The cognitive neuroscience of visual working memory

Visual working memory allows us to temporarily maintain and manipulate visual information in order to solve a task. The study of the brain mechanisms underlying this function began more than half a century ago, with Scoville and Milner’s (1957) seminal discoveries with amnesic patients. This timely collection of papers brings together diverse perspectives on the cognitive neuroscience of visual working memory from multiple fields that have traditionally been fairly disjointed: human neuroimaging, electrophysiological, behavioural and animal lesion studies, investigating both the developing and the adult brain

The medial prefrontal cortex and the dorsomedial striatum are necessary for working memory in rats: role of NMDA receptors

Working memory is a form of short-term memory involved in the storage (maintenance) of information over time and reorganization (manipulation) of a memory set necessary for complex cognition. The human frontal cortex and striatum are involved with working memory; however, the mechanisms through which these structures contribute to working memory are incompletely understood. Given the similarities between cortical and striatal areas in the human and rodent brain, I used rats to elucidate the contrbutions of N-methyl-D-aspartate (NMDA) receptors in medial prefrontal cortex (mPFC) and dorsomedial striatum (dmSTR) using two working memory tasks. The trial unique non-match to location (TUNL) task is a delayed-non-match-to-sample visual working memory task performed in touchscreen equipped operant conditioning chambers. TUNL enables the concurrent assessment of delay-dependent and “pattern separation” effects that were not possible with previous delayed-non-match-to-sample-tasks. The odour span task (OST) measures working memory capacity using an incremental delayed-non-match-to-sample paradigm that involves the addition of stimuli (scented bowls) after each correct response. Results obtained following systemic treatment of rats with a broad spectrum NMDA receptor antagonist showed that NMDA receptors contribute to performance of both tasks. Given the contribution of cortical GluN2B-containing NMDA receptors to working memory in primates, we tested the role of these receptors in the TUNL task and OST. Systemic injections of the GluN2B-containing NMDA receptor antagonist Ro 25-6981 impaired OST but not TUNL accuracy. Additional experiments with intracranial infusions showed NMDA receptors in mPFC or dmSTR contribute to TUNL task accuracy. Ro 25-6981 infusions into dmSTR, but not mPFC impaired OST. These experiments contribute to our understanding of the role NMDA receptors perform in mPFC and dmSTR in working memory

