Cerebral Blood Flow In Cortex Research Articles

Short, frequent physical activity breaks improve working memory while preserving cerebral blood flow in adolescents during prolonged sitting - AbbaH teen, a randomized crossover trial

PurposePhysical activity (PA) breaks during school lessons have been suggested as a promising strategy to improve working memory performance in children and adolescents. There is a lack of studies investigating the underlying physiological mechanisms of PA on cognition, especially among adolescents. This study aimed to investigate the effects of different types of short frequent PA on adolescents’ cognitive task-related changes in cerebral blood flow in the prefrontal cortex (PFC) and working memory performance compared to prolonged sitting.MethodsIn this randomized crossover study, adolescents visited the laboratory on three different occasions for 80-minute sessions of prolonged sitting interrupted by four breaks for three minutes of simple resistance training (SRA), step-up at a pre-determined pace (STEP), or remaining seated (SOCIAL). Before and after each session, cognitive task-related changes in cerebral blood flow (oxygenated-hemoglobin, Oxy-Hb) during working memory tasks (1-, 2-, 3-back tests) were measured using functional near-infrared spectroscopy in the PFC. Accuracy and reaction time were derived from the working memory tasks. Linear mixed-effect models were used to analyze the data.ResultsA total of 17 students participated (mean age 13.6 years, 11 girls). Significant time x condition interactions were noted for Oxy-Hb in the most demanding working memory task (3-back), with a decrease following prolonged sitting in the SOCIAL condition compared to both the SRA (β 0.18, 95% CI 0.12, 0.24) and the STEP (β 0.11, 95% CI 0.05, 0.17). This was observed in parallel with improvements in reaction time following SRA (β -30.11, 95% CI -59.08, -1.13) and STEP (β -34.29, 95% CI -69.22, 0.63) although this was only significant for the SRA and no improvements in the SOCIAL condition.ConclusionWe found that short frequent PA breaks during prolonged sitting among adolescents can prevent the decrease in cognitive task-related changes in cerebral blood flow that occur following prolonged sitting. This was observed simultaneously with improvements in working memory, indicating that changes in cerebral blood flow could be one factor explaining the effects on working memory. Future studies should investigate the efficacy of implementing these PA breaks in schools.Trial registrationRetrospectively registered on 21/09/2020, ClinicalTrial (NCT04552626).

Capture of emotional responses under a simulated earthquake experience using near-infrared spectroscopy and virtual reality.

In a previous study, we reported that watching two-dimensional videos of earthquakes significantly reduced sympathetic nerve activity in healthy young adults. In the present study, we aimed to investigate the emotional responses to earthquakes using immersive virtual reality (VR), which can provide a more realistic experience. In total, 24 healthy young adults (12 males, 21.4 ± 0.2 years old) participated. Participants were required to watch earthquake and neutral videos while wearing a head-mounted display and near-infrared spectroscopy (NIRS), during which physiological signals, including pulse rate and cerebral blood flow (CBF) in the dorsolateral prefrontal cortex, were measured. We also analyzed changes in sympathetic and parasympathetic indices and obtained seven emotion ratings: valence, arousal, dominance, fear, astonishment, anxiety, and panic. The VR earthquake videos evoked negative subjective emotions, and the pulse rate significantly decreased. Sympathetic nerve activity tended to decrease, whereas CBF in the left prefrontal cortex showed a slight increase, although this was not significant. This study showed that measurements combined with NIRS and immersive VR have the potential to capture emotional responses to different stimuli.

Cerebral Blood Flow and Mood in Adolescents With Bipolar Disorder

ObjectiveMultiple prior studies have examined cerebral blood flow (CBF) in relation to mood states in adults with bipolar disorder (BD). This study examined CBF related to mood states in adolescents early in the course of BD, about which little is known. MethodThe study recruited 155 adolescents (mean [SD] age = 17.23 [1.62] years), including 81 with BD (32 hypomanic/mixed, 25 depressed, 24 euthymic) and 74 healthy controls. CBF was ascertained using pseudocontinuous arterial spin labeling magnetic resonance imaging. Region-of-interest analysis (amygdala, anterior cingulate cortex, middle frontal gyrus) controlling for age, sex, and race was complemented by whole-brain voxel-wise analyses. Within-BD regression analysis using age and sex as covariates examined the association of mania and depression severity with CBF. ResultsIn region-of-interest analyses, there were no group differences in CBF. Within the overall BD group, higher depression scores were associated with lower anterior cingulate cortex CBF (β = −.27, p = .01). In corrected voxel-wise analyses, CBF in the euthymic BD group was significantly higher compared with healthy controls in temporal and precentral regions. ConclusionThe finding of elevated regional CBF in adolescents with euthymic BD diverges from prior findings of reduced regional CBF in adults with BD. Higher CBF in adolescents with euthymic BD may reflect a developmentally specific compensatory perfusion mechanism required to maintain euthymia. However, longitudinal studies are needed to understand the temporal association of CBF and mood state in adolescents with BD, ideally followed into adulthood. Diversity & Inclusion StatementWe worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Effects of Savoring Meditation on Positive Emotions and Pain-Related Brain Function: A Mechanistic Randomized Controlled Trial in People With Rheumatoid Arthritis

