Jesus Minguillon

The first generation of invasive brain-computer interfaces was conceived as a centralized and monolithic technology composed of an array of microelectrodes implanted on the brain surface and wired to an external unit for telemetry and power supply. Although this technology exceeded the expectations and possibilities of the noninvasive one, risks associated with implantation of wired devices and procedures appeared. Advances in electronics miniaturization and wireless power transfer methods, among others, have favored the proposal of wireless submillimeter implantable devices with stimulation and telemetry capabilities. This constitutes the foundation stone of a next generation of submilliliter implanted neurosensors (NG-SINs) based on massive distributed networks of untethered neuroimplants deployed on the brain. This particular ecosystem, because of the inherent severe restrictions in size, power consumption, electromagnetic safety, and computational capacity, presents significant challenges in the field of communications and internetworking, such as media access control, addressing, data error rate, and others. In this study, we propose a combination of orthogonal multiple access (OMA) and nonorthogonal media access (NOMA) as the base for the telemetry of the NG-SINs, with a focus on the detection of neural spikes in real time. Specifically, we propose the use of asynchronous code division multiple access (aCDMA) and power domain non orthogonal media access (PD-NOMA) with successive interference cancelation (SIC) over backscattered communications. While aCDMA mimics the spontaneous nature of brain activity, and provides addressing and grant-free random-access mechanism, its inherent near-far issue can be conveniently used to improve the performance by means of PD-NOMA and SIC. Based on our simulations, we conclude that this combination of NOMA and OMA techniques is a viable and promising approach for the NG-SINs applied to neural spikes detection that enables scalability with improved performance.

Although biomedical engineering (BME) is a profession with ethical responsibilities comparable to those in medicine, it has, until now, lacked a counterpart to the Hippocratic Oath. While professional societies have established codes of ethics for biomedical engineers, these documents lack the symbolic and ceremonial significance of an oath or pledge. By contrast, the recitation of the Hippocratic Oath, or its modern version, the “Physician’s Pledge,” serves as a powerful rite of passage for medical students, fostering a strong sense of ethical duty at the start of their professional journey. However, the content of the Hippocratic Oath includes elements specific to clinical practice and is not directly applicable to biomedical engineering. To fill this gap, we have created a “Biomedical Engineer’s Pledge,” comprising a preamble, ten promises, and a concluding statement, to inspire ethical awareness and establish a meaningful graduation tradition. Graphical abstract

The level of student attention in class greatly affects their academic performance. Teachers typically rely on visual inspection to react to students’ attention in time, but this subjective method leads to inconsistencies across classes. Online education exacerbates the issue as students can turn off cameras and microphones to keep their own privacy. To address this, we present a novel, low-cost EEG-based platform for assessing students’ attention and estimating their academic performance. In a study involving 34 secondary school students (aged 14 to 16), participants watched an academic video and answered evaluation questions while their EEG activity was recorded using a commercial headset. The results demonstrate a significant correlation (0.53, p-value = 0.003) between the power spectral density (PSD) of the EEG beta band (12–30 Hz) and students’ academic performance. Additionally, there was a notable difference in PSD-beta between high and low academic performers. These findings encourage the use of PSD-beta for the immediate and objective assessment of both the student attention and the subsequent academic performance. The platform offers valuable and objective feedback to teachers, enhancing the effectiveness of both face-to-face and online teaching and learning environments.

Cardiorespiratory fitness is one of the most important markers of health. Several studies have demonstrated the relationship between cardiorespiratory fitness and brain functioning in healthy children. Some of these works suggested that cardiorespiratory fitness may have a protective role on the executive function, which represents a set of cognitive mechanisms used to control and coordinate other cognitive abilities. This is particularly relevant in children with overweight or obesity. In these studies, neuroelectric activity is recorded using medical imaging techniques or electroencephalography (EEG). Among the EEG studies, analyses based on the P3 event related potential stand out. However, complementary analyses are necessary to understand the neural mechanisms underlying the associations between cardiorespiratory fitness and brain functioning. EEG complexity, a useful feature that measures the regularity of neuroelectric activity, has been previously associated with cardiorespiratory fitness in adolescents. In this work, we evaluate this association in a group of 87 Caucasian children with overweight/obesity. Our results reveal that the children with higher cardiorespiratory fitness present less EEG complexity while performing a cognitive task that challenges the executive function. In addition, they suggest that the line length, the metric that we used to estimate EEG complexity, performs equally well as those metrics based on the P3 and better than other complexity metrics like sample entropy, as an indicator of cardiorespiratory fitness. Finally, the line length has advantages over the P3: more consistency across EEG regions and cognitive loads, lower experimental complexity, lower computational cost, and higher automatization capability.

