Structural Cerebral Abnormalities Research Articles

Exploring cerebral structural and functional abnormalities in a mouse model of post-traumatic headache induced by mild traumatic brain injury

Exploring cerebral structural and functional abnormalities in a mouse model of post-traumatic headache induced by mild traumatic brain injury

Cerebral neurovascular alterations in stable chronic obstructive pulmonary disease: a preliminary fMRI study.

Cognitive impairment (CI) is very common in patients with chronic obstructive pulmonary disease (COPD). Cerebral structural and functional abnormalities have been reported in cognitively impaired patients with COPD, and the neurovascular coupling changes are rarely investigated. To address this issue, arterial spin labeling (ASL) and resting-state blood oxygenation level dependent (BOLD) fMRI techniques were used to determine whether any neurovascular changes in COPD patients. Forty-five stable COPD patients and forty gender- and age-matched healthy controls were recruited. Furthermore, resting-state BOLD fMRI and ASL were acquired to calculate degree centrality (DC) and cerebral blood flow (CBF) respectively. The CBF-DC coupling and CBF/DC ratio were compared between the two groups. COPD patients showed abnormal CBF, DC and CBF/DC ratio in several regions. Moreover, lower CBF/DC ratio in the left lingual gyrus negatively correlated with naming scores, lower CBF/DC ratio in medial frontal cortex/temporal gyrus positively correlated with the Montreal Cognitive Assessment (MoCA), visuospatial/executive and delayed recall scores. These findings may provide new potential insights into neuropathogenesis of cognition decline in stable COPD patients.

Feasibility and safety of intranasally administered mesenchymal stromal cells after perinatal arterial ischaemic stroke in the Netherlands (PASSIoN): a first-in-human, open-label intervention study

Perinatal arterial ischaemic stroke (PAIS) is an important cause of neurodevelopmental disabilities. In this first-in-human study, we aimed to assess the feasibility and safety of intranasally delivered bone marrow-derived allogeneic mesenchymal stromal cells (MSCs) to treat PAIS in neonates. In this open-label intervention study in collaboration with all neonatal intensive care units in the Netherlands, we included neonates born at full term (≥36 weeks of gestation) with MRI-confirmed PAIS in the middle cerebral artery region. All eligible patients were transferred to the neonatal intensive care unit of the Wilhelmina Children's Hospital. Neonates received one dose of 45-50 × 106 bone-marrow derived MSCs intranasally within 7 days of presenting signs of PAIS. The primary endpoints were acute and subacute safety outcomes, including vital signs, blood markers, and the occurrence of toxicity, adverse events, and serious adverse events. The occurrence of unexpected cerebral abnormalities by a repeat MRI at 3 months of age was a secondary endpoint. As part of standard clinical follow-up at Wilhelmina Children's Hospital, we assessed corticospinal tract development on MRI and performed motor assessments at 4 months of age. This study is registered with ClinicalTrials.gov, NCT03356821. Between Feb 11, 2020, and April 29, 2021, ten neonates were enrolled in the study. Intranasal administration of MSCs was well tolerated in all ten neonates. No serious adverse events were observed. One adverse event was seen: a mild transient fever of 38°C without the need for clinical intervention. Blood inflammation markers (C-reactive protein, procalcitonin, and leukocyte count) were not significantly different pre-administration versus post-administration and, although thrombocyte levels increased (p=0·011), all were within the physiological range. Follow-up MRI scans did not show unexpected structural cerebral abnormalities. All ten patients had initial pre-Wallerian changes in the corticospinal tracts, but only four (40%) patients showed asymmetrical corticospinal tracts at follow-up MRI. Abnormal early motor assessment was found in three (30%) infants. This first-in-human study demonstrates that intranasal bone marrow-derived MSC administration in neonates after PAIS is feasible and no serious adverse events were observed in patients followed up until 3 months of age. Future large-scale placebo-controlled studies are needed to determine the therapeutic effect of intranasal MSCs for PAIS. Netherlands Organization for Health Research and Development (ZonMw).

