Orthogonalizing the Activity of Two Neural Units for 2D Cursor Movement Control.

In the design of brain-machine interface (BMI), as the number of electrodes used to collect neural spike signals declines slowly, it is important to be able to decode with fewer units. We tried to train a monkey to control a cursor to perform a two-dimensional (2D) center-out task smoothly with spiking activities only from two units (direct units). At the same time, we studied how the direct units did change their tuning to the preferred direction during BMI training and tried to explore the underlying mechanism of how the monkey learned to control the cursor with their neural signals. In this study, we observed that both direct units slowly changed their preferred directions during BMI learning. Although the initial angles between the preferred directions of 3 pairs units are different, the angle between their preferred directions approached 90 degrees at the end of the training. Our results imply that BMI learning made the two units independent of each other. To our knowledge, it is the first time to demonstrate that only two units could be used to control a 2D cursor movements. Meanwhile, orthogonalizing the activities of two units driven by BMI learning in this study implies that the plasticity of the motor cortex is capable of providing an efficient strategy for motor control.

Separation of Subcutaneous Fat From Muscle in Surface Electrical Impedance Myography Measurements Using Model Component Analysis.

OBJECTIVE: Electrical impedance myography (EIM) is a relatively new technique to assess neuromuscular disorders (NMD). Although the application of EIM using surface electrodes (sEIM) has been adopted by the neurology community in recent years to evaluate NMD status, sEIM's sensitivity as a biomarker of skeletal muscle condition is impacted by subcutaneous fat (SF) tissue. Here, we develop a method that is able to remove the contribution of SF from sEIM data. METHODS: We evaluate independent component analysis (ICA) and principal component analysis (PCA) for this purpose. Then, we introduce the so-called model component analysis (MCA). All methods are validated with numerical simulations using impedivity data from SF and muscle tissues. The methods are then tested with measurements performed in diseased individuals ( n=3). RESULTS: Simulations demonstrate that MCA is the most accurate method at separating the impedivity of SF and muscle tissues with the accuracy being 99.2%, followed by ICA with 51.4%, and finally PCA with 38.5%. Experimental results from sEIM data measured on the triceps brachii of patients are consistent with muscle grayscale level values obtained using ultrasound imaging. CONCLUSION: MCA can be used to separate the impedivity of SF and muscle tissues from sEIM data, thus increasing the sensitivity to detect changes in the muscle. SIGNIFICANCE: MCA can make the sEIM technique a better diagnostic tool and biomarker of disease progression and response to therapy by removing the confounding effect of SF tissue in NMD patients with excess subcutaneous fat tissue for any reason.

Computationally Efficient Algorithms for Sparse, Dynamic Solutions to the EEG Source Localization Problem.

OBJECTIVE: Electroencephalography (EEG) and magnetoencephalography noninvasively record scalp electromagnetic fields generated by cerebral currents, revealing millisecond-level brain dynamics useful for neuroscience and clinical applications. Estimating the currents that generate these fields, i.e., source localization, is an ill-conditioned inverse problem. Solutions to this problem have focused on spatial continuity constraints, dynamic modeling, or sparsity constraints. The combination of these key ideas could offer significant performance improvements, but substantial computational costs pose a challenge for practical application of such approaches. Here, we propose a new method for EEG source localization that combines: 1) covariance estimation for both source and measurement noises; 2) linear state-space dynamics; and 3) sparsity constraints, using 4) novel computationally efficient estimation algorithms. METHODS: For source covariance estimation, we use a locally smooth basis alongside sparsity enforcing priors. For EEG measurement noise covariance estimation, we use an inverse Wishart prior density. We estimate these model parameters using an expectation-maximization algorithm that employs steady-state filtering and smoothing to expedite computations. RESULTS: We characterized the performance of our method by analyzing simulated data and experimental recordings of eyes-closed alpha oscillations. Our sparsity enforcing priors significantly improved estimation of both the spatial distribution and time course of simulated data, while improving computational time by more than 12-fold over previous dynamic methods. CONCLUSION: We developed and demonstrated a novel method for improved EEG source localization employing spatial covariance estimation, dynamics, and sparsity. SIGNIFICANCE: Our approach provides substantial performance improvements over existing methods using computationally efficient algorithms that will facilitate practical applications in both neuroscience and medicine.

Modulation depth estimation and variable selection in state-space models for neural interfaces.

