human
***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: Abstract : In a double-blind , parallel groups study , 60 healthy student volunteers ( 29 men and 31 women , aged 19 - 22 years ) were r and omly allocated to receive placebo , 100 or 200 mg modafinil . Two hours later , in the early evening , they completed an extensive cognitive battery . The 3 groups did not differ in self-ratings of sleepiness or tiredness before the testing session , and there were no treatment-associated changes in these or in mood ratings during the tests . Modafinil was without effect in several tests of reaction time and attention , but the 200-mg group was faster at simple color naming of dots and performed better than placebo in the Rapid Visual Information Processing test of sustained attention . Modafinil was without effect on spatial working memory , but the 100-mg group performed better in the backward part of the digit span test . Modafinil was without effect on verbal short-term memory ( story recall ) , but 100 mg improved digit span forward , and both doses improved pattern recognition , although this was accompanied by a slowing of response latency in the 200-mg group . There were no significant effects of modafinil compared with placebo in tests of long-term memory , executive function , visuospatial and constructional ability , or category fluency . These results suggest that the benefits of modafinil are not clearly dose-related , and those from 100 mg are limited to the span of immediate verbal recall and short-term visual recognition memory , which is insufficient for it to be considered as a cognitive enhancer in non-sleep-deprived individuals Abstract Rationale . Modafinil , a novel wake-promoting agent , has been shown to have a similar clinical profile to that of conventional stimulants such as methylpheni date . We were therefore interested in assessing whether modafinil , with its unique pharmacological mode of action , might offer similar potential as a cognitive enhancer , without the side effects commonly experienced with amphetamine-like drugs . Objectives . The main aim of this study was to evaluate the cognitive enhancing potential of this novel agent using a comprehensive battery of neuropsychological tests . Methods . Sixty healthy young adult male volunteers received either a single oral dose of placebo , or 100 mg or 200 mg modafinil prior to performing a variety of tasks design ed to test memory and attention . A r and omised double-blind , between-subjects design was used . Results . Modafinil significantly enhanced performance on tests of digit span , visual pattern recognition memory , spatial planning and stop-signal reaction time . These performance improvements were complemented by a slowing in latency on three tests : delayed matching to sample , a decision-making task and the spatial planning task . Subjects reported feeling more alert , attentive and energetic on drug . The effects were not clearly dose dependent , except for those seen with the stop-signal paradigm . In contrast to previous findings with methylpheni date , there were no significant effects of drug on spatial memory span , spatial working memory , rapid visual information processing or attentional set-shifting . Additionally , no effects on paired associates learning were identified . Conclusions . These data indicate that modafinil selectively improves neuropsychological task performance . This improvement may be attributable to an enhanced ability to inhibit pre-potent responses . This effect appears to reduce impulsive responding , suggesting that modafinil may be of benefit in the treatment of attention deficit hyperactivity disorder Functional magnetic resonance imaging ( fMRI ) can be used to detect regional brain responses to changes in sensory stimuli . We have used fMRI to determine the amount of visual and auditory cortical activation in 12 normal subjects and 12 subjects with the narcoleptic syndrome , using a multiplexed visual and auditory stimulation paradigm . In both normal and narcoleptic subjects , mean cortical activation levels during the presentation of periodic visual and auditory stimulation showed no appreciable differences with either age or sex . Normal subjects showed higher levels of visual activation at 10:00 hours than 15:00 hours , with a reverse pattern in narcoleptic subjects ( P = 0.007 ) . The group differences in spatial extent of cortical activation between control and narcoleptic subjects were small and statistically insignificant . The alerting action , and imaging response , to a single oral dose of the sleep-preventing drug modafinil 400 mg were then determined and compared with placebo in both the 12 normal ( 8 given modafinil , 4 placebo ) and 12 narcoleptic subjects ( 8 modafinil , 4 placebo ) . Modafinil caused an increase in self-reported levels of alertness in 7 of 8 narcoleptic subjects , but there was no significant difference between mean pretreatment