Long-Term Bidirectional Neuron Interfaces for Robotic Control, and In Vitro Learning Studies

There are two fundamentally different goals for neural interfacing. On the biology side, to interface living neurons to external electronics allows the observation and manipulation of neural circuits to elucidate their fundamental mechanisms. On the engineering side, neural interfaces in animals, people, or in cell culture have the potential to restore missing functionality, or someday, to enhance existing functionality. At the Laboratory for NeuroEngineering at Georgia Tech, we are developing new technologies to help make both goals attainable. We culture dissociated mammalian neurons on multi-electrode arrays, and use them as the brain of a 'Hybrot', or hybrid neural-robotic system. Distributed neural activity patterns are used to control mobile robots. We have created the hardware and software necessary to feed the robots' sensory inputs back to the cultures in real time, as electrical stimuli. By embodying cultured networks, we study learning and memory at the cellular and network level, using 2-photon laser-scanning microscopy to image plasticity while it happens. We have observed a very rich dynamical landscape of activity patterns in networks of only a few thousand cells. We can alter this landscape via electrical stimuli, and use the hybrot system to study the emergent properties of networks in vitro

Role of spontaneous bursts in functional plasticity and spatiotemporal dynamics of dissociated cortical cultures

What changes in our brain when we learn? This is perhaps the most intriguing question of science in this century. In an attempt to learn more about the inner workings of neural circuitry, I studied cultured 2-dimensional networks of neurons on multi-electrode arrays (MEAs). MEAs are ideal tools for studying long-term neural ensemble activity because many individual cells can be studied continuously for months, through electrical stimulation and recording. One of the most prominent patterns of activity observed in these cultures is network-wide spontaneous bursting, during which most of the active electrodes in the culture show elevated firing rates. We view the persistence of spontaneous bursting in vitro as a sign of arrested development due to deafferentation. Substituting distributed electrical stimulation for afferent input transformed the activity in dissociated cultures from bursting to more dispersed spiking, reminiscent of activity in the adult brain. Burst suppression reduced the variability in neural responses making it easier to induce and detect functional plasticity caused by tetanic stimulation. This suggests that spontaneous bursts interfere with the effects of external stimulation and that a burst-free environment leads to more stable connections and predictable effects of tetanization. Moreover, our culture models continuously receive input stimulation in the form of background electrical stimulation, and so better resemble the intact brain than isolated (non-continuously stimulated) cultures. The proportion of GABAergic neurons in the cultures was significantly increased (p<1e-2, paired t-test) after burst-quieting for 2 days, suggesting that burst suppression operated through the homeostatic control of inhibitory neurotransmitter levels. We also studied the role of spontaneous bursts as potential carriers of information in the network by clustering these spatiotemporally diverse bursts. Spontaneous burst clusters were stable over hours and tetanic stimulation significantly reorganized the distribution of the clusters. In summary, this body of work explores the rules of network-level functional plasticity and provides the input (electrical stimulation) output (spatiotemporal patterns) mappings for behavioral studies in embodied hybrid systems. The results of this study may also have clinical implications in the development of sensory prostheses and treatment of diseases of aberrant network activity such as epilepsy.Ph.D.Committee Chair: Potter, Steve; Committee Member: Butera, Robert; Committee Member: DeWeerth, Stephen; Committee Member: Schumacher, Eric; Committee Member: Wenner, Pet

