The spectro-contextual encoding and retrieval theory of episodic memory.

The spectral fingerprint hypothesis, which posits that different frequencies of oscillations underlie different cognitive operations, provides one account for how interactions between brain regions support perceptual and attentive processes (Siegel etal., 2012). Here, we explore and extend this idea to the domain of human episodic memory encoding and retrieval. Incorporating findings from the synaptic to cognitive levels of organization, we argue that spectrally precise cross-frequency coupling and phase-synchronization promote the formation of hippocampal-neocortical cell assemblies that form the basis for episodic memory. We suggest that both cell assembly firing patterns as well as the global pattern of brain oscillatory activity within hippocampal-neocortical networks represents the contents of a particular memory. Drawing upon the ideas of context reinstatement and multiple trace theory, we argue that memory retrieval is driven by internal and/or external factors which recreate these frequency-specific oscillatory patterns which occur during episodic encoding. These ideas are synthesized into a novel model of episodic memory (the spectro-contextual encoding and retrieval theory, or "SCERT") that provides several testable predictions for future research

Awake Reactivation of Prior Experiences Consolidates Memories and Biases Cognition.

After experiences are encoded into memory, post-encoding reactivation mechanisms have been proposed to mediate long-term memory stabilization and transformation. Spontaneous reactivation of hippocampal representations, together with hippocampal-cortical interactions, are leading candidate mechanisms for promoting systems-level memory strengthening and reorganization. While the replay of spatial representations has been extensively studied in rodents, here we review recent fMRI work that provides evidence for spontaneous reactivation of nonspatial, episodic event representations in the human hippocampus and cortex, as well as for experience-dependent alterations in systems-level hippocampal connectivity. We focus on reactivation during awake post-encoding periods, relationships between reactivation and subsequent behavior, how reactivation is modulated by factors that influence consolidation, and the implications of persistent reactivation for biasing ongoing perception and cognition

Neural Mechanisms of Episodic Memory formation

In order to remember what you had for breakfast today, you must rely on episodic memory, the memory for personal events situated within a spatiotemporal context. In this dissertation, I use electroencephalographic (EEG) recordings to measure the neural correlates of successful episodic memory formation. The recorded EEG signals simultaneously sample local field potentials throughout the brain, and can be analyzed in terms of specific time-varying oscillatory or spectral components of neural activity which are thought to reflect the concerted activity of neuronal populations. I collected EEG recordings while participants engage in free recall, an episodic memory task during which participants must study and then recall a list of items. In the first chapter, I compare the spectral correlates during encoding of items later remembered to those later forgotten using two separate recording modalities, scalp and intracranial EEG. I find that memory formation is characterized by broad low frequency spectral power decreases and high frequency power increases across both datasets, suggesting that scalp EEG can resolve high frequency activity (HFA) and that low frequency decreases in intracranial EEG are unlikely due to pathology. In the next chapter, I connect these HFA increases to memory-specific processes by comparing study items based on how they are re- called, not whether they are recalled. I find increased HFA in left lateral cortex and hippocampus during the encoding of subsequently clustered items, those items recalled consecutively with their study neighbors at test. The precise time course of these results suggests that context updating mechanisms and item-to-context associative mechanisms support successful memory formation. In the third chapter, I measure how the formation of these episodic associations is modulated by pre-existing semantic associations by including a semantic orienting task during the encoding interval. I find that semantic processing interferes with the formation of new, episodic memories. In the final chapter, I show that the memory benefit for emotionally valenced items is better explained by a contextual mechanism than an attentional mechanism. Together, my work supports the theory that contextual encoding associative mechanisms, reflected by HFA increases in the memory network, support memory formation

