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Background: Altered neural activity based on the fractional amplitude of low-frequency fluctuations (fALFF) has been reported in patients with diabetes. However, whether fALFF can differentiate healthy controls from diabetic animals under anesthesia remains unclear. The study aimed to elucidate the changes in fALFF in a rat model of diabetes under isoflurane anesthesia. Methods: The first group of rats (n = 5) received a single intraperitoneal injection of 70 mg/kg streptozotocin (STZ) to cause the development of diabetes. The second group of rats (n = 7) received a single intraperitoneal injection of the same volume of solvent. Resting-state functional magnetic resonance imaging was used to assess brain activity at 4 weeks after STZ or solvent administration. Results: Compared to the healthy control animals, rats with diabetes showed significantly decreased fALFF in various brain regions, including the cingulate cortex, somatosensory cortex, insula, and striatum (all P < 0.05). The decreased fALFF suggests the aberrant neural activities in the diabetic rats. No regions were detected in which the control group had a lower fALFF than that in the diabetes group. Conclusions: The results of this study demonstrated that the fALFF could be used to differentiate healthy controls from diabetic animals, providing meaningful information regarding the neurological pathophysiology of diabetes in animal models. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Cerebrovascular reactivity (CVR) is a specific indicator of autoregulatory efficiency. Studies have demonstrated that CVR depends on the baseline vascular dilation status between groups. Within the brain, there also exist spatial variations in both the resting cerebral blood flow (CBF) and CVR across different cerebral regions. However, the relationship between the regional CBF and CVR remains unclear. Hence, the primary goal of this study was to investigate the relationship between the resting CBF using pseudocontinuous arterial spin labeling (pCASL) technique and CVR using blood oxygenation level‐dependent (BOLD) technique across different cerebral regions. Eleven male and 14 female young volunteers were recruited in this study. Each subject was asked to perform the breath‐holding challenge to evaluate CVR at 3 T. The resting CBF was measured using pCASL in each subject. The relationships between CBF and CVR across the lobes were evaluated using the Spearman's rank test. The results showed that, for both sexes, the frontal lobe had the maximal resting perfusion but minimal vascular response to hypercapnia, whereas the occipital lobe had the lowest baseline CBF but maximal reactivity to hypercapnia, suggesting low and high autoregulatory efficiencies at high and low resting CBF in the brain, respectively. Sex‐related differences were observed in CBF but not in CVR. These findings may be of clinical interest in the assessment of cerebrovascular reserve and regional‐dependent vascular diseases. [ABSTRACT FROM AUTHOR]

By reducing the cerebral blood flow and thereby increasing the resting deoxyhaemoglobin concentration, many human studies have shown that caffeine has a beneficial effect on enhancing the magnitude of blood‐oxygenation‐level‐dependent (BOLD) responses. However, the effect of caffeine on BOLD responses in animals under anaesthesia has not been demonstrated. In this study, we aimed to determine the effect of systemic caffeine administration on BOLD responses in rats under alpha‐chloralose. By applying electric whisker pad stimulation to male Sprague‐Dawley rats, we performed fMRI measurements before and after the caffeine injection (40 mg/kg, n = 7) or an equivalent volume of saline (n = 6) at 7T. To understand the potential perturbation of animal physiology during stimulation, arterial blood pressure was measured in a separate group of animals (n = 3) outside the scanner. Caffeine significantly decreased baseline BOLD signals (p =.05) due to the increased deoxyhaemoglobin level. Both BOLD responses and t‐values in the primary somatosensory cortex were significantly increased (both p <.05). The blood pressure changed insignificantly (p >.05). No significant differences in BOLD responses and t‐values were observed in the control condition of saline injection (both p >.05). These findings suggested that, although the cerebral activity was lower under alpha‐chloralose anaesthesia, the higher level of deoxygemoglobin at the baseline under the caffeinated condition can benefit the magnitude of BOLD responses in rats. These findings suggest that animal models might serve as potential platforms for further caffeine‐related fMRI research studies. [ABSTRACT FROM AUTHOR]

