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1.
J Neurosci ; 44(11)2024 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-38242698

RESUMO

Luminance-independent changes in pupil diameter (PD) during wakefulness influence and are influenced by neuromodulatory, neuronal, and behavioral responses. However, it is unclear whether changes in neuromodulatory activity in a specific brain area are necessary for the associated changes in PD or whether some different mechanisms cause parallel fluctuations in both PD and neuromodulation. To answer this question, we simultaneously recorded PD and cortical neuronal activity in male and female mice. Namely, we measured PD and neuronal activity during adaptation to sound contrast, which is a well-described adaptation conserved in many species and brain areas. In the primary auditory cortex (A1), increases in the variability of sound level (contrast) induce a decrease in the slope of the neuronal input-output relationship, neuronal gain, which depends on cortical neuromodulatory zinc signaling. We found a previously unknown modulation of PD by changes in background sensory context: high stimulus contrast sounds evoke larger increases in evoked PD compared with low-contrast sounds. To explore whether these changes in evoked PD are controlled by cortical neuromodulatory zinc signaling, we imaged single-cell neural activity in A1, manipulated zinc signaling in the cortex, and assessed PD in the same awake mouse. We found that cortical synaptic zinc signaling is necessary for increases in PD during high-contrast background sounds compared with low-contrast sounds. This finding advances our knowledge about how cortical neuromodulatory activity affects PD changes and thus advances our understanding of the brain states, circuits, and neuromodulatory mechanisms that can be inferred from pupil size fluctuations.


Assuntos
Córtex Auditivo , Camundongos , Masculino , Feminino , Animais , Estimulação Acústica , Córtex Auditivo/fisiologia , Pupila , Zinco , Som , Percepção Auditiva/fisiologia
2.
Int J Neuropsychopharmacol ; 27(6)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38742426

RESUMO

BACKGROUND: The principle of gain control determines the efficiency of neuronal processing and can be enhanced with pharmacological or brain stimulation methods. It is a key factor for cognitive control, but the degree of how much gain control may be enhanced underlies a physical limit. METHODS: To investigate whether methylphenidate (MPH) and transcranial direct current stimulation (tDCS) share common underlying mechanisms and cognitive effects, we administered MPH and anodal tDCS (atDCS) over the right inferior frontal gyrus both separately and combined, while healthy adult participants (n = 104) performed a response selection and inhibition task. The recorded EEG data were analyzed with a focus on theta band activity, and source estimation analyses were conducted. RESULTS: The behavioral data show that MPH and atDCS revealed interactive effects on the ability to inhibit responses. Both MPH and atDCS modulated task-related theta oscillations in the supplementary motor area when applied separately, making a common underlying mechanism likely. When both stimulation methods were combined, there was no doubling of effects in the supplementary motor area but a shift to inferior frontal areas in the cortical network responsible for theta-driven processing. CONCLUSIONS: The results indicate that both MPH and atDCS likely share a common underlying neuronal mechanism, and interestingly, they demonstrate interactive effects when combined, which are most likely due to the physical limitations of gain control increases. The current study provides critical groundwork for future combined applications of MPH and non-invasive brain stimulation.


Assuntos
Inibição Psicológica , Metilfenidato , Ritmo Teta , Estimulação Transcraniana por Corrente Contínua , Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Metilfenidato/farmacologia , Ritmo Teta/fisiologia , Ritmo Teta/efeitos dos fármacos , Eletroencefalografia , Estimulantes do Sistema Nervoso Central/farmacologia , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Motor/fisiologia , Córtex Motor/efeitos dos fármacos
3.
EMBO Rep ; 23(8): e54361, 2022 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-35735260

RESUMO

The striatum is a subcortical brain region responsible for the initiation and termination of voluntary movements. Striatal spiny projection neurons receive major excitatory synaptic input from neocortex and thalamus, and cyclic nucleotides have long been known to play important roles in striatal function. Yet, the precise mechanism of action is unclear. Here, we combine optogenetic stimulation, 2-photon imaging, and genetically encoded scavengers to dissect the regulation of striatal synapses in mice. Our data show that excitatory striatal inputs are tonically depressed by phosphodiesterases (PDEs), in particular PDE1. Blocking PDE activity boosts presynaptic calcium entry and glutamate release, leading to strongly increased synaptic transmission. Although PDE1 degrades both cAMP and cGMP, we uncover that the concentration of cGMP, not cAMP, controls the gain of striatal inputs. Disturbing this gain control mechanism in vivo impairs motor skill learning in mice. The tight dependence of striatal excitatory synapses on PDE1 and cGMP offers a new perspective on the molecular mechanisms regulating striatal activity.


