Optoelectronic systems can exert precise control over targeted neurons and pathways throughout the brain in untethered animals, but similar technologies for the spinal cord are not well established. Here, we describe a novel system for ultrafast, wireless, closed-loop manipulation of targeted neurons and pathways across the entire dorsoventral spinal cord in untethered mice. We developed a soft stretchable carrier integrating micro-LEDs that conforms to the dura matter of the spinal cord. A coating of silicone-phosphor matrix over the micro-LEDs provides mechanical protection and light conversion for compatibility with the large library of opsins. A lightweight, head-mounted wireless platform powers the micro-LEDs and performs low-latency on-chip processing of sensed physiological signals to control photostimulation in a closed-loop. We use the device to reveal the role of various neuronal subtypes, sensory pathways and supraspinal projections in the control of locomotion in healthy and spinal-cord injured mice.

Background and Purpose: Oncological neurosurgery relies heavily on making continuous, intra-operative tumor-brain delineations based on image-guidance. Limitations of currently available imaging techniques call for the development of realtime image-guided resection tools, which allow for reliable functional and anatomical information in an intra-operative setting. Functional ultrasound (fUS), is a new mobile neuro-imaging tool with unprecedented spatiotemporal resolution, which allows for the detection of small changes in blood dynamics that reflect changes in metabolic activity of activated neurons through neurovascular coupling. We have applied fUS during conventional awake brain surgery to determine its clinical potential for both intraoperative functional and vascular brain mapping, with the ultimate aim of achieving maximum safe tumor resection. Methods: During awake brain surgery, fUS was used to image tumor vasculature and task-evoked brain activation with electrocortical stimulation mapping (ESM) as a gold standard. For functional imaging, patients were presented with motor, language or visual tasks, while the probe was placed over (ESM-defined) functional brain areas. For tumor vascular imaging, tumor tissue (pre-resection) and tumor resection cavity (postresection) were imaged by moving the hand-held probe along a continuous trajectory over the regions of interest. Results: A total of 10 patients were included, with predominantly intra-parenchymal frontal and temporal lobe tumors of both low and higher histopathological grades. fUS was able to detect (ESM-defined) functional areas deep inside the brain for a range of functional tasks including language processing. Brain tissue could be imaged at a spatial

Objectives Current strategies for motor recovery after spinal cord injury (SCI) aim to facilitate motor performance through modulation of afferent input to the spinal cord using epidural electrical stimulation (EES). The dorsal root ganglion (DRG) itself, the first relay station of these afferent inputs, has not yet been targeted for this purpose. The current study aimed to determine whether DRG stimulation can facilitate clinically relevant motor response in motor complete SCI. Materials and Methods Five patients with chronic motor complete SCI were implanted with DRG leads placed bilaterally on level L4 during five days. Based on personalized stimulation protocols, we aimed to evoke dynamic (phase 1) and isotonic (phase 2) motor responses in the bilateral quadriceps muscles. On days 1 and 5, EMG‐measurements (root mean square [RMS] values) and clinical muscle force measurements (MRC scoring) were used to measure motor responses and their reproducibility. Results In all patients, DRG‐stimulation evoked significant phase 1 and phase 2 motor responses with an MRC ≥4 for all upper leg muscles (rectus femoris, vastus lateralis, vastus medialis, and biceps femoris) (p < 0.05 and p < 0.01, respectively), leading to a knee extension movement strong enough to facilitate assisted weight bearing. No significant differences in RMS values were observed between days 1 and 5 of the study, indicating that motor responses were reproducible. Conclusion The current paper provides first evidence that bilateral L4 DRG stimulation can evoke reproducible motor responses in the upper leg, sufficient for assisted weight bearing in patients with chronic motor complete SCI. As such, a new target for SCI treatment has surfaced, using existing stimulation devices, making the technique directly clinically accessible.

ObjectiveThe outcome of female patients after adult cardiac surgery has been reported to be less favourable compared with the outcome of male patients. This study compares men with women with respect to patient and procedural characteristics and early mortality in a contemporary national cohort of patients who underwent aortic valve (AV) and combined aortic valve/coronary (CABG/AV) surgery.MethodsAll patients who underwent AV (n=8717, 56% male) or a combined CABG/AV surgery (n=5867, 67% male) in the Netherlands between January 2007 and December 2011 were included.ResultsIn both groups, women were generally older than men (p<0.001) and presented with higher logistic EuroSCORES. In isolated AV surgery, men and women had comparable in-hospital mortality (OR 1.20, 95% CI 0.90 to 1.61; p=0.220). In concomitant CABG/AV surgery, in-hospital mortality was higher in women compared with men (OR 2.00, 95% CI 1.44 to 2.79; p<0.001). The area under the curve for logistic EuroSCORE 1 was systematically higher for men versus women in isolated AV surgery 0.82 (95% CI 0.78 to 0.86) vs 0.75 (95% CI 0.69 to 0.80) and in concomitant CABG/AV surgery 0.78 (95% CI 0.73 to 0.82) vs 0.69 (95% CI 0.63 to 0.74). Finally, (the weight of) risk factors associated with in-hospital mortality differed between men and women.ConclusionsThere are substantial male-female differences in patient presentation and procedural aspects in isolated AV and concomitant CABG/AV surgery in the Netherlands. Further studies are necessary to explore the mechanisms underlying the observed differences. In addition, the observation that standard risk scores perform worse in women warrants exploration of male-female specific risk models for patients undergoing cardiac surgery.Brief title:

The field of Neuro-Engineering seems to be on the fast track towards accomplishing its ultimate goal of potentially replacing the nervous system in the face of disease. Meanwhile, the patients and professionals involved are continuously dealing with human bodily experience and especially how neuro-engineering devices could become part of a user's body schema: the domain of 'embodied phenomenology'. This focus on embodiment, however, is not sufficiently reflected in the current literature on ethical and philosophical issues in neuro-engineering. In this article we will focus on this lacuna by explaining existing data on neuro-engineering user's experiences by using phenomenological concepts such as transparency and the concepts that may facilitate this: functionality, sensorimotor feedback and affective tolerance. By introducing and applying these concepts to four real life case examples, we will discuss practical implications and guidelines which can contribute to the actual success of incorporation of the device by the patient. First, we will discuss the importance of a 'Patient Preference Diagnosis' (PPD), which can serve as a way to prepare the patient for the existential reorientation involved in the process. In addition, a Patient Transparency Diagnosis (PTD) during and after such a process is also relevant when wanting to provide the medical field in general with feedback, and the patient in particular with possibilities to fine-tune the device. From these practical guidelines we will conclude that the phenomenological approach can be very valuable when applied to the field of neuro-engineering.

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