Positive emotions are a promising target for intervention in chronic pain, but mixed findings across trials to date suggest that existing interventions may not be optimized to efficiently engage the target. The aim of the current pilot mechanistic randomized controlled trial was to test the effects of a positive emotion-enhancing intervention called Savoring Meditation on pain-related neural and behavioral targets in patients with rheumatoid arthritis. Participants included 44 patients with a physician-confirmed diagnosis of rheumatoid arthritis (n = 29 included in functional magnetic resonance imaging (fMRI) analyses), who were randomized to either Savoring Meditation or a Slow Breathing control. Both meditation interventions were brief (four 20-minute sessions). Self-report measures were collected pre-and post-intervention. An fMRI task was conducted at post-intervention, during which participants practiced the meditation technique on which they had been trained while exposed to non-painful and painful thermal stimuli. Savoring significantly reduced experimental pain intensity ratings relative to rest (P < .001). Savoring also increased cerebral blood flow in the ventromedial prefrontal cortex and increased connectivity between the ventromedial prefrontal cortex and caudate during noxious thermal stimulation relative to Slow Breathing (z = 2.3 voxelwise, false discovery rate cluster corrected P = .05). Participants in the Savoring condition also reported significantly increased positive emotions (ps < .05) and reduced anhedonic symptoms (P < .01) from pre- to post-intervention. These findings suggest that Savoring recruits reward-enhancing corticostriatal circuits in the face of pain, and future work should extend these findings to evaluate if these mechanisms of Savoring are associated with improved clinical pain outcomes in diverse patient populations. PerspectiveSavoring Meditation is a novel positive emotion-enhancing intervention designed for patients with chronic pain. The present findings provide preliminary evidence that Savoring Meditation is acutely analgesic, and engages neural and subjective emotional targets that are relevant to pain self-management. Future work should evaluate the clinical translation of these findings.

Dapagliflozin improves diabetic cognitive impairment via indirectly modulating the mitochondria homeostasis of hippocampus in diabetic mice.

Cognitive impairment is increasingly recognized as an important comorbidity of diabetes progression; however, the underlying molecular mechanism is unclear. Dapagliflozin, an inhibitor of sodium-glucose co-transporter 2 (SGLT2), has shown promising effects against diabetes in rodent experiments and human clinical assays. This study aimed to determine the underlying mechanism and examine the effect of dapagliflozin on diabetic cognitive impairment. To create an in vivo model of diabetic cognitive impairment, streptozotocin (STZ)-induced diabetic mice were used. Dapagliflozin was administered to mice for 8 weeks. The context fear condition and Morris water maze test was used to evaluate mice's behavioral change. Western blotting was used to evaluate protein expression. Hematoxylin and eosin (HE) and Nissl staining were applied to monitor morphological and structural changes. Congo red staining was performed to identify the formation of senile plaques. Mitochondria morphology was examined using a transmission electron microscope, and blood flow in the mouse cerebral cortex was measured using a laser Doppler imaging assay. Comparison to the diabetes mellitus (DM) group, the dapagliflozin group had lower glucose levels. Behavioral studies have shown that dapagliflozin can restore memory deficits in diabetic mice. The murky cell membrane edges and Nissl bodies more difficult to identify in the DM group were revealed by HE and Nissl staining, which were both improved by dapagliflozin treatment. Dapagliflozin inhibited the progression of Aβ generation and the reduced cerebral blood flow in the DM group was rescued. After dapagliflozin treatment, damaged mitochondria and lack of SGLT2 in the hippocampus and cortex of diabetic mice were repaired. Diabetes-induced cognitive dysfunction was attenuated by dapagliflozin and the effect was indirect rather than direct.

Waggle needling Yanglingquan (GB34) enhances cerebral blood flow and ameliorates condition of spastic paresis in rats with middle cerebral artery occlusion induced by surgical nylon suture.

