Cognitive impulsivity in Parkinson's disease patients: Assessment and pathophysiology

Impulsivity may be induced by therapeutic interventions (dopamine replacement therapies and sub‐thalamic nucleus (STN) stimulation) in patients with Parkinson's disease (PD). The present review has two goals. First, to describe the most frequently encountered facets of cognitive impulsivity and to stress the links between cognitive impulsivity and aspects such as reward‐related decision making, risk‐taking, and time‐processing in healthy population. The most widely used related cognitive impulsivity paradigms are presented. Second, to review the results of studies on cognitive impulsivity in healthy volunteers and in patients with PD, the latter support the applicability and clinical relevance of this construct in PD population. Data show that PD treatments may favor impulsivity via different mechanisms. Suggestions on the roles of dopamine and STN in the pathophysiology of cognitive impulsivity are proposed. © 2009 Movement Disorder Society     

Memory impairment suggests hippocampal dysfunction in abstinent ecstasy users

Previous studies have consistently shown impairments of memory and learning in regular users of the neurotoxic drug ecstasy (3,4-methylenedioxymethamphetamine [MDMA]). In addition, deficits in working memory, planning ability and central executive control, as well as high cognitive impulsivity, were also reported in some studies. Hence, the memory decrements may be secondary due to other cognitive failures. The purpose of this study was to analyze the nature of the cognitive deficits of ecstasy users. Tests of memory, working memory, central executive function and cognitive impulsivity were administered to 60 currently abstinent ecstasy users and to 30 nonusers. Heavy ecstasy users (n=30, lifetime dose > or =80 ecstasy tablets) had lower memory performance than both nonusers and moderate users (n=30, lifetime dose <80 ecstasy tablets). In contrast, we found no group differences in central executive function, working memory, planning ability and cognitive impulsivity between ecstasy users and controls. Poorer memory and working memory performance was associated with a heavier pattern of ecstasy use. Low working memory, planning ability and central executive control and high cognitive impulsivity did not predict poor memory performance. Our results indicate primary memory dysfunction in heavy ecstasy users, which may be related to a particularly high vulnerability of the hippocampus to the neurotoxic effects of MDMA. Hippocampal dysfunction after ecstasy use may be a risk factor for earlier onset and/or more severe age-related memory decline in later years.     

The Role of Executive Cognitive Functions in Changing Substance Use: What We Know and What We Need to Know

Background  Executive cognitive functions (ECF) have been linked to skills such as planning, organizing, problem solving, decision-making, initiating and self-regulating behavior, working memory, and motivation; critical activities needed to monitor and change substance use behavior. Purpose  The purpose of this study is to investigate how ECF may impact important variables associated with changing substance use behavior. Methods  This study is a critical review of the extant literature about how ECF may influence substance abuse treatment outcomes and behavior change. Results  A review of the literature found evidence that poorer ECF likely hinders substance use behavior change and is often associated with behavior labeled as denial. However, the relationship between ECF and substance abuse appears to be highly complex. Conclusions  Traditional methods of substance abuse assessment, interpretation of behavior, and intervention may need to be reconsidered in light of new research about executive cognitive dysfunction. Implications for future research are discussed.     

Conceptualizing impulsivity and risk taking in bipolar disorder: importance of history of alcohol abuse

Background:  Elevated levels of impulsivity and increased risk taking are thought to be core features of both bipolar disorder (BD) and addictive disorders. Given the high rates of comorbid alcohol abuse in BD, alcohol addiction may exacerbate impulsive behavior and risk-taking propensity in BD. Here we examine multiple dimensions of impulsivity and risk taking, using cognitive tasks and self-report measures, in BD patients with and without a history of alcohol abuse.
Methods:  Thirty-one BD subjects with a prior history of alcohol abuse or dependence (BD-A), 24 BD subjects with no history of alcohol abuse/dependence (BD-N), and 25 healthy control subjects (HC) were assessed with the Barratt Impulsiveness Scale (BIS) and the computerized Balloon Analogue Risk Task (BART).
Results:  Both BD groups scored significantly higher than controls on the BIS. In contrast, only the BD-A group showed impaired performance on the BART. BD-A subjects popped significantly more balloons than the BD-N and HC groups. In addition, subjects in the BD-A group failed to adjust their performance after popping balloons. Severity of mood symptomatology was not associated with performance on either task.
Discussion:  The current study supports a primary role of prior alcohol abuse in risk-taking propensity among patients with bipolar disorder. In addition, findings suggest that impulsivity and risky behavior, as operationalized by self-report and experimental cognitive probes, respectively, are separable constructs that tap distinct aspects of the bipolar phenotype.     

