5,793 research outputs found

    Development of variable and robust brain wiring patterns in the fly visual system

    Get PDF
    Precise generation of synapse-specific neuronal connections are crucial for establishing a robust and functional brain. Neuronal wiring patterns emerge from proper spatiotemporal regulation of axon branching and synapse formation during development. Several neuropsychiatric and neurodevelopmental disorders exhibit defects in neuronal wiring owing to synapse loss and/or dys-regulated axon branching. Despite decades of research, how the two inter-dependent cellular processes: axon branching and synaptogenesis are coupled locally in the presynaptic arborizations is still unclear. In my doctoral work, I investigated the possible role of EGF receptor (EGFR) activity in coregulating axon branching and synapse formation in a spatiotemporally restricted fashion, locally in the medulla innervating Dorsal Cluster Neuron (M- DCN)/LC14 axon terminals. In this work I have explored how genetically encoded EGFR randomly recycles in the axon branch terminals, thus creating an asymmetric, non-deterministic distribution pattern. Asymmetric EGFR activity in the branches acts as a permissive signal for axon branch pruning. I observed that the M-DCN branches which stochastically becomes EGFR ‘+’ during development are synaptogenic, which means they can recruit synaptic machineries like Syd1 and Bruchpilot (Brp). My work showed that EGFR activity has a dual role in establishing proper M-DCN wiring; first in regulating primary branch consolidation possibly via actin regulation prior to synaptogenesis. Later in maintaining/protecting the levels of late Active Zone (AZ) protein Brp in the presynaptic branches by suppressing basal autophagy level during synaptogenesis. When M-DCNs lack optimal EGFR activity, the basal autophagy level increases resulting in loss of Brp marked synapses which is causal to increased exploratory branches and post-synaptic target loss. Lack of EGFR activity affects the M-DCN wiring pattern that makes adult flies more active and behave like obsessive compulsive in object fixation assay. In the second part of my doctoral work, I have asked how non-genetic factors like developmental temperature affects adult brain wiring. To test that, I increased or decreased rearing temperature which is known to inversely affect pupal developmental rate. We asked if all the noisy cellular processes of neuronal assembly: filopodial dynamics, axon branching, synapse formation and postsynaptic connections scale up or down accordingly. I observed that indeed all the cellular processes slow down at lower developmental temperature and vice versa, which changes the DCN wiring pattern accordingly. Interestingly, behavior of flies adapts to their developmental temperature, performing best at the temperature they have been raised at. This shows that optimal brain function is an adaptation of robust brain wiring patterns which are specified by noisy developmental processes. In conclusion, my doctoral work helps us better understand the developmental regulation of axon branching and synapse formation for establishing precise brain wiring pattern. We need all the cell intrinsic developmental processes to be highly regulated in space and time. It is infact a combinatorial effect of such stochastic processes and external factors that contribute to the final outcome, a functional and robust adult brain

    Chronic pulmonary fibrosis alters the functioning of the respiratory neural network

    Get PDF
    Some patients with idiopathic pulmonary fibrosis present impaired ventilatory variables characterised by low forced vital capacity values associated with an increase in respiratory rate and a decrease in tidal volume which could be related to the increased pulmonary stiffness. The lung stiffness observed in pulmonary fibrosis may also have an effect on the functioning of the brainstem respiratory neural network, which could ultimately reinforce or accentuate ventilatory alterations. To this end, we sought to uncover the consequences of pulmonary fibrosis on ventilatory variables and how the modification of pulmonary rigidity could influence the functioning of the respiratory neuronal network. In a mouse model of pulmonary fibrosis obtained by 6 repeated intratracheal instillations of bleomycin (BLM), we first observed an increase in minute ventilation characterised by an increase in respiratory rate and tidal volume, a desaturation and a decrease in lung compliance. The changes in these ventilatory variables were correlated with the severity of the lung injury. The impact of lung fibrosis was also evaluated on the functioning of the medullary areas involved in the elaboration of the central respiratory drive. Thus, BLM-induced pulmonary fibrosis led to a change in the long-term activity of the medullary neuronal respiratory network, especially at the level of the nucleus of the solitary tract, the first central relay of the peripheral afferents, and the Pre-Bötzinger complex, the inspiratory rhythm generator. Our results showed that pulmonary fibrosis induced modifications not only of pulmonary architecture but also of central control of the respiratory neural network

