Inhibition and the right inferior frontal cortex

It is controversial whether different cognitive functions can be mapped to discrete regions of the prefrontal cortex (PFC). The localisationist tradition has associated one cognitive function - inhibition - by turns with dorsolateral prefrontal cortex (DLPFC), inferior frontal cortex (IFC), or orbital frontal cortex (OFC). Inhibition is postulated to be a mechanism by which PFC exerts its effects on subcortical and posterior-cortical regions to implement executive control. We review evidence concerning inhibition of responses and task-sets. Whereas neuroimaging implicates diverse PFC foci, advances in human lesion-mapping support the functional localization of such inhibition to right IFC alone. Future research should investigate the generality of this proposed inhibitory function to other task domains, and its interaction within a wider network.     

Juvenile offspring of rats exposed to restraint stress in late gestation have impaired cognitive performance and dysregulated progestogen formation

Gestational stress may have lasting effects on the physical and neurocognitive development of offspring. The mechanisms that may underlie these effects are of interest. Progesterone and its 5α-reduced metabolites, dihydroprogesterone and 5α-pregnan-3α-ol-20-one (3α,5α-THP), maintain pregnancy, have neurotrophic effects, and can enhance cognitive performance. We hypothesized that some of the deleterious effects of gestational stress on the cognitive performance of offspring may be related to progestogen formation. Pregnant rat dams were exposed to restraint under a bright light (thrice daily for 45 min) on gestational days 17-21 or were minimally handled controls. Dams that were exposed to restraint had lower circulating levels of 3α,5α-THP and significantly greater concentrations of corticosterone at the time of birth than did control dams. Male and female offspring, that were gestationally stressed or not, were cross-fostered to non-manipulated dams. Between postnatal days 28-30, offspring were assessed for object recognition, a prefrontal cortex (PFC)-dependent cognitive task. Restraint-exposed offspring performed more poorly in the object recognition task than did control offspring, irrespective of sex. As well, progesterone turnover to its 5α-reduced metabolites in the medial PFC (but not the diencephalon) was significantly reduced among restraint-exposed, compared to control, offspring. Progesterone turnover, and levels of 3α,5α-THP, positively correlated with performance in the object recognition task. Thus, restraint stress in late pregnancy impaired cognitive development and dysregulated progestogen formation in brain.     

Evidence for the Involvement of the Rat Prefrontal Cortex in Sustained Attention

Previous studies suggest that, in both humans and rats, the prefrontal cortex (PFC) is involved in both selective and divided attention. We have also shown that the PFC is involved in response selection and that its involvement is modulated by the cognitive effort required by the task. However, the role of the PFC is much less clear when no response selection is required. The purpose of the present experiments was to assess the role of the PFC in attentional functions with a low response-selection demand. We used two tasks in which information processing was effortful but where the demand on a response selection process is low. Moreover, we assessed two different types of visual attentional functions: selective attention (Experiment 1) and sustained attention (Experiment 2). The results showed a differential involvement of the PFC in the two tasks. Selective attention was not impaired by prefrontal lesions when the number of possible positions for the stimulus on which the subjects must focus was restricted to two (Experiment 1). In contrast, prefrontal rats were unable to sustain their attention long enough to detect, and react to, subtle variations in brightness (Experiment 2). This result suggests a dissociation between different types of attentional functions depending upon the integrity of the PFC. More specifically, results in Experiment 2 suggest an involvement of the PFC in sustained attention. Finally, the overall results show that even in tasks involving low demands on response selection the PFC is involved in attentional functions.     

重复经颅磁刺激对轻度认知障碍的干预效果

轻度认知障碍(mild cognitive impairment, MCI)是介于正常认知老化和老年痴呆的中间状态, 目前尚无有效的药物治疗方案。重复经颅磁刺激(repetitive transcranial magnetic stimulation, rTMS)可通过诱导突触可塑性的改变来改善大脑的认知功能。对rTMS干预MCI认知功能的有效性及神经机制进行分析。未来研究应优化定位手段, 延长对干预效果的随访评估, 考察不同刺激参数和刺激靶区对干预有效性的影响, 以及结合脑成像技术来探索rTMS的干预机制。     

