Altered task-induced cerebral blood flow and oxygen metabolism underlies motor impairment in multiple sclerosis.
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ABSTRACT:
SUBMITTER: West KL
PROVIDER: S-EPMC7747162 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:To examine regional cerebral blood flow (rCBF) in incident mild cognitive impairment (MCI) and Alzheimer disease (AD) by using continuous arterial spin-labeling (CASL) magnetic resonance (MR) imaging.This study was approved by the local institutional review board and was compliant with HIPAA regulations. Informed consent was obtained. rCBF was measured in 38 control subjects, 29 MCI patients, and 37 AD patients who were participating in a longitudinal epidemiologic study. Multisection CASL MR imaging with alternating single and double adiabatic inversion pulses and ramp-sampled echo-planar imaging were performed to acquire 19 contiguous axial sections. Voxel-level rCBF was compared among groups by using an analysis of variance design; clusters of voxels with significant group differences were identified. Multiple regression models controlled for age, sex, and presence of hypertension and related the mean rCBF in those clusters to the presence of MCI and AD.MCI and AD patients had decreased rCBF in the posterior cingulate gyrus (P = .01) with extension to the medial precuneus compared with that in control subjects. MCI patients had increased rCBF in the left hippocampus (P < .001), right amygdala (P = .007), and rostral head of the right caudate nucleus and ventral putamen and globus pallidus (P = .003) compared with that in control subjects. AD patients had decreased rCBF relative to that in control subjects and MCI patients in the left inferior parietal (P = .005), left lateral frontal (P < .001), left superior temporal (P = .001), and left orbitofrontal (P = .003) cortices. AD patients had increased rCBF in the right anterior cingulate gyrus (P = .02) compared with that in control subjects.The transition from normal cognition to AD is associated with dynamic pathologic processes in the brain, and this is reflected by both decreases and increases in rCBF. Increases in rCBF suggest a cellular and vascular compensatory process associated with incipient AD.http://radiology.rsnajnls.org/cgi/content/full/2503080751/DC1.
| S-EPMC2680168 | biostudies-literature
Project description:During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, neurological symptoms increasingly moved into the focus of interest. In this prospective cohort study, we assessed neurological and cognitive symptoms in hospitalized coronavirus disease-19 (COVID-19) patients and aimed to determine their neuronal correlates. Patients with reverse transcription-PCR-confirmed COVID-19 infection who required inpatient treatment primarily because of non-neurological complications were screened between 20 April 2020 and 12 May 2020. Patients (age > 18 years) were included in our cohort when presenting with at least one new neurological symptom (defined as impaired gustation and/or olfaction, performance < 26 points on a Montreal Cognitive Assessment and/or pathological findings on clinical neurological examination). Patients with ≥2 new symptoms were eligible for further diagnostics using comprehensive neuropsychological tests, cerebral MRI and 18fluorodeoxyglucose (FDG) PET as soon as infectivity was no longer present. Exclusion criteria were: premorbid diagnosis of cognitive impairment, neurodegenerative diseases or intensive care unit treatment. Of 41 COVID-19 inpatients screened, 29 patients (65.2 ± 14.4 years; 38% female) in the subacute stage of disease were included in the register. Most frequently, gustation and olfaction were disturbed in 29/29 and 25/29 patients, respectively. Montreal Cognitive Assessment performance was impaired in 18/26 patients (mean score 21.8/30) with emphasis on frontoparietal cognitive functions. This was confirmed by detailed neuropsychological testing in 15 patients. 18FDG PET revealed pathological results in 10/15 patients with predominant frontoparietal hypometabolism. This pattern was confirmed by comparison with a control sample using voxel-wise principal components analysis, which showed a high correlation (R2 = 0.62) with the Montreal Cognitive Assessment performance. Post-mortem examination of one patient revealed white matter microglia activation but no signs of neuroinflammation. Neocortical dysfunction accompanied by cognitive decline was detected in a relevant fraction of patients with subacute COVID-19 initially requiring inpatient treatment. This is of major rehabilitative and socioeconomic relevance.