    Multi-scale and cross-dimensional TMS mapping: A proof of principle in patients with Parkinson’s disease and deep brain stimulation

    Get PDF
    IntroductionTranscranial magnetic stimulation (TMS) mapping has become a critical tool for exploratory studies of the human corticomotor (M1) organization. Here, we propose to gather existing cutting-edge TMS-EMG and TMS-EEG approaches into a combined multi-dimensional TMS mapping that considers local and whole-brain excitability changes as well as state and time-specific changes in cortical activity. We applied this multi-dimensional TMS mapping approach to patients with Parkinson’s disease (PD) with Deep brain stimulation (DBS) of the sub-thalamic nucleus (STN) ON and OFF. Our goal was to identifying one or several TMS mapping-derived markers that could provide unprecedent new insights onto the mechanisms of DBS in movement disorders.MethodsSix PD patients (1 female, mean age: 62.5 yo [59–65]) implanted with DBS-STN for 1 year, underwent a robotized sulcus-shaped TMS motor mapping to measure changes in muscle-specific corticomotor representations and a movement initiation task to probe state-dependent modulations of corticospinal excitability in the ON (using clinically relevant DBS parameters) and OFF DBS states. Cortical excitability and evoked dynamics of three cortical areas involved in the neural control of voluntary movements (M1, pre-supplementary motor area – preSMA and inferior frontal gyrus – IFG) were then mapped using TMS-EEG coupling in the ON and OFF state. Lastly, we investigated the timing and nature of the STN-to-M1 inputs using a paired pulse DBS-TMS-EEG protocol.ResultsIn our sample of patients, DBS appeared to induce fast within-area somatotopic re-arrangements of motor finger representations in M1, as revealed by mediolateral shifts of corticomuscle representations. STN-DBS improved reaction times while up-regulating corticospinal excitability, especially during endogenous motor preparation. Evoked dynamics revealed marked increases in inhibitory circuits in the IFG and M1 with DBS ON. Finally, inhibitory conditioning effects of STN single pulses on corticomotor activity were found at timings relevant for the activation of inhibitory GABAergic receptors (4 and 20 ms).ConclusionTaken together, these results suggest a predominant role of some markers in explaining beneficial DBS effects, such as a context-dependent modulation of corticospinal excitability and the recruitment of distinct inhibitory circuits, involving long-range projections from higher level motor centers and local GABAergic neuronal populations. These combined measures might help to identify discriminative features of DBS mechanisms towards deep clinical phenotyping of DBS effects in Parkinson’s Disease and in other pathological conditions

    Analysis of the impact of synaptic plasticity genes and Human Accelerated Regions on brain function and structure: from the healthy brain to schizophrenia

