Blood Oxygenation Level-dependent fMRI Research Articles

Neurovascular Uncoupling: Multimodal Imaging Delineates the Acute Effects of 3,4-Methylenedioxymethamphetamine.

Psychedelic compounds such as 3,4-methylenedioxymethamphetamine (MDMA) have attracted increasing interest in recent years because of their therapeutic potential in psychiatric disorders. To understand the acute effects of psychedelic drugs invivo, blood-oxygenation-level-dependent (BOLD) functional MRI (fMRI) has been widely used. In particular, fMRI studies have suggested that MDMA leads to inhibition of brain activity, challenging previous hypotheses indicating mainly excitatory effects based, among others, on increased metabolism shown by 18F-FDG functional PET (fPET). However, interpretation of hemodynamic changes induced by psychedelics is difficult because of their potent vascular effects. Methods: We aimed to delineate the acute effects of MDMA using simultaneous PET/fMRI in rats. For this purpose, hemodynamic changes measured by BOLD fMRI were related to alterations in glucose utilization and serotonin transporter (SERT) occupancy using 18F-FDG fPET/fMRI and 11C-DASB PET/fMRI. Results: We show that MDMA induces localized increases in glucose metabolism in limbic projection areas involved in emotional processing. The increased glucose metabolism was accompanied by global cerebral and extracerebral hemodynamic decreases. We further demonstrated a strong correlation between SERT occupancies and regional BOLD reductions after acute MDMA administration. Conclusion: Our data indicate that hemodynamic decreases after acute MDMA administration are of a nonneuronal nature and initiate peripherally. Within the brain, MDMA triggers neuronal activation in limbic projection areas, whereas increased serotonin levels induced by SERT blockage cause neurovascular uncoupling through direct vascular effects. Correct understanding of the invivo mechanism of MDMA not only supports ongoing research but also warrants a reassessment of previous studies on neuronal effects of psychedelics relying on neurovascular coupling and recommends 18F-FDG fPET as a potentially more robust measure for pharmacologic research.

Single Center to Evaluate and Compare Anisometropic Amblyopia in Adults Using Blood Oxygenation Level-Dependent Functional Magnetic Resonance Imaging and Diffusion Kurtosis Imaging.

BackgroundAnisometropic amblyopia results from the unequal ability to focus between the right and left eyes. Blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) measures the proportion of oxygenated hemoglobin in specific areas. Diffusion kurtosis imaging (DKI) is a method of diffusion tensor imaging that estimates the skewed distribution of water diffusion probability. We aimed to evaluate and compare 11 adult patients with anisometropic amblyopia (AA) with 13 normally sighted healthy controls (HC) using BOLD-fMRI and DKI.Material/MethodsEleven adults with AA (age range 20–49; mean age 29.18±8.089) and 13 HC adults (age range 22–50; mean age 28.00±5.79) were recruited. DKI scanning used a single excitation echo-planar imaging sequence and a region of interest to obtain DKI parameters for optic radiation; the corpus callosum was manually placed, including mean kurtosis (MK), fractional anisotropic (FA), and mean diffusivity (MD) values; and BOLD data used a gradient-echo echo-planar imaging sequence.ResultsThe AA group had lower MK and FA of bilateral optic radiation than the HC group (P=0.008 and P=0.006, respectively) and higher MD than the HC group (P=0.005). The MK of the corpus callosum in the AA group was lower than that of HC group (P=0.012).Compared with the non-dominant eyes of the HC group, the amblyopic eyes in the AA group had less activation range and intensity in Brodmann areas 17, 18, and 19.ConclusionsThe combined use of DKI and BOLD-fMRI detected microstructural changes associated with local visual pathways and identified damage to the visual cortex in patients with amblyopia.

