Aberrant Functional Connectivity of the Orbitofrontal Cortex Is Associated With Excited Symptoms in First-Episode Drug-Naïve Patients With Schizophrenia

Abstract

BackgroundSchizophrenia (SZ) is associated with the highest disability rate among serious mental disorders. Excited symptoms are the core symptoms of SZ, which appear in the early stage, followed by other stages of the disease subsequently. These symptoms are destructive and more prone to violent attacks, posing a serious economic burden to the society. Abnormal spontaneous activity in the orbitofrontal cortex had been reported to be associated with excited symptoms in patients with SZ. However, whether the abnormality appears in first-episode drug-naïve patients with SZ has still remained elusive.MethodsA total of 56 first-episode drug-naïve patients with SZ and 27 healthy controls underwent resting-state functional magnetic resonance imaging (rs-fMRI) and positive and negative syndrome scale (PANSS). First, differences in fractional amplitude of low-frequency fluctuations (fALFF) between first-episode drug-naïve patients with SZ and healthy controls were examined to identify cerebral regions exhibiting abnormal local spontaneous activity. Based on the fALFF results, the resting-state functional connectivity analysis was performed to determine changes in cerebral regions exhibiting abnormal local spontaneous activity. Finally, the correlation between abnormal functional connectivity and exciting symptoms was analyzed.ResultsCompared with the healthy controls, first-episode drug-naïve patients with SZ showed a significant decrease in intrinsic activity in the bilateral precentral gyrus, bilateral postcentral gyrus, and the left orbitofrontal cortex. In addition, first-episode drug-naïve patients with SZ had significantly reduced functional connectivity values between the left orbitofrontal cortex and several cerebral regions, which were mainly distributed in the bilateral postcentral gyrus, the right middle frontal gyrus, bilateral paracentral lobules, the left precentral gyrus, and the right median cingulate. Further analyses showed that the functional connectivity between the left orbitofrontal cortex and the left postcentral gyrus, as well as bilateral paracentral lobules, was negatively correlated with excited symptoms in first-episode drug-naïve patients with SZ.ConclusionOur results indicated the important role of the left orbitofrontal cortex in first-episode drug-naïve patients with SZ and suggested that the abnormal spontaneous activity of the orbitofrontal cortex may be valuable to predict the occurrence of excited symptoms. These results may provide a new direction to explore the excited symptoms of SZ.

Physical Activity Alters Functional Connectivity of Orbitofrontal Cortex Subdivisions in Healthy Young Adults: A Longitudinal fMRI Study

“…In this context, we found only two previous works reporting a change in the FC of the OFC to an area of the postcentral gyrus: Research on children with externalizing disorders found that adolescents with a positive family history of substance use disorders had a stronger negative FC between the left lateral OFC and the right postcentral gyrus [77]. Another study reported a decreased FC of the left OFC to several areas of the (bilateral) postcentral gyrus in patients with schizophrenia [57]. While this again points towards the relevance of that connection in psychiatric disorders, there is not enough evidence to make further assumptions.…”

“…Based on a detailed parcellation of the OFC by Kahnt et al [11], small spherical regions of interest (ROIs) around the reported center coordinates (Table 1) were generated. As some studies reported differential functions of the left and right OFC [57,58], seeds were created separately for the left and right hemispheres (see Figure 1). We chose a radius of 4 mm, as a 5 mm radius resulted in multiple voxels overlapping and, therefore, being unsuitable for a differential analysis, although the smaller 4 mm was still sufficiently large for our data.…”

Deficits in Key Brain Network for Social Interaction in Individuals with Schizophrenia

“…In Cheon's study, negative symptom scores showed predominantly stronger positive associations with ALFF in the temporal and frontal brain regions [77]. However, Chen's research demonstrated that OFC-related re-fc was negatively correlated with excited symptoms in first-episode patients with SZ [78]. Therefore, further evidence on the relationship between spontaneous brain activity and clinical symptoms in SZ patients is required for consensus.…”

Neural basis underlying the sense of coherence in medical professionals revealed by the fractional amplitude of low-frequency fluctuations

“…Second, spontaneous brain activity was evaluated via fALFF in the context of functional segregation. Although this approach has been applied as a reliable method of localizing brain regions in relation to personality/behavioral traits [23,24], future studies should combine the functional connectivity approach with fALFF to gain further insights into the network context [63]. In addition, studies repeatedly reported that gray matter density and white matter integrity were associated with individual differences in various types of social cognitive abilities in healthy subjects and clinical populations [64][65][66][67].…”