Investigation of Brain Functional Networks in Children Suffering from Attention Deficit Hyperactivity Disorder.

ADHD defects the recognition of facial emotions. This study assesses the neurophysiological differences between children with ADHD and matched healthy controls during a face emotional recognition task. The study also explores how brain connectivity is affected by ADHD. Electroencephalogram (EEG) signals were recorded from 64 scalp electrodes. Event-related phase coherence (ERPCOH) method was applied to pre-processed signals, and functional connectivity between any pair of electrodes was computed in different frequency bands. A logistic regression (LR) classifier with elastic net regularization (ENR) was trained to classify ADHD and HC participants using the functional connectivity of frequency bands as a potential biomarker. Subsequently, the brain network is constructed using graph-theoretic techniques, and graph indices such as clustering coefficient (C) and shortest path length (L) were calculated. Significant intra-hemispheric and the inter-hemispheric discrepancy between ADHD and healthy control (HC) groups in the beta band was observed. The graph features indicate that the clustering coefficient is significantly higher in the ADHD group than that in the HC group. At the same time, the shortest path length is significantly lower in the beta band. ADHD's brain networks have a problem in transferring information among various neural regions, which can cause a deficiency in the processing of facial emotions. The beta band seems better to reflect the differences between ADHD and HC. The observed functional connectivity and graph differences could also be helpful in ADHD investigations.

The overlap across psychotic disorders: A functional network connectivity analysis.

Functional network connectivity (FNC) has previously been shown to distinguish patient groups from healthy controls (HC). However, the overlap across psychiatric disorders such as schizophrenia (SZ), bipolar (BP), and schizoaffective disorder (SAD) is not evident yet. This study focuses on studying the overlap across these three psychotic disorders in both dynamic and static FNC (dFNC/sFNC). We used resting-state fMRI, demographics, and clinical information from the Bipolar-Schizophrenia Network on Intermediate Phenotypes cohort (BSNIP). The data includes three groups of patients with schizophrenia (SZ, N = 181), bipolar (BP, N = 163), and schizoaffective (SAD, N = 130) and HC (N = 238) groups. After estimating each individual's dFNC, we group them into three distinct states. We evaluated two dFNC features, including occupancy rate (OCR) and distance travelled over time. Finally, the extracted features, including both sFNC and dFNC, are tested statistically across patients and HC groups. In addition, we explored the link between the clinical scores and the extracted features. We evaluated the connectivity patterns and their overlap among SZ, BP, and SAD disorders (false discovery rate or FDR corrected p < 0.05). Results showed dFNC captured unique information about overlap across disorders where all disorder groups showed similar pattern of activity in state 2. Moreover, the results showed similar patterns between SZ and SAD in state 1 which was different than BP. Finally, the distance travelled feature of SZ (average R = 0.245, p < 0.01) and combined distance travelled from all disorders was predictive of the PANSS symptoms scores (average R = 0.147, p < 0.01).

Uncovering Effects of Schizophrenia upon a Maximally Significant, Minimally Complex Subset of Default Mode Network Connectivity Features.

A common analysis approach for resting state functional magnetic resonance imaging (rs-fMRI) dynamic functional network connectivity (dFNC) data involves clustering windowed correlation time-series and assigning time windows to clusters (i.e., states) that can be quantified to summarize aspects of the dFNC dynamics. However, those methods can be dominated by a select few features and obscure key dynamics related to less dominant features. This study presents an iterative feature learning approach to identify a maximally significant and minimally complex subset of dFNC features within the default mode network (DMN) in schizophrenia (SZ). Utilizing dFNC data from individuals with SZ and healthy controls (HC), our approach uncovers a subset of features that has a greater number of dFNC states with disorder-related dynamics than is found when all features are present in the clustering. We find that anterior cingulate cortex/posterior cingulate cortex (ACC/PCC) interactions are consistently related to SZ across the most significant iterations of the feature learning analysis and that individuals with SZ tend to spend more time in states with greater intra-ACC anticorrelation and almost no time in a state of high intra-ACC correlation that HCs periodically enter. Our findings highlight the need for nuanced analyses to reveal disorder-related dynamics and advance our understanding of neuropsychiatric disorders.

