Faculty Bibliography

Deep venous drainage (DVD) is considered a negative prognostic factor in AVM surgery, yet its effect on postoperative functional decline remains incompletely defined. This study evaluates whether DVD predicts worsened functional status after surgical resection of Spetzler-Martin Grade II-III AVMs. This retrospective multicenter study analyzed 129 patients with Spetzler-Martin Grade II-III AVMs across nine centers in North America and Europe who underwent primary surgical resection. We excluded cases with prior endovascular or stereotactic interventions. The primary outcome measured was poor functional status, defined as modified Rankin Scale (mRS) score 3-6 at last follow up. Among 129 patients with Spetzler-Martin Grade II-III AVMs, 38 (29.5%) exhibited deep venous drainage (DVD). Poor functional outcome (mRS ≥ 3) at last follow-up occurred in 14 patients (10.9%). This occurred in 6 of 38 patients with DVD (15.8%) compared with 8 of 91 without DVD (8.8%; Fisher's exact p = 0.244). On univariate Firth-penalized logistic regression, DVD was not significantly associated with poor outcome (OR 1.96, 95% CI 0.65-5.89; p = 0.228). In the primary reduced Firth model adjusting for age and pre-existing functional disability, DVD was independently associated with poor outcome (OR 6.87, 95% CI 1.07-44.20; p = 0.042). Increasing age (OR 1.08 per year, 95% CI 1.02-1.13; p = 0.004) and pre-existing functional disability (OR 6.53, 95% CI 1.63-26.22; p = 0.008) were also independently associated with poor outcome. DVD is associated with functional decline following surgical resection of Spetzler-Martin Grade II-III AVMs after adjustment for age and pre-existing functional disability.

OBJECTIVE:This study was undertaken to evaluate whether seizure freedom in pregnancy predicts seizure freedom in the postpartum period in women with epilepsy (WWE). Prior studies have shown that seizure freedom prior to conception strongly predicts seizure freedom during pregnancy. The postpartum period is considered especially vulnerable to recurrent seizures given rapid hormonal changes, shifting antiseizure medication pharmacokinetics, and disrupted sleep. There is a lack of sufficient data on whether seizure freedom during pregnancy predicts postpartum outcomes. METHODS:Pregnant WWE (aged 14-45 years) were enrolled at <20 weeks gestation in the prospective Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs study. Participants completed electronic daily seizure and medication diaries with study visits each trimester, and at 6-12 weeks and 6 and 9 months postpartum. Participants also reported retrospective seizure frequency for the 9 months preconception. We used logistic regression to assess whether seizure freedom during pregnancy predicted seizure freedom postpartum, with additional analyses by seizure types. In participants with seizures during pregnancy, we evaluated median percent change in seizure frequency. RESULTS:This analysis included 331 pregnant WWE. Overall, 60.7% were seizure-free during pregnancy and 61.0% postpartum. Seizure freedom during pregnancy strongly predicted seizure freedom postpartum (odds ratio [OR] = 6.78, 95% confidence interval [CI] = 4.15-11.1, p < .0001), with a predictive value of 78% (95% CI = 72%-84%). Retrospectively reported preconception seizure freedom was also independently associated with postpartum seizure freedom (OR = 5.84, 95% CI = 3.57-9.58, p < .0001). Long-term seizure freedom during pregnancy and preconception was associated with 85% postpartum seizure freedom, whereas long-term presence of seizures was associated with only 36% postpartum seizure freedom. There were no significant differences by seizure type. Among participants with seizures during pregnancy, median postpartum seizure frequency declined by 77% (interquartile range = seizure-free to 31% reduced). SIGNIFICANCE/CONCLUSIONS:Our data demonstrated that seizure freedom during pregnancy was a robust predictor of seizure freedom during the postpartum period. These data can be used to counsel patients about seizure risk in the postpartum period.

We present a functional magnetic resonance (fMRI) dataset collected as part of an adversarial collaboration aimed at arbitrating between the Global Neuronal Workspace theory (GNWT) and the Integrated Information Theory (IIT) of consciousness. Participants (N = 118) were presented with suprathreshold visual stimuli belonging to four different categories (faces, objects, letters, false fonts) with three orientations (front, left, right view), and three durations (0.5, 1.0, 1.5 seconds). Participants were asked to identify infrequent targets that changed in each block, thereby rendering two categories task-relevant and two task-irrelevant. The simplicity of the experimental design and of the task given to the participants ensures that these data are broadly reusable. Besides testing predictions from other theories of consciousness, these data can be used to examine various aspects of visual processing. The anonymized data were converted to Brain Imaging Data Structure (BIDS), and can be easily accessed through a web platform or an API. The dataset contains quality reports, demographics, behavioral performance, and eye-tracking data. We also provide code for preprocessing and analyzing the data.

