Biology subjects

Howard, C. M.

Publications and source records attributed to Howard, C. M..

7 recordsLinked to original sources

bioRxiv2026

White-matter connectivity shapes visual and semantic representations in the aging brain

Multiple lines of evidence indicate that aging is associated with a reduction in the quality of sensory information coupled with increased reliance on semantic information. Consistent with this evidence, functional MRI studies have repeatedly found that, compared to younger adults, older adults show weaker visual representations but stronger semantic representations. However, the factors that engender this visuo-semantic representational shift (VSRS) remain unclear. Here, we test whether structural connectivity within the representational network predicts these shifts. In the face of typical age-related declines in visual memory and structural connectivity, we find that structural connectivity (i) mediates age-related decline in perceptual representation, and (ii) supports semantic and perceptual mnemonic representations in older adults. These findings outline a potential mechanism of age-related perceptual processing declines and highlight the adaptability of the memory system with age.

neuroscience↗

bioRxiv2025

Trial-Level Representational Similarity Analysis

Neural representation refers to the brain activity that stands in for ones cognitive experience, and in cognitive neuroscience, a prominent method of studying neural representations is representational similarity analysis (RSA). While there are several recent advances in RSA, the classic RSA (cRSA) approach examines the structure of representations across numerous items by assessing the correspondence between two representational similarity matrices (RSMs): usually one based on a theoretical model of stimulus similarity and the other based on similarity in measured neural data. However, because cRSA cannot weigh the contributions of individual trials (RSM rows/columns), it is fundamentally limited in its ability to assess subject-, stimulus-, and trial-level variances that all influence representation. Here, we formally introduce trial-level RSA (tRSA), an analytical framework that estimates the strength of neural representation for singular experimental trials and evaluates hypotheses using multi-level models. First, we verified the correspondence between tRSA and cRSA in quantifying the overall representation strength across all trials. Second, we compared the statistical inferences drawn from both approaches using simulated data that reflected a wide range of scenarios. Compared to cRSA, the multi-level framework of tRSA was both more theoretically appropriate and significantly sensitive to true effects. Third, using real fMRI datasets, we further demonstrated several issues with cRSA, to which tRSA was more robust. Finally, we presented some novel findings of neural representations that could only be assessed with tRSA and not cRSA. In summary, tRSA proves to be a robust and versatile analytical approach for cognitive neuroscience and beyond.

neuroscience↗

bioRxiv2024

Semantic Dimensions Support the Cortical Representation of Object Memorability

Recent work in vision sciences contends that objects carry an intrinsic property, memorability, that describes the likelihood that an object can be successfully encoded and later retrieved from memory. It has been shown that object memorability is supported by semantic information, but the neural correlates involved are largely unexplored. The present study explores these premises and asks whether neural correlates of object memorability can be accounted for by semantic dimensions. To investigate these questions, we combine three datasets: (1) feature norms for a database of [~]1000 natural object images, (2) normative conceptual and perceptual memory data for those objects, and (3) neuroimaging data from an fMRI study collected using a subset (n=360) of those objects. We found that object-wise memorability elicits consistent brain activation across participants in key mnemonic regions (e.g., hippocampus and rhinal cortex), and that a substantial portion of the variance in this brain activity is mediated by the semantic factors describing these images. Regions with the strongest mediation effects are associated with sensory, motor, and visual processes, suggesting that the relationship between memorability and semantics may align with a sensory-functional account of the representation of concepts in the brain.

neuroscience↗

bioRxiv2024

Cortico-hippocampal interactions underlie schema-supported memory encoding in older adults

Although episodic memory is typically impaired in older adults (OAs) compared to young adults (YAs), this deficit is attenuated when OAs can leverage their rich semantic knowledge, such as their knowledge of schemas. Memory is better for items consistent with pre-existing schemas and this effect is larger in OAs. Neuroimaging studies have associated schema use with the ventromedial prefrontal cortex (vmPFC) and hippocampus (HPC), but most of this research has been limited to YAs. This fMRI study investigated the neural mechanisms underlying how schemas boost episodic memory in OAs. Participants encoded scene-object pairs with varying congruency, and memory for the objects was tested the following day. Congruency with schemas enhanced object memory for YAs and, more substantially, for OAs. FMRI analyses examined how cortical modulation of HPC predicted subsequent memory. Congruency-related vmPFC modulation of left HPC enhanced subsequent memory in both age groups, while congruency-related modulation from angular gyrus (AG) boosted subsequent memory only in OAs. Individual differences in cortico-hippocampal modulations indicated that OAs preferentially used their semantic knowledge to facilitate encoding via an AG-HPC interaction, suggesting a compensatory mechanism. Collectively, our findings illustrate age-related differences in how schemas influence episodic memory encoding via distinct routes of cortico-hippocampal interactions.