연합기억에서의 해마의 역할: 절제 연구와 뇌파 연결성 연구로부터의 통찰

학위논문(박사) -- 서울대학교대학원 : 자연과학대학 뇌인지과학과, 2023. 8. 정천기.연합 기억은 서로 관련없는 항목들의 관계에 대한 기억으로 정의됩니다. 해마는 연합기억에서 대체할 수 없는 중요한 역할을 하는 것으로 알려져 있습니다. 그러나, 해마가 단독으로 작용하여 연합 기억을 수행하는 것은 아니라는 점에 유의하는 것은 중요합니다. 연합 기억은 뇌의 여러 영역이 상호 작용하여 작동합니다. 따라서 연합 기억을 수행할 때 단순히 특정 영역이 활성화 되는 것 보다 해마와 기억 관련 네트워크 간의 기능적 연결이 더 중요할 수 있습니다. 먼저 해마가 연합 기억에 어떤 기여를 하는지 알아보기 위해 내측 측두엽 뇌전증으로 수술을 받은 환자를 대상으로 해마의 절제 여부와 수술 후 다양한 기억력 검사에서 나타난 기억력 변화 사이의 관계를 조사했습니다. 절제 영역과 위치의 개인차를 반영하는 복셀 기반 분석을 통해 해마의 절제가 항목 기억보다는 연합 기억의 저하와 관련이 있음을 발견했습니다. 이러한 이해를 바탕으로 저는 기억의 성공과 실패를 예측하기 위해 해마와 기억 관련 대뇌 피질 네트워크 영역 사이의 단일 시행 뇌파 연결성을 활용했습니다. 그 결과, 기억의 수행도를 예측할 때 평균 90% 이상의 정확도를 달성했습니다. 이 정확도는 특정 영역의 뇌 활동만을 예측에 사용하는 것과 비교했을 때 현저히 높은 수치입니다. 요약하자면, 이 논문은 연합 기억에서 해마와 해마의 연결성의 중요한 역할을 강조합니다. 이 연구는 연합 기억 과정을 이해하는 데 있어 특정 뇌 영역에만 초점을 맞추는 것이 아니라 대규모 기억 네트워크의 역할을 이해하는 것이 중요하다는 점을 강조합니다.Associative memory refers to the ability to remember the relationships between unrelated items. The hippocampus (HC) is known to play a critical and irreplaceable role in associative memory. However, it is important to note that the HC does not operate in isolation when it comes to performing associative memory; instead, it interacts with various regions of the brain. Therefore, in the context of associative memory, the functional connectivity between the HC and memory-related networks may be more important than the mere activation of specific regions. To investigate the specific contribution of the HC to associative memory, I examined the relationship between hippocampal resection and postoperative memory changes on various memory tests in patients who underwent surgery for medial temporal lobe epilepsy (MTLE). Through a voxel-based analysis that accounts for individual differences in the resection, it was found that resection of the HC was associated with a decline in associative memory rather than item memory. This finding emphasizes the specific involvement of the HC in associative memory processes. Expanding upon this understanding, I utilized single-trial EEG connectivity between the HC and neocortical regions to predict memory success and failure. The results achieved an average accuracy of over 90% in predicting subsequent memory performance. Notably, this level of accuracy was higher compared to utilizing brain activity in specific regions. In summary, this thesis highlights the significant role of the HC and its connectivity in associative memory. It underscores the significance of hippocampal communication with large-scale brain networks, rather than solely focusing on specific brain regions, in understanding memory processes.Abstract i Contents iii List of Figures v List of Tables vi List of Abbreviations vii I. INTRODUCTION 1 1.1 Associative Memory and the Hippocampus 1 1.2 Associative Memory beyond the MTL 5 1.2.1 Successful Memory Encoding and the Default Mode Network 5 1.2.2 Subsequent Memory Effects 9 1.3 Purpose of the Present Study 13 II. METHODS 14 2.1 Participants 14 2.1.1 Experiment 1. Medial Temporal Lobe Epilepsy Patients 14 2.1.2 Experiment 2. EEG Study Participants 18 2.2 Experimental Design 19 2.2.1 Experiment 1. Pre- and Post-operative Memory Test 19 2.2.2 Expereiment 2. EEG Experimental Paradigm 20 2.3 Data Analysis 22 2.3.1 Experiment 1. MRI Image and Statistical Analysis 22 2.3.2 Experiment 2. EEG Connectivity Analysis for Memory Performance Prediction 25 III. RESULTS 30 3.1 Experiment 1. Postoperative Memory Change Analysis Results 30 3.1.2 Neuropsychological Outcome 30 3.1.3 Voxel-based Analysis 32 3.2 Experiment 2. Memory Performance Prediction Results 35 3.2.1 Behavioral Results 35 3.2.2 Differences in Connectivity Features 35 3.2.3 Classification Accuracy 35 IV. DISCUSSION 40 4.1 Summary 40 4.2 Experiment 1. Associative Memory and Hippocampal Resection 41 4.3 Experiment 2. Prediction of Associative Memory Performance Using Hippocampal Connectivity 44 4.4 Conclusion 50 V. BIBLIOGRAPHY 51 Abstract in Korean 66박

