Kwangsun Yoo

Quantitative analysis of hemodynamic and metabolic changes in subcortical vascular dementia using simultaneous near-infrared spectroscopy and fMRI measurements.

Subcortical vascular dementia (SVD) is a form of vascular dementia from small vessel disease with white matter lesions and lacunes. We hypothesized that hemodynamic and metabolic changes in the cortex during a simple motor task may reflect the impaired neurovascular coupling in SVD. We used fMRI and near-infrared spectroscopy (NIRS) simultaneously, which together provided multiple hemodynamic responses as well as a robust estimation of the cerebral metabolic rate of oxygen (CMRO(2)). During the task periods, the oxy-hemoglobin, total-hemoglobin, blood oxygenation level-dependent (BOLD) response, cerebral blood flow (CBF), and CMRO(2) decreased statistically significantly in the primary motor and somatosensory cortices of SVD patients, whereas the oxygen extraction fraction increased when compared with controls. Notably, the flow-metabolism coupling ratio, n representing the ratio of oxygen supply to its utilization, showed a robust reduction in the SVD patient group (n(Control)=1.99 ± 0.23; n(SVD)=1.08 ± 0.24), which implies a loss of metabolic reserve. These results support the pathological small vessel compromise, including an increased vessel stiffness, impaired vascular reactivity, and impaired neurovascular coupling in SVD. In conclusion, simultaneous measurement by NIRS and fMRI can reveal various hemodynamic and metabolic changes and may be used for as an early detection or monitoring of SVD.

Tool-use practice induces changes in intrinsic functional connectivity of parietal areas

Intrinsic functional connectivity from resting state functional magnetic resonance imaging (rsfMRI) has increasingly received attention as a possible predictor of cognitive function and performance. In this study, we investigated the influence of practicing skillful tool manipulation on intrinsic functional connectivity in the resting brain. Acquisition of tool-use skill has two aspects such as formation of motor representation for skillful manipulation and acquisition of the tool concept. To dissociate these two processes, we chose chopsticks-handling with the non-dominant hand. Because participants were already adept at chopsticks-handling with their dominant hand, practice with the non-dominant hand involved only acquiring the skill for tool manipulation with existing knowledge. Eight young participants practiced chopsticks-handling with their non-dominant hand for 8 weeks. They underwent functional magnetic resonance imaging (fMRI) sessions before and after the practice. As a result, functional connectivity among tool-use-related regions of the brain decreased after practice. We found decreased functional connectivity centered on parietal areas, mainly the supramarginal gyrus (SMG) and superior parietal lobule (SPL) and additionally between the primary sensorimotor area and cerebellum. These results suggest that the parietal lobe and cerebellum purely mediate motor learning for skillful tool-use. This decreased functional connectivity may represent increased efficiency of functional network.

Progressive changes in hippocampal resting-state connectivity across cognitive impairment: a cross-sectional study from normal to Alzheimer disease.

We investigate the changes in functional connectivity of the left and right hippocampus by comparing the resting-state low-frequency fluctuations in the blood oxygen level-dependent signal from these regions with relation to Alzheimer disease (AD) progression. AD patients were divided into subgroups based on the clinical dementia rating (CDR) scores. Patients with amnestic mild cognitive impairment (aMCI) were also analyzed as an intermediate stage between normal controls and AD. We found that the total functional connectivity of both the right and left hippocampus was maintained during aMCI and the early stages of AD and that it decreased in the later stages of AD. However, when total functional connectivity was broken down into specific regions of the brain, we observed increased or decreased connectivity to specific regions beginning with aMCI. Direct correlation analysis in seeding the left hippocampus revealed a significant decrease in the functional connectivity with the posterior cingulate cortex region and lateral parietal areas, and an increase in functional connectivity in and the anterior cingulate cortex beginning with aMCI. In this study, we were able to quantify the deterioration of resting-state hippocampal connectivity with disease severity and formation of compensatory recruitment in the early stages of AD.

