Increase In Cerebral Blood Flow Research Articles

Increase in Cerebral Blood Flow After Catheter Ablation of Atrial Fibrillation.

Recent studies have found that atrial fibrillation (AF) is a risk factor for cognitive impairment. Brain hypoperfusion is hypothesized as an underlying mechanism of cognitive decline in AF patients. This study sought to assess changes in cerebral blood flow (CBF) and brain volume after catheter ablation of AF. Patients undergoing catheter ablation of AF were enrolled in this prospective study. AF patients being treated with pharmaceuticals alone served as a control group. Brain magnetic resonance imaging was performed before and 6months after catheter ablation. CBF was assessed by 2-dimensional phase-contrast magnetic resonance angiography. Brain volume and bilateral hippocampal volume were measured using FreeSurfer software. Of the 57 study patients (age 64 ± 11 years; 45 men; paroxysmal AF: n=22; nonparoxysmal AF: n=35), 48patients were freed from tachyarrhythmia recurrence beyond a 3-month blanking period. Changes in CBF and brain perfusion over 6months were significantly greater in the study patients than control (CBF: 39.26 vs -34.86mL; P = 0.01, ANCOVA; brain perfusion: 3.78 vs -3.02mL/100mL/min; P = 0.009, ANCOVA), while changes in total brain volume and bilateral hippocampal volume were similar between 2 groups (total brain volume: 2.57 vs -2.15mL; P = 0.32, ANCOVA; bilateral hippocampal volume: 0.03 vs 0.04mL; P = 0.8, ANCOVA). Nonparoxysmal AF at baseline was an independent predictor of an increase in CBF of >32.6mL/min. Catheter ablation of AF has favorable effects on CBF, particularly in nonparoxysmal AF. Our results maypartially explain the association between cognitive decline and AF.

Experimental study of transcranial pulsed current stimulation on relieving athlete's mental fatigue.

To explore the effect of independently developed transcranial pulsed current stimulation (tPCS) on alleviating athlete's mental fatigue. A total of 60 college athletes were randomly divided into the active stimulation group (current intensity:1.5 mA, lasting for 15 min) and the sham stimulation group. Subjective questionnaires, behavior test, and functional near-infrared spectroscopy (fNIRS) test were conducted before and after the experiment. Two-way ANOVA with repeated measures was used to compare the differences in mental fatigue indexes before and after the two experimental conditions. After 7 days of exercise training, there was a significant difference in the main effect of the time factor in all indexes of the two groups (p < 0.05). The scores of rated perceived exertion (RPE) scale, positive and negative affect schedule (PANAS), critical flicker frequency (CFF), and reaction time (RT), in the tPCS treatment group, were better than those in the sham stimulation group (p < 0.05). After 7 days of exercise training, all the subjects had different degrees of athlete's mental fatigue; the subjects in the active stimulation group have a good evaluation of the tPCS developed by the research group without adverse actions. tPCS intervention can improve emotional state, reduce the subjective evaluation of fatigue, improve behavioral levels such as attention and reaction time and increase cerebral prefrontal blood flow and oxygen supply.

Hippocampal blood flow rapidly and preferentially increases after a bout of moderate-intensity exercise in older adults with poor cerebrovascular health.

Over the course of aging, there is an early degradation of cerebrovascular health, which may be attenuated with aerobic exercise training. Yet, the acute cerebrovascular response to a single bout of exercise remains elusive, particularly within key brain regions most affected by age-related disease processes. We investigated the acute global and region-specific cerebral blood flow (CBF) response to 15minutes of moderate-intensity aerobic exercise in older adults (≥65years; n = 60) using arterial spin labeling magnetic resonance imaging. Within 0-6min post-exercise, CBF decreased across all regions, an effect that was attenuated in the hippocampus. The exercise-induced CBF drop was followed by a rebound effect over the 24-minute postexercise assessment period, an effect that was most robust in the hippocampus. Individuals with low baseline perfusion demonstrated the greatest hippocampal-specific CBF effect post-exercise, showing no immediate drop and a rapid increase in CBF that exceeded baseline levels within 6-12minutes postexercise. Gains in domain-specific cognitive performance postexercise were not associated with changes in regional CBF, suggesting dissociable effects of exercise on acute neural and vascular plasticity. Together, the present findings support a precision-medicine framework for the use of exercise to target brain health that carefully considers age-related changes in the cerebrovascular system.

Assessment of cerebrovascular function in patients with sickle cell disease using transfer function analysis.