Assuntos
Corpo Estriado , Sinapses , Animais , Corpo Estriado/metabolismo , Ácido Glutâmico/metabolismo , Camundongos , Neurônios/metabolismo , Sinapses/fisiologia , Transmissão Sináptica , Tálamo/metabolismo
4.
J Neurosci ; 42(7): 1292-1302, 2022 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-34921048

RESUMO

Response nonlinearities are ubiquitous throughout the brain, especially within sensory cortices where changes in stimulus intensity typically produce compressed responses. Although this relationship is well established in electrophysiological measurements, it remains controversial whether the same nonlinearities hold for population-based measurements obtained with human fMRI. We propose that these purported disparities are not contingent on measurement type and are instead largely dependent on the visual system state at the time of interrogation. We show that deploying a contrast adaptation paradigm permits reliable measurements of saturating sigmoidal contrast response functions (10 participants, 7 female). When not controlling the adaptation state, our results coincide with previous fMRI studies, yielding nonsaturating, largely linear contrast responses. These findings highlight the important role of adaptation in manifesting measurable nonlinear responses within human visual cortex, reconciling discrepancies reported in vision neuroscience, re-establishing the qualitative relationship between stimulus intensity and response across different neural measures and the concerted study of cortical gain control.SIGNIFICANCE STATEMENT Nonlinear stimulus-response relationships govern many essential brain functions, ranging from the sensory to cognitive level. Certain core response properties previously shown to be nonlinear with nonhuman electrophysiology recordings have yet to be reliably measured with human neuroimaging, prompting uncertainty and reconsideration. The results of this study stand to reconcile these incongruencies in the vision neurosciences, demonstrating the profound impact adaptation can have on brain activation throughout the early visual cortex. Moving forward, these findings facilitate the study of modulatory influences on sensory processing (i.e., arousal and attention) and help establish a closer link between neural recordings in animals and hemodynamic measurements from human fMRI, resuming a concerted effort to understand operations in the mammalian cortex.


Assuntos
Adaptação Fisiológica/fisiologia , Sensibilidades de Contraste/fisiologia , Córtex Visual/fisiologia , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Estimulação Luminosa
5.
J Neurophysiol ; 130(3): 652-670, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37584096

RESUMO

Visual motion drives smooth pursuit eye movements through a sensory-motor decoder that uses multiple parallel neural pathways to transform the population response in extrastriate area MT into movement. We evaluated the decoder by challenging pursuit in monkeys with reduced motion reliability created by reducing coherence of motion in patches of dots. Our strategy was to determine how reduced dot coherence changes the population response in MT. We then predicted the properties of a decoder that transforms the MT population response into dot coherence-induced deficits in the initiation of pursuit and steady-state tracking. During pursuit initiation, decreased dot coherence reduces MT population response amplitude without changing the preferred speed at its peak. The successful decoder reproduces the measured eye movements by multiplication of 1) the estimate of target speed from the peak of the population response with 2) visual-motor gain based on the amplitude of the population response. During steady-state tracking, the decoder that worked for pursuit initiation failed to reproduce the paradox that steady-state eye speeds do not accelerate to the target speed despite persistent image motion. It predicted eye acceleration to target speed even when monkeys' eye speeds were steady at well below the target speed. To account for the effect of dot coherence on steady-state eye speed, we postulate that the decoder uses sensory-motor gain to modulate the eye velocity positive feedback that normally sustains perfect steady-state tracking. Then, poor steady-state tracking persists because of balance between eye deceleration caused by low positive feedback gain and acceleration driven by MT.NEW & NOTEWORTHY By challenging a sensory-motor system with degraded sensory stimuli, we reveal how the sensory-motor decoder transforms the population response in extrastriate area MT into commands for the initiation and steady-state behavior of smooth pursuit eye movements. Conclusions are based on measuring population responses in MT for multiple target speeds and different levels of motion reliability and evaluating a decoder with a biologically motivated architecture to determine the decoder properties that create the measured eye movements.


