Alterations In Cerebral Blood Flow Research Articles

Visualization of brain microvasculature and blood flow in vivo: Feasibility study using confocal laser endomicroscopy.

Qualitative and quantitative analyses of blood flow in normal and pathologic brain and spinal cord microvasculature were performed using confocal laser endomicroscopy (CLE). Blood flow in cortical, dural, and spinal cord microvasculature was assessed in vivo in swine. We assessed microvasculature under normal conditions and after vessel occlusion, brain injury due to cold or surgical trauma, and cardiac arrest. Tumor-associated microvasculature was assessed in vivo and ex vivo in 20 patients with gliomas. We observed erythrocyte flow in vessels 5-500µm in diameter. Thrombosis, flow arrest and redistribution, flow velocity changes, agglutination, and cells rolling were assessed in normal and injured brain tissue. Microvasculature in in vivo CLE images of gliomas was classified as normal in 68% and abnormal in 32% of vessels on the basis of morphological appearance. Dural lymphatic channels were discriminated from blood vessels. Microvasculature CLE imaging was possible for up to 30minutes after a 1mg/kg intravenous dose of fluorescein. CLE imaging allows assessment of cerebral and tumor microvasculature and blood flow alterations with subcellular resolution intraoperative imaging demonstrating precise details of real-time cell movements. Research and clinical scenarios may benefit from this novel intraoperative in vivo microscopic fluorescence imaging modality.

Glucose Control Has an Impact on Cerebral Blood Flow Alterations in Chronic Tinnitus Patients.

PurposeBoth tinnitus and type 2 diabetes mellitus (T2DM) are linked with cognitive decline and brain dysfunction. This study used arterial spin labeling (ASL) perfusion functional magnetic resonance imaging (fMRI) to examine the abnormal cerebral blood flow (CBF) patterns existed in tinnitus patients and potential relationships between the abnormal CBF and cognitive performance. The impact of T2DM on CBF alterations in tinnitus patients was further explored.MethodsSixty tinnitus patients and 40 non-tinnitus subjects were recruited. CBF images were collected and analyzed using ASL perfusion fMRI. Brain regions with CBF alterations between tinnitus patients and non-tinnitus controls were identified by one-way analysis of variance. Interaction effects between tinnitus and T2DM for CBF changes were also selected. Then, correlation analyses were calculated to specify the link between CBF changes and cognitive performance and between CBF changes and diabetic characteristics.ResultsTinnitus patients showed decreased CBF, primarily in the auditory area and default mode network (DMN), compared with non-tinnitus controls. Decreased CBF in these regions was correlated with executive function and attention. The interaction effect between tinnitus and T2DM was significant in the right medial prefrontal gyrus. Additionally, CBF in the right medial prefrontal gyrus was correlated with tinnitus distress and cognitive performance. In tinnitus patients, Hemoglobin A1c was associated with CBF in the right medial prefrontal gyrus.ConclusionTinnitus affects brain perfusion in the auditory area and DMN. T2DM and uncontrolled glucose levels may aggravate a CBF decrease in tinnitus patients. These new findings implied that tinnitus patients may benefit from blood glucose control in terms of their cognitive function and tinnitus distress.

The enigma of cerebral blood flow and cognition.

The enigma of cerebral blood flow and cognition.

Impact of CNS Diseases on Drug Delivery to Brain Extracellular and Intracellular Target Sites in Human: A "WHAT-IF" Simulation Study.

The blood–brain barrier (BBB) is equipped with unique physical and functional processes that control central nervous system (CNS) drug transport and the resulting concentration–time profiles (PK). In CNS diseases, the altered BBB and CNS pathophysiology may affect the CNS PK at the drug target sites in the brain extracellular fluid (brainECF) and intracellular fluid (brainICF) that may result in changes in CNS drug effects. Here, we used our human CNS physiologically-based PK model (LeiCNS-PK3.0) to investigate the impact of altered cerebral blood flow (CBF), tight junction paracellular pore radius (pararadius), brainECF volume, and pH of brainECF (pHECF) and of brainICF (pHICF) on brainECF and brainICF PK for 46 small drugs with distinct physicochemical properties. LeiCNS-PK3.0 simulations showed a drug-dependent effect of the pathophysiological changes on the rate and extent of BBB transport and on brainECF and brainICF PK. Altered pararadius, pHECF, and pHICF affected both the rate and extent of BBB drug transport, whereas changes in CBF and brainECF volume modestly affected the rate of BBB drug transport. While the focus is often on BBB paracellular and active transport processes, this study indicates that also changes in pH should be considered for their important implications on brainECF and brainICF target site PK.