In patients with sickle cell disease (SCD), the delivery of oxygen to the brain is compromised by anemia, abnormal rheology, and steno‐occlusive vascular disease. Successful compensation depends on an increase in oxygen supply such as that provided by an increase in cerebral blood flow (CBF). We used magnetic resonance imaging to provide a high‐resolution assessment of the ability of SCD patients to respond to a vasoactive stimulus in middle, anterior, and posterior cerebral artery territories for both white and gray matter. Cerebrovascular reactivity (CVR) was measured as the blood oxygen level dependent signal (a surrogate for CBF) response to an increase in the end tidal partial pressure of CO2 (PETCO2). The dynamic aspect of the response was measured as the time constant of the first order response kinetics (tau). To confirm and support these findings we used an alternative examination of the response, transfer function analysis (TFA), to measure the responsiveness (gain), the speed of response (phase), and the consistency of the response over time (coherence). We tested 34 patients with SCD and compared the results to those of 24 healthy controls participants. The results from a three‐way ANOVA showed that patients with SCD have reduced CVR (p < 0.001) and lower coherence (p < 0.001) in gray matter and white matter and reduced gain in gray matter only (p < 0.001). In terms of the speed of the response to CO2, tau (p < 0.001) and TFA phase (p < 0.001) were increased in SCD patients compared to healthy control subjects. These findings show that the cerebrovascular responsiveness to CO2 in patients with SCD is both decreased and slowed compared to healthy controls.

COMPARATIVE ANALYSIS OF BRAIN BIOELECTRICAL ACTIVITY AND CIRCULATORY SUPPLY IN ADOLESCENTS WITH ACUTE HYPOXIA

Brain bioelectrical activity and the degree of cerebral blood supply directly determine physiological brain activity. There is insufficient evidence on the regularity and continuity of these processes. The aim of the study is to conduct a comparative analysis of brain bioelectrical activity and circulatory supply in adolescents with acute hypoxia. Materials and Methods. The authors examined 100 adolescent males of two age groups: Group 1 consisted of boys aged 12–14 years old, Group 2 included those aged 15–17. Results. The authors revealed a positive correlation between blood supply, metabolism and brain function. In early pubertal adolescents, puberty-associated endocrine changes have a significant effect on EEG and REG indices in adolescents with hypoxia. An increase in the rheographic index is accompanied by an increase in the alpha- and a decrease in the delta-rhythm indices. In pubertal adolescents, an increase in the rheographic index causes a decrease in alpha rhythm and an increase in slow-wave delta oscillations in the frontal and occipital leads. Under short-term hypoxia, an increase in the brain filling with blood is observed. Under oxygen depletion (14%), despite the increase in pulmonary and blood minute volumes, tissue hypoxia develops in pubertal adolescents. It is especially evident in the early puberty, as there is even a decrease in oxygen consumption in adolescents aged 12–14. In adolescents with hypoxia cerebral blood flow increases.

Improvement of brain perfusion in patients with chronic brain ischemia at epidural spinal cord electrical stimulation.

ObjectiveIncreasing life expectancy and aging of the population is accompanied by a steady increase in the number of elderly patients with chronic cerebral ischemia and age-related cognitive impairment associated with cerebral hypoperfusion and microangiopathy. The aim of this study was to identify long-term changes in cerebral blood flow (CBF) in patients with chronic cerebral ischemia at the epidural electrical stimulation of the spinal cord (SCS).Materials and methodsChanges in cerebral blood flow were studied according to CT perfusion in 59 patients (aged 55–78 years) with vertebrogenic pain syndromes and chronic cerebral ischemia during epidural electrical stimulation of the spinal cord at the cervical (C3–C5) and lower thoracic (Th9–Th10) levels.ResultsIn all patients, on the 5th day of trial SCS, an increase in cerebral blood flow by from 58.6 ± 1.13 ml/100 ml/min to 64.8 ± 1.21 ml/100 ml/min (p < 0.01) with stimulation at the Th9-Th10 level and from 58.8 ± 1.12 ml/100 ml/min to 68.2 ± 1.42 ml/100 ml/min (p < 0, 01) with stimulation at the C3-C5 level. These changes in brain perfusion were preserved during the follow-up examination 1 year after the implantation of chronic SCS system. The greatest increase in CBF was registered in the frontotemporal regions, subcortical structures and white matter of the brain. Changes in cerebral perfusion did not correlate with the degree of reduction in the severity of the accompanying pain syndrome. The change in CBF in the control group (32 patients) in all periods was not statistically significant.ConclusionOur results show that SCS is accompanied by a persistent improvement in brain perfusion, which may be potentially useful for developing methods for reducing age-related vascular disorders in the elderly.

