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1.
Brain Stimul ; 15(1): 244-253, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34990876

RESUMO

BACKGROUND: Visual phenomena like brightness illusions impressively demonstrate the highly constructive nature of perception. In addition to physical illumination, the subjective experience of brightness is related to temporal neural dynamics in visual cortex. OBJECTIVE: Here, we asked whether biasing the temporal pattern of neural excitability in visual cortex by transcranial alternating current stimulation (tACS) modulates brightness perception of concurrent rhythmic visual stimuli. METHODS: Participants performed a brightness discrimination task of two flickering lights, one of which was targeted by same-frequency electrical stimulation at varying phase shifts. tACS was applied with an occipital and a periorbital active control montage, based on simulations of electrical currents using finite element head models. RESULTS: Experimental results reveal that flicker brightness perception is modulated dependent on the phase shift between sensory and electrical stimulation, solely under occipital tACS. Phase-specific modulatory effects by tACS were dependent on flicker-evoked neural phase stability at the tACS-targeted frequency, recorded prior to electrical stimulation. Further, the optimal timing of tACS application leading to enhanced brightness perception was correlated with the neural phase delay of the cortical flicker response. CONCLUSIONS: Our results corroborate the role of temporally coordinated neural activity in visual cortex for brightness perception of rhythmic visual input in humans. Phase-specific behavioral modulations by tACS emphasize its efficacy to transfer perceptually relevant temporal information to the cortex. These findings provide an important step towards understanding the basis of visual perception and further confirm electrical stimulation as a tool for advancing controlled modulations of neural activity and related behavior.


Assuntos
Estimulação Transcraniana por Corrente Contínua , Córtex Visual , Viés , Humanos , Estimulação Luminosa , Estimulação Transcraniana por Corrente Contínua/métodos , Percepção Visual/fisiologia
2.
Neuroimage ; 237: 118179, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34015486

RESUMO

Transcranial alternating current stimulation (tACS), applied to two brain sites with different phase lags, has been shown to modulate stimulation-outlasting functional EEG connectivity between the targeted regions. Given the lack of knowledge on mechanisms of tACS aftereffects, it is difficult to further enhance effect sizes and reduce variability in experiments. In this computational study, we tested if spike-timing-dependent plasticity (STDP) can explain stimulation-outlasting connectivity modulation by dual-site tACS and explored the effects of tACS parameter choices. Two populations of spiking neurons were coupled with synapses subject to STDP, and results were validated via a re-analysis of EEG data. Our simulations showed stimulation-outlasting connectivity changes between in- and anti-phase tACS, dependent on both tACS frequency and synaptic conduction delays. Importantly, both a simple network entraining to a wide range of tACS frequencies as well as a more realistic network that spontaneously oscillated at alpha frequency predicted that the largest effects would occur for short conduction delays between the stimulated regions. This finding agreed with experimental EEG connectivity modulation by 10Hz tACS, showing a clear negative correlation of tACS effects with estimated conduction delays between regions. In conclusion, STDP can explain connectivity aftereffects of dual-site tACS. However, not all combinations of tACS frequency and application sites are expected to effectively modulate connectivity via STDP. We therefore suggest using appropriate computational models and/or EEG analysis for planning and interpretation of dual-site tACS studies relying on aftereffects.


Assuntos
Potenciais de Ação/fisiologia , Córtex Cerebral/fisiologia , Conectoma , Eletroencefalografia , Rede Nervosa/fisiologia , Plasticidade Neuronal/fisiologia , Estimulação Transcraniana por Corrente Contínua , Córtex Cerebral/diagnóstico por imagem , Simulação por Computador , Humanos , Rede Nervosa/diagnóstico por imagem
3.
PLoS Biol ; 18(10): e3000829, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33048920

