scholarly journals Mapping inter-individual functional connectivity variability in TMS targets for major depressive disorder

2021 ◽  
Author(s):  
Shreyas Harita ◽  
Davide Momi ◽  
Frank Mazza ◽  
John David Griffiths
Keyword(s):  
Major Depressive Disorder ◽  
Individual Differences ◽  
Functional Connectivity ◽  
Depressive Disorder ◽  
Brain Regions ◽  
Functional Networks ◽  
Major Depressive ◽  
Default Mode ◽  
Brain Physiology ◽  
Subject Variability

Transcranial magnetic stimulation (TMS) is an emerging alternative to existing treatments for major depressive disorder (MDD). The effects of TMS on both brain physiology and therapeutic outcomes are known to be highly variable from subject to subject, however. Proposed reasons for this variability include individual differences in neurophysiology, in cortical geometry, and in brain connectivity. Standard approaches to TMS target site definition tend to focus on coordinates or landmarks within the individual brain regions implicated in MDD, such as the dorsolateral prefrontal cortex (dlPFC) and orbitofrontal cortex (OFC). Additionally considering the network connectivity of these sites (i.e. the wider set of brain regions that may be mono- or poly-synaptically activated by TMS stimulation) has the potential to improve subject-specificity of TMS targeting and, in turn, improve treatment outcomes. In this study, we looked at the functional connectivity (FC) of dlPFC and OFC TMS targets, based on induced electrical field (E-field) maps, estimated using the SimNIBS library. We hypothesized that individual differences in spontaneous functional brain dynamics would contribute more to downstream network engagement than individual differences in cortical geometry (i.e., E-field variability). We generated individualized E-field maps on the cortical surface for 12 subjects (4 female) from the Human Connectome Project database using tetrahedral head models generated from T1-weighted MR images. F3 and Fp1 electrode positions were used to target the left dlPFC and left OFC, respectively. We analyzed inter-subject variability in the shape and location of these TMS target E-field patterns, their FC, and the major functional networks to which they belong. Our results revealed the key differences in TMS target FC between the dlPFC and OFC, and also how this connectivity varies across subjects. Three major functional networks were targeted across the dlPFC and OFC: the ventral attention, fronto-parietal and default-mode networks in the dlPFC, and the fronto-parietal and default mode networks in the OFC. Inter-subject variability in cortical geometry and in FC was high. Our analyses showed that use of normative neuroimaging reference data (group-average or representative FC and subject E-field) allow prediction of which networks are targeted, but fail to accurately quantify the relative loading of TMS targeting on each of the principal networks. Our results characterize the FC patterns of canonical therapeutic TMS targets, and the key dimensions of their variability across subjects. The high inter-individual variability in cortical geometry and FC, leading to high variability in distributions of targeted brain networks, may account for the high levels of variability in physiological and therapeutic TMS outcomes. These insights should, we hope, prove useful as part of the broader effort by the psychiatry, neurology, and neuroimaging communities to help improve and refine TMS therapy, through a better understanding of the technology and its neurophysiological effects.

scholarly journals Reduced Default Mode Network Functional Connectivity in Patients with Recurrent Major Depressive Disorder

2018 ◽  
Author(s):  
Chao-Gan Yan ◽  
Xiao Chen ◽  
Le Li ◽  
Francisco Xavier Castellanos ◽  
Tong-Jian Bai ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Functional Connectivity ◽  
Depressive Disorder ◽  
Default Mode Network ◽  
Resting State ◽  
Resting State Fmri ◽  
Research Groups ◽  
Major Depressive ◽  
Default Mode ◽  
Normal Controls

ABSTRACTMajor Depressive Disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol prior to aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. Finally, all resting-state fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.SIGNIFICANCE STATEMENTFunctional connectivity within the default mode network in major depressive disorder patients has been frequently reported abnormal but with contradicting directions in previous small sample size studies. In creating the REST-meta-MDD consortium containing neuroimaging data of 1,300 depressed patients and 1,128 normal controls from 25 research groups in China, we found decreased default mode network functional connectivity in depressed patients, driven by patients with recurrent depression, and associated with current medication treatment but not with disease duration. These findings suggest that default mode network functional connectivity remains a prime target for understanding the pathophysiology of depression, with particular relevance to revealing mechanisms of effective treatments.

scholarly journals Disruption of Neural Activity and Functional Connectivity in Adolescents With Major Depressive Disorder Who Engage in Non-suicidal Self-Injury: A Resting-State fMRI Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Qian Huang ◽  
Muni Xiao ◽  
Ming Ai ◽  
Jianmei Chen ◽  
Wo Wang ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Functional Connectivity ◽  
Depressive Disorder ◽  
Neural Activity ◽  
Resting State ◽  
Brain Regions ◽  
Major Depressive ◽  
Superior Frontal Gyrus ◽  
Self Injury ◽  
The Right

