RESUMO
Deficits in impulse control are discussed as key mechanisms for major worldwide health problems such as drug addiction and obesity. For example, obese subjects have difficulty controlling their impulses to overeat when faced with food items. Here, we investigated the role of neural impulse control mechanisms for dietary success in middle-aged obese subjects. Specifically, we used a food-specific delayed gratification paradigm and functional magnetic resonance imaging to measure eating-related impulse-control in middle-aged obese subjects just before they underwent a twelve-week low calorie diet. As expected, we found that subjects with higher behavioral impulse control subsequently lost more weight. Furthermore, brain activity before the diet in VMPFC and DLPFC correlates with subsequent weight loss. Additionally, a connectivity analysis revealed that stronger functional connectivity between these regions is associated with better dietary success and impulse control. Thus, the degree to which subjects can control their eating impulses might depend on the interplay between control regions (DLPFC) and regions signaling the reward of food (VMPFC). This could potentially constitute a general mechanism that also extends to other disorders such as drug addiction or alcohol abuse.
Assuntos
Encéfalo/fisiopatologia , Comportamento Impulsivo/fisiopatologia , Vias Neurais/fisiologia , Obesidade/fisiopatologia , Redução de Peso/fisiologia , Adulto , Idoso , Mapeamento Encefálico , Dieta Redutora , Comportamento Alimentar/fisiologia , Feminino , Humanos , Hiperfagia/fisiopatologia , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recompensa , Adulto JovemRESUMO
Two experiments are reported in which rats with selective hippocampal lesions were tested on 2 prefrontal-dependent tasks. In Experiment 1, we compared the effects of lesions of the ventral hippocampus (vHC), dorsal hippocampus (dHC), and sham control surgery on the 5-choice reaction time task. Whereas rats with lesions of the dHC were indistinguishable from sham controls, those with vHC lesions showed increased premature responses and reduced accuracy throughout the experiment. The subsequent administration of systemic escitalopram (5 mg/kg), a selective serotonin reuptake inhibitor, reduced the number of premature responses in the vHC animals to control levels. In contrast, systemic injections of GBR 12909, a dopamine reuptake inhibitor, failed to ameliorate the impulsive deficit in the vHC group and, in addition, elevated perseverative responding in the vHC group only. In Experiment 2, we tested a separate group of rats with vHC lesions on a touchscreen visual discrimination and reversal learning task. Rats with vHC lesions acquired the visual discrimination as well as sham controls and showed normal inhibitory control of a previously reinforced response during reversal learning. These data support a role for the vHC in inhibitory control functions, especially in the inhibitory control of impulsive actions.
Assuntos
Comportamento de Escolha/fisiologia , Discriminação Psicológica/fisiologia , Hipocampo/lesões , Comportamento Impulsivo/fisiopatologia , Inibição Psicológica , Análise de Variância , Animais , Atenção/efeitos dos fármacos , Atenção/fisiologia , Comportamento de Escolha/efeitos dos fármacos , Citalopram/farmacologia , Discriminação Psicológica/efeitos dos fármacos , Inibidores da Captação de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Preferências Alimentares/efeitos dos fármacos , Preferências Alimentares/fisiologia , Hipocampo/fisiologia , Comportamento Impulsivo/induzido quimicamente , Masculino , Estimulação Luminosa , Piperazinas/farmacologia , Ratos , Ratos Long-Evans , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Reversão de Aprendizagem/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Sacarose/administração & dosagem , Edulcorantes/administração & dosagemRESUMO
Delay discounting, a measure of impulsive choice, has been associated with decreased control of the prefrontal cortex over striatum responses. The anatomical connectivity between both brain regions in delaying gratification remains unknown. Here, we investigate whether the quality of frontostriatal (FS) white matter tracts can predict individual differences in delay-discounting behavior. We use tract-based diffusion tensor imaging and magnetization transfer imaging to measure the microstructural properties of FS fiber tracts in 40 healthy young adults (from 18 to 25 years). We additionally explored whether internal sex hormone levels affect the integrity of FS tracts, based on the hypothesis that sex hormones modulate axonal density within prefrontal dopaminergic circuits. We calculated fractional anisotropy (FA), mean diffusivity (MD), longitudinal diffusivity, radial diffusivity (RD), and magnetization transfer ratio (MTR), a putative measure of myelination, for the FS tract. Results showed that lower integrity within the FS tract (higher MD and RD and lower FA), predicts faster discounting in both sexes. MTR was unrelated to delay-discounting performance. In addition, testosterone levels in males were associated with a lower integrity (higher RD) within the FS tract. Our study provides support for the hypothesis that enhanced structural integrity of white matter fiber bundles between prefrontal and striatal brain areas is associated with better impulse control.