The selection of the appropriate hemodynamic response function (HRF) for signal modeling in functional magnetic resonance imaging (fMRI) is important. Although the use of the boxcar-shaped hemodynamic response function (BHRF) and canonical hemodynamic response (CHRF) has gained increasing popularity in rodent fMRI studies, whether the selected HRF affects the results of rodent fMRI has not been fully elucidated. Here we investigated the signal change and t -statistic sensitivities of BHRF, CHRF, and impulse response function (IRF). The effect of HRF selection on different tasks was analyzed by using data collected from two groups of rats receiving either 3 mA whisker pad or 3 mA forepaw electrical stimulations (n = 10 for each group). Under whisker pad stimulation with large blood-oxygen-level dependent (BOLD) signal change (4.31 ± 0.42%), BHRF significantly underestimated signal changes (P < 0.001) and t -statistics (P < 0.001) compared with CHRF or IRF. CHRF and IRF did not provide significantly different t -statistics (P > 0.05). Under forepaw stimulation with small BOLD signal change (1.71 ± 0.34%), different HRFs provided insignificantly different t -statistics (P > 0.05). Therefore, the selected HRF can influence data analysis in rodent fMRI experiments with large BOLD responses but not in those with small BOLD responses. [ABSTRACT FROM AUTHOR]

Cerebrovascular reactivity (CVR) can give insight into the cerebrovascular function. CVR can be estimated by measuring a blood‐oxygen‐level‐dependent (BOLD) response combined with breath‐holding (BH). The reproducibility of this technique has been addressed and existing studies have focused on short‐term reproducibility using a 3 T magnetic resonance imaging (MRI) system. However, little is known about the long‐term reproducibility of this procedure and the corresponding reproducibility using a 1.5 T MRI system. Here, we systematically examined the short‐ and long‐term reproducibility of BOLD responses to BH across field strengths. Nine subjects participated in three MRI sessions separated by 30 minutes (sessions 1 and 2: short term) and 68–92 days (sessions 1 and 3, long term) at both 1.5 and 3 T MRI. Our findings revealed that significant differences between field strengths were detected in the activated gray matter volume and BOLD signal change (both P < 0.001), with smaller magnitudes at 1.5 T. However, activation patterns were reproducible, independent of the time interval, brain region or field strength. All interscan coefficient of variation values were below the 33% fiducial limit, and the intraclass correlation coefficient values were above 0.4, which is usually considered the acceptability limit in functional studies. These findings suggest that the response of BOLD signal to BH for assessing CVR is reproducible over time at 1.5 and 3 T. This technique can be considered a tool for monitoring longitudinal changes in patients with cerebrovascular diseases, and its use should be encouraged for clinical 1.5 T MRI systems. [ABSTRACT FROM AUTHOR]

Abstract Functional connectivity MRI, based on Blood-Oxygenation-Level-Dependent (BOLD) signals, is typically performed while the subject is at rest. On the other hand, BOLD is also widely used in physiological imaging such as cerebrovascular reactivity (CVR) mapping using hypercapnia (HC) as a modulator. We therefore hypothesize that hypercapnia BOLD data can be used to extract FC metrics after factoring out the effects of the physiological modulation, which will allow simultaneous assessment of neural and vascular function and may be particularly important in populations such as aging and cerebrovascular diseases. The present work aims to systematically examine the feasibility of hypercapnia BOLD-based FC mapping using three commonly applied analysis methods, specifically dual-regression Independent Component Analysis (ICA), region-based FC matrix analysis, and graph-theory based network analysis, in a large cohort of 170 healthy subjects ranging from 20 to 88 years old. To validate the hypercapnia BOLD results, we also compared these FC metrics with those obtained from conventional resting-state data. ICA analysis of the hypercapnia BOLD data revealed FC maps that strongly resembled those reported in the literature. FC matrix using region-based analysis showed a correlation of 0.97 on the group-level and 0.54 ± 0.10 on the individual-level, when comparing between hypercapnia and resting-state results. Although the correspondence on the individual-level was moderate, this was primarily attributed to variations intrinsic to FC mapping, because a corresponding resting-vs-resting comparison in a sub-cohort (N = 39) revealed a similar correlation of 0.57 ± 0.09. Graph-theory computations were also feasible in hypercapnia BOLD data and indices of global efficiency, clustering coefficient, modularity, and segregation were successfully derived. Hypercapnia FC results revealed age-dependent differences in which within-network connections generally exhibited an age-dependent decrease while between-network connections showed an age-dependent increase. Highlights • Hypercapnia BOLD data can be used to compute functional connectivity metrics. • ICA, region based, and graph-theory based results were all feasible. • Hypercapnia FC metrics were compatible with those obtained with resting-state data. • Hypercapnia FC metrics showed age-dependence similar to those in resting-state data. [ABSTRACT FROM AUTHOR]