Amyloid ß deposition in subcortical stroke patients and effects of educational achievement: A pilot study.

OBJECTIVE: A direct causal relationship of cerebrovascular risk factors/stroke to amyloid ß (Aß) deposition has yet to be shown. We conducted [11 C] Pittsburgh compound B (PiB)-positron emission tomography (PET) analysis on subacute ischemic stroke patients and healthy controls. We hypothesized that subacute ischemic stroke patients would show focal Aß accumulation in cortical regions, which would increase and extend over time during the chronic phase after stroke onset. METHODS: Patients were recruited 14 to 28 days after acute subcortical ischemic stroke and examined with [11 C]PiB-PET scans. Regional time-activity data were analyzed with the Logan graphical method. Whole brain voxel-based analysis was conducted to compare stroke patients with healthy controls. We also performed longitudinal comparison of patients with successive [11 C]PiB-PET scans 1 year after stroke. RESULTS: Voxel-based analysis revealed a significant increase of [11 C]PiB-BPND of the precuneus/posterior cingulate cortex (PCu/PCC) in stroke patients at the subacute stage. Based on stepwise multiple regression analysis of [11 C]PiB-BP changes during follow-up as the dependent variable, years of education was the best independent correlate. There was a significant negative relationship between changes in [11 C]PiB-BP and years of education. CONCLUSIONS: Our results suggest that processes before and after the onset of ischemic stroke may trigger Aß deposition in the PCu/PCC, whereby amyloid deposition begins at an early stage of Alzheimer's disease (AD). Our findings support the existence of a cooperative association between vascular risk factors/stroke and AD progression. Further, educational achievement had a protective effect against the increase in Aß accumulation.

Detection of brain amyloid-ß deposits due to the repetitive head trauma in a former karate player.

Head trauma is a well-established epidemiological risk factor for Alzheimer's disease, but a study of early detection of its pathology has not yet been performed in human patients in vivo. To address this issue, we performed 11 C-labelled Pittsburgh compound B-positron emission tomography on a right-handed 30-year-old man with cognitive deterioration after repetitive head trauma during karate matches. Structural magnetic resonance imaging was also performed on this patient. The same positron emission tomography analysis was performed on elderly healthy controls (15 men, mean age: 70.7 ± 6.2 years). To analyze grey matter volume, structural magnetic resonance imaging was performed on age-matched healthy controls (15 men, mean age: 28.5 ± 3.6 years). The cognitive deterioration in our patient was fixed and partially improved in the 10 years after the repetitive head trauma. However, Pittsburgh compound B-non-displaceable binding potential was significantly elevated in the patient. Volume reduction was shown in the medial temporal region, cerebellum, and the basal frontal cortex, while amyloid-ß increase was shown in the bilateral prefrontal cortex. This is the first study to show an early degenerative process due to head trauma in the prefrontal cortex, where structural damage is not yet visible. Early recognition of the degenerative pathology due to repetitive head trauma by amyloid and possibly tau imaging would help clinicians determine how to treat those with early symptoms.

Vascular responses to abrupt blood flow change after bypass surgery for complex intracranial aneurysms.

BACKGROUND: Bypass surgery for complex intracranial aneurysms (IAs) results in drastic blood flow changes in intracranial arteries. The aim of the study was to elucidate how vessels adapt to blood flow changes after bypass surgery with phase-contrast magnetic resonance imaging (PC-MRI). METHODS: This is a prospective observational study to assess changes of the blood flow in intracranial arteries after bypass surgery for IAs. Flow rates and vessel diameters were measured with PC-MRI in 52 intracranial arteries of 7 healthy volunteers and 31 arteries of 8 IA patients who underwent bypass surgery. Wall shear stress (WSS) was calculated with the Hagen-Poiseuille formula. In 18 arteries of 5 patients, the same measurement was performed 1, 3, and 12 months after surgery. RESULTS: PC-MRI showed a strong positive correlation between the flow rate and the third power of vessel diameter in both healthy volunteers (r = 0.82, P < 0.0001) and IA patients (r = 0.90, P < 0.0001), indicating the constant WSS. Of the 18 arteries in 5 patients, WSS increased in 7 arteries and decreased in 11 arteries immediately after surgery. In the WSS-increased group, WSS returned to the preoperative value in the third postoperative month. In the WSS-decreased group, WSS increased in the 12th month, but did not return to the preoperative level. CONCLUSIONS: In a physiological state, WSS was constant in intracranial arteries. Changed WSS after bypass surgery tended to return to the preoperative value, suggesting that vessel diameter and flow rate might be controlled so that WSS remains constant.