장소와 그 가치를 저장하는 배측과 중간 해마의 차별적 역할

학위논문(박사) -- 서울대학교대학원 : 자연과학대학 뇌인지과학과, 2021.8. 강민수.오래전부터 해마는 자신의 경험, 즉 일화 사건의 기억에 필수적인 영역으로 알려져왔습니다. 이러한 일화 사건에는 특정 장소에서 겪은 감정적 경험들이 기억으로 저장됩니다. 이러한 일화 기억의 특성을 고려하면, 해마는 감정 정보를 처리할 가능성이 매우 높고, 실제로 중간 해마와 복측 해마는 편도체로부터 해부학적으로 직접 연결되어 있습니다. 또한 중간 해마는 배측 해마로부터 많은 공간 정보를 받아드린다고 알려져있습니다. 따라서 중간 해마는 장소의 위치와 그 장소에서 경험한 감정정보를 연합할 가능성이 높습니다. 하지만, 중간 해마의 이러한 장소-감정 연합 기억의 역할은 거의 알려지지 않았다. 그래서, 저는 중간 해매가 특정 공간에서 발생하는 사건의 가치를 저장하는데 중요하고, 배측 해마는 정확한 위치 정보를 표상하는데 중요하다는 가설을 세웠습니다. 이를 검증하기 위해 쥐의 배측과 중간 해마의 개별 뉴런을 동시에 리코딩하였으며, 선호도가 다른 먹이를 이용해 장소의 가치 정보를 변화시키는 실험을 진행했습니다. 이 학위 논문의 첫 파트에서는 쥐가 2차원 공간에서 자유롭게 돌아다닐 때의 배측부터 복측해마의 장소 세포가 어떻게 달라지는지 살펴보았습니다. 구체적으로, 중간해마보다 배측 해마에서 장소 선택적 활동이 더 강하게 나타났으며, 복측 해마에서는 장소 세포의 활동이 거의 관찰되지 않았습니다. 두번째 파트에서, 해마가 필요없는 간단한 과제에서 먹이의 가치가 바뀐 이후에, 배측과 복측 해마의 장소 세포의 공간 표상 변화를 살펴보았습니다. 주어진 공간에서 제공되던 맛있는 먹이가 맛없는 먹이로 바뀌고 나면, 중간 해마의 장소세포는 재빠르게 공간 표상을 재배열하게 됩니다. 하지만, 동일한 조작에서 배측 해마의 장소세포는 공간 표상을 일정하게 유지하였습니다. 마지막으로, 세번째 파트에서는 해마가 필요한 기억 과제에서 가치-의존적 공간 재배열을 추가적으로 알아보았습니다. T 모양의 미로에서 장소 선호 과제를 진행하는 동안, 중간 해마의 장소 세포는 맛있는 먹이가 나오는 공간을 집중적으로 표상하며, 이러한 집중된 표상은 맛있는 먹이의 위치가 바뀌어도 동일하게 관찰됩니다. 반면, 배측 해마 장소 세포의 공간 표상은 이러한 조작에 거의 영향을 받지 않습니다. 그리고 이 장소 선호 학습을 하는 동안, 배측 해마보다 중간 해마의 신경망 상태가 빠르게 변하는 모습을 보였습니다. 종합하자면, 위 결과들은 배측 해마와 복측 해마는 서로 다른 기능을 맡고 있다는 점을 보여줍니다. 즉, 배측 해마는 동물의 정확한 장소를 표상하는데 특화되어 있으며, 중간 해마는 장소와 그 가치 정보를 연합하는 역할을 맡고 있습니다. 이러한 발견은 중간 해마가 행동 선택과 밀접한 정보를 처리하며, 이러한 정보를 내측 전두엽을 통해 다른 뇌 영역과 소통하는 기능적으로 중요한 영역이라는 것을 시사합니다.It has long been postulated that the hippocampus is vital for memorizing autobiographical episodic events. Because an episodic event often entails memories for certain places associated with their emotional and motivational significance, it is promising that the hippocampus processes spatial information in conjunction with its associated valence. Among the hippocampal subregions (i.e., dorsal, intermediate, and ventral), the amygdala, which plays key roles in processing valence information, sends direct axonal projection to the intermediate and ventral hippocampus. Also, there are extensive recurrent collaterals and associational projections (presumably spatial information) from the dorsal hippocampus to the intermediate hippocampus. Thus, the intermediate hippocampus may integrate emotional/motivational information in association with locational information. However, it is largely unknown that how the intermediate hippocampus process value-associated spatial information processing. Therefore, I hypothesized that encoding the value of an event at a specific location takes priority in the intermediate hippocampus, compared to the dorsal hippocampus, whose priority resides in representing the precise location of an animal, presumably in the cognitive map. To test this hypothesis, I simultaneously recorded single units from the dorsal and intermediate hippocampus while rats performed a battery of tasks in which the level of motivational significance of a place was controlled by foods with different palatability. In this dissertation of Chapter 1, I examined the changes in spatial firing patterns along the dorsoventral axis while rats foraged in an open field maze. Specifically, spatially selective firing was more eminent in the dorsal than in the intermediate hippocampus, and spatial signals were hardly observed in the ventral hippocampus. In Chapter 2, after changes in reward value during non-mnemonic tasks, differential global remappings of place cells were found between the dorsal and intermediate hippocampus. When more-palatable reward (i.e., sunflower seeds) were replaced with less-palatable one (Cheerios) in a given location, place cells in the intermediate hippocampus remapped immediately. In contrast, place fields recorded from the dorsal hippocampus maintained their spatial representations stably in the same manipulation. In Chapter 3, value-dependent remappings were further investigated in hippocampal-dependent tasks. During the place-preference task in the T-maze, place fields obtained from the intermediate