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Executive function, the cognitive processes that allow the voluntary control of goal-directed behaviour, can be studied through the examination of inhibition of action. The countermanding paradigm has been shown to be a powerful tool to examine a subject’s ability to withhold responses to a go stimulus when a stop signal is presented occasionally. Logan and Cowan (1984) developed a race model to account for countermanding performance in humans, proposing that independent go and stop process initiated by the go and stop signals respectively, race toward a finish line whereby the first process to cross its finish line determines the behavioural outcome. The model allows estimation of the stop signal response time, a variable that is not directly observable. The race model has yet to be validated for countermanding performance in rats. Using a new rodent countermanding task inspired directly from human studies, male Wistar rats were trained to respond to a visual stimulus (go signal) by pressing a lever below an illuminated light for food reward, but to countermand lever the press (25% of trials) subsequent to an auditory tone (stop signal) presented after a variable delay. The ability to cancel a response decreased as stop signal delay increased. The stop signal response time for rats was estimated to be 157 ms, a value within the range of human estimates. Predictions of countermanding performance made by the race model were generally respected. Response times of movements that escape inhibition: 1) were shorter than those of movements made in the absence of a stop signal; 2) gradually lengthened with increasing stop signal delay; and most importantly, 3) were predicted by the race model. These findings demonstrate that the countermanding performance of rodents can be accounted for by a simple race model, which has been applied successfully in human studies and nonhuman primate models. This new animal model will permit complementary invasive investigations of brain mechanisms underlying inhibitory control and refine the existing rodent models of neurological disease and impulsivity. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2008-09-30 11:35:44.713

Social interactions in early life influence the organization of neural and behavioural systems of developing mammalian young. Deprivation of social interactions with the primary caregiver and other immediate conspecifics (early social deprivation) has lasting consequences on behavioural functioning in later life. The purpose of this thesis was to investigate how early social deprivation affects the motivational aspects of behaviour in the context of appetitive stimuli. Rats were reared in complete isolation from the mother and litter using the method of artificial rearing (AR). Control rats were maternally reared (MR). In adulthood, rats were tested in a series of behavioural paradigms designed to assess the motivational impact of primary food reward and reward-related cues on food-seeking behaviour. AR increased the behavioural responsiveness of rats to the motivational impact of reward-related cues, but not to primary rewards themselves. Specifically, there were no significant effects of AR on food consumption or goal-directed instrumental responding for food. However, AR enhanced instrumental responding triggered by a previously conditioned reward cue. AR also increased the expression of approach behaviour towards a localizable conditioned reward cue and instrumental responding when the same cue was used as a reinforcer. An assessment of the mediating factors during development revealed that the lack of tactile stimulation normally received from the mother, but not sustained exposure to the stress hormone corticosterone, contributed to the long-term effects of AR. These findings represent a potential link between early-life social adversity and vulnerability to the development of problems with behavioural inhibition and attention in the presence of appetitive environmental cues.

Social interactions in early life influence the organization of neural and behavioural systems of developing mammalian young. Deprivation of social interactions with the primary caregiver and other immediate conspecifics (early social deprivation) has lasting consequences on behavioural functioning in later life. The purpose of this thesis was to investigate how early social deprivation affects the motivational aspects of behaviour in the context of appetitive stimuli. Rats were reared in complete isolation from the mother and litter using the method of artificial rearing (AR). Control rats were maternally reared (MR). In adulthood, rats were tested in a series of behavioural paradigms designed to assess the motivational impact of primary food reward and reward-related cues on food-seeking behaviour. AR increased the behavioural responsiveness of rats to the motivational impact of reward-related cues, but not to primary rewards themselves. Specifically, there were no significant effects of AR on food consumption or goal-directed instrumental responding for food. However, AR enhanced instrumental responding triggered by a previously conditioned reward cue. AR also increased the expression of approach behaviour towards a localizable conditioned reward cue and instrumental responding when the same cue was used as a reinforcer. An assessment of the mediating factors during development revealed that the lack of tactile stimulation normally received from the mother, but not sustained exposure to the stress hormone corticosterone, contributed to the long-term effects of AR. These findings represent a potential link between early-life social adversity and vulnerability to the development of problems with behavioural inhibition and attention in the presence of appetitive environmental cues.

