bluuebunny/crossref_metadata_2025_split huggingface dataset:
478 Single-Neuron and Columnar Computations in the Human Prefrontal Cortex Underlying Transformations From Conscious Visual Perception to Speech Production
Authors: Munoz William , Williams Ziv 
Published: March 2024

INTRODUCTION:
The basic functional unit of the mammalian neocortex is the cortical column. It consists of a vast diversity of circuit elements and interconnected layers supporting a range of computations for cognitive functions. While much progress has been made in our understanding of its functional architecture in animal models, its role in complex, uniquely human cognitive processes remain unknown.

METHODS:
We utilized a new columnar recording approach in humans participating of cognitive tasks, while undergoing awake neurosurgical procedures. The novelty of this approach hinged on utilizing state-of-the-art Neuropixels probes for our recordings, a silicon-based electrophysiology recording electrodes with high channel count and recording site density. This technology allows us to measure neural activity with single cell resolution throughout the neocortical column and its layers, and at a scale that is far beyond the capabilities of current clinically-approved devices. The participants performed a naturalistic visual priming-based sentence production task that provided them with pictorial representations of events that had to be articulated in specific form and order.

RESULTS:
We observed distinct spatiotemporal activity dynamics throughout the cortical column in the language-dominant prefrontal cortex that encoded a preparatory mode for speech generation, as well as visual perception and sentence construction processing stages during natural speech. Furthermore, we observed the emergence of this columnar activity pattern with optimal visual inspection of presented images (by high resolution eye and pupil tracking) and associated improved performance during the task.

CONCLUSIONS:
These results highlight a functional organization of the cortical column in the human prefrontal cortex subserving sensory-motor transformations for visual conscious perception and speech production, with profound implications for future brain machine interfaces that aim to restore complex human cogntive functions.
482 Identification of Candidate Neural Biomarkers of Obsessive-compulsive Symptom Intensity and Response to DBS
Authors: Provenza Nicole , Katlowitz Kalman , Rajesh Sameer Vikram , Diab Nabeel , Reyes Gabriel , Allam Anthony , Reddy Sandesh , Hinduja Saurabh , Avendano-Ortega Michelle , McKay Sarah , Giridharan Nisha , Banks Garrett P. , Shofty Ben , Storch Eric , Cohn Jeffrey , Goodman Wayne , Sheth Sameer A. 
Published: March 2024

INTRODUCTION:
Despite the success of DBS for the treatment of refractory OCD, there are currently no robust neural signatures for obsessive-compulsive (OC) symptoms or initial mood and energy improvements associated with DBS. This gap may be due to limited opportunities available for conducting intracranial electrophysiological recordings during natural symptom fluctuations. Recently available DBS platforms offer a way over this hurdle, allowing for streaming of intracranial local field potentials (LFP) at home and in the clinic.

METHODS:
We conducted longitudinal intracranial recordings in 10 patients with refractory OCD implanted with recording-capable DBS devices targeted to ventral capsule/ventral striatum (VC/VS). Five of the 10 were additionally implanted with ECoG strip electrodes over the orbitofrontal cortex (OFC). We captured LFP at home during naturalistic exposures to OCD triggers and in the clinic during variations in stimulation amplitude.

RESULTS:
All 5 participants who have completed the study so far are clinical responders to DBS therapy. Using the intracranial data collected during OCD exposures, we identified low delta-band power as a candidate neural biomarker of OC symptom intensity during symptom provocations (left VC/VS: R = -0.59, p = 0.01; right VC/VS: R = -0.56, p = 0.04). Electrophysiological analysis of acute response to stimulation revealed a narrow band increase in 30 Hz power specific to lateral OFC that was associated with increased talkativeness and approach behaviors that are typical harbingers of clinical response

CONCLUSIONS:
These signals have potential utility for classification of symptom intensity and increased mood and energy to enable adaptive DBS systems for OCD. Our data suggest that the neural biomarkers of these two clinical features might be separable, thus possibly allowing for simultaneous optimization of both.
487 Cholinergic Blockade Alters Hippocampal-posterior Cingulate Cortex Synchrony During Episodic Memory Encoding
Authors: Schmitt Kelsey , Wang David , Lega Bradley Charles 
Published: March 2024

INTRODUCTION:
The posterior cingulate cortex (PC) is an important region for episodic memory. Its synchrony with the hippocampus in the theta frequency, in particular, has been shown to underlie successful memory encoding. Cholinergic signaling is another important component of episodic memory, and manipulation of cholinergic signaling is often employed to better understand memory. However, the specific relationship between cholinergic signaling and hippocampal-PC synchrony has not been explored.

