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Effects of subjects' taste sensitivity (expressed as taste detection threshold), tastant quality and taste transduction mechanism on pulsation-induced taste enhancement were tested. Taste intensities of pulsatile MSG and NaCl stimuli at pulsation periods below, at and above individual taste fusion periods (TFP in seconds) were compared to taste intensities of a continuous reference of the same net tastant concentration and quality. In line with results previously reported for sucrose, pulsation-induced taste enhancement peaked around TFP for both MSG and NaCl and did not require perception of tastant pulsation. TFP and pulsation effects were independent of the taste transduction mechanism (G-protein-coupled receptor for MSG versus ion-channel for NaCl). The absence of a relation between TFP and taste sensitivity suggests that temporal gustatory resolution and taste sensitivity are not necessarily influenced by the same factors. The results support earlier findings that early stages of taste transduction are involved in pulsation-induced taste enhancement. Pulsation-induced taste enhancement is determined by the pulsation rate (i.e. TFP) which is longer for MSG than NaCl. This is probably due to the tastant-specific interaction with the receptor rather than the taste transduction mechanism (G-protein-coupled receptor versus ion-channel) involved. [ABSTRACT FROM AUTHOR]

Abstract: Pulsatile stimulation enhances taste intensity compared to continuous stimulation with stimuli of the same net tastant concentration. In the present work, we studied the effects of pulsatile delivery of aroma and taste on their combined contribution to taste intensity. Effects on taste perception were evaluated for aroma and taste pulsation and the aroma pulse–taste pulse phase shift. High-concentration sucrose pulses were alternated with water rinses every 2.5s. Four different aroma (isoamyl acetate) versions were presented: (1) no aroma, (2) continuous aroma (3) aroma pulses in-phase and (4) aroma pulses out-of-phase with taste pulses. Aroma–taste combinations were evaluated for sweetness intensity by a 15-member trained panel using time-intensity analysis. Sweetness intensity was enhanced by pulsatile stimulation of sucrose or isoamyl acetate. In addition, taste enhancement by aroma and tastant pulses was additive if both were presented out-of-phase which resulted a sweetness intensity enhancement by more than 35% compared to a continuous sucrose reference of the same net sucrose concentration. Aroma-induced sweetness enhancement can be explained by cross-modal aroma-taste integration. Amplification of aroma-taste integration by pulsatile stimulation may be attributed to a potentiated afferent input of aroma and taste information prior to aroma-taste integration. Alternative mechanisms include the importance of swallowing on aