Methylphenidate boosts choices of mental labor over leisure depending on striatal dopamine synthesis capacity.

The cognitive enhancing effects of methylphenidate are well established, but the mechanisms remain unclear. We recently demonstrated that methylphenidate boosts cognitive motivation by enhancing the weight on the benefits of a cognitive task in a manner that depended on striatal dopamine. Here, we considered the complementary hypothesis that methylphenidate might also act by changing the weight on the opportunity cost of a cognitive task, that is, the cost of foregoing alternative opportunity.

Countermanding Perceptual Decision-Making.

We investigated whether a task requiring concurrent perceptual decision-making and response control can be performed concurrently, whether evidence accumulation and response control are accomplished by the same neurons, and whether perceptual decision-making and countermanding can be unified computationally. Based on neural recordings in a prefrontal area of macaque monkeys, we present behavioral, neural, and computational results demonstrating that perceptual decision-making of varying difficulty can be countermanded efficiently, that single prefrontal neurons instantiate both evidence accumulation and response control, and that an interactive race between stochastic GO evidence accumulators for each alternative and a distinct STOP accumulator fits countermanding choice behavior and replicates neural trajectories. Thus, perceptual decision-making and response control, previously regarded as distinct mechanisms, are actually aspects of a common neuro-computational mechanism supporting flexible behavior.

A consensus guide to capturing the ability to inhibit actions and impulsive behaviors in the stop-signal task.

Response inhibition is essential for navigating everyday life. Its derailment is considered integral to numerous neurological and psychiatric disorders, and more generally, to a wide range of behavioral and health problems. Response-inhibition efficiency furthermore correlates with treatment outcome in some of these conditions.

Neuro-Cognitive Effects of Acute Tyrosine Administration on Reactive and Proactive Response Inhibition in Healthy Older Adults.

The aging brain is characterized by altered dopamine signaling. The amino acid tyrosine, a catecholamine precursor, is known to improve cognitive performance in young adults, especially during high environmental demands. Tyrosine administration might also affect catecholamine transmission in the aging brain, thereby improving cognitive functioning.

Children with ADHD symptoms show deficits in reactive but not proactive inhibition, irrespective of their formal diagnosis.

Background: Attenuated inhibitory control is one of the most robust findings in the neuropsychology of attention-deficit/hyperactivity disorder (ADHD). However, it is unclear whether this represents a deficit in outright stopping (reactive inhibition), whether it relates to a deficit in anticipatory response slowing (proactive inhibition), or both. In addition, children with other development disorders, such as autism spectrum disorder (ASD), often have symptoms of inattention, impulsivity, and hyperactivity similar to children with ADHD.

Reliable estimation of inhibitory efficiency: to anticipate, choose or simply react?

Response inhibition is an important executive process studied by clinical and experimental psychologists, neurophysiologists and cognitive neuroscientists alike. Stop-signal paradigms are popular because they are grounded in a theory that provides methods to estimate the latency of an unobservable process: the stop-signal reaction time (SSRT). Critically, SSRT estimates can be biased by skew of the response time distribution and gradual slowing over the course of the experiment.

The role of stop-signal probability and expectation in proactive inhibition.

The subjective belief of what will happen plays an important role across many cognitive domains, including response inhibition. However, tasks that study inhibition do not distinguish between the processing of objective contextual cues indicating stop-signal probability and the subjective expectation that a stop-signal will or will not occur. Here we investigated the effects of stop-signal probability and the expectation of a stop-signal on proactive inhibition.

Capturing the dynamics of response variability in the brain in ADHD.

ADHD is characterized by increased intra-individual variability in response times during the performance of cognitive tasks. However, little is known about developmental changes in intra-individual variability, and how these changes relate to cognitive performance. Twenty subjects with ADHD aged 7-24 years and 20 age-matched, typically developing controls participated in an fMRI-scan while they performed a go-no-go task.

Common and unique neural networks for proactive and reactive response inhibition revealed by independent component analysis of functional MRI data.

Response inhibition involves proactive and reactive modes. Proactive inhibition is goal-directed, triggered by warning cues, and serves to restrain actions. Reactive inhibition is stimulus-driven, triggered by salient stop-signals, and used to stop actions completely.

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).

