Here you can find a list of publishable project dissemination items:
UPSIDE’s project poster as presented during the EIC Summit 2022
UPSIDE’ s project one slide intro as presented during the EIC Summit 2022
UPSIDE’s open access publication about LIFU as an emerging method for treating major depressive disorder.
UPSIDE’s open access publication about the complexity of neuronal networks of depression & Epidural-focused ultrasound as a promising therapy
UPSIDE’s open access publication discusses the opportunities surrounding low-intensity focused ultrasound in the treatment of major depressive disorder in minimally invasive manner
Power and area efficient on-chip feature extraction is needed for future closed-loop neural interfaces. This paper presents a feature extraction unit for neural oscillatory synchrony that bypasses the phase extraction step to reduce hardware complexity.
Published in: 2023 IEEE International Symposium on Circuits and Systems (ISCAS)
UPSIDE’s open access publication puts in perspective the Neural Interfaces as a review article that covers all the main parts, explains their functionality, and promotes new ideas and a solution-centric way of thinking.
UPSIDE’s introductory leaflet from our team available for project’s dissemination purposes.
UPSIDE’s brand new Newsletter is out that summarizes our Year 1 progresses so far.
Understanding and modulating neural networks requires high-resolution acquisition of neural activity over time, real-time analysis, and minimally invasive stimulation methods with high specificity. Such procedures are particularly needed for treatment of sensory disfunction (e.g. hearing loss), and certain neurological diseases (e.g. epilepsy). The lack of soft, biocompatible, hybrid and smart neural interfaces hinders our capacity to study complex neural dynamics and efficiently apply responsive neuromodulation therapy. Here, I am presenting the vision of Neural Waves lab towards designing and developing materials and novel fully implantable, contained and responsive neural interfaces that will allow long-term acquisition and closed-loop manipulation of neural circuits with high spatiotemporal resolution over extended period of time to reveal neural dynamics in different neurological pathways and alleviate disfunctions and diseases. I will cover our studies on i) creating artificial basilar membrane based on acousto-sensitive ion-based transistors and soft electronics, ii) innovating electroencephalography interfaces, and iii) utilizing organic perforated multielectrode arrays to investigate the effect of photopharmacological interventions on Cortical Seizures.
Published in: Materials for Sustainable Development Conference (MATSUS)
Proceedings of MATSUS Fall 2023 Conference (MATSUSFall23)
UPSIDE open access publication explores the potential of neuroimaging techniques, specifically non-invasive electroencephalography (EEG), in detecting biomarkers for depression.
UPSIDE’s brand new Newsletter is out and summarizes our progress so far in Year 2.
Piezoelectric Micromachined Ultrasonic Transducers (PMUT) and Capacitive Micromachined Ultrasonic Transducers (CMUT) have seen great developments in recent years, both in terms of performance and scope of applications within the biomedical ultrasound domain. This paper presents a review of the state-of-the-art of PMUT and CMUT technologies, focusing on their principle of operation, microfabrication techniques and use in different biomedical imaging and therapeutic applications. The advantages and drawbacks of PMUT and CMUT technologies in comparison with conventional bulk transducers are highlighted, the trade-offs among PMUTs and CMUTs are discussed, and their relevance in the current landscape of medical diagnostics and therapeutic uses is outlined, thus providing a clear overview of these promising technologies for the present and the next generation biomedical ultrasound applications.
Published in: IEEE Access (Volume: 12)
Epilepsy is a chronic neurological disorder characterized by recurrent seizures, affecting millions of people worldwide. Current treatment methods have limitations such as side effects and incomplete seizure control. One potential approach to address these challenges is by targeting the adenosine type 1 receptor, which is abundantly present in the body, for epilepsy suppression. However, it is important to note that this approach may introduce multiple undesired side effects such as dizziness, sleep disturbances, mood, cognitive, memory changes etc.
Optopharmacology is an emerging approach for the treatment of focal epileptic seizures by activating and deactivating photoswitchable/photocaged molecules with light. It is a particularly interesting treatment solution which could result in powerful suppression of focal seizures with a limited number of side effects. In this work, we study the neural dynamics of epileptic networks (in rodent model) and the effect of timely photo-release of a caged adenosine type 1 receptor agonist (caged CPA; N6-cyclopentyladenosine) hereon. To achieve that, we had to develop: i) animal protocols with evoked epileptic seizures, ii) illumination protocols proper for photorelease of the novel caged CPA molecule, iii) efficient microelectrode arrays, to trace the corresponding electrophysiology, that can simultaneously offer large spatial epidural coverage and high signal to noise ratio without sacrificing resolution or hindering illumination and drug appliance. In more detail, we performed craniotomies on several subjects to place semitransparent microelectrode array based on organic electronics on dura and trace electrophysiology. To provoke focal random epileptic seizures 4 – Aminopyridine (4-AP) was microinjected in different areas of the rat brain through specifically designed perforation paths. Upon microinjection of caged CPA epileptic activity continued but when the brain was exposed to pulses of 405nm light for uncaging of cCPA, local epileptic activity was strongly attenuated. The results of this study provide a better understanding of propagation of 4AP induced seizures and confinement dynamics upon spatially resolved These findings are significant because they will positively impact the development of optopharmacological molecules and protocols, microelectrode arrays and therapeutic systems.
