Proactive Control Strategies for Overt and Covert Go/NoGo Tasks: An Electrical Neuroimaging Study

Proactive and reactive inhibition are generally intended as mechanisms allowing the withholding or suppression of overt movements. Nonetheless, inhibition could also play a pivotal role during covert actions (i.e., potential motor acts not overtly performed, despite the activation of the motor system), such as Motor Imagery (MI). In a previous EEG study, we analyzed cerebral activities reactively triggered during two cued Go/NoGo tasks, requiring execution or withholding of overt or covert imagined actions, respectively. This study revealed activation of pre-supplementary motor area (pre-SMA) and right inferior frontal gyrus (rIFG), key nodes of the network underpinning reactive inhibition of overt responses in NoGo trials, also during MI enactment, enabling the covert nature of the imagined motor response. Taking into account possible proactive engagement of inhibitory mechanisms by cue signals, for an exhaustive interpretation of these previous findings in the present study we analyzed EEG activities elicited during the preparatory phase of our cued overt and covert Go/NoGo tasks. Our results demonstrate a substantial overlap of cerebral areas activated during proactive recruitment and subsequent reactive implementation of motor inhibition in both overt and covert actions; also, different involvement of pre-SMA and rIFG emerged, in accord with the intended type (covert or overt) of incoming motor responses. During preparation of the overt Go/NoGo task, the cue is encoded in a pragmatic mode, as it primes the possible overt motor response programs in motor and premotor cortex and, through preactivation of a pre-SMA-related decisional mechanism, it triggers a parallel preparation for successful response selection and/or inhibition during the response phase. Conversely, the preparatory strategy for the covert Go/NoGo task is centered on priming of an inhibitory mechanism in rIFG, tuned to the instructed covert modality of motor performance and instantiated during subsequent MI, which allows the imagined response to remain a potential motor act.     

Motor Inhibition during Overt and Covert Actions: An Electrical Neuroimaging Study

Given ample evidence for shared cortical structures involved in encoding actions, whether or not subsequently executed, a still unsolved problem is the identification of neural mechanisms of motor inhibition, preventing “covert actions” as motor imagery from being performed, in spite of the activation of the motor system. The principal aims of the present study were the evaluation of: 1) the presence in covert actions as motor imagery of putative motor inhibitory mechanisms; 2) their underlying cerebral sources; 3) their differences or similarities with respect to cerebral networks underpinning the inhibition of overt actions during a Go/NoGo task. For these purposes, we performed a high density EEG study evaluating the cerebral microstates and their related sources elicited during two types of Go/NoGo tasks, requiring the execution or withholding of an overt or a covert imagined action, respectively. Our results show for the first time the engagement during motor imagery of key nodes of a putative inhibitory network (including pre-supplementary motor area and right inferior frontal gyrus) partially overlapping with those activated for the inhibition of an overt action during the overt NoGo condition. At the same time, different patterns of temporal recruitment in these shared neural inhibitory substrates are shown, in accord with the intended overt or covert modality of action performance. The evidence that apparently divergent mechanisms such as controlled inhibition of overt actions and contingent automatic inhibition of covert actions do indeed share partially overlapping neural substrates, further challenges the rigid dichotomy between conscious, explicit, flexible and unconscious, implicit, inflexible forms of motor behavioral control.     

Evoked activity of the human brain during perception of illusory stimuli

Evoked activity of the human brain was studied in 19 right-handed men during the perception of illusory images in Go/NoGo tasks. It was found that the recognition of illusory images was associated with changes in the amplitudes of both early (P1 and P2) and late (P3a and P3b) components of the evoked potentials and with an increase in the latencies of the late components recorded from the occipital, central, and frontal cortical areas, which could be explained by the necessity to store a template in the memory, compare a perceived image with the template, and prepare and execute (or inhibit) a motor response. At the same time, the operation of the brain was more differentiated during the NoGo task compared to the Go task.     

