Anterior medial prefrontal cortex exhibits activation during task preparation but deactivation during task execution

Background

The anterior prefrontal cortex (PFC) exhibits activation during some cognitive tasks, including episodic memory, reasoning, attention, multitasking, task sets, decision making, mentalizing, and processing of self-referenced information. However, the medial part of anterior PFC is part of the default mode network (DMN), which shows deactivation during various goal-directed cognitive tasks compared to a resting baseline. One possible factor for this pattern is that activity in the anterior medial PFC (MPFC) is affected by dynamic allocation of attentional resources depending on task demands. We investigated this possibility using an event related fMRI with a face working memory task.

Methodology/Principal Findings

Sixteen students participated in a single fMRI session. They were asked to form a task set to remember the faces (Face memory condition) or to ignore them (No face memory condition), then they were given 6 seconds of preparation period before the onset of the face stimuli. During this 6-second period, four single digits were presented one at a time at the center of the display, and participants were asked to add them and to remember the final answer. When participants formed a task set to remember faces, the anterior MPFC exhibited activation during a task preparation period but deactivation during a task execution period within a single trial.

Conclusions/Significance

The results suggest that the anterior MPFC plays a role in task set formation but is not involved in execution of the face working memory task. Therefore, when attentional resources are allocated to other brain regions during task execution, the anterior MPFC shows deactivation. The results suggest that activation and deactivation in the anterior MPFC are affected by dynamic allocation of processing resources across different phases of processing.     

The prefrontal cortex and working memory: physiology and brain imaging

Sustained activity has been recorded in the prefrontal cortex during working memory tasks. First, we compare the anatomical distribution of this activity in humans and monkeys. Then, we show that it reflects many factors, maintenance of the items presented, preparation for the response, transformation of the items during the delay, task rules and task goals. Finally, we point out that sustained activity has also been recorded in other areas, such as the parietal cortex. We suggest that the key to prefrontal cortex lies not in the maintenance of sensory information but in the prospective use of that information for behaviour.     

A model for integrating elementary neural functions into delayed-response behavior

It is well established that various cortical regions can implement a wide array of neural processes, yet the mechanisms which integrate these processes into behavior-producing, brain-scale activity remain elusive. We propose that an important role in this respect might be played by executive structures controlling the traffic of information between the cortical regions involved. To illustrate this hypothesis, we present a neural network model comprising a set of interconnected structures harboring stimulus-related activity (visual representation, working memory, and planning), and a group of executive units with task-related activity patterns that manage the information flowing between them. The resulting dynamics allows the network to perform the dual task of either retaining an image during a delay (delayed-matching to sample task), or recalling from this image another one that has been associated with it during training (delayed-pair association task). The model reproduces behavioral and electrophysiological data gathered on the inferior temporal and prefrontal cortices of primates performing these same tasks. It also makes predictions on how neural activity coding for the recall of the image associated with the sample emerges and becomes prospective during the training phase. The network dynamics proves to be very stable against perturbations, and it exhibits signs of scale-invariant organization and cooperativity. The present network represents a possible neural implementation for active, top-down, prospective memory retrieval in primates. The model suggests that brain activity leading to performance of cognitive tasks might be organized in modular fashion, simple neural functions becoming integrated into more complex behavior by executive structures harbored in prefrontal cortex and/or basal ganglia.     

Right prefrontal activity reflects the ability to overcome sleepiness during working memory tasks: a functional near-infrared spectroscopy study

It has been speculated that humans have an inherent ability to overcome sleepiness that counteracts homeostatic sleep pressure. However, it remains unclear which cortical substrate activities are involved in the ability to overcome sleepiness during the execution of cognitive tasks. Here we sought to confirm that this ability to overcome sleepiness in task execution improves performance on cognitive tasks, showing activation of neural substrates in the frontal cortex, by using a modified n-back (2- and 0-back) working memory task and functional near-infrared spectroscopy. The change in alertness was just correlated with performances on the 2-back task. Activity in the right prefrontal cortex changed depending on alertness changes on the 2- and 0-back tasks independently, which indicates that activity in this region clearly reflects the ability to overcome sleepiness; it may contribute to the function of providing sufficient activity to meet the task load demands. This study reveals characteristics of the ability to overcome sleepiness during the n-back working memory task which goes beyond the attention-control function traditionally proposed.     

