Intracortical brain-computer interfaces (iBCIs) for decoding intended speech have provided individuals with ALS and severe dysarthria an intuitive method for high-throughput communication. These advances have been demonstrated in individuals who are still able to vocalize and move speech articulators. Here, we decoded intended speech from an individual with longstanding anarthria, locked-in syndrome, and ventilator dependence due to advanced symptoms of ALS.
View Article and Find Full Text PDFAneurysmal subarachnoid hemorrhage (aSAH) contributes disproportionately to stroke-related disability due to its prevalence in younger patients. Large vessel vasospasm complicates aSAH and is often treated with endovascular rescue therapy (ERT). However, clinical trials have not demonstrated a clear link between vasospasm improvement and better outcomes.
View Article and Find Full Text PDFIntracortical brain-computer interfaces (iBCIs) restore motor function to people with paralysis by translating brain activity into control signals for external devices. In current iBCIs, instabilities at the neural interface result in a degradation of decoding performance, which necessitates frequent supervised recalibration using new labeled data. One potential solution is to use the latent manifold structure that underlies neural population activity to facilitate a stable mapping between brain activity and behavior.
View Article and Find Full Text PDFRecognizing keyboard typing as a familiar, high information rate communication paradigm, we developed an intracortical brain computer interface (iBCI) typing neuroprosthesis providing bimanual QWERTY keyboard functionality for people with paralysis. Typing with this iBCI involves only attempted finger movements, which are decoded accurately with as few as 30 calibration sentences. Sentence decoding is improved using a 5-gram language model.
View Article and Find Full Text PDFbioRxiv
September 2024
Understanding how the body is represented in motor cortex is key to understanding how the brain controls movement. The precentral gyrus (PCG) has long been thought to contain largely distinct regions for the arm, leg and face (represented by the "motor homunculus"). However, mounting evidence has begun to reveal a more intermixed, interrelated and broadly tuned motor map.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2024
How the human cortex integrates ("binds") information encoded by spatially distributed neurons remains largely unknown. One hypothesis suggests that synchronous bursts of high-frequency oscillations ("ripples") contribute to binding by facilitating integration of neuronal firing across different cortical locations. While studies have demonstrated that ripples modulate local activity in the cortex, it is not known whether their co-occurrence coordinates neural firing across larger distances.
View Article and Find Full Text PDFAnn Clin Transl Neurol
October 2023
Objective: To develop an automated, physiologic metric of immune effector cell-associated neurotoxicity syndrome among patients undergoing chimeric antigen receptor-T cell therapy.
Methods: We conducted a retrospective observational cohort study from 2016 to 2020 at two tertiary care centers among patients receiving chimeric antigen receptor-T cell therapy with a CD19 or B-cell maturation antigen ligand. We determined the daily neurotoxicity grade for each patient during EEG monitoring via chart review and extracted clinical variables and outcomes from the electronic health records.
Synchronous bursts of high frequency oscillations ('ripples') are hypothesized to contribute to binding by facilitating integration of neuronal firing across cortical locations. We tested this hypothesis using local field-potentials and single-unit firing from four 96-channel microelectrode arrays in supragranular cortex of 3 patients. Neurons in co-rippling locations showed increased short-latency co-firing, prediction of each-other's firing, and co-participation in neural assemblies.
View Article and Find Full Text PDFBackground And Objectives: Brain-computer interfaces (BCIs) are being developed to restore mobility, communication, and functional independence to people with paralysis. Though supported by decades of preclinical data, the safety of chronically implanted microelectrode array BCIs in humans is unknown. We report safety results from the prospective, open-label, nonrandomized BrainGate feasibility study (NCT00912041), the largest and longest-running clinical trial of an implanted BCI.
View Article and Find Full Text PDFBackground: Immune effector cell-associated neurotoxicity syndrome (ICANS) is a clinical and neuropsychiatric syndrome that can occur days to weeks following administration chimeric antigen receptor (CAR) T-cell therapy. Manifestations of ICANS range from encephalopathy and aphasia to cerebral edema and death. Because the onset and time course of ICANS is currently unpredictable, prolonged hospitalization for close monitoring following CAR T-cell infusion is a frequent standard of care.
