Patients with basal ganglia damage show preserved learning in an economic game.

Both basal ganglia (BG) and orbitofrontal cortex (OFC) have been widely implicated in social and non-social decision-making. However, unlike OFC damage, BG pathology is not typically associated with disturbances in social functioning. Here we studied the behavior of patients with focal lesions to either BG or OFC in a multi-strategy competitive game known to engage these regions. We find that whereas OFC patients are significantly impaired, BG patients show intact learning in the economic game. By contrast, when information about the strategic context is absent, both cohorts are significantly impaired. Computational modeling further shows a preserved ability in BG patients to learn by anticipating and responding to the behavior of others using the strategic context. These results suggest that apparently divergent findings on BG contribution to social decision-making may instead reflect a model where higher-order learning processes are dissociable from trial-and-error learning, and can be preserved despite BG damage

Investigating the influence of smoking on willed action and cognitive function in individuals with brain injury

Rationale: Smoking triggers dopamine release, particularly in the mesocorticolimbic dopamine system. Activation of this system has a major overlap with functioning of the frontostriatal circuitry, which has been labelled the 'willed action system'. 'Willed action' describes action that is non-automatic, internally generated, effortful, and involves conscious control. It is implicated in initiation and motivation. There is evidence that abstinence from smoking leads to acute impairments in a range of cognitive and motivational measures, many of which are associated with frontal / frontostriatal functioning. Aims: The current study aimed to investigate the effects of smoking on willed action in 18 brain-injured smokers. Method: A within-subjects cross-over design was utilised, to compare performance after an acute (>2 hours) period of abstinence from smoking with performance after smoking. The test battery included measures of reward responsivity (objective and subjective measures of motivation), initiation (verbal fluency), and working memory. Results: Reward responsivity was enhanced after a cigarette had been smoked compared to the abstinent condition. Additionally, performance on the card sorting task was particularly enhanced after smoking on the first occasion, i.e. when the task was novel. There was no significant enhancement on any other measure. Conclusion: The results suggest that reward responsivity is modulated by acute smoking status, suggesting a specific effect of nicotine on aspects of motivation. Enhancement of performance is particularly seen when the task is novel. These conclusions are partially in concordance with a willed action framework. Implications are discussed with reference to routine neuropsychological assessments, and a possible role for nicotine as a therapeutic agent for enhancing motivation after acquired brain injury

Extending the knowledge on performance monitoring in obsessive-compulsive disorder: Insights gained by electrophysiological recordings and deep brain stimulation.