The lateral and ventromedial prefrontal cortex work as a dynamic integrated system: evidence from FMRI connectivity analysis

Recent functional magnetic resonance imaging (fMRI) investigations of the interaction between cognition and reward processing have found that the lateral prefrontal cortex (PFC) areas are preferentially activated to both increasing cognitive demand and reward level. Conversely, ventromedial PFC (VMPFC) areas show decreased activation to the same conditions, indicating a possible reciprocal relationship between cognitive and emotional processing regions. We report an fMRI study of a rewarded working memory task, in which we further explore how the relationship between reward and cognitive processing is mediated. We not only assess the integrity of reciprocal neural connections between the lateral PFC and VMPFC brain regions in different experimental contexts but also test whether additional cortical and subcortical regions influence this relationship. Psychophysiological interaction analyses were used as a measure of functional connectivity in order to characterize the influence of both cognitive and motivational variables on connectivity between the lateral PFC and the VMPFC. Psychophysiological interactions revealed negative functional connectivity between the lateral PFC and the VMPFC in the context of high memory load, and high memory load in tandem with a highly motivating context, but not in the context of reward alone. Physiophysiological interactions further indicated that the dorsal anterior cingulate and the caudate nucleus modulate this pathway. These findings provide evidence for a dynamic interplay between lateral PFC and VMPFC regions and are consistent with an emotional gating role for the VMPFC during cognitively demanding tasks. Our findings also support neuropsychological theories of mood disorders, which have long emphasized a dysfunctional relationship between emotion/motivational and cognitive processes in depression.     

��Better the devil you know��: a preliminary study of the differential modulating effects of reputation on reward processing for boys with and without externalizing behavior problems

Very little is known about the neurobiological correlates of reward processing during social decision-making in the developing brain and whether prior social and moral information (reputations) modulates reward responses in youth as has been demonstrated in adults. Moreover, although externalizing behavior problems in youth are associated with deficits in reward processing and social cognition, a real-life social interaction paradigm using functional neuroimaging (fMRI) has not yet been applied to probe reward processing in such youth. Functional neuroimaging was used to examine the neural correlates of reward-related decision-making during a trust task in two samples of age-matched 11 to 16-year-old boys: with (n?=?10) and without (n?=?10) externalizing behavior problems. The task required subjects to decide whether to share or keep monetary rewards from partners they themselves identified during a real-life peer sociometric procedure as interpersonally aggressive or kind (vs. neutral). Results supported the notion that prior social and moral information (reputations) modulated reward responses in the adolescent brain. Moreover, boys with externalizing problems showed differential activation in the bilateral insula during the decision phase of the game as well as the caudate and anterior insula during the outcome phase of the game. Similar activation in adolescents in response to reward related stimuli as found in adults suggests some developmental continuity in corticostriatal circuits. Group differences are interpreted with caution given the small group sizes in the current study. Notwithstanding this limitation, the study provides preliminary evidence for anomalous reward responses in boys with externalizing behavior problems, thereby providing a possible biological correlate of well-established social-cognitive and reward-related theories of externalizing behavior disorders.     

Reward-based decision-making and aging

Healthy aging is associated with a number of neuroanatomical and neurobiological alterations that result in various cognitive changes. Both, the dopaminergic as well as the serotonergic system are subject to change during aging. Receptor loss and severe structural changes in PFC and striatum have been reported. Aging is associated with a progressive decline in several cognitive functions, such as episodic memory, working memory, and processing speed. Furthermore, it is associated with deficits in tasks requiring adaptation to external feedback of right or wrong, or task-switching. Here, we develop the hypothesis that this loss of behavioral flexibility is caused by structural and functional alterations of the reward system leading to impairments in reward processing, learning stimulus reinforcement associations, and reward-based decision-making. We review (a) data on neural correlates and substrates of reward processing in young healthy animals and humans, (b) evidence for age related functional and structural alterations of the reward system, and (c) behavioral and neuroimaging data of age effects on reward-based decision-making processes. Implications for neuroeconomics and neurodegenerative diseases are discussed.     