| S-EPMC8083602 | biostudies-literature
Project description:Despite their wide-spread use, only limited information is available on the comparative test-retest reliability of task-based functional and resting state magnetic resonance imaging measures of blood oxygen level dependence (tb-fMRI and rs-fMRI) and cerebral blood flow (CBF) using arterial spin labeling. This information is critical to designing properly powered longitudinal studies. Here we comprehensively quantified and compared the test-retest reliability and reproducibility performance of 8 commonly applied fMRI tasks, 6 rs-fMRI metrics and CBF in 30 healthy volunteers. We find large variability in test-retest reliability performance across the different tb-fMRI paradigms and rs-fMRI metrics, ranging from poor to excellent. A larger extent of activation in tb-fMRI is linked to higher between-subject reliability of the respective task suggesting that differences in the amount of activation may be used as a first reliability estimate of novel tb-fMRI paradigms. For rs-fMRI, a good reliability of local activity estimates is paralleled by poor performance of global connectivity metrics. Evaluated CBF measures provide in general a good to excellent test-reliability matching or surpassing the best performing tb-fMRI and rs-fMRI metrics. This comprehensive effort allows for direct comparisons of test-retest reliability between the evaluated MRI domains and measures to aid the design of future tb-fMRI, rs-fMRI and CBF studies.
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Project description:Many studies have shown abnormal cerebral blood flow (CBF) in schizophrenia; however, it remains unclear how topological properties of CBF network are altered in this disorder. Here, arterial spin labeling (ASL) MRI was employed to measure resting-state CBF in 96 schizophrenia patients and 91 healthy controls. CBF covariance network of each group was constructed by calculating across-subject CBF covariance between 90 brain regions. Graph theory was used to compare intergroup differences in global and nodal topological measures of the network. Both schizophrenia patients and healthy controls had small-world topology in CBF covariance networks, implying an optimal balance between functional segregation and integration. Compared with healthy controls, schizophrenia patients showed reduced small-worldness, normalized clustering coefficient and local efficiency of the network, suggesting a shift toward randomized network topology in schizophrenia. Furthermore, schizophrenia patients exhibited altered nodal centrality in the perceptual-, affective-, language-, and spatial-related regions, indicating functional disturbance of these systems in schizophrenia. This study demonstrated for the first time that schizophrenia patients have disrupted topological properties in CBF covariance network, which provides a new perspective (efficiency of blood flow distribution between brain regions) for understanding neural mechanisms of schizophrenia.
| S-EPMC4927570 | biostudies-literature
Project description:BackgroundVagus nerve stimulation (VNS) is an established palliative surgical treatment for refractory epilepsy. Recently, pairing VNS with rehabilitation received growing attention for their joint effect on neural plasticity. However, objective biological measurements proving the interaction between VNS effects and cortical recruitment are lacking. Studies reported that VNS induced little blood flow increase in the cerebral cortex.ObjectiveThis study tested the hypothesis that pairing VNS with a cognitive task amplifies task-induced cerebral blood flow (CBF).MethodsThis study included 21 patients implanted with vagus nerve stimulator to treat refractory epilepsy. Near-infrared spectroscopy (NIRS) with sensors on the forehead measured CBF changes in the frontal cortices in response to VNS. Cerebral blood flow was measured when VNS was delivered during a resting state or a verbal fluency task. We analyzed the VNS effect on CBF in relation to stimulation intensity and clinical responsiveness.ResultsWe observed no CBF change when VNS was delivered during rest, irrespective of stimulation intensity or responsiveness. Cerebral blood flow changed significantly when a verbal fluency task was paired with VNS in a stimulation intensity-dependent manner. Cerebral blood flow changes in the non-responders showed no intensity-dependency.ConclusionOur results could be an important biological proof of the interaction between VNS effects and cortical recruitment, supporting the validity of pairing VNS with rehabilitation.