Obsessive-compulsive disorder (OCD) is characterized by alterations in frontostriatal circuits and associated impairments in performance monitoring. The overactivity of the performance monitoring system is reflected by enhanced electrophysiological correlates during decision conflict (conflict-theta) and error processing (error-theta and error-related negativity, ERN). Besides the mediofrontal cortex, composing the source of these correlates, further brain structures are fundamentally involved in these cognitive processes. Particularly, the anterior limb of internal capsule (ALIC) and nucleus accumbens (NAc) are not only involved in performance monitoring but show partially also altered activity in OCD. Despite the importance of ALIC/NAc in performance monitoring observation of its electrophysiological activity during decision conflict and error processing are limited. Notably, ALIC/NAc has been established as target region for deep brain stimulation (DBS) for treatment resistant OCD and has proved to be clinically effective. Although, it is still unknown whether stimulation of the ALIC/NAc affects the aforementioned cortical correlates. In the first part of the present dissertation, electrophysiological activity during decision conflict and error processing from the cortex and the ALIC/NAc (by means of local-filed potentials, LFP) was investigated in patients with OCD (LFP-study). As expected, previous findings were successfully replicated cortical correlates of decision conflict (conflict-theta) and error processing (error-theta and ERN) were observed. Additionally, it was hypothesized that LFPs from the ALIC/NAc also comprises correlates of decision conflict (LFP-conflict-theta) and error processing (LFP-error-theta and LFP-ERN). Indeed, all three performance monitoring modulations were observed in the ALIC/NAc. Accordingly, ALIC/NAc seems to be involved in processes associated with monitoring of decision conflict and performance errors. Presumably, it provides the signal for the need of increased cognitive control to resolve the conflict and of behavioral adaptation to improve performance, respectively. Although, it was expected to find increased frontostriatal connectivity during decision conflict and error monitoring, this was not confirmed. Putatively, this could be explained by increased connectivity between both structures irrespective of cognitive control demands in OCD. Finally, possible interrelations between striatal correlates and symptom severity or symptom improvement by DBS in OCD were explored. Our results indicated an association of patients who exhibited smaller error signals (LFP-error-theta and LFP-ERN) with lesser symptom severity and with greater DBS efficacy. This links ALIC/NAc performance monitoring modulations to OCD symptomatology, possibly reflecting hyperactive performance monitoring, and connect this to attenuated response to DBS. In the second part of the present dissertation, the modulatory effect of DBS on cortical correlates of decision conflict (conflict-theta) and error processing (ERN) was investigated by comparing the correlates from pre-DBS state with stimulation on and stimulation off (Stimulation-study). It was hypothesized that acute DBS reduces conflict-theta and the ERN and that these effects would rebound after cessation of stimulation. In line with our hypotheses, the correlates were decreased by acute stimulation, indicating DBS-induced reduction of the pathologically overactive performance monitoring system. Contrary to our hypotheses, the rebound effect after cessation of stimulation was not observed for conflict-theta but at trend level for the ERN. Likely, DBS has only acute and no long-term effects on the performance monitoring system, which might become clearer by extending the stimulation off phase. Finally, possible interrelations between clinical efficacy of DBS with pre-DBS conflict-theta and the ERN and their changes through stimulation were explored. Our results associated patients who exhibited smaller pre-DBS ERN with greater DBS efficacy. In conclusion, this dissertation provides new insights on electrophysiological correlates of performance monitoring in OCD derived from ALIC/NAc and on the modulation of their cortical pendants by DBS. Further investigations, particularly involving long-term acquisition of LFPs, are required to further characterize ALIC/NAc activity during performance monitoring and its association with the pathophysiology of DBS. Also, additional studies are needed to confirm the interrelation between electrophysiological correlates and clinical parameters with regard to clinical applications in the future. Particularly, it should be further explored whether increased cortical and striatal error signals point toward a hyperactive performance monitoring system and are also related to attenuated clinical efficacy

Reduced reward-related probability learning in schizophrenia patients

Although it is known that individuals with schizophrenia demonstrate marked impairment in reinforcement learning, the details of this impairment are not known. The aim of this study was to test the hypothesis that reward-related probability learning is altered in schizophrenia patients. Twenty-five clinically stable schizophrenia patients and 25 age- and gender-matched controls participated in the study. A simple gambling paradigm was used in which five different cues were associated with different reward probabilities (50%, 67%, and 100%). Participants were asked to make their best guess about the reward probability of each cue. Compared with controls, patients had significant impairment in learning contingencies on the basis of reward-related feedback. The correlation analyses revealed that the impairment of patients partially correlated with the severity of negative symptoms as measured on the Positive and Negative Syndrome Scale but that it was not related to antipsychotic dose. In conclusion, the present study showed that the schizophrenia patients had impaired reward-based learning and that this was independent from their medication status

Reduced neural connectivity but increased task-related activity during working memory in de novo Parkinson patients

Objective: Patients with Parkinson's disease (PD) often suffer from impairments in executive functions, such as working memory deficits. It is widely held that dopamine depletion in the striatum contributes to these impairments through decreased activity and connectivity between task-related brain networks. We investigated this hypothesis by studying task-related network activity and connectivity within a sample of de novo patients with PD, versus healthy controls, during a visuospatial working memory task. Methods: Sixteen de novo PD patients and 35 matched healthy controls performed a visuospatial n-back task while we measured their behavioral performance and neural activity using functional magnetic resonance imaging. We constructed regions-of-interest in the bilateral inferior parietal cortex (IPC), bilateral dorsolateral prefrontal cortex (DLPFC), and bilateral caudate nucleus to investigate group differences in task-related activity. We studied network connectivity by assessing the functional connectivity of the bilateral DLPFC and by assessing effective connectivity within the frontoparietal and the frontostriatal networks. Results: PD patients, compared with controls, showed trend-significantly decreased task accuracy, significantly increased task-related activity in the left DLPFC and a trend-significant increase in activity of the right DLPFC, left caudate nucleus, and left IPC. Furthermore, we found reduced functional connectivity of the DLPFC with other task-related regions, such as the inferior and superior frontal gyri, in the PD group, and group differences in effective connectivity within the frontoparietal network. Interpretation: These findings suggest that the increase in working memory-related brain activity in PD patients is compensatory to maintain behavioral performance in the presence of network deficits. Hum Brain Mapp 36:1554-1566, 2015. (c) 2015 Wiley Periodicals, Inc