To evaluate the therapeutic efficacy and the influence on cerebral blood supply of waggle needling Yanglingquan (GB34) on spastic paresis (SP) rats after middle cerebral artery occlusion (MCAO) induced and investigate its mechanism of relieving neurobehavior deficiency. SP rat model was produced by permanent MCAO. Rats were divided into five groups: blank control group (Control), sham operation group (Sham), model group (Model), waggle needling group (WN) and perpendicular needling group (PN). SP rats were treated with acupuncture from day 3 after MCAO, once a day for 6 d. The modified neurological severity score (mNSS) and modified Ashworth scale (MAS) were conducted on days 0, 1, 3, 5, 7 and 9. Cerebral blood flow (CBF) in ischemic cortex was measured by laser speckle imaging 5 min pre ischemia, 5 min post ischemia, and after intervention on day 9. All rats were sacrificed at day 9 and the protein and mRNA expressions of γ2 subunit of the γ-aminobutyric acid receptor A (GABAAγ2) and K+-Cl?cotransporter 2 (KCC2) in the ischemic cortex and lumber enlargement was measured by Western blotting and real-time quantitative polymerase chain reaction. Both Control and Sham groups showed no changes in mNSS and MAS scores and in the regional CBF. Compared with Model group, both WN and PN treatments significantly ameliorated neurological deficit ( 0.01), decreased muscle tone ( 0.05), and enhanced CBF ( 0.001) in SP rats; moreover, WN showed superior effects than PN ( 0.001). In line with the improvement in neurobehavior, acupuncture interventions up-regulated the expressions of GABAAγ2 and KCC2 in the ischemic cortex as well as lumber enlargement ( 0.01) in SP rats, and those changes were more obvious in WN ( 0.05). Acupuncture at Yanglingquan (GB34) enhanced cerebral blood flow and ameliorated SP in permanent MCAO rats, while waggle needling was superior to regular perpendicular needling. Waggle needling Yanglingquan (GB34) would be a potential complementary therapy for SP.

Type 1 respiratory failure-induced hypoxemia triggers complex signaling responses and apoptosis in the rat brain

Type 1 respiratory failure (T1RF)is caused by lung injury or low partial pressure of O 2 (PO 2 ) in air. It is associated with secondary acute brain injury (sABI), but the mechanisms behind it are not clear and could include primary hypoxic injury, increased intracranial pressure due to hypoxemia or due to mechanical ventilation, or could be mediated by lung injury-triggered inflammation. This study aimed to elucidate the effects of T1RF-induced hypoxemia on the brain in the absence of lung injury. SD rats were exposed to 8%O 2 in N 2 for up to 48h. We measured tissue PO 2 (Pt O2 ) and cerebral blood flow (CBF) in the cerebral cortex (CC) and estimated lactate concentrations and apoptosis in the CC, ependymal layer (EL) and choroid plexuses (CPs) during the time course of hypoxemia using the TUNEL assay. Cerebrospinal fluid (CSF) samples were collected during normoxia, after 24h and 48h hypoxemia. The concentrations of 32 signaling molecules were estimated in these samples by multiplex assays. Expressions of 84 signaling molecules and 5 housekeeping genes in the CC were explored by RT 2 Profiler TM PCR Array. Numerical values are presented as mean (SD). Data was compared with one-way ANOVA and the Kruskal-Wallis test. The Mann-Kendall test was used to assess whether CBF was increasing or decreasing during hypoxemia. Fold changes in the expressions of the tested mRNAs were estimated using GeneGlobe software. Statistical significance was set at p&lt;0.05. Hypoxemia exerted a significant effect on Pt O2 in the CC (p&lt;0.01), which was 49.5 (2.99) mmHg (n=10) during normoxia but declined to 6.4 (3.8) mmHg (n=5) after 1h hypoxemia (p&lt;0.01 vs. normoxia) and then slowly increased, reaching 18.5 (2.8) mmHg (n=6) after 43h hypoxemia (p&lt;0.01 vs. normoxia and 1h hypoxemia). This was accompanied by a significant increase in lactate concentrations in the CC and CSF (p&lt;0.01), but not in plasma (p=0.055). Hypoxemia exerted significant effect on the number of apoptotic cells in the CC (p&lt;0.01), EL (p&lt;0.01) and CPs (p&lt;0.01). In the CC the number of apoptotic cells was 5.63 (4.76) during normoxia, 20.48 (4.1) % after 24h hypoxemia (p&lt;0.01 vs. control) and 32.37 (6.5) % after 48h hypoxemia (p&lt;0.01 vs. control, p&lt;0.05 vs. 24h hypoxemia). Any monotonic increase or decrease in the CBF during hypoxemia could not be detected (p&gt;0.05). There was a significant effect of the duration of hypoxemia on the concentrations for the following cytokines in the CSF: IL-15, IL-17A, CXCL10, VEGF, Erythropoietin, FGF21, FSTL-1, GDF8/Myostatin, LIF and SPARC. When compared to normoxia, the expression of 11 mRNAs, most of them for pro-inflammatory cytokines, were 2-2.5 folds lower after 6h hypoxemia. Expression of mRNAs for angiogenic VEGF and pro-inflamatory IL7 were 2 folds and 2-5 folds higher after 24h and 48h hypoxemia, respectively. Our findings revealed a complex response by thebrain during T1RF-induced hypoxemiaand suggest an association between TIRF-induced hypoxemia, tissue hypoxia and sABI. This study was supported by the Kuwait University Research Sector Grants no YM 05/18 and MY 02/18. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