Towards a multimodal neuroimaging-based risk score for mild cognitive impairment by combining clinical studies with a large (N>37000) population-based study.

Alzheimer's disease (AD) is the most common form of age-related dementia, leading to a decline in memory, reasoning, and social skills. While numerous studies have investigated the genetic risk factors associated with AD, less attention has been given to identifying a brain imaging-based measure of AD risk. This study introduces a novel approach to assess mild cognitive impairment MCI, as a stage before AD, risk using neuroimaging data, referred to as a brain-wide risk score (BRS), which incorporates multimodal brain imaging. To begin, we first categorized participants from the Open Access Series of Imaging Studies (OASIS)-3 cohort into two groups: controls (CN) and individuals with MCI. Next, we computed structure and functional imaging features from all the OASIS data as well as all the UK Biobank data. For resting functional magnetic resonance imaging (fMRI) data, we computed functional network connectivity (FNC) matrices using fully automated spatially constrained independent component analysis. For structural MRI data we computed gray matter (GM) segmentation maps. We then evaluated the similarity between each participant's neuroimaging features from the UK Biobank and the difference in the average of those features between CN individuals and those with MCI, which we refer to as the brain-wide risk score (BRS). Both GM and FNC features were utilized in determining the BRS. We first evaluated the differences in the distribution of the BRS for CN vs MCI within the OASIS-3 (using OASIS-3 as the reference group). Next, we evaluated the BRS in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort (using OASIS-3 as the reference group), showing that the BRS can differentiate MCI from CN in an independent data set. Subsequently, using the sMRI BRS, we identified 10 distinct subgroups and similarly, we identified another set of 10 subgroups using the FNC BRS. For sMRI and FNC we observed results that mutually validate each other, with certain aspects being complementary. For the unimodal analysis, sMRI provides greater differentiation between MCI and CN individuals than the fMRI data, consistent with prior work. Additionally, by utilizing a multimodal BRS approach, which combines both GM and FNC assessments, we identified two groups of subjects using the multimodal BRS scores. One group exhibits high MCI risk with both negative GM and FNC BRS, while the other shows low MCI risk with both positive GM and FNC BRS. Moreover, in the UKBB we have 46 participants diagnosed with AD showed FNC and GM patterns similar to those in high-risk groups, defined in both unimodal and multimodal BRS. Finally, to ensure the reproducibility of our findings, we conducted a validation analysis using the ADNI as an additional reference dataset and repeated the above analysis. The results were consistently replicated across different reference groups, highlighting the potential of FNC and sMRI-based BRS in early Alzheimer's detection.

Systems biology dissection of PTSD and MDD across brain regions, cell types, and blood.

The molecular pathology of stress-related disorders remains elusive. Our brain multiregion, multiomic study of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) included the central nucleus of the amygdala, hippocampal dentate gyrus, and medial prefrontal cortex (mPFC). Genes and exons within the mPFC carried most disease signals replicated across two independent cohorts. Pathways pointed to immune function, neuronal and synaptic regulation, and stress hormones. Multiomic factor and gene network analyses provided the underlying genomic structure. Single nucleus RNA sequencing in dorsolateral PFC revealed dysregulated (stress-related) signals in neuronal and non-neuronal cell types. Analyses of brain-blood intersections in >50,000 UK Biobank participants were conducted along with fine-mapping of the results of PTSD and MDD genome-wide association studies to distinguish risk from disease processes. Our data suggest shared and distinct molecular pathology in both disorders and propose potential therapeutic targets and biomarkers.

Towards a multimodal neuroimaging-based risk score for Alzheimer's disease by combining clinical and large N>37000 population data.

