Totally Implantable Bidirectional Neural Prostheses: A Flexible Platform for Innovation in Neuromodulation.

Implantable neural prostheses are in widespread use for treating a variety of brain disorders. Until recently, most implantable brain devices have been unidirectional, either delivering neurostimulation without brain sensing, or sensing brain activity to drive external effectors without a stimulation component. Further, many neural interfaces that incorporate a sensing function have relied on hardwired connections, such that subjects are tethered to external computers and cannot move freely. A new generation of neural prostheses has become available, that are both bidirectional (stimulate as well as record brain activity) and totally implantable (no externalized connections). These devices provide an opportunity for discovering the circuit basis for neuropsychiatric disorders, and to prototype personalized neuromodulation therapies that selectively interrupt neural activity underlying specific signs and symptoms

Reviews

Francis Botto, Dictionary of Multimedia and Internet Applications ‐ A Guide for Developers and Users, Chichester, UK: John Wiley & Sons, 1999. ISBN: 0–471–986240. Hardback, x+362 pages, £34.95

Beta Oscillations in Working Memory, Executive Control of Movement and Thought, and Sensorimotor Function

Beta oscillations (~13 to 30Hz) have been observed during many perceptual, cognitive and motor processes in a plethora of brain recording studies. While the function of beta oscillations (hereafter ‘beta’ for short) is unlikely to be explained by any single monolithic description, we here discuss several convergent findings. In prefrontal cortex, increased beta appears at the end of a trial when working memory information needs to be erased. A similar clear-out function might apply during the stopping of action and the stopping of long-term memory retrieval (stopping thoughts), where increased prefrontal beta is also observed. A different apparent role for beta in prefrontal cortex occurs during the delay period of working memory tasks: it might serve to maintain the current contents and/or to prevent interference from distraction. We confront the challenge of relating these observations to the large literature on beta recorded from sensorimotor cortex. Potentially, the clear-out of working memory in prefrontal cortex has its counterpart in the post-movement clear-out of the motor plan in sensorimotor cortex. However, recent studies support alternative interpretations. In addition, we flag emerging research on different frequencies of beta and the relationship between beta and single neuron spiking. We also discuss where beta might be generated: basal ganglia, cortex, or both. We end by considering the clinical implications for adaptive deep brain stimulation

Research options and imperatives in computerized conferencing

This is the report resulting from a computerized conferencing workshop held on the subject of potential research opportunities and requirements in the area of utilizing a computer to aid human communications. It was sponsored by the Division of Mathematical and Computer Sciences of the National Science Foundation (grant # MCS76-80514). The views expressed in this report are those of the authors, and do not necessarily reflect NSF views or policy. The workshop utilized the Electronic Information Exchange System (EIES) at the New Jersey Institute of Technology

Washout of chronic therapeutic deep brain stimulation increases cortical phase-amplitude coupling.

Invasive human brain recordings have shown that acute therapeutic deep brain stimulation (DBS) reduces cortical synchronization, measured by coupling of beta phase to gamma amplitude. Here we show by noninvasive scalp electroencephalography that withdrawal of chronic DBS elevates phase-amplitude coupling, in proportion to the worsening of contralateral rigidity

Multi-night cortico-basal recordings reveal mechanisms of NREM slow-wave suppression and spontaneous awakenings in Parkinson's disease

Sleep disturbance is a prevalent and disabling comorbidity in Parkinson’s disease (PD). We performed multi-night (n = 57) at-home intracranial recordings from electrocorticography and subcortical electrodes using sensing-enabled Deep Brain Stimulation (DBS), paired with portable polysomnography in four PD participants and one with cervical dystonia (clinical trial: NCT03582891). Cortico-basal activity in delta increased and in beta decreased during NREM (N2 + N3) versus wakefulness in PD. DBS caused further elevation in cortical delta and decrease in alpha and low-beta compared to DBS OFF state. Our primary outcome demonstrated an inverse interaction between subcortical beta and cortical slow-wave during NREM. Our secondary outcome revealed subcortical beta increases prior to spontaneous awakenings in PD. We classified NREM vs. wakefulness with high accuracy in both traditional (30 s: 92.6 ± 1.7%) and rapid (5 s: 88.3 ± 2.1%) data epochs of intracranial signals. Our findings elucidate sleep neurophysiology and impacts of DBS on sleep in PD informing adaptive DBS for sleep dysfunction

Altered Prefrontal Theta and Gamma Activity during an Emotional Face Processing Task in Parkinson Disease.