Effects of Stroop task duration on subsequent cognitive and physical performance

The strength model of self-control purports to explain why brief cognitive response inhibition tasks impair subsequent isometric handgrip endurance. According to the model, ego depleting tasks requiring self-control resources impair performance on subsequent tasks that also require self-control resources. However, several lines of evidence challenge this model, including evidence of improved exercise performance following longer cognitive tasks. Our study investigated the effects of cognitive task duration on (1) subsequent physical endurance performance, (2) concurrent cognitive task performance, and (3) subsequent novel cognitive task performance. Adopting an experimental design, with Stroop task type (incongruent, congruent) and duration (5, 10, 20 min) as between-participant factors, participants (N = 180) completed a color word Stroop task, an isometric handgrip to exhaustion task, and a novel 5-min incongruent number word Stroop task. In the handgrip task, endurance performance was worse following incongruent word Stroop than congruent word Stroop for 10-min tasks but not 5-min and 20-min tasks. In the word Stroop task, accuracy was lower and speed was slower following incongruent word Stroop than congruent word Stroop. Importantly, reaction times improved with longer task durations. In the novel number Stroop task, accuracy was higher following incongruent word Stroop than congruent word Stroop. In conclusion, the finding that the ego depletion effect was moderated by cognitive task duration is better explained by the expected value of control model than the strength model.     

Context processing in older adults: evidence for a theory relating cognitive control to neurobiology in healthy aging.

A theory of cognitive aging is presented in which healthy older adults are hypothesized to suffer from disturbances in the processing of context that impair cognitive control function across multiple domains, including attention, inhibition, and working memory. These cognitive disturbances are postulated to be directly related to age-related decline in the function of the dopamine (DA) system in the prefrontal cortex (PFC). A connectionist computational model is described that implements specific mechanisms for the role of DA and PFC in context processing. The behavioral predictions of the model were tested in a large sample of older (N = 81) and young (N = 175) adults performing variants of a simple cognitive control task that placed differential demands on context processing. Older adults exhibited both performance decrements and, counterintuitively, performance improvements that are in close agreement with model predictions.     

How am I doing? Performance feedback mitigates the effects of mental fatigue on endurance exercise performance

Mental fatigue induced by an earlier cognitive task can impair performance on a subsequent physical task. The current study investigated whether such performance impairment could be mitigated by performance feedback. In an experimental sequential-task design, 63 sport science students completed a series of three tasks: 5-min physical (pre-test), 20-min cognitive, 5-min physical (post-test). Participants were randomly allocated to one of three groups: feedback (n = 23), no feedback (n = 20), control (n = 20). The physical tasks, which assessed force production during a self-paced rhythmic handgrip task as a measure of physical endurance performance, were performed with (feedback group) or without (no feedback group, control group) visual performance feedback. The cognitive tasks involved either completing a 2-back memory task to induce mental fatigue (feedback and no feedback groups) or watching a didactic film (control group). Self-report measures (fatigue, exertion, vigor, motivation) were collected throughout. The 2-back cognitive task increased mental fatigue, mental exertion and general fatigue in the feedback and no feedback groups compared to the control group. Relative to the pre-test physical task, post-test endurance performance declined in the no feedback group (−14.4%) but did not change in the control (−2.6%) and feedback (−2.4%) groups. This mitigation of performance effect was not accompanied by parallel changes in fatigue, exertion, vigor, or motivation. In conclusion, visual performance feedback mitigates the negative effects of mental fatigue on physical endurance performance.     

前额叶在老年阶段的可塑性及相关机制

大量研究表明, 前额叶的结构和功能更容易受年老化影响; 然而, 近年来的研究发现, 前额叶的结构和功能在老年阶段具有一定的可塑性。对老年人进行认知训练, 能够延缓前额叶皮层厚度的萎缩, 提高白质完整性, 改善神经网络的功能连接和分化, 并可能通过调节多巴胺系统的活动改变前额叶皮质和皮质下结构的功能激活模式。有氧锻炼能够改善心脑血管功能, 保护和促进神经元的存活和生长, 引起前额叶灰质、白质体积的增加及功能激活的变化。认知训练与有氧锻炼等相结合的整合性训练不仅引起前额叶及相关认知功能的改变, 而且具有更好的生态学效度, 使老年人日常认知能力和生活质量得到提高。未来研究应采用多种技术手段, 从多个层面理解老年阶段前额叶的可塑性及相关机制; 加强对与前额叶关系密切的多种认知功能可塑性神经机制的研究; 并重视与整合性训练有关的前额叶可塑性。     