A Study on Uthiravatha Suronitham

The aim of the study was to evaluate the efficacy of the drug CHANDAMARUTHA CHENDURAM (Internal) and POONAGA THYLAM (External) in Uthiravatha Suronitham. ❖ Before initiating the clinical trial, approval was got from the Institutional Animal Ethical Committee and Institutional Ethical Committee for conducting the pre clinical studies and clinical studies respectively by submitting the well defined protocol and proforma. ❖ The raw drugs were authenticated by the concerned department and the trial drug was prepared by the investigator in the Gunapadam lab of National Institute of Siddha as per the Standard Operating Procedure mentioned in the protocol. ❖ The medicine was then subjected to pre clinical toxicity studies (Acute and long term toxicity studies) as per the protocol and the safety of the drug was ensured. ❖ The qualitative and quantitative bio chemical studies were done at the bio chemistry lab of National Institute of Siddha and IIT Chennai respectively. ❖ Among the 60 cases screened at the OPD of department of Maruthuvam NIS, 40 cases were recruited for the trial as per the inclusion and exclusion criteria. ❖ Clinical diagnosis of Uthiravatha suronitham was made by Siddha and Modern methodology. ❖ Before inducement into the trial informed consent was obtained from the patients. Out of the 40 cases 27 cases were treated in OPD and 13 cases in IPD. ❖ A day before the trial drug administration, puragation was given to correct the elevated Vatha thathu and bring other two deranged thathus to equilibrium. ❖ The trial medicines selected for both Internal and External treatment were CHANDAMARUTHA CHENDURAM 65 mg b.i.d with the adjuvant palm jaggery and POONAGA THYLAM referred under Siddha literature Anupoga Vaithiya Navaneetham IV part respectively. * During the treatment period of 48 days the trial drug CHANDAMARUTHA CHENDURAM (Internal) is given for 7 days followed by a break (re dieting) of 5 days. Likewise the medicine is given till the end of the course as given in Siddha Literature. * Every first day of the break (re dieting) started with head bath with the paste of Ajowan seeds with cow's milk as indicated in Siddha text. ❖ Diet restriction was strictly followed during the period of drug administration as well as re dieting period (Diet free of salt, tamarind etc) as per noted in the form IV E (Dietary advice form). ❖ Required lab investigations were carried out before and after the treatment and the concerned data was recorded in the proforma. ❖ Clinical assessment was done daily in all the IP patients and in OP patients it was assessed once in 12 days. ❖ During the study period, there was no event of any adverse reactions owing to the drug or disease. ❖ In these studies out of 40 cases, 95% of cases showed reduction in pain, 5% of cases showed no improvement in pain. Regarding HAQ questionnaire the score was improved in 97.5% of cases. There was improvement in other clinical symptoms before and after treatment revealing the effect of drug in reducing the pain and other clinical symptoms. Thus improvement of the patients in their daily life activities. ❖ As per the Siddha Literature and modern science reviews and research articles, the ingredients of the trial drugs were found to have the property of controlling the Vatha diseases, some drugs exhibited anti inflammatory and analgesic action owing to the disease manifestations. ❖ In case of Clinical Lab parameters there was reduction in RA factor, CRP and ESR which showed the therapeutic effect of the drug in controlling the disease to a greater extent. ❖ Statistical analysis showed significant reduction in pain scale and health assessment score assessed before and after the treatment. Statistical analysis on lab parameters and toxicity studies also showed significant outcome. ❖ Oral toxicity studies conducted ensured the safety usage of the drug to animals up to a maximum dose of 23.4 mg/animal. ❖ Bio chemical analysis showed the presence of inevitable constituents like Calcium, Iron, Sulphur which played a role in repairing and preventing the joint damage in the disease. The minimum particle size (2 i.t) unveiled in the (Particle Per Million size) PPM analysis shows the existence of the drug in micro particle size which contributes its therapeutic effect by the increased bio availability. CONCLUSION: Clinical study revealed the therapeutic efficacy of the trial drug by showing, reduction in pain 95% of cases out of 40 cases. Regarding HAQ questionnaire the score was improved in 97.5% of cases. There was improvement in other clinical symptoms before and after treatment ➢ The safety studies (Acute toxicity and Long term toxicity) studies conducted revealed that the trial drug was safe even at higher dosage of 23.4 mg/animal. There were no abnormalities found in blood investigation and histopathological examination .Hence it can be reasonably assumed that the drug is safe for human. ➢ There is a significant reduction in the elevated lab parameters (Serum Rheumatoid factor, C reactive protein etc) after the treatment revealing the contol of the disease. ➢ There were no adverse reactions complained during the trial. ➢ Because of the encouraging clinical outcome, the study may be further carried out with the same drug in a large number of cases