Relationship of neurite architecture to brain activity during task-based fMRI

Functional MRI (fMRI) has been widely used to examine changes in neuronal activity during cognitive tasks. Commonly used measures of gray matter macrostructure (e.g., cortical thickness, surface area, volume) do not consistently appear to serve as structural correlates of brain function. In contrast, gray matter microstructure, measured using neurite orientation dispersion and density imaging (NODDI), enables the estimation of indices of neurite density (neurite density index; NDI) and organization (orientation dispersion index; ODI) in gray matter. Our study explored the relationship among neurite architecture, BOLD (blood-oxygen-level-dependent) fMRI, and cognition, using a large sample (n = 750) of young adults of the human connectome project (HCP) and two tasks that index more cortical (working memory) and more subcortical (emotion processing) targeting of brain functions. Using NODDI, fMRI, structural MRI and task performance data, hierarchical regression analyses revealed that higher working memory- and emotion processing-evoked BOLD activity was related to lower ODI in the right DLPFC, and lower ODI and NDI values in the right and left amygdala, respectively. Common measures of brain macrostructure (i.e., DLPFC thickness/surface area and amygdala volume) did not explain any additional variance (beyond neurite architecture) in BOLD activity. A moderating effect of neurite architecture on the relationship between emotion processing task-evoked BOLD response and performance was observed. Our findings provide evidence that neuro-/social-affective cognition-related BOLD activity is partially driven by the local neurite organization and density with direct impact on emotion processing. In vivo gray matter microstructure represents a new target of investigation providing strong potential for clinical translation.

Aging Effect, Reproducibility, and Test-Retest Reliability of a New Cerebral Amyloid Angiopathy MRI Severity Marker-Cerebrovascular Reactivity to Visual Stimulation.

Decreased cerebrovascular reactivity, measured as changes in blood-oxygen-level-dependent (BOLD) signal, is a potential new cerebral amyloid angiopathy (CAA) severity marker. Before clinical application, the effect of aging on BOLD parameters, and reproducibility and test-retest reliability of these parameters should be assessed. Assess the effect of healthy aging on cerebrovascular reactivity (BOLD amplitude, time to peak, and time to baseline). And determine reproducibility and test-retest reliability of these parameters. Prospective-observational. Eighty-six healthy adults (mean age 56 years, 55% female), 10 presymptomatic D-CAA mutation carriers (mean age 34 years, 70% female), and 10 symptomatic D-CAA mutation carriers (mean age 54 years, 70% female). 3-T, three-dimensional (3D) T1-weighted MRI and gradient echo BOLD fMRI. To assess test-retest reliability of BOLD parameters, i.e. BOLD amplitude, time to peak, and time to baseline, BOLD fMRI scans were repeated three times immediately after each other, in both controls and mutation carriers. To assess reproducibility, BOLD fMRI scans were repeated with a 3-week interval for each subject. Linear regression analyses and two-way mixed absolute agreement intra-class correlation approach. Healthy aging was associated with decreased BOLD amplitude (β=-0.711) and prolonged time to baseline (β=0.236) in the visual cortex after visual stimulation Reproducibility of BOLD amplitude was excellent (ICC 0.940) in the subgroup of healthy adults. Test-retest reliability for BOLD amplitude was excellent in healthy adults (ICC 0.856-0.910) and presymptomatic D-CAA mutation carriers (ICC 0.959-0.981). In symptomatic D-CAA mutation carriers, test-retest reliability was poor for all parameters (ICCs < 0.5). Healthy aging is associated with decreased cerebrovascular reactivity, measured by changes in BOLD response to visual stimulation. The BOLD amplitude appears to be a robust measurement in healthy adults and presymptomatic D-CAA mutation carriers, but not in symptomatic D-CAA mutation carriers.

Multimodal Presurgical Evaluation of Medically Refractory Focal Epilepsy in Adults: An Update for Radiologists.

Surgery is a potentially curative treatment option for patients with medically refractory focal epilepsy. Advanced neuroimaging modalities often improve surgical outcomes by contributing key information during the highly individualized surgical planning process and intraoperative localization. Hence, neuroradiologists play an integral role in the multidisciplinary management team. In this review, we initially present the conceptual background and practical framework of the presurgical evaluation process, including a description of the surgical treatment approaches used for medically refractory focal epilepsy in adults. This background is followed by an overview of the advanced modalities commonly used during the presurgical workup at level IV epilepsy centers, including diffusion imaging techniques, blood oxygenation level-dependent functional MRI (fMRI), PET, SPECT, and subtraction ictal SPECT, and by introductions to 7-T MRI and electrophysiologic techniques including electroencephalography and magnetoencephalography. We also provide illustrative case examples of multimodal neuroimaging including PET/MRI, PET/MRI-diffusion-tensor imaging (DTI), subtraction ictal SPECT, and image-guided stereotactic planning with fMRI-DTI.

