Exercise Training and Functional Connectivity Changes in Mild Cognitive Empairment and Healthy Elders

Background: Effective interventions are needed to improve brain function in mild cognitive impairment (MCI), an early stage of Alzheimer’s disease (AD). The posterior cingulate cortex (PCC)/precuneus is a hub of the default mode network (DMN) and is preferentially vulnerable to disruption of functional connectivity in MCI and AD. Objective: We investigated whether 12 weeks of aerobic exercise could enhance functional connectivity of the PCC/precuneus in MCI and healthy elders. Methods: Sixteen MCI and 16 healthy elders (age range = 60–88) engaged in a supervised 12-week walking exercise intervention. Functional MRI was acquired at rest; the PCC/precuneus was used as a seed for correlated brain activity maps. Results: A linear mixed effects model revealed a significant interaction in the right parietal lobe: the MCI group showed increased connectivity while the healthy elders showed decreased connectivity. In addition, both groups showed increased connectivity with the left postcentral gyrus. Comparing pre to post intervention changes within each group, the MCI group showed increased connectivity in 10 regions spanning frontal, parietal, temporal and insular lobes, and the cerebellum. Healthy elders did not demonstrate any significant connectivity changes. Conclusion: The observed results show increased functional connectivity of the PCC/precuneus in individuals with MCI after 12 weeks of moderate intensity walking exercise training. The protective effects of exercise training on cognition may be realized through the enhancement of neural recruitment mechanisms, which may possibly increase cognitive reserve. Whether these effects of exercise training may delay further cognitive decline in patients diagnosed with MCI remains to be demonstrated

Working Memory Impairment in Fibromyalgia Patients Associated with Altered Frontoparietal Memory Network

BACKGROUND: Fibromyalgia (FM) is a disorder characterized by chronic widespread pain and frequently associated with other symptoms. Patients with FM commonly report cognitive complaints, including memory problem. The objective of this study was to investigate the differences in neural correlates of working memory between FM patients and healthy subjects, using functional magnetic resonance imaging (MRI). METHODOLOGY/PRINCIPAL FINDINGS: Nineteen FM patients and 22 healthy subjects performed an n-back memory task during MRI scan. Functional MRI data were analyzed using within- and between-group analysis. Both activated and deactivated brain regions during n-back task were evaluated. In addition, to investigate the possible effect of depression and anxiety, group analysis was also performed with depression and anxiety level in terms of Beck depression inventory (BDI) and Beck anxiety inventory (BAI) as a covariate. Between-group analyses, after controlling for depression and anxiety level, revealed that within the working memory network, inferior parietal cortex was strongly associated with the mild (r = 0.309, P = 0.049) and moderate (r = 0.331, P = 0.034) pain ratings. In addition, between-group comparison revealed that within the working memory network, the left DLPFC, right VLPFC, and right inferior parietal cortex were associated with the rating of depression and anxiety? CONCLUSIONS/SIGNIFICANCE: Our results suggest that the working memory deficit found in FM patients may be attributable to differences in neural activation of the frontoparietal memory network and may result from both pain itself and depression and anxiety associated with pain

Interaction between Dysfunctional Connectivity at Rest and Heroin Cues-Induced Brain Responses in Male Abstinent Heroin-Dependent Individuals