Cumulative effect of simvastatin, l-arginine, and tetrahydrobiopterin on cerebral blood flow and cognitive function in Alzheimer’s disease

Background and objectivesVascular disease is a known risk factor for Alzheimer’s disease (AD). Endothelial dysfunction has been linked to reduced cerebral blood flow. Endothelial nitric oxide synthase pathway (eNOS) upregulation is known to support endothelial health. This single-center, proof-of-concept study tested whether the use of three medications known to augment the eNOS pathway activity improves cognition and cerebral blood flow (CBF).MethodsSubjects with mild AD or mild cognitive impairment (MCI) were sequentially treated with the HMG-CoA reductase synthesis inhibitor simvastatin (weeks 0–16), l-arginine (weeks 4–16), and tetrahydrobiopterin (weeks 8–16). The primary outcome of interest was the change in CBF as measured by MRI from baseline to week 16. Secondary outcomes included standard assessments of cognition.ResultsA total of 11 subjects were deemed eligible and enrolled. One subject withdrew from the study after enrollment, leaving 10 subjects for data analysis. There was a significant increase in CBF from baseline to week 8 by ~13% in the limbic and ~15% in the cerebral cortex. Secondary outcomes indicated a modest but significant increase in the MMSE from baseline (24.2±3.2) to week 16 (26.0±2.7). Exploratory analysis indicated that subjects with cognitive improvement (reduction of the ADAS-cog 13) had a significant increase in their respective limbic and cortical CBF.ConclusionsTreatment of mild AD/MCI subjects with medications shown to augment the eNOS pathway was well tolerated and associated with modestly increased cerebral blood flow and cognitive improvement.Trial registrationThis study is registered in https://www.clinicaltrials.gov; registration identifier: NCT01439555; date of registration submitted to registry: 09/23/2011; date of first subject enrollment: 11/2011.

Periodic electroencephalographic discharges and epileptic spasms involve cortico-striatal-thalamic loops on Arterial Spin Labeling Magnetic Resonance Imaging.

Periodic discharges are a rare peculiar electroencephalogram pattern, occasionally associated with motor or other clinical manifestations, usually observed in critically ill patients. Their underlying pathophysiology remains poorly understood. Epileptic spasms in clusters and periodic discharges with motor manifestations share similar electroencephalogram pattern and some aetiologies of unfavourable prognosis such as subacute sclerosing panencephalitis or herpes encephalitis. Arterial spin labelling magnetic resonance imaging identifies localizing ictal and inter-ictal changes in neurovascular coupling, therefore assumed able to reveal concerned cerebral structures. Here, we retrospectively analysed ictal and inter-ictal arterial spin labelling magnetic resonance imaging in patients aged 6 months to 15 years (median 3 years 4 months) with periodic discharges including epileptic spasms, and compared these findings with those of patients with drug-resistant focal epilepsy who never presented periodic discharges nor epileptic spasms as well as to those of age-matched healthy controls. Ictal electroencephalogram was recorded either simultaneously with arterial spin labelling magnetic resonance imaging or during the close time lapse of patients' periodic discharges, whereas inter-ictal examinations were performed during the patients' active epilepsy but without seizures during the arterial spin labelling magnetic resonance imaging. Ictal arterial spin labelling magnetic resonance imaging was acquired in five patients with periodic discharges [subacute sclerosing panencephalitis (1), stroke-like events (3), West syndrome with cortical malformation (1), two of them also had inter-ictal arterial spin labelling magnetic resonance imaging]. Inter-ictal group included patients with drug-resistant epileptic spasms of various aetiologies (14) and structural drug-resistant focal epilepsy (8). Cortex, striatum and thalamus were segmented and divided in six functional subregions: prefrontal, motor (rostral, caudal), parietal, occipital and temporal. Rest cerebral blood flow values, absolute and relative to whole brain, were compared with those of age-matched controls for each subregion. Main findings were diffuse striatal as well as cortical motor cerebral blood flow increase during ictal examinations in generalized periodic discharges with motor manifestations (subacute sclerosing panencephalitis) and focal cerebral blood flow increase in corresponding cortical-striatal-thalamic subdivisions in lateralized periodic discharges with or without motor manifestations (stroke-like events and asymmetrical epileptic spasms) with straight topographical correlation with the electroencephalogram focus. For inter-ictal examinations, patients with epileptic spasms disclosed cerebral blood flow changes in corresponding cortical-striatal-thalamic subdivisions (absolute-cerebral blood flow decrease and relative-cerebral blood flow increase), more frequently when compared with the group of drug-resistant focal epilepsies, and not related to Vigabatrin treatment. Our results suggest that corresponding cortical-striatal-thalamic circuits are involved in periodic discharges with and without motor manifestations, including epileptic spasms, opening new insights in their pathophysiology and new therapeutical perspectives. Based on these findings, we propose a model for the generation of periodic discharges and of epileptic spasms combining existing pathophysiological models of cortical-striatal-thalamic network dynamics.