hippocampus accumulated near the arm associated with more-preferred rewards, and overrepresented patterns shifted toward opposite arm after the locations of more-preferred and less-preferred rewards were reversed. However, spatial representations of place cells in the dorsal hippocampus were rarely affected by such manipulation. And, during the acquisition of the place-preference task, the ensemble network state in the iHP changed faster than that in the dHP. Taken together, our results suggest that there are functional segregations between the dorsal and intermediate subregions of the hippocampus. That is, the dorsal hippocampus is specialized in representing the animal's precise locations in the environment, whereas the intermediate hippocampus takes part in the integration of spatial information and its motivational values. These findings imply that the intermediate hippocampus is a functionally significant hippocampal subregion through which critical action-related information (i.e., spatial information from the dorsal hippocampus and emotional/motivational information from the amygdala) is integrated and communicated to the rest of the brain via the medial prefrontal cortex.BACKGROUND AND HYPOTHESIS. 1 1.1 BACKGROUND 1 1.1.1 Episodic memory and hippocampus. 2 1.1.2 Introduction of the rodent hippocampal researches. 2 1.1.3 Single-cell recording from the rodent hippocampus 4 1.1.3.1 Basic firing properties of place cells 4 1.1.3.2 Spatial representation of place cells. 5 1.1.3.3 Non-spatial representation of place cells 6 1.1.3.4 Value representation in the hippocampus. 6 1.1.4 Difference in anatomical connectivities along the dorsoventral axis. 7 1.1.5 Difference in functions along the dorsoventral axis. 10 1.2 HYPOTHESIS 12 CHAPTER 1. 13 2.1 Introduction. 14 2.2 Methods. 15 2.2.1 Subjects. 15 2.2.2 Maze familiarization and pre-training 15 2.2.3 Surgical implantation of the hyperdrive. 15 2.2.4 Electrophysiological recording procedures 16 2.2.5 Histological verification of tetrode tracks 16 2.2.6 Unit isolation 16 2.2.7 Basic firing properties 17 2.2.8 Definition of place fields 17 2.2.9 Theta-modulation and burst index 18 2.3 Results. 19 2.3.1 Anatomical boundary between dorsal, intermediate and ventral hippocampus. 19 2.3.2 Comparison of basic firing properties between hippocampal subregions 20 2.3.3 Degree of spatially selective firing patterns sharply decreased at the border between dHP and iHP. 23 2.4 Discussion. 28 CHAPTER 2. 30 3.1 Introduction. 31 3.2 Methods. 32 3.2.1 Behavior paradigm. 32 3.2.1.1 Food preference test. 32 3.2.1.2 Spatial alternation task. 33 3.2.2 Post-surgical training and main recording 33 3.2.3 Constructing the population rate map. 34 3.2.4 Categorization of place field responses 34 3.2.5 Reward-type coding analysis. 34 3.2.6 Speed-correlated cells. 35 3.3 Results. 35 3.3.1 Rat's food preference for sunflower seeds and Froot Loops over Cheerios. 35 3.3.2 Place cells in iHP, but not dHP, encode changes in motivational values of place via global remapping. 36 3.3.3 Identity of reward type is coded in the iHP by rate remapping, but not in the dHP. 49 3.3.4 Neural activity of single cells of vHP in response to motivational value changes. 51 3.4.5 Immediate coding of the changes in motivational values in iHP, but not in dHP. 53 3.4 Discussion 60 CHAPTER 3. 64 4.1 Introduction 65 4.2 Methods 65 4.2.1 Behavior paradigm. 65 4.2.2 Principal component analysis for neural ensemble state 66 4.2.3 Synchronization of spiking activity. 67 4.3 Results. 68 4.3.1 Overrepresentation of the motivationally significant place by the place cells in iHP, but not in dHP 68 4.2.2 Rapid changes of the ensemble network changes in iHP, compared to those in dHP. 77 4.2.3 Place cells in the dHP and iHP co-fire more strongly during a mnemonic task than non-mnemonic tasks. 79 4.4 Discussion 82 GENERAL DISCUSSION. 87 5.1 Conclusion 88 5.2 Limitation 88 5.3 Implication and perspective. 89 5.4 Future research direction. 93 BIBLIOGRAPHY 94 ACKNOWLEDGMENT 111 국문초록 112박

