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OBJECTIVES: The aim of this study was to conduct an economic evaluation for the treatment of subjective tinnitus using different modalities of cognitive behavioral therapy (CBT) in Australia. DESIGN: A decision tree model was used to conduct a cost-utility analysis for CBT to determine the cost effectiveness for tinnitus treatments, in terms of cost per responder and cost per quality-adjusted life-year (QALY), from a health system perspective using a 2-year time horizon. Meta-analysis was used to differentiate the levels of effectiveness between three delivery methods for CBT: individual face-to-face care (fCBT), group sessions (gCBT), and a supported internet program (iCBT). One-way sensitivity analysis and probabilistic sensitivity analysis (PSA) explored the uncertainty surrounding model inputs and outcomes. Results were presented as incremental cost-effectiveness ratios compared with no treatment, and as net monetary benefit at a $50,000 willingness-to-pay threshold. RESULTS: Compared with no treatment, the incremental cost per responder was $700 for gCBT, $871 for iCBT, and $1380 for fCBT. The base case incremental cost-effectiveness ratio was $35,363 per QALY for fCBT, $17,935 per QALY for gCBT, and $22,321 per QALY for iCBT compared with no treatment, although there was substantial uncertainty around the QALY gain for responders. Net monetary benefit was $356 (fCBT), $555 (gCBT), and $487 (iCBT), indicating the treatments were cost effective compared with no treatment. One-way sensitivity analysis revealed the results were most sensitive to the probability of a positive response to treatment and treatment length. The PSA found the probability of being cost effective compared with no treatment for gCBT was 99.8%, iCBT 98.4%, and fCBT 71.5% at a willingness-to-pay of $50,000 per QALY, although QALY gain remained at a fixed value in the PSA. CONCLUSIONS: CBT for tinnitus was likely to be cost effective compared with no treatment regardless of treatment modality, assuming they are not mutually exclusive. Of the interventions, gCBT was the lowest cost per responder and lowest cost per QALY. Internet CBT obtained comparable economic outcomes due to similar treatment effectiveness and cost. Group CBT and iCBT warrant greater adoption in clinical practice for the treatment of subjective tinnitus. Further research on preference-based utility measures for varying levels of tinnitus severity and the durability of treatment effect is required to enhance the quality of economic evaluation in this field.
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Terapia Cognitivo-Comportamental , Zumbido , Terapia Cognitivo-Comportamental/métodos , Análise Custo-Benefício , Humanos , Masculino , Antígeno Prostático Específico , Anos de Vida Ajustados por Qualidade de Vida , Zumbido/terapiaRESUMO
Anxiety disorders involve distorted perception of the world including increased saliency of stress-associated cues. However, plasticity in the initial sensory regions of the brain following a fearful experience has never been examined. The cochlear nucleus (CN) is the first station in the central auditory system, with heterogeneous collections of neurons that not only project to but also receive projections from cortico-limbic regions, suggesting a potential for experience-dependent plasticity. Using wireless neural recordings in freely behaving rats, we demonstrate for the first time that neural gain in the CN is significantly altered by fear conditioning to auditory sequences. Specifically, the ventral subnuclei significantly increased firing rate to the conditioned tone sequence, while the dorsal subnuclei significantly decreased firing rate during the conditioning session overall. These findings suggest subregion-specific changes in the balance of inhibition and excitation in the CN as a result of conditioning experience. Heart rate was measured as the conditioned response (CR), which showed that while pre-conditioned stimulus (CS) responding did not change across baseline and conditioning sessions, significant changes in heart rate were observed to the tone sequence followed by shock. Heart-rate findings support acquisition of conditioned fear. Taken together, the present study presents first evidence for potential experience-dependent changes in auditory perception that involve novel plasticity within the first site of processing auditory information in the brain.
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This study assessed the developmental profile of unisensory and multisensory processes, and their contribution to children's intellectual abilities (8- and 11-year olds, N = 38, compared to adults, N = 19) using a simple audiovisual detection task and three incidental associative learning tasks with different sensory signals: visual-verbal with pseudowords, novel audiovisual, and visual-visual. The level of immaturity throughout childhood was dependent on both, the sensory signal type and the task. Associative learning was significantly enhanced with verbal sounds, compared to novel audiovisual and unisensory visual learning. Visual-verbal learning was also the best predictor of children's general intellectual abilities. The results demonstrate a separate developmental trajectory for visual and verbal multisensory processes and independent contributions to the development of cognitive abilities throughout childhood.