Patients with Parkinson disease (PD) often experience nonmotor symptoms including cognitive deficits, depression, and anxiety. Cognitive and affective processes are thought to be mediated by prefrontal cortico-basal ganglia circuitry. However, the topography and neurophysiology of prefrontal cortical activity during complex tasks are not well characterized. We used high-resolution electrocorticography in pFC of patients with PD and essential tremor, during implantation of deep brain stimulator leads in the awake state, to understand disease-specific changes in prefrontal activity during an emotional face processing task. We found that patients with PD had less task-related theta-alpha power and greater task-related gamma power in the dorsolateral pFC, inferior frontal cortex, and lateral OFC. These findings support a model of prefrontal neurophysiological changes in the dopamine-depleted state, in which focal areas of hyperactivity in prefrontal cortical regions may compensate for impaired long-range interactions mediated by low-frequency rhythms. These distinct neurophysiological changes suggest that nonmotor circuits undergo characteristic changes in PD

Human Body Composition and Immunity: Visceral Adipose Tissue Produces IL-15 and Muscle Strength Inversely Correlates with NK Cell Function in Elderly Humans

Natural killer (NK) lymphocyte-mediated cytotoxicity and cytokine secretion control infections and cancers, but these crucial activities decline with age. NK cell development, homeostasis, and function require IL-15 and its chaperone, IL-15 receptor alpha (IL-15Rα). Macrophages and dendritic cells (DC) are major sources of these proteins. We had previously postulated that additional IL-15 and IL-15Rα is made by skeletal muscle and adipose tissue. These sources may be important in aging, when IL-15-producing immune cells decline. NK cells circulate through adipose tissue, where they may be exposed to local IL-15. The objectives of this work were to determine (1) if human muscle, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) are sources of IL-15 and IL-15 Rα, and (2) whether any of these tissues correlate with NK cell activity in elderly humans. We first investigated IL-15 and IL-15Rα RNA expression in paired muscle and SAT biopsies from healthy human subjects. Both tissues expressed these transcripts, but IL-15Rα RNA levels were higher in SAT than in skeletal muscle. We also investigated tissue obtained from surgeries and found that SAT and VAT expressed equivalent amounts of IL-15 and IL-15Rα RNA, respectively. Furthermore, stromal vascular fraction cells expressed more IL-15 RNA than did adipocytes. To test if these findings related to circulating IL-15 protein and NK cell function, we tested 50 healthy adults aged \u3e 70 years old. Plasma IL-15 levels significantly correlated with abdominal VAT mass in the entire cohort and in non-obese subjects. However, plasma IL-15 levels did not correlate with skeletal muscle cross-sectional area and correlated inversely with muscle strength. Plasma IL-15 did correlate with NK cell cytotoxic granule exocytosis and with CCL4 (MIP-1β) production in response to NKp46-crosslinking. Additionally, NK cell responses to K562 leukemia cells correlated inversely with muscle strength. With aging, immune function declines while infections, cancers, and deaths increase. We propose that VAT-derived IL-15 and IL-15Rα is a compensatory NK cell support mechanism in elderly humans

GJ 3236: a new bright, very low-mass eclipsing binary system discovered by the MEarth observatory

We report the detection of eclipses in GJ 3236, a bright (I = 11.6) very low mass binary system with an orbital period of 0.77 days. Analysis of light- and radial velocity curves of the system yielded component masses of 0.38 +/- 0.02 and 0.28 +/- 0.02 Msol. The central values for the stellar radii are larger than the theoretical models predict for these masses, in agreement with the results for existing eclipsing binaries, although the present 5% observational uncertainties limit the significance of the larger radii to approximately 1 sigma. Degeneracies in the light curve models resulting from the unknown configuration of surface spots on the components of GJ 3236 currently dominate the uncertainties in the radii, and could be reduced by obtaining precise, multi-band photometry covering the full orbital period. The system appears to be tidally synchronized and shows signs of high activity levels as expected for such a short orbital period, evidenced by strong Halpha emission lines in the spectra of both components. These observations probe an important region of mass-radius parameter space around the predicted transition to fully-convective stellar interiors, where there are a limited number of precise measurements available in the literature.Comment: 14 pages, 5 figures, 10 tables, emulateapj format. Accepted for publication in Ap

Comparison of Tissue Injury from Focused Ultrasonic Propulsion of Kidney Stones Versus Extracorporeal Shock Wave Lithotripsy

Purpose Focused ultrasonic propulsion is a new non-invasive technique designed to move kidney stones and stone fragments out of the urinary collecting system. However, the extent of tissue injury associated with this technique is not known. As such, we quantitated the amount of tissue injury produced by focused ultrasonic propulsion under simulated clinical treatment conditions, and under conditions of higher power or continuous duty cycles, and compared those results to SWL injury. Materials and Methods A human calcium oxalate monohydrate stone and/or nickel beads were implanted (with ureteroscopy) into 3 kidneys of live pigs (45–55 kg) and repositioned using focused ultrasonic propulsion. Additional pig kidneys were exposed to SWL level pulse intensities or continuous ultrasound exposure of 10 minutes duration (ultrasound probe either transcutaneous or on the kidney). These kidneys were compared to 6 kidneys treated with an unmodified Dornier HM3 Lithotripter (2400 shocks, 120 SWs/min and 24 kV). Histological analysis was performed to assess the volume of hemorrhagic tissue injury created by each technique (% functional renal volume, FRV). Results SWL produced a lesion of 1.56±0.45% FRV. Ultrasonic propulsion produced no detectable lesion with the simulated clinical treatment. A lesion of 0.46±0.37% FRV or 1.15±0.49% FRV could be produced if excessive treatment parameters were used while the ultrasound probe was placed on the kidney. Conclusions Focused ultrasonic propulsion produced no detectable morphological injury to the renal parenchyma when using clinical treatment parameters and produced injury comparable in size to SWL when using excessive treatment parameters