and post-treatment activation levels as determined by fMRI for either normal or narcoleptic syndrome subjects given modafinil . However , in the modafinil-treated group of 8 normal and 8 narcoleptic subjects , there was a clock time independent correlation between the initial level of activation as determined by the pretreatment scan and the post-treatment change in activation ( visual , P = 0.002 ; and auditory , P = 0.001 ) . No correlation was observed in placebo-treated subjects ( P = 0.99 and 0.77 , respectively ) . Although limited by the small number of subjects , and the lack of an objective measure of alertness , the findings of this study suggest that low cortical activation levels in both normal and narcoleptic subjects are increased following the administration of modafinil . Functional magnetic resonance imaging may be a valuable addition to established studies of attention Methamphetamine (MA)-dependent individuals exhibit deficits in cognition and prefrontal cortical function . Therefore , medications that improve cognition in these subjects may improve the success of therapy for their addiction , especially when cognitive behavioral therapies are used . Modafinil has been shown to improve cognitive performance in neuropsychiatric patients and healthy volunteers . We therefore conducted a r and omized , double-blind , placebo-controlled , cross-over study , using functional magnetic resonance imaging , to examine the effects of modafinil on learning and neural activity related to cognitive function in abstinent , MA-dependent , and healthy control participants .  Modafinil ( 200 mg ) and placebo were administered orally ( one single dose each ) , in counterbalanced fashion , 2 h before each of two testing sessions . Under placebo conditions , MA-dependent participants showed worse learning performance than control participants . Modafinil boosted learning in MA-dependent participants , bringing them to the same performance level as control subjects ; the control group did not show changes in performance with modafinil . After controlling for performance differences , MA-dependent participants showed a greater effect of modafinil on brain activation in bilateral insula/ventrolateral prefrontal cortex and anterior cingulate cortices than control participants . The findings suggest that modafinil improves learning in MA-dependent participants , possibly by enhancing neural function in regions important for learning and cognitive control . These results suggest that modafinil may be a suitable pharmacological adjunct for enhancing the efficiency of cognitive-based therapies for MA dependence Improving cognition in people with neuropsychiatric disorders remains a major clinical target . By themselves pharmacological and non-pharmacological approaches have shown only modest effects in improving cognition . In the present study we tested a recently-proposed methodology to combine CT with a ' cognitive-enhancing ' drug to improve cognitive test scores and exp and ed on previous approaches by delivering combination drug and CT , over a long intervention of repeated sessions , and used multiple tasks to reveal the cognitive processes being enhanced . We also aim ed to determine whether gains from this combination approach generalised to untrained tests . In this proof of principle r and omised-controlled trial thirty-three healthy volunteers were r and omised to receive either modafinil or placebo combined with daily cognitive training over two weeks . Volunteers were trained on tasks of new- language learning , working memory and verbal learning following 200 mg modafinil or placebo for ten days . Improvements in trained and untrained tasks were measured . Rate of new- language learning was significantly enhanced with modafinil , and effects were greatest over the first five sessions . Modafinil improved within-day learning rather than between-day retention . No enhancement of gains with modafinil was observed in working memory nor rate of verbal learning . Gains in all tasks were retained post drug-administration , but transfer effects to broad cognitive abilities were not seen . This study shows that combining CT with modafinil specifically elevates learning over early training sessions compared to CT with placebo and provides a proof of principle experimental paradigm for pharmacological enhancement of cognitive remediation Background Surgeons are usually exposed to high workloads leading to fatigue and stress . This not only increases the likelihood of mistakes during surgery but also puts pressure on surgeons to use drugs to counteract fatigue , distress , concentration deficits , burnout or symptoms of depression . The prevalence of surgeons taking pharmacological cognitive enhancement ( CE ) or mood enhancement ( ME ) drugs  has not been systematic ally assessed so far . Methods Surgeons who attended five international conferences in 2011 were surveyed with an anonymous self-report