Electronics that are capable of intimate, non-invasive integration with the soft, curvilinear surfaces of biological tissues offer important opportunities for diagnosing and treating disease and for improving brain-machine interfaces. This paper describes a material strategy for a type of biointerfaced system that relies on ultrathin electronics supported by bioresorbable substrates of silk fibroin. Mounting such devices on tissue and then allowing the silk to dissolve and resorb initiates a spontaneous, conformal wrapping process driven by capillary forces at the biotic/abiotic interface. Specialized mesh designs and ultrathin forms for the electronics ensure minimal stresses on the tissue and highly conformal coverage, even for complex curvilinear surfaces, as confirmed by experimental and theoretical studies. In vivo, neural mapping experiments on feline animal

Arrays of electrodes for recording and stimulating the brain are used throughout clinical medicine and basic neuroscience research, yet are unable to sample large areas of the brain while maintaining high spatial resolution because of the need to individually wire each passive sensor at the electrode-tissue interface. To overcome this constraint, we have developed new devices integrating ultrathin and flexible silicon nanomembrane transistors into the electrode array, enabling new dense arrays of thousands of amplified and multiplexed sensors connected using many fewer wires. We used this system to record novel spatial properties of brain activity in vivo, including sleep spindles, single-trial visual evoked responses, and electrographic seizures. Our electrode array allowed us to discover that seizures may manifest as recurrent spiral waves which propagate in the neocortex. The developments reported here herald a new generation of diagnostic and therapeutic brain-machine interface (BMI) devices. KeywordsMultielectrode array; electrode array; flexible electronics; multiplexed electrode; cortical surface electrode; foldable electrode; ECoG; μECoG; brain machine interface; high temporal resolution; high spatial resolution; spindle; visual neuroscience; spiral wave; epilepsy; seizure; epileptiform spike; interhemispheric fissure; silicon nanoribbonThe utility of high-resolution neural recordings from the cortical surface for basic research and clinical medicine has been shown for a wide range of applications. Spatial spectral analysis of electrocorticograms (ECoG) from the superior temporal gyrus and motor cortex demonstrate that electrode spacing should be 1.25 mm or closer in humans to sufficiently capture the rich spatial information available 1 . Motor control signals 2 and spoken words 3 can be decoded with substantially improved performance utilizing electrodes spaced 1 mm apart or less. In occipital cortex, arrays with 500 μm spacing have demonstrated micro-field evoked potentials that can distinguish ocular dominance columns 4 . The spatial scale for some pathologic signals is also submillimeter, based on observations of microseizures, microdischarges and high frequency oscillations in epileptic brain 5,6 .Yet the subdural electrodes in use clinically, for example, in the diagnosis and treatment of epilepsy, are much larger (~3 mm diameter) and have large interspacing (~10mm) because of the clinical need to record from large areas of the brain surface (80 mm × 80 mm) in order to accurately localize seizure generating brain regions. Large area electrode arrays with high spatial resolution are also needed in BMI applications to account for variability in the location of brain functions, which can vary by ~5mm across subjects [7][8][9][10] . High-resolution interface over a large area has previously been impossible due to the infeasibility of connecting thousands of wires in the small intracranial space. Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptMuch of the existing researc...

Cerebrocortical injuries, such as stroke, are a major source of disability. Maladaptive consequences can result from post-injury local reorganization of cortical circuits. For example, epilepsy is a common sequela of cortical stroke, yet mechanisms responsible for seizures following cortical injuries remain unknown. In addition to local reorganization, long-range, extra-cortical connections might be critical for seizure maintenance. Here we report in rats the first evidence that the thalamus – a structure remote from but connected to the injured cortex – is required to maintain cortical seizures. Thalamocortical neurons connected to the injured epileptic cortex undergo changes in HCN channel expression and become hyperexcitable. Targeting these neurons with a closed-loop optogenetic strategy demonstrates that reducing their activity in real-time is sufficient to immediately interrupt electrographic and behavioral seizures. This approach is of therapeutic interest for intractable epilepsy, since it spares cortical function between seizures, in contrast to existing treatments such as surgical lesioning or drugs.

Extreme delta brush is a novel EEG finding seen in many patients with anti-NMDAR encephalitis. The presence of this pattern is associated with a more prolonged illness. Although the specificity of this pattern is unclear, its presence should raise consideration of this syndrome.

