Divergent and Convergent Imaging Markers Between Bipolar and Unipolar Depression Based on Machine Learning.

Distinguishing bipolar depression (BD) from unipolar depression (UD) based on symptoms only is challenging. Brain functional connectivity (FC), especially dynamic FC, has emerged as a promising approach to identify possible imaging markers for differentiating BD from UD. However, most of such studies utilized conventional FC and group-level statistical comparisons, which may not be sensitive enough to quantify subtle changes in the FC dynamics between BD and UD. In this paper, we present a more effective individualized differentiation model based on machine learning and the whole-brain "high-order functional connectivity (HOFC)" network. The HOFC, capturing temporal synchronization among the dynamic FC time series, a more complex "chronnectome" metric compared to the conventional FC, was used to classify 52 BD, 73 UD, and 76 healthycontrols (HC). We achieved a satisfactory accuracy (70.40%) in BD vs. UD differentiation. The resultant contributing features revealed the involvement of the coordinated flexible interactions among sensory (e.g., olfaction, vision, and audition), motor, and cognitive systems. Despite sharing common chronnectome of cognitive and affective impairments, BD and UD also demonstrated unique dynamic FC synchronization patterns. UD is more associated with abnormal visual-somatomotor inter-network connections, while BD is more related to impaired ventral attention-frontoparietal inter-network connections. Moreover, we found that the illness duration modulated the BD vs. UD separation, with the differentiation performance hampered by the secondary disease effects. Our findings suggest that BD and UD may have divergent and convergent neural substrates, which further expand our knowledge of the two different mental disorders.

Online Learning Performances of Children and Adolescents With Attention Deficit Hyperactivity Disorder During the COVID-19 Pandemic.

To investigate attention deficit hyperactivity disorder (ADHD) core symptoms that impair executive function (EF), emotional state, learning motivation, and the family and parenting environment of children and adolescents with ADHD, both with and without severe difficulties. This will be explored within an online learning environment during the period of COVID-19 pandemic. A total of 183 ADHD children diagnosed using DSM-V criteria were selected and divided into 2 groups high difficulties during online learning (HDOL) and low difficulties during online learning (LDOL) according to the answer of Home Quarantine Investigation of the Pandemic (HQIP). The participants filled out a set of questionnaires to assess their emotional state and learning motivation, and their parents also filled out the questionnaires about ADHD core symptoms, EF, and family and parenting environment. Compared with ADHD children in the LDOL group, the children in the HDOL group had significant symptoms of inattention, hyperactivity, oppositional defiant, behavioral and emotional problems according to the Swanson, Nolan, and Pelham Rating Scale (SNAP). They also had more severely impaired EF according to the Behavior Rating Inventory of Executive Function (BRIEF), more difficulties and disturbances in the family by the Chinese version of Family Environment Scale (FES-CV), and lower parenting efficacy and satisfaction by Parenting Sense of Competence (PSOC). With regard to the self-rating questionnaires of children and adolescents, the HDOL group reported lower learning motivation according to the Students Learning Motivation Scale (SLMS). By Screening for Child Anxiety-Related Emotional Disorders and Depression Self-Rating Scale for Children (DSRSC), those in HDOL presented more negative emotions. The HDOL group spent significantly more time on both video games and social software per day and significantly less time on multiple activities per week, when compared to those in the LDOL group. This study demonstrated that ADHD children and adolescents with HDOL had more inattention-related behaviors, more severe emotional problems and EF impairment, weaker learning motivation, and poorer family and parenting environment. Meanwhile, digital media use should be supervised and appropriate extracurricular activities should be encouraged by parents and schools.

Callous-unemotional traits in Chinese preschool children with attention-deficit/hyperactivity disorder.

