Somatosensory Cortex Microstimulation: Behavioral Effects of Phase Duration and Asymmetric Waveforms

Urdaneta, Morgan E.; Kunigk, Nicolas G.; Delgado, Francisco; Otto, Kevin J.

doi:10.1109/embc.2019.8856579

Cited by 5 publications

(6 citation statements)

References 14 publications

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“…One key goal of the study was to assess how the sensitivity of S1 to ICMS changed across cortical depth and over time. To measure the ability of animals to detect ICMS we used a conditioned avoidance behavioral paradigm ( Heffner and Heffner, 1995 ; Urdaneta et al, 2019 , 2021 ; Saldanha et al, 2021 ). In this task, water-deprived rats were trained to stop licking from a spout upon presentation of an ICMS stimulus ( Figure 2A , referred to as a “hit”).…”

Section: Resultsmentioning

confidence: 99%

The Long-Term Stability of Intracortical Microstimulation and the Foreign Body Response Are Layer Dependent

et al. 2022

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Intracortical microstimulation (ICMS) of the somatosensory cortex (S1) can restore sensory function in patients with paralysis. Studies assessing the stability of ICMS have reported heterogeneous responses across electrodes and over time, potentially hindering the implementation and translatability of these technologies. The foreign body response (FBR) and the encapsulating glial scar have been associated with a decay in chronic performance of implanted electrodes. Moreover, the morphology, intrinsic properties, and function of cells vary across cortical layers, each potentially affecting the sensitivity to ICMS as well as the degree of the FBR across cortical depth. However, layer-by-layer comparisons of the long-term stability of ICMS as well as the extent of the astrocytic glial scar change across cortical layers have not been well explored. Here, we implanted silicon microelectrodes with electrode sites spanning all the layers of S1 in rats. Using a behavioral paradigm, we obtained ICMS detection thresholds from all cortical layers for up to 40 weeks. Our results showed that the sensitivity and long-term performance of ICMS is indeed layer dependent. Overall, detection thresholds decreased during the first 7 weeks post-implantation (WPI). This was followed by a period in which thresholds remained stable or increased depending on the interfacing layer: thresholds in L1 and L6 exhibited the most consistent increases over time, while those in L4 and L5 remained the most stable. Furthermore, histological investigation of the tissue surrounding the electrode showed a biological response of microglia and macrophages which peaked at L1, while the area of the astrocytic glial scar peaked at L2/3. Interestingly, the biological response of these FBR markers is less exacerbated at L4 and L5, suggesting a potential link between the FBR and the long-term stability of ICMS. These findings suggest that interfacing depth can play an important role in the design of chronically stable implantable microelectrodes.

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Section: Resultsmentioning

confidence: 99%

The Long-Term Stability of Intracortical Microstimulation and the Foreign Body Response Are Layer Dependent

et al. 2022

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“…A potential limitation of our results is that all of the electrodes in our study were subject to intracortical microstimulation (ICMS) experiments ( Urdaneta et al, 2019 ; Kunigk et al, 2022 ; Urdaneta et al, 2022 ); it is unclear how this ICMS may have affected recording performance. Despite the lack of unstimulated electrodes as a control group, all microstimulation charges were distributed across all channels.…”

Section: Discussionmentioning

confidence: 99%

Layer-dependent stability of intracortical recordings and neuronal cell loss

et al. 2023

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Intracortical recordings can be used to voluntarily control external devices via brain-machine interfaces (BMI). Multiple factors, including the foreign body response (FBR), limit the stability of these neural signals over time. Current clinically approved devices consist of multi-electrode arrays with a single electrode site at the tip of each shank, confining the recording interface to a single layer of the cortex. Advancements in manufacturing technology have led to the development of high-density electrodes that can record from multiple layers. However, the long-term stability of neural recordings and the extent of neuronal cell loss around the electrode across different cortical depths have yet to be explored. To answer these questions, we recorded neural signals from rats chronically implanted with a silicon-substrate microelectrode array spanning the layers of the cortex. Our results show the long-term stability of intracortical recordings varies across cortical depth, with electrode sites around L4-L5 having the highest stability. Using machine learning guided segmentation, our novel histological technique, DeepHisto, revealed that the extent of neuronal cell loss varies across cortical layers, with L2/3 and L4 electrodes having the largest area of neuronal cell loss. These findings suggest that interfacing depth plays a major role in the FBR and long-term performance of intracortical neuroprostheses.