Impact of perinatal management on neurodevelopmental outcomes in congenital heart disease

With advancements in cardiopulmonary bypass technique and perioperative care, there has been a progressive decline in mortality associated with neonatal surgical correction of congenital heart disease (CHD). Thus, there is now increased focus on improving neurodevelopmental outcomes in CHD survivors. While the cause of these neurodevelopmental impairments is multifactorial, there is increasing evidence that structural and functional cerebral abnormalities are present before cardiac corrective repair. This suggests that in addition to patient specific risk factors, underlying cardiac physiology and clinical hemodynamics are critical to brain health and development. Prenatal diagnosis of CHD and subsequent optimization of perinatal care may therefore be important modifiable factors for long-term neurodevelopmental outcome.This article reviews the impact that prenatal diagnosis of CHD has on perinatal care and the preoperative clinical status of a neonate, as well as the potential influence this may have on lessening the degree of cerebral injury and long-term neurodevelopmental impairments.

Distinct neuroanatomic subtypes in antipsychotic-treated patients with schizophrenia classified by the predefined classification in a never-treated sample.

Distinct neuroanatomic subtypes have been identified in never-treated patients with schizophrenia based on cerebral structural abnormalities, but whether antipsychotic-treated patients would be stratified under the guidance of such previously formed classification remains unclear. The present study aimed to investigate alterations of brain structures in antipsychotic-treated patients with schizophrenia based on a predefined morphological classification and their relationships with cognitive performance. Cortical thickness, surface area, and subcortical volume were extracted from 147 antipsychotic-treated patients with schizophrenia using structural magnetic resonance imaging for classification. The Brief Assessment of Cognition in Schizophrenia (BACS) and Positive and Negative Syndrome Scale (PANSS) were used to assess cognition and symptoms. Antipsychotic-treated patients were categorized into three subtypes with distinct patterns of brain morphological alterations. Subtypes 1 and 2 were characterized by widespread deficits in cortical thickness but relatively limited deficits in surface area. In contrast, subtype 3 demonstrated cortical thickening mainly in parietal-occipital regions and widespread deficits in surface area. All three subgroups demonstrated cognitive deficits compared with healthy controls. Significant associations between neuroanatomic and cognitive abnormalities were only observed in subtype 1, where cortical thinning in the left lingual gyrus was conversely related to symbol coding performance. Similar to drug-naïve patients, neuroanatomic heterogeneity exists in antipsychotic-treated patients, with disparate associations with cognition. These findings promote our understanding of relationships between neuroanatomic abnormalities and cognitive performance in the context of heterogeneity. Moreover, these results suggest that neurobiological heterogeneity needs to be considered in cognitive research in schizophrenia.

Cerebral Structural Abnormalities and Their Associations With Peripheral Cytokine Levels in a Group of Untreated Patients With Nasopharyngeal Carcinoma.

The current study is to characterize the alterations of peripheral cytokines and anatomical brain changes, and their relationships in untreated nasopharyngeal carcinoma (NPC) patients with depressive symptoms. Twenty-nine newly diagnosed NPC patients without any treatment and 46 matched healthy comparisons were recruited, scanned with high-resolution T1 images and assessed psychologically using Hamilton Rating Scale for Depression (HAMD). Serum levels of interleukin-1 beta (IL-1β), IL-2, IL-6, IL-8, IL-10, interferon-gamma (IFN-γ) and transforming growth factor-beta (TGF-β) were measured by quantitative chemiluminescence assay. Inter-group comparisons of anatomical brain measures were performed, and regions with significant inter-group differences were correlated to HAMD scores and cytokines in NPC patients. A subgroup analysis especially within NPC patients with depression was conducted to precisely characterize the associations among serum cytokines, brain changes and depressive symptoms. Relative to healthy subjects, NPC patients showed significantly decreased cortical thickness in the left parahippocampal gyrus, increased surface area in the right superior parietal lobule and precentral gyrus, and increased gray matter volume in the right postcentral gyrus, bilateral caudate nucleus and right thalamus, as well as significantly elevated IL-1β, IL-2 and IL-10. The elevated IL-2 and IL-10 were negatively correlated with surface area in right superior parietal lobule, whilst IL-1β level was positively correlated to HAMD scores. In patients with depression, specific brain changes and evaluated IL-1β were identified, and the IL-1β interacted with right precentral gyrus to significantly affect the depressive symptoms. Our findings provide novel evidence indicating potential effects of inflammation on brain structure and behavior in NPC patients.

