Event-related brain potentials in the study of inhibition: cognitive control, source localization and age-related modulations

In the previous 15 years, a variety of experimental paradigms and methods have been employed to study inhibition. In the current review, we analyze studies that have used the high temporal resolution of the event-related potential (ERP) technique to identify the temporal course of inhibition to understand the various processes that contribute to inhibition. ERP studies with a focus on normal aging are specifically analyzed because they contribute to a deeper understanding of inhibition. Three time windows are proposed to organize the ERP data collected using inhibition paradigms: the 200 ms period following stimulus onset; the period between 200 and 400 ms after stimulus onset; and the period between 400 and 800 ms after stimulus onset. In the first 200 ms, ERP inhibition research has primarily focused on N1 and P1 as the ERP components associated with inhibition. The inhibitory processing in the second time window has been associated with the N2 and P3 ERP components. Finally, in the third time window, inhibition has primarily been associated with the N400 and N450 ERP components. Source localization studies are analyzed to examine the association between the inhibition processes that are indexed by the ERP components and their functional brain areas. Inhibition can be organized in a complex functional structure that is not constrained to a specific time point but, rather, extends its activity through different time windows. This review characterizes inhibition as a set of processes rather than a unitary process

Neural correlates of impulse control disorder in Parkinson,s Disease: FMRI evidence from motor, inhibition and semantic domains.

222 p.Parkinson's disease (PD) is the second most common neurodegenerative disorder associated with aging. Approximately 40% of the PD patients treated with dopaminergic medication will develop Impulse Control Disorder (ICD). PD patients with ICD engage in pathological behaviors akin to behavioral addictions, as a result of a malfunction of their reward system due to chronic exposure to dopaminergic medication. Cognitive neuroscience research has investigated cognitive impulsivity and reward mechanisms in PD patients with ICD. However, functional and molecular imaging evidence indicates abnormalities in regions and networks that are not associated with cognitive impulsivity, but with domains such as movement, inhibitory control, and semantic processing. These domains have either not been previously investigated in this population, or previous literature shows mixed results. This doctoral dissertation aims at examining the neural correlates of three different domains in a group of patients with PD and ICD, a group of patients with PD and no ICD, and a group of healthy control participants using functional magnetic resonance imaging (fMRI). The three domains examined in each Experiment are motor function through a sequential finger-tapping task (Experiment I), inhibitory control through measures of response inhibition (Experiment II), and semantic processing via an auditory processing task (Experiment III). We were particularly interested in group differences in the functional networks and regions implicated in these tasks. Our results revealed that, across the three examined domains (i.e., motor, response inhibition, semantic processing), PD patients with ICD showed differential functional coupling among regions relative to their control counterparts, which remarks the importance of neural networks in cognitive neuroscience. Although the domains examined here had not received special attention in PD patients with ICD, we show that these patients exhibit functional differences beyond the reward system circuitry.bcbl: basque center on cognition, brain and languag

Substantia nigra activity level predicts trial-to-trial adjustments in cognitive control

Effective adaptation to the demands of a changing environment requires flexible cognitive control. The medial and the lateral frontal cortices are involved in such control processes, putatively in close interplay with the BG. In particular, dopaminergic projections from the midbrain (i.e., from the substantia nigra [SN] and the ventral tegmental area) have been proposed to play a pivotal role in modulating the activity in these areas for cognitive control purposes. In that dopaminergic involvement has been strongly implicated in reinforcement learning, these ideas suggest functional links between reinforcement learning, where the outcome of actions shapes behavior over time, and cognitive control in a more general context, where no direct reward is involved. Here, we provide evidence from functional MRI in humans that activity in the SN predicts systematic subsequent trial-to-trial RT prolongations that are thought to reflect cognitive control in a stop-signal paradigm. In particular, variations in the activity level of the SN in one trial predicted the degree of RT prolongation on the subsequent trial, consistent with a modulating output signal from the SN being involved in enhancing cognitive control. This link between SN activity and subsequent behavioral adjustments lends support to theoretical accounts that propose dopaminergic control signals that shape behavior both in the presence and in the absence of direct reward. This SN-based modulatory mechanism is presumably mediated via a wider network that determines response speed in this task, including frontal and parietal control regions, along with the BG and the associated subthalamic nucleus

Functional correlates of response inhibition in impulse control disorders in Parkinson’s disease

