Point process modeling and estimation: advances in the analysis of dynamic neural spiking data

A common interest of scientists in many fields is to understand the relationship between the dynamics of a physical system and the occurrences of discrete events within such physical system. Seismologists study the connection between mechanical vibrations of the Earth and the occurrences of earthquakes so that future earthquakes can be better predicted. Astrophysicists study the association between the oscillating energy of celestial regions and the emission of photons to learn the Universe's various objects and their interactions. Neuroscientists study the link between behavior and the millisecond-timescale spike patterns of neurons to understand higher brain functions. Such relationships can often be formulated within the framework of state-space models with point process observations. The basic idea is that the dynamics of the physical systems are driven by the dynamics of some stochastic state variables and the discrete events we observe in an interval are noisy observations with distributions determined by the state variables. This thesis proposes several new methodological developments that advance the framework of state-space models with point process observations at the intersection of statistics and neuroscience. In particular, we develop new methods 1) to characterize the rhythmic spiking activity using history-dependent structure, 2) to model population spike activity using marked point process models, 3) to allow for real-time decision making, and 4) to take into account the need for dimensionality reduction for high-dimensional state and observation processes. We applied these methods to a novel problem of tracking rhythmic dynamics in the spiking of neurons in the subthalamic nucleus of Parkinson's patients with the goal of optimizing placement of deep brain stimulation electrodes. We developed a decoding algorithm that can make decision in real-time (for example, to stimulate the neurons or not) based on various sources of information present in population spiking data. Lastly, we proposed a general three-step paradigm that allows us to relate behavioral outcomes of various tasks to simultaneously recorded neural activity across multiple brain areas, which is a step towards closed-loop therapies for psychological diseases using real-time neural stimulation. These methods are suitable for real-time implementation for content-based feedback experiments

Emergent Bio-Functional Similarities in a Cortical-Spike-Train-Decoding Spiking Neural Network Facilitate Predictions of Neural Computation

Despite its better bio-plausibility, goal-driven spiking neural network (SNN) has not achieved applicable performance for classifying biological spike trains, and showed little bio-functional similarities compared to traditional artificial neural networks. In this study, we proposed the motorSRNN, a recurrent SNN topologically inspired by the neural motor circuit of primates. By employing the motorSRNN in decoding spike trains from the primary motor cortex of monkeys, we achieved a good balance between classification accuracy and energy consumption. The motorSRNN communicated with the input by capturing and cultivating more cosine-tuning, an essential property of neurons in the motor cortex, and maintained its stability during training. Such training-induced cultivation and persistency of cosine-tuning was also observed in our monkeys. Moreover, the motorSRNN produced additional bio-functional similarities at the single-neuron, population, and circuit levels, demonstrating biological authenticity. Thereby, ablation studies on motorSRNN have suggested long-term stable feedback synapses contribute to the training-induced cultivation in the motor cortex. Besides these novel findings and predictions, we offer a new framework for building authentic models of neural computation

Limb-state information encoded by peripheral and central somatosensory neurons:Implications for an afferent interface

A major issue to be addressed in the development of neural interfaces for prosthetic control is the need for somatosensory feedback. Here, we investigate two possible strategies: electrical stimulation of either dorsal root ganglia (DRG) or primary somatosensory cortex (S1). In each approach, we must determine a model that reflects the representation of limb state in terms of neural discharge. This model can then be used to design stimuli that artificially activate the nervous system to convey information about limb state to the subject. Electrically activating DRG neurons using naturalistic stimulus patterns, modeled on recordings made during passive limb movement, evoked activity in S1 that was similar to that of the original movement. We also found that S1 neural populations could accurately discriminate different patterns of DRG stimulation across a wide range of stimulus pulse-rates. In studying the neural coding in S1, we also decoded the kinematics of active limb movement using multi-electrode recordings in the monkey. Neurons having both proprioceptive and cutaneous receptive fields contributed equally to this decoding. Some neurons were most informative of limb state in the recent past, but many others appeared to signal upcoming movements suggesting that they also were modulated by an efference copy signal. Finally, we show that a monkey was able to detect stimulation through a large percentage of electrodes implanted in area 2. We discuss the design of appropriate stimulus paradigms for conveying time-varying limb state information, and the relative merits and limitations of central and peripheral approaches

Developing implant technologies and evaluating brain-machine interfaces using information theory