Mechanisms of Network Changes in Cognitive Impairment in Multiple Sclerosis.

Background and ObjectivesCognitive impairment in multiple sclerosis (MS) is associated with functional connectivity abnormalities. While there have been calls to use functional connectivity measures as biomarkers, there remains to be a full understanding of why they are affected in MS. In this cross-sectional study, we tested the hypothesis that functional network regions may be susceptible to disease-related “wear and tear” and that this can be observable on co-occurring abnormalities on other magnetic resonance metrics. We tested whether functional connectivity abnormalities in cognitively impaired patients with MS co-occur with (1) overlapping, (2) local, or (3) distal changes in anatomic connectivity and cerebral blood flow abnormalities.MethodsMultimodal 3T MRI and assessment with the Brief Repeatable Battery of Neuropsychological tests were performed in 102 patients with relapsing-remitting MS and 27 healthy controls. Patients with MS were classified as cognitively impaired if they scored ≥1.5 SDs below the control mean on ≥2 tests (n = 55) or as cognitively preserved (n = 47). Functional connectivity was assessed with Independent Component Analysis and dual regression of resting-state fMRI images. Cerebral blood flow maps were estimated, and anatomic connectivity was assessed with anatomic connectivity mapping and fractional anisotropy of diffusion-weighted MRI. Changes in cerebral blood flow and anatomic connectivity were assessed within resting-state networks that showed functional connectivity abnormalities in cognitively impaired patients with MS.ResultsFunctional connectivity was significantly decreased in the anterior and posterior default mode networks and significantly increased in the right and left frontoparietal networks in cognitively impaired relative to cognitively preserved patients with MS (threshold-free cluster enhancement corrected at p ≤ 0.05, 2 sided). Networks showing functional abnormalities showed altered cerebral blood flow and anatomic connectivity locally and distally but not in overlapping locations.DiscussionWe provide the first evidence that functional connectivity abnormalities are accompanied by local cerebral blood flow and structural connectivity abnormalities but also demonstrate that these effects do not occur in exactly the same location. Our findings suggest a possibly shared pathologic mechanism for altered functional connectivity in brain networks in MS.

AUTS2 Regulates RNA Metabolism and Dentate Gyrus Development in Mice.

Human AUTS2 mutations are linked to a syndrome of intellectual disability, autistic features, epilepsy, and other neurological and somatic disorders. Although it is known that this unique gene is highly expressed in developing cerebral cortex, the molecular and developmental functions of AUTS2 protein remain unclear. Using proteomics methods to identify AUTS2 binding partners in neonatal mouse cerebral cortex, we found that AUTS2 associates with multiple proteins that regulate RNA transcription, splicing, localization, and stability. Furthermore, AUTS2-containing protein complexes isolated from cortical tissue bound specific RNA transcripts in RNA immunoprecipitation and sequencing assays. Deletion of all major functional isoforms of AUTS2 (full-length and C-terminal) by conditional excision of exon 15 caused breathing abnormalities and neonatal lethality when Auts2 was inactivated throughout the developing brain. Mice with limited inactivation of Auts2 in cerebral cortex survived but displayed abnormalities of cerebral cortex structure and function, including dentate gyrus hypoplasia with agenesis of hilar mossy neurons, and abnormal spiking activity on EEG. Also, RNA transcripts that normally associate with AUTS2 were dysregulated in mutant mice. Together, these findings indicate that AUTS2 regulates RNA metabolism and is essential for development of cerebral cortex, as well as subcortical breathing centers.

