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Background Dilated perivascular spaces (dPVS) are associated with aging and various disorders; however, the effect of age on dPVS burden in young populations and normative data have not been fully evaluated. Purpose To investigate the dPVS burden and provide normative data according to age in a healthy population, including children. Materials and Methods In this retrospective study, three-dimensional T2-weighted brain MRI scans from the Human Connectome Project data sets were used for visual grading (grade 0, 1, 2, 3, 4 for 0, 1-10, 11-20, 21-40, and40 dPVS on a single section of either hemispheric region) and automated volumetry of dPVS in basal ganglia (BGdPVS) and white matter (WMdPVS). Linear and nonlinear regression were performed to assess the association of dPVS volume with age. Optimal cutoff ages were determined with use of the maximized continuous-scale C-index. Participants were grouped by cutoff values. Linear regression was performed to assess the age-dPVS volume relationship in each age group. Normative data of dPVS visual grades were provided per age decade. Results A total of 1789 participants (mean age, 35 years; age range, 8-100 years; 1006 female participants) were evaluated. Age was related to dPVS volume in all regression models (

Background Group comparison results associating cortical thinning and Parkinson disease (PD) dementia (PDD) are limited in their application to clinical settings. Purpose To investigate whether cortical thickness from MRI can help predict conversion from mild cognitive impairment (MCI) to dementia in PD at an individual level using a machine learning-based model. Materials and Methods In this retrospective study, patients with PD and MCI who underwent MRI from September 2008 to November 2016 were included. Features were selected from clinical and cortical thickness variables in 10 000 randomly generated training sets. Features selected 5000 times or more were used to train random forest and support vector machine models. Each model was trained and tested in 10 000 randomly resampled data sets, and a median of 10 000 areas under the receiver operating characteristic curve (AUCs) was calculated for each. Model performances were validated in an external test set. Results Forty-two patients progressed to PDD (converters) (mean age, 71 years ± 6 [standard deviation]; 22 women), and 75 patients did not progress to PDD (nonconverters) (mean age, 68 years ± 6; 40 women). Four PDD converters (mean age, 74 years ± 10; four men) and 20 nonconverters (mean age, 67 years ± 7; 11 women) were included in the external test set. Models trained with cortical thickness variables (AUC range, 0.75-0.83) showed fair to good performances similar to those trained with clinical variables (AUC range, 0.70-0.81). Model performances improved when models were trained with both variables (AUC range, 0.80-0.88). In pair-wise comparisons, models trained with both variables more frequently showed better performance than others in all model types. The models trained with both variables were successfully validated in the external test set (AUC range, 0.69-0.84). Conclusion Cortical thickness from MRI helped predict conversion from mild cognitive impairment to dementia in Parkinson disease at an individual level, with improved performance when integrated with clinical variables. © RSNA, 2021

The aims of the study are to evaluate idiopathic normal-pressure hydrocephalus (INPH)-related cerebral blood flow (CBF) abnormalities and to investigate their relation to cortical thickness in INPH patients. We investigated cortical CBF utilizing surface-based early-phase

Fatigue is one of the most common non-motor symptoms in Parkinson’s disease (PD). Despite its clinical importance, there are few studies on the cause or mechanism of fatigue. Our aim was to find brain areas related to fatigue and to explore the association between striatal dopaminergic dysfunction and fatigue. We consecutively screened forty-seven patients with de novo PD from 2012 to 2017 and enrolled 32 patients. The gray matter volumes, white matter tracts, and striatal dopaminergic activity between PD without fatigue and with fatigue were compared. The correlation between fatigue and striatal dopaminergic activity was also analyzed. Our data did not show any significant difference in gray matter volume between PD without fatigue and with fatigue (familywise error [FWE] corrected p > 0.05) but revealed significantly higher mean fractional anisotropy (FA) values for all analyzed white matter tracts in PD with fatigue (false discovery rate [FDR] corrected p 0.06); lower mean diffusivity (MD) values for all analyzed white matter tracts in PD with fatigue (FDR corrected p 0.05). The mean radial diffusivity (RD) values, except for the left CH (FDR corrected p = 0.0576), were also significantly lower (FDR corrected p 0.50). The alteration of the white matter tract may reflect the degree of fatigue in PD. This is not true of the gray matter and striatal dopaminergic activity. These results show the possibility that white matter changes can be used as a biomarker for fatigue.

Considering brain structural alterations as neurodegenerative consequences of Parkinson's disease (PD), we sought to infer the progression of PD via the ordering of brain structural alterations from cross-sectional MRI observations. Having measured cortical thinning in gray matter (GM) regions and disintegrity in white matter (WM) regions as MRI markers of structural alterations for 130 patients with PD (69 ± 10 years, 72 men), stochastic simulation based on the probabilistic relationship between the brain regions was conducted to infer the ordering of structural alterations across all brain regions and the staging of structural alterations according to changes in clinical status. The ordering of structural alterations represented WM disintegrity tending to occur earlier than cortical thinning. The staging of structural alterations indicated structural alterations happening mostly before major disease complications such as postural instability and dementia. Later disease states predicted by the sequence of structural alterations were significantly related to more severe clinical symptoms. The relevance of the ordering of brain structural alterations to the severity of clinical symptoms suggests the clinical feasibility of predicting PD progression states.