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Aprendizagem por Associação , Desenvolvimento Infantil , Inteligência , Estimulação Acústica , Adulto , Análise de Variância , Aprendizagem por Associação/fisiologia , Criança , Feminino , Humanos , Aprendizagem , Masculino , Estimulação Luminosa , Psicometria , Tempo de Reação , Adulto JovemRESUMO
OBJECTIVE: The objective of the study was to quantify effective connectivity from the piriform cortex to mediodorsal thalamus, in Genetic Absence Epilepsy Rats from Strasbourg (GAERS). METHODS: Local field potentials (LFPs) were recorded using microelectrode arrays implanted in the mediodorsal thalamus and piriform cortex, in three urethane anesthetized GAERS and three control rats. Screw electrodes were placed in the primary motor cortex to identify epileptiform discharges. We used transfer entropy to measure effective connectivity from piriform cortex to mediodorsal thalamus prior to and during generalized epileptiform discharges. RESULTS: We observed increased theta band effective connectivity from piriform cortex to mediodorsal thalamus, prior to and during epileptiform discharges in GAERS compared with controls. Increased effective connectivity was also observed in beta and gamma bands from the piriform cortex to mediodorsal thalamus, but only during epileptiform discharges. CONCLUSIONS: This preliminary study suggests that increased effective theta connectivity from the piriform cortex to the mediodorsal thalamus may be a feature of the 'epileptic network' associated with genetic absence epilepsy. Our findings indicate an underlying predisposition of this direct pathway to propagate epileptiform discharges in genetic absence epilepsy.
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Epilepsia Tipo Ausência/genética , Epilepsia Tipo Ausência/patologia , Núcleo Mediodorsal do Tálamo/patologia , Córtex Piriforme/patologia , Animais , Eletrodos Implantados , Eletroencefalografia , Entropia , Epilepsia Generalizada/patologia , Masculino , Córtex Motor/fisiopatologia , Rede Nervosa/fisiopatologia , Ratos , Ritmo TetaRESUMO
OBJECTIVE: The objective of the study were to investigate patterns of multiunit cluster firing in the piriform cortex (PC) and mediodorsal thalamus (MDT) in a rat model of genetic generalized epilepsy (GGE) with absence seizures and to assess whether these regions contribute to the initiation or spread of generalized epileptiform discharges. METHODS: Multiunit clusters and their corresponding local field potentials (LFPs) were recorded from microelectrode arrays implanted in the PC and MDT in urethane anesthetized Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and nonepileptic control (NEC) rats. Peristimulus time histograms (PSTHs) and cross-correlograms were used to observe transient changes in both the rate of firing and synchrony over time. The phase locking of multiunit clusters to LFP signals (spike-LFP phase locking) was calculated for frequency bands associated with olfactory communication between the two brain regions. RESULTS: There were significant increases in both rate of firing and synchronous activity at the onset of generalized epileptiform discharges in both PC and MDT. Prior to and following these increases in synchronous activity, there were periods of suppression. Significant increases in spike-LFP phase locking were observed within the PC prior to the onset of epileptiform discharges across all spectral bands. There were also significant increases in spike-LFP phase locking within the theta band of the MDT prior to onset. Between the two brain regions, there was a significant decrease in spike-LFP phase locking -0.5â¯s prior to onset in the theta band which coincided with a significant elevation in spike-LFP phase locking in the gamma band. CONCLUSIONS: Both the PC and MDT are engaged in the absence epilepsy network. Early spike-LFP phase locking between these two brain regions suggests potential involvement in the initiation of seizure activity.