Assuntos
Percepção de Movimento , Acompanhamento Ocular Uniforme , Animais , Movimentos Oculares , Tempo de Reação/fisiologia , Reprodutibilidade dos Testes , Macaca mulatta , Percepção de Movimento/fisiologia , Estimulação Luminosa/métodos
6.
Biol Cybern ; 117(6): 411-431, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37702831

RESUMO

Divisive normalization is a model of canonical computation of brain circuits. We demonstrate that two cascaded divisive normalization processors (DNPs), carrying out intensity/contrast gain control and elementary motion detection, respectively, can model the robust motion detection realized by the early visual system of the fruit fly. We first introduce a model of elementary motion detection and rewrite its underlying phase-based motion detection algorithm as a feedforward divisive normalization processor. We then cascade the DNP modeling the photoreceptor/amacrine cell layer with the motion detection DNP. We extensively evaluate the DNP for motion detection in dynamic environments where light intensity varies by orders of magnitude. The results are compared to other bio-inspired motion detectors as well as state-of-the-art optic flow algorithms under natural conditions. Our results demonstrate the potential of DNPs as canonical building blocks modeling the analog processing of early visual systems. The model highlights analog processing for accurately detecting visual motion, in both vertebrates and invertebrates. The results presented here shed new light on employing DNP-based algorithms in computer vision.


Assuntos
Drosophila , Percepção de Movimento , Animais , Visão Ocular , Encéfalo , Movimento (Física)
7.
Eur J Appl Physiol ; 123(2): 381-393, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36443490

RESUMO

PURPOSE: The neurotransmitter serotonin has a strong effect on behaviour and motor control. Regarding motor control, serotonin contributes to the development of fatigue and is also involved in the ability of motor neurones to operate across a large range of forces (gain control). The consumption of tryptophan-rich supplements (such as α-lactalbumin) is of interest because this amino acid is the only precursor for brain serotonin synthesis. Therefore, the purpose of this study was to determine the effects of α-lactalbumin supplementation on neuromuscular performance. METHODS: Using a randomised double-blind cross-over design, 16 healthy participants performed plantar flexor and handgrip maximal voluntary contractions, a 30-s submaximal handgrip contraction, and a plantar flexor fatigue protocol before and 90 min after consuming either 40 g of α-lactalbumin, an isonitrogenous beverage (Zein) or an isocaloric beverage (corn-starch). Sleepiness, mood, and cognition were assessed to evaluate any psychological effects. RESULTS: α-Lactalbumin decreased force steadiness by 25% during the sustained submaximal handgrip contraction (p < 0.01) and induced greater fatigue (15% reduction in total torque-time integral, p = 0.01) during the fatigue protocol. These effects were not observed for the other control beverages. No effects were found for maximal or explosive strength, or psychological measurements. CONCLUSIONS: 40 g of α-lactalbumin increased handgrip force variability and reduced performance during fatiguing muscle contractions but did not influence brief maximal contractions or psychological parameters in healthy individuals. These findings support the hypothesis that the consumption of α-lactalbumin can increase motor neurone input-output gain and exacerbate central fatigue during sustained maximal exercise.