Mutual effect of cerebral amyloid ß and peripheral lymphocytes in cognitively normal older individuals.

OBJECTIVE: We hypothesized that cerebral amyloid accumulation is reflected in the periphery in the pre-dementia stage and used flow cytometry to investigate the peripheral lymphocytes as an easily accessible biomarker to observe neuro-inflammation. We aimed to determine whether peripheral lymphocytes are related to the cortical amyloid burden or vice versa in cognitively normal older subjects. METHODS: We applied [11 C] Pittsburgh compound B (PiB)-positron emission tomography to 36 cognitively normal older individuals, and Aß deposition was quantified by cortical binding potential (PiB-BPND ). Blood samples were obtained, and lymphocyte subsets were evaluated. We examined differences between low and high PiB-BPND groups in the percentage of B cells, T cells, helper T cells, cytotoxic T cells, regulatory T cells, and natural killer cells. RESULTS: Subjects with high PiB-BPND showed significantly higher percentage of cytotoxic T cells (%CD3+ ). Correlation analysis revealed a significant relationship between the percentage of cytotoxic T cells and global cortical mean PiB-BPND . Hierarchical regression analyses showed that cytotoxic T cells were significantly related to the value of global cortical mean PiB-BPND and vice versa. CONCLUSIONS: Our results indicated that a specific peripheral immune response, reflected in the increased ratio of cytotoxic T cells, could be regarded as a preclinical sign of AD and could be attributed to the Aß neuropathological mechanism. Copyright © 2017 John Wiley & Sons, Ltd.

High amyloid-ß deposition related to depressive symptoms in older individuals with normal cognition: a pilot study.

OBJECTIVE: Previous studies have reported depressive symptoms in the preclinical stages of Alzheimer's disease (AD). The objective of this study was to determine whether depressive symptoms are associated with cortical amyloid burden. In order to do this, we measured cortical amyloid via (11) C-labeled Pittsburgh Compound B ([(11) C]PIB) uptake using positron emission tomography (PET) in cognitively normal subjects. METHODS: We performed [(11) C]PIB-PET in 29 cognitively normal, older participants. Depressive symptoms were assessed using the 15-item Geriatric Depression Scale (GDS). Aß deposition was quantified by binding potential (BPND ), and the association between cortical mean BPND values and GDS scores was evaluated. Analysis of parametric BPND images was performed to examine the relationship between regional BPND and GDS scores. RESULTS: We found a positive correlation between depressive symptoms and mean cortical PIB-BPND in groups of subjects with middle to high PIB-BPND . There was little change in GDS-depression score between subjects with low and middle PIB-BPND levels, while an increase in GDS was shown in the high PIB-BPND group. The main BPND increase was localized to the precuneus/posterior cingulate cortex (PCu/PCC) in subjects with high PIB-BPND , and we found a significant positive relationship between PIB-BPND in this area and depressive symptoms. CONCLUSIONS: Emotional dysregulation because of Aß neuropathology in the PCu/PCC may relate to depressive symptoms. More specifically, we found that older, cognitively normal patients with depressive episodes were more likely to have underlying AD pathology. Thus, depressive symptoms may increase the predictive ability of the identification of future AD cases. Copyright © 2016 John Wiley & Sons, Ltd.

A structural model of age, grey matter volumes, education, and personality traits.