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Project description:Background: Depression is common in Alzheimer's disease (AD) with an unclear neural mechanism. This study aimed to investigate the underlying cerebral perfusion associated with depression in AD and evaluate its clinical significance. Method: Twenty-one AD patients and 21 healthy controls (HCs) were enrolled in this study. The depressive symptom was defined according to the Hamilton Depression Rating Scale (HAMD). Nine patients were diagnosed as AD with depression symptoms (HAMD >7). Three-dimensional pseudocontinuous arterial spin labeling MR imaging was conducted to measure regional cerebral blood flow (CBF). Neuropsychological tests covered cognition and depressive scores. Between-group comparisons on clinical variables and regional CBFs, relationship between regional CBF and depressive score, and identification of AD patients with depression were performed using covariance analysis, linear regression, and receiver operating characteristic (ROC) analysis, respectively. Results: Compared with HCs, AD patients without depression exhibited lower gray matter CBF (p = 0.016); compared with AD patients without depression, AD patients with depression had higher CBF in the right supplementary motor area (39.23 vs. 47.91 ml/100 g/min, p = 0.017) and right supramarginal gyrus (35.54 vs. 43.85 ml/100 g/min, p = 0.034). CBF in the right supplementary motor area was correlated with depressive score (β = 0.46, p = 0.025). The combination of CBF in the right supplementary motor area and supramarginal gyrus and age could identify AD patients with depression from those without depression with a specificity of 100%, sensitivity of 66.67%, accuracy of 85.71%, and area under the curve of 0.87. Conclusions: Our findings suggested that hyperperfusion of the right supplementary motor area and right supramarginal gyrus were associated with depression syndrome in AD, which could provide a potential neuroimaging marker to evaluate the depression state in AD.
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Project description:Standard magnetic resonance imaging approaches offer high-resolution but indirect measures of neural activity, limiting understanding of the physiological processes associated with imaging findings. Here, we used calibrated functional magnetic resonance imaging during the resting state to recover low-frequency fluctuations of the cerebral metabolic rate of oxygen (CMRO2 ). We tested whether functional connections derived from these fluctuations exhibited organization properties similar to those established by previous standard functional and anatomical connectivity studies. Seventeen participants underwent 20 min of resting imaging during dual-echo, pseudocontinuous arterial spin labeling, and blood-oxygen-level dependent (BOLD) signal acquisition. Participants also underwent a 10 min normocapnic and hypercapnic procedure. Brain-wide, CMRO2 low-frequency fluctuations were subjected to graph-based and voxel-wise functional connectivity analyses. Results demonstrated that connections derived from resting CMRO2 fluctuations exhibited complex, small-world topological properties (i.e., high integration and segregation, cost efficiency) consistent with those observed in previous studies using functional and anatomical connectivity approaches. Voxel-wise CMRO2 connectivity also exhibited spatial patterns consistent with four targeted resting-state subnetworks: two association (i.e., frontoparietal and default mode) and two perceptual (i.e., auditory and occipital-visual). These are the first findings to support the use of calibration-derived CMRO2 low-frequency fluctuations for detecting brain-wide organizational properties typical of healthy participants. We discuss interpretations, advantages, and challenges in using calibration-derived oxygen metabolism signals for examining the intrinsic organization of the human brain.
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Project description:There is increasing evidence of central hyperexcitability in chronic whiplash-associated disorders (cWAD). However, little is known about how an apparently simple cervical spine injury can induce changes in cerebral processes. The present study was designed (1) to validate previous results showing alterations of regional cerebral blood flow (rCBF) in cWAD, (2) to test if central hyperexcitability reflects changes in rCBF upon non-painful stimulation of the neck, and (3) to verify our hypothesis that the missing link in understanding the underlying pathophysiology could be the close interaction between the neck and midbrain structures. For this purpose, alterations of rCBF were explored in a case-control study using H2(15)O positron emission tomography, where each group was exposed to four different conditions, including rest and different levels of non-painful electrical stimulation of the neck. rCBF was found to be elevated in patients with cWAD in the posterior cingulate and precuneus, and decreased in the superior temporal, parahippocampal, and inferior frontal gyri, the thalamus and the insular cortex when compared with rCBF in healthy controls. No differences in rCBF were observed between different levels of electrical stimulation. The alterations in regions directly involved with pain perception and interoceptive processing indicate that cWAD symptoms might be the consequence of a mismatch during the integration of information in brain regions involved in pain processing.
| S-EPMC5006659 | biostudies-literature
Project description:In sickle cell disease (SCD), oxygen delivery is impaired due to anemia, especially during times of increased metabolic demand, and cerebral blood flow (CBF) must increase to meet changing physiologic needs. But hyperemia limits cerebrovascular reserve (CVR) and ischemic risk prevails despite elevated CBF. The cerebral metabolic rate of oxygen (CMRO2 ) directly reflects oxygen supply and consumption and may therefore be more insightful than flow-based CVR measures for ischemic risk in SCD. We hypothesized that adults with SCD have impaired CMRO2 at rest and that a vasodilatory challenge with acetazolamide would improve CMRO2 . CMRO2 was calculated from CBF and oxygen extraction fraction (OEF), measured with arterial spin labeling and T2 -prepared tissue relaxation with inversion recovery (T2 -TRIR) MRI. We studied 36 adults with SCD without a clinical history of overt stroke, and nine healthy controls. As expected, CBF was higher in patients with SCD versus controls (mean?±?SD: 74?±?16 versus 46?±?5?mL/100?g/min, P?<?.001), resulting in similar oxygen delivery (SCD: 377?±?67 versus controls: 368?±?42??mol O2 /100g/min, P = .69). OEF was lower in patients versus controls (27?±?4 versus 35?±?4%, P?<?.001), resulting in lower CMRO2 in patients versus controls (102?±?24 versus 127?±?20??mol O2 /100g/min, P = .002). After acetazolamide, CMRO2 declined further in patients (P?<?.01) and did not decline significantly in controls (P = .78), indicating that forcing higher CBF worsened oxygen utilization in SCD patients. This lower CMRO2 could reflect variation between healthy and unhealthy vascular beds in terms of dilatory capacity and resistance whereby dysfunctional vessels become more oxygen-deprived, hence increasing the risk of localized ischemia.
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Project description:The neonatal brain is extremely vulnerable to injury during periods of hypoxia and/or ischemia. Risk of brain injury is increased during neonatal cardiac surgery, where pre-existing hemodynamic instability and metabolic abnormalities are combined with long periods of low cerebral blood flow and/or circulatory arrest. Our understanding of events associated with cerebral hypoxia-ischemia during cardiopulmonary bypass (CPB) remains limited, largely due to inadequate tools to quantify cerebral oxygen delivery and consumption non-invasively and in real-time. This pilot study aims to evaluate cerebral blood flow (CBF) and oxygen metabolism (CMRO2) intraoperatively in neonates by combining two novel non-invasive optical techniques: frequency-domain near-infrared spectroscopy (FD-NIRS) and diffuse correlation spectroscopy (DCS). CBF and CMRO2 were quantified before, during and after deep hypothermic cardiopulmonary bypass (CPB) in nine neonates. Our results show significantly decreased CBF and CMRO2 during hypothermic CPB. More interestingly, a change of coupling between both variables is observed during deep hypothermic CPB in all subjects. Our results are consistent with previous studies using invasive techniques, supporting the concept of FD-NIRS/DCS as a promising technology to monitor cerebral physiology in neonates providing the potential for individual optimization of surgical management.
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