Assuntos
Lactalbumina , Fadiga Muscular , Humanos , Lactalbumina/farmacologia , Estudos Cross-Over , Fadiga Muscular/fisiologia , Força da Mão , Serotonina , Contração Muscular , Fadiga , Eletromiografia/métodos , Músculo Esquelético/fisiologia , Contração Isométrica/fisiologia
8.
Sensors (Basel) ; 23(13)2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37447973

RESUMO

A 28 GHz fully differential eight-channel beamforming IC (BFIC) with multimode operations is implemented in 65 nm CMOS technology for use in phased array transceivers. The BFIC has an adjustable gain and phase control on each channel to achieve fine beam steering and beam pattern. The BFIC has eight differential beamforming channels each consisting of the two-stage bi-directional amplifier with a precise gain control circuit, a six-bit phase shifter, a three-bit digital step attenuator, and a tuning bit for amplitude and phase variation compensation. The Tx and Rx mode overall gains of the differential eight-channel BFIC are around 11 dB and 9 dB, respectively, at 27.0-29.5 GHz. The return losses of the Tx mode and Rx mode are >10 dB at 27.0-29.5 GHz. The maximum phase of 354° with a phase resolution of 5.6° and the maximum attenuation of 31 dB, including the gain control bits with an attenuation resolution of 1 dB, is achieved at 27.0-29.5 GHz. The root mean square (RMS) phase and amplitude errors are <3.2° and <0.6 dB at 27.0-29.5 GHz, respectively. The chip size is 3.0 × 3.5 mm2, including pads, and Tx mode current consumption is 580 mA at 2.5 V supply voltage.


Assuntos
Amplificadores Eletrônicos , Tecnologia sem Fio , Desenho de Equipamento , Tecnologia , Carmustina
9.
Entropy (Basel) ; 25(7)2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37510024

RESUMO

This study presents a general framework for the control of unknown dynamic systems with unknown input delay. A concise output feedback control system is structured with tuning stabilization/dynamic response by an output feedback low gain, removing steady state error against step reference with a feedforward gain. A series of stability analyses are presented for the designed control systems, (1) a gain/phase margin theorem is proposed for stability analysis by regulating the feedback gain, and (2) a stability theorem based on rational function approximation of the time delay is presented for dealing with the transcendental polynomial characteristic equations, which is equivalent to the analysis from the algebraic polynomial characteristic equation. Both approaches give coherent results for stability analysis by regulating the feedback gain. The approaches are applicable to nonlinear systems, which are linearizable in the neighborhood of the operating points. The low complexity of the controllers does not require hard analytical derivation/numerical calculations to produce an acceptable control performance for the considered systems. Several representative simulation case studies provide demonstrations of computational experiments against those analytically derived and guidance for potential applications.

10.
Cereb Cortex ; 31(5): 2364-2381, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33300581

RESUMO

Sensory cortices must flexibly adapt their operations to internal states and external requirements. Sustained modulation of activity levels in different inhibitory interneuron populations may provide network-level mechanisms for adjustment of sensory cortical processing on behaviorally relevant timescales. However, understanding of the computational roles of inhibitory interneuron modulation has mostly been restricted to effects at short timescales, through the use of phasic optogenetic activation and transient stimuli. Here, we investigated how modulation of inhibitory interneurons affects cortical computation on longer timescales, by using sustained, network-wide optogenetic activation of parvalbumin-positive interneurons (the largest class of cortical inhibitory interneurons) to study modulation of auditory cortical responses to prolonged and naturalistic as well as transient stimuli. We found highly conserved spectral and temporal tuning in auditory cortical neurons, despite a profound reduction in overall network activity. This reduction was predominantly divisive, and consistent across simple, complex, and naturalistic stimuli. A recurrent network model with power-law input-output functions replicated our results. We conclude that modulation of parvalbumin-positive interneurons on timescales typical of sustained neuromodulation may provide a means for robust divisive gain control conserving stimulus representations.


Assuntos
Córtex Auditivo/fisiologia , Interneurônios/fisiologia , Neurônios/metabolismo , Animais , Córtex Auditivo/metabolismo , Optogenética/métodos , Parvalbuminas/metabolismo , Somatostatina/metabolismo
11.
Mol Cell Proteomics ; 19(5): 828-838, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32127492