Assuntos
Comportamento Impulsivo/fisiopatologia , Fibras Nervosas Mielinizadas/patologia , Vias Neurais/fisiopatologia , Adolescente , Adulto , Anisotropia , Imagem de Tensor de Difusão , Ensaio de Imunoadsorção Enzimática , Estradiol/análise , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Comportamento Impulsivo/metabolismo , Masculino , Saliva/química , Fatores Sexuais , Testosterona/análise , Adulto JovemRESUMO
Numerous studies have shown that people adjust their intake directly to that of their eating companions. A potential explanation for this modelling effect is that the eating behaviour of others operates as an external eating cue that stimulates food intake. The present study explored whether this cue-reactive mechanism can account for modelling effects on intake. It was investigated whether attentional bias towards dynamic eating cues and impulsivity would influence the degree of modelling. Participants completed one individual session and one session in which an experimental confederate accompanied them. In the first session, eye movements were recorded as an index of attentional bias to dynamic eating cues. In addition, self-reported impulsivity and response inhibition were assessed. The second session employed a between-participants design with three experimental conditions in which participants were exposed to a same-sex confederate instructed to eat nothing, a low or a large amount of M&Ms. A total of eighty-five young women participated. The participants' self-reported impulsivity determined the occurrence of modelling; only low-impulsive women adjusted their intake to that of their eating companion. Attention towards eating cues and response inhibition, however, did not moderate modelling of food intake. The present study suggests that cue-reactive mechanisms may not underlie modelling of food intake. Instead, the results emphasise the importance of social norms in explaining modelling effects, whereas it is suggested that the degree of impulsivity may play a role in whether or not women adhere to the intake norms set by their eating companion.
Assuntos
Atenção , Dieta , Ingestão de Energia , Comportamento Alimentar , Comportamento Impulsivo/fisiopatologia , Relações Interpessoais , Modelos Psicológicos , Adolescente , Adulto , Doces , Sinais (Psicologia) , Dieta/efeitos adversos , Dieta/psicologia , Comportamento Alimentar/psicologia , Feminino , Preferências Alimentares , Humanos , Hiperfagia/etiologia , Hiperfagia/prevenção & controle , Hiperfagia/psicologia , Comportamento Imitativo , Comportamento Impulsivo/prevenção & controle , Comportamento Impulsivo/psicologia , Inibição Psicológica , Países Baixos , Controles Informais da Sociedade , Adulto JovemRESUMO
Schizophrenia (n=68) and control (n=62) participants matched on cigarette smoking history were assessed on executive function, decision-making and impulsivity tasks. In controls, executive function and decision-making correlated positively with each other and negatively with impulsivity. There were no inter-task correlations in schizophrenia participants. The significance of these findings is discussed.
Assuntos
Transtornos Cognitivos/fisiopatologia , Tomada de Decisões/fisiologia , Função Executiva/fisiologia , Comportamento Impulsivo/fisiopatologia , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Transtornos Cognitivos/psicologia , Feminino , Humanos , Comportamento Impulsivo/psicologia , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Transtornos Psicóticos/fisiopatologia , Transtornos Psicóticos/psicologia , Adulto JovemRESUMO
The aim of the present study was to examine neurocognitive function associated with chronic nicotine use. A total of 2163 healthy participants (1002 smokers, 1161 never-smoking controls) participated in a population-based case-control design. The main outcome measures were six cognitive domain factors derived from a neuropsychological test battery. In smokers, the battery was administered after controlled smoking of one cigarette. Analyses included age, sex and education as covariates. Results demonstrated small, but significant deficits in smokers for visual attention (P<0.001) and cognitive impulsivity (P<0.006), while verbal episodic memory, verbal fluency, verbal working memory, and Stroop-interference did not differ between groups. These attention/impulsivity deficits were also present in smokers with only a low amount of cigarette consumption. Lifetime nicotine use (pack-years) was not correlated with cognition in smokers. In conclusion, this study confirmed subtle and specific cognitive deficits in non-deprived smokers. The independence of these deficits from consumption intensity may argue for an a priori deficit of some cognitive abilities in smokers. These specific deficits may constitute intermediate phenotypes for genetic research on nicotine use.
