***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: No human fMRI studies have examined ketamine effects on the BOLD signal change associated with cognitive task performance . We wished to distinguish between effects on 1 ) cerebral blood flow , with result ant change in BOLD signal ; and 2 ) cognition and neural mechanisms underlying BOLD signal change associated with task performance . Eight right‐h and ed men ( mean age 28.75 years ) received ketamine or saline i.v . in a r and omized , double‐blind manner ( bolus 0.23 mg/kg ; 0.5 mg/kg over 45 min to a maximum 1 hr ) . Subjects viewed 10 alternating 30‐sec blocks of faces with neutral expressions and a fixation cross and discriminated gender of faces . Gradient echo echoplanar images were acquired on a GE Signa 1.5 T Neurovascular system . One hundred T2‐weighted images depicting BOLD contrast were acquired over 5 min ( for each task ) at each of 14 near‐axial noncontiguous 7‐mm thick planes . Ketamine significantly increased dissociative phenomena and negative symptoms , but did not affect performance of the gender discrimination task . Significant BOLD signal change was demonstrated predominantly in occipitotemporal cortex with both ketamine and placebo . Only two clusters in middle occipital gyrus ( BA 18 ) and pre central gyrus ( BA 4 ) showed significantly decreased BOLD signal change  during ketamine compared to  placebo . BOLD signal change was not significantly greater in any region during ketamine . Our findings demonstrate subtle rather than major differences between the effects of ketamine and placebo upon the BOLD signal change during perception of face – non face contrast . We suggest that they represent task‐dependent effects of the drug/placebo , rather than task‐independent effects of the drug per se , and indicate that the effects of ketamine on cerebral blood flow are predominantly focal and task‐dependent , rather than global and task‐independent . Hum . Brain Mapping 18:135–145 , 2003 . © 2002 Wiley‐Liss , UNLABELLED The combination of propofol and ketamine has been used for total IV anesthesia . This study was design ed to clarify the effects of propofol-ketamine anesthesia on cerebral circulation by using transcranial Doppler ultrasonography . In Study 1 , we examined the time course of time-mean middle cerebral artery blood flow velocity ( Vmca ) after ketamine  ( n = 10 ) or  saline ( n = 6 ) administration during propofol anesthesia . In Study 2 , CO(2 ) responses were measured under the following conditions :  awake ( Group C , n = 7 ) , propofol anesthesia ( Group D , n = 7 ) , and propofol-ketamine anesthesia ( Group E , n = 8) .  Ketamine administration during propofol anesthesia administration did not affect Vmca , mean arterial pressure , or heart rate . Vmca under normocapnia in Groups D and E were 36 + /- 3 and 37 + /- 3 cm/s ( mean + /- SE ) , respectively . The values were significantly lower than that of Group C ( 70 + /- 3 cm/s ) . The CO(2 ) response slopes of Groups D and E were significantly lower than that of Group C , although there was no significant difference between Groups D and E. These results suggest that ketamine does not influence Vmca or the cerebrovascular CO(2 ) response during propofol anesthesia administration , although the sample size in each group was small . IMPLICATION S Our study suggests that ketamine does not influence middle cerebral artery blood flow velocity or the cerebrovascular CO(2 ) response assessed by transcranial Doppler ultrasonography during propofol anesthesia administration in patients without neurological complications Traumatic brain injury ( TBI ) remains a major public health problem , and there is a great medical need for a pharmacological treatment that could improve long-term outcome . The excitatory neurotransmitter , glutamate , has been implicated in processes leading to neurodegeneration . Traxoprodil ( CP-101,606 ) is a novel and potent glutamate receptor antagonist that is highly selective for the NR2B subunit of the NMDA receptor ; it has been shown to be neuroprotective in animal models of brain injury and