Alzheimer's disease (AD) is the most prevalent age-related dementia and causes memory, reasoning, and social skills to deteriorate. In recent years many studies have explored the genetic risk of AD, but less work has been done to identify a brain imaging-based AD risk measure. The current study proposed a new neuroimaging-based measure of AD risk, called brain-wide risk score or BRS, based on multimodal brain features. Using the proposed AD BRS, we identified four AD biotypes from a large sample of subjects (N>37,000) from the UK Biobank dataset: one with high AD BRS, one with low AD BRS, and two with moderate AD BRS. Next, we further showed that the cognitive scores of the biotype with lower AD BRS are significantly better than those of other biotypes.

Disrupted Dynamic Functional Network Connectivity Among Cognitive Control Networks in the Progression of Alzheimer's Disease.

Background: Alzheimer's disease (AD) is the most common age-related dementia that promotes a decline in memory, thinking, and social skills. The initial stages of dementia can be associated with mild symptoms, and symptom progression to a more severe state is heterogeneous across patients. Recent work has demonstrated the potential for functional network mapping to assist in the prediction of symptomatic progression. However, this work has primarily used static functional connectivity (sFC) from resting-state functional magnetic resonance imaging. Recently, dynamic functional connectivity (dFC) has been recognized as a powerful advance in functional connectivity methodology to differentiate brain network dynamics between healthy and diseased populations. Methods: Group independent component analysis was applied to extract 17 components within the cognitive control network (CCN) from 1385 individuals across varying stages of AD symptomology. We estimated dFC among 17 components within the CCN, followed by clustering the dFCs into 3 recurring brain states, and then estimated a hidden Markov model and the occupancy rate for each subject. Then, we investigated the link between CCN dFC features and AD progression. Also, we investigated the link between sFC and AD progression and compared its results with dFC results. Results: Progression of AD symptoms was associated with increases in connectivity within the middle frontal gyrus. Also, the very mild AD (vmAD) showed less connectivity within the inferior parietal lobule (in both sFC and dFC) and between this region and the rest of CCN (in dFC analysis). Also, we found that within-middle frontal gyrus connectivity increases with AD progression in both sFC and dFC results. Finally, comparing with vmAD, we found that the normal brain spends significantly more time in a state with lower within-middle frontal gyrus connectivity and higher connectivity between the hippocampus and the rest of CCN, highlighting the importance of assessing the dynamics of brain connectivity in this disease. Conclusion: Our results suggest that AD progress not only alters the CCN connectivity strength but also changes the temporal properties in this brain network. This suggests the temporal and spatial pattern of CCN as a biomarker that differentiates different stages of AD.

Cerebro-cerebellar functional neuroplasticity mediates the effect of electric field on electroconvulsive therapy outcomes.

Electroconvulsive therapy (ECT) is the most effective treatment for severe depression and works by applying an electric current through the brain. The applied current generates an electric field (E-field) and seizure activity, changing the brain's functional organization. The E-field, which is determined by electrode placement (right unilateral or bitemporal) and pulse amplitude (600, 700, or 800 milliamperes), is associated with the ECT response. However, the neural mechanisms underlying the relationship between E-field, functional brain changes, and clinical outcomes of ECT are not well understood. Here, we investigated the relationships between whole-brain E-field (Ebrain, the 90th percentile of E-field magnitude in the brain), cerebro-cerebellar functional network connectivity (FNC), and clinical outcomes (cognitive performance and depression severity). A fully automated independent component analysis framework determined the FNC between the cerebro-cerebellar networks. We found a linear relationship between Ebrain and cognitive outcomes. The mediation analysis showed that the cerebellum to middle occipital gyrus (MOG)/posterior cingulate cortex (PCC) FNC mediated the effects of Ebrain on cognitive performance. In addition, there is a mediation effect through the cerebellum to parietal lobule FNC between Ebrain and antidepressant outcomes. The pair-wise t-tests further demonstrated that a larger Ebrain was associated with increased FNC between cerebellum and MOG and decreased FNC between cerebellum and PCC, which were linked with decreased cognitive performance. This study implies that an optimal E-field balancing the antidepressant and cognitive outcomes should be considered in relation to cerebro-cerebellar functional neuroplasticity.

Novel methods for elucidating modality importance in multimodal electrophysiology classifiers.

