Top-down control-signal dynamics in anterior cingulate and prefrontal cortex neurons following task switching

The prefrontal cortex (PFC) and anterior cingulate cortex (ACC) have both been implicated in cognitive control, but their relative roles remain unclear. Here we recorded the activity of single neurons in both areas while monkeys performed a task that required them to switch between trials in which they had to look toward a flashed stimulus (prosaccades) and trials in which they had to look away from the stimulus (antisaccades). We found that ACC neurons had a higher level of task selectivity than PFC neurons during the preparatory period on trials immediately following a task switch. In ACC neurons, task selectivity was strongest after the task switch and declined throughout the task block, whereas task selectivity remained constant in the PFC. These results demonstrate that the ACC is recruited when cognitive demands increase and suggest a role for both areas in task maintenance and the implementation of top-down control.     

Prefrontal neurons predict choices during an auditory same-different task

The detection of stimuli is critical for an animal's survival [1]. However, it is not adaptive for an animal to respond automatically to every stimulus that is present in the environment [2-5]. Given that the prefrontal cortex (PFC) plays a key role in executive function [6-8], we hypothesized that PFC activity should be involved in context-dependent responses to uncommon stimuli. As a test of this hypothesis, monkeys participated in a same-different task, a variant of an oddball task [2]. During this task, a monkey heard multiple presentations of a "reference" stimulus that were followed by a "test" stimulus and reported whether these stimuli were the same or different. While they participated in this task, we recorded from neurons in the ventrolateral prefrontal cortex (vPFC; a cortical area involved in aspects of nonspatial auditory processing [9, 10]). We found that vPFC activity was correlated with the monkeys' choices. This finding demonstrates a direct link between single neurons and behavioral choices in the PFC on a nonspatial auditory task.     

Prefrontal coding of temporally discounted values during intertemporal choice

Reward from a particular action is seldom immediate, and the influence of such delayed outcome on choice decreases with delay. It has been postulated that when faced with immediate and delayed rewards, decision makers choose the option with maximum temporally discounted value. We examined the preference of monkeys for delayed reward in an intertemporal choice task and the neural basis for real-time computation of temporally discounted values in the dorsolateral prefrontal cortex. During this task, the locations of the targets associated with small or large rewards and their corresponding delays were randomly varied. We found that prefrontal neurons often encoded the temporally discounted value of reward expected from a particular option. Furthermore, activity tended to increase with [corrected] discounted values for targets [corrected] presented in the neuron's preferred direction, suggesting that activity related to temporally discounted values in the prefrontal cortex might determine the animal's behavior during intertemporal choice.     

Exploring the cortical evidence of a sensory-discrimination process

Humans and monkeys have similar abilities to discriminate the difference in frequency between two consecutive mechanical vibrations applied to their fingertips. This task can be conceived as a chain of neural operations: encoding the two consecutive stimuli, maintaining the first stimulus in working memory, comparing the second stimulus with the memory trace left by the first stimulus and communicating the result of the comparison to the motor apparatus. We studied this chain of neural operations by recording and manipulating neurons from different areas of the cerebral cortex while monkeys performed the task. The results indicate that neurons of the primary somatosensory cortex (S1) generate a neural representation of vibrotactile stimuli which correlates closely with psychophysical performance. Discrimination based on microstimulation patterns injected into clusters of S1 neurons is indistinguishable from that produced by natural stimuli. Neurons from the secondary somatosensory cortex (S2), prefrontal cortex and medial premotor cortex (MPC) display at different times the trace of the first stimulus during the working-memory component of the task. Neurons from S2 and MPC appear to show the comparison between the two stimuli and correlate with the behavioural decisions. These neural operations may contribute to the sensory-discrimination process studied here.     