RESUMO

Task-related activity in the ventral thalamus, a major target of basal ganglia output, is often assumed to be permitted or triggered by changes in basal ganglia activity through gating- or rebound-like mechanisms. To test those hypotheses, we sampled single-unit activity from connected basal ganglia output and thalamic nuclei (globus pallidus-internus [GPi] and ventrolateral anterior nucleus [VLa]) in monkeys performing a reaching task. Rate increases were the most common peri-movement change in both nuclei. Moreover, peri-movement changes generally began earlier in VLa than in GPi. Simultaneously recorded GPi-VLa pairs rarely showed short-time-scale spike-to-spike correlations or slow across-trials covariations, and both were equally positive and negative. Finally, spontaneous GPi bursts and pauses were both followed by small, slow reductions in VLa rate. These results appear incompatible with standard gating and rebound models. Still, gating or rebound may be possible in other physiological situations: simulations show how GPi-VLa communication can scale with GPi synchrony and GPi-to-VLa convergence, illuminating how synchrony of basal ganglia output during motor learning or in pathological conditions may render this pathway effective. Thus, in the healthy state, basal ganglia-thalamic communication during learned movement is more subtle than expected, with changes in firing rates possibly being dominated by a common external source.


Assuntos
Potenciais de Ação/fisiologia , Gânglios da Base/fisiologia , Análise e Desempenho de Tarefas , Tálamo/fisiologia , Animais , Mapeamento Encefálico , Simulação por Computador , Bases de Dados como Assunto , Feminino , Globo Pálido/fisiologia , Macaca , Microeletrodos , Movimento , Neurônios/fisiologia , Tempo de Reação/fisiologia , Descanso/fisiologia , Núcleos Ventrais do Tálamo/fisiologia
4.
Brain Stimul ; 13(5): 1254-1262, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32534253

RESUMO

BACKGROUND: Oscillatory phase has been proposed as a key parameter defining the spatiotemporal structure of neural activity. To enhance our understanding of brain rhythms and improve clinical outcomes in pathological conditions, modulation of neural activity by transcranial alternating current stimulation (tACS) emerged as a promising approach. However, the phase-specificity of tACS effects in humans is still critically debated. OBJECTIVE: Here, we investigated the phase-specificity of tACS on visually evoked steady state responses (SSRs) in 24 healthy human participants. METHODS: We used an intermittent electrical stimulation protocol and assessed the influence of tACS on SSR amplitude in the interval immediately following tACS. A neural network model served to validate the plausibility of experimental findings. RESULTS: We observed a modulation of SSR amplitudes dependent on the phase shift between flicker and tACS. The tACS effect size was negatively correlated with the strength of flicker-evoked activity. Supported by simulations, data suggest that strong network synchronization limits further neuromodulation by tACS. Neural sources of phase-specific effects were localized in the parieto-occipital cortex within flicker-entrained regions. Importantly, the optimal phase shift between flicker and tACS associated with strongest SSRs was correlated with SSR phase delays in the tACS target region. CONCLUSIONS: Overall, our data provide electrophysiological evidence for phase-specific modulations of rhythmic brain activity by tACS in humans. As the optimal timing of tACS application was dependent on cortical SSR phase delays, our data suggest that tACS effects were not mediated by retinal co-stimulation. These findings highlight the potential of tACS for controlled, phase-specific modulations of neural activity.


Assuntos
Ondas Encefálicas/fisiologia , Encéfalo/fisiologia , Potenciais Evocados Visuais/fisiologia , Estimulação Transcraniana por Corrente Contínua/métodos , Adulto , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Adulto Jovem
5.
eNeuro ; 6(5)2019.
Artigo em Inglês | MEDLINE | ID: mdl-31601635