    Full text link
    [eng] Schizophrenia is a severe psychiatric disorder affecting around 24 million people worldwide. While we begin to disentangle the biological actors implicated in the origin of the disorder, the precise aetiological mechanisms remain largely unknown. Therefore, psychiatry research efforts still need to focus on a better understanding of the complex biological foundations of the disorder to achieve more precise diagnoses and the development of novel therapeutic strategies improving the patients’ quality of life. The prevailing etiopathological hypothesis considers that schizophrenia originates from the interplay between subtle genetic and environmental insults that disrupt the perfectly orchestrated mechanisms guiding neurodevelopment. Additionally, from an evolutionary perspective, it is suggested that schizophrenia represents a costly trade-off in the evolution of human-specific ontogenic neurodevelopmental processes sustaining the inherent complexity and variability of brain functioning, cognition, and behaviour. Along the neurodevelopmental process, the synapse formation and the organisation and maturation of neural circuits anchor the emergence of distinctive human cortical brain functions. In turn, multidisciplinary evidence indicates that synaptic alterations participate in brain dysfunctions, eventually leading to the emergence of the symptoms and cognitive deficits of schizophrenia. Accordingly, it is suggested that synaptic plasticity impairments play a critical role in the pathophysiology of the disorder. Among genes converging in neurodevelopmental and synaptic plasticity pathways, there are genes mediating signalling pathways involved in neural homeostasis, dendritic spine development and neural excitability, such as KCNH2, DISC1, CACNA1C and ZNF804A, all of them previously associated with the risk for schizophrenia. Moreover, evolutionary approaches have identified regions that accumulated human-specific changes since the divergence from chimpanzees, like Human Accelerated Regions (HARs). These regions act as transcriptional regulatory elements that endow human neurodevelopment with unique characteristics and harbour schizophrenia genetic susceptibility variants. To facilitate the identification of the genetic and biological mechanisms involved in schizophrenia aetiology, the use of brain-based intermediate phenotypes is a valuable strategy. Following two approaches centred on the genetic-phenotypic correlates of synaptic plasticity candidate genes and HARs sequences in the brain-based alterations in schizophrenia, this thesis includes four original articles and one systematic review. In these articles, we report the effect of common polymorphisms in KCNH2, DISC1, CACNA1C and ZNF804A genes and the polygenic load of HARs-informative sets on the differences observed between healthy brains and brains with schizophrenia. Overall, the results validate the efficacy of neuroimaging phenotypes to identify the genetic determinants of schizophrenia and point out the complementarity of candidate genes and genome-wide approaches in the study of the genetic architecture of the disorder. First, we describe the role of KCNH2 and DISC1 genetic variability in modulating the attentional and working memory-related functional responses in a diagnosis- dependent manner. Furthermore, we identify that the epistasis between two schizophrenia GWAS-associated genes, CACNAC1C and ZNF804A, influence the functional ability to adapt to increased working memory difficulty euqally in healthy controls and patients with schizophrenia. Second, we present a review of how HARs underlie human neurodevelopmental signatures, brain configuration, functioning and susceptibility behind psychiatric disorders. Likewise, we report the modulatory effect of HARs polygenicity on brain cortical architectural differences in schizophrenia and provide evidence on the importance of foetal-active regulatory HARs in patients' cortical surface area variability. Globally, the findings exposed in this thesis point towards the fact that the aetiological foundations of schizophrenia are related to the individual genetic differences altering neurodevelopment and synaptic plasticity trajectories but also to the genomic make-up that defines us as a species. This thesis provides a drop in the ocean of knowledge on disorders inherently linked to the human condition and has sought to comprehend the unique characteristics of our brain to help unravel what it means to be human.