Critical Points and Traveling Wave in Locomotion: Experimental Evidence and Some Theoretical Considerations

The central pattern generator (CPG) architecture for rhythm generation remains partly elusive. We compare cat and frog locomotion results, where the component unrelated to pattern formation appears as a temporal grid, and traveling wave respectively. Frog spinal cord microstimulation with N-methyl-D-Aspartate (NMDA), a CPG activator, produced a limited set of force directions, sometimes tonic, but more often alternating between directions similar to the tonic forces. The tonic forces were topographically organized, and sites evoking rhythms with different force subsets were located close to the constituent tonic force regions. Thus CPGs consist of topographically organized modules. Modularity was also identified as a limited set of muscle synergies whose combinations reconstructed the EMGs. The cat CPG was investigated using proprioceptive inputs during fictive locomotion. Critical points identified both as abrupt transitions in the effect of phasic perturbations, and burst shape transitions, had biomechanical correlates in intact locomotion. During tonic proprioceptive perturbations, discrete shifts between these critical points explained the burst durations changes, and amplitude changes occurred at one of these points. Besides confirming CPG modularity, these results suggest a fixed temporal grid of anchoring points, to shift modules onsets and offsets. Frog locomotion, reconstructed with the NMDA synergies, showed a partially overlapping synergy activation sequence. Using the early synergy output evoked by NMDA at different spinal sites, revealed a rostrocaudal topographic organization, where each synergy is preferentially evoked from a few, albeit overlapping, cord regions. Comparing the locomotor synergy sequence with this topography suggests that a rostrocaudal traveling wave would activate the synergies in the proper sequence for locomotion. This output was reproduced in a two-layer model using this topography and a traveling wave. Together our results suggest two CPG components: modules, i.e., synergies; and temporal patterning, seen as a temporal grid in the cat, and a traveling wave in the frog. Animal and limb navigation have similarities. Research relating grid cells to the theta rhythm and on segmentation during navigation may relate to our temporal grid and traveling wave results. Winfree’s mathematical work, combining critical phases and a traveling wave, also appears important. We conclude suggesting tracing, and imaging experiments to investigate our CPG model

Closed-Loop Brain-Computer Interfaces for Memory Restoration Using Deep Brain Stimulation

The past two decades have witnessed the rapid growth of therapeutic brain-computer interfaces (BCI) targeting a diversity of brain dysfunctions. Among many neurosurgical procedures, deep brain stimulation (DBS) with neuromodulation technique has emerged as a fruitful treatment for neurodegenerative disorders such as epilepsy, Parkinson\u27s disease, post-traumatic amnesia, and Alzheimer\u27s disease, as well as neuropsychiatric disorders such as depression, obsessive-compulsive disorder, and schizophrenia. In parallel to the open-loop neuromodulation strategies for neuromotor disorders, recent investigations have demonstrated the superior performance of closed-loop neuromodulation systems for memory-relevant disorders due to the more sophisticated underlying brain circuitry during cognitive processes. Our efforts are focused on discovering unique neurophysiological patterns associated with episodic memories then applying control theoretical principles to achieve closed-loop neuromodulation of such memory-relevant oscillatory activity, especially, theta and gamma oscillations. First, we use a unique dataset with intracranial electrodes inserted simultaneously into the hippocampus and seven cortical regions across 40 human subjects to test for the presence of a pattern that the phase of hippocampal theta oscillation modulates gamma oscillations in the cortex, termed cross-regional phase-amplitude coupling (xPAC), representing a key neurophysiological mechanism that promotes the temporal organization of interregional oscillatory activities, which has not previously been observed in human subjects. We then establish that the magnitude of xPAC predicts memory encoding success along with other properties of xPAC. We find that strong functional xPAC occurs principally between the hippocampus and other mesial temporal structures, namely entorhinal and parahippocampal cortices, and that xPAC is overall stronger for posterior hippocampal connections. Next, we focus on hippocampal gamma power as a `biomarker\u27 and use a novel dataset in which open-loop DBS was applied to the posterior cingulate cortex (PCC) during the encoding of episodic memories. We evaluate the feasibility of modulating hippocampal power by a precise control of stimulation via a linear quadratic integral (LQI) controller based on autoregressive with exogenous input (ARX) modeling for in-vivo use. In the simulation framework, we demonstrate proposed BCI system achieves effective control of hippocampal gamma power in 15 out of 17 human subjects and we show our DBS pattern is physiologically safe with realistic time scales. Last, we further develop the PCC-applied binary-noise (BN) DBS paradigm targeting the neuromodulation of both hippocampal theta and gamma oscillatory power in 12 human subjects. We utilize a novel nonlinear autoregressive with exogenous input neural network (NARXNN) as the plant paired with a proportional–integral–derivative (PID) controller (NARXNN-PID) for delivering a precise stimulation pattern to achieve desired oscillatory power level. Compared to a benchmark consisted of a linear state-space model (LSSM) with a PID controller, we not only demonstrate that the superior performance of our NARXNN plant model but also show the greater capacity of NARXNN-PID architecture in controlling both hippocampal theta and gamma power. We outline further experimentation to test our BCI system and compare our findings to emerging closed-loop neuromodulation strategies

