Negative BOLD effect on somato-motor inhibitory processing: An fMRI study

Inhibiting inappropriate behavior and thoughts in the current context is an essential ability for humans, but the neural mechanisms for response inhibitory processing are a matter of continuous debate. The aim of this event-related functional magnetic resonance imaging (fMRI) study was to evaluate the negative blood oxygen level dependent (BOLD) effect on inhibitory processing during go/no-go paradigms. Fifteen subjects performed two different types of somatosensory go/no-go paradigm: (1) button press and (2) count. Go and no-go stimuli were presented with an even probability. We observed a common negative activation during Movement No-go and Count No-go trials in the right SFG, corresponding to BA 8. These findings suggest that the right SFG region was responsible for the negative BOLD effect on inhibitory processing, which was independent of the required response mode. We hypothesized several possible explanations for the deactivation of the SFG during no-go trials.     

未治疗的甲基苯丙胺所致精神障碍患者的Go/NoGo任务及其事件相关电位特征

目的探讨未经治疗的甲基苯丙胺所致精神障碍患者执行功能的Go/NoGo任务及其事件相关电位特征。方法共随机选取年龄在18~60岁之间符合美国《精神障碍诊断与统计手册》第四版(DSM-4)甲基苯丙胺所致精神障碍诊断标准患者35例作为研究组,选择年龄、性别、受教育年限与研究组受试者相匹配的35例健康者作为对照组。两组受试者均予以Go/NoGo检测,并记录事件相关电位(ERPs)P3波幅,将结果加以分析。结果两组之间Go/NoGo任务比较,研究组的正确率较低、错误率较高,差异均有统计学意义(t=2.26~5.39,P0.05或0.01),研究组的反应时长于对照组,差异有统计学意义(t=3.02,P0.01);两组之间Go/NoGo模式ERPs比较,研究组各位点的P3波幅均显著低于对照组,差异有统计学意义(t=2.38~6.69,P0.05或0.01)。结论甲基苯丙胺所致精神障碍患者未治疗前存在执行功能障碍。     

躯体形式障碍患者的执行功能及Go/NoGo任务下的事件相关电位

目的探讨躯体形式障碍患者的执行功能及Go/NoGo任务下的事件相关电位特征。方法共随机选取年龄在18~65岁之间符合美国《精神障碍诊断与统计手册》第四版(DSM-4)诊断标准的患者30例作为研究组,同时选择年龄、性别、受教育年限与研究组相匹配的30例健康者作为对照组。两组受试者均予以威斯康星卡片测验(WCST)及Go/NoGo范式的事件相关电位(ERPs)检测,并将结果加以分析。结果两组之间比较,研究组各电极位点的P3波幅均低于对照组,差异均有统计学意义(t=2.32~8.01,P0.01或0.05);研究组WCST测验的正确应答数及概念化水平百分数项目的分值低于对照组,而错误应答数、选择错误率(%),持续性错误数及持续性错误的百分数项目的分值均高于对照组,差异均有统计学意义(t=2.27~4.77,P0.05或0.01);两组之间的其余WCST项目评分比较,差异均无统计学意义(t=0.48~1.55,P0.05)。结论躯体形式障碍患者存在执行功能障碍。     

Spatial selectivity of go/no-go neurons in monkey prefrontal cortex

We examined single-unit activity in the inferior prefrontal cortex during a visual go/no-go discrimination task under maintained visual fixation. The monkeys had to base their response on either the color, shape, or position of a discriminative cue, and the relevant task condition was indicated by the color of the fixation spot. We analyzed the spatial selectivity of 128 go/no-go neurons showing a marked differential cue-period activity that depended on whether the stimulus signaled a go or no-go response. Most of these neurons (n = 106, 83%) showed asymmetry between their responses to stimuli in the contralateral and ipsilateral visual fields. Seventy-seven of these neurons had a contralateral preferential field, and 29 had an ipsilateral preferential field. These results show that in many inferior prefrontal neurons a degree of differentiation in their responses to go and no-go stimuli depends on the cue positions, and that the coding of behavioral meaning is carried out mainly in the contralateral hemisphere.     