Available online 11 September 2021.Impulse control disorder is a prevalent side-effect of Parkinson’s disease (PD) medication, with a strong negative impact on the quality of life of those affected. Although impulsivity has classically been associated with response inhibition deficits, previous evidence from PD patients with impulse control disorder (ICD) has not revealed behavioral dysfunction in response inhibition. In this study, 18 PD patients with ICD, 17 PD patients without this complication, and 15 healthy controls performed a version of the conditional Stop Signal Task during functional magnetic resonance imaging. Whole-brain contrasts, regions of interest, and functional connectivity analyses were conducted. Our aim was to investigate the neural underpinnings of two aspects of response inhibition: proactive inhibition, inhibition that has been prepared beforehand, and restrained inhibition, inhibition of an invalid inhibitory tendency. We observed that, in respect to the other two groups, PD patients with ICD exhibited hyperactivation of the stopping network bilaterally while performing proactive inhibition. When engaged in restrained inhibition, they showed hyperactivation of the left inferior frontal gyrus, an area linked to action monitoring. Restrained inhibition also resulted in changes to the functional co-activation between inhibitory regions and left inferior parietal cortex and right supramarginal gyrus. Our findings indicate that PD patients with ICD completed the inhibition task correctly, showing altered engagement of inhibitory and attentional areas. During proactive inhibition they showed bilateral hyperactivation of two inhibitory regions, while during restrained inhibition they showed additional involvement of attentional areas responsible for alerting and orienting.This work was supported by grants from the Carlos III Institute of Health (PI11/02109) and the ERA-Neuron program (PIM2010ERN- 0033). Additionally, the authors received the following grants and honoraria: T.E.-P. received a grant from the Spanish Ministry of Economy and Competitiveness (BES-2016-079489). P.M.P.-A. was supported by grants from the Spanish Ministry of Economy and Competitiveness (RYC-2014-15440), the Spanish Ministry of Science and Innovation (PGC2018-093408-B-I00), and the Fundación Tatiana Pérez de Guzmán el Bueno. I.N.-G. was the recipient of a Rio Hortega grant (CM16/00033) from the Carlos III Institute of Health. I.N.-G. received honoraria from Zambon and TEVA for travel and accommodation to attend scientific meetings. M.C.R.-O. received financial support for her research from national and local government institutions in Spain (Carlos III Institute of Health, Basque Country Government, Diputacion Foral Guipuzcoa, and CIBERNED). M.C.R.-O. received honoraria from Zambon, Bial, and Boston Scientific for lectures, travel, and accommodation to attend scientific meetings. BCBL acknowledges support from the Basque Government through the BERC 2018-2021 program

Functional correlates of response inhibition in impulse control disorders in Parkinson’s disease

Impulse control disorder is a prevalent side-effect of Parkinson’s disease (PD) medication, with a strong negative impact on the quality of life of those affected. Although impulsivity has classically been associated with response inhibition deficits, previous evidence from PD patients with impulse control disorder (ICD) has not revealed behavioral dysfunction in response inhibition. In this study, 18 PD patients with ICD, 17 PD patients without this complication, and 15 healthy controls performed a version of the conditional Stop Signal Task during functional magnetic resonance imaging. Whole-brain contrasts, regions of interest, and functional connectivity analyses were conducted. Our aim was to investigate the neural underpinnings of two aspects of response inhibition: proactive inhibition, inhibition that has been prepared beforehand, and restrained inhibition, inhibition of an invalid inhibitory tendency. We observed that, in respect to the other two groups, PD patients with ICD exhibited hyperactivation of the stopping network bilaterally while performing proactive inhibition. When engaged in restrained inhibition, they showed hyperactivation of the left inferior frontal gyrus, an area linked to action monitoring. Restrained inhibition also resulted in changes to the functional co-activation between inhibitory regions and left inferior parietal cortex and right supramarginal gyrus. Our findings indicate that PD patients with ICD completed the inhibition task correctly, showing altered engagement of inhibitory and attentional areas. During proactive inhibition they showed bilateral hyperactivation of two inhibitory regions, while during restrained inhibition they showed additional involvement of attentional areas responsible for alerting and orientin

Functional correlates of response inhibition in impulse control disorders in Parkinson’s disease