RESUMO

Rhythmic neuronal activity in the gamma range is a signature of cortical processing and its synchronization across distant sites has been proposed as a fundamental mechanism of network interactions. While this has been shown within sensory streams, we tested whether cross talk between the senses relies on similar mechanisms. Direct sensory interactions in humans (male and female) were studied with a visual-tactile amplitude matching paradigm. In this task, congruent stimuli are associated with behavioral benefits, which are proposed to be mediated by increased binding between sensory cortices through coherent gamma oscillations. We tested this hypothesis by applying 4-in-1 multi-electrode transcranial alternating current stimulation (tACS) with 40 Hz over visual and somatosensory cortices. In phase stimulation (0°) was expected to strengthen binding and thereby enhance the congruence effect, while anti-phase (180°) stimulation was expected to have opposite effects. Gamma tACS was controlled by alpha (10 Hz) and sham stimulation, as well as by applying tACS unilaterally while visual-tactile stimuli were presented lateralized. Contrary to our expectations, gamma tACS over the relevant hemisphere delayed responses to congruent trials. Additionally, reanalysis of EEG data revealed decoupling of sensory gamma oscillations during congruent trials. We propose that gamma tACS prevented sensory decoupling and thereby limited the congruence effect. Together, our results favor the perspective that processing multisensory congruence involves corticocortical communication rather than feature binding. Furthermore, we found control stimulation over the irrelevant hemisphere to speed responses under alpha stimulation and to delay responses under gamma stimulation, consistent with the idea that contralateral alpha/gamma dynamics regulate cortical excitability.


Assuntos
Sincronização Cortical/fisiologia , Ritmo Gama/fisiologia , Córtex Sensório-Motor/fisiologia , Adulto , Feminino , Humanos , Masculino , Estimulação Transcraniana por Corrente Contínua , Adulto Jovem
6.
Brain Stimul ; 12(5): 1187-1196, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31101568

RESUMO

BACKGROUND: Long-range functional connectivity in the brain is considered fundamental for cognition and is known to be altered in many neuropsychiatric disorders. To modify such coupling independent of sensory input, noninvasive brain stimulation could be of utmost value. OBJECTIVE: First, we tested if transcranial alternating current stimulation (tACS) is able to influence functional connectivity in the human brain. Second, we investigated the specificity of effects in frequency and space. METHODS: Participants were stimulated bifocally with high-definition tACS in counterbalanced order (1) in-phase, with identical electric fields in both hemispheres, (2) anti-phase, with phase-reversed electric fields in the two hemispheres, and (3) jittered-phase, generated by subtle frequency shifts continuously changing the phase relation between the two fields. EEG aftereffects were analyzed systematically in sensor and source space. RESULTS: While total power and spatial distribution of the fields were comparable between conditions, global pre-post stimulation changes in EEG connectivity were larger after in-phase stimulation than after anti-phase or jittered-phase stimulation. Those differences in connectivity were restricted to the stimulated frequency band and decayed within the first 120 s after stimulation offset. Source reconstruction localized the maximum effect between the stimulated occipito-parietal areas. CONCLUSION: The relative phase of bifocal alpha-tACS modulated alpha-band connectivity between the targeted regions. As side effects are not expected to differ between the stimulation conditions, we conclude that neural activity was phase-specifically influenced by the electric fields. We thus suggest bifocal high-definition tACS as a tool to manipulate long-range cortico-cortical coupling which outlasts the stimulation period.


Assuntos
Córtex Cerebral/fisiologia , Eletroencefalografia/métodos , Estimulação Transcraniana por Corrente Contínua/métodos , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
7.
Eur J Neurosci ; 45(8): 1000-1012, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27350120

RESUMO

Neural synchrony in the basal ganglia, especially in the beta frequency band (13-30 Hz), is a hallmark of Parkinson's disease and considered as antikinetic. In contrast, the healthy basal ganglia show low levels of synchrony. It is currently unknown where synchrony and oscillations arise in the parkinsonian brain and how they are transmitted through the basal ganglia, as well as what makes them dependent on dopamine. The external part of the globus pallidus has recently been identified as a hub nucleus in the basal ganglia, possessing intrinsic inhibitory connections and possibly also gap junctions. In this study, we show that in a conductance-based network model of the basal ganglia, the combination of sparse, high-conductance inhibitory synapses and sparse, low-conductance gap junctions in the external part of the globus pallidus could effectively desynchronize the whole network. However, when gap junction coupling became strong enough, the effect was impeded and activity synchronized. In particular, sustained periods of beta coherence occurred between some neuron pairs. As gap junctions can change their conductance with the dopamine level, we suggest pallidal gap junction coupling as a mechanism contributing to the development of beta synchrony in the parkinsonian basal ganglia.


