Default mode network connectivity in alzheimer's disease

PubMed ID: 32594490Amaç: Alzheimer hastalığı (AH) beyinde yapısal ve işlevsel değişimler meydana getiren nörodejeneratif bir hastalıktır. Gelişen beyin görüntüleme yöntemleri sayesinde AH patolojisine eşlik eden yapısal ve işlevsel bağlantılardaki bozulmalar gitgide daha görünür hale gelmiştir. AH’de dinlenim durumu bağlantısallığında, özellikle de olağan durum ağı (default mode network - DMN) olarak adlandırılan içsel bağlantısallık ağında farklılaşmalar görülmektedir. Bu çalışmada DMN bağlantısallık bulgularının incelenmesi ve tartışılması amaçlanmıştır. Yöntem: İşlevsel manyetik rezonans görüntüleme (fMRI) çalışmalarında en yaygın kullanılan 2 temel metodoloji (tohum temelli ve bağımsız bileşen analizi) temel alınarak alanda yapılan çalışmalar incelenmiştir. Bulgular: Çalışmalar genel olarak, DMN bağlantısallığının AH süreci boyunca ilerleyici bir şekilde bozulduğunu göstermektedir. DMN alt sistemlerinin AH’nin preklinik ve prodromal evrelerinde farklı bağlantısallık örüntüleri gösterdiği de belirtilmektedir. DMN’deki bozulmanın diğer bağlantısallık ağlarındaki farklılaşma ile ilişkili olabileceğini öne süren kanıtlar da mevcuttur. Buna ek olarak, bulgular DMN’nin AH ile ilişkili nöropatoloji ve genetik risk faktörleri ile olan ilişkisine de işaret etmektedir. Sonuç: AH’nin beyinde başta DMN olmak üzere diğer dinlenim durumu ağlarında işlevsel bozulmalara yol açan yaygın bir diskonneksiyon sendromu olduğu öne sürülebilir. Buna ek olarak, preklinik vakalarda ve risk taşıyan kişilerde de saptanabilen AH ile ilişkili işlevsel bağlantısallık değişimleri AH için muhtemel bir biyo-belirteç olabilir.Objective: Alzheimer's Disease (AD) is a neurodegenerative condition characterized by functional and structural changes in the brain that are increasingly better visualized with the advances in new brain imaging techniques. Connectivity changes under the resting state condition especially in the internal connectivity network, named as the default mode network (DMN), are observed in AD. This paper aimed to investigate and discuss the findings on DMN connectivity. Method: The studies carried out by functional magnetic resonance imaging (fMRI), using the two most widely applied techniques, the seed-based method and independent component analysis (ICA), have been investigated. Results: Studies generally indicate a progressive impairment in DMN connectivity during the course of AD. It has been also stated that DMN subsystems show differential connectivity patterns in the preclinical and prodromal stages of AD. There is also evidence suggesting that impairment in DMN connectivity could be associated with different connectivity patterns in other networks. Furthermore, findings point towards a relationship between DMN and AD-related neuropathology and genetic risk factors. Conclusion: It may be proposed that AD is a generalized disconnection syndrome that causes functional impairments in resting state networks, particularly in DMN. In addition to this, AD-related functional connectivity changes observed in preclinical cases and risk carriers might be a potential bio-marker for AD.Publisher's Versio

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

Age-related Differences in Prestimulus Subsequent Memory Effects Assessed with Event-related Potentials