We investigated gait performance utilizing a quantitative gait analysis for 2 groups: (1) idiopathic normal-pressure hydrocephalus (INPH) patients who had a positive response to the cerebrospinal fluid tap test (CSFTT) and (2) healthy controls. The aims of the study were (1) to analyze the characteristics of gait features, (2) to characterize changes in gait parameters before and after the CSFTT, and (3) to determine whether there was any relationship between stride time and stride length variability and Frontal Assessment Battery (FAB) scores in INPH patients. Twenty-three INPH patients and 17 healthy controls were included in this study. Compared with healthy controls, the gait of INPH patients was characterized by lower velocity, shorter stride length, and more broad-based gait. Patients with INPH had a longer stance phase with increased double-limb support. Variability in stride time and stride length was increased in INPH patients. Stride time and stride length variability were correlated with FAB score. After the CSFTT, gait velocity, stride length, and step width significantly improved. There were significant decreases in stride time and stride length variability. These results suggest that the CSFTT for INPH patients might improve the so-called balance-related gait parameter (ie, step width) as well. Stride time and stride length variability also responded to the CSFTT. Association between FAB scores and both stride time and stride length variability suggests involvement of similar circuits producing gait variability and frontal lobe functions in INPH patients.

To apply an AT (Aβ/tau) classification system to subcortical vascular cognitive impairment (SVCI) patients following recently developed biomarker-based criteria of Alzheimer’s disease (AD), and to investigate its clinical significance. We recruited 60 SVCI patients who underwent the neuropsychological tests, brain MRI, and 18F-florbetaben and 18F-AV1451 PET at baseline. As a control group, we further recruited 27 patients with AD cognitive impairment (ADCI; eight Aβ PET-positive AD dementia and 19 amnestic mild cognitive impairment). ADCI and SVCI patients were classified as having normal or abnormal Aβ (A−/A+) and tau (T−/T+) based on PET results. Across the three SVCI groups (A−, A+T−, and A+T+SVCI), we compared longitudinal changes in cognition, hippocampal volume (HV), and cortical thickness using linear mixed models. Among SVCI patients, 33 (55%), 20 (33.3%), and seven (11.7%) patients were A−, A+T−, and A+T+, respectively. The frequency of T+ was lower in A+SVCI (7/27, 25.9%) than in A+ADCI (14/20, 70.0%, p = 0.003) which suggested that cerebral small vessel disease affected cognitive impairments independently of A+. A+T−SVCI had steeper cognitive decline than A−SVCI. A+T+SVCI also showed steeper cognitive decline than A+T−SVCI. Also, A+T−SVCI had steeper decrease in HV than A−SVCI, while cortical thinning did not differ between the two groups. A+T+SVCI had greater global cortical thinning compared with A+T−SVCI, while declines in HV did not differ between the two groups. This study showed that the AT system successfully characterized SVCI patients, suggesting that the AT system may be usefully applied in a research framework for clinically diagnosed SVCI.

Orthostatic hypotension (OH) is relatively common in the early stage of Parkinson’s disease (PD). It is divided into delayed OH and classical OH. Classical OH in PD has been investigated widely, however, the clinical implications of delayed OH in PD have seldom been studied. The purpose of this study is to characterize delayed OH in PD. A total of 285 patients with early drug-naïve PD were enrolled and divided into three groups according to orthostatic change: no-OH, delayed OH, and classical OH. The disease severity in terms of motor, non-motor, and cognitive functions was assessed. The cortical thickness of 82 patients was analyzed with brain magnetic resonance imaging. The differences among groups and linear tendency in the order of no-OH, delayed OH, and classical OH were investigated. Seventy-seven patients were re-evaluated. Initial and follow-up evaluations were explored to discern any temporal effects of orthostasis on disease severity. Sixty-four (22.5%) patients were defined as having delayed OH and 117 (41.1%) had classical OH. Between-group comparisons revealed that classical OH had the worst outcomes in motor, non-motor, cognitive, and cortical thickness, compared to the other groups. No-OH and delayed OH did not differ significantly. Linear trends across the pre-ordered OH subtypes found that clinical parameters worsened along with the orthostatic challenge. Clinical scales deteriorated and the linear gradient was maintained during the follow-up period. This study suggests that delayed OH is a mild form of classical OH in PD. PD with delayed OH has milder disease severity and progression.

We investigated differences in cortical thickness between idiopathic normal-pressure hydrocephalus (INPH) patients and healthy controls. We also explored whether a relationship exists between cortical thinning and gait disturbance in INPH patients. Forty-nine INPH patients and 26 healthy controls were imaged with MRI, including 3-dimensional volumetric images, for automated surface-based cortical thickness analysis across the entire brain. Compared with age- and gender-matched healthy controls, unexpectedly, INPH patients showed statistically significant cortical thickening mainly in areas located in the high convexity of the frontal, parietal, and occipital regions. Additionally, cortical thinning mainly in temporal and orbitofrontal regions was observed in the INPH group relative to the control group. The Gait Status Scale (GSS) scores were negatively correlated with cortical thickness in the medial orbital part of the superior frontal gyrus, gyrus rectus, superior temporal gyrus, temporal pole, and insula. A distinctive pattern of cortical thickness changes was found in INPH patients. We cautiously suggest that cortical thickening in INPH can result from reactive gliosis. Further, our results support the hypothesis that cortical thinning in INPH can result from neuronal degeneration. In addition, cortical thinning can play an important role in gait disturbances in INPH patients.

OBJECTIVE Increased cerebral white matter intensities associated with blood pressure (BP) lability were reported in patients with Parkinson's disease. However, this type of cardiovascular dysautonomia has seldom been associated with disruptions in deep gray matter structures in Parkinson's disease. In the present study, the associations between BP lability and subcortical deep gray matter structures in early Parkinson's disease were evaluated. METHODS The present study included 98 early nondemented Parkinson's disease patients. Supine and orthostatic BPs were measured using head-up tilt tests. BP variabilities, measured as standard deviations of 24-h daytime and nighttime BPs, were assessed using 24-h ambulatory BP monitoring. Every patient underwent brain MRI and measurement of deep gray matter volumes. The associations between BP lability and deep gray matter structures were analyzed. RESULTS Parkinson's disease patients with orthostatic hypotension had smaller volumes of striatum, particularly caudate, than patients without OH after adjusting for covariates of age, sex, disease duration, and Mini-Mental Status Examination score. Nocturnal BP variability was inversely associated with thalamus, hippocampus, and globus pallidus volumes. CONCLUSION The results from the present study showed that BP lability was adversely associated with structural changes in early Parkinson's disease. Different forms of BP fluctuations influenced distinct deep gray matter structures.

While drug-induced parkinsonism (DIP) is mainly caused by blockage of the dopaminergic pathway, multiple neurotransmitter systems besides the dopaminergic system are involved in Parkinson’s disease (PD). Therefore, alterations found in both DIP and PD might be manifestations of dopaminergic dysfunction. To prove this hypothesis, we aimed to define the areas commonly involved in DIP and PD and determine whether the overlapping areas were associated with the dopaminergic system. 68 PD patients, 69 DIP patients and 70 age-and sex-matched controls underwent resting-state functional MRI (rsfMRI). Regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF) and fractional ALFF were calculated and compared. Afterwards, we compared mean rsfMRI values extracted from the overlapping areas with uptake quantitatively measured on dopamine transporter (DAT) images and neuropsychological test results. Compared to the controls, both PD and DIP patients revealed altered rsfMRI values in the right insular cortex, right temporo-occipital cortex, and cerebellum. Among them, decreased ALFF in the right insular cortex and decreased ReHo in the right occipital cortex were correlated with decreased DAT uptake in the caudate as well as executive, visuospatial, and language function. Increased ReHo in the cerebellum was also correlated with decrease DAT uptake in the posterior and ventral anterior putamen, but not with cognitive function. In conclusion, the insular cortex, occipital cortex, and cerebellum were commonly affected in both PD and DIP patients and might be associated with altered dopaminergic modulation.

We utilized three-dimensional, surface-based, morphometric analysis to investigate ventricle shape between 2 groups: (1) idiopathic normal-pressure hydrocephalus (INPH) patients who had a positive response to the cerebrospinal fluid tap test (CSFTT) and (2) healthy controls. The aims were (1) to evaluate the location of INPH-related structural abnormalities of the lateral ventricles and (2) to investigate relationships between lateral ventricular enlargement and cortical thinning in INPH patients. Thirty-three INPH patients and 23 healthy controls were included in this study. We used sparse canonical correlation analysis to show correlated regions of ventricular surface expansion and cortical thinning. Significant surface expansion in the INPH group was observed mainly in clusters bilaterally located in the superior portion of the lateral ventricles, adjacent to the high convexity of the frontal and parietal regions. INPH patients showed a significant bilateral expansion of both the temporal horns of the lateral ventricles and the medial aspects of the frontal horns of the lateral ventricles to surrounding brain regions, including the medial frontal lobe. Ventricular surface expansion was associated with cortical thinning in the bilateral orbitofrontal cortex, bilateral rostral anterior cingulate cortex, left parahippocampal cortex, left temporal pole, right insula, right inferior temporal cortex, and right fusiform gyrus. These results suggest that patients with INPH have unique patterns of ventricular surface expansion. Our findings encourage future studies to elucidate the underlying mechanism of lateral ventricular morphometric abnormalities in INPH patients.

Background: The first aim of our study was to determine whether cortical 18F-florbetaben retention was different between healthy controls and idiopathic normal-pressure hydrocephalus (INPH) patients. Our second aim was to investigate whether there were any relationships between 18F-florbetaben retention and either hippocampal volume or clinical symptoms in INPH patients. Methods: Seventeen patients diagnosed with INPH and 8 healthy controls underwent studies with magnetic resonance imaging and 18F-florbetaben positron emission tomography imaging. Results: Automated region-of-interest analysis showed significant increases in 18F-florbetaben uptake in several brain regions in INPH patients compared to control subjects, with especially remarkable increases in the frontal (bilateral), parietal (bilateral), and occipital (bilateral) cortices. In the INPH group, right hippocampal volume was found to be negatively correlated with right frontal 18F-florbetaben retention. Korean-Mini Mental State Examination scores negatively correlated with right occipital 18F-florbetaben retention. Higher 18F-florbetaben retention correlated significantly with a higher Clinical Dementia Rating Scale score in the right occipital cortex. Conclusions: Our results indicate that INPH might be a disease exhibiting a characteristic pattern of cortical 18F-florbetaben retention. 18F-florbetaben retention in the frontal cortex may be related to hippocampal neuronal degeneration. Our findings may also help us understand the potential pathophysiology of cognitive impairments associated with INPH.

