and adults with ADHD. The present study examined sub-second sensorimotor timing and its neural substrates in ADHD adults.
Methods
Using fMRI, we examined paced and unpaced finger tapping in a sample of 20 unmedicated adults with ADHD and 19 controls comparable on age, sex and estimated-IQ. The blood oxygenation level-dependent contrast response was used to estimate task-related neural activity.
Results
Behavioral data showed no between-group differences in mean tapping rates but greater within-subject variability in tap-to-tap intervals for ADHD adults relative to controls. Importantly, ADHD adults had greater clock rather than motor variability, consistent with a central timing locus for the atypical movements. The imaging results demonstrated that, relative to controls, ADHD adults showed less activity in a number of regions associated with sensorimotor timing, including prefrontal and precentral gyri, basal ganglia, cerebellum, inferior parietal lobule, superior temporal gyri and insula.
Conclusions
Our findings show that sub-second timing abnormalities in ADHD youth persist into adulthood and suggest that abnormalities in the temporal structure of behavior observed in ADHD adults result from atypical function of cortico-cerebellar and cortico-striatal timing systems.
doi:10.1016/j.biopsych.2010.05.012
PMCID: PMC2917236  PMID: 20619827
ADHD; fMRI; timing; cerebellum; frontal cortex; basal ganglia
10.  Behavioral and genetic evidence for a novel animal model of Attention-Deficit/Hyperactivity Disorder Predominantly Inattentive Subtype 
Background
According to DSM-IV there are three subtypes of Attention-Deficit/Hyperactivity Disorder, namely: ADHD predominantly inattentive type (ADHD-PI), ADHD predominantly Hyperactive-Impulsive Type (ADHD-HI), and ADHD combined type (ADHD-C). These subtypes may represent distinct neurobehavioral disorders of childhood onset with separate etiologies. The diagnosis of ADHD is behaviorally based; therefore, investigations into its possible etiologies should be based in behavior. Animal models of ADHD demonstrate construct validity when they accurately reproduce elements of the etiology, biochemistry, symptoms, and treatment of the disorder. Spontaneously hypertensive rats (SHR) fulfill many of the validation criteria and compare well with clinical cases of ADHD-C. The present study describes a novel rat model of the predominantly inattentive subtype (ADHD-PI).
Methods
ADHD-like behavior was tested with a visual discrimination task measuring overactivity, impulsiveness and inattentiveness. Several strains with varied genetic background were needed to determine what constitutes a normal comparison. Five groups of rats were used: SHR/NCrl spontaneously hypertensive and WKY/NCrl Wistar/Kyoto rats from Charles River; SD/NTac Sprague Dawley and WH/HanTac Wistar rats from Taconic Europe; and WKY/NHsd Wistar/Kyoto rats from Harlan. DNA was analyzed to determine background differences in the strains by PCR genotyping of eight highly polymorphic microsatellite markers and 2625 single nucleotide polymorphisms (SNPs).
Results
Compared to appropriate comparison strains (WKY/NHsd and SD/NTac rats), SHR/NCrl showed ADHD-C-like behavior: striking overactivity and poor sustained attention. Compared to WKY/NHsd rats, WKY/NCrl rats showed inattention, but no overactivity or impulsiveness. WH/HanTac rats deviated significantly from the other control groups by being more active and less attentive than the WKY/NHsd and SD/NTac rats. We also found substantial genomic differences between the WKY/NCrl and WKY/NHsd rats for eight short tandem repeat loci and 2625 SNPs. About 33.5 percent of the genome differs between the two WKY rat substrains, with large stretches of divergence on each chromosome.
Discussion
These data provide solid behavioral and genetic evidence that the WKY/NCrl and WKY/NHsd rats should be considered as separate substrains. Moreover, the behavioral features of the WKY/NCrl rat indicate that it should be a useful model for ADHD-PI, the primarily inattentive subtype of ADHD. The SD/NTac and the WH/HanTac rats show significant genetic and/or behavioral differences from WKY/NHsd rats and appear not to be appropriate controls in studies using the SHR/NCrl. The present results support the conclusion that SHR/NCrl is the best validated animal model of ADHD-C. The overactivity, impulsiveness and deficient sustained attention of the SHR/NCrl strain are independent behaviors. Thus, overactivity does not account for this strain's impulsiveness and deficient sustained attention. Finally, the present study shows that great care has to be exercised to select the model and comparison groups.
doi:10.1186/1744-9081-4-56
PMCID: PMC2628673  PMID: 19046438
11.  The Neural Basis of Decision-Making and Reward Processing in Adults with Euthymic Bipolar Disorder or Attention-Deficit/Hyperactivity Disorder (ADHD) 
PLoS ONE  2012;7(5):e37306.