Assuntos
Atenção/fisiologia , Comportamento Impulsivo/fisiopatologia , Testes Neuropsicológicos/estatística & dados numéricos , Fumar/fisiopatologia , Adolescente , Adulto , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Estudos de Casos e Controles , Cognição/efeitos dos fármacos , Endofenótipos , Feminino , Predisposição Genética para Doença , Alemanha , Humanos , Masculino , Memória de Curto Prazo/fisiologia , Pessoa de Meia-Idade , Nicotina/farmacologia , Análise de Componente Principal , Tempo de Reação/fisiologia , Fumar/genética , Fumar/psicologia , Tabagismo/genética , Tabagismo/fisiopatologia , Tabagismo/psicologia , Aprendizagem Verbal/fisiologia , Adulto JovemRESUMO
Deficits in short-term memory are common in adolescents with attention-deficit/hyperactivity disorder (ADHD), but their current ADHD symptoms cannot well predict their short-term performance. Taking a developmental perspective, we wanted to clarify the association between ADHD symptoms at early childhood and short-term memory in late childhood and adolescence. The participants included 401 patients with a clinical diagnosis of DSM-IV ADHD, 213 siblings, and 176 unaffected controls aged 8-17 years (mean age, 12.02 ± 2.24). All participants and their mothers were interviewed using the Chinese Kiddie Epidemiologic version of the Schedule for Affective Disorders and Schizophrenia to obtain information about ADHD symptoms and other psychiatric disorders retrospectively, at an earlier age first, then currently. The participants were assessed with the Wechsler Intelligence Scale for Children--3rd edition, including Digit Span, and the Spatial working memory task of the Cambridge Neuropsychological Test Automated Battery. Multi-level regression models were used for data analysis. Although crude analyses revealed that inattention, hyperactivity, and impulsivity symptoms significantly predicted deficits in short-term memory, only inattention symptoms had significant effects (all p<0.001) in a model that included all three ADHD symptoms. After further controlling for comorbidity, age of assessment, treatment with methylphenidate, and Full-scale IQ, the severity of childhood inattention symptoms was still significantly associated with worse verbal (p = 0.008) and spatial (p ranging from 0.017 to 0.002) short-term memory at the current assessment. Therefore, our findings suggest that earlier inattention symptoms are associated with impaired verbal and visuo-spatial short-term memory at a later development stage. Impaired short-term memory in adolescence can be detected earlier by screening for the severity of inattention in childhood.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtornos da Memória/diagnóstico , Memória de Curto Prazo/fisiologia , Testes Neuropsicológicos , Percepção Espacial/fisiologia , Aprendizagem Verbal/fisiologia , Adolescente , Atenção/fisiologia , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Estudos de Casos e Controles , Criança , Comorbidade , Feminino , Humanos , Comportamento Impulsivo/diagnóstico , Comportamento Impulsivo/epidemiologia , Comportamento Impulsivo/fisiopatologia , Masculino , Programas de Rastreamento/métodos , Transtornos da Memória/epidemiologia , Transtornos da Memória/fisiopatologia , Acuidade Visual/fisiologiaRESUMO
Previous studies have shown that drugs which block the reuptake of catecholamine neurotransmitters improve impulse control in diseases such as attention deficit hyperactivity disorder (ADHD). Serotonin-specific reuptake inhibitors (SSRI) lack efficacy in ADHD and have been linked to increased suicide risk. The present study investigated drugs with affinity for one or more of the monoamine reuptake transporters using the 5-choice serial reaction time task, a model of attention and impulsivity in rodents. We also tested the effects of the alpha(2)-adreoceptor antagonist, idazoxan and novel antidepressant, agomelatine, which both increase cortical noradrenaline concentrations through non-reuptake mechanisms. Improvements in impulse control were observed with venlafaxine, a serotonin and noradrenaline re-uptake inhibitor (SNRI) but not bupropion (dopamine and noradrenaline re-uptake inhibitor). Sibutramine (SNRI) reduced premature responses by ~50% at the highest dose tested but this was not significant. All three of the SSRIs tested reduced premature responding in a dose-dependent manner, although also slowed response and collection latencies. Neither idazoxan nor agomelatine significantly reduced premature responding, suggesting a lack of efficacy at the doses tested. None of the drugs tested improved attention in this task but sibutramine (SNRI), fluoxetine (SSRI) and paroxetine (SSRI) all increased omissions at the highest dose tested. These data suggest that the SNRIs and SSRIs reduce premature responding but tend to be less specific than noradrenaline specific reuptake inhibitors in this model. SSRIs did not induce any specific impairment in impulse control in this model.