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Epilepsia Tipo Ausência/fisiopatologia , Núcleo Mediodorsal do Tálamo/fisiopatologia , Córtex Piriforme/fisiopatologia , Animais , Análise por Conglomerados , Progressão da Doença , Eletroencefalografia , Fenômenos Eletrofisiológicos , Epilepsia Generalizada/fisiopatologia , Lateralidade Funcional/fisiologia , Potenciais da Membrana , Ratos , Convulsões/fisiopatologia , Olfato/fisiologia , Ritmo TetaRESUMO
Recordings of neural activity can be used to aid communication, control prosthetic devices or alleviate disease symptoms. Chronic recordings require a high signal-to-noise ratio that is stable for years. Current cortical devices generally fail within months to years after implantation. Development of novel devices to increase lifetime requires valid testing protocols and a knowledge of the critical parameters controlling electrophysiological performance. Here we present electrochemical and electrophysiological protocols for assessing implantable electrodes. Biological noise from neural recording has significant impact on signal-to-noise ratio. A recently developed surgical approach was utilised to reduce biological noise. This allowed correlation of electrochemical and electrophysiological behaviour. The impedance versus frequency of modified electrodes was non-linear. It was found that impedance at low frequencies was a stronger predictor of electrophysiological performance than the typically reported impedance at 1 kHz. Low frequency impedance is a function of electrode area, and a strong correlation of electrode area with electrophysiological response was also seen. Use of these standardised testing protocols will allow future devices to be compared before transfer to preclinical and clinical trials.
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Eletrodos Implantados , Eletrofisiologia/métodos , Colículos Inferiores/fisiologia , Microeletrodos , Condução Nervosa/fisiologia , Animais , Impedância Elétrica , Eletrofisiologia/instrumentação , Polímeros/química , Ratos Wistar , Sensibilidade e Especificidade , Razão Sinal-RuídoRESUMO
Although it is well known that attention can modulate multisensory processes in adults and infants, this relationship has not been investigated in school-age children. Attention abilities of 53 children (ages 7-13â¯years) were assessed using three subscales of the Test of Everyday Attention for Children (TEA-Ch): visuospatial attention (Sky Search [SS]), auditory sustained attention (Score), and audiovisual dual task (SSDT, where the SS and Score tasks are performed simultaneously). Multisensory processes were assessed using the McGurk effect (a verbal illusion where speech perception is altered by vision) and the Stream-Bounce (SB) effect (a nonverbal illusion where visual perception is altered by sound). The likelihood of perceiving both multisensory illusions tended to increase with age. The McGurk effect was significantly more pronounced in children who scored high on the audiovisual dual attention index (SSDT). In contrast, the SB effect was more pronounced in children with higher sustained auditory attention abilities as assessed by the Score index. These relationships between attention and the multisensory illusory percepts could not be explained solely by age or children's intellectual abilities. This study suggests that the interplay between attention and multisensory processing depends on both the nature of the multisensory task and the type of attention needed to effectively merge information across the senses.
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Atenção/fisiologia , Percepção Auditiva/fisiologia , Percepção da Fala/fisiologia , Percepção Visual/fisiologia , Estimulação Acústica , Adolescente , Criança , Feminino , Humanos , Ilusões , Masculino , Testes Neuropsicológicos , Estimulação LuminosaRESUMO
In this review, we consider how the piriform cortex is engaged in both focal and generalized epilepsy networks and postulate the various neural pathways that can be effectively neuromodulated by stimulation at this site. This highlights the common involvement of the piriform cortex in epilepsy. We address both current and future preclinical studies of deep brain stimulation (DBS) of the piriform cortex, with attention to the critical features of these trials that will enable them to be of greatest utility in informing clinical translation. Although recent DBS trials have utilized thalamic targets, electrical stimulation of the piriform cortex may also be a useful intervention for people with epilepsy. However, more work is required to develop a solid foundation for this approach before considering human trials.
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Estimulação Encefálica Profunda/métodos , Epilepsia/terapia , Córtex Piriforme , Humanos , Resultado do TratamentoRESUMO
In contrast to adult rodents, juvenile rodents fail to show relapse following extinction of conditioned fear. Using different retrograde tracers injected into the infralimbic cortex (IL) and the ventral hippocampus (vHPC) in conjunction with c-Fos and parvalbumin (PV) immunochemistry, we investigated the neurocircuitry of extinction in juvenile and adult rats. Regardless of fear extinction or retrieval, juvenile rats had more c-Fos+ neurons in the basolateral amygdala (BLA) compared to adults, and showed a higher proportion of c-Fos+ IL-projecting neurons. Adult rats had more activated vHPC-projecting BLA neurons following extinction compared to retrieval, a difference not observed in juvenile rats. The number of activated vHPC- or IL-projecting BLA neurons was significantly correlated with freezing levels in adult, but not juvenile, rats. We also identified activated neurons in the BLA that simultaneously project to the IL and vHPC in the retrieval groups at both ages. This study provides novel insight into the neural process underlying extinction, especially in the juvenile period.