Hemodynamic and structural brain measures in high and low sedentary older adults

Due to its cardiovascular effects sedentary behaviour might impact cerebrovascular function in the long term, affecting cerebrovascular regulatory mechanisms and perfusion levels. Consequently this could underly potential structural brain abnormalities associated with cognitive decline. We therefore assessed the association between sedentary behaviour and brain measures of cerebrovascular perfusion and structural abnormalities in community-dwelling older adults. Using accelerometery (GENEActiv) data from The Irish Longitudinal Study on Ageing (TILDA) we categorised individuals by low- and high-sedentary behaviour (≤8 vs >8 hours/day). We examined prefrontal haemoglobin oxygenation levels using Near-Infrared Spectroscopy during rest and after an orthostatic challenge in 718 individuals (66 ± 8 years, 52% female). Global grey matter cerebral blood flow, total grey and white matter volume, total and subfield hippocampal volumes, cortical thickness, and white matter hyperintensities were measured using arterial spin labelling, T1, and FLAIR MRI in 86 individuals (72 ± 6 years, 55% female). While no differences in prefrontal or global cerebral hemodynamics were found between groups, high-sedentary individuals showed lower hippocampal volumes and increased white matter hyperintensities compared to their low-sedentary counterparts. Since these structural cerebral abnormalities are associated with cognitive decline and Alzheimer’s disease, future work exploring the causal pathways underlying these differences is needed.

Cortical morphometric changes associated with completeness, level, and duration of spinal cord injury in humans: A case-control study.

ObjectiveThis study investigated how the injury completeness, level, and duration of spinal cord injury (SCI) affect cortical morphometric changes in humans.MethodsT1‐weighted images were acquired from 59 SCI patients and 37 healthy controls. Voxel‐based morphometry analyses of the gray matter volume (GMV) were performed between SCI patients and healthy controls, complete SCI and incomplete SCI, and tetraplegia and paraplegia. Correlation analyses were performed to explore the associations between GMV and clinical variables in SCI patients.ResultsCompared to healthy controls, SCI patients showed decreased GMV in bilateral middle frontal gyrus, left superior frontal gyrus (SFG), left medial frontal gyrus in the whole‐brain analysis, while increased GMV in right supplementary motor area and right pallidum in ROI analysis. The complete SCI had lower GMV in left primary somatosensory cortex (S1) and higher GMV in left primary motor cortex compared with incomplete SCI. Lower GMV was identified in left thalamus and SFG in tetraplegia than that in paraplegia. Moreover, time since injury was positive with the GMV in right pallidum, positive correlations were observed between the GMV in bilateral S1 and total motor and sensory scores, whereas the GMV in left cuneus was negatively correlated with total motor and sensory scores in SCI patients.ConclusionsThe study provided imaging evidence for identifying cerebral structural abnormalities in SCI patients and significant differences in complete/incomplete and paraplegia/tetraplegia subgroups. These results suggested brain structural changes occur after SCI and these changes may depend on the injury completeness, level, and duration.

Pericallosal berry aneurysm associated with azygous anterior cerebral artery – a case report

Introduction. Azygos anterior cerebral artery is a rare variant of the anterior segment of the circle of Willis caused by an unusual fusion of the normally paired A2 segments of the anterior cerebral artery (ACA). Despite its rare occurrence, it is associated with various vascular and structural cerebral abnormalities, particularly berry aneurysms. Aim. We aimed to present a case of a 41-year-old female patient who presented to our neurology department with complaints of headache. Description of the case. She had a positive paternal history of aneurysmal subarachnoid hemorrhage. Magnetic resonance angiography (MRA) of her brain revealed an azygos ACA (bifurcating into two pericallosal arteries) which was associated with a saccular aneurysm at its bifurcation point. She was referred to the interventional radiology department for preventive endovascular treatment. Conclusion. Azygos ACA carries a high risk of aneurysm development and its occlusion can potentially compromise blood supply to both cerebral hemispheres. It is therefore crucial for clinicians to be aware of its significance and to report its presence in angiographic studies.

