Abnormal Functional Activities In Brains Of Early Bipolar ? Disorder:a Resting-State FMRI Study

Purpose: Using resting-state functional magnetic resonance imaging(resting-state f MRI),we investigated the spontaneous brain activities and the feature of brain functional connectivity in resting state in patients of bipolar ? disorder(BD?),and studied the abnormal biological characteristics and the pathological mechanism of brain function impairment in bipolar ? disorder.We aimed to provide reliable theoretical basis for the clinical diagnosis and treatment of bipolar ? disorder.Methods:12 participants diagnosed to be patients of bipolar ? disorder within 2years from onset,and 15 healthy controls,matched for age,gender and education level were recruited and scanned.We examined the brain functional activities in early bipolar ? disorder based on resting state f MRI data using different methods,including Amplitude of Low frequency Fluctuations(ALFF),Regional Homogeneity(Re Ho),Voxel-Mirrored Homotopic Connectivity(VMHC)and voxel-based Functional Connectivity(FC).(ALFF evaluates the power of brain spontaneous neural activities;Re Ho evaluates the homogeneity of regional neural activities;VMHC evaluates the synchronicity of bilateral cerebral hemisphere activities;and FC evaluates the correlation of time series for neural activities in specific brain regions.)Data preprocessing and statistical analysis were performed using SPM12 and DPABI toolkits.Two sample T-test was used for analyzing the difference across the groups,with the significance threshold of p-value set at less than 0.05 in combination with Alphasim correction.Pearson correlation test was also employed using SPSS23 for studying correlation between the strength of functional connectivity and clinical scale scores.Results:1.ALFF analysis: the BD group showed significant ALFF increase in bilateral medial orbitofrontal gyrus,bilateral superior orbitofrontal gyrus and right middle orbitofrontal gyrus,and decrease in caudate and thalamus.The increased ALFF values were positively correlated with the HAMA scale scores;whereas the decreased ALFF values were negatively correlated with the HAMA scale scores.2.Re Ho analysis: the BD group showed significant Re Ho increase in bilateral orbital frontal gyrus,left dorsolateral superior frontal gyrus,left middle frontal gyrus and bilateral medial superior frontal gyrus.3.VMHC analysis: the BD group showed significant VMHC increase in middle frontal gyrus and dorsolateral superior frontal gyrus.4.FC analysis: In the BD group,we found decreased FC strength between right medial orbital superior frontal gyrus and p ACC and increased FC strength between right caudate-precuneus/right orbital inferior frontal gyrus and orbital middle frontal gyrus/left medial superior frontal gyrus /right middle frontal gyrus.5.Scale related FC analysis: In the BD group,the FC strength between bilateral orbital frontal gyrus and right caudate was negatively correlated with the HAMA scale scores(right:r=-0.6,p=0.039;left:r=-0.629,p =0.029),and the FC strength between right orbital inferior frontal gyrus and left middle frontal gyrus was positively correlated with the HAMD scale scores(r=0.67,p=0.017).Conclusion:1.Patients of BD II showed ALFF abnormalities in orbital frontal gyrus,caudate and thalamus,and their HAMA scores were sensitive to such abnormalities,suggesting that anxiety is an important symptom in early bipolar ?disorder,and anxiety is closely related to the regional spontaneous activities in these brain regions.Moreover,the functional connectivity between orbital frontal gyrus and right caudate could be a biological marker for anxiety symptoms.2.The resting state f MRI data showed that the Re Ho values were increased in orbital frontal gyrus,left medial superior frontal gyrus,left dorsolateral superior frontal gyrus and left middle frontal gyrus.These findings suggested substantial impairment of regional ability in these regions in patients of BD ?,because orbitofrontal lobes are responsible for emotional and cognitive function,and middle frontal gyrus is also associated with emotion.The pathological basis of brain function of negative emotion during depressive phase may exist in orbital frontal gyrus and middle frontal gyrus.Moreover,the functional connectivity between right inferior orbital frontal gyrus and left middle frontal gyrus could be a biological marker for depression symptoms.3.Patients of early BD II showed increased VMHC values in middle frontal gyrus and dorsolateral superior frontal gyrus.These findings suggested that bilateral prefrontal gyrus functions were impaired,and the brain activities were compensated.4.ALFF,Re Ho,VMHC and FC methods are effective approaches for analyzing resting state f MRI data,thereby effectively identifying abnormal brain activities in patient brains of BD II at resting state.