Fatigue is one of the most common non-motor symptoms in Parkinson's disease (PD). Despite its clinical importance, there are few studies on the cause or mechanism of fatigue. Our aim was to find brain areas related to fatigue and to explore the association between striatal dopaminergic dysfunction and fatigue. We consecutively screened forty-seven patients with de novo PD from 2012 to 2017 and enrolled 32 patients. The gray matter volumes, white matter tracts, and striatal dopaminergic activity between PD without fatigue and with fatigue were compared. The correlation between fatigue and striatal dopaminergic activity was also analyzed. Our data did not show any significant difference in gray matter volume between PD without fatigue and with fatigue (familywise error [FWE] corrected p 0.05) but revealed significantly higher mean fractional anisotropy (FA) values for all analyzed white matter tracts in PD with fatigue (false discovery rate [FDR] corrected p 0.05), except left cingulum-hippocampus (CH), right superior longitudinal fasciculus, and right longitudinal fasciculus temporal part (FDR corrected p 0.06); lower mean diffusivity (MD) values for all analyzed white matter tracts in PD with fatigue (FDR corrected p 0.05), except in the left CH and uncinate fasciculus (FDR corrected p 0.05). The mean radial diffusivity (RD) values, except for the left CH (FDR corrected p = 0.0576), were also significantly lower (FDR corrected p 0.05). There was no difference in dopaminergic deficits between PD without fatigue and PD with fatigue (p 0.50). The alteration of the white matter tract may reflect the degree of fatigue in PD. This is not true of the gray matter and striatal dopaminergic activity. These results show the possibility that white matter changes can be used as a biomarker for fatigue.

PURPOSE Based on the possibility that early-phase florbetaben (E-FBB) brain PET can be a surrogate for brain perfusion imaging, we conducted this study to investigate the clinical utility of E-FBB PET instead of F-FDG brain PET. MATERIALS AND METHODS This prospective study included 35 patients with clinical suspicion of cognitive decline or dementia and 5 healthy controls. Brain MRI, E-FBB PET, late-phase FBB PET, and FDG PET were acquired. The regional SUV ratios (SUVRs) were calculated by cortical surface region of interest analysis using individual MRI, and relationship between E-FBB and FDG PET was analyzed. All PET scans were scored and analyzed as per visual scoring system, which represent tracer uptake abnormality. Moreover, uptake patterns were analyzed to determine the disease. RESULTS Among the 40 subjects, 19 were amyloid-positive and 21 were amyloid-negative on late-phase FBB PET. Cortical surface region of interest analysis conducted for comparing between E-FBB and FDG PET revealed significant correlations (P < 0.0001) for regional SUVR among all brain regions; however, the SUVR values of FDG PET were statistically higher than those of E-FBB PET. Similarly, although the visually rated scores for E-FBB and FDG PET showed significant correlation (P < 0.0001), it was considered that the tracer uptake was more severely decreased for FDG PET. The disease types, specified by E-FBB and FDG PET, were statistically correlated. CONCLUSIONS E-FBB PET could potentially be a useful biomarker for the diagnosis of dementia in place of FDG PET. Nevertheless, the severity of the disease was more accurately determined by FDG PET.

We describe detailed clinical, biochemical, neuroimaging and neuropathological features in adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), encompassing hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD), linked to colony-stimulating factor 1 receptor (CSF1R) mutations in four Korean cases. Clinical, biochemical, neuroimaging and neuropathological findings were obtained by direct evaluation and from previous medical records. The genetic analysis of the CSF1R gene was done in two autopsy-confirmed ALSP cases and two cases where ALSP was suspected based on the clinical and neuroimaging characteristics. We identified two known mutations: c.2342C>T (p.A781V) in one autopsy-proven HDLS and clinically ALSP-suspected case and c.2345G>A (p.R782H) in another autopsy-proven POLD case. We also found a novel mutation (c.2296A>G; p.M766V) in a patient presenting with hand tremor, stuttering and hesitant speech, and abnormal behavior whose father died from a possible diagnosis of spinocerebellar ataxia. To the best of our knowledge, this is the first documented ALSP-linked CSF1R mutation in Korea and supports the suggestion that HDLS and POLD, with pathological characteristics that are somewhat different but which are caused by CSF1R mutations, are the same spectrum of disease, ALSP.

The first aim of our study was to determine whether cortical 18F-florbetaben retention was different between healthy controls and idiopathic normal-pressure hydrocephalus (INPH) patients. Our second aim was to investigate whether there were any relationships between 18F-florbetaben retention and either hippocampal volume or clinical symptoms in INPH patients.Seventeen patients diagnosed with INPH and 8 healthy controls underwent studies with magnetic resonance imaging and 18F-florbetaben positron emission tomography imaging.Automated region-of-interest analysis showed significant increases in 18F-florbetaben uptake in several brain regions in INPH patients compared to control subjects, with especially remarkable increases in the frontal (bilateral), parietal (bilateral), and occipital (bilateral) cortices. In the INPH group, right hippocampal volume was found to be negatively correlated with right frontal 18F-florbetaben retention. Korean-Mini Mental State Examination scores negatively correlated with right occipital 18F-florbetaben retention. Higher 18F-florbetaben retention correlated significantly with a higher Clinical Dementia Rating Scale score in the right occipital cortex.Our results indicate that INPH might be a disease exhibiting a characteristic pattern of cortical 18F-florbetaben retention. 18F-florbetaben retention in the frontal cortex may be related to hippocampal neuronal degeneration. Our findings may also help us understand the potential pathophysiology of cognitive impairments associated with INPH.

