***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: This study explored the possible use of caffeine as an agent to improve the  BOLD ( blood oxygen level-dependent ) signal response in fMRI . Previous research has demonstrated that caffeine has the ability to reset the level of coupling between blood flow and neuronal activity . In the present study , it has been shown that caffeine causes a decrease in cerebral perfusion by as much as 13.2 % without a change in performance . Caffeine is a cerebral vasoconstrictor that causes an increase in the concentration of deoxyhemoglobin and thus a decrease in the BOLD baseline resting signal by 4.4 % . During activation , the vasculature responds from below-normal baseline levels with a normal increase in blood flow and volume , result ing in an overall increase in the BOLD contrast . This increase can be as large as 22 - 37 % during the performance of a visually cued motor task . The benefit of such a large increase in the BOLD contrast could be used to improve the image resolution , the acquisition scheme , or the task design of fMRI experiments . Caffeine has the potential to be used as a contrast booster for fMRI experiments The modulation of blood oxygenation level-dependent ( BOLD ) cerebral MRI contrast by the vasoconstrictive drug indomethacin ( i.v . 0.2 mg/kg b.w . ) was investigated in 10 healthy young adults without and with functional challenge ( repetitive and sustained visual activation ) . For comparison , isotonic saline ( placebo , 20 mL ) and acetylsalicylate ( i.v . 500 mg ) were investigated as well , each in separate sessions using identical protocol s. After indomethacin , dynamic T2 * -weighted echo-planar MRI at 2.0 T revealed a rapid decrease in MRI signal intensity by 2.1%-2.6 % in different gray matter regions ( P < or = 0.001 compared to placebo ) , which was not observed for acetylsalicylate and the placebo condition . Regional signal differences were not significant within gray matter , but all gray matter regions differed significantly from the signal decrease of only 1.2 % + /- 0.7 % observed in white matter ( P = 0.001 ) . For the experimental parameters used , a 1 % MRI signal decrease in response to indomethacin was estimated to correlate with a decrease of the cerebral blood flow by about 12 ml/100 g/minute , and an increase of the oxygen extraction fraction by about 15 % . Responses to visual activation were not affected by saline or acetylsalicylate , and yielded 5.0%-5.5 % BOLD MRI signal increases both before and after drug application . In contrast , indomethacin reduced the initial response strength to 82%-85 % of that obtained without the drug . The steady-state response during sustained activation reached only 47 % of the corresponding pre-drug level ( P < 0.01 ) . During repetitive activation the BOLD contrast was reduced to 66 % of that observed for control conditions ( P < 0.001 ) . In conclusion , indomethacin attenuates the vasodilatory force at functional brain activation , indicating different mechanisms governing neurovascular coupling KEY POINTS Cerebral blood flow increases during hypercapnia and decreases during hypocapnia ; it is unknown if vasomotion of the internal carotid artery is implicated in these responses . Indomethacin , a non-selective cyclooxygenase inhibitor ( used to inhibit prostagl and in synthesis ) , has a unique ability to blunt cerebrovascular carbon dioxide reactivity , while other cyclooxygenase inhibitors have no effect . We show significant dilatation and constriction of the internal carotid artery during hypercapnia and hypocapnia , respectively . Indomethacin , but not ketorolac or naproxen , reduced the dilatatory response of the internal carotid artery to hypercapnia The differential effect of indomethacin compared to ketorolac and naproxen suggests that indomethacin inhibits vasomotion of the internal carotid artery independent of prostagl and in synthesis inhibition . ABSTRACT Extra-cranial cerebral blood vessels are implicated in the regulation of cerebral blood flow during changes in arterial CO2 ; however , the mechanisms governing CO2 -mediated vasomotion of these vessels in humans remain unclear . We determined if cyclooxygenase inhibition with indomethacin ( INDO ) reduces the vasomotor response of the internal carotid artery ( ICA ) to changes in end-tidal CO2 ( P ETC O2 ) . Using a r and omized single-blinded placebo-controlled study , participants ( n = 10 ) were tested on two occasions , before and 90 min following oral INDO ( 1.2 mg kg(-1 ) ) or placebo . Concurrent measurements of beat-by-beat velocity , diameter and blood flow of the ICA were made at rest and during steady-state stages ( 4 min ) of iso-oxic hypercapnia ( + 3 , + 6 , + 9 mmHg P ETC O2 ) and hypocapnia ( -3 , -6 , -9 mmHg P ETC O2 ) . To examine if INDO affects ICA vasomotion independent of cyclooxygenase inhibition , two participant subsets ( each n = 5 ) were tested before and following oral ketorolac ( post 45 min , 0.25 mg kg(-1 ) ) or naproxen ( post 90 min , 4.2 mg kg(-1 ) ) . During pre-drug testing in the INDO trial , the ICA dilatated during hypercapnia at + 6 mmHg ( 4.72 ± 0.45 vs. 4.95 ± 0.51 mm ; P < 0.001 ) and + 9 mmHg ( 4.72 ± 0.45 mm vs. 5.12 ± 0.47 mm ; P < 0.001 ) , and constricted during hypocapnia at -6 mmHg ( 4.95 ± 0.33 vs. 4.88 ± 0.27 mm ; P < 0.05 ) and -9 mmHg ( 4.95 ± 0.33 vs. 4.82 ± 0.27 mm ; P < 0.001 ) . Following INDO , vasomotor responsiveness of the ICA to hypercapnia was reduced by 67 ± 28 % ( 0.045 ± 0.015 vs. 0.015 ± 0.012 mm mmHg P ETC O2(-1 ) ) . There was no effect of the drug in the ketorolac and naproxen trials . We conclude that : ( 1 ) INDO markedly reduces the vasomotor response of the ICA to changes in P ETC O2 ; and ( 2 ) INDO may be reducing CO2 -mediated vasomotion via a mechanism(s ) independent of cyclooxygenase inhibition Nitric oxide ( NO ) regulates basal CBF . In a number of animal models NO has been implicated in the mediation of the regional changes in CBF ( rCBF ) that accompany neuronal activation ( vasoneuronal coupling ) . However , some results in animal models have failed to confirm this finding , and the validity of extrapolation to man from animal data is uncertain . To determine the contribution of NO to basal global CBF and activation-induced changes in rCBF , the authors have performed quantitative H215O positron emission tomography ( PET ) studies before and after administration of the non-isoform-specific NO synthase inhibitor , NG-monomethyl-l-arginine ( L-NMMA ) , in 10 healthy male volunteers .  Learning a novel sequence of finger movements was used as a paradigm to induce regional frontal cortex activation . The effect of NO synthase inhibition on the magnitude and pattern of activation was determined . Resting global CBF fell from 33.3 ± 5.3 mL·100 g−1·min−1 at rest before L-NMMA , to 26.5 ± 7.7 mL·100 g−1·min−1 after L-NMMA ( P = 0.001 ) . This fall was reversed by l-arginine administration . Learning sequential finger movements induced increases in rCBF in the left motor , right prefrontal , and bilateral premotor cortices . After NO synthase inhibition with L-NMMA , there was no change in this pattern of activation and no reduction in the magnitude of rCBF responses at the foci of maximal stimulation before and after L-NMMA . These findings confirm that NO production contributes to basal CBF regulation in man , but show that systemic NO synthase inhibition with L-NMMA does not impair regional vasoneuronal coupling 
    Output:
    
This analysis points to the existence of an unknown signalling mechanism accounting for approximately one third of the neurovascular response