Pollo, C. | Search bioRxiv

bioRxiv2021

Probing cortical excitability under GABAergic modulation

Cortical excitability, the variable response to a given cortical input, is widely studied in neuroscience, from slice experiments and in silico modeling work to human clinical settings. However, a unifying definition and a translational approach to the phenomenon are currently lacking. For example, at the onset of epileptic seizures, cortical excitability may impair resilience to perturbations (external or endogenous). In this study, we tested in vivo whether changes in cortical excitability quantified as evoked response to small perturbation corresponded to changes in resilience to larger perturbations. To do so, we used both cell-type circuit specific optogenetic stimulation in mice and direct intracranial stimulation in one human subject and quantified 1) evoked cortical responses to single pulses of varying intensity, and 2) evoked cortical facilitation and suppression to paired pulses at varying intervals. In the presence of a gamma-Aminobutyric acid (GABA) agonist or antagonist, we found that 1) cortical response to single pulses and 2) cortical facilitation decreased and increased, respectively. Additionally, using trains of opto-pulses in mice in the presence of a GABA agonist, we found increased resilience to the induction of seizures. With this study, we provide evidence for a tight correlation between cortical excitability and resilience, exploring a range of cortical dynamics, from physiological excitability, to pathological discharges. Our study carried out with two different stimulation methods in two species suggests that varying cortical excitability can be tracked with simple protocols involving minute short-lived perturbative stimuli.

neuroscience↗

bioRxiv2021

The sensitivity of ECG contamination to surgical implantation site in adaptive closed-loop neurostimulation systems

BackgroundBrain sensing devices are approved today for Parkinsons, essential tremor, and epilepsy therapies. Clinical decisions for implants are often influenced by the premise that patients will benefit from using sensing technology. However, artifacts, such as ECG contamination, can render such treatments unreliable. Therefore, clinicians need to understand how surgical decisions may affect artifact probability. ObjectivesInvestigate neural signal contamination with ECG activity in sensing enabled neurostimulation systems, and in particular clinical choices such as implant location that impact signal fidelity. MethodsElectric field modelling and empirical signals from 85 patients were used to investigate the relationship between implant location and ECG contamination.a ResultsThe impact on neural recordings depends on the difference between ECG signal and noise floor of the electrophysiological recording. Empirically, we demonstrate that severe ECG contamination was more than 3.2x higher in left-sided subclavicular implants (48.3%), when compared to right-sided implants (15.3%). Cranial implants did not show ECG contamination. ConclusionsGiven the relative frequency of corrupted neural signals, we conclude that implant location will impact the ability of brain sensing devices to be used for "closed-loop" algorithms. Clinical adjustments such as implant location can significantly affect signal integrity and need consideration. HighlightsO_LIChronic embedded brain sensing promises algorithm-based neurostimulation C_LIO_LIAlgorithms for closed-loop stimulation can be impaired by artifacts C_LIO_LIThe relationship of implant location to cardiac dipole has relevant impact on neural signal fidelity; simple models can provide guidance on the sensitivity C_LIO_LIECG artifacts are present in up to 50% of neural signals from left subclavicular DBS systems C_LIO_LIImplanting DBS in a right subclavicular location significantly reduces frequency of ECG artifacts C_LIO_LICranial-mounted implants are relatively immune to artifacts C_LI

neuroscience↗