To identify brain cortical regions relevant to HIV-associated neurocognitive disorder (HAND) in HIV patients. HIV patients with HAND (n = 10), those with intact cognition (HIV-IC; n = 12), and age-matched, seronegative controls (n = 11) were recruited. All participants were male and underwent 3-dimensional T1-weighted imaging. Both vertex-wise and region of interest (ROI) analyses were performed to analyse cortical thickness. Compared to controls, both HIV-IC and HAND showed decreased cortical thickness mainly in the bilateral primary sensorimotor areas, extending to the prefrontal and parietal cortices. When directly comparing HIV-IC and HAND, HAND showed cortical thinning in the left retrosplenial cortex, left dorsolateral prefrontal cortex, left inferior parietal lobule, bilateral superior medial prefrontal cortices, right temporoparietal junction and left hippocampus, and cortical thickening in the left middle occipital cortex. Left retrosplenial cortical thinning showed significant correlation with slower information processing, declined verbal memory and executive function, and impaired fine motor skills. This study supports previous research suggesting the selective vulnerability of the primary sensorimotor cortices and associations between cortical thinning in the prefrontal and parietal cortices and cognitive impairment in HIV-infected patients. Furthermore, for the first time, we propose retrosplenial cortical thinning as a possible major contributor to HIV-associated cognitive impairment. • Primary sensorimotor and supplementary motor cortices were selectively vulnerable to HIV infection • Prefrontal and parietal cortical thinning was associated with HIV-associated cognitive impairment • Retrosplenial cortical thinning might be a major contributor to HIV-associated cognitive impairment

Most of default mode network (DMN) studies in patient with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) were based only on the comparing two groups, namely patients and controls. Information derived from comparing the three groups, normal, aMCI, and AD group, simultaneously may lead us to better understand the progression of dementia. The purpose of this study was to evaluate functional connectivity of DMN in the continuum from normal through aMCI to AD. Differences in functional connectivity were compared between the three groups using independent component analysis. The relationship between the functional connectivity and disease progression was investigated using multiple regression analysis with Mini-Mental State Examination (MMSE) scores. The results revealed differences throughout the left posterior cingulate cortex (PCC), left middle temporal gyrus (MTG), right middle frontal gyrus (MFG), and bilateral parahippocampal gyrus (PHG). Both patients with aMCI and AD showed decreased connectivity in the left PCC and left PHG compared with healthy subjects. Furthermore, patient with AD also showed decreased connectivity in the left MTG and right PHG. Increased functional connectivity was observed in the right MFG of patients with AD compared with other groups. MMSE scores exhibited significant positive and negative correlations with functional connectivity in PCC, MTG and MFG regions. Taken together, an increased functional connectivity in the MFG for AD patients might compensate for the loss of function in the PCC, MTG via compensatory mechanisms in cortico-cortical connections.

Objective: Cerebral microbleeds (CMBs) are a neuroimaging marker of small vessel disease (SVD) with relevance for understanding disease mechanisms in cerebrovascular disease, cognitive impairment, and normal aging. It is hypothesized that lobar CMBs are due to cerebral amyloid angiopathy (CAA) and deep CMBs are due to subcortical ischemic SVD. We tested this hypothesis using structural magnetic resonance imaging (MRI) markers of subcortical SVD and in vivo imaging of amyloid in patients with cognitive impairment. Methods: We included 226 patients: 89 with Alzheimer disease–related cognitive impairment (ADCI) and 137 with subcortical vascular cognitive impairment (SVCI). All subjects underwent amyloid imaging with [ 11 C] Pittsburgh compound B (PiB) positron emission tomography, and MRI to detect CMBs and markers of subcortical SVD, including the volume of white matter hyperintensities (WMH) and the number of lacunes. Results: Parietal and occipital lobar CMBs counts were higher in PiB 1 ADCI with moderate WMH than PiB 1 ADCI with minimal WMH, whereas PiB 2 patients with SVCI (ie, “pure” SVCI) showed both lobar and deep CMBs. In multivariate analyses of the whole cohort, WMH volume and lacuna counts were positively associated with both lobar and deep CMBs, whereas amyloid burden (PiB) was only associated with lobar CMBs. There was an interaction between lacuna burden and PiB retention on lobar (but not deep) CMBs (p

There are some studies identifying the association between kidney dysfunction and cognitive impairment through various mechanisms including small vessel disease. However, results concerning the relationship between kidney dysfunction and cortical atrophy have been inconsistent. Thus, we aimed to evaluate the relationship among kidney dysfunction, small vessel disease, and cortical thinning in probable Alzheimer's disease (AD) dementia patients. Patients consisted of 162 subjects with probable AD dementia who underwent high-resolution T1-weighted volumetric magnetic resonance imaging (MRI) scans using the same scanner. The estimated glomerular filtration rate (GFR) was calculated and divided into the quartiles of patients for comparison. Volume of white matter hyperintensities (WMH) was automatically measured. Two neurologists counted the number of lacunes. Cortical thickness was measured using a surface-based method. GFR was not associated with WMH and the number of lacunes. However, the lowest quartile group of GFR (GFR 1) had cortical thinning in each lobe, compared to the highest quartile group of GFR (GFR 4). The topography of cortical thinning in the GFR 1 group was distributed predominantly in temporoparietal regions, compared to GFR 4. After further adjustment of small vessel disease MRI markers, the association between GFR and the cortical thinning remained. Our findings suggested that kidney dysfunction, represented by GFR, was related to temporoparietal thinning independent of small vessel disease in probable AD dementia patients.

