Modified Neuropixels probes for recording human neurophysiology in the operating room.

Neuropixels are silicon-based electrophysiology-recording probes with high channel count and recording-site density. These probes offer a turnkey platform for measuring neural activity with single-cell resolution and at a scale that is beyond the capabilities of current clinically approved devices. Our team demonstrated the first-in-human use of these probes during resection surgery for epilepsy or tumors and deep brain stimulation electrode placement in patients with Parkinson's disease. Here, we provide a better understanding of the capabilities and challenges of using Neuropixels as a research tool to study human neurophysiology, with the hope that this information may inform future efforts toward regulatory approval of Neuropixels probes as research devices. In perioperative procedures, the major concerns are the initial sterility of the device, maintaining a sterile field during surgery, having multiple referencing and grounding schemes available to de-noise recordings (if necessary), protecting the silicon probe from accidental contact before insertion and obtaining high-quality action potential and local field potential recordings. The research team ensures that the device is fully operational while coordinating with the surgical team to remove sources of electrical noise that could otherwise substantially affect the signals recorded by the sensitive hardware. Prior preparation using the equipment and training in human clinical research and working in operating rooms maximize effective communication within and between the teams, ensuring high recording quality and minimizing the time added to the surgery. The perioperative procedure requires ~4 h, and the entire protocol requires multiple weeks.

Bilateral Synovial Cysts as a Rare Cause of Myelopathy in a 38-year-old Woman.

Synovial cysts are rare, and they occur even more rarely bilaterally or in the cervical spine. A 38-year-old previously healthy female presented with acute onset of numbness and tingling down her arms and weakness in her legs, which progressed steadily over 2-3 weeks to include significant gait disturbance. She denied bowel or bladder symptoms, saddle anesthesia, night sweats, weight loss, fever, or chills. MRI spine revealed a C7-T1 extradural mass consistent with bilateral synovial cysts emanating from bilateral neuroforamina resulting in critical spinal cord compression with T2 signal change in the cord. There was questionable patch enhancement after gadolinium contrast. The patient underwent C7-T1 laminectomies and partial bilateral medial facetectomies with excision of the cysts. Intraoperative cultures unexpectedly grew Staphylococcus aureus, suggesting superinfection of cysts. The patient recovered neurologic function postoperatively and was discharged on a 6-week course of IV antibiotics. We report and discuss the clinical presentation, pathogenesis, and neuroradiological findings in an adult case of bilateral synovial cysts at the C-T-spine junction. Immediate resection at symptom onset is indicated due to the good clinical outcome following resection and the real risk of paralysis if cysts are not excised in a timely fashion.

Adult-onset focal expression of mutated human tau in the hippocampus impairs spatial working memory of rats.

Tauopathy in the hippocampus is one of the earliest cardinal features of Alzheimer's disease (AD), a condition characterized by progressive memory impairments. In fact, density of tau neurofibrillary tangles (NFTs) in the hippocampus strongly correlates with severity of cognitive impairments in AD. In the present study, we employed a somatic cell gene transfer technique to create a rodent model of tauopathy by injecting a recombinant adeno-associated viral vector with a mutated human tau gene (P301L) into the hippocampus of adult rats. The P301L mutation is causal for frontotemporal dementia with parkinsonism-17 (FTDP-17), but it has been used for studying memory effects characteristic of AD in transgenic mice. To ascertain if P301L-induced mnemonic deficits are persistent, animals were tested for 6 months. It was hypothesized that adult-onset, spatially restricted tau expression in the hippocampus would produce progressive spatial working memory deficits on a learned alternation task. Rats injected with the tau vector exhibited persistent impairments on the hippocampal-dependent task beginning at about 6 weeks post-transduction compared to rats injected with a green fluorescent protein vector. Histological analysis of brains for expression of human tau revealed hyperphosphorylated human tau and NFTs in the hippocampus in experimental animals only. Thus, adult-onset, vector-induced tauopathy spatially restricted to the hippocampus progressively impaired spatial working memory in rats. We conclude that the model faithfully reproduces histological and behavioral findings characteristic of dementing tauopathies. The rapid onset of sustained memory impairment establishes a preclinical model particularly suited to the development of potential tauopathy therapeutics.