Association Between Serum NT-proBNP and Gray Matter Atrophy Patterns in an Older Japanese Population: The Hisayama Study.

Several population-based studies have reported that higher serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are associated with brain morphological changes. However, no population-based studies have examined the relationship between serum NT-proBNP and various regional brain volumes in detail. We here analyzed the brain MRI data of 1 201 community-dwelling Japanese aged ≥65 years. Regional gray matter volumes (GMV) and intracranial volume (ICV) were estimated by applying voxel-based morphometry (VBM) methods. The associations of serum NT-proBNP with regional GMV/ICV were examined by analysis of covariance. The regional gray matter atrophy patterns associated with elevated serum NT-proBNP levels were investigated using VBM without a priori regions of interest. The multivariable-adjusted means of the frontal, temporal, hippocampal, parahippocampal, and entorhinal GMV/ICV decreased significantly with elevated serum NT-proBNP levels (all p for trend and q values of false discovery rate correction < .05). In VBM, elevated serum NT-proBNP levels were correlated with atrophy of the bilateral hippocampi, bilateral amygdalas, bilateral parahippocampal gyri, bilateral entorhinal areas, bilateral fusiform gyri, left middle temporal gyrus, left inferior temporal gyrus, right central operculum, right posterior orbital gyrus, bilateral middle frontal gyri, anterior cingulate gyrus and bilateral medial frontal cortices. In a sensitivity analysis excluding 254 participants with mild cognitive impairment or dementia, serum NT-proBNP levels were correlated with atrophy of the bilateral hippocampi, bilateral amygdalas, bilateral parahippocampal gyri, bilateral fusiform gyri, and left middle frontal gyrus. Our data suggest that elevated serum NT-proBNP levels are associated with gray matter atrophy in brain regions that play an important role in cognitive function.

Association between preoperative white matter hyperintensities and postoperative new ischemic lesions on magnetic resonance imaging in patients with cognitive decline after carotid endarterectomy.

Although cognitive decline after carotid endarterectomy (CEA) is mainly related to postoperative cerebral hyperperfusion, approximately 30% of patients with cognitive decline do not have postoperative cerebral hyperperfusion. In patients with acute ischemic events, the development of cognitive decline after such events is associated with the presence of chronic cerebral white matter hyperintensities (WMHs). The present prospective observational study aimed to determine whether preoperative WMHs and postoperative new ischemic lesions (PNILs) are associated with cognitive decline after CEA in patients without cerebral hyperperfusion after CEA. Brain magnetic resonance imaging (MRI) was performed preoperatively, and WMHs were graded according to the Fazekas scale in patients undergoing CEA for severe stenosis of the ipsilateral internal carotid. Diffusion-weighted MRI was performed before and after CEA to determine the development of PNILs. Neuropsychological testing was performed preoperatively and at 2 months postoperatively to determine the development of postoperative cognitive decline (PCD). In 142 patients without postoperative cerebral hyperperfusion, logistic regression analysis revealed that preoperative Fazekas scale of periventricular WMHs (PVWMHs) (95% confidence interval [CI]: 1.78-28.10; P = 0.0055) and PNILs in the eloquent areas (95% CI: 7.42-571.89; P = 0.0002) were significantly associated with PCD. The specificity and positive-predictive value for the prediction of PCD were significantly greater for the combination of preoperative Fazekas scale 2 or 3 of PVWMHs and PNILs in the eloquent areas than for each individually. Preoperative PVWMHs, PNILs in the eloquent areas, and the combination of both were associated with PCD in patients without cerebral hyperperfusion after CEA.

Uniformly positive or negative correlation of cerebral gray matter regions with driving safety behaviors of healthy older drivers.

This study investigated the relationship between cerebral gray matter (GM) regions and driving safety behaviors (DSBs) of 98 older drivers without dementia (mean age, 77.72 ± 3.677 years). Their DSBs were evaluated on actual vehicles running on a closed-circuit course. The DSB was scored in six categories: DSB1, visual search behavior; DSB2, speeding; DSB3, signaling of the indicator; DSB4, vehicle stability; DSB5, positioning; and DSB6, steering. The scores were calculated by a single driving instructor; larger scores indicated safer driving performances. Regional GM volumes were measured with voxel-based morphometry by magnetic resonance imaging (MRI). Out of 56 GM regions, 18 were correlated with DSB categories except for DSB4. When a single GM region was correlated with multiple DSB categories, a positive or negative response was uniformly determined for the respective region despite clear differences in the DSB categories. This result suggests the possible existence of two contradictory mechanisms in the brain for DSB. The left postcentral gyrus may largely function in regulating DSBs because it was negatively correlated with five of six DSB categories. Thus, MRI's measurement of regional GM volumes may help deepen the understanding of the diversity and complexity inherent in brain functions for DSBs.