METHODS:
Eight patients with intracranial electrodes underwent two sessions of a free recall task, one in which they were given scopolamine and the other, saline. EEG recordings from these sessions during early and late encoding were then analyzed. The phases of high (5-9 Hz) and low (2-5 Hz) theta frequencies were calculated with hilbert transform, and synchrony was measured with phase-locking value (PLV), calculated for each electrode pair. Permutation tests were used to compare PLV between saline and scopolamine conditions for each electrode pair, producing a distribution of z-scores for each region-region connection. Electrodes were grouped into the regions anterior hippocampus (AH), posterior hippocampus(PH), and PC. The z-score distributions were compared against a distribution centered at zero with a t-test.

RESULTS:
The z-score distributions from permutation were significantly different from a null distribution for AH-PC connections in the left and right hemispheres during late encoding in high theta frequencies; AH-PH and PH-PC connections in the right hemisphere during early encoding in low theta frequencies; and PH-PC connections in the right hemisphere during late encoding in low theta frequencies.

CONCLUSIONS:
Changes in synchrony between PC, AH, and PH due to cholinergic blockade differ between low and high theta as well as early and late encoding.
488 National Trends in the Treatment of Refractory Epilepsy: A Nationwide Inpatient SampleBased Propensity Score Matching Analysis
Authors: Lee Seung J. , Ghaith Abdul Karim , El-Hajj; Marc Ghanem Victor Gabriel , Bydon Mohamad , Grewal Sanjeet Singh 
Published: March 2024

INTRODUCTION:
Epilepsy is considered one of the most prevalent and severe chronic neurological disorders worldwide.

METHODS:
Using the NIS database from 2010-2020, patients with focal intractable epilepsy who underwent Laser Interstitial Thermal Therapy (LITT), open surgical resection, Vagal Nerve Stimulation (VNS), or Responsive Neuro-Stimulation (RNS) were identified. Outcomes such as discharge disposition, length of stay, complications, and mortality were analyzed. Propensity score matching was used to compare outcomes between pre-pandemic and pandemic (first peak of COVID-19) periods.

RESULTS:
A total of 33,969 focal intractable epilepsy cases were found with 3,343 patients receiving different treatment modalities including surgical resection (77.83%), VNS (8.21%), RNS (7.83%), and LITT (6.13%). Most of these patients (89.32%) were treated during the pre-COVID pandemic era (2010-2019), while a minority (10.67%) underwent treatment during the COVID pandemic (2020). Among all treated patients, 2.7% had postoperative neurologic complications and 0.3% died. After propensity-score matching, 658 patients (329 in each group) were included. During the pandemic period, 7% presented with preoperative paralysis/aphasia, and 0.6% had subarachnoid hemorrhages, which was significantly higher than the pre-pandemic rate (1.8%; p < 0.001). There were no statistical differences in neurologic complications, discharge disposition, or LOS between the pre-pandemic and pandemic periods. On the other hand, the mortality rate was slightly higher during the pandemic compared to the pre-pandemic period (N = 4; 1.2% vs. N = 1; 0.2%; p = 0.026).

CONCLUSIONS:
Our study shows an increase in the diagnosis of focal intractable epilepsy and a decrease in resections, while LITT and RNS usage is rising. Improving access to surgery and encouraging newer treatment modalities for DRE is crucial. Further research is needed to optimize patient outcomes and identify factors that influence treatment choices.
494 Evaluating ERK1 2 Phosphorylation as a Predictive Biomarker for Survival in Recurrent Glioblastoma Patients: A REMARK Criteria-guided Analysis of a Clinical Trial Cohort Treated With Intracerebral PD-1 and CTLA-4 Blockade
Authors: Arrieta Victor Andrés , Duerinck Johnny , Burdett Kirsten B. , Geens Wietse , Schwarze Julia K. , Gould Andrew , Habashy Karl , Chen Li , McCord Matthew , Horbinski Craig , Zhang Hui , Stupp Roger , Neyns Bart , Sonabend Adam M. 
Published: March 2024

INTRODUCTION:
Glioblastoma patients exhibit variable clinical responses to anti-PD-1 immunotherapy. Our previous work identified ERK1/2 phosphorylation (p-ERK) in pre-treatment tumor samples as a predictive biomarker of overall survival in two independent cohorts of recurrent glioblastoma patients undergoing adjuvant anti-PD-1 therapy (Arrieta et al, Nat Cancer, 2021). This biomarker, however, has not yet been explored with alternative immune checkpoint blockade strategies nor assessed using REMARK criteria.