Cognitive Control Deficits in Individuals with Differing Levels of Autistic Traits

This item is only available electronically.Deficits in inhibitory control are common in Autism Spectrum Disorders (ASD) and are associated with higher levels of repetitive behaviours. Inhibitory deficits may present as an inability to stop a prepotent motor response (reactive inhibition), or as an inability to delay a response onset before it is performed (proactive inhibition). Previous studies have found conflicting results in reactive inhibition deficits in children with ASD indicating heterogeneity in stopping ability, while limited research into proactive inhibition has demonstrated more consistent deficits. This study aims to explore deficits in both types of inhibition in individuals from the general population with differing levels of autistic traits, by comparing two tasks measuring proactive and reactive inhibition. A Stop Signal Task (SST) and reinforcement learning task were administered to 152 participants (18-81 years). Level of autistic traits was measured using the AQ-28 scale. Stop Signal Reaction Time (SSRT) (an index of reactive inhibition) and post-error slowing (a measure of proactive inhibition) were examined in the SST, while another measure of proactive inhibition (reaction time between trials of high and low conflict) was obtained from the reinforcement learning task. Results indicated no significant deficits in both reactive and proactive inhibition regardless of self-reported autistic trait level. A modest interaction effect between age and SSRT predicted Routine subscale score on the AQ-28, suggesting that repetitive behaviour level can be altered by reactive inhibition ability changes across the lifespan. Cognitive control deficits in ASD therefore may be related to factors outside of response inhibition alone.Thesis (B.PsychSc(Hons)) -- University of Adelaide, School of Psychology, 202

Investigation of neuronal structures and networks on the modulation of decision-making and impulse control by temporary inactivation via local microinfusion of the GABAA receptor agonist muscimol in rats

Impulsivity is determined by deficits in decision-making (impulsive choice) and impulse control (impulsive action). Using reversible inactivation via microinfusion of the GABAA receptor agonist muscimol the thesis aimed to elucidate the participation of the ventral medial prefrontal cortex (vmPFC), the nucleus accumbens (NAc) core and shell as well as the connections of the vmPFC and the NAc subregions in both forms of impulsivity in rats. The present results indicate that impulse control is regulated by both structures, while impulsive decision-making is principally modulated by the NAc, and not the vmPFC. The current investigation suggests both functional dissociations and close interactions between the vmPFC and NAc in terms of impulsive action, depending on the involved accumbal subregion. The NAc shell constitutes the critical region mediating both types of impulsivity, whereas the NAc core seems to be implicated in non-specific impairments beyond impulsive choice. Consequently, this work points towards various specific frontostriatal systems differentially contributing to delay-based decision-making and particularly impulse control

Frontostriatal anatomical connections predict age- and difficulty-related differences in reinforcement learning

Contains fulltext : 167812.pdf (Publisher’s version ) (Closed access)Reinforcement learning (RL) is supported by a network of striatal and frontal cortical structures that are connected through white-matter fiber bundles. With age, the integrity of these white-matter connections declines. The role of structural frontostriatal connectivity in individual and age-related differences in RL is unclear, although local white-matter density and diffusivity have been linked to individual differences in RL. Here we show that frontostriatal tract counts in young human adults (aged 18-28), as assessed noninvasively with diffusion-weighted magnetic resonance imaging and probabilistic tractography, positively predicted individual differences in RL when learning was difficult (70% valid feedback). In older adults (aged 63-87), in contrast, learning under both easy (90% valid feedback) and difficult conditions was predicted by tract counts in the same frontostriatal network. Furthermore, network-level analyses showed a double dissociation between the task-relevant networks in young and older adults, suggesting that older adults relied on different frontostriatal networks than young adults to obtain the same task performance. These results highlight the importance of successful information integration across striatal and frontal regions during RL, especially with variable outcomes.12 p