Assuntos
Comportamento Animal/efeitos dos fármacos , Comportamento de Escolha/efeitos dos fármacos , Comportamento Impulsivo/fisiopatologia , Tempo de Reação/efeitos dos fármacos , Acetamidas/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 2/farmacologia , Animais , Antidepressivos/farmacologia , Bupropiona/farmacologia , Ciclobutanos/farmacologia , Cicloexanóis/farmacologia , Fluoxetina/farmacologia , Hipnóticos e Sedativos/farmacologia , Idazoxano/farmacologia , Masculino , Norepinefrina/farmacologia , Paroxetina/farmacologia , Ratos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Cloridrato de VenlafaxinaRESUMO
Neuroeconomics integrates behavioral economics and cognitive neuroscience to understand the neurobiological basis for normative and maladaptive decision making. Delay discounting is a behavioral economic index of impulsivity that reflects capacity to delay gratification and has been consistently associated with nicotine dependence. This preliminary study used functional magnetic resonance imaging to examine delay discounting for money and cigarette rewards in 13 nicotine dependent adults. Significant differences between preferences for smaller immediate rewards and larger delayed rewards were evident in a number of regions of interest (ROIs), including the medial prefrontal cortex, anterior insular cortex, middle temporal gyrus, middle frontal gyrus, and cingulate gyrus. Significant differences between money and cigarette rewards were generally lateralized, with cigarette choices associated with left hemisphere activation and money choices associated with right hemisphere activation. Specific ROI differences included the posterior parietal cortex, medial and middle frontal gyrus, ventral striatum, temporoparietal cortex, and angular gyrus. Impulsivity as measured by behavioral choices was significantly associated with both individual ROIs and a combined ROI model. These findings provide initial evidence in support of applying a neuroeconomic approach to understanding nicotine dependence.
Assuntos
Encéfalo/fisiopatologia , Tomada de Decisões/fisiologia , Recompensa , Tabagismo/fisiopatologia , Adulto , Mapeamento Encefálico , Economia Comportamental , Feminino , Neuroimagem Funcional , Humanos , Processamento de Imagem Assistida por Computador , Comportamento Impulsivo/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Tabagismo/psicologiaRESUMO
Sweet preference and impulsivity are predictors of cocaine self-administration; however, no research has been conducted to investigate neuronal activation in key brain reward areas after first time exposure to cocaine in rats that differ in their propensity for cocaine-seeking and -taking behavior. In this study we used rats that had been selectively bred for high vs. low saccharin intake and rats selected for high vs. low impulsivity for food. The goal of this study was to investigate whether there are differences of c-Fos reactivity between high and low phenotypes and determine whether these differences are similar between the two animal models. A group of rats was bred for high or low saccharin intake. Another group of rats was selected as high or low impulsive based on performance in a delay-discounting task. Subsequently, rats were given an acute injection of cocaine or saline and then c-Fos expression was observed and analyzed in several brain regions. The low reward-seeking phenotypes showed higher cocaine-induced c-Fos expression in several of these regions. Low saccharin preferring rats showed higher cocaine-induced c-Fos expression in the nucleus accumbens shell, and low impulsive rats showed higher cocaine-induced c-Fos expression in the orbitofrontal cortex and cingulate gyrus 1 area. In addition, both low impulsive and low saccharin rats had higher cocaine-induced c-Fos in the dorsal medial and dorsal lateral caudate putamen. The results indicate that individual differences in neuronal reactivity exist prior to chronic exposure to drugs of abuse. Furthermore, similar differences between the two animal models may be indicative of a common mechanism underlying vulnerability to drugs of abuse.
Assuntos
Cocaína/administração & dosagem , Inibidores da Captação de Dopamina/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Comportamento Impulsivo/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Sacarina/administração & dosagem , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Condicionamento Operante/efeitos dos fármacos , Comportamento Impulsivo/fisiopatologia , Masculino , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Recompensa , AutoadministraçãoRESUMO
RATIONALE: Overactivation of serotonin (5-hydroxytryptamine, 5-HT)(2A) receptors causes impulsivity and attentional deficits. Since 5-HT(2A) receptors are known to entertain antagonistic interactions with metabotropic glutamate (mGlu)2/3 receptors, this interaction may provide an alternative target for a novel class of antipsychotics. OBJECTIVES/METHODS: The study characterizes interactions between 5-HT(2A) and mGlu2/3 receptors implicated in impulse control. Hooded Lister rats were trained in a 5-choice serial reaction time task (5-CSRTT) and treated with the 5-HT(2A/2C) receptor agonist (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropan hydrochloride (DOI, 0.1 mg/kg) and the mGlu2/3 receptor agonist LY379268 (1 mg/kg). In addition, associated drug-induced changes in neuronal activity were assessed via c-Fos immunoreactivity (Fos IR), and co-localization of c-Fos and GABAergic markers was detected using double immunofluorescence labeling. RESULTS: Systemic DOI caused impulsive overresponding that was attenuated in animals pre-treated with LY379268. LY379268 itself had no significant effect on the rats' performance in the 5-CSRTT. DOI enhanced Fos IR within fronto-cortical and limbic brain structures, and this effect was blocked by LY379268 pre-treatment. Double immunofluorescence labeling showed a specific co-localization of DOI-elicited Fos IR with GABAergic (GAD(67)-positive) cells lacking the calcium-binding protein parvalbumin while LY379268 increased Fos IR in GABAergic and non-GABAergic cells. CONCLUSION: Our results suggest that impulsivity is possibly due to a primary increase in Glu transmission mediated via 5-HT(2A) receptor activation. Thus, mGlu2/3 receptor agonists might have some potential for treating motor impulsivity-related impairments while their cognitive enhancing effects were not confirmed in this study.