Background
Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) share DSM-IV criteria in adults and cause problems in decision-making. Nevertheless, no previous report has assessed a decision-making task that includes the examination of the neural correlates of reward and gambling in adults with ADHD and those with BD.
Methodology/Principal Findings
We used the Iowa gambling task (IGT), a task of rational decision-making under risk (RDMUR) and a rapid-decision gambling task (RDGT) which elicits behavioral measures as well as event-related potentials (ERPs: fERN and P3) in connection to the motivational impact of events. We did not observe between-group differences for decision-making under risk or ambiguity (RDMUR and IGT); however, there were significant differences for the ERP-assessed RDGT. Compared to controls, the ADHD group showed a pattern of impaired learning by feedback (fERN) and insensitivity to reward magnitude (P3). This ERP pattern (fERN and P3) was associated with impulsivity, hyperactivity, executive function and working memory. Compared to controls, the BD group showed fERN- and P3-enhanced responses to reward magnitude regardless of valence. This ERP pattern (fERN and P3) was associated with mood and inhibitory control. Consistent with the ERP findings, an analysis of source location revealed reduced responses of the cingulate cortex to the valence and magnitude of rewards in patients with ADHD and BD.
Conclusions/Significance
Our data suggest that neurophysiological (ERPs) paradigms such as the RDGT are well suited to assess subclinical decision-making processes in patients with ADHD and BD as well as for linking the cingulate cortex with action monitoring systems.
doi:10.1371/journal.pone.0037306
PMCID: PMC3356275  PMID: 22624011
12.  Investigating the behavioral and self-report constructs of impulsivity domains using principal component analysis 
Behavioural Pharmacology  2009;20(5-6):390-399.
Impulsivity, often defined as a human behavior characterized by the inclination of an individual to act on urge rather than thought, with diminished regard to consequences, encompasses a range of maladaptive behaviors which are in turn affected by distinct neural systems. Congruent with the above definition, behavioral studies have consistently shown that the underlying construct of impulsivity is multidimensional in nature. However, research to date has been inconclusive regarding the different domains or constructs that constitute this behavior. In addition there is also no clear consensus as to whether self-report and laboratory based measures of impulsivity measure the same or different domains. The current study aimed to: 1) characterize the underlying multidimensional construct of impulsivity using a sample with varying degrees of putative impulsivity related to substance misuse, including subjects who were at-risk of substance use or addicted (ARA), and 2) assess relationships between self-report and laboratory measures of impulsivity, using a principal component-based factor analysis. In addition, our supplementary goal was to evaluate the structural constructs of impulsivity within each group separately (healthy and ARA). We used five self-report measures (Behavioral Inhibition System/Behavioral Activation System (BIS/BAS), Barratt Impulsivity Scale-11, Padua Inventory, Zuckerman Sensation Seeking Scale (SSS), and Sensitivity to Punishment and Sensitivity to Reward Questionnaire) and two computer based laboratory tasks (Balloon Analog Risk Task and the Experiential Delay Task) to measure aspects of impulsivity in a total of 176 adult subjects. Subjects included healthy controls (N=89), non-alcoholic subjects with family histories of alcoholism (FHP; N=36) and both former (N=20) and current (N=31) cocaine users. Subjects with a family history of alcoholism and cocaine abusers were grouped together as “at-risk/addicted” (ARA) to evaluate our supplementary goal. Our overall results revealed the multidimensional nature of the impulsivity construct as captured optimally through a five factor solution that accounted for nearly 70% of the total variance. The five factors/components were imputed as follows “Self-Reported Behavioral Activation”, “Self-Reported Compulsivity and Reward/Punishment”, “Self-Reported Impulsivity”, “Behavioral Temporal Discounting” and “Behavioral Risk-Taking.” We also found that contrary to previously published reports, there was significant overlap between certain laboratory and self-report measures, indicating that they might be measuring the same impulsivity domain. In addition, our supplemental analysis also suggested that the impulsivity constructs were largely, but not entirely the same within the healthy and ARA groups.
