Waiting Impulsivity: The Influence of Acute Methylphenidate and Feedback.

BACKGROUND: The ability to wait and to weigh evidence is critical to behavioral regulation. These behaviors are known as waiting and reflection impulsivity. In Study 1, we examined the effects of methylphenidate, a dopamine and norepinephrine reuptake inhibitor, on waiting and reflection impulsivity in healthy young individuals. In study 2, we assessed the role of learning from feedback in disorders of addiction. METHODS: We used the recently developed 4-Choice Serial Reaction Time task and the Beads task. Twenty-eight healthy volunteers were tested twice in a randomized, double-blind, placebo-controlled cross-over trial with 20mg methylphenidate. In the second study, we analyzed premature responses as a function of prior feedback in disorders of addiction. RESULTS: Study 1: Methylphenidate was associated with greater waiting impulsivity to a cue predicting reward along with faster responding to target onset without a generalized effect on reaction time or attention. Methylphenidate influenced reflection impulsivity based on baseline impulsivity. Study 2: More premature responses occurred after premature responses in stimulant-dependent subjects. CONCLUSIONS: We show that methylphenidate has dissociable effects on waiting and reflection impulsivity. Chronic stimulant exposure impairs learning from prior premature responses, suggesting a failure to learn that premature responding is suboptimal. These findings provide a greater mechanistic understanding of waiting impulsivity.

Disrupted avoidance learning in functional neurological disorder: Implications for harm avoidance theories.

BACKGROUND: Functional neurological disorder (FND) is an elusive disorder characterized by unexplained neurological symptoms alongside aberrant cognitive processing and negative affect, often associated with amygdala reactivity. METHODS: We examined the effect of negative conditioning on cognitive function and amygdala reactivity in 25 FND patients and 20 healthy volunteers (HV). Participants were first conditioned to stimuli paired with negative affective or neutral (CS +/CS -) information. During functional MRI, subjects then performed an instrumental associative learning task to avoid monetary losses in the context of the previously conditioned stimuli. We expected that FND patients would be better at learning to avoid losses when faced with negatively conditioned stimuli (increased harm avoidance). Multi-echo resting state fMRI was also collected from the same subjects and a robust denoising method was employed, important for removing motion and physiological artifacts. RESULTS: FND subjects were more sensitive to the negative CS + compared to HV, demonstrated by a reinforcement learning model. Contrary to expectation, FND patients were generally more impaired at learning to avoid losses under both contexts (CS +/CS -), persisting to choose the option that resulted in a negative outcome demonstrated by both behavioural and computational analyses. FND patients showed enhanced amygdala but reduced dorsolateral prefrontal cortex responses when they received negative feedback. Patients also had increased resting state functional connectivity between these two regions. CONCLUSIONS: FND patients had impaired instrumental avoidance learning, findings that parallel previous observations of impaired action-outcome binding. FND patients further show enhanced behavioural and neural sensitivity to negative information. However, this did not translate to improved avoidance learning. Put together, our findings do not support the theory of harm avoidance in FND. We highlight a potential mechanism by which negative contexts interfere with adaptive behaviours in this under-explored disorder.

Sexually dimorphic brain volume interaction in college-aged binge drinkers.

BACKGROUND: Binge consumption of alcohol is a major societal problem associated with important cognitive, physiological and neurotoxic consequences. Converging evidence highlights the need to assess binge drinking (BD) and its effects on the developing brain while taking into account gender differences. Here, we compared the brain volumetric differences between genders in college-aged binge drinkers and healthy volunteers. METHOD: T1-weighted magnetic resonance imaging (MRI) images of 30 binge drinkers (18 males) and 46 matched healthy volunteers (23 males) were examined using voxel-based morphometry. The anatomical scans were covaried with Alcohol Use Disorders Identification Test (AUDIT) scores. Whole brain voxel-wise group comparisons were performed using a cluster extent threshold correction. RESULTS: Several large clusters qualified with group-by-gender interactions were observed in prefrontal, striatal and medial temporal areas, whereby BD females had more volume than non-BD females, while males showed the inverse pattern of decreased volume in BD males and increased volume in non-BD males. AUDIT scores negatively correlated with volume in the right superior frontal cortex and precentral gyrus. CONCLUSIONS: These findings dovetail with previous studies reporting that a state effect of BD in college-aged drinkers and the severity of alcohol use are associated with volumetric alterations in the cortical and subcortical areas of the brain. Our study indicates that these widespread volumetric changes vary differentially by gender, suggesting either sexual dimorphic endophenotypic risk factors, or differential neurotoxic sensitivities for males and females.