Increased cerebral blood flow in the right anterior cingulate cortex and fronto-orbital cortex during go/no-go task in children with ADHD

Objective Arterial spin labeling (ASL) is a relatively new imaging modality in the field of the cognitive neuroscience. In the present study, we aimed to compare the dynamic regional cerebral blood flow alterations of children with ADHD and healthy controls during a neurocognitive task by using event-related ASL scanning. Methods The study comprised of 17 healthy controls and 20 children with ADHD. The study subjects were scanned on 3 Tesla MRI scanner to obtain ASL imaging data. Subjects performed go/no-go task during the ASL image acquisition. The image analyses were performed by FEAT (fMRI Expert Analysis Tool) Version 6. Results The mean age was 10.88 ± 1.45 and 11 ± 1.91 for the control and ADHD group, respectively (p = .112). The go/no-go task was utilized during the ASL scanning. The right anterior cingulate cortex (BA32) extending into the frontopolar and orbitofrontal cortices (BA10 and 11) displayed greater activation in ADHD children relative to the control counterparts (p < .001). With a lenient significance threshold, greater activation was revealed in the right-sided frontoparietal regions during the go session, and in the left precuneus during the no-go session. Conclusion These results indicate that children with ADHD needed to over-activate frontopolar cortex, anterior cingulate as well as the dorsal and ventral attention networks to compensate for the attention demanded in a given cognitive task.

Neurovascular coupling alterations in type 2 diabetes: a 5-year longitudinal MRI study

IntroductionRespective alterations in resting-state brain neural activity and cerebral blood flow (CBF) in type 2 diabetes mellitus (T2DM) have been reported. However, their coupling alteration in T2DM remains largely unknown.Research...

Mathematical Modelling in Hydrocephalus.

Various studies highlight the significance of alterations in cerebrospinal fluid (CSF) and cerebral blood flow (CBF) dynamics in the pathogenesis of hydrocephalus and suggest the role of mathematical modeling in studying these complex interactions. This narrative review discusses mathematical models of CSF and CBF dynamics, including Marmarou's compartmental model of CSF spaces and a model of cardiac changes in cerebral arterial blood volume. The diagnostic utility of CSF compensatory parameters is described along with current information on secondary model-based indices of cerebral hemodynamics in hydrocephalus. Compensatory parameters derived from the model of CSF circulation have long been used in the diagnosis and management of hydrocephalus patients. However, recent studies using mathematical models of cerebral circulation also show alterations in CBF dynamics, and model-based indices of cerebral hemodynamics, which can be calculated non-invasively using transracranial Doppler ultrasonography, can be used as a complementary source of information about the state of the cerebrospinal space.

Disrupted Regional Cerebral Blood Flow and Functional Connectivity in Pontine Infarction: A Longitudinal MRI Study.

