Athina Apostolelli

Ultra-flexible electrodes, due to their superior biocompatibility, are likely to lead the future of neuroprosthetics. However, identifying the precise positions of implanted high-density ultra-flexible electrodes in the brain for accurately assigning neural signals to specific structures remains a major challenge. To address this, we developed magnetic resonance identification (MRID)-tags. Each ultra-flexible electrode bundle carries an MRID-tag with unique barcode patterns visible in MRI (MRI-barcodes) for identification of the bundle. Individual bars in MRI-barcodes allow an accurate 3D reconstruction of the ultra-flexible electrode bundle’s trajectory in the brain and determine the anatomical positions of individual electrodes. We generate the MRI-barcodes by patterning superparamagnetic iron-oxide nanoparticles into electrode fibers (10 µm ² ) with dot-matrix nanoparticle coating technique. We chronically tested MRID-tagged ultra-flexible electrodes in vivo in the dorsal hippocampus of freely-moving rats, where distinct electrophysiological landmarks validated our electrode localization results. We were able to localize individual electrodes with a mean accuracy of 95 μm. MRID-tagged ultra-flexible electrodes demonstrated high long-term recording stability with mean single-unit signal-to-noise ratios as high as 20.

Ultra-flexible electrodes, due to their superior biocompatibility, are likely to lead the future of neuroprosthetics. However, identifying the locations of high-density ultra-flexible electrodes in the brain for accurately assigning neural signals to specific structures remains a major challenge. To address this, we developed magnetic resonance identification (MRID) -tags. Each ultra-flexible electrode bundle carries an MRID-tag with unique barcode patterns visible in MRI (MRI-barcodes) for identification of the bundle and the anatomical positions of individual electrodes. We generate the MRI-barcodes by patterning superparamagnetic iron-oxide nanoparticles into electrode fibers (10µm ² ) with dot-matrix nanoparticle coating technique. We chronically tested MRID-tagged ultra-flexible electrodes in vivo in the dorsal hippocampus of freely-moving rats, where distinct electrophysiological landmarks validated our electrode localization results. We were able to localize individual electrodes with a mean accuracy of 83 µm. MRID-tagged ultra-flexible electrodes demonstrated months-long recording stability with mean single-unit signal-to-noise ratios as high as 20.

Neurons in the hippocampus are correlated with different variables, including space, time, sensory cues, rewards and actions, in which the extent of tuning depends on ongoing task demands^{1,2,3,4,5,6,7,8}. However, it remains uncertain whether such diverse tuning corresponds to distinct functions within the hippocampal network or whether a more generic computation can account for these observations⁹. Here, to disentangle the contribution of externally driven cues versus internal computation, we developed a task in mice in which space, auditory tones, rewards and context were juxtaposed with changing relevance. High-density electrophysiological recordings revealed that neurons were tuned to each of these modalities. By comparing movement paths and action sequences, we observed that external variables had limited direct influence on hippocampal firing. Instead, spiking was influenced by online action plans and modulated by goal uncertainty. Our results suggest that internally generated cell assembly sequences are selected and updated by action plans towards deliberate goals. The apparent tuning of hippocampal neuronal spiking to different sensory modalities might emerge due to alignment to the afforded action progression within a task rather than representation of external cues.

Neurons in the hippocampus are correlated with different variables, including space, time, sensory cues, rewards, and actions, where the extent of tuning depends on ongoing task demands. However, it remains uncertain whether such diverse tuning corresponds to distinct functions within the hippocampal network or if a more generic computation can account for these observations. To disentangle the contribution of externally driven cues versus internal computation, we developed a task in mice where space, auditory tones, rewards, and context were juxtaposed with changing relevance. High-density electrophysiological recordings revealed that neurons were tuned to each of these modalities. By comparing movement paths and action sequences, we observed that external variables had limited direct influence on hippocampal firing. Instead, spiking was influenced by online action plans modulated by goal uncertainty. Our results suggest that internally generated cell assembly sequences are selected and updated by action plans toward deliberate goals. The apparent tuning of hippocampal neuronal spiking to different sensory modalities might emerge due to alignment to the afforded action progression within a task rather than representation of external cues.