Deep brain stimulation (DBS) is a targeted manipulation of brain circuitry to treat neurological and neuropsychiatric conditions. Optimal DBS lead placement is essential for treatment efficacy. Current targeting practice is based on preoperative and intraoperative brain imaging, intraoperative electrophysiology, and stimulation mapping. Electrophysiological mapping using extracellular microelectrode recordings aids in identifying functional subdomains, anatomical boundaries, and disease-correlated physiology. The shape of single-unit action potentials may differ due to different biophysical properties between cell-types and brain regions. Here, we describe a technique to parameterize the structure and duration of sorted spike units using a novel algorithmic approach based on canonical response parameterization, and illustrate how it may be used on DBS microelectrode recordings. Isolated spike shapes are parameterized then compared using a spike similarity metric and grouped by hierarchical clustering. When spike morphology is associated with anatomy, we find regional clustering in the human globus pallidus. This method is widely applicable for spike removal and single-unit characterization and could be integrated into intraoperative array-based technologies to enhance targeting and clinical outcomes in DBS lead placement.

High-frequency oscillations (HFOs) in intracranial EEG (iEEG) recordings are critical biomarkers for localizing the seizure onset zone (SOZ) in patients with focal refractory epilepsy. Despite their clinical significance, HFO analysis is often compromised by high-frequency artifacts that bypass conventional detectors, resulting in false-positive events that dilute the reliability of the HFO pool. To address this challenge, this study aimed to develop an automated method to accurately identify and eliminate false-positive events, ensuring more robust and artifact-free HFO analysis for clinical applications. Using iEEG data from 15 patients with focal epilepsy, we implemented an attention-based cascaded residual dictionary learning framework coupled with a random forest classifier. Events passing an initial amplitude detector underwent a second-stage refinement to remove artifacts and non-neural noise that mimicked HFOs. This was achieved by evaluating event reconstruction quality using a dictionary learned from genuine HFOs. Compared to visual assessments by three human experts, the proposed method demonstrated 92.14% classification accuracy in distinguishing real HFOs from pseudo-HFOs. Additionally, the method improved SOZ localization accuracy in noisy iEEG data by 20% (p=6e-5) and in clean iEEG data by 4% (p=3.3e-3). The learned dictionary effectively captured raw HFO morphology in shallow layers, while deeper layers identified ripple and fast ripple components, all without human supervision. These findings highlight the algorithm's effectiveness in detecting pseudo-HFOs in corrupted iEEG data, thereby enhancing the clinical utility of HFOs as biomarkers for SOZ in epilepsy.

Numerous physiological processes are cyclical, but sampling these processes densely enough to perform frequency decomposition and subsequent analyses can be challenging. Mathematical approaches for decomposition and reconstruction of sparsely and irregularly sampled signals are well established but have been under-utilized in physiological applications. We developed a basis pursuit denoising with polynomial detrending (BPWP) model that recovers oscillations and trends from sparse and irregularly sampled timeseries. We validated this model on a unique dataset of long-term inter-ictal epileptiform discharge (IED) rates from human hippocampus recorded with a novel investigational device with continuous local field potential sensing. IED rates have well established circadian and multiday cycles related to sleep, wakefulness, and seizure clusters. Given sparse and irregular samples of IED rates from multi-month intracranial EEG recordings from ambulatory humans, we used BPWP to compute narrowband spectral power and polynomial trend coefficients and identify IED rate cycles in three subjects. In select cases, we propose that random and irregular sampling may be leveraged for frequency decomposition of physiological signals. Trial Registration: NCT03946618.

Single-pulse electrical stimulation in the nervous system, often called cortico-cortical evoked potential (CCEP) measurement, is an important technique to understand how brain regions interact with one another. Voltages are measured from implanted electrodes in one brain area while stimulating another with brief current impulses separated by several seconds. Historically, researchers have tried to understand the significance of evoked voltage polyphasic deflections by visual inspection, but no general-purpose tool has emerged to understand their shapes or describe them mathematically. We describe and illustrate a new technique to parameterize brain stimulation data, where voltage response traces are projected into one another using a semi-normalized dot product. The length of timepoints from stimulation included in the dot product is varied to obtain a temporal profile of structural significance, and the peak of the profile uniquely identifies the duration of the response. Using linear kernel PCA, a canonical response shape is obtained over this duration, and then single-trial traces are parameterized as a projection of this canonical shape with a residual term. Such parameterization allows for dissimilar trace shapes from different brain areas to be directly compared by quantifying cross-projection magnitudes, response duration, canonical shape projection amplitudes, signal-to-noise ratios, explained variance, and statistical significance. Artifactual trials are automatically identified by outliers in sub-distributions of cross-projection magnitude, and rejected. This technique, which we call "Canonical Response Parameterization" (CRP) dramatically simplifies the study of CCEP shapes, and may also be applied in a wide range of other settings involving event-triggered data.