RESUMO

Mass spectrometry (MS)-based proteomics has great potential for overcoming the limitations of antibody-based immunoassays for antibody-independent, comprehensive, and quantitative proteomic analysis of single cells. Indeed, recent advances in nanoscale sample preparation have enabled effective processing of single cells. In particular, the concept of using boosting/carrier channels in isobaric labeling to increase the sensitivity in MS detection has also been increasingly used for quantitative proteomic analysis of small-sized samples including single cells. However, the full potential of such boosting/carrier approaches has not been significantly explored, nor has the resulting quantitation quality been carefully evaluated. Herein, we have further evaluated and optimized our recent boosting to amplify signal with isobaric labeling (BASIL) approach, originally developed for quantifying phosphorylation in small number of cells, for highly effective analysis of proteins in single cells. This improved BASIL (iBASIL) approach enables reliable quantitative single-cell proteomics analysis with greater proteome coverage by carefully controlling the boosting-to-sample ratio (e.g. in general <100×) and optimizing MS automatic gain control (AGC) and ion injection time settings in MS/MS analysis (e.g. 5E5 and 300 ms, respectively, which is significantly higher than that used in typical bulk analysis). By coupling with a nanodroplet-based single cell preparation (nanoPOTS) platform, iBASIL enabled identification of ∼2500 proteins and precise quantification of ∼1500 proteins in the analysis of 104 FACS-isolated single cells, with the resulting protein profiles robustly clustering the cells from three different acute myeloid leukemia cell lines. This study highlights the importance of carefully evaluating and optimizing the boosting ratios and MS data acquisition conditions for achieving robust, comprehensive proteomic analysis of single cells.


Assuntos
Marcação por Isótopo/métodos , Proteômica/métodos , Processamento de Sinais Assistido por Computador , Análise de Célula Única , Automação , Linhagem Celular , Humanos
12.
Sensors (Basel) ; 22(8)2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35459013

RESUMO

Automatic speech recognition (ASR) is an essential technique of human-computer interactions; gain control is a commonly used operation in ASR. However, inappropriate gain control strategies can lead to an increase in the word error rate (WER) of ASR. As there is a current lack of sufficient theoretical analyses and proof of the relationship between gain control and WER, various unconstrained gain control strategies have been adopted on realistic ASR systems, and the optimal gain control with respect to the lowest WER, is rarely achieved. A gain control strategy named maximized original signal transmission (MOST) is proposed in this study to minimize the adverse impact of gain control on ASR systems. First, by modeling the gain control strategy, the quantitative relationship between the gain control strategy and the ASR performance was established using the noise figure index. Second, through an analysis of the quantitative relationship, an optimal MOST gain control strategy with minimal performance degradation was theoretically deduced. Finally, comprehensive comparative experiments on a Mandarin dataset show that the proposed MOST gain control strategy can significantly reduce the WER of the experimental ASR system, with a 10% mean absolute WER reduction at -9 dB gain.


Assuntos
Percepção da Fala , Interface para o Reconhecimento da Fala , Humanos , Ruído , Fala
13.
Sensors (Basel) ; 22(2)2022 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-35062640

RESUMO

The performance of global navigation satellite system (GNSS) receivers is significantly affected by interference signals. For this reason, several research groups have proposed methods to mitigate the effect of different kinds of jammers. One effective method for wide-band interference mitigation (IM) is the high-rate DFT-based data manipulator (HDDM) pulse blanker (PB). It provides good performance to pulsed and frequency sparse interference. However, it and many other methods have poor performance against wide-band noise signals, which are not frequency-sparse. This article proposes to include automatic gain control (AGC) in the HDDM structure to attenuate the signal instead of removing it: the HDDM-AGC. It overcomes the wide-band noise limitation for IM at the cost of limiting mitigation capability to other signals. Previous studies with this approach were limited to only measuring the carrier-to-noise density ratio (C/N0) performance of tracking, but this article extends the analysis to include the impact of the HDDM-AGC algorithm on the position, velocity, and time (PVT) solution. It allows an end-to-end evaluation and impact assessment of mitigation to a GNSS receiver. This study compares two commercial receivers: one high-end and one low-cost, with and without HDDM IM against laboratory-generated interference signals. The results show that the HDDM-AGC provides a PVT availability and precision comparable to high-end commercial receivers with integrated mitigation for most interference types. For pulse interferences, its performance is superior. Further, it is shown that degradation is minimized against wide-band noise interferences. Regarding low-cost receivers, the PVT availability can be increased up to 40% by applying an external HDDM-AGC.

