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bioRxiv · 10.1101/2022.11.11.516221

Biomimetic microstimulation of sensory cortices

Hughes, C.·Kozai, T.
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Abstract

BackgroundIntracortical microstimulation (ICMS) is an emerging approach to restore sensation to people with neurological injury or disease. Biomimetic microstimulation, or stimulus trains that mimic neural activity in the brain through encoding of onset and offset transients, could improve the utility of ICMS for BCI applications, but how biomimetic microstimulation affects neural activation is not understood. Stimulus induced depression of neural activity (decreases in evoked intensity over time) is also a potential barrier to clinical implementation of sensory feedback, and biomimetic microstimulation may reduce this effect. ObjectiveWe evaluated how biomimetic trains change the calcium response, spatial distribution, and depression of neurons in the somatosensory and visual cortices. MethodsCalcium responses of neurons were measured in Layer 2/3 of visual and somatosensory cortices of anesthetized GCaMP6s mice in response to ICMS trains with fixed amplitude and frequency (Fixed) and three biomimetic ICMS trains that increased the stimulation intensity during the onset and offset of stimulation by modulating the amplitude (BioAmp), frequency (BioFreq), or amplitude and frequency (BioBoth). ICMS was provided for either 1-s with 4-s breaks (Short) or for 30-s with 15-s breaks (Long). ResultsBioAmp and BioBoth trains evoked distinct onset and offset transients in recruited neural populations, while BioFreq trains evoked population activity similar to Fixed trains. Individual neurons had heterogeneous responses primarily based on how quickly they depressed to ICMS, where neurons farther from the electrode depressed faster and a small subpopulation (1-5%) were modulated by BioFreq trains. Neurons that depressed to Short trains were also more likely to depress to Long trains, but Long trains induced more depression overall due to the increased stimulation length. Increasing the amplitude during the hold phase resulted in an increase in recruitment and intensity which resulted in more depression and reduced offset responses. Biomimetic amplitude modulation reduced stimulation induced depression by 14.6{+/-}0.3% for Short and 36.1{+/-}0.6% for Long trains. Ideal observers were 0.031{+/-}0.009 s faster for onset detection and 1.33{+/-}0.21 s faster for offset detection with biomimetic amplitude encoding. ConclusionsBiomimetic amplitude modulation evokes distinct onset and offset transients, reduces depression of neural calcium activity, and decreases total charge injection for sensory feedback in brain-computer interfaces by lowering recruitment of neurons during long maintained periods of ICMS. In contrast, biomimetic frequency modulation evokes distinct onset and offset transients in a small subpopulation of neurons but also reduces depression in recruited neurons by reducing the rate of activation.

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Hughes, C., Kozai, T.. 2022-11-13. Biomimetic microstimulation of sensory cortices. https://doi.org/10.1101/2022.11.11.516221

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