Neural synchrony during response production and inhibition

Inhibition of irrelevant information (conflict monitoring) and/or of prepotent actions is an essential component of adaptive self-organized behavior. Neural dynamics underlying these functions has been studied in humans using event-related brain potentials (ERPs) elicited in Go/NoGo tasks that require a speeded motor response to the Go stimuli and withholding a prepotent response when a NoGo stimulus is presented. However, averaged ERP waveforms provide only limited information about the neuronal mechanisms underlying stimulus processing, motor preparation, and response production or inhibition. In this study, we examine the cortical representation of conflict monitoring and response inhibition using time-frequency analysis of electroencephalographic (EEG) recordings during continuous performance Go/NoGo task in 50 young adult females. We hypothesized that response inhibition would be associated with a transient boost in both temporal and spatial synchronization of prefrontal cortical activity, consistent with the role of the anterior cingulate and lateral prefrontal cortices in cognitive control. Overall, phase synchronization across trials measured by Phase Locking Index and phase synchronization between electrode sites measured by Phase Coherence were the highest in the Go and NoGo conditions, intermediate in the Warning condition, and the lowest under Neutral condition. The NoGo condition was characterized by significantly higher fronto-central synchronization in the 300-600 ms window, whereas in the Go condition, delta- and theta-band synchronization was higher in centro-parietal regions in the first 300 ms after the stimulus onset. The present findings suggest that response production and inhibition is supported by dynamic functional networks characterized by distinct patterns of temporal and spatial synchronization of brain oscillations.     

Differential effects of normal aging on sources of standard N1, target N1 and target P300 auditory event-related brain potentials revealed by low resolution electromagnetic tomography (LORETA)

The P300 event-related potential (ERP) is considered to be closely related to cognitive processes. In normal aging, P300 scalp latencies increase, parietal P300 scalp amplitudes decrease and the scalp potential field shifts to a relatively more frontal distribution. Based on ERPs recorded in 172 normal healthy subjects aged between 20 and 88 years in an auditory oddball paradigm, the effects of age on the electrical activity in the brain corresponding to N1 and P300 components were estimated by means of low resolution electromagnetic tomography (LORETA). This distributed approach directly computes a unique 3-dimensional electrical source distribution by assuming that neighbouring neurons are simultaneously and synchronously active. N1 LORETA generators, located predominantly in both auditory cortices and also symmetrically in prefrontal areas, increased with advancing age for standards but remained stable for targets. P300 LORETA generators, located symmetrically in the prefrontal cortex, in the parieto-occipital junction and in the inferior parietal cortex (supramarginal gyrus) and medially in the superior parietal cortex, were differentially affected by age. While age did not affect parieto-occipital sources, superior parietal and right prefrontal sources decreased pronouncedly. Thus, in normal aging, P300 current density decreased in regions were a fronto-parietal network for sustained attention was localized.     

Bright light exposure before bedtime impairs response inhibition the following morning: a non-randomized crossover study

Introduction: Bright light exposure in the late evening can affect cognitive function the following morning either by changing the biological clock and/or disturbing sleep, but the evidence for this effect is scarce, and the underlying mechanism remains unknown. In this study, we first aimed to evaluate the effect of bright light exposure before bedtime on frontal lobe activity the following morning using near-infrared spectroscopy (NIRS) during a Go/NoGo task. Second, we aimed to evaluate the effects of bright light exposure before bedtime on polysomnographic measures and on a frontal lobe function test the following morning.

Methods: Twenty healthy, young males (mean age, 25.5 years) were recruited between September 2013 and August 2014. They were first exposed to control light (150 lux) before bedtime (from 20:00 h to 24:00 h) for 2 days and then to bright light (1,000 lux) before bedtime for an additional 5 days. We performed polysomnography (PSG) on the final night of each light exposure period (on nights 2 and night 7) and performed NIRS, which measures the concentrations of oxygenated and deoxygenated hemoglobin (OxyHb and DeoxyHb, respectively), coupled with a Go/NoGo task the following morning (between 09:30 h and 11:30 h). The participants also completed frontal lobe function tests the following morning.

Results: NIRS showed decreased hemodynamic activity (lower OxyHb and a tendency toward higher DeoxyHb concentration) in the right frontal lobe during the NoGo block after 1000-lux light exposure compared with that during the NoGo block after 150-lux light exposure. The commission error rate (ER) during the Go/NoGo task was higher after 1000-lux light exposure than that during the Go/NoGo task after 150-lux light exposure (1.24 ± 1.09 vs. 0.6 ± 0.69, P = 0.002), suggesting a reduced inhibitory response.