14.
Proc Natl Acad Sci U S A ; 115(38): E8825-E8834, 2018 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-30166448

RESUMO

When making decisions, humans are often distracted by irrelevant information. Distraction has a different impact on perceptual, cognitive, and value-guided choices, giving rise to well-described behavioral phenomena such as the tilt illusion, conflict adaptation, or economic decoy effects. However, a single, unified model that can account for all these phenomena has yet to emerge. Here, we offer one such account, based on adaptive gain control, and additionally show that it successfully predicts a range of counterintuitive new behavioral phenomena on variants of a classic cognitive paradigm, the Eriksen flanker task. We also report that blood oxygen level-dependent signals in a dorsal network prominently including the anterior cingulate cortex index a gain-modulated decision variable predicted by the model. This work unifies the study of distraction across perceptual, cognitive, and economic domains.


Assuntos
Atenção/fisiologia , Cognição/fisiologia , Tomada de Decisões/fisiologia , Giro do Cíngulo/fisiologia , Modelos Neurológicos , Mapeamento Encefálico/métodos , Simulação por Computador , Retroalimentação Sensorial/fisiologia , Neuroimagem Funcional/métodos , Voluntários Saudáveis , Humanos , Oxigênio/sangue
15.
J Neurosci ; 39(21): 4077-4099, 2019 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-30867259

RESUMO

Phase locking of auditory-nerve-fiber (ANF) responses to the fine structure of acoustic stimuli is a hallmark of the auditory system's temporal precision and is important for many aspects of hearing. Period histograms from phase-locked ANF responses to low-frequency tones exhibit spike-rate and temporal asymmetries, but otherwise retain an approximately sinusoidal shape as stimulus level increases, even beyond the level at which the mean spike rate saturates. This is intriguing because apical cochlear mechanical vibrations show little compression, and mechanoelectrical transduction in the receptor cells is thought to obey a static sigmoidal nonlinearity, which might be expected to produce peak clipping at moderate and high stimulus levels. Here we analyze phase-locked responses of ANFs from cats of both sexes. We show that the lack of peak clipping is due neither to ANF refractoriness nor to spike-rate adaptation on time scales longer than the stimulus period. We demonstrate that the relationship between instantaneous pressure and instantaneous rate is well described by an exponential function whose slope decreases with increasing stimulus level. Relatively stereotyped harmonic distortions in the input to the exponential can account for the temporal asymmetry of the period histograms, including peak splitting. We show that the model accounts for published membrane-potential waveforms when assuming a power-of-three, but not a power-of-one, relationship to exocytosis. Finally, we demonstrate the relationship between the exponential transfer functions and the sigmoidal pseudotransducer functions obtained in the literature by plotting the maxima and minima of the voltage responses against the maxima and minima of the stimuli.SIGNIFICANCE STATEMENT Phase locking of auditory-nerve-fiber responses to the temporal fine structure of acoustic stimuli is important for many aspects of hearing, but the mechanisms underlying phase locking are not fully understood. Intriguingly, period histograms retain an approximately sinusoidal shape across sound levels, even when the mean rate has saturated. We find that neither refractoriness nor spike-rate adaptation is responsible for this behavior. Instead, the peripheral auditory system operates as though it contains an exponential transfer function whose slope changes with stimulus level. The underlying mechanism is distinct from the comparatively weak cochlear mechanical compression in the cochlear apex, and likely resides in the receptor cells.


Assuntos
Nervo Coclear/fisiologia , Potenciais Evocados Auditivos/fisiologia , Audição/fisiologia , Fibras Nervosas/fisiologia , Estimulação Acústica , Potenciais de Ação/fisiologia , Animais , Vias Auditivas/fisiologia , Gatos , Feminino , Masculino
16.
Neuroimage ; 204: 116243, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610297