Fast and functionally specific cortical thickness changes induced by visual stimulation.

Structural characteristics of the human brain serve as important markers of brain development, aging, disease progression, and neural plasticity. They are considered stable properties, changing slowly over time. Multiple recent studies reported that structural brain changes measured with magnetic resonance imaging (MRI) may occur much faster than previously thought, within hours or even minutes. The mechanisms behind such fast changes remain unclear, with hemodynamics as one possible explanation. Here we investigated the functional specificity of cortical thickness changes induced by a flickering checkerboard and compared them to blood oxygenation level-dependent (BOLD) functional MRI activity. We found that checkerboard stimulation led to a significant thickness increase, which was driven by an expansion at the gray-white matter boundary, functionally specific to V1, confined to the retinotopic representation of the checkerboard stimulus, and amounted to 1.3% or 0.022mm. Although functional specificity and the effect size of these changes were comparable to those of the BOLD signal in V1, thickness effects were substantially weaker in V3. Furthermore, a comparison of predicted and measured thickness changes for different stimulus timings suggested a slow increase of thickness over time, speaking against a hemodynamic explanation. Altogether, our findings suggest that visual stimulation can induce structural gray matter enlargement measurable with MRI.

More pronounced hemodynamic alterations in patients with brain arteriovenous malformation-associated epilepsy.

Epileptic seizures in patients with brain arteriovenous malformations (bAVMs) may be caused by hemodynamic alterations due to the complex angioarchitecture of bAVMs. In particular, an arterial steal phenomenon and venous outflow disruption may play an etiological role in seizure development but remain challenging to demonstrate quantitatively. Blood oxygenation level-dependent (BOLD) cerebrovascular reactivity (CVR) imaging is an emerging technique that can measure both arterial steal phenomenon (as a paradoxical BOLD signal decrease during a vasodilatory stimulus) and impaired perinidal BOLD-CVR (which has been found in the presence of venous congestion on conventional angiography in bAVM patients with epilepsy). By applying this innovative BOLD-CVR technique, the aim is to better study CVR patterns and their correlation with morphological features on conventional angiography in patients with bAVM with and without epilepsy. Twenty-two patients with unruptured and previously untreated bAVMs (8 with and 14 without epilepsy) were included in this case-control study. Quantitative CVR measurements were derived from BOLD functional MRI volumes using a novel standardized and precise hypercapnic stimulus (i.e., % BOLD/mm Hg CO2). In addition, 22 matched healthy controls underwent an identical BOLD-CVR study. Evaluation of venous congestion was performed on conventional angiography for all patients with bAVM. Patients with bAVM-associated epilepsy showed impaired whole-brain BOLD-CVR compared to those in the nonepilepsy group, even after correction for AVM volume and AVM grade (epilepsy vs nonepilepsy group: 0.17 ± 0.07 vs 0.25 ± 0.07, p = 0.04). A BOLD-CVR-derived arterial steal phenomenon was observed in 2 patients with epilepsy (25%). Venous congestion was noted in 3 patients with epilepsy (38%) and in 1 patient without epilepsy (7%; p = 0.08). These data suggest that whole-brain CVR impairment, and more pronounced hemodynamic alterations (i.e., arterial steal phenomenon and venous outflow restriction), may be more present in patients with bAVM-associated epilepsy. The association of impaired BOLD-CVR and bAVM-associated epilepsy will need further investigation in a larger patient cohort.

Brain Activation During Processing of Depression Emotion in College Students With Premenstrual Syndrome in China: Preliminary Findings.