Mismatch responses: Probing probabilistic inference in the brain

Sensory signals are governed by statistical regularities and carry valuable information about the unfolding of environmental events. The brain is thought to capitalize on the probabilistic nature of sequential inputs to infer on the underlying (hidden) dynamics driving sensory stimulation. Mis-match responses (MMRs) such as the mismatch negativity (MMN) and the P3 constitute prominent neuronal signatures which are increasingly interpreted as reflecting a mismatch between the current sensory input and the brain’s generative model of incoming stimuli. As such, MMRs might be viewed as signatures of probabilistic inference in the brain and their response dynamics can provide insights into the underlying computational principles. However, given the dominance of the auditory modality in MMR research, the specifics of brain responses to probabilistic sequences across sensory modalities and especially in the somatosensory domain are not well characterized. The work presented here investigates MMRs across the auditory, visual and somatosensory modality by means of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). We designed probabilistic stimulus sequences to elicit and characterize MMRs and employed computational modeling of response dynamics to inspect different aspects of the brain’s generative model of the sensory environment. In the first study, we used a volatile roving stimulus paradigm to elicit somatosensory MMRs and performed single-trial modeling of EEG signals in sensor and source space. Model comparison suggested that responses reflect Bayesian inference based on the estimation of transition probability and limited information integration of the recent past in order to adapt to a changing environment. The results indicated that somatosensory MMRs reflect an initial mismatch between sensory input and model beliefs represented by confidence-corrected surprise (CS) followed by model adjustment dynamics represented by Bayesian surprise (BS). For the second and third study we designed a tri-modal roving stimulus paradigm to delineate modality specific and modality general features of mismatch processing. Computational modeling of EEG signals in study 2 suggested that single-trial dynamics reflect Bayesian inference based on estimation of uni-modal transition probabilities as well as cross-modal conditional dependencies. While early mismatch processing around the MMN tended to reflect CS, later MMRs around the P3 rather reflect BS, in correspondence to the somatosensory study. Finally, the fMRI results of study 3 showed that MMRs are generated by an interaction of modality specific regions in higher order sensory cortices and a modality general fronto-parietal network. Inferior parietal regions in particular were sensitive to expectation violations with respect to the cross-modal contingencies in the stimulus sequences. Overall, our results indicate that MMRs across the senses reflect processes of probabilistic inference in a complex and inherently multi-modal environment.Sensorische Signale sind durch statistische Regularitäten bestimmt und beinhalten wertvolle Informationen über die Entwicklung von Umweltereignissen. Es wird angenommen, dass das Gehirn die Wahrscheinlichkeitseigenschaften sequenzieller Reize nutzt um auf die zugrundeliegenden (verborgenen) Dynamiken zu schließen, welche sensorische Stimulation verursachen. Diskrepanz-Reaktionen ("Mismatch responses"; MMRs) wie die "mismatch negativity" (MMN) und die P3 sind bekannte neuronale Signaturen die vermehrt als Signale einer Diskrepanz zwischen der momentanen sensorischen Einspeisung und dem generativen Modell, welches das Gehirn von den eingehenden Reizen erstellt angesehen werden. Als solche können MMRs als Signaturen von wahrscheinlichkeitsbasierter Inferenz im Gehirn betrachtet werden und ihre Reaktionsdynamiken können Einblicke in die zugrundeliegenden komputationalen Prinzipien geben. Angesichts der Dominanz der auditorischen Modalität in der MMR-Forschung, sind allerdings die spezifischen Eigenschaften von Hirn-Reaktionen auf Wahrscheinlichkeitssequenzen über sensorische Modalitäten hinweg und vor allem in der somatosensorischen Modalität nicht gut charakterisiert. Die hier vorgestellte Arbeit untersucht MMRs über die auditorische, visuelle und somatosensorische Modalität hinweg anhand von Elektroenzephalographie (EEG) und funktioneller Magnetresonanztomographie (fMRT). Wir gestalteten wahrscheinlichkeitsbasierte Reizsequenzen, um MMRs auszulösen und zu charakterisieren und verwendeten komputationale Modellierung der Reaktionsdynamiken, um verschiedene Aspekte des generativen Modells des Gehirns von der sensorischen Umwelt zu untersuchen. In der ersten Studie verwendeten wir ein volatiles "Roving-Stimulus"-Paradigma, um somatosensorische MMRs auszulösen und modellierten die Einzel-Proben der EEG-Signale im sensorischen und Quell-Raum. Modellvergleiche legten nahe, dass die Reaktionen Bayes’sche Inferenz abbilden, basierend auf der Schätzung von Transitionswahrscheinlichkeiten und limitierter Integration von Information der jüngsten Vergangenheit, welche eine Anpassung an Umweltänderungen ermöglicht. Die Ergebnisse legen nahe, dass somatosen-sorische MMRs eine initiale Diskrepanz zwischen sensorischer Einspeisung und Modellüberzeugung reflektieren welche durch "confidence-corrected surprise" (CS) repräsentiert ist, gefolgt von Modelanpassungsdynamiken repräsentiert von "Bayesian surprise" (BS). Für die zweite und dritte Studie haben wir ein Tri-Modales "Roving-Stimulus"-Paradigma gestaltet, um modalitätsspezifische und modalitätsübergreifende Eigenschaften von Diskrepanzprozessierung zu umreißen. Komputationale Modellierung von EEG-Signalen in Studie 2 legte nahe, dass Einzel-Proben Dynamiken Bayes’sche Inferenz abbilden, basierend auf der Schätzung von unimodalen Transitionswahrscheinlichkeiten sowie modalitätsübergreifenden bedingten Abhängigkeiten. Während frühe Diskrepanzprozessierung um die MMN dazu tendierten CS zu reflektieren, so reflektierten spätere MMRs um die P3 eher BS, in Übereinstimmung mit der somatosensorischen Studie. Abschließend zeigten die fMRT-Ergebnisse der Studie 3 dass MMRs durch eine Interaktion von modalitätsspezifischen Regionen in sensorischen Kortizes höherer Ordnung mit einem modalitätsübergreifenden fronto-parietalen Netzwerk generiert werden. Inferior parietale Regionen im Speziellen waren sensitiv gegenüber Erwartungsverstoß in Bezug auf die modalitätsübergreifenden Wahrscheinlichkeiten in den Reizsequenzen. Insgesamt weisen unsere Ergebnisse darauf hin, dass MMRs über die Sinne hinweg Prozesse von wahrscheinlichkeitsbasierter Inferenz in einer komplexen und inhärent multi-modalen Umwelt darstellen