RESUMO

Goal-directed behavior is affected by subliminally and consciously induced conflicts. Both seem to be modulated by catecholamines, especially dopamine. On the basis of cognitive theoretical and neurobiological considerations, we investigated the effects of dopamine D1 and D2 signaling with the help of unweighted polygenic scores in n = 207 healthy young human subjects. We used a task that combines subliminal primes with conscious flankers to induce conflicts. Dopamine D1 scores were formed based on DRD1 rs4532, CALY rs2298122 and TH rs10770141 single nucleotide polymorphisms (SNPs), while dopamine D2 scores were formed based on DRD2 rs6277 and NPY2R rs2234759 SNPs. We used EEG recordings and source localization analyses to identify differentially modulated neurophysiological sub-processes and functional neuroanatomical structures. Increased dopamine D1 signaling was associated with decreases in consciously induced conflicts. This decrease was due to enhanced stimulus-response mapping in the premotor cortex (BA6), as reflected by an increased P3 amplitude in incongruent trials. Attentional processes remained unaffected by dopamine D1 signaling. The effect of dopamine D2 signaling on conscious conflicts did not reach significance. Subliminally induced conflicts were neither modulated by dopamine D1, nor by dopamine D2 signaling. Our findings suggest that dopamine D1 signaling benefits consciously induced conflicts, presumably by improving the suppression of distracting information via gain control-initiated increases in top-down control processes associated with pre-motor regions. Dopamine D2 signaling does not seem to mediate behavioral differences. Probably, this is because the D2 state facilitates switching between (conflicting) top-down-selected mental representations, but not necessarily between top-down processes and bottom-up distractor information.


Assuntos
Atenção/fisiologia , Conflito Psicológico , Potenciais Evocados P300/fisiologia , Função Executiva/fisiologia , Córtex Motor/fisiologia , Desempenho Psicomotor/fisiologia , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Transdução de Sinais/fisiologia , Adolescente , Adulto , Eletroencefalografia , Feminino , Humanos , Masculino , Córtex Motor/metabolismo , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , Receptores de Dopamina D1/genética , Receptores de Dopamina D2/genética , Estimulação Subliminar , Adulto Jovem
17.
J Neurophysiol ; 123(3): 1133-1143, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32023140

RESUMO

Neocortical circuits exhibit a rich dynamic repertoire, and their ability to achieve entrainment (adjustment of their frequency to match the input frequency) is thought to support many cognitive functions and indicate functional flexibility. Although previous studies have explored the influence of various circuit properties on this phenomenon, the role of divisive gain modulation (or divisive inhibition) is unknown. This gain control mechanism is thought to be delivered mainly by the soma-targeting interneurons in neocortical microcircuits. In this study, we use a neural mass model of the neocortical microcircuit (extended Wilson-Cowan model) featuring both soma-targeting and dendrite-targeting interneuronal subpopulations to investigate the role of divisive gain modulation in entrainment. Our results demonstrate that the presence of divisive inhibition in the microcircuit, as delivered by the soma-targeting interneurons, enables its entrainment to a wider range of input frequencies. Divisive inhibition also promotes a faster entrainment, with the microcircuit needing less time to converge to the fully entrained state. We suggest that divisive inhibition, working alongside subtractive inhibition, allows for more adaptive oscillatory responses in neocortical circuits and, thus, supports healthy brain functioning.NEW & NOTEWORTHY We introduce a computational neocortical microcircuit model that features two inhibitory neural populations, with one providing subtractive and the other divisive inhibition to the excitatory population. We demonstrate that divisive inhibition widens the range of input frequencies to which the microcircuit can become entrained and diminishes the time needed to reach full entrainment. We suggest that divisive inhibition enables more adaptive oscillatory activity, with important implications for both normal and pathological brain function.