Conclusion: This study shows that exposure to bright light before bedtime for 5 days impairs right frontal lobe activation and response inhibition the following morning.     

Mapping P300 waves onto inhibition: Go/NoGo discrimination

Subjects viewed letters presented at 2 sec intervals and prepared a fast button press whenever an “O” appeared. If the next letter was an “X” the button press was executed (Go signal), but if the letter was a non-X character (T, H, Z) suppression of the response was required (NoGo cue). NoGo signals elicited a P300-like wave that was larger at central and frontal scalp sites contralateral to the prepared movement, compared to P300s elicited by Go cues which were symmetric about the sagittal midline and dominant at parietal sites. Subtraction of preparatory CNVs from the NoGo P300 did not remove differences in scalp topography, or reduce the amplitude of the NoGo P300 to that seen following control letters that required perceptual identification but did not call for suppression of prepared motor responses. Principal components analysis identified a middle positive wave following X-alone control stimuli whose topography resembled the NoGo P300. These findings suggest that the source of augmented NoGo P300s is a generator involved with sensorimotor inhibition. We discuss the mechanism of P300 waves and evidence linking these waves with inhibition in other task arrangements.     

ERP Correlates of Proactive and Reactive Cognitive Control in Treatment-Na?ve Adult ADHD

This study investigated whether treatment naïve adults with Attention Deficit Hyperactivity Disorder (ADHD; n = 33; 19 female) differed from healthy controls (n = 31; 17 female) in behavioral performance, event-related potential (ERP) indices of preparatory attention (CueP3 and late CNV), and reactive response control (Go P3, NoGo N2, and NoGo P3) derived from a visual cued Go/NoGo task. On several critical measures, Cue P3, late CNV, and NoGo N2, there were no significant differences between the groups. This indicated normal preparatory processes and conflict monitoring in ADHD patients. However, the patients had attenuated Go P3 and NoGoP3 amplitudes relative to controls, suggesting reduced allocation of attentional resources to processes involved in response control. The patients also had a higher rate of Go signal omission errors, but no other performance decrements compared with controls. Reduced Go P3 and NoGo P3 amplitudes were associated with poorer task performance, particularly in the ADHD group. Notably, the ERPs were not associated with self-reported mood or anxiety. The results provide electrophysiological evidence for reduced effortful engagement of attentional resources to both Go and NoGo signals when reactive response control is needed. The absence of group differences in ERP components indexing proactive control points to impairments in specific aspects of cognitive processes in an untreated adult ADHD cohort. The associations between ERPs and task performance provided additional support for the altered electrophysiological responses.     

Female menstrual phases modulate human prefrontal asymmetry: A magnetoencephalographic study

We previously reported that the trait/baseline prefrontal cortex (PFC) activity expresses a dynamic plasticity during female menstrual cycle. The shift of asymmetric lateralization of PFC baseline activity pinpoints a possible emotional regulation of negative affection. The current emotional Go/NoGo study aimed to investigate the state PFC responses of different menstrual phases during fear facial stimulation in fourteen healthy women. Our data disclosed that the menstrual cycle was coupled with a shift of asymmetric lateralization of frontal activation across different menstrual phases. Evoked magnetic field activity in the time window 200-300 ms (M1) and 300-450 ms (M2) after stimulus onset demonstrated significant interactions between hemispheric side and menstrual phase. The right hemispheric dominance in periovulatory phase (OV) changed to left hemispheric dominance in menstrual (MC) phase. Significant association between the anxiety score and the left PFC activation was particularly observed in MC phase. Our study revealed a plastic resilience of functional organization of human brain and a dynamic automaticity of inter-hemispheric synergism for possible adaptive regulation under the aversive confrontation in accordance with hormonal fluctuation during the menstrual cycle.     

