Methylphenidate In The Regulation Of Go/nogo Task In Normal Adult Brain: FMRI Study

Objective:Previous studies demonstrate that the regulation of motor execution and motor inhibitory by Methylphenidate(MPH) are induced by dopamine system.But recent animal studies determine that MPH also regulate the motor function through 5-HT system.It may be efficient directly by 5-HT,also it may effect the dopamine system and regulate the motor function indirectly.The present study tries to compare the brain activation when subjects take placebo or MPH and perform go/nogo task to see if there are differences in 5-HT related brain areas.So that it may indicate that the regulation of motor function by MPH not only through classic dopamine pathway but also through 5-HT pathway.Methods:Eighteen healthy male university students participated in the study. WAIS-R,handedness questionnaire,fMRI scan,and attention test were given to the subjects.The experiment was within subjects design with two factors,medicine and task. After taking MPH or placebo,subjects were scanned in MRI and performed go/nogo task.fMRI data were analyzed with SPM software.Results:The differences between behavioral data after MPH and after placebo are not statistically significant.The fMRI activation areas are as following.The areas activated as main effect of medicine include left Superior Orbital Gyrus,left middle Frontal Gyrus,left anterior Cingulate Cortex,left Temporal Parietal Junction,left Hippocampus,right Cerebellum,and right middle Orbital Gyrus.The areas activated as main effect of task include bilateral Thalamus,left Pallidum,right Superior Medial Gyrus,left inferior Frontal Gyrus,left Primary Motor Cortex(BA 4),left middle Cingulate Cortex,bilateral Superior Frontal Gyrus,left superior Frontal Gyrus,right Putamen,left Posterior Insular,left Cuneus,and right Insula Lobe.The areas activated as interaction between medicine and task include bilateral Pallidum,left Cerebellum, left Middle Orbital Gyrus,Raphe Nuclei,and right superior Frontal Gyrus.Conclusions:MPH mainly decreases the activation in orbital-prefrontal cortex and increase the activation in right cerebellum,hippocampus.Task related main effect are mainly represented in motor areas.The interaction between medicine and task indicates that MPH can increase the activation in Raphe Nuclei during motor inhibition.The areas which have same activation mode include pallidum and left cerebellum.The Raphe Neuclei is the source of 5-HT in the whole brain and the pallidum and cerebellum all receive projection from it.It implicates that MPH may take effect by the 5-HT circuit directly or indirectly.Our results may dedicate in knowing the mechanism of MPH therapy.