Autism spectrum disorder (ASD) is an immature neurodevelopmental disorder characterized by impaired emotional expression, social interaction, and repetitive and stereotyped behavior¹. Valproic acid (VPA) is a well know antiepileptic drugs and thought to alter mood stability like modifying gamma-aminobutyric acid (GABA) levels^2,3. Many studies indicated that VPA was associated with an increased risk of ASD^4,5. The VPA-induced model of ASD has been established by implementing a single intraperitoneal injection of VPA to pregnant rats, whose offspring produce genetic and behavioral phenotype that is similar to clinical significance of ASD⁶. Previous study indicated that VPA-induced ASD rats don't influence neural growth or stunting in motor cortex, but rather change the pattern of dendritic development⁷. VPA has been demonstrated that it can inhibit connectivity in motor circuits in the primary motor (M1) → pre-motor cortex (PMd) and M1 → supplementary area motor (SMA)⁸. Moreover, a study also reported that the growth rate of striatal structures increase in ASD subjects and involved in repetitive behavior⁹. Therefore, our hypothesis is that M1 and caudate-putamen (CPu) may play a part in ASD physiopathology. In this study, we used resting-state functional MRI (rsfMRI) to evaluate the changes of age-related brain functional connectivity at cortico-cortical and cortico-striatal pathway in VPA-induced model of ASD. Adult female Sprage Dawley rats (weight 250-300 g) were housed in the animal facility under 12:12-h light/dark cycle (lights on at 7:00 am) with controlling temperature at 22 ± 2°C and then the rats were mated. The pregnant rats in VPA group were received a single intraperitoneal injection of VPA (0.5 g/Kg) at the pregnancy day of 12-13¹⁰ and the rats in control group were injected with saline. Offspring of two groups were evaluated by a standard behavioral social testing. The social testing included three chambered facility, including empty, central, and social, and how long the rats spent in each facility were calculated11. For fMRI experiments, rats were anesthetized with 0.1 mg/kg Dexdomitor® subcutaneously. MRI was performed on a Bruker Biospec 7T system with a 30-cm diameter bore and a single-shot GE-EPI sequence (TR/TE=2000/20 ms, BW=200 kHz, 80×80 matrix, FOV=25×25 mm², thickness=1 mm, slice number = 10) was used to acquire rsfMRI images totaling 260 scanning images for 10 dummy scanning and 250 images. Functional connectivity were calculated by using Resting State fMRI Data Analysis Toolkit (REST) v1.7 with seed-based method within a 2 x 2 pixel region of interest (ROI) in left/right primary motor (M1_L/M1_R) and in left/right CPu (Str_L/Str_R). Pattern comparison of functional connectivity was computed by one sample t-test and alphasim correction and the variables of functional connectivity were assessed by Student’s t-test. The significant difference between groups was considered if p value < 0.05. Functional connectivity showed that the magnitudes and regions of activation correlation significantly increased with weeks in bilateral M1, bilateral CPu and ipsilateral M1 to CPu in control group (Fig 1A). In the VPA group, there is no significant increase of activation correlation in bilateral M1 and CPu at 5^th, 6^th and 7^th weeks while the activation correlation significantly increase in the bilateral M1 and bilateral CPu at 8th week (Fig 1B). However, the magnitudes and regions of activation correlation in ipsilateral M1 to CPu is no significant increase over time (Fig 1B). These results suggest that VPA-induced ASD rats have the most influence of functional connectivity in motor related brain areas before 7^th week. Identically, the behavioral social testing showed that rats in the control group have longer social period than those in the VPA group at 5^th week (Fig 2A), as well as there is no significant difference of social period between the control and VPA groups at 8^th week (Fig 2B). Results of functional connectivity and behavioral social testing indicate that the interaction between the ipsilateral motor cortico-striatal pathway^7,8, bilateral motor cortico-cortex and bilateral striatal-striatum may be crucial in ASD. The activations may be produced by several neuropathological mechanisms, therefore, mechanisms of ASD merit further investigation.This study demonstrates changes of functional connectivity is age-related difference at motor cortex and striatum in VPA-induced ASD rats. These changes showed the activation correlation of ipsilateral motor cortico-striatal pathway, bilateral motor cortico-cortex, and bilateral striatal-striatum are lower in ASD rats before 7^th week which suggests the connection between motor related brain areas could be a index to evaluate the progress of ASD. The further investigation of this study will develop the potential therapeutic approach for ASD based on improvement of functional connectivity in motor-related areas, such as deep brain stimulation.