Methylphenidate and if-then plans are comparable in modulating the P300 and increasing response inhibition in children with ADHD

A disturbed functioning of the prefrontal cortex, the anterior cingulate cortex, and an accordingly reduced P300 presumably underlies executive function deficits of children with attention deficit hyperactivity disorder (ADHD). Using a combined classification and Go/NoGo task paradigm, the present study investigated whether medication with methylphenidate (MPH) modulates the P300 as measured by a high-density electroencephalogram (EEG) and facilitates response inhibition in children with ADHD. Further, effects of MPH were compared with effects of self-regulation by if-then plans (Gollwitzer in Am Psychol 54: 493-503, 1999). MPH as well as if-then plans modulated the P300 and improved inhibition of an unwanted response on a Go/NoGo task to the same level observed in children without ADHD. Importantly, self-regulation strategies might be a valuable alternative to medication with MPH in children with ADHD.     

Changes in the α rhythm upon introduction of Go/NoGo stimuli in the context of an experiment with a set to an angry face

In the middle of a 16-s pause between the target (facial image) and a triggering stimuli, conditioning Go/NoGo signals were presented to healthy adults (n = 35). The absence of significant changes in the plasticity of a set to an angry face upon introduction of an additional cognitive task is due to an increase in induced synchronization of the α rhythm in the pauses between target, conditioning, and triggering stimuli. This indicates an increase in the top-down inhibitory control, which suppresses the effects of irrelevant factors, and, thereby, facilitates processing relevant information. In the time interval between the NoGo and triggering stimuli, the induced synchronization of low-frequency and high-frequency α rhythm is recorded locally in the motor area of the left hemisphere only (C ₃, FC ₃). The theory on the inhibitory nature of this electrophysiological phenomenon is experimentally confirmed. The concepts of differentiating and delayed inhibition from the physiology of higher nervous activity are considered as part of the theory of top-down inhibitory control from the prefrontal cortex.     

The effects of sleep deprivation and time of day on cognitive performance

The extent to which the diurnal fluctuations of different cognitive processes could be affected by sleep loss may be explored to predict performance decrements observed in the real world. Twenty healthy male subjects voluntarily took part in 8 test sessions at 06:00, 10:00, 14:00, and 18:00 h, following either a night with or without sleep in random order. Measurements included oral temperature, simple reaction time, sign cancelation, Go/NoGo, and the Purdue pegboard test. The results indicate that simple reaction time and motor coordination had morning–afternoon variations closely following the rhythms of temperature and vigilance. Inhibitory attention (Go/NoGo) presented no morning–afternoon variations. Sleep deprivation may affect the profiles of cognitive performance depending on the processes solicited. Sustained and inhibitory attention are particularly affected in the morning (after 24 and 28 waking hours), while a complex task (visuo-motor coordination) would be affected after 32 waking hours only.     

A cognitive hypothesis of the development of differentiative cortical inhibition in humans

Positive and inhibitory conditioning stimuli (Go/NoGo) were presented to healthy adults (n = 35) in an experimental setting for angry face recognition with short intervals between the setting (face), conditioning, and triggering stimuli. A modification of the previously used experimental conditions that consisted in a reduction of the duration of the interstimulus intervals promoted an increase in attitude flexibility (expansion of the group of subjects that made no identification errors at the stage of set testing). The improvement of cognitive performance was accompanied by expansion of the zone of α-oscillation synchronization induced by the NoGo inhibitory conditioning stimulus. Synchronization of α-oscillations was less pronounced in subjects with a rigid cognitive set. Thus, the cognitive hypothesis of cortical inhibition (termed “internal inhibition” by I.P. Pavlov) has been confirmed. The concept of the emergence of top-down inhibitory effects in the prefrontal cortex, implicit internal representation, and selective modulation of attention is discussed.     