The effect of warning stimulus modality on blink startle modification in reaction time tasks

The present study investigated the effects of lead stimulus modality on modification of the acoustic startle reflex during three reaction time tasks. In Experiment 1, participants (N = 48) were required to press a button at the offset of one stimulus (task relevant) and to ignore presentations of a second (task irrelevant). Two tones that differed in pitch or two lights served as signal stimuli. Blink startle was elicited during some of the stimuli and during interstimulus intervals. Skin conductance responses were larger during task-relevant stimuli in both groups. Larger blink facilitation during task-relevant stimuli was found only in the group presented with auditory stimuli, whereas larger blink latency shortening during task-relevant stimuli was found in both groups. Experiment 2 (N = 32) used only a task-relevant stimulus. Blink magnitude facilitation was significant only in the group presented with tones, whereas blink latency shortening was significant in both groups. Experiment 3 (N = 80) used a go/nogo task that required participants to press a button if one element of a compound stimulus ended before the second, but not if the asynchrony was reversed. The offset asynchrony was varied between groups as a manipulation of task difficulty. Startle magnitude facilitation was larger during acoustic than during visual stimuli and larger in the easy condition. The present data indicate that startle facilitation in a reaction time task is affected by stimulus modality and by task demands. The effects of the task demands seem to be independent of lead stimulus modality.     

Role of primate basal ganglia and frontal cortex in the internal generation of movements

Summary This study is a part of a project investigating neuronal activity in the basal ganglia and frontal cortex and describes externally and internally induced preparatory activity in the supplementary motor area (SMA), which forms a closed neuronal loop with the striatum. Monkeys made self-initiated arm reaching movements toward a constant target in the absence of phasic external stimuli. In separate blocks of trials, animals performed in a delayed go no-go task in which an instruction cue prepared for subsequent movement or no-movement to a trigger stimulus. A total of 328 neurons were tested in the delay task. Of these, 91 responded transiently to the instruction light with a median latency of 262 ms. Three quarters of these responses were restricted to the instruction preparing for arm movement, as opposed to with-holding it, and thus may be involved in movement preparation processes. Sustained activation during the instruction-trigger interval was found for 67 neurons and occurred nearly exclusively in movement trials. Activation usually increased gradually after the cue and ended abruptly upon movement onset and thus could be related to the setting and maintenance of processes underlying the preparation of movement. Time-locked responses to the trigger stimulus were found in 38 neurons and were usually restricted to movement trials (median latency 80 ms). Activity time-locked to movement execution occurred in 67 neurons, beginning up to 252 ms before movement onset. A total of 266 neurons were tested with self-initiated arm movements. Of these, 43 showed premovement activity beginning 610–3030 ms before movement onset (median 1430 ms). The activity increased slowly and reached its peak at 370 ms before movement onset. It ended before movement onset or continued until the arm began to move or reached the target. This activity appears to reflect neuronal processes related to the internal generation of movements. Two thirds of activations preceding self-initiated movements occurred in neurons not activated before externally instructed movements, suggesting a selectivity for the internal generation process. Activity related to the execution of self-initiated movements occurred in 67 neurons: it began during and up to 420 ms before movement onset and was usually not associated with pre-movement activity. Most of these neurons were also activated with stimulus-triggered movements, suggesting a lack of selectivity for the execution of self-initiated movements. In comparison with the striatum, more SMA neurons showed preparatory activity preceding externally instructed movements (transient 27% vs 16%, sustained 20% vs 12%) and self-initiated movements (16% vs 11%). Whereas transient responses showed similar latencies and durations in the two structures, sustained preparatory activity preceding externally instructed or self-initiated movements began and reached its peak earlier in SMA compared to striatal neurons. However, due to the long durations, sustained activation largely overlapped in the two structures, and thus essentially occurred simultaneously. Instruction-induced or internally generated preparatory activity may originate outside of the SMA and striatum or may derive from activity reverberating in cortico-basal ganglia loops, possibly in conjunction with other, closely associated cortical and subcortical structures. These data would favor a conjoint role for SMA and striatum in the internal generation of individual behavioral acts and the preparation of behavioral reactions.     