Adult attention-deficit/hyperactivity disorder traits in healthy adults associated with brain volumetric data identify precuneus involvement in traffic crashes.

This large-scale study including 2548 healthy adults with no clinical attention-deficit/hyperactivity disorder (ADHD) diagnosis intended to clarify the complex relationships between cerebral grey matter volumes (GMVs), ADHD traits, and driving safety behaviours. Path analysis of magnetic resonance imaging (MRI) results and questionnaires about ADHD traits and traffic crashes over the past decade revealed significant correlations of ADHD traits with different brain regions relevant to different cognitive functions. The left precuneus responsible for visuospatial cognition was the sole region correlated with all ADHD trait categories, suggesting it plays an important role in understanding driving safety and traffic crashes. For the first time, a strong relationship was found among regional GMVs, ADHD traits, and real-life traffic crashes. These insights into the complex interplay may inform the development of an effective intervention with MRI examination to prevent traffic crashes. Large-scale brain volumetric data may further open social applications of behaviour science and neuroimaging.

Vacuoles related to tissue neuron-astrocyte ratio and infiltration of macrophages/monocytes contribute to hyperintense brain signals on diffusion-weighted magnetic resonance imaging in sporadic Creutzfeldt-Jakob disease.

BACKGROUND: Radiological features in patients with sporadic Creutzfeldt-Jakob disease (sCJD) are hyperintensity of the cerebral cortex and the basal ganglia displayed by diffusion-weighted magnetic resonance imaging (DW-MRI). We performed a quantitative study on neuropathological and radiological findings. METHODS: Patient 1 received a definite diagnosis of MM1-type sCJD, while patient 2 received a definite diagnosis of MM1 + 2-type sCJD. Two DW-MRI scans were performed on each patient. DW-MRI was either taken the day before or on the day of the patient's death, and several hyperintense or isointense areas were marked as a region of interest (ROI). Mean signal intensity of the ROI was measured. Pathological quantitative assessments of the vacuoles, astrocytosis, infiltration of monocytes/macrophages, and proliferation of microglia was performed. Vacuole load (% area vacuole), glial fibrillary acidic protein (GFAP), CD68, and Iba-1 load were calculated. We defined spongiform change index (SCI) to indicate vacuoles related to a tissue neuron-astrocyte ratio. We assessed the correlation of intensity of the last DW-MRI and the pathological findings as well as association of changes of the signal intensity on the sequential images and the pathological findings. RESULT: We observed a strong positive correlation between SCI and DW-MRI intensity. In the analysis using serial DW-MRI and pathological findings, we found that CD68 load was significantly larger in areas where signal intensity decreased, as compared to those areas where hyperintensity remained unchanged. CONCLUSION: DW-MRI intensity in sCJD is associated with the ratio of neuron to astrocyte in the vacuoles and the infiltration of macrophages and/or monocytes.

Parietal and occipital leukoaraiosis due to cerebral ischaemic lesions decrease the driving safety performance of healthy older adults.

Leukoaraiosis, a common ischaemic lesion diagnosed using magnetic resonance imaging (MRI), can influence driving safety performance (DSP). Most older drivers with leukoaraiosis are unaware of their affliction. Japan is a super-aged country, where preventing accidents caused by older drivers is an urgent national issue. We investigated the subcortical and periventricular leukoaraiosis regions that were most involved in DSP decline. The driving skills of 101 drivers (49 men, 52 women; mean age, 77.88 ± 3.77 years) without dementia were assessed by official driving instructors, using actual vehicles on a closed-circuit course. Parietal and occipital (but not frontal or temporal) leukoaraiosis volumes were significantly correlated with decreased DSP scores regardless of age, especially when turning right at intersections, which needs more attention than turning left because left-side driving is legally enforced in Japan. Occipital leukoaraiosis was also involved via a decline in dynamic visual cognitive function. MRI-based assessment of leukoaraiosis volume and localisation may enable the identification of older drivers prone to DSP deterioration. Risk factors for leukoaraiosis include smoking and lifestyle-related diseases such as hypertension. Thus, brain healthcare in patients with MRI-diagnosed leukoaraiosis may be particularly useful for the risk management of traffic accidents caused by the elderly in Japan.