Influence of ROI selection on resting state functional connectivity: an individualized approach for resting state fMRI analysis

The differences in how our brain is connected are often thought to reflect the differences in our individual personalities and cognitive abilities. Individual differences in brain connectivity has long been recognized in the neuroscience community however it has yet to manifest itself in the methodology of resting state analysis. This is evident as previous studies use the same region of interest (ROIs) for all subjects. In this paper we demonstrate that the use of ROIs which are standardized across individuals leads to inaccurate calculations of functional connectivity. We also show that this problem can be addressed by taking an individualized approach by using subject-specific ROIs. Finally we show that ROI selection can affect the way we interpret our data by showing different changes in functional connectivity with aging.

Neural correlates of progressive reduction of bradykinesia in de novo Parkinson's disease

BACKGROUND A progressive reduction in the speed and amplitude of repetitive action is an essential component of bradykinesia, which is called sequence effect (SE). Because SE is specific to Parkinsons disease (PD) and is suggested to be associated with motor arrest, its features are of great interest. The aim of this study was, for the first time, to find the neural correlates of SE and to demonstrate whether dopaminergic deficit is correlated with SE. METHODS We enrolled 12 patients with de novo PD at a tertiary referral hospital. Correlations between SE severity and alterations in gray and white matter were studied. The association between severity of the SE and striatal dopaminergic deficits was also analyzed. RESULTS There was a significant negative correlation between the volumetric changes in the anterior cingulate cortex (ACC) and the inferior semilunar lobule of the cerebellum and the degree of SE. There was a significant correlation between the long association fibers (the superior longitudinal fasciculus, the uncinate fasciculus, and the inferior fronto-occipital fasciculus) connecting the frontal lobes to the temporal, parietal, and occipital lobes and SE. There was a significant negative correlation between SE in the more affected hand and the caudate dopamine transporter binding in the more affected hemisphere. CONCLUSIONS Our results suggest that the ACC and the cerebellum (inferior semilunar lobule) are associated with the severity of SE. Taken together with DTI findings, the present study proposes that ACC may have an important role. Our data show that the caudate dopaminergic activity may be related to SE.

An example-based multi-atlas approach to automatic labeling of white matter tracts

We present an example-based multi-atlas approach for classifying white matter (WM) tracts into anatomic bundles. Our approach exploits expert-provided example data to automatically classify the WM tracts of a subject. Multiple atlases are constructed to model the example data from multiple subjects in order to reflect the individual variability of bundle shapes and trajectories over subjects. For each example subject, an atlas is maintained to allow the example data of a subject to be added or deleted flexibly. A voting scheme is proposed to facilitate the multi-atlas exploitation of example data. For conceptual simplicity, we adopt the same metrics in both example data construction and WM tract labeling. Due to the huge number of WM tracts in a subject, it is time-consuming to label each WM tract individually. Thus, the WM tracts are grouped according to their shape similarity, and WM tracts within each group are labeled simultaneously. To further enhance the computational efficiency, we implemented our approach on the graphics processing unit (GPU). Through nested cross-validation we demonstrated that our approach yielded high classification performance. The average sensitivities for bundles in the left and right hemispheres were 89.5% and 91.0%, respectively, and their average false discovery rates were 14.9% and 14.2%, respectively.

Neural substrates of motor and non-motor symptoms in Parkinson's disease: a resting FMRI study.