It is well established that methadone maintenance (MM) reduces but does not eliminate the self-administration of other illicit drugs. For those on MM, there is considerable variation in consumption patterns, route of heroin administration, additional non-opioid substances routinely administered and the clinical disorders associated with these patterns of use. While there is a large literature base documenting these phenomena, studies have been almost exclusively descriptive in nature, with little attempt to develop a theoretical model in which to understand such use. In the following thesis, a model proposed by Gray was tested, the Reinforcement Sensitivity Theory (RST). This biopsychosocial model broadly describes two action tendencies; approach (Behavioural Activation System) and avoidance or withdrawal (Flight Fight Freeze System and the Behavioural Inhibition System). The model proposes that a heightened sensitivity to punishment underlies anxiety disorders. Conversely, a heightened sensitivity to rewarding stimuli may predispose some individuals to engage in highly rewarding behaviour and is associated with conduct disorder and antisocial personality disorder. According to the Joint Subsystems Hypothesis, these personality styles are mutually dependent, whereby BIS and BAS interact to influence reward mediated and punishment mediated behaviours. Based on Gray's model, this thesis tests whether opiate dependent individuals with heightened sensitivity to punishment are more likely to use anxiolytic drugs (such as benzodiazepines), and individuals with heightened reward sensitivity will show a preference for substances that have high reward potential (such as stimulants). At time one, the participant sample (N= 120) comprised 71 males (59%) and 49 females who were opioid dependent and recruitment took place over an eight-month period in two city opioid replacement clinics. A range of measures was administered to assess substance use, mood, anxiety and the personality dimensions of reward sensitivity and punishment sensitivity, with substance use again measured at three months. Results of the first study suggested that a large proportion of the variance was accounted for by personality within the models. A total of 98 participants (81%) participated in the 12-week follow-up study. Sensitivity to punishment and reward significantly predicted drug preference. Although psychopathology symptoms were not able to moderate the relationship between personality and drug use, anxiety symptoms negatively mediated the relationship between punishment sensitivity and anxiolytic use, whereby the relationship became non-significant. In contrast, sensitivity to reward remained the strongest predictor of amphetamine use over antisocial characteristics. Individual differences were not able to predict treatment retention nor susceptibility to relapse during a 12-week initiation to a MM programme.