Towards Central Nervous System Involvement in Adults with Hereditary Myopathies.

There is increasing evidence of central nervous system involvement in numerous neuromuscular disorders primarily considered diseases of skeletal muscle. Our knowledge on cerebral affection in myopathies is expanding continuously due to a better understanding of the genetic background and underlying pathophysiological mechanisms. Intriguingly, there is a remarkable overlap of brain pathology in muscular diseases with pathomechanisms involved in neurodegenerative or neurodevelopmental disorders. A rapid progress in advanced neuroimaging techniques results in further detailed insight into structural and functional cerebral abnormalities. The spectrum of clinical manifestations is broad and includes movement disorders, neurovascular complications, paroxysmal neurological symptoms like migraine and epileptic seizures, but also behavioural abnormalities and cognitive dysfunction. Cerebral involvement implies a high socio-economic and personal burden in adult patients sometimes exceeding the everyday challenges associated with muscle weakness. It is especially important to clarify the nature and natural history of brain affection against the background of upcoming specific treatment regimen in hereditary myopathies that should address the brain as a secondary target. This review aims to highlight the character and extent of central nervous system involvement in patients with hereditary myopathies manifesting in adulthood, however also includes some childhood-onset diseases with brain abnormalities that transfer into adult neurological care.

Cerebral structural abnormalities and cognitive function in end-stage renal disease patients undergoing maintenance hemodialysis

Cerebral structural abnormalities and cognitive function in end-stage renal disease patients undergoing maintenance hemodialysis

Association of peripheral cytokine levels with cerebral structural abnormalities in schizophrenia

A large body of evidence indicates that both the altered cytokines that mediate the immune-inflammatory process and abnormal gray matter are associated with schizophrenia. Whether peripheral cytokines are related to cerebral structural abnormality remains unclear. Therefore, we aimed to investigate the association of peripheral cytokine levels with gray matter abnormalities at the whole brain level in schizophrenia. Forty-four outpatients with schizophrenia and 44 controls were recruited. The serum levels of interleukin-1 beta (IL-1β), IL-2, IL-6, IL-8, interferon-gamma (IFN-γ), transforming growth factor-beta (TGF-β), and IL-10 were measured using a quantitative chemiluminescence assay. High-resolution T1 weighted images were acquired from all subjects and processed using FreeSurfer software to obtain the cortical thickness, surface area, and cortical and subcortical gray matter volumes. The cytokines and cerebral structures were compared between patients and controls using analysis of covariance (ANCOVA). The association between the cytokines and whole cerebral structures was performed using stepwise linear regression. Patients had higher levels of IL-2, IL-6, IL-8, and IL-10 than controls. In patients, the IL-6 level was significantly associated with the cortical thickness in the left pars opercularis, right pars triangularis, left superior temporal gyrus, and right middle temporal gyrus, which showed structural differences between the two groups. Altered cytokine levels may be associated with particular but not all cortical abnormalities in schizophrenia, especially IL-6, which was significantly associated with the abnormal cortical thickness of the bilateral Broca’s area and temporal gyrus, which provided neuroimaging evidence to support the relationship between peripheral cytokines and the cerebral cortex in schizophrenia.

Brain Modulation by Electric Currents in Fibromyalgia: A Structured Review on Non-invasive Approach With Transcranial Electrical Stimulation.