Musical instrumental reading affects middle cerebral blood flow and cognitive function.

Playing a musical instrument includes reading music scores, playing, and listening in parallel. It is unclear which of these activities are responsible for an increase in cerebral blood flow. We investigated the factors increasing middle cerebral artery velocity (MCAv) during musical performance, and examined whether playing and reading music affects cognitive function. Seventeen musicians played an instrument with reading music, played music from memory, and read music scores in a randomized order, for 10 min each. The MCAv was continuously recorded from 5 min before to 10 min after the performance. A Stroop test was performed before and after performance. The MCAv increased significantly with reading music, playing from memory, and reading music. Stroop test scores increased significantly after music reading. These findings suggest that both music reading and playing an instrument are involved in the increase in MCAv during music performance. Cognitive function was transiently improved by playing musical instruments.

Role of transcranial Doppler in assessment of cerebral blood flow in full term neonates with extreme unconjugated hyperbilirubinemia

PurposeTo evaluate the difference in cerebral blood flow in neonates with and without extreme unconjugated hyperbilirubinemia.MethodsTranscranial Doppler parameters of 26 full term newborns with extreme unconjugated hyperbilirubinemia (UCH) were compared to 13 postnatal age and sex matched normal healthy neonates serving as controls. Resistance index (RI), pulsatility index (PI) and peak systolic velocity (PSV) were measured in the middle cerebral, internal carotid and posterior cerebral arteries on both sides by transcranial color Doppler ultrasound.ResultsAn increase in cerebral blood flow (decreased RI, PI and increased PSV) was observed in the extreme unconjugated hyperbilirubinemia (UCH) group. There was positive correlation between total serum bilirubin level and peak systolic velocity and vice versa with resistivity and pulsatility indices. Eight neonates developed clinical features of acute bilirubin encephalopathy and showed significantly increased peak systolic velocity in the right middle cerebral artery compared to those with normal outcome. Resistivity index and pulsatility index were lower in patients managed by exchange transfusion compared to those managed with phototherapy.ConclusionAn increase in cerebral blood flow was observed in neonates with UCH compared to those without hyperbilirubinemia. By assessing the cerebral blood flow velocity, resistivity index (RI), and pulsatility index (PI) of particular intracranial arteries, the transcranial Doppler can identify the at-risk neonates, for development of neurological affliction in extreme unconjugated hyperbilirubinemia.

Close association between spreading depolarization and development of infarction under experimental ischemia in anesthetized male mice

Clinical and experimental evidence suggests that spreading depolarizations (SD) usually occur in patients with ischemic or hemorrhagic stroke when the gray matter of the brain is affected. In this study, we evaluated spatiotemporal changes of cerebral blood flow (CBF) during middle cerebral artery (MCA) occlusion and examined the relationship between SD occurrence and cerebral infarct development. In male isoflurane-anesthetized C57BL/6J mice, CBF changes over the ipsilateral parietal bone were recorded by laser speckle flowgraphy during and after transient (45 min, n = 22) or permanent occlusion (n = 22) of the distal MCA. Infarct volume was evaluated 24 hr after the operation. Upon MCA occlusion, CBF decreased by −55.6 ± 8.5 % in the lowest CBF and linearly recovered with increasing distance from the region. At 1–10 min after onset of occlusion, SD occurred and concentrically propagated from the core region, showing a decrease of CBF in the whole observed area along with a transient hyperemia and oligemia in the normal region. SD spontaneously re-occurred and propagated around the ischemic area in 37 % of mice, accompanied with a marked decrease of CBF in the core or a marked increase of CBF in the normal region. The CBF response to SDs gradually changed from the core to the normal area, depending upon the distance from the core region. Infarction was not observed in transiently (n = 2) or permanently (n = 4) occluded mice without SD. The infarct area tended to be larger with increasing number of SDs in transiently occluded mice. In conclusion, our findings suggest that the occurrence of SD during ischemia might elicit infarct formation and/or influence infarct development.

Passive exercise increases cerebral blood flow velocity and supports a postexercise executive function benefit.