Isolation of a central bottleneck of information processing with time-resolved FMRI

When humans attempt to perform two tasks at once, execution of the first task usually leads to postponement of the second one. This task delay is thought to result from a bottleneck occurring at a central, amodal stage of information processing that precludes two response selection or decision-making operations from being concurrently executed. Using time-resolved functional magnetic resonance imaging (fMRI), here we present a neural basis for such dual-task limitations, e.g. the inability of the posterior lateral prefrontal cortex, and possibly the superior medial frontal cortex, to process two decision-making operations at once. These results suggest that a neural network of frontal lobe areas acts as a central bottleneck of information processing that severely limits our ability to multitask.     

Neural correlates of the difference between working memory speed and simple sensorimotor speed: an fMRI study

The difference between the speed of simple cognitive processes and the speed of complex cognitive processes has various psychological correlates. However, the neural correlates of this difference have not yet been investigated. In this study, we focused on working memory (WM) for typical complex cognitive processes. Functional magnetic resonance imaging data were acquired during the performance of an N-back task, which is a measure of WM for typical complex cognitive processes. In our N-back task, task speed and memory load were varied to identify the neural correlates responsible for the difference between the speed of simple cognitive processes (estimated from the 0-back task) and the speed of WM. Our findings showed that this difference was characterized by the increased activation in the right dorsolateral prefrontal cortex (DLPFC) and the increased functional interaction between the right DLPFC and right superior parietal lobe. Furthermore, the local gray matter volume of the right DLPFC was correlated with participants' accuracy during fast WM tasks, which in turn correlated with a psychometric measure of participants' intelligence. Our findings indicate that the right DLPFC and its related network are responsible for the execution of the fast cognitive processes involved in WM. Identified neural bases may underlie the psychometric differences between the speed with which subjects perform simple cognitive tasks and the speed with which subjects perform more complex cognitive tasks, and explain the previous traditional psychological findings.     

Prefrontal Neurons Encode Actions and Outcomes in Conjunction with Spatial Location in Rats Performing a Dynamic Delayed Non-Match to Position Task

To respond adaptively to change organisms must utilize information about recent events and environmental context to select actions that are likely to produce favorable outcomes. We developed a dynamic delayed nonmatching to position task to study the influence of spatial context on event-related activity of medial prefrontal cortex neurons during reinforcement-guided decision-making. We found neurons with responses related to preparation, movement, lever press responses, reinforcement, and memory delays. Combined event-related and video tracking analyses revealed variability in spatial tuning of neurons with similar event-related activity. While all correlated neurons exhibited spatial tuning broadly consistent with relevant task events, for instance reinforcement-related activity concentrated in locations where reinforcement was delivered, some had elevated activity in more specific locations, for instance reinforcement-related activity in one of several locations where reinforcement was delivered. Timing analyses revealed a limited set of distinct response types with activity time-locked to critical behavioral events that represent the temporal organization of dDNMTP trials. Our results suggest that reinforcement-guided decision-making emerges from discrete populations of medial prefrontal neurons that encode information related to planned or ongoing movements and actions and anticipated or actual action-outcomes in conjunction with information about spatial context.     

Dissociating memory retrieval processes using fMRI: evidence that priming does not support recognition memory

We employed event-related fMRI to constrain cognitive accounts of memory retrieval. Studies of explicit retrieval reveal that lateral and medial parietal, dorsal middle frontal gyrus, and anterior prefrontal cortex respond more for studied than new words, reflecting a correlate of "retrieval success." Studies of implicit memory suggest left temporal cortex, ventral and dorsal inferior frontal gyrus respond less for studied than new words, reflecting a correlate of "conceptual priming." In the present study, responses for old and new items were compared during performance on explicit recognition (old/new judgement) and semantic (abstract/concrete judgement) tasks. Regions associated with priming were only modulated during the semantic task, whereas regions associated with retrieval success were modulated during both tasks. These findings constrain functional-anatomic accounts of the networks, suggesting that processes associated with priming do not support explicit recognition judgments.     

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     

Neural correlates of internal-model loading

Skilled object manipulation requires knowledge, or internal models, of object dynamics relating applied force to motion , and our ability to handle myriad objects indicates that the brain maintains multiple models . Recent behavioral studies have shown that once learned, an internal model of an object with novel dynamics can be rapidly recruited and derecruited as the object is grasped and released . We used event-related fMRI to investigate neural activity linked to grasping an object with recently learned dynamics in preparation for moving it after a delay. Subjects also performed two control tasks in which they either moved without the object in hand or applied isometric forces to the object. In all trials, subjects received a cue indicating which task to perform in response to a go signal delivered 5-10 s later. We examined BOLD responses during the interval between the cue and go and assessed the conjunction of the two contrasts formed by comparing the primary task to each control. The analysis revealed significant activity in the ipsilateral cerebellum and the contralateral and supplementary motor areas. We propose that these regions are involved in internal-model recruitment in preparation for movement execution.     