성공기억에서의 해마의 특징적 뇌 기전

학위논문 (박사) -- 서울대학교 대학원 : 자연과학대학 뇌인지과학과, 2020. 8. 정천기.One of the most intriguing of the human brain's complex functions is the ability to store information provided by experience and to retrieve much of it at will. This capability of memory processing is critical to humans survival – that is, humans guide their actions based on a given stimulus (e.g., item) in an environment, and can do so even when the stimulus is no longer present owing to the memory of the stimulus. A fundamental question of memory is why some experiences are remembered whereas others are forgotten. Since Scoville and Milners characterization of patient H.M., who demonstrated severe recognition memory deficits following damage to the medial temporal lobe (MTL), the hippocampus has been extensively studied as one of the key neural substrates for memory. In line with this, several experiments have been conducted on exploring the roles of the hippocampus in various ways. One is confirming the causality of the hippocampus in the memory process using direct electrical stimulation to the hippocampal region. The other is investigating the neural correlates of hippocampus using intracranial electroencephalography (iEEG) field potential and single neurons action potential known as spike recorded directly from the hippocampus. The present thesis is focused on providing direct electrophysiological evidence of human hippocampus in episodic memory that may help fill the gap that remained in the field for several years. Here, I will show how direct hippocampal stimulation affect human behavior and present characterized neural correlates of successful memory in the hippocampus. In the first study, building on the previous findings on the hippocampus, I sought to address whether the hippocampus would show functional causality with memory tasks and elicit different neural characteristics depending on memory tasks applied. I found hippocampal stimulation modulated memory performance in a task-dependent manner, improving associative memory performance, while impairing item memory performance. These results of the task-specific memory modulation suggest that the associative task elicited stronger theta oscillations than the single-item task. In the second study, I tested whether successful memory formation relies on the hippocampal neuronal activity that engaged preceding an event. I found that hippocampal pre-stimulus spiking activity (elicited by a cue presented just before a word) predicted subsequent memory. Stimulus activity during encoding (during-stimulus) also showed a trend of predicting subsequent memory but was simply a continuation of pre-stimulus activity. These findings indicate that successful memory formation in human is predicted by a pre-stimulus activity and suggests that the preparatory mobilization of neural processes before encoding benefits episodic memory performance. Throughout the study, the current finding suggests the possibility that the intervals of poor memory encoding can be identified even before the stimulus presented and may be rescued with targeted stimulation to the hippocampus even before the stimulus presented.인간의 복잡한 뇌 기능 중 흥미로운 하나는 경험에 의거하여 정보를 저장하고 의지에 따라 저장된 정보를 재인하는 기억 능력 이다. 인간은 주어진 자극에 기반하여 행동을 정하며 심지어 자극이 없는 상황에서도 자극에 대한 기억을 바탕으로 행동을 결정하기 때문에 기억 능력은 생존에 있어 매우 결정적이며, 이러한 기억과 관련된 가장 기본적인 질문은 기억의 저장 메커니즘, 즉, 어떤 기억은 저장이 되고 어떤 기억은 잊혀지는 가일 것이다. 스코빌과 밀너가 처음 보고한 기억상실증 환자 H.M.은 측두영역의 손상을 입은 후 심각한 인지 기억 능력의 장애를 보였고, 이후 사람 뇌의 해마 영역은 기억을 관장하는 뇌의 중요한 영역 중 하나로 널리 연구되었다. 해마가 기억에 미치는 영향과 역할에 대해서는 다양한 방법으로 실험이 진행되어 왔다. 