Differential effects of age on subcomponents of response inhibition

Inhibitory deficits contribute to cognitive decline in the aging brain. Separating subcomponents of response inhibition may help to resolve contradictions in the existing literature. A total of 49 healthy participants underwent functional magnetic resonance imaging (fMRI) while performing a Go/no-go-, a Simon-, and a Stop-signal task. Regression analyses were conducted to identify correlations of age and activation patterns. Imaging results revealed a differential effect of age on subcomponents of response inhibition. In a simple Go/no-go task (no spatial discrimination), aging was associated with increased activation of the core inhibitory network and parietal areas. In the Simon task, which required spatial discrimination, increased activation in additional inhibitory control regions was present. However, in the Stop-signal task, the most demanding of the three tasks, aging was associated with decreased activation. This suggests that older adults increasingly recruit the inhibitory network and, with increasing load, additional inhibitory regions. However, if inhibitory load exceeds compensatory capacity, performance declines in concert with decreasing activation. Thus, the present findings may refine current theories of cognitive aging.     

The time course of alerting effect over orienting in the attention network test

In the present experiment we used a version of the attention network test (ANT) similar to that of Callejas et al. (Exp Brain Res 167:27–37, 2005) to assess the Posner’s attention networks (alerting, orienting and conflict), and their interactions. We observed shorter reaction times with alerting tone than with no alerting tone trials (the alerting effect); with cued than with uncued trials (the orienting effect); and with congruent than with incongruent trials (the conflict effect). These results replicate previous findings with the ANT. We also manipulated cue–target interval at five stimulus onset asynchrony (SOA) values (100, 300, 500, 800, and 1,200 ms) to trace the alerting network influence over the orienting network. The SOA manipulation showed that cuing effects peaked at 300 ms SOA irrespective of whether an alerting tone was present or not, and the alerting tone improved the cuing effect equally for 100–500 SOAs, but it did not at the longest 800–1,200 ms SOAs. These results suggest that alerting improves rather than accelerates orienting effects, a result that agrees with data from neuropsychological rehabilitation of parietal patients with spatial bias.

Targets and non-targets in the aging brain: A go/nogo event-related potential study

This study tested whether older adults show enhanced suppression of inappropriate processing of non-target information, as marked with the nogo-P3 event-related potential (ERP). Healthy younger and older adults were tested on a simple go/nogo task with visually presented numbers. Unlike in most of the previous studies, go and nogo stimuli were matched for frequency and conflict level in order to minimize the impact of task difficulty, probability monitoring, or conflict detection and resolution on the age-related ERP differences. Older adults showed slower go responses but a comparable accuracy to younger controls. The parietal go-P3 latency was also delayed with aging, while the central nogo-P3 was more pronounced in older adults than in younger controls. The amplitude of this component negatively correlated with go-RTs. In line with previous studies, this suggests that a partial response preparation to nogo events is strongly suppressed in older adults, especially faster ones.     

Age-related spatiotemporal reorganization during response inhibition

As a key high-level cognitive function in human beings, response inhibition is crucial for adaptive behavior. Previous neuroimaging studies have shown that older individuals exhibit greater neural activation than younger individuals during response inhibition tasks. This finding has been interpreted within a neural compensation framework, in which additional neural resources are recruited in response to age-related cognitive decline. Although this interpretation has received empirical support, the precise event-related temporal course of this age-related compensatory neural response remains unexplored. In the present study, we conducted source analysis on inhibition-related ERP components (i.e., N2 and P3) that were recorded while healthy younger and older adults participated in a visual Go/NoGo task. We found that older adults showed increased source current densities of the N2 and P3 components than younger adults, which support previous hemodynamic findings. Further, such age-related differences in neural activation were successfully separated between the N2 and P3 periods by source localization analysis. Interestingly, the increased activations in older adults were primarily localized to the right precentral and postcentral gyri during the N2 period, which shifted to the right dorsolateral prefrontal cortex and the right inferior frontal gyrus during the P3 period. Taken together, our results clearly illustrate the spatiotemporal dynamics of age-related functional brain reorganization, and further specify the exact temporal course at the millisecond scale by which age-related compensatory neural responses occur during response inhibition.     