METHODS:
Adhering to REMARK criteria for biomarker validation, we investigated p-ERK as a predictor of survival in 24 evaluable recurrent glioblastoma patients from a clinical trial (NCT03233152; Duerinck J, et al, JITC, 2021). Patients underwent intracerebral administration of immune checkpoint inhibitors within a phase I clinical trial, receiving either ipilimumab (10 mg), or a combination of ipilimumab (5 mg) and nivolumab (10 mg), followed by postsurgical intravenous nivolumab (10 mg). We quantified p-ERK+ cell density in tumor regions and conducted a double-blinded statistical analysis of p-ERK’s association with survival outcomes, performed by an independent statistical team.

RESULTS:
Although analysis of the entire cohort revealed no statistically significant survival difference between patients with high and low p-ERK tumors (p = 0.29), a focused examination of wild-type IDH GBM patients demonstrated a significantly prolonged survival for those with high p-ERK tumors (median survival = 55.6 weeks, 95% CI 33.86-NA) compared to those with low p-ERK tumors (median OS of 30 weeks, 95% CI 16.14-NA; p = 0.036).

CONCLUSIONS:
Despite the limited sample size, this study highlights the promising predictive potential of p-ERK as a biomarker in a third independent prospective glioblastoma cohort treated with a novel immune checkpoint blockade administration approach, emphasizing the need for further investigation and validation in larger cohorts.
702 Multimodal CT Imaging of Ischemic Stroke Thrombi Identifies Scale-invariant Radiomic Features That Reflect Clot Biology
Authors: Santo Briana , Sarayi Seyyed , McCall Andrew , Monteiro Andre , Donnelly Brianna M , Baig Ammad , Siddiqui Adnan Hussain , Tutino Vincent 
Published: March 2024

INTRODUCTION:
Biological interpretability of ischemic stroke clot imaging remains challenging. Paired CT/microCT imaging of ischemic stroke clots resected by thrombectomy has the potential to identify interpretable image features that are correlated among pre-treatment image modalities and post-treatment histopathology.

METHODS:
We performed multimodal CT-imaging and histology for 10 stroke clots retrieved by mechanical thrombectomy. Clots were manually segmented from co-registered, pre-treatment CTA and nCCT. For the same cases, resected clots were iodine-stained, and imaged with a ScanCo microCT-100 (4.9μm resolution). Afterwards, clots were subjected to histological processing (H&E staining) and whole slide scanned (40X). Clot radiomic features(RFs) (n = 93 per modality, 279 total) were extracted using PyRadiomics and histological composition was computed using Orbit Image Analysis. Correlation analysis was used to test associations between microCT and CTA (or nCCT) RFs as well as between RFs and histological composition. Statistical significance was considered at R = 0.65 and q < 0.05.

RESULTS:
From paired RF correlation analysis, we identified 23 scale-invariant RFs significantly correlated between microCT and CTA (18), and microCT and nCCT (5). Correlation of unpaired RFs identified 377 positively and 36 negatively correlated RFs between microCT and CTA, and 168 positively and 41 negatively correlated RFs between microCT and nCCT. Scale invariant RFs computed from CTA and nCCT demonstrated significant correlation with red blood cell and fibrin-platelet components, while microCT RFs were found to be correlated with WBC percent composition.

CONCLUSIONS:
This study is the first to complete a detailed statistical analysis of radiomic features across scale, and investigation of their relationship to histological composition. Our findings suggest that RFs from resected clot microCT can be used to identify strong and significant correlations between histology and pre-thrombectomy CT, with increased biological interpretability.
703 Identifying Unruptured Cavernous Internal Carotid Artery Aneurysms Growth and Rupture Over Time
Authors: Jha Rohan , Zhao Maryann , Ghannam Jack , Chalif Joshua , Altshuler Marcelle , Du Rose 
Published: March 2024

INTRODUCTION:
Aneurysms in the Cavernous Segment of the Internal Carotid Artery (ICA) often present in an indolent fashion with limited morbidity. However, their growth progression and possible rupture over time remains poorly defined, thereby limiting optimization of serial follow-up.

METHODS:
We identified a retrospective cohort of 179 patients with cavernous ICA aneurysms. Patient demographic data, possible risk factors, presenting symptoms, radiographic features of aneurysms, size progression, rupture status, and concomitant non-cavernous aneurysm rupture data were manually extracted.