ischemia . A r and omized , double-blind , placebo-controlled study was therefore conducted to assess the efficacy and safety of a 72-h infusion of traxoprodil compared to placebo in subjects with computed tomography scan evidence of severe TBI ( GCS 4 - 8 ) . A total of 404 males and non-pregnant females , aged 16 - 70 , were treated within 8 h of injury . At baseline , subjects were stratified by motor score severity . The results showed that a greater proportion of the traxoprodil-treated subjects had a favorable outcome on the dichotomized Glasgow Outcome Scale ( dGOS ) at 6 months ( delta 5.5 % , OR 1.3 , p = 0.21 , 95 % CI:[0.85 , 2.06 ] ) and at last visit ( delta 7.5 % , OR 1.47 , p = 0.07 , 95 % CI:[0.97 , 2.25 ] ) . The mortality rate with traxoprodil treatment was 7 % less than with placebo treatment ( OR 1.45 , p = 0.08 , 95 % CI:[0.96 , 2.18 ] ) . Differences between treatment groups were more pronounced in the severest subset ( delta 11.8 % for the dGOS at last visit and delta 16.6 % for mortality ) . Traxoprodil was well tolerated . Although these results are intriguing , no definitive cl aim of efficacy can be made for traxoprodil for the treatment of severe TBI The purpose of the present study was to assess the effects of low-dose ketamine on spontaneous brain electrical activity ( EEG ) and intracranial blood flow velocity .  Twenty healthy volunteers were divided into two groups : Group I ( n=10 ) received 0.25 mg·kg−1 ketamine iv ; Group II ( n=10 ) received 0.5 mg·kg−1 ketamine iv . Mean arterial blood pressure ( MAP ) , heart rate ( HR ) , end-tidal PCO2 ( PetCO2 ) , and arterial oxygen saturation ( SaO2 ) were measured . The EEG  was recorded from temporo-occipital recording sites over both hemispheres . Blood flow velocity in the middle cerebral artery was measured using a transcranial Doppler ultrasound system . All variables were evaluated at baseline and for 60 min following ketamine . Administration of ketamine result ed in increases of MAP and HR in both groups to a similar degree . ThePetCO2 and SaO2 did not change in either group over time . Ketamine caused a dose-dependent , transient shift in the EEG to synchronous high-voltage slow waves with an increase in total power ( Group 1 : 301±38 % ; Group II : 104±28 % ) . These changes were associated with dose-dependent increases in mean blood flow velocity ( Group I : 35±7 % ; Group II : 68±10 % ) . Our data suggest that increases in intracranial blood flow velocity are closely correlated to increases in neuronal activity and are not secondary to changes in systemic haemodynamic variables . RésuméLe but de cette étude était d’évaluer les effets de petites doses de kétamine sur l’activité electrique spontanée du cerveau ( EEG ) en corrélation avec le changement de la vélocité du débit sanguin cérébral . Vingt volontaires saïns étaient divisés en deux groupes d’une façon r and omisée . Le groupe I ( n=10 ) a recu une dose de 0,25 mg·kg−1 de ketamine ; le groupe II ( n=10 ) a reçu 0,5 mg·kg−1 de ketamine par voie intraveineuse . Les paramètres suivants étaient mésurés : la pression arterielle moyenne ( MAP ) , la fréquence cardiaque ( HR ) , la PCO2 en fin d’expiration ( PetCO2 ) et la saturation artérielle en oxygène ( SaO2 ) . L’EEG était enregistré à l’aide d’électrodes adhésives placées sur la région temporo-occipitale des deux hémisphères . La vélocité du débit sanguin dans l’artère cérébrale moyenne ( MCA ) était mesurée par un doppler trans-crânien ( TCD ) . Tous les paramètres étaient évalués au début et jusqu ’ aux 60 minutes après l’application de kétamine . Dans les deux groupes , l’administration de kétamine évoquait une augmentation de la pression artérielle moyenne et de la fréquence cardiaque au même niveau ; laPetCO2 et la SaO2 n’ont subi aucune modification pendant toute la durée du protocol e. Dépendant de la dose appliquée la kétamine a évoqué une modification passagère du tracé EEG vers des ondes synchrones de basse fréquence et un voltage de gr and e amplitude ainsi qu’une augmentation du spectre de puissance ( groupe I : 301±38 % ; group II : 104±28 % ) . Ces changements