Abnormal cerebral blood flow (CBF) and resting-state functional connectivity (rs-FC) are sensitive biomarkers of disease progression and prognosis. This study investigated neural underpinnings of motor and cognitive recovery by longitudinally studying the changes of CBF and FC in pontine infarction (PI). Twenty patients underwent three-dimensional pseudo-continuous arterial spin labeling (3D-pcASL), resting-state functional magnetic resonance imaging (rs-fMRI) scans, and behavioral assessments at 1 week, 1, 3, and 6 months after stroke. Twenty normal control (NC) subjects underwent the same examination once. First, we investigated CBF changes in the acute stage, and longitudinal changes from 1 week to 6 months after PI. Brain regions with longitudinal CBF changes were then used as seeds to investigate longitudinal FC alterations during the follow-up period. Compared with NC, patients in the left PI (LPI) and right PI (RPI) groups showed significant CBF alterations in the bilateral cerebellum and some supratentorial brain regions at the baseline stage. Longitudinal analysis revealed that altered CBF values in the right supramarginal (SMG_R) for the LPI group, while the RPI group showed significantly dynamic changes of CBF in the left calcarine sulcus (CAL_L), middle occipital gyrus (MOG_L), and right supplementary motor area (SMA_R). Using the SMG_R as the seed in the LPI group, FC changes were found in the MOG_L, middle temporal gyrus (MTG_L), and prefrontal lobe (IFG_L). Correlation analysis showed that longitudinal CBF changes in the SMG_R and FC values between the SMG_R and MOG_L were associated with motor and memory scores in the LPI group, and longitudinal CBF changes in the CAL_L and SMA_R were related to memory and motor recovery in the RPI group. These longitudinal CBF and accompany FC alterations may provide insights into the neural mechanism underlying functional recovery after PI, including that of motor and cognitive functions.

Age-related impairment of cerebral blood flow response to KATP channel opener in Alzheimer’s disease mice with presenilin-1 mutation

Local cerebral blood flow (CBF) responses to neuronal activity are essential for cognition and impaired CBF responses occur in Alzheimer’s disease (AD). In this study, regional CBF (rCBF) responses to the KATP channel opener diazoxide were investigated in 3xTgAD, WT and mutant Presenilin 1(PS1M146V) mice from three age groups using Laser-Doppler flowmetry. The rCBF response was reduced early in young 3xTgAD mice and almost absent in old 3xTgAD mice, up to 30%–40% reduction with altered CBF velocity and mean arterial pressure versus WT mice. The impaired rCBF response in 3xTgAD mice was associated with progression of AD pathology, characterized by deposition of intracellular and vascular amyloid-β (Aβ) oligomers, senile plaques and tau pathology. The nitric oxide synthase (NOS) inhibitor Nω-nitro-L-arginine abolished rCBF response to diazoxide suggesting NO was involved in the mediation of vasorelaxation. Levels of phosphor-eNOS (Ser1177) diminished in 3xTgAD brains with age, while the rCBF response to the NO donor sodium nitroprusside remained. In PS1M146V mice, the rCBF response to dizoxide reduced and high molecular weight Abeta oligomers were increased indicating PS1M146V contributed to the dysregulation of rCBF response in AD mice. Our study revealed an Aβ oligomer-associated compromise of cerebrovascular function in rCBF response to diazoxide in AD mice with PS1M146V mutation.

Association between fetoplacental Doppler results, placental pathology, and angiogenic factors among pregnant women with anxiety

ObjectiveThis study aimed to evaluate whether state and trait anxiety among pregnant women were associated with fetoplacental Doppler findings, abnormal placental pathology, and placental angiogenic factors. Materials and methodsA total of 102 pregnant women at 32–35 gestational weeks were recruited and examined prospectively. State and trait anxiety were measured using the State-Trait Anxiety Inventory. Using Doppler ultrasound, pulsatility index (PI) of the umbilical artery (UA), middle cerebral artery (MCA), and uterine artery (UtA) and cerebroplacental ratio (CPR) were determined. Doppler parameters were converted into multiples of the median (MoM). Abnormal placental pathology was classified into 2 groups: vascular underperfusion (VU) and histological chorioamnionitis (HCA). Immunohistochemical analysis was performed to examine placental cells staining positive for placental growth factor (PLGF) and hypoxia-inducible factor-1-α (HIF-1α), which are markers for angiogenesis and hypoxic status, respectively. ResultsWomen with high state anxiety scores had low MCA-PI MoM and CPR MoM, while those with high trait anxiety scores had low MCA-PI MoM. VU was associated with a higher incidence of high trait anxiety scores, and HCA was associated with a higher incidence of high state and trait anxiety scores. Regression analysis showed a relationship between maternal state anxiety on MCA-PI MoM and HCA after controlling for covariates. Maternal trait anxiety exhibited relationships with VU and HCA after adjustment. ConclusionOur results demonstrated that maternal anxiety is associated with altered fetal cerebral blood flow and abnormal placental pathology but is not associated with uteroplacental insufficiency and placental angiogenic factors.

