Potential Indicators Distinguishing Between Bipolar Ⅰ And Ⅱ Disorders Based On Event-related Potential And Behavioral Characteristics

BackgroundBipolar disorder is a group of chronic mental disorders marked by recurrent fluctuations in affective state and energy.It has been listed as one of the top five disabling mental disorders because of its high rates of prevalence,recurrence,suicidal attempt and fatality.Currently,there are difficulties in differential diagnosis and treatment of its two major types,i.e.,bipolar Ⅰ(BD Ⅰ)and bipolar Ⅱ(BD Ⅱ),which might be due to the failure to find stable and effective biomarkers clearly distinguishing them.Although a large number of studies have demonstrated impaired neurocognitive function in patients with bipolar disorder,the neural mechanisms of these dysfunctions in BD Ⅰ and BD Ⅱ are still overlapped,and some conclusions are contradictory.Some neuroimaging studies have found different atrophy in the two types in areas such as prefrontal lobes,and suggested different abnormalities in the function of related brain regions under emotional and non-emotional tasks.So more differences might be found in the function involving regions like prefrontal cortex The core pathological characteristic of bipolar disorder patients is emotion dysregulation,which is correlated with their abnormal emotion processing,incapability to isolate themselves from emotional conditions so as to attend normal cognitive activities,as well as inhibition deficiency of emotional response(which involves executive control dysfunction).Moreover,all these processes involve the activation of prefrontal cortex,suggesting that BD Ⅰ and BD Ⅱ might differ in the impairments of emotion processing,cognition under emotional distractors,and executive control functionAims1.We aimed to explore the real-time characteristics of cortical processing of facial expressions in BD Ⅰ and BD Ⅱ by recording the scalp electrical signals of the two types in the recognition of facial expressions of emotion,and to look for the different characteristics of BD Ⅰ and BD Ⅱ independent from their affective states,by evaluating the correlations between their affective states and cerebral potentials2.We aimed to further clarify the influences of external emotional stimulation and internal affective states on attention function in BD Ⅰ and BD Ⅱ by recording the scalp electrical signals of oddball task in different emotional conditions,and to look for the different characteristics of BD Ⅰ and BD Ⅱ independent from their affective states,by evaluating the correlations between their affective states and cerebral potentials3.We aimed to provide new evidence upon the prefrontal executive control function in BD Ⅰ and BD Ⅱ under altered state of consciousness,via the assessment of their hypnotic susceptibility.Meanwhile,by evaluating the predictive effect of hypnotic susceptibility on participants’concurrent affective states,we aimed to lay foundation for the application of targeted hypnotherapy in the two types of bipolar disorder.Methods1.39 patients of BD Ⅰ,25 of BDⅡ,and 54 healthy volunteers(Controls)underwent facial emotion recognition task of Neutral,Happiness,Anger,and Sadness,and their event-related potentials(ERPs)were recorded.The Mood Disorder Questionnaire(MDQ),Hypomania Checklist-32(HCL-32)and Plutchik-van Praag Depression Inventory(PVP)were used to assess participants’ affective states over the past two weeks.ANOVA was used to compare the latencies and amplitudes of ERP components and response time of BD Ⅰ,BD Ⅱ,and Controls in response to various facial emotions.Chi-square test was used for group comparison upon response accuracy.3D source reconstruction under time windows of abnormal ERP components were used to explore their cerebral activation and differences.Correlation analysis was used to explore the relationships between ERP components and affective states in participants2.31 BD Ⅰ,27 BD Ⅱ and 47 Controls underwent visual oddball ERP test in external emotional conditions such as Disgust,Fear,Sadness,Erotica,Happiness and Neutral.Meanwhile,MDQ,HCL-32 and PVP were used to assess participants’affective states over the past two weeks.ANOVA was used to compare the latencies and amplitudes of ERP components and response time in BDⅠ,BD Ⅱ,and Controls in various emotional conditions.Chi-square test was used for group comparison upon response accuracy.3D source reconstruction under time windows of abnormal ERP components were used to explore the cerebral activation,and differences in patients with bipolar disorder.Correlation analysis was used to explore the