Mechanisms of visual feature binding

Visual feature binding is the method by which coherent objects and scenes are perceived. Advances in the science of perception have indicated that visual features such as colour, motion, and orientation are to some extent, processed separately in primate early visual cortex. However, the mechanism by which these features are integrated remains unclear. Phenomenologically, the process of binding features to form objects appears to be an efficient and automatic process. Some research also shows a high temporal resolution for binding features together, in addition to populations of neurons that jointly code for features. However, dominant theories of feature binding and the majority of the binding literature indicate that the feature binding process is severely limited by a relatively low temporal resolution, especially when compared to other perceptual properties such as feature detection. To identify and resolve the discrepancy in the feature binding literature, I investigate the feature binding process and its inter-relationship with perceptual surface segregation. Surface segregation has been postulated as the method by which features can be rapidly bound together, giving them impression of a high temporal resolution. In Chapter 2, displays are used that alternate between two arrays of differently coloured, oppositely moving dots. The alternation frequency is modified in order to gauge the temporal resolution of binding. This is combined with surface segregation cues such as coherent motion, consistency of dot configuration, and colour. In Chapter 3, coloured, oriented gratings are used to investigate colour-orientation binding. Angular separation, spatial and temporal coincidence, and stimulus presentation duration are varied. Across these experiments, a number of these surface segregation cues are manipulated in order to measure the corresponding effects on feature binding, perceptual interpretation of the stimulus, and its neural representation. The results of the psychophysical experiments indicate that feature binding, surface segregation, and temporal integration are inextricably linked. These findings are reinforced by data gathered through functional magnetic resonance imaging (fMRI) of human subjects. Both surface segregation and feature pairs were found to modulate neural activity in early visual cortex, providing evidence that similar neural substrates are recruited for both feature binding and surface segregation. Overall, the two complementary sets of experiments using stimulus conjunctions of colour-motion and colour-orientation stimuli provide converging evidence and insight into the dynamics of the underlying binding mechanisms. A discussion of the implications of the research follows, concluding that rapidly formed surface representations can be maintained across presentation intervals by temporal integration. Attentional selection of one feature (e.g. orientation) can then be used to boost the response to the paired feature (colour) in order to identify and extract the correct feature pairing. Based on the known properties of the visual system, several potential neural mechanisms are proposed that are consistent with both the psychophysical and neural data, in addition to suggested future directions for the study of visual feature binding

Characterizing the Cortical Contributions to Working Memory-Guided Obstacle Locomotion