PRELIMINARY ANALYSIS OF BRAIN PERFUSION OBTAINED WITH ARTERIAL SPIN LABELING METHOD (ASL) USED TO EVALUATE THE EFFECTS OF TYPE 2 DIABETES IN MORBIDLY OBESE PATIENTS

Introduction: Earlier studies demonstrated that obesity was associated with lower cerebral perfusion in obese participants, as compared to participants at normal weight, especially in frontal grey matter regions. On the other hand, type 2 diabetes is a common co-morbid condition among obese patients, and it is associated per se with brain structural and metabolic abnormalities that are related to lower cerebral blood flow (CBF). Unfortunately, only two studies evaluated the effects on co-morbid T2D on CBF, one of them in adolescent population. Therefore, the aim of this study was to establish a pipeline process to quantify CBF images that were obtained in an independent project evaluating brain abnormalities associated with morbid obesity and their resolution with intragastric balloon – an invasive method to reduce weight. Furthermore, we compared CBF between obese patients with and without type 2 diabetes, as well as controls at normal weight. Methods: A processing pipeline utilizing SPM12 toolbox and digital maps (AAL, Brodmann) was established to automatically pre-process scans and toolbox REX was used to prepare data for statistical analysis. We used it to analyze data for six morbidly obese patients with type 2 diabetes T2D (O-T2D) (average age = 48.5 ± 7.9, average body weight = 125.0 ± 29.8 kg, average BMI = 42.0 ± 9.4), eight morbidly obese patients without T2D (O-NT2D) (average age = 39.1 ± 16.1, average body weight = 138.2 ± 14.9 kg, average BMI = 50.2 ± 6.5) and eight healthy controls with normal weight (CON) (average age = 43.5 ± 11.5, average body weight = 67.4 ± 14.6 kg, average BMI = 23.4 ± 3.5). All studies were performed at the CNS Lab MRI Centre, NIBBE. Results: These preliminary analyses demonstrated lower cerebral blood flow in frontal cortex in obese patients with T2D, as compared to obese patients without T2D and controls. Conclusion: A pipeline to numerically process ASL-CBF data was created and used to analyse the small dataset. The analyses indicated that not morbid obesity per se, but morbid obesity combined with co-morbid type 2 diabetes is associated with widespread reductions in cerebral perfusion. The results are in line with other studies that were limited to subjects with lower stages of overweight and obesity. We believe that this methodology may be applied to study changes in brain perfusion evoked by simulated hypergravity with Lower Body Negative Pressure (LBNP) device placed within a magnetic resonance scanner or perfusion changes induced by hypoxia.

Soybean isoflavones alleviate cerebral ischemia/reperfusion injury in rats by inhibiting ferroptosis and inflammatory cascade reaction

