Electrophysiological devices are critical for mapping eloquent and diseased brain regions and for therapeutic neuromodulation in clinical settings and are extensively used for research in brain-machine interfaces. However, the existing clinical and experimental devices are often limited in either spatial resolution or cortical coverage. Here, we developed scalable manufacturing processes with a dense electrical connection scheme to achieve reconfigurable thin-film, multithousand-channel neurophysiological recording grids using platinum nanorods (PtNRGrids). With PtNRGrids, we have achieved a multithousand-channel array of small (30 μm) contacts with low impedance, providing high spatial and temporal resolution over a large cortical area. We demonstrated that PtNRGrids can resolve submillimeter functional organization of the barrel cortex in anesthetized rats that captured the tissue structure. In the clinical setting, PtNRGrids resolved fine, complex temporal dynamics from the cortical surface in an awake human patient performing grasping tasks. In addition, the PtNRGrids identified the spatial spread and dynamics of epileptic discharges in a patient undergoing epilepsy surgery at 1-mm spatial resolution, including activity induced by direct electrical stimulation. Collectively, these findings demonstrated the power of the PtNRGrids to transform clinical mapping and research with brain-machine interfaces.

Detailed information regarding the alloy deposition/ dealloying and fabrication steps, the energy dispersive X-ray spectral characterization, histology on chronically implanted mice and characterization of explanted electrodes, electrochemical impedance spectroscopy and their small signal components, sterilization effects of autoclave, ethylene oxide, and sterrad, on impedance distribution, comparison of surface and depth recorded single units and extracted composite receptive fields in songbird experiments, and comparison of recordings using PtNR devices and NeuroNexus ECoG Pt electrodes on NHP and corresponding power-frequency plots (PDF)

Objective. Electrical stimulation via microelectrodes implanted in cortex has been suggested as a potential treatment for a wide range of neurological disorders. Despite some success however, the effectiveness of conventional electrodes remains limited, in part due to an inability to create specific patterns of neural activity around each electrode and in part due to challenges with maintaining a stable interface. The use of implantable micro-coils to magnetically stimulate the cortex has the potential to overcome these limitations because the asymmetric fields from coils can be harnessed to selectively activate some neurons, e.g. vertically-oriented pyramidal neurons while avoiding others, e.g. horizontally-oriented passing axons. In vitro experiments have shown that activation is indeed confined with micro-coils but their effectiveness in the intact brain of living animals has not been evaluated. Approach. To assess the efficacy of stimulation, a 128-channel custom recording microelectrode array was positioned on the surface of the visual cortex (ECoG) in anesthetized mice and responses to magnetic and electric stimulation were compared. Stimulation was delivered from electrodes or micro-coils implanted through a hole in the center of the recording array at a rate of 200 pulses per second for 100 ms. Main results. Both electric and magnetic stimulation reliably elicited cortical responses, although activation from electric stimulation was spatially expansive, often extending more than 1 mm from the stimulation site, while activation from magnetic stimulation was typically confined to a ∼300 µm diameter region around the stimulation site. Results were consistent for stimulation of both cortical layer 2/3 and layer 5 as well as across a range of stimulus strengths. Significance. The improved focality with magnetic stimulation suggests that the effectiveness of cortical stimulation can be improved. Improved focality may be particularly attractive for cortical prostheses that require high spatial resolution, e.g. devices that target sensory cortex, as it may lead to improved acuity.

BackgroundSpecies phylogenies are not estimated directly, but rather through phylogenetic analyses of different gene datasets. However, true gene trees can differ from the true species tree (and hence from one another) due to biological processes such as horizontal gene transfer, incomplete lineage sorting, and gene duplication and loss, so that no single gene tree is a reliable estimate of the species tree. Several methods have been developed to estimate species trees from estimated gene trees, differing according to the specific algorithmic technique used and the biological model used to explain differences between species and gene trees. Relatively little is known about the relative performance of these methods.ResultsWe report on a study evaluating several different methods for estimating species trees from sequence datasets, simulating sequence evolution under a complex model including indels (insertions and deletions), substitutions, and incomplete lineage sorting. The most important finding of our study is that some fast and simple methods are nearly as accurate as the most accurate methods, which employ sophisticated statistical methods and are computationally quite intensive. We also observe that methods that explicitly consider errors in the estimated gene trees produce more accurate trees than methods that assume the estimated gene trees are correct.ConclusionsOur study shows that highly accurate estimations of species trees are achievable, even when gene trees differ from each other and from the species tree, and that these estimations can be obtained using fairly simple and computationally tractable methods.