BackgroundThis study aimed to investigate the neural substrates of processing depression emotion in premenstrual syndrome (PMS) and healthy subjects of college students using blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI).MethodsDuring BOLD-fMRI scanning, 13 PMS patients and 15 healthy controls (HC) performed a picture visual stimulation task during luteal and follicular phases, in which participants and HC were asked to see pictures containing depression and non-depression emotions. Simultaneously, self-rating depression scales (SDS) were employed to evaluate the emotional status of participants.ResultsCompared to HC, right inferior occipital gyrus, right middle occipital gyrus, right lingual gyrus, right fusiform gyrus, right inferior temporal gyrus, cerebelum_crus1_R, cerebelum_6_R, culmen, the cerebellum anterior lobe, tuber, and cerebellar tonsil of PMS patients showed enhanced activation. In contrast, sub-lobar, sub-gyral, extra-nuclear, right orbit part of superior frontal gyrus, right middle temporal gyrus, right orbit part of inferior frontal gyrus, limbic lobe, right insula, bilateral anterior and adjacent cingulate gyrus, bilateral caudate, caudate head, bilateral putamen, and left globus pallidus exhibited decreased activation.ConclusionThe findings indicate that abnormal functional regulation of brain regions such as occipital lobe and cerebellum leads to abnormal changes in emotional regulation, cognitive ability, and attention distribution in PMS patients, implying significant central pathogenesis.

Lag-Optimized Blood Oxygenation Level Dependent Cerebrovascular Reactivity Estimates Derived From Breathing Task Data Have a Stronger Relationship With Baseline Cerebral Blood Flow.

Cerebrovascular reactivity (CVR), an important indicator of cerebrovascular health, is commonly studied with the Blood Oxygenation Level Dependent functional MRI (BOLD-fMRI) response to a vasoactive stimulus. Theoretical and empirical evidence suggests that baseline cerebral blood flow (CBF) modulates BOLD signal amplitude and may influence BOLD-CVR estimates. We address how acquisition and modeling choices affect the relationship between baseline cerebral blood flow (bCBF) and BOLD-CVR: whether BOLD-CVR is modeled with the inclusion of a breathing task, and whether BOLD-CVR amplitudes are optimized for hemodynamic lag effects. We assessed between-subject correlations of average GM values and within-subject spatial correlations across cortical regions. Our results suggest that a breathing task addition to a resting-state acquisition, alongside lag-optimization within BOLD-CVR modeling, can improve BOLD-CVR correlations with bCBF, both between- and within-subjects, likely because these CVR estimates are more physiologically accurate. We report positive correlations between bCBF and BOLD-CVR, both between- and within-subjects. The physiological explanation of this positive correlation is unclear; research with larger samples and tightly controlled vasoactive stimuli is needed. Insights into what drives variability in BOLD-CVR measurements and related measurements of cerebrovascular function are particularly relevant when interpreting results in populations with altered vascular and/or metabolic baselines or impaired cerebrovascular reserve.

Static and dynamic BOLD fMRI components along white matter fibre tracts and their dependence on the orientation of the local diffusion tensor axis relative to the B0-field

Recent studies have reported functional MRI (fMRI) activation within cerebral white matter (WM) using blood-oxygenation-level-dependent (BOLD) contrast. Many blood vessels in WM run parallel to the fibre bundles, and other studies observed dependence of susceptibility contrast-based measures of blood volume on the local orientation of the fibre bundles relative to the magnetic field or B0 axis. Motivated by this, we characterized the dependence of gradient-echo BOLD fMRI on fibre orientation (estimated by the local diffusion tensor) relative to the B0 axis to test whether the alignment between bundles and vessels imparts an orientation dependence on resting-state BOLD fluctuations in the WM. We found that the baseline signal level of the T2*-weighted data is 11% higher in voxels containing fibres parallel to B0 than those containing perpendicular fibres, consistent with a static influence of either fibre or vessel orientation on local T2* values. We also found that BOLD fluctuations in most bundles exhibit orientation effects expected from oxygenation changes, with larger amplitudes from voxels containing perpendicular fibres. Different magnitudes of this orientation effect were observed across the major WM bundles, with inferior fasciculus, corpus callosum and optic radiation exhibiting 14–19% higher fluctuations in voxels containing perpendicular compared to parallel fibres.

