Decreased dynamic variability of the cerebellum in the euthymic patients with bipolar disorder

Chen et al. BMC Psychiatry (2024) 24:137 https://doi.org/10.1186/s12888-024-05596-4 BMC Psychiatry RESEARCH Open Access Decreased dynamic variability of the cerebellum in the euthymic patients with bipolar disorder Zhenzhu Chen1,2†, Zhifang Zhang1†, Feng Li1,2, Lei Zhao1,2, Qijing Bo1,2*, Yuan Zhou1,4,5* and Chuanyue Wang1,2,3 Abstract Background Bipolar disorder (BD) is a complex mental illness characterized by different mood states, including depression, mania/hypomania, and euthymia. This study aimed to comprehensively evaluate dynamic changes in intrinsic brain activity by using dynamic fractional amplitude of low-frequency fluctuations (dfALFF) and dynamic degree centrality (dDC) in patients with BD euthymia or depression and healthy individuals. Methods The resting-state functional magnetic resonance imaging data were analyzed from 37 euthymic and 28 depressed patients with BD, as well as 85 healthy individuals. Using the sliding-window method, the dfALFF and dDC were calculated for each participant. These values were compared between the 3 groups using one-way analysis of variance (ANOVA). Additional analyses were conducted using different window lengths, step width, and window type to ensure the reliability of the results. Results The euthymic group showed significantly lower dfALFF and dDC values of the left and right cerebellum posterior lobe compared with the depressed and control groups (cluster level PFWE < 0.05), while the latter two groups were comparable. Brain regions showing significant group differences in the dfALFF analysis overlapped with those with significant differences in the dDC analysis. These results were consistent across different window lengths, step width, and window type. Conclusions These findings suggested that patients with euthymic BD exhibit less flexibility of temporal functional activities in the cerebellum posterior lobes compared to either depressed patients or healthy individuals. These results could contribute to the development of neuropathological models of BD, ultimately leading to improved diagnosis and treatment of this complex illness. Highlights • This study highlights the importance of investigating dynamic intrinsic brain activity in patients with bipolar disorder (BD) during different mood states. † Zhenzhu Chen and Zhifang Zhang contributed equally to this work. *Correspondence: Qijing Bo Yuan Zhou Full list of author information is available at the end of the article © The Author(s) 2024. 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The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Chen et al. BMC Psychiatry (2024) 24:137 Page 2 of 10 • The patients with euthymic BD showed significantly less flexibility of temporal functional activities in the left and right cerebellum posterior lobe compared to patients with depressed BD or healthy individuals. • The use of dynamic fractional amplitude of low-frequency fluctuations and dynamic degree centrality allowed for a comprehensive analysis of brain activity, providing reliable and objective results. Keywords Bipolar disorder, Resting-state fMRI, Dynamic fractional amplitude of low-frequency fluctuations, Dynamic degree centrality, Cerebellum posterior lobe Introduction Bipolar disorder (BD) is a serious mental illness characterized by alternating mood states of depression, mania/ hypomania and euthymia. These changes adversely affect emotion, cognition, activity level, social function, and quality of life even when the patient is euthymic [1]. The diversity of mood states, which occur over the entire course of BD, greatly challenges clinical decisions regarding diagnosis and treatment. Before the disease is fully exposed BD may be misdiagnosed as unipolar depression, and in error patients are easily given antidepressant monotherapy [2]. On the other hand, hypomania is often ignored by the patient and those around them, or sometimes the manic state is difficult to distinguish from schizophrenia [3]. Clinical characteristics associated with different mood states may reflect specific pathological alterations [4], including cognitive and functional impairment [5, 6]. Therefore, it is of great importance to differentiate the mood states of BD, including the euthymic. Resting-state functional magnetic resonance imaging (fMRI) is a technique that measures the intrinsic, spontaneous activity of the brain during rest, which consumes a significant amount of energy [7]. This makes restingstate fMRI a valuable tool for studying the underlying neurobiological mechanisms of neuropsychiatric diseases, including BD [8]. Resting-state fMRI provides various functional metrics that can supply disease-related information from different perspectives. For example, the fractional amplitude of low-frequency fluctuations (fALFF) is a functional metric that reflects the intensity of spontaneous brain activity from a given brain region. fALFF is derived from the amplitude of low-frequency fluctuations (ALFF) and represents the relative contribution of low frequency fluctuations within the frequency range. The advantages of fALFF as an evaluative functional metric include eliminating the influence of physiological noise and its better sensitivity and specificity for detecting spontaneous brain activity [9]. Degree centrality (DC) is another functional metric provided by restingstate fMRI. It is a derivative indicator based on functional connectivity and graph theory, which can reflect the importance of specific nodes in the brain functional connectome [10]. By measuring the degree of connectivity between different brain regions, DC can provide valuable information about the underlying neural networks that support cognitive and behavioral processes. Overall, the functional metrics provided by resting-state fMRI, such as fALFF and DC, can provide valuable insights into the underlying neurobiological mechanisms of neuropsychiatric diseases and better understand the complex functioning of the brain in health and disease. Several studies (...truncated)