It has been suggested that the function of sleep is to actively clear metabolites and toxins from the brain. Enhanced clearance is also said to occur during anesthesia. Here, we measure clearance and movement of fluorescent molecules in the brains of male mice and show that movement is, in fact, independent of sleep and wake or anesthesia. Moreover, we show that brain clearance is markedly reduced, not increased, during sleep and anesthesia.

Implantable neural interfaces for central nervous system research have been designed with wire, polymer, or micromachining technologies over the past 70 years. Research on biocompatible materials, ideal probe shapes, and insertion methods has resulted in building more and more capable neural interfaces. Although the trend is promising, the long-term reliability of such devices has not yet met the required criteria for chronic human application. The performance of neural interfaces in chronic settings often degrades due to foreign body response to the implant that is initiated by the surgical procedure, and related to the probe structure, and material properties used in fabricating the neural interface. In this review, we identify the key requirements for neural interfaces for intracortical recording, describe the three different types of probes—microwire, micromachined, and polymer-based probes; their materials, fabrication methods, and discuss their characteristics and related challenges.

This paper describes a platform to achieve targeted drug delivery in the next-generation wireless capsule endoscopy. The platform consists of two highly novel subsystems: one is a micropositioning mechanism which can deliver 1 ml of targeted medication and the other is a holding mechanism, which gives the functionality of resisting peristalsis. The micropositioning mechanism allows a needle to be positioned within a 22.5° segment of a cylindrical capsule and be extendible by up to 1.5 mm outside the capsule body. The mechanism achieves both these functions using only a single micromotor and occupying a total volume of just 200 mm ³ . The holding mechanism can be deployed diametrically opposite the needle in 1.8 s and occupies a volume of just 270 mm ³ . An in-depth analysis of the mechanics is presented and an overview of the requirements necessary to realize a total system integration is discussed. It is envisaged that the targeted drug delivery platform will empower a new breed of capsule microrobots for therapy in addition to diagnostics for pathologies such as ulcerative colitis and small intestinal Crohn's disease.

Neuromodulation has wide ranging potential applications in replacing impaired neural function (prosthetics), as a novel form of medical treatment (therapy), and as a tool for investigating neurons and neural function (research). Voltage and current controlled electrical neural stimulation (ENS) are methods that have already been widely applied in both neuroscience and clinical practice for neuroprosthetics. However, there are numerous alternative methods of stimulating or inhibiting neurons. This paper reviews the state-of-the-art in ENS as well as alternative neuromodulation techniques - presenting the operational concepts, technical implementation and limitations - in order to inform system design choices.

Implantable brain machine interfaces (BMIs) are now on a trajectory to go mainstream, wherein what was once considered last resort will progressively become elective at earlier stages in disease treatment. First-in-human successes have demonstrated the ability to decode highly dexterous motor skills such as handwriting, and speech from human cortical activity. These have been used for cursor and prosthesis control, direct-to-text communication and speech synthesis. Along with these breakthrough studies, technology advancements have enabled the observation of more channels of neural activity through new concepts for centralised/distributed implant architectures. This is complemented by research in flexible substrates, packaging, surgical workflows and data processing. New regulatory guidance and funding has galvanised the field. This culmination of resource, efforts and capability is now attracting significant investment for BMI commercialisation. This paper reviews recent developments and describes the paradigm shift in BMI development that is leading to new innovations, insights and BMI translation.

This paper presents an 8 channel energy-efficient neural stimulator for generating charge-balanced asymmetric pulses. Power consumption is reduced by implementing a fully-integrated DC-DC converter that uses a reconfigurable switched capacitor topology to provide 4 output voltages for Dynamic Voltage Scaling (DVS). DC conversion efficiencies of up to 82% are achieved using integrated capacitances of under 1 nF and the DVS approach offers power savings of up to 50% compared to the front end of a typical current controlled neural stimulator. A novel charge balancing method is implemented which has a low level of accuracy on a single pulse and a much higher accuracy over a series of pulses. The method used is robust to process and component variation and does not require any initial or ongoing calibration. Measured results indicate that the charge imbalance is typically between 0.05%-0.15% of charge injected for a series of pulses. Ex-vivo experiments demonstrate the viability in using this circuit for neural activation. The circuit has been implemented in a commercially-available 0.18 μm HV CMOS technology and occupies a core die area of approximately 2.8 mm ² for an 8 channel implementation.