Yifang Zhou

Amplitude of low-frequency fluctuations in bipolar disorder: a resting state fMRI study.

OBJECTIVES The spontaneous low frequency fluctuations (LFF) of blood oxygenation level-dependent (BOLD) signal in resting state have been identified as a biological measure of baseline spontaneous activity in the brain. Increasingly, studies of spontaneous resting state functional connectivity have demonstrated neural network abnormalities in bipolar disorder (BD). This study used the amplitude of low frequency fluctuations (ALFF) to explore the regional functional changes in BD during resting state. METHODS Twenty-nine BD participants and 29 matched healthy controls (HC) were recruited to undergo resting-state functional magnetic resonance imaging scan on a 3.0T magnetic resonance imaging system. The ALFF of BOLD signal in gray matter for each participant was calculated, and then was compared between BD and HC using ALFF maps. RESULTS Compared to the HC group, the BD group showed increased ALFF in ventral prefrontal cortex, dorsal lateral prefrontal cortex, frontal eye field, insula, and putamen with extension into the ventral striatum, as well as decreased ALFF in the lingual gyrus (p<0.05, corrected). LIMITATIONS Although we observed differences in ALFF between BD and HC, we cannot conclusively state that these differences are caused by the pathophysiology of BD since most of BD participants were being treated with medications at the time of scanning. CONCLUSIONS Our results revealed altered regional brain activity in BD during resting state. The affected regions have been associated with BD pathophysiology. This suggests that methods using ALFF method may potentially be useful in further studies of this disorder.

A comparative diffusion tensor imaging study of corpus callosum subregion integrity in bipolar disorder and schizophrenia

Structural magnetic resonance imaging (MRI) studies have provided evidence for corpus callosum (CC) white matter abnormalities in bipolar disorder (BD) and schizophrenia (SZ). These findings include alterations in shape, volume, white matter intensity and structural integrity compared to healthy control populations. Although CC alterations are implicated in both SZ and BD, no study of which we are aware has investigated callosal subregion differences between these two patient populations. We used diffusion tensor imaging (DTI) to assess CC integrity in patients with BD (n=16), SZ (n=19) and healthy controls (HC) (n=24). Fractional anisotropy (FA) of CC subregions was measured using region of interest (ROI) analysis and compared in the three groups. Significant group differences of FA values were revealed in five CC subregions, including the anterior genu, middle genu, posterior genu, posterior body and anterior splenium. FA values of the same subregions were significantly reduced in patients with SZ compared with HC. FA values were also significantly reduced in patients with BD compared to the HC group in the same subregions, excepting the middle genu. No significant difference was found between patient groups in any region. Most of the alterations in CC subregions were present in both the BD and SZ groups. These results imply an overlap in potential pathology, possibly relating to risk factors common to both disorders. The one region that differed between patient groups, the middle genu area, may serve as an illness marker and is perhaps involved in the different cognitive impairments observed in BD and SZ.

Neural activity changes in unaffected children of patients with schizophrenia: A resting-state fMRI study

Previous neuroimaging studies have suggested that individuals at risk for schizophrenia exhibit structural and functional brain abnormalities. However, few studies focus on resting state baseline activity in individuals with genetic high-risk for schizophrenia (HR). We examined cerebral spontaneous neural activity in HR by measuring the amplitude of low frequency fluctuations (ALFF) in the blood oxygen level-dependent (BOLD) functional magnetic resonance signal during resting state. Using a 3T MRI scanner, 28 non-psychotic young adult participants with at least one parent with schizophrenia and 44 matched unrelated healthy comparison subjects (HC) were scanned during the resting-state. The ALFF of the BOLD signal for each participant was calculated, and these values were then compared between-groups using voxel-based analysis of the ALFF maps. The HR group showed significantly increased ALFF compared to the HC group in the striatum, including the left caudate nucleus extending to the putamen and the right caudate nucleus. There was also increased ALFF in HR relative to controls in the left medial temporal region including hippocampus, parahippocampal gyrus and the fusiform gyrus, as well as regions including the left lateral thalamus, bilateral ventral and dorsal anterior cingulate cortex, bilateral calcarine sulcus and precuneus. There was significantly decreased ALFF in the HR group relative to controls in the left inferior parietal lobule/postcentral gyrus. Our findings suggest that altered intrinsic neuronal activity in cortico-striato-thalamic networks may represent genetic vulnerability for the development of schizophrenia.

