Biology subjects

Stieglitz, T.

Publications and source records attributed to Stieglitz, T..

12 recordsLinked to original sources

bioRxiv2026

In Search for Biomarkers Reflecting Neural Implant-Induced Tissue Response Dynamics

Extracellular matrix (ECM) remodeling is a fundamental determinant of neural tissue repair and implant integration, yet its conserved regulatory architecture remains undefined. While transcriptomic alterations following neural injury and implantation have been described, the ECM-centered programs that unify traumatic injury and neural implant responses remain unclear. Here, integrative systems-level transcriptomic analysis identifies a dominant and conserved ECM regulatory axis linking traumatic brain injury (BI), spinal cord injury (SCI), and neural implant-induced injury. By integrating transcriptomic datasets from brain and spinal cord injury models using weighted gene co-expression network analysis (WGCNA), six conserved ECM-associated gene modules are identified, with hyaluronan (HA)-centered networks emerging as the dominant and conserved regulatory axis across both injury types. Modules enriched for low-molecular-weight HA (LMW-HA) are linked to Toll-like receptor signaling and pro-inflammatory cytokine expression, whereas high-molecular-weight HA (HMW-HA)-associated modules correlate with Cd44 signaling, tissue stabilization and repair. Furthermore, independent validation in thin-film intracortical microelectrode datasets confirms robust activation of HA damage-associated molecular pattern (HA-DAMP) signaling following implantation, with 9/10 injury-derived modules preserved and 88% of transcripts exhibiting resolving temporal dynamics. These findings indicate that neural implants engage conserved trauma-associated ECM programs rather than a conventional foreign-body response, highlighting HA-related metabolisms. Given that HA fragments and HA-modifying enzymes are detectable in cerebrospinal fluid and peripheral circulation, HA-associated signatures may serve as minimally invasive biomarkers of neural injury and implant biocompatibility, enabling longitudinal monitoring and informing next-generation neural interface design.

bioengineering↗

bioRxiv2025

Effects of Soft Encapsulation on the Receive Performance of PMUTs for Implantable Devices

Recent studies present ultrasound (US) as a promising candidate for powering implantable devices, requiring in-tegrated and encapsulated receivers to ensure longevity. Conventional hermetic packaging can hinder acoustic transmission, making polymer-based approaches desirable. This study evaluates how polymers commonly used for implants (i.e., thermoplastic polyurethane, parylene-C, medical-grade silicones, and polyimide) affect the receive performance of piezoelectric micromachined ultrasound transducers (PMUTs). Simulations and measurements between 1 and 7 MHz show transmission coefficients above 94 % for material thicknesses in the nm and m ranges. A theoretical analysis of the mechanical properties guides material selection for later PMUT encapsulation, focusing on polyurethane, parylene-C, and two medical-grade silicones (MED-1000, MED2-4213). In a complete system comprising encapsulated PMUTs, mechanical and acoustic properties, along with interface mismatch between the encapsulation and the PMUTs, influence the receive performance of the devices. Finite element modeling (FEM) and measurements evaluate the impedance and receive sensitivity of encapsulated PMUTs. The results show that residual stress or higher stiffness in some polymers, reduces the receive sensitivity, an effect not evident from only analysing the acoustic transmission through coatings. However, this study demonstrates that upon careful consideration of the acoustic and mechanical properties as well as thickness selection, polymers commonly used for implantable devices can effectively be used for PMUT encapsulation.

bioengineering↗

bioRxiv2024

A hybrid micro-ECoG for functionally targeted multi-site and multi-scale investigation

Brain function relies on coordinated activity across a wide range of spatial and temporal scales. The activity of single neurons depends on their unique pattern of local and long-range connectivity and thus on large-scale patterns of distributed activity across brain-wide networks. Understanding integrated, whole brain function requires new tools capable of recording from anatomically connected populations in distributed brain areas to bridge local and global dynamics. Here, we present high-density, micro-electrocorticography arrays that facilitate multi-scale studies of brain activity. The hybrid arrays integrate the desirable features of silicone elastomers and polyimide films. The silicone elastomer superstructure provides optical transparency and permits repeated penetration with rigid intracortical arrays. The polyimide films enable fine feature definition through photolithography. This combination facilitates high-throughput functional mapping of brain areas to define functionally characterized targets and permits targeted insertion of depth electrodes through the same array for dense local sampling. We demonstrate their suitability for functional mapping of cortical regions in rats, cats and marmosets and the benefit of the resulting functional maps for targeting functionally defined populations for multi-area laminar recordings. Finally, we demonstrate the utility of the hybrid {micro}ECoG for local optogenetic stimulation and its use in investigating cortico-cortical interactions through feedforward optogenetic stimulation. Together, these capabilities make the hybrid {micro}ECoG a compelling tool for systems neuroscience.