BACKGROUND: Children with early onset of Callous-Unemotional (CU) traits are at a higher risk for long-term, persistent psychosocial problems. The current study aimed to explore the characteristics of CU in preschool children with Attention Deficit Hyperactivity Disorder (ADHD) and the diagnostic significance of CU traits in ADHD. METHODS: A total of 176 preschool children (89 with ADHD and 87 Typically Developing Children [TDC]) aged 4-5 years old were recruited to the study. The participants were assessed for CU traits, emotional and behavioral problems, and how their executive functioning was associated with ADHD using multiple assessment scales. Multiple linear regression analysis was performed to assess the incremental validity of the Inventory of Callous-Unemotional Traits (ICU), adjusting for possible covariates by child's sex, conduct problems, and oppositional defiant symptoms. RESULTS: The results showed that there was a significant difference of ICU scores between the ADHD and TDC groups (F = 30.12, P < 0.001). In terms of callousness, ADHD + Oppositional Defiant Disorder (ODD) group showed a significant high score, and the ADHD only group scored significantly higher than the TDC group (F = 20.42, P < 0.001). The ICU was negatively associated with the prosocial behaviour subscale (γ = - 0.57, P < 0.01) and showed low to moderate positive correlations with emotional and behavioural problems, as well as executive function (γ = 0.24-0.67, P < 0.05). The ICU scores explained 6% of the incremental validity in ADHD symptoms. The diagnostic value of the ICU for ADHD was medium and acceptable. CONCLUSIONS: The current study indicated that early identification of CU traits may help clinicians better understand symptoms and behavioural problems in children with ADHD. CU traits therefore could be considered as a useful assessment tool for ADHD.

Influences of digital media use on children and adolescents with ADHD during COVID-19 pandemic.

OBJECTIVE: To explore the influences of digital media use on the core symptoms, emotional state, life events, learning motivation, executive function (EF) and family environment of children and adolescents diagnosed with attention deficit hyperactivity disorder (ADHD) during the novel coronavirus disease 2019 (COVID-19) pandemic. METHOD: A total of 192 participants aged 8-16 years who met the diagnostic criteria for ADHD were included in the study. Children scoring higher than predetermined cut-off point in self-rating questionnaires for problematic mobile phone use (SQPMPU) or Young's internet addiction test (IAT), were defined as ADHD with problematic digital media use (PDMU), otherwise were defined as ADHD without PDMU. The differences between the two groups in ADHD symptoms, EF, anxiety and depression, stress from life events, learning motivation and family environment were compared respectively. RESULTS: When compared with ADHD group without PDMU, the group with PDMU showed significant worse symptoms of inattention, oppositional defiant, behavior and emotional problems by Swanson, Nolan, and Pelham Rating Scale (SNAP), more self-reported anxiety by screening child anxiety-related emotional disorders (SCARED) and depression by depression self-rating scale for children (DSRSC), more severe EF deficits by behavior rating scale of executive function (BRIEF), more stress from life events by adolescent self-rating life events checklist (ASLEC), lower learning motivation by students learning motivation scale (SLMS), and more impairment on cohesion by Chinese version of family environment scale (FES-CV). The ADHD with PDMU group spent significantly more time on both video game and social media with significantly less time spend on physical exercise as compared to the ADHD without PDMU group. CONCLUSION: The ADHD children with PDMU suffered from more severe core symptoms, negative emotions, EF deficits, damage on family environment, pressure from life events, and a lower motivation to learn. Supervision of digital media usage, especially video game and social media, along with increased physical exercise, is essential to the management of core symptoms and associated problems encountered with ADHD.

The concurrent disturbance of dynamic functional and structural brain connectome in major depressive disorder: the prefronto-insular pathway.

BACKGROUND: Robust evidence has shown that abnormal function networks, particularly the salience network (SN), are observed in depressed patients. Although white matter structural connectivity may predict time-varying functional connectivity, including symptom phenotype, in psychiatric disorders, there is still a gap in elucidating the concurrent dynamic functional and structural connectivity profiles of the SN in depressed patients. METHODS: We measured static and dynamic functional connectivity (FC) of the SN using resting-state fMRI BOLD time series in 76 subjects (21 with major depressive disorder (MDD), 27 with bipolar depression (BD), and 28 healthy controls (HC)). Hamilton Depression Scale total score was used to measure depression severity. Furthermore, we investigated the concurrent structural connectivity using diffusion kurtosis imaging (DKI)-based tractography. RESULTS: Our findings suggested that in the presence of MDD, both structural and dynamic (but not static) FC were reduced in the SN, particularly affecting the left prefronto-insular pathways (L.aPFC-L.insula). MDD patients showed decreased connectivity variability within the SN compared with HC. The aberrant dynamic FC in the prefronto-insular pathways of the SN related to severity of depressive symptoms in MDD. Furthermore, compared with BD patients, those with MDD showed significantly decreased dynamic FC in the left prefronto-parietal system (L.aPFC-lateral parietal cortex). LIMITATIONS: The generalizability of our findings is, to some extent, constrained by the small sample size. CONCLUSIONS: The integrity of SN connectivity, particularly the prefronto-insular pathway, appears to be a crucial signature of MDD. The perturbed dynamic interaction of SN with prefrontal regions may underlie the clinical severity in depressed patients.

The Insular Subregions Topological Characteristics of Patients With Bipolar Depressive Disorder.

The insular cortex appears to have a crucial role in emotional processing and cognitive control in bipolar disorder (BD). However, most previous studies focused on the entire insular region of BD, neglecting the topological profile of its subregions. Our study aimed to investigate its subregion topological characteristics using the resting-state functional connectivity (rsFC) in patients with BD on depression episode. The magnetic resonance imaging (MRI) data of 28 depressed BD patients and 28 age- and gender-matched healthy controls (HCs) were acquired. We observed that compared to HCs, depressed patients with BD exhibited significantly decreased rsFC between the right ventral anterior insula (vAI) and the left middle temporal gyrus/the right angular, the right dorsal anterior insula (dAI) and the left precuneus, as well as the right posterior insula and the right lingual gyrus. Furthermore, hyperconnectivity was observed between the left dAI and the left medial frontal gyrus, as well as right dAI and left superior temporal gyrus in BD depression. However, no significant group effect was observed between aberrant FC patterns and clinical variables. These findings revealed the functional connectivity patterns of insular subregions for the depressed BD patients, suggesting the potential neural substrate of insular subregions involved in depressive episode of BD. Hence, these results may provide a neural substrate for the potential treatment target of BD on depression episode.

The preattentive change detection in preschool children with attention deficit hyperactivity disorder: a mismatch negativity study.

To investigate the preattentive change detection in preschool children with attention deficit hyperactivity disorder (ADHD), we compared the mismatch negativity (MMN) and P3a of event-related potentials (ERPs) between preschool ADHD and normal children using three-stimulus oddball paradigm. Analyzing MMN and P3a components, we found that MMN elicited by deviants and P3a elicited by novelty were significantly reduced in patients than in controls. In addition, the P3a amplitude was positive correlated to IQ and negatively correlated to hyperactivity, antagonistic defiance and conduct problems in Swanson, Nolan, and Pelham IV Rating Scale, parent version. These data provided new neurophysiological evidence for the dysfunction of preattentive change detection and attentional shift in ADHD children.