Sex Differences in the Correlation between Fatigue Perception and Regional Gray Matter Volume in Healthy Adults: A Large-Scale Study.

The relationship between fatigue perception and regional gray matter volume (rGMV) has seldom been studied in healthy adults. Therefore, this study aimed to analyze sex differences in the correlation between rGMV and fatigue perception using Chalder's fatigue questionnaire (CFQ). The CFQ was used to analyze the sexual features of rGMV related to the degree of perceived fatigue in 2955 healthy adults (male = 1560, female = 1395) of various ages (20-89 years, median 56). A higher CFQ score denotes a higher perceived fatigue level by the participant. According to the CFQ scores in males, the volumes of the right orbital part of the inferior frontal gyrus and left precuneus were negatively correlated (i.e., smaller rGMV had a higher CFQ score), whereas the left angular gyrus was positively correlated. In females, the right inferior temporal gyrus was negative, whereas the left middle temporal gyrus and right putamen were positive (i.e., larger rGMV had a higher CFQ score). The lack of identified regions in this large-scale study between males and females might be related to sex differences in clinical or pathological fatigue morbidities. Additionally, the sex differences in the negative or positive correlations between rGMV and fatigue perception may contribute to a better understanding of the neuronal mechanism in the early stages of fatigue development.

Cerebral gray matter volume correlates with fatigue and varies between desk workers and non-desk workers.

Chronic fatigue syndrome (CFS), a clinical entity of chronic fatigue, has been associated with a decrease in regional gray matter volume (rGMV). In this study targeting a large number of healthy middle-aged individuals without CFS, the relationship between fatigue perception and rGMV was investigated. Considering that the work setting is an environmental factor that influences fatigue perception among healthy individuals, the differences between desk workers and non-desk workers were investigated. Chalder Fatigue Questionnaire (CFQ) scores were used for perceptional evaluation of fatigue, and rGMV of 110 brain regions was adapted with Statistical Parametric Mapping (SPM) 8 on 1.5 T magnetic resonance imaging (MRI) results for the volumetric calculation of gray matter. The CFQ scores were negatively correlated with the right supplementary motor area (SMC) and positively correlated with the right superior parietal lobule (SPL) and left basal forebrain in all participants (n = 1,618). In desk workers and non-desk workers, the CFQ scores correlated with different regions and yielded different mechanisms of fatigue perception in the brain. Identifying the gray matter regions correlated with fatigue perception in healthy individuals may help understand the early stage of fatigue progression and establish future preventive measures.

Associations of depressive symptoms with white matter abnormalities and regional cerebral blood flow in patients with amnestic mild cognitive impairment.

AIM: Depressive symptoms are one of the most common neuropsychiatric symptoms in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD), although the pathophysiologies of the depressive symptoms that occur in these diseases have not been elucidated to date. In this study, we therefore investigated the associations between depressive symptoms and cognitive performance, white matter abnormalities, and regional cerebral blood flow (rCBF) in amnestic MCI patients. METHODS: Thirty-eight patients with amnestic MCI were analyzed. The volumes of periventricular hyperintensities (PVH) and deep white matter hyperintensities (DWMH) were measured on T2-fluid-attenuated inversion recovery magnetic resonance imaging using the imaging software 3D-slicer. Associations between the Geriatric Depression Scale (GDS) score and other neuropsychological test scores on the one hand and the PVH and DWMH volumes on the other were analyzed. Voxel-wise correlations of rCBF with GDS score, after controlling for the effects of age, were investigated using SPM8 software. RESULTS: Significant correlations were identified between GDS score, Trail Making Test B and apathy scale scores on the one hand and PVH volume on the other. A significant negative association between GDS score and rCBF was identified in the right dominant bilateral dorsolateral prefrontal cortex (DLPFC). CONCLUSIONS: Depressive symptoms are significantly associated with PVH volume in MCI patients. The rCBF of the DLPFC was significantly associated with depressive symptoms, suggesting that this area might be closely involved in the pathogenesis of the depressive symptoms observed in MCI patients. Geriatr Gerontol Int 2022; 22: 846-850.

