Using the ReHo method, our study found that compared with controls, patients with schizophrenia exhibited significantly reduced ReHo in bilateral precentral gyrus, left middle occipital gyrus, and left posterior insula, as well as significantly increased ReHo in the right medial prefrontal cortex and bilateral anterior insula during the resting state. ReHo in the slow-4 band were higher in the fusiform gyrus, and superior frontal gyrus, and lower in the culmen, parahippocampal gyrus, putamen, and dorsal middle prefrontal gyrus, in comparison to ReHo in slow-5. We also found that ReHo in the inferior occipital gyrus and caudate body exhibited a significant interaction between frequency band and group. Our findings demonstrate that schizophrenia is associated with abnormal coherence of spontaneous neural activity in the regional brain, and these abnormalities are modulated by the frequency band.
Our study replicates the findings of Liu et al. 
that patients with schizophrenia exhibited decreased ReHo in regions including the precentral gyrus and middle occipital cortex. Cortical volume reduction in the precentral gyrus has been found in schizophrenia 
. The precentral gyrus may contribute to the processing of multiple motor-related cognitive functioning, which has been found to be abnormal in schizophrenia 
. Cortical thinning and gray matter density and volume reduction were also found in the occipital cortex of patients with schizophrenia 
. The occipital cortex may be a neurobiological substrate of some of the deficits observed in early visual processing in schizophrenia, such as visual hallucinations and object-recognition deficits 
However, we did not find any significant decrease in ReHo in regions identified in the previous study, such as the cerebellum, brainstem, and parahippocampal areas. One possible explanation is that the previous study recruited only 18 patients, which may have resulted in false positive findings. It is also worth noting that the characteristics of patients with schizophrenia, regarding age and illness duration, were different between the two ReHo studies. Schizophrenia patients in Liu et al.’s study were younger (mean age
23.7±4.4 years) and had shorter illness duration (26.8±19.2 months) in comparison with those in our sample. Further investigations using ReHo methods are needed to clarify these inconsistent findings.
In contrast to the previous study, which reported no significant increase in ReHo in schizophrenia, we also found increased ReHo in the medial prefrontal cortex and anterior insula in schizophrenia. Increased ReHo in the medial prefrontal cortex seems to contradict the prior functional imaging finding of hypofrontality 
. One possible reason is that the reliability of hemodynamic hypofrontality in schizophrenia seems controversial. A recent argument in task-related fMRI is whether task-related hypofrontality in schizophrenia represents an intrinsic cerebral malfunction – in other words, a subtle alteration of biological lesion – or whether it merely reﬂects the fact that schizophrenia patients typically have poorer cognitive performance and so activate their functional areas to a correspondingly lesser degree. Supporting this possibility, Frith et al. found that when patients with schizophrenia and healthy controls were matched for performance by the use of a paced form of verbal ﬂuency task, no significant results showing hypofrontality were found 
. Also, a number of current studies have found evidence of increased activation in the prefrontal cortex in schizophrenia during performance of working memory tasks 
. Schizophrenia patients in fact exhibit a failure of task-related deactivation in the medial frontal cortex 
. Our finding of enhanced ReHo in medial PFC in schizophrenia in the resting state may help explain the hyperfrontality in the task state.
The anterior insula integrates external sensory input with the limbic system and is integral to the awareness of the body’s state, such as identifying self-generated from externally-generated sensory information 
. Insular volume reduction has consistently been found in schizophrenia 
. Functional neuroimaging studies have shown that compared to healthy controls, patients with schizophrenia have an increased response in the left insula when attending to speech prosody 
. Abnormal ReHo activity in the insula may contribute to their disruption in sensory-affect processing in schizophrenia and lead to internally generated sensory information being attributed to an external source, therefore contributing to hallucinations in schizophrenia.
There were significant interactions between frequency band and group in several regions, including the inferior occipital gyrus and caudate body. These findings indicate that ReHo changes in schizophrenia are frequency dependent, although the nature of these interactions is not clear and awaits further investigation. Using the typical frequency band may miss these new findings, and such frequency specific ReHo could carry important information for disease diagnosis and our understanding of the pathology of schizophrenia.
Some limitations in our study are worth mentioning. First, we did not collect physiological measures (respiration, heart rate), which may contribute to low-frequency BOLD fluctuations 
. Moreover, it is possible that LFOs in a specific frequency band are particularly sensitive to physiological noises. Future studies may use simultaneous cardiac recording and regress out these facts to minimize the impact of the noises or develop better methods to reduce such noise (e.g. train participants to breathe regularly). Second, the origin and functional significance of ReHo are not yet clear, which limits the implication of ReHo group differences. Furthermore, it is still unknown whether and how ReHo abnormalities contribute to inter-regional functional connectivity and other large scale brain networks. Future studies are necessary to examine ReHo together with other LFO measures (e.g. amplitudes of LFO and functional connectivity) to acquire better understanding of their associations. It would also be interesting to study ReHo in both resting and task-based fMRI and examine whether ReHo, which represents baseline neural activity in local regions, predicts task induced signal changes in those regions. Finally, the nature of these data does not allow us to establish causal links. Prospective studies are needed to assess whether ReHo deficits are a cause or a consequence of schizophrenia.
In conclusion, this study not only revealed a typical decrease of ReHo in the precentral gyrus, middle occipital gyrus, and posterior insula, but also an atypical increase of ReHo in the medial prefrontal cortex and anterior insula. Our findings of increased ReHo in schizophrenia might suggest an altered coherence of local resting-state activity in brain regions responsible for high cognitive function. Furthermore, we first showed that ReHo varied with frequency bands, presenting slow-4> slow-5 in the fusiform gyrus and superior frontal gyrus, and slow-5> slow-4 in basal ganglia, parahippocampus, and dorsal middle prefrontal gyrus. We also demonstrated that ReHo abnormalities in schizophrenia were frequency-dependent in the inferior occipital gyrus and caudate body. Our work may carry potential implications for neural psychopathology of schizophrenia. Future work will be needed to examine the functional significance of these interactions (e.g., frequency band×group) and test similar frequency dependent changes in other psychiatric disorders.