Understanding speech in noisy environments is difficult for many people, and current hearing aids often fail because they amplify all sounds rather than the talker of interest. Auditory attention decoding (AAD) offers a potential solution by using the listener's brain signals to identify and enhance the attended speaker, but it has been unclear whether this can provide real-time perceptual benefits. Here we used high-resolution intracranial electroencephalography in patients undergoing neurosurgical procedures to implement a closed-loop system that achieves the decoding fidelity necessary to dynamically amplify the attended talker. Across multiple experiments, the system improved speech intelligibility, reduced listening effort and was consistently preferred by subjects. It also tracked both instructed and self-initiated attention shifts. By providing direct evidence that a real-time, brain-controlled hearing system can enhance perception, this work establishes a key performance benchmark for future auditory brain-computer interfaces and advances AAD from a theoretical concept to a validated solution for personalized assistive hearing.

Blood inflammatory marker studies in aging and Alzheimer's disease (AD) research have faced numerous interpretative and methodological challenges that have hindered the field's understanding of the relationship between immune network regulation/dysregulation and aging health factors. We examined how blood inflammation markers directly relate to each other in typical aging, cognitively unimpaired adults using a conditional network analytic modeling approach. We further evaluated how blood inflammation networks relate to key aging risk factors by decomposing the networks into eigenvectors with associated hub proteins and then evaluated the associations of the resulting eigenproteins with demographic information, core biomarkers of AD pathobiology in CSF and blood, and immune health history. Networks of blood inflammation markers showed both divergent and convergent relationships with outcomes, including strong associations between a CXCL5-driven blood inflammation network and age, sex, and CSF Aβ42/Aβ40, and an IL-6- and FGF-21-driven network and sex, CSF Aβ42/Aβ40, and Qalb (CSF-serum albumin ratio). An IFN-gamma- and CXCL9-driven network was associated with both age and CSF Aβ42/Aβ40, whereas blood inflammation networks with hub proteins of CXCL11/CXCL9 and CCL19/CCL4, respectively, were associated solely with sex. Finally, an MCP-3-, MCP-4-, and CXCL6-driven network was associated with cumulative surgical procedure exposures. Despite associations between CSF Aβ42/Aβ40 and multiple networks, plasma Aβ42/Aβ40 was not significantly associated with any blood inflammatory network. Our findings highlight the importance and the challenges of inferring immune pathophysiology from blood-based markers; mirroring the complex pleiotropic biology of inflammation, blood inflammatory markers show associations with multiple demographic and salient health factors in aging adults.

BACKGROUND:Elp1, a subunit of the Elongator complex, is essential for tRNA modification and neuronal development. Mutations in ELP1 underlie familial dysautonomia (FD), a disorder marked by sensory and autonomic neuropathy. While loss of Elp1 disrupts trigeminal ganglion formation and survival, the downstream molecular consequences remain poorly defined. RESULTS:We performed quantitative proteomic profiling of trigeminal ganglia from Elp1 conditional knockout (CKO) and control embryos at E13.5. Across 5650 detected proteins, 25 were significantly up-regulated and 26 down-regulated in Elp1 CKO embryos. EnrichR analysis revealed enrichment of up-regulated proteins in amino acid transport and tRNA aminoacylation pathways, with links to neuromuscular and neuropathic diseases. Down-regulated proteins were associated with RNA modification, cholesterol biosynthesis, and synaptic organization. Validation by immunohistochemistry confirmed decreased expression of the neurotrophic receptor Gfra3 and the neuropeptide Galanin, and increased levels of the chromatin regulator Chd1, in Elp1 CKO embryos relative to controls. CONCLUSIONS:These findings demonstrate that Elp1 loss disrupts metabolic, RNA modification, and neurotrophic signaling pathways in the developing trigeminal ganglion. Proteomic analysis thus provides new insight into the molecular consequences of Elp1 deficiency and highlights candidate mechanisms contributing to sensory neuron vulnerability in FD.