Periodic Reporting for period 1 - Wide-Band Ephys (Large-scale and wide-band brain dynamics mediating memory consolidation in the freely moving rat)
Berichtszeitraum: 2023-09-01 bis 2025-10-31
Dementia is a major healthcare challenge worldwide due to its high incidence and its strong impact on the life quality
of patients and on society as a whole. Development of treatments for the mitigation of memory impairment in patients
with dementia has proven very challenging, partly due to our limited understanding of the underlying mechanisms
of memory consolidation. Memory consolidation is mediated by communication between large-scale networks in
the brain, particularly the hippocampal formation and cortical circuits, coordinated by oscillations in neuronal activity. In humans, this coordination is
associated with complex resting-state network (RSN) dynamics that are reflected in infra-slow
(<0.5Hz) brain activity across the entire brain that can be measured using bulky fMRI systems. However, the link between RSNs dynamics and well-understood fast neuronal dynamics underlying memory consolidation in animal models remains a major knowledge gap due to technical limitations.
Wide-Band Ephys is addressing this gap by mapping extracellular potentials with high spatial and temporal
resolution from extremely slow fluctuations to fast neuronal dynamics. Using customized graphene-based neural probes in combination with high density intracortical probes and closed-loop neuromodulation, I aim to investigate the topographical coupling between the neuronal activity in various cortical regions and in the hippocampus during the process of memory consolidation and understanding how infra-slow network dynamics shape this communication. Furthermore, the project is exploring novel concepts for neural interfaces that minimize the invasiveness of large-scale brain mapping in order to maximize its potential for clinical applications.
of patients and on society as a whole. Development of treatments for the mitigation of memory impairment in patients
with dementia has proven very challenging, partly due to our limited understanding of the underlying mechanisms
of memory consolidation. Memory consolidation is mediated by communication between large-scale networks in
the brain, particularly the hippocampal formation and cortical circuits, coordinated by oscillations in neuronal activity. In humans, this coordination is
associated with complex resting-state network (RSN) dynamics that are reflected in infra-slow
(<0.5Hz) brain activity across the entire brain that can be measured using bulky fMRI systems. However, the link between RSNs dynamics and well-understood fast neuronal dynamics underlying memory consolidation in animal models remains a major knowledge gap due to technical limitations.
Wide-Band Ephys is addressing this gap by mapping extracellular potentials with high spatial and temporal
resolution from extremely slow fluctuations to fast neuronal dynamics. Using customized graphene-based neural probes in combination with high density intracortical probes and closed-loop neuromodulation, I aim to investigate the topographical coupling between the neuronal activity in various cortical regions and in the hippocampus during the process of memory consolidation and understanding how infra-slow network dynamics shape this communication. Furthermore, the project is exploring novel concepts for neural interfaces that minimize the invasiveness of large-scale brain mapping in order to maximize its potential for clinical applications.
The project has so far successfully developed and validated high-density, multiplexed graphene neural probes enabling DC-coupled, large-scale electrophysiological recordings across cortical and hippocampal networks. These tools allowed the characterization of infra-slow local field potential (isLFP) dynamics across brain regions and layers, providing new insights into the origin of infra-slow potentials and their relation to neuronal synchronization, sleep substates, and memory consolidation.
Using these recording capabilities, the project established a physiological framework linking infra-slow extracellular potential patterns to sustained neuronal synchrony that may generate stationary dipoles through extracellular potassium gradients. These isLFP dynamics are correlated with neuromodulatory signals, and modulate sleep spindles, an oscillatory pattern related to memory consolidation during sleep.
Building on these scientific results, the project advanced toward translationally relevant system concepts by conceiving and validating a modular, distributed neural interface architecture based on miniaturized nodes capable of differential recording and stimulation across the skull. Key technical achievements include experimental validation of signal preservation across the dura, demonstration of the advantages of differential referencing for spatial precision, and the definition of a wireless, battery-free system architecture suitable for closed-loop neuromodulation. These outcomes collectively mark a transition from laboratory proof-of-concept to robust methodologies for future clinical translation
Using these recording capabilities, the project established a physiological framework linking infra-slow extracellular potential patterns to sustained neuronal synchrony that may generate stationary dipoles through extracellular potassium gradients. These isLFP dynamics are correlated with neuromodulatory signals, and modulate sleep spindles, an oscillatory pattern related to memory consolidation during sleep.
Building on these scientific results, the project advanced toward translationally relevant system concepts by conceiving and validating a modular, distributed neural interface architecture based on miniaturized nodes capable of differential recording and stimulation across the skull. Key technical achievements include experimental validation of signal preservation across the dura, demonstration of the advantages of differential referencing for spatial precision, and the definition of a wireless, battery-free system architecture suitable for closed-loop neuromodulation. These outcomes collectively mark a transition from laboratory proof-of-concept to robust methodologies for future clinical translation
The project delivers results that go beyond the state of the art in both neuroscience and neural interface engineering. Scientifically, it demonstrates that infra-slow electrophysiological dynamics can be reliably mapped at large spatial scales using DC-coupled graphene-based probes, enabling access to physiological information that is typically inaccessible with conventional AC-coupled systems. This provides a new experimental window into brain-wide coordination mechanisms underlying memory consolidation and arousal regulation, which could be leveraged to detect physiological or pathological brain states based on slow signal features.
Technologically, the project moves beyond monolithic neural interfaces by introducing a distributed, modular architecture for neural sensing and stimulation. This approach addresses key limitations of existing systems in terms of invasiveness, scalability, and chronic usability by decoupling spatial coverage from device size and intracranial footprint. The concept of differential sensing across the skull represents a novel strategy for achieving high spatial precision while minimizing intrusion into the intracranial space.
To ensure further uptake and success, key needs include continued system integration, demonstration of fully wireless closed-loop operation, and validation in clinically relevant settings. Access to advanced microelectronics fabrication, regulatory guidance, and IPR protection will be essential for transitioning the technology toward clinical and commercial use.
Technologically, the project moves beyond monolithic neural interfaces by introducing a distributed, modular architecture for neural sensing and stimulation. This approach addresses key limitations of existing systems in terms of invasiveness, scalability, and chronic usability by decoupling spatial coverage from device size and intracranial footprint. The concept of differential sensing across the skull represents a novel strategy for achieving high spatial precision while minimizing intrusion into the intracranial space.
To ensure further uptake and success, key needs include continued system integration, demonstration of fully wireless closed-loop operation, and validation in clinically relevant settings. Access to advanced microelectronics fabrication, regulatory guidance, and IPR protection will be essential for transitioning the technology toward clinical and commercial use.