While walking in complex environments, the ability to acquire information about objects in our surroundings is essential for successful obstacle negotiation. Furthermore, the ease with which most animals can traverse cluttered terrain while grazing, exploring, or hunting is facilitated by the capacity to store obstacle information in working memory (WM). However, the underlying neural substrates supporting such complex behaviours are poorly understood. Therefore, the goal of this thesis is to examine the neural underpinnings of WM-guided obstacle negotiation in the walking cat. Obstacle locomotion was studied in two main paradigms, characterized by whether obstacle presence was detected via vision or touch. In both paradigms, walking was delayed following foreleg obstacle clearance. When walking resumed, elevated hindleg stepping demonstrated that animals successfully remembered the obstacle beneath them. The tactile paradigm was first examined to assess the ability of animals to remember an unexpected obstacle over which the forelegs had tripped. Such tactile input to the forelegs was capable of producing a robust, long-lasting WM of the obstacle, similar to what has been previously described using the visual paradigm. Next, to assess whether regions of the brain associated with spatial representation and movement planning contribute to these behaviours, parietal area 5 was reversibly deactivated as visual or tactile obstacle WM was tested. Such deactivations resulted in substantial WM deficits precluding successful avoidance in both paradigms. To further characterize this cortical contribution, neural activity was then recorded with multi-electrode arrays implanted in area 5. While diverse patterns of task-related modulation were observed, only a small proportion of neurons demonstrated WM-related activity. These neurons exhibited the hallmark property of sustained delay period activity associated with WM maintenance, and were able to reliably discern whether or not the animal had stepped over an obstacle prior to the delay. Therefore, only a specialized subset of area 5 neurons is capable of maintaining stable representations of obstacle information in WM. Altogether, this work extends our understanding of WM-guided obstacle locomotion in the cat. Additionally, these findings provide insight into the neural circuitry within the posterior parietal cortex, which likely supports a variety of WM-guided behaviours

Decision Making: The Neuroethological Turn

Neuroeconomics applies models from economics and psychology to inform neurobiological studies of choice. This approach has revealed neural signatures of concepts like value, risk, and ambiguity, which are known to influence decision making. Such observations have led theorists to hypothesize a single, unified decision process that mediates choice behavior via a common neural currency for outcomes like food, money, or social praise. In parallel, recent neuroethological studies of decision making have focused on natural behaviors like foraging, mate choice, and social interactions. These decisions strongly impact evolutionary fitness and thus are likely to have played a key role in shaping the neural circuits that mediate decision making. This approach has revealed a suite of computational motifs that appear to be shared across a wide variety of organisms. We argue that the existence of deep homologies in the neural circuits mediating choice may have profound implications for understanding human decision making in health and disease

Generalisation of prior information for rapid Bayesian time estimation

To enable effective interaction with the environment, the brain combines noisy sensory information with expectations based on prior experience. There is ample evidence showing that humans can learn statistical regularities in sensory input and exploit this knowledge to improve perceptual decisions and actions. However, fundamental questions remain regarding how priors are learned and how they generalise to different sensory and behavioural contexts. In principle, maintaining a large set of highly specific priors may be inefficient and restrict the speed at which expectations can be formed and updated in response to changes in the environment. On the other hand, priors formed by generalising across varying contexts may not be accurate. Here we exploit rapidly induced contextual biases in duration reproduction to reveal how these competing demands are resolved during the early stages of prior acquisition. We show that observers initially form a single prior by generalising across duration distributions coupled with distinct sensory signals. In contrast, they form multiple priors if distributions are coupled with distinct motor outputs. Together, our findings suggest that rapid prior acquisition is facilitated by generalisation across experiences of different sensory inputs, but organised according to how that sensory information is acted upon

Working memory in the prefrontal cortex

The prefrontal cortex participates in a variety of higher cognitive functions. The concept of working memory is now widely used to understand prefrontal functions. Neurophysiological studies have revealed that stimulus-selective delay-period activity is a neural correlate of the mechanism for temporarily maintaining information in working memory processes. The central executive, which is the master component of Baddeley’s working memory model and is thought to be a function of the prefrontal cortex, controls the performance of other components by allocating a limited capacity of memory resource to each component based on its demand. Recent neurophysiological studies have attempted to reveal how prefrontal neurons achieve the functions of the central executive. For example, the neural mechanisms of memory control have been examined using the interference effect in a dual-task paradigm. It has been shown that this interference effect is caused by the competitive and overloaded recruitment of overlapping neural populations in the prefrontal cortex by two concurrent tasks and that the information-processing capacity of a single neuron is limited to a fixed level, can be flexibly allocated or reallocated between two concurrent tasks based on their needs, and enhances behavioral performance when its allocation to one task is increased. Further, a metamemory task requiring spatial information has been used to understand the neural mechanism for monitoring its own operations, and it has been shown that monitoring the quality of spatial information represented by prefrontal activity is an important factor in the subject's choice and that the strength of spatially selective delay-period activity reflects confidence in decision-making. Although further studies are needed to elucidate how the prefrontal cortex controls memory resource and supervises other systems, some important mechanisms related to the central executive have been identified