BACKGROUND: When the relationship between ageing and changes in personality traits is considered, it is important to know how they are influenced by biological and environmental factors. The present study examined the relationships between various factors associated with the effect of ageing on personality traits, including structural changes of the brain and environmental factors such as education. METHODS: We recruited 41 healthy subjects. We administered the NEO Five-Factor Inventory to assess personality factors. Magnetic resonance imaging was performed, and regional grey matter (GM) volumes were obtained. We identified associations in the correlation analysis of age, cerebral GM volume, years of education, and the personality trait of openness. Path analysis was used to estimate the relationships among these factors. RESULTS: The path analysis model of age, GM volume, years of education, and the personality trait of openness revealed that age has an indirect negative association with openness through GM volume and years of education. Ageing was related to a decrease in GM volume, which was in turn related to a decrease in the openness score. Older subjects generally had fewer years of education, which was related to a lower openness score. CONCLUSIONS: Maintaining openness against the effects of ageing is desirable, and our results imply that interventions against age-related cerebral atrophy and the promotion of opportunities for higher education may contribute to the development and stability of a healthy personality during the adult life course.

Low amyloid-ß deposition correlates with high education in cognitively normal older adults: a pilot study.

OBJECTIVE: Several epidemiological studies have found a lower incidence of Alzheimer's disease in highly educated populations, but the protective mechanism of education against the disease is still unclear. Our objective was to investigate the association between education and (11) C-labeled Pittsburgh Compound B (PIB) uptake with positron emission tomography in participants with normal cognitive ability. METHODS: We performed (11) C-labeled PIB positron emission tomography and neuropsychological testing in 30 cognitively normal older participants. Of the participants, 16 had a period of education less than 12 years (low-education group) and 14 had more than 13 years (high-education group). Amyloid-ß deposition was quantified by binding potential (BPND ) in several brain regions and was compared between the groups with different education levels. RESULTS: We found significantly higher cortical PIB-BPND in the cognitively normal participants with low education compared with the ones with high education. None of the brain regions in low-education group showed significantly lower BPND values. This finding was not affected by the inclusion of possible confounding variables such as age, sex, and general intelligence. Our findings indicated a reduced amyloid pathology in highly educated, cognitively normal, participants. CONCLUSIONS: Our findings lead to the proposal that early-life education has a negative association with Alzheimer's disease pathology. This proposal is not in opposition to the brain reserve hypothesis. People with more education might be prone to a greater inhibitory effect against amyloid-ß deposition before the preclinical stage. At the same time, they have a greater reserve capacity, and greater pathological changes are required for dementia to manifest.

Delayed atrophy in posterior cingulate cortex and apathy after stroke.

OBJECTIVE: A few studies have been performed on chronic structural changes after stroke. The primary purpose of the present study was to investigate regional cortical volume changes after the onset of stroke and to examine how the cortical volume changes affected neuropsychiatric symptoms. METHODS: Participants were 20 stroke patients and 14 control subjects. T1-MRI was performed twice, once at the subacute stage and again 6 months later, and whole brain voxel-based morphometric (VBM) analysis was used to detect significant cortical gray matter volume changes in patients. We also assessed the correlation between changes in cortical volumes and changes in neuropsychiatric symptoms during the 6 months following a stroke. RESULTS: In the present study, we found significant volume reductions in the anterior part of the posterior cingulate cortex (PCC) over the 6 months following a stroke by exploratory VBM analysis. We also found that the amount of volume change was significantly correlated with the change in apathy-scale scores during the 6 months poststroke. CONCLUSIONS: The present study suggests that delayed atrophic change is evident in the PCC 6 months after a stroke. There was greater apathetic change in the stroke patients with the larger volume reductions. The delayed atrophy of the PCC may reflect degeneration secondary to neuronal loss due to stroke. Such degeneration might have impaired control of goal-directed behavior, leading to the observed increase in apathy.

Microstructural abnormality in white matter, regulatory T lymphocytes, and depressive symptoms after stroke.