Background Recently, non-motor symptoms of Parkinson’s disease (PD) have been considered crucial factors in determining a patient’s quality of life and have been proposed as the predominant features of the premotor phase. Researchers have investigated the relationship between non-motor symptoms and the motor laterality; however, this relationship remains disputed. This study investigated the neural connectivity correlates of non-motor and motor symptoms of PD with respect to motor laterality. Methods Eight-seven patients with PD were recruited and classified into left-more-affected PD (n = 44) and right-more affected PD (n = 37) based on their MDS-UPDRS (Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale) motor examination scores. The patients underwent MRI scanning, which included resting fMRI. Brain regions were labeled as ipsilateral and contralateral to the more-affected body side. Correlation analysis between the functional connectivity across brain regions and the scores of various symptoms was performed to identify the neural connectivity correlates of each symptom. Results The resting functional connectivity centered on the ipsilateral inferior orbito-frontal area was negatively correlated with the severity of non-motor symptoms, and the connectivity of the contralateral inferior parietal area was positively correlated with the severity of motor symptoms (p < 0.001, |r| > 0.3). Conclusions These results suggest that the inferior orbito-frontal area may play a crucial role in non-motor dysfunctions, and that the connectivity information may be utilized as a neuroimaging biomarker for the early diagnosis of PD.

Default Mode Network Functional Connectivity in Early and Late Mild Cognitive Impairment Results From the Alzheimer's Disease Neuroimaging Initiative

Background:Default mode network (DMN) functional connectivity is one of the neuroimaging candidate biomarkers of Alzheimer disease. However, no studies have investigated DMN connectivity at different stages of mild cognitive impairment (MCI). The aim of this study was to investigate patterns of DMN connectivity and its breakdown among cognitively normal (CN), early MCI (EMCI), and late MCI (LMCI) subjects. Methods:Magnetic resonance imaging data and neuropsychological test scores from 130 subjects (CN=43, EMCI=47, LMCI=40) were obtained from the Alzheimer’s Disease Neuroimaging Initiative. DMN functional connectivity was extracted using independent components analysis and compared between groups. Results:Functional connectivity in the precuneus, bilateral medial frontal, parahippocampal, middle temporal, right superior temporal, and left angular gyri was decreased in EMCI subjects compared with CN subjects. When the 2 MCI groups were directly compared, LMCI subjects exhibited decreased functional connectivity in the precuneus, bilateral medial frontal gyri, and left angular gyrus. There was no significant difference in gray matter volume among the 3 groups. Amyloid-positive EMCI subjects revealed more widespread breakdown of DMN connectivity than amyloid-negative EMCI subjects. A quantitative index of DMN connectivity correlated well with measures of cognitive performance. Conclusions:Our results suggest that the breakdown of DMN connectivity may occur in the early stage of MCI.

The relationship between cognitive performance and insulin resistance in non‐diabetic patients with mild cognitive impairment

Insulin resistance (IR) is a distinct and early feature of type 2 diabetes mellitus and metabolic syndrome. IR is thought to play a vital role in cognitive impairment. We conducted this study to understand the early characteristics of cognitive dysfunctions attributable to IR.

Glucose Metabolic Brain Networks in Early-Onset vs. Late-Onset Alzheimer's Disease

Objective: Early-onset Alzheimers disease (EAD) shows distinct features from late-onset Alzheimers disease (LAD). To explore the characteristics of EAD, clinical, neuropsychological, and functional imaging studies have been conducted. However, differences between EAD and LAD are not clear, especially in terms of brain connectivity and networks. In this study, we investigated the differences in metabolic connectivity between EAD and LAD by adopting graph theory measures. Methods: We analyzed 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) images to investigate the distinct features of metabolic connectivity between EAD and LAD. Using metabolic connectivity and graph theory analysis, metabolic network differences between LAD and EAD were explored. Results: Results showed the decreased connectivity centered in the cingulate gyri and occipital regions in EAD, whereas decreased connectivity in the occipital and temporal regions as well as increased connectivity in the supplementary motor area were observed in LAD when compared with age-matched control groups. Global efficiency and clustering coefficients were decreased in EAD but not in LAD. EAD showed progressive network deterioration as a function of disease severity and clinical dementia rating (CDR) scores, mainly in terms of connectivity between the cingulate gyri and occipital regions. Global efficiency and clustering coefficients were also decreased along with disease severity. Conclusion: These results indicate that EAD and LAD have distinguished features in terms of metabolic connectivity, with EAD demonstrating more extensive and progressive deterioration.