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“…To determine detection thresholds in freely behaving rats, a modified conditioned avoidance behavioral paradigm (Urdaneta et al, 2019) was implemented. Water-deprived rats were placed in an enclosure with a metal spout capable of both detecting contact and producing a small cutaneous shock.…”

Section: Behavioral Paradigmmentioning

confidence: 99%

“…For all experiments reported herein, the total charge injected through each electrode site was limited to 20 nC/phase. Constant stimulation parameters were chosen to be consistent with previous work (Urdaneta et al, 2019(Urdaneta et al, , 2021Saldanha et al, 2021). All stimulation experiments were performed using Synapse stimulation software (Tucker-Davis Technologies, Alachua, FL, United States), which provided the capability to stimulate from more than one electrode-site at once.…”

Section: Intracortical Stimulation Parametersmentioning

confidence: 99%

Reducing Behavioral Detection Thresholds per Electrode via Synchronous, Spatially-Dependent Intracortical Microstimulation

et al. 2022

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Intracortical microstimulation (ICMS) has shown promise in restoring quality of life to patients suffering from paralysis, specifically when used in the primary somatosensory cortex (S1). However, these benefits can be hampered by long-term degradation of electrode performance due to the brain’s foreign body response. Advances in microfabrication techniques have allowed for the development of neuroprostheses with subcellular electrodes, which are characterized by greater versatility and a less detrimental immune response during chronic use. These probes are hypothesized to enable more selective, higher-resolution stimulation of cortical tissue with long-term implants. However, microstimulation using physiologically relevant charges with these smaller-scale devices can damage electrode sites and reduce the efficacy of the overall device. Studies have shown promise in bypassing this limitation by spreading the stimulation charge between multiple channels in an implanted electrode array, but to our knowledge the usefulness of this strategy in laminar arrays with electrode sites spanning each layer of the cortex remains unexplored. To investigate the efficacy of simultaneous multi-channel ICMS in electrode arrays with stimulation sites spanning cortical depth, we implanted laminar electrode arrays in the primary somatosensory cortex of rats trained in a behavioral avoidance paradigm. By measuring detection thresholds, we were able to quantify improvements in ICMS performance using a simultaneous multi-channel stimulation paradigm. The charge required per site to elicit detection thresholds was halved when stimulating from two adjacent electrode sites, although the overall charge used by the implant was increased. This reduction in threshold charge was more pronounced when stimulating with more than two channels and lessened with greater distance between stimulating channels. Our findings suggest that these improvements are based on the synchronicity and polarity of each stimulus, leading us to conclude that these improvements in stimulation efficiency per electrode are due to charge summation as opposed to a summation of neural responses to stimulation. Additionally, the per-site charge reductions are seen regardless of the cortical depth of each utilized channel. This evocation of physiological detection thresholds with lower stimulation currents per electrode site has implications for the feasibility of stimulation regimes in future advanced neuroprosthetic devices, which could benefit from reducing the charge output per site.

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Somatosensory Cortex Microstimulation: Behavioral Effects of Phase Duration and Asymmetric Waveforms

Cited by 5 publications

References 14 publications

The Long-Term Stability of Intracortical Microstimulation and the Foreign Body Response Are Layer Dependent

The Long-Term Stability of Intracortical Microstimulation and the Foreign Body Response Are Layer Dependent

Layer-dependent stability of intracortical recordings and neuronal cell loss

Reducing Behavioral Detection Thresholds per Electrode via Synchronous, Spatially-Dependent Intracortical Microstimulation

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