Background: Recently we reported the design and evaluation of floating semi-implantable devices that receive power from and bidirectionally communicate with an external system using coupling by volume conduction. The approach, of which the semi-implantable devices are proof-of-concept prototypes, may overcome some limitations presented by existing neuroprostheses, especially those related to implant size and deployment, as the implants avoid bulky components and can be developed as threadlike devices. Here, it is reported the first-in-human acute demonstration of these devices for electromyography (EMG) sensing and electrical stimulation. Methods: A proof-of-concept device, consisting of implantable thin-film electrodes and a non-implantable miniature electronic circuit connected to them, was deployed in the upper or lower limb of six healthy participants. Two external electrodes were strapped around the limb and were connected to the external system which delivered high frequency current bursts. Within these bursts, 13 commands were modulated to communicate with the implant. Results: Four devices were deployed in the biceps brachii and the gastrocnemius medialis muscles, and the external system was able to power and communicate with them. Limitations regarding insertion and communication speed are reported. Sensing and stimulation parameters were configured from the external system. In one participant, electrical stimulation and EMG acquisition assays were performed, demonstrating the feasibility of the approach to power and communicate with the floating device. Conclusions: This is the first-in-human demonstration of EMG sensors and electrical stimulators powered and operated by volume conduction. These proof-of-concept devices can be miniaturized using current microelectronic technologies, enabling fully implantable networked neuroprosthetics.

Accumulation and interaction of amyloid-beta (Aβ) and tau proteins during progression of Alzheimer’s disease (AD) are shown to tilt neuronal circuits away from balanced excitation/inhibition (E/I). Current available techniques for noninvasive interrogation of E/I in the intact human brain, e.g., magnetic resonance spectroscopy (MRS), are highly restrictive (i.e., limited spatial extent), have low temporal and spatial resolution and suffer from the limited ability to distinguish accurately between different neurotransmitters complicating its interpretation. As such, these methods alone offer an incomplete explanation of E/I. Recently, the aperiodic component of neural power spectrum, often referred to in the literature as the ‘ 1/f slope’, has been described as a promising and scalable biomarker that can track disruptions in E/I potentially underlying a spectrum of clinical conditions, such as autism, schizophrenia, or epilepsy, as well as developmental E/I changes as seen in aging. Using 1/f slopes from resting-state spectral data and computational modelling we developed a new method for inferring E/I alterations in AD. We tested our method on recent freely and publicly available electroencephalography (EEG) and magnetoencephalography (MEG) datasets of patients with AD or prodromal disease and demonstrated the method’s potential for uncovering regional patterns of abnormal excitatory and inhibitory parameters. Our results provide a general framework for investigating circuit-level disorders in AD and developing therapeutic interventions that aim to restore the balance between excitation and inhibition.