219-OR: Intranasal Insulin Enhanced Resting-State Functional Connectivity of Medio-Prefrontal Cortex in Type 2 Diabetes: A Substudy of the Memory Advancement with Type 2 Diabetes (MemAID) Randomized Control Trial

Type 2 diabetes mellitus (T2DM) is associated with impairment of resting-state functional connectivity (rsFC) and cognition. Intranasal insulin (INI) has emerged as potential treatment for T2DM-related cognitive decline. INI treatment has increased perfusion and low-frequency fluctuations in medio-prefrontal cortex (mPFC) . We aimed to evaluate the effect of INI treatment on mPFC rsFC.MemAIDs trial consisted of 24-week of treatment with 40 IU of intranasal insulin (Novolin® R, off label use) or placebo (sterile saline) once daily and 24-week follow-up period. Of 244 randomized participants (115 T2DM and 129 controls, &amp;gt; 50 years old) , T2DM participants (eight INI, three placebo, &amp;gt; 50 years old) completed the baseline and end-of-treatment blood oxygen level dependent (BOLD) fMRI scans.INI treatment increased resting state mPFC-postcentral rsFC (p=0.005) and decreased mPFC-cerebellum rsFC (p&amp;lt;0.001) . The mPFC rsFC changes after INI treatment were different from those from placebo (Figure 1) .INI treatment can modulate resting state connectivity between pre-frontal and sensorimotor cortex and cerebellum, indicating its potential effects on decision making and goal-oriented behaviors. These findings warrant further investigation. Disclosure Z.Zhang: None. V.Novak: None. P.Novak: Stock/Shareholder; Moderna, Inc., Novavax, Pfizer Inc., Prothena. C.Mantzoros: Advisory Panel; Novo Nordisk. L.H.Ngo: None. V.Lioutas: None. W.Dai: None. Funding Funded by NIH-NIDDK (1R01DK103902) , FDA (IND#107690) , Novo Nordisk, Inc. (ISS-001063) , Medtronic Inc. (NERP15-0310) and registered on www.clinicaltrials.gov (NCT02415556.)

0739 Cerebrovascular Response to Intermittent Hypoxia During Sleep in OSA Patients

Abstract Introduction Obstructive sleep apnea (OSA) is associated with increased risks of cerebrovascular accidents, but it remains unclear how OSA impacts the cerebral vasculature. Intermittent hypoxia is a hallmark feature of OSA and recurs throughout sleep. In awake humans, the cerebrovascular response to intermittent hypoxia has been well characterized, as an increase of blood perfusion that begins at least a few seconds after the start of hypoxia. Functional magnetic resonance imaging (fMRI) that measures the blood oxygen level dependent (BOLD) signal has revealed significant differences between the cerebrovascular responses in awake humans with and without OSA. However, intermittent hypoxia occurs primarily during sleep in OSA, yet the cerebrovascular response to intermittent hypoxia has not been studied during sleep. Methods Eight adult patients with severe OSA were recruited to this study. Each subject first underwent an acclimatization session in which they tried to sleep in the MRI scanner while listening to sound recordings of the fMRI. Each acclimatized subject then underwent an overnight study in which T2*-weighed BOLD fMRI of the whole brain was conducted for 1.5-3 hours in total (TE: 35 ms, TR: 2.0 s, 35 sagittal slices, 3.5 mm isotropic). Oxygen saturation (SaO2), chest movement, end-tidal carbon dioxide and scalp encephalography (EEG) were simultaneously recorded with the fMRI. After rigid-body motion correction and removal of artifacts, the temporal correlation between BOLD signal and the SaO2 signal was analyzed on a voxel-by-voxel basis. Results Four subjects (50%) were acclimatized to sleep in the MRI scanner and completed this study. In all subjects, the BOLD fMRI signal showed an initial decrease corresponding to the decrease of SaO2, followed by a delayed increase corresponding to the hyperperfusion, throughout the gray matter of cerebral cortex. The time course of BOLD fMRI signal was significantly advanced in time, by 2-4 seconds, in the visual cortex compared to the rest of cerebral cortex in all subjects. This phenomenon was also observed in some other brain regions, but not consistently across subjects. Conclusion This study is, to our knowledge, the first study of the cerebrovascular response to intermittent hypoxia during sleep in humans. In patients with OSA, we observed spatiotemporal heterogeneity of the cerebrovascular response, such that the response in the visual cortex was significantly advanced in time than other brain regions. This phenomenon has not been reported before, and future studies are needed to understand how this heterogeneity is associated with OSA. Support (If Any) AASM Foundation

Modeling the Hemodynamic Response Function Using EEG-fMRI Data During Eyes-Open Resting-State Conditions and Motor Task Execution