Introduction: Multimodal classification is increasingly common in electrophysiology studies. Many studies use deep learning classifiers with raw time-series data, which makes explainability difficult, and has resulted in relatively few studies applying explainability methods. This is concerning because explainability is vital to the development and implementation of clinical classifiers. As such, new multimodal explainability methods are needed. Methods: In this study, we train a convolutional neural network for automated sleep stage classification with electroencephalogram (EEG), electrooculogram, and electromyogram data. We then present a global explainability approach that is uniquely adapted for electrophysiology analysis and compare it to an existing approach. We present the first two local multimodal explainability approaches. We look for subject-level differences in the local explanations that are obscured by global methods and look for relationships between the explanations and clinical and demographic variables in a novel analysis. Results: We find a high level of agreement between methods. We find that EEG is globally the most important modality for most sleep stages and that subject-level differences in importance arise in local explanations that are not captured in global explanations. We further show that sex, followed by medication and age, had significant effects upon the patterns learned by the classifier. Discussion: Our novel methods enhance explainability for the growing field of multimodal electrophysiology classification, provide avenues for the advancement of personalized medicine, yield unique insights into the effects of demographic and clinical variables upon classifiers, and help pave the way for the implementation of multimodal electrophysiology clinical classifiers.

The link between static and dynamic brain functional network connectivity and genetic risk of Alzheimer's disease.

Apolipoprotein E (APOE) polymorphic alleles are genetic factors associated with Alzheimer's disease (AD) risk. Although previous studies have explored the link between AD genetic risk and static functional network connectivity (sFNC), to the best of our knowledge, no previous studies have evaluated the association between dynamic FNC (dFNC) and AD genetic risk. Here, we examined the link between sFNC, dFNC, and AD genetic risk with a data-driven approach. We used rs-fMRI, demographic, and APOE data from cognitively normal individuals (N = 886) between 42 and 95 years of age (mean = 70 years). We separated individuals into low, moderate, and high-risk groups. Using Pearson correlation, we calculated sFNC across seven brain networks. We also calculated dFNC with a sliding window and Pearson correlation. The dFNC windows were partitioned into three distinct states with k-means clustering. Next, we calculated the proportion of time each subject spent in each state, called occupancy rate or OCR and frequency of visits. We compared both sFNC and dFNC features across individuals with different genetic risks and found that both sFNC and dFNC are related to AD genetic risk. We found that higher AD risk reduces within-visual sensory network (VSN) sFNC and that individuals with higher AD risk spend more time in a state with lower within-VSN dFNC. We also found that AD genetic risk affects whole-brain sFNC and dFNC in women but not men. In conclusion, we presented novel insights into the links between sFNC, dFNC, and AD genetic risk.

Two-step clustering-based pipeline for big dynamic functional network connectivity data.

Background: Dynamic functional network connectivity (dFNC) estimated from resting-state functional magnetic imaging (rs-fMRI) studies the temporally varying functional integration between brain networks. In a conventional dFNC pipeline, a clustering stage to summarize the connectivity patterns that are transiently but reliably realized over the course of a scanning session. However, identifying the right number of clusters (or states) through a conventional clustering criterion computed by running the algorithm repeatedly over a large range of cluster numbers is time-consuming and requires substantial computational power even for typical dFNC datasets, and the computational demands become prohibitive as datasets become larger and scans longer. Here we developed a new dFNC pipeline based on a two-step clustering approach to analyze large dFNC data without having access to huge computational power. Methods: In the proposed dFNC pipeline, we implement two-step clustering. In the first step, we randomly use a sub-sample dFNC data and identify several sets of states at different model orders. In the second step, we aggregate all dFNC states estimated from all iterations in the first step and use this to identify the optimum number of clusters using the elbow criteria. Additionally, we use this new reduced dataset and estimate a final set of states by performing a second kmeans clustering on the aggregated dFNC states from the first k-means clustering. To validate the reproducibility of results in the new pipeline, we analyzed four dFNC datasets from the human connectome project (HCP). Results: We found that both conventional and proposed dFNC pipelines generate similar brain dFNC states across all four sessions with more than 99% similarity. We found that the conventional dFNC pipeline evaluates the clustering order and finds the final dFNC state in 275 min, while this process takes only 11 min for the proposed dFNC pipeline. In other words, the new pipeline is 25 times faster than the traditional method in finding the optimum number of clusters and finding the final dFNC states. We also found that the new method results in better clustering quality than the conventional approach (p < 0.001). We show that the results are replicated across four different datasets from HCP. Conclusion: We developed a new analytic pipeline that facilitates the analysis of large dFNC datasets without having access to a huge computational power source. We validated the reproducibility of the result across multiple datasets.