To explore the mechanism that mediates the effect of soybean isoflavones (SI) against cerebral ischemia/reperfusion (I/R) injury in light of the regulation of regional cerebral blood flow (rCBF), ferroptosis, inflammatory response and blood-brain barrier (BBB) permeability. A total of 120 male SD rats were equally randomized into sham-operated group (Sham group), cerebral I/R injury group and SI pretreatment group (SI group). Focal cerebral I/R injury was induced in the latter two groups using a modified monofilament occlusion technique, and the intraoperative changes of real-time cerebral cortex blood flow were monitored using a laser Doppler flowmeter (LDF). The postoperative changes of cerebral pathological morphology and the ultrastructure of the neurons and the BBB were observed with optical and transmission electron microscopy. The neurological deficits of the rats was assessed, and the severities of cerebral infarction, brain edema and BBB disruption were quantified. The contents of Fe2+, GSH, MDA and MPO in the ischemic penumbra were determined with spectrophotometric tests. Serum levels of TNF-α and IL-1βwere analyzed using ELISA, and the expressions of GPX4, MMP-9 and occludin around the lesion were detected with Western blotting and immunohistochemistry. The rCBF was sharply reduced in the rats in I/R group and SI group after successful insertion of the monofilament. Compared with those in Sham group, the rats in I/R group showed significantly increased neurological deficit scores, cerebral infarction volume, brain water content and Evans blue permeability (P < 0.01), decreased Fe2+ level, increased MDA level, decreased GSH content and GPX4 expression (P < 0.01), increased MPO content and serum levels of TNF-α and IL-1β (P < 0.01), increased MMP-9 expression and lowered occludin expression (P < 0.01). All these changes were significantly ameliorated in rats pretreated with IS prior to I/R injury (P < 0.05 or 0.01). SI preconditioning reduces cerebral I/R injury in rats possibly by improving rCBF, inhibiting ferroptosis and inflammatory response and protecting the BBB.

Greater subjective cognitive decline severity is associated with worse memory performance and lower entorhinal cerebral blood flow in healthy older adults.

Subjective cognitive decline (SCD) is a potential early risk marker for Alzheimer's disease (AD), but its utility may vary across individuals. We investigated the relationship of SCD severity with memory function and cerebral blood flow (CBF) in areas of the middle temporal lobe (MTL) in a cognitively normal and overall healthy sample of older adults. Exploratory analyses examined if the association of SCD severity with memory and MTL CBF was different in those with lower and higher cardiovascular disease (CVD) risk status. Fifty-two community-dwelling older adults underwent magnetic resonance imaging, neuropsychological testing, and were administered the Everyday Cognition Scale (ECog) to measure SCD. Regression models investigated whether ECog scores were associated with memory performance and MTL CBF, followed by similar exploratory regressions stratified by CVD risk status (i.e., lower vs higher stroke risk). Higher ECog scores were associated with lower objective memory performance and lower entorhinal cortex CBF after adjusting for demographics and mood. In exploratory stratified analyses, these associations remained significant in the higher stroke risk group only. Our preliminary findings suggest that SCD severity is associated with cognition and brain markers of preclinical AD in otherwise healthy older adults with overall low CVD burden and that this relationship may be stronger for individuals with higher stroke risk, although larger studies with more diverse samples are needed to confirm these findings. Our results shed light on individual characteristics that may increase the utility of SCD as an early risk marker of cognitive decline.

Association between cerebrovasoreactivity and stroke in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Impaired cerebrovasoreactivity is thought to play an important role in the pathophysiology of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We aimed to clarify the association between cerebrovascular reactivity and stroke in patients with CADASIL. We retrospectively recruited 14 patients with CADASIL, eight of whom had symptomatic stroke. They underwent quantitative single-photon emission computed tomography using an autoradiographic method at rest and after acetazolamide (ACZ) administration. Regional cerebral blood flow (rCBF) in the cerebral cortex, lenticular nucleus, thalamus, and cerebellum was measured. We compared the rCBF parameters between patients with and without stroke. The baseline characteristics and magnetic resonance imaging findings were similar between the two groups, except for a higher frequency of pyramidal tract sign (75% vs. 0%) and a larger number of old lacunes (15.4 ± 8.8 vs. 2.2 ± 1.8) in the patients with stroke. Of the rCBF parameters measured, significantly lower flow (mL/100 g/min) was observed in ACZ-rCBF in the thalamus (35.6 ± 9.4 vs. 51.1 ± 7.6, p = 0.01) and ΔrCBF in the thalamus (10.6 ± 3.7 vs. 21.0 ± 7.9, p = 0.02) in the patients with stroke. Cerebrovasoreactivity in the thalamus was significantly associated with stroke in patients with CADASIL.

Electroacupuncture on the Ophthalmic Branch of the Trigeminal Nerve Affects Cerebral Blood Flow in the Frontopolar Cortex During Mental Arithmetic: A Randomized Crossover Trial