Comparison of Transcranial Direct Current Stimulation Electrode Montages for the Lower Limb Motor Cortex

Transcranial direct current stimulation (tDCS) has been widely explored as a neuromodulatory adjunct to modulate corticomotor excitability and improve motor behavior. However, issues with the effectiveness of tDCS have led to the exploration of empirical and experimental alternate electrode placements to enhance neuromodulatory effects. Here, we conducted a preliminary study to compare a novel electrode montage (which involved placing 13 cm2 electrodes anterior and posterior to the target location) to the traditionally used electrode montage (13 cm2 stimulating electrode over the target area and the 35 cm2 reference electrode over the contralateral orbit). We examined the effects of tDCS of the lower limb motor area (M1) by measuring the corticomotor excitability (CME) of the tibialis anterior muscle using transcranial magnetic stimulation in twenty healthy participants. We examined behavioral effects using a skilled motor control task performed with the ankle. We did not find one electrode montage to be superior to the other for changes in the CME or motor control. When the group was dichotomized into responders and non-responders (based on upregulation in CME), we found that the responders showed significant upregulation from baseline after tDCS for both montages. However, only the responders in the traditional montage group showed significant changes in motor control after tDCS. These results do not support the superiority of the new anterior&ndash;posterior montage over the traditional montage. Further work with a larger cohort and multiple cumulative sessions may be necessary to confirm our results

STIMULATING NEWS FOR MEA ENTHUSIASTS

Micro-electrode arrays (MEAs) have been used to record from a variety of neural preparations, as well as for stimulating extracellularly. In stimulation experiments reported to date, a large variety of different stimulation waveforms have been employed, but no systematic study has been published about the different effects of different waveforms. We are interested in identifying a class of stimuli that can be used for long term stimulation experiments on dissociated rat (E18) cortical cultures grown on MEAs [1]. Our goals are: • To influence the morphology and functional connectivity of developing neuronal networks by patterned stimulation; • To find reproducible response patterns that can be used to control an animat [2]. This study investigates: • The relative impact of stimulus amplitude and duration for voltage controlled stimuli as well as for current controlled stimuli

CONTROL OF BURSTING IN DISSOCIATED CORTICAL CULTURES ON MULTI-ELECTRODE ARRAYS

We are investigating whether often repeated firing patterns can rewire the connections in a neuronal culture as many reports of spike-timing dependent plasticity suggest. The goal of this work was to seek a stimulation protocol that reduces the amount of spontaneous or uncontrolled activity relative to induced spikes, by the continuous application of stimulation patterns to cultured rat cortical networks. Cultures controlled in this manner will then be used in the study of stimulus-induced plasticity and information processing in these distributed systems [Potter-2001]. Also, by reducing spontaneous activity or enhancing our level of control over the network activity we can study learning in animats (simulated animals) [DeMarse-2001]. Dissociated cultures of cortical neurons in vitro exhibit complex, spontaneous bursts of activity. These bursts or &quot;barrages &quot; are sudden increases in spike frequencies that occur simultaneously on a large fraction of recorded cells in the culture [Gross-93, Kamioka-96, Jimbo-99]. During experiments involving persistent stimulation, we noticed that the number of spikes in these barrages dominates the activity, potentially swamping out the effects of stimulation. Pharmacological methods can be used to reduce barrages. Commonly, the concentration of extracellular Mg 2+ is increased to reduce the frequency of spontaneous activity [Tateno-99]. When we increased concentration of Mg 2+ above 2mM, the number of uncontrolled barrages was reduced, but this was accompanied by a decrease in th

AES 2011 Abstract Title: Temporal theta oscillation enhancement predicts successful memory encoding

Abstract Rationale Theta oscillations The amplitude of these oscillations was correlated to successful memory retrieval in a verbal memory task Methods Epileptic patients implanted with subdural electrodes for seizure localization were tested on two tasks. The first one was a classic multi-item short-term memory task The subjects had to indicate using a key press whether the test image was part of the previous image series or not. In the second task, the subjects were shown a series of 4-6 images. After a short delay, the patients were instructed to arrange the previously presented objects in the order in which they appeare