Executive function entails high-level cognitive control supporting activities of daily living. Literature has shown that a single-bout of exercise involving volitional muscle activation (i.e., active exercise) improves executive function and that an increase in cerebral blood flow (CBF) may contribute to this benefit. It is, however, unknown whether non-volitional exercise (i.e., passive exercise) wherein an individual's limbs are moved via an external force elicits a similar executive function benefit. This is a salient question given that proprioceptive and feedforward drive from passive exercise increases CBF independent of the metabolic demands of active exercise. Here, in a procedural validation participants (n=2) used a cycle ergometer to complete separate 20-min active and passive (via mechanically driven flywheel) exercise conditions and a non-exercise control condition. Electromyography showed that passive exercise did not increase agonist muscle activation or increase ventilation or gas exchange variables (i.e., V̇O2 and V̇CO2 ). In a main experiment participants (n=28) completed the same exercise and control conditions and transcranial Doppler ultrasound showed that active and passive exercise (but not the control condition) increased CBF through the middle cerebral artery (ps <.001); albeit the magnitude was less during passive exercise. Notably, antisaccade reaction times prior to and immediately after each condition showed that active (p < .001) and passive (p=.034) exercise improved an oculomotor-based measure of executive function, whereas no benefit was observed in the control condition (p=.85). Accordingly, results evince that passive exercise 'boosts' an oculomotor-based measure of executive function and supports convergent evidence that increased CBF mediates this benefit.

Inducing Paranoia is Linked to Increased Resting Amygdala Cerebral Blood Flow in Healthy Individuals

Among individuals with schizophrenia, paranoia has been linked to increased resting cerebral blood flow (CBF) in amygdala, suggesting that amygdala hyperactivity may be a mechanism for paranoid ideation. The present study tested this possible mechanism by assessing whether experimentally inducing paranoia in non-clinical, healthy participants resulted in increased amygdala CBF. Sixty-three undergraduates completed initial measurements of paranoia and resting CBF, via pseudo-continuous arterial spin labeling (pCASL) imaging, and were then randomly assigned to either a paranoia induction ( n = 32) or control ( n = 31) condition before completing a second pCASL scan and another paranoia assessment. Following the induction procedure, individuals in the paranoia induction condition reported fewer positive perceptions of others and greater state anxiety. Resting relative CBF values extracted from right amygdala also demonstrated an increase in CBF over time for individuals in the paranoia induction condition but a decrease in CBF over time for individuals in the control condition. Left amygdala showed no significant effects. These results support the idea that increased resting activity of the amygdala may be a neurobiological mechanism for paranoia.

Hypoxia alters posterior cingulate cortex metabolism during a memory task: A 1H fMRS study

Environmental hypoxia (fraction of inspired oxygen (FIO2) ∼ 0.120) is known to trigger a global increase in cerebral blood flow (CBF). However, regionally, a heterogeneous response is reported, particularly within the posterior cingulate cortex (PCC) where decreased CBF is found after two hours of hypoxic exposure. Furthermore, hypoxia reverses task-evoked BOLD signals within the PCC, and other regions of the default mode network, suggesting a reversal of neurovascular coupling. An alternative explanation is that the neural architecture supporting cognitive tasks is reorganised. Therefore, to confirm if this previous result is neural or vascular in origin, a measure of neural activity that is not haemodynamic-dependant is required.To achieve this, we utilised functional magnetic resonance spectroscopy to probe the glutamate response to memory recall in the PCC during normoxia (FIO2 = 0.209) and after two hours of poikilocapnic hypoxia (FIO2 = 0.120). We also acquired ASL-based measures of CBF to confirm previous findings of reduced CBF within the PCC in hypoxia.Consistent with previous findings, hypoxia induced a reduction in CBF within the PCC and other regions of the default mode network. Under normoxic conditions, memory recall was associated with an 8% increase in PCC glutamate compared to rest (P = 0.019); a change which was not observed during hypoxia. However, exploratory analysis of other neurometabolites showed that PCC glucose was reduced during hypoxia compared to normoxia both at rest (P = 0.039) and during the task (P = 0.046).We conclude that hypoxia alters the activity-induced increase in glutamate, which may reflect a reduction in oxidative metabolism within the PCC. The reduction in glucose in hypoxia reflects continued metabolism, presumably by non-oxidative means, without replacement of glucose due to reduced CBF.