Background: Non-suicidal self-injury (NSSI), which commonly occurs during adolescence, often co-occurs with major depressive disorder (MDD). However, the underlying neurobiological mechanisms in adolescents with MDD who engage in NSSI remain unclear. The current study examined the aberrant local neural activity in certain areas of the visual regions and the default mode network (DMN) and the resting-state functional connectivity (rs-FC) in changed brain regions in adolescents with MDD who engage in NSSI and adolescents with MDD only.Methods: A total of 67 adolescents with MDD were divided into two groups based on their NSSI behavior: the NSSI group (n = 31) and an age-, gender-, and education-matched MDD group (n = 36). The Hamilton Depression Rating Scale (HAMD) was used to assess the severity of MDD. Amplitude of low-frequency fluctuation (ALFF) analysis was used to detect alterations in local neural activity. Brain regions with aberrant neural activity were considered regions of interest (ROI). ALFF-based rs-FC analysis was used to further explore the underlying changes in connectivity between ROI and other areas in the NSSI group. Correlation analyses were performed to examine the relationship between neural changes and clinical characteristics.Results: There was no significant difference in HAMD scores between the two groups. ALFF analysis revealed that, compared to adolescents with MDD only, adolescents with MDD who engaged in NSSI displayed significantly enhanced neural activity in the right fusiform gyrus (FFG. R) and the right median cingulate and paracingulate gyri (DCG. R). Significantly reduced rs-FC of the FFG. R-bilateral medial orbital of the superior frontal gyrus (ORBsupmed. L/R)/bilateral medial superior frontal gyrus (SFGmed. L/R), FFG. R-bilateral posterior cingulate gyrus (PCG. L/R), DCG. R-left pallidum (PAL. L), DCG. R-right superior temporal gyrus (STG. R), and DCG. R-right postcentral gyrus (PoCG. R)/right inferior parietal lobule (IPL. R) was found in adolescents with MDD who were engaged in NSSI. Additionally, no significant correlations were observed between ALFF or rs-FC values and the HAMD scores between the two groups.Limitations: Owing to the cross-sectional design, the alterations in ALFF and rs-FC values in the FFG. R and DCG. R could not demonstrate that it was a state or feature in adolescents with MDD who engaged in NSSI. Additionally, the sample size was relatively small.Conclusions: This study highlights changes in regional brain activity and remote connectivity in the FFG. R and DCG. R in adolescents with MDD who engage in NSSI. This could provide a new perspective for further studies on the neurobiological mechanism of NSSI behavior in adolescents with MDD.

scholarly journals Age-Related Decrease in Default-Mode Network Functional Connectivity Is Accelerated in Patients With Major Depressive Disorder

2022 ◽  
Vol 13 ◽  
Author(s):  
Shixiong Tang ◽  
Zhipeng Wu ◽  
Hengyi Cao ◽  
Xudong Chen ◽  
Guowei Wu ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Functional Connectivity ◽  
Depressive Disorder ◽  
Default Mode Network ◽  
Regression Models ◽  
Accelerated Aging ◽  
Major Depressive ◽  
Default Mode ◽  
Age Related ◽  
Main Effect

Major depressive disorder (MDD) is a common psychiatric disorder which is associated with an accelerated biological aging. However, little is known whether such process would be reflected by a more rapid aging of the brain function. In this study, we tested the hypothesis that MDD would be characterized by accelerated aging of the brain’s default-mode network (DMN) functions. Resting-state functional magnetic resonance imaging data of 971 MDD patients and 902 healthy controls (HCs) was analyzed, which was drawn from a publicly accessible, multicenter dataset in China. Strength of functional connectivity (FC) and temporal variability of dynamic functional connectivity (dFC) within the DMN were calculated. Age-related effects on FC/dFC were estimated by linear regression models with age, diagnosis, and diagnosis-by-age interaction as variables of interest, controlling for sex, education, site, and head motion effects. The regression models revealed (1) a significant main effect of age in the predictions of both FC strength and dFC variability; and (2) a significant main effect of diagnosis and a significant diagnosis-by-age interaction in the prediction of FC strength, which was driven by stronger negative correlation between age and FC strength in MDD patients. Our results suggest that (1) both healthy participants and MDD patients experience decrease in DMN FC strength and increase in DMN dFC variability along age; and (2) age-related decrease in DMN FC strength may occur at a faster rate in MDD patients than in HCs. However, further longitudinal studies are still needed to understand the causation between MDD and accelerated aging of brain.

