Faculty Bibliography

BACKGROUND:and purpose: Fatigue is among the most common persistent symptoms following post-acute sequelae of Sars-COV-2 infection (PASC). The current study investigated the potential therapeutic effects of High-Definition transcranial Direct Current Stimulation (HD-tDCS) associated with rehabilitation program for the management of PASC-related fatigue. METHODS:Seventy patients with PASC-related fatigue were randomized to receive 3 mA or sham HD-tDCS targeting the left primary motor cortex (M1) for 30 min paired with a rehabilitation program. Each patient underwent 10 sessions (2 sessions/week) over five weeks. Fatigue was measured as the primary outcome before and after the intervention using the Modified Fatigue Impact Scale (MFIS). Pain level, anxiety severity and quality of life were secondary outcomes assessed, respectively, through the McGill Questionnaire, Hamilton Anxiety Rating Scale (HAM-A) and WHOQOL. RESULTS:Active HD-tDCS resulted in significantly greater reduction in fatigue compared to sham HD-tDCS (mean group MFIS reduction of 22.11 points vs 10.34 points). Distinct effects of HD-tDCS were observed in fatigue domains with greater effect on cognitive (mean group difference 8.29 points; effect size 1.1; 95% CI 3.56-13.01; P < .0001) and psychosocial domains (mean group difference 2.37 points; effect size 1.2; 95% CI 1.34-3.40; P < .0001), with no significant difference between the groups in the physical subscale (mean group difference 0.71 points; effect size 0.1; 95% CI 4.47-5.90; P = .09). Compared to sham, the active HD-tDCS group also had a significant reduction in anxiety (mean group difference 4.88; effect size 0.9; 95% CI 1.93-7.84; P < .0001) and improvement in quality of life (mean group difference 14.80; effect size 0.7; 95% CI 7.87-21.73; P < .0001). There was no significant difference in pain (mean group difference -0.74; no effect size; 95% CI 3.66-5.14; P = .09). CONCLUSION/CONCLUSIONS:An intervention with M1 targeted HD-tDCS paired with a rehabilitation program was effective in reducing fatigue and anxiety, while improving quality of life in people with PASC.

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.

BACKGROUND/UNASSIGNED:Currently, there are no FDA approved therapies for persistent post-traumatic headache (PPTH) secondary to traumatic brain injury (TBI). As such neither headache nor TBI specialists have an effective means to manage PPTH. Thus, the objective of the present pilot trial was to evaluate the feasibility and preliminary efficacy of a four-week at-home remotely supervised transcranial direct current stimulation (RS-tDCS) intervention for veterans with PPTH. METHODS/UNASSIGNED: = 13) RS-tDCS, with anodal stimulation over left dlPFC and cathodal over occipital pole. Following a four-week baseline, participants completed 20-sessions of active or sham RS-tDCS with real-time video monitoring over a period of four-weeks. Participants were assessed again at the end of the intervention and at four-weeks post-intervention. Primary outcomes were overall adherence rate (feasibility) and change in moderate-to-severe headache days per month (efficacy). Secondary outcomes were changes in total number of headache days, and PPTH-related functional outcomes. RESULTS/UNASSIGNED: = 0.03), compared to sham during-treatment (-4.0 ± 5.2 vs. 1.5 ± 3.8), and 4-week follow-up (-2.1 ± 7.2 vs. -0.2 ± 4.4). CONCLUSION/UNASSIGNED:The current results indicate our RS-tDCS paradigm provides a safe and effective means for reducing the severity and number of headache days in veterans with PPTH. High treatment adherence rate and the remote nature of our paradigm indicate RS-tDCS may be a feasible means to reduce PPTH, especially for veterans with limited access to medical facilities.Clinical Trial Registration: ClinicalTrials.gov, identifier [NCT04012853].

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.

The relationship between conscious experience and brain activity has intrigued scientists and philosophers for centuries. In the last decades, several theories have suggested different accounts for these relationships. These theories have developed in parallel, with little to no cross-talk among them. To advance research on consciousness, we established an adversarial collaboration between proponents of two of the major theories in the field, Global Neuronal Workspace and Integrated Information Theory. Together, we devised and preregistered two experiments that test contrasting predictions of these theories concerning the location and timing of correlates of visual consciousness, which have been endorsed by the theories' proponents. Predicted outcomes should either support, refute, or challenge these theories. Six theory-impartial laboratories will follow the study protocol specified here, using three complementary methods: Functional Magnetic Resonance Imaging (fMRI), Magneto-Electroencephalography (M-EEG), and intracranial electroencephalography (iEEG). The study protocol will include built-in replications, both between labs and within datasets. Through this ambitious undertaking, we hope to provide decisive evidence in favor or against the two theories and clarify the footprints of conscious visual perception in the human brain, while also providing an innovative model of large-scale, collaborative, and open science practice.

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.

Due to shared hippocampal dysfunction, patients with Alzheimer's dementia and late-onset epilepsy (LOE) report memory decline. Multiple studies have described the epidemiological, pathological, neurophysiological, and behavioral overlap between Alzheimer's Disease and LOE, implying a bi-directional relationship. We describe the neurobiological decline occurring at different spatial in AD and LOE patients, which may explain why their phenotypes overlap and differ. We provide suggestions for clinical recognition of dual presentation and novel approaches for behavioral testing that reflect an "inside-out," or biologically-based approach to testing memory. New memory and language assessments could detect-and treat-memory impairment in AD and LOE at an earlier, actionable stage.

GABAergic inhibitory neurons are the principal source of inhibition in the brain. Traditionally, their role in maintaining the balance of excitation-inhibition has been emphasized. Beyond homeostatic functions, recent circuit mapping and functional manipulation studies have revealed a wide range of specific roles that GABAergic circuits play in dynamically tilting excitation-inhibition coupling across spatio-temporal scales. These span from gating of compartment- and input-specific signaling, gain modulation, shaping input-output functions and synaptic plasticity, to generating signal-to-noise contrast, defining temporal windows for integration and rate codes, as well as organizing neural assemblies, and coordinating inter-regional synchrony. GABAergic circuits are thus instrumental in controlling single-neuron computations and behaviorally-linked network activity. The activity dependent modulation of sensory and mnemonic information processing by GABAergic circuits is pivotal for the formation and maintenance of episodic memories in the hippocampus. Here, we present an overview of the local and long-range GABAergic circuits that modulate the dynamics of excitation-inhibition and disinhibition in the main output area of the hippocampus CA1, which is crucial for episodic memory. Specifically, we link recent findings pertaining to GABAergic neuron molecular markers, electrophysiological properties, and synaptic wiring with their function at the circuit level. Lastly, given that area CA1 is particularly impaired during early stages of Alzheimer's disease, we emphasize how these GABAergic circuits may contribute to and be involved in the pathophysiology.