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Study Title and Description

Caffeine alters resting-state functional connectivity measured by blood oxygenation level-dependent MRI.



Key Questions Addressed
1 For [population], is caffeine intake above [exposure dose], compared to intakes [exposure dose] or less, associated with adverse effects on cardiovascular outcomes?
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Primary Publication Information
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TitleData
Title Caffeine alters resting-state functional connectivity measured by blood oxygenation level-dependent MRI.
Author WC Wu,SH Lien,JH Chang,SC Yang,
Country
Year 2014
Numbers

Secondary Publication Information
There are currently no secondary publications defined for this study.


Extraction Form: Cardiovascular Design
Design Details
Question... Follow Up Answer Follow-up Answer
What outcome is being evaluated in this paper? Cardiovascular
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What is the objective of the study (as reported by the authors)? This study aimed to investigate the pharmacological effect of caffeine on functional connectivity measured by resting-state blood oxygenation level-dependent (BOLD) MRI in the motor cortex, visual cortex and default mode network (DMN).
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Provide a general description of the methods as reported by the authors. Information should be extracted based on relevance to the SR (i.e., caffeine related methods) Subjects: Twenty healthy volunteers (10 women and 10 men; age, 21–35 years) were recruited. All subjects provided written informed consent, before which they were informed of their participation in a single-blind caffeine/placebo experiment. Three were excluded from data analysis because of excessive motion (a man aged 28 years and two women aged 22 and 30 years). The subjects were instructed to abstain from caffeine intake 24 h before the experiment. All participants self-reported to be right-handed, and none had been habitual caffeine consumers within the last 6 months (<300mg per week). The subjects were given a headphone to attenuate the acoustic noise from the scanner. Foam pads were wedged between the subject’s head and the coil for stabilization. During the resting-state BOLD and ASL imaging, the subjects were asked to keep their eyes open and to avoid cognitive activities. After the pre-dose session, the subjects were brought out of the scanner, requested to take a 200-mg over-the-counter caffeine pill and allowed to rest outside the scanner for 30 min. They were then repositioned for the post-dose session. The post-dose functional imaging started approximately 45min after oral ingestion to permit appropriate absorption and distribution of caffeine. No adverse effects were reported during and after the experiment. As a control arm, 10 subjects were asked to repeat the above experiment with the same procedure (on a different day), except that they were all given placebo. Task paradigm and signal recording: The subjects were instructed via the intercom to use their right hand to tap the thumb against the fingers in a sequential order at a self-paced speed. For visual stimulation, an 8-Hz, whole-field, black/white flashing checkerboard was projected onto a screen and viewed by the subject via a mirror attached to the head coil. A block design was adopted to include five 20-s ‘on’ epochs interleaved with ‘off’ epochs of varied durations (20–60 s), such that the motor and visual tasks were semi-random to each other. For the prospective recording of the physiological signals, a pulse oximeter was clipped to the subjects’ left index finger, and a pneumatic respiratory belt was placed on their upper abdomen. Transistor–transistor logic pulse data from the scanner were also recorded for subsequent identification of the cardiac and respiratory phases at which the images were acquired. MRI: MRI was performed on a 3-T whole-body scanner (Tim Trio, Siemens, Erlangen, Germany) using the body coil to transmit radiofrequency pulses and a 12-channel phased-array head coil to receive signals. The experiment comprised two identical sessions (pre-dose and post-dose), each including a scout, T1-weighted, three-dimensional, magnetization-prepared rapid gradient-echo anatomical imaging sequence [TR/TE/TI, 2530/3/ 1100ms; flip angle, 7°; voxel size, 1 x 1 x1mm3; generalized autocalibrating partially parallel acquisition (GRAPPA) acceleration factor, 2], task-based BOLD imaging sequence, resting-state ASL and BOLD imaging. For ASL and BOLD imaging, 19 axial slices were prescribed, with the center slice at the level of the corpus callosum (slice thickness, 5mm; interslice gap, 1mm; in-plane matrix, 64 x 64; field of view, 20cm; single-shot, gradient-echo, echo-planar readout). In particular, the following settings were used for task-based and resting-state BOLD imaging: TR = 2 s; TE = 30ms; measurements, 170 and 240, respectively. For ASL imaging: TR = 4 s; TE = 18ms; measurements, 60 (i.e. 30 pairs of tag and control images). A pseudocontinuous version of ASL was adopted with a tagging duration of 1 s and post-labeling delay of 1.2 s. Calibration and reference scans were obtained for the correction of the tagging efficiency and coil sensitivity, as well as for flow quantification.
