Cortical Network Synchrony Under Applied Electrical Field

Synchronous network activity plays a crucial role in complex brain functions. Stimulating the nervous system with applied electric field (EF) is a common tool for probing network responses. We used a gold wire-embedded silk protein film-based interface culture to investigate the effects of applied EFs on random cortical networks of in vitro cultures. Two-week-old cultures were exposed to EF of 27 mV/mm for \u3c1 h and monitored by time-lapse calcium imaging. Network activity was represented by calcium signal time series mapped to source neurons and analyzed by using a community detection algorithm. Cortical cultures exhibited large scale, synchronized oscillations under alternating EF of changing frequencies. Field polarity and frequency change were both found to be necessary for network synchrony, as monophasic pulses of similar frequency changes or EF of a constant frequency failed to induce correlated activities of neurons. Group-specific oscillatory patterns were entrained by network-level synchronous oscillations when the alternating EF frequency was increased from 0.2 Hz to 200 kHz. Binary responses of either activity increase or decrease contributed to the opposite phase patterns of different sub-populations. Conversely, when the EF frequency decreased over the same range span, more complex behavior emerged showing group-specific amplitude and phase patterns. These findings formed the basis of a hypothesized network control mechanism for temporal coordination of distributed neuronal activity, involving coordinated stimulation by alternating polarity, and time delay by change of frequency. These novel EF effects on random neural networks have important implications for brain functional studies and neuromodulation applications

Neurostimulator with Waveforms Inspired by Nature for Wearable Electro-Acupuncture

The work presented here has 3 goals: establish the need for novel neurostimulation waveform solutions through a literature review, develop a neurostimulation pulse generator, and verify the operation of the device for neurostimulation applications. The literature review discusses the importance of stimulation waveforms on the outcomes of neurostimulation, and proposes new directions for neurostimulation research that would help in improving the reproducibility and comparability between studies. The pulse generator circuit is then described that generates signals inspired by the shape of excitatory or inhibitory post-synaptic potentials (EPSP, IPSP). The circuit analytical equations are presented, and the effects of the circuit design components are discussed. The circuit is also analyzed with a capacitive load using a simplified Randles model to represent the electrode-electrolyte interface, and the output is measured in phosphate-buffered saline (PBS) solution as the load with acupuncture needles as electrodes. The circuit is designed to be used in different types of neurostimulators depending on the needs of the application, and to study the effects of varying neurostimulation waveforms. The circuit is used to develop a remote-controlled wearable veterinary electro-acupuncture machine. The device has a small form-factor and 3D printed enclosure, and has a weight of 75 g with leads attached. The device is powered by a 500 mAh lithium polymer battery, and was tested to last 6 hours. The device is tested in an electro-acupuncture animal study on cats performed at the Louisiana State University School of Veterinary Medicine, where it showed expected electro-acupuncture effects. Then, a 2-channel implementation of the device is presented, and tested to show independent output amplitude, frequency, and stimulation duration per channel. Finally, the software and hardware requirements for control of the wearable veterinary electro-acupuncture machine are detailed. The number of output channels is limited to the number of hardware PWM timers available for use. The Arduino software implements PWM control for the output amplitude and frequency. The stimulation duration control is provided using software timers. The communications protocol between the microcontroller board and Android App are described, and communications are performed via Bluetooth

Advances in Clinical Neurophysiology

Including some of the newest advances in the field of neurophysiology, this book can be considered as one of the treasures that interested scientists would like to collect. It discusses many disciplines of clinical neurophysiology that are, currently, crucial in the practice as they explain methods and findings of techniques that help to improve diagnosis and to ensure better treatment. While trying to rely on evidence-based facts, this book presents some new ideas to be applied and tested in the clinical practice. Advances in Clinical Neurophysiology is important not only for the neurophysiologists but also for clinicians interested or working in wide range of specialties such as neurology, neurosurgery, intensive care units, pediatrics and so on. Generally, this book is written and designed to all those involved in, interpreting or requesting neurophysiologic tests

Cortical Network Synchrony Under Applied Electrical Field in vitro

Synchronous network activity plays a crucial role in complex brain functions. Stimulating the nervous system with applied electric field (EF) is a common tool for probing network responses. We used a gold wire-embedded silk protein film-based interface culture to investigate the effects of applied EFs on random cortical networks of in vitro cultures. Two-week-old cultures were exposed to EF of 27 mV/mm for <1 h and monitored by time-lapse calcium imaging. Network activity was represented by calcium signal time series mapped to source neurons and analyzed by using a community detection algorithm. Cortical cultures exhibited large scale, synchronized oscillations under alternating EF of changing frequencies. Field polarity and frequency change were both found to be necessary for network synchrony, as monophasic pulses of similar frequency changes or EF of a constant frequency failed to induce correlated activities of neurons. Group-specific oscillatory patterns were entrained by network-level synchronous oscillations when the alternating EF frequency was increased from 0.2 Hz to 200 kHz. Binary responses of either activity increase or decrease contributed to the opposite phase patterns of different sub-populations. Conversely, when the EF frequency decreased over the same range span, more complex behavior emerged showing group-specific amplitude and phase patterns. These findings formed the basis of a hypothesized network control mechanism for temporal coordination of distributed neuronal activity, involving coordinated stimulation by alternating polarity, and time delay by change of frequency. These novel EF effects on random neural networks have important implications for brain functional studies and neuromodulation applications

Dynamics of embodied dissociated cortical cultures for the control of hybrid biological robots.