Being able to accurately quantify the hemodynamic response function (HRF) that links the blood oxygen level dependent functional magnetic resonance imaging (BOLD-fMRI) signal to the underlying neural activity is important both for elucidating neurovascular coupling mechanisms and improving the accuracy of fMRI-based functional connectivity analyses. In particular, HRF estimation using BOLD-fMRI is challenging particularly in the case of resting-state data, due to the absence of information about the underlying neuronal dynamics. To this end, using simultaneously recorded electroencephalography (EEG) and fMRI data is a promising approach, as EEG provides a more direct measure of neural activations. In the present work, we employ simultaneous EEG-fMRI to investigate the regional characteristics of the HRF using measurements acquired during resting conditions. We propose a novel methodological approach based on combining distributed EEG source space reconstruction, which improves the spatial resolution of HRF estimation and using block-structured linear and nonlinear models, which enables us to simultaneously obtain HRF estimates and the contribution of different EEG frequency bands. Our results suggest that the dynamics of the resting-state BOLD signal can be sufficiently described using linear models and that the contribution of each band is region specific. Specifically, it was found that sensory-motor cortices exhibit positive HRF shapes, whereas the lateral occipital cortex and areas in the parietal cortex, such as the inferior and superior parietal lobule exhibit negative HRF shapes. To validate the proposed method, we repeated the analysis using simultaneous EEG-fMRI measurements acquired during execution of a unimanual hand-grip task. Our results reveal significant associations between BOLD signal variations and electrophysiological power fluctuations in the ipsilateral primary motor cortex, particularly for the EEG beta band, in agreement with previous studies in the literature.

Monash DaCRA fPET-fMRI: A dataset for comparison of radiotracer administration for high temporal resolution functional FDG-PET.

Background“Functional” [18F]-fluorodeoxyglucose positron emission tomography (FDG-fPET) is a new approach for measuring glucose uptake in the human brain. The goal of FDG-fPET is to maintain a constant plasma supply of radioactive FDG in order to track, with high temporal resolution, the dynamic uptake of glucose during neuronal activity that occurs in response to a task or at rest. FDG-fPET has most often been applied in simultaneous BOLD-fMRI/FDG-fPET (blood oxygenation level–dependent functional MRI fluorodeoxyglucose functional positron emission tomography) imaging. BOLD-fMRI/FDG-fPET provides the capability to image the 2 primary sources of energetic dynamics in the brain, the cerebrovascular haemodynamic response and cerebral glucose uptake.FindingsIn this Data Note, we describe an open access dataset, Monash DaCRA fPET-fMRI, which contrasts 3 radiotracer administration protocols for FDG-fPET: bolus, constant infusion, and hybrid bolus/infusion. Participants (n = 5 in each group) were randomly assigned to each radiotracer administration protocol and underwent simultaneous BOLD-fMRI/FDG-fPET scanning while viewing a flickering checkerboard. The bolus group received the full FDG dose in a standard bolus administration, the infusion group received the full FDG dose as a slow infusion over the duration of the scan, and the bolus-infusion group received 50% of the FDG dose as bolus and 50% as constant infusion. We validate the dataset by contrasting plasma radioactivity, grey matter mean uptake, and task-related activity in the visual cortex.ConclusionsThe Monash DaCRA fPET-fMRI dataset provides significant reuse value for researchers interested in the comparison of signal dynamics in fPET, and its relationship with fMRI task-evoked activity.

Association between cardiorespiratory fitness and cerebrovascular reactivity to a breath-hold stimulus in older adults: influence of aerobic exercise training.