scholarly journals The neuroprogressive nature of major depressive disorder: evidence from an intrinsic connectome analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jin Liu ◽  
Yiming Fan ◽  
Ling-Li Zeng ◽  
Bangshan Liu ◽  
Yumeng Ju ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Functional Connectivity ◽  
Depressive Disorder ◽  
Executive Control ◽  
First Episode ◽  
Recurrent Depression ◽  
Major Depressive ◽  
Attention Networks ◽  
Default Mode ◽  
Control Networks

AbstractMajor depressive disorder (MDD) is a prevailing chronic mental disorder with lifetime recurring episodes. Recurrent depression (RD) has been reported to be associated with greater severity of depression, higher relapse rate and prominent functioning impairments than first-episode depression (FED), suggesting the progressive nature of depression. However, there is still little evidence regarding brain functional connectome. In this study, 95 medication-free MDD patients (35 with FED and 60 with RD) and 111 matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (fMRI) scanning. After six months of treatment with paroxetine, 56 patients achieved clinical remission and finished their second scan. Network-based statistics analysis was used to explore the changes in functional connectivity. The results revealed that, compared with HCs, patients with FED exhibited hypoconnectivity in the somatomotor, default mode and dorsal attention networks, and RD exhibited hyperconnectivity in the somatomotor, salience, executive control, default mode and dorsal attention networks, as well as within and between salience and executive control networks. Moreover, the disrupted components in patients with current MDD did not change significantly when the patients achieved remission after treatment, and sub-hyperconnectivity and sub-hypoconnectivity were still found in those with remitted RD. Additionally, the hypoconnectivity in FED and hyperconnectivity in RD were associated with the number of episodes and total illness duration. This study provides initial evidence supporting that impairment of intrinsic functional connectivity across the course of depression is a progressive process.

scholarly journals Effects of escitalopram therapy on resting-state functional connectivity of subsystems of the default mode network in unmedicated patients with major depressive disorder

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jian Cui ◽  
Yun Wang ◽  
Rui Liu ◽  
Xiongying Chen ◽  
Zhifang Zhang ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Functional Connectivity ◽  
Depressive Disorder ◽  
Default Mode Network ◽  
Resting State ◽  
Fmri Data ◽  
Healthy Controls ◽  
Resting State Functional Connectivity ◽  
Major Depressive ◽  
Default Mode

AbstractAntidepressants are often the first-line medications prescribed for patients with major depressive disorder (MDD). Given the critical role of the default mode network (DMN) in the physiopathology of MDD, the current study aimed to investigate the effects of antidepressants on the resting-state functional connectivity (rsFC) within and between the DMN subsystems. We collected resting-state functional magnetic resonance imaging (rs-fMRI) data from 36 unmedicated MDD patients at baseline and after escitalopram treatment for 12 weeks. The rs-fMRI data were also collected from 61 matched healthy controls at the time point with the same interval. Then, we decomposed the DMN into three subsystems based on a template from previous studies and computed the rsFC within and between the three subsystems. Finally, repeated measures analysis of covariance was conducted to identify the main effect of group and time and their interaction effect. We found that the significantly reduced within-subsystem rsFC in the DMN core subsystem in patients with MDD at baseline was increased after escitalopram treatment and became comparable with that in the healthy controls, whereas the reduced within-subsystem rsFC persisted in the DMN dorsal medial prefrontal cortex (dMPFC) and medial temporal subsystems in patients with MDD following escitalopram treatment. In addition, the reduced between-subsystem rsFC between the core and dMPFC subsystem showed a similar trend of change after treatment in patients with MDD. Moreover, our main results were confirmed using the DMN regions from another brain atlas. In the current study, we found different effects of escitalopram on the rsFC of the DMN subsystems. These findings deepened our understanding of the neuronal basis of antidepressants’ effect on brain function in patients with MDD. The trial name: appropriate technology study of MDD diagnosis and treatment based on objective indicators and measurement. URL: http://www.chictr.org.cn/showproj.aspx?proj=21377. Registration number: ChiCTR-OOC-17012566.

scholarly journals Reduced default mode network functional connectivity in patients with recurrent major depressive disorder

2019 ◽  
Vol 116 (18) ◽  
pp. 9078-9083 ◽  
Author(s):  
Chao-Gan Yan ◽  
Xiao Chen ◽  
Le Li ◽  
Francisco Xavier Castellanos ◽  
Tong-Jian Bai ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Functional Connectivity ◽  
Depressive Disorder ◽  
Default Mode Network ◽  
Statistical Power ◽  
Resting State Fmri ◽  
Response To Treatment ◽  
First Episode ◽  
Major Depressive ◽  
Default Mode

Major depressive disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol before aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor, and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. All R-fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.

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