relationships between ERP components and affective states in participants.3.The Stanford Hypnotic Susceptibility Scale,Form C(SHSS:C)was used to characterize responses to hypnotic suggestions in 62 BD Ⅰ,35 BD Ⅱ and 120 Controls.Meanwhile,MDQ,HCL-32 and PVP were used to assess participants’ affective states over past two weeks.The passing rates of SHSS:C items in BD Ⅰ,BD Ⅱ and Controls were compared by Chi-square analysis.Moreover,predictions of participants’hypnotic susceptibility on their concurrent affective states were analyzed by Multiple Linear Regression(backward method).ResultsIn all three tests,BD Ⅰ and BD Ⅱ had higher scores on PVP than Controls did;BDⅠ had higher score on MDQ than BD Ⅱ and Controls did;and BD Ⅰ and BD Ⅱ had higher scores than Controls did,and BDⅠ had higher scores than BD Ⅱ did on HCL-32.In addition,we found that:1.BD Ⅰ had lower recognition accuracy for Sadness than BD Ⅱ did;BD Ⅱ had prolonged N1 latency for Neutral and Happiness,and lower P3b amplitude for Sadness than Controls did,which were independent from the affective states.Differ from the bilateral activated superior frontal gyri and secondary visual cortices in Controls,BD Ⅰmainly activated the right fusiform gyrus,with slightly increased activity in bilateral superior frontal gyri,while BD Ⅱ mainly activated the right inferior temporal gyrus,with decreased activity of the inferior frontal gyri,during P3b time window for Sadness Within N1 time window for Neutral and Happiness,Controls mainly activated the secondary visual cortices,while BD Ⅱ mainly activated the right inferior temporal gyrus In addition,both BD Ⅰ and BD Ⅱshowed right hemispheric dominance for processing of facial emotions2.BD Ⅰ had prolonged N2 latencies in Fear and Happiness conditions,and decreased P3 amplitudes in Disgust and Erotica conditions;meanwhile,BD Ⅱ showed decreased P3 amplitudes in Disgust,Erotica,Happiness,and Neutral conditions.The source reconstruction analysis revealed that BD Ⅰ and BD Ⅱ had different activation abnormalities in the inferior frontal gyrus,medial prefrontal gyrus,postcentral gyrus,and regions of the temporal lobe,occipital lobe,and limbic system,at specific stages of attention under different emotional conditions.However,in BD Ⅰ and BD Ⅱ patients,the ERP abnormalities were independent from their concurrent affective states3.There was no significant difference in the total score of SHSS:C among the three groups,but the passing rate of BD I in items such as the ideomotor suggestion"Moving hands apart",was significantly higher than that of Controls,while the passing rate of BD I in perceptual-cognitive suggestion "Mosquito hallucination" was lower than that of Controls.In addition,the passing rate of "Mosquito hallucination" in Controls,of challenge suggestion "Arm rigidity" in BD I,and of perceptual-cognitive suggestion "Age regression" in BD Ⅱ predicted their MDQ scores respectivelyConclusions1.When recognizing the facial expressions of emotion,both BD Ⅰ and BD Ⅱshowed right hemispheric dominance.While BD Ⅰ had a lower ability to recognize sad face than BD Ⅱ did,and BD Ⅱ was characterized by a more generalized impairment of facial emotion processing,e.g.,the slowed early structural coding stage of relative positive facial expressions and abnormal activation of right inferior temporal gyrus,the deficient working memory updating and classification-evaluation stage of negative facial emotions and decreased activity in the superior frontal gyrus2.When referring to attention,BD Ⅰ and BD Ⅱ also had impaired functions independent of their emotional states.BD I patients had slowed automatic attention in happy and fearful situations,lower brain activity for target recognition or primary visual coding,and lowed active attention in disgust and erotic situations,with over-activation of emotion regulation regions.BD Ⅱ patients were less able to pay voluntary attention to target in disgust,happy,erotic,and neutral situations,and the areas responsible for somatosensory,auditory,and emotional perception or regulation were over-activated3.In terms of hypnotic susceptibility,BD Ⅰ was more likely to have physical dissociation than conscious dissociation under hypnosis;while no abnormal performance was found in BD Ⅱ.In addition,both bipolar patients and healthy volunteers showed associations between manic states while awake and physical or conscious suggestion susceptibility under hypnosis.These results suggested that the prefrontal executive function was more impaired in BD I under the altered conscious state,which might lay foundation for the hypnotherapy in bipolar patients.