Connectivity analyses and computational modeling of human brain function from fMRI data frequently require the specification of regions of interests (ROIs). Several analyses have relied on atlases derived from anatomical or cyto-architectonic boundaries to specify these ROIs, yet the suitability of atlases for resting state functional connectivity studies has yet to be established. This paper introduces a data-driven method for generating an ROI atlas by parcellating whole brain resting-state fMRI data into spatially coherent regions of homogeneous functional connectivity. Several clustering statistics are used to compare methodological trade-offs as well as determine an adequate number of clusters. Additionally, we evaluate the suitability of the parcellation atlas against four ROI atlases (Talairach and Tournoux, Harvard-Oxford, Eickoff-Zilles, and Automatic Anatomical Labeling) and a random parcellation approach. The evaluated anatomical atlases exhibit poor ROI homogeneity and do not accurately reproduce functional connectivity patterns present at the voxel scale. In general, the proposed functional and random parcellations perform equivalently for most of the metrics evaluated. ROI size and hence the number of ROIs in a parcellation had the greatest impact on their suitability for functional connectivity analysis. With 200 or fewer ROIs, the resulting parcellations consist of ROIs with anatomic homology, and thus offer increased interpretability. Parcellation results containing higher numbers of ROIs (600 or 1000) most accurately represent functional connectivity patterns present at the voxel scale and are preferable when interpretability can be sacrificed for accuracy. The resulting atlases and clustering software have been made publicly available at: http://www.nitrc.org/projects/cluster_roi/.

clinicaltrials.gov Identifier: NCT00149838.

Background The vast majority of people worldwide have been impacted by coronavirus disease (COVID-19). In addition to the millions of individuals who have been infected with the disease, billions of individuals have been asked or required by local and national governments to change their behavioral patterns. Previous research on epidemics or traumatic events suggests that this can lead to profound behavioral and mental health changes; however, researchers are rarely able to track these changes with frequent, near-real-time sampling or compare their findings to previous years of data for the same individuals. Objective By combining mobile phone sensing and self-reported mental health data among college students who have been participating in a longitudinal study for the past 2 years, we sought to answer two overarching questions. First, have the behaviors and mental health of the participants changed in response to the COVID-19 pandemic compared to previous time periods? Second, are these behavior and mental health changes associated with the relative news coverage of COVID-19 in the US media? Methods Behaviors such as the number of locations visited, distance traveled, duration of phone usage, number of phone unlocks, sleep duration, and sedentary time were measured using the StudentLife smartphone sensing app. Depression and anxiety were assessed using weekly self-reported ecological momentary assessments of the Patient Health Questionnaire-4. The participants were 217 undergraduate students, with 178 (82.0%) students providing data during the Winter 2020 term. Differences in behaviors and self-reported mental health collected during the Winter 2020 term compared to previous terms in the same cohort were modeled using mixed linear models. Results During the first academic term impacted by COVID-19 (Winter 2020), individuals were more sedentary and reported increased anxiety and depression symptoms ( P <.001) relative to previous academic terms and subsequent academic breaks. Interactions between the Winter 2020 term and the week of the academic term (linear and quadratic) were significant. In a mixed linear model, phone usage, number of locations visited, and week of the term were strongly associated with increased amount of COVID-19–related news. When mental health metrics (eg, depression and anxiety) were added to the previous measures (week of term, number of locations visited, and phone usage), both anxiety ( P <.001) and depression ( P =.03) were significantly associated with COVID-19–related news. Conclusions Compared with prior academic terms, individuals in the Winter 2020 term were more sedentary, anxious, and depressed. A wide variety of behaviors, including increased phone usage, decreased physical activity, and fewer locations visited, were associated with fluctuations in COVID-19 news repo...

Context Deep brain stimulation (DBS) may be an effective intervention for treatment-resistant depression (TRD), but available data are limited. Objective To assess the efficacy and safety of subcallosal cingulate DBS in patients with TRD with either major depressive disorder (MDD) or bipolar II disorder (BP). Design Open-label trial with a sham lead-in phase. Setting Academic medical center. Patients Men and women aged 18 to 70 years with a moderate-to-severe major depressive episode after at least 4 adequate antidepressant treatments. Ten patients with MDD and 7 with BP were enrolled from a total of 323 patients screened. Intervention Deep brain stimulation electrodes were implanted bilaterally in the subcallosal cingulate white matter. Patients received single-blind sham stimulation for 4 weeks followed by active stimulation for 24 weeks. Patients then entered a single-blind discontinuation phase; this phase was stopped after the first 3 patients because of ethical concerns. Patients were evaluated for up to 2 years after the onset of active stimulation. Main Outcome Measures Change in depression severity and functioning over time, and response and remission rates after 24 weeks were the primary efficacy end points; secondary efficacy end points were 1 year and 2 years of active stimulation. Results A significant decrease in depression and increase in function were associated with chronic stimulation. Remission and response were seen in 3 patients (18%) and 7 (41%) after 24 weeks (n=17), 5 (36%) and 5 (36%) after 1 year (n=14), and 7 (58%) and 11 (92%) after 2 years (n=12) of active stimulation. No patient achieving remission experienced a spontaneous relapse. Efficacy was similar for patients with MDD and those with BP. Chronic DBS was safe and well tolerated, and no hypomanic or manic episodes occurred. A modest sham stimulation effect was found, likely due to a decrease in depression after the surgical intervention but prior to entering the sham phase. Conclusions The findings of this study support the long-term safety and antidepressant efficacy of subcallosal cingulate DBS for TRD and suggest equivalent safety and efficacy for TRD in patients with BP.