Assuntos
Gânglios da Base/fisiologia , Sincronização Cortical/fisiologia , Modelos Neurológicos , Neurônios/fisiologia , Algoritmos , Animais , Ritmo beta/fisiologia , Simulação por Computador , Dopamina/metabolismo , Junções Comunicantes/metabolismo , Humanos , Inibição Neural/fisiologia , Vias Neurais/fisiologia , Ratos , Software
8.
J Neural Eng ; 12(2): 026005, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25650741

RESUMO

OBJECTIVE: Continuous application of high-frequency deep brain stimulation (DBS) often effectively reduces motor symptoms of Parkinson's disease patients. While there is a growing need for more effective and less traumatic stimulation, the exact mechanism of DBS is still unknown. Here, we present a methodology to exploit the plasticity of GABAergic synapses inside the external globus pallidus (GPe) for the optimization of DBS. APPROACH: Assuming the existence of spike-timing-dependent plasticity (STDP) at GABAergic GPe-GPe synapses, we simulate neural activity in a network model of the subthalamic nucleus and GPe. In particular, we test different DBS protocols in our model and quantify their influence on neural synchrony. MAIN RESULTS: In an exemplary set of biologically plausible model parameters, we show that STDP in the GPe has a direct influence on neural activity and especially the stability of firing patterns. STDP stabilizes both uncorrelated firing in the healthy state and correlated firing in the parkinsonian state. Alternative stimulation protocols such as coordinated reset stimulation can clearly profit from the stabilizing effect of STDP. These results are widely independent of the STDP learning rule. SIGNIFICANCE: Once the model settings, e.g., connection architectures, have been described experimentally, our model can be adjusted and directly applied in the development of novel stimulation protocols. More efficient stimulation leads to both minimization of side effects and savings in battery power.


Assuntos
Estimulação Encefálica Profunda/métodos , Globo Pálido/fisiopatologia , Modelos Neurológicos , Plasticidade Neuronal , Doença de Parkinson/fisiopatologia , Doença de Parkinson/terapia , Simulação por Computador , Humanos , Rede Nervosa/fisiopatologia , Terapia Assistida por Computador/métodos
9.
Mov Disord ; 29(12): 1486-94, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25124148

RESUMO

Although increased synchrony of the neural activity in the basal ganglia may underlie the motor deficiencies exhibited in Parkinson's disease (PD), how this synchrony arises, propagates through the basal ganglia, and changes under dopamine replacement remains unknown. Gap junctions could play a major role in modifying this synchrony, because they show functional plasticity under the influence of dopamine and after neural injury. In this study, confocal imaging was used to detect connexin-36, the major neural gap junction protein, in postmortem tissues of PD patients and control subjects in the putamen, subthalamic nucleus (STN), and external and internal globus pallidus (GPe and GPi, respectively). Moreover, we quantified how gap junctions affect synchrony in an existing computational model of the basal ganglia. We detected connexin-36 in the human putamen, GPe, and GPi, but not in the STN. Furthermore, we found that the number of connexin-36 spots in PD tissues increased by 50% in the putamen, 43% in the GPe, and 109% in the GPi compared with controls. In the computational model, gap junctions in the GPe and GPi strongly influenced synchrony. The basal ganglia became especially susceptible to synchronize with input from the cortex when gap junctions were numerous and high in conductance. In conclusion, connexin-36 expression in the human GPe and GPi suggests that gap junctional coupling exists within these nuclei. In PD, neural injury and dopamine depletion could increase this coupling. Therefore, we propose that gap junctions act as a powerful modulator of synchrony in the basal ganglia.