[cat] L’esquizofrènia és un trastorn neuropsiquiàtric greu que afecta a 24 milions de persones a tot el món. Tot i que comencem a conèixer els mecanismes biològics implicats en l’origen del trastorn, els processos etiològics precisos continuen essent en gran part desconeguts. Per tant, els esforços en la recerca encara necessiten dirigir-se en millorar el coneixement dels fonaments biològics del trastorn, per tal d’aconseguir un diagnòstic més precís i el desenvolupament de noves estratègies terapèutiques que millorin la qualitat de vida dels pacients. La hipòtesi etiopatogènica predominant considera que el trastorn s’origina a partir de la interacció entre factors genètics i ambientals que pertorben els mecanismes perfectament orquestrats que guien el neurodesenvolupament. A més, des d’una perspectiva evolutiva, s’ha suggerit que l’esquizofrènia representaria el “preu a pagar” per evolució dels processos ontogènics específicament humans que sustenten la complexitat i la variabilitat inherent al funcionament del cervell, la cognició i el comportament de la nostra espècie. Al llarg del neurodevenvolupament, la formació de sinapsis i l’organització i maduració dels circuits neurals ancoren l’aparició de funcions cerebrals corticals distintivament humanes. Al seu torn, evidències multidisciplinàries indiquen que les alteracions sinàptiques participen en disfuncions cerebrals que tenen com a resultat l’aparició dels símptomes cognitius i clínics de l’esquizofrènia. En conseqüència, s’ha proposat que les alteracions de la plasticitat sinàptica tenen un paper crític en la fisiopatologia del trastorn. Entre els gens que conflueixen en vies del neurodesenvolupament i de plasticitat sinàptica, hi ha gens que participen en vies de senyalització implicades en l’homeòstasi neuronal, el desenvolupament de les espines dendrítiques i l’excitabilitat neuronal, com els gens KCNH2, el DISC1, el CACNA1C i el ZNF804A, tots prèviament associats amb el risc per a l’esquizofrènia. A més, aproximacions evolutives han identificat regions que han acumulat canvis específicament en humans des de la divergència amb els ximpanzés, com les Regions Humanes Accelerades (o Human Accelerated Regions, HARs en anglès). Aquestes regions actuen com a elements reguladors de la transcripció atorgant característiques úniques al neurodesenvolupament humà, i contenen variants genètiques de susceptibilitat per a l’esquizofrènia. Per tal de facilitar l’identificar els mecanismes genètics i biològics implicats en l’etiologia de l’esquizofrènia, la utilització de fenotips cerebrals intermedis, com mesures de neuroimatge funcional i estructural, representa una estratègia molt útil. Seguint dues aproximacions centrades en l’anàlisi dels correlats genètics-fenotípics entre gens candidats relacionats amb la plasticitat sinàptica i regions HARs i les alteracions cerebrals de l’esquizofrènia, aquesta tesi inclou quatre articles originals i una revisió sistemàtica. En aquests articles, exposem l’efecte de polimorfismes en els gens KCNH2, DISC1, CACNA1C i ZNF804A i la càrrega poligènica en conjunts informatius de HARs sobre les diferències observades entre cervells de persones sanes i persones amb esquizofrènia. En conjunt, els resultats validen l’efectivitat dels fenotips de neuroimatge per identificar els determinants genètics de l’esquizofrènia i posen de manifest la complementarietat de les aproximacions centrades tant en gens candidats com en la variabilitat global del genoma per a l’estudi de l’arquitectura genètica del trastorn. Primer, descrivim el paper de la variabilitat genètica dels genes KCNH2 i DISC1 en la modulació de la resposta funcional a l’atenció i la memòria de treball de manera condicionada al diagnòstic. També, identifiquem que l’epistasi entre dos gens associats amb l’esquizofrènia a nivell de GWAS, el CACNAC1C i el ZNF804A, influeix en la capacitat funcionalde cervell per adaptar-se a l’increment de requeriments cognitius en memòria de treball en controls sans i pacients amb esquizofrènia. En segon lloc, oferim una revisió sobre com les HARs sustenten les característiques del neurodesenvolupament humà, la configuració cerebral, el funcionament i la susceptibilitat per als trastorns psiquiàtrics Així mateix, informem de l'efecte modulador de la poligenicitat de les HARs sobre les diferències en l’arquitectura cortical en l'esquizofrènia i proporcionem evidències sobre l’especial rellevància de les HARs associades amb elements reguladors de la transcripció actius durant l’etapa fetal. De manera global, els resultats d’aquesta tesi indiquen que els fonaments etiològics de l’esquizofrènia estan relacionats amb diferències genètiques individuals que impacten en les trajectòries del neurodesenvolupament i les vies de plasticitat sinàptica, així com amb la composició genòmica que ens defineix com a espècie. Aquesta tesi aporta una gota en l’oceà del coneixement sobre els trastorns intrínsecament vinculats a la condició humana i ha pretès contribuir en la comprensió de les característiques úniques del nostre cervell per ajudar a entendre què vol dir ser humà.