Association Between Diabetes and Gray Matter Atrophy Patterns in a General Older Japanese Population: The Hisayama Study.

OBJECTIVE: To examine the association between diabetes and gray matter atrophy patterns in a general older Japanese population. RESEARCH DESIGN AND METHODS: In 2012, a total of 1,189 community-dwelling Japanese aged ≥65 years underwent brain MRI scans. Regional gray matter volumes (GMV) and intracranial volume (ICV) were measured by applying voxel-based morphometry (VBM) methods. The associations of diabetes and related parameters with the regional GMV/ICV were examined using an ANCOVA. The regional gray matter atrophy patterns in the subjects with diabetes or elevated fasting plasma glucose (FPG) or 2-h postload glucose (2hPG) levels were investigated using VBM. RESULTS: Subjects with diabetes had significantly lower mean values of GMV/ICV in the frontal lobe, temporal lobe, insula, deep gray matter structures, and cerebellum than subjects without diabetes after adjusting for potential confounders. A longer duration of diabetes was also significantly associated with lower mean values of GMV/ICV in these brain regions. The multivariable-adjusted mean values of the temporal, insular, and deep GMV/ICV decreased significantly with elevating 2hPG levels, whereas higher FPG levels were not significantly associated with GMV/ICV of any brain regions. In the VBM analysis, diabetes was associated with gray matter atrophy in the bilateral superior temporal gyri, right middle temporal gyrus, left inferior temporal gyrus, right middle frontal gyrus, bilateral thalami, right caudate, and right cerebellum. CONCLUSIONS: The current study suggests that a longer duration of diabetes and elevated 2hPG levels are significant risk factors for gray matter atrophy in various brain regions.

Individual voxel-based morphometry adjusting covariates in multiple system atrophy.

INTRODUCTION: This study aimed to evaluate whether novel individual voxel-based morphometry adjusting covariates (iVAC), such as age, sex, and total intracranial volume, could increase the accuracy of a diagnosis of multiple system atrophy (MSA) and enable the differentiation of MSA from Parkinson's disease (PD). METHODS: We included 53 MSA patients (MSA-C: 33, MSA-P: 20), 53 PD patients, and 189 healthy controls in this study. All participants underwent high-resolution T1-weighted imaging (WI) and T2-WI with a 3.0-T MRI scanner. We evaluated the occurrence of significant atrophic findings in the pons/middle cerebellar peduncle (MCP) and putamen on iVAC and compared these findings with characteristic changes on T2-WI. RESULTS: On iVAC, abnormal findings were observed in the pons/MCP of 96.2% of MSA patients and in the putamen of 80% of MSA patients; however, on T2-WI, they were both observed at a frequency of 60.4% in MSA patients. On iVAC, all but one MSA-P patient (98.1%) showed significant atrophic changes in the pons/MCP or putamen. By contrast, 69.8% of patients with MSA showed abnormal signal changes in the pons/MCP or putamen on T2-WI. iVAC yielded 95.0% sensitivity and 96.2% specificity for differentiating MSA-P from PD. CONCLUSION: iVAC enabled us to recognize the morphological characteristics of MSA visually and with high accuracy compared to T2-WI, indicating that iVAC is a potential diagnostic screening tool for MSA.

Assessment of Impaired Cerebrovascular Reactivity in Chronic Cerebral Ischemia using Intravoxel Incoherent Motion Magnetic Resonance Imaging.