Frontal and central oscillatory changes related to different aspects of the motor process: a study in go/no-go paradigms

We studied alpha and beta EEG oscillatory changes in healthy volunteers during two different auditory go/no-go paradigms, in order to investigate their relationship with different components of the motor process. In the first paradigm (S2-centered), the initial tone (S1) was constant (warning), and the second tone (S2) indicated the subject whether to move or not. In the second paradigm (S1-centered), S1 indicated whether to move or not, while S2 just indicated the timing of the movement. A medial frontal beta energy increase was found in all conditions after the stimulus that forces the subject to decide whether to move or not (S1 or S2 depending on the paradigm). In both go conditions, a central alpha and beta energy decrease began after the go decision, reaching minimum values during the movement; it was followed by a beta post-movement increase, limited to the central contralateral area. In the no-go conditions, a marked fronto-central beta synchronization appeared after the decision not to move. In conclusion, our study was able to dissociate the beta oscillatory changes related to movement preparation and execution (central decrease/increase) from those associated with decision-making (medial frontal increase) and motor inhibition (fronto-central increase).     

Estrogen modulates inhibitory control in healthy human females: evidence from the stop-signal paradigm

Animal studies point to a role of estrogen in explaining gender differences in striatal dopaminergic functioning, but evidence from human studies is still lacking. Given that dopamine is crucial for controlling and organizing goal-directed behavior, estrogen may have a specific impact on cognitive control functions, such as the inhibition of prepotent responses. We compared the efficiency of inhibitory control (as measured by the stop-signal task) in young women across the three phases of their menstrual cycle (salivary estradiol and progesterone concentrations were assessed) and in young men. Women were less efficient in inhibiting prepotent responses in their follicular phase, which is associated with higher estradiol levels and with higher dopamine turnover rates, than in their luteal or menstruation phase. Likewise, women showed less efficient inhibitory control than men in their follicular phase but not in their luteal or menstruation phase. Our results are consistent with models assuming that the over-supply of striatal dopamine in the follicular phase weakens inhibitory pathways, thus leading to enhanced competition between responses. We conclude that gender differences in response inhibition are variable and state dependent but not structural.     

Stimulus modality and Go/NoGo effects on P3 during parallel visual and auditory continuous performance tasks

Task and modality effects on P3 latency, amplitude, and scalp topography were studied during parallel versions of visual (VCPT) and auditory (ACPT) continuous performance tasks using a Go/NoGo paradigm (A-X CPT). Both the ACPT and VCPT incorporated five conditions including Go and NoGo stimulus sequences as well as three other nontarget conditions. The goal was to evaluate the functional significance and modality specificity of the P300 response and the NoGo P3. Analyses were performed using both raw and normalized data to make comparisons across modalities. For both modalities, the Target X (Go) and three nontarget conditions elicited maximum P3 amplitudes over the posterior scalp sites and qualified as classical P300 responses. The NoGo condition was associated with an increase in central-frontal amplitude compared to the Target X condition. The scalp topography of the P300/P3 for Go and NoGo conditions, as well as all other conditions, was the same for both modalities, supporting the modality independent nature of both P300 and the NoGo P3. Min-Max normalization of P3 amplitudes did not change the condition-topography relationships.     