Default mode network dynamic functional network connectivity predicts psychotic symptom severity.

Neuropsychiatric disorders affect millions of people worldwide every year. Recent studies showed that the symptomatic overlaps across neuropsychiatric disorders mislead schizophrenia and bipolar disorder diagnosis. Additionally, recent studies claimed that schizoaffective disorder as a condition overlapped with both schizophrenia and bipolar disorder. Since symptomatic overlap among these disorders causes misdiagnosis, a need for neuroimaging biomarkers differentiating these disorders for a more accurate diagnosis is crucial. This study investigates dynamics functional network connectivity (dFNC) in the default mode network (DMN) of schizophrenia, bipolar, and schizoaffective disorder patients and compares them with their relative and healthy control. Additionally, it explored whether DMN dFNC features can predict the symptom severity of these neuropsychiatric disorders. Here, we found that dFNC features can differentiate schizophrenia from bipolar disorder. At the same time, we did not see a significant difference between schizoaffective with other conditions. Additionally, we found dFNC features can predict symptom severity of these three conditions.

A two-step clustering-based pipeline for big dynamic functional network connectivity data.

Dynamic functional network connectivity (dFNC) estimated from resting-state functional magnetic imaging (rs-fMRI) studies the temporal properties of FNC among brain networks by putting them into distinct states using the clustering method. The computational cost of clustering dFNCs has become a significant practical barrier given the availability of enormous neuroimaging datasets. To this end, we developed a new dFNC pipeline to analyze large dFNC data without accessing hug processing capacity. We validated our proposed pipeline and compared it with the standard one using a publicly available dataset. We found that both standard and iSparse kmeans generate similar dFNC states while our approach is 27 times faster than the traditional method in finding the optimum number of clusters and creating better clustering quality.

An Unsupervised Feature Learning Approach for Elucidating Hidden Dynamics in rs-fMRI Functional Network Connectivity.

Dynamic functional network connectivity (dFNC) data extracted from resting state functional magnetic resonance imaging (rs-fMRI) recordings has played a significant role in characterizing the role that brain network interactions play in a variety of brain disorders and cognitive functions. dFNC analyses frequently use clustering methods to identify states of network activity. However, it is possible that these states are dominated by a few highly influential networks or nodes, which could obscure condition-related insights that might be gained from networks or nodes less influential to the clustering. In this study, we propose a novel feature learning-based approach that could contribute to the identification of condition-related activity in formerly less influential networks or nodes. We demonstrate the viability of our approach within the context of schizophrenia (SZ), applying our approach to a dataset consisting of 151 participants with SZ and 160 controls (HCs). We find that the removal of some connectivity pairs significantly affects the underlying states and magnifies the differences between participants with SZ and HCs in each state. Given our findings, we hope that our approach will contribute to the characterization and improved diagnosis of a variety of neurological conditions and functions. Clinical Relevance- Our approach could contribute to the characterization and diagnosis of many neurological conditions.

Whole-Brain Functional Connectivity Dynamics Associated With Electroconvulsive Therapy Treatment Response.