Working memory and default mode network abnormalities in unaffected siblings of schizophrenia patients.

Background: Impaired working memory (WM) is a hallmark of schizophrenia. In addition to classical WM regions such as the dorsolateral prefrontal cortex (DLPFC) and the striatum, dysfunctions in the default-mode network (DMN) contribute to these WM deficits. Unaffected siblings of patients also show WM impairments.

Transcranial magnetic stimulation and functional MRI reveal cortical and subcortical interactions during stop-signal response inhibition.

Stopping an action requires suppression of the primary motor cortex (M1). Inhibitory control over M1 relies on a network including the right inferior frontal cortex (rIFC) and the supplementary motor complex (SMC), but how these regions interact to exert inhibitory control over M1 is unknown. Specifically, the hierarchical position of the rIFC and SMC with respect to each other, the routes by which these regions control M1, and the causal involvement of these regions in proactive and reactive inhibition remain unclear.

Expectations and violations: delineating the neural network of proactive inhibitory control.

The ability to stop a prepared response (reactive inhibition) appears to depend on the degree to which stopping is expected (proactive inhibition). Functional MRI studies have shown that activation during proactive and reactive inhibition overlaps, suggesting that the whole neural network for reactive inhibition becomes already activated in anticipation of stopping. However, these studies measured proactive inhibition as the effect of stop-signal probability on activation during go trials.

A functional and structural investigation of the human fronto-basal volitional saccade network.

Almost all cortical areas are connected to the subcortical basal ganglia (BG) through parallel recurrent inhibitory and excitatory loops, exerting volitional control over automatic behavior. As this model is largely based on non-human primate research, we used high resolution functional MRI and diffusion tensor imaging (DTI) to investigate the functional and structural organization of the human (pre)frontal cortico-basal network controlling eye movements. Participants performed saccades in darkness, pro- and antisaccades and observed stimuli during fixation.

Reduced proactive inhibition in schizophrenia is related to corticostriatal dysfunction and poor working memory.

Background: Inhibitory control is central to executive functioning and appears deficient in schizophrenia. However, it is unclear how inhibitory control is affected, what the underlying neural mechanisms are, whether these deficits are related to the illness itself or to increased risk for the illness, and whether there is a relation to impairments in other executive functions.

Methods: We used functional magnetic resonance imaging to investigate two forms of inhibitory control: proactive inhibition (anticipation of stopping) and reactive inhibition (outright stopping).

On the role of the striatum in response inhibition.

Background: Stopping a manual response requires suppression of the primary motor cortex (M1) and has been linked to activation of the striatum. Here, we test three hypotheses regarding the role of the striatum in stopping: striatum activation during successful stopping may reflect suppression of M1, anticipation of a stop-signal occurring, or a slower response build-up.

Methodology/principal Findings: Twenty-four healthy volunteers underwent functional magnetic resonance imaging (fMRI) while performing a stop-signal paradigm, in which anticipation of stopping was manipulated using a visual cue indicating stop-signal probability, with their right hand.

Reduced functional coupling in the default-mode network during self-referential processing.

Activity within the default-mode network (DMN) is thought to be related to self-referential processing, such as thinking about one's preferences or personality traits. Although the DMN is generally considered to function as a network, evidence is starting to accumulate that suggests that areas of the DMN are each specialized for different subfunctions of self-referential processing. Here, we address the issue of functional specialization by investigating changes in coupling between areas of the DMN during self-referential processing.

Cardiorespiratory effects on default-mode network activity as measured with fMRI.

The default-mode network (DMN) consists of areas showing more activation during rest than during a task. Several authors propose some form of cognitive processing to underlie BOLD signal changes in the DMN as activity within the network is modulated by the level of effort required by the task and is positively correlated with self-referential processing. Alternatively, BOLD signal changes within the DMN may be caused by cardiorespiratory processes (CR) affecting BOLD signal measurements independent of neuronal activity.

Within-subject variation in BOLD-fMRI signal changes across repeated measurements: quantification and implications for sample size.

Functional magnetic resonance imaging (fMRI) can be used to detect experimental effects on brain activity across measurements. The success of such studies depends on the size of the experimental effect, the reliability of the measurements, and the number of subjects. Here, we report on the stability of fMRI measurements and provide sample size estimations needed for repeated measurement studies.