Differential effects of inactivation of the orbitofrontal cortex on strategy set-shifting and reversal learning

Different subregions of the rodent prefrontal cortex (PFC) mediate dissociable types of behavioral flexibility. For example, lesions of the medial or orbitofrontal (OFC) regions of the PFC impair extradimensional shifts and reversal learning, respectively, when novel stimuli are used during different phases of the task. In the present study, we assessed the effects of inactivation of the OFC on strategy set-shifting and reversal learning, using a maze based set-shifting task mediated by the medial PFC. Long–Evans rats were trained initially on a visual-cue discrimination to obtain food. On the subsequent day, rats had to shift to using a response strategy (e.g., always turn left). On Day 3 (reversal), rats were required to reverse the direction of their turn (e.g., always turn right). Infusions of the local anesthetic bupivacaine into the OFC did not impair initial visual discrimination learning, nor did it impair performance on the set-shift. In contrast, inactivation of the OFC did impair reversal learning; yet, these rats ceased using the previously acquired response rule as readily as controls. Instead, rats receiving OFC inactivations made a disproportionate number of erroneous arm entries towards the visual-cue, suggested that these animals reverted back to using the original visual-cue based strategy. These findings, in addition to previous data, further support the notion that the OFC and medial PFC play dissociable roles in reversal learning and set-shifting. Furthermore, the lack of effect of OFC inactivations on the set-shift indicates that this type of behavioral flexibility does not require cognitive operations related to reversal learning.     

Cognitive reappraisal reduces perceived exertion during endurance exercise

Emotion regulation may influence psychological responses to exercise. We examined whether the emotion regulation strategies, cognitive reappraisal and distraction, influenced psychological state and prefrontal cortex oxygenation during endurance exercise. Twenty-four endurance runners ran for 90 min at 75–85% maximum heart rate in three separate sessions with no instruction or with instructions to use cognitive reappraisal or distraction. Participants rated their emotional arousal, emotional valence, and perceived exertion before, every 30 min during, and after exercise. Functional near-infrared spectroscopy quantified changes in prefrontal cortex oxygenation. Participants felt lower emotional arousal and physical exertion when instructed to utilize cognitive reappraisal than when given no emotion regulation instruction. Such responses to distraction did not differ from the other conditions. Emotion regulation strategies did not influence emotional valence or prefrontal cortex oxygenation. Participants’ analytical interpretation of the cognitive reappraisal instruction could contribute to small effect sizes and limited effects. Further research should determine contexts under which emotion regulation strategies most benefit endurance exercise experience.     

基于事件的前瞻记忆与认知控制

前瞻记忆和认知控制是人类认知能力的重要组成部分。Bugg等人(2013)发现前瞻记忆多重加工模型和双重认知控制理论具有共性。此后,越来越多的研究者关注认知控制在意图执行中和执行完成后的作用。本文对近年来关于前瞻记忆与认知控制的研究进行了梳理,发现认知控制对前瞻记忆的完成起支持作用,但二者也在脑机制层面存在差异。本研究能为未来更深入地探讨前瞻记忆的加工机制及生理基础提供新的视角。     

The role of the prefrontal cortex in the go/no-go task in humans: a positron emission tomography study

To study the localization of response inhibition in the human brain, especially the role of the prefrontal cortex and laterality of its activation, we used positron emission tomography (PET) to measure regional cerebral blood flow in 11 right-handed participants while they performed a go/no-go and a simple control reaction-time task. In the control task, the participants responded to a target stimulus following a cue stimulus. In the go/no-go task they were instructed to inhibit the required response if the target stimulus did not appear. These tasks were performed using each hand. The right prefrontal cortex was found to be significantly activated when the go/no-go task was compared with the control task, regardless of the responding hand. The results indicated that response inhibition per se may be controlled by the right prefrontal cortex regardless of response hand for right-handed participants.     