question naire ( AQ ) regarding the use of prescription or illicit drugs for CE and ME and factors associated with their use . The R and omized Response Technique ( RRT ) was used in addition . The RRT guarantees a high degree of anonymity and confidentiality when a person is asked about stigmatizing issues , such as drug abuse . Results A total of 3,306 question naires were distributed and 1,145 entered statistical analysis ( response rate : 36.4 % ) . According to the AQ , 8.9 % of all surveyed surgeons confessed to having used a prescription or illicit drug exclusively for CE at least once during lifetime . As one would expect , the prevalence rate assessed by RRT was approximately 2.5-fold higher than that of the AQ ( 19.9 % ; 95 % confidence interval ( CI ) , 15.9 % to 23.9 % , N = 1,105 ) . An even larger discrepancy between the RRT and AQ was observed for the use of antidepressants with a 6-fold higher prevalence ( 15.1 % ; 95 % CI , 11.3 % to 19.0 % , N = 1,099 ) as compared to 2.4 % with the AQ . Finally , logistic regression analysis revealed that pressure to perform at work ( odds ratio ( OR ) : 1.290 ; 95 % CI , 1.000 to 1.666 ; P = 0.05 ) or in private life ( OR : 1.266 ; 95 % CI , 1.038 to 1.543 ; P = 0.02 ) , and gross income ( OR : 1.337 ; 95 % CI , 1.091 to 1.640 ; P = 0.005 ) , were positively associated with the use of drugs for CE or ME . Conclusions The use of illicit and prescription drugs for CE or ME is an underestimated phenomenon among surgeons which is generally attributable to high workload , perceived workload , and private stress . Such intake of drugs is associated with attempts to counteract fatigue and loss of concentration . However , drug use for CE may lead to addiction and to overestimation of one ’s own capabilities , which can put patients at risk . Coping strategies should be taught during medical education Modafinil differs from other arousal-enhancing agents in chemical structure , neurochemical profile , and behavioral effects . Most functional neuroimaging studies to date examined the effect of modafinil only on information processing underlying executive cognition , but cognitive enhancers in general have been shown to have pronounced effects on emotional behavior , too . We examined the effect of modafinil on neural circuits underlying affective processing and cognitive functions . Healthy volunteers were enrolled in this double-blinded placebo-controlled trial ( 100 mg/day for 7 days ) . They underwent BOLD fMRI while performing an emotion information-processing task that activates the amygdala and two prefrontally dependent cognitive tasks — a working memory ( WM ) task and a variable attentional control ( VAC ) task . A clinical assessment that included measurement of blood pressure , heart rate , the Hamilton anxiety scale , and the profile of mood state ( POMS ) question naire was also performed on each test day . BOLD fMRI revealed significantly decreased amygdala reactivity to fearful stimuli on modafinil compared with the placebo condition . During executive cognition tasks , a WM task and a VAC task , modafinil reduced BOLD signal in the prefrontal cortex and anterior cingulate . Although not statistically significant , there were trends for reduced anxiety , for decreased fatigue-inertia and increased vigor-activity , as well as decreased anger-hostility on modafinil . Modafinil in low doses has a unique physiologic profile compared with stimulant drugs : it enhances the efficiency of prefrontal cortical cognitive information processing , while dampening reactivity to threatening stimuli in the amygdala , a brain region implicated in anxiety Rationale Modafinil is a well-tolerated psychostimulant drug with low addictive potential that is used to treat patients with narcolepsy or attention deficit disorders and to enhance vigilance in sleep-deprived military personal . So far , underst and ing of the cognitive enhancing effects of modafinil and the relevant neurobiological mechanisms are incomplete . Objectives The aim of this study was to investigate the effects of modafinil on working memory processes in humans and how they are related to noradrenergic stimulation of the prefrontal cortex . Methods Sixteen healthy volunteers ( aged 20–29 years ) received either modafinil 200 mg or placebo using a double blind crossover design . Two computerized working memory tasks were administered , a numeric manipulation task that requires short-term maintenance of digit-sequences and different degrees of manipulation as well as delayed matching task that assesses maintenance of visuo-spatial information over varying delay lengths . The battery was supplemented by st and ardized 
    Output:
    
agent
We found that whilst most studies employing basic testing paradigms show that modafinil intake enhances executive function , only half show improvements in attention and learning and memory , and a few even report impairments in divergent creative thinking .