The developmental relationship between specific cognitive domains and grey matter in the cerebellum

There is growing evidence that the cerebellum is involved in cognition and cognitive development, yet little is known about the developmental relationship between cerebellar structure and cognitive subdomains in children. We used voxel-based morphometry to assess the relationship between cerebellar grey matter (GM) and language, reading, working memory, executive function, and processing speed in 110 individuals aged 8–17 years from the Pediatric Imaging, Neurocognition, and Genetics (PING) Study. Further, we examined the effect of age on the relationships between cerebellar GM and cognition. Higher scores on vocabulary, reading, working memory, and set-shifting were associated with increased GM in the posterior cerebellum (lobules VI–IX), in regions which are typically engaged during cognitive tasks in healthy adults. For reading, working memory, and processing speed, the relationship between cerebellar GM and cognitive performance changed with age in specific cerebellar subregions. As in adults, posterior lobe cerebellar GM was associated with cognitive performance in a pediatric population, and this relationship mirrored the known developmental trajectory of posterior cerebellar GM. These findings provide further evidence that specific regions of the cerebellum support cognition and cognitive development, and suggest that the strength of this relationship depends on developmental stage.     

Neuropharmacological modulation of cognition

PURPOSE OF REVIEW: Problems relating to impulsivity, attention, and working memory occur in many neuropsychiatric disorders and represent important targets for pharmacological intervention. The purpose of this article is to review recent neuropharmacological manipulation studies in humans relating to these domains. RECENT FINDINGS: Serotonin manipulations in healthy volunteers did not affect response inhibition, a cognitive function implicated in impulsive symptoms of attention deficit hyperactivity disorder, trichotillomania, and substance abuse. Serotonin manipulations did affect performance on cognitive tests involving emotionally salient rewards and feedback, suggesting involvement of this neurochemical in affective aspects of impulsivity. Attentional deficits in attention deficit hyperactivity disorder and visuospatial neglect were ameliorated by noradrenergic drugs. Noradrenergic beta-blockade suppressed the encoding of emotionally arousing unpleasant stimuli and reduced amygdala activation in healthy volunteers, with potential implications for posttraumatic stress disorder. Dopaminergic manipulations affected aspects of working memory in healthy volunteers and in patients with Parkinson's disease, with evidence for bidirectional effects depending on baseline performance. SUMMARY: Recent findings raise exciting prospects for modulating impulsivity, attention, and working memory in a variety of neuropsychiatric disorders. Future studies should use computerized cognitive assessment, measures of functional genetic polymorphisms, and neuroimaging techniques, in order to further elucidate the neurochemical substrates of cognition and optimize treatment approaches.     

Parkinson's disease and arithmetics: the role of executive functions

Brain imaging studies as well as neuropsychological case studies suggest an important role for basal ganglia in arithmetic processing. Aim of this study was to assess possible numerical deficits in PD and functional relations between numerical and other cognitive deficits. Fifteen non-demented patients with early PD (stable responders treated by l-dopa) were compared to 28 healthy age and education matched controls. Both groups underwent a neuropsychological assessment focussing on numerical abilities (quantity processing, arithmetic fact retrieval, complex mental and written calculation, transcoding, arithmetic set-shifting, calculation span), working memory and executive functions. Patients with PD showed deficits in complex mental calculation and calculation span tasks. Results of this study suggest that impairments in working memory as well as in executive functions, such as inhibition of interference, lead to secondary deficits in numerical processing. The study contributes to better understanding the specific cognitive deficits in early PD and the neurocognitive architecture of arithmetic processing.     

Prefrontal cortex and impulsivity: Interest of noninvasive brain stimulation

IntroductionImpulsivity has been reported in many psychiatric conditions and includes deficits in several cognitive functions such as attention, inhibitory control, risk taking, delay discounting and planning. Many studies have shown that noninvasive brain stimulation (NIBS) techniques modulate the activity of the prefrontal cortex and the functions involved in impulsivity.ObjectiveThis article aims to review the literature on the effect of NIBS on impulsivity in healthy subjects aged 18–65 years old, and to highlight research avenues to develop therapeutic alternatives for such disorders.MethodWe performed a systematic review of the literature in the PubMed database following PRISMA method with “transcranial magnetic stimulation”, “repetitive transcranial magnetic stimulation”, “transcranial direct current stimulation”, “inhibition”, “risk”, “impulsive behavior”, “attention”, “reward”, “delay discounting”, “delay task”, “planning”, “prefrontal cortex” as key words.ResultsWe selected fifty-six studies showing modulation of the cognitive functions involved in impulsivity through NIBS.ConclusionsThe data led us to consider new therapeutic alternatives in impulsive disorders by modulating prefrontal cortex activity through NIBS.     

Cognitive impulsivity and HIV serostatus in substance dependent males.