Covariations between pupil diameter and supplementary eye field activity suggest a role in cognitive effort implementation

In both human and nonhuman primates (NHP), the medial prefrontal region, defined as the supplementary eye field (SEF), can indirectly influence behavior selection through modulation of the primary selection process in the oculomotor structures. To perform this oculomotor control, SEF integrates multiple cognitive signals such as attention, memory, reward, and error. As changes in pupil responses can assess these cognitive efforts, a better understanding of the precise dynamics by which pupil diameter and medial prefrontal cortex activity interact requires thorough investigations before, during, and after changes in pupil diameter. We tested whether SEF activity is related to pupil dynamics during a mixed pro/antisaccade oculomotor task in 2 macaque monkeys. We used functional ultrasound (fUS) imaging to examine temporal changes in brain activity at the 0.1-s time scale and 0.1-mm spatial resolution concerning behavioral performance and pupil dynamics. By combining the pupil signals and real-time imaging of NHP during cognitive tasks, we were able to infer localized cerebral blood volume (CBV) responses within a restricted part of the dorsomedial prefrontal cortex, referred to as the SEF, an area in which antisaccade preparation activity is also recorded. Inversely, SEF neurovascular activity measured by fUS imaging was found to be a robust predictor of specific variations in pupil diameter over short and long-time scales. Furthermore, we directly manipulated pupil diameter and CBV in the SEF using reward modulations. These results bring a novel understanding of the physiological links between pupil and SEF, but it also raises questions about the role of anterior cingulate cortex (ACC), as CBV variations in the ACC seems to be negligible compared to CBV variations in the SEF.

Ultrafast functional imaging reveals short- and long-term covariations between pupil diameter and activity in the Supplementary Eye Field (SEF) of awake behaving non-human primates, yielding a novel understanding of the physiological links between the pupil and SEF.     

Dynamics of population code for working memory in the prefrontal cortex

Some neurons (delay cells) in the prefrontal cortex elevate their activities throughout the time period during which the animal is required to remember past events and prepare future behavior, suggesting that working memory is mediated by continuous neural activity. It is unknown, however, how working memory is represented within a population of prefrontal cortical neurons. We recorded from neuronal ensembles in the prefrontal cortex as rats learned a new delayed alternation task. Ensemble activities changed in parallel with behavioral learning so that they increasingly allowed correct decoding of previous and future goal choices. In well-trained rats, considerable decoding was possible based on only a few neurons and after removing continuously active delay cells. These results show that neural activity in the prefrontal cortex changes dynamically during new task learning so that working memory is robustly represented and that working memory can be mediated by sequential activation of different neural populations.     

Cognitive Control in Auditory Working Memory Is Enhanced in Musicians

Musical competence may confer cognitive advantages that extend beyond processing of familiar musical sounds. Behavioural evidence indicates a general enhancement of both working memory and attention in musicians. It is possible that musicians, due to their training, are better able to maintain focus on task-relevant stimuli, a skill which is crucial to working memory. We measured the blood oxygenation-level dependent (BOLD) activation signal in musicians and non-musicians during working memory of musical sounds to determine the relation among performance, musical competence and generally enhanced cognition. All participants easily distinguished the stimuli. We tested the hypothesis that musicians nonetheless would perform better, and that differential brain activity would mainly be present in cortical areas involved in cognitive control such as the lateral prefrontal cortex. The musicians performed better as reflected in reaction times and error rates. Musicians also had larger BOLD responses than non-musicians in neuronal networks that sustain attention and cognitive control, including regions of the lateral prefrontal cortex, lateral parietal cortex, insula, and putamen in the right hemisphere, and bilaterally in the posterior dorsal prefrontal cortex and anterior cingulate gyrus. The relationship between the task performance and the magnitude of the BOLD response was more positive in musicians than in non-musicians, particularly during the most difficult working memory task. The results confirm previous findings that neural activity increases during enhanced working memory performance. The results also suggest that superior working memory task performance in musicians rely on an enhanced ability to exert sustained cognitive control. This cognitive benefit in musicians may be a consequence of focused musical training.     

