Faculty Bibliography

Digital spatial profiling (DSP) facilitates RNA sequencing (RNA-seq) of small populations of cells, specifically ~20 pyramidal neurons in postmortem formalin-fixed paraffin-embedded (FFPE) human brain tissue. This approach enables precise expression profiling via RNA-seq data linked to spatially characterized samples utilizing tissue-bound probes. We present a comprehensive protocol for manual slide preparation using the GeoMx DSP system as preliminary steps to spatial characterization of lamina-specific pyramidal neurons in human postmortem Brodmann area 9 (BA9) frontal cortex brain tissue.

INTRODUCTION/BACKGROUND:Data on how sleep architecture relates to progression of plasma Alzheimer's disease biomarkers remains limited. METHODS:Sixty-four cognitively unimpaired older adults (ages 55-90) underwent plasma collection twice 2.6 years apart and polysomnography proximate to the first plasma collection. Plasma amyloid beta (Aβ) 42 and 40 were measured via mass spectrometry. RESULTS:Frontal slow-wave activity (SWA) was inversely associated with plasma Aβ42/40 at cross-section in bivariate analysis and in a covariate-adjusted model. In comparison, low rapid eye movement (REM) sleep percentage was associated with a large longitudinal decline in annualized blood-based Aβ42/40. In exploratory analyses, the association between low REM sleep percentage and faster decline in Aβ42/40 ratio was stronger in the amyloid-positive group. DISCUSSION/CONCLUSIONS:In cognitively unimpaired older adults, non-REM SWA correlates with cross-sectional amyloid load, whereas REM sleep may predict accelerated amyloid accumulation in preclinical stage, suggesting both may serve as early biomarkers and modifiable interventional targets.

Myocardial strain imaging enables quantification of cardiac deformation. Cardiovascular magnetic resonance imaging (CMR) is well suited for strain assessment due to the ability to image in any given plane with high spatial and contrast resolution. CMR strain measures have incremental diagnostic and prognostic utility over conventional clinical imaging parameters across disease states. Routine integration of CMR strain assessment in clinical practice has been hindered by the lack of agreement on imaging protocols and analysis methods, variability due to noise sensitivity, and a paucity of robust normative age-, sex- and ethnicity-specific reference ranges. In recognition of the expanding applications of strain techniques in clinical and research CMR, this joint SCMR/RSNA/EACVI scientific statement integrates data from original research studies, guidelines, and opinions from experts across the field to guide responsible and evidence-based utilization of CMR strain.

Myocardial strain imaging enables quantification of cardiac deformation. Cardiovascular magnetic resonance imaging (CMR) is well suited for strain assessment due to the ability to image in any given plane with high spatial and contrast resolution. CMR strain measures have incremental diagnostic and prognostic utility over conventional clinical imaging parameters across disease states. Routine integration of CMR strain assessment in clinical practice has been hindered by the lack of agreement on imaging protocols and analysis methods, variability due to noise sensitivity, and a paucity of robust normative age-, sex- and ethnicity-specific reference ranges. In recognition of the expanding applications of strain techniques in clinical and research CMR, this joint SCMR/RSNA/EACVI scientific statement integrates data from original research studies, guidelines, and opinions from experts across the field to guide responsible and evidence-based utilization of CMR strain.

OBJECTIVE/UNASSIGNED:We evaluated the Spatial AI model on the Fortell AI hearing aids to see if it improves speech intelligibility in single-azimuth multitalker babble relative to a commercially available control hearing aid employing neural-network-based noise-reduction. DESIGN/UNASSIGNED:In a pre-registered, double-blind, randomised controlled trial, hearing aid users completed a QuickSIN test wearing the Fortell and control devices. Both devices were set to maximise directionality and noise reduction. Objective metrics were also calculated. SAMPLE/UNASSIGNED:Thirty adults with mild to moderately-severe bilateral sensorineural hearing loss. RESULTS/UNASSIGNED:≪ 0.0001). The SNR-50 improved by 9.2 dB and all participants identified more words correctly using the investigational device. Lab measurements showed an SNR improvement over unaided of 2.3 dB with the control device and 15.5 dB with the investigational hearing aid. HASPI v2 showed a similar level of SNR improvement. CONCLUSIONS/UNASSIGNED:Spatial AI yields substantial intelligibility benefits in a controlled single-azimuth multitalker configuration. The effect sizes greatly exceeded established thresholds for clinical significance, suggesting that the algorithm may help address the cocktail party problem for hearing-impaired listeners.