Neural Activity Changes Associated with Impulsive Responding in the Sustained Attention to Response Task

Humans can anticipate and prepare for uncertainties to achieve a goal. However, it is difficult to maintain this effort over a prolonged period of time. Inappropriate behavior is impulsively (or mindlessly) activated by an external trigger, which can result in serious consequences such as traffic crashes. Thus, we examined the neural mechanisms underlying such impulsive responding using functional magnetic resonance imaging (fMRI). Twenty-two participants performed a block-designed sustained attention to response task (SART), where each task block was composed of consecutive Go trials followed by a NoGo trial at the end. This task configuration enabled us to measure compromised preparation for NoGo trials during Go responses using reduced Go reaction times. Accordingly, parametric modulation analysis was conducted on fMRI data using block-based mean Go reaction times as an online marker of impulsive responding in the SART. We found that activity in the right dorsolateral prefrontal cortex (DLPFC) and the bilateral intraparietal sulcus (IPS) was positively modulated with mean Go reaction times. In addition, activity in the medial prefrontal cortex (MPFC) and the posterior cingulate cortex (PCC) was negatively modulated with mean Go reaction times, albeit statistically weakly. Taken together, spontaneously reduced activity in the right DLPFC and the IPS and spontaneously elevated activity in the MPFC and the PCC were associated with impulsive responding in the SART. These results suggest that such a spontaneous transition of brain activity pattern results in impulsive responding in monotonous situations, which in turn, might cause human errors in actual work environments.     

Topography, independent component analysis and dipole source analysis of movement related potentials

The objective of this study was to test, in single subjects, the hypothesis that the signs of voluntary movement-related neural activity would first appear in the prefrontal region, then move to both the medial frontal and posterior parietal regions, progress to the medial primary motor area, lateralize to the contralateral primary motor area and finally involve the cerebellum (where feedback-initiated error signals are computed). Six subjects performed voluntary finger movements while DC coupled EEG was recorded from 64 scalp electrodes. Event-related potentials (ERPs) averaged on the movements were analysed both before and after independent component analysis (ICA) combined with dipole source analysis (DSA) of the independent components. Both a simple topographic analysis of undecomposed ERPs and the ICA/DSA analysis suggested that the original hypothesis was inadequate. The major departure from its predictions was that, while activity over many brain regions did appear at the expected times, it also appeared at unexpected times. Overall, the results suggest that the neuroscientific ‘standard model’, in which neural activity occurs sequentially in a series of discrete local areas each specialized for a particular function, may reflect the true situation less well than models in which large areas of brain shift simultaneously into and out of common activity states. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.

Deficits in inhibitory control in smokers during a Go/NoGo task: an investigation using event-related brain potentials

Introduction

The role of inhibitory control in addictive behaviors is highlighted in several models of addictive behaviors. Although reduced inhibitory control has been observed in addictive behaviors, it is inconclusive whether this is evident in smokers. Furthermore, it has been proposed that drug abuse individuals with poor response inhibition may experience greater difficulties not consuming substances in the presence of drug cues. The major aim of the current study was to provide electrophysiological evidence for reduced inhibitory control in smokers and to investigate whether this is more pronounced during smoking cue exposure.

Methods

Participants (19 smokers and 20 non-smoking controls) performed a smoking Go/NoGo task. Behavioral accuracy and amplitudes of the N2 and P3 event-related potential (ERP), both reflecting aspects of response inhibition, were the main variables of interest.

Results

Reduced NoGo N2 amplitudes in smokers relative to controls were accompanied by decreased task performance, whereas no differences between groups were found in P3 amplitudes. This was found to represent a general lack of inhibition in smokers, and not dependent on the presence of smoking cues.

Conclusions

The current results suggest that smokers have difficulties with response inhibition, which is an important finding that eventually can be implemented in smoking cessation programs. More research is needed to clarify the exact role of cue exposure on response inhibition.     

Coherence and phase locking in the scalp EEG and between LORETA model sources, and microstates as putative mechanisms of brain temporo-spatial functional organization.

Brain electric mechanisms of temporary, functional binding between brain regions are studied using computation of scalp EEG coherence and phase locking, sensitive to time differences of few milliseconds. However, such results if computed from scalp data are ambiguous since electric sources are spatially oriented. Non-ambiguous results can be obtained using calculated time series of strength of intracerebral model sources. This is illustrated applying LORETA modeling to EEG during resting and meditation. During meditation, time series of LORETA model sources revealed a tendency to decreased left-right intracerebral coherence in the delta band, and to increased anterior-posterior intracerebral coherence in the theta band. An alternate conceptualization of functional binding is based on the observation that brain electric activity is discontinuous, i.e., that it occurs in chunks of up to about 100 ms duration that are detectable as quasi-stable scalp field configurations of brain electric activity, called microstates. Their functional significance is illustrated in spontaneous and event-related paradigms, where microstates associated with imagery- versus abstract-type mentation, or while reading positive versus negative emotion words showed clearly different regions of cortical activation in LORETA tomography. These data support the concept that complete brain functions of higher order such as a momentary thought might be incorporated in temporal chunks of processing in the range of tens to about 100 ms as quasi-stable brain states; during these time windows, subprocesses would be accepted as members of the ongoing chunk of processing.     

