Biology subjects

Risk, B. B.

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

5 recordsLinked to original sources

bioRxiv2026

Emergence of Task-Related Motor Cortical Dysfunction in Mice with Progressive Parkinsonism

There are substantial functional changes in the primary motor cortex (M1) in Parkinsons disease (PD). However, the temporal relationship between midbrain dopaminergic (DA) neurodegeneration, M1 circuit dysfunction, and Parkinsonian motor symptoms remains poorly understood. Using a genetic mouse model of progressive nigrostriatal DA degeneration ("MitoPark" mice), we determine the time course of M1 cellular dysfunction and skilled movement impairment as the midbrain DA neurons gradually degenerate. M1 pyramidal neuronal subtypes were identified using AAV-mediated retrograde labeling. During progressive DA loss, MitoPark mice developed gradually impaired performance in a reach-to-grasp single-food-pellet task. These impairments were detectable at a moderate motor stage of Parkinsonism. In vivo GCaMP6f imaging revealed that impaired skilled movement was associated with reduced cellular activity and movement responsiveness of M1 pyramidal neurons at a moderate motor stage of Parkinsonism. While both the corticospinal (CSp) and intratelencephalic (IT) neurons send glutamatergic inputs to the striatum, only the CSp neurons showed a selective and significant reduction in cellular activity and movement responsiveness during reaches. At the population level, we found that M1 pyramidal neurons include heterogeneous functional clusters with distinct temporal profiles in response to skilled movement. While movement encoding by different functional clusters is longitudinally stable in control mice, it degrades and diverges significantly in MitoPark mice. The impaired stability is further supported by a longitudinal analysis of individual neuronal activity related to movements. Together, these results provide novel insights into the emergence of M1 circuit pathophysiology at cellular and neural population levels during progressive Parkinsonism.

neuroscience↗

bioRxiv2023

The impact of multiband and in-plane acceleration on white matter microstructure analysis

Accelerated imaging has been broadly adopted in diffusion MRI studies, yet little is known about its impacts. Acceleration can achieve higher spatial and q-space resolution in shorter time, reduce motion artifacts, and reduce patient burden. However, it leads to noise amplification, and its impacts in clinical cohorts are poorly understood. This study examined the impact of multiband (also called simultaneous multislice, or SMS) and in-plane acceleration (IPA, also called phase acceleration) in diffusion imaging in forty older adults differing in cognitive status. We evaluated a total of 400 scans from five acquisitions: no acceleration (S1P1); SMS=3 with no in-plane acceleration (S3P1); SMS=3 with IPA=2 (S3P2); S6P1; and S6P2. The number of diffusion directions and b-values was kept constant such that acquisition times varied from 21:28 to 3:56. We found that diffusion metrics were highly sensitive to acceleration factor, with a trend towards higher fractional anisotropy (FA) and lower orientation dispersion (OD) with acceleration. The differences between accelerated and unaccelerated acquisitions could be partly explained by the noise amplification (g-factor) and reduced motion. Intraclass correlations (ICCs) of FA and OD in white matter were excellent in both S1P1 and S3P1 (median >0.8), good but lower in S3P2 and S6P1 (medians around 0.70), and poor to fair in S6P2 (medians 0.46 and 0.57). In-plane acceleration decreased ICC, including areas of high susceptibility distortion. In a comparison of mild cognitive impairment versus healthy controls, acceleration tended to reduce group differences, particularly in the fornix, with greater costs in OD than FA. Our results provide guidance regarding the costs of acceleration (possible biases and reduced effect sizes) while also characterizing the benefits (reduced motion, good reliability at higher multiband with no in-plane).

bioengineering↗

bioRxiv2022

Accounting for motion in fMRI: What part of the spectrum are we characterizing in autism spectrum disorder?