그 중의 하나는 뇌에 직접적인 전기자극을 가해 기억 과정 중 해마의 역할을 확인하는 방법인데, 이는 뇌전증 환자의 모델을 통해 사람의 뇌에 접근이 가능해지면서 이루어져 왔다. 두 번째 방법은 전기생리학적 방법을 통하는 것인데 세포 외 활동 전위인 스파이크를 통해 성공기억에서의 뉴런의 활동성을 밝히는 것이다. 이 논문은 이 분야에서 오랫동안 논란이 되었고 부족했던 성공 기억에 관련된 해마의 역할과 기전을 물리적 자극 및 신경세포의 신호를 측정해서 전기생리학적 특성을 제시하는데 초점을 맞추고 있다. 논문에서 본 저자는 사람의 성공기억형성과 재인에 대해 뇌 자극과 단위세포활동을 보고할 것이다. 해마와 기억의 인과관계 및 기억 과정 중의 해마의 뇌 기전과 관련된 기존의 실험적, 행동적 발견들에 근거하여 본 저자는 (ㄱ) 해마에 직접적인 전기 자극을 주고 기억 수행능력의 차이 및 기억 과제에 따른 해마의 신경 기전을 밝히고, (ㄴ) 성공 기억이 형성되는 과정에서 나타나는 신경세포의 발화 패턴의 특성을 살펴보았다. 본 연구를 통해 저자는 향후 기억의 형성 과정에서, 자극이 제시되는 구간뿐 만 아니라 자극이 주어지기 전 단계에서도 해마를 타깃 하여 전기 자극을 줌으로써 기억 실패로 이어질 수 있는 자극을 성공 기억으로 저장할 수 있도록 유도할 수 있을 것이라 기대한다.SECTION 1. INTRODUCTION 1 CHAPTER 1: Human Memory System 1 1.1. The hippocampus and memory 2 1.2. The structure of the hippocampus 3 CHAPTER 2: Human Memory Research: how to see a memory 4 2.1 Clinical rationale for invasive recordings with intracranial electrodes 4 2.2. Human intracranial EEG 6 2.3. Single unit activity recording and spike sorting in human 7 2.4. Direct brain stimulation study 9 CHAPTER 3: Human Memory Research: hippocampal activity for understanding successful memory formation 11 3.1. Functional role of human intracranial oscillatory activity in successful memory mechanism 11 3.1.1. Theta Oscillations 11 3.1.2. Gamma oscillations 13 3.2. Brain stimulation for memory enhancement 14 3.3. Single unit activity study in memory 15 CHAPTER 4: Purpose of the Present Study 17 SECTION 2. EXPERIMENTAL STUDY 19 CHAPTER 5: The importance of the hippocampal oscillatory activity for successful memory: direct brain stimulation study 19 5.1. Abstract 20 5.2. Introduction 22 5.3. Materials and Methods 25 5.3.1. Patients 25 5.3.2. Electrode localization 25 5.3.3. Memory task 29 5.3.4. Brain stimulation 30 5.3.5. Neuropsychological memory test 31 5.3.6. Analysis of memory performance and electrophysiological data 32 5.4. Results 37 5.4.1. Hippocampal stimulation improves associative memory but impairs item memory 37 5.4.2. Stimulation-induced memory enhancement is reflected in increased theta power during retrieval 38 5.4.3. Associative memory elicits higher theta power than item memory during encoding 42 5.4.4. Successful memory encoding elicits higher theta power in both memory task 44 5.4.5. Stimulation-mediated memory effect is greater in subject with poorer baseline cognitive function 46 5.5. Discussion 48 5.5.1. Summary 48 5.5.2. Task-dependent effects of hippocampal stimulation on memory 49 5.5.3. Theta activity as a neural signature for memory enhancement 51 5.5.4. Clinical implications 52 5.5.5. Limitations 54 5.5.6. Conclusion 55 CHAPTER 6: Hippocampal pre-stimulus activity predicts later memory success 57 6.1. Abstract 58 6.2. Introduction 59 6.3. Materials and Methods 62 6.3.1. Patients 62 6.3.2. Electrodes 63 6.3.3. Task and Stimuli 64 6.3.4. Electrophysiological recordings and Spike sorting 65 6.3.5. Analysis of iEEG field potentials 66 6.4. Results 68 6.4.1. Behavioral results 68 6.4.2. Spiking properties of hippocampal neurons 68 6.4.3. Hippocampal pre-stimulus activity correlates with successful memory 70 6.4.4. Hippocampal pre-stimulus spiking activity correlates with high gamma field potentials 74 6.5. Discussion 78 6.5.1. Summary 78 6.5.2. Comparison with previous findings 78 6.5.3. Possible mechanism underlying pre-stimulus activity 79 6.5.4. Conclusion 82 SECTION 3. GENERAL CONCLUSION 83 CHAPTER 7: General Conclusion and Perspective 83 Bibliography 84 Abstract in Korean (국문초록) 93Docto

Learning and Production of Movement Sequences: Behavioral, Neurophysiological, and Modeling Perspectives