neuroscience↗

bioRxiv2021

Chronic Benzene Exposure Aggravates Pressure Overload-Induced Cardiac Dysfunction

Benzene is a ubiquitous environmental pollutant abundant in household products, petrochemicals and cigarette smoke. Benzene is a well-known carcinogen in humans and experimental animals; however, little is known about the cardiovascular toxicity of benzene. Recent population-based studies indicate that benzene exposure is associated with an increased risk for heart failure. Nonetheless, it is unclear whether benzene exposure is sufficient to induce and/or exacerbate heart failure. We examined the effects of benzene (50 ppm, 6 h/day, 5 days/week, 6 weeks) or HEPA-filtered air exposure on transverse aortic constriction (TAC)-induced pressure overload in male C57BL/6J mice. Our data show that benzene exposure had no effect on cardiac function in the Sham group; however, it significantly compromised cardiac function as depicted by a significant decrease in fractional shortening and ejection fraction, as compared with TAC/Air-exposed mice. RNA-seq analysis of the cardiac tissue from the TAC/benzene-exposed mice showed a significant increase in several genes associated with adhesion molecules, cell-cell adhesion, inflammation, and stress response. In particular, neutrophils were implicated in our unbiased analyses. Indeed, immunofluorescence studies showed that TAC/benzene exposure promotes infiltration of CD11b+/S100A8+/myeloperoxidase+-positive neutrophils in the hearts by 3-fold. In vitro, the benzene metabolites, hydroquinone and catechol, induced the expression of P-selectin in cardiac microvascular endothelial cells by 5-fold and increased the adhesion of neutrophils to these endothelial cells by 1.5-2.0-fold. Benzene metabolite-induced adhesion of neutrophils to the endothelial cells was attenuated by anti-P-selectin antibody. Together, these data suggest that benzene exacerbates heart failure by promoting endothelial activation and neutrophil recruitment.

pharmacology and toxicology↗

bioRxiv2020

Spontaneous activity changes in large-scale cortical networks in older adults couple to distinct hemodynamic morphology

Neurovascular coupling is a dynamic core mechanism supporting brain energy demand. Therefore, even spontaneous changes in neural activity are expected to evoke a vascular hemodynamic response (HDR). Here, we developed a novel procedure for estimating transient states in intrinsic activity of neural networks based on source-localized electroencephalogram in combination with HDR estimation based on simultaneous rapid-acquisition functional magnetic resonance imaging. We demonstrate a readily apparent spatiotemporal correspondence between electrophysiological and HDR signals, describing for the first time how features of neurovascular coupling may differ among large-scale brain networks. In the default mode network, the HDR pattern in our older adult participants was associated with a surrogate marker of cerebrovascular deterioration and predicted alterations in temporal structure of fast intrinsic electrophysiological activity linked to memory decline. These results show the potential of our technique for making inferences about neural and vascular processes in higher-level cognitive networks in healthy and at-risk populations.

neuroscience↗

bioRxiv2020

Computed tomography reveals hip dysplasia in Smilodon: Implications for social behavior in an extinct Pleistocene predator

Reconstructing the behavior of extinct species is challenging, particularly for those with no living analogues. However, damage preserved as paleopathologies on bone can record how an animal moved in life, potentially reflecting behavioral patterns. Here, we assess hypothesized etiologies of pathology in a pelvis and associated right femur of a Smilodon fatalis saber-toothed cat, one of the best-studied species from the Pleistocene-age Rancho La Brea asphalt seeps, California, USA, using visualization by computed tomography (CT). The pelvis exhibits massive destruction of the right hip socket that was interpreted, for nearly a century, to have developed from trauma and infection. CT imaging reveals instead that the pathological distortions characterize chronic remodeling that began at birth and led to degeneration of the joint over the animals life. These results suggest that this individual suffered from hip dysplasia, a congenital condition common in domestic dogs and cats. This individual reached adulthood but could not have hunted properly nor defended territory on its own, likely relying on a social group for feeding and protection. While extant social felids are rare, these fossils and others with similar pathologies are consistent with a spectrum of social strategies in Smilodon supported by a predominance of previous studies.

paleontology↗