Assuntos
Interneurônios/fisiologia , Modelos Neurológicos , Neocórtex/fisiologia , Rede Nervosa/fisiologia , Inibição Neural/fisiologia , Redes Neurais de Computação , Animais , Humanos
18.
J Neurophysiol ; 123(4): 1536-1551, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32186432

RESUMO

Contrast gain control is the systematic adjustment of neuronal gain in response to the contrast of sensory input. It is widely observed in sensory cortical areas and has been proposed to be a canonical neuronal computation. Here, we investigated whether shunting inhibition from parvalbumin-positive interneurons-a mechanism involved in gain control in visual cortex-also underlies contrast gain control in auditory cortex. First, we performed extracellular recordings in the auditory cortex of anesthetized male mice and optogenetically manipulated the activity of parvalbumin-positive interneurons while varying the contrast of the sensory input. We found that both activation and suppression of parvalbumin interneuron activity altered the overall gain of cortical neurons. However, despite these changes in overall gain, we found that manipulating parvalbumin interneuron activity did not alter the strength of contrast gain control in auditory cortex. Furthermore, parvalbumin-positive interneurons did not show increases in activity in response to high-contrast stimulation, which would be expected if they drive contrast gain control. Finally, we performed in vivo whole-cell recordings in auditory cortical neurons during high- and low-contrast stimulation and found that no increase in membrane conductance was observed during high-contrast stimulation. Taken together, these findings indicate that while parvalbumin-positive interneuron activity modulates the overall gain of auditory cortical responses, other mechanisms are primarily responsible for contrast gain control in this cortical area.NEW & NOTEWORTHY We investigated whether contrast gain control is mediated by shunting inhibition from parvalbumin-positive interneurons in auditory cortex. We performed extracellular and intracellular recordings in mouse auditory cortex while presenting sensory stimuli with varying contrasts and manipulated parvalbumin-positive interneuron activity using optogenetics. We show that while parvalbumin-positive interneuron activity modulates the gain of cortical responses, this activity is not the primary mechanism for contrast gain control in auditory cortex.


Assuntos
Córtex Auditivo/fisiologia , Interneurônios/fisiologia , Inibição Neural/fisiologia , Parvalbuminas , Animais , Masculino , Camundongos , Optogenética , Parvalbuminas/metabolismo , Técnicas de Patch-Clamp
19.
J Exp Biol ; 223(Pt 3)2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-31822550

RESUMO

Toothed whales have evolved flexible biosonar systems to find, track and capture prey in diverse habitats. Delphinids, phocoenids and iniids adjust inter-click intervals and source levels gradually while approaching prey. In contrast, deep-diving beaked and sperm whales maintain relatively constant inter-click intervals and apparent output levels during the approach followed by a rapid transition into the foraging buzz, presumably to maintain a long-range acoustic scene in a multi-target environment. However, it remains unknown whether this rapid biosonar adjustment strategy is shared by delphinids foraging in deep waters. To test this, we investigated biosonar adjustments of a deep-diving delphinid, the Risso's dolphin (Grampus griseus). We analyzed inter-click interval and apparent output level adjustments recorded from sound recording tags to quantify in situ sensory adjustment during prey capture attempts. Risso's dolphins did not follow typical (20logR) biosonar adjustment patterns seen in shallow-water species, but instead maintained stable repetition rates and output levels up to the foraging buzz. Our results suggest that maintaining a long-range acoustic scene to exploit complex, multi-target prey layers is a common strategy amongst deep-diving toothed whales. Risso's dolphins transitioned rapidly into the foraging buzz just like beaked whales during most foraging attempts, but employed a more gradual biosonar adjustment in a subset (19%) of prey approaches. These were characterized by higher speeds and minimum specific acceleration, indicating higher prey capture efforts associated with evasive prey. Thus, tracking and capturing evasive prey using biosonar may require a more gradual switch between multi-target echolocation and single-target tracking.


Assuntos
Golfinhos/fisiologia , Ecolocação , Comportamento Predatório , Acústica , Animais , Oceano Atlântico , Mergulho , Portugal , Espectrografia do Som
20.
IEEE Trans Control Syst Technol ; 28(1): 163-171, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32390782

RESUMO

In this paper, we introduce a variable-gain control strategy for mechanical ventilators in the respiratory systems. Respiratory systems assist the patients who have difficulty breathing on their own. For the comfort of the patient, fast pressure buildup (and release) and a stable flow response are desired. However, linear controllers typically need to balance between these conflicting objectives. In order to balance this tradeoff in a more desirable manner, a variable-gain controller is proposed, which switches the controller gain based on the magnitude of the patient flow. The effectiveness of the control strategy is demonstrated in experiments on different test lungs.

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