Electrical parameters of transcranial direct current stimulation that effectively alter cerebral blood flow in experimental animals: a systematic review

Objective: To identify the electrical parameters of transcranial direct current stimulation (tDCS) that effectively alter cerebral blood flow in rats. Methodology: Six eletronic databases were searched with no time or language restrictions to identify experimental studies with rats using tDCS with anodal and/or cathodal stimulation with or without a comparison group. Internal validity was assessed via the following criteria: housing, lighting, temperature, water/food, groups randomization and ethical aspects. The ‘Laboratory Systematic Review Center for Laboratory animal Experimentation’ (SYRCLE) tool was used to assess risk of bias. The tDCS electrical parameters and cerebral blood flow were considered as primary outcomes and cerebral histological alterations as the secondary outcome. Results: Four articles were included. All four studies were considered to present a high level of scientific bias. The electrical tDCS parameters implemented were heterogeneous but overall, tDCS with anodal stimulation promoted an increase in cerebral blood flow while the cathodal stimulation decreased it. Cerebral histological alterations were assessed in two studies and tissue necrosis was reported in only one animal per study. Conclusion: The identification of tDCS electrical parameters that effectively alter cerebral blood flow in rats was not possible due to the heterogeneity of tDCS protocols being implemented in the literature. Considering the high risk of scientific bias in the included studies, the current available evidence regarding tDCS efficacy is insufficient and inconclusive.

Quantitative cerebrovascular reactivity MRI in mice using acetazolamide challenge.

To develop a quantitative MRI method to estimate cerebrovascular reactivity (CVR) in mice. We described an MRI procedure to measure cerebral vasodilatory response to acetazolamide (ACZ), a vasoactive agent previously used in human clinical imaging. Vascular response was determined by cerebral blood flow (CBF) measured with phase-contrast or pseudo-continuous arterial spin labeling MRI. Vasodilatory input intensity was determined by plasma ACZ level using high-performance liquid chromatography. We verified the source of the CVR MRI signal by comparing ACZ injection to phosphate-buffered saline injection and noninjection experiments. Dose dependence and feasibility of regional CVR measurement were also investigated. Cerebral blood flow revealed an exponential increase following intravenous ACZ injection, with a time constant of 1.62 min. In contrast, phosphate-buffered saline or noninjection exhibited a slow linear CBF increase, consistent with a gradual accumulation of anesthetic agent, isoflurane, used in this study. When comparing different ACZ doses, injections of 30, 60, 120, and 180 mg/kg yielded a linear increase in plasma ACZ concentration (p < 0.0001). On the other hand, CBF changes under these doses were not different from each other (p=0.50). The pseudo-continuous arterial spin labeling MRI with multiple postlabeling delays revealed similar vascular responses at different postlabeling delay values. There was a regional difference in CVR (p=0.005), with isocortex (0.81 ± 0.17%/[μg/ml]) showing higher CVR than deep-brain regions. Mice receiving multiple ACZ injections lived for a minimum of 6months after the study without noticeable aberrant behavior or appearance. We demonstrated the proof-of-principle of a new quantitative CVR mapping technique in mice.

Short periods of bipolar anodal TDCS induce no instantaneous dose-dependent increase in cerebral blood flow in the targeted human motor cortex

Anodal transcranial direct current stimulation (aTDCS) of primary motor hand area (M1-HAND) can enhance corticomotor excitability, but it is still unknown which current intensity produces the strongest effect on intrinsic neural firing rates and synaptic activity. Magnetic resonance imaging (MRI) combined with pseudo-continuous Arterial Spin Labeling (pcASL MRI) can map regional cortical blood flow (rCBF). The measured rCBF signal is sensitive to regional changes in neuronal activity due to neurovascular coupling. Therefore, concurrent TDCS and pcASL MRI may reveal the relationship between current intensity and TDCS-induced changes in overall firing rates and synaptic activity in the cortical target. Here we employed pcASL MRI to map acute rCBF changes during short-duration aTDCS of left M1-HAND. Using the rCBF response as a proxy for regional neuronal activity, we investigated if short-duration aTDCS produces an instantaneous dose-dependent rCBF increase in the targeted M1-HAND that may be useful for individual dosing. Nine healthy right-handed participants received 30 s of aTDCS at 0.5, 1.0, 1.5, and 2.0 mA with the anode placed over left M1-HAND and cathode over the right supraorbital region. Concurrent pcASL MRI at 3 T probed TDCS-related rCBF changes in the targeted M1-HAND. Movement-induced rCBF changes were also assessed. Apart from a subtle increase in rCBF at 0.5 mA, short-duration aTDCS did not modulate rCBF in the M1-HAND relative to no-stimulation periods. None of the participants showed a dose-dependent increase in rCBF during aTDCS, even after accounting for individual differences in TDCS-induced electrical field strength. In contrast, finger movements led to robust activation of left M1-HAND before and after aTDCS. Short-duration bipolar aTDCS does not produce consistant instantaneous dose-dependent rCBF increases in the targeted M1-HAND at conventional intensity ranges. Therefore, the regional hemodynamic response profile to short-duration aTDCS may not be suited to inform individual dosing of TDCS intensity.

