***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: In the present study , we used positron emission tomography to investigate changes in regional cerebral blood flow ( rCBF ) during a general anesthetic infusion set to produce a gradual transition from the awake state to unconsciousness . Five right-h and ed human volunteers participated in the study . They were given propofol with a computer-controlled infusion pump to achieve three stable levels of plasma concentrations corresponding to mild sedation , deep sedation , and unconsciousness , the latter defined as unresponsiveness to verbal comm and s. During awake baseline and each of the three levels of sedation , two scans were acquired after injection of an H215O bolus .  Global as well as regional CBF were determined and correlated with propofol concentrations . In addition , blood flow changes in the thalamus were correlated with those of the entire scanned volume to determine areas of coordinated changes . In addition to a generalized decrease in global CBF , large regional decreases in CBF occurred bilaterally in the medial thalamus , the cuneus and precuneus , and the posterior cingulate , orbitofrontal , and right angular gyri . Furthermore , a significant covariation between the thalamic and midbrain blood flow changes was observed , suggesting a close functional relationship between the two structures . We suggest that , at the concentrations attained , propofol preferentially decreases rCBF in brain regions previously implicated in the regulation of arousal , performance of associative functions , and autonomic control . Our data support the hypothesis that anesthetics induce behavioral changes via a preferential , concentration-dependent effect on specific neuronal networks rather than through a nonspecific , generalized effect on the brain We investigated the effects of the general anesthetic agent propofol on cerebral structures involved in the processing of vibrotactile information . Using positron emission tomography ( PET ) and the H(2)(15)O bolus technique , we measured regional distribution of cerebral blood flow ( CBF ) in eight healthy human volunteers . They were scanned under five different levels of propofol anesthesia . Using a computer-controlled infusion , the following plasma levels of propofol were targeted : Level W ( Waking , 0 microg/ml ) , Level 1 ( 0.5 microg/ml ) , Level 2 ( 1.5 microg/ml ) , Level 3 ( 3.5 microg/ml ) , and Level R ( Recovery ) . At each level of anesthesia , two 3-min scans were acquired with vibrotactile stimulation of the right forearm either on or off . The level of consciousness was evaluated before each scan by the response of the subject to a verbal comm and . At Level W , all volunteers were fully awake . They reported being slightly drowsy at Level 1 , they had a slurred speech and slow response at Level 2 , and they were not responding at all at Level 3 . The following variations in regional CBF ( rCBF ) were observed . During the waking state ( Level W ) , vibrotactile stimulation induced a significant rCBF increase in the left thalamus and in several cortical regions , including the left primary somatosensory cortex and the left and right secondary somatosensory cortex . During anesthesia , propofol reduced in a dose-dependent manner rCBF in the thalamus as well as in a number of visual , parietal , and prefrontal cortical regions . At Level 1 through 3 , propofol also suppressed vibration-induced increases in rCBF in the primary and secondary somatosensory cortex , whereas the thalamic rCBF response was abolished only at Level 3 , when volunteers lost consciousness . We conclude that propofol interferes with the processing of vibrotactile information first at the level of the cortex before attenuating its transfer through the thalamus While ubiquitous , pharmacological manipulation of consciousness remains poorly defined and incompletely understood ( Prys-Roberts , 1987 ) . This retards anesthetic drug development , confounds interpretation of animal studies conducted under anesthesia , and limits the sensitivity of clinical monitors of cerebral function to intact perception . Animal and human studies propose a functional “ switch ” at the level of the thalamus , with inhibition of thalamo-cortical transmission characterizing loss of consciousness ( Alkire et al. , 2000 ; Mashour , 2006 ) . We investigated the effects of propofol , widely used for anesthesia and sedation , on spontaneous and evoked cerebral activity using functional magnetic resonance imaging ( fMRI ) . A series of auditory and noxious stimuli was presented to eight healthy volunteers at three behavioral states : awake , “ se date d ” and “ unresponsive . ” Performance in a verbal task and the absence of a response to verbal stimulation , rather than propofol concentrations , were used to define these states clinical ly . Analysis of stimulus-related blood oxygenation level-dependent signal changes identified reductions in cortical and subcortical responses to auditory and noxious stimuli in se date d and unresponsive states . A specific reduction in