Assuntos
Aminoácidos/farmacologia , Anfetaminas/antagonistas & inibidores , Encéfalo/fisiologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Comportamento Impulsivo/induzido quimicamente , Comportamento Impulsivo/tratamento farmacológico , Receptores de Glutamato Metabotrópico/agonistas , Aminoácidos/uso terapêutico , Anfetaminas/farmacologia , Animais , Animais não Endogâmicos , Encéfalo/efeitos dos fármacos , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Comportamento de Escolha/efeitos dos fármacos , Comportamento de Escolha/fisiologia , Neurônios GABAérgicos/efeitos dos fármacos , Neurônios GABAérgicos/fisiologia , Genes fos/fisiologia , Comportamento Impulsivo/fisiopatologia , Imagem Molecular/métodos , Imagem Molecular/psicologia , Ratos , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Aprendizagem Seriada/efeitos dos fármacos , Aprendizagem Seriada/fisiologia , Agonistas do Receptor de Serotonina/farmacologia , Agonistas do Receptor de Serotonina/fisiologiaRESUMO
Acute challenges with psychostimulants such as amphetamine affect impulsive behavior in both animals and humans. With regard to amphetamine, it is important to unravel how this drug affects impulsivity since it is not only a widely abused recreational drug but also regularly prescribed to ameliorate maladaptive impulsivity. Therefore, we studied the effects of amphetamine in two rat models of impulsivity, the five-choice serial reaction time task and the delayed-reward task, providing measures of inhibitory control and impulsive choice, respectively. We focused on the role of opioid receptor activation in amphetamine-induced impulsivity as there is ample evidence indicating an important role for endogenous opioids in several behavioral and neurochemical effects of amphetamine. Results showed that amphetamine-induced inhibitory control deficits were dose-dependently attenuated by the preferential µ-opioid receptor antagonist naloxone, but not by the selective δ-opioid receptor antagonist naltrindole or κ-opioid receptor antagonist nor-BNI (nor-binaltorphimine dihydrochloride). In contrast, naloxone did not affect amphetamine-induced improvements in impulsive decision making. Naloxone also completely prevented inhibitory control deficits induced by GBR 12909 [1-(2-[bis(4-fluorophenyl)methoxy] ethyl)-4-(3-phenylpropyl)piperazine dihydrochloride], a selective dopamine transporter inhibitor. Intracranial infusions of naloxone, the selective µ-opioid receptor antagonist CTAP (H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2)), morphine, and the selective µ-opioid receptor agonist DAMGO ([D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin acetate salt) revealed that µ-opioid receptor activation in the shell rather than the core subregion of the nucleus accumbens (NAc) modulates inhibitory control and subserves the effect of amphetamine thereon. Together, these results indicate an important role for NAc shell µ-opioid receptors in the regulation of inhibitory control, probably via an interaction between these receptors and the mesolimbic dopamine system.
Assuntos
Anfetamina/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Comportamento de Escolha/efeitos dos fármacos , Inibição Psicológica , Núcleo Accumbens/efeitos dos fármacos , Receptores Opioides mu/metabolismo , Analgésicos Opioides/farmacologia , Animais , Atenção/efeitos dos fármacos , Comportamento de Escolha/fisiologia , Condicionamento Operante/efeitos dos fármacos , Dopamina/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Ala(2)-MePhe(4)-Gly(5)-Encefalina/farmacologia , Comportamento Impulsivo/induzido quimicamente , Comportamento Impulsivo/fisiopatologia , Masculino , Motivação/efeitos dos fármacos , Naloxona/farmacologia , Naltrexona/análogos & derivados , Naltrexona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Núcleo Accumbens/metabolismo , Peptídeos/farmacologia , Ratos , Ratos Wistar , Tempo de Reação/efeitos dos fármacos , Receptores Opioides mu/efeitos dos fármacos , Esquema de ReforçoRESUMO
Impulsivity is a pathological hallmark of drug addiction. However, little is known about the neuropsychological underpinnings of this impaired impulsive control network on drug addiction. Twenty two abstinent heroin dependent (HD) subjects and 15 cognitively normal (CN) subjects participated in this study. Resting-state functional connectivity MRI was employed to measure abnormalities in the intrinsic amygdala functional connectivity (iAFC) network activity and the Barratt Impulsive Scale, 11th version was used to measure impulsivity. Linear regression analysis was applied to detect the neural constructs underlying impulsivity by correlating iAFC network activity with impulsive scores. In the HD group, higher impulsivity scores and significantly enhanced iAFC network activity were found, especially in bilateral thalamus, right insula, and inferior frontal gyrus. Markedly decreased anticorrelated iAFC network activity was seen in the left precuneus, and even switched to positive correlation pattern in right precuneus, relative to the CN group. The iAFC network strengths in the HD group were positively correlated with impulsivity in the right subcallosal gyrus, insula, thalamus and posterior cingulate cortex, and negatively correlated in left fusiform area. In the CN group, the left pre-somamotor area-amygdala connectivity was positively correlated, and right orbital frontal cortex-amygdala and precuneus-amygdala connectivity were negatively correlated with impulsivity scores. Our study demonstrates different constructs of the impulsive network in HD and CN subjects. Altered iAFC network connectivity in HD subjects may contribute to the loss of impulsive control. This further facilitates our understanding of the neural underpinnings of behavior dysfunction in addiction.