Dissociation of Neural Substrates of Response Inhibition to Negative Information between Implicit and Explicit Facial Go/Nogo Tasks: Evidence from an Electrophysiological Study

Background

Although ample evidence suggests that emotion and response inhibition are interrelated at the behavioral and neural levels, neural substrates of response inhibition to negative facial information remain unclear. Thus we used event-related potential (ERP) methods to explore the effects of explicit and implicit facial expression processing in response inhibition.

Methods

We used implicit (gender categorization) and explicit emotional Go/Nogo tasks (emotion categorization) in which neutral and sad faces were presented. Electrophysiological markers at the scalp and the voxel level were analyzed during the two tasks.

Results

We detected a task, emotion and trial type interaction effect in the Nogo-P3 stage. Larger Nogo-P3 amplitudes during sad conditions versus neutral conditions were detected with explicit tasks. However, the amplitude differences between the two conditions were not significant for implicit tasks. Source analyses on P3 component revealed that right inferior frontal junction (rIFJ) was involved during this stage. The current source density (CSD) of rIFJ was higher with sad conditions compared to neutral conditions for explicit tasks, rather than for implicit tasks.

Conclusions

The findings indicated that response inhibition was modulated by sad facial information at the action inhibition stage when facial expressions were processed explicitly rather than implicitly. The rIFJ may be a key brain region in emotion regulation.     

Electrophysiological Indices of Response Inhibition in a Go/NoGo Task Predict Self-Control in a Social Context

Recent research demonstrates that response inhibition—a core executive function—may subserve self-regulation and self-control. However, it is unclear whether response inhibition also predicts self-control in the multifaceted, high-level phenomena of social decision-making. Here we examined whether electrophysiological indices of response inhibition would predict self-control in a social context. Electroencephalography was recorded as participants completed a widely used Go/NoGo task (the cued Continuous Performance Test). Participants then interacted with a partner in an economic exchange game that requires self-control. Results demonstrated that greater NoGo-Anteriorization and larger NoGo-P300 peak amplitudes—two established electrophysiological indices of response inhibition—both predicted more self-control in this social game. These findings support continued integration of executive function and self-regulation and help extend prior research into social decision-making processes.     

Altered Brain Network Centrality in Patients with Diabetic Optic Neuropathy: A Resting-State FMRI Study

Objective: Recent studies have suggested that diabetic optic neuropathy (DON) independently increases the incidence of brain diseases like cerebral infarction and hemorrhage. In this study, voxel-level degree centrality (DC) was used to study potential changes in functional network brain activity in DON patients.Methods: The study included 14 DON patients and 14 healthy controls (HCs) matched by age, sex, and weight. All subjects underwent resting functional magnetic resonance imaging. Receiver operating characteristic curves and Pearson correlation analysis were performed.Results: The DC values of the left frontal mid-orb and right middle frontal gyrus/right frontal sup were significantly lower in DON patients compared to HCs. The DC value of the left temporal lobe was also significantly higher than in HCs.Conclusion: Three different brain regions show DC changes in DON patients, suggesting common optic neuropathy in the context of diabetes and providing new ideas for treating optic nerve disease in patients with long-term diabetes.Abbreviations: AUC = area under the curve; BCVA = best corrected visual acuity; DC = degree centrality; DON = diabetic optic neuropathy; fMRI = functional magnetic resonance imaging; HC = healthy control; LFMO = left frontal mid orb; LTL = left temporal lobe; RFS = right frontal sup; RMFG = right middle frontal gyrus; ROC = receiver operating characteristic