Intrinsic gray-matter connectivity of the brain in major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) has been assumed to be associated with aberrant brain connectivity. However, research suggests that brain connectivity abnormalities should not be restricted to extrinsic white matter connectivity, but may also impact on intrinsic gray matter connectivity. Therefore, our study aimed to investigate the intrinsic gray-matter connectivity in MDD. METHODS: The participants were 16 first-episode, drug-naïve patients with MDD and 16 healthy controls matched on age and gender. All participants were scanned by 3.0T structural magnetic resonance imaging. Global and local intrinsic gray-matter connectivity were measured based on surface-based geodesic distances, including mean coritical separation distances (MSDs), perimeter function, and radius function. RESULTS: MDD patients had significantly lower MSDs in the left postcentral gyrus and higher MSDs in the left superior parietal cortex. Marginally significant correlation was observed between MSDs in the left postcentral gyrus and symptoms of depression. Compared with healthy controls, depressed subjects had abnormal local intrinsic gray-matter connectivity in the left postcentral gyrus, the left transverse temporal gyrus, the right lingual gyrus, the right lateral occipital cortex, and the right superior frontal gyrus. Furthermore, local intrinsic gray matter connections of these brain areas were associated with some symptoms of depression. LIMITATIONS: The small sample size limited the interpretability of our potential conclusions. CONCLUSION: Aberrant intrinsic gray-matter connectivity was observed in depressed subjects, indicating abnormal intrinsic wiring cost of brain architecture. This might help explain the aberrant topological properties of brain functional connectivity and provide insights into the vulnerability of MDD.

Aberrant Neural Activity in Patients With Bipolar Depressive Disorder Distinguishing to the Unipolar Depressive Disorder: A Resting-State Functional Magnetic Resonance Imaging Study.

This study aims to explore the intrinsic patterns of spontaneous activity of bipolar depression (BD) patients by analyzing the fractional amplitude of low frequency fluctuation (fALFF) that help differentiate BD from unipolar depressive disorder(UD). Twenty eight patients with BD, 47 patients with UD and 29 healthy controls were enrolled to receive the resting-state functional magnetic resonance imaging (rs-fMRI) scans. The group differences of fALFF values were calculated among three groups. In addition, the correlations between the clinical variables and mfALFF values were estimated. The brain regions with activation discrepancies among three groups are located in precuneus, the left middle temporal gyrus (MTG) and left inferior parietal lobe (IPL) and lingual gyrus. Compared with HC group, BD group shows decreased fALFF in precuneus, the left IPL and increased fALFF in lingual gyrus remarkably; UD group shows significantly decreased fALFF in precuneus, the left MTG and the left IPL. On the contrast of patients with UD, patients with BD have significantly increased fALFF value in the left precuneus, the left MGT and lingual gyrus. Furthermore, a negative correlation is found between the mfALFF values in precuneus and the scores of cognitive impairment factor in the UD group. The similar pattern of intrinsic activity in PCC suggests depressive state-dependent change. The aberrant patterns of intrinsic activity in precuneus, the IPL and lingual gyrus might be provide quantitative nodes that help to conduct further study for better distinguishing between BD and UD.

Increased cognition connectivity network in major depression disorder: a FMRI study.

OBJECTIVE: Evidence of the brain network involved in cognitive dysfunction has been inconsistent for major depressive disorder (MDD), especially during early stage of MDD. This study seeks to examine abnormal cognition connectivity network (CCN) in MDD within the whole brain. METHODS: Sixteen patients with MDD and 16 health controls were scanned during resting-state using 3.0 T functional magnetic resonance imaging (fMRI). All patients were first episode without any history of antidepressant treatment. Both the left and right dorsolateral prefrontal cortex (DLPFC) were used as individual seeds to identify CCN by the seed-target correlation analysis. Two sample t test was used to calculate between-group differences in CCN using fisher z-transformed correlation maps. RESULTS: The CCN was constructed by bilateral seed DLPFC in two groups separately. Depressed subjects exhibited significantly increased functional connectivity (FC) by left DLPFC in one cluster, overlapping middle frontal gyrus, BA7, BA43, precuneus, BA6, BA40, superior temporal gyrus, BA22, inferior parietal lobule, precentral gyrus, BA4 and cingulate gyrus in left cerebrum. Health controls did not show any cluster with significantly greater FC compared to depressed subjects in left DLPFC network. There was no significant difference of FC in right DLPFC network between depressed subjects and the health controls. CONCLUSION: There are differences in CCN during early stage of MDD, as identified by increased FCs among part of frontal gyrus, parietal cortex, cingulate cortex, and BA43, BA22, BA4 with left DLPFC. These brain areas might be involved in the underlying mechanisms of cognitive dysfunction in MDD.