Assuntos
Junções Comunicantes/fisiologia , Globo Pálido/patologia , Doença de Parkinson/patologia , Idoso , Idoso de 80 Anos ou mais , Gânglios da Base/metabolismo , Gânglios da Base/patologia , Simulação por Computador , Conexinas/metabolismo , Feminino , Globo Pálido/metabolismo , Glutamato Descarboxilase/metabolismo , Humanos , Masculino , Microscopia Confocal , Modelos Neurológicos , Proteína delta-2 de Junções Comunicantes
10.
Front Syst Neurosci ; 7: 60, 2013 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-24109437

RESUMO

The mechanisms for the emergence and transmission of synchronized oscillations in Parkinson's disease, which are potentially causal to motor deficits, remain debated. Aside from the motor cortex and the subthalamic nucleus, the external globus pallidus (GPe) has been shown to be essential for the maintenance of these oscillations and plays a major role in sculpting neural network activity in the basal ganglia (BG). While neural activity of the healthy GPe shows almost no correlations between pairs of neurons, prominent synchronization in the ß frequency band arises after dopamine depletion. Several studies have proposed that this shift is due to network interactions between the different BG nuclei, including the GPe. However, recent studies demonstrate an important role for the properties of neurons within the GPe. In this review, we will discuss these intrinsic GPe properties and review proposed mechanisms for activity decorrelation within the dopamine-intact GPe. Failure of the GPe to desynchronize correlated inputs can be a possible explanation for synchronization in the whole BG. Potential triggers of synchronization involve the enhancement of GPe-GPe inhibition and changes in ion channel function in GPe neurons.

11.
IEEE Trans Med Imaging ; 32(5): 862-72, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23340590

RESUMO

Electrophysiological modeling of cardiac tissue is commonly based on functional and structural properties measured in experiments. Our knowledge of these properties is incomplete, in particular their remodeling in disease. Here, we introduce a methodology for quantitative tissue characterization based on fluorescent labeling, 3-D scanning confocal microscopy, image processing and reconstruction of tissue micro-structure at sub-micrometer resolution. We applied this methodology to normal rabbit ventricular tissue and tissue from hearts with myocardial infarction. Our analysis revealed that the volume fraction of fibroblasts increased from 4.83±0.42% (mean ± standard deviation) in normal tissue up to 6.51±0.38% in myocardium from infarcted hearts. The myocyte volume fraction decreased from 76.20±9.89% in normal to 73.48±8.02% adjacent to the infarct. Numerical field calculations on 3-D reconstructions of the extracellular space yielded an extracellular longitudinal conductivity of 0.264±0.082 S/m with an anisotropy ratio of 2.095±1.11 in normal tissue. Adjacent to the infarct, the longitudinal conductivity increased up to 0.400±0.051 S/m, but the anisotropy ratio decreased to 1.295±0.09. Our study indicates an increased density of gap junctions proximal to both fibroblasts and myocytes in infarcted versus normal tissue, supporting previous hypotheses of electrical coupling of fibroblasts and myocytes in infarcted hearts. We suggest that the presented methodology provides an important contribution to modeling normal and diseased tissue. Applications of the methodology include the clinical characterization of disease-associated remodeling.


Assuntos
Coração/fisiologia , Imageamento Tridimensional/métodos , Microscopia Confocal/métodos , Modelos Cardiovasculares , Miocárdio/química , Miocárdio/citologia , Animais , Conexinas/química , Condutividade Elétrica , Fenômenos Eletrofisiológicos , Fibroblastos/citologia , Corantes Fluorescentes/química , Junções Comunicantes/química , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miócitos Cardíacos/citologia , Coelhos
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