BACKGROUND AND PURPOSE: The higher cortical burden of Lewy body and Alzheimer disease–type pathology has been reported to be associated with a faster onset of cognitive impairment of Parkinson disease. So far, there has been a few studies only about the changes of gray matter volume depending on duration of cognitive impairment in Parkinson disease. Therefore, our aim was to evaluate the different patterns of structural and functional changes in Parkinson disease with mild cognitive impairment according to the duration of parkinsonism before mild cognitive impairment. MATERIALS AND METHODS: Fifty-nine patients with Parkinson disease with mild cognitive impairment were classified into 2 groups on the basis of shorter (

Cortical surface area has been largely overlooked in genetic studies of human brain morphometry, even though phylogenetic differences in cortical surface area between individuals are known to be influenced by differences in genetic endowment. In this study, we examined the relative contribution of genetic and environmental influences on cortical surface areas in both the native and stereotaxic spaces for a cohort of homogeneously-aged healthy pediatric twins. Bilateral hemispheric surface and all lobar surface areas except the occipital lobes in native space showed high heritable estimates, while the common environmental effect on bilateral occipital lobes reached statistical significance. The proportion of genetic variance for cortical surface areas measured in stereotaxic space was lower than that measured in native space, whereas the unique environmental influences increased. This is reasonable since whole brain volume is also known to be heritable itself and so removing that component of areal variance due to overall brain size via stereotaxic transformation will reduce the genetic proportion. These findings further suggest that cortical surface areas involved in cognitive, attention and emotional processing, as well as in creating and retaining of long-term memories are likely to be more useful for examining the relationship between genotype and behavioral phenotypes.

Recent studies suggest that the role of the cerebellum extends into cognitive regulation and that subcortical vascular dementia (SVaD) can result in cerebellar atrophy. However, there has been no evaluation of the cerebellar volume in the preclinical stage of SVaD. We aimed to compare cerebellar volume among patients with amnestic mild cognitive impairment (aMCI) and subcortical vascular mild cognitive impairment (svMCI) and evaluate which factors could have contributed to the cerebellar volume. Participants were composed of 355 patients with aMCI, svMCI, Alzheimer's disease (AD), and SVaD. Cerebellar volumes were measured using automated methods. A direct comparison of the cerebellar volume in SVaD and AD groups showed that the SVaD group had a statistically smaller cerebellar volume than the AD group. Additionally, the svMCI group had a smaller cerebellar volume than the aMCI group, with the number of lacunes (especially in the supratentorial regions) being associated with cerebellar volume. Cerebellar volumes were associated with some neuropsychological tests, digit span backward and ideomotor apraxia. These findings suggest that cerebellar atrophy may be useful in differentiating subtypes of dementia and the cerebellum plays a potential role in cognition.

The autism phenotype is associated with an excess of brain volume due in part to decreased pruning during development. Here we aimed at assessing brain volume early in development to further elucidate previous findings in autism and determine whether this pattern is restricted to idiopathic autism or shared within the autistic phenotype (fragile X syndrome [FXS]). We investigated brain volume in 37 participants, using the fully automated Civet pipeline anatomical magnetic resonance imaging. 3 groups with intellectual deficiency: autism (AUT); its most associated FXS; and its most opposite Williams syndrome (WS) were compared with each other and with normal controls (NC). We report increased total and regional gray and white matter brain volume in AUT and FXS relative to WS and NC. These findings are discussed in light of the possibilities leading for the enlarged brain volume in children with the AUT phenotype. We speculate that this excess suggests reduced regression of neuronal processes “pruning” in cortical and subcortical regions in AUT/FXS, which may be due to a mutation in specific genes involved in pruning and/or a lack of socio-emotional environmental experience during a critical developmental period.

Background Genetically Williams syndrome (WS) promises to provide essential insight into the pathophysiology of cortical development because its ∼28 deleted genes are crucial for cortical neuronal migration and maturation. Phenotypically, WS is one of the most puzzling childhood neurodevelopmental disorders affecting most intellectual deficiencies (i.e. low-moderate intelligence quotient, visuospatial deficits) yet relatively preserving what is uniquely human (i.e. language and social-emotional cognition). Therefore, WS provides a privileged setting for investigating the relationship between genes, brain and the consequent complex human behaviour. Methods We used in vivo anatomical magnetic resonance imaging analysing cortical surface-based morphometry, (i.e. surface area , cortical volume , cortical thickness , gyrification index ) and cortical complexity , which is of particular relevance to the WS genotype–phenotype relationship in 22 children (2.27–14.6 years) to compare whole hemisphere and lobar surface-based morphometry between WS (n = 10) and gender/age matched normal controls healthy controls (n = 12). Results Compared to healthy controls, WS children had a (1) relatively preserved Cth; (2) significantly reduced SA and CV; (3) significantly increased GI mostly in the parietal lobe; and (4) decreased CC specifically in the frontal and parietal lobes. Conclusion Our findings are then discussed with reference to the Rakic radial-unit hypothesis of cortical development, arguing that WS gene deletions may spare Cth yet affecting the number of founder cells/columns/radial units, hence decreasing the SA and CV. In essence, cortical brain structure in WS may be shaped by gene-dosage abnormalities.