BACKGROUND: The purpose of the present study was to investigate the existence of microstructure abnormalities in the white matter circuit in stroke patients and its relationship to depressive episodes. To target the prevention of depression, we also investigated the relationship between lymphocyte subsets and cerebral abnormalities in patients. METHODS: Participants included 18 patients with acute ischemic stroke and 22 healthy control subjects. Diffusion tensor imaging was performed. Whole-brain voxel-based analysis was used to compare fractional anisotropy (FA) between groups. Blood samples were obtained, and the lymphocyte subsets were evaluated using flow cytometry. Follow-up examinations were conducted on 12 patients at 6 months. RESULTS: FA was decreased in the bilateral anterior limb of the internal capsule in stroke patients. At the 6-month follow-up examination, there was a significant increase in FA, which was associated with a lower depression scale score. Patients showed a decreased percentage of circulated regulatory T lymphocytes, and the degree of reduction was related to the decrease in the FA value in the internal capsule. CONCLUSIONS: FA reductions in the anterior limb of the internal capsule cause abnormality in the frontal-subcortical circuits and confer a biological vulnerability, which in combination with environmental stressors results in the onset of depression. Our findings also demonstrated the possibility of preventing post-stroke depression by targeting the role of regulatory T lymphocytes in brain tissue repair and regeneration after stroke.

Implantation study of small-caliber "biotube" vascular grafts in a rat model.

We developed autologous vascular grafts, called "biotubes," by simple and safe in-body tissue architecture technology, which is a practical concept of regenerative medicine, without using special sterile conditions or complicated in vitro cell treatment processes. In this study, biotubes of extremely small caliber were first auto-implanted to rat abdominal aortas. Biotubes were prepared by placing silicone rods (outer diameter 1.5 mm, length 30 mm) used as a mold into dorsal subcutaneous pouches in rats for 4 weeks. After argatroban coating, the obtained biotubes were auto-implanted to abdominal aortas (n = 6) by end-to-end anastomosis using a custom-designed sutureless vascular connecting system under microscopic guidance. Graft status was evaluated by contrast-free time-of-flight magnetic resonance angiography (TOF-MRA). All grafts were harvested at 12 weeks after implantation. The patency rate was 66.7 % (4/6). MRA showed little stenosis and no aneurysmal dilation in all biotubes. The original biotube had wall thickness of about 56.2 ± 26.5 µm at the middle portion and mainly random and sparse collagen fibers and fibroblasts. After implantation, the wall thickness was 235.8 ± 24.8 µm. In addition, native-like vascular structure was regenerated, which included (1) a completely endothelialized luminal surface, (2) a mesh-like elastin fiber network, and (3) regular circumferential orientation of collagen fibers and α-SMA positive cells. Biotubes could be used as small-caliber vascular prostheses that greatly facilitate the healing process and exhibit excellent biocompatibility in vascular regenerative medicine.

Microstructural white matter changes following gait training with Hybrid Assistive Limb initiated within 1 week of stroke onset.

The early initiation of robot-assisted gait training in patients with acute stroke could promote neuroplasticity. The aim of this study was to clarify the microstructural changes of white matter associated with gait training using Hybrid Assistive Limb (HAL) by diffusion tensor imaging (DTI). Patients with first-ever stroke and requiring a walking aid started gait training within 1 week of stroke onset. The patients were quasi-randomly assigned either to the conventional physical therapy (CPT) group or gait training using HAL (HAL) group. Motor function and DTI were examined at baseline and after 3-5 months. Voxel-based statistical analyses of fractional anisotropy (FA) images were performed using diffusion metric voxel-wise analyses. Volume of interest (VOI)-based analyses were used to assess changes in FA (ΔFA). Twenty-seven patients (17 in the CPT group and 10 in the HAL group) completed the study. There were improvements in motor function and independency in the CPT and HAL groups (p < .001). Compared to baseline, there were decreases in FA in the ipsi-lesional cerebral peduncle in the CPT group (p < .001) and increases in the contra-lesional rostrum of the corpus callosum in the HAL group (p < .001) at the second assessment, consistent with the mean ΔFA in each group from VOI analysis (CPT/HAL: cerebral peduncle, -0.066/-0.027, p = .027; corpus callosum, 0.002/0.042, p < .001). Gait training using HAL initiated within 1 week after stroke onset facilitated the recovery of inter-hemispheric communication and prevented the progression of Wallerian degeneration of the affected pyramidal tract.

Dendrite complexity of the posterior cingulate cortex as a substrate for recovery from post-stroke depression: A pilot study.