Assuntos
Tonsila do Cerebelo/fisiologia , Mapeamento Encefálico , Dependência de Heroína/fisiopatologia , Comportamento Impulsivo/fisiopatologia , Vias Neurais/fisiologia , Adulto , Estudos de Casos e Controles , Dependência de Heroína/complicações , Humanos , Comportamento Impulsivo/complicações , Imageamento por Ressonância Magnética , Masculino , Análise por Pareamento , Valores de ReferênciaRESUMO
The nucleus accumbens (NAc) is gaining interest as a target for deep brain stimulation (DBS) in refractory neuropsychiatric disorders with impulsivity as core symptom. The nucleus accumbens is composed of two subterritories, core and shell, which have different anatomical connections. In animal models, it has been shown that DBS of the NAc changes impulsive action. Here, we tested the hypothesis that a change in impulsive action by DBS of the NAc is associated with changes in dopamine levels. Rats received stimulating electrodes either in the NAc core or shell, and underwent behavioral testing in a reaction time task. In addition, in a second experiment, the effect of DBS of the NAc core and shell on extracellular dopamine and serotonin levels was assessed in the NAc and medial prefrontal cortex. Control subjects received sham surgery. We have found that DBS of the NAc shell stimulation induced more impulsive action but less perseverative checking. These effects were associated with increased levels of dopamine and serotonin in the NAc, but not in the medial prefrontal cortex. DBS of the NAc core had no effect on impulsive action, but decreased perseverative responses indicative of a better impulse control. In these subjects, no effects were found on neurotransmitter levels. Our data point out that DBS of the NAc shell has negative effects on impulsive action which is accompanied by increases of dopamine and serotonin levels in the NAc, whereas DBS of the NAc core has beneficial behavioral effects.
Assuntos
Dopamina/metabolismo , Comportamento Impulsivo/fisiopatologia , Núcleo Accumbens/fisiopatologia , Serotonina/metabolismo , Análise de Variância , Animais , Comportamento Animal/fisiologia , Cromatografia Líquida de Alta Pressão , Estimulação Encefálica Profunda , Comportamento Impulsivo/metabolismo , Masculino , Atividade Motora/fisiologia , Núcleo Accumbens/metabolismo , Ratos , Ratos Endogâmicos Lew , Tempo de Reação/fisiologiaRESUMO
We have recently shown that damage to the insula leads to a profound disruption of addiction to cigarette smoking (Naqvi et al., Science 315:531-534, 2007). Yet, there is little understanding of why the insula should play such an important role in an addictive behavior. A broad literature (much of it reviewed in this issue) has addressed the role of the insula in processes related to conscious interoception, emotional experience, and decision-making. Here, we review evidence for the role of the insula in drug addiction, and propose a novel theoretical framework for addiction in which the insula represents the interoceptive effects of drug taking, making this information available to conscious awareness, memory and executive functions. A central theme of this framework is that a primary goal for the addicted individual is to obtain the effects of the drug use ritual upon the body, and representations of this goal in interoceptive terms by the insula contribute to how addicted individuals feel, remember, and decide about taking drugs. This makes drug addiction like naturally motivated behaviors, such as eating and sex, for which an embodied ritual is the primary goal.
Assuntos
Conscientização/fisiologia , Córtex Cerebral/fisiopatologia , Prazer/fisiologia , Autoimagem , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Animais , Humanos , Comportamento Impulsivo/fisiopatologia , Comportamento Impulsivo/psicologiaRESUMO
Recent anatomical and clinical evidence has shown that the cerebellum, primarily considered a motor control structure, is also involved in higher cognitive functions and behavioural changes, such as impulsive behaviour. Impulsive behaviour has been shown in several studies to be increased by lesions of the mediodorsal (MD) thalamic nucleus. We performed deep brain stimulation (DBS) of the mediodorsal and ventrolateral (VL) thalamic nuclei in rats, clinically mimicking such a lesion, and tested them for changes in impulsive behaviour in a choice reaction time test. We then analysed the effects of this stimulation on c-Fos expression in both the deep cerebellar nuclei (DCbN) and the prefrontal cortex (PFC), and correlated these outcomes to the measured changes in impulsive behaviour. DBS of the MD thalamic nucleus increased impulsive behaviour without changing motor parameters. This was accompanied by a decrease in the c-Fos expression in all cerebellar nuclei; with a corresponding increase in c-Fos expression in the PFC. DBS of the VL thalamic nucleus caused no significant change in behaviour or c-Fos expression in either region. The present study demonstrates that impulsive behaviour involves the cerebellar nuclei, possibly through a decreased selective attention caused by a disruption of the cerebello-thalamo-cortical pathways through the MD thalamic nucleus.