BACKGROUND: The severity of chronic cerebral ischemia can be assessed using cerebrovascular reactivity (CVR) to acetazolamide (ACZ) challenge, which is measured by single-photon emission computed tomography (SPECT); however, this is an invasive method. We investigated whether intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) can assess impaired CVR in preoperative patients with chronic cerebral ischemia and compared it to SPECT-CVR. METHODS: Forty-seven patients with unilateral cervical carotid artery stenosis underwent diffusion-weighted MRI with 11 b-values in the range of 0-800 s/mm2 and cerebral perfusion SPECT with the ACZ challenge. The perfusion fraction (f) and diffusion coefficient (D) of the IVIM parameters were calculated using a bi-exponential model. The f and D values and these ratios of the ipsilateral middle cerebral artery territory against the contralateral side were compared with the CVR values of the affected side calculated from the SPECT data. RESULTS: The IVIM-f and D values in the affected side were significantly higher than those in the unaffected side (median: 7.74% vs. 7.45%, p = 0.027; 0.816 vs. 0.801 10-3mm2/s, p < 0.001; respectively). However, there were no significant correlations between the f or D values and SPECT-CVR values in the affected side. In contrast, the f ratio showed a moderate negative correlation with the SPECT-CVR values (r = -0.40, p = 0.006) and detected impaired CVR (< 18.4%) with a sensitivity/specificity of 0.71/0.90. CONCLUSION: The IVIM perfusion parameter, f, can noninvasively assess impaired CVR with high sensitivity and specificity in patients with unilateral cervical carotid artery stenosis.

Association of regional white matter hyperintensity volumes with cognitive dysfunction and vascular risk factors in patients with amnestic mild cognitive impairment.

AIM: White matter hyperintensities (WMH) obtained by magnetic resonance imaging (MRI) have been reported to promote neurodegeneration and cognitive decline in patients with mild cognitive impairment (MCI). However, little is known about the association between regional WMH (rWMH) and cognitive dysfunction in MCI. We hence investigated the associations between rWMH volumes and cognitive dysfunction in MCI. METHODS: Thirty-eight subjects with amnestic MCI were analysed. The volumes of periventricular hyperintensities (PVH) and deep WMH (DWMH) were measured on a T2-FLAIR MRI using a 3D-slicer, and regional PVH and DWMH (rPVH and rDWMH) volumes were calculated. The associations of rPVH and rDWMH volumes with cognition and blood levels of various molecules were investigated. Furthermore, rPVH and rDWMH volumes were compared between MCI with vascular risk factors, such as hypertension, diabetes mellitus (DM), and dyslipidemia, and those without these risk factors. RESULTS: rPVH volume (bilateral cornu frontale, pars parietalis, and cornu occipitale) positively correlated with Trail Making Test-A/B scores and CysC level, whereas rDWMH volume did not correlate with any of the items. rPVH volumes (right cornu frontale, bilateral pars parietalis and cornu occipitale, and right pars temporalis) and rDWMH volumes (left frontal and parietal lobes) were significantly larger in MCI patients with DM than in those without. CONCLUSIONS: PVH volumes (bilateral areas of cornu frontale, pars parietalis, and cornu occipitale) were closely associated with attention and executive dysfunction. Serum CysC level and DM were associated with WMH volume, suggesting that CysC level and DM might be important markers for determining treatment strategies for white matter abnormalities in MCI. Geriatr Gerontol Int 2021; 21: 644-650.

Increase in masseter muscle activity by newly fabricated complete dentures improved brain function.

Purpose To reveal effects of improvement of masseter muscle activity on brain function in elderly people wearing complete dentures.Methods Subjects were 14 edentulous patients with a chief complaint of the inconvenience of their complete dentures. The surface electromyographic (EMG) activity of the masseter muscles was measured. Brain activities were analyzed with functional magnetic resonance imaging (fMRI), employing chewing gum as the task program. Cognitive functions were evaluated with Trail Making Test Part A (TMT-A), Rey Auditory Verbal Learning Test (RAVLT) and Rey-Osterrieth Complex Figure Test (R-OCFT). Those evaluations were performed in which subjects wore their old dentures (OD) or newly fabricated dentures (ND).Results We compared ND condition with OD condition. The masseter muscle activity significantly increased in ND condition (p < 0.05, Wilcoxon signed rank test). The brain activity increased significantly in the superior frontal gyrus, precentral gyrus, putamen, inferior parietal lobule, cerebellum, inferior frontal lobe, and middle frontal gyrus under the ND condition than under the OD condition (p < 0.01, uncorrected, cluster size > 10 voxels). Results of TMT-A, RAVLT, and R-OCFT were also significantly improved (p < 0.05, Wilcoxon signed rank test).Conclusions In the edentulous elderly, the brain activity was increased following the improvement of the masseter muscle activity. Consequently, it is possible that the improvement of the masseter muscle activity might influence on the attention, verbal skills, and visual memory.