Electrical stimulation of deep brain structures is an established therapy for drug-resistant focal epilepsy. The emerging implantable neural sensing and stimulating (INSS) technology enables simultaneous delivery of chronic deep brain stimulation (DBS) and recording of electrical brain activity from deep brain structures while patients live in their home environment. Long-term intracranial electroencephalography (iEEG) iEEG signals recorded by INSS devices represent an opportunity to investigate brain neurophysiology and how DBS affects neural circuits. However, novel algorithms and data processing pipelines need to be developed to facilitate research of these long-term iEEG signals. Early-stage analytical infrastructure development for INSS applications can be limited by lacking iEEG data that might not always be available. Here, we investigate the feasibility of utilizing the Deep Generative Adversarial Network (DCGAN) for synthetic iEEG data generation. We trained DCGAN using 3-second iEEG segments and validated synthetic iEEG usability by training a classification model, using synthetic iEEG only and providing a good classification performance on unseen real iEEG with an F1 score 0.849. Subsequently, we demonstrated the feasibility of utilizing the synthetic iEEG in the INSS application development by training a deep learning network for DBS artifact removal using synthetic data only and demonstrated the performance on real iEEG signals. The presented strategy of on-demand generating synthetic iEEG will benefit early-stage algorithm development for INSS applications.

Recent development in implantable devices for electrical brain stimulation includes sensing and embedded computing capabilities that enable adaptive stimulation strategies. Applications include stimulation triggered by pathologic brain activity and endogenous rhythms, such as circadian rhythms. We developed and tested a system that integrates an electrical brain stimulation & sensing implantable device with embedded computing and uses a distributed system with commercial electronics, smartphone and smartwatch for patient annotations, extensive behavioral testing, and adaptive stimulation in subjects in their natural environments. The system enables precise time synchronization of the external components with the brain stimulating device and is coupled with automated analysis of continuous streaming electrophysiology synchronized with patient reports. The system leverages a real-time bi-directional interface between devices and patients with epilepsy living in their natural environment.

Most invasive Brain Computer Interfaces (iBCIs) use spike and Local Field Potentials (LFPs) from the motor or parietal cortices to decode movement intentions. It has been debated whether harvesting signals from other brain areas that encode global cognitive variables, such as the allocation of attention and eye movement goals in a variety of spatial reference frames, may improve the outcome of iBCIs. Here, we explore the ability of LFP signals, sampled from the lateral prefrontal cortex (LPFC) of macaque monkeys, to encode eye-movement intention during the pre-movement fixation period of a delayed saccade task. We use spectral dimensionality reduction to examine the spatiotemporal properties of the extracted non-rhythmic broadband activity and explore its usefulness in decoding saccade goals. The dynamics of the broadband signal in low spatial dimensions across the pre-movement fixation period uncovered saccade target separation; its discriminative potential was confirmed using support vector machine classifications. These findings reveal that broadband LFP from the LPFC can be used to decode intended saccade target location during pre-movement periods. We further provide a general workflow that can be implemented in iBCIs and it is relatively robust to the loss of spikes in individual electrodes.

Brain networks can be explored by delivering brief pulses of electrical current in one area while measuring voltage responses in other areas. We propose a convergent paradigm to study brain dynamics, focusing on a single brain site to observe the average effect of stimulating each of many other brain sites. Viewed in this manner, visually-apparent motifs in the temporal response shape emerge from adjacent stimulation sites. This work constructs and illustrates a data-driven approach to determine characteristic spatiotemporal structure in these response shapes, summarized by a set of unique "basis profile curves" (BPCs). Each BPC may be mapped back to underlying anatomy in a natural way, quantifying projection strength from each stimulation site using simple metrics. Our technique is demonstrated for an array of implanted brain surface electrodes in a human patient. This framework enables straightforward interpretation of single-pulse brain stimulation data, and can be applied generically to explore the diverse milieu of interactions that comprise the connectome.