Disrupted structural and functional connectivity in prefrontal-hippocampus circuitry in first-episode medication-naïve adolescent depression

Background Evidence implicates abnormalities in prefrontal-hippocampus neural circuitry in major depressive disorder (MDD). This study investigates the potential disruptions in prefrontal-hippocampus structural and functional connectivity, as well as their relationship in first-episode medication-naïve adolescents with MDD in order to investigate the early stage of the illness without confounds of illness course and medication exposure. Methods Diffusion tensor imaging and resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 26 first-episode medication-naïve MDD adolescents and 31 healthy controls (HC). Fractional anisotropy (FA) values of the fornix and the prefrontal-hippocampus functional connectivity was compared between MDD and HC groups. The correlation between the FA value of fornix and the strength of the functional connectivity in the prefrontal cortex (PFC) region showing significant differences between the two groups was identified. Results Compared with the HC group, adolescent MDD group had significant lower FA values in the fornix, as well as decreased functional connectivity in four PFC regions. Significant negative correlations were observed between fornix FA values and functional connectivity from hippocampus to PFC within the HC group. There was no significant correlation between the fornix FA and the strength of functional connectivity within the adolescent MDD group. Conclusions First-episode medication-naïve adolescent MDD showed decreased structural and functional connectivity as well as deficits of the association between structural and functional connectivity shown in HC in the PFC-hippocampus neural circuitry. These findings suggest that abnormal PFC-hippocampus neural circuitry may present in the early onset of MDD and play an important role in the neuropathophysiology of MDD.

White Matter Integrity in Genetic High-Risk Individuals and First-Episode Schizophrenia Patients: Similarities and Disassociations

White matter (WM) neuroimaging studies have shown varied findings at different stages of schizophrenia (SZ). Understanding these variations may elucidate distinct markers of genetic vulnerability and conversion to psychosis. To examine the similarities and differences in WM connectivity between those at-risk for and in early stages of SZ, a cross-sectional diffusion tensor imaging study of 48 individuals diagnosed with first-episode SZ (FE-SZ), 37 nonpsychotic individuals at a high genetic risk of SZ (GHR-SZ), and 67 healthy controls (HC) was conducted. Decreased fractional anisotropy (FA) in the corpus callosum (CC), anterior cingulum (AC), and uncinate fasciculus (UF) was observed in both the GHR-SZ and FE-SZ groups, while decreased FAs in the superior longitudinal fasciculus (SLF) and the fornix were only seen in the FE-SZ participants. Additionally, both GHR-SZ and FE-SZ showed worse executive performance than HC. The left SLF III FA was significantly positively correlated with hallucinations, and right SLF II was positively correlated with thought disorder. The presence of shared WM deficits in both FE-SZ and GHR-SZ individuals may reflect the genetic liability to SZ, while the disparate FA changes in the FE-SZ group may represent symptom-generating circuitry that mediates perceptual and cognitive disturbances of SZ and ultimately culminates in the onset of psychotic episodes.

Trait-Related Cortical-Subcortical Dissociation in Bipolar Disorder: Analysis of Network Degree Centrality.

BACKGROUND Bipolar disorder is a systemic brain disorder. Accumulated evidence suggested that cortical-subcortical imbalance could be a trait-related pathogenic factor of bipolar disorder. Degree centrality, a robust index of focal connectivity in which the number of direct connections from one node to all nodes is counted, has not previously been studied in bipolar disorder as a whole. METHODS Resting state functional magnetic resonance imaging was performed on 52 patients with DSM-IV bipolar I disorder and 70 healthy controls recruited between September 2009 and July 2014. Degree centrality was calculated within cerebral gray matter for each subject and compared between patients with bipolar disorder and healthy controls. Hub distributions of both groups were explored. Effects of medication exposure and mood state on degree centrality, as well as cortical-subcortical degree centrality correlations, were explored. RESULTS Compared to healthy controls, patients with bipolar disorder exhibited significant decrease in degree centrality in cortical regions, including the middle temporal pole, inferior temporal gyrus, and ventral prefrontal cortex, but showed significant increase in degree centrality mainly in subcortical regions, including caudate, thalamus, parahippocampal gyrus, hippocampi, anterior cingulate, insula, and amygdala, and a small portion of cortical regions, such as superior and middle frontal gyrus (P < .05, corrected). Spatial distributions of the 2 groups were very similar. No significant effects of medication exposure or mood state on degree centrality were found. Patients with bipolar disorder also showed significant decrease in cortical-subcortical degree centrality correlation (P = .003). CONCLUSIONS These findings further contribute to the mounting evidence of cortical-subcortical dissociation in bipolar disorder pathophysiology. In addition, this study supports the continued development and implementation of graph-based techniques to enhance our understanding of the underlying neural mechanisms in mental disorders such as bipolar disorder, which are increasingly viewed as systemic brain disorders rather than disorders arising from disruption within a single structure or a limited number of structures. Due to the heterogeneity of our sample, as well as the small sample size of each medication and mood state subgroups, further investigation is needed to support our findings.

Amygdala-Prefrontal Cortex Resting-State Functional Connectivity Varies with First Depressive or Manic Episode in Bipolar Disorder.

BACKGROUND Bipolar disorder (BD) is one of the most complex mental illnesses, characterized by interactive depressive and manic states that are 2 contrary symptoms of disease states. The bilateral amygdala and prefrontal cortex (PFC) appear to play critical roles in BD; however, abnormalities seem to manifest differently in the 2 states and may provide further insight into underlying mechanisms. METHODS Sixteen participants with first-episode depressive and 13 participants with first-episode manic states of bipolar disorder as well as 30 healthy control (HC) participants underwent resting-state functional magnetic resonance imaging (fMRI). Resting-state functional connectivity (rsFC) between the bilateral amygdala and PFC was compared among the 3 groups. RESULTS Compared with depressive state participants of the BD group, manic state participants of the BD group showed a significant decrease in rsFC between the amygdala and right orbital frontal cortex (p<0.05, corrected). In addition, rsFC between the amygdala and left middle frontal cortex was significantly decreased in depressive and manic state participants of the BD group when compared with the HC group (p<0.05, corrected). CONCLUSIONS Our findings suggest that mood state during the first episodes of BD may be related to abnormality in hemispheric lateralization. The abnormalities in amygdala- left PFC functional connectivity might present the trait feature for BD, while deficits in amygdala- right PFC functional connectivity might be specific to manic episode, compared to depressive episode.