A growing wave of behavioral studies, using a wide variety of paradigms that were introduced or greatly refined in recent years, has generated a new wealth of parametric observations about serial order behavior. What was a mere trickle of neurophysiological studies has grown to a more steady stream of probes of neural sites and mechanisms underlying sequential behavior. Moreover, simulation models of serial behavior generation have begun to open a channel to link cellular dynamics with cognitive and behavioral dynamics. Here we summarize the major results from prominent sequence learning and performance tasks, namely immediate serial recall, typing, 2XN, discrete sequence production, and serial reaction time. These populate a continuum from higher to lower degrees of internal control of sequential organization. The main movement classes covered are speech and keypressing, both involving small amplitude movements that are very amenable to parametric study. A brief synopsis of classes of serial order models, vis-à-vis the detailing of major effects found in the behavioral data, leads to a focus on competitive queuing (CQ) models. Recently, the many behavioral predictive successes of CQ models have been joined by successful prediction of distinctively patterend electrophysiological recordings in prefrontal cortex, wherein parallel activation dynamics of multiple neural ensembles strikingly matches the parallel dynamics predicted by CQ theory. An extended CQ simulation model-the N-STREAMS neural network model-is then examined to highlight issues in ongoing attemptes to accomodate a broader range of behavioral and neurophysiological data within a CQ-consistent theory. Important contemporary issues such as the nature of working memory representations for sequential behavior, and the development and role of chunks in hierarchial control are prominent throughout.Defense Advanced Research Projects Agency/Office of Naval Research (N00014-95-1-0409); National Institute of Mental Health (R01 DC02852

Neocortical Connectivity during Episodic Memory Formation

During the formation of new episodic memories, a rich array of perceptual information is bound together for long-term storage. However, the brain mechanisms by which sensory representations (such as colors, objects, or individuals) are selected for episodic encoding are currently unknown. We describe a functional magnetic resonance imaging experiment in which participants encoded the association between two classes of visual stimuli that elicit selective responses in the extrastriate visual cortex (faces and houses). Using connectivity analyses, we show that correlation in the hemodynamic signal between face- and place-sensitive voxels and the left dorsolateral prefrontal cortex is a reliable predictor of successful face–house binding. These data support the view that during episodic encoding, “top-down” control signals originating in the prefrontal cortex help determine which perceptual information is fated to be bound into the new episodic memory trace

Brain Mechanisms of Persuasion: How "Expert Power" Modulates Memory and Attitudes

Human behavior is affected by various forms of persuasion. The general persuasive effect of high expertise of the communicator, often referred to as "expert power", is well documented. We found that a single exposure to a combination of an expert and an object leads to a long-lasting positive effect on memory for and attitude towards the object. Using functional magnetic resonance imaging (fMRI), we probed the neural processes predicting these behavioral effects. Expert context was associated with distributed left-lateralized brain activity in prefrontal and temporal cortices related to active semantic elaboration. Furthermore, experts enhanced subsequent memory effects in the medial temporal lobe (i.e. in hippocampus and parahippocampal gyrus) involved in memory formation. Experts also affected subsequent attitude effects in the caudate nucleus involved in trustful behavior, reward processing and learning. These results may suggest that the persuasive effect of experts is mediated by modulation of caudate activity resulting in a re-evaluation of the object in terms of its perceived value. Results extend our view of the functional role of the dorsal striatum in social interaction and enable us to make the first steps toward a neuroscientific model of persuasion.neuroeconomics;social influence;attitude;expertise;persuasion;celebrities;memory encoding

Cortico-ocular coupling in the service of episodic memory formation

Encoding of visual information is a necessary requirement for most types of episodic memories. In search for a neural signature of memory formation, amplitude modulation of neural activity has been repeatedly shown to correlate with and suggested to be functionally involved in successful memory encoding. We here report a complementary view on why and how brain activity relates to memory, indicating a functional role of cortico-ocular interactions for episodic memory formation. Recording simultaneous magnetoencephalography and eye tracking in 35 human participants, we demonstrate that gaze variability and amplitude modulations of alpha/beta oscillations (10–20 Hz) in visual cortex covary and predict subsequent memory performance between and within participants. Amplitude variation during pre-stimulus baseline was associated with gaze direction variability, echoing the co-variation observed during scene encoding. We conclude that encoding of visual information engages unison coupling between oculomotor and visual areas in the service of memory formation