Specialization in the left prefrontal cortex for sentence comprehension

Using functional magnetic resonance imaging (fMRI), we examined cortical activation under syntactic decision tasks and a short-term memory task for sentences, focusing on essential properties of syntactic processing. By comparing activation in these tasks with a short-term memory task for word lists, we found that two regions in the left prefrontal cortex showed selective activation for syntactic processing: the dorsal prefrontal cortex (DPFC) and the inferior frontal gyrus (IFG). Moreover, the left DPFC showed more prominent activation under the short-term memory task for sentences than that for word lists, which cannot be explained by general cognitive factors such as task difficulty and verbal short-term memory. These results support the proposal of specialized systems for sentence comprehension in the left prefrontal cortex.     

Time Course of Functional Connectivity in Primate Dorsolateral Prefrontal and Posterior Parietal Cortex during Working Memory

The dorsolateral prefrontal and posterior parietal cortex play critical roles in mediating attention, working memory, and executive function. Despite proposed dynamic modulation of connectivity strength within each area according to task demands, scant empirical data exist about the time course of the strength of effective connectivity, particularly in tasks requiring information to be sustained in working memory. We investigated this question by performing time-resolved cross-correlation analysis for pairs of neurons recorded simultaneously at distances of 0.2–1.5 mm apart of each other while monkeys were engaged in working memory tasks. The strength of effective connectivity determined in this manner was higher throughout the trial in the posterior parietal cortex than the dorsolateral prefrontal cortex. Significantly higher levels of parietal effective connectivity were observed specifically during the delay period of the task. These differences could not be accounted for by differences in firing rate, or electrode distance in the samples recorded in the posterior parietal and prefrontal cortex. Differences were present when we restricted our analysis to only neurons with significant delay period activity and overlapping receptive fields. Our results indicate that dynamic changes in connectivity strength are present but area-specific intrinsic organization is the predominant factor that determines the strength of connections between neurons in each of the two areas.     

The planning of action: can one separate attention from intention?

Attention and motor preparation are two intimately linked processes. However, they can be dissociated in the laboratory in order to study their neuronal basis. Behavioral neurophysiology has thus shown that neurons that discharge in relation with attention or with motor preparation (or intention) exist in a variety of brain regions in the monkey, especially the prefrontal and premotor cortices. When examined more carefully, these two regions appear different in both the proportion of cells that respond during attention versus intention, and in the information coded in the so-called "preparatory activity". This activity reflects sensory selection in the prefrontal cortex (spatial attention/memory), motor selection in the premotor cortex. Furthermore, two regions in the dorsal aspect of premotor cortex can be distinguished on the basis of their relative involvement in attention: a rostral (anterior) region, functionally close to prefrontal cortex, and a caudal one, which appears functionally close to motor cortex. Using an experimental design derived from monkey experiments, a functional magnetic resonance imaging (fMRI) study recently indicated that the functional specialization within the premotor cortex is similar in monkey and man.     

Medial prefrontal and subcortical mechanisms underlying the acquisition of motor and cognitive action sequences in humans

The anterior medial prefrontal cortex (AMPC) in humans is involved in affect and in regulating goal-directed behaviors. The precise function of the AMPC, however, is poorly understood. Using magnetic resonance imaging, we found that bilateral regions in the AMPC were selectively recruited to compute the reliability of subjects' expectations that developed when subjects were learning sequences of cognitive tasks. In contrast, regions similarly recruited in learning sequences of motor acts were found in the ventral striatum. Our results show that beyond the execution of motor acts, the AMPC is selectively engaged in computing the relevance of cognitive goals that subjects intend to achieve. This indicates that the fronto-striatal circuit, including the ventral striatum and AMPC, subserves hierarchically distinct evaluative processes mediating the human ability to build behavioral plans, ranging from motor to cognitive action plans.     