1310-P: Effects of Insulin Resistance on Brain Responses to Caloric Sugars and Nonnutritive Sweetener

Evidence suggests that insulin resistance (IR) affects feeding behavior by modulating neural responses to post-ingestive signals, including nutrients and taste. We examined associations between IR and activation of the hypothalamus and insula, brain regions involved in homeostasis and taste processing, to ingestion of sugars and the non-nutritive sweetener (NNS) , sucralose. Seventy-four participants (23.4±4 years; 42%male; BMI 27.2±5; HOMA-IR 5.3±5) completed 4 MRI visits with ingestion of drinks containing 75g sucrose, 75g glucose, sucralose, or water in a randomized cross-over design. Arterial spin labeling MRI was performed before, 15min and 30min after drink ingestion to measure cerebral blood flow (CBF) . Primary outcomes were associations between HOMA-IR and hypothalamic and insular CBF responses to glucose vs. sucrose, sucralose vs. water, and sucrose vs. sucralose. Mixed effects models included the following factors: drink contrasts, sex, time point, and BMI and HOMA-IR as continuous variables. Bonferroni-Holm was used to adjust for multiple comparisons. In the hypothalamus, HOMA-IR, independent of BMI, was associated with a greater hypothalamic CBF response to sucralose vs. water (p&amp;lt;0.03) , but there was no association between HOMA-IR and hypothalamic response to sugar. In the insula, there was a drink by HOMA-IR interaction in the insular response to sucralose vs. water (p&amp;lt;0.02) ; persons with IR showed greater increases in CBF after sucralose vs. water. We also found a main effect of HOMA-IR; persons with higher IR had greater insular CBF increases to sugar (p&amp;lt;0.05) , and a drink by HOMA-IR interaction revealed a stronger association between IR and insular response to glucose vs. sucrose (p&amp;lt;0.03) . There was no association between HOMA-IR and brain responses to sucralose vs. sucrose. These findings show that IR is associated with greater activation of brain regions involved in taste and energy homeostasis to ingestion of sugar and NNS, which may promote eating behavior. Disclosure S. Kullmann: Other Relationship; Novo Nordisk. R. Veit: None. K. Jann: None. S.H. Luo: None. B.C. Angelo: None. J.M. Alves: None. J.R. Monterosso: None. K.A. Page: None. Funding NIDDK R01DK102794

Effect of Cyclooxygenase Inhibitor on Hypoxia Stimulated Cerebral Blood Flow Using Arterial Spin Labeling Magnetic Resonance

IntroductionThe purpose of this study was twofold: 1) to determine microvascular cerebral blood flow (CBF) during hypoxia and 2) to investigate the effect of Ketorolac, a cyclooxygenase (COX) inhibitor, on hypoxia stimulated CBF. Acute exposure to hypoxic conditions leads to an increase in CBF, which may be regionally specific. Studies investigating the effect of hypoxia on CBF have utilized varying gradations and durations of hypoxia and different measuring techniques (transcranial doppler ultrasound or magnetic resonance imaging (MRI)). COX has been shown to significantly contribute to CBF at rest, however during hypoxia research has shown conflicting data on COX contribution to hypoxic CBF. Utilizing arterial spin labeling (ASL), an MRI technique that provides microvascular global and regional perfusion, during hypoxia stimulated CBF and the role of COX. We hypothesized hypoxia will increase CBF non‐uniformly, and COX inhibition with Ketorolac will reduce hypoxic dilation in some, but not all brain regions.Methods6 healthy young adults subjects (24 ± 3 years, 22.4 ± 0.7 BMI, 4 male) were included in this analysis using an institutional review board (IRB)‐approved protocol. Subjects completed an ASL MRI scans (5.5 min each) under the 3 distinct conditions: normoxia, hypoxia, and hypoxia + ketorolac drug infusion. The first ASL scan occurred while the subject breathed ambient air (baseline). Isocapnic hypoxia was then induced by breathing reduced O2 (9‐13%) to reduce arterial saturation to 80‐85% for steady state hypoxia followed by the first hypoxia ASL scan. While hypoxia was maintained, Ketorolac was infused at a rate of 0.495 mg/kg over 3 minutes (average dose 33.9 ± 2.8 mg), the third ASL scan was then completed (hypoxia+ketorolac). ASL analysis included smoothing grey matter, co‐registering and normalizing raw data, brain masking and region of interest processing. Statistics were determined using a Two‐Way Repeated Measures ANOVA with Tukey’s post‐hoc analysis.ResultsData are mean ± SD. SpO2 (98 ± 1%, 82 ± 2%, 82 ± 1%) and ETCO2 (36 ± 1mmHg, 35 ± 2mmHg, 34 ± 2) at baseline, hypoxia, and hypoxia+ketorolac, respectively. Baseline Global CBF (58 ± 15 ml/100g‐1/min‐1) was not significantly different from hypoxia (61 ± 14 ml/100g‐1/min‐1) (p=0.47). Regionally, CBF between baseline and hypoxia were not different in the right/left temporal, occipital, parietal, or frontal lobes (R/L: p=0.47/p=0.98, p=0.59/p=0.49, p=0.46/p=0.63, and p=0.18/0.19, respectively). Ketorolac did not change global CBF during hypoxia (60 ± 17 ml/100g‐1/min‐1) (p=0.96). Regional CBF during hypoxia and hypoxia+ketorolac was not changed in the right/left temporal, occipital, parietal, or frontal lobes (R/L: p=0.96/0.91, p=0.57/0.88, p=0.86/0.99, and p=0.38/0.35, respectively).DiscussionContrary to our hypothesis CBF did not change globally or regionally with hypoxia stimulation. Furthermore, COX inhibition via Ketorolac did not change CBF during hypoxia in any region. This finding corroborates previous studies in animals and macrovascular flow in humans that COX inhibitor Ketorolac acts differently in the brain compared to Indomethacin, despite similar pharmacology. In conclusion, acute hypoxia exposure with Ketorolac did not alter microvascular CBF.

