Faculty Bibliography

The utility of symptom (SVT) and performance (PVT) validity tests has been independently established in neuropsychological evaluations, yet research on the relationship between these two types of validity indices is limited to circumscribed populations and measures. This study examined the relationship between SVTs on the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) and PVTs in a mixed neuropsychiatric setting. This cross-sectional study included data from 181 diagnostically and demographically diverse patients with neuropsychiatric conditions referred for outpatient clinical neuropsychological evaluation at an academic medical center. All patients were administered a uniform neuropsychological battery, including the MMPI-2-RF and five PVTs (i.e., Dot Counting Test; Medical Symptom Validity Test; Reliable Digit Span; Test of Memory Malingering-Trial 1; Word Choice Test). Nonsignificant associations emerged between SVT and PVT performance. Although the Response Bias Scale was most predictive of PVT performance, MMPI-2-RF SVTs generally had low classification accuracy for predicting PVT performance. Neuropsychological test performance was related to MMPI-2-RF SVT status only when overreporting elevations were at extreme scores. The current study further supports that SVTs and PVTs measure unique and dissociable constructs among diverse patients with neuropsychiatric conditions, consistent with literature from other clinical contexts. Therefore, objective evidence of symptom overreporting on MMPI-2-RF SVTs cannot be interpreted as definitively indicating invalid performance on tests of neurocognitive abilities. As such, clinicians should include both SVTs and PVTs as part of a comprehensive neuropsychological evaluation as they provide unique information regarding performance and symptom validity.

BACKGROUND/UNASSIGNED:"Targeted" epidural blood patches (EBP)" successfully treat "focal dural tears (DT)" diagnosed on thin-cut MR or Myelo-CT studies. These DT are largely attributed to; epidural steroid injections (ESI), lumbar punctures (LP), spinal anesthesia (SA), or spontaneous intracranial hypotension (SICH). Here we asked whether "targeted EBP" could similarly treat MR/Myelo-CT documented recurrent post-surgical CSF leaks/DT that have classically been effectively managed with direct surgical repair. METHODS/UNASSIGNED:Utilizing ultrasound, fluoroscopy, or O-arm guidance, "targeted EBP" effectively manage "focal DT" attributed to ESI, LP, SA, or SICH. Here we reviewed the literature to determine whether similar "targeted EBP" could effectively manage recurrent postoperative CSF leaks/DT. RESULTS/UNASSIGNED:We were only able to identify 3 studies involving just 20 patients that attempted to utilize EBP to control postoperative CSF fistulas/DT. EBP controlled CSF fistulas/DT in 6 patients in the first study, and 9 of 10 patients (i.e. 90%: 2/2 cervical; 7/8 lumbar) in the second study. However, in the third study, 3 (60%) of 5 EBP failed to avert recurrent CSF leaks/DT in 4 patients (i.e. 1 cervical patient (2 EBP failed attempts), 3 lumbar patients (1 failed EBP)). CONCLUSION/UNASSIGNED:Early direct surgical repair of recurrent postoperative spinal CSF leaks/DT remains the treatment of choice. Our literature review revealed 3 underpowered studies including just 20 patients where 20% of EBP failed to control recurrent postoperative fistulas (range of failure from 0-60% per study). Although there are likely other studies we failed to identify in this review, they too are likely insufficiently powered to document significant efficacy for performing EBP over direct surgical repair for recurrent postoperative CSF leaks/DT.

INTRODUCTION/UNASSIGNED:Extracting regularities from ongoing stimulus streams to form predictions is crucial for adaptive behavior. Such regularities exist in terms of the content of the stimuli and their timing, both of which are known to interactively modulate sensory processing. In real-world stimulus streams such as music, regularities can occur at multiple levels, both in terms of contents (e.g., predictions relating to individual notes vs. their more complex groups) and timing (e.g., pertaining to timing between intervals vs. the overall beat of a musical phrase). However, it is unknown whether the brain integrates predictions in a manner that is mutually congruent (e.g., if "beat" timing predictions selectively interact with "what" predictions falling on pulses which define the beat), and whether integrating predictions in different timing conditions relies on dissociable neural correlates. METHODS/UNASSIGNED:= 20) performing a repetition detection task. RESULTS/UNASSIGNED:Our results reveal that temporal predictions based on beat or interval timing modulated mismatch responses to violations of "what" predictions happening at the predicted time points, and that these modulations were shared between types of temporal predictions in terms of the spatiotemporal distribution of EEG signals. Effective connectivity analysis using dynamic causal modeling showed that the integration of "what" and "when" predictions selectively increased connectivity at relatively late cortical processing stages, between the superior temporal gyrus and the fronto-parietal network. DISCUSSION/UNASSIGNED:Taken together, these results suggest that the brain integrates different predictions with a high degree of mutual congruence, but in a shared and distributed cortical network. This finding contrasts with recent studies indicating separable mechanisms for beat-based and memory-based predictive processing.

