Experiment Study Of Effects Of Modafinil On Working Memory During The Total Sleep Deprivation

Sleep deprivation (SD) or sleep loss (SL) is a very common phenomenon in the military activities, which is one of the main reasons for fatigue, decreasing combating abilities and personnel loss in military performance. Tremendous researches have been performed in the fields of the military and special profession. The results show that arousal level and cognitive functions lowered after SD, among which working memory lowers most significantly. Based on that phenonmone, we investigated the effects of SD on executive function which needs higher conscious level and used functional MRI to measure the activities of brain areas on different components and processes of working memory, and the anti-effect of modafinil on psychological function after SD. According to a randomized, double-blind self-controlled design, 14 healthy young males (25.9±2.3 years) attended the experiment four times on their own wills (Norm, SD36h+placebo, SD36h+Modafinil and SD36h+Caffeine). The experiment was divided into three parts. Firstly, Letter Cancellation Test (LCT), alertness/sleepy subjective assessment, attention span test and visual Go/no-go test were used to investigate the effects of SD on attention. Secondly, effects of SD on working memory were studied. Based on the model by Bandeley, we chose n-back pattern to investigate verbal working memory, spatial working memory and object working memory. Lastly, effects of modafinil on psychological function and its anti-effect aganist SD were investigated. In the three times 36 h sleep deprivation period, the subjects were administrated by modafinil 400mg, caffeine or placebo 400mg were administrated at 28 and 32 h during 36 h sleep deprivation.Main results and conclusions are the followings:Attention ability declined and vigilance level lowered after SD. Sleep deprivation have great impact on people's cognitive function. Acording to the results of LCT, 20 h TSD can induce the decline of attention and executive control function. The calculate ability was also declined after 18 h TSD. TSD has little impact on memory span test, for number memory span and spatial memory span there also have different degree. The results of mental scale researches indicated that 36 h sleep deprivation aggravates the alert level and emotion state of the subjects. And this may be one reason of decline of cognition activities.SD induced decrease of executive control function. TSD induced positive and negative BOLD signal include the superior prefrontal cortex, inferior prefrontal cortex, et al. and with negative BOLD signal in the anterior cingulated cortex (ACC) and right lingual gyrus et al. These results suggested that the increased activation may be related to the compensatory response since more attention resources are needed to perform the Go/No-go task after 36 h TSD and the decreased activation in the ACC may reflect the impact on response inhibition by the TSD. Working memory was impaired after SD, and aggravated as timeprolonged. SD has different influence on working memory tasks. The brain areas which have close relationship with the working memory are prefrontal cortex, posterior parietal cortex and anterior cingulated gyrus, parietal cortex, cuneus, cerebellum and supplementary motor area, et al. SD has different influence on the working memory tasks. The influence of SD on object and spatial working memory mainly are deactivating of brain areas related to working memory storage and process. As far as verbal working memory is concerned, besides the deactivation of brain areas related to working memory storage and process, the areas related the attention system activated which has close relationship with fatigue. The individual adaptation to SD is mainly demonstrated by the prefrontal compenstion. The increase of prefrontal cortex function for compensation is an important characteristic after SD.Sleep deprivation keeps the brain at the low arousal level, aggravated the emotion and declined the cognitive function. Central stimulation medicine can make human stay in a high arousal state via lowering the activities of limbic system and thus improve the cognitive function. There were greater changes of activities in the Limbic-related areas in a state of high arousal state compared with that of lower arousal state. It is suggested that lowering Limbic-related areas activities is one component of central stimulants resisting sleep deprivation. In our study, 400 mg modafinil can effectively improve the declined working memory ability and better than 400 mg Caffeine. But if the decline activities in Limbic-related areas are the direct effect of drug or the ex-presense of pharmacologic action remains to be further studied.The influence of SD on cognition is a consistent changing process. The negative changes are consistently existed for the cognitive function during SD. Modafinil can effectively maintains the consciousness state, but it can not always maintain the best performance. On opposite the short-time acute sleep deprivation. Using Modafinil can be an effective method to resist acute SD for short time, but not the ustimate one. Because Modafinil can make the people hard to fall asleep, so combined with sedativehypnotics and recovery sleep may be a good choice for recovery of cognitive brain function. In the special military operation, Modafinil is the first choice to maintain the working performance under the non-sleep situation. Also, combination of central stimulants and sedativehypnotics will be more effective on opposite SD effects on cognition. This will guide the research of antagonization of SD.