Surface vulnerability of cerebral cortex to major depressive disorder.

Major depressive disorder (MDD) is accompanied by atypical brain structure. This study first presents the alterations in the cortical surface of patients with MDD using multidimensional structural patterns that reflect different neurodevelopment. Sixteen first-episode, untreated patients with MDD and 16 matched healthy controls underwent a magnetic resonance imaging (MRI) scan. The cortical maps of thickness, surface area, and gyrification were examined using the surface-based morphometry (SBM) approach. Increase of cortical thickness was observed in the right posterior cingulate region and the parietal cortex involving the bilateral inferior, left superior parietal and right paracentral regions, while decreased thickness was noted in the parietal cortex including bilateral pars opercularis and left precentral region, as well as the left rostral-middle frontal regions in patients with MDD. Likewise, increased or decreased surface area was found in five sub-regions of the cingulate gyrus, parietal and frontal cortices (e.g., bilateral inferior parietal and superior frontal regions). In addition, MDD patients exhibited a significant hypergyrification in the right precentral and supramarginal region. This integrated structural assessment of cortical surface suggests that MDD patients have cortical alterations of the frontal, parietal and cingulate regions, indicating a vulnerability to MDD during earlier neurodevelopmental process.

Altered spontaneous neural activity in first-episode, unmedicated patients with major depressive disorder.

Abnormal brain function is presumed to be a pathophysiological aspect of major depressive disorder (MDD). However, the underlying patterns of spontaneous neural activity have been poorly characterized and replicated to date. In this study, we applied a novel approach of fractional amplitude of low-frequency fluctuation (fALFF) to investigate the alteration of spontaneous neural activity in MDD. Sixteen first-episode, unmedicated patients with MDD and 16 healthy controls were recruited and subjected to resting-state fMRI scans to measure the fALFF across the whole brain. Compared with healthy controls, MDD patients exhibited decreased fALFF in the right angular gyrus, left middle temporal gyrus, left superior temporal gyrus, right putamen, right precuneus, and the right superior temporal gyrus. Differences in fALFF between MDD patients and controls indicated that altered spontaneous neural activity was distributed across a number of specific brain regions among MDD patients. These atypical functional regions may help explain some of the neural processes underlying the clinical symptoms accompanying MDD.

Altered brain network modules induce helplessness in major depressive disorder.

OBJECTIVE: The abnormal brain functional connectivity (FC) has been assumed to be a pathophysiological aspect of major depressive disorder (MDD). However, it is poorly understood, regarding the underlying patterns of global FC network and their relationships with the clinical characteristics of MDD. METHODS: Resting-state functional magnetic resonance imaging data were acquired from 16 first episode, medication-naïve MDD patients and 16 healthy control subjects. The global FC network was constructed using 90 brain regions. The global topological patterns, e.g., small-worldness and modularity, and their relationships with depressive characteristics were investigated. Furthermore, the participant coefficient and module degree of MDD patients were measured to reflect the regional roles in module network, and the impairment of FC was examined by network based statistic. RESULTS: Small-world property was not altered in MDD. However, MDD patients exhibited 5 atypically reorganized modules compared to the controls. A positive relationship was also found among MDD patients between the intra-module I and helplessness factor evaluated via the Hamilton Depression Scale. Specifically, eight regions exhibited the abnormal participant coefficient or module degree, e.g., left superior orbital frontal cortex and right amygdala. The decreased FC was identified among the sub-network of 24 brain regions, e.g., frontal cortex, supplementary motor area, amygdala, thalamus, and hippocampus. LIMITATION: The limited size of MDD samples precluded meaningful study of distinct clinical characteristics in relation to aberrant FC. CONCLUSIONS: The results revealed altered patterns of brain module network at the global level in MDD patients, which might contribute to the feelings of helplessness.