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Frederick, B. B.

Publications and source records attributed to Frederick, B. B..

3 recordsLinked to original sources

Cognition-centric brain activity across diverse imaging tasks constrains the representation of mental health in task-evoked brain function

Large-scale neuroimaging studies best powered to investigate mental health biomarkers continue to administer a set of in-scanner tasks that, to date, yield weak brain-mental health associations. Triangulating the source of these weak associations is critical to directing the focus of future work. Using these tasks strong brain-cognition associations as a positive control, we analyzed potential sources of weak brain-mental health associations across five popular fMRI tasks and dozens of task-evoked brain networks. Across tasks and networks, latent mental health factors showed substantially weaker brain associations than cognition despite comparable measurement reliability and greater interindividual variability. Moreover, increasing brain-feature dimensionality improved cognitive but not mental health signal, and task-evoked network profiles were 1.8-2.3 times more homogeneous and 3.5 times lower-dimensional than mental health profiles. Findings implicate a signal evocation bottleneck: common fMRI tasks elicit little interindividual variation in mental health-related brain activity relative to the diversity of mental health itself. Overall, these findings motivate a shift in focus to the development and use of tasks in large-scale studies more explicitly designed to evoke mental health-relevant brain activity. Significance StatementIdentification of robust individual-specific mental health-related brain signals from fMRI remains elusive, limiting the clinical utility of brain imaging. To investigate why, we systematically evaluated brain signals evoked by tasks used by the Human Connectome Project-Young Adult study, which are now commonly included in many large-scale neuroimaging studies. Our findings suggest that, more so than analytical or measurement constraints on detecting these signals, a primary limitation is a failure of these prevalent fMRI tasks to evoke mental health-relevant brain signals in the first place. These findings suggest that progress in psychiatric neuroimaging may require tasks more explicitly designed to evoke mental health-relevant brain activity.

neuroscience↗

Brain-wide functional connectivity artifactually inflates throughout fMRI scans: a problem and solution

The fMRI blood oxygen level-dependent (BOLD) signal is a mainstay of neuroimaging assessment of neuronal activity and functional connectivity in vivo. Thus, a chief priority is maximizing this signals reliability and validity. To this end, the fMRI community has invested considerable effort into optimizing both experimental designs and physiological denoising procedures to improve the accuracy, across-scan reproducibility, and subject discriminability of BOLD-derived metrics like functional connectivity. Despite these advances, we discover that a substantial and ubiquitous defect remains in fMRI datasets: functional connectivity throughout the brain artifactually inflates during the course of fMRI scans - by an average of more than 70% in 15 minutes of scan time - at spatially heterogeneous rates, producing both spatial and temporal distortion of brain connectivity maps. We provide evidence that this inflation is driven by a previously unrecognized time-dependent increase of non-neuronal, systemic low-frequency oscillation (sLFO) blood flow signal during fMRI scanning. This signal is not removed by standard denoising procedures such as independent component analysis (ICA). However, we demonstrate that a specialized sLFO denoising procedure - Regressor Interpolation at Progressive Time Delays (RIPTiDe) - can be added to standard denoising pipelines to significantly attenuate functional connectivity inflation. We confirm the presence of sLFO-driven functional connectivity inflation in multiple independent fMRI datasets - including the Human Connectome Project - as well as across resting-state, task, and sleep-state conditions, and demonstrate its potential to produce false positive findings. Collectively, we present evidence for a previously unknown physiological phenomenon that spatiotemporally distorts estimates of brain connectivity in human fMRI datasets, and present a solution for mitigating this artifact.

neuroscience↗

Resting-state functional connectivity, cortical GABA and neuroactive steroids in peripartum and peripartum depressed women: a functional magnetic imaging and resonance study

Postpartum depression (PPD) is associated with abnormalities in resting-state functional connectivity (RSFC) but the underlying neurochemistry is unclear. We hypothesized that peripartum GABAergic neuroactive steroids (NAS) are related to cortical GABA concentrations and RSFC in PPD as compared to healthy comparison women (HCW). To test this, we measured RSFC with fMRI and GABA+/Creatine (Cr) concentrations with proton magnetic resonance spectroscopy (1H MRS) in the pregenual anterior cingulate (pgACC) and occipital cortices (OCC) and quantified peripartum plasma NAS. We examined between-group differences in RSFC and the relationship between cortical GABA+/Cr concentrations with RSFC. We investigated the relationship between NAS, RSFC and cortical GABA+/Cr concentrations. Within the default mode network (DMN) an area of the dorsomedial prefrontal cortex (DMPFC) had greater connectivity with the rest of the DMN in PPD (peak voxel: MNI coordinates (2, 58, 32), p=0.002) and was correlated to depression scores (peak HAM-D17 voxel: MNI coordinates (0, 60, 34), p=0.008). pgACC GABA+/Cr correlated positively with DMPFC RSFC in a region spanning the right anterior/posterior insula and right temporal pole (r=+0.661, p=0.000). OCC GABA+/Cr correlated positively with regions spanning both amygdalae (right amygdala: r=+0.522, p=0.000; left amygdala: r=+0.651, p=0.000) as well as superior parietal areas. Plasma allopregnanolone was higher in PPD (p=0.03) and positively correlated with intra DMPFC connectivity (r=+0.548, p=0.000) but not GABA+/Cr. These results provide initial evidence that PPD is associated with altered DMN connectivity; cortical GABA+/Cr concentrations are associated with postpartum RSFC and allopregnanolone is associated with postpartum intra-DMPFC connectivity.

neuroscience↗