Search bioRxiv⌕ Search

Biology subjects

Vatsyayan, R.

Publications and source records attributed to Vatsyayan, R..

3 recordsLinked to original sources

Towards individualized deep brain stimulation: A stereoencephalography-based workflow for unbiased neurostimulation target identification

ObjectivesDeep brain stimulation (DBS) is increasingly being used to treat a variety of neuropsychiatric conditions, many of which exhibit idiosyncratic symptom presentations and neural correlates across individuals. Thus, we have utilized inpatient stereoelectroencephalography (sEEG) to identify personalized therapeutic stimulation sites for chronic implantation of DBS. Informed by our experience, we have developed a statistics-driven framework for stimulation testing to identify therapeutic targets. Materials and MethodsFourteen participants (major depressive disorder = 6, chronic pain = 6, obsessive-compulsive disorder = 2) underwent inpatient testing using sEEG and symptom monitoring to identify personalized stimulation targets for subsequent DBS implantation. We present a structured approach to this sEEG testing, integrating a Stimulation Testing Decision Tree with power analysis and effect size considerations to inform adequately powered results to detect therapeutic stimulation sites with statistical rigor. ResultsEffect sizes (Hedges g) of stimulation-induced symptom score changes ranged from -1.5 to +2.39. The standard deviation of sham trial responses was a strong predictor of stimulation response variability, as confirmed by a leave-one-out cross-validated linear regression (R2 = 0.67, permutation p<0.001). Thus, early sham trial data could be used to estimate the variability of stimulation responses for power analysis calculations. We show that approximately 10 sham trials were needed to robustly estimate sham variability. Power analysis (using a paired-t test) showed that for effect sizes [&ge;] 1.1, roughly 10 trials should be used per stimulation site for sufficiently powered results. ConclusionsThe presented workflow is adaptable to multiple indications and is specifically designed to overcome key challenges experienced during stimulation site testing. Through incorporating sham trials, effect size calculations, and tolerability testing, the described approach can be used to identify personalized and clinically efficacious stimulation sites.

neuroscience↗

Graphene-polymer Nanofibers Enable Optically Induced Electrical Maturation in Stem Cell-Derived Cardiomyocytes and Brain Organoids

Human pluripotent stem cell (hPSC)-derived electrically excitable cells provide a unique window into development, but they remain electrically immature partially due to the lack of chronic stimulation. Here, we fabricated electrospun polymer nanofibers containing light-reactive reduced graphene oxide (rGO) as part of a new classes of on-demand, electrically active biomaterials to enhance cell function. Fiber size, stiffness, and electrical conductivity varied with rGO concentration, which impacted hPSC-derived cardiomyocyte and neuron responses; with acute light stimulation, cardiomyocytes exhibited increased, synchronous calcium handling, and neurons showed more calcium peaks with higher frequency. Chronic, repetitive nanofiber light stimulation caused brain organoids to become increasingly electrically active and to activate photoreceptor pathways. This work outlines a tunable method where electrical cell functions can be titrated with rGO fibers and light stimulation, and it suggests that repetitive light stimulation may provide a novel method for retinal differentiation. HIGHLIGHTSO_LIElectrospun graphene-polymer nanofibers electrically respond to light stimulation C_LIO_LILight reactive graphene nanofibers stimulate electrically excitable cells in real-time C_LIO_LIStem cell-derived cardiomyocytes and neurons on nanofibers functionally improve C_LIO_LILight-training of brain organoids induces retinal and excitable neuron maturation C_LI

bioengineering↗

Flexible, Scalable, High Channel Count Stereo-Electrode for Recording in the Human Brain

Over the past decade, stereotactically placed electrodes have become the gold standard for deep brain recording and stimulation for a wide variety of neurological and psychiatric diseases. Current electrodes, however, are limited in their spatial resolution and ability to record from small populations of neurons, let alone individual neurons. Here, we report on a novel, reconfigurable, monolithically integrated human-grade flexible depth electrode capable of recording from up to 128 channels and able to record at a depth of 10 cm in brain tissue. This thin, stylet-guided depth electrode is capable of recording local field potentials and single unit neuronal activity (action potentials), validated across species. This device represents a major new advance in manufacturing and design approaches which extends the capabilities of a mainstay technology in clinical neurology. One-Sentence SummaryA human-grade thin-film depth electrode offers new opportunities in spatial and temporal resolution for recording brain activity.

neuroscience↗