HIV-seropositive (HIV+) drug users show impaired performance on measures of integrity of prefrontal-subcortical systems. The Iowa Gambling Task (GT) is mediated primarily through ventromedial-prefrontal systems, and poor performance on this measure ("cognitive impulsivity") is common among substance dependent individuals (SDIs) as well as patients with disease involving prefrontal-subcortical systems (e.g., Huntington disease). We hypothesized that HIV+ SDIs might be more vulnerable to cognitive impulsivity when compared with HIV-seronegative (HIV-) SDIs because recent studies report evidence of additive effects of HIV serostatus and drug dependence on cognition. Further, working memory is considered a key component of GT performance and is reliably impaired among HIV+ SDIs compared to controls. We administered the GT to 46 HIV+ and 47 well-matched HIV- males with a past or current history of substance dependence. In addition, we evaluated correlations between subjects' scores on the GT and on a delayed nonmatch to sample (DNMS) task in order to test if working memory deficits accounted for cognitive impulsivity among the HIV+ subjects. The HIV+ subjects performed significantly more poorly on the GT compared to the HIV- group but this effect could not be explained by working memory deficits. Implications of these findings for future basic and applied studies of HIV and substance dependence are discussed.     

Neuropsychological consequences of chronic opioid use: A quantitative review and meta-analysis

INTRODUCTION: It is widely assumed within the accumulated literature that neuropsychological function is commonly impaired as a consequence of chronic opioid use. METHOD: Quantitative and systematic review of the literature on the neuropsychology of chronic opioid use using the meta-analysis of observational studies in epidemiology (MOOSE) and the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. RESULTS: This meta-analysis suggests that chronic opioid exposure is associated with deficits across a range of different neuropsychological domains. However, the only domains where meta-analysis suggests robust impairment were those of verbal working memory, cognitive impulsivity (risk taking) and cognitive flexibility (verbal fluency). The magnitude of effect across these cognitive domains was medium according to Cohen's benchmark criteria. DISCUSSION: This analysis highlighted methodological problems present in the literature used and the value of utilising meta-analytic techniques to help further elucidate the neuropsychological consequences of chronic opioid use from 'core' addiction phenotypes.     

Cognitive processes in the development of TOL performance

Components of executive function continue to develop through adolescence. There is limited knowledge of how these cognitive components impact complex cognitive function requiring their integration. This study examines the development of response planning, a complex cognitive function, and the contributions of selected cognitive processes, including speed of processing, response inhibition, and working memory to its development. We tested 100 healthy 8-30 year old individuals with a computerized version to the Tower of London (TOL) task and cognitive oculomotor tests including the visually guided saccade, oculomotor delayed response, and antisaccade tasks. Speed of processing, response inhibition, working memory, and TOL performance all demonstrated maturation in adolescence. While all processes were correlated with the development of TOL performance, antisaccade performance showed the strongest association indicating an important role for response inhibition in planning. These results indicate that the development of converging cognitive processes in adolescence, including response inhibition and working memory, support response planning and may serve as a model for the development of performance in other complex problem solving tasks.     

Self-reported impulsivity in Huntington’s disease patients and relationship to executive dysfunction and reward responsiveness

Introduction: Few studies have directly investigated impulsivity in Huntington’s disease (HD) despite known changes in dopaminergic and frontal functioning, changes that have been associated with impulsivity in other disorders and in the normal population. This study sought to further categorize impulsivity in HD through examining differences in self-reported impulsivity between community controls and HD patients, the relationship between executive dysfunction and impulsivity, and the relationship of a reward/punishment behavioral inhibition task in relation to these self-report measures. It was expected that HD patients would report higher impulsivity and executive dysfunction and that these measures would relate to a reward/punishment behavioral inhibition task. Method: The Barratt Impulsivity Scale (BIS–11) and Behavioral Inhibition/Behavioral Activation Scale (BIS/BAS) were completed, and the Mini-Mental State Examination (MMSE) and a reward-based flanker task with punishing and rewarding conditions were administered to 22 HD patients and 14 control participants. Results: HD patients reported higher trait impulsivity (BIS–11) and executive dysfunction (Frontal Systems Behavior Scale, FrSBE) but not increased impulsivity on the BIS/BAS relative to controls. Higher BIS–11 scores were related to increased self-reported executive dysfunction and the attention/working memory factor of the MMSE. On a reward/punishment behavioral inhibition task, BAS was uniquely related to increased accuracy on rewarding trials of the flanker task, but was not related to punishing trials in HD patients. Conclusions: The relationships found suggest that trait impulsivity is reported higher in HD and may not be driven by altered reward evaluation and the appetitive nature of stimuli but rather by increased executive dysfunction and lack of sensitivity to punishment. Impulsivity in HD may represent a combination of trait impulsivity, altered dopaminergic circuitry, and executive dysfunction. Understanding impulsivity in HD is important as it is related to increased risk to the patient and difficult behaviors for the caregiver, and sheds light on the disease process.     