Assuntos
Núcleos Cerebelares/fisiopatologia , Comportamento Impulsivo/fisiopatologia , Vias Neurais/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Animais , Núcleos Cerebelares/metabolismo , Estimulação Encefálica Profunda , Imuno-Histoquímica , Masculino , Núcleo Mediodorsal do Tálamo/fisiopatologia , Córtex Pré-Frontal/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Núcleos Ventrais do Tálamo/fisiologia , Núcleos Ventrais do Tálamo/fisiopatologiaRESUMO
Adolescence is a developmental period, during which the brain and particularly medial prefrontal cortical (mPFC) regions thereof have not fully matured. Because epidemiological data have suggested that adolescent nicotine use may result in disturbances in cognitive function in adulthood, we investigated the long-term effects of adolescent nicotine exposure in rats. Male Wistar rats were exposed to either nicotine (three times daily, 0.4 mg/kg s.c.) or saline for 10 days during (postnatal day (PND) 34-43) or following (PND 60-69) adolescence. After 5 weeks during adulthood, separate groups of animals were tested in operant paradigms taxing attention and distinct measures of impulsivity. Visuospatial attention and impulsive action were tested in the five-choice serial reaction time task, whereas impulsive choice was assessed in the delayed reward task. Our data show that adolescent, but not postadolescent, nicotine exposure affects cognitive performance in adulthood and results in diminished attentional performance and increments in impulsive action, while leaving impulsive choice intact. This altered cognitive performance appeared to be associated with enhanced releasability of dopamine in the mPFC. Together, these data suggest that adolescence is a time window during which the brain is vulnerable to long-lasting cognitive disturbances resulting from nicotine exposure.
Assuntos
Atenção/efeitos dos fármacos , Cognição/efeitos dos fármacos , Comportamento Impulsivo/fisiopatologia , Nicotina/farmacologia , Envelhecimento , Análise de Variância , Animais , Comportamento de Escolha/efeitos dos fármacos , Dopamina/metabolismo , Masculino , Nicotina/administração & dosagem , Núcleo Accumbens/metabolismo , Córtex Pré-Frontal/metabolismo , Ratos , Ratos Wistar , Tempo de Reação , RecompensaRESUMO
OBJECTIVE: Cannabis is the most used illicit drug worldwide, however only a few studies have examined cognitive deficits related to its use. Clinical manifestations associated with those deficits include a motivational syndrome, impairment in cognitive flexibility, inattention, deficits in abstract reasoning and concept formation, aspects intimately related to the executive functions, which potentially exert a central role in substance dependence. The objective was to make a review about consequences of cannabis use in executive functioning. METHOD: This review was carried out on reports drawn from MedLine, SciELO, and Lilacs. DISCUSSION: In studies investigating acute use effects, higher doses of tetrahydrocannabinol are associated to impairments in performance of nonsevere users in planning and control impulse tasks. However, chronic cannabis users do not show those impairments. Although demonstration of residual effects of cannabis in the executive functioning is controversial, persistent deficits seem to be present at least in a subgroup of chronic users after 28 days of abstinence. CONCLUSIONS: The neuropsychological studies found did not have as a main aim the evaluation of executive functioning. A criterial selection of standardized neuropsychological tests, more appropriate study designs as well as concomitant investigations with structural and functional neuroimaging techniques may improve the understanding of eventual neurotoxicity associated with cannabis use.
