Fractional amplitude of low-frequency fluctuations and gray matter volume alterations in patients with bipolar depression

Highlights

• Patients with BD showed significant decreased GMV and increased fALFF values in the bilateral superior frontal gyrus and right superior frontal gyrus.

• Significantly reduced fALFF values in the lingual gyrus were observed in the patients with BD.

• Significant negative correlations were observed between GMV values in the left SFG and vocabulary memory.

Abstract

Purpose

We used fractional amplitude of low-frequency fluctuations (fALFF) and gray matter volume (GMV) jointly to explore the mechanism of brain function and structure in unmedicated patients with bipolar disorder (BD).

Methods

Thirty first episode drug-naive patients with and thirty healthy controls (HCs) were recruited in this study; All the subjects underwent Magnetic Resonance Imaging (MRI) scanning and performed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), all the patients with MDD finished the 17-item Hamilton Depression Rating Scale (HAMD17). Data Processing and Analysis for Brain Imaging (DPABI) and SPM8 were used to find potential differences in fALFF and GMV between the two groups. A Pearson correlation model was used to analyze associations of functional and morphometric changes with clinical symptoms and cognitive tests.

Results

Compared to healthy controls, the BD group had significantly reduced fALFF values in the lingual gyrus and increased fALFF values in the bilateral superior frontal gyrus and superior frontal gyrus. With regards to VBM, patients with BD showed significant GMV decreases in the bilateral superior temporal gyrus, bilateral superior frontal gyrus, right superior frontal gyrus, right parahippocampal gyrus and precuneus. Additionally, we found an overlap of brain regions focused on the left SFG. Significant negative correlations were observed between abnormal GMV values in the left SFG and vocabulary memory.

Conclusion

The superior frontal gyrus was the site of the most robust and reliable abnormality, with an overlap of abnormal structural and functional MRI features that play an important role in pathology in BD.

Introduction

Bipolar disorder (BD), which is characterized by recurrent episodes of depression and mania or hypomania, has a high prevalence, high recurrence rate, high suicide rate, and high disease burden [1,2]. But the mechanism of BD's psychopathology is not clear.

Fortunately, brain imaging offers a noninvasive and dynamic diagnostic approach, making it a hotspot in research into the pathological mechanism of mood disorders [3]. Various neuroimaging studies in bipolar disorder have reported functional and structural abnormalities that can help us better understand the underlying neurobiology of BD. Many studies emphasize emotional brain network dysfunction over a wide range, including networks involved in emotional processing, cognitive emotion regulation and other functions [[4], [5], [6]]. A meta-analysis of resting-state functional MRI (rs-fMRI) has reported differences in frontal-limbic structure activation in BD, including the inferior frontal cortex (IFC) and medial temporal gyrus (MTG), putamen, hippocampus, and amygdala [7]. Recently, a resting-state functional connectivity (rs-FC) study confirmed the abnormality of the bilateral insula and right fronto-polar prefrontal cortex (FPPFC) [8]. The amplitude of low-frequency fluctuations (ALFF), as a functional indicator, has been used to analyze aberrant regional brain responses in BD and MDD [9,10]. Since ALFF is sensitive to physiological noise, Zou et al. proposed an improved index known as fractional ALFF (fALFF) [11]. However, in a systematic literature review, fALFF research seemed to be rarely used in the study of bipolar disorder [12]. Meanwhile, the technique of voxel-based morphometry (VBM) has been widely used for structural MRI. VBM studies include gray matter volume (GMV) analysis and gray matter density (GMD) analysis. Compared to HCs, BD exhibited reduced gray matter density in the parietal and occipital cortices [13]. In a large study of 1710 BD patients and 2594 healthy controls, researchers found consistent volumetric reductions in BD patients for mean hippocampus, thalamus and enlarged lateral ventricles [14]. In assessing GMV at baseline and one year following a first manic episode, researchers found that the recurrent BD group had greater GMV loss than the HC group in the left frontal and bilateral temporal regions and remission BD patients involving the bilateral frontal, temporal and left parietal regions [15]. Meanwhile, several of meta-analysis have confirmed GMV alterations. These findings show that BD might involve abnormalities of the cortico-limbic systems in structure, as mentioned above (although those were functional changes), which includes the left medial frontal gyrus (MFG), right inferior/precentral gyrus (IFG), ventrolateral prefrontal cortex (VLPFC), anterior cingulate cortex (ACC), amygdala, hippocampus, and insula [[16], [17], [18], [19], [20]]. A study reported the dissociation of anatomical and functional abnormalities in patients with depression [21], but it remains unclear whether this dissociation of altered brain regions is similar in BD.

However, There is still a lack of objective and reliable biomarkers for biological diagnosis of bipolar disorder, and clinical diagnosis is still based on symptoms. Therefore, it is greatly affected by the subjective feelings and judgments of doctors. Current research confuses factors such as emotional state and medication status during illness onset, and the research results are very different, the dispute and discussion were constantly in heterogeneous research. The current study first combined functional and structure MRI, using spontaneous activity (fALFF), gray matter volume (VBM) to analyze potential differences. We further analyzed the correlation between these alterations and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) score [22].