Automated white matter hyperintensity (WMH) segmentation on magnetic resonance imaging is greatly advantageous for various clinical studies using large-sample data. Accurate localization of WMH can provide more beneficial information for clinical studies, as differences of regional WMH existence may be linked to clinical symptoms. We suggest a fully automated method for WMH quantification and localization without human interaction using T1-weighted and fluid-attenuated inversion-recovery (FLAIR) images. The known sources of false-positive results in the subarachnoid space and brain-cerebrospinal fluid (CSF) interface were removed by applying a WMH candidate-region mask. WMH segmentation was performed based on the Markov random field model. The intensity-substitution method was developed for the accurate localization of WMH, with proper tissue classification and nonlinear registration. The performance of the method was evaluated via comparison with manual delineation; the similarity index and the overlap ratio were 89.94 and 81.90, respectively. © 2011 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 21, 193–200, 2011 (This work was supported by the Global Science experimental Data hub Center (GSDC) funded by the Korea Institute of Science and Technology Information (KISTI) (N-10-NM-IR05), in which main calculations were performed by using the supercomputing resource of the KISTI.)

Our aims were to (1) examine possible neuroanatomical abnormalities associated with the Disruptive Behavior Disorders (DBDs) as a group and (2) assess neuroanatomical anomalies specific to each DBD (i.e., conduct disorder [CD] and oppositional defiant disorder). Cortical thickness analysis and voxel-based morphometry were analyzed in 47 8-year-old boys (22 DBDs with and without CD and/or ODD and 25 healthy controls) from Magnetic Resonance Imaging brain scans. DBD symptoms were assessed using the Dominic-R. In DBD subjects relative to controls, we found (1) a decreased overall mean cortical thickness; (2) thinning of the cingulate, prefrontal and insular cortices; and (3) decreased gray matter density (GMd) in the same brain regions. We also found that scores on the Dominic-R were negatively correlated with GMd in the prefrontal and precuneus/superior temporal regions. There was a subdiagnostic main effect for CD, related to thinning of the middle/medial frontal, and for ODD in the left rectal/orbitofrontal. Findings suggest that thinning and decreased GMd of the insula disorganizes prefrontal circuits, diminishing the inhibitory influence of the prefrontal cortex on anger, aggression, cruelty, and impulsivity, and increasing a person's likelihood of aggressive behavior. These findings have implications for pathophysiologic models of the DBDs, their diagnostic classification system, and for designing more effective intervention programs.

Recent quantitative analyses of the corpus callosum (CC) have tried to assess the interhemispheric connectivity. Based on histological results showing an expansion of callosal extent at the midsagittal plane, without fiber density alterations, callosal extent was interpreted as an index of interhemispheric connectivity. The microstructural properties of the CC have also been investigated extensively using diffusion tensor imaging, to assess interhemispheric connectivity. The relationships between axonal density and callosal extent need to be investigated to understand how these parameters reflect interhemispheric connectivity. We used a semi-automated CC segmentation scheme in T1-weighted magnetic resonance image and fractional anisotropy (FA) image, respectively. The parameterization method of the segmented CC was applied to 47 right-handed healthy adult subjects. The callosal extent and microstructural properties were measured using the callosal thickness and diffusion indices (FA, mean diffusivity, and axial and radial diffusivity), respectively. Our results revealed a correlation between callosal thickness and FA on the posterior body and isthmus of the CC, which suggests that these regions are more sensitive to fiber alterations than other regions. Based on this result, we suggest that both the extent of the CC and its microstructural properties should be considered together in the estimation of interhemispheric connectivity in healthy adult populations.

Twin studies are one of the most powerful study designs for estimating the relative contribution of genetic and environmental influences on phenotypic variation inhuman brain morphology. In this study, we applied deformation based morphometry, a technique that provides a voxel-wise index of local tissue growth or atrophy relative to a template brain, combined with univariate ACE model, to investigate the genetic and environmental effects on the human brain structural variations in a cohort of homogeneously aged healthy pediatric twins. In addition, anatomical regions of interest (ROIs) were defined in order to explore global and regional genetic effects. ROI results showed that the influence of genetic factors on cerebrum (h(2)=0.70), total gray matter (0.67), and total white matter (0.73) volumes were significant. In particular, structural variability of left-side lobar volumes showed a significant heritability. Several subcortical structures such as putamen (h(ROI)(2)=0.79/0.77(L/R),h(MAX)(2)=0.82/0.79) and globus pallidus (0.81/0.76, 0.88/0.82) were also significantly heritable in both voxel-wise and ROI-based results. In the voxel-wise results, lateral parts of right cerebellum (c(2)=0.68) and the posterior portion of the corpus callosum (0.63) were rather environmentally determined, but it failed to reach statistical significance. Pediatric twin studies are important because they can discriminate several influences on developmental brain trajectories and identify relationships between gene and behavior. Several brain structures showed significant genetic effects and might therefore serve as biological markers for inherited traits, or as targets for genetic linkage and association studies.

Tourette syndrome (TS) implicates the disinhibition of the cortico-striatal-thalamic-cortical circuitry (CSTC). Previous studies used a volumetric approach to investigate this circuitry with inconsistent findings. Cortical thickness may represent a more reliable measure than volume due to the low variability in the cytoarchitectural structure of the grey matter.66 magnetic resonance imaging scans were acquired from 34 TS subjects (age range 10-25, mean 17.19+/-4.1) and 32 normal controls (NC) (age range 10-20, mean 16.33+/-3.56). Brain morphology was assessed using the fully automated CIVET pipeline at the Montreal Neurological Institute.We report (1) significant cortical thinning in the fronto-parietal and somatosensory-motor cortices in TS relative to NC (p.05); (2) TS boys showed thinner cortex relative to TS girls in the fronto-parietal cortical regions (p.05); (3) significant decrease in the fronto-parietal mean cortical thickness in TS subjects with age relative to NC and in the pre-central cortex in TS boys relative to TS girls; (4) significant negative correlations between tic severity and the somatosensory-motor cortical thickness.TS revealed important thinning in brain regions particularly involved in the somatosensory/motor bodily representations which may play an important role in tics. Our findings are in agreement with Leckman et al. (1991) hypothesis stating that facial tics would be associated with dysfunction in an orofacial subset of the motor circuit, eye blinking with the occulo-motor circuit, whereas lack of inhibition to a dysfunction in the prefrontal cortex. Gender and age differences may reflect differential etiological factors, which have significant clinical relevance in TS and should be considered in developing and using diagnostic and therapeutic interventions.