neuroscience↗

bioRxiv2023

Biomimetic computer-to-brain communication restoring naturalistic touch sensations via peripheral nerve stimulation

Artificial communication with the brain through peripheral nerve stimulation recently showed promising results in people with sensorimotor deficits. However, these efforts fall short in delivering close-to-natural rich sensory experience, resulting in the necessity to propose novel venues for converting sensory information into neural stimulation patterns, which would possibly enable intuitive and natural sensations. To this aim, we designed and tested a biomimetic neurostimulation framework inspired by nature, able "to write" physiologically plausible information back into the residual healthy nervous system. Starting from the in-silico model of mechanoreceptors, we designed biomimetic policies of stimulation, emulating the activity of different afferent units. Then, we experimentally assessed these novel paradigms, alongside mechanical touch and commonly used, linear neuromodulations. We explored the somatosensory neuroaxis by stimulating the nerve while recording the neural responses at the dorsal root ganglion and spinal cord of decerebrated cats. Biomimetic stimulation resulted in a neural activity that travels consistently along the neuroaxis, producing the spatio-temporal neural dynamic more like the naturally evoked one. Finally, we then implemented these paradigms within the bionic device and tested it with patients. Biomimetic neurostimulations resulted in higher mobility and decreased mental effort compared to traditional approaches. The results of this neuroscience-driven technology inspired by the human body could be a model for the development of novel assistive neurotechnologies.

neuroscience↗

bioRxiv2021

Transcriptional characterization of the glial response due to chronic neural implantation of flexible microprobes

Long term implantation of (micro-)probes into neural tissue cause unique and disruptive responses to these foreign bodies. In this study, we present the transcriptional trajectory of glial cells responding to chronic implantation of flexible micro-probes for up to 18 weeks. Transcriptome analysis shows a rapid activation of microglial cells and a strong upregulation of reactive astrocytic genes, which is lost over the full duration of the implant period. Most interestingly, animals that were implanted for 18 weeks show a transcriptional profile similar to non-implanted controls, with increased expression of genes associated with wound healing and angiogenesis, which raises hope of a normalization of the neuropil to the pre-injury state when using flexible probes. Nevertheless, our data show, that a subset of genes upregulated after 18 weeks belong to the family of immediate early genes, which would indicate that structural and functional remodeling has not been completed at this time point. Our results confirm and extend previous work on the molecular changes resulting from the presence of intraneural probes and provide a rational basis for developing intervention strategies to control them.

neuroscience↗

bioRxiv2020

A psychometric platform to collect somatosensory sensations for neuroprosthetic use

Somatosensory neuroprostheses exploit invasive and non-invasive feedback technologies to restore sensorimotor functions lost to disease or trauma. These devices use electrical stimulation to communicate sensory information to the brain. A sensation characterization procedure is thus necessary to determine the appropriate stimulation parameters and to establish a clear personalized map of the sensations that can be restored. Several questionnaires have been described in the literature to collect the quality, type, location and intensity of the evoked sensations, but there is still no standard psychometric platform. Here we propose a new psychometric system containing previously validated questionnaires on evoked sensations, which can be applied to any kind of somatosensory neuroprosthesis. The platform collects stimulation parameters used to elicit sensations; records subjects percepts in terms of sensation location, type, quality, perceptual threshold, and intensity. It further collects data using standardized assessment questionnaires and scales, performs measurements over time, and collects phantom limb pain syndrome data. The psychometric platform is user-friendly and provides clinicians with all the information needed to assess the sensory feedback. The psychometric platform was validated with three trans-radial amputees. They platform was used to assess intraneural sensory feedback provided through implanted peripheral nerve interfaces. The proposed platform could act as a new standardized assessment toolbox to homogenize the reporting of results obtained with different technologies in the field of somatosensory neuroprosthetics.

neuroscience↗

bioRxiv2020

Thin Film Metallization Stacks Serve as Reliable Conductors on Ceramic-based Substrates for Active Implants

