Deep Brain Stimulation of the Subthalamic Nucleus Improves Reward-Based Decision-Learning in Parkinson's Disease

Recently, the subthalamic nucleus (STN) has been shown to be critically involved in decision-making, action selection, and motor control. Here we investigate the effect of deep brain stimulation (DBS) of the STN on reward-based decision-learning in patients diagnosed with Parkinson's disease (PD). We determined computational measures of outcome evaluation and reward prediction from PD patients who performed a probabilistic reward-based decision-learning task. In previous work, these measures covaried with activation in the nucleus caudatus (outcome evaluation during the early phases of learning) and the putamen (reward prediction during later phases of learning). We observed that stimulation of the STN motor regions in PD patients served to improve reward-based decision-learning, probably through its effect on activity in frontostriatal motor loops (prominently involving the putamen and, hence, reward prediction). In a subset of relatively younger patients with relatively shorter disease duration, the effects of DBS appeared to spread to more cognitive regions of the STN, benefiting loops that connect the caudate to various prefrontal areas importantfor outcome evaluation. These results highlight positive effects of STN stimulation on cognitive functions that may benefit PD patients in daily-life association-learning situations

Eating to stop: Tyrosine supplementation enhances inhibitory control but not response execution

Animal studies and research in humans have shown that the supplementation of tyrosine, or tyrosine-containing diets, increase the plasma tyrosine and enhance brain dopamine (DA). However, the strategy of administering tyrosine (and the role of DA therein) to enhance cognition is unclear and heavily debated. We studied, in a healthy population, whether tyrosine supplementation improves stopping overt responses, a core cognitive-control function. In a double-blind, placebo-controlled, within-subject design, one hour following the administration of tyrosine (corresponding to the beginning of the 1 h-peak of the plasma concentration) or placebo, participants performed a stop-signal task—which taps into response inhibition and response execution speed. Participants in the Tyrosine condition were more efficient in inhibiting unwanted action tendencies but not in reacting to go signals. This is the first demonstration that the supplementation of tyrosine selectively targets, and reliably improves the ability to stop overt responses

Is (poly-) substance use associated with impaired inhibitory control? A mega-analysis controlling for confounders.

Many studies have reported that heavy substance use is associated with impaired response inhibition. Studies typically focused on associations with a single substance, while polysubstance use is common. Further, most studies compared heavy users with light/non-users, though substance use occurs along a continuum. The current mega-analysis accounted for these issues by aggregating individual data from 43 studies (3610 adult participants) that used the Go/No-Go (GNG) or Stop-signal task (SST) to assess inhibition among mostly "recreational" substance users (i.e., the rate of substance use disorders was low). Main and interaction effects of substance use, demographics, and task-characteristics were entered in a linear mixed model. Contrary to many studies and reviews in the field, we found that only lifetime cannabis use was associated with impaired response inhibition in the SST. An interaction effect was also observed: the relationship between tobacco use and response inhibition (in the SST) differed between cannabis users and non-users, with a negative association between tobacco use and inhibition in the cannabis non-users. In addition, participants' age, education level, and some task characteristics influenced inhibition outcomes. Overall, we found limited support for impaired inhibition among substance users when controlling for demographics and task-characteristics

Neurocognitive mechanisms of cognitive control: The role of prefrontal cortex in action selection, response inhibition, performance monitoring, and reward-based learning

International audienceno abstrac

Lifespan changes in global and selective stopping and performance adjustments

This study examined stopping and performance adjustments in four age groups (M ages: 8, 12, 21, and 76 years). All participants performed on three tasks, a standard two-choice task and the same task in which stop-signal trials were inserted requiring either the suppression of the response activated by the choice stimulus (global stop task) or the suppression of the response when one stop signal was presented but not when the other stop signal occurred (selective stop task). The results showed that global stopping was faster than selective stopping in all age groups. Global stopping matured more rapidly than selective stopping. The developmental gain in stopping was considerably more pronounced compared to the loss observed during senescence. All age groups slowed the response on trials without a stop signal in the stop task compared to trials in the choice task, the elderly in particular. In addition, all age groups slowed on trials following stop-signal trials, except the elderly who did not slow following successful inhibits. By contrast, the slowing following failed inhibits was disproportionally larger in the elderly compared to young adults. Finally, sequential effects did not alter the pattern of performance adjustments. The results were interpreted in terms of developmental change in the balance between proactive and reactive control

Impaired inhibition of prepotent motor actions in patients with Tourette syndrome

BACKGROUND: Evidence that tic behaviour in individuals with Tourette syndrome reflects difficulties inhibiting prepotent motor actions is mixed. Response conflict tasks produce sensitive measures of response interference from prepotent motor impulses and the proficiency of inhibiting these impulses as an act of cognitive control. We tested the hypothesis that individuals with Tourette syndrome show a deficit in inhibiting prepotent motor actions. METHODS: Healthy controls and older adolescents/adults with persistent Tourette syndrome without a history of obsessive–compulsive disorder or attention-deficit/hyperactivity disorder and presenting with stable mood functioning (i.e., no history of well-treated anxiety or depression) participated in this study. They performed a Simon task that induced conflict between prepotent actions and goal-directed actions. A novel theoretical framework distinguished group differences in acting impulsively (i.e., fast motor errors) from the proficiency of inhibiting interference by prepotent actions (i.e., slope of interference reduction). RESULTS: We included 27 controls and 28 individuals with Tourette syndrome in our study. Both groups showed similar susceptibility to making fast, impulsive motor errors (Tourette syndrome 26% v. control 23%; p = 0.10). The slope (m) reduction of the interference effect was significantly less pronounced among participants with Tourette syndrome than controls (Tourette syndrome: m = −0.07 v. control: m = −0.23; p = 0.022), consistent with deficient inhibitory control over prepotent actions in Tourette syndrome. LIMITATIONS: This study does not address directly the role of psychiatric comorbidities and medication effects on inhibitory control over impulsive actions in individuals with Tourette syndrome. CONCLUSION: The results offer empirical evidence for deficient inhibitory control over prepotent motor actions in individuals with persistent Tourette syndrome with minimal to absent psychiatric comorbidities. These findings also suggest that the frontal–basal ganglia circuits involved in suppressing unwanted motor actions may underlie deficient inhibitory control abilities in individuals with Tourette syndrome

Frontostriatal activity and connectivity increase during proactive inhibition across adolescence and early adulthood

During adolescence, functional and structural changes in the brain facilitate the transition from childhood to adulthood. Because the cortex and the striatum mature at different rates, temporary imbalances in the frontostriatal network occur. Here, we investigate the development of the subcortical and cortical components of the frontostriatal network from early adolescence to early adulthood in 60 subjects in a cross-sectional design, using functional MRI and a stop-signal task measuring two forms of inhibitory control: reactive inhibition (outright stopping) and proactive inhibition (anticipation of stopping). During development, reactive inhibition improved: older subjects were faster in reactive inhibition. In the brain, this was paralleled by an increase in motor cortex suppression. The level of proactive inhibition increased, with older subjects slowing down responding more than younger subjects when anticipating a stop-signal. Activation increased in the right striatum, right ventral and dorsal inferior frontal gyrus, and supplementary motor area. Moreover, functional connectivity during proactive inhibition increased between striatum and frontal regions with age. In conclusion, we demonstrate that developmental improvements in proactive inhibition are paralleled by increases in activation and functional connectivity of the frontostriatal network. These data serve as a stepping stone to investigate abnormal development of the frontostriatal network in disorders such as schizophrenia and attention-deficit hyperactivity disorder