In contrast , when more complex assessment s are used , modafinil appears to consistently engender enhancement of attention , executive functions , and learning .
Importantly , we did not observe any preponderances for side effects or mood changes .
***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: Abstract : In a double-blind , parallel groups study , 60 healthy student volunteers ( 29 men and 31 women , aged 19 - 22 years ) were r and omly allocated to receive placebo , 100 or 200 mg modafinil . Two hours later , in the early evening , they completed an extensive cognitive battery . The 3 groups did not differ in self-ratings of sleepiness or tiredness before the testing session , and there were no treatment-associated changes in these or in mood ratings during the tests . Modafinil was without effect in several tests of reaction time and attention , but the 200-mg group was faster at simple color naming of dots and performed better than placebo in the Rapid Visual Information Processing test of sustained attention . Modafinil was without effect on spatial working memory , but the 100-mg group performed better in the backward part of the digit span test . Modafinil was without effect on verbal short-term memory ( story recall ) , but 100 mg improved digit span forward , and both doses improved pattern recognition , although this was accompanied by a slowing of response latency in the 200-mg group . There were no significant effects of modafinil compared with placebo in tests of long-term memory , executive function , visuospatial and constructional ability , or category fluency . These results suggest that the benefits of modafinil are not clearly dose-related , and those from 100 mg are limited to the span of immediate verbal recall and short-term visual recognition memory , which is insufficient for it to be considered as a cognitive enhancer in non-sleep-deprived individuals Abstract Rationale . Modafinil , a novel wake-promoting agent , has been shown to have a similar clinical profile to that of conventional stimulants such as methylpheni date . We were therefore interested in assessing whether modafinil , with its unique pharmacological mode of action , might offer similar potential as a cognitive enhancer , without the side effects commonly experienced with amphetamine-like drugs . Objectives . The main aim of this study was to evaluate the cognitive enhancing potential of this novel agent using a comprehensive battery of neuropsychological tests . Methods . Sixty healthy young adult male volunteers received either a single oral dose of placebo , or 100 mg or 200 mg modafinil prior to performing a variety of tasks design ed to test memory and attention . A r and omised double-blind , between-subjects design was used . Results . Modafinil significantly enhanced performance on tests of digit span , visual pattern recognition memory , spatial planning and stop-signal reaction time . These performance improvements were complemented by a slowing in latency on three tests : delayed matching to sample , a decision-making task and the spatial planning task . Subjects reported feeling more alert , attentive and energetic on drug . The effects were not clearly dose dependent , except for those seen with the stop-signal paradigm . In contrast to previous findings with methylpheni date , there were no significant effects of drug on spatial memory span , spatial working memory , rapid visual information processing or attentional set-shifting . Additionally , no effects on paired associates learning were identified . Conclusions . These data indicate that modafinil selectively improves neuropsychological task performance . This improvement may be attributable to an enhanced ability to inhibit pre-potent responses . This effect appears to reduce impulsive responding , suggesting that modafinil may be of benefit in the treatment of attention deficit hyperactivity disorder Functional magnetic resonance imaging ( fMRI ) can be used to detect regional brain responses to changes in sensory stimuli . We have used fMRI to determine the amount of visual and auditory cortical activation in 12 normal subjects and 12 subjects with the narcoleptic syndrome , using a multiplexed visual and auditory stimulation paradigm . In both normal and narcoleptic subjects , mean cortical activation levels during the presentation of periodic visual and auditory stimulation showed no appreciable differences with either age or sex . Normal subjects showed higher levels of visual activation at 10:00 hours than 15:00 hours , with a reverse pattern in narcoleptic subjects ( P = 0.007 ) . The group differences in spatial extent of cortical activation between control and narcoleptic subjects were small and statistically insignificant . The alerting action , and imaging response , to a single oral dose of the sleep-preventing drug modafinil 400 mg were then determined and compared with placebo in both the 12 normal ( 8 