Rapid developments in neural interface technology are making it possible to record increasingly large signal sets of neural activity. Various factors such as asymmetrical information distribution and across-channel redundancy may, however, limit the benefit of high-dimensional signal sets, and the increased computational complexity may not yield corresponding improvement in system performance. High-dimensional system models may also lead to overfitting and lack of generalizability. To address these issues, we present a generalized modulation depth measure using the state-space framework that quantifies the tuning of a neural signal channel to relevant behavioral covariates. For a dynamical system, we develop computationally efficient procedures for estimating modulation depth from multivariate data. We show that this measure can be used to rank neural signals and select an optimal channel subset for inclusion in the neural decoding algorithm. We present a scheme for choosing the optimal subset based on model order selection criteria. We apply this method to neuronal ensemble spike-rate decoding in neural interfaces, using our framework to relate motor cortical activity with intended movement kinematics. With offline analysis of intracortical motor imagery data obtained from individuals with tetraplegia using the BrainGate neural interface, we demonstrate that our variable selection scheme is useful for identifying and ranking the most information-rich neural signals. We demonstrate that our approach offers several orders of magnitude lower complexity but virtually identical decoding performance compared to greedy search and other selection schemes. Our statistical analysis shows that the modulation depth of human motor cortical single-unit signals is well characterized by the generalized Pareto distribution. Our variable selection scheme has wide applicability in problems involving multisensor signal modeling and estimation in biomedical engineering systems.

Reliability of directional information in unsorted spikes and local field potentials recorded in human motor cortex.

OBJECTIVE: Action potentials and local field potentials (LFPs) recorded in primary motor cortex contain information about the direction of movement. LFPs are assumed to be more robust to signal instabilities than action potentials, which makes LFPs, along with action potentials, a promising signal source for brain-computer interface applications. Still, relatively little research has directly compared the utility of LFPs to action potentials in decoding movement direction in human motor cortex. APPROACH: We conducted intracortical multi-electrode recordings in motor cortex of two persons (T2 and [S3]) as they performed a motor imagery task. We then compared the offline decoding performance of LFPs and spiking extracted from the same data recorded across a one-year period in each participant. MAIN RESULTS: We obtained offline prediction accuracy of movement direction and endpoint velocity in multiple LFP bands, with the best performance in the highest (200-400 Hz) LFP frequency band, presumably also containing low-pass filtered action potentials. Cross-frequency correlations of preferred directions and directional modulation index showed high similarity of directional information between action potential firing rates (spiking) and high frequency LFPs (70-400 Hz), and increasing disparity with lower frequency bands (0-7, 10-40 and 50-65 Hz). Spikes predicted the direction of intended movement more accurately than any individual LFP band, however combined decoding of all LFPs was statistically indistinguishable from spike-based performance. As the quality of spiking signals (i.e. signal amplitude) and the number of significantly modulated spiking units decreased, the offline decoding performance decreased 3.6[5.65]%/month (for T2 and [S3] respectively). The decrease in the number of significantly modulated LFP signals and their decoding accuracy followed a similar trend (2.4[2.85]%/month, ANCOVA, p = 0.27[0.03]). SIGNIFICANCE: Field potentials provided comparable offline decoding performance to unsorted spikes. Thus, LFPs may provide useful external device control using current human intracortical recording technology. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT00912041.).

Intra-day signal instabilities affect decoding performance in an intracortical neural interface system.

OBJECTIVE: Motor neural interface systems (NIS) aim to convert neural signals into motor prosthetic or assistive device control, allowing people with paralysis to regain movement or control over their immediate environment. Effector or prosthetic control can degrade if the relationship between recorded neural signals and intended motor behavior changes. Therefore, characterizing both biological and technological sources of signal variability is important for a reliable NIS. APPROACH: To address the frequency and causes of neural signal variability in a spike-based NIS, we analyzed within-day fluctuations in spiking activity and action potential amplitude recorded with silicon microelectrode arrays implanted in the motor cortex of three people with tetraplegia (BrainGate pilot clinical trial, IDE). MAIN RESULTS: 84% of the recorded units showed a statistically significant change in apparent firing rate (3.8 ± 8.71 Hz or 49% of the mean rate) across several-minute epochs of tasks performed on a single session, and 74% of the units showed a significant change in spike amplitude (3.7 ± 6.5 µV or 5.5% of mean spike amplitude). 40% of the recording sessions showed a significant correlation in the occurrence of amplitude changes across electrodes, suggesting array micro-movement. Despite the relatively frequent amplitude changes, only 15% of the observed within-day rate changes originated from recording artifacts such as spike amplitude change or electrical noise, while 85% of the rate changes most likely emerged from physiological mechanisms. Computer simulations confirmed that systematic rate changes of individual neurons could produce a directional 'bias' in the decoded neural cursor movements. Instability in apparent neuronal spike rates indeed yielded a directional bias in 56% of all performance assessments in participant cursor control (n = 2 participants, 108 and 20 assessments over two years), resulting in suboptimal performance in these sessions. SIGNIFICANCE: We anticipate that signal acquisition and decoding methods that can adapt to the reported instabilities will further improve the performance of intracortically-based NISs.

Functional biases in visual cortex neurons with identified projections to higher cortical targets.