Association of White Matter Hyperintensity Progression with Cognitive Decline in Patients with Amnestic Mild Cognitive Impairment.

BACKGROUND: White matter hyperintensities (WMH) on MRI have been reported to increase the risk of conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). However, effects of the progression of WMH on the cognition of patients with MCI remains unclear to date. OBJECTIVE: To investigate the association between WMH progression and cognitive decline in amnestic MCI patients. METHODS: Thirty-eight subjects with amnestic MCI were analyzed prospectively every year for 2 years. Fourteen MCI subjects dropped out on the final visit, and therefore 24 subjects with MCI were analyzed for the entire duration. The volumes of periventricular hyperintensities (PVH) and deep WMH (DWMH) were measured on T2 FLAIR using the 3D-slicer. The associations between PVH/DWMH progression and cognitive decline were investigated. RESULTS: An increase in DWMH volume significantly correlated with changes in Mini-Mental State Examination and category verbal fluency scores, whereas an increase in PVH volume did not correlate with changes in any item. CONCLUSION: DWMH progression was closely associated with a decline in frontal lobe function and semantic memory, suggesting that WMH progression might affect some AD pathophysiologies in amnestic MCI patients.

Guidelines for Management of Idiopathic Normal Pressure Hydrocephalus (Third Edition): Endorsed by the Japanese Society of Normal Pressure Hydrocephalus.

Among the various disorders that manifest with gait disturbance, cognitive impairment, and urinary incontinence in the elderly population, idiopathic normal pressure hydrocephalus (iNPH) is becoming of great importance. The first edition of these guidelines for management of iNPH was published in 2004, and the second edition in 2012, to provide a series of timely, evidence-based recommendations related to iNPH. Since the last edition, clinical awareness of iNPH has risen dramatically, and clinical and basic research efforts on iNPH have increased significantly. This third edition of the guidelines was made to share these ideas with the international community and to promote international research on iNPH. The revision of the guidelines was undertaken by a multidisciplinary expert working group of the Japanese Society of Normal Pressure Hydrocephalus in conjunction with the Japanese Ministry of Health, Labour and Welfare research project. This revision proposes a new classification for NPH. The category of iNPH is clearly distinguished from NPH with congenital/developmental and acquired etiologies. Additionally, the essential role of disproportionately enlarged subarachnoid-space hydrocephalus (DESH) in the imaging diagnosis and decision for further management of iNPH is discussed in this edition. We created an algorithm for diagnosis and decision for shunt management. Diagnosis by biomarkers that distinguish prognosis has been also initiated. Therefore, diagnosis and treatment of iNPH have entered a new phase. We hope that this third edition of the guidelines will help patients, their families, and healthcare professionals involved in treating iNPH.

Aging Brains Degrade Driving Safety Performances of the Healthy Elderly.

The relationship between aging brains and driving safety performances (DSPs) of elderly drivers was studied. A total of 90 dementia-free participants (63 men and 27 women, mean age 75.31 ± 4.795 years) were recruited and their DSPs were analyzed on actual vehicles running through a closed-circuit course. DSPs were comprehensively evaluated on the basis of driving instructors' scores (DIS). Signaling and visual research behaviors, part of DSPs, were measured to supplement the DIS evaluation by driving recorders (DR) and wearable wireless sensors (WS), respectively. Aging brains were evaluated via magnetic resonance imaging (MRI) findings and experimentally assigned to two grades (high vs. low) of brain atrophy (BA) and leukoaraiosis (LA). Regression analyses on DIS and DR data, and logistic analysis on WS scores showed significant correlations of aging brains with degradation of DSPs. The participant group with more advanced BAs and LAs showed lower DIS, DR data, and WS scores representing degraded DSP regardless of age. These results suggest that MRI examinations from both volumetric and pathological perspectives of brains have the potential to help identify elderly drivers with dangerous driving behaviors. Brain healthcare, lifestyle improvements and medical treatments to suppress BA and LA, may contribute to preventing DSP degradation of elderly drivers with aging brains.

Association between the superior longitudinal fasciculus and perceptual organization and working memory: A diffusion tensor imaging study.