Objective: The aim of this study was to examine the effect of cerebral blood flow (CBF) in the frontopolar cortex (FPC) during mental arithmetic tasks by 0.2 mA electroacupuncture (EA) stimulation of the trigeminal nerve's ophthalmic branch. Materials and Methods: This study was a crossover, randomized clinical trial. The participants (19) were divided into a control and an EA group, and both groups performed 10-minute mental-arithmetic tasks. Subsequently, the control group was seated for 5 minutes, while the EA group received EA stimulated at 0.2 mA, 100 Hz, for 5 minutes. Then, the mental-arithmetic tasks were repeated. The primary outcome was oxygenated hemoglobin (OxyHb) levels in the FPC during the mental-arithmetic tasks. Data from 15 of the original 19 participants were analyzed. Results: EA stimulation elevated OxyHb levels significantly. In the right FPC, this occurred in channel (Ch) 4 and 6 (P < 0.05) and Ch 3 (P < 0.01). In the left FPC, this occurred in Ch 10 and 15 (P < 0.05) and Ch 11 and 14 (P < 0.01). EA stimulation affected Ch 11 especially. There was also a significant positive correlation between OxyHb levels during the mental-arithmetic tasks in Ch 11 and changes in the numbers of answers and correct answers (ρ = 0.48; P < 0.05). Conclusions: These results suggest that 0.2 mA EA stimulation increased OxyHb levels in the FPC, particularly associated with increased CBF in the left FPC. Furthermore, the OxyHb levels in the left FPC positively correlated with the changes in the numbers of answers and correct answers.

Lateralization of cerebral blood flow in the auditory cortex of patients with idiopathic tinnitus and healthy controls: An arterial spin labeling study.

To assess the lateralization of cerebral blood flow (CBF) in the auditory cortex of idiopathic tinnitus patients and healthy controls (HCs) using 3D pseudocontinuous arterial spin labeling (pcASL). Thirty-six patients with idiopathic tinnitus and 43 sex- and age-matched HCs underwent 3D-pcASL scanning using a 3.0 T MRI system. For both groups, region of interest analysis was performed on the primary auditory cortex (PAC), auditory associative cortex (AAC), and secondary auditory cortex (SAC). The clinical data of all subjects were analyzed. In both tinnitus patients and HCs, CBF of the left PAC was significantly higher than that of the right (HCs: P = 0.02; patients: P = 0.043), but CBF of the right AAC and SAC was significantly higher than that of the left (AAC: HCs, P < 0.001; patients: P < 0.001. SAC: HCs, P < 0.001; patients: P = 0.001). Compared with HCs, tinnitus patients exhibited significantly higher CBF in the bilateral PAC (right: P = 0.008; left: P = 0.022). CBF in the left PAC was positively correlated with tinnitus severity (r = 0.399, P = 0.016). This study confirms the asymmetry of the auditory cortex and investigates the underlying neuropathology of idiopathic tinnitus in terms of CBF.

Vascular topology and blood flow are acutely impacted by experimental febrile status epilepticus

Febrile status epilepticus (FSE) is an important risk factor for temporal lobe epilepsy and early identification of those at high risk for epilepsy is vital. In a rat model of FSE, we identified an acute (2 hrs) novel MRI signal where reduced T2 relaxation values in the basolateral amygdala (BLA) predicted epilepsy in adulthood; this T2 signal remains incompletely understood and we hypothesized that it may be influenced by vascular topology. Experimental FSE induced in rat pups reduced blood vessel density of the cortical vasculature in a lateralized manner at 2 hrs post FSE. Middle cerebral artery (MCA) exhibited abnormal topology in FSE pups but not in controls. In the BLA, significant vessel junction reductions and decreased vessel diameter were observed, together with a strong trend for reduced vessel length. Perfusion weighted MRI (PWI) was acutely increased cerebral blood flow (CBF) in cortex, amygdala and hippocampus of FSE pups that correlated to decreased T2 relaxation values compared to controls. This is consistent with increased levels of deoxyhemoglobin associated with increased metabolic demand. In summary, FSE acutely modifies vascular topological and CBF in cortex and BLA that may underlie acute MRI signal changes that predict progression to future epilepsy.

Effect of the Application of Virtual Reality on Pain Reduction and Cerebral Blood Flow in Robot-Assisted Gait Training in Burn Patients.

Burn injuries and their treatment are extremely painful. This study aimed to determine whether virtual reality (VR) could reduce pain during robot-assisted gait training (RAGT) in burn patients by analyzing the cerebral blood flow (CBF) in the prefrontal cortex over time using functional near-infrared spectroscopy (fNIRS). The patients included in this study complained of a pain score ≥5 on a visual analog scale (VAS) during RAGT, which was performed 10 times for 2 weeks. Each session consisted of 15 min of VR application, with a 2-min break, and 15 min without VR. The average values of oxyhemoglobin and deoxyhemoglobin concentrations in the prefrontal cortex on fNIRS were calculated at four stages: temporal delay time with only RAGT, RAGT without VR, temporal delay time with RAGT and VR, and RAGT with VR. The pain scores and CBF were evaluated in sessions 1, 5, and 10 of the RAGT. The mean VAS pain scores were significantly lower (p < 0.05) in the experimental condition than in the control condition. Oxyhemoglobin in the prefrontal lobe significantly increased when RAGT was performed with VR. In conclusion, VR may be a strong nonpharmacological pain reduction technique for burn patients during physical therapy.