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Encéfalo/citologia , Encéfalo/crescimento & desenvolvimento , Extinção Psicológica/fisiologia , Medo/fisiologia , Animais , Condicionamento Psicológico/fisiologia , Reação de Congelamento Cataléptica , Masculino , Vias Neurais/citologia , Vias Neurais/crescimento & desenvolvimento , Técnicas de Rastreamento Neuroanatômico , Neurônios/citologia , Neurônios/fisiologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos Sprague-DawleyRESUMO
OBJECTIVE: In this paper we propose a novel application of reinforcement learning to the area of auditory neural stimulation. We aim to develop a simulation environment which is based off real neurological responses to auditory and electrical stimulation in the cochlear nucleus (CN) and inferior colliculus (IC) of an animal model. Using this simulator we implement closed loop reinforcement learning algorithms to determine which methods are most effective at learning effective acoustic neural stimulation strategies. APPROACH: By recording a comprehensive set of acoustic frequency presentations and neural responses from a set of animals we created a large database of neural responses to acoustic stimulation. Extensive electrical stimulation in the CN and the recording of neural responses in the IC provides a mapping of how the auditory system responds to electrical stimuli. The combined dataset is used as the foundation for the simulator, which is used to implement and test learning algorithms. MAIN RESULTS: Reinforcement learning, utilising a modified n-Armed Bandit solution, is implemented to demonstrate the model's function. We show the ability to effectively learn stimulation patterns which mimic the cochlea's ability to covert acoustic frequencies to neural activity. Time taken to learn effective replication using neural stimulation takes less than 20 min under continuous testing. SIGNIFICANCE: These results show the utility of reinforcement learning in the field of neural stimulation. These results can be coupled with existing sound processing technologies to develop new auditory prosthetics that are adaptable to the recipients current auditory pathway. The same process can theoretically be abstracted to other sensory and motor systems to develop similar electrical replication of neural signals.
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Implantes Cocleares , Aprendizagem/fisiologia , Algoritmos , Animais , Interfaces Cérebro-Computador , Núcleo Coclear/fisiologia , Estimulação Elétrica , Eletrodos Implantados , Humanos , Colículos Inferiores/fisiologia , Aprendizado de Máquina , Desenho de Prótese , Ratos , Ratos Wistar , Reforço Psicológico , SoftwareRESUMO
The maternal environment influences a broad range of phenotypic outcomes for offspring, with anxiety-like behavior being particularly susceptible to maternal environmental perturbations. Much less is known regarding paternal environmental influences. To investigate this, adult male rats were exposed to 25% calorie restriction (CR) or glucocorticoid elevation (CORT; 200 µg/ml of corticosterone in drinking water) for â¼ 6 weeks prior to breeding. Elevated plus maze (EPM), open field (OF), predator odor (cat urine), and acoustic startle/pre-pulse inhibition (AS/PPI) were characterised in the adult male offspring. Plasma concentrations of corticotrophin-releasing hormone (CRF), adrenocorticotropin hormone (ACTH), and serum leptin were characterised in both sires and offspring. Maternal care received by litters was additionally observed. Expectedly, CR and CORT treatment attenuated weight gain, whilst only CR induced anxiolytic behavior in the EPM. The adult offspring sired by CR males also demonstrated a reduction in weight gain, food intake and serum leptin levels when compared to controls. Moreover, CR offspring demonstrated an anxiolytic-like profile in the EPM and OF, enhanced habituation to the AS pulse, reduced PPI, but no alteration to predator odor induced defensiveness compared to control. CORT offspring failed to demonstrate any behavioral differences from controls, however, exhibited a trend towards reduced ACTH and leptin concentration. Collectively, the results indicate that a reduction in calories in males prior to conception can affect the behavior of adult offspring. The phenotypic transmission of CR experiences from fathers to the progeny could potentially be mediated epigenetically. The role of glucocorticoid elevation and maternal care are also discussed.