An investigation into the neural substrates of virtue to determine the key place of virtues in human moral development

Virtues, as described by Aristotle and Aquinas, are understood as dispositions of character to behave in habitual, specific, positive ways; virtue is a critical requirement for human flourishing. From the perspective of Aristotelian-Thomistic anthropology which offers an integrated vision of the material and the rational in the human person, I seek to identify the neural bases for the development and exercise of moral virtue. First I review current neuroscientific knowledge of the capacity of the brain to structure according to experience, to facilitate behaviours, to regulate emotional responses and support goal election. Then, having identified characteristics of moral virtue in the light of the distinctions between cardinal virtues, I propose neural substrates by mapping neuroscientific knowledge to these characteristics. I then investigate the relationship between virtue, including its neurobiological features, and human flourishing. This process allows a contemporary and evidence-based corroboration for a model of moral development based on growth in virtue as understood by Aristotle and Aquinas, and a demonstration of a biological aptitude and predisposition for the development of virtue. Conclusions are drawn with respect to science, ethics, and parenting

Continuous versus Discontinuous Drawing: Possible Cerebellar Involvement in the Development of Temporal Consistency

The capability to generate drawing and writing movements of high spatial and temporal qualities is one of the most important developmental achievements during the early school years. Recently, Spencer et al., (2003) proposed that the cerebellum controls the 'explicit timing' underlying temporal consistency during discontinuous drawing, but not 'implicit timing' during continuous drawing. Alternatively, the cerebellum might be involved in the control of limb dynamics, which differ between continuous and discontinuous drawing (Bastian et al., 2000). In the current study, we examine the hypothesis that the developing cerebellum might play an important role in the development of temporal consistency in drawing skills in children. Specifically, we examined: 1) whether there were age-related differences between continuous and discontinuous circle drawing, 2) whether the children's performance in the circle drawing tasks was the same as their performance in the dynamically simpler line drawing tasks, and 3) whether children with Developmental Coordination Disorder (DCD) performed similarly to the children who were typically developing in these four types of movements. Thirty-two children who were typically developing between the ages of five and eleven years and ten children with DCD performed the continuous, discontinuous circle- and line-drawing tasks in random order. Participants were asked to move as consistently as possible for 20 seconds after synchronizing their movements with a metronome for 15 beats. Regression analysis in children who were typically developing showed that high temporal variability existed only in the discontinuous circling in the youngest children but not the older children. Children with DCD showed a similar pattern to their age- and gender-matched controls. However, individual comparison for each child with DCD and normal performance defined by children who were typically developing revealed that two of the ten children with DCD showed timing deficit in the discontinuous movements, an additional three children had timing problem in the discontinuous line drawing. Limb dynamic control played an important role in the development of drawing skills in children. The possibility of a compromised cerebellar function may only exist in a subgroup of children with DCD supporting others observation of the heterogeneous nature of this population

Multimodal Sensory Integration for Perception and Action in High Functioning Children with Autism Spectrum Disorder