doi:10.1097/FBP.0b013e32833113a3
PMCID: PMC3268653  PMID: 19724194
impulsivity; behavior; substance abuse; cocaine; alcohol; factor analysis; PCA; BIS-BAS; BIS-11; EDT; BART; Zuckerman; SPSRQ; human
13.  Processing Speed Weakness in Children and Adolescents with Non-Hyperactive but Inattentive ADHD (ADD) 
DSM-IV-TR defines ADHD-Predominantly Inattentive as allowing up to five symptoms of hyperactivity/impulsivity, while theories of the inattentive type usually assume a group that is hypoactive and characterized by processing speed and cognitive interference deficits. In a community-recruited sample of 572 children and adolescents, a pure inattentive subtype of ADHD (ADD) was defined as those who met DSM-IV-TR criteria for ADHD-PI but had two or fewer hyperactive/impulsive symptoms. Processing and output speeds of those with ADD were compared to those identified with DSM-IV-TR ADHD combined type and non-ADHD controls. These results were then contrasted with those found when DSM-IV-TR defined ADHD-PI was compared with ADHD-C and controls. Processing and output speed were assessed with the Trailmaking A and B and the Stroop Naming Tests. Cognitive interference control was assessed with the interference score from the Stroop Task. Slower cognitive interference speed was found in the ADD vs. ADHD-C and controls comparisons, but not the ADHD-PI versus ADHD-C and controls comparisons. On output speed measures, ADD exhibited the slowest performance, significantly different from controls and the effect size for the set-shifting speed contrast (Trailmaking B) contrast was double that of the ADHD-PI vs. control comparison. ADHD-Inattentive type as defined by the DSM-IV-TR is a heterogeneous condition with a meaningful proportion of those affected exhibiting virtually no hyperactive/impulsive symptoms. This subgroup may represent a distinct inattentive condition characterized by poor cognitive interference control and slow processing or output speed.
doi:10.1080/09297049.2010.485126
PMCID: PMC2943531  PMID: 20560083
attention-deficit/hyperactivity disorder; inattentive subtype; processing speed; Stroop color/word test; ADD
14.  Executive functions, impulsivity, and inhibitory control in adolescents: A structural equation model 
Background. Adolescence represents a critical period for brain development, addressed by neurodevelopmental models to frontal, subcortical-limbic, and striatal activation, a pattern associated with rise of impulsivity and deficits in inhibitory control. The present study aimed at studying the association between self-report measures of impulsivity and inhibitory control with executive function in adolescents, employing structural equation modeling. Method. Tests were administered to 434 high school students. Acting without thinking was measured through the Barratt Impulsiveness Scale and the Dickman Impulsivity Inventory, reward sensitivity through the Behavioral Activation System, and sensation seeking through the Zuckerman–Kuhlman–Aluja Personali- ty Questionnaire. Inhibitory control was assessed through the Behavioral Inhibition System. The performance at the Wisconsin Card Sorting Task indicated executive function. Three models were specified using Sample Covariance Matrix, and the estimated parameters using Maximum Likelihood. Results. In the final model, impulsivity and inhibitory control predicted executive function, but sensation seeking did not. The fit of the model to data was excellent. Conclusions. The hypothesis that inhibitory control and impulsivity are predictors of executive function was supported. Our results appear informative of the validity of self-report measures to examine the relation between impulsivity traits rather than others to regulatory function of cognition and behavior.
doi:10.5709/acp-0154-5
PMCID: PMC4118776  PMID: 25157298
executive function; impulsivity; inhibitory control; sensation seeking; personality
15.  Dopamine Agonists and the Suppression of Impulsive Motor Actions in Parkinson’s Disease 
Journal of cognitive neuroscience  2012;24(8):1709-1724.