[spa] La esquizofrenia es un trastorno psiquiátrico que afecta a 24 millones de personas en todo el mundo. A pesar de que empezamos a conocer los mecanismos biológicos implicados en el origen del trastorno, los procesos etiológicos precisos continúan siendo en gran parte desconocidos. Por ello, los esfuerzos investigadores todavía necesitan dirigirse en mejorar el conocimiento de los fundamentos biológicos del trastorno, para así conseguir una mayor precisión en el diagnóstico y desarrollar nuevas estrategias terapéuticas que mejoren la calidad de vida de los pacientes. La hipótesis etiopatogénica predominante considera que el trastorno se origina de la interacción entre factores genéticos y ambientales que modifican los mecanismos perfectamente orquestados que guían el neurodesarrollo. Además, desde una perspectiva evolutiva, se sostiene que la esquizofrenia representa “el precio a pagar” por la evolución de los procesos ontogénicos específicamente humanos que sustentan la complejidad y la variabilidad inherente al funcionamiento del cerebro, así como la cognición y comportamiento de nuestra especie. A lo largo del neurodesarrollo, la formación de sinapsis y la organización y maduración de los circuitos neurales anclan la aparición de funciones cerebrales corticales distintivamente humanas. Por su parte, evidencias multidisciplinares indican que las alteraciones sinápticas participan en disfunciones cerebrales asociadas a la aparición de los síntomas cognitivos y clínicos de la esquizofrenia. En consecuencia, se ha propuesto que las alteraciones de la plasticidad sináptica tienen un papel crítico en la fisiopatología del trastorno. Entre los genes que confluyen en vías del neurodesarrollo y de plasticidad sináptica, hay genes que participan en vías de señalización implicadas en la homeostasis neuronal, el desarrollo de las espinas dendríticas y la excitabilidad neural, como el KCNH2, el DISC1, el CACNA1C y el ZNF804A, todos ellos previamente asociados con el riesgo para la esquizofrenia. Además, aproximaciones evolutivas han identificado regiones que han acumulado cambios específicamente humanos desde la divergencia con los chimpancés, como las Regiones Humanas Aceleradas (o Human Accelerated Regions, HARs en inglés). Estas regiones actúan como elementos reguladores de la transcripción otorgando características únicas al neurodesarrollo humano, y albergan variantes genéticas de susceptibilidad para la esquizofrenia. Para facilitar la identificación de los mecanismo genéticos y biológicos implicados en la etiología del trastorno, el uso de fenotipos cerebrales intermedios, como medidas de neuroimagen funcional y estructural, es una herramienta de gran valor. Siguiendo dos aproximaciones centradas en el análisis de los correlatos genético- fenotípicos entre genes candidatos relacionados con la plasticidad sináptica y secuencias HARs y las alteraciones cerebrales en la esquizofrenia, esta tesis incluye cuatro artículos originales y una revisión sistemática. En estos artículos, exponemos el efecto de polimorfismos en los genes KCNH2, DISC1, CACNA1C y ZNF804A y la carga poligénica en conjuntos informativos de HARs sobre las diferencias observadas entre cerebros sanos y cerebros con esquizofrenia. En su conjunto, los resultados validan la efectividad de los fenotipos de neuroimagen para identificar los mecanismos genéticos de la esquizofrenia y ponen de manifiesto la complementariedad de las aproximaciones centradas tanto en genes candidatos como en la variabilidad global del genoma para estudiar la arquitectura genética del trastorno. Primero describimos el papel de la variabilidad genética de los genes KCNH2 y DISC1 en la modulación de la respuesta funcional a la atención y la memoria de trabajo de manera condicional al diagnóstico. Además, identificamos que la epistasis entre dos genes asociados con la esquizofrenia a nivel de GWAS, el CACNAC1C y el ZNF804A, influye en la capacidad funcional de cerebro para adaptarse al incremento de requerimientos cognitivos en memoria de trabajo tanto en controles sanos como en pacientes con esquizofrenia. En segundo lugar, ofrecemos una revisión sobre cómo las HARs sustentan las características del neurodesarrollo humano, la configuración y el funcionamiento cerebral y la susceptibilidad para trastornos psiquiátricos. Así mismo, informamos del efecto modulador de la poligenicidad de las HARs sobre las diferencias en la arquitectura cortical en la esquizofrenia y proporcionamos evidencias sobre la especial relevancia de las HARs asociadas con elementos reguladores de la transcripción activos durante la etapa fetal. De manera global, los resultados de esta tesis indican que los fundamentos etiológicos de la esquizofrenia están relacionados con diferencias genéticas individuales que impactan en las trayectorias del neurodesarrollo y en las vías de plasticidad sináptica, así como en la composición genética que nos define como especie. Esta tesis aporta una gota en el océano del conocimiento sobre los trastornos intrínsicamente vinculados a la condición humana y ha pretendido contribuir en la comprensión de las características únicas de nuestro cerebro para ayudar a entender qué quiere decir ser humano