Sensory experience typically depends on the ensemble activity of hundreds or thousands of neurons, but little is known about how populations of neurons faithfully encode behaviorally important sensory information. We examined how precisely speed of movement is encoded in the population activity of magnocellular-projecting parasol retinal ganglion cells (RGCs) in macaque monkey retina. Multi-electrode recordings were used to measure the activity of approximately 100 parasol RGCs simultaneously in isolated retinas stimulated with moving bars. To examine how faithfully the retina signals motion, stimulus speed was estimated directly from recorded RGC responses using an optimized algorithm that resembles models of motion sensing in the brain. RGC population activity encoded speed with a precision of approximately 1%. The elementary motion signal was conveyed in approximately 10 ms, comparable to the interspike interval. Temporal structure in spike trains provided more precise speed estimates than time-varying firing rates. Correlated activity between RGCs had little effect on speed estimates. The spatial dispersion of RGC receptive fields along the axis of motion influenced speed estimates more strongly than along the orthogonal direction, as predicted by a simple model based on RGC response time variability and optimal pooling. on and off cells encoded speed with similar and statistically independent variability. Simulation of downstream speed estimation using populations of speed-tuned units showed that peak (winner take all) readout provided more precise speed estimates than centroid (vector average) readout. These findings reveal how faithfully the retinal population code conveys information about stimulus speed and the consequences for motion sensing in the brain.

Thalamic relay neurons have well-characterized dual firing modes: bursting and tonic spiking. Studies in brain slices have led to a model in which rhythmic synchronized spiking (phasic firing) in a population of relay neurons leads to hyper-synchronous oscillatory cortico-thalamo-cortical rhythms that result in absence seizures. This model suggests that blocking thalamocortical phasic firing would treat absence seizures. However, recent in vivo studies in anesthetized animals have questioned this simple model. Here we resolve this issue by developing a real-time mode-switching approach to drive thalamocortical neurons into or out of a phasic firing mode in two freely-behaving genetic rodent models of absence epilepsy. Toggling between phasic and tonic firing in thalamocortical neurons launched and aborted absence seizures, respectively. Thus a synchronous thalamocortical phasic firing state is required for absence seizures and switching to tonic firing rapidly halts absences. This approach should be useful for modulating other networks that have mode-dependent behaviors.

In patients with lung cancer awaiting LRS, HBETP was feasible and improved exercise tolerance and muscle strength. This may be clinically relevant because poor exercise capacity and muscle weakness are predictors of postoperative complications.

A B S T R A C T PurposeSelenium has been reported to have chemopreventive benefits in lung cancer. We conducted a double-blind, placebo-controlled trial to evaluate the incidence of second primary tumors (SPTs) in patients with resected non-small-cell lung cancer (NSCLC) receiving selenium supplementation. Patients and MethodsPatients with completely resected stage I NSCLC were randomly assigned to take selenized yeast 200 g versus placebo daily for 48 months. Participation was 6 to 36 months postoperatively and required a negative mediastinal node biopsy, no excessive vitamin intake, normal liver function, negative chest x-ray, and no other evidence of recurrence. ResultsThe first interim analysis in October 2009, with 46% of the projected end points accumulated, showed a trend in favor of the placebo group with a low likelihood that the trial would become positive; thus, the study was stopped. One thousand seven hundred seventy-two participants were enrolled, with 1,561 patients randomly assigned. Analysis was updated in June 2011 with the maturation of 54% of the planned end points. Two hundred fifty-two SPTs (from 224 patients) developed, of which 98 (from 97 patients) were lung cancer (38.9%). Lung and overall SPT incidence were 1.62 and 3.54 per 100 person-years, respectively, for selenium versus 1.30 and 3.39 per 100 person-years, respectively, for placebo (P ϭ .294). Five-year disease-free survival was 74.4% for selenium recipients versus 79.6% for placebo recipients. Grade 1 to 2 toxicity occurred in 31% of selenium recipients and 26% of placebo recipients, and grade Ն 3 toxicity occurred in less than 2% of selenium recipients versus 3% of placebo recipients. Compliance was excellent. No increase in diabetes mellitus or skin cancer was detected. ConclusionSelenium was safe but conferred no benefit over placebo in the prevention of SPT in patients with resected NSCLC.