Top-down control of motor cortex ensembles by dorsomedial prefrontal cortex

Dorsomedial prefrontal cortex is critical for the temporal control of behavior. Dorsomedial prefrontal cortex might alter neuronal activity in areas such as motor cortex to inhibit temporally inappropriate responses. We tested this hypothesis by recording from neuronal ensembles in rodent dorsomedial prefrontal cortex during a delayed-response task. One-third of dorsomedial prefrontal neurons were significantly modulated during the delay period. The activity of many of these neurons was predictive of premature responding. We then reversibly inactivated dorsomedial prefrontal cortex while recording ensemble activity in motor cortex. Inactivation of dorsomedial prefrontal cortex reduced delay-related firing, but not response-related firing, in motor cortex. Finally, we made simultaneous recordings in dorsomedial prefrontal cortex and motor cortex and found strong delay-related temporal correlations between neurons in the two cortical areas. These data suggest that functional interactions between dorsomedial prefrontal cortex and motor cortex might serve as a top-down control signal that inhibits inappropriate responding.     

Single neurons in posterior parietal cortex of monkeys encode cognitive set

The primate posterior parietal cortex (PPC), part of the dorsal visual pathway, is best known for its role in encoding salient spatial information. Yet there are indications that neural activity in the PPC can also be modulated by nonspatial task-related information. In this study, we tested whether neurons in the PPC encode signals related to cognitive set, that is, the preparation to perform a particular task. Cognitive set has previously been associated with the frontal cortex but not the PPC. In this study, monkeys performed a cognitive set shifting paradigm in which they were cued in advance to apply one of two different task rules to the subsequent stimulus on every trial. Here we show that a subset of neurons in the PPC, concentrated in the lateral bank of the intraparietal sulcus and on the angular gyrus, responds selectively to cues for different task rules.     

Influences of rewarding and aversive outcomes on activity in macaque lateral prefrontal cortex

Both appetitive and aversive outcomes can reinforce animal behavior. It is not clear, however, whether the opposing kinds of reinforcers are processed by specific or common neural mechanisms. To investigate this issue, we studied macaque monkeys that performed a memory-guided saccade task for three different outcomes, namely delivery of liquid reward, avoidance of air puff, and feedback sound only. Animals performed the task best in rewarded trials, intermediately in aversive trials, and worst in sound-only trials. Most task-related activity in lateral prefrontal cortex was differentially influenced by the reinforcers. Aversive avoidance had clear effects on some prefrontal neurons, although the effects of rewards were more common. We also observed neurons modulated by both positive and negative reinforcers, reflecting reinforcement or attentional processes. Our results demonstrate that information about positive and negative reinforcers is processed differentially in prefrontal cortex, which could contribute to the role of this structure in goal-directed behavior.     

Neurons that program what to do and in what order

In this issue of Neuron, describe the activity of single neurons in the SEF of monkeys, an oculomotor area of the frontal lobe, during the performance of stereotyped sequences of saccades. The monkey had to look at one of two identical stimuli, but the only way to choose the "correct" stimulus was to learn and remember its position in each presentation of the sequence. SEF neurons could do it.     

与作业无关的新异刺激对猕猴额叶神经元延缓期反应的作用

在猕猴执行延缓辨别作业和单纯辨别作业时,观察了与作业无关的新异刺激对额叶神经元延缓期放电的影响。在这两种作业中,延缓期在1—4s之间随机变化。此时,动物必须高度注意信号的变化,稍不注意即导致操作错误。此外,在延缓辨别作业中,动物在延缓期还要暂时记住暗示期的信号,单纯辨别作业则无此要求。在203个与作业相关的神经元中,有70个神经元在延缓期出现放电频率变化,其中见于延缓辨别作业者41个,见于单纯辨别作业者29个。实验结果表明,在这两种作业的延缓期所出现的神经元放电增多的反应,有着许多相同的特点。与课题无关的声、光、触、痛等刺激引起分心时,神经元的延缓期反应出现明显的变化,随之出现操作错误。多数神经元的反应受到抑制,但也有出现反应增强者,而且同一神经元对不同感觉模式的无关刺激可出现不同的效应,表现出不同程度的感觉模式特异性。此外,无关刺激在延缓期和在测试间歇期可产生不同甚至相反的效应。上述在延缓期出现反应的神经元主要位于额叶弓状沟上支内侧部的一定范围内。本文对实验结果进行了讨论,认为额叶神经元的延缓期反应,可能在很大程度上与注意有关。额叶神经元感觉模式各种程度的特异性可能是注意的通道选择性的神经基础。额叶的背内侧部,包括前额叶后部和运动前区前部     

