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1. Closed-loop stimulation using a multiregion brain-machine interface has analgesic effects in rodents

   https://doi.org/10.1126/scitranslmed.abm5868  

   Sun, Guanghao ; Zeng, Fei ; McCartin, Michael ; Zhang, Qiaosheng ; Xu, Helen ; Liu, Yaling ; Chen, Zhe Sage ; Wang, Jing ( June 2022 , Science Translational Medicine)

   Pain relief on-demand Chronic pain is a debilitating condition for which there are no effective treatments. The primary somatosensory cortex (S1) and the anterior cingulate cortex (ACC) are involved in decoding pain components, and electrical stimulation of the prefrontal cortex (PFC) has been shown to exert analgesic effects. Here, Sun et al. developed a multiregion brain-machine interface (BMI) able to detect pain from electrical signals in S1 and ACC and provide on-demand PFC stimulation. The BMI was able to accurately detect and treat acute and chronic pain in rats; the analgesic effects were stable over time. The results suggest that BMI approaches might be effective for treating chronic pain of different etiologies. 

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2. Kapton Polyimide-Based EEG Microelectrode Array and Interfaces for Mice Brainwave Recordings and Analysis

   https://doi.org/DOI: 10.1117/12.2305145  

   D. Gupta, M. Islama ( April 2018 , Proc. SPIE 10662, Smart Biomedical and Physiological Sensor Technology XV 106620D)

   There is a rise in the study of functional connectivity among various cortical regions and investigations to uncover causal links between a stimulus and the corresponding neural dynamics through electrophysiological imaging of the human brain. Animal model that exhibit simplistic representations of such networks open a doorway for such investigations and are gaining rapid popularity. In this study, we investigate and compare resting state network and auditory stimulus related activity with minimal invasive technology along computational spectral analysis on a C57/BL6 based mouse model. Somatosensory, motor and visual cortex are observed to be highly active and significantly correlated (p-value<0.05). Moreover, given the spatial limitation due to small size of the mouse head, we also describe a low-cost and effective fabrication process for the mouse EEG Polyimide Based Microelectrodes (PBM) array. The easy-to-implement fabrication process involves transfer of the pattern on a copper layer of the Kapton film followed by gold electroplating and application of insulation paint. Acoustic stimulation is done by using tube extensions for avoiding electrical coupling to EEG signals. Unlike multi-electrode array type of invasive methods that are local to a cortical region, the methods established in this study can be used for examining functional connectivity analysis, neural dynamics and cortical response at a global level. 

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3. Rapid, Activity-Dependent Intrinsic Plasticity in the Developing Zebra Finch Auditory Cortex

   https://doi.org/10.1523/JNEUROSCI.0354-23.2023  

   Lu, Yao ; Sciaccotta, Francesca ; Kiely, Leah ; Bellanger, Benjamin ; Erisir, Alev ; Meliza, C. Daniel ( August 2023 , The Journal of Neuroscience)

   The acoustic environment an animal experiences early in life shapes the structure and function of its auditory system. This process of experience-dependent development is thought to be primarily orchestrated by potentiation and depression of synapses, but plasticity of intrinsic voltage dynamics may also contribute. Here, we show that in juvenile male and female zebra finches, neurons in a cortical-level auditory area, the caudal mesopallium (CM), can rapidly change their firing dynamics. This plasticity was only observed in birds that were reared in a complex acoustic and social environment, which also caused increased expression of the low-threshold potassium channel K_v1.1 in the plasma membrane and endoplasmic reticulum (ER). Intrinsic plasticity depended on activity, was reversed by blocking low-threshold potassium currents, and was prevented by blocking intracellular calcium signaling. Taken together, these results suggest that K_v1.1 is rapidly mobilized to the plasma membrane by activity-dependent elevation of intracellular calcium. This produces a shift in the excitability and temporal integration of CM neurons that may be permissive for auditory learning in complex acoustic environments during a crucial period for the development of vocal perception and production.

   SIGNIFICANCE STATEMENTNeurons can change not only the strength of their connections to other neurons, but also how they integrate synaptic currents to produce patterns of action potentials. In contrast to synaptic plasticity, the mechanisms and functional roles of intrinisic plasticity remain poorly understood. We found that neurons in the zebra finch auditory cortex can rapidly shift their spiking dynamics within a few minutes in response to intracellular stimulation. This plasticity involves increased conductance of a low-threshold potassium current associated with the K_v1.1 channel, but it only occurs in birds reared in a rich acoustic environment. Thus, auditory experience regulates a mechanism of neural plasticity that allows neurons to rapidly adapt their firing dynamics to stimulation.

    

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4. Artifact propagation in electrocorticography stimulation

   Lim, J. ; Wang, P.T. ; Shaw, S.J. ; Armacost, M. ; Gong, H. ; Liu, C.Y. ; Heydari, P. ; Do, A.H. ; Nenadic, Z. ( May 2018 , Seventh International BCI Meeting, Abstract Book)

