Pediatric bipolar disorder (PBD) is characterized by recurrent depressive, manic, and hypomanic episodes (Johnson et al., 2000). The prevalence of PBD in the adolescent population is 1% (Johnson et al., 2000). PBD differs from adult bipolar disorder (BD) in that its symptoms are more atypical (Perlis et al., 2004). The differential diagnosis of PBD-I and PBD-II is more difficult due to the atypical symptoms of PBD. The presence or absence of a manic episode is a major feature for distinguishing PBD-I from PBD-II disorders (Johnson et al., 2000). It is crucial to identify PBD-I versus PBD-II biomarkers, as they differ in medication therapy and risk prevention (Perlis et al., 2004). Early diagnosis with biomarkers is essential, as PBD-I may begin with a depressive or hypomanic episode in the early emotional stage, making it easy to misdiagnose without a manic episode (Parker and Fletcher, 2014). Some researches have showed differences in biological mechanisms compared BD-I with BD-II (Parker and Fletcher, 2014, Phillips and Kupfer, 2013). Psychosis (Parker and Fletcher, 2014), neurotoxic processes (Uemura et al., 2011), neurochemical (Atagun et al., 2018) and cognitive dysfunction (Bora et al., 2011) are more common in BD-I than in BD-II. The Magnetic resonance imaging (MRI) researches have showed that there are difference of cortical-subcortical system compared BD-I with BD-II in volumes (Toma et al., 2019, Ambrosi et al., 2013, Abe et al., 2016), thickness (Toma et al., 2019, Abe et al., 2018), white matter lesions (Ambrosi et al., 2013), metabolism (Li et al., 2012) and functional connectivity (Caseras et al., 2015). However, studies on MRI differences between PBD-I and PBD-II are lacking.

The emergence of studies have found that researching the functional connectivity of bipolar disorder can clarify the neuropathological mechanism of this disorder. The latest meta-analysis in 2021 found alteration in functional connectivity of the default network (DMN), limbic system, salience network (SN) and fronto-parietal network (FPN) in bipolar disorder (Gong et al., 2021). To date, few resting state fMRI studies have been conducted specifically in PBD. Our earlier study has adopted the Independent Components Analysis (ICA) to find discrepancy in resting state DMN functional connectivity in PBD (Zhong et al., 2019). Aberrant functional connectivity of the DMN indicates the shortage of integration of internal thoughts, which may show decreased cognitive flexibility and impaired self-monitoring process of BD (Gong et al., 2021). Dysfunctional connectivity of the limbic system is related to the severity of manic mood (Lee et al., 2019). And SN involved in goal-directed adjustment of external stimulus and internal thought, its dysfunctional connectivity shows imbalanced communication between the neural networks (Gong et al., 2019). The abnormal functional connectivity of the FPN in BD subjects may be the basis of impulsivity and attention deficit in BD (Gong et al., 2021, Oertel-Knochel et al., 2015).

However, no studies have analyzed the functional connectivity in the DMN, FPN, SN, and limbic system compared PBD-I with PBD-II patients. The clinical manifestations of PBD-I were found to be more severe than PBD-II in terms of manic symptoms and cognitive dysfunction (Baek et al., 2011), but whether the functional connectivity of the neural circuits serves as the neural underpinning is not clear and needs to be explored. To detect whole-brain connectivity mode, we used the model-free methods to explore connectivity patterns without defining prior seed regions. Comparing with the seed-based approach, the model-free approach aims to find widespread mode of connectivity in the whole brain. The ICA-based approach is probably the most generally used and has demonstrated a high degree of consistency (Ma and MacDonald, 2021).

The aim of our research was to compare the differences in functional connectivity between PBD-I and PBD-II. Our hypothesis was that there might be differences in functional connectivity of the DMN, FPN, SN and limbic system compared PBD-I with PBD-II. Furthermore, we examined the correlation between manic symptoms, depressive symptoms, sleep quality, suicide risk, cognitive function and the functional connectivity of the intrinsic networks to see if differences in fMRI indicators were related to clinical symptoms and cognitive impairment. To our knowledge, this was the first functional connectivity research to assess wide neural circuits compared PBD-I with PBD-II.