BACKGROUND: Depressive episodes (DEPs), characterized by abnormalities in cognitive functions and mood, are a leading cause of disability. Electroconvulsive therapy (ECT), which involves a brief electrical stimulation of the anesthetized brain, is one of the most effective treatments used in patients with DEP due to its rapid efficacy. METHODS: In this work, we investigated how dynamic brain functional connectivity responds to ECT and whether the dynamic responses are associated with treatment outcomes and side effects in patients. We applied a fully automated independent component analysis-based pipeline to 110 patients with DEP (including diagnosis of unipolar depression or bipolar depression) and 60 healthy control subjects. The dynamic functional connectivity was analyzed by a combination of the sliding window approach and clustering analysis. RESULTS: Five recurring connectivity states were identified, and patients with DEPs had fewer occurrences in one brain state (state 1) with strong positive and negative connectivity. Patients with DEP changed the occupancy of two states (states 3 and 4) after ECT, resulting in significantly different occurrences of one additional state (state 3) compared with healthy control subjects. We further found that patients with DEP had diminished global metastate dynamism, two of which recovered to normal after ECT. The changes in dynamic connectivity characteristics were associated with the changes in memory recall and Hamilton Depression Rating Scale of DEP after ECT. CONCLUSIONS: These converging results extend current findings on subcortical-cortical dysfunction and dysrhythmia in DEP and demonstrate that ECT might cause remodeling of brain functional dynamics that enhance the neuroplasticity of the diseased brain.

Brain age gap difference between healthy and mild dementia subjects: Functional network connectivity analysis.

Brain age gap, the difference between an individual's brain predicted age and their chronological age, is used as a biomarker of brain disease and aging. To date, although previous studies used structural magnetic resonance imaging (MRI) data to predict brain age, less work has used functional network connectivity (FNC) estimated from functional MRI to predict brain age and its association with Alzheimer's disease progression. This study used FNC estimated from 951 normal cognitive functions (NCF) individuals aged 42-95 years to train a support vector regression (SVR) to predict brain age. In the next step, we tested the trained model on two unseen datasets, including NCF and mild dementia (MD) subjects with similar age distribution (between 50-80 years old, N=70). The mean brain age gap for the NCF and MD groups was -2.25 and 2.08, respectively. We also found a significant difference between the brain age gap of NCF and MD groups. This piece of evidence introduces the brain age gap estimated from FNC as a biomarker of Alzheimer's disease progression.

Dynamic patterns within the default mode network in schizophrenia subgroups.

In this study, resting-state functional magnetic resonance imaging (rs-fMRI) data of 125 schizophrenia (SZ) subjects were analyzed. Based on SZ demographic information and cognitive scores and using an unsupervised clustering method, we identified subgroups of patients and compared DMN dynamic functional connectivity (dFC) between the groups. We captured seven independent subnodes, including anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and precuneus (PCu), in the DMN by applying group independent component analysis (group-ICA) and estimated dFC between component time courses using a sliding window approach. By using k-means clustering, we separated the dFCs into three reoccurring brain states. Using the statistical method, we compared the state-specific DMN connectivity pattern between two SZ subgroups. In addition, we used a transition probability matrix of a hidden Markov model (HMM) and occupancy rate (OCR) of each state between two SZ subgroups. We found SZ subjects with higher positive and negative syndrome scale (PNASS) showed lower within ACC and lower ACC and PCC connectivity (or ACC/PCC). In addition, we found the transition from state1 to same state is significantly different between two groups, while this result was not significant after multiple comparison tests.

Multiple overlapping dynamic patterns of the visual sensory network in schizophrenia.

Although visual processing impairments have been explored in schizophrenia (SZ), their underlying neurobiology of the visual processing impairments has not been widely studied. Also, while some research has hinted at differences in information transfer and flow in SZ, there are few investigations of the dynamics of functional connectivity within visual networks. In this study, we analyzed resting-state fMRI data of the visual sensory network (VSN) in 160 healthy control (HC) subjects and 151 SZ subjects. We estimated 9 independent components within the VSN. Then, we calculated the dynamic functional network connectivity (dFNC) using the Pearson correlation. Next, using k-means clustering, we partitioned the dFNCs into five distinct states, and then we calculated the portion of time each subject spent in each state, which we termed the occupancy rate (OCR). Using OCR, we compared HC with SZ subjects and investigated the link between OCR and visual learning in SZ subjects. Besides, we compared the VSN functional connectivity of SZ and HC subjects in each state. We found that this network is indeed highly dynamic. Each state represents a unique connectivity pattern of fluctuations in VSN FNC, and all states showed significant disruption in SZ. Overall, HC showed stronger connectivity within the VSN in states. SZ subjects spent more time in a state in which the connectivity between the middle temporal gyrus and other regions of VNS is highly negative. Besides, OCR in a state with strong positive connectivity between the middle temporal gyrus and other regions correlated significantly with visual learning scores in SZ.