JuSpace: A tool for spatial correlation analyses of magnetic resonance imaging data with nuclear imaging derived neurotransmitter maps.

Recent studies have shown that drug‐induced spatial alteration patterns in resting state functional activity as measured using magnetic resonance imaging (rsfMRI) are associated with the distribution of specific receptor systems targeted by respective compounds. Based on this approach, we introduce a toolbox (JuSpace) allowing for cross‐modal correlation of MRI‐based measures with nuclear imaging derived estimates covering various neurotransmitter systems including dopaminergic, serotonergic, noradrenergic, and GABAergic (gamma‐aminobutric acid) neurotransmission. We apply JuSpace to two datasets covering Parkinson's disease patients (PD) and risperidone‐induced changes in rsfMRI and cerebral blood flow (CBF). Consistently with the predominant neurodegeneration of dopaminergic and serotonergic system in PD, we find significant spatial associations between rsfMRI activity alterations in PD and dopaminergic (D2) and serotonergic systems (5‐HT1b). Risperidone induced CBF alterations were correlated with its main targets in serotonergic and dopaminergic systems. JuSpace provides a biologically meaningful framework for linking neuroimaging to underlying neurotransmitter information.

Arterial spin-labelling and magnetic resonance spectroscopy as imaging biomarkers for detection of epileptogenic zone in non-lesional focal impaired awareness epilepsy

BackgroundThe proper identification of an epileptic focus is a pivotal diagnostic issue; particularly in non-lesional focal impaired awareness epilepsy (FIAE). Seizures are usually accompanied by alterations of regional cerebral blood flow (rCBF) and metabolism. Arterial spin labeling-MRI (ASL-MRI) and proton magnetic resonance spectroscopy (1H-MRS) are MRI techniques that can, non-invasively, define the regions of cerebral perfusion and metabolic changes, respectively. The aim of the current study was to recognize the epileptogenic zone in patients with non-lesional FIAE by evaluating the interictal changes in rCBF and cerebral metabolic alterations, using PASL-MRI and 1H-MRS.ResultsFor identification of the epileptogenic zone, increased ASLAI% assessed by PASL-MRI (at a cut-off value ≥ 5.96%) showed 95.78% accuracy, and increased %AF (at a cut-off value ≥ 9.98%) showed 98.14% accuracy, while decreased NAA/(Cho + Cr) ratio estimated by multi-voxels (MV) 1H-MRS (at a cut-off value ≥ 0.59) showed 97.74% accuracy. Moreover, the combined use of PASL-MRI and MV 1H-MRS yielded 100% sensitivity, 98.45% specificity and 98.86% accuracy.ConclusionThe combined use of PASL-MRI and MV 1H-MRS can be considered as in-vivo proficient bio-marker for proper identification of epileptogenic zone in patients with non-lesional FIAE.

Cerebral blood flow alterations associated with high volume caudal block in infants

BackgroundHigh-volume (1.5 ml kg−1) caudal block in infants results in major reductions of cerebral blood flow velocity (CBFV) and cerebral oxygenation, caused by rostral CSF movement which increases intracranial pressure. The primary aim of this study was to determine the relationship between injected volume and CBFV changes. We hypothesised that this volume–blood flow relationship would have a similar albeit inverted shape to the well-known intracranial pressure volume–pressure curve. MethodsFifteen subjects, age 0–6 months, mean (range) weight 4.9 (2.1–6.4) kg, were studied. A 1.5 ml kg−1 caudal injection of 0.2% ropivacaine was administered in three phases separated by two pauses. Subjects were randomised into five groups, in whom the pauses were implemented at different pre-set proportions of the total injected volume. Middle cerebral artery Doppler ultrasonography was used for CBFV measurements (Vmax, peak CBF velocity; Vmin, lowest CBF velocity; velocity time index). Mean flow velocity, pulsatility index, and resistivity index were calculated, and haemodynamic parameters were recorded. ResultsCBFV parameters decreased in all patients. The most affected parameter, Vmin, was reduced by ∼50% (range 15–68%) compared with baseline. There was a nonlinear relationship between the volume of the first phase injection and the CBFV measurement during the first pause. Across all time points, there was a linear relationship between volume administered and CBFV. Systemic haemodynamic parameters remained stable throughout the study. ConclusionsInjection pauses appear to attenuate adverse CBFV increases during administration of a high-volume caudal block.