The superior longitudinal fasciculus (SLF) is a white matter structure that has long bidirectional projections among the prefrontal, temporal, occipital, and parietal cortices and extends over a wide area in a human brain. Recently, anatomical details of the SLF have been clarified using a diffusion tensor imaging (DTI) template of subjects from the Human Connectome Project. However, the neurobehavioral functions of the SLF have not been fully elucidated. It is speculated that the SLF contributes to a broad cognitive domain including visuospatial nonverbal cognitive ability and verbal memory ability because of its anatomical location; however, previous findings in imaging studies are inconsistent. Showing the contribution of the SLF to cognitive function may be important for improving our understanding of the functional role of white matter structures in the human brain. This study aimed to identify the relationship between DTI indices of the SLF and the Verbal Comprehension, Perceptual Organization, Working Memory and Processing Speed Indices of the Wechsler Adult Intelligence Scale-Third Edition using regression analysis, accounting for the effects of age, sex and scanner type in 583 healthy volunteers. We showed significant correlations between the fractional anisotropy of the left SLF and the Perceptual Organization Index (ß = 0.21, p =  4.5×10-4) and Working Memory Index (ß = 0.19, p =  4.0×10-4). These findings may have implications for the rehabilitation of cognitive function in patients with neurological disorders.

Detection of impaired cerebrovascular reactivity in patients with chronic cerebral ischemia using whole-brain 7T MRA.

BACKGROUND: Cerebrovascular reactivity (CVR) to acetazolamide (ACZ) on single-photon emission computed tomography (SPECT) can be used to assess the severity of chronic cerebral ischemia; however, this is an invasive method. We examined whether whole-brain magnetic resonance angiography (MRA) at 7T could non-invasively detect impaired CVR in patients with chronic cerebral ischemia by demonstrating the leptomeningeal collaterals (LMCs). METHODS: Fifty-seven patients with symptomatic unilateral cervical stenosis underwent whole-brain time-of-flight MRA at 7T and cerebral perfusion SPECT before/after the ACZ challenge. MRA images were visually assessed based on 6-point grading systems to evaluate the development of LMCs toward the middle cerebral artery (MCA) and antegrade flow of MCA. CVR of the affected side was calculated from the SPECT data. Subsequently, we compared the LMC grades on MRA with CVR on SPECT. RESULTS: CVR was significantly lower in grades ≥ 2 of LMCs than in grades 0-1 (P < 0.05) when applying LMCs from the anterior cerebral artery (ACA) and/or posterior cerebral artery (PCA). These differences were more evident than those in the grading of the antegrade MCA flow. The LMC grades from ACA/PCA readily detected reduced CVR (< 18.4%) with a sensitivity/specificity of 0.79/0.82. CONCLUSION: The development of LMCs on whole-brain MRA at 7T can non-invasively detect reduced CVR with a high sensitivity/specificity in patients with unilateral cervical stenosis.

Promoter Activity-Based Case-Control Association Study on SLC6A4 Highlighting Hypermethylation and Altered Amygdala Volume in Male Patients With Schizophrenia.

Associations between altered DNA methylation of the serotonin transporter (5-HTT)-encoding gene SLC6A4 and early life adversity, mood and anxiety disorders, and amygdala reactivity have been reported. However, few studies have examined epigenetic alterations of SLC6A4 in schizophrenia (SZ). We examined CpG sites of SLC6A4, whose DNA methylation levels have been reported to be altered in bipolar disorder, using 3 independent cohorts of patients with SZ and age-matched controls. We found significant hypermethylation of a CpG site in SLC6A4 in male patients with SZ in all 3 cohorts. We showed that chronic administration of risperidone did not affect the DNA methylation status at this CpG site using common marmosets, and that in vitro DNA methylation at this CpG site diminished the promoter activity of SLC6A4. We then genotyped the 5-HTT-linked polymorphic region (5-HTTLPR) and investigated the relationship among 5-HTTLPR, DNA methylation, and amygdala volume using brain imaging data. We found that patients harboring low-activity 5-HTTLPR alleles showed hypermethylation and they showed a negative correlation between DNA methylation levels and left amygdala volumes. These results suggest that hypermethylation of the CpG site in SLC6A4 is involved in the pathophysiology of SZ, especially in male patients harboring low-activity 5-HTTLPR alleles.