MemAID: Memory advancement with intranasal insulin vs. placebo in type 2 diabetes and control participants: a randomized clinical trial.

BackgroundThis study aimed at assessing the long-term effects of intranasal insulin (INI) on cognition and gait in older people with and without type 2 diabetes mellitus (T2DM).MethodsPhase 2 randomized, double-blinded trial consisted of 24 week treatment with 40 IU of INI (Novolin® R, off-label use) or placebo (sterile saline) once daily and 24 week follow-up. Primary outcomes were cognition, normal (NW), and dual-task (DTW) walking speeds. Of 244 randomized, 223 completed baseline (51 DM-INI, 55 DM-Placebo, 58 Control-INI, 59 Control-Placebo; 109 female, 65.8 ± 9.1; 50–85 years old); 174 completed treatment (84 DM, 90 Controls); 156 completed follow-up (69 DM).ResultsDM-INI had faster NW (~ 7 cm/s; p = 0.025) and DTW on-treatment (p = 0.007; p = 0.812 adjusted for baseline difference) than DM-Placebo. Control-INI had better executive functioning on-treatment (p = 0.008) and post-treatment (p = 0.007) and verbal memory post-treatment (p = 0.004) than Control-Placebo. DM-INI increased cerebral blood flow in medio-prefrontal cortex (p < 0.001) on MRI. Better vasoreactivity was associated with faster DTW (p < 0.008). In DM-INI, plasma insulin (p = 0.006) and HOMA-IR (p < 0.013) decreased post-treatment. Overall INI effect demonstrated faster walking (p = 0.002) and better executive function (p = 0.002) and verbal memory (p = 0.02) (combined DM-INI and Control-INI cohort, hemoglobin A1c-adjusted). INI was not associated with serious adverse events, hypoglycemic episodes, or weight gain.ConclusionThere is evidence for positive INI effects on cognition and gait. INI-treated T2DM participants walked faster, showed increased cerebral blood flow and decreased plasma insulin, while controls improved executive functioning and verbal memory. The MemAID trial provides proof-of-concept for preliminary safety and efficacy and supports future evaluation of INI role to treat T2DM and age-related functional decline.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s00415-022-11119-6.

70 Effect of of Virtual Reality on Pain Reduction in Robot Training in Burn Patients

IntroductionBurn injuries and their treatment are extremely painful. This study aimed to determine whether virtual reality (VR) can reduce pain during robot-assisted gait training (RAGT) in burn patients, by analyzing the cerebral blood flow (CBF) in the prefrontal cortex over time, using functional near-infrared spectroscopy (fNIRS).MethodsThe patients included in this study complained of a pain score≥5 on a visual analog scale (VAS) during RAGT, which was performed 10 times for 2 weeks. Each session consisted of 15 min of VR application, a 2 min break, and 15 min without VR. The average values of oxy-hemoglobin and deoxy-hemoglobin in the prefrontal cortex using fNIRS were calculated at four stages: temporal delay time with only RAGT, RAGT without VR, temporal delay time with RAGT and VR, and RAGT with VR. The pain scores and CBF were evaluated in sessions 1, 5, and 10 of the RAGT.ResultsThe mean VAS pain scores were significantly lower (P< 0.05) in the experimental condition than in the control condition. Oxy-hemoglobin in the prefrontal lobe increased significantly when RAGT was performed with VR.ConclusionsTherefore, VR may be a strong non-pharmacological pain reduction technique for burn patients during physical therapy.

The Impact of Ischemic Stroke on Gray and White Matter Injury Correlated With Motor and Cognitive Impairments in Permanent MCAO Rats: A Multimodal MRI-Based Study.