Prestimulus subsequent memory effects (preSMEs)—differences in neural activity elicited by a task cue at encoding that are predictive of later memory performance—are thought to reflect differential engagement of preparatory processes that benefit episodic memory encoding. We investigated age differences in preSMEs indexed by differences in ERP amplitude just before the onset of a study item. Young and older adults incidentally encoded words for a subsequent memory test. Each study word was preceded by a task cue that signaled a judgment to perform on the word. Words were presented for either a short (300 msec) or long (1000 msec) duration with the aim of placing differential benefits on engaging preparatory processes initiated by the task cue. ERPs associated with subsequent successful and unsuccessful recollection, operationalized here by source memory accuracy, were estimated time-locked to the onset of the task cue. In a late time window (1000–2000 msec after onset of the cue), young adults demonstrated frontally distributed preSMEs for both the short and long study durations, albeit with opposite polarities in the two conditions. This finding suggests that preSMEs in young adults are sensitive to perceived task demands. Although older adults showed no evidence of preSMEs in the same late time window, significant preSMEs were observed in an earlier time window (500–1000 msec) that was invariant with study duration. These results are broadly consistent with the proposal that older adults differ from their younger counterparts in how they engage preparatory processes during memory encoding

Neural Correlates Of Episodic Memory Formation In Children And Adults

The medial temporal lobe (MTL) and prefrontal cortex (PFC) are two key brain regions that support episodic memory formation in both children and adults, but the functional developmental of these regions remains unclear. In this study, we investigated the development of neural correlates of episodic memory formation using functional MRI with a subsequent memory paradigm, administered to a cross-sectional sample of 83 children and adults. We found that MTL subregions showed an age-related increase in activation supporting memory formation of complex scenes. In addition, a functionally defined scene-sensitive region in the posterior MTL also showed similar increase and predicted better memory for complex scenes. Within the PFC we found age-related increase in both activation and deactivation that support memory formation. Finally, we found age-related increase in the functional connectivity between dorsal lateral PFC and posterior MTL regions. Taken together, these findings suggest that the continued functional development of the MTL and the PFC is crucial for age-related improvements in memory

The Association of Aerobic Fitness with Resting State Functional Connectivity and Verbal Learning and Memory in Healthy Young Adults

The beneficial effects of exercise and cardiopulmonary fitness on general health, quality of life, and reduction of mortality are well known in older adults. There is evidence to support the positive effects of exercise and aerobic fitness on psychiatric and neurocognitive function in children, adults, and older adults. Indeed, many studies have explored the positive effects of aerobic fitness on slowing cognitive decline associated with normal and pathological aging. However, comparatively fewer empirical studies in the literature exist to support and understand the effects of aerobic fitness on the developing brain, particularly during adolescence and young adulthood, especially as it relates to resting state functional connectivity during this dynamic stage of development. The current study investigated the association of aerobic fitness on functional connectivity with the left hippocampus in healthy young adults and the degree to which differential resting state functional connectivity is associated with verbal learning and memory. The sample was comprised of healthy young adults with varying degrees of aerobic fitness as part of a larger study of the effects of cardiorespiratory health on neurocognitive performance, brain structure and function. Results of the study indicated that better aerobic fitness is associated with increased functional connectivity to the left parahippocampal gyrus, a region known for its role in working memory and encoding. Results from this study contribute to a better understanding of the factors that may underlie the beneficial effects of exercise on brain health and neurocognition and further offer insights into the value of early preventive health behaviors to reduce the risk of later of cognitive decline and impairment

Effects of age on prestimulus neural activity predictive of successful memory encoding: An fMRI study

Prestimulus subsequent memory effects (SMEs)-differences in neural activity preceding the onset of study items that are predictive of later memory performance-have consistently been reported in young adults. The present functional magnetic resonance imaging experiment investigated potential age-related differences in prestimulus SMEs. During study, healthy young and older participants made one of two semantic judgments on images, with the judgment signaled by a preceding cue. In test phase, participants first made an item recognition judgment and, for each item judged old, a source memory judgment. Age-invariant prestimulus SMEs were observed in left dorsomedial prefrontal cortex, left hippocampus, and right subgenual cortex. In each case, the effects reflected lower blood oxygen level dependent signal for later recognized items, regardless of source accuracy, than for unrecognized items. A similar age-invariant pattern was observed in left orbitofrontal cortex, but this effect was specific to items attracting a correct source response compared to unrecognized items. In contrast, the left angular gyrus and fusiform cortex demonstrated negative prestimulus SMEs that were exclusive to young participants. The findings indicate that age differences in prestimulus SMEs are regionally specific and suggest that prestimulus SMEs reflect multiple cognitive processes, only some of which are vulnerable to advancing age

