Biology subjects

Bruce, R.

Publications and source records attributed to Bruce, R..

3 recordsLinked to original sources

bioRxiv2026

Neighborhood-Level Disadvantage Impacts Multiple Measures of Brain Health: An Imaging Epidemiology Study

BackgroundThe relationship between neighborhood-level socioeconomic disadvantage and brain health is an emerging area of research with critical implications for public health and clinical practice, yet its influence on brain structure remains unclear. PurposeTo investigate the epidemiological association between neighborhood-level socioeconomic disadvantage [Area Deprivation Index (ADI)] and morphometric neuroimaging variables in a consecutive, non-disease enriched patient population. Materials and MethodsThis study, conducted at an academic medical center and associated community partners, used consecutive cross-sectional MRI neuroimaging data from 2,826 inpatient and outpatient individuals without radiological evidence of disease from January 2024 to June 2024. ADI, a geospatially determined index of neighborhood-level disadvantage, was calculated for each individual. Linear regressions tested the relationship between ADI and multiple morphometric variables: brain age gap (BAG; estimated - chronological BA), total brain tissue volume (TBV; total gray + white matter), five subcortical region volumes (hippocampus, thalamus, caudate, putamen, and nucleus accumbens) and four cortical region volumes [anterior cingulate cortex, posterior cingulate cortex, medial prefrontal cortex (MPFC), lateral PFC (LPFC)]. Volumetric measures were normalized to intracranial volume. Models controlled for age, sex, and total white matter hyperintensity volume (WMHV). Results2,826 individuals (mean age, 52.7 {+/-} 18.8 [standard deviation]; 1732 women) were evaluated. Residence in the 20% most disadvantaged neighborhoods was associated with a higher BAG ({beta}s > 2.12, Ps < .01) and decreased TBV ({beta}s < -5.12, Ps < .05). Additionally, increased WMHV was higher among those in the most disadvantaged neighborhoods (ts < - 2.50, Ps < .05) and associated with lower volume in most regions. Interaction models showed increased negative associations between WMHV and volumes of the caudate, nucleus accumbens, and lateral prefrontal cortex among those in the most disadvantaged neighborhoods. ConclusionsNeighborhood disadvantage is associated with adverse brain morphometry, including higher BAG, lower TBV, and amplified vascular-related regional volume loss. Key ResultsO_LIIn 2,826 adults (mean age, 53 years {+/-} 19; 1,732 women), residence in the most disadvantaged neighborhoods (national: 116/2,826, 4%; state: 129/2826, 5%) was associated with higher brain age gap at the national ({beta} = 2.12, 95% CI = 0.81 to 3.43, P = .001) and state levels ({beta} = 2.36; 95% CI = 1.10 to 3.61, P < .001). C_LIO_LITotal brain tissue volume was lower at the national ({beta} = -5.12, 95% CI = -10.13 to -0.11, P = .045) and state levels ({beta} = -6.13, 95% CI = -10.90 to -1.37, P = .011). C_LIO_LIWhite matter hyperintensity volume was higher in the most disadvantaged group (national: P = .013; state: P = .003) and demonstrated amplified associations with caudate, nucleus accumbens, and lateral prefrontal cortex volumes in the most disadvantaged group at the national and/or state levels (Ps < .05). C_LI

neuroscience↗

bioRxiv2023

Complementary cognitive roles for D2-MSNs and D1-MSNs in interval timing

The role of striatal pathways in cognitive processing is unclear. We studied dorsomedial striatal cognitive processing during interval timing, an elementary cognitive task that requires mice to estimate intervals of several seconds and involves working memory for temporal rules as well as attention to the passage of time. We harnessed optogenetic tagging to record from striatal D2- dopamine receptor-expressing medium spiny neurons (D2-MSNs) in the indirect pathway and from D1-dopamine receptor-expressing MSNs (D1-MSNs) in the direct pathway. We found that D2-MSNs and D1-MSNs exhibited distinct dynamics over temporal intervals as quantified by principal component analyses and trial-by-trial generalized linear models. MSN recordings helped construct and constrain a four-parameter drift-diffusion computational model in which MSN ensemble activity represented the accumulation of temporal evidence. This model predicted that disrupting either D2-MSNs or D1-MSNs would increase interval timing response times and alter MSN firing. In line with this prediction, we found that optogenetic inhibition or pharmacological disruption of either D2-MSNs or D1-MSNs increased interval timing response times. Pharmacologically disrupting D2-MSNs or D1-MSNs also changed MSN dynamics and degraded trial-by-trial temporal decoding. Together, our findings demonstrate that D2-MSNs and D1-MSNs had opposing dynamics yet played complementary cognitive roles, implying that striatal direct and indirect pathways work together to shape temporal control of action. These data provide novel insight into basal ganglia cognitive operations beyond movement and have implications for human striatal diseases and therapies targeting striatal pathways.

neuroscience↗

bioRxiv2021

Experience-related remapping of temporal encoding by striatal ensembles.

Temporal control of action is key for a broad range of behaviors and is disrupted in human diseases such as Parkinsons disease and schizophrenia. A brain structure that is critical for temporal control is the dorsal striatum. Experience and learning can influence dorsal striatal neuronal activity, but it is unknown how these neurons change with experience in contexts which require precise temporal control of movement. We investigated this question by recording from medium-spiny neurons (MSNs) in the dorsal striatum of mice as they gained experience controlling their actions in time. We leveraged an interval timing task optimized for mice which required them to "switch" response ports after enough time had passed without receiving a reward. We report three main results. First, we found that time-related ramping activity and response-related activity increased with more experience. Second, temporal decoding by MSN ensembles improved with experience and was predominantly driven by time-related ramping activity. Finally, we found that some MSNs had differential modulation on error trials. These findings enhance our understanding of dorsal striatal temporal processing by demonstrating how MSN ensembles can evolve with experience. Our results can be linked to temporal habituation and illuminate striatal flexibility during interval timing, which may be relevant for human disease.

neuroscience↗