Background Deep brain stimulation (DBS) of subcallosal cingulate white matter (SCC) is an evolving investigational treatment for major depression. Mechanisms of action are hypothesized to involve modulation of activity within a structurally defined network of brain regions involved in mood regulation. Diffusion tensor imaging (DTI) was used to model white matter connections within this network to identify those critical for successful antidepressant response to SCC DBS. Methods Pre-operative high-resolution MRI data, including DTI, were acquired in 16 patients with treatment-resistant depression who then received SCC DBS. Computerized tomography was used post-operatively to locate DBS contacts. The activation volume around the active contacts used for chronic stimulation was modeled for each patient retrospectively. Probabilistic tractography was used to delineate the white matter tracts that traveled through each activation volume. Patient-specific tract maps were calculated using whole-brain analysis. Clinical evaluations of therapeutic outcome from SCC DBS were defined at 6 months and 2 years. Results Whole brain activation volume tractography (AVT) demonstrated that all DBS responders at six months (n=6) and 2 years (n=12) shared bilateral pathways from their activation volumes to (1) medial frontal cortex via forceps minor and uncinate fasciculus, (2) rostral and dorsal cingulate cortex via the cingulum bundle, and (3) subcortical nuclei. Non-responders did not consistently show these connections. Specific anatomical coordinates of the active contacts did not discriminate responders from non-responders. Conclusions Patient-specific AVT modeling may identify critical tracts that mediate SCC DBS antidepressant response. This suggests a novel method for patient-specific target and stimulation parameter selection.

Target identification and contact selection are known contributors to variability in efficacy across different clinical indications of deep brain stimulation surgery. A retrospective analysis of responders to subcallosal cingulate deep brain stimulation (SCC DBS) for depression demonstrated the common impact of the electrical stimulation on a stereotypic connectome of converging white matter bundles (forceps minor, uncinate fasciculus, cingulum and fronto-striatal fibers). To test the utility of a prospective connectomic approach for SCC DBS surgery, this pilot study used the four-bundle tractography “connectome blueprint” to plan surgical targeting in eleven participants with treatment-resistant depression. Before surgery, targets were selected individually using deterministic tractography. Selection of contacts for chronic stimulation was made by matching the postoperative probabilistic tractography map to the presurgical deterministic tractography map for each subject. Intraoperative behavioral responses were used as a secondary verification of location. A probabilistic tract map of all participants demonstrated inclusion of the four bundles as intended, matching the connectome blueprint previously defined. Eight of 11 patients (72.7%) were responders and 5 were remitters after 6 months of open-label stimulation. At one year, nine of 11 patients (81.8%) were responders, with six of them in remission. These results support the utility of a group probabilistic tractography map as a connectome blueprint for individualized, patient-specific, deterministic tractography targeting, confirming retrospective findings previously published. This new method represents a connectomic approach to guide future SCC DBS studies.

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Background: Deep brain stimulation (DBS) of the subcallosal cingulate white matter (SCC) has shown promise as an intervention for patients with chronic, unremitting depression (TRD). To test the safety and efficacy of DBS for TRD, a prospective, randomized, sham-controlled trial was conducted. Methods: Participants with TRD were implanted with a DBS system targeting bilateral SCC white matter and randomized to six months of active versus sham DBS followed by six months open-label SCC DBS. The primary outcome was response rate at the end of the six-month double-blind phase. Response was defined as a 40% or greater reduction in depression severity from baseline. A futility analysis was performed when approximately half of the proposed sample received DBS implantation and completed the double-blind phase. At the conclusion of the 12-month study, a subset of patients continued to be followed for up to 24 months. Findings: Prior to the futility analysis, 90 participants were randomized to active (N=60) versus sham (N=30) stimulation. Both groups showed improvement, but there was no statistically significant difference in response rate during the double-blind, sham-controlled phase. Participants continued to improve during the six months open-label phase. Long-term response and remission rates for all participants receiving active DBS open-label were, respectively, 40% and 19% at 12 months, 51%