    On the Utility of Representation Learning Algorithms for Myoelectric Interfacing

    Get PDF
    Electrical activity produced by muscles during voluntary movement is a reflection of the firing patterns of relevant motor neurons and, by extension, the latent motor intent driving the movement. Once transduced via electromyography (EMG) and converted into digital form, this activity can be processed to provide an estimate of the original motor intent and is as such a feasible basis for non-invasive efferent neural interfacing. EMG-based motor intent decoding has so far received the most attention in the field of upper-limb prosthetics, where alternative means of interfacing are scarce and the utility of better control apparent. Whereas myoelectric prostheses have been available since the 1960s, available EMG control interfaces still lag behind the mechanical capabilities of the artificial limbs they are intended to steer—a gap at least partially due to limitations in current methods for translating EMG into appropriate motion commands. As the relationship between EMG signals and concurrent effector kinematics is highly non-linear and apparently stochastic, finding ways to accurately extract and combine relevant information from across electrode sites is still an active area of inquiry.This dissertation comprises an introduction and eight papers that explore issues afflicting the status quo of myoelectric decoding and possible solutions, all related through their use of learning algorithms and deep Artificial Neural Network (ANN) models. Paper I presents a Convolutional Neural Network (CNN) for multi-label movement decoding of high-density surface EMG (HD-sEMG) signals. Inspired by the successful use of CNNs in Paper I and the work of others, Paper II presents a method for automatic design of CNN architectures for use in myocontrol. Paper III introduces an ANN architecture with an appertaining training framework from which simultaneous and proportional control emerges. Paper Iv introduce a dataset of HD-sEMG signals for use with learning algorithms. Paper v applies a Recurrent Neural Network (RNN) model to decode finger forces from intramuscular EMG. Paper vI introduces a Transformer model for myoelectric interfacing that do not need additional training data to function with previously unseen users. Paper vII compares the performance of a Long Short-Term Memory (LSTM) network to that of classical pattern recognition algorithms. Lastly, paper vIII describes a framework for synthesizing EMG from multi-articulate gestures intended to reduce training burden

    Neuromotor and electrocortical activity characteristics of dynamic postural control

    Get PDF
    Subconcussive impacts to the head have become a growing area of research and concern in the athletic setting. While knowledge on the short- and long-term consequences of concussions has been identified, there is relatively less research on the effects of repetitive subconcussive impacts. Research has shown that neuromotor deficits (i.e., dynamic balance) can be detected acutely after repeatedly heading a soccer ball (a laboratory-based way to induce subconcussive head impacts), but this has typically been done with expensive and non-portable laboratory equipment. However, the AccWalker smartphone application may allow for an objective cost-effective test to examine the effective of repetitive subconcussive exposure. Nonetheless, while cost-effective and portable (e.g., a smartphone app), there is a need for examination of its reliability. Moreover, the extent to which cortical activity is related to dynamic balance control is not well understood. If an association between cortical activity is observed, an increase or decrease in the strength of the association after repeated subconcussive head impacts could be used as an indicator of nervous system impact. These gaps in the literature will be addressed through three specific aims in this dissertation 1) to investigate the reliability of the AccWalker app as a test for neuromotor performance before and after light athletic activity (e.g., kicking a soccer ball); 2) compare EEG spectral power characteristics of dynamic balance across three different AccWalker conditions, and 3) to examine correlations between EEG spectral power characteristics and temporal and spatial kinematic data during a stepping in place task (mTBI Assessment of Readiness Gait Evaluation Test (TARGET)). It was hypothesized that, 1) temporal and spatial characteristics of dynamic balance will not significantly change between pre- and post-soccer kicking activity, 2) EEG power spectral density (PSD) within the delta and theta frequency bands will increase across the three AccWalker conditions, and 3) EEG PSD within the delta and theta frequency bands will correlate with the temporal and spatial kinematic variables measured using the AccWalker TARGET protocol. Twenty-four participants were enrolled in this study. Aim 1 used a pre-test/post-test design. Both pre- and post-testing included using the TARGET protocol before and after kicking ten soccer balls. The findings for aim 1 indicated that that the AccWalker TARGET protocol displayed good test-retest reliability with similar data characteristics to previous work. Aim 2 results revealed that EEG PSD measures increased compared to the resting condition. Finally, for aim 3, several significant correlations between the AccWalker spatial metrics within the Delta and Theta frequencies were found. These findings suggest that postural control assessment can be measured reliably in a pre- to post-test design. This may be important as the AccWalker TARGET protocol may offer a reliable test for changes in neuromotor performance and the body’s ability to adapt to “real-life” (or more dynamic) situations. Additionally, this study has expanded on previous literature indicating increased involvement of the frontal-central and central regions of the brain during perturbed balance. Further, this study expands upon the simultaneous use of EEG and balance assessment; specifically, as it is the first study to use a truly dynamic balance task along with a 32-electrode mobile EEG system. This may be important for continued study of not only unaffected balance, but that study of neural changes due to injury or pathological processes

    Modular architecture facilitates noise-driven control of synchrony in neuronal networks