Working Memory Cells' Behavior May Be Explained by Cross-Regional Networks with Synaptic Facilitation

Neurons in the cortex exhibit a number of patterns that correlate with working memory. Specifically, averaged across trials of working memory tasks, neurons exhibit different firing rate patterns during the delay of those tasks. These patterns include: 1) persistent fixed-frequency elevated rates above baseline, 2) elevated rates that decay throughout the tasks memory period, 3) rates that accelerate throughout the delay, and 4) patterns of inhibited firing (below baseline) analogous to each of the preceding excitatory patterns. Persistent elevated rate patterns are believed to be the neural correlate of working memory retention and preparation for execution of behavioral/motor responses as required in working memory tasks. Models have proposed that such activity corresponds to stable attractors in cortical neural networks with fixed synaptic weights. However, the variability in patterned behavior and the firing statistics of real neurons across the entire range of those behaviors across and within trials of working memory tasks are typical not reproduced. Here we examine the effect of dynamic synapses and network architectures with multiple cortical areas on the states and dynamics of working memory networks. The analysis indicates that the multiple pattern types exhibited by cells in working memory networks are inherent in networks with dynamic synapses, and that the variability and firing statistics in such networks with distributed architectures agree with that observed in the cortex.     

Dynamic visuomotor transformation involved with remote flying of a plane utilizes the 'Mirror Neuron' system

Brain regions involved with processing dynamic visuomotor representational transformation are investigated using fMRI. The perceptual-motor task involved flying (or observing) a plane through a simulated Red Bull Air Race course in first person and third person chase perspective. The third person perspective is akin to remote operation of a vehicle. The ability for humans to remotely operate vehicles likely has its roots in neural processes related to imitation in which visuomotor transformation is necessary to interpret the action goals in an egocentric manner suitable for execution. In this experiment for 3(rd) person perspective the visuomotor transformation is dynamically changing in accordance to the orientation of the plane. It was predicted that 3(rd) person remote flying, over 1(st), would utilize brain regions composing the 'Mirror Neuron' system that is thought to be intimately involved with imitation for both execution and observation tasks. Consistent with this prediction differential brain activity was present for 3(rd) person over 1(st) person perspectives for both execution and observation tasks in left ventral premotor cortex, right dorsal premotor cortex, and inferior parietal lobule bilaterally (Mirror Neuron System) (Behaviorally: 1(st)>3(rd)). These regions additionally showed greater activity for flying (execution) over watching (observation) conditions. Even though visual and motor aspects of the tasks were controlled for, differential activity was also found in brain regions involved with tool use, motion perception, and body perspective including left cerebellum, temporo-occipital regions, lateral occipital cortex, medial temporal region, and extrastriate body area. This experiment successfully demonstrates that a complex perceptual motor real-world task can be utilized to investigate visuomotor processing. This approach (Aviation Cerebral Experimental Sciences ACES) focusing on direct application to lab and field is in contrast to standard methodology in which tasks and conditions are reduced to their simplest forms that are remote from daily life experience.     

Parietal and hippocampal contribution to topokinetic and topographic memory.

This paper reviews the involvement of the parietal cortex and the hippocampus in three kinds of spatial memory tasks which all require a memory of a previously experienced movement in space. The first task compared, by means of positron emission tomography (PET) scan techniques, the production, in darkness, of self-paced saccades (SAC) with the reproduction, in darkness, of a previously learned sequence of saccades to visual targets (SEQ). The results show that a bilateral increase of activity was seen in the depth of the intraparietal sulcus and the medial superior parietal cortex (superior parietal gyrus and precuneus) together with the frontal sulcus but only in the SEQ task, which involved memory of the previously seen targets and possibly also motor memory. The second task is the vestibular memory contingent task, which requires that the subject makes, in darkness, a saccade to the remembered position of a visual target after a passively imposed whole-body rotation. Deficits in this task, which involves vestibular memory, were found predominantly in patients with focal vascular lesions in the parieto-insular (vestibular) cortex, the supplementary motor area-supplementary eye field area, and the prefrontal cortex. The third task requires mental navigation from the memory of a previously learned route in a real environment (the city of Orsay in France). A PET scan study has revealed that when subjects were asked to remember visual landmarks there was a bilateral activation of the middle hippocampal regions, left inferior temporal gyrus, left hippocampal regions, precentral gyrus and posterior cingulate gyrus. If the subjects were asked to remember the route, and their movements along this route, bilateral activation of the dorsolateral cortex, posterior hippocampal areas, posterior cingulate gyrus, supplementary motor areas, right middle hippocampal areas, left precuneus, middle occipital gyrus, fusiform gyrus and lateral premotor area was found. Subtraction between the two conditions reduced the activated areas to the left hippocampus, precuneus and insula. These data suggest that the hippocampus and parietal cortex are both involved in the dynamic aspects of spatial memory, for which the name ''topokinetic memory'' is proposed. These dynamic aspects could both overlap and be different from those involved in the cartographic and static aspects of ''topographic'' memory.