Assuntos
Canabinoides/farmacologia , Transtornos Cognitivos/induzido quimicamente , Cognição/efeitos dos fármacos , Abuso de Maconha/psicologia , Fumar Maconha/efeitos adversos , Atenção/efeitos dos fármacos , Transtornos Cognitivos/fisiopatologia , Formação de Conceito/efeitos dos fármacos , Tomada de Decisões , Dronabinol/toxicidade , Lobo Frontal/efeitos dos fármacos , Humanos , Comportamento Impulsivo/induzido quimicamente , Comportamento Impulsivo/fisiopatologia , Comportamento Impulsivo/psicologia , Fumar Maconha/fisiopatologia , Fumar Maconha/psicologia , Testes NeuropsicológicosRESUMO
OBJETIVO: A maconha é a droga ilícita mais consumida no mundo, porém ainda existem poucos estudos examinando eventuais prejuízos cognitivos relacionados ao seu uso. As manifestações clínicas associadas a esses déficits incluem síndrome amotivacional, prejuízo na flexibilidade cognitiva, desatenção, dificuldade de raciocínio abstrato e formação de conceitos, aspectos intimamente ligados às funções executivas, as quais potencialmente exercem um papel central na dependência de substâncias. O objetivo do estudo foi fazer uma revisão a respeito das implicações do uso da maconha no funcionamento executivo. MÉTODO: Esta revisão foi conduzida utilizando-se bases de dados eletrônicas (MedLine, Pubmed, SciELO and Lilacs). DISCUSSÃO: Em estudos de efeito agudo, doses maiores de tetrahidrocanabinol encontram-se associadas a maior prejuízo no desempenho de usuários leves em tarefas de controle inibitório e planejamento; porém, este efeito dose-resposta não ocorre em usuários crônicos. Embora haja controvérsias no que se refere a efeitos residuais da maconha, déficits persistentes parecem estar presentes após 28 dias de abstinência, ao menos em um subgrupo de usuários crônicos. CONCLUSÕES: Os estudos encontrados não tiveram como objetivo principal a avaliação das funções executivas. A seleção de testes padronizados, desenhos de estudos mais apropriados e o uso concomitante com técnicas de neuroimagem estrutural e funcional podem auxiliar na melhor compreensão das conseqüências deletérias do uso crônico da maconha no funcionamento executivo.
OBJECTIVE: Cannabis is the most used illicit drug worldwide, however only a few studies have examined cognitive deficits related to its use. Clinical manifestations associated with those deficits include amotivational syndrome, impairment in cognitive flexibility, inattention, deficits in abstract reasoning and concept formation, aspects intimately related to the executive functions, which potentially exert a central role in substance dependence. The objective was to make a review about consequences of cannabis use in executive functioning. METHOD: This review was carried out on reports drawn from MedLine, SciELO, and Lilacs. DISCUSSION: In studies investigating acute use effects, higher doses of tetrahydrocannabinol are associated to impairments in performance of nonsevere users in planning and control impulse tasks. However, chronic cannabis users do not show those impairments. Although demonstration of residual effects of cannabis in the executive functioning is controversial, persistent deficits seem to be present at least in a subgroup of chronic users after 28 days of abstinence. CONCLUSIONS: The neuropsychological studies found did not have as a main aim the evaluation of executive functioning. A criterial selection of standardized neuropsychological tests, more appropriate study designs as well as concomitant investigations with structural and functional neuroimaging techniques may improve the understanding of eventual neurotoxicity associated with cannabis use.
Assuntos
Humanos , Canabinoides/farmacologia , Transtornos Cognitivos/induzido quimicamente , Cognição/efeitos dos fármacos , Abuso de Maconha/psicologia , Fumar Maconha/efeitos adversos , Atenção/efeitos dos fármacos , Transtornos Cognitivos/fisiopatologia , Formação de Conceito/efeitos dos fármacos , Tomada de Decisões , Lobo Frontal/efeitos dos fármacos , Comportamento Impulsivo/induzido quimicamente , Comportamento Impulsivo/fisiopatologia , Comportamento Impulsivo/psicologia , Fumar Maconha/fisiopatologia , Fumar Maconha/psicologia , Testes Neuropsicológicos , Dronabinol/toxicidadeRESUMO
BACKGROUND: Although heavy smoking has been associated with impulsivity in humans, it is not clear whether poor impulse control represents a risk factor in the etiology of nicotine dependence. METHODS: To address this issue, rats were selected on the basis of individual differences in impulsivity in the delayed reward task (impulsive choice) and the 5-choice serial reaction time task (impulsive action). Subsequently, rats were subjected to a nicotine self-administration (SA) paradigm tailored to measure the motivational properties of nicotine and nicotine-associated stimuli. In separate groups, differences in electrically evoked dopamine release in slice preparations obtained from several mesolimbic brain regions were determined. RESULTS: Impulsive action was associated with an enhanced motivation to initiate and maintain nicotine SA. In contrast, impulsive choice predicted a diminished ability to inhibit nicotine seeking during abstinence and an enhanced vulnerability to relapse upon re-exposure to nicotine cues. Impulsive action was associated with reduced dopamine release in the accumbens core and impulsive choice with reduced dopamine release in accumbens core, shell, and medial prefrontal cortex. CONCLUSIONS: The strong association between sub-dimensions of impulsivity and nicotine SA implies that interventions aimed to improve impulse control might help to reduce susceptibility to nicotine dependence and/or lead to successful smoking cessation.