Hermetic and non-hermetic packages of active implantable medical devices are often fabricated of ceramics like alumina. Screen printed PtAu paste is the state of the art metallization for functional structures. Due to solid state and liquid diffusion of Au at thermal exposure, solder times are limited; otherwise metal structures tend to delaminate. Moreover, it was shown that PtAu with solder fails after 37.4 years. We established a thin film metallization on alumina process to overcome these disadvantages. The metallization consists of sputtered platinum with an underlying adhesion layer made of tungsten-titanium to increase the adhesion strength to the alumina substrate. We avoided using gold in this work due to its high diffusion tendency. Instead, the materials in use provide relatively low diffusion properties, which potentially increases the long term mechanical performance and usability during assembly and packaging.Utilizing the Design of Experiment (DoE) methodology, we derived an optimal Pt thickness of 500 nm with 43 nm of WTi as adhesion promoting layer. After accelerated aging at 150 °C, corresponding to 125 years at body temperature (37 °C), the contact pad adhesion strength was with 32.75 MPa ± 7.08 MPa still significantly higher than the safety limit of 17 MPa, following the recommendations for a robust screen-printing metallization process. Moreover, soldering times of up to 120 s did not influence the adhesive strength. The new process reduced the minimum track distance to 50% of screen printing values and is capable of rapid prototyping. It helps to make the assembly process independent of the manufacturing person, to increase the yield of device fabrication and -most important in implantable device manufacturing-to make it more robust and thereby more safe for the patient.Competing Interest StatementThe authors have declared no competing interest.View Full Text

bioengineering↗

bioRxiv2019

On the Reliability of Chronically Implanted Thin-Film Electrodes in Human Arm Nerves for Neuroprosthetic Applications

Direct stimulation of peripheral nerves can successfully provide sensory feedback to amputees while using hand prostheses. Recent clinical studies have addressed this important limitation of current prostheses solutions using different implantable electrode concepts. Longevity of the electrodes is key to success. We have improved the long-term stability of the polyimide-based transverse intrafascicular multichannel electrode (TIME) that showed promising performance in clinical trials by integration of silicon carbide adhesion layers. The TIMEs were implanted in the median and ulnar nerves of three trans-radial amputees for up to six months. Here, we present the characterization of the electrical properties of the thin-film metallization as well as material status post explantationem for the first time. The TIMEs showed reliable performance in terms of eliciting sensation and stayed within the electrochemical safe limits maintaining a good working range with respect to amplitude modulation. After termination of the trials and explantation of the probes, no signs of corrosion or morphological change to the thin-film metallization was observed by means of electrochemical and optical analysis. Damage to the metallization was assigned exclusively to mechanical impacts during explantation and handling. The results indicate that thin-film metallization on polymer substrates is applicable in permanent implant system.

bioengineering↗

bioRxiv2019

Stability of Thin-Film Metallization in Flexible Stimulation Electrodes: Analysis and Improvement of in vivo Performance

Micro-fabricated neural interfaces based on polyimide (PI) are achieving increasing importance in translational research. The ability to produce well-defined micro-structures with properties that include chemical inertness, mechanical flexibility and low water uptake are key advantages for these devices. This paper reports the development of the transverse intrafascicular multichannel electrode (TIME) used to deliver intraneural sensory feedback to an upper-limb amputee in combination with a sensorized hand prosthesis. A first-in-human study limited to 30 days was performed. About 90 % of the stimulation contact sites of the TIMEs maintained electrical functionality and stability during the full implant period. However, optical analysis post-explantation revealed that 62.5 % of the stimulation contacts showed signs of mechanical damage at the metallization-PI interface. Such damage likely occurred due to handling during explantation and subsequent analysis, since a significant change in impedance was not observed in vivo. Nevertheless, whereas device integrity is mandatory for long-term functionality in chronic implantation, measures to increase the bonding strength of the metallization-PI interface deserve further investigation. We report here that silicon carbide (SiC) is an effective adhesion-promoting layer resisting heavy electrical stimulation conditions in vivo. Optical analysis of the new electrodes revealed that the metallization remained unaltered after delivering over 14 million pulses in vivo without signs of delamination at the metallization-PI interface. Reliable adhesion of thin-film metallization to substrate has been proven using SiC, improving the potential transfer of micro-fabricated neural electrodes for chronic clinical applications.

bioengineering↗

bioRxiv2019

Context-specific modulation of intrinsic coupling modes shapes multisensory processing