Anterior cingulate cortex and cognitive control: Neuropsychological and electrophysiological findings in two patients with lesions to dorsomedial prefrontal cortex

Whereas neuroimaging studies of healthy subjects have demonstrated an association between the anterior cingulate cortex (ACC) and cognitive control functions, including response monitoring and error detection, lesion studies are sparse and have produced mixed results. Due to largely normal behavioral test results in two patients with medial prefrontal lesions, a hypothesis has been advanced claiming that the ACC is not involved in cognitive operations. In the current study, two comparably rare patients with unilateral lesions to dorsal medial prefrontal cortex (MPFC) encompassing the ACC were assessed with neuropsychological tests as well as Event-Related Potentials in two experimental paradigms known to engage prefrontal cortex (PFC). These included an auditory Novelty Oddball task and a visual Stop-signal task. Both patients performed normally on the Stroop test but showed reduced performance on tests of learning and memory. Moreover, altered attentional control was reflected in a diminished Novelty P3, whereas the posterior P3b to target stimuli was present in both patients. The error-related negativity, which has been hypothesized to be generated in the ACC, was present in both patients, but alterations of inhibitory behavior were observed. Although interpretative caution is generally called for in single case studies, and the fact that the lesions extended outside the ACC, the findings nevertheless suggest a role for MPFC in cognitive control that is not restricted to error monitoring.     

Avoiding another mistake: Error and posterror neural activity associated with adaptive posterror behavior change

The magnitude of posterior medial frontal cortex (pMFC) activity during commission of an error has been shown to relate to adaptive posterror changes in response behavior on the trial immediately following. In the present article, we examined neural activity during and after error commission to identify its relationship to sustained posterror behavior changes that led to performance improvements several trials into the future. The standard task required participants to inhibit a prepotent motor response during infrequent lure trials, which were randomly interspersed among numerous go trials. Posterror behavior was manipulated by introducing a dynamic condition, in which an error on a lure trial ensured that the next lure would appear within two to seven go trials. Behavioral data indicated significantly higher levels of posterror slowing and accuracy during the dynamic condition, as well as fewer consecutive lure errors. Bilateral prefrontal cortex (PFC) and pMFC activity during the posterror period, but not during commission of the error itself, was associated with increased posterror slowing. Activity within two of these regions (right PFC and pMFC) also predicted success on the next lure trial. The findings support a relationship between pMFC/PFC activity and adaptive posterror behavior change, and the discrepancy between these findings and those of previous studies-in the present study, this relationship was detected during the posterror period rather than during commission of the error itself--may have resulted from the requirements of the present task. Implications of this discrepancy for the flexibility of cognitive control are discussed.     

Effects of transcranial direct current stimulation on neural activity and functional connectivity during fear extinction

Background/ObjectiveAnxiety disorders are highly prevalent and negatively impact daily functioning and quality of life. Transcranial direct current stimulation (tDCS) targeting the dorsolateral prefrontal cortex (dlPFC), especially in the right hemisphere impacts extinction learning; however, the underlying neural mechanisms are elusive. Therefore, we aimed to investigate the effects of cathodal tDCS stimulation to the right dlPFC on neural activity and connectivity patterns during delayed fear extinction in healthy participants.MethodsWe conducted a two-day fear conditioning and extinction procedure. On the first day, we collected fear-related self-reports, clinical questionnaires, and skin conductance responses during fear acquisition. On the second day, participants in the tDCS group (n = 16) received 20-min offline tDCS before fMRI and then completed the fear extinction session during fMRI. Participants in the control group (n = 18) skipped tDCS and directly underwent fMRI to complete the fear extinction procedure. Whole-brain searchlight classification and resting-state functional connectivity analyses were performed.ResultsWhole-brain searchlight classification during fear extinction showed higher classification accuracy of threat and safe cues in the left anterior dorsal and ventral insulae and hippocampus in the tDCS group than in the control group. Functional connectivity derived from the insula with the dlPFC, ventromedial prefrontal cortex, and inferior parietal lobule was increased after tDCS.ConclusiontDCS over the right dlPFC may function as a primer for information exchange among distally connected areas, thereby increasing stimulus discrimination. The current study did not include a sham group, and one participant of the control group was not randomized. Therefore, to address potential allocation bias, findings should be confirmed in the future with a fully randomized and sham controlled study.     