Day-to-Day Change in Pulsatility Index Describes Anterior Cerebral Circulation Disturbance and Functional Outcomes in Pediatric Traumatic Brain Injury.

Traumatic brain injury (TBI) is a significant source of morbidity and mortality in children. Transcranial Doppler (TCD) ultrasound measures the cerebral arterial circulation allowing for the calculation of pulsatility indices (PIs) that provide an assessment of cerebral blood flow alterations. However, the use of PI in children with TBI is poorly understood and may be an important measure for the nursing care of children. The purpose of this article is to define day-to-day PI change and to describe its relationship to injury characteristics and functional outcomes in children with TBI. We performed a secondary analysis of a prospective observational parent study of 40 children aged 2 months to 15 years with mild or moderate-severe TBI who had serial TCDs. Sequential TCD PI measurements of day-to-day change revealed several consistencies among the TBI severity groups. Day-to-day PI change was higher in children with a moderate-severe injury (40%) when compared with those with a mild injury (21%). Greater day-to-day PI change was seen in children whose Glasgow Outcome Scale-Extended Pediatrics scores worsened (25%) compared with those who had an improved (19%) or unchanged (23%) scores. This study is the first to report day-to-day PI change in children with TBI and provides early insights into anterior cerebral artery circulation alterations of children with TBI. Although further research is needed, this study provides early evidence that TCD may be a valuable noninvasive neuromonitoring option in the management of children with TBI.

Cerebral Hemodynamic Changes to Transcranial Doppler in Asymptomatic Patients with Fabry's Disease.

Background: Patients with Fabry’s disease (FD) may be asymptomatic or show a spectrum of clinical manifestations, including cerebrovascular disease, mainly affecting posterior circulation. Few and conflicting studies on cerebral blood flow (CBF) velocity by transcranial Doppler sonography (TCD) in asymptomatic FD (aFD) subjects have been published. Our study aims to assess TCD in aFD subjects to identify any preclinical CBF change. Methods: A total of 30 aFD subjects were consecutively recruited and compared to 28 healthy controls. Brain magnetic resonance imaging was normal in all participants. TCD was used to study blood flow velocity and indices of resistance of intracranial arteries from the middle cerebral artery (MCA), bilaterally, and from the basilar artery (BA). Cerebral vasomotor reactivity (CVR) was also evaluated from MCA. Results: No difference was found between groups for MCA parameters of CBF velocity and CVR. Compared to controls, a higher mean blood flow velocity and a lower resistance index from BA were observed in FD subjects. No correlation was found between any BA-derived TCD parameter and the level of lyso-globotriaosylceramide. Conclusions: aFD subjects show evidence of altered CBF velocity in posterior circulation. Preclinical detection of neurovascular involvement in FD might allow appropriate management and prevention of future cerebrovascular complications and disability.

Regional cortical thinning and cerebral hypoperfusion in patients with panic disorder

