Advances in therapeutic neuromodulation devices have enabled concurrent stimulation and electrophysiology in the central nervous system. However, stimulation artifacts often obscure the sensed underlying neural activity. Here, we develop a method, termed Period-based Artifact Reconstruction and Removal Method (PARRM), to remove stimulation artifacts from neural recordings by leveraging the exact period of stimulation to construct and subtract a high-fidelity template of the artifact. Benchtop saline experiments, computational simulations, five unique in vivo paradigms across animal and human studies, and an obscured movement biomarker are used for validation. Performance is found to exceed that of state-of-the-art filters in recovering complex signals without introducing contamination. PARRM has several advantages: (1) it is superior in signal recovery; (2) it is easily adaptable to several neurostimulation paradigms; and (3) it has low complexity for future on-device implementation. Real-time artifact removal via PARRM will enable unbiased exploration and detection of neural biomarkers to enhance efficacy of closed-loop therapies.
Central pain disorders, such as central post-stroke pain, remain clinically challenging to treat, despite many decades of pharmacological advances and the evolution of neuromodulation. For treatment refractory cases, previous studies have highlighted some benefits of cortical stimulation. Recent advances in new targets for pain and the optimization of neuromodulation encouraged our group to develop a dual cortical target approach paired with Bayesian optimization to provide a personalized treatment. Here, we present a case report of a woman who developed left-sided facial pain after multiple thalamic strokes. All previous pharmacologic and interventional treatments failed to mitigate the pain, leaving her incapacitated due to pain and medication side effects. She subsequently underwent a single burr hole for placement of motor cortex (M1) and dorsolateral prefrontal cortex (dlPFC) paddles for stimulation with externalization. By using Bayesian optimization to find optimal stimulation parameters and stimulation sites, we were able to reduce pain from an 8.5/10 to a 0/10 during a 5-day inpatient stay, with pain staying at or below a 2/10 one-month post-procedure. We found optimal treatment to be simultaneous stimulation of M1 and dlPFC without any evidence of seizure induction. In addition, we found no worsening in cognitive performance during a working memory task with dlPFC stimulation. This personalized approach using Bayesian optimization may provide a new foundation for treating central pain and other functional disorders through systematic evaluation of stimulation parameters.
Objective. Precision medicine holds substantial promise for tailoring neuromodulation techniques to the symptomatology of individual patients. Precise selection of stimulation parameters for individual patients requires the development of robust optimization techniques. However, standard optimization approaches, like Bayesian optimization, have historically been assessed and developed for applications with far less noise than is typical in neuro-psychiatric outcome measures and with minimal focus on parameter safety. Approach. We conducted a literature review of individual effects in neurological and psychiatric applications to build a series of simulated patient responses of varying signal to noise ratio. Using these simulations, we assessed whether existing standards in Bayesian optimization are sufficient for robustly optimizing such effects. Main results. For effect sizes below a Cohen’s d of 0.3, standard Bayesian optimization methods failed to consistently identify optimal parameters. This failure primarily results from over-sampling of the boundaries of the space as the number of samples increases, because the variance on the edges becomes disproportionately greater than in the remainder of parameter space. Using a combination of an input warp and a boundary avoiding Iterated Brownian-bridge kernel we demonstrated robust Bayesian optimization performance for problems with a Cohen’s d effect size as low as 0.1. Significance. Our results demonstrate that caution should be taken when applying standard Bayesian optimization in neuromodulation applications with potentially low effect sizes, as standard algorithms are at high risk of converging to local rather than global optima. Mitigating techniques, like boundary avoidance, are effective and should be used to improve robustness.
Operant animal behavior training and monitoring is fundamental to scientific inquiry across fields necessitating evaluation via controlled laboratory tasks. However, current commercial and open-source systems enforce particular hardware and software, limiting reproducibility and technique and data sharing across sites. To address this issue, we developed OSCAR: an open-source controller for animal research that enables flexible control of a variety of industry standard hardware with platform-independent software. OSCAR offers millisecond latency with a flexible array of inputs and outputs at a fraction of the cost of commercial options. These features position OSCAR as a valuable option for improving consistency of behavioral experiments across studies.
Objective: To improve the ability of psychiatry researchers to build, deploy, maintain, reproduce, and share their own psychophysiological tasks. Psychophysiological tasks are a useful tool for studying human behavior driven by mental processes such as cognitive control, reward evaluation, and learning. Neural mechanisms during behavioral tasks are often studied via simultaneous electrophysiological recordings. Popular online platforms such as Amazon Mechanical Turk (MTurk) and Prolific enable deployment of tasks to numerous participants simultaneously. However, there is currently no task-creation framework available for flexibly deploying tasks both online and during Methods: We developed a task creation template, termed Honeycomb, that standardizes best practices for building jsPsych-based tasks. Honeycomb offers continuous deployment configurations for seamless transition between use in research settings and at home. Further, we have curated a public library, termed BeeHive, of ready-to-use tasks. Results: We demonstrate the benefits of using Honeycomb tasks with a participant in an ongoing study of deep brain stimulation for obsessive compulsive disorder, who completed repeated tasks both in the clinic and at home. Conclusion: Honeycomb enables researchers to deploy tasks online, in clinic, and at home in more ecologically valid environments and during concurrent electrophysiology.