Biology subjects

McLain, N.

Publications and source records attributed to McLain, N..

3 recordsLinked to original sources

bioRxiv2026

Functional Connectivity Differences Underly Variable Centralized Symptom Relief After Hysterectomy

Approximately 1 in 4 women with chronic pelvic pain (CPP) report persistent pelvic pain after hysterectomy. Centralized symptoms-fatigue, multisite pain, and sleep disturbance, quantified using the Fibromyalgia Survey Score (FSS)-often co-occur with this risk, but the trajectory of centralized symptom burden after surgery, independent of pelvic pain outcome, is not well understood. Whether presurgical differences in central nervous system pain processing distinguish women whose centralized symptoms improve (improvers) from those whose do not (non-improvers) has not been tested. In this observational study, we assessed whether individuals who do and do not report improvement in FSS scores six months post-operatively differ in their baseline/pre-operative phenotypes and brain function. Sensory sensitivity scores were significantly higher in non-improvers than in improvers at baseline. We identified no significant, presurgical differences in age, average pelvic pain intensity, widespread pain, or pain interference between improvers and non-improvers. Functional connectivity was examined at rest and during the application of a distal, sustained pressure pain. We identified no significant group differences at rest. During sustained pressure pain, non-improvers showed greater connectivity than improvers between primary somatosensory cortex and posterior thalamic seeds with frontal, motor, cerebellar and limbic regions, but lower connectivity between the periaqueductal gray and subgenual cingulate cortex. Non-improvers also showed a greater pain-evoked increase in connectivity between the pelvic and leg representations of the primary sensory cortex and other sensorimotor regions in the pain-versus-rest contrast. Overall, non-improvers showed increased functional connectivity between regions associated with the multisensory integration of ascending pain, and decreased connectivity between regions associated with descending pain modulation. In exploratory analyses, some of these connections were additionally associated with symptom burden: sensory sensitivity, number of painful regions, and pain interference. This work may inform mechanisms of persistent symptom burden and guide surgical decision-making in patients with high central sensitization.

neuroscience↗

bioRxiv2026

Concordance between the fast and efficient mixed-effects algorithm (FEMA) and conventional mixed-effects modeling for whole-brain connectivity in longitudinal chronic pain

Researchers increasingly have access to neuroimaging data with repeated measures within subjects. Linear mixed-effects modeling offers a valuable way to analyze such data, but its application remains limited in the neuroimaging literature due to high computational cost and a lack of mainstream analysis packages. Here we benchmark a recently published algorithm, the Fast and Efficient Mixed-Effects Algorithm (FEMA), against a conventional implementation (MATLAB's fitlme, restricted maximum likelihood) across 94,830 functional connectivity edges. In contrast to the Adolescent Brain Cognitive Development (ABCD) Study Dataset used in the development and testing of FEMA, the dataset used in the current analysis has a smaller sample size (n = 378) and comprises individuals with chronic pelvic pain scanned at up to four visits over three years. Despite these differences, the two implementations produced highly concordant results: fixed-effect estimates and test statistics correlated at r [≥] 0.999 (Lin's concordance correlation coefficient [≥] 0.999), and the two approaches reached the same statistical conclusion for 99.98% of edges. FEMA completed each analysis roughly 20 times faster. Agreement was weaker for the estimated variance components, where FEMA attributed systematically less variance to the participant random effect, yielding a slightly lower intraclass correlation in approximately 82% of edges. We further show that most residual disagreement reflected FEMA's default variance-grid resolution rather than the estimator itself, and could be eliminated at negligible computational cost. These findings support the use of FEMA for connectome-wide analysis of repeated-measures neuroimaging data.

neuroscience↗

bioRxiv2022

Neuronal membrane proteasomes homeostatically regulate neural circuit activity in vivo and are required for learning-induced behavioral plasticity

Protein degradation is critical for brain function through processes that remain poorly understood. Here we investigated the in vivo function of a recently reported neuronal membrane-associated proteasome (NMP) in the brain of Xenopus laevis tadpoles. We demonstrated that NMPs are present in the tadpole brain with biochemistry and electron microscopy, and showed that they actively degrade neuronal activity-induced nascent proteins. Using in vivo calcium imaging in the optic tectum, we showed that acute inhibition of NMP function rapidly increased spontaneous neuronal activity, resulting in hyper-synchronization among tectal neurons. At the circuit level, inhibiting NMPs abolished learning-dependent improvement in a visuomotor behavior paradigm in live animals. Our data provide the first in vivo characterization of NMP functions in the vertebrate nervous system and suggest that NMP-mediated degradation of activity-induced nascent proteins may serve as a homeostatic modulatory mechanism in neurons that is critical for regulating neuronal activity and experience-dependent circuit plasticity.

neuroscience↗