Neuronal correlates of metacognition in primate frontal cortex

Humans are metacognitive: they monitor and control their cognition. Our hypothesis was that neuronal correlates of metacognition reside in the same brain areas responsible for cognition, including frontal cortex. Recent work demonstrated that nonhuman primates are capable of metacognition, so we recorded from single neurons in the frontal eye field, dorsolateral prefrontal cortex, and supplementary eye field of monkeys (Macaca mulatta) that performed a metacognitive visual-oculomotor task. The animals made a decision and reported it with a saccade, but received no immediate reward or feedback. Instead, they had to monitor their decision and bet whether it was correct. Activity was correlated with decisions and bets in all three brain areas, but putative metacognitive activity that linked decisions to appropriate bets occurred exclusively in the SEF. Our results offer a survey of neuronal correlates of metacognition and implicate the SEF in linking cognitive functions over short periods of time.     

Contribution of area MT to stereoscopic depth perception: choice-related response modulations reflect task strategy

Due to the diversity of tuning properties in sensory cortex, only a fraction of neurons are engaged in a particular task. Characterizing the tuning properties of neurons that are functionally linked to behavior is essential for understanding how activity is "read out" from sensory maps to guide decisions. We recorded from middle temporal (MT) neurons while monkeys performed a depth discrimination task, and we characterized the linkage between MT responses and behavioral choices. Trial-to-trial response fluctuations of MT neurons with odd-symmetric ("Near," "Far") disparity tuning were predictive of monkeys' choices, whereas responses of neurons with even-symmetric tuning were not. This result cannot be explained by neuronal sensitivity or any other response property of MT neurons that we examined but is simply explained by the task strategy that monkeys learned during training. We suggest that this approach provides a physiological means to explore how task strategies are implemented in the brain.     

猕猴额叶神经元视辨别机能可塑性的研究

我们曾经提出,额叶神经元的反应,主要不是取决于刺激物的物理属性,而是与信号意义有密切的关系。为了验证这一看法,设计了两套作业,即视延缓辨别作业(作业Ⅰ)和视辨别反应作业(作业Ⅰ),对4只成年猕猴进行实验。两套作业都由1—4期组成,在第2期都有伪随机出现的红绿灯光信号,在第3期都要求动物密切注意随后的灯光信号变化。但是,作业Ⅰ要求动物对第2期出现的红绿灯光进行辨别,作业Ⅰ则要求对第4期的红绿灯光进行辨别。待动物学会作业,正确率达90％以上,在动物进行作业的同时引导额叶神经元放电。共记录作业相关神经元163个。其中作业Ⅰ98个,作业Ⅱ 65个。在作业Ⅰ中,神经元的反应多数出现在第2、3期,占该作业反应总数的70％。而在作业Ⅱ中,反应多数出现在第3、4期,也占该作业反应总数的70％。其次,作业Ⅰ第2期的神经元反应绝大多数对红、绿灯光有明显的特异性,而作业Ⅱ第2期的则没有,只有第4期的反应才有明显的特异性。本实验结果进一步支持了我们的上述看法,并且表明,额叶神经元对信号的反应主要是在学习中逐渐形成的,有很大的可塑性。     

Effect of expected reward magnitude on the response of neurons in the dorsolateral prefrontal cortex of the macaque

The dorsolateral prefrontal cortex plays a critical role in guiding actions that ensue seconds after an instruction. We recorded from neurons in area 46 and the frontal eye field (FEF) while monkeys performed a memory-guided eye movement task. A visual cue signaled whether a small or large liquid reward would accompany a correct response. Many neurons in area 46 responded more when the monkey expected a larger reward. Reward-related enhancement was evident throughout the memory period and was most pronounced when the remembered target appeared in the neuron's response field. Enhancement was not present in the FEF. The mixture of neural signals representing spatial working memory and reward expectation appears to be a distinct feature of area 46.     