Fibromyalgia syndrome (FMS) is a complex disorder where widespread musculoskeletal pain is associated with many heterogenous symptoms ranging from affective disturbances to cognitive dysfunction and central fatigue. FMS is currently underdiagnosed and often very poorly responsive to pharmacological treatment. Pathophysiology of the disease remains still obscure even if in the last years fine structural and functional cerebral abnormalities have been identified, principally by neurophysiological and imaging studies delineating disfunctions in pain perception, processing and control systems. On such basis, recently, neurostimulation of brain areas involved in mechanism of pain processing and control (primary motor cortex: M1 and dorsolateral prefrontal cortex: DLPFC) has been explored by means of different approaches and particularly through non-invasive brain stimulation techniques (transcranial magnetic and electric stimulation: TMS and tES). Here we summarize studies on tES application in FMS. The great majority of reports, based on direct currents (transcranial direct currents stimulation: tDCS) and targeting M1, showed efficacy on pain measures and less on cognitive and affective symptoms, even if several aspects as maintenance of therapeutical effects and optimal stimulation parameters remain to be established. Differently, stimulation of DLPFC, explored in a few studies, was ineffective on pain and showed limited effects on cognitive and affective symptoms. Very recently new tES techniques as high-density tDCS (HD-tDCS), transcranial random noise stimulation (tRNS) and tDCS devices for home-based treatment have been explored in FMS with interesting even if very preliminary results opening interesting perspectives for more effective, well tolerated, cheap and easy therapeutic approaches.

Sleep disturbance and cognition in people with TBI.

Sleep disturbance plays a significant role in cognitive impairment following traumatic brain injury (TBI). To summarize recent findings that examine sleep disturbance and cognition in TBI. Epidemiological information on sleep disorders in people with TBI is presented. A simple introduction to the role of sleep in normal cognition provides context for the literature on clinical populations. Current theory on the mechanisms underlying cognitive problems in people with sleep disorder is briefly described. Findings on the relationship between sleep disorder and cognitive problems in TBI is examined in more detail. Consistent reports of an association between sleep duration and cognition include several studies noting positive associations (shorter sleep duration accompanies cognitive impairment) and others observing negative associations (longer sleep duration accompanies cognitive problems). Both insomnia and hypersomnolence are forms of sleep disturbance that disrupt key mental processes such as memory consolidation. Obstructive sleep apnea, cerebral structural abnormalities, neurochemical changes and psychiatric pathology are implicated. Additional information is needed on how severity of injury impacts sleep and cognition. Hypothesized mechanisms underlying the effects of sleep on cognition in TBI should be empirically tested. Further, discrepancies between objective and subjective measures of sleep and cognition must be explored.

Cognitive Function Estimation in Children with Tuberous Sclerosis

Tuberous sclerosis (TSC) is a genetic disease characterized by cerebral structural abnormalities (such as cortical tubers, subependymal nodes and abnormal cerebral white matter) which are detected by means of neuroimaging methods (e.g., MRI). Typically, these events cause neurological complications (i.e., epilepsy).Objective: cognitive function estimation in TSC children considering severity and nature of clinical course of the disease. 15 children with tuberous sclerosis (i.e., experimental group) and 46 children with normal development (i.e., control group) aged 6-16 years old underwent neuropsychological examination. As a result, polymorphic disorders of higher mental functions were revealed in TSC children. Neuropsychological deficit (p<0.05) was detected. Namely, voluntary attention and memorization impairments were found in TSC children with normaldevelopment. Operational thinking disorders, immaturity of dynamic and kinesthetic movement basis, somatosensory gnosis, optical spatial or quasi-three-dimensional imaging, as well as insufficient oral/aural and semantical memorization were mentioned in TSC children with mental retardation. Regardless of mental development, TSC children demonstrate neurodynamic activity disorder (p<0.05) presented by slow task performance, increased exhaustibility and attention fluctuation. According to comparison between research findings and clinical course data, severity of cognitive disorders substantially depends on epilepsy onset age because early onset results in more severe developmental disorder (p<0.05). Since tuberous sclerosis is a dynamic disease with new potential symptoms arising over a lifetime, neuropsychological testing will provide timely mental status qualification and development of corrective actions to activate the cognitive activity of a child.
 Keywords: tuberous sclerosis, children, higher mental function (HMF) developmental disorders.

Structural and functional neuroimaging in attention-deficit/hyperactivity disorder.

