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 onset. 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 individuals, but this approach has not been applied in depression.

The brainstem's red nucleus was evolutionarily upgraded to support goal-directed action.

The red nucleus is a large brainstem structure that coordinates limb movement for locomotion in quadrupedal animals (Basile et al., 2021). The humans red nucleus has a different pattern of anatomical connectivity compared to quadrupeds, suggesting a unique purpose (Hatschek, 1907).

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. 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, but these approaches have never been applied to individuals with depression.

A somato-cognitive action network alternates with effector regions in motor cortex.

Motor cortex (M1) has been thought to form a continuous somatotopic homunculus extending down the precentral gyrus from foot to face representations, despite evidence for concentric functional zones and maps of complex actions. Here, using precision functional magnetic resonance imaging (fMRI) methods, we find that the classic homunculus is interrupted by regions with distinct connectivity, structure and function, alternating with effector-specific (foot, hand and mouth) areas. These inter-effector regions exhibit decreased cortical thickness and strong functional connectivity to each other, as well as to the cingulo-opercular network (CON), critical for action and physiological control, arousal, errors and pain.

Functional Connectivity Mapping for rTMS Target Selection in Depression.

Objective: Repetitive transcranial magnetic stimulation (rTMS) protocols increasingly use subgenual anterior cingulate cortex (sgACC) functional connectivity to individualize treatment targets. However, the efficacy of this approach is unclear, with conflicting findings and varying effect sizes across studies. Here, the authors investigated the effect of the stimulation site's functional connectivity with the sgACC (sgACC-StimFC) on treatment outcome to rTMS in 295 patients with major depression.

Precision mapping and transcranial magnetic stimulation of individual-specific functional brain networks in humans.

Spatial targeting in transcranial magnetic stimulation protocols does not typically account for the idiosyncratic functional organization of individual human brains. Here, we provide a protocol for implementing targeted functional network stimulation (TANS), which accounts for each individual's unique functional neuroanatomy and cortical folding patterns. Using an example dataset, we describe how to create a head model and estimate the best coil placement and stimulation intensity to minimize off-target effects.

Regional gene expression signatures are associated with sex-specific functional connectivity changes in depression.

The neural substrates of depression may differ in men and women, but the underlying mechanisms are incompletely understood. Here, we show that depression is associated with sex-specific patterns of abnormal functional connectivity in the default mode network and in five regions of interest with sexually dimorphic transcriptional effects. Regional differences in gene expression in two independent datasets explained the neuroanatomical distribution of abnormal connectivity.

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.

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.

Estimated Regional White Matter Hyperintensity Burden, Resting State Functional Connectivity, and Cognitive Functions in Older Adults.

Objective: White matter hyperintensities (WMH) are linked to deficits in cognitive functioning, including cognitive control and memory; however, the structural, and functional mechanisms are largely unknown. We investigated the relationship between estimated regional disruptions to white matter fiber tracts from WMH, resting state functional connectivity (RSFC), and cognitive functions in older adults.

Design: Cross-sectional study.

Improving precision functional mapping routines with multi-echo fMRI.

Rapidly developing approaches to acquiring and analyzing densely-sampled, single-subject fMRI data have opened new avenues for understanding the neurobiological basis of individual differences in behavior and could allow fMRI to become a more clinically useful tool. Here, we review briefly key insights from these precision functional mapping studies and a highlight significant barrier to their clinical translation. Specifically, that reliable delineation of functional brain networks in individual humans can require hours of resting-state fMRI data per-subject.

Rapid Precision Functional Mapping of Individuals Using Multi-Echo fMRI.

Resting-state functional magnetic resonance imaging (fMRI) is widely used in cognitive and clinical neuroscience, but long-duration scans are currently needed to reliably characterize individual differences in functional connectivity (FC) and brain network topology. In this report, we demonstrate that multi-echo fMRI can improve the reliability of FC-based measurements. In four densely sampled individual humans, just 10 min of multi-echo data yielded better test-retest reliability than 30 min of single-echo data in independent datasets.

Prevalent and sex-biased breathing patterns modify functional connectivity MRI in young adults.

Resting state functional connectivity magnetic resonance imaging (fMRI) is a tool for investigating human brain organization. Here we identify, visually and algorithmically, two prevalent influences on fMRI signals during 440 h of resting state scans in 440 healthy young adults, both caused by deviations from normal breathing which we term deep breaths and bursts. The two respiratory patterns have distinct influences on fMRI signals and signal covariance, distinct timescales, distinct cardiovascular correlates, and distinct tendencies to manifest by sex.

A Critical, Event-Related Appraisal of Denoising in Resting-State fMRI Studies.