The neural basis of recovery from a depressive state remains poorly understood. The main purpose of this study was to determine the neural basis of vulnerability/resilience to depression in stroke patients in terms of changes in regional microstructure. The study included 20 individuals with acute ischaemic stroke. Symptoms of depression were assessed, and the intraneurite volume fraction and neurite orientation-dispersion index (ODI) were evaluated by a multi-shell diffusion imaging and neurite-orientation dispersion and density imaging model. Patients underwent follow-up examinations after 2 months and were classified into depression improvement and depression deterioration groups. A significant interaction effect of group × time on the ODI was shown by voxel-based analysis in the posterior cingulate cortex (PCC). The ODI change in the PCC was negatively correlated with the change in the depression scale scores at the 2-month time point. The increase in ODI in the PCC that occurred during the 2-month interval was thought to be associated with decreased depressive symptom scores. As the ODI represents the pattern of sprawling dendrite progression, our findings indicate that the dendritic complexity of the PCC is a substrate for recovery in individuals who experienced post-stroke psychosocial and biological stress.

123I-Labeled oxLDL Is Widely Distributed Throughout the Whole Body in Mice.

PURPOSE: Oxidized low-density lipoprotein (oxLDL) plays a key role in endothelial dysfunction, vascular inflammation, and atherogenesis. The aim of this study was to assess blood clearance and in vivo kinetics of radiolabeled oxLDL in mice. METHODS: We synthesized 123I-oxLDL by the iodine monochloride method, and performed an uptake study in CHO cells transfected with lectin-like oxLDL receptor-1 (LOX-1). In addition, we evaluated the consistency between the 123I-oxLDL autoradiogram and the fluorescence image of DiI-oxLDL after intravenous injection for both spleen and liver. Whole-body dynamic planar images were acquired 10 min post injection of 123I-oxLDL to generate regional time-activity curves (TACs) of the liver, heart, lungs, kidney, head, and abdomen. Regional radioactivity for those excised tissues as well as the bladder, stomach, gut, and thyroid were assessed using a gamma counter, yielding percent injected dose (%ID) and dose uptake ratio (DUR). The presence of 123I-oxLDL in serum was assessed by radio-HPLC. RESULTS: The cellular uptakes of 123I-oxLDL were identical to those of DiI-oxLDL, and autoradiograms and fluorescence images also exhibited consistent distributions. TACs after injection of 123I-oxLDL demonstrated extremely fast kinetics. The radioactivity uptake at 10 min post-injection was highest in the liver (40.8 ± 2.4% ID). Notably, radioactivity uptake was equivalent throughout the rest of the body (39.4 ± 2.7% ID). HPLC analysis revealed no remaining 123I-oxLDL or its metabolites in the blood. CONCLUSION: 123I-OxLDL was widely distributed not only in the liver, but also throughout the whole body, providing insight into the pathophysiological effects of oxLDL.

Significant correlation between openness personality in normal subjects and brain myelin mapping with T1/T2-weighted MR imaging.

BACKGROUND: The objective of this study was to examine the relationship between the myelination and the psychological trait of openness to experience in young cognitively normal volunteers using regional T1-weighted (T1w)/T2w ratios on magnetic resonance imaging (MRI). It was hypothesized that axonal myelination would be related to openness, thus linking trait creativity and mental illness. METHODS: We recruited 37 healthy subjects and administered the NEO Five-Factor Inventory to assess personality factors. Regional T1w/T2w MRI values were computed as surrogate indicators of myelination status and correlations between T1w/T2w values and various personality factors (e.g., trait of openness) were calculated with a voxel-based analysis using statistical parametric mapping. RESULTS: Significant negative correlations were identified between the trait of openness and T1w/T2w values in the medial frontal cortex, anterior cingulate cortex, posterior cingulate cortex, and posterior insula/adjacent putamen. These relationships remained significant even after adjusting for age, sex, and education as covariates. There were no significant correlations between other personality factors and regional volumes. CONCLUSIONS: Individual differences in openness may be associated with variations in intra-cortical myelination, specifically in the imaginative network of the brain including the midline core 'hubs' of the default mode network (anterior cingulate/medial frontal cortex and posterior cingulate cortex) and regions related to motivational state (posterior insula and adjacent putamen). Signal interference related to decreased myelination may facilitate flexible imagination and the trait of openness. Our findings assist in understanding the relationship between myelination and openness, as a link between creativity and mental illness.