Objective. To develop and in vivo demonstrate threadlike wireless implantable neuromuscular microstimulators that are digitally addressable. Approach. These devices perform, through its two electrodes, electronic rectification of innocuous high frequency current bursts delivered by volume conduction via epidermal textile electrodes. By avoiding the need of large components to obtain electrical energy, this approach allows the development of thin devices that can be intramuscularly implanted by minimally invasive procedures such as injection. For compliance with electrical safety standards, this approach requires a minimum distance, in the order of millimeters or a very few centimeters, between the implant electrodes. Additionally, the devices must cause minimal mechanical damage to tissues, avoid dislocation and be adequate for long-term implantation. Considering these requirements, the implants were conceived as tubular and flexible devices with two electrodes at opposite ends and, at the middle section, a hermetic metallic capsule housing the electronics. Main results. The developed implants have a submillimetric diameter (0.97 mm diameter, 35 mm length) and consist of a microcircuit, which contains a single custom-developed integrated circuit, housed within a titanium capsule (0.7 mm diameter, 6.5 mm length), and two platinum–iridium coils that form two electrodes (3 mm length) located at opposite ends of a silicone body. These neuromuscular stimulators are addressable, allowing to establish a network of microstimulators that can be controlled independently. Their operation was demonstrated in an acute study by injecting a few of them in the hind limb of anesthetized rabbits and inducing controlled and independent contractions. Significance. These results show the feasibility of manufacturing threadlike wireless addressable neuromuscular stimulators by using fabrication techniques and materials well established for chronic electronic implants. Although long-term operation still must be demonstrated, the obtained results pave the way to the clinical development of advanced motor neuroprostheses formed by dense networks of such wireless devices.

Objective: Wireless power transfer (WPT) is used as an alternative to batteries to accomplish miniaturization in electronic medical implants. However, established WPT methods require bulky parts within the implant or cumbersome external systems, hindering minimally invasive deployments and the development of networks of implants. As an alternative, we propose a WPT approach based on volume conduction of high frequency (HF) current bursts. These currents are applied through external electrodes and are collected by the implants through two electrodes at their opposite ends. This approach avoids bulky components, enabling the development of flexible threadlike implants. Methods: We study in humans if HF (6.78 MHz) current bursts complying with safety standards and applied through two textile electrodes strapped around a limb can provide substantial powers from pairs of implanted electrodes. Results: Time averaged electric powers obtained from needle electrodes (diameter = 0.4 mm, length = 3 mm, separation = 30 mm) inserted into arms and lower legs of five healthy participants were 5.9 ± 0.7 mW and 2.4 ± 0.3 mW respectively. We also characterize the coupling between the external system and the implants using personalized two-port impedance models generated from medical images. Conclusions: The results demonstrate that innocuous and imperceptible HF current bursts that flow through the tissues by volume conduction can be used to wirelessly power threadlike implants. Significance: This is the first time that WPT based on volume conduction is demonstrated in humans. This method overcomes the limitations of existing WPT methods in terms of minimal invasiveness and usability.

Objective: To develop and in vivo demonstrate threadlike wireless implantable neuromuscular microstimulators that are digitally addressable. Approach: These devices perform, through its two electrodes, electronic rectification of innocuous high frequency current bursts delivered by volume conduction via epidermal textile electrodes. By avoiding the need of large components to obtain electrical energy, this approach allows the development of thin devices that can be intramuscularly implanted by minimally invasive procedures such as injection. For compliance with electrical safety standards, this approach requires a minimum distance, in the order of millimeters or a very few centimeters, between the implant electrodes. Additionally, the devices must cause minimal mechanical damage to tissues, avoid dislocation and be adequate for long-term implantation. Considering these requirements, the implants were conceived as tubular and flexible devices with two electrodes at opposite ends and, at the middle section, a hermetic metallic capsule housing the electronics. Main results: The developed implants have a submillimetric diameter (0.97 mm diameter, 35 mm length) and consist of a microcircuit, which contains a single custom-developed integrated circuit, housed within a titanium capsule (0.7 mm diameter, 6.5 mm length), and two platinum-iridium coils that form two electrodes (3 mm length) located at opposite ends of a silicone body. These neuromuscular stimulators are addressable, allowing to establish a network of microstimulators that can be controlled independently. Their operation was demonstrated by injecting a few of them in the hind limb of anesthetized rabbits and inducing controlled and independent contractions. Significance: These results show the feasibility of manufacturing threadlike wireless addressable neuromuscular stimulators by using fabrication techniques and materials well established for chronic electronic implants. This paves the way to the clinical development of advanced motor neuroprostheses formed by dense networks of such wireless devices.