Recording advances for neural prosthetics

An important challenge for neural prosthetics research is to record from populations of neurons over long periods of time, ideally for the lifetime of the patient. Two new advances toward this goal are described, the use of local field potentials (LFPs) and autonomously positioned recording electrodes. LFPs are the composite extracellular potential field from several hundreds of neurons around the electrode tip. LFP recordings can be maintained for longer periods of time than single cell recordings. We find that similar information can be decoded from LFP and spike recordings, with better performance for state decodes with LFPs and, depending on the area, equivalent or slightly less than equivalent performance for signaling the direction of planned movements. Movable electrodes in microdrives can be adjusted in the tissue to optimize recordings, but their movements must be automated to be a practical benefit to patients. We have developed automation algorithms and a meso-scale autonomous electrode testbed, and demonstrated that this system can autonomously isolate and maintain the recorded signal quality of single cells in the cortex of awake, behaving monkeys. These two advances show promise for developing very long term recording for neural prosthetic applications

Brucellosis remains a neglected disease inthe developing world: a call forinterdisciplinary action

Brucellosis places significant burdens on the human healthcare system and limits the economic growth of individuals, communities, and nations where such development is especially important to diminish the prevalence of poverty. The implementation of public policy focused on mitigating the socioeconomic effects of brucellosis in human and animal populations is desperately needed. When developing a plan to mitigate the associated consequences, it is vital to consider both the abstract and quantifiable effects. This requires an interdisciplinary and collaborative, or One Health, approach that consists of public education, the development of an infrastructure for disease surveillance and reporting in both veterinary and medical fields, and campaigns for control in livestock and wildlife species

Motor Preparatory Activity in Posterior Parietal Cortex is Modulated by Subjective Absolute Value

For optimal response selection, the consequences associated with behavioral success or failure must be appraised. To determine how monetary consequences influence the neural representations of motor preparation, human brain activity was scanned with fMRI while subjects performed a complex spatial visuomotor task. At the beginning of each trial, reward context cues indicated the potential gain and loss imposed for correct or incorrect trial completion. FMRI-activity in canonical reward structures reflected the expected value related to the context. In contrast, motor preparatory activity in posterior parietal and premotor cortex peaked in high “absolute value” (high gain or loss) conditions: being highest for large gains in subjects who believed they performed well while being highest for large losses in those who believed they performed poorly. These results suggest that the neural activity preceding goal-directed actions incorporates the absolute value of that action, predicated upon subjective, rather than objective, estimates of one's performance

A simulation study on the effects of neuronal ensemble properties on decoding algorithms for intracortical brain-machine interfaces

Background: Intracortical brain-machine interfaces (BMIs) harness movement information by sensing neuronal activities using chronic microelectrode implants to restore lost functions to patients with paralysis. However, neuronal signals often vary over time, even within a day, forcing one to rebuild a BMI every time they operate it. The term "rebuild" means overall procedures for operating a BMI, such as decoder selection, decoder training, and decoder testing. It gives rise to a practical issue of what decoder should be built for a given neuronal ensemble. This study aims to address it by exploring how decoders' performance varies with the neuronal properties. To extensively explore a range of neuronal properties, we conduct a simulation study. Methods: Focusing on movement direction, we examine several basic neuronal properties, including the signal-to-noise ratio of neurons, the proportion of well-tuned neurons, the uniformity of their preferred directions (PDs), and the non-stationarity of PDs. We investigate the performance of three popular BMI decoders: Kalman filter, optimal linear estimator, and population vector algorithm. Results: Our simulation results showed that decoding performance of all the decoders was affected more by the proportion of well-tuned neurons that their uniformity. Conclusions: Our study suggests a simulated scenario of how to choose a decoder for intracortical BMIs in various neuronal conditions

Reach and grasp by people with tetraplegia using a neurally controlled robotic arm

Paralysis following spinal cord injury (SCI), brainstem stroke, amyotrophic lateral sclerosis (ALS) and other disorders can disconnect the brain from the body, eliminating the ability to carry out volitional movements. A neural interface system (NIS)1–5 could restore mobility and independence for people with paralysis by translating neuronal activity directly into control signals for assistive devices. We have previously shown that people with longstanding tetraplegia can use an NIS to move and click a computer cursor and to control physical devices6–8. Able-bodied monkeys have used an NIS to control a robotic arm9, but it is unknown whether people with profound upper extremity paralysis or limb loss could use cortical neuronal ensemble signals to direct useful arm actions. Here, we demonstrate the ability of two people with long-standing tetraplegia to use NIS-based control of a robotic arm to perform three-dimensional reach and grasp movements. Participants controlled the arm over a broad space without explicit training, using signals decoded from a small, local population of motor cortex (MI) neurons recorded from a 96-channel microelectrode array. One of the study participants, implanted with the sensor five years earlier, also used a robotic arm to drink coffee from a bottle. While robotic reach and grasp actions were not as fast or accurate as those of an able-bodied person, our results demonstrate the feasibility for people with tetraplegia, years after CNS injury, to recreate useful multidimensional control of complex devices directly from a small sample of neural signals