Microstructural Differences in the Corpus Callosum in Patients With Bipolar Disorder and Major Depressive Disorder.

OBJECTIVE: It is difficult to distinguish between bipolar disorder and major depressive disorder (MDD) in patients lacking a clear history of mania. There is an urgent need for an objective biomarker for differential diagnosis. Using diffusion tensor imaging, this study investigated the differences in the brain white matter microstructure between patients with bipolar disorder and MDD. METHODS: Participants included 16 patients with bipolar disorder and 23 patients with MDD having depressed or euthymic states based on DSM-IV-TR criteria and 23 healthy volunteers. Whole-brain voxel-based morphometric analysis was used to detect any significant differences in fractional anisotropy between patients with bipolar disorder and MDD. The study was conducted between August 2011 and July 2015. RESULTS: We found a significant decrease in fractional anisotropy values in the anterior part of the corpus callosum in patients with bipolar disorder compared with MDD (P < .001), which did not depend on the patients' affective state. This decrease was associated with increased radial diffusivity values (P < .05), which was also found in patients with bipolar disorder when compared with healthy volunteers (P < .05). We predicted bipolar disorder and MDD in all patients using the fractional anisotropy values, with a correct classification rate of 76.9%. CONCLUSIONS: The present study revealed that patients with bipolar disorder have microstructural abnormalities in the corpus callosum during depressed or euthymic states, which may deteriorate the exchange of emotional information between the cerebral hemispheres, resulting in emotional dysregulation. Our results indicate the possible use of diffusion tensor imaging as a differential diagnostic tool.

Use of T1-weighted/T2-weighted magnetic resonance ratio to elucidate changes due to amyloid ß accumulation in cognitively normal subjects.

The ratio of signal intensity in T1-weighted (T1w) and T2-weighted (T2w) magnetic resonance imaging (MRI) was recently proposed to enhance the sensitivity of detecting changes in disease-related signal intensity. The objective of this study was to test the effectiveness of T1w/T2w image ratios as an easily accessible biomarker for amyloid beta (Aß) accumulation. We performed the T1w/T2w analysis in cognitively normal elderly individuals. We applied [11C] Pittsburgh Compound B (PiB)-PET to the same individuals, and Aß deposition was quantified by its binding potential (PiB-BPND). The subjects were divided into low and high PiB-BPND groups, and group differences in regional T1w/T2w values were evaluated. In the regions where we found a significant group difference, we conducted a correlation analysis between regional T1w/T2w values and PiB-BPND. Subjects with high global cortical PiB-BPND showed a significantly higher regional T1w/T2w ratio in the frontal cortex and anterior cingulate cortex. We found a significant positive relationship between the regional T1w/T2w ratio and Aß accumulation. Moreover, with a T1w/T2w ratio of 0.55 in the medial frontal regions, we correctly discriminated subjects with high PiB-BPND from the entire subject population with a sensitivity of 84.6% and specificity of 80.0%. Our results indicate that early Aß-induced pathological changes can be detected using the T1w/T2w ratio on MRI. We believe that the T1w/T2w ratio is a prospective stable biological marker of early Aß accumulation in cognitively normal individuals. The availability of such an accessible marker would improve the efficiency of clinical trials focusing on the initial disease stages by reducing the number of subjects who require screening by Aß-PET scan or lumbar puncture.

Interhemispheric functional disconnection because of abnormal corpus callosum integrity in bipolar disorder type II.

BACKGROUND: A significantly lower fractional anisotropy (FA) value has been shown in anterior parts of the corpus callosum in patients with bipolar disorder. AIMS: We investigated the association between abnormal corpus callosum integrity and interhemispheric functional connectivity (IFC) in patients with bipolar disorder. METHODS: We examined the association between FA values in the corpus callosum (CC-FA) and the IFC between homotopic regions in the anterior cortical structures of bipolar disorder (n=16) and major depressive disorder (n=22) patients with depressed or euthymic states. RESULTS: We found a positive correlation between the CC-FA and IFC values between homotopic regions of the ventral prefrontal cortex and insula cortex, and significantly lower IFC between these regions in bipolar disorder patients. CONCLUSIONS: The abnormal corpus callosum integrity in bipolar disorder patients is relevant to the IFC between homotopic regions, possibly disturbing the exchange of emotional information between the cerebral hemispheres resulting in emotional dysregulation. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

Association between chronic stress-induced structural abnormalities in Ranvier nodes and reduced oligodendrocyte activity in major depression.