activity within the putamen was noted and further investigated with functional connectivity analysis . Progressive failure to perceive or respond to auditory or noxious stimuli was associated with a reduction in the functional connectivity between the putamen and other brain regions , while thalamo-cortical connectivity was relatively preserved . This result has not been previously described and suggests that disruption of subcortical thalamo-regulatory systems may occur before , or even precipitate , failure of thalamo-cortical transmission with the induction of unconsciousness Applying graph theoretical analysis of spontaneous BOLD fluctuations in functional magnetic resonance imaging ( fMRI ) , we investigated whole-brain functional connectivity of 11 healthy volunteers during wakefulness and propofol-induced loss of consciousness ( PI-LOC ) . After extraction of regional fMRI time series from 110 cortical and subcortical regions , we applied a maximum overlap discrete wavelet transformation and investigated changes in the brain 's intrinsic spatiotemporal organization . During PI-LOC , we observed a breakdown of subcortico-cortical and corticocortical connectivity . Decrease of connectivity was pronounced in thalamocortical connections , whereas no changes were found for connectivity within primary sensory cortices . Graph theoretical analyses revealed significant changes in the degree distribution and local organization metrics of brain functional networks during PI-LOC : compared with a r and om network , normalized clustering was significantly increased , as was small-worldness . Furthermore we observed a profound decline in long-range connections and a reduction in whole-brain spatiotemporal integration , supporting a topological reconfiguration during PI-LOC . Our findings shed light on the functional significance of intrinsic brain activity as measured by spontaneous BOLD signal fluctuations and help to underst and propofol-induced loss of consciousness Background : Anesthetics may affect the regional cerebral blood flow ( rCBF ) response associated with increased brain activity in humans . rCBF was measured as auditory stimulus rate was increased during propofol and thiopental administration . Methods : After informed consent , 10 right-h and ed male volunteer participants ( aged 33.5 ± 10.4 yr , weighing 74.5 ± 8.4 kg )  received thiopental ( n = 4 ) or propofol ( n = 6 ) intravenously at stepwise target concentrations of propofol 1.2 and 2.5–3 , or thiopental 4 and 7–9 & mgr;g/ml , representing sedative and hypnotic drug concentrations . The latter made volunteers unresponsive to voice or mild stimulation . Quantitative positron emission tomographic brain images were obtained at 0 , 20 , and 40 auditory words per minute at each drug concentration . Using SPM99 analysis , 10-mm spherical regions of interest were identified by peak covariation of word rate with rCBF across all conditions and drug concentrations . Individual mean rCBF responses in these and primary auditory cortex ( Heschl ’s gyri ) were obtained . Results : Significant increases in rCBF with auditory word rate occurred in temporal lobes bilaterally at baseline ( significance , T = 4.95 ) . There was no change in this response during sedation ( T = 5.60 ) . During unresponsiveness seven of 10 participants had a diminished response in the left temporal lobe ( T = 3.18 ) . Global CBF , corrected for changes in Pco2 ( 3 % · mmHg Pco2−1 ) , was reduced 15 % by sedation and 27 % during unresponsiveness . Conclusion : The presence of propofol or thiopental does not affect the rCBF response to increasing stimulus rate during consciousness . Thus , changes in rCBF activation patterns with sedative concentrations of these drugs represent effects on brain activity itself . The neuroanatomical targets of drug effect on memory and attention may be revealed by changes in rCBF patterns associated with these cognitive activities Background : Dynamic action of anesthetic agents was compared at cortical and subcortical levels during induction of anesthesia . Unconsciousness involved the cortical brain but suppression of movement in response to noxious stimuli was mediated through subcortical structures . Methods : Twenty-five patients with Parkinson disease , previously implanted with a deep-brain stimulation electrode , were enrolled during the implantation of the definitive pulse generator . During induction of anesthesia with propofol ( n = 13 ) or sevoflurane ( n = 12 ) alone , cortical ( EEG ) and subcortical ( ESCoG ) electrogenesis were obtained , respectively , from a frontal montage ( F3–C3 ) and through the deep-brain electrode ( p0–p3 ) . In EEG and ESCoG spectral analysis , spectral edge ( 90 % ) frequency , median power frequency , and nonlinear analysis dimensional activation calculations were determined . Results : Sevoflurane and propofol decreased EEG and ESCoG activity in a dose-related fashion . EEG values decreased dramatically at loss of consciousness , whereas there was little change in ESCoG values . Quantitative parameters derived from EEG but not from ESCoG