BACKGROUND: The majority of previous heroin cue-reactivity functional magnetic resonance imaging (fMRI) studies focused on local function impairments, such as inhibitory control, decision-making and stress regulation. Our previous studies have demonstrated that these brain circuits also presented dysfunctional connectivity during the resting state. Yet few studies considered the relevance of resting state dysfunctional connectivity to task-related neural activity in the same chronic heroin user (CHU). METHODOLOGY/PRINCIPAL FINDINGS: We employed the method of graph theory analysis, which detected the abnormality of brain regions and dysregulation of brain connections at rest between 16 male abstinent chronic heroin users (CHUs) and 16 non-drug users (NDUs). Using a cue-reactivity task, we assessed the relationship between drug-related cue-induced craving activity and the abnormal topological properties of the CHUs' resting networks. Comparing NDUs' brain activity to that of CHUs, the intensity of functional connectivity of the medial frontal gyrus (meFG) in patients' resting state networks was prominently greater and positively correlated with the same region's neural activity in the heroin-related task; decreased functional connectivity intensity of the anterior cingulate cortex (ACC) in CHUs at rest was associated with more drug-related cue-induced craving activities. CONCLUSIONS: These results may indicate that there exist two brain systems interacting simultaneously in the heroin-addicted brain with regards to a cue-reactivity task. The current study may shed further light on the neural architecture that supports craving responses in heroin dependence

Resting-state cortical connectivity predicts motor skill acquisition

Many studies have examined brain states in an effort to predict individual differences in capacity for learning, with overall moderate results. The present study investigated how measures of cortical network function acquired at rest using dense-array EEG (256 leads) predict subsequent acquisition of a new motor skill. Brain activity was recorded in 17 healthy young subjects during three minutes of wakeful rest prior to a single motor skill training session on a digital version of the pursuit rotor task. Practice was associated with significant gains in task performance (% time on target increased from 24% to 41%, p < 0.0001). Using a partial least squares regression (PLS) model, coherence with the region of the left primary motor area (M1) in resting EEG data was a strong predictor of motor skill acquisition (R(2) = 0.81 in a leave-one-out cross-validation analysis), exceeding the information provided by baseline behavior and demographics. Within this PLS model, greater skill acquisition was predicted by higher connectivity between M1 and left parietal cortex, possibly reflecting greater capacity for visuomotor integration, and by lower connectivity between M1 and left frontal-premotor areas, possibly reflecting differences in motor planning strategies. EEG coherence, which reflects functional connectivity, predicts individual motor skill acquisition with a level of accuracy that is remarkably high compared to prior reports using EEG or fMRI measures

Reorganization of brain function after a short-term behavioral intervention for stuttering

This study investigated changes in brain function that occurred over a 7-day behavioral intervention for adults who stutter (AWS). Thirteen AWS received the intervention (AWS+), and 13 AWS did not receive the intervention (AWS-). There were 13 fluent controls (FC-). All participants were scanned before and after the intervention. Wholebrain analysis pre-intervention showed significant differences in task-related brain activation between AWS and FC- in the right inferior frontal cortex (IFC) and left middle temporal cortex, but there were no differences between the two AWS groups. Across the 7-day period of the intervention, AWS+ alone showed a significant increase of brain activation in the left ventral IFC/insula. There were no changes in brain function for the other two groups. Further analysis revealed that the change did not correlate with resting-state functional connectivity (RSFC) that AWS showed in the cerebellum (Lu, et al., 2012). However, both changes in task-related brain function and RSFC correlated with changes in speech fluency level. Together, these findings suggest that functional reorganization in a brain region close to the left IFC that shows anomalous function in AWS, occurs after a short-term behavioral intervention for stuttering

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

Dissociating refreshing and elaboration and their impacts on memory

Maintenance of information in working memory (WM) is assumed to rely on refreshing and elaboration, but clear mechanistic descriptions of these cognitive processes are lacking, and it is unclear whether they are simply two labels for the same process. This fMRI study investigated the extent to which refreshing, elaboration, and repeating of items in WM are distinct neural processes with dissociable behavioral outcomes in WM and long-term memory (LTM). Multivariate pattern analyses of fMRI data revealed differentiable neural signatures for these processes, which we also replicated in an independent sample of older adults. In some cases, the degree of neural separation within an individual predicted their memory performance. Elaboration improved LTM, but not WM, and this benefit increased as its neural signature became more distinct from repetition. Refreshing had no impact on LTM, but did improve WM, although the neural discrimination of this process was not predictive of the degree of improvement. These results demonstrate that refreshing and elaboration are separate processes that differently contribute to memory performance