The suppression of spontaneous motor impulses is an essential facet of cognitive control that is linked to frontal-basal ganglia circuitry. Basal ganglia dysfunction caused by Parkinson’s disease (PD) disrupts the proficiency of action suppression, but how pharmacotherapy for PD impacts impulsive motor control is poorly understood. Dopamine agonists improve motor symptoms of PD, but can also provoke impulsive-compulsive behaviors (ICB). We investigated whether dopamine agonist medication has a beneficial or detrimental effect on impulsive action control in thirty-eight PD patients, half of whom had current ICB. Participants performed the Simon conflict task, which measures susceptibility to acting on spontaneous action impulses as well as the proficiency of suppressing these impulses. Compared to an off agonist state, patients on their agonist were no more susceptible to reacting impulsively, but were less proficient at suppressing the interference from the activation of impulsive actions. Importantly, agonist effects depended on baseline performance in the off agonist state; more proficient suppressors off agonist experienced a reduction in suppression on agonist, whereas less proficient suppressors off agonist showed improved suppression on agonist. Patients with active ICB were actually less susceptible to making fast, impulsive response errors than patients without ICB, suggesting that behavioral problems in this subset of patients may be less related to impulsivity in motor control. Our findings provide further evidence that dopamine agonist medication impacts specific cognitive control processes and that the direction of its effects depends on individual differences in performance off medication.
doi:10.1162/jocn_a_00241
PMCID: PMC3657467  PMID: 22571461
Parkinson’s disease; simon task; inhibition; dopamine agonist; impulse control
16.  Trait Impulsivity and Response Inhibition in Antisocial Personality Disorder 
Journal of psychiatric research  2009;43(12):1057-1063.
Background
Impulsive behavior is a prominent characteristic of antisocial personality disorder. Impulsivity is a complex construct, however, representing distinct domains of cognition and action. Leading models refer to impulsivity as an inability to evaluate a stimulus fully before responding to it (rapid-response impulsivity), and as an inability to delay responding despite a larger reward (reward-delay impulsivity). We investigated these models in terms of the diagnosis and severity of antisocial personality disorder.
Methods
Thirty-four male subjects on probation/parole who met DSM-IV criteria for ASPD, and 30 male healthy comparison subjects, matched by ethnicity, were recruited from the community. The Barratt Impulsiveness Scale (BIS-11) provided an integrated measure of trait impulsivity. Rapid-response impulsivity was assessed using the Immediate Memory Task (IMT), a continuous performance test. Reward delay impulsivity was assessed using the Two-choice Impulsivity Paradigm (TCIP), where subjects had the choice of smaller-sooner or larger-delayed rewards, and the Single Key Impulsivity Paradigm (SKIP), a free operant responding task.
Results
Compared to controls, subjects with ASPD had higher BIS-11 scores (Effect Size (E.S.) = 0.95). They had slower reaction times to IMT commission errors (E.S. = 0.45). Correct detections, a measure of attention, were identical to controls. On the SKIP, they had a shorter maximum delay for reward (E.S. = 0.76), but this was not significant after correction for age and education. The groups did not differ on impulsive choices on the TCIP (E.S. < 0.1). On probit analysis with age and education as additional independent variables, BIS-11 score, IMT reaction time to a commission error, and IMT positive response bias contributed significantly to diagnosis of ASPD; SKIP delay for reward did not. Severity of ASPD, assessed by the number of ASPD symptoms endorsed on the SCID-II, correlated significantly with commission errors (impulsive responses) on the IMT, and with liberal IMT response bias. This relationship persisted with correction for age and education.
Discussion
These results suggest that ASPD is characterized by increased rapid-response impulsivity. Aspects of impulsivity related to reward-delay or attention appear relatively intact.
doi:10.1016/j.jpsychires.2009.03.003
PMCID: PMC2716408  PMID: 19345957
Antisocial personality disorder; impulsive behavior; impulse control disorders; attention; reward
17.  MEG event-related desynchronization and synchronization deficits during basic somatosensory processing in individuals with ADHD 
Background
Attention-Deficit/Hyperactivity Disorder (ADHD) is a prevalent, complex disorder which is characterized by symptoms of inattention, hyperactivity, and impulsivity. Convergent evidence from neurobiological studies of ADHD identifies dysfunction in fronto-striatal-cerebellar circuitry as the source of behavioural deficits. Recent studies have shown that regions governing basic sensory processing, such as the somatosensory cortex, show abnormalities in those with ADHD suggesting that these processes may also be compromised.