Dissociable stages of problem solving (II): first evidence for process-contingent temporal order of activation in dorsolateral prefrontal cortex

In a companion study, eye-movement analyses in the Tower of London task (TOL) revealed independent indicators of functionally separable cognitive processes during problem solving, with processes of building up an internal representation of the problem preceding actual planning processes. These results imply that processes of internalization and planning should also be distinguishable in time and space with respect to concomitant brain activation patterns. To investigate this possibility, here we conducted analyses of fMRI data for left and right dorsolateral prefrontal cortex (dlPFC) during problem solving in the TOL task by accounting for the trial-by-trial variability of onsets and durations of the different cognitive processing stages. Comparisons between stimulus-locked and response-locked modeling approaches affirmed that activation in left dlPFC was elicited particularly during early processes of internalization, comprising the extraction of goal information and the generation of an internal problem representation, whereas activation in right dlPFC was predominantly attributable to later processes of mental transformations on this representation, that is planning proper. Thus, present data corroborate the proposal that often observed bilateral dlPFC activation patterns during complex cognitive tasks such as problem solving may reflect functionally and, to some extent, even temporally separable processes with opposing lateralizations.     

A developmental neuroimaging investigation of the change paradigm

This neuroimaging study examines the development of cognitive flexibility using the Change task in a sample of youths and adults. The Change task requires subjects to inhibit a prepotent response and substitute an alternative response, and the task incorporates an algorithm that adjusts task difficulty in response to subject performance. Data from both groups combined show a network of prefrontal and parietal areas that are active during the task. For adults vs. youths, a distributed network was more active for successful change trials versus go, baseline, or unsuccessful change trials. This network included areas involved in rule representation, retrieval (lateral PFC), and switching (medial PFC and parietal regions). These results are consistent with data from previous task-switching experiments and inform developmental understandings of cognitive flexibility.     

Alpha2A-adrenoceptor stimulation improves prefrontal cortical regulation of behavior through inhibition of cAMP signaling in aging animals

The working-memory functions of the prefrontal cortex (PFC) are improved by stimulation of postsynaptic, alpha2A-adrenoceptors, especially in aged animals with PFC cognitive deficits. Thus, the alpha2A-adrenoceptor agonist, guanfacine, greatly improves working-memory performance in monkeys and rats following systemic administration or intra-PFC infusion. Alpha2A-adrenoceptors are generally coupled to Gi, which can inhibit adenylyl cyclases and reduce the production of cAMP. However, no study has directly examined whether the working-memory enhancement observed with guanfacine or other alpha2A-adrenoceptor agonists results from cAMP inhibition. The current study confirmed this hypothesis in both rats and monkeys, showing that treatments that increase cAMP-mediated signaling block guanfacine's beneficial effects. In aged rats, guanfacine was infused directly into the prelimbic PFC and was challenged with co-infusions of the cAMP analog, Sp-cAMPS. In aging monkeys, systemically administered guanfacine was challenged with the phosphodiesterase 4 inhibitor, rolipram, using intramuscular doses known to have no effect on their own. In both studies, agents that mimicked the actions of cAMP (rats) or increased endogenous cAMP (monkeys) completely blocked the enhancing effects of guanfacine on working-memory performance. These results are consistent with alpha2A-adrenoceptor stimulation enhancing PFC working-memory function via inhibition of cAMP-mediated signaling.     

Subliminal food images compromise superior working memory performance in women with restricting anorexia nervosa

Prefrontal cortex (PFC) is dysregulated in women with restricting anorexia nervosa (RAN). It is not known whether appetitive non-conscious stimuli bias cognitive responses in those with RAN. Thirteen women with RAN and 20 healthy controls (HC) completed a dorsolateral PFC (DLPFC) working memory task and an anterior cingulate cortex (ACC) conflict task, while masked subliminal food, aversive and neutral images were presented. During the DLPFC task, accuracy was higher in the RAN compared to the HC group, but superior performance was compromised when subliminal food stimuli were presented: errors positively correlated with self-reported trait anxiety in the RAN group. These effects were not observed in the ACC task. Appetitive activation is intact and anxiogenic in women with RAN, and non-consciously interacts with working memory processes associated with the DLPFC. This interaction mechanism may underlie cognitive inhibition of appetitive processes that are anxiety inducing, in people with AN.     

Medial prefrontal cortex is selectively involved in response selection using visual context in the background

The exact roles of the medial prefrontal cortex (mPFC) in conditional choice behavior are unknown and a visual contextual response selection task was used for examining the issue. Inactivation of the mPFC severely disrupted performance in the task. mPFC inactivations, however, did not disrupt the capability of perceptual discrimination for visual stimuli. Normal response selection was also observed when nonvisual cues were used as conditional stimuli. The results strongly suggest that the mPFC is not necessarily involved in the inhibition of response or flexible response selection in general, but is rather critical when response selection is required conditionally using visual context in the background.