Movement disorders are the earliest observed features of autism spectrum disorder (ASD) present in infancy. Yet we do not understand the neural basis for impaired goal-directed movements in this population. To reach for an object, it is necessary to perceive the state of the arm and the object using multiple sensory modalities (e.g. vision, proprioception), to integrate those sensations into a motor plan, to execute the plan, and to update the plan based on the sensory consequences of action. In this dissertation, I present three studies in which I recorded hand paths of children with ASD and typically developing (TD) controls as they grasped the handle of a robotic device to control a cursor displayed on a video screen. First, participants performed discrete and continuous movements to capture targets. Cursor feedback was perturbed from the hand\u27s actual position to introduce visuo-spatial conflict between sensory and proprioceptive feedback. Relative to controls, children with ASD made greater errors, consistent with deficits of sensorimotor adaptive and strategic compensations. Second, participants performed a two-interval forced-choice discrimination task in which they perceived two movements of the visual cursor and/or the robot handle and then indicated which of the two movements was more curved. Children with ASD were impaired in their ability to discriminate movement kinematics when provided visual and proprioceptive information simultaneously, suggesting deficits of visuo-proprioceptive integration. Finally, participants made goal-directed reaching movements against a load while undergoing simultaneous functional magnetic resonance imaging (MRI). The load remained constant (predictable) within an initial block of trials and then varied randomly within four additional blocks. Children with ASD exhibited greater movement variability compared to controls during both constant and randomly-varying loads. MRI analysis identified marked differences in the extent and intensity of the neural activities supporting goal-directed reaching in children with ASD compared to TD children in both environmental conditions. Taken together, the three studies revealed deficits of multimodal sensory integration in children with ASD during perception and execution of goal-directed movements and ASD-related motor performance deficits have a telltale neural signature, as revealed by functional MR imaging

Development of a Unique Whole-Brain Model for Upper Extremity Neuroprosthetic Control

Neuroprostheses are at the forefront of upper extremity function restoration. However, contemporary controllers of these neuroprostheses do not adequately address the natural brain strategies related to planning, execution and mediation of upper extremity movements. These lead to restrictions in providing complete and lasting restoration of function. This dissertation develops a novel whole-brain model of neuronal activation with the goal of providing a robust platform for an improved upper extremity neuroprosthetic controller. Experiments (N=36 total) used goal-oriented upper extremity movements with real-world objects in an MRI scanner while measuring brain activation during functional magnetic resonance imaging (fMRI). The resulting data was used to understand neuromotor strategies using brain anatomical and temporal activation patterns. The study\u27s fMRI paradigm is unique and the use of goal-oriented movements and real-world objects are crucial to providing accurate information about motor task strategy and cortical representation of reaching and grasping. Results are used to develop a novel whole-brain model using a machine learning algorithm. When tested on human subject data, it was determined that the model was able to accurately distinguish functional motor tasks with no prior knowledge. The proof of concept model created in this work should lead to improved prostheses for the treatment of chronic upper extremity physical dysfunction

Hierarchical models of goal-directed and automatic actions

Decision-making processes behind instrumental actions can be divided into two categories: goal-directed actions, and automatic actions. The structure of automatic actions, their interaction with goal-directed actions, and their behavioral and computational properties are the topics of the current thesis. We conceptualize the structure of automatic actions as sequences of actions that form a single response unit and are integrated within goal-directed processes in a hierarchical manner. We represent this hypothesis using the computational framework of reinforcement learning and develop a new normative computational model for the acquisition of action sequences, and their hierarchical interaction with goal-directed processes. We develop a neurally plausible hypothesis for the role of neuromodulator dopamine as a teaching signal for the acquisition of action sequences. We further explore the predictions of the proposed model in a two-stage decision-making task in humans and we show that the proposed model has higher explanatory power than its alternatives. Finally, we translate the two-stage decision-making task to an experimental protocol in rats and show that, similar to humans, rats also use action sequences and engage in hierarchical decision-making. The results provide a new theoretical and experimental paradigm for conceptualizing and measuring the operation and interaction of goal-directed and automatic actions

Hierarchical models of goal-directed and automatic actions

Decision-making processes behind instrumental actions can be divided into two categories: goal-directed actions, and automatic actions. The structure of automatic actions, their interaction with goal-directed actions, and their behavioral and computational properties are the topics of the current thesis. We conceptualize the structure of automatic actions as sequences of actions that form a single response unit and are integrated within goal-directed processes in a hierarchical manner. We represent this hypothesis using the computational framework of reinforcement learning and develop a new normative computational model for the acquisition of action sequences, and their hierarchical interaction with goal-directed processes. We develop a neurally plausible hypothesis for the role of neuromodulator dopamine as a teaching signal for the acquisition of action sequences. We further explore the predictions of the proposed model in a two-stage decision-making task in humans and we show that the proposed model has higher explanatory power than its alternatives. Finally, we translate the two-stage decision-making task to an experimental protocol in rats and show that, similar to humans, rats also use action sequences and engage in hierarchical decision-making. The results provide a new theoretical and experimental paradigm for conceptualizing and measuring the operation and interaction of goal-directed and automatic actions