Cerebrovascular reactivity (CVR) to a physiological stimulus is a commonly used surrogate of cerebrovascular health. Cross-sectional studies using blood oxygen level dependent (BOLD) neuroimaging demonstrated lower BOLD-CVR to hypercapnia among adults with high compared with lower cardiorespiratory fitness (CRF) in contrast to transcranial Doppler studies. However, whether BOLD-CVR changes following chronic aerobic exercise in older, cognitively intact adults is unclear. This study evaluated relations between BOLD-CVR with CRF (V̇o2peak) using a cross-sectional and interventional study design. We hypothesized that 1) greater CRF would be associated with lower BOLD-CVR in older adults (n = 114; 65 ± 6.5 yr) with a wide range of CRF and 2) BOLD-CVR would be attenuated after exercise training in a subset (n = 33) randomized to 3-mo of moderate- or light-intensity cycling. CVR was quantified as the change in the BOLD signal in response to acute hypercapnia using a blocked breath-hold design from a region-of-interest analysis for cortical networks. In the cross-sectional analysis, there was a quadratic relation between V̇o2peak (P = 0.03), but not linear (P = 0.87) and cortical BOLD-CVR. BOLD-CVR increased until a V̇o2peak ∼28 mL/kg/min after which BOLD-CVR declined. The nonlinear trend was consistent across all networks (P = 0.04-0.07). In the intervention, both the active and light-intensity exercise groups improved CRF similarly (6% vs. 10.8%, P = 0.28). The percent change in CRF was positively associated with change in BOLD-CVR in the default mode network only. These data suggest that BOLD-CVR is nonlinearly associated with CRF and that in lower-fit adults default mode network may be most sensitive to CRF-related increases in BOLD-CVR.NEW & NOTEWORTHY Earlier studies evaluating associations between cardiorespiratory fitness (CRF) and cerebrovascular reactivity (CVR) have demonstrated conflicting findings dependent on imaging modality or subject characteristics in individuals across a narrow range of CRF. This study demonstrates that CRF is nonlinearly associated with CVR measured by blood oxygen level dependent (BOLD) fMRI in a large sample of middle-aged and older adults across a wide range of CRF, suggesting that conflicting prior findings are related to the range of CRFs studied.

Molecular Effects of Low-Intensity Shock Wave Therapy on L6 Dorsal Root Ganglion/Spinal Cord and Blood Oxygenation Level-Dependent (BOLD) Functional Magnetic Resonance Imaging (fMRI) Changes in Capsaicin-Induced Prostatitis Rat Models.

Neurogenic inflammation and central sensitization play a role in chronic prostatitis/chronic pelvic pain syndrome. We explore the molecular effects of low-intensity shock wave therapy (Li-ESWT) on central sensitization in a capsaicin-induced prostatitis rat model. Male Sprague–Dawley rats underwent intraprostatic capsaicin (10 mM, 0.1 cm3) injections. After injection, the prostate received Li-ESWT twice, one day apart. The L6 dorsal root ganglion (DRG)/spinal cord was harvested for histology and Western blotting on days 3 and 7. The brain blood oxygenation level-dependent (BOLD) functional images were evaluated using 9.4 T fMRI before the Li-ESWT and one day after. Intraprostatic capsaicin injection induced increased NGF-, BDNF-, and COX-2-positive neurons in the L6 DRG and increased COX-2, NGF, BDNF, receptor Trk-A, and TRPV1 protein expression in the L6 DRG and the dorsal horn of the L6 spinal cord, whose effects were significantly downregulated after Li-ESWT on the prostate. Intraprostatic capsaicin injection increased activity of BOLD fMRI responses in brain regions associated with pain-related responses, such as the caudate putamen, periaqueductal gray, and thalamus, whose BOLD signals were reduced after Li-ESWT. These findings suggest a potential mechanism of Li-ESWT on modulation of peripheral and central sensitization for treating CP/CPPS.

Toward an integrative neurovascular framework for studying brain networks.

.Brain functional connectivity based on the measure of blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signals has become one of the most widely used measurements in human neuroimaging. However, the nature of the functional networks revealed by BOLD fMRI can be ambiguous, as highlighted by a recent series of experiments that have suggested that typical resting-state networks can be replicated from purely vascular or physiologically driven BOLD signals. After going through a brief review of the key concepts of brain network analysis, we explore how the vascular and neuronal systems interact to give rise to the brain functional networks measured with BOLD fMRI. This leads us to emphasize a view of the vascular network not only as a confounding element in fMRI but also as a functionally relevant system that is entangled with the neuronal network. To study the vascular and neuronal underpinnings of BOLD functional connectivity, we consider a combination of methodological avenues based on multiscale and multimodal optical imaging in mice, used in combination with computational models that allow the integration of vascular information to explain functional connectivity.