TheRelationship between brain network organization and variability in episodic memory outcomes and abilities:

Thesis advisor: Maureen RitcheyThesis advisor: Elizabeth KensingerOur brains afford us the remarkable ability to remember past events from our lives, to travel back in time in our minds' eye and relive our memories anew. What are the brain processes that support this ability? In this thesis I investigated this question across three experiments. In Chapter 1, I examined how the brain regions previously linked to episodic cognition (i.e., the hippocampus, parahippocampal cortex, retrosplenial cortex, posterior cingulate cortex, precuneus, angular gyrus, and medial prefrontal cortex) support recollection by building a model that incorporates both region-specific and network-level contributions. I found that these brain regions form ventral and dorsal subnetworks and that their contributions to recollection outcomes are largely explained by subnetwork-level rather than region-specific engagement. In Chapter 2, I used an openly available MRI dataset to test whether individual differences in functional connectivity were related to individual differences in memory ability, finding that network connectivity outside of the classic episodic networks supports individual differences in our ability to remember. In Chapter 3, I tested a neuroscience inspired hypothesis that individuals would have different capacities to bind their memories around social-emotional and visual-spatial content, ultimately finding inconclusive evidence for or against my hypothesis. Together, these results help to solidify our understanding of the brain as an interconnected network of brain regions and shed new light on how these networks support individual differences in memory.Thesis (PhD) — Boston College, 2023.Submitted to: Boston College. Graduate School of Arts and Sciences.Discipline: Psychology

Effects of healthy ageing on the precision of episodic memory

Episodic memory decline is one of the hallmarks of human cognitive ageing, but our understanding of the neurocognitive mechanisms underlying this decline remains limited. In particular, it is unclear whether healthy ageing differentially affects distinct components of episodic memory retrieval; specifically, the probability of successfully retrieving information from memory, and the quality, or precision, of the retrieved memory representations. The research reported in this PhD thesis used continuous measures of memory retrieval to dissociate these two alternative sources of age-related memory deficits and their cognitive and neural underpinnings, providing more detailed insight into the nature of age-related episodic memory decline. Two behavioural experiments reported in Chapter 2 provided initial evidence for differential effects of healthy ageing on the success and precision of episodic memory retrieval, suggesting greater sensitivity of mnemonic precision to age-related declines. Chapter 3 assessed whether these decreases in memory precision are specific to long-term memory or may be explained by age-related decreases in the fidelity of perceptual or working memory processes. The results from this experiment demonstrated that age-related reductions in the precision of episodic memory retrieval persisted after controlling for decreases in the fidelity of perception and working memory, suggesting a predominantly long-term memory basis for this deficit. The functional and structural magnetic resonance imaging experiments reported in Chapters 4 and 5 sought to elucidate the neural basis of age-related changes in the success and precision of episodic memory retrieval. Results from Chapter 4 revealed distinct encoding and retrieval contributions to the decreases in these two aspects of memory retrieval exhibited by older adults. At retrieval, age-related reductions in activity associated with successful memory retrieval were observed in the hippocampus, while decreases in activity underlying the precision of memory retrieval were evident in the angular gyrus. Furthermore, at encoding, age-related decreases in activity predicting both later success and precision of memory retrieval were evident in the fusiform gyrus, while prefrontal reductions were observed in the encoding activity predicting the subsequent success of memory retrieval only. In addition to these functional changes, Chapter 5 provided evidence for the role of structural integrity of the lateral parietal cortex in individual differences in mnemonic precision across older adults. Together, the results reported in this thesis highlight the sensitivity of memory precision to age-related cognitive decline, and suggest both distinct and common factors underlying age-related decreases in the success and precision of episodic memory retrieval