Attention-Deficit / Hyperactivity Disorder (ADHD) is characterized by higher than normal levels of inattention, hyperactivity and impulsivity. Behavioural inhibition is proposed to be a primary deficit in children with ADHD, and is included as a component of a number of models accounting for the core behavioural symptoms of ADHD. Children with ADHD often show deficits in their performance on behavioural inhibition tasks relative to typically developing children of the same age, although inconsistent findings have been observed. Stimulant medication is associated with reduction in the core symptoms of ADHD in the majority of children. The primary goal of this thesis was to examine the effects of stimulant medication on behavioural inhibition in children with ADHD. Furthermore, this thesis sought to determine whether children with ADHD who have, and have not taken stimulant medication differ from normally developing children in terms of behavioural inhibition. In order to achieve these aims, it was necessary to firstly determine which tasks provide the best measures of behavioural inhibition. While many tasks have been used to measure inhibitory control amongst children with ADHD, it was unclear from previous research which tasks measure the same constructs. Study 1 investigated relationships in task performance among seven measures of inhibitory control, including the Stop-Signal task, Go / No-go task, Sustained Attention to Response Task (SART; analogous the not-X Continuous Performance Task), Eriksen Flanker task, Stroop, Opposite Worlds task and Task-Switching task. Significant developmental changes in a variety of cognitive abilities occur across childhood and adolescence. To limit the possibility that developmental changes in task performance would be observed, the age range for children included in the study was restricted to seven to 10 years. Nevertheless, to interpret correlations among inhibition measures from the tasks, it was necessary to determine whether children showed comparable developmental trends in their performance across tasks. Study 1A investigated developmental changes in the performances of the seven tasks purported to measure inhibitory control in normally developing children aged seven to 10 years. The results of this study suggested that the tasks chosen were appropriate for use among this age group, and that there is little change in behavioural inhibition across the seven to 10 years age range. In Study 1B, inhibition measures from each of the tasks were included in an exploratory factor analysis to determine those tasks measuring the same constructs. The results of Study 1B suggested that the Stop-Signal, Go / No-go and SART tasks provided the best measures of the behavioural inhibition construct. Performance on the Eriksen Flanker task was also related to the performance on these tasks, but in a direction contrary to that predicted. The Stroop and Opposite Worlds tasks measured the same construct, which appeared to be interference control. Performance on the Task-Switching task was not related to the performance on any other task, suggesting that this task did not measure behavioural inhibition or interference control. Study 2 investigated the performance of children with ADHD on the three tasks shown to be the best measures of behavioural inhibition in Study 1B (i.e., the Stop-Signal task, Go / No-go task and Sustained Attention to Response task). Children with ADHD were aged from seven to 11 years, and were tested both when they had, and had not taken their regularly prescribed stimulant medication. The performance of children with ADHD on these tasks was compared to that of normally developing children matched in age. The results of Study 2 suggested that stimulant medication leads to significant improvement in behavioral inhibition amongst children with ADHD, such that children with ADHD do not differ from matched controls. However, this effect was not observed across all three tasks. Reasons for this, along with study limitations, and directions for future research are discussed.

Attention-Deficit / Hyperactivity Disorder (ADHD) is characterized by higher than normal levels of inattention, hyperactivity and impulsivity. Behavioural inhibition is proposed to be a primary deficit in children with ADHD, and is included as a component of a number of models accounting for the core behavioural symptoms of ADHD. Children with ADHD often show deficits in their performance on behavioural inhibition tasks relative to typically developing children of the same age, although inconsistent findings have been observed. Stimulant medication is associated with reduction in the core symptoms of ADHD in the majority of children. The primary goal of this thesis was to examine the effects of stimulant medication on behavioural inhibition in children with ADHD. Furthermore, this thesis sought to determine whether children with ADHD who have, and have not taken stimulant medication differ from normally developing children in terms of behavioural inhibition. In order to achieve these aims, it was necessary to firstly determine which tasks provide the best measures of behavioural inhibition. While many tasks have been used to measure inhibitory control amongst children with ADHD, it was unclear from previous research which tasks measure the same constructs. Study 1 investigated relationships in task performance among seven measures of inhibitory control, including the Stop-Signal task, Go / No-go task, Sustained Attention to Response Task (SART; analogous the not-X Continuous Performance Task), Eriksen Flanker task, Stroop, Opposite Worlds task and Task-Switching task. Significant developmental changes in a variety of cognitive abilities occur across childhood and adolescence. To limit the possibility that developmental changes in task performance would be observed, the age range for children included in the study was restricted to seven to 10 years. Nevertheless, to interpret correlations among inhibition measures from the tasks, it was necessary to determine whether children showed comparable developmental trends in their performance across tasks. Study 1A investigated developmental changes in the performances of the seven tasks purported to measure inhibitory control in normally developing children aged seven to 10 years. The results of this study suggested that the tasks chosen were appropriate for use among this age group, and that there is little change in behavioural inhibition across the seven to 10 years age range. In Study 1B, inhibition measures from each of the tasks were included in an exploratory factor analysis to determine those tasks measuring the same constructs. The results of Study 1B suggested that the Stop-Signal, Go / No-go and SART tasks provided the best measures of the behavioural inhibition construct. Performance on the Eriksen Flanker task was also related to the performance on these tasks, but in a direction contrary to that predicted. The Stroop and Opposite Worlds tasks measured the same construct, which appeared to be interference control. Performance on the Task-Switching task was not related to the performance on any other task, suggesting that this task did not measure behavioural inhibition or interference control. Study 2 investigated the performance of children with ADHD on the three tasks shown to be the best measures of behavioural inhibition in Study 1B (i.e., the Stop-Signal task, Go / No-go task and Sustained Attention to Response task). Children with ADHD were aged from seven to 11 years, and were tested both when they had, and had not taken their regularly prescribed stimulant medication. The performance of children with ADHD on these tasks was compared to that of normally developing children matched in age. The results of Study 2 suggested that stimulant medication leads to significant improvement in behavioral inhibition amongst children with ADHD, such that children with ADHD do not differ from matched controls. However, this effect was not observed across all three tasks. Reasons for this, along with study limitations, and directions for future research are discussed.