The thesis presents a new paradigm for studying the importance of interactions between an organism and its environment using a combination of biology and technology: embodying cultured cortical neurons via robotics. From this platform, explanations of the emergent neural network properties leading to cognition are sought through detailed electrical observation of neural activity. By growing the networks of neurons and glia over multi-electrode arrays (MEA), which can be used to both stimulate and record the activity of multiple neurons in parallel over months, a long-term real-time 2-way communication with the neural network becomes possible. A better understanding of the processes leading to biological cognition can, in turn, facilitate progress in understanding neural pathologies, designing neural prosthetics, and creating fundamentally different types of artificial cognition. Here, methods were first developed to reliably induce and detect neural plasticity using MEAs. This knowledge was then applied to construct sensory-motor mappings and training algorithms that produced adaptive goal-directed behavior. To paraphrase the results, most any stimulation could induce neural plasticity, while the inclusion of temporal and/or spatial information about neural activity was needed to identify plasticity. Interestingly, the plasticity of action potential propagation in axons was observed. This is a notion counter to the dominant theories of neural plasticity that focus on synaptic efficacies and is suggestive of a vast and novel computational mechanism for learning and memory in the brain. Adaptive goal-directed behavior was achieved by using patterned training stimuli, contingent on behavioral performance, to sculpt the network into behaviorally appropriate functional states: network plasticity was not only induced, but could be customized. Clinically, understanding the relationships between electrical stimulation, neural activity, and the functional expression of neural plasticity could assist neuro-rehabilitation and the design of neuroprosthetics. In a broader context, the networks were also embodied with a robotic drawing machine exhibited in galleries throughout the world. This provided a forum to educate the public and critically discuss neuroscience, robotics, neural interfaces, cybernetics, bio-art, and the ethics of biotechnology.Ph.D.Committee Chair: Steve M. Potter; Committee Member: Eric Schumacher; Committee Member: Robert J. Butera; Committee Member: Stephan P. DeWeerth; Committee Member: Thomas D. DeMars

Comparison of the Effects of Sensorimotor Rhythm and Slow Cortical Potential Neurofeedback in Epilepsy

Current conventional epilepsy treatments do not always aim to improve epilepsy comorbidities. For a treatment to be effective, is not necessary for it to keep the patient seizure-free; it is sufficient to show improvement in functions to help people who suffer from epilepsy to become more independent and productive in life. There is an urgent need to explore non- pharmaceutical/non-invasive interventions that can help in that regard. The earlier patients are treated with this condition, the more likely it is to prevent severe disabilities over time. Neurofeedback is a self-modulatory brain activity oscillatory intervention that previous researchers have found to reduce seizure frequency in patients with epilepsy. The aim of this work was to compare two Neurofeedback techniques that have shown some efficacy in improving symptoms in epilepsy. The novelty of this study is to explore further and included clinical, neurophysiological and cognitive outcomes in order to assess in more detail the effectiveness of epilepsy comorbidities. Forty-four patients, between the ages of 12 and 18 years, and diagnosed with focal epilepsy, divided randomly into three groups: sensorimotor rhythm (SMR) training, slow cortical potential (SCP) training, and control. The patients completed 25 sessions of intervention. The results showed that the SMR group training had an advantage in improving reaction time compared with SCP and control. Regression analysis revealed a significant correlation between the patients who learned to modify their brain activity in the SMR group and improving reaction time in two different tasks. In addition, the quality of life scale significantly improved in all three groups. The study supplies preliminary data to support that SMR neurofeedback training as an intervention should further be explored as a therapeutic option for children who suffer from focal epilepsy.CONACYT (Mexican Council of science and technology

Electrostimulation Contingencies and Attention, Electrocortical Activity and Neurofeedback

There is a growing body of evidence for diverse ways of modulating neuronal processing to improve cognitive performance. These include brain-based feedback, self-regulation techniques such as EEG-neurofeedback, and stimulation strategies, alone or in combination. The thesis goal was to determine whether a combined strategy would have advantages for normal cognitive function; specifically operant control of EEG activity in combination with transcutaneous electro-acustimulation. In experiment one the association between transcutaneous electroacustimulation (EA) and improved perceptual sensitivity was demonstrated with a visual GO/NOGO attention task (Chen et al, 2011). Furthermore reduced commission errors were related to an electrocortical motor inhibition component during and after alternating high and low frequency EA, whereas habituation in the control group with sham stimulation was related to different independent components. Experiment two applied frequency-domain ICA to detect changes in EEG power spectra from the eyes-closed to the eyes-open state (Chen et al, 2012). A multiple step approach was provided for analysing the spatiotemporal dynamics of default mode and resting state networks of cerebral EEG sources, preferable to conventional scalp EEG data analysis. Five regions were defined, compatible with fMRI studies. In experiment three the EA approach of Exp I was combined with sensorimotor rhythm (SMR) neurofeedback. SMR training improved perceptual sensitivity, an effect not found in a noncontingent feedback group. However, non-significant benefits resulted from EA. With ICA spectral power analysis changes in frontal beta power were associated with contingent SMR training. Possible long-term effects on an attention network in the resting EEG were also found after SMR training, compared with mock SMR training. In conclusion, this thesis has supplied novel evidence for significant cognitive and electrocortical effects of neurofeedback training and transcutaneous electro-acustimulation in healthy humans. Possible implications of these findings and suggestions for future research are considered