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Ansiedade , Restrição Calórica , Pai , Exposição Paterna , Efeitos Tardios da Exposição Pré-Natal/psicologia , Hormônio Adrenocorticotrópico/sangue , Animais , Ansiedade/genética , Peso Corporal , Corticosterona/farmacologia , Hormônio Liberador da Corticotropina/sangue , Ingestão de Líquidos , Ingestão de Alimentos , Feminino , Leptina/sangue , Masculino , Comportamento Materno , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/genética , Inibição Pré-Pulso , RatosRESUMO
In vivo intracellular responses to auditory stimuli revealed that, in a particular population of cells of the ventral nucleus of the lateral lemniscus (VNLL) of rats, fast inhibition occurred before the first action potential. These experimental data were used to constrain a leaky integrate-and-fire (LIF) model of the neurons in this circuit. The post-synaptic potentials of the VNLL cell population were characterized using a method of triggered averaging. Analysis suggested that these inhibited VNLL cells produce action potentials in response to a particular magnitude of the rate of change of their membrane potential. The LIF model was modified to incorporate the VNLL cells' distinctive action potential production mechanism. The model was used to explore the response of the population of VNLL cells to simple speech-like sounds. These sounds consisted of a simple tone modulated by a saw tooth with exponential decays, similar to glottal pulses that are the repeated impulses seen in vocalizations. It was found that the harmonic component of the sound was enhanced in the VNLL cell population when compared to a population of auditory nerve fibers. This was because the broadband onset noise, also termed spectral splatter, was suppressed by the fast onset inhibition. This mechanism has the potential to greatly improve the clarity of the representation of the harmonic content of certain kinds of natural sounds.
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Vias Auditivas/fisiologia , Tronco Encefálico/fisiologia , Estimulação Acústica/métodos , Potenciais de Ação/fisiologia , Animais , Eletrofisiologia/métodos , Masculino , Modelos Biológicos , Neurônios/fisiologia , Ratos , Ratos Wistar , Som , Potenciais Sinápticos/fisiologiaRESUMO
Electrode impedance is used to assess the thermal noise and signal-to-noise ratio for brain-machine interfaces. An intermediate frequency of 1 kHz is typically measured, although other frequencies may be better predictors of device performance. PEDOT-PSS, PEDOT-DBSA and PEDOT-pTs conducting polymer modified electrodes have reduced impedance at 1 kHz compared to bare metal electrodes, but have no correlation with the effective electrode area. Analytical solutions to impedance indicate that all low-intermediate frequencies can be used to compare the electrode area at a series RC circuit, typical of an ideal metal electrode in a conductive solution. More complex equivalent circuits can be used for the modified electrodes, with a simplified Randles circuit applied to PEDOT-PSS and PEDOT-pTs and a Randles circuit including a Warburg impedance element for PEDOT-DBSA at 0 V. The impedance and phase angle at low frequencies using both equivalent circuit models is dependent on the electrode area. Low frequencies may therefore provide better predictions of the thermal noise and signal-to-noise ratio at modified electrodes. The coefficient of variation of the PEDOT-pTs impedance at low frequencies was lower than the other conducting polymers, consistent with linear and steady-state electroactive area measurements. There are poor correlations between the impedance and the charge density as they are not ideal metal electrodes.
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Interfaces Cérebro-Computador , Dextranos/química , Poliestirenos/química , Sulfonamidas/química , Tiofenos/química , Espectroscopia Dielétrica , Impedância Elétrica , Eletrodos , HumanosRESUMO
Chemosensory cues signaling predators reliably stimulate innate defensive responses in rodents. Despite the well-documented role of the amygdala in predator odor-induced fear, evidence for the relative contribution of the specific nuclei that comprise this structurally heterogeneous structure is conflicting. In an effort to clarify this we examined neural activity, via electrophysiological recordings, in amygdala subnuclei to controlled and repeated presentations of a predator odor: cat urine. Defensive behaviors, characterized by avoidance, decreased exploration, and increased risk assessment, were observed in adult male hooded Wistar rats (n = 11) exposed to a cloth impregnated with cat urine. Electrophysiological recordings of the amygdala (777 multiunit clusters) were subsequently obtained in freely breathing anesthetized rats exposed to cat urine, distilled water, and eugenol via an air-dilution olfactometer. Recorded units selectively responded to cat urine, and frequencies of responses were distributed differently across amygdala nuclei; medial amygdala (MeA) demonstrated the greatest frequency of responses to cat urine (51.7%), followed by the basolateral and basomedial nuclei (18.8%) and finally the central amygdala (3.0%). Temporally, information transduction occurred primarily from the cortical amygdala and MeA (ventral divisions) to other amygdala nuclei. Interestingly, MeA subnuclei exhibited distinct firing patterns to predator urine, potentially revealing aspects of the underlying neurocircuitry of predator odor processing and defensiveness. These findings highlight the critical involvement of the MeA in processing olfactory cues signaling predator threat and converge with previous studies to indicate that amygdala regulation of predator odor-induced fear is restricted to a particular set of subnuclei that primarily include the MeA, particularly the ventral divisions.