Methods
We used event-related magnetoencephalography (MEG) to examine patterns of cortical rhythms in the primary (SI) and secondary (SII) somatosensory cortices in response to median nerve stimulation, in 9 adults with ADHD and 10 healthy controls. Stimuli were brief (0.2 ms) non-painful electrical pulses presented to the median nerve in two counterbalanced conditions: unpredictable and predictable stimulus presentation. We measured changes in strength, synchronicity, and frequency of cortical rhythms.
Results
Healthy comparison group showed strong event-related desynchrony and synchrony in SI and SII. By contrast, those with ADHD showed significantly weaker event-related desynchrony and event-related synchrony in the alpha (8–12 Hz) and beta (15–30 Hz) bands, respectively. This was most striking during random presentation of median nerve stimulation. Adults with ADHD showed significantly shorter duration of beta rebound in both SI and SII except for when the onset of the stimulus event could be predicted. In this case, the rhythmicity of SI (but not SII) in the ADHD group did not differ from that of controls.
Conclusion
Our findings suggest that somatosensory processing is altered in individuals with ADHD. MEG constitutes a promising approach to profiling patterns of neural activity during the processing of sensory input (e.g., detection of a tactile stimulus, stimulus predictability) and facilitating our understanding of how basic sensory processing may underlie and/or be influenced by more complex neural networks involved in higher order processing.
doi:10.1186/1744-9081-4-8
PMCID: PMC2266931  PMID: 18269747
18.  Individual Differences in Impulsivity Predict Anticipatory Eye Movements 
PLoS ONE  2011;6(10):e26699.
Impulsivity is the tendency to act without forethought. It is a personality trait commonly used in the diagnosis of many psychiatric diseases. In clinical practice, impulsivity is estimated using written questionnaires. However, answers to questions might be subject to personal biases and misinterpretations. In order to alleviate this problem, eye movements could be used to study differences in decision processes related to impulsivity. Therefore, we investigated correlations between impulsivity scores obtained with a questionnaire in healthy subjects and characteristics of their anticipatory eye movements in a simple smooth pursuit task. Healthy subjects were asked to answer the UPPS questionnaire (Urgency Premeditation Perseverance and Sensation seeking Impulsive Behavior scale), which distinguishes four independent dimensions of impulsivity: Urgency, lack of Premeditation, lack of Perseverance, and Sensation seeking. The same subjects took part in an oculomotor task that consisted of pursuing a target that moved in a predictable direction. This task reliably evoked anticipatory saccades and smooth eye movements. We found that eye movement characteristics such as latency and velocity were significantly correlated with UPPS scores. The specific correlations between distinct UPPS factors and oculomotor anticipation parameters support the validity of the UPPS construct and corroborate neurobiological explanations for impulsivity. We suggest that the oculomotor approach of impulsivity put forth in the present study could help bridge the gap between psychiatry and physiology.
doi:10.1371/journal.pone.0026699
PMCID: PMC3202566  PMID: 22046334
19.  Behavioral models of impulsivity in relation to ADHD: Translation between clinical and preclinical studies 
Clinical psychology review  2006;26(4):379-395.
Impulsivity, broadly defined as action without foresight, is a component of numerous psychiatric illnesses including attention deficit/hyperactivity disorder (ADHD), mania and substance abuse. In order to investigate the mechanisms underpinning impulsive behavior, the nature of impulsivity itself needs to be defined in operational terms that can be used as the basis for empirical investigation. Due to the range of behaviors that the term impulsivity describes, it has been suggested that impulsivity is not a unitary construct, but encompasses a variety of related phenomena that may differ in their biological basis. Through fractionating impulsivity into these component parts, it has proved possible to devise different behavioral paradigms to measure various aspects of impulsivity in both humans and laboratory animals. This review describes and evaluates some of the current behavioral models of impulsivity developed for use with rodents based on human neuropsychological tests, focusing on the five-choice serial reaction time task, the stop-signal reaction time task and delay-discounting paradigms. Furthermore, the contributions made by preclinical studies using such methodology to improve our understanding of the neural and neurochemical basis of impulsivity and ADHD are discussed, with particular reference to the involvement of both the serotonergic and dopaminergic systems, and frontostriatal circuitry.
doi:10.1016/j.cpr.2006.01.001
PMCID: PMC1892795  PMID: 16504359
ADHD; Impulsivity; Frontal cortex; Inhibition; Serotonin; Dopamine
20.  Behavioral models of impulsivity in relation to ADHD: Translation between clinical and preclinical studies 
Clinical Psychology Review  2006;26(4):379-395.