It's not too late: The onset of the frontocentral P3 indexes successful response inhibition in the stop‐signal paradigm

The frontocentral P3 event‐related potential has been proposed as a neural marker of response inhibition. However, this association is disputed: some argue that P3 latency is too late relative to the timing of action stopping (stop‐signal reaction time; SSRT) to index response inhibition. We tested whether P3 onset latency is a marker of response inhibition, and whether it coincides with the timing predicted by neurocomputational models. We measured EEG in 62 participants during the stop‐signal task, and used independent component analysis and permutation statistics to measure the P3 onset in each participant. We show that P3 onset latency is shorter when stopping is successful, that it is highly correlated with SSRT, and that it coincides with the purported timing of the inhibition process (towards the end of SSRT). These results demonstrate the utility of P3 onset latency as a noninvasive, temporally precise neural marker of the response inhibition process.     

Excitatory and inhibitory processes in primary motor cortex during the foreperiod of a warned reaction time task are unrelated to response expectancy

Reaction time (RT) is shortened when a warning signal precedes the response signal, a finding attributed to response preparation during the foreperiod between the warning and response signals. In a previous experiment, we delivered transcranial magnetic stimulation (TMS) during the short constant foreperiod of a warned RT task and found simultaneous suppression of motor evoked potential (MEP) amplitude and reduction of short-interval intracortical inhibition (SICI) on warned trials (Sinclair and Hammond in Exp Brain Res 186:385–392, 2008). To investigate the extent to which these phenomena are associated with response preparation we measured MEP amplitude and SICI during the foreperiod of a warned RT task in which three different warning signals specified the probability (0, 0.5, or 0.83) of response signal presentation. MEP amplitude was suppressed (Experiment 1) and SICI reduced (Experiment 2) equally in all of the warned conditions relative to when TMS was delivered in the inter-trial interval (ITI) suggesting that the modulation of primary motor cortex excitability during the foreperiod does not depend on momentary response expectancy induced by the warning signal. The reduction of SICI and suppression of MEP amplitude can be explained by assuming that a warning signal induces automatic motor cortical activation which is balanced by a competing inhibition to prevent premature response. A composite measure which weighted both speed and accuracy of response was positively correlated with the MEP amplitude during both the foreperiod and the ITI, suggesting that high motor cortical excitability is associated with optimized preparatory strategies for fast and accurate response.     

基于Go/NoGo任务的青年吸烟者抑制控制能力的事件相关电位研究

目的:基于Go/NoGo任务,探讨18到25周岁的青年吸烟者的事件相关电位成分（N200、P300）与抑制控制能力是否存在变化。方法:采集Go/NoGo任务下30名青年吸烟者和30名青年不吸烟者的脑电图,比较青年吸烟者和不吸烟者的事件相关电位波幅和任务表现。结果:青年吸烟组的P300波幅显著低于不吸烟组（t=-2.357, P=0.023）,N200的波幅没有显著差异（t=-0.904, P=0.375）。并且青年吸烟组的NoGo错误数显著高于不吸烟组（t=4.316, P=0.000）。Pearson相关性分析显示,青年吸烟组的P300波幅和NoGo错误数显著相关（r=0.37, P=0.044）。结论:青年吸烟者相对于青年不吸烟者在抑制控制能力方面具有缺陷。本研究可为青年吸烟者吸烟成瘾研究提供一定的参考,而且能为从事治疗吸烟成瘾的医疗人员和心理咨询师提供有效帮助。     

Reduced intracortical inhibition during the foreperiod of a warned reaction time task