were able to predict consciousness versus unconsciousness . Conversely , quantitative parameters derived from ESCoG but not from EEG were able to predict movement in response to laryngoscopy . Conclusion : These data suggest that in humans , unconsciousness mainly involves the cortical brain , but that suppression of movement in response to noxious stimuli is mediated through the effect of anesthetic agents on subcortical structures Background Functional magnetic resonance imaging of blood oxygenation level – dependent signal changes offers a very promising approach to investigate activated neural networks during anesthesia . Methods Sixteen healthy male volunteers , assigned into two groups of eight subjects ( isoflurane group , control group ) , were investigated by functional magnetic resonance imaging during different experimental conditions . The isoflurane group successively breathed air ( baseline condition ) , isoflurane in air ( 0.42 vol% inspiratory ; isoflurane condition ) and air again ( recovery condition ) while performing a visual search task , whereas the control group breathed air during all experimental conditions . Functional magnetic resonance images were acquired during the entire experimental session . In addition , reaction times and error rates were recorded . Results A significant isoflurane-related decrease ( z > 3.1 corresponding to P < 0.001 ) in task-induced brain activation was found in three distinct cortical regions : the right anterio-superior insula ( Talairach coordinates : x = 32 , y = 22 , z = 8) and the banks of the left and right intraparietal sulcus ( Talairach coordinates : x = −34 , y = −36 , z = 32 ; x = 22 , y = −60 , z = 41 , respectively ) . Subcortical structures ( lateral geniculate nucleus ) and the primary cortices ( motor cortex , visual cortex ) were not affected . All measured parameters indicated a nearly complete recovery of the affected networks within 5 min . Conclusions Our findings indicate that subanesthetic isoflurane affected task-induced activation in specific neural networks rather than causing a global decrease in functional activation Background This study was design ed to identify neuroanatomical locations of propofol 's effects on episodic memory by producing minimal and maximal memory impairment during conscious sedation . Drug-related changes in regional cerebral blood flow ( rCBF ) were located in comparison with rCBF increases during a simple word memory task . Methods Regional cerebral blood flow changes were assessed in 11 healthy volunteers using H215O positron emission tomography ( PET ) and statistical parametric mapping ( SPM99 ) at 600 and 1,000 ng/ml propofol target concentrations . Study groups were based on final recognition scores of auditory words memorized during PET scanning . rCBF changes during propofol administration were compared with those during the word memory task at baseline . Results Nonoverlapping memory effects were evident : low ( n = 4 ; propofol concentration 523 ± 138 ng/ml ; 44 ± 13 % decrement from baseline memory ) and high ( n = 7 ; 829 ± 246 ng/ml ; 87 ± 6 % decrement from baseline ) groups differed in rCBF reductions primarily in right-sided prefrontal and parietal regions , close to areas activated in the baseline memory task , particularly R dorsolateral prefrontal cortex ( Brodmann area 46 ; x , y , z = 51 , 38 , 22 ) . The medial temporal lobe region exhibited relative rCBF increases . Conclusions As amnesia becomes maximal , rCBF reductions induced by propofol occur in brain regions identified with working memory processes . In contrast , medial temporal lobe structures were resistant to the global CBF decrease associated with propofol sedation . The authors postulate that the episodic memory effect of propofol is produced by interference with distributed cortical processes necessary for normal memory function rather than specific effects on medial temporal lobe structures 
    Output:
    
In the unconscious state , propofol sharply reduces the regional glucose metabolism rate ( rGMR ) and regional cerebral blood flow ( rCBF ) in all brain regions , particularly in the thalamus .
However , GMR , such as in the occipital , temporal , and frontal lobes , was obviously decreased at a sedative dosage of propofol , whereas , changes in the thalamus were not obvious .
Using fMRI , several studies observed a decrease of connectivity of the thalamus versus an increase of connectivity within the pons of the brainstem during propofol-induced mild sedation .
During deep sedation , propofol preserves cortical sensory reactivity , the specific thalamocortical network is moderately affected , whereas the nonspecific thalamocortical network is severely suppressed .
In contrast , several recent fMRI studies are consistent on the systemic decreased effects of propofol in the frontoparietal network .
Accumulating evidence suggest that propofol-induced unconsciousness is associated with a global metabolic and vascular depression in the human brain and especially with a significant reduction in the thalamocortical network and the frontoparietal network