Intrinsically generated patterns of coupled neuronal activity are associated with the dynamics of specific brain states. Sensory inputs are extrinsic factors that can perturb these intrinsic coupling modes, creating a complex scenario in which forthcoming stimuli are processed. Studying this intrinsic-extrinsic interplay is necessary to better understand perceptual integration and selection. Here, we show that this interplay leads to a reconfiguration of functional cortical connectivity that acts as a mechanism to facilitate stimulus processing. Using audiovisual stimulation in anesthetized ferrets, we found that this reconfiguration of coupling modes is context-specific, depending on long-term modulation by repetitive sensory inputs. These reconfigured coupling modes, in turn, lead to changes in latencies and power of local field potential responses that support multisensory integration. Our study demonstrates that this interplay extends across multiple time scales and involves different types of intrinsic coupling. These results suggest a novel large-scale mechanism that facilitates multisensory integration.

neuroscience↗

bioRxiv2018

Synchrony surfacing: epicortical recording of correlated action potentials

Synchronous spiking of multiple neurons is a key phenomenon in normal brain function and pathologies. Recently, approaches to record spikes from the intact cortical surface using small high-density arrays of microelectrodes have been reported. It remained unaddressed how epicortical spiking relates to intracortical unit activity. We introduce a mesoscale approach using an array of 64 electrodes with intermediate diameter (250 {micro}m) and combined large-coverage epicortical recordings in ferrets with intracortical recordings via laminar probes. Empirical data and modeling strongly suggest that our epicortical electrodes selectively captured synchronized spiking of neurons in the subjacent cortex. As a result, responses to sensory stimulation were more robust and less noisy as compared to intracortical activity, and receptive field properties were well preserved in epicortical recordings. This should promote insights into assembly-coding beyond the informative value of subdural EEG or single-unit spiking, and be advantageous to real-time applications in brain-machine interfacing.\n\nSignificance statementElectrocorticography allows chronic, low-noise recordings from the intact cortical surface - a prerequisite for investigations into brain network dynamics and brain-machine interfaces. Novel electrodes can capture spiking activity at the surface, which should boost precision in the spatial - and time domain, compared to conventional EEG-like measurements. To clarify how surface spiking relates to intracortically fired action potentials, we recorded both types of signal simultaneously from sensory cortices in anesthetized ferrets. Results suggest that mesoscale (250 {micro}m) surface electrodes can selectively capture synchronized spiking from nearby cortical columns, which reduces contamination by non-representative, jittering spikes. Given the high relevance of neural synchrony for sensorimotor and cognitive processing, the novel methodology may improve signal decoding in brain-machine interface approaches.\n\nAuthor contributionsE.G.L., T.B. and A.K.E. conceptualized the research; E.G.L. and F.P. performed experiments; T.B. and E.G.L. wrote Matlab routines for data analysis; T.B. and E.G.L. analyzed the data; T.S. provided technical resources; T.B., E.G.L. and A.K.E. wrote the manuscript; G.E. administrated the project; A.K.E. acquired funding.

neuroscience↗

bioRxiv2018

A closed-loop hand prosthesis with simultaneous intraneural tactile and position feedback

Current myoelectric prostheses allow upper-limb amputees to regain voluntary motor control of their artificial limb by exploiting residual muscle function in the forearm1. However, the over-reliance on visual cues resulting from a lack of sensory feedback is a common complaint2,3. Recently, several groups have provided tactile feedback in upper-limb amputees by using implanted electrodes4,5,6,7,8, surface nerve stimulation9,10 or sensory substitution11,12. These approaches have led to improved function and prosthesis embodiment4,5,6,7,13,14. Nevertheless, the provided information remains limited to a subset of the rich sensory cues available to healthy individuals. More specifically, proprioception, the sense of limb position and movement, is predominantly absent from current systems. Here we show that sensory substitution based on intraneural stimulation can deliver position feedback in real-time and in conjunction with somatotopic tactile feedback. This approach allowed two trans-radial amputees to regain high and close-to-natural remapped proprioceptive acuity, with a median joint angle reproduction accuracy of 9.1{degrees} and a median threshold to detection of passive movements of 9.5{degrees}, which was compatible with results obtained in healthy subjects15,16,17. The simultaneous delivery of position information and somatotopic tactile feedback allowed both amputees to discriminate object size and compliance with high levels of accuracy (75.5%). These results demonstrate that touch information delivered via somatotopic neural stimulation and position information delivered via sensory substitution can be exploited simultaneously and efficiently by trans-radial amputees. This study paves the way towards more sophisticated bidirectional bionic limbs conveying rich, multimodal sensations.

neuroscience↗