View Article and Find Full Text PDFNeurol Clin Pract
February 2022
Background And Objectives: To examine the relationship between transcranial Doppler (TCD) mean flow velocity (MFV) and the severity and temporal onset of neurotoxicity after chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed lymphoma.
Methods: We identified a cohort of 165 patients with relapsed or refractory B-cell lymphoma who received CAR T-cell therapy. TCDs were performed at baseline, treatment day 5, and throughout hospitalization based on development of neurologic symptoms.
J Neuropsychiatry Clin Neurosci
October 2022
Objective: The investigators aimed to describe the clinical experience of a single center reporting on neuropsychiatric findings among patients experiencing persistent symptoms as part of post-acute sequelae of SARS-CoV-2 (PASC) infection.
Methods: Data were collected retrospectively (between February 2020 and May 2021) from a cohort (N=100) within a COVID-19 survivors study of patients with persistent symptoms enrolled after a short inpatient stay or who had been outpatients never hospitalized. Patients without confirmatory positive PCR or antibody diagnostic test results were grouped separately as presumptive cases (N=13).
Consolidation of memory is believed to involve offline replay of neural activity. While amply demonstrated in rodents, evidence for replay in humans, particularly regarding motor memory, is less compelling. To determine whether replay occurs after motor learning, we sought to record from motor cortex during a novel motor task and subsequent overnight sleep.
View Article and Find Full Text PDFBackground: Patients with aneurysmal subarachnoid hemorrhage (aSAH) with electroencephalographic epileptiform activity (seizures, periodic and rhythmic patterns, and sporadic discharges) are frequently treated with antiseizure medications (ASMs). However, the safety and effectiveness of ASM treatment for epileptiform activity has not been established. We used observational data to investigate the effectiveness of ASM treatment in patients with aSAH undergoing continuous electroencephalography (cEEG) to develop a causal hypothesis for testing in prospective trials.
View Article and Find Full Text PDFNeurologic symptoms are commonly seen in patients with cancer and can be among the most challenging to diagnose and manage. It is often difficult to determine if new neurologic symptoms are secondary to direct effects of a malignant lesion, systemic complications of disease, paraneoplastic disorders, or side effects of cancer treatment itself. However, early diagnosis and treatment of each of these conditions can improve patients' quality of life and long-term functional outcomes.
View Article and Find Full Text PDFBackground: While EEG is frequently reported as abnormal after chimeric antigen receptor (CAR) T-cell therapy, its clinical significance remains unclear. We aim to systematically describe EEG features in a large single-center cohort and correlate them with clinical and radiological findings.
Methods: We retrospectively identified patients undergoing CAR T-cell therapy who had continuous EEG.
Chimeric antigen receptor (CAR) T cell therapy has become an indispensable tool in the treatment of advanced malignancy, however, it is associated with significant neurologic toxicity. The pathophysiology of CAR T-cell associated neurotoxicity is incompletely understood, and the specific risk factors have only recently begun to be characterized. Despite a growing clinical experience with CAR T cell therapy, the unpredictability of neurologic symptoms remains a source of great anxiety for patients and practitioners alike, and a major limitation for more widespread adoption of this important treatment modality.
View Article and Find Full Text PDFIn November 2019, the Food and Drug Administration (FDA) approved cefiderocol for the treatment of complicated urinary tract infections (cUTI) including pyelonephritis caused by susceptible gram-negative bacteria in adults with limited to no alternative treatment options based on a randomized, double-blind, noninferiority cUTI trial (APEKS-cUTI). In a randomized, open-label trial (CREDIBLE-CR) in patients with cUTI, nosocomial pneumonia, bloodstream infections, or sepsis due to carbapenem-resistant gram-negative bacteria, an increase in all-cause mortality was observed in patients treated with cefiderocol as compared to best available therapy. The cause of the increased mortality was not established, but some deaths were attributed to treatment failure.
View Article and Find Full Text PDFThis is a report of a 65-year-old female presenting with symptoms of dysphagia due to a coiled left internal carotid artery, treated with resection and primary repair. Dysphagia lusoria is more commonly caused by aortic arch anomalies, aberrant subclavian or common carotid arteries. Internal carotid tortuosity as a cause of severe dysphagia and burning mouth syndrome is highly unusual.
View Article and Find Full Text PDF