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Potenciais de Ação , Tonsila do Cerebelo/fisiologia , Medo , Odorantes , Percepção Olfatória , Animais , Mapeamento Encefálico , Discriminação Psicológica , Masculino , Comportamento Predatório , Ratos , Ratos WistarRESUMO
Neural stimulation is used in the cochlear implant, bionic eye, and deep brain stimulation, which involves implantation of an array of electrodes into a patient's brain. The current passed through the electrodes is used to provide sensory queues or reduce symptoms associated with movement disorders and increasingly for psychological and pain therapies. Poor control of electrode properties can lead to suboptimal performance; however, there are currently no standard methods to assess them, including the electrode area and charge density. Here we demonstrate optical and electrochemical methods for measuring these electrode properties and show the charge density is dependent on electrode geometry. This technique highlights that materials can have widely different charge densities but also large variation in performance. Measurement of charge density from an electroactive area may result in new materials and electrode geometries that improve patient outcomes and reduce side effects.
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Encéfalo/fisiologia , Estimulação Elétrica , Técnicas Eletroquímicas/métodos , Eletrodos , Polímeros/química , HumanosRESUMO
Early life events, such as calorie restriction (CR) and elevated glucocorticoids, can calibrate the lifelong behavioural and physiological profile of an individual. Stress reactivity in adulthood is particularly sensitive to early life events; however, the consequence to fear and anxiety-like behaviour is less clear. Consequently, the current study sought to examine the effects of post-natal CR and glucocorticoid elevation, long considered powerful programming stimuli, on the subsequent fear and anxiety behaviour of the adult offspring. Rat dams received either corticosterone (200 µg/ml) supplementation in drinking water (CORT) or a 25% CR from post-natal day (PND) 1 to 11. Responses to the elevated plus maze (EPM), open field and a predator odour (TMT; 2,5-dihydro-2,4,5-trimethylthiazoline) were characterised in the adult male offspring. Both treatment conditions resulted in enhanced fear responses to TMT, characterised by heightened risk assessment and increased avoidance of TMT. CORT nursed offspring further demonstrated an anxiogenic profile in the open field. Basal hypothalamic-pituitary-adrenal function was unchanged in CORT adult offspring, whilst corticosterone concentration was elevated by post-natal CR. CR and CORT treated dams both exhibited greater anxiety-like behaviour in the EPM. A modest and temporary enhancement of maternal care was observed in CR and CORT treated dams, with CR dams further exhibiting rapid pup retrieval latencies. The results indicate enhanced emotionality in the adult male progeny of dams exposed to CR and corticosterone supplementation during the post-natal period. The modest enhancement of maternal care observed by both treatments is unlikely to have influenced the behavioural profile of the offspring.
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Ansiedade , Comportamento Animal/efeitos dos fármacos , Restrição Calórica/psicologia , Corticosterona/farmacologia , Medo , Lactação , Envelhecimento , Animais , Animais Lactentes , Ansiedade/etiologia , Restrição Calórica/efeitos adversos , Corticosterona/metabolismo , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Medo/efeitos dos fármacos , Feminino , Glucocorticoides/farmacologia , Masculino , Ratos , Ratos WistarRESUMO
New materials and designs for neural implants are typically tested separately, with a demonstration of performance but without reference to other implant characteristics. This precludes a rational selection of a particular implant as optimal for a particular application and the development of new materials based on the most critical performance parameters. This article develops a protocol for in vitro and in vivo testing of neural recording electrodes. Recommended parameters for electrochemical and electrophysiological testing are documented with the key steps and potential issues discussed. This method eliminates or reduces the impact of many systematic errors present in simpler in vivo testing paradigms, especially variations in electrode/neuron distance and between animal models. The result is a strong correlation between the critical in vitro and in vivo responses, such as impedance and signal-to-noise ratio. This protocol can easily be adapted to test other electrode materials and designs. The in vitro techniques can be expanded to any other nondestructive method to determine further important performance indicators. The principles used for the surgical approach in the auditory pathway can also be modified to other neural regions or tissue.