Repeated stressful events are associated with the onset of major depressive disorder (MDD). We previously showed oligodendrocyte (OL)-specific activation of the serum/glucocorticoid-regulated kinase (SGK)1 cascade, increased expression of axon-myelin adhesion molecules, and elaboration of the oligodendrocytic arbor in the corpus callosum of chronically stressed mice. In the current study, we demonstrate that the nodes and paranodes of Ranvier in the corpus callosum were narrower in these mice. Chronic stress also led to diffuse redistribution of Caspr and Kv 1.1 and decreased the activity in white matter, suggesting a link between morphological changes in OLs and inhibition of axonal activity. OL primary cultures subjected to chronic stress resulted in SGK1 activation and translocation to the nucleus, where it inhibited the transcription of metabotropic glutamate receptors (mGluRs). Furthermore, the cAMP level and membrane potential of OLs were reduced by chronic stress exposure. We showed by diffusion tensor imaging that the corpus callosum of patients with MDD exhibited reduced fractional anisotropy, reflecting compromised white matter integrity possibly caused by axonal damage. Our findings suggest that chronic stress disrupts the organization of the nodes of Ranvier by suppressing mGluR activation in OLs, and that specific white matter abnormalities are closely associated with MDD onset.

Resting-state synchrony between the retrosplenial cortex and anterior medial cortical structures relates to memory complaints in subjective cognitive impairment.

Subjective cognitive impairment (SCI) is a clinical state characterized by subjective cognitive deficits without cognitive impairment. To test the hypothesis that this state might involve dysfunction of self-referential processing mediated by cortical midline structures, we investigated abnormalities of functional connectivity in these structures in individuals with SCI using resting-state functional magnetic resonance imaging. We performed functional connectivity analysis for 23 individuals with SCI and 30 individuals without SCI. To reveal the pathophysiological basis of the functional connectivity change, we performed magnetic resonance-diffusion tensor imaging. Positron emission tomography-amyloid imaging was conducted in 13 SCI and 15 nonSCI subjects. Individuals with SCI showed reduced functional connectivity in cortical midline structures. Reduction in white matter connections was related to reduced functional connectivity, but we found no amyloid deposition in individuals with SCI. The results do not necessarily contradict the possibility that SCI indicates initial cognitive decrements, but imply that reduced functional connectivity in cortical midline structures contributes to overestimation of the experience of forgetfulness.

Microstructural changes of the nucleus accumbens due to increase of estradiol level during menstrual cycle contribute to recurrent manic episodes--a single case study.

We examined a rapid-cycling bipolar disorder patient who demonstrated manic episode regularly at around day 7 of the menstrual cycle. We hypothesize that gonadal hormones may induce a state-dependent change in cerebral microstructure and function. Following this hypothesis, the serum levels of estradiol and progesterone were analyzed and diffusion tensor imaging data were examined between the manic and euthymic states of the patient. Estradiol levels increased in the late follicular phase at manic state when compared to the luteal or early follicular phase at euthymic state. DTI results showed that the patient had increased fractional anisotropy values at manic state in the bilateral nucleus accumbens (NAc) and its connected areas, which is a major projection field of the mesolimbic dopamine (DA) system, perhaps reflecting microstructural changes due to neuronal activation related to manic episodes. According to these results, we consider that the mesolimbic DA system of this patient has hypersensitivity to estradiol, and elevation of the estradiol level increases the activity of the dopaminergic system, which in turn may contribute to recurrent manic episodes. Our findings provide a clue for understanding how fluctuations in gonadal hormone may amplify or ameliorate the symptomatology of psychiatric disorders related to the menstrual cycle.