The link between object perception and neural activity in visual cortical areas is a problem of fundamental importance in neuroscience. Here we show that electrical potentials from the ventral temporal cortical surface in humans contain sufficient information for spontaneous and near-instantaneous identification of a subject's perceptual state. Electrocorticographic (ECoG) arrays were placed on the subtemporal cortical surface of seven epilepsy patients. Grayscale images of faces and houses were displayed rapidly in random sequence. We developed a template projection approach to decode the continuous ECoG data stream spontaneously, predicting the occurrence, timing and type of visual stimulus. In this setting, we evaluated the independent and joint use of two well-studied features of brain signals, broadband changes in the frequency power spectrum of the potential and deflections in the raw potential trace (event-related potential; ERP). Our ability to predict both the timing of stimulus onset and the type of image was best when we used a combination of both the broadband response and ERP, suggesting that they capture different and complementary aspects of the subject's perceptual state. Specifically, we were able to predict the timing and type of 96% of all stimuli, with less than 5% false positive rate and a ~20ms error in timing.

The functional significance of electrical rhythms in the mammalian brain remains uncertain. In the motor cortex, the 12-20 Hz beta rhythm is known to transiently decrease in amplitude during movement, and to be altered in many motor diseases. Here we show that the activity of neuronal populations is phase-coupled with the beta rhythm on rapid timescales, and describe how the strength of this relation changes with movement. To investigate the relationship of the beta rhythm to neuronal dynamics, we measured local cortical activity using arrays of subdural electrocorticographic (ECoG) electrodes in human patients performing simple movement tasks. In addition to rhythmic brain processes, ECoG potentials also reveal a spectrally broadband motif that reflects the aggregate neural population activity beneath each electrode. During movement, the amplitude of this broadband motif follows the dynamics of individual fingers, with somatotopically specific responses for different fingers at different sites on the pre-central gyrus. The 12-20 Hz beta rhythm, in contrast, is widespread as well as spatially coherent within sulcal boundaries and decreases in amplitude across the pre- and post-central gyri in a diffuse manner that is not finger-specific. We find that the amplitude of this broadband motif is entrained on the phase of the beta rhythm, as well as rhythms at other frequencies, in peri-central cortex during fixation. During finger movement, the beta phase-entrainment is diminished or eliminated. We suggest that the beta rhythm may be more than a resting rhythm, and that this entrainment may reflect a suppressive mechanism for actively gating motor function.

A brain-computer interface (BCI) creates a direct communication pathway between the brain and an external device, and can thereby restore function in people with severe motor disabilities. A core component in a BCI system is the decoding algorithm that translates brain signals into action commands of an output device. Most of current decoding algorithms are based on linear models (e.g., derived using linear regression) that may have important shortcomings. The use of nonlinear models (e.g., neural networks) could overcome some of these shortcomings, but has difficulties with high dimensional feature spaces. Here we propose another decoding algorithm that is based on the sparse gaussian process with pseudo-inputs (SPGP). As a nonparametric method, it can model more complex relationships compared to linear methods. As a kernel method, it can readily deal with high dimensional feature space. The evaluations shown in this paper demonstrate that SPGP can decode the flexion of finger movements from electrocorticographic (ECoG) signals more accurately than a previously described algorithm that used a linear model. In addition, by formulating problems in the bayesian probabilistic framework, SPGP can provide estimation of the prediction uncertainty. Furthermore, the trained SPGP offers a very effective way for identifying important features.

Recent studies have identified broadband phenomena in the electric potentials produced by the brain. We report the finding of power-law scaling in these signals using subdural electrocorticographic recordings from the surface of human cortex. The power spectral density (PSD) of the electric potential has the power-law form P(f ) approximately Af(-chi) from 80 to 500 Hz. This scaling index, chi = 4.0+/-0.1, is conserved across subjects, area in the cortex, and local neural activity levels. The shape of the PSD does not change with increases in local cortical activity, but the amplitude, A, increases. We observe a "knee" in the spectra at f(0) approximately 75 Hz, implying the existence of a characteristic time scale tau = (2pif(0))(-1) approximately 2 - 4ms. Below f(0), we explore two-power-law forms of the PSD, and demonstrate that there are activity-related fluctuations in the amplitude of a power-law process lying beneath the alpha/beta rhythms. Finally, we illustrate through simulation how, small-scale, simplified neuronal models could lead to these power-law observations. This suggests a new paradigm of non-oscillatory "asynchronous," scale-free, changes in cortical potentials, corresponding to changes in mean population-averaged firing rate, to complement the prevalent "synchronous" rhythm-based paradigm.