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Técnicas Eletroquímicas/instrumentação , Eletrodos Implantados , Eletrofisiologia/instrumentação , Neurônios/fisiologia , Animais , Benzenossulfonatos , Compostos Bicíclicos Heterocíclicos com Pontes , Materiais Revestidos Biocompatíveis , Técnicas Eletroquímicas/métodos , Eletrofisiologia/métodos , Polímeros , Pirróis , Ratos , SulfatosRESUMO
In mice a 50% calorie restriction (CR) for 28days attenuates sickness behavior after lipopolysaccharide (LPS) and these mice demonstrate a central anti-inflammatory bias. This study examined the dose-dependent effect of CR on sickness behavior (fever, anorexia, cachexia) and peripheral immune markers post-LPS. Male Sprague-Dawley rats fed ad libitum or CR by 50% for 14, 21, or 28days were injected on day 15, 22, or 29 with 50µg/kg of LPS or saline (1mL/500g). Changes in body temperature (Tb), locomotor activity, body weight, and food intake were determined. A separate cohort of rats was fed ad libitum or CR by 50% for 28days and serum levels of corticosterone (CORT), interleukin 6 (IL-6), and IL-10 were determined at 0, 2, and 4h post-LPS. The rats CR for 28days demonstrated the largest attenuation of sickness behavior: no fever, limited reduction in locomotor activity, no anorexia, and reduced cachexia following LPS. Rats CR for 14 and 21days demonstrated a partial attenuation of sickness behavior. Rats CR for 14days demonstrated a larger increase in Tb, larger reduction in locomotor activity, and larger weight loss compared to rats CR for 21days. Serum CORT was increased at 2h post-LPS in ad libitum and CR groups; however it was two times larger in the CR animals. Levels of IL-6 were significantly attenuated at 2h post-LPS in the CR animals. IL-10 levels were similar post-LPS. CR results in an enhanced anti-inflammatory response in the form of increased CORT and diminished pro-inflammatory signals.
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Restrição Calórica , Corticosterona/sangue , Febre/dietoterapia , Comportamento de Doença , Interleucina-6/sangue , Animais , Peso Corporal , Ingestão de Alimentos , Inflamação , Interleucina-10/sangue , Lipopolissacarídeos , Masculino , Atividade Motora , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: Neural recording electrodes suffer from poor signal to noise ratio, charge density, biostability and biocompatibility. This paper investigates the ability of conducting polymer coated electrodes to record acute neural response in a systematic manner, allowing in depth comparison of electrochemical and electrophysiological response. APPROACH: Polypyrrole (Ppy) and poly-3,4-ethylenedioxythiophene (PEDOT) doped with sulphate (SO4) or para-toluene sulfonate (pTS) were used to coat iridium neural recording electrodes. Detailed electrochemical and electrophysiological investigations were undertaken to compare the effect of these materials on acute in vivo recording. MAIN RESULTS: A range of charge density and impedance responses were seen with each respectively doped conducting polymer. All coatings produced greater charge density than uncoated electrodes, while PEDOT-pTS, PEDOT-SO4 and Ppy-SO4 possessed lower impedance values at 1 kHz than uncoated electrodes. Charge density increased with PEDOT-pTS thickness and impedance at 1 kHz was reduced with deposition times up to 45 s. Stable electrochemical response after acute implantation inferred biostability of PEDOT-pTS coated electrodes while other electrode materials had variable impedance and/or charge density after implantation indicative of a protein fouling layer forming on the electrode surface. Recording of neural response to white noise bursts after implantation of conducting polymer-coated electrodes into a rat model inferior colliculus showed a general decrease in background noise and increase in signal to noise ratio and spike count with reduced impedance at 1 kHz, regardless of the specific electrode coating, compared to uncoated electrodes. A 45 s PEDOT-pTS deposition time yielded the highest signal to noise ratio and spike count. SIGNIFICANCE: A method for comparing recording electrode materials has been demonstrated with doped conducting polymers. PEDOT-pTS showed remarkable low fouling during acute implantation, inferring good biostability. Electrode impedance at 1 kHz was correlated with background noise and inversely correlated with signal to noise ratio and spike count, regardless of coating. These results collectively confirm a potential for improvement of neural electrode systems by coating with conducting polymers.