A Pilot Study to Investigate the Effect of Hypercapnia Training on Cerebrovascular Reactivity in Healthy Adults

ObjectiveHypercapnia, an elevated concentration of carbon dioxide (CO2) in the blood, is known to promote acute increases in cerebral blood flow (CBF). This pilot study aimed to investigate whether a novel training method involving repeated bouts of hypercapnia, would influence cerebrovascular reactivity response in healthy adults.HypothesisRepeated bouts of hypercapnia (as interval training) may promote beneficial adaptation to increase cerebrovascular reactivity.MethodsAdults over 40yrs old without known disease or cardiovascular risk factors, were recruited for a non‐randomized cross‐over design pilot study. Subjects completed a 2‐week control period followed by a 2‐week intervention. The intervention involved a progressive hypercapnia training program of six sessions, whereby subjects completed 4‐6 intervals of rebreathing oxygen until a target end‐tidal CO2 (up to 25mmHg above resting) was reached, separated by recovery intervals breathing room air. Cerebrovascular reactivity was measured during study testing visits at baseline, 2‐weeks (between control and intervention) and 4‐weeks (after intervention). During study visits subjects underwent a stepped CO2 protocol, involving 5‐min stages of inspired room air, 2% CO2, 4% CO2, and 6% CO2, while measuring middle cerebral artery velocity (CBFv) using transcranial doppler ultrasound, mean arterial pressure (MAP) by finger plethysmography, ventilation, and end‐tidal CO2. Cerebrovascular conductance (CVCi) was calculated as CBFv/MAP. The reactivity of CBFv (in cm/s/mmHg), CVCi (in cm/s/mmHg2), and MAP (in mmHg/mmHg) were calculated as the linear regression slope against end‐tidal CO2 during the stepped CO2 protocol. Chemosensitivity (in L/min/mmHg) is the linear regression slope of VE vs end‐tidal CO2.ResultsSix healthy adults (age: 56 ± 10; 2 females) completed the study. Study visit data are displayed in Table 1. Individual training data are presented in Table 2. Following the control period there was a large reduction from baseline in CBFv reactivity [2.81 ± 1.50 to 2.03 ± 1.03; effect size 0.9], CVCi reactivity [0.020 ± 0.015 to 0.015 ± 0.010; effect size 0.7], and MAP reactivity [0.95 ± 0.63 to 0.62 ± 0.42; effect size 0.6] with no change in chemosensitivity [0.99 ± 0.68 to 0.98 ± 0.51; effect size 0.0]. Following the intervention there was no change from the 2‐week study visit in CBFv reactivity [2.03 ± 1.03 to 2.01 ± 1.09; effect size 0.0], CVCi reactivity [0.015 ± 0.010 to 0.014 ± 0.010; effect size 0.1], and MAP reactivity [0.62 ± 0.42 to 0.72 ± 0.44; effect size 0.1] with a small increase in chemosensitivity [0.98 ± 0.51 to 1.04 ± 0.53; effect size 0.3].ConclusionPreliminary findings suggest a very brief progressive hypercapnia training program does not increase or desensitize cerebrovascular reactivity in healthy adults. These data also suggest an exaggerated cerebrovascular reactivity response may occur to an initial exposure of a stepped CO2 protocol (without familiarization), which appears to be driven by blood pressure response not chemosensitivity. Further research, particularly in populations with impaired cerebrovascular reactivity, is of interest for CBF regulation.