BackgroundIdentifying the alterations of the cerebral gray and white matter is an important prerequisite for developing potential pharmacological therapy for stroke. This study aimed to assess the changes of gray and white matter after permanent middle cerebral artery occlusion (pMCAO) in rats using magnetic resonance imaging (MRI), and to correlate them with the behavior performance.MethodsRats were subjected to pMCAO or sham surgery and reared for 30 days. Motor and cognitive function of the rats were examined by gait and Morris water maze (MWM) tests, respectively. Multimodal MRI was conducted to examine the functional and structural changes of the gray and white matter followed with luxol fast blue (LFB) staining.ResultsThe gait and MWM tests revealed significant motor and cognitive dysfunction in pMCAO rats, respectively. Magnetic resonance angiography presented abnormal intracranial arteries in pMCAO rats with reduced signal intensity of the anterior cerebral artery, anterior communicating cerebral artery, internal carotid artery, and increased basilar artery vessel signal compared with sham rats. Arterial spin labeling confirmed the decreased cerebral blood flow in the infarcted sensorimotor cortex and striatum. Structural T2-weighted imaging and T2 mapping showed brain atrophy and elevation of T2 value in the gray (sensorimotor cortex, striatum) and white (external capsule, internal capsule) matter of pMCAO rats. The results from diffusion tensor imaging (DTI) corresponded well with LFB staining showing reduced relative FA accompanied with increased relative AD and RD in the gray and white matter of pMCAO rats compared with sham rats. Fiber tracking derived from DTI further observed significantly reduced fiber density and length in the corresponding brain regions of pMCAO rats compared with sham rats. Specially, the DTI parameters (especially FA) in the relevant gray matter and white matter significantly correlated with the behavior performance in the gait and MWM tests.ConclusionCollectively, the gray and white matter damages could be non-invasively monitored in pMCAO rats by multimodal MRI. DTI-derived parameters, particularly the FA, might be a good imaging index to stage gray and white matter damages associated with post-stroke motor and cognitive impairments.

Cerebral blood flow dynamics before, during, and after seizures from epilepsy and the periictal state

Changes in cerebral blood flow (CBF) in the human cerebral cortex during surgery were reported by Penfield. However, data on continuous CBF during seizures were not available until Carter et al developed a subdural CBF probe for measuring continuous CBF. This probe used thermal resistor methodology and was developed to study patients with head trauma. With such a probe, changes in continuous CBF and electroencephalography during and after a seizure were reported by Oommen et al. Such changes were later confirmed examining the same phenomenon by using cerebral perfusion with laser Doppler methodology with epidural electroencephalography. This review details the evolution of our knowledge of CBF from observational reports to recordings from the animal and human cortices, by varying methodologies.

Dynamic MR imaging of cerebral perfusion during bicycling exercise

Habitual physical activity is beneficial for cerebrovascular health and cognitive function. Physical exercise therefore constitutes a clinically relevant cerebrovascular stimulus. This study demonstrates the feasibility of quantitative cerebral blood flow (CBF) measurements during supine bicycling exercise with pseudo-continuous arterial spin labeling (pCASL) magnetic resonance imaging (MRI) at 3 Tesla.Twelve healthy volunteers performed a steady-state exercise-recovery protocol on an MR-compatible bicycle ergometer, while dynamic pCASL data were acquired at rest, during moderate (60% of the age-predicted supine maximal heart rate (HRmax)) and vigorous (80% of supine HRmax) exercise, and subsequent recovery. These CBF measurements were compared with 2D phase-contrast MRI measurements of blood flow through the carotid arteries. Procedures were repeated on a separate day for an assessment of measurement repeatability.Whole-brain (WB) CBF was 41.2 ± 6.9 mL/100 g/min at rest (heart rate 63 [57-71] beats/min), remained similar at moderate exercise (102 [97-107] beats/min), decreased by 10% to 37.1 ± 5.7 mL/100 g/min (p = 0.001) during vigorous exercise (139 [136-142] beats/min) and decreased further to 34.2 ± 6.0 mL/100 g/min (p < 0.001) during recovery. Hippocampus CBF decreased by 12% (p = 0.001) during moderate exercise, decreased further during vigorous exercise (-21%; p < 0.001) and was even lower during recovery (-31%; p < 0.001). In contrast, motor cortex CBF increased by 12% (p = 0.027) during moderate exercise, returned to resting-state values during vigorous exercise, and decreased by 17% (p = 0.006) during recovery. The inter-session repeatability coefficients for WB CBF were approximately 20% for all stages of the exercise-recovery protocol. Phase-contrast blood flow measurements through the common carotid arteries overestimated the WB CBF because of flow directed to the face and scalp. This bias increased with exercise.We have demonstrated the feasibility of dynamic pCASL-MRI of the human brain for a quantitative evaluation of cerebral perfusion during bicycling exercise. Our spatially resolved measurements revealed a differential response of CBF in the motor cortex as well as the hippocampus compared with the brain as a whole. Caution is warranted when using flow through the common carotid arteries as a surrogate measure for cerebral perfusion.