Intraoperative neural signals predict rapid antidepressant effects of deep brain stimulation.

Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) is a promising intervention for treatment-resistant depression (TRD). Despite the failure of a clinical trial, multiple case series have described encouraging results, especially with the introduction of improved surgical protocols. Recent evidence further suggests that tractography targeting and intraoperative exposure to stimulation enhances early antidepressant effects that further evolve with ongoing chronic DBS. Accelerating treatment gains is critical to the care of this at-risk population, and identification of intraoperative electrophysiological biomarkers of early antidepressant effects will help guide future treatment protocols. Eight patients underwent intraoperative electrophysiological recording when bilateral DBS leads were implanted in the SCC using a connectomic approach at the site previously shown to optimize 6-month treatment outcomes. A machine learning classification method was used to discriminate between intracranial local field potentials (LFPs) recorded at baseline (stimulation-naïve) and after the first exposure to SCC DBS during surgical procedures. Spectral inputs (theta, 4-8 Hz; alpha, 9-12 Hz; beta, 13-30 Hz) to the model were then evaluated for importance to classifier success and tested as predictors of the antidepressant response. A decline in depression scores by 45.6% was observed after 1 week and this early antidepressant response correlated with a decrease in SCC LFP beta power, which most contributed to classifier success. Intraoperative exposure to therapeutic stimulation may result in an acute decrease in symptoms of depression following SCC DBS surgery. The correlation of symptom improvement with an intraoperative reduction in SCC beta power suggests this electrophysiological finding as a biomarker for treatment optimization.

Abnormal Dynamic Functional Network Connectivity Estimated from Default Mode Network Predicts Symptom Severity in Major Depressive Disorder.

Background: Major depressive disorder (MDD) is a severe mental illness marked by a continuous sense of sadness and a loss of interest. The default mode network (DMN) is a group of brain areas that are more active during rest and deactivate when engaged in task-oriented activities. The DMN of MDD has been found to have aberrant static functional network connectivity (FNC) in recent studies. In this work, we extend previous findings by evaluating dynamic functional network connectivity (dFNC) within the DMN subnodes in MDD. Methods: We analyzed resting-state functional magnetic resonance imaging data of 262 patients with MDD and 277 healthy controls (HCs). We estimated dFNCs for seven subnodes of the DMN, including the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and precuneus (PCu), using a sliding window approach, and then clustered the dFNCs into five brain states. Classification of MDD and HC subjects based on state-specific FC was performed using a logistic regression classifier. Transition probabilities between dFNC states were used to identify relationships between symptom severity and dFNC data in MDD patients. Results: By comparing state-specific FNC between HC and MDD, a disrupted connectivity pattern was observed within the DMN. In more detail, we found that the connectivity of ACC is stronger, and the connectivity between PCu and PCC is weaker in individuals with MDD than in those of HC subjects. In addition, MDD showed a higher probability of transitioning from a state with weaker ACC connectivity to a state with stronger ACC connectivity, and this abnormality is associated with symptom severity. This is the first research to look at the dFC of the DMN in MDD with a large sample size. It provides novel evidence of abnormal time-varying DMN configuration in MDD and offers links to symptom severity in MDD subjects. Impact Statement This study is the first attempt that explored the temporal change on default mode network (DMN) connectivity in a relatively large cohort of patients with major depressive disorder (MDD). We also introduced a new hypothesis that explains the inconsistency in DMN functional network connectivity (FNC) comparison between MDD and healthy control based on static FNC in the previous literature. Additionally, our findings suggest that within anterior cingulate cortex connectivity and the connectivity between the precuneus and posterior cingulate cortex are the potential biomarkers for the future intervention of MDD.