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How many outcome-specific endpoints are evaluated? 1
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What is the (or one of the) endpoint(s) evaluated? (Each endpoint listed separately) Cerebral blood flow
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List additional health endpoints (separately). 2
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List additional health endpoints (separately).3
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List additional health endpoints (separately).4
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List additional health endpoints (separately).5
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List additional health endpoints (separately).6
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Clinical, physiological, other Physiological
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What is the study design? Controlled Trial
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Randomized or Non-Randomized? NCT
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What were the diagnostics or methods used to measure the outcome? Objective
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Optional: Name of Method or short description MRI was performed on a 3-T whole-body scanner (Tim Trio, Siemens, Erlangen, Germany) using the body coil to transmit radiofrequency pulses and a 12-channel phased-array head coil to receive signals.
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Caffeine (general) Caffeine (general)
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Coffee, Chocolate, energy drink, gum, medicine/supplement, soda, tea, other?
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Measured or self reported? Measured
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Children, adolescents, adults, or pregnant included? Adults
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What was the reference, comparison, or control group(s)? (e.g. high vs low consumption, number of cups, etc.) Baseline and post-exposure blood flow results as well as a placebo arm were used.
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What were the listed confounders or modifying factors as stated by the authors? (e.g. multi-variable components of models.  Copy from methods) Data analysis: Complex data were reconstructed online into magnitude images and then exported to a laptop computer for offline processing. All echo-planar images underwent realignment series by series for motion correction. Physiological noise, including cardiac pulsations and respiratory motion, was removed from the resting-state BOLD images following the RETROICOR algorithm. For the ASL series, the tag and control images were separately realigned and averaged, followed by co-registration to the series mean. Perfusion-weighted images were generated by subtraction and then converted to quantitative perfusion maps in units of mL/100mL/min after tagging efficiency calibration and coil sensitivity correction. Gray matter masks were created to include the voxels classified as gray matter at a probability level of 0.90 in both the highresolution anatomical images and the reference images for flow calculation. For per-subject analysis, all images (including the masks) were co-registered to the mean echo-planar images of the two sessions. To detect activated areas, a boxcar function of the experimental paradigm convolved with a hemodynamic response function was fed to the general linear model, with the criteria of family-wise corrected p of ≤0.05 and cluster size of ≥3 voxels. Seeds were determined for the motor and visual cortices as the voxels detected in both sessions and contained in the gray matter mask. For DMN, the posterior cingulate cortex (PCC) was manually defined on the gray matter mask in reference to the anatomical landmarks and used as the seed. Functional connectivity was calculated using the general linearmodel with regressors of the seed, global signal and signal fluctuations estimated in the lateral ventricles. Voxels were deemed to be connected if all the following criteria were met: family-wise corrected p of ≤0.05, cluster size of ≥3 voxels and contained in the gray matter mask. To avoid bias in the selection of regions of interest, the intersession comparison of functional connectivity was performed on three contiguous slices that included the greatest number of connected voxels identified by both sessions. For group analysis, the above results were normalized to the Montreal Neurological Institute templates. The threshold of cluster size was set to 20 to account for the change in voxel dimension after spatial normalization (3.1 x 3.1 x 5mm3 versus 2x2x2mm3). All data analyses were performed using Statistical Parametric Mapping software (http://www.fil.ion.ucl.ac.uk/spm/) and homemade programs under the environment of MATLAB (http:// www.mathworks.com).
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What conflicts of interest were reported? Not mentioned.
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Refid 24478235
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What were the sources of funding? This work was supported by the National Science Council of Taiwan (grants 103-2420-H-002-006-MY2 and 102-2221-E-002-219).
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Results & Comparisons

No Results found.