Control of the superior colliculus by the lateral prefrontal cortex

Several decades of patient, functional imaging and neurophysiological studies have supported a model in which the lateral prefrontal cortex (PFC) acts to suppress unwanted saccades by inhibiting activity in the oculomotor system. However, recent results from combined PFC deactivation and neural recordings of the superior colliculus in monkeys demonstrate that the primary influence of the PFC on the oculomotor system is excitatory, and stands in direct contradiction to the inhibitory model of PFC function. Although erroneous saccades towards a visual stimulus are commonly labelled reflexive in patients with PFC damage or dysfunction, the latencies of most of these saccades are outside of the range of express saccades, which are triggered directly by the visual stimulus. Deactivation and pharmacological manipulation studies in monkeys suggest that response errors following PFC damage or dysfunction are not the result of a failure in response suppression but can best be understood in the context of a failure to maintain and implement the proper task set.     

Suppressing Emotions Impairs Subsequent Stroop Performance and Reduces Prefrontal Brain Activation

Abundant behavioral evidence suggests that the ability to self-control is limited, and that any exertion of self-control will increase the likelihood of subsequent self-control failures. Here we investigated the neural correlates underlying the aftereffects of self-control on future control processes using functional magnetic resonance imaging (fMRI). An initial act of self-control (suppressing emotions) impaired subsequent performance in a second task requiring control (Stroop task). On the neural level, increased activity during emotion suppression was followed by a relative decrease in activity during the Stroop task in a cluster in the right lateral prefrontal cortex (PFC) including the dorsolateral prefrontal cortex (DLPFC), an area engaged in the effortful implementation of control. There was no reliable evidence for reduced activity in the medial frontal cortex (MFC) including the anterior cingulate cortex (ACC), which is involved in conflict detection processes and has previously also been implicated in self-control. Follow-up analyses showed that the detected cluster in the right lateral PFC and an area in the MFC were involved in both the emotion suppression task and the Stroop task, but only the cluster in the right lateral PFC showed reduced activation after emotion suppression during the Stroop task. Reduced activity in lateral prefrontal areas relevant for the implementation of control may be a critical consequence of prior self-control exertion if the respective areas are involved in both self-control tasks.     

Evidence Accumulation and Choice Maintenance Are Dissociated in Human Perceptual Decision Making

Perceptual decision making in monkeys relies on decision neurons, which accumulate evidence and maintain choices until a response is given. In humans, several brain regions have been proposed to accumulate evidence, but it is unknown if these regions also maintain choices. To test if accumulator regions in humans also maintain decisions we compared delayed and self-paced responses during a face/house discrimination decision making task. Computational modeling and fMRI results revealed dissociated processes of evidence accumulation and decision maintenance, with potential accumulator activations found in the dorsomedial prefrontal cortex, right inferior frontal gyrus and bilateral insula. Potential maintenance activation spanned the frontal pole, temporal gyri, precuneus and the lateral occipital and frontal orbital cortices. Results of a quantitative reverse inference meta-analysis performed to differentiate the functions associated with the identified regions did not narrow down potential accumulation regions, but suggested that response-maintenance might rely on a verbalization of the response.     

猕猴执行痛,热延缓辨别作业时额叶神经元及肌电...