Voxel-Based Morphometry in Individuals at Genetic High Risk for Schizophrenia and Patients with Schizophrenia during Their First Episode of Psychosis

Background Understanding morphologic changes in vulnerable and early disease state of schizophrenia (SZ) may provide further insight into the development of psychosis. Method Whole brain voxel-based morphometry was performed to identify gray matter (GM) regional differences in 60 individuals with SZ during their first psychotic episode (FE-SZ), 31 individuals at genetic high risk for SZ (GHR-SZ) individuals, and 71 healthy controls. Results Significant differences were found in several regions including the prefrontal cortex, parietal lobe, temporal lobe, hippocampus, occipital lobe, and cerebellum among the three groups (p<0.05, corrected). Compared to the HC group, the FE-SZ group had significantly decreased GM volumes in several regions including the cerebellum, hippocampus, fusiform gyrus, lingual gyrus, supramarginal gyrus, and superior, middle, and inferior temporal gyri and significantly increased GM volumes in the middle frontal gyrus and inferior operculum frontal gyrus (p<0.05). The GHR-SZ group had significant decreases in GM volumes in the supramaginal gyrus, precentral gyrus, and rolandic operculum and significant increases in GM volumes in the cerebellum, fusiform gyrus, middle frontal gyrus, inferior operculum frontal gyrus, and superior, middle, and inferior temporal gyri when compared to the HC group (p<0.05). Compared to the GHR-SZ group, the FE-SZ group had significant decreases in GM volumes in several regions including the cerebellum, fusiform gyrus, supramarginal gyrus, and superior, middle, and inferior temporal gyri (p<0.05). Conclusions The findings herein implicate the involvement of multisensory integration in SZ development and pathophysiology. Additionally, the patterns of observed differences suggest possible indicators of disease, vulnerability, and resiliency in SZ.

Alteration of cortico-limbic-striatal neural system in major depressive disorder and bipolar disorder

BACKGROUND It is often difficult to differentiate major depressive disorder (MDD) and bipolar disorder (BD) merely according to clinical symptoms. Similarities and differences in neural activity between the two disorders remain unclear. In current study, we use amplitude of low-frequency fluctuations (ALFF) to compare neural activation changes between MDD and BD patients. METHODS One hundred and eighty-three adolescents and young adults (57 MDD, 46 BD and 80 healthy controls, HC) were scanned during resting state. The ALFF for each participant was calculated, and were then compared among all groups using voxel-based analysis. RESULTS There was a significant effect of diagnosis in the core regions of cortico-limbic-striatal neural system. Furthermore, MDD showed left-sided abnormal neural activity while BD showed a bilateral abnormality in this neural system. LIMITATIONS This study was underpowered to consider medications, mood states and neural developmental effects on the neural activation. CONCLUSIONS Differences in lateralization of ALFF alterations were found. Alterations predominated in the left hemisphere for MDD, whereas alterations were bilateral for BD.

Shared and distinct regional homogeneity changes in bipolar and unipolar depression

BACKGROUND Bipolar depression (BD) is easily misdiagnosed as unipolar depression (UD) or major depressive disorder (MDD) because the depressive symptoms can overlap. Regional homogeneity (ReHo), a measure commonly used for analyzing resting-state fMRI data, has been applied to the study of various neuropsychiatric disorders. However, to date, studies directly comparing BD and UD using ReHo have been relatively scarce. Further investigation is needed to study the latent pathophysiological mechanisms of BD and UD. METHODS Fifty-five patients with BD and 76 patients with UD, as well as 113 healthy controls (HC), underwent resting-state functional magnetic resonance imaging (fMRI). We compared the voxel-wise ReHo across the whole brain for subjects in each of the three groups. RESULTS Significant differences were found in the left frontal cluster (LFC) across the three groups. There were differences between BD and UD in the LFC and left temporal cluster (LTC). In addition, differences between UD and HC existed in the LFC and the occipital cluster (OC). When comparing BD subjects with HC subjects, significant differences were found in all three clusters. No correlations were observed between the 17-item Hamilton Depression Rating Scale (HDRS-17) scores or sub-scores and the ReHo values of BD or UD patients. CONCLUSION ReHo values in the LFC differed significantly among BD, UD, and HC subjects. ReHo in the LTC showed significant differences between BD and UD that might serve as neuroimaging markers of BD. Further, BD and UD shared ReHo changes in the cuneus, suggesting that the cuneus might provide a depressive state neuroimaging marker of BD and UD patients.