The exclusion of high-motion participants can reduce the impact of motion in functional Magnetic Resonance Imaging (fMRI) data. However, the exclusion of high-motion participants may change the distribution of clinically relevant variables in the study sample, and the resulting sample may not be representative of the population. Our goals are two-fold: 1) to document the biases introduced by common motion exclusion practices in functional connectivity research and 2) to introduce a framework to address these biases by treating excluded scans as a missing data problem. We use a study of autism spectrum disorder in children without an intellectual disability to illustrate the problem and the potential solution. We aggregated data from 545 children (8-13 years old) who participated in resting-state fMRI studies at Kennedy Krieger Institute (173 autistic and 372 typically developing) between 2007 and 2020. We found that autistic children were more likely to be excluded than typically developing children, with 28.5% and 16.1% of autistic and typically developing children excluded, respectively, using a lenient criterion and 81.0% and 60.1% with a stricter criterion. The resulting sample of autistic children with usable data tended to be older, have milder social deficits, better motor control, and higher intellectual ability than the original sample. These measures were also related to functional connectivity strength among children with usable data. This suggests that the generalizability of previous studies reporting naive analyses (i.e., based only on participants with usable data) may be limited by the selection of older children with less severe clinical profiles because these children are better able to remain still during an rs-fMRI scan. We adapt doubly robust targeted minimum loss based estimation with an ensemble of machine learning algorithms to address these data losses and the resulting biases. The proposed approach selects more edges that differ in functional connectivity between autistic and typically developing children than the naive approach, supporting this as a promising solution to improve the study of heterogeneous populations in which motion is common.

neuroscience↗

bioRxiv2021

Impact of an Urban Sanitation Intervention on Enteric Pathogen Detection in Soils

Environmental fecal contamination is common in many low-income cities, contributing to a high burden of enteric infections and associated negative sequelae. To evaluate the impact of a shared onsite sanitation intervention in Maputo, Mozambique on enteric pathogens in the domestic environment, we collected 179 soil samples at shared latrine entrances from intervention (n= 49) and control (n= 51) compounds during baseline (pre-intervention) and after 24 months (post-intervention) as part of the Maputo Sanitation Trial. We tested soils for the presence of nucleic acids associated with 20 enteric pathogens using a multiplex reverse transcription qPCR platform. We detected at least one pathogen-associated target in 91% (163/179) of soils and a median of 3 (IQR=1.5, 5) pathogens. Using a difference-in-difference analysis and adjusting for compound population, visibly wet soil, sun exposure, wealth, temperature, animal presence, and visible feces, we estimate the intervention reduced the probability of [≥]1 pathogen detected by 15% (adjusted prevalence ratio, aPR=0.85; 95% CI: 0.70, 1.0) and the total number of pathogens detected by 35% (aPR =0.65; 0.44, 0.95) in soil 24 months following the intervention. These results suggest that the intervention reduced the presence of some fecal contamination in the domestic environment, but pathogen detection remained prevalent 24-months following the introduction of new latrines.

molecular biology↗

bioRxiv2018

Impacts of Simultaneous Multislice Acquisition on Sensitivity and Specificity in fMRI

Simultaneous multislice (SMS) acquisition can be used to decrease the time between acquisition of fMRI volumes, which can increase sensitivity by facilitating the removal of higher-frequency artifacts and boosting effective sample size. The technique requires an additional processing step in which the slices are separated, or unaliased, to recover the whole brain volume. However, this may result in signal \"leakage\" between aliased locations, i.e., slice \"leakage,\" and lead to spurious activation (decreased specificity). SMS can also lead to noise amplification, which can reduce the benefits of decreased repetition time. In this study, we evaluate the original slice-GRAPPA (no leak block) reconstruction algorithm and acquisition scenarios used in the young adult Human Connectome Project (HCP), as well as split slice-GRAPPA (leak block). In addition to slice leakage, signal leakage can result from spatial smoothing, i.e., smoothing leakage, which leads to inflated regions of activation. Previous studies have generally found that SMS acquisition results in higher test statistics and/or a greater number of activated voxels. Here, we use simulations to disentangle this phenomenon into true positives (sensitivity) and false positives (decreased specificity). Slice leakage was greatly decreased by split slice-GRAPPA. Noise amplification was decreased by using moderate acceleration factors (AF = 4). We examined slice leakage in unprocessed fMRI motor task data from the HCP, which used the original slice-GRAPPA. When data were smoothed, we found evidence of slice leakage in some, but not all, subjects. We also found evidence of SMS noise amplification in unprocessed task and processed resting-state HCP data.

neuroscience↗