How does parental care affect the brain development of human children? Answering this question is quite important, given its potential relevance to the health of the hundreds of millions of left-behind children (LBC) in developing countries whose parents migrated for economic or political reasons. In China alone, there are more than 61 million children growing up without one or both parents—a population larger than California and New York combined. Studies of LBC have shown increased levels of social anxiety, more neglect and a lower quality of life. These factors may account for their increased rates of psychiatric syndromes later in life, particularly mood and anxiety disorders and posttraumatic stress disorder. However, it is still unclear where and how the brain is affected in these children who do not receive direct parental care. Therefore, we aimed to explore the gray matter volume and white matter micro structure alteration in LBC in relative to those lived in the nuclear family.This study was IRB approved and written informed consent was obtained from guardians. Thirty-eight LBC (mean age=9.6±1.8yrs, age range: 7-13yrs; mean separation time=7.00±2.17yrs, range: 2-11yrs) and 30 non-LBC (living with parents) (mean age=10.0±1.95yrs, age range: 7-14yrs) with age, gender, handedness, ethnicity, birth weight, weight, height, delivery mode, IQ (verbal, performance, full scale) and the annual family income well-matched were included and performed a 3.0T MR scan. The LBC is defined as children who living with the absence of one or both of their biological parents for a period over six months3. Image preprocessing and statistical analyses for gray matter volume were performed with optimized voxel-based morphometry in SPM8 (www.fil.ion.ucl.ac.uk/spm). DTI preprocessing was performed using FSL software (FMRIB Software Library, http://www.fmrib.ox.ac.uk/fsl). The statistic significance of all the analyses was set as p<0.05, corrected with false discovery rate (FDR). Pearson correlation was used to explore the potential relationship between gray matter volume and age.Compared to controls, LBC showed significantly greater gray matter volume in bilateral fusiform gyri, bilateral parahippocampus, right superior parietal lobe, right thalamus, right superior occipital gyrus, left cuneus, right superior temporal gyrus, right superior medial frontal gyrus, left postcentral gyrus, left middle occipital gyrus and left putaman (Figure 1, p<0.05). However, there was no significant difference of FA or MD between the LBC and non-LBC. The negative results obtained from our study suggest that the only absence of direct parental care in the childhood did not show prominent effect on the early development of white matter. Furthermore, the gray matter volume is negatively correlated to age in LBC (p<0.05).To our knowledge, this study provided the first empirical evidence of larger gray matter volume in LBC than non-LBC, especially in emotional circuit, suggesting the early parental care would affect the brain development of gray matter rather than white matter. Since the larger gray matter volume in children may reflect insufficient pruning and mature of brain1,2, the negative correlation between the gray matter volume and age suggest those differences might to some degree normalize with age during later childhood, perhaps due to positive influences of increased peer-related socialization. From a public health perspective, the study highlighted the importance of parental care in children and indicated early intervention and stimulation are needed to LBC.