Reaction time (RT) is shortened when the response signal is preceded by a warning signal, a finding that has been attributed to response preparation during the foreperiod between the warning and response signals. Research suggests an increased excitability of cortical movement representations associated with response preparation during the foreperiod of a warned RT task (Davranche et al. in Eur J Neurosci 25:3766–3774, 2007). However when the foreperiod duration is short and constant, the motor evoked potential (MEP) amplitude elicited by transcranial magnetic stimulation (TMS) during the foreperiod is suppressed (Touge et al. in Clin Neurophysiol 111:1216–1226, 1998), suggesting a competing inhibitory process. Three experiments measured MEP amplitude and intracortical inhibition during the foreperiod of a warned RT task in which the response was a flexion of the right index finger. Experiments 1 and 2 measured short-interval intracortical inhibition (SICI) with paired TMS pulses separated by inter-stimulus intervals (ISIs) of 3 (SICI₃) and 1.5 ms (SICI_1.5), respectively. Experiment 3 measured long-interval intracortical inhibition (LICI) with paired TMS pulses with an ISI of 100 ms (LICI₁₀₀). In all experiments MEP amplitude was smaller in the warned condition than in the unwarned condition. There was less SICI₃ in the warned condition than in the unwarned condition (Experiment 1) whereas SICI_1.5 was similar in both conditions (Experiment 2). There was less LICI₁₀₀ in the warned condition than in the unwarned condition (Experiment 3). The intracortical inhibitory processes measured here cannot explain the suppression of MEP amplitude in the warned condition. We propose that the suppression of MEP amplitude is the result of an inhibitory mechanism, which acts on primary motor cortex to prevent premature response during the foreperiod.     

Event-related brain potentials and error-related processing: An analysis of incorrect responses to go and no-go stimuli

Recent research has suggested that there is a component of the event-related brain potential, the error-related negativity (ERN), that is associated with error detection and remedial actions such as error inhibition, immediate error correction, or error compensation. The present experiment used a go/no-go task to define more precisely the functional significance of this component. In this task, an ERN was observed for incorrect responses on go trials (errors of choice) and for response on no-go trials (errors of action). Because errors of action cannot be corrected immediately by executing another response, these results indicate that the process manifested by the ERN is not dependent on immediate error correction. Other aspects of the data converge in suggesting that the ERN process is more U related to error detection and that the connections between detection and remedial actions may depend on the task situation.     

The time course of segment and tone encoding in Chinese spoken production: an event-related potential study

The present study investigated the time course of segment and tone encoding in Chinese spoken production with an event-related brain potentials (ERPs) experiment. Native Chinese speakers viewed a series of pictures and made Go/noGo decisions along dimensions of segmental onset or tone information of picture names. Behavioral data and onset latency of the N200 effect indicated that segmental information became available prior to tonal information. Moreover, the results of scalp distributions and onset latency patterns of the N200 effect on segmental and tonal decisions suggest that segmental and metrical encoding is relatively disassociated in Chinese spoken production. Our findings provide additional evidence from Chinese as a kind of non-alphabetic language concerning theories of phonological encoding based on alphabetic languages.     

Characteristics of No-go-P300 component during somatosensory Go/No-go paradigms

The present study investigated one of the characteristics of No-go-related brain activity during somatosensory Go/No-go paradigms, by manipulating the stimulus site and response hand. Somatosensory event-related potentials (ERPs) were recorded in ten right-handed subjects. Electrical stimulation was delivered to the second and fifth digit of one hand, and the subjects had to respond to a Go stimulus by pushing a button with the thumb contralateral to the stimulated side as quickly as possible. We focused on the peak amplitude and latency of Som-Go-P300 (P300 evoked by somatosensory Go stimuli) and Som-No-go-P300 (P300 evoked by somatosensory No-go stimuli) components. The amplitude of Som-No-go-P300, which is very similar to No-go-P300 components following visual and auditory stimulation, was significantly larger than that of Som-Go-P300 at fronto-central electrodes, indicating ‘anteriorization’ of the No-go-P300. The amplitude of Som-No-go-P300 was significantly larger in right than left hemispheres during right hand response conditions, but this difference was not found under left hand conditions. In addition, the difference in amplitude between Som-Go- and Som-No-go-P300, which is frequently described as ‘the Go/No-go effect’ on P300, was significant in the left hemisphere under right hand response conditions, whereas a significant effect was found in both the left and the right hemispheres under left hand response conditions. Our findings suggested that the anteriorization of No-go-P300 was independent of stimulus modalities such as visual, auditory, and somatosensory, and the amplitude of No-go-P300 and Go/No-go effects on P300 was affected by the response hand.