Study On The Changes Of Resting State FMRI After Discontinuation Of Medication In Children With Attention Deficit Hyperactivity Disorder Who Is Systemically Treated And Respond To Methylphenidate

Objectives:To investigate the changes of Resting State Functional Magnetic Resonance Imaging (RS- fMRI), cognitive function and clinical symptoms after 6-8 weeks of drug withdrawal in patients with attention deficit hyperactivity disorder(ADHD), who is systemically treated and respond to methylphenidate(MPH). Furthermore?to explore the influencing factors which may contribute to the differences of the above changes and to give reference for individualized treatment in clinical practice,especially to guide the timing of discontinuation of MPH.Methods:13 DSM-? defined patients with ADHD who were effectively treated with MPH for more than 8 weeks (effective group), and 12 utreated patients with ADHD who matched the age,sex,IQ and severity of clinical symptoms with the effective group (control group) were enrolled in the present study.The clinical data of all patients were evaluated, including the demographics, clinical symptoms, and cognitive functions. Attention deficit hyperactivity disorder rating scale-? home version (ARS) and Conners parent symptom questionnaire (PSQ) were used to assess clinical symptoms, and continuous performance task(CPT), Rey complex figure test(RCFT), Chinese trail making test (TMT) and Chinese version of the Stroop color word test (Stroop) were applied to evaluate cognitive functions .of ADHD patients.RS- fMRI scanning were performed for all the subjects in both groups using Philips 3.0T magnetic resonance scanner. After acquiring RS- fMRI image data, the data was then preprocessed and statistical analyzed using Matlab, DPARSF, REST and other auxiliary softwares. Regional homogeneity (ReHo)and functional connectivity analysis .were used to .describe the RS-fMRI brain activity.Cingulum_Ant_R was selected as seed region (region of interest, ROI) because it was the biggest mass in ReHo. Finally, the statistical parameter map were overlaid to montreal neurological institute C(MN1) standard 3D template brain which is with known anatomical automatic labeling (AAL) partition to describe the significant differences of the brain area,and to record statistical significance of mass(cluster), the size of the brain regions and peak MNI coordinates and Peak intensity.Using the paired T test to compare the differences on clinical symptoms,cognitive function and RS- fMRI between medication period and withdrawal period in effective group(n=9), medication period in effective group and the control group(n=12), and withdrawal period in effective group and the control group(n=8).Results:1? A total of 13 children with ADHD were included in the effective group (12 boys and 1 girl,9.77 ± 1.69 years old, IQ: 94.54 ± 6.06)and only 9 patients completed the RS- fMRI scanning after discontinuation of MPH; A total of 12 children with ADHD were included in the control group.2. ARS and PSQ scores statistically increased after discontinuation of MPH in effective group (both P <0.05); The degree of increase in ARS scores were smaller in older group (> 9 years old) than that of younger group (?9 years old) (P <0.05); The ReHo value decreased statistically in Frontal_Mid_Orb_L,Frontal Inf Orb_L,Cingulum_Ant_R,Frontal_Sup_R and Frontal_Sup_Medial_R,while increased in cerebellum after discontinuation of MPH in the effective group (all P<0.05). Frontal_Sup_Orb_L,Frontal_Sup_Orb_R and Frontal_Inf_Orb_L showed decreased functional connectivity with the ROI, while Parietal_Sup_L,Parietal_Sup_R, Temporal_Mid_R, Occipital_Mid_R and cerebellum showed increased functional connectivity with the ROI after discontinuation of MPH in the effective group (all P <0.05).3.Compared with the control group, ARS score, PSQ score, Inattention score and CPT error number T value were significantly lower during treatment period in the effective group (all P <0.05) . Compared with the control group, ReHo value of Frontal_Sup_Medial_L and Cingulum_Ant_R were significantly higher,while that of Parietal(Sup{R were significantly lower during treatment period in the effective group. (all P <0.05).4. Compared with the control group, PSQ score were significantly lower during withdrawal period in the effective group, while the grade of RCFT and Stroop were significantly higher (all P <0.05) . Compared with the control group, ReHo value of Frontal_Mid_L were significantly higher,while that of cerebellum were significantly lower during withdrawal period in the effective group (all P <0.05).Conclusions:Clinical symptoms will aggravate and RS- fMRI brain activity will decline in patients with ADHD who have been systemically and effectively treated by MPH after discontinuation of drug, especially in prefrontal cortex and cingulete gyrus ;even so, clinical manifestation, cognitive function and RS-fMRI activity during withdrawal period of effectively treated patients are still better than those of untreated patients; the present study only found that the age is the influential factor on the degree of clinical symptoms aggravation after MPH withdrawal, and the degree of clinical symptoms aggravation after withdrawal in patients with ADHD who is older(> 9) is lower than that who is younger (?9).