given modafinil , 4 placebo ) and 12 narcoleptic subjects ( 8 modafinil , 4 placebo ) . Modafinil caused an increase in self-reported levels of alertness in 7 of 8 narcoleptic subjects , but there was no significant difference between mean pretreatment and post-treatment activation levels as determined by fMRI for either normal or narcoleptic syndrome subjects given modafinil . However , in the modafinil-treated group of 8 normal and 8 narcoleptic subjects , there was a clock time independent correlation between the initial level of activation as determined by the pretreatment scan and the post-treatment change in activation ( visual , P = 0.002 ; and auditory , P = 0.001 ) . No correlation was observed in placebo-treated subjects ( P = 0.99 and 0.77 , respectively ) . Although limited by the small number of subjects , and the lack of an objective measure of alertness , the findings of this study suggest that low cortical activation levels in both normal and narcoleptic subjects are increased following the administration of modafinil . Functional magnetic resonance imaging may be a valuable addition to established studies of attention Methamphetamine (MA)-dependent individuals exhibit deficits in cognition and prefrontal cortical function . Therefore , medications that improve cognition in these subjects may improve the success of therapy for their addiction , especially when cognitive behavioral therapies are used . Modafinil has been shown to improve cognitive performance in neuropsychiatric patients and healthy volunteers . We therefore conducted a r and omized , double-blind , placebo-controlled , cross-over study , using functional magnetic resonance imaging , to examine the effects of modafinil on learning and neural activity related to cognitive function in abstinent , MA-dependent , and healthy control participants .  Modafinil ( 200 mg ) and placebo were administered orally ( one single dose each ) , in counterbalanced fashion , 2 h before each of two testing sessions . Under placebo conditions , MA-dependent participants showed worse learning performance than control participants . Modafinil boosted learning in MA-dependent participants , bringing them to the same performance level as control subjects ; the control group did not show changes in performance with modafinil . After controlling for performance differences , MA-dependent participants showed a greater effect of modafinil on brain activation in bilateral insula/ventrolateral prefrontal cortex and anterior cingulate cortices than control participants . The findings suggest that modafinil improves learning in MA-dependent participants , possibly by enhancing neural function in regions important for learning and cognitive control . These results suggest that modafinil may be a suitable pharmacological adjunct for enhancing the efficiency of cognitive-based therapies for MA dependence Improving cognition in people with neuropsychiatric disorders remains a major clinical target . By themselves pharmacological and non-pharmacological approaches have shown only modest effects in improving cognition . In the present study we tested a recently-proposed methodology to combine CT with a ' cognitive-enhancing ' drug to improve cognitive test scores and exp and ed on previous approaches by delivering combination drug and CT , over a long intervention of repeated sessions , and used multiple tasks to reveal the cognitive processes being enhanced . We also aim ed to determine whether gains from this combination approach generalised to untrained tests . In this proof of principle r and omised-controlled trial thirty-three healthy volunteers were r and omised to receive either modafinil or placebo combined with daily cognitive training over two weeks . Volunteers were trained on tasks of new- language learning , working memory and verbal learning following 200 mg modafinil or placebo for ten days . Improvements in trained and untrained tasks were measured . Rate of new- language learning was significantly enhanced with modafinil , and effects were greatest over the first five sessions . Modafinil improved within-day learning rather than between-day retention . No enhancement of gains with modafinil was observed in working memory nor rate of verbal learning . Gains in all tasks were retained post drug-administration , but transfer effects to broad cognitive abilities were not seen . This study shows that combining CT with modafinil specifically elevates learning over early training sessions compared to CT with placebo and provides a proof of principle experimental paradigm for pharmacological enhancement of cognitive remediation Background Surgeons are usually exposed to high workloads leading to fatigue and stress . This not only increases the likelihood of mistakes during surgery but also puts pressure on surgeons to use drugs to counteract fatigue , distress , concentration deficits , burnout or symptoms of depression . The prevalence