Frontostriatal salience network expansion in individuals in depression.

Decades of neuroimaging studies have shown modest differences in brain structure and connectivity in depression, hindering mechanistic insights or the identification of risk factors for disease onset1. Furthermore, whereas depression is episodic, few longitudinal neuroimaging studies exist, limiting understanding of mechanisms that drive mood-state transitions. The emerging field of precision functional mapping has used densely sampled longitudinal neuroimaging data to show behaviourally meaningful differences in brain network topography and connectivity between and in healthy individuals2-4, but this approach has not been applied in depression. Here, using precision functional mapping and several samples of deeply sampled individuals, we found that the frontostriatal salience network is expanded nearly twofold in the cortex of most individuals with depression. This effect was replicable in several samples and caused primarily by network border shifts, with three distinct modes of encroachment occurring in different individuals. Salience network expansion was stable over time, unaffected by mood state and detectable in children before the onset of depression later in adolescence. Longitudinal analyses of individuals scanned up to 62 times over 1.5 years identified connectivity changes in frontostriatal circuits that tracked fluctuations in specific symptoms and predicted future anhedonia symptoms. Together, these findings identify a trait-like brain network topology that may confer risk for depression and mood-state-dependent connectivity changes in frontostriatal circuits that predict the emergence and remission of depressive symptoms over time.

Expansion of a frontostriatal salience network in individuals with depression.

Hundreds of neuroimaging studies spanning two decades have revealed differences in brain structure and functional connectivity in depression, but with modest effect sizes, complicating efforts to derive mechanistic pathophysiologic insights or develop biomarkers. 1 Furthermore, although depression is a fundamentally episodic condition, few neuroimaging studies have taken a longitudinal approach, which is critical for understanding cause and effect and delineating mechanisms that drive mood state transitions over time. The emerging field of precision functional mapping using densely-sampled longitudinal neuroimaging data has revealed unexpected, functionally meaningful individual differences in brain network topology in healthy individuals, 2-5 but these approaches have never been applied to individuals with depression. Here, using precision functional mapping techniques and 11 datasets comprising n=187 repeatedly sampled individuals and >21,000 minutes of fMRI data, we show that the frontostriatal salience network is expanded two-fold in most individuals with depression. This effect was replicable in multiple samples, including large-scale, group-average data (N=1,231 subjects), and caused primarily by network border shifts affecting specific functional systems, with three distinct modes of encroachment occurring in different individuals. Salience network expansion was unexpectedly stable over time, unaffected by changes in mood state, and detectable in children before the subsequent onset of depressive symptoms in adolescence. Longitudinal analyses of individuals scanned up to 62 times over 1.5 years identified connectivity changes in specific frontostriatal circuits that tracked fluctuations in specific symptom domains and predicted future anhedonia symptoms before they emerged. Together, these findings identify a stable trait-like brain network topology that may confer risk for depression and mood-state dependent connectivity changes in frontostriatal circuits that predict the emergence and remission of depressive symptoms over time.

Automated optimization of TMS coil placement for personalized functional network engagement.

Transcranial magnetic stimulation (TMS) is used to treat multiple psychiatric and neurological conditions by manipulating activity in particular brain networks and circuits, but individual responses are highly variable. In clinical settings, TMS coil placement is typically based on either group average functional maps or scalp heuristics. Here, we found that this approach can inadvertently target different functional networks in depressed patients due to variability in their functional brain organization. More precise TMS targeting should be feasible by accounting for each patient's unique functional neuroanatomy. To this end, we developed a targeting approach, termed targeted functional network stimulation (TANS). The TANS approach improved stimulation specificity in silico in 8 highly sampled patients with depression and 6 healthy individuals and in vivo when targeting somatomotor functional networks representing the upper and lower limbs. Code for implementing TANS and an example dataset are provided as a resource.

Individual Differences in the Affective Response to Pandemic-Related Stressors in COVID-19 Health Care Workers.

BACKGROUND: We investigated the evolving prevalence of mood and anxiety symptoms among health care workers from May 2020 to January 2021, risk factors for adverse outcomes, and characteristic modes of affective responses to pandemic-related stressors. METHODS: A total of 2307 health care workers (78.9% female, modal age 25-34 years) participated in an online survey assessing depression (Patient Health Questionnaire-9) and anxiety (Generalized Anxiety Disorder-7 scale) symptoms, demographic variables, and self-reported impact of pandemic-related stressors. A total of 334 subjects were reassessed ∼6 months later. RESULTS: The prevalence of clinically significant depression and anxiety was 45.3% and 43.3%, respectively, and a majority (59.9%-62.9%) of those individuals had persistent significant symptoms at 6-month follow-up. Younger age, female gender, and specific occupations (support staff > nurses > physicians) were associated with increased depressive and anxiety symptoms. The most important risk factors were social isolation and fear of contracting COVID-19. The prevalence of clinically significant mood and anxiety symptoms increased by 39.8% from May 2020 to January 2021. Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 scores were highly correlated and associated with nearly identical risk factors, suggesting that they are not capturing independent constructs in this sample. Principal component analysis identified seven orthogonal symptom domains with unique risk factors. CONCLUSIONS: Clinically significant mood and anxiety symptoms are highly prevalent and persistent among health care workers, and are associated with numerous risk factors, the strongest of which are related to pandemic stressors and potentially modifiable. Interventions aimed at reducing social isolation and mitigating the impact of fear of infection warrant further study.