The relative contributions of processing speed and cognitive load to working memory accuracy in multiple sclerosis

Cognitive symptoms of multiple sclerosis (MS) include processing-speed deficits and working memory impairment. The precise manner in which these deficits interact in individuals with MS remains to be explicated. We hypothesized that providing more time on a complex working memory task would result in performance benefits for individuals with MS relative to healthy controls. Fifty-three individuals with clinically definite MS and 36 matched healthy controls performed a computerized task that systematically manipulated cognitive load. The interval between stimuli presentations was manipulated to provide increasing processing time. The results confirmed that individuals with MS who have processing-speed deficits significantly improve in performance accuracy when given additional time to process the information in working memory. Implications of these findings for developing appropriate cognitive rehabilitation interventions are discussed.     

Delay discounting and future-directed thinking in anhedonic individuals

Anhedonia (lack of reactivity to pleasurable stimuli) and a negatively skewed view of the future are important components of depression that could affect economic decisions in depressed individuals. Delay discounting paradigms might be useful for probing putative affective and cognitive underpinnings of such decisions. As a first step to evaluate whether difficulties experiencing pleasure might affect delay discounting, 36 undergraduate students with varying levels of anhedonia performed a delay discounting task in which they made choices between a small immediate and larger future monetary reward. Increasing levels of anhedonia (Snaith-Hamilton Pleasure Scale) were negatively associated with delay discounting rate, indicating that anhedonic individuals tended to choose the larger, albeit delayed reward. These correlations remained after controlling for variables previously linked to delay discounting (working memory capacity and impulsivity) and pessimistic future-directed thinking. The current findings provide preliminary evidence indicating that anhedonic individuals make less myopic decisions about their future, possibly due to their decreased responsiveness to immediate rewards.     

Long-term improvements in cognitive performance through computer-assisted cognitive training: a pilot study in a residential home for older people

The aim of the present pilot study was to investigate the effects of computer-assisted cognitive training on aging-associated memory deficits, information processing speed, learning, and interference tendency in older people. Residents of a home for older people (15 women, four men; mean age 83.5; range 75-91) participated in a 14-week computer-assisted cognitive training program. The Niirnberg Aging Inventory and the California Verbal Learning Test were administered prior to the program, immediately after the program and after a period of five months to assess the effectiveness of the cognitive training. After the cognitive training program there were significant improvements in primary working memory and also secondary working memory (for verbal and visual stimuli), on parameters of information processing speed, learning and interference tendency. Improvements in the last two cognitive parameters were maintained five months after completion of the training program. The present study indicates that computerized cognitive training programs can be used in older people to achieve long-term improvements in some important aspects of fluid intelligence. It is suggested that computers could be employed more extensively to prevent and treat cognitive deficits in older people.     

(Social) Cognitive skills and social information processing in children with mild to borderline intellectual disabilities

The purpose of this study was to examine the unique contributions of (social) cognitive skills such as inhibition, working memory, perspective taking, facial emotion recognition, and interpretation of situations to the variance in social information processing in children with mild to borderline intellectual disabilities. Respondents were 79 children with mild to borderline intellectual disabilities in the age of 8-12 who were given tasks on social cognitive skills and social information processing. The results from the present study show that emotion recognition, interpretation, working memory and inhibition skills predict social information processing skills. It is concluded that especially emotion recognition and interpretation skills are important cognitive skills that predict social information processing, and therefore should be the focus of treatment.     

Antipsychotic treatment in schizophrenia: the role of computerized neuropsychological assessment

The present study analyzes the role of neurocognitive assessment instruments in the detection of the contribution of antipsychotic treatment to cognitive functioning. Recently, a panel of experts suggested six main domains (working memory; attention/vigilance; verbal/visual learning and memory; reasoning and problem solving; speed of processing) implicated in schizophrenia-related cognitive deficits, which serve as a theoretical base for creation of real-time computerized neurocognitive batteries. The high sensitivity of computerized neuropsychological testing is based on their ability to adopt the reaction time (RT) paradigm for the assessment of brain function in a real-time regime. This testing is highly relevant for the monitoring of the cognitive effects of antipsychotics. Computerized assessment assists in the identification of state- and trait-related cognitive impairments. The optimal real-time computerized neurocognitive battery should composite balance between broad and narrow coverage of cognitive domains relevant to the beneficial effects of antipsychotics and will enable better planning of treatment and rehabilitation programs.