Cognitive Control Signals for Neural Prosthetics

Recent development of neural prosthetics for assisting paralyzed patients has focused on decoding intended hand trajectories from motor cortical neurons and using this signal to control external devices. In this study, higher level signals related to the goals of movements were decoded from three monkeys and used to position cursors on a computer screen without the animals emitting any behavior. Their performance in this task improved over a period of weeks. Expected value signals related to fluid preference, the expected magnitude, or probability of reward were decoded simultaneously with the intended goal. For neural prosthetic applications, the goal signals can be used to operate computers, robots, and vehicles, whereas the expected value signals can be used to continuously monitor a paralyzed patient's preferences and motivation

Differential effects of iron chelators on iron burden and long-term morbidity and mortality outcomes in a large cohort of transfusion-dependent β-thalassemia patients who remained on the same monotherapy over 10 years

We conducted a retrospective cohort study on 663 transfusion-dependent β-thalassemia patients receiving the same iron chelation monotherapy with deferoxamine, deferiprone, or deferasirox for up to 10 years (median age 31.8 years, 49.9 % females). Patients on all three iron chelators had a steady and significant decline in serum ferritin over the 10 years (median deferoxamine: -170.7 ng/mL, P = 0.049, deferiprone: -236.7 ng/mL, P = 0.001; deferasirox: -323.7 ng/mL, P < 0.001) yet had no significant change in liver iron concentration or cardiac T2*; while noting that patients generally had low hepatic and cardiac iron levels at study start. Median absolute, relative, and normalized changes were generally comparable between the three iron chelators. Patients receiving deferasirox had the highest morbidity and mortality-free survival probability among the three chelators, although the difference was only statistically significant when compared with deferoxamine (P = 0.037). On multivariate Cox regression analysis, there was no significant association between iron chelator type and the composite outcome of morbidity or mortality. In a real-world setting, there is comparable long-term iron chelation effectiveness between the three available iron chelators for patients with mild-to-moderate iron overload

Revisiting iron overload status and change thresholds as predictors of mortality in transfusion-dependent β-thalassemia: a 10-year cohort study

Data on iron overload status and change thresholds that can predict mortality in patients with transfusion-dependent β-thalassemia (TDT) are limited. This was a retrospective cohort study of 912 TDT patients followed for up to 10 years at treatment centers in Italy (median age 32 years, 51.6% female). The crude mortality rate was 2.9%. Following best-predictive threshold identification through receiver operating characteristic curve analyses, data from multivariate Cox-regression models showed that patients with Period Average Serum Ferritin (SF) > 2145 vs ≤ 2145 ng/mL were 7.1-fold (P < 0.001) or with Absolute Change SF > 1330 vs ≤ 1330 ng/mL increase were 21.5-fold (P < 0.001) more likely to die from any cause. Patients with Period Average Liver Iron Concentration (LIC) > 8 vs ≤ 8 mg/g were 20.2-fold (P < 0.001) or with Absolute Change LIC > 1.4 vs ≤ 1.4 mg/g increase were 27.6-fold (P < 0.001) more likely to die from any cause. Patients with Index (first) cardiac T2* (cT2*) < 27 vs ≥ 27 ms were 8.6-fold (P < 0.001) more likely to die from any cause. Similarly, results at varying thresholds were identified for death from cardiovascular disease. These findings should support decisions on iron chelation therapy by establishing treatment targets, including safe iron levels and clinically meaningful changes over time

Emerging Therapies

At present, the only definitive cure for β-thalassemia is a bone marrow transplant (BMT); however, HLA–blood-matched donors are scarcely available. Current therapies undergoing clinical investigation with most potential for therapeutic benefit are the β-globin gene transfer of patient-specific hematopoietic stem cells followed by autologous BMT. Other emerging therapies deliver exogenous regulators of several key modulators of erythropoiesis or iron homeostasis. This review focuses on current approaches for the treatment of hemoglobinopathies caused by disruptions of β-globin. © 2017 Elsevier Inc