OBJECTIVE:People with blindness and low vision face substantial challenges when navigating both indoor and outdoor environments. While various solutions are available to facilitate travel to and from public transit hubs, there is a notable absence of solutions for navigating within transit hubs, often referred to as the "middle mile". Although research pilots have explored the middle mile journey, no solutions exist at scale, leaving a critical gap for commuters with disabilities. In this paper, we proposed a novel mobile application, Commute Booster, that offers full trip planning and real-time guidance inside the station. METHODS AND PROCEDURES/METHODS:Our system consists of two key components: the general transit feed specification (GTFS) and optical character recognition (OCR). The GTFS dataset generates a comprehensive list of wayfinding signage within subway stations that users will encounter during their intended journey. The OCR functionality enables users to identify relevant navigation signs in their immediate surroundings. By seamlessly integrating these two components, Commute Booster provides real-time feedback to users regarding the presence or absence of relevant navigation signs within the field of view of their phone camera during their journey. RESULTS:As part of our technical validation process, we conducted tests at three subway stations in New York City. The sign detection achieved an impressive overall accuracy rate of 0.97. Additionally, the system exhibited a maximum detection range of 11 meters and supported an oblique angle of approximately 110 degrees for field of view detection. CONCLUSION/CONCLUSIONS:The Commute Booster mobile application relies on computer vision technology and does not require additional sensors or infrastructure. It holds tremendous promise in assisting individuals with blindness and low vision during their daily commutes. Clinical and Translational Impact Statement: Commute Booster translates the combination of OCR and GTFS into an assistive tool, which holds great promise for assisting people with blindness and low vision in their daily commute.

BACKGROUND/UNASSIGNED:The 2016 WHO classification described a subtype of midline gliomas harboring histone 3 (H3) K27M alterations, and the 2021 edition added a new subtype of hemispheric diffuse gliomas with H3 G34R/V mutations. The incidence and clinical behavior of leptomeningeal disease (LMD) in these patients is not well defined. METHODS/UNASSIGNED:Retrospective study of patients with H3-altered gliomas diagnosed from 01/2012 to 08/2021; histone mutations were identified through next-generation sequencing (NGS) of tumor biopsy and/or cerebrospinal fluid (CSF). RESULTS/UNASSIGNED:< .0001). CONCLUSIONS/UNASSIGNED:In our cohort, 50% of patients developed LMD. Although further studies are needed, CSF ctDNA characterization may aid in identifying molecular tumor profiles in glioma patients with LMD, and neuroaxis imaging and CSF NGS should be considered for early LMD detection.

BACKGROUND/UNASSIGNED:Patients with postoperative spinal epidural hematomas (pSEH) typically require emergency treatment to avoid paralysis; these hematomas should not be ignored. pSEH patients need to undergo immediate MR studies to document the location/extent of their hematomas, and emergent surgical decompression with/ without fusion if warranted. METHODS/UNASSIGNED:The frequencies of symptomatic pSEH ranged in various series from 0.1%-4.46%. Major predisposing factors included; perioperative/postoperative coagulation abnormalities/disorders, multilevel spine surgeries, previous spine surgery, and intraoperative cerebrospinal fluid (CSF) leaks. For surgery at all spinal levels, one study observed pSEH developed within an average of 2.7 postoperative hours. Another series found 100% of cervical/thoracic, and 50% of lumbar pSEH were symptomatic within 24 postoperative hrs., while a third series noted a 24-48 postoperative window for pSEH to develop. RESULTS/UNASSIGNED:Early recognition of postoperative symptoms/signs of pSEH, warrant immediate MR examinations to diagnose the local/extent of hemorrhages. Subsequent emergent spinal decompressions/fusions are critical to limit/avert permanent postoperative neurological deficits. Additionally, patients undergoing open or minimally invasive spinal procedures where pSEH are suspected, warrant immediate postoperative MR studies. CONCLUSION/UNASSIGNED:Patients undergoing spinal surgery at any level typically become symptomatic from pSEH within 2.7 to 24 postoperative hours. Early recognition of new neurological deficits, immediate MR studies, and emergent surgery (i.e., if indicated) should limit/minimize postoperative neurological sequelae. Thus, pSEH should be treated, not ignored.

Phosphorylated tau is the main protein present in neurofibrillary tangles, the presence of which is a key neuropathological hallmark of Alzheimer's disease (AD). The toxic effects of phosphorylated tau are likely mediated by interacting proteins; however, methods to identify these interacting proteins comprehensively in human brain tissue are limited. Here, we describe a method that enables the efficient identification of hundreds of proteins that interact with phosphorylated tau (pTau), using affinity purification-mass spectrometry (AP-MS) on human, fresh-frozen brain tissue from donors with AD. Tissue is homogenized using a gentle technique that preserves protein-protein interactions, and co-immunoprecipitation of pTau and its interacting proteins is performed using the PHF1 antibody. The resulting protein interactors are then identified using label-free quantitative liquid chromatography-mass spectrometry (LC-MS)/MS. The Significance Analysis of INTeractome (SAINT) algorithm is used to determine which proteins significantly interact with pTau. This approach enables the detection of an abundance of all 6 isoforms of tau, 23 phosphorylated residues on tau, and 125 significant pTau protein interactors, in human AD brain tissue.