étaient associés à l’augmentation de la vélocité du flot sanguin cérébral . Nous concluons que les altérations des paramètres hémodynamiques cérébrales ont une meilleure corrélation avec l’activité neuronale du cerveau et ne sont pas secondaire au changement des paramètres cardiovasculaires Background Animal experiments have demonstrated neuroprotection by ketamine . However , because of its propensity to increase cerebral blood flow , metabolism , and intracranial pressure , its use in neurosurgery or trauma patients has been question ed . Methods 15O-labeled water , oxygen , and carbon monoxide were used as positron emission tomography tracers to determine quantitative regional cerebral blood flow ( rCBF ) , metabolic rate of oxygen ( rCMRO2 ) , and blood volume ( rCBV ) , respectively , on selected regions of interest of nine healthy male volunteers at baseline and during three escalating concentrations of ketamine ( targeted to 30 , 100 , and 300 ng/ml ) . In addition , voxel-based analysis for relative changes in rCBF and rCMRO2 was performed using statistical parametric mapping . Results The mean ± SD measured ketamine serum concentrations were 37 ± 8 , 132 ± 19 , and 411 ± 71 ng/ml . Mean arterial pressure was slightly elevated ( maximally by 15.3 % , P < 0.001 ) during ketamine infusion . Ketamine  increased rCBF in a concentration-dependent manner . In the region-of-interest analysis , the greatest absolute changes were detected at the highest ketamine concentration level in the anterior cingulate ( 38.2 % increase from baseline , P < 0.001 ) , thalamus ( 28.5 % , P < 0.001 ) , putamen ( 26.8 % , P < 0.001 ) , and frontal cortex ( 25.4 % , P < 0.001 ) . Voxel-based analysis revealed marked relative rCBF increases in the anterior cingulate , frontal cortex , and insula . Although absolute rCMRO2 was not changed in the region-of-interest analysis , subtle relative increases in the frontal , parietal , and occipital cortices and decreases predominantly in the cerebellum were detected in the voxel-based analysis . rCBV increased only in the frontal cortex ( 4 % , P = 0.022 ) . Conclusions Subanesthetic doses of ketamine  induced a global increase in rCBF but no changes in rCMRO2 . Consequently , the regional oxygen extraction fraction was decreased . Disturbed coupling of cerebral blood flow and metabolism is , however , considered unlikely because ketamine has been previously shown to increase cerebral glucose metabolism . Only a minor increase in rCBV was detected . Interestingly , the most profound changes in rCBF were observed in structures related to pain processing Schizophrenia may be related to dysfunctional glutamatergic activity , specifically hypofunction of the N-methyl-D-aspartate receptor ( NMDAR ) . In addition , it has been proposed that NMDAR hypofunction may paradoxically cause an increase in glutamate release and hypermetabolism in corticolimbic regions . If a state of partial , chronic NMDAR blockade underlies schizophrenia , then schizophrenic volunteers ( SV ) may have greater glutamate release and associated elevations in regional cerebral blood flow ( rCBF ) than normal volunteers ( NV ) , following drug-induced NMDAR antagonism . Therefore , we have given acute ketamine , a noncompetitive NMDAR antagonist , to NV ( n=13 ) and medicated volunteers with schizophrenia ( n=10 ) in conjunction with serial positron emission tomography blood flow studies . Drug administration caused marked rCBF elevations in frontal and cingulate regions in both groups . Contrasts between NV and SV ketamine groups showed that SV had greater relative blood flow increases in the anterior cingulate than NV . Maximum blood flow , and the area under the curve for blood flow in the anterior cingulate cortex , significantly correlated with changes in psychosis ratings in SV and NV ( maximum rCBF only ) . These changes are consistent with a relatively 
    Output:
    
Animal models indicate an increase in global CBF and rCBF with ketamine administration , with a trend to vasodilation of medium-sized intracranial vessels through a calcium-dependent mechanism .