Comparison of test\u2013retest reliability of BOLD and pCASL fMRI in a two-center study

BackgroundThe establishment of test–retest reliability and reproducibility (TRR) is an important part of validating any research tool, including functional magnetic resonance imaging (fMRI). The primary objective of this study is to investigate the reliability of pseudo-Continuous Arterial Spin Labeling (pCASL) and Blood Oxygen Level Dependent (BOLD) fMRI data acquired across two different scanners in a sample of healthy adults. While single site/single scanner studies have shown acceptable repeatability, TRR of both in a practical multisite study occurring in two facilities spread out across the country with weeks to months between scans is critically needed.MethodsTen subjects were imaged with similar 3 T MRI scanners at the University of Pittsburgh and Massachusetts General Hospital. Finger-tapping and Resting-state data were acquired for both techniques. Analysis of the resting state data for functional connectivity was performed with the Functional Connectivity Toolbox, while analysis of the finger tapping data was accomplished with FSL. pCASL Blood flow data was generated using AST Toolbox. Activated areas and networks were identified via pre-defined atlases and dual-regression techniques. Analysis for TRR was conducted by comparing pCASL and BOLD images in terms of Intraclass correlation coefficients, Dice Similarity Coefficients, and repeated measures ANOVA.ResultsBoth BOLD and pCASL scans showed strong activation and correlation between the two locations for the finger tapping tasks. Functional connectivity analyses identified elements of the default mode network in all resting scans at both locations. Multivariate repeated measures ANOVA showed significant variability between subjects, but no significant variability for location. Global CBF was very similar between the two scanning locations, and repeated measures ANOVA showed no significant differences between the two scanning locations.ConclusionsThe results of this study show that when similar scanner hardware and software is coupled with identical data analysis protocols, consistent and reproducible functional brain images can be acquired across sites. The variability seen in the activation maps is greater for pCASL versus BOLD images, as expected, however groups maps are remarkably similar despite the low number of subjects. This demonstrates that multi-site fMRI studies of task-based and resting state brain activity is feasible.

Cerebral hemodynamic response to caffeine: effect of dietary caffeine consumption.

Caffeine has a significant effect on cerebrovascular systems, and the dual action of caffeine on both neural and vascular responses leads to concerns for the interpretation of blood oxygenation level-dependent (BOLD) functional MRI. However, potential differences in the brain response to caffeine with regard to consumption habits have not been fully elucidated, as BOLD responses may vary with the dietary caffeine consumption history. The main aim of this study was to characterize the acute effect of caffeine on cerebral hemodynamic responses in participants with different patterns of caffeine consumption habits. Fifteen non-habitual and 11 habitual volunteers were included in this study. The cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to the breath-hold challenge were measured before and after 200 mg caffeine administration. The non-habitual individuals exhibited a pattern of progressive reduction in CBF with time. The CVR was diminished in the caffeinated condition (P < 0.05). In the habitual group, the pattern of CBF decrease was smaller and homogeneous across the brain, and reached steady state rapidly. The CVR was not affected in the presence of caffeine (P > 0.05). Our results demonstrated that the cerebral hemodynamic response to caffeine was subject to the habitual consumption patterns of the participants. The compromised CVR following caffeine administration in the non-habitual group may partially explain the suppressed BOLD response to a visual stimulation in low-caffeine-level users.

Perception is associated with the brain's metabolic response to sensory stimulation.

Processing of incoming sensory stimulation triggers an increase of cerebral perfusion and blood oxygenation (neurovascular response) as well as an alteration of the metabolic neurochemical profile (neurometabolic response). Here, we show in human primary visual cortex (V1) that perceived and unperceived isoluminant chromatic flickering stimuli designed to have similar neurovascular responses as measured by blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) have markedly different neurometabolic responses as measured by proton functional magnetic resonance spectroscopy (1H-fMRS). In particular, a significant regional buildup of lactate, an index of aerobic glycolysis, and glutamate, an index of malate-aspartate shuttle, occurred in V1 only when the flickering was perceived, without any relation with other behavioral or physiological variables. Whereas the BOLD-fMRI signal in V1, a proxy for input to V1, was insensitive to flickering perception by design, the BOLD-fMRI signal in secondary visual areas was larger during perceived than unperceived flickering, indicating increased output from V1. These results demonstrate that the upregulation of energy metabolism induced by visual stimulation depends on the type of information processing taking place in V1, and that 1H-fMRS provides unique information about local input/output balance that is not measured by BOLD-fMRI.