   Introduction:Current brain-computer interfaces (BCIs) primarily rely on visual feedback. However, visual feedback may not be sufficient for applications such as movement restoration, where somatosensory feedback plays a crucial role. For electrocorticography (ECoG)-based BCIs, somatosensory feedback can be elicited by cortical surface electro-stimulation [1]. However, simultaneous cortical stimulation and recording is challenging due to stimulation artifacts. Depending on the orientation of stimulating electrodes, their distance to the recording site, and the stimulation intensity, these artifacts may overwhelm the neural signals of interest and saturate the recording bioamplifiers, making it impossible to recover the underlying information [2]. To understand how these factors affect artifact propagation, we performed a preliminary characterization of ECoG signals during cortical stimulation.Materials/Methods/ResultsECoG electrodes were implanted in a 39-year old epilepsy patient as shown in Fig. 1. Pairs of adjacent electrodes were stimulated as a part of language cortical mapping. For each stimulating pair, a charge-balanced biphasic square pulse train of current at 50 Hz was delivered for five seconds at 2, 4, 6, 8 and 10 mA. ECoG signals were recorded at 512 Hz. The signals were then high-pass filtered (≥1.5 Hz, zero phase), and the 5-second stimulation epochs were segmented. Within each epoch, artifact-induced peaks were detected for each electrode, except the stimulating pair, where signals were clipped due to amplifier saturation. These peaks were phase-locked across electrodes and were 20 ms apart, thus matching the pulse train frequency. The response was characterized by calculating the median peak within the 5-second epochs. Fig. 1 shows a representative response of the right temporal grid (RTG), with the stimulation channel at RTG electrodes 14 and 15. It also shows a hypothetical amplifier saturation contour of an implantable, bi-directional, ECoG-based BCI prototype [2], assuming the supply voltage of 2.2 V and a gain of 66 dB. Finally, we quantify the worstcase scenario by calculating the largest distance between the saturation contour and the midpoint of each stimulating channel.Discussion:Our results indicate that artifact propagation follows a dipole potential distribution with the extent of the saturation region (the interior of the white contour) proportional to the stimulation amplitude. In general, the artifacts propagated farthest when a 10 mA current was applied with the saturation regions extending from 17 to 32 mm away from the midpoint of the dipole. Consistent with the electric dipole model, this maximum spread happened along the direction of the dipole moment. An exception occurred at stimulation channel RTG11-16, for which an additional saturation contour emerged away from the dipole contour (not shown), extending the saturation region to 41 mm. Also, the worst-case scenario was observed at 6 mA stimulation amplitude. This departure could be a sign of a nonlinear, switch-like behavior, wherein additional conduction pathways could become engaged in response to sufficiently high stimulation.Significance:While ECoG stimulation is routinely performed in the clinical setting, quantitative studies of the resulting signals are lacking. Our preliminary study demonstrates that stimulation artifacts largely obey dipole distributions, suggesting that the dipole model could be used to predict artifact propagation. Further studies are necessary to ascertain whether these results hold across other subjects and combinations of stimulation/recording grids. Once completed, these studies will reveal practical design constraints for future implantable bi-directional ECoG-based BCIs. These include parameters such as the distances between and relative orientations of the stimulating and recording electrodes, the choice of the stimulating electrodes, the optimal placement of the reference electrode, and the maximum stimulation amplitude. These findings would also have important implications for the design of custom, low-power bioamplifiers for implantable bi-directional ECoG-based BCIs.References:[1] Hiremath, S. V., et al. "Human perception of electrical stimulation on the surface of somatosensory cortex." PloS one 12.5 (2017): e0176020.[2] Rouse, A. G., et al. "A chronic generalized bi-directional brain-machine interface." Journal of Neural Engineering 8.3 (2011): 036018 

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5. Epidural cerebellar stimulation drives widespread neural synchrony in the intact and stroke perilesional cortex.

   https://doi.org/10.1186/s12984-021-00881-9  

   Abbasi, A. ; Danielsen, N.P. ; Leung, J. ; Muhammad, A.K.M.G. ; Patel, S. ; Gulati, T. ( May 2021 , Journal of neuroengineering and rehabilitation)

   Manto, Mario (Ed.)

   Background Cerebellar electrical stimulation has shown promise in improving motor recovery post-stroke in both rodent and human studies. Past studies have used motor evoked potentials (MEPs) to evaluate how cerebellar stimulation modulates ongoing activity in the cortex, but the underlying mechanisms are incompletely understood. Here we used invasive electrophysiological recordings from the intact and stroke-injured rodent primary motor cortex (M1) to assess how epidural cerebellar stimulation modulates neural dynamics at the level of single neurons as well as at the level of mesoscale dynamics. Methods We recorded single unit spiking and local field potentials (LFPs) in both the intact and acutely stroke-injured M1 contralateral to the stimulated cerebellum in adult Long-Evans rats under anesthesia. We analyzed changes in the firing rates of single units, the extent of synchronous spiking and power spectral density (PSD) changes in LFPs during and post-stimulation. Results Our results show that post-stimulation, the firing rates of a majority of M1 neurons changed significantly with respect to their baseline rates. These firing rate changes were diverse in character, as the firing rate of some neurons increased while others decreased. Additionally, these changes started to set in during stimulation. Furthermore, cross-correlation analysis showed a significant increase in coincident firing amongst neuronal pairs. Interestingly, this increase in synchrony was unrelated to the direction of firing rate change. We also found that neuronal ensembles derived through principal component analysis were more active post-stimulation. Lastly, these changes occurred without a significant change in the overall spectral power of LFPs post-stimulation. Conclusions Our results show that cerebellar stimulation caused significant, long-lasting changes in the activity patterns of M1 neurons by altering firing rates, boosting neural synchrony and increasing neuronal assemblies’ activation strength. Our study provides evidence that cerebellar stimulation can directly modulate cortical dynamics. Since these results are present in the perilesional cortex, our data might also help explain the facilitatory effects of cerebellar stimulation post-stroke. 

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