Augmentation of Brain Function: Facts, Fiction and Controversy. Volume III: From Clinical Applications to Ethical Issues and Futuristic Ideas

The final volume in this tripartite series on Brain Augmentation is entitled “From Clinical Applications to Ethical Issues and Futuristic Ideas”. Many of the articles within this volume deal with translational efforts taking the results of experiments on laboratory animals and applying them to humans. In many cases, these interventions are intended to help people with disabilities in such a way so as to either restore or extend brain function. Traditionally, therapies in brain augmentation have included electrical and pharmacological techniques. In contrast, some of the techniques discussed in this volume add specificity by targeting select neural populations. This approach opens the door to where and how to promote the best interventions. Along the way, results have empowered the medical profession by expanding their understanding of brain function. Articles in this volume relate novel clinical solutions for a host of neurological and psychiatric conditions such as stroke, Parkinson’s disease, Huntington’s disease, epilepsy, dementia, Alzheimer’s disease, autism spectrum disorders (ASD), traumatic brain injury, and disorders of consciousness. In disease, symptoms and signs denote a departure from normal function. Brain augmentation has now been used to target both the core symptoms that provide specificity in the diagnosis of a disease, as well as other constitutional symptoms that may greatly handicap the individual. The volume provides a report on the use of repetitive transcranial magnetic stimulation (rTMS) in ASD with reported improvements of core deficits (i.e., executive functions). TMS in this regard departs from the present-day trend towards symptomatic treatment that leaves unaltered the root cause of the condition. In diseases, such as schizophrenia, brain augmentation approaches hold promise to avoid lengthy pharmacological interventions that are usually riddled with side effects or those with limiting returns as in the case of Parkinson’s disease. Brain stimulation can also be used to treat auditory verbal hallucination, visuospatial (hemispatial) neglect, and pain in patients suffering from multiple sclerosis. The brain acts as a telecommunication transceiver wherein different bandwidth of frequencies (brainwave oscillations) transmit information. Their baseline levels correlate with certain behavioral states. The proper integration of brain oscillations provides for the phenomenon of binding and central coherence. Brain augmentation may foster the normalization of brain oscillations in nervous system disorders. These techniques hold the promise of being applied remotely (under the supervision of medical personnel), thus overcoming the obstacle of travel in order to obtain healthcare. At present, traditional thinking would argue the possibility of synergism among different modalities of brain augmentation as a way of increasing their overall effectiveness and improving therapeutic selectivity. Thinking outside of the box would also provide for the implementation of brain-to-brain interfaces where techniques, proper to artificial intelligence, could allow us to surpass the limits of natural selection or enable communications between several individual brains sharing memories, or even a global brain capable of self-organization. Not all brains are created equal. Brain stimulation studies suggest large individual variability in response that may affect overall recovery/treatment, or modify desired effects of a given intervention. The subject’s age, gender, hormonal levels may affect an individual’s cortical excitability. In addition, this volume discusses the role of social interactions in the operations of augmenting technologies. Finally, augmenting methods could be applied to modulate consciousness, even though its neural mechanisms are poorly understood. Finally, this volume should be taken as a debate on social, moral and ethical issues on neurotechnologies. Brain enhancement may transform the individual into someone or something else. These techniques bypass the usual routes of accommodation to environmental exigencies that exalted our personal fortitude: learning, exercising, and diet. This will allow humans to preselect desired characteristics and realize consequent rewards without having to overcome adversity through more laborious means. The concern is that humans may be playing God, and the possibility of an expanding gap in social equity where brain enhancements may be selectively available to the wealthier individuals. These issues are discussed by a number of articles in this volume. Also discussed are the relationship between the diminishment and enhancement following the application of brain-augmenting technologies, the problem of “mind control” with BMI technologies, free will the duty to use cognitive enhancers in high-responsibility professions, determining the population of people in need of brain enhancement, informed public policy, cognitive biases, and the hype caused by the development of brain- augmenting approaches