RESULTS:
179 patients (mean age at diagnosis 57.2 ± 15.9 years; 86.0% Female) had total 198 cavernous aneurysms. 44.4% of patients had no concomitant non-cavernous aneurysms, 41.9% had 1, and 13.6% had 2. No cavernous aneurysms ruptured during clinical follow-up. 17 non-cavernous concomitant aneurysm ruptured during follow up. 91.5% of cavernous aneurysms showed no change in size, 4.2% increased in size, and 4.2% were initially treated at time of diagnosis. Of the cavernous aneurysms that increased in size, there was a mean increase of 0.97 ± 0.4 mm and 1.1 mm ± 0.7 mm in long and short axis diameter across 5.2 ± 2.3 years. Weakness as a presenting symptom was the only predictor of cavernous aneurysm growth (p-value 0.022). Number of concomitant non-cavernous aneurysms (p-value 0.007) and sub-arachnoid hemorrhage (SAH) as a presenting symptom (p-value <0.0001) were associated with concomitant non-cavernous aneurysmal rupture.

CONCLUSIONS:
Cavernous ICA aneurysms demonstrate no rupture and limited growth over years of clinical follow-up. No patient radiographic or risk factor suggests increased risk of rupture or other symptomology, thus except for select individuals with concomitant non-cavernous aneurysms and SAH on presentation, there is likely limited clinical benefits in serially following these aneurysms over time.
759 Revisiting the ETV Success Score Using Machine Learning Can We Do Better?
Authors: Adil Syed M. , Seas Andreas , Sexton Daniel , Warman Pranav , Carter Lacey , Kolls Brad , Fuller Anthony , Lad Nandan P. , Dunn Timothy , Fuchs Herbert E. , Vestal Matthew , Grant Gerald 
Published: March 2024

INTRODUCTION:
The endoscopic third ventriculostomy (ETV) success score (ETVSS) is a useful decision-making heuristic when considering the probability of surgical success, defined as no repeat CSF diversion surgery needed within six months. Nonetheless, the original dataset published in 2009 was relatively small (n = 618) and logistic regression (LR) model performance modest.

METHODS:
We queried the MarketScan national database for the years 2005-2020 to identify patients <18 years of age who underwent a first-time ETV and subsequently had at least 6 months of continuous enrollment in the database. We collected data on predictors matching the original ETVSS—age, etiology of hydrocephalus, and history of any previous shunt placement. Next, we used six ML algorithms—LR, support vector classifier, random forest, k-nearest neighbors, XGBoost, and Naive Bayes—to develop predictive models. Finally, we used nested cross-validation to assess models’ comparative performances on unseen data.

RESULTS:
We identified 1698 patients that met inclusion criteria, and 1139 (67%) had successful ETVs. Performance of all models exceeded that of the original ETVSS, with the LR model still performing best with area under the receiver operating characteristic curve (AUROC) 0.90 (95% confidence interval, 0.86-0.94), sensitivity 0.79 (0.70-0.88), and specificity 0.91 (0.87-0.95) at Youden’s index. The random forest was the second-best ML algorithm following closely behind. This compares favorably to the original ETVSS with AUROC 0.80 (0.76-0.84, p < 0.01), sensitivity 0.65 (0.47-0.85, p < 0.01), and specificity 0.71 (0.65-0.75, p < 0.01).

CONCLUSIONS:
Our predictions for ETV success outperform the current gold standard. Logistic regression may still be the most interpretable and predictive algorithm; further work is underway to externally validate these models.
873 Code Brain Ultra-Early Clinical Pathway for Patient Identification and Management in Spontaneous Non-traumatic Intracranial Hemorrhage Single-Institution Study
Authors: Sivakumar Walavan , Guan Jian , Langevin Jean-Philippe , Martin Neil A. , Barkhoudarian Garni , Kelly Daniel F. , Berry John Franklin , Iyer Aditya K. 
Published: March 2024

INTRODUCTION:
Spontaneous non-traumatic intracranial hemorrhage causes high morbidity and mortality. Clinical pathways for the management of acute ischemic stroke are well established but fall short in identifying intracranial hemorrhage, preventing early therapy.

METHODS:
Using Class 1 recommendations from the AHA/ASA Spontaneous Intracranial Hemorrhage Guidelines, our multi-disciplinary stroke team developed a hyper-acute clinical pathway. Once the hemorrhagic stroke patient was identified, protocolized measures were immediately initiated to lower systolic blood pressure to 140 mmHg, institute factor replacement therapies in coagulopathic patients and anti-platelet reversal when appropriate. Key performance indicators and quality metrics were established to compare post-intervention groups to the baseline cohort.

