Faculty Bibliography

INTRODUCTION/BACKGROUND:Alzheimer's disease (AD), primary age-related tauopathy (PART), and chronic traumatic encephalopathy (CTE) all feature hyperphosphorylated tau (p-tau)-immunoreactive neurofibrillary degeneration, but differ in neuroanatomical distribution and progression of neurofibrillary degeneration and amyloid beta (Aβ) deposition. METHODS:We used Nanostring GeoMx Digital Spatial Profiling to compare the expression of 70 proteins in neurofibrillary tangle (NFT)-bearing and non-NFT-bearing neurons in hippocampal CA1, CA2, and CA4 subregions and entorhinal cortex of cases with autopsy-confirmed AD (n = 8), PART (n = 7), and CTE (n = 5). RESULTS:There were numerous subregion-specific differences related to Aβ processing, autophagy/proteostasis, inflammation, gliosis, oxidative stress, neuronal/synaptic integrity, and p-tau epitopes among these different disorders. DISCUSSION/CONCLUSIONS:These results suggest that there are subregion-specific proteomic differences among the neurons of these disorders, which appear to be influenced to a large degree by the presence of hippocampal Aβ. These proteomic differences may play a role in the differing hippocampal p-tau distribution and pathogenesis of these disorders. HIGHLIGHTS/CONCLUSIONS:Alzheimer's disease neuropathologic change (ADNC), possible primary age-related tauopathy (PART), definite PART, and chronic traumatic encephalopathy (CTE) can be differentiated based on the proteomic composition of their neurofibrillary tangle (NFT)- and non-NFT-bearing neurons. The proteome of these NFT- and non-NFT-bearing neurons is largely correlated with the presence or absence of amyloid beta (Aβ). Neurons in CTE and definite PART (Aβ-independent pathologies) share numerous proteomic similarities that distinguish them from ADNC and possible PART (Aβ-positive pathologies).

BACKGROUND:This study primarily aimed to explore the etiology of the phenotypic relationships between personality traits and executive functions. We assessed common genetic and environmental sources of variance in these phenomena by examining different dimensions of the Five Factor Model (FFM) and executive function factors. An additional research question focused on whether specific facets within the FFM share a greater genetic overlap with executive functions compared to broader personality dimensions. METHODS:The NEO-PI-R, the Wisconsin Card Sorting Test, the Trail Making Test, and verbal fluency tests were applied to a sample of 468 twins from the Serbian Twin Advanced Registry (153 monozygotic twin pairs). RESULTS:Several facets from all domains had significant genetic associations with executive functions, with Ideas and Values showing the highest positive correlations, and Order and Vulnerability showing the highest negative genetic correlations. Most phenotypic associations between the two domains of individual differences were almost entirely explained by shared genetic influences. CONCLUSIONS:These findings underscore the importance of examining personality traits at the facet level, as facet-level analysis provides more detailed insights into the relationship between personality and executive functions than broader personality dimensions. The results emphasize the role of shared genetic influences in shaping both personality and executive abilities, suggesting that future research should investigate the underlying neural mechanisms driving these associations.

BACKGROUND:Arteriovenous malformations (AVMs) are uncommon cerebral lesions that can cause significant neurological complications. Surgical resection is the gold standard for treatment, but endovascular embolization and stereotactic radiosurgery (SRS) are viable alternatives. OBJECTIVE:To compare the outcomes of endovascular embolization versus SRS in the treatment of AVMs with Spetzler-Martin grades I-III. METHODS:This study combined retrospective data from 10 academic institutions in North America and Europe. Patients aged 1 to 90 years who underwent endovascular embolization or SRS for AVMs with Spetzler-Martin grades I-III between January 2010 and December 2023 were included. RESULTS:The study included 244 patients, including 84 who had endovascular embolization and 160 who had SRS. Before propensity score matching (PSM), complete obliteration at the last follow-up was achieved in 74.5% of the SRS group compared with 57.8% of the embolization group (OR=0.47; 95% CI 0.26 to 0.48; P=0.01). After propensity score matching, SRS still achieved significantly higher occlusion rates at last follow-up (78.9% vs 55.3%; OR=0.32; 95% CI 0.12 to 0.90; P=0.03).Hemorrhagic complications were higher in the embolization group than in the SRS group, although this difference did not reach statistical significance after PSM (13.2% vs 2.6%; OR=5.6; 95% CI 0.62 to 50.47; P=0.12). Similarly, re-treatment rate was higher in the embolization group (10.5% vs 5.3%; OR=2.11; 95% CI 0.36 to 12.31; P=0.40) compared with the SRS group. CONCLUSION/CONCLUSIONS:Our findings indicate that SRS has a significantly higher obliteration rate at last follow-up compared with endovascular embolization. Also, SRS has a higher tendency for fewer hemorrhagic complications and lower re-treatment rate. Further prospective studies are needed.