Available online 11 September 2021.Impulse control disorder is a prevalent side-effect of Parkinson’s disease (PD) medication, with a strong negative impact on the quality of life of those affected. Although impulsivity has classically been associated with response inhibition deficits, previous evidence from PD patients with impulse control disorder (ICD) has not revealed behavioral dysfunction in response inhibition. In this study, 18 PD patients with ICD, 17 PD patients without this complication, and 15 healthy controls performed a version of the conditional Stop Signal Task during functional magnetic resonance imaging. Whole-brain contrasts, regions of interest, and functional connectivity analyses were conducted. Our aim was to investigate the neural underpinnings of two aspects of response inhibition: proactive inhibition, inhibition that has been prepared beforehand, and restrained inhibition, inhibition of an invalid inhibitory tendency. We observed that, in respect to the other two groups, PD patients with ICD exhibited hyperactivation of the stopping network bilaterally while performing proactive inhibition. When engaged in restrained inhibition, they showed hyperactivation of the left inferior frontal gyrus, an area linked to action monitoring. Restrained inhibition also resulted in changes to the functional co-activation between inhibitory regions and left inferior parietal cortex and right supramarginal gyrus. Our findings indicate that PD patients with ICD completed the inhibition task correctly, showing altered engagement of inhibitory and attentional areas. During proactive inhibition they showed bilateral hyperactivation of two inhibitory regions, while during restrained inhibition they showed additional involvement of attentional areas responsible for alerting and orienting.This work was supported by grants from the Carlos III Institute of Health (PI11/02109) and the ERA-Neuron program (PIM2010ERN- 0033). Additionally, the authors received the following grants and honoraria: T.E.-P. received a grant from the Spanish Ministry of Economy and Competitiveness (BES-2016-079489). P.M.P.-A. was supported by grants from the Spanish Ministry of Economy and Competitiveness (RYC-2014-15440), the Spanish Ministry of Science and Innovation (PGC2018-093408-B-I00), and the Fundación Tatiana Pérez de Guzmán el Bueno. I.N.-G. was the recipient of a Rio Hortega grant (CM16/00033) from the Carlos III Institute of Health. I.N.-G. received honoraria from Zambon and TEVA for travel and accommodation to attend scientific meetings. M.C.R.-O. received financial support for her research from national and local government institutions in Spain (Carlos III Institute of Health, Basque Country Government, Diputacion Foral Guipuzcoa, and CIBERNED). M.C.R.-O. received honoraria from Zambon, Bial, and Boston Scientific for lectures, travel, and accommodation to attend scientific meetings. BCBL acknowledges support from the Basque Government through the BERC 2018-2021 program

Proactive Inhibitory Control of Response as the Default State of Executive Control

Refraining from reacting does not only involve reactive inhibitory mechanisms. It was recently found that inhibitory control also relies strongly on proactive mechanisms. However, since most available studies have focused on reactive stopping, little is known about how proactive inhibition of response is implemented. Two behavioral experiments were conducted to identify the temporal dynamics of this executive function. They manipulated respectively the time during which inhibitory control must be sustained until a stimulus occurs, and the time limit allowed to set up inhibition before a stimulus occurs. The results show that inhibitory control is not set up after but before instruction, and is not transient and sporadic but sustained across time. Consistent with our previous neuroimaging findings, these results suggest that proactive inhibition of response is the default mode of executive control. This implies that top-down control of sensorimotor reactivity would consist of a temporary release (up to several seconds), when appropriate (when the environment becomes predictable), of the default locking state. This conclusion is discussed with regard to current anatomo-functional models of inhibitory control, and to methodological features of studies of attention and sensorimotor control

Rewards enhance proactive and reactive control in adolescence and adulthood

Cognitive control allows the coordination of cognitive processes to achieve goals. Control may be sustained in anticipation of goal-relevant cues (proactive control) or transient in response to the cues themselves (reactive control). Adolescents typically exhibit a more reactive pattern than adults in the absence of incentives. We investigated how reward modulates cognitive control engagement in a letter array working memory (WM) task in 30 adolescents (12-17 years) and 20 adults (23-30 years) using a mixed block- and event-related functional magnetic resonance imaging design. After a Baseline run without rewards, participants performed a Reward run where 50% trials were monetarily rewarded. Accuracy and reaction time (RT) differences between Reward and Baseline runs indicated engagement of proactive control, which was associated with increased sustained activity in the bilateral anterior insula (AI), right dorsolateral prefrontal cortex (PFC) and right posterior parietal cortex (PPC). RT differences between Reward and No reward trials of the Reward run suggested additional reactive engagement of cognitive control, accompanied with transient activation in bilateral AI, lateral PFC, PPC, supplementary motor area, anterior cingulate cortex, putamen and caudate. Despite behavioural and neural differences during Baseline WM task performance, adolescents and adults showed similar modulations of proactive and reactive control by reward

The Effects of Reward and Risk Level Associated with Speeded Actions: Evidence from Behavior and Electroencephalography

Choosing a course of action in our daily lives requires an accurate assessment of the associated risks as well as the potential rewards. The present two studies investigated the mechanism of how reward and risk level influence the motor decisions of speeded actions (Chapter 2) and its neural dynamics (Chapter 3) by focusing on the beta band (15-30 Hz) oscillation patterns reflected in the EEG signals. Participants performed a modified version of the Go-NoGo task, in which they earned reward points based on the speed and accuracy of response. On each trial, the reward points at stake (120 vs. 6) and the probability that a Go signal would follow (Go-probability) were presented prior to a Go/NoGo signal (Trial Information Period). The behavioral results (from both Chapters 2 and 3) showed that larger amount of rewards can motivate people to respond faster, and this effect was modulated by the assessed risk, suggesting that decisions for actions are based on a systematic trade-off between rewards and risks. The EEG data showed that motor beta oscillations from the two studied brain regions reflected different levels of motivation towards a motor response across different reward and risk levels. Specifically, the lower beta power associated with higher reward and lower risk level. Collectively, the results provide a mechanistic understanding of how motivational cues are translated into action outcomes via modulating patterns of brain oscillations