Impulsivity, broadly defined as action without foresight, is a component of numerous psychiatric illnesses including attention deficit/hyperactivity disorder (ADHD), mania and substance abuse. In order to investigate the mechanisms underpinning impulsive behavior, the nature of impulsivity itself needs to be defined in operational terms that can be used as the basis for empirical investigation. Due to the range of behaviors that the term impulsivity describes, it has been suggested that impulsivity is not a unitary construct, but encompasses a variety of related phenomena that may differ in their biological basis. Through fractionating impulsivity into these component parts, it has proved possible to devise different behavioral paradigms to measure various aspects of impulsivity in both humans and laboratory animals. This review describes and evaluates some of the current behavioral models of impulsivity developed for use with rodents based on human neuropsychological tests, focusing on the five-choice serial reaction time task, the stop-signal reaction time task and delay-discounting paradigms. Furthermore, the contributions made by preclinical studies using such methodology to improve our understanding of the neural and neurochemical basis of impulsivity and ADHD are discussed, with particular reference to the involvement of both the serotonergic and dopaminergic systems, and frontostriatal circuitry.
doi:10.1016/j.cpr.2006.01.001
PMCID: PMC1892795  PMID: 16504359
ADHD; Impulsivity; Frontal cortex; Inhibition; Serotonin; Dopamine
21.  Event-related fMRI of inhibitory control in the Predominantly Inattentive and Combined Subtypes of AD/HD 
Background and Purpose
To examine the neurophysiological basis for the pronounced differences in hyperactivity and impulsiveness that distinguish the Predominantly Inattentive type of Attention-Deficit/Hyperactivity Disorder (ADHD-PI) from the combined type of the disorder (ADHD-C).
Methods
Event-related brain responses to a go/no-go test of inhibitory control were measured with functional magnetic resonance imaging (fMRI) in 11 children with ADHD-C and nine children with ADHD-PI, aged 7 to 13 years, who were matched for age, sex, and intelligence.
Results
There were no significant group differences in task performance. Children with ADHD-C and ADHD-PI activated overlapping regions of right inferior frontal gyrus, right superior temporal lobe, and left inferior parietal lobe during inhibitory control. However, the magnitude of the activation in the temporal and parietal regions, as well as in the bilateral middle frontal gyrus, was greater in children with ADHD-PI than those with ADHD-C. Conversely, children with ADHD-C activated bilateral medial occipital lobe to a greater extent than children with ADHD-PI.
Conclusions
The results provide preliminary evidence that phenotypic differences between the ADHD-C and ADHD-PI subtypes are associated with differential activation of regions that have previously been implicated in the pathophysiology of ADHD and are thought to mediate executive and attentional processes.
doi:10.1111/j.1552-6569.2008.00289.x
PMCID: PMC2711513  PMID: 19594667
22.  Impulsivity in Adolescents with Bipolar Disorder and/or Attention-Deficit/Hyperactivity Disorder and Healthy Controls as Measured by the Barratt Impulsiveness Scale 
Abstract
Objective
To compare the type and degree of impulsivity among adolescents with bipolar disorder (BD), adolescents with attention-deficit/hyperactivity disorder (ADHD), and healthy comparison subjects using the Barratt Impulsiveness Scale, Version 11 (BIS-11).
Methods
Manic adolescents with BD (n=31), adolescents with ADHD (n=30), and healthy subjects (n=25) completed the BIS-11, a 30-item, self-report scale with three subscales (cognitive, motor, and nonplanning). The BIS-11 total and subscale scores were compared among groups. We also examined associations among the BIS-11, Young Mania Rating Scale and co-occurring disruptive behavioral disorders (DBDs) within the BD group.
Results
Total and each subscale scores were significantly higher for the BD group than for the healthy controls (p<0.05). The total scores and the cognitive and motor subscale scores were significantly higher for the ADHD group than for the healthy control group (p<0.05). However, there was no statistically significant difference between the nonplanning subscale scores of the ADHD group and the healthy control group (p>0.05). There were no significant differences between the BD and ADHD groups or between the BD groups with and without ADHD. The BD patients with DBDs (i.e., oppositional defiant disorder or conduct disorder) scored significantly higher on the motor subscale than did BD patients without DBDs. There were no statistically significant associations between the Young Mania Rating Scale and BIS-11 scores within the BD group.