Bulk piezoelectric ultrasound transducers on integrated circuits offer unique properties for therapeutic applications of ultrasound neuromodulation. However, current implementations of such transducers are not optimized for the high transmit efficiency required to stimulate neurons. This is mainly due to the challenge of implementing a metal layer on top of the piezoelectric film using microfabrication techniques. Here, we propose a micromachined capping structure providing an electrical connection on top of the piezoelectric film with minimal acoustic losses. The structure can potentially be used as a common ground connection in phased-array ultrasound transducers.
Published in: Proceedings of XXXV EUROSENSORS Conference
Reserpine (RES), a Vesicular Monoamine Transporter 2 (VMAT2) inhibitor agent, has been used in preclinical research for many years to create animal models for depression and to test experimental antidepressant strategies. Nevertheless, evidence of the potential use and validity of RES as a chronic pharmacological model for depression is lacking, and there are no comprehensive studies of the behavioral effects in conjunction with molecular outcomes.
Published in: Progress in Neuro-Psychopharmacology and Biological Psychiatry Volume 133
Developing an implantable/wearable 2D ultrasound phased array for ultrasound neuromodulation poses several challenges, including power requirements for driving the piezoelectric transducers to generate sufficient pressure at the focal spot. Therefore, minimizing power consumption is crucial to minimize excessive thermal dissipation and to ensure long-term usability without frequent charging or battery replacement. Prior work has improved efficiency based on transducer fabrication and circuit design optimizations. To further address this issue, we propose a new approach to minimize power consumption by tailoring the driving amplitude of each element in a 2D phased array based on their individual contribution to the focal spot pressure.
Published in: 2024 IEEE Ultrasonics, Ferroelectrics, and Frequency Control Joint Symposium (UFFC-JS)
Medial Forebrain Bundle Deep Brain Stimulation (MFB-DBS) can have rapid and long lasting antidepressant effects in Treatment Resistant Depression (TRD) patients. The mechanisms are not well understood, but one hypothesis stipulates that modulation of the dopaminergic (DAergic) fibers contribute to the therapeutic outcome. Acute DBS effects on DA release have been studied; however, longitudinal studies with acute-repetitive DBS are lacking. Long-Evans accumbal DA release and Ventral Tegmental Area (VTA) calcium tonic and phasic signaling to different mfb-DBS parameters were measured using fiber photometry over 8 weeks, following acute and repetitive stimulation in behaving and non-behaving animals. DBS-induced release was observed in both targets, with increased frequency and DBS duration. 130 Hz stimulation increased phasic and tonic DA response over time, with the latter being a potential mechanism for its long-term clinical effectiveness. VTA calcium transients decreased, while phasic activity increased with frequency. Pulse width (PW)-mediated differential peak release timing also suggests potential parallel activation of diverse fiber types. Additionally, decreased DA transients rate during Elevated Plus Maze (EPM) suggests context and stimulation duration-dependent DA release. The data confirm chronic antidromic/orthodromic DAergic responses with stimulation parameter dependent variability, providing novel insights into temporal adaptations, connectivity and fiber recruitment on mfb DBS.
Deep brain stimulation (DBS) of the medial forebrain bundle (mfb) demonstrated anti-depressant effects both clinically and experimentally. Modulation of mesocorticolimbic dopaminergic (DA) activity could contribute—in part—to the therapeutic effects. By comparing selective and pathway specific midbrain DA optogenetic stimulation with the global, non-pathway specific mfb-DBS, the study explored changes in gene-expression of key biomarkers associated with neurocircuitry of depression. Rats received either optogenetic DAergic or mfb-DBS, delivered as acute/single or chronic/repeated stimulation. Micro-dissected regions were prepared for in situ hybridization targeting biomarkers of GABAergic, glutamatergic, and dopaminergic systems. Mfb-DBS mediated DA independent pathway increased GABAergic biomarkers (GABAA, GAD1) in frontal and accumbal regions, not in midbrain. The combinations of low frequency/high pulse width and high frequency/low pulse width stimulation generally increased biomarker expression similarly, but chronic/repetitive stimulation had no accumulative effect. Interestingly, unilateral stimulation had bilateral effects, but stimulation modalities had little impact on DAT and Vglut2 expression. In conclusion, both low and high frequency, acute/single and chronic/repetitive mfb-DBS—but not selective optogenetic stimulation -activated gene expression of biomarkers associated with GABAergic transmission. The increased expression was transitory and less chronic than predicted. Importantly, the study provides evidence that the anti-depressant therapeutic effects of clinical medial forebrain bundle DBS occurs—in part—be via modulation of GABAergic signalling which in turn could regulate the release of dopamine in frontal and accumbal regions. In addition, clinical implication of the data is that unilateral stimulation had bilateral consequences on the gene expression, although the physiological and functional sequelae of this are yet unknown.