of surgeons taking pharmacological cognitive enhancement ( CE ) or mood enhancement ( ME ) drugs  has not been systematic ally assessed so far . Methods Surgeons who attended five international conferences in 2011 were surveyed with an anonymous self-report question naire ( AQ ) regarding the use of prescription or illicit drugs for CE and ME and factors associated with their use . The R and omized Response Technique ( RRT ) was used in addition . The RRT guarantees a high degree of anonymity and confidentiality when a person is asked about stigmatizing issues , such as drug abuse . Results A total of 3,306 question naires were distributed and 1,145 entered statistical analysis ( response rate : 36.4 % ) . According to the AQ , 8.9 % of all surveyed surgeons confessed to having used a prescription or illicit drug exclusively for CE at least once during lifetime . As one would expect , the prevalence rate assessed by RRT was approximately 2.5-fold higher than that of the AQ ( 19.9 % ; 95 % confidence interval ( CI ) , 15.9 % to 23.9 % , N = 1,105 ) . An even larger discrepancy between the RRT and AQ was observed for the use of antidepressants with a 6-fold higher prevalence ( 15.1 % ; 95 % CI , 11.3 % to 19.0 % , N = 1,099 ) as compared to 2.4 % with the AQ . Finally , logistic regression analysis revealed that pressure to perform at work ( odds ratio ( OR ) : 1.290 ; 95 % CI , 1.000 to 1.666 ; P = 0.05 ) or in private life ( OR : 1.266 ; 95 % CI , 1.038 to 1.543 ; P = 0.02 ) , and gross income ( OR : 1.337 ; 95 % CI , 1.091 to 1.640 ; P = 0.005 ) , were positively associated with the use of drugs for CE or ME . Conclusions The use of illicit and prescription drugs for CE or ME is an underestimated phenomenon among surgeons which is generally attributable to high workload , perceived workload , and private stress . Such intake of drugs is associated with attempts to counteract fatigue and loss of concentration . However , drug use for CE may lead to addiction and to overestimation of one ’s own capabilities , which can put patients at risk . Coping strategies should be taught during medical education Modafinil differs from other arousal-enhancing agents in chemical structure , neurochemical profile , and behavioral effects . Most functional neuroimaging studies to date examined the effect of modafinil only on information processing underlying executive cognition , but cognitive enhancers in general have been shown to have pronounced effects on emotional behavior , too . We examined the effect of modafinil on neural circuits underlying affective processing and cognitive functions . Healthy volunteers were enrolled in this double-blinded placebo-controlled trial ( 100 mg/day for 7 days ) . They underwent BOLD fMRI while performing an emotion information-processing task that activates the amygdala and two prefrontally dependent cognitive tasks — a working memory ( WM ) task and a variable attentional control ( VAC ) task . A clinical assessment that included measurement of blood pressure , heart rate , the Hamilton anxiety scale , and the profile of mood state ( POMS ) question naire was also performed on each test day . BOLD fMRI revealed significantly decreased amygdala reactivity to fearful stimuli on modafinil compared with the placebo condition . During executive cognition tasks , a WM task and a VAC task , modafinil reduced BOLD signal in the prefrontal cortex and anterior cingulate . Although not statistically significant , there were trends for reduced anxiety , for decreased fatigue-inertia and increased vigor-activity , as well as decreased anger-hostility on modafinil . Modafinil in low doses has a unique physiologic profile compared with stimulant drugs : it enhances the efficiency of prefrontal cortical cognitive information processing , while dampening reactivity to threatening stimuli in the amygdala , a brain region implicated in anxiety Rationale Modafinil is a well-tolerated psychostimulant drug with low addictive potential that is used to treat patients with narcolepsy or attention deficit disorders and to enhance vigilance in sleep-deprived military personal . So far , underst and ing of the cognitive enhancing effects of modafinil and the relevant neurobiological mechanisms are incomplete . Objectives The aim of this study was to investigate the effects of modafinil on working memory processes in humans and how they are related to noradrenergic stimulation of the prefrontal cortex . Methods Sixteen healthy volunteers ( aged 20–29 years ) received either modafinil 200 mg or placebo using a double blind crossover design . Two computerized working memory tasks were administered , a numeric manipulation task that requires short-term maintenance of digit-sequences and different degrees of manipulation as well as delayed matching task that assesses maintenance of visuo-spatial information over varying delay lengths . The battery was supplemented by st and ardized 
    Output:
    