Conclusion
Our findings suggest that impulsivity is elevated in adolescents with BD as well as adolescents with ADHD, except for nonplanning impulsivity, which was not significantly different between adolescents with ADHD and the healthy comparison group. This may suggest that nonplanning impulsivity is relatively specific to adolescents with BD. Additionally, our data indicate that elevations in impulsivity, as measured by the BIS-11, may be independent of symptoms severity and, therefore, may be a stable, trait-related component of BD.
doi:10.1089/cap.2010.0096
PMCID: PMC3205791  PMID: 22040191
23.  The influence of serotonin- and other genes on impulsive behavioral aggression and cognitive impulsivity in children with attention-deficit/hyperactivity disorder (ADHD): Findings from a family-based association test (FBAT) analysis 
Background
Low serotonergic (5-HT) activity correlates with increased impulsive-aggressive behavior, while the opposite association may apply to cognitive impulsiveness. Both types of impulsivity are associated with attention-deficit/hyperactivity disorder (ADHD), and genes of functional significance for the 5-HT system are implicated in this disorder. Here we demonstrate the separation of aggressive and cognitive components of impulsivity from symptom ratings and test their association with 5-HT and functionally related genes using a family-based association test (FBAT-PC).
Methods
Our sample consisted of 1180 offspring from 607 families from the International Multicenter ADHD Genetics (IMAGE) study. Impulsive symptoms were assessed using the long forms of the Conners and the Strengths and Difficulties parent and teacher questionnaires. Factor analysis showed that the symptoms aggregated into parent- and teacher-rated behavioral and cognitive impulsivity. We then selected 582 single nucleotide polymorphisms (SNPs) from 14 genes directly or indirectly related to 5-HT function. Associations between these SNPs and the behavioral/cognitive groupings of impulsive symptoms were evaluated using the FBAT-PC approach.
Results
In the FBAT-PC analysis for cognitive impulsivity 2 SNPs from the gene encoding phenylethanolamine N-methyltransferase (PNMT, the rate-limiting enzyme for adrenalin synthesis) attained corrected gene-wide significance. Nominal significance was shown for 12 SNPs from BDNF, DRD1, HTR1E, HTR2A, HTR3B, DAT1/SLC6A3, and TPH2 genes replicating reported associations with ADHD. For overt aggressive impulsivity nominal significance was shown for 6 SNPs from BDNF, DRD4, HTR1E, PNMT, and TPH2 genes that have also been reported to be associated with ADHD. Associations for cognitive impulsivity with a SERT/SLC6A4 variant (STin2: 12 repeats) and aggressive behavioral impulsivity with a DRD4 variant (exon 3: 3 repeats) are also described.
Discussion
A genetic influence on monoaminergic involvement in impulsivity shown by children with ADHD was found. There were trends for separate and overlapping influences on impulsive-aggressive behavior and cognitive impulsivity, where an association with PNMT (and arousal mechanisms affected by its activity) was more clearly involved in the latter. Serotonergic and dopaminergic mechanisms were implicated in both forms of impulsivity with a wider range of serotonergic mechanisms (each with a small effect) potentially influencing cognitive impulsivity. These preliminary results should be followed up with an examination of environmental influences and associations with performance on tests of impulsivity in the laboratory.
doi:10.1186/1744-9081-4-48
PMCID: PMC2577091  PMID: 18937842
24.  Biological and Rearing Mother Influences on Child ADHD Symptoms: Revisiting the Developmental Interface between Nature and Nurture 
Background
Families of children with attention deficit hyperactivity disorder (ADHD) report more negative family relationships than families of children without ADHD. Questions remain as to the role of genetic factors underlying associations between family relationships and children’s ADHD symptoms, and the role of children’s ADHD symptoms as an evocative influence on the quality of relationships experienced within such families. Utilizing the attributes of two genetically sensitive research designs, the present study examined associations between biologically related and non-biologically related maternal ADHD symptoms, parenting practices, child impulsivity/activation, and child ADHD symptoms. The combined attributes of the study designs permit assessment of associations while controlling for passive genotype-environment correlation and directly examining evocative genotype-environment correlation (rGE); two relatively under examined confounds of past research in this area.
