Faculty Bibliography

Anatomical connections link the cerebellar cortex with multiple sensory, motor, association, and paralimbic cerebral areas. The majority of fibers that exit cerebellar cortex synapse in dentate nuclei (DN) before reaching extracerebellar structures such as cerebral cortex, but the functional neuroanatomy of human DN remains largely unmapped. Neuroimaging research has redefined broad categories of functional division in the human brain showing that primary processing, attentional (task positive) processing, and default-mode (task negative) processing are three central poles of neural macroscale functional organization. This broad spectrum of human neural processing categories is represented not only in the cerebral cortex, but also in the thalamus, striatum, and cerebellar cortex. Whether functional organization in DN obeys a similar set of macroscale divisions, and whether DN are yet another compartment of representation of a broad spectrum of human neural processing categories, remains unknown. Here, we show for the first time that human DN are optimally divided into three functional territories as indexed by high spatio-temporal resolution resting-state MRI in 77 healthy humans, and that these three distinct territories contribute uniquely to default-mode, salience-motor, and visual cerebral cortical networks. Our findings provide a systems neuroscience substrate for cerebellar output to influence multiple broad categories of neural control.

OBJECTIVES/OBJECTIVE:The aim of this study is to analyze changes in the Social Determinants of Health (SDH) in patients undergoing epilepsy surgery in Mexico. MATERIALS AND METHODS/METHODS:We retrospectively analyzed 102 adult patients who underwent brain resection for focal epilepsy (2002-2014) with at least 4 years of follow-up; described clinical variables (age, race, sex, age of onset of epilepsy, age at the time of surgery, type of surgery, side of surgery) and sociodemographic variables including education, income, race/ethnicity, occupation, and marital status. STATISTICAL ANALYSIS/METHODS:Descriptive and inferential statistics were used. RESULTS:54.9% (56) of the participants were women, with a mean age of 38.2 (±9.6) years at the time of the survey. The average and mean duration of drug-resistant epilepsy before surgery after diagnosis was 19.6 (±9.3) years; 77.9% (77) had temporal lobe surgeries and 24.5% (25) had extra-temporal lobe surgeries; 80.4% (82) and 19.6% (20) of patients were classified as Engel I and Engel II, respectively, with at least 4 years of postoperative follow-up. Education level (26.9%, p=<0.001), employment rate (4.9%, p= <0.001), and income (9.8%, p = 0.024) increased after surgery; 20.5% of patients were married after surgery. CONCLUSIONS:Following focal resective epilepsy surgery there was a significant increase in the education level, financial income and employment at 4 years' postoperative follow-up.

Background and Purpose- We aimed to compare functional and procedural outcomes of patients with acute ischemic stroke with none-to-minimal (modified Rankin Scale [mRS] score, 0-1) and moderate (mRS score, 2-3) prestroke disability treated with mechanical thrombectomy. Methods- Consecutive adult patients undergoing mechanical thrombectomy for an anterior circulation stroke were prospectively identified at 2 comprehensive stroke centers from 2012 to 2018. Procedural and 90-day functional outcomes were compared among patients with prestroke mRS scores 0 to 1 and 2 to 3 using χ², logistic, and linear regression tests. Primary outcome and significant differences in secondary outcomes were adjusted for prespecified covariates. Results- Of 919 patients treated with mechanical thrombectomy, 761 were included and 259 (34%) patients had moderate prestroke disability. Ninety-day mRS score 0 to 1 or no worsening of prestroke mRS was observed in 36.7% and 26.7% of patients with no-to-minimal and moderate prestroke disability, respectively (odds ratio, 0.63 [0.45-0.88], P=0.008; adjusted odds ratio, 0.90 [0.60-1.35], P=0.6). No increase in the disability at 90 days was observed in 22.4% and 26.7%, respectively. Rate of symptomatic intracerebral hemorrhage (7.3% versus 6.2%, P=0.65), successful recanalization (86.7% versus 83.8%, P=0.33), and median length of hospital stay (5 versus 5 days, P=0.06) were not significantly different. Death by 90 days was higher in patients with moderate prestroke disability (14.3% versus 40.3%; odds ratio, 4.06 [2.82-5.86], P<0.001; adjusted odds ratio, 2.83 [1.84, 4.37], P<0.001). Conclusions- One-third of patients undergoing mechanical thrombectomy had a moderate prestroke disability. There was insufficient evidence that functional and procedural outcomes were different between patients with no-to-minimal and moderate prestroke disability. Patients with prestroke disability were more likely to die by 90 days.

Long-lasting, high-resolution neural interfaces that are ultrathin and flexible are essential for precise brain mapping and high-performance neuroprosthetic systems. Scaling to sample thousands of sites across large brain regions requires integrating powered electronics to multiplex many electrodes to a few external wires. However, existing multiplexed electrode arrays rely on encapsulation strategies that have limited implant lifetimes. Here, we developed a flexible, multiplexed electrode array, called "Neural Matrix," that provides stable in vivo neural recordings in rodents and nonhuman primates. Neural Matrix lasts over a year and samples a centimeter-scale brain region using over a thousand channels. The long-lasting encapsulation (projected to last at least 6 years), scalable device design, and iterative in vivo optimization described here are essential components to overcoming current hurdles facing next-generation neural technologies.

BACKGROUND:Observe the relationship of anxiety and depression on quality of life outcomes after open and endovascular cerebrovascular procedures. METHODS:We retrospectively analyzed 349 patients who underwent a procedure for aneurysm, arteriovenous malformation, intraparenchymal hemorrhage, carotid stenosis, acute stroke, and conventional catheter angiogram over three years at a community hospital. We correlated pre-procedural anxiety and depression with Global Physical Health, Global Mental Health, and Modified Rankin Scale scores. We performed univariate and multivariate linear and logistic regression analyses adjusting for past medical history and sociodemographic factors. RESULTS:Anxiety or depression occurred in 18 % of patients. Patients with anxiety or depression were more likely to be female (81% vs 60.8%; p = 0.002) and younger (54 vs. 59 years old; p = 0.025). The groups did not differ in type or urgency of procedure, smoking or history of diabetes. Patients with anxiety or depression reported lower mental health scores at 30 days (45.1 vs 48.2; p = 0.002) post-procedure. In multivariate analyses, anxious or depressed patients had worse mental health scores at 30 days (t = - 2.893; p = 0.008) than those who did not have a history of anxiety or depression. There was no difference between groups in length of stay, mortality, physical health t-scores, functionality scores, or six month quality of life outcomes. CONCLUSIONS:Patients undergoing cerebrovascular procedures who self-reported anxiety or depression showed a significant difference in mental health outcomes at 30 days, but six month mental health and other medical and functional outcomes measures were similar to patients without these diagnoses.

PURPOSE/OBJECTIVE:Rindopepimut is a vaccine targeting the tumor-specific EGF driver mutation, EGFRvIII. The ReACT study investigated whether the addition of rindopepimut to standard bevacizumab improved outcome for patients with relapsed, EGFRvIII-positive glioblastoma. PATIENTS AND METHODS/METHODS:In this double-blind, randomized, phase II study (NCT01498328) conducted at 26 hospitals in the United States, bevacizumab-naïve patients with recurrent EGFRvIII-positive glioblastoma were randomized to receive rindopepimut or a control injection of keyhole limpet hemocyanin, each concurrent with bevacizumab. The primary endpoint was 6-month progression-free survival (PFS6) by central review with a one-sided significance of 0.2. RESULTS:< 0.0001). CONCLUSIONS:.