Over the last decade, there has been a dramatic increase in the number of neuroimaging studies in attention-deficit/hyperactivity disorder (ADHD). In terms of brain structure, magnetic resonance imaging (MRI), and diffusion tensor imaging studies have evidenced differences in volume, surface-based measures (cortical thickness, surface area, and gyrification), and white matter integrity in different cerebral regions, in children and adults with ADHD compared to population norms. Abnormalities in the basal ganglia, prefrontal structures, and the corpus callosum have been the most consistently reported findings across studies. Hemodynamic (functional MRI, functional near-infrared spectroscopy, positron emission tomography, single-photon emission computed tomography) and magnetoencephalography measurements have also shown differences in neural activity during the execution of neuropsychological tasks and during rest, in widespread regions of the brain. Importantly, multimodal studies combining structural and functional methods have shown an intercorrelation between structural and functional abnormalities in ADHD. Further longitudinal studies are needed to clarify the effects of age and medication on brain structure and function in individuals with ADHD. WHAT THIS PAPER ADDS: In attention-deficit/hyperactivity disorder (ADHD), the brain is characterized by abnormal neural network interplay. Structural and functional cerebral abnormalities in ADHD are intercorrelated. Currently there is no neural biomarker that can be used in diagnosis. Longitudinal studies have shed light on the brain correlates of ADHD over the lifespan. The effects of stimulant intake on the brain correlates of ADHD remain unclear.

Brain structural network topological alterations of the left prefrontal and limbic cortex in psychogenic erectile dysfunction

ABSTRACTAim: Despite increasing understanding of the cerebral functional changes and structural abnormalities in erectile dysfunction, alterations in the topological organization of brain networks underlying psychogenic erectile dysfunction remain unclear.Materials and methods: Here, based on the diffusion tensor image data of 25 patients and 26 healthy controls, we investigated the topological organization of brain structural networks and its correlations with the clinical variables using the graph theoretical analysis.Results: Patients displayed a preserved overall small-world organization and exhibited a less connectivity strength in the left inferior frontal gyrus, amygdale and the right inferior temporal gyrus. Moreover, an abnormal hub pattern was observed in patients, which might disturb the information interactions of the remaining brain network. Additionally, the clustering coefficient of the left hippocampus was positively correlated with the duration of patients and the normalized betweenness centrality of the right anterior cingulate gyrus and the left calcarine fissure were negatively correlated with the sum scores of the 17-item Hamilton Depression Rating Scale.Conclusions: These findings suggested that the damaged white matter and the abnormal hub distribution of the left prefrontal and limbic cortex might contribute to the pathogenesis of psychogenic erectile dysfunction and provided new insights into the understanding of the pathophysiological mechanisms of psychogenic erectile dysfunction.

Deficiency of superoxide dismutase promotes cerebral vascular hypertrophy and vascular dysfunction in hyperhomocysteinemia.

There is an emerging consensus that hyperhomocysteinemia is an independent risk factor for cerebral vascular disease and that homocysteine-lowering therapy protects from ischemic stroke. However, the mechanisms by which hyperhomocysteinemia produces abnormalities of cerebral vascular structure and function remain largely undefined. Our objective in this study was to define the mechanistic role of superoxide in hyperhomocysteinemia-induced cerebral vascular dysfunction and hypertrophy. Unlike previous studies, our experimental design included a genetic approach to alter superoxide levels by using superoxide dismutase 1 (SOD1)-deficient mice fed a high methionine/low folate diet to produce hyperhomocysteinemia. In wild-type mice, the hyperhomocysteinemic diet caused elevated superoxide levels and impaired responses to endothelium-dependent vasodilators in cerebral arterioles, and SOD1 deficiency compounded the severity of these effects. The cross-sectional area of the pial arteriolar wall was markedly increased in mice with SOD1 deficiency, and the hyperhomocysteinemic diet sensitized SOD1-deficient mice to this hypertrophic effect. Analysis of individual components of the vascular wall demonstrated a significant increase in the content of smooth muscle and elastin. We conclude that superoxide is a key driver of both cerebral vascular hypertrophy and vasomotor dysfunction in this model of dietary hyperhomocysteinemia. These findings provide insight into the mechanisms by which hyperhomocysteinemia promotes cerebral vascular disease and ischemic stroke.