Methods
A cross-sectional adoption-at-conception design (Cardiff IVF Study; C-IVF) and a longitudinal adoption-at-birth design (Early Growth and Development Study; EGDS) were used. The C-IVF sample included 160 mothers and children (age 5–8 years). The EGDS sample included 320 linked sets of adopted children (age 6 years), adoptive-, and biologically-related mothers. Questionnaires were used to assess maternal ADHD symptoms, parenting practices, child impulsivity/activation, and child ADHD symptoms. A cross-rater approach was used across measures of maternal behavior (mother reports) and child ADHD symptoms (father reports).
Results
Significant associations were revealed between rearing mother ADHD symptoms, hostile parenting behavior, and child ADHD symptoms in both samples. Because both samples consisted of genetically-unrelated mothers and children, passive rGE was removed as a possible explanatory factor underlying these associations. Further, path analysis revealed evidence for evocative rGE processes in the longitudinal adoption-at-birth study (EGDS) from biologically-related maternal ADHD symptoms to biologically-unrelated maternal hostile parenting through early disrupted child behavior (impulsivity/activation), with maternal hostile parenting and disrupted child behavior associated with later child ADHD symptoms, controlling for concurrent adoptive mother ADHD symptoms.
Conclusions
Results highlight the importance of genetically-influenced child ADHD-related temperamental attributes on genetically-unrelated maternal hostility that in turn links to later child ADHD symptoms. Implications for intervention programs focusing on early family processes and the precursors of child ADHD symptoms are discussed.
doi:10.1111/jcpp.12100
PMCID: PMC3767192  PMID: 24007415
ADHD; parenting; gene-environment correlation; adoption
25.  Preparatory neural networks are impaired in adults with attention-deficit/hyperactivity disorder during the antisaccade task☆ 
NeuroImage : Clinical  2012;2:63-78.
Adults with attention-deficit/hyperactivity disorder (ADHD) often display executive function impairments, particularly in inhibitory control. The antisaccade task, which measures inhibitory control, requires one to suppress an automatic prosaccade toward a salient visual stimulus and voluntarily make an antisaccade in the opposite direction. ADHD patients not only have longer saccadic reaction times, but also make more direction errors (i.e., a prosaccade was executed toward the stimulus) during antisaccade trials. These deficits may stem from pathology in several brain areas that are important for executive control. Using functional MRI with a rapid event-related design, adults with combined subtype of ADHD (coexistence of attention and hyperactivity problems), who abstained from taking stimulant medication 20 h prior to experiment onset, and age-match controls performed pro- and antisaccade trials that were interleaved with pro- and anti-catch trials (i.e., instruction was presented but no target appeared, requiring no response). This method allowed us to examine brain activation patterns when participants either prepared (during instruction) or executed (after target appearance) correct pro or antisaccades. Behaviorally, ADHD adults displayed several antisaccade deficits, including longer and more variable reaction times and more direction errors, but saccade metrics (i.e., duration, velocity, and amplitude) were normal. When preparing to execute an antisaccade, ADHD adults showed less activation in frontal, supplementary, and parietal eye fields, compared to controls. However, activation in these areas was normal in the ADHD group during the execution of a correct antisaccade. Interestingly, unlike controls, adults with ADHD produced greater activation than controls in dorsolateral prefrontal cortex during antisaccade execution, perhaps as part of compensatory mechanisms to optimize antisaccade production. Overall, these data suggest that the saccade deficits observed in adults with ADHD do not result from an inability to execute a correct antisaccade but rather the failure to properly prepare (i.e., form the appropriate task set) for the antisaccade trial. The data support the view that the executive impairments, including inhibitory control, in ADHD adults are related to poor response preparation.
Highlights
► The neural correlates of inhibitory control in adults with ADHD were examined. ► We used an interleaved pro and antisaccade task simultaneously with functional MRI. ► This enabled the dissociation of automatic versus voluntary control. ► Patients had less activity in fronto-parietal areas during antisaccade preparation. ► Overall, antisaccade deficits in ADHD adults likely arise from poor preparation.
doi:10.1016/j.nicl.2012.10.006
PMCID: PMC3777763  PMID: 24179760
ADHD; Saccade; fMRI; Preparation; Inhibition

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