RESULTS:
Of 180 patients, 113 and 67 patients were treated pre- and post-protocol, respectively. From pre- to post-protocol, diagnosis of hemorrhagic stroke using the alert increased from 59% to 81%. Anti-hypertensive initiation within 60 minutes increased from 79.5% to 88.7%, with the average time from CT result decreasing from 32.7 to 21.7 minutes. Time to reversal agent decreased from 53 to 23 minutes for pro-coagulation agents and 106 to 55 minutes for DDAVP. Reversal agent initiation within 60 minutes of CT result increased from 66.6% to 100% for pro-coagulation agents and 28.5% to 84.6% for DDAVP.

CONCLUSIONS:
The initiation of this management protocol for hemorrhagic stroke resulted in a higher proportion of patients being rapidly identified and earlier initiation of anti-hypertensive and hemostatic therapies. These processes are the key to important interventions designed to reduce injury extension associated with intracranial hemorrhage, like “time to thrombolysis” measures for acute ischemic stroke.
Repeat Resection for Recurrent Glioblastoma in the WHO 2021 Era: A Prospective Matched Case-Control Study
Authors: Askun Melike Mut , Zengin Yagmur , Azizova Aynur , Karli-Oguz Kader , Saydam Okay , Strobel Thomas , Soylemezoglu Figen 
Published: March 2024

INTRODUCTION:
The role of resection for recurrent glioblastoma remains unclear.

METHODS:
Patients who underwent repeat resection for recurrent IDH-wild-type glioblastoma were prospectively matched with 1:1 control cohort (n = 30:30). The two groups signed the consent and were matched for age, gender, comorbidities, eloquent vs. non-eloquent location, preoperative tumor volume and extent of resection in first surgery, neuropathological features as in WHO 2021 classification, time to progression, tumor volume at the time of recurrence, Park Score, ventricular wall involvement, use of steroids or multiple antiseizure medications and adjuvant therapy. Primary aim was to evaluate the overall survival in two cohorts. The secondary aim was to determine predictive factors for long term survival after repeat resection.

RESULTS:
After matching, patients had a long term follow up until death. Median overall survival times for patients who underwent repeat and one resection was 23.8 months vs 9.1 months, respectively (Log-Rank p < 0.001). Two predictive factors for long term survival after repeat resection were preoperative Karnofsky Performance Score >70 and Glasgow Coma Scale >13 (Fisher p = 0.07 and p < 0.001, respectively) while age, time to surgery, preoperative volume, extend of resection in repeat resection, location of tumor, its extension to ventricular wall, ependymal enhancement, comorbidities, tumor histological and molecular features did not correlate with postoperative survival.

CONCLUSIONS:
This is the first prospective matched case-control study revealing survival benefit of repeat resection for recurrent gliomas with long term follow up in a select group.
Circulating Biomarkers for Tumour Monitoring, Prognosis Predictions and Detection of Temozolomide Resistance Mutations in Glioma
Authors: Jones Jordan John , Drummond Katherine Jann , Morokoff Andrew 
Published: March 2024

INTRODUCTION:
The potential benefits of circulating biomarkers have been well demonstrated in other cancers. Despite this, no circulating biomarker exists for glioma due to poor sensitivity and hetereogeneity of results.

METHODS:
Serum miRNA and plasma ctDNA was isolated in a cohort of 212 gliomas using next-generation sequencing (NGS) and digital droplet PCR (ddPCR). Differentially expressed miRNAs were discovered using a machine learning algorithm and compared to tumor volume on MRI. A Lasso-regression model identified miRNAs that were associated with both progression-free and overall survival. Tumor mutations and ctDNA was compared in 49 plasma samples from 10 patients with tumor tissue available from at least two operations using NGS. Identified mutations were validated using ddPCR in the whole cohort.

RESULTS:
A 9-gene miRNA signature was found that could distinguish between glioma and healthy controls with 99.8% accuracy, including two that demonstrated dynamic changes that correlated with tumor volume on MRI. We found a separate 4-gene miRNA signature that was predictive of survival outcomes and could be incorporated into a clinical nomogram. Common glioma mutations were identified within 93% of plasma samples, including 25% that were not found in the tumor tissue. Mutations in the mismatch repair genes (MMR) were frequently detected in the plasma following temozolomide treatment and observed prior to their appearance in tissue at progression.

CONCLUSIONS:
We have identified serum miRNA biomarker signatures that can monitor tumour burden and improve prognostic predictions. We also show that contrary to previous reports, ctDNA can be reliably detected in the plasma of gliomas. We found that ctDNA offers complementary information to tissue biopsy alone and provides early evidence of temozolomide resistance through mutations in MMR genes.