Recurrent attractor networks are widely thought to form the basis of working memory^1-3, but how they can be rapidly switched on and off is unclear^4-7. Here we investigate stability and switching in a recurrent circuit of the fly navigation centre⁸. h∆K and PFG neurons are recurrently connected in a ring structure and exhibit shared persistent bump activity that turns on with odour and terminates at the end of a goal-directed run. Using whole-cell recordings, we show that persistence in h∆K depends on recurrence, and that h∆K receives slow recurrent excitation and fast inhibition from its synaptic partners. Computational modelling reveals that these synaptic dynamics yield persistent attractor dynamics over a range of synaptic strengths. Next we examine the mechanisms of rapid switching. We find that whereas both populations show similar activity during runs, they become decoupled during turns and rest. We can reproduce these differential dynamics in our model by using inhibition to dynamically uncouple activity in h∆K from PFG. When h∆K is inhibited, PFG neurons follow their inputs from the compass system; when h∆K is disinhibited, recurrent interactions lock this input into place, forming a heading memory. Consistent with this model, we find that inhibitory inputs onto h∆K increase during turns and are suppressed during odour and goal-directed runs. Our work reveals how disinhibition can serve as a gate to rapidly write an ongoing measurement to a recurrent circuit.

Myocardial strain imaging enables quantification of cardiac deformation. Cardiovascular magnetic resonance imaging (CMR) is well suited for strain assessment due to the ability to image in any given plane with high spatial and contrast resolution. CMR strain measures have incremental diagnostic and prognostic utility over conventional clinical imaging parameters across disease states. Routine integration of CMR strain assessment in clinical practice has been hindered by the lack of agreement on imaging protocols and analysis methods, variability due to noise sensitivity, and a paucity of robust normative age-, sex- and ethnicity-specific reference ranges. In recognition of the expanding applications of strain techniques in clinical and research CMR, this joint SCMR/RSNA/EACVI scientific statement integrates data from original research studies, guidelines, and opinions from experts across the field to guide responsible and evidence-based utilization of CMR strain. © 2026 The Author(s). Published by Elsevier Inc. on behalf of Society for Cardiovascular Magnetic Resonance, by Oxford University Press on behalf of European Society of Cardiology, and by RSNA. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by/4.0/). Supplemental material is available for this article. This paper was jointly developed by Journal of Cardiovascular Magnetic Resonance, European Heart Journal - Cardiovascular Imaging, and Radiology and jointly published by Elsevier Inc, Oxford University Press, and RSNA. The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. Any citation can be used when citing this article.

Deep neural networks (DNNs) are promising computational models for understanding visual object recognition. Yet, whether DNNs use similar visual cues for object recognition as humans do remains unknown. We created an image set that systematically untangles global shape, internal parts, and texture information, and compared human recognition behavior against >200 DNNs spanning diverse architectures, training diets, and training objectives. No DNNs replicated humans' cue-reliance profile, including those with recurrence or specialized training. Fine-tuned text-image contrastive-trained models, regardless of architecture, were most human-like overall, but lost their human-alignment when the global shape was disrupted. Strikingly, all DNNs substantially underperformed humans when the global shape cue alone was critical to object recognition. Furthermore, alignment with ventral stream neural recordings in an existing database did not predict alignment to human behavior, and model performance does not always predict its human-alignment. Together, these findings reveal systematic and persistent differences between human and machine vision.

Aggression is an innate behavior conserved across species, serving as a critical means to compete for food, mating opportunities, and other essential resources. A central question in aggression research is the extent to which inter-individual variability in aggression is shaped by genetic factors. Here, we examine aggressive behaviors in naïve male mice across seven genetically defined strains and find large cross-strain differences. We find a tight correlation between aggressiveness and anxiety levels across strains, but not within the same strain, suggesting strong genetic control of both traits. Pharmacologically elevating anxiety in high-aggression strains reduces aggression, revealing a causal relationship between these behaviors. We further demonstrate that differences in the synaptic and cellular properties of neurons in the ventrolateral ventromedial hypothalamus (VMHvl) largely account for cross-strain variability in male aggression, and that chemogenetically increasing VMHvl excitability enhances attack behavior in a low-aggression strain. Together, these findings reveal the neuronal implementation of the genetic control of innate aggression level.

The transcription factor early B-cell factor 1 (EBF1) plays critical developmental roles in numerous organ systems, including B-cells, kidney, bone, and heart. During cardiogenesis, cardiomyocyte expression of EBF1 is reportedly undetectable and its effects on myocyte development and proliferation are thought to reflect a non-cell autonomous mechanism, acting via intercellular communication from EBF1 expressing non-myocyte cells. Here, using single-cell transcriptional profiling, we confirm the absence of Ebf1 transcripts in cardiomyocytes. Furthermore, employing computational receptor-ligand interaction analysis of dissociated cells from wildtype and EBF1-deficient hearts, we show that loss of function of this pioneer transcription factor enhances fibroblast to myocyte signaling via the collagen-integrin pathway. Finally, we generated fibroblast-specific EBF1 knockout mice using a PDGFRα-Cre transgenic driver, and found a nearly identical phenotype to that of the generalized knockout, with runting, premature death, an increase in left ventricular relative wall thickness and cardiomyocyte hyperplasia. These findings provide further mechanistic insight into the non-cell autonomous mechanism of action of EBF1 in cardiac growth and development.