BACKGROUND:With transradial access (TRA) being more progressively used in neuroendovascular procedures, we compared TRA with transfemoral access (TFA) in middle meningeal artery embolization (MMAE) for chronic subdural hematoma (cSDH). METHODS:Consecutive patients undergoing MMAE for cSDH at 14 North American centers (2018-23) were included. TRA and TFA groups were compared using propensity score matching (PSM) controlling for: age, sex, concurrent surgery, previous surgery, hematoma thickness and side, midline shift, and pretreatment antithrombotics. The primary outcome was access site and overall complications, and procedure duration; secondary endpoints were surgical rescue, radiographic improvement, and technical success and length of stay. RESULTS:872 patients (median age 73 years, 72.9% men) underwent 1070 MMAE procedures (54% TFA vs 46% TRA). Access site hematoma occurred in three TFA cases (0.5%; none required operative intervention) versus 0% in TRA (P=0.23), and radial-to-femoral conversion occurred in 1% of TRA cases. TRA was more used in right sided cSDH (58.4% vs 44.8%; P<0.001). Particle embolics were significantly higher in TFA while Onyx was higher in TRA (P<0.001). Following PSM, 150 matched pairs were generated. Particles were more utilized in the TFA group (53% vs 29.7%) and Onyx was more utilized in the TRA group (56.1% vs 31.5%) (P=0.001). Procedural duration was longer in the TRA group (median 68.5 min (IQR 43.1-95) vs 59 (42-84); P=0.038), and radiographic success was higher in the TFA group (87.3% vs 77.4%; P=0.036). No differences were noted in surgical rescue (8.4% vs 10.1%, P=0.35) or technical failures (2.4% vs 2%; P=0.67) between TFA and TRA. Sensitivity analysis in the standalone MMAE retained all associations but differences in procedural duration. CONCLUSIONS:In this study, TRA offered comparable outcomes to TFA in MMAE for cSDH in terms of access related and overall complications, technical feasibility, and functional outcomes. Procedural duration was slightly longer in the TRA group, and radiographic success was higher in the TFA group, with no differences in surgical rescue rates.

Syntax, the abstract structure of language, is a hallmark of human cognition. Despite its importance, its neural underpinnings remain obscured by inherent limitations of non-invasive brain measures and a near total focus on comprehension paradigms. Here, we address these limitations with high-resolution neurosurgical recordings (electrocorticography) and a controlled sentence production experiment. We uncover three syntactic networks that are broadly distributed across traditional language regions, but with focal concentrations in middle and inferior frontal gyri. In contrast to previous findings from comprehension studies, these networks process syntax mostly to the exclusion of words and meaning, supporting a cognitive architecture with a distinct syntactic system. Most strikingly, our data reveal an unexpected property of syntax: it is encoded independent of neural activity levels. We propose that this "low-activity coding" scheme represents a novel mechanism for encoding information, reserved for higher-order cognition more broadly.

Sentence production is the uniquely human ability to transform complex thoughts into strings of words. Despite the importance of this process, language production research has primarily focused on single words. It remains an untested assumption that insights from this literature generalize to more naturalistic utterances like sentences. Here, we investigate this using high-resolution neurosurgical recordings (ECoG) and an overt production experiment where patients produce six words in isolation (picture naming) and in sentences (scene description). We trained machine learning models to identify the unique brain activity pattern for each word during picture naming, and used these patterns to decode which words patients were processing while they produced sentences. Our findings reveal that words share cortical representations across tasks. In sensorimotor cortex, words were consistently activated in the order in which they were said in the sentence. However, in inferior and middle frontal gyri (IFG and MFG), the order in which words were processed depended on the syntactic structure of the sentence. This dynamic interplay between sentence structure and word processing reveals that sentence production is not simply a sequence of single word production tasks, and highlights a regional division of labor within the language network. Finally, we argue that the dynamics of word processing in prefrontal cortex may impose a subtle pressure on language evolution, explaining why nearly all the world's languages position subjects before objects.

BACKGROUND:The Uniform Determination of Death Act requires brain death/death by neurologic criteria (BD/DNC) determination to be in accordance with "accepted medical standards." The medical organizations responsible for delineating these guidelines are only specified statutorily in two states. State health organizations (SHOs) are composed of policy experts and medical professionals who are responsible for addressing medical, ethical, and legislative problems related to health. We sought to evaluate information publicly available on SHO websites regarding BD/DNC. METHODS:From December 2023 to August 2024, we searched SHO (health department, medical board, medical society, and hospital association) websites for the 48 states without statutory guidance regarding what constitutes accepted medical standards for information regarding BD/DNC using the terms "brain death," "brain stem," and "determination of death." All posts related to BD/DNC were reviewed and categorized via thematic analysis. RESULTS:Of the 192 SHO websites searched, there were 35 from 28 states that provided information regarding BD/DNC: 14 medical societies, 12 health departments, 8 hospital associations, and 1 medical board. Of these 35 SHOs, 12 referenced the state's legal statute, 11 referenced hospital/state/model policies or guidance, 3 referenced both legal statutes and hospital/state/model policies or guidelines, 3 referenced explicit support for standardized BD/DNC guidelines, and 6 made other mention of BD/DNC. New York was the only state with an SHO that provided clear guidance regarding accepted medical standards for BD/DNC determination. CONCLUSIONS:For most states, the accepted medical standards for BD/DNC determination are not identified on SHO websites or statutorily. This contributes to inconsistencies across hospital BD/DNC determination policies, leading to medical, ethical, and legal challenges. Delineation of the accepted medical standards for BD/DNC determination in each state could help facilitate consistency and accuracy in BD/DNC determination, prevent false positive determinations of death, and promote public trust in BD/DNC determination and the medical system overall.