Mapping the structure and function of the brain with non-invasive brain imaging techniques has become a world-wide enterpise in the last 20 years. The core concept that drives this rapid growth has been the use of a standardized 3D coordinate space for combining data from many subjects and/or time-points. This has allowed geographically-separated laboratories to reproduce experiments in precise detail, to share data or to perform meta-analysis in ways that go far beyond the traditional reviewing of summary results in journal publications. A further corollary of the brain mapping approach is the natural fostering of multi-center collaboration among distant sites. This article describes recent progress in trans-Pacific collaboration between Canadian and Asian laboratories in the study of neuroanatomical networks obtained from MRI data, both in the normal brain and in neurodegenerative disorders.

We proposed pattern classification based on principal components of cortical thickness between schizophrenic patients and healthy controls, which was trained using a leave-one-out cross-validation. The cortical thickness was measured by calculating the Euclidean distance between linked vertices on the inner and outer cortical surfaces. Principal component analysis was applied to each lobe for practical computational issues and stability of principal components. And, discriminative patterns derived at every vertex in the original feature space with respect to support vector machine were analyzed with definitive findings of brain abnormalities in schizophrenia for establishing practical confidence. It was simulated with 50 randomly selected validation set for the generalization and the average accuracy of classification was reported. This study showed that some principal components might be more useful than others for classification, but not necessarily matching the ordering of the variance amounts they explained. In particular, 40–70 principal components rearranged by a simple two-sample t -test which ranked the effectiveness of features were used for the best mean accuracy of simulated classification (frontal: (left(%)|right(%)) = 91.07|88.80, parietal: 91.40|91.53, temporal: 93.60|91.47, occipital: 88.80|91.60). And, discriminative power appeared more spatially diffused bilaterally in the several regions, especially precentral, postcentral, superior frontal and temporal, cingulate and parahippocampal gyri. Since our results of discriminative patterns derived from classifier were consistent with a previous morphological analysis of schizophrenia, it can be said that the cortical thickness is a reliable feature for pattern classification and the potential benefits of such diagnostic tools are enhanced by our finding.

We evaluated relationships between diffusion tensor imaging (DTI) findings and clinical profiles in idiopathic normal-pressure hydrocephalus (INPH) patients, along with differences in DTI parameters between cerebrospinal fluid tap test (CSFTT) responders and non-responders. Fifty-four INPH patients constituted the final group for analysis. Fractional anisotropy (FA), axial diffusivity, radial diffusivity, and mean diffusivity were assessed using atlas-based tract-mapping methods on 20 different fiber tracts. Uncorrected results revealed that CSFTT non-responders, when compared to responders, exhibited lower FA in the left anterior thalamic radiation (ATR), left cingulum-hippocampus (CgH), and left inferior fronto-occipital fasciculus (IFO) and higher axial diffusivity, radial diffusivity, and mean diffusivity in the left CgH and left inferior longitudinal fasciculus (ILF). FA values in the ATR (bilateral), corticospinal tract (right), IFO (bilateral), and ILF (bilateral) were negatively correlated with Unified Parkinson's Disease Rating Scale motor scores. In the right CgH, FA values showed significant positive correlations with Korean-Mini Mental State Examination scores and negative correlations with Clinical Dementia Rating Scale scores. Our findings may suggest a possibility for considering microstructural changes of white matter in patients with ventriculomegaly as potential imaging markers for the prediction of CSFTT responders. Unique patterns of white matter microstructural changes, as measured using DTI, might underlie impairments in distinct symptom domains in patients with INPH.

The Gyrification Index (GI) represents the degree of cortical folding and is of special interest in schizophrenia, since alterations in cortical folding indirectly reflect white matter development and axonal connectivity underneath. To the best of our knowledge, very few studies have investigated the effect of sex on GI in schizophrenia. Differences in the GI between patients with schizophrenia and healthy controls and the relation between sex, age symptoms and duration of illness with GI were investigated.T1-images were acquired from schizophrenia patients (24 males [SZ-M] and 24 females [SZ-F]) and healthy volunteers (24 males [NC-M] and 24 females [NC-F]) matched for age, sex and handedness. GI analyses were performed using the fully automated CIVET pipeline.Significantly lower GI was found in patients relative to controls bilaterally in frontal, temporal, and parietal cortex. Sex differences were found: negative correlation was found between the duration of illness and the right parietal GI and right occipital GI in SZ-M, while SZ-F was found in the left frontal and bilateral temporal GI. Patients, regardless of sex, showed positive correlations between negative symptoms and GI in the right occipital. NC-F had greater GI values than SZ-F and both male groups.Since GI reflects, in part, alterations in cerebral development and connectivity, the decrease in GI observed in patients is in agreement with the neurodevelopmental model of disconnectivity in schizophrenia; in addition, we emphasize the importance of sex differences in schizophrenia.