This article advances two parallel lines of argument about resting-state functional magnetic resonance imaging (fMRI) signals, one empirical and one conceptual. The empirical line creates a four-part organization of the text: (1) head motion and respiration commonly cause distinct, major, unwanted influences (artifacts) in fMRI signals; (2) head motion and respiratory changes are, confoundingly, both related to psychological and clinical and biological variables of interest; (3) many fMRI denoising strategies fail to identify and remove one or the other kind of artifact; and (4) unremoved artifact, due to correlations of artifacts with variables of interest, renders studies susceptible to identifying variance of noninterest as variance of interest. Arising from these empirical observations is a conceptual argument: that an event-related approach to task-free scans, targeting common behaviors during scanning, enables fundamental distinctions among the kinds of signals present in the data, information which is vital to understanding the effects of denoising procedures.

Causes and Consequences of Diagnostic Heterogeneity in Depression: Paths to Discovering Novel Biological Depression Subtypes.

Depression is a highly heterogeneous syndrome that bears only modest correlations with its biological substrates, motivating a renewed interest in rethinking our approach to diagnosing depression for research purposes and new efforts to discover subtypes of depression anchored in biology. Here, we review the major causes of diagnostic heterogeneity in depression, with consideration of both clinical symptoms and behaviors (symptomatology and trajectory of depressive episodes) and biology (genetics and sexually dimorphic factors). Next, we discuss the promise of using data-driven strategies to discover novel subtypes of depression based on functional neuroimaging measures, including dimensional, categorical, and hybrid approaches to parsing diagnostic heterogeneity and understanding its biological basis.

Precision Functional Mapping of Corticostriatal and Corticothalamic Circuits: Parallel Processing Reconsidered.

In this issue of Neuron, Greene et al. (2020) identify zones of network specificity and multi-network integration in the basal ganglia and thalamus of individual human subjects. Such information could aid in the development of personalized and more effective brain stimulation therapies for neuropsychiatric disorders.

Characteristics of respiratory measures in young adults scanned at rest, including systematic changes and "missed" deep breaths.

Breathing rate and depth influence the concentration of carbon dioxide in the blood, altering cerebral blood flow and thus functional magnetic resonance imaging (fMRI) signals. Such respiratory fluctuations can have substantial influence in studies of fMRI signal covariance in subjects at rest, the so-called "resting state functional connectivity" technique. If respiration is monitored during fMRI scanning, it is typically done using a belt about the subject's abdomen to record abdominal circumference.

Distinctions among real and apparent respiratory motions in human fMRI data.

Head motion estimates in functional magnetic resonance imaging (fMRI) scans appear qualitatively different with sub-second image sampling rates compared to the multi-second sampling rates common in the past. Whereas formerly the head appeared still for much of a scan with brief excursions from baseline, the head now appears to be in constant motion, and motion estimates often seem to divulge little information about what is happening in a scan. This constant motion has been attributed to respiratory oscillations that do not alias at faster sampling rates, and investigators are divided on the extent to which such motion is "real" motion or only "apparent" pseudomotion.

Precision Inhibitory Stimulation of Individual-Specific Cortical Hubs Disrupts Information Processing in Humans.

Noninvasive brain stimulation (NIBS) is a promising treatment for psychiatric and neurologic conditions, but outcomes are variable across treated individuals. In principle, precise targeting of individual-specific features of functional brain networks could improve the efficacy of NIBS interventions. Network theory predicts that the role of a node in a network can be inferred from its connections; as such, we hypothesized that targeting individual-specific "hub" brain areas with NIBS should impact cognition more than nonhub brain areas.

Three Distinct Sets of Connector Hubs Integrate Human Brain Function.

Control over behavior is enabled by the brain's control networks, which interact with lower-level sensory motor and default networks to regulate their functions. Such interactions are facilitated by specialized "connector hub" regions that interconnect discrete networks. Previous work has treated hubs as a single category of brain regions, although their unitary nature is dubious when examined in individual brains.

Executive Dysfunction in Autism Spectrum Disorder Is Associated With a Failure to Modulate Frontoparietal-insular Hub Architecture.

Background: Comorbid executive dysfunction in autism spectrum disorder (ASD) is a barrier to adaptive functioning, despite remittance of core social-communication symptoms. Network models of ASD address core symptoms but not comorbid executive dysfunction. Following recent demonstrations in healthy adults that, with increasing executive demands, hubs embedded within frontoparietal-insular control networks interact with a more diverse set of networks, we hypothesized that the capability of hubs to do so is perturbed in ASD and predicts executive behavior.

The Default Mode Network in Autism.

Autism spectrum disorder (ASD) is characterized by deficits in social communication and interaction. Since its discovery as a major functional brain system, the default mode network (DMN) has been implicated in a number of psychiatric disorders, including ASD. Here we review converging multimodal evidence for DMN dysfunction in the context of specific components of social cognitive dysfunction in ASD: 'self-referential processing' - the ability to process social information relative to oneself and 'theory of mind' or 'mentalizing' - the ability to infer the mental states such as beliefs, intentions, and emotions of others.