BACKGROUND: Visual perception involves information flow from lower- to higher-order cortical areas, which are known to process different kinds of information. How does this functional specialization arise? As a step toward addressing this question, we combined fluorescent retrograde tracing with in vivo two-photon calcium imaging to simultaneously compare the tuning properties of neighboring neurons in areas 17 and 18 of ferret visual cortex that have different higher cortical projection targets. RESULTS: Neurons projecting to the posterior suprasylvian sulcus (PSS) were more direction selective and preferred shorter stimuli, higher spatial frequencies, and higher temporal frequencies than neurons projecting to area 21, anticipating key differences between the functional properties of the target areas themselves. These differences could not be explained by a correspondence between anatomical and functional clustering within early visual cortex, and the largest differences were in properties generated within early visual cortex (direction selectivity and length preference) rather than in properties present in its retinogeniculate inputs. CONCLUSIONS: These projection cell groups, and hence the higher-order visual areas to which they project, likely obtain their functional properties not from biased retinogeniculate inputs but from highly specific circuitry within the cortex.

Localized stimulation and recording in the spinal cord with microelectrode arrays.

The use of microelectrodes for both recording and stimulation of cortical tissue is a well-established technique in neuroscience. We demonstrate that the use of existing microelectrode arrays and instrumentation can be extended to studying the spinal cord. We show that microelectrode arrays can be used to perform stimulation and recording in the corticospinal tract of an animal model commonly used in spinal cord injury (SCI) research. This technique could not only provide fundamental insights into the structure and function of the spinal cord, but also ultimately serve as the basis of a therapeutic treatment for severe spinal cord injuries.

Denoising two-photon calcium imaging data.

Two-photon calcium imaging is now an important tool for in vivo imaging of biological systems. By enabling neuronal population imaging with subcellular resolution, this modality offers an approach for gaining a fundamental understanding of brain anatomy and physiology. Proper analysis of calcium imaging data requires denoising, that is separating the signal from complex physiological noise. To analyze two-photon brain imaging data, we present a signal plus colored noise model in which the signal is represented as harmonic regression and the correlated noise is represented as an order autoregressive process. We provide an efficient cyclic descent algorithm to compute approximate maximum likelihood parameter estimates by combing a weighted least-squares procedure with the Burg algorithm. We use Akaike information criterion to guide selection of the harmonic regression and the autoregressive model orders. Our flexible yet parsimonious modeling approach reliably separates stimulus-evoked fluorescence response from background activity and noise, assesses goodness of fit, and estimates confidence intervals and signal-to-noise ratio. This refined separation leads to appreciably enhanced image contrast for individual cells including clear delineation of subcellular details and network activity. The application of our approach to in vivo imaging data recorded in the ferret primary visual cortex demonstrates that our method yields substantially denoised signal estimates. We also provide a general Volterra series framework for deriving this and other signal plus correlated noise models for imaging. This approach to analyzing two-photon calcium imaging data may be readily adapted to other computational biology problems which apply correlated noise models.

Efficient decoding with steady-state Kalman filter in neural interface systems.

The Kalman filter is commonly used in neural interface systems to decode neural activity and estimate the desired movement kinematics. We analyze a low-complexity Kalman filter implementation in which the filter gain is approximated by its steady-state form, computed offline before real-time decoding commences. We evaluate its performance using human motor cortical spike train data obtained from an intracortical recording array as part of an ongoing pilot clinical trial. We demonstrate that the standard Kalman filter gain converges to within 95% of the steady-state filter gain in 1.5±0.5 s (mean ±s.d.). The difference in the intended movement velocity decoded by the two filters vanishes within 5 s, with a correlation coefficient of 0.99 between the two decoded velocities over the session length. We also find that the steady-state Kalman filter reduces the computational load (algorithm execution time) for decoding the firing rates of 25±3 single units by a factor of 7.0±0.9. We expect that the gain in computational efficiency will be much higher in systems with larger neural ensembles. The steady-state filter can thus provide substantial runtime efficiency at little cost in terms of estimation accuracy. This far more efficient neural decoding approach will facilitate the practical implementation of future large-dimensional, multisignal neural interface systems.

Modeling two-photon calcium fluorescence of episodic V1 recordings using multifrequency analysis.

The use of two-photon microscopy allows for imaging of deep neural tissue in vivo. This paper examines frequency-based analysis to two-photon calcium fluorescence images with the goal of deriving smooth tuning curves. We present a multifrequency analysis approach for improved extraction of calcium responses in episodic stimulation experiments, that is, when the stimulus is applied for a number of frames, then turned off for the next few frames, and so on. Episodic orientation stimulus was applied while recording from the primary visual cortex of an anesthetized mouse. The multifrequency model demonstrated improved tuning curve descriptions of the neurons. It also offers perspective regarding the characteristics of calcium fluorescence imaging of the brain.

A statistical model for multiphoton calcium imaging of the brain.

Multiphoton calcium fluorescence imaging has gained prominence as a valuable tool for the study of brain cells, but the corresponding analytical regimes remain rather naive. In this paper, we develop a statistical framework that facilitates principled quantitative analysis of multiphoton images. The proposed methods discriminate the stimulus-evoked response of a neuron from the background firing and image artifacts. We develop a harmonic regression model with colored noise, and estimate the model parameters with computationally efficient algorithms. We apply this model to in vivo characterization of cells from the ferret visual cortex. The results demonstrate substantially improved tuning curve fitting and image contrast.