The immune system has been suggested as crucial in brain and psychological functioning. More precisely, immune markers reflecting immune system activity are important for psychological and mental health, as evident by their role in the physiopathology of depression and in the impairment of executive functions. Frontal alpha asymmetry (FAA), an electroencephalographic marker of brain function, has also been linked to such psychopathology and is thought to reflect psychological processes underlying approach- versus withdrawal-related motivation and higher-order inhibitory control. Only a few studies have linked FAA to immune markers but notably found a negative association between IL-6, a pleiotropic pro-inflammatory cytokine, and FAA. The aim of the present work is thus to study the relationship between various immune markers (including pro-inflammatory cytokines and IL-6) and FAA. 35 healthy young male participants underwent a resting EEG recording and blood sampling from which immune markers were measured. The results did not suggest an association between IL-6 and FAA. No other immune markers were either suggested to be associated to FAA. The complexity of the immune system (e.g., effect of cytokines) is underlined and may explain the results. Despite such results, the implication of true negative correlations between FAA and circulating immune markers, as suggested in previous studies, is discussed in the light of the theoretical models of FAA.

Social anxiety disorder, also known as social phobia, is one of the most prevalent anxiety disorders, affecting 7-13% of subjects in the community at some time in their lives. Despite being eminently treatable, it remains largely under-recognised and, therefore, undertreated. The disorder is characterized by a fear of scrutiny by others, with sufferers experiencing excessive anxiety in social and performance situations. This excessive anxiety usually leads to avoidance behaviour that can severely affect normal daily living. With onset commonly occurring during childhood or adolescence, social anxiety disorder may disrupt normal patterns of development of social and personal relationships, often having a long-term impact on emotional stability in social or working life. If left untreated, the course of social anxiety disorder is frequently complicated with comorbid conditions, particularly major depression or substance abuse. This review assesses the size of the clinical problem by evaluating current and lifetime prevalence estimates, age of onset, risk factors and evolution of the clinical course; thereby providing the rationale for early recognition and prompt treatment.

Social anxiety disorder, also known as social phobia, is one of the most prevalent anxiety disorders, affecting 7-13% of subjects in the community at some time in their lives. Despite being eminently treatable, it remains largely under-recognised and, therefore, undertreated. The disorder is characterized by a fear of scrutiny by others, with sufferers experiencing excessive anxiety in social and performance situations. This excessive anxiety usually leads to avoidance behaviour that can severely affect normal daily living. With onset commonly occurring during childhood or adolescence, social anxiety disorder may disrupt normal patterns of development of social and personal relationships, often having a long-term impact on emotional stability in social or working life. If left untreated, the course of social anxiety disorder is frequently complicated with comorbid conditions, particularly major depression or substance abuse. This review assesses the size of the clinical problem by evaluating current and lifetime prevalence estimates, age of onset, risk factors and evolution of the clinical course; thereby providing the rationale for early recognition and prompt treatment.