Brain-machine interfaces (BMIs) hold promise for restoring motor functions in severely paralyzed individuals. Invasive BMIs are capable of recording signals from individual neurons and typically provide the highest signal-to-noise ratio. Despite many efforts in the scientific community, BMI technology is still not reliable enough for widespread clinical application. The most prominent challenges include biocompatibility, stability, longevity, and lack of good models for informed signal processing and BMI comparison. To address the problem of low signal quality of chronic probes, in the first part of the thesis one such design, the Neurotrophic Electrode, was modified by increasing its channel capacity to form a Neurotrophic Array (NA). Specifically, single wires were replaced with stereotrodes and the total number of recording wires was increased. This new array design was tested in a rhesus macaque performing a delayed saccade task. The NA recorded little single unit spiking activity, and its local field potentials (LFPs) correlated with presented visual stimuli and saccade locations better than did extracted spikes. The second part of the thesis compares the NA to the Utah Array (UA), the only other micro-array approved for chronic implantation in a human brain. The UA recorded significantly more spiking units, which had larger amplitudes than NA spikes. This was likely due to differences in the array geometry and construction. LFPs on the NA electrodes were more correlated with each other than those on the UA. These correlations negatively impacted the NA's information capacity when considering more than one recording site. The final part of this dissertation applies information theory to develop objective measures of BMI performance. Currently, decoder information transfer rate (ITR) is the most popular BMI information performance metric. However, it is limited by the selected decoding algorithm and does not represent the full task information embedded in the recorded neural signal. A review of existing methods to estimate ITR is presented, and these methods are interpreted within a BMI context. A novel Gaussian mixture Monte Carlo method is developed to produce good ITR estimates with a low number of trials and high number of dimensions, as is typical for BMI applications

Low-frequency local field potentials in primate motor cortex and their application to neural interfaces

PhD ThesisFor patients with spinal cord injury and paralysis, there are currently very limited options for clinical therapy. Brain-machine interfaces (BMIs) are neuroprosthetic devices that are being developed to record from the motor cortex in such patients, bypass the spinal lesion, and use decoded signals to control an effector, such as a prosthetic limb. The ideal BMI would be durable, reliable, totally predictable, fully-implantable, and have generous battery life. Current, state-of-the-art BMIs are limited in all of these domains; partly because the typical signals used—neuronal action potentials, or ‘spikes’—are very susceptible to micro-movement of recording electrodes. Recording spikes from the same neurons over many months is therefore difficult, and decoder behaviour may be unpredictable from day-today. Spikes also need to be digitized at high frequencies (~104 Hz) and heavily processed. As a result, devices are energy-hungry and difficult to miniaturise. Low-frequency local field potentials (lf-LFPs; < 5 Hz) are an alternative cortical signal. They are more stable and can be captured and processed at much lower frequencies (~101 Hz). Here we investigate rhythmical lf-LFP activity, related to the firing of local cortical neurons, during isometric wrist movements in Rhesus macaques. Multichannel spike-related slow potentials (SRSPs) can be used to accurately decode the firing rates of individual motor cortical neurons, and subjects can control a BMI task using this synthetic signal, as if they were controlling the actual firing rate. Lf-LFP–based firing rate estimates are stable over time – even once actual spike recordings have been lost. Furthermore, the dynamics of lf-LFPs are distinctive enough, that an unsupervised approach can be used to train a decoder to extract movement-related features for use in biofeedback BMIs. Novel electrode designs may help us optimise the recording of these signals, and facilitate progress towards a new generation of robust, implantable BMIs for patients.Research Studentship from the MRC, and Andy Jackson’s laboratory (hence this work) is supported by the Wellcome Trust

Developing an oculomotor brain-computer interface and charactering its dynamic functional network

To date, invasive brain-computer interface (BCI) research has largely focused on replacing lost limb functions using signals from hand/arm areas of motor cortex. However, the oculomotor system may be better suited to BCI applications involving rapid serial selection from spatial targets, such as choosing from a set of possible words displayed on a computer screen in an augmentative and alternative communication application. First, we develop an intracortical oculomotor BCI based on the delayed saccade paradigm and demonstrate its feasibility to decode intended saccadic eye movement direction in primates. Using activity from three frontal cortical areas implicated in oculomotor production – dorsolateral prefrontal cortex, supplementary eye field, and frontal eye field – we could decode intended saccade direction in real time with high accuracy, particularly at contralateral locations. In a number of analyses in the decoding context, we investigated the amount of saccade-related information contained in different implant regions and in different neural measures. A novel neural measure using power in the 80-500 Hz band is proposed as the optimal signal for this BCI purpose. In the second part of this thesis, we characterize the interactions between the neural signals recorded from electrodes in these three implant areas. We employ a number of techniques to quantify the spectrotemporal dynamics in this complex network, and we describe the resulting functional connectivity patterns between the three implant regions in the context of eye-movement production. In addition, we compare and contrast the amount of saccade-related information present in the coupling strengths in the network, on both an electrode-to-electrode scale and an area-to-area scale. Different frequency bands stand out during different epochs of the task, and their information contents are distinct between implant regions. For example, the 13-30 Hz band stands out during the delay epoch, and the 8-12 Hz band is relevant during target and response epochs. This work extends the boundary of BCI research into the oculomotor domain, and invites potential applications by showing its feasibility. Furthermore, it elucidates the complex dynamics of the functional coupling underlying oculomotor production across multiple areas of frontal cortex

Modeling and Analysis of Neural Spike Trains

open