Biology subjects

Staba, R.

Publications and source records attributed to Staba, R..

3 recordsLinked to original sources

bioRxiv2025

Unbiased Population-Based Statistics to Obtain Pathologic Burden of Injury after Experimental TBI

Reproducibility of scientific data is a current concern throughout the neuroscience field. There are multiple on-going efforts to help resolve this problem. Within the preclinical neuroimaging field, the continued use of a region-of interest (ROI) type approaches combined with the well-known spatial heterogeneity of traumatic brain injury pathology is a barrier to the replicability and repeatability of data. Here we propose the conjoint use of an unbiased analysis of the whole brain after injury together with a population-based statistical analysis of sham-control brains as one approach that has been used in clinical research to help resolve this issue. The approach produces two volumes of pathology that are outside the normal range of sham brains, and can be interpreted as whole brain burden of injury. Using diffusion weighted imaging derived scalars from a tensor analysis of data acquired from adult, male rats at 2, 9 days, 1 and 5 months after lateral fluid percussion injury (LFPI) and in shams (n=73 and 12, respectively), we compared a data-driven, z-score mapping method to a whole brain and white matter-specific analysis, as well as an ROI-based analysis with brain regions preselected by virtue of their large group effect sizes. We show that the data-driven approach is statistically robust, providing the advantage of a large group effect size typical of a ROI analysis of mean scalar values derived from the tensor in regions of gross injury, but without the large multi-region statistical correction required for interrogating multiple brain areas, and without the potential bias inherent with using preselected ROIs. We show that the technique correctly captures the expected longitudinal time-course of the diffusion scalar volumes based on the spatial extent of the pathology and the known temporal changes in scalar values in the LFPI model.

neuroscience↗

bioRxiv2024

The Surgical Method of Craniectomy Differentially Affects Acute Seizures, Brain Deformation and Behavior in a TBI Animal Model

Traumatic brain injury (TBI) is the leading cause of morbidity and mortality worldwide. Multiple injury models have been developed to study this neurological disorder. One such model is the lateral fluid-percussion injury (LFPI) rodent model. The LFPI model can be generated with different surgical procedures that could affect the injury and be reflected in neurobehavioral dysfunction and acute EEG changes. A craniectomy was performed either with a trephine hand drill or with a trephine electric drill that was centered over the left hemisphere of adult, male Sprague Dawley rats. Sham craniectomy groups were assessed by hand-drilled (ShamHMRI) and electric-drilled (ShamEMRI) to evaluate by MRI. Then, TBI was induced in separate groups (TBIH) and (TBIE) using a fluid-percussion device. Sham-injured rats (ShamH/ShamE) underwent the same surgical procedures as the TBI rats. During the same surgery session, rats were implanted with screw and microwire electrodes positioned in the neocortex and hippocampus and the EEG activity was recorded 24 hours for the first 7 days after TBI for assessing the acute EEG seizure and Gamma Event Coupling (GEC). The electric drilling craniectomy induced greater tissue damage and sensorimotor deficits compared to the hand drill. Analysis of the EEG revealed acute seizures in at least one animal from each group after the procedure. Both TBI and Sham rats from the electric drill groups had a significant greater total number of seizures than the animals that were craniectomized manually (p<0.05). Similarly, EEG functional connectivity was lower in ShamE compared to ShamH rats. These results suggest that electrical versus hand drilling craniectomies produce cortical injury in addition to the LFPI which increases the likelihood for acute post-traumatic seizures. Differences in the surgical approach could be one reason for the variability in the injury that makes it difficult to replicate results between preclinical TBI studies.

neuroscience↗

bioRxiv2024

Different Trajectories of Functional Connectivity Captured with Gamma-Event Coupling and Broadband Measures of EEG in the Rat Fluid Percussion Injury Model.

Functional connectivity (FC) after TBI is affected by an altered excitatory-inhibitory balance due to neuronal dysfunction, and the mechanistic changes observed could be reflected differently by contrasting methods. Local gamma event coupling FC (GEC-FC) is believed to represent multiunit fluctuations due to inhibitory dysfunction, and we hypothesized that FC derived from widespread, broadband amplitude signal (BBA-FC) would be different, reflecting broader mechanisms of functional disconnection. We tested this during sleep and active periods defined by high delta and theta EEG activity, respectively, at 1,7 and 28d after rat fluid-percussion-injury (FPI) or sham injury (n=6/group) using 10 indwelling, bilateral cortical and hippocampal electrodes. We also measured seizure and high-frequency oscillatory activity (HFOs) as markers of electrophysiological burden. BBA-FC analysis showed early hyperconnectivity constrained to ipsilateral sensory-cortex-to-CA1-hippocampus that transformed to mainly ipsilateral FC deficits by 28d compared to shams. These changes were conserved over active epochs, except at 28d when there were no differences to shams. In comparison, GEC-FC analysis showed large regions of hyperconnectivity early after injury within similar ipsilateral and intrahemispheric networks. GEC-FC weakened with time, but hyperconnectivity persisted at 28d compared to sham. Edge- and global connectivity measures revealed injury-related differences across time in GEC-FC as compared to BBA-FC, demonstrating greater sensitivity to FC changes post-injury. There was no significant association between sleep fragmentation, HFOs, or seizures with FC changes. The within-animal, spatial-temporal differences in BBA-FC and GEC-FC after injury may represent different mechanisms driving FC changes as a result of primary disconnection and interneuron loss. Significance statementThe present study adds to the understanding of functional connectivity changes in preclinical models of traumatic brain injury. In previously reported literature, there is heterogeneity in the directionality of connectivity changes after injury, resulting from factors such as severity of injury, frequency band studied, and methodology used to calculate FC. This study aims to further clarify differential mechanisms that result in altered network topography after injury, by using Broadband Amplitude-Derived FC and Gamma Event Coupling-Derived FC in EEG. We found post-injury changes that differ in complexity and directionality between measures at and across timepoints. In conjunction with known results and future studies identifying different neural drivers underlying these changes, measures derived from this study could provide useful means from which to minimally-invasively study temporally-evolving pathology after TBI.

neuroscience↗