    Get PDF
    H.Y., A.H.-I., and S.S. acknowledge MEXT Grant-in-Aid for Transformative Research Areas (B) “Multicellular Neurobiocomputing” (21H05164), JSPS KAKENHI (18H03325, 19H00846, 20H02194, 20K20550, 22H03657, 22K19821, 22KK0177, and 23H03489), JST-PRESTO (JMPJPR18MB), JST-CREST (JPMJCR19K3), and Tohoku University RIEC Cooperative Research Project Program for financial support. F.P.S., V.P., and J.Z. received support from the Max-Planck-Society. F.P.S. acknowledges funding by SMARTSTART, the joint training program in computational neuroscience by the VolkswagenStiftung and the Bernstein Network. F.P.S. and V.P. were funded by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG), SFB-1528–Cognition of Interaction. V.P. was supported by the DFG under Germany’s Excellence Strategy EXC 2067/1- 390729940. V.B. and A.L. were supported by a Sofja Kovalevskaja Award from the Alexander von Humboldt Foundation, endowed by the Federal Ministry of Education and Research. A.L. is a member of the Machine Learning Cluster of Excellence EXC 2064/1- 39072764. M.A.M. acknowledges the Spanish Ministry and Agencia Estatal de investigación (AEI) through Project of I + D + i (PID2020-113681GB-I00), financed by MICIN/AEI/10.13039/501100011033 and FEDER “A way to make Europe”, and the Consejería de Conocimiento, Investigación Universidad, Junta de Andalucía and European Regional Development Fund (P20-00173) for financial support. J.Z. received financial support from the Joachim Herz Stiftung. J.S. acknowledges Horizon 2020 Future and Emerging Technologies (grant agreement 964877-NEUChiP), Ministerio de Ciencia, Innovación y Universidades (PID2019-108842GB-C21), and Departament de Recerca i Universitats, Generalitat de Catalunya (2017-SGR-1061 and 2021-SGR-00450) for financial support.Supplementary Materials This PDF file includes: Supplementary Text, file:///D:/Modular-architecture-facilitates-.pdfHigh-level information processing in the mammalian cortex requires both segregated processing in specialized circuits and integration across multiple circuits. One possible way to implement these seemingly opposing demands is by flexibly switching between states with different levels of synchrony. However, the mechanisms behind the control of complex synchronization patterns in neuronal networks remain elusive. Here, we use precision neuroengineering to manipulate and stimulate networks of cortical neurons in vitro, in combination with an in silico model of spiking neurons and a mesoscopic model of stochastically coupled modules to show that (i) a modular architecture enhances the sensitivity of the network to noise delivered as external asynchronous stimulation and that (ii) the persistent depletion of synaptic resources in stimulated neurons is the underlying mechanism for this effect. Together, our results demonstrate that the inherent dynamical state in structured networks of excitable units is determined by both its modular architecture and the properties of the external inputs.D+i: P20-00173, PID2020-113681GB-I00Innovación y Universidades PID2019-108842GB-C21Horizon2020 Future and Emerging Technologies 964877-NEUChiPMinisterio de Ciencia, Innovación y Universidades (PID2019-108842GB-C21)Departament de Recerca i Universitats, Generalitat de Catalunya (2017-SGR-1061, 2021-SGR-00450)MICIN/AEI/10.13039/501100011033FEDER “A way to make Europe”Junta de AndalucíaEuropean Regional Development Fun

    Study of soft materials, flexible electronics, and machine learning for fully portable and wireless brain-machine interfaces

    Get PDF
    Over 300,000 individuals in the United States are afflicted with some form of limited motor function from brainstem or spinal-cord related injury resulting in quadriplegia or some form of locked-in syndrome. Conventional brain-machine interfaces used to allow for communication or movement require heavy, rigid components, uncomfortable headgear, excessive numbers of electrodes, and bulky electronics with long wires that result in greater data artifacts and generally inadequate performance. Wireless, wearable electroencephalograms, along with dry non-invasive electrodes can be utilized to allow recording of brain activity on a mobile subject to allow for unrestricted movement. Additionally, multilayer microfabricated flexible circuits, when combined with a soft materials platform allows for imperceptible wearable data acquisition electronics for long term recording. This dissertation aims to introduce new electronics and training paradigms for brain-machine interfaces to provide remedies in the form of communication and movement for these individuals. Here, training is optimized by generating a virtual environment from which a subject can achieve immersion using a VR headset in order to train and familiarize with the system. Advances in hardware and implementation of convolutional neural networks allow for rapid classification and low-latency target control. Integration of materials, mechanics, circuit and electrode design results in an optimized brain-machine interface allowing for rehabilitation and overall improved quality of life.Ph.D
    corecore