To study the functional implication of neuronal responses in frontal cortex to noxious and innocuous heat stimuli, experiments were carried out on two monkeys (Macaca mulatta) during performing a delayed discrimination GO/NO-GO task. The animals were trained to hold a lever for at least 3 s in the response period when an innocuous heat stimulus had been applied to the forearm in the cue period, or release it within 1 s with a noxious one. After a criterion of 90% of correct responses in 3 successive days was reached, single neuronal activity was recorded from the frontal cortex along with EMGs from six muscles in both arms. Of 142 task-related neurons recorded, 87 (66.4%) were related to heat, 34 to visual, and 21 to both visual and heat stimuli. Among the heat-related neurons, 22 were responsive to noxious heat, 18 to innocuous heat, and 47 to both. Of the neurons responding to both noxious and innocuous heat stimuli, 4 neurons showed changes in discharge rates, depending on the type of stimuli. In most cases, muscular activities just appeared at the moment of lever pressing and/or releasing in m. extensor digitorium communis, m. flexor carpi ulnaris and m. flexor carpi radialis of the performing arm. No regular muscular activities appeared in other muscles and in other periods of the task. The result showed that the neuronal responses in frontal cortex elicited by heat stimuli in the cue period were not related directly to the initiation and modulation of behaviours.(ABSTRACT TRUNCATED AT 250 WORDS)     

Modelling relative recency discrimination tasks using a stochastic working memory model

Relative recency discrimination (RD) task is typically used to assess the temporal organization function of the prefrontal cortex (PFC). Subjects look at a series of cards (with words or drawings on them) and on seeing a test card determine which of the two items was seen more recently. Results show that patients with damage to the prefrontal cortex are severely impaired on this task. We propose a memory trace-priming mechanism, based on automatic time-marking process hypothesis (Schacter, D.L., 1987. Memory, amnesia, and frontal lobe dysfunction: a critique and interpretation. Psychobiology 15, 21-36), to offer a computational account of the results. In this model, successive words seen by subjects leave decaying memory traces in PFC, which subsequently prime the representations in higher sensory areas such as inferior temporal Cortex (IT) during discrimination judgements. The paper focuses on the evaluation of a probabilistic pre-frontal trace mechanism using a pool of clusters of neurons with self-sustained firing that ends at a random time. The results show that the probabilistic behavior of subjects can be accounted for by the stochasticity of the trace model. A good fit to experimental data is obtained with a PFC memory persistence probability with a decay time constant of tau = approximately 30 s. The model allows for a distributed representation in IT and PFC, but the best fit suggests a sparse representation. It is concluded that further data are needed on representations in IT and PFC, on the connectivity between these two areas, and on the statistical and dynamic properties of memory neurons in PFC.     

Variability of Prefrontal Neuronal Discharges before and after Training in a Working Memory Task

Variability of neural discharges can be revealing about the computations and network properties of neuronal populations during the performance of cognitive tasks. We sought to quantify neuronal variability in the prefrontal cortex of naïve monkeys that were only required to fixate, and to examine how this measure was altered by learning and execution of a working memory task. We therefore performed analysis of a large database of recordings in the same animals, using the same stimuli, before and after training. Our results indicate that the Fano Factor, a measure of variability, differs across neurons depending on their functional properties both before and after learning. Fano Factor generally decreased after learning the task. Variability was modulated by task events and displayed lowest values during the stimulus presentation. Nonetheless, the decrease in variability after training was present even prior to the presentation of any stimuli, in the fixation period. The greatest decreases were observed comparing populations of neurons that exhibited elevated firing rate during the trial events. Our results offer insights on how properties of the prefrontal network are affected by performance of a cognitive task.     

Posterior parietal cortex: Space--and beyond

How do we decide how to react to a stimulus or event? To do so requires recognition of the stimulus itself as well as an appreciation of the context within which that stimulus is encountered. In this issue of Neuron, Stoet and Snyder report that neurons in the parietal cortex of monkeys can carry contextual information related to the rules that are relevant for solving a visual discrimination task.