BackgroundAlthough recent neuroimaging studies have suggested that functional deficits in facial perception are associated with panic disorder (PD), the possibility of cortical thickness and perfusion abnormalities have not been studied in patients with PD. We aimed to investigate alterations in cortical thickness and regional cerebral blood flow (CBF) between PD patients and healthy controls (HCs) using three-dimensional (3D) T1-weighted magnetic resonance imagery (MRI) and 3D arterial spin labeling (ASL) perfusion MRI. MethodAn automated surface-based method (Cat12) measured the cortical thickness of each subject. Z-score normalization for CBF maps was used to generate Z-score maps. Statistical comparisons were performed using statistical parametric mapping with two-sample t-tests. ResultsSubjects with PD, unlike HCs, displayed cortical thinning in the right fusiform gyrus (FG). Post hoc analysis also revealed a decreased Z-score in the right FG. There was significant positive correlation between the Z-score and the cortical thickness of the right FG. The cortical thickness and Z-score were negatively correlated with the Panic Disorder Severity Scale and Hamilton Rating Scale for Anxiety scores. LimitationsThe small sample size may have restricted the identification of additional differences. Other caveats included the use of medication by nine participants. ConclusionsThese results provide further evidence of the significant role structural and functional deficits in the right FG play in patients with PD. Due to the observed regional specificity, this finding bears important clinical implications for potential treatment strategies.

Aberrant resting-state cerebral blood flow and its connectivity in primary dysmenorrhea on arterial spin labeling MRI

PurposeThis study aimed to clarify the resting-state cerebral blood flow alteration patterns induced by primary dysmenorrhea, investigate the relationships between cerebral blood flow alterations and clinical parameters of patients with primary dysmenorrhea, and explore whether brain regions with abnormal cerebral blood flow also feature functional connectivity changes. MethodsArterial spin labeling imaging and clinical parameters were acquired in 42 patients with primary dysmenorrhea and 41 healthy controls during their menstrual phases. Differences in cerebral blood flow were compared between the two groups, and the clusters with significant group differences were selected as the regions of interest for further statistical analyses. ResultsCompared to healthy controls, patients with primary dysmenorrhea exhibited increased cerebral blood flow in the bilateral precuneus, left posterior cingulate cortex, and right rolandic operculum. Among patients with primary dysmenorrhea, we identified a negative correlation between the cerebral blood flow in the right rolandic operculum and the visual analogue score for anxiety, and greater correlation between the functional connectivity in the precuneus/posterior cingulate cortex and the right middle cingulate cortex, and between the right rolandic operculum and the left inferior parietal lobule and the bilateral postcentral gyrus. DiscussionCerebral blood flow abnormalities associated with primary dysmenorrhea were mainly concentrated in the areas comprising the default mode network in primary dysmenorrhea patients, which could be involved in the central mechanism of primary dysmenorrhea. Cerebral blood flow alteration in the rolandic operculum may underlie an anxiety-induced compulsive tendency in patients with primary dysmenorrhea. Investigating the enhanced connectivity among various pain-related brain regions could improve understanding of the onset and development of primary dysmenorrhea.

The influence of obesity on cerebral blood flow in young adults using arterial spin labeling MRI.

Obesity causes damage to several organs, including the brain. Recent studies have been focusing on understanding the mechanisms through which obesity affects brain structure and function using neuroimaging techniques. A functional biomarker, such as cerebral blood flow (CBF), is a powerful tool that can be used to explore neural dysfunction. However, there is currently limited information regarding the association between CBF and obesity. The study was conducted to investigate the potential effect of obesity on brain perfusion in a young cohort aged 20-30 years. A total of 21 obese (body mass index (BMI) > 26 kg/m2 ) and 21 lean (BMI < 24 kg/m2 ) right-handed volunteers were included in this study. CBF was acquired using the 2D single post-labeling delay (PLD) arterial spin labeling (ASL) technique on a 3 T MRI scanner. A multiple regression analysis was performed to examine the difference in global and regional gray matter (GM) CBF between the groups. CBF value was assigned as the dependent variable, whereas age, sex, and group (obese or lean) were considered as the independent variables. Results showed that group-related differences in CBF were homogeneous across brain regions, as obese subjects had significantly lower global GM CBF than lean subjects (P < 0.05). In the voxelwise analysis, obese individuals had significantly lower CBF in the left pulvinar of the thalamus and visual association areas, including Brodmann area (BA) 7, BA18, and BA19, than lean subjects. Although the signal-to-noise ratio was slightly compromised for 2D sequences and subject-specific arterial transit time was not estimated due to a single PLD sequence, this study demonstrated alterations in CBF in obese subjects, particularly in regions of the pulvinar of the thalamus and its synchronously related areas such as visual association areas. These results suggest that ASL provides a potential platform for further obesity-related research.

Altered cerebral perfusion in bipolar disorder: A pCASL MRI study.

Neurovascular abnormalities are relevant to the pathophysiology of bipolar disorder (BD), which can be assessed using cerebral blood flow (CBF) imaging. CBF alterations have been identified in BD, but studies to date have been small and inconclusive. We aimed to determine cortical gray matter CBF (GM-CBF) differences between BD and healthy controls (HC) and to identify relationships between CBF and clinical or cognitive measures. Cortical GM-CBF maps were generated using Pseudo-Continuous Arterial Spin Labeling (pCASL) for 109 participants (BD, n=61; HC, n=48). We used SnPM13 to perform non-parametric voxel-wise two-sample t-tests comparing CBF between groups. We performed multiple linear regression to relate GM-CBF with clinical and cognitive measures. Analysis was adjusted for multiple comparisons with 10,000 permutations. Significance was set at a voxel level threshold of P<.001 followed by AlphaSim cluster-wise correction of P<.05. Compared to HCs, BD patients had greater GM-CBF in the left lateral occipital cortex, superior division and lower CBF in the right lateral occipital, angular and middle temporal gyrus. Greater GM-CBF in the left lateral occipital cortex correlated with worse working memory, verbal memory, attention and speed of processing. We found using voxel-wise regression that decreased gray matter CBF in the bilateral thalamus and cerebellum, and increased right fronto-limbic CBF were associated with worse working memory. No clusters were associated with clinical variables after FDR correction. Cortical GM-CBF alterations are seen in BD and may be related to cognitive function, which suggest neurovascular unit dysfunction as a possible pathophysiologic mechanism.

The preponderance of initial orthostatic hypotension in postural tachycardia syndrome.

Reduced systolic/diastolic blood pressure (BP) by >40/20 mmHg defines initial orthostatic hypotension (IOH). Rapid resolution of hypotension and lightheadedness follows, but tachycardia may be prolonged. We aimed to examine IOH in controls and patients with postural tachycardia syndrome (POTS) using indices of spontaneous fluctuations of heart rate (HR) and systolic BP as measures of cardiac baroreflex differences. We recruited otherwise healthy IOH patients without POTS (n = 20, 16 ± 3 yr), healthy volunteers (n = 32, 17 ± 3 yr), and POTS patients (n = 39, 17 ± 4 yr). Subjects were instrumented for electrocardiography and beat-to-beat BP. After 10 min supine, subjects stood for 5 min. Following supine recovery, subjects underwent 70° head-up tilt for 10 min to test for POTS. BP, HR, and time, referenced to standing, were measured at events during standing: minimum BP, BP recovery, peak HR, HR minimum, and steady state. Baseline HR and BP were higher in POTS compared with healthy groups. IOH occurred in 13% of controls and 51% of POTS patients. The BP minimum was lower in POTS. Parasympathetic modulation of cardiac baroreflex was decreased in all POTS and control-IOH subjects. Sympathetic indices were increased. Events following BP minimum occurred progressively later in all POTS and control-IOH subjects compared with non-IOH controls. IOH is more frequent in POTS than in controls with a lower minimum BP. POTS has markedly reduced heart rate variability and baroreflex, indicating reduced HR buffering of BP. POTS-IOH and control-IOH subjects had similar peak HR despite decreased minimum BP in POTS. IOH data indicate modest parasympathetic and cardiovagal baroreflex deficits in control-IOH subjects. Parasympathetic deficits are more severe in all POTS patients.NEW & NOTEWORTHY Significant initial orthostatic hypotension (IOH) occurs in ~50% of postural tachycardia syndrome (POTS) patients and 13% of controls. Heart rate and blood pressure recovery are prolonged in IOH sustaining lightheadedness; IOH is more prevalent and severe in POTS. Altered cerebral blood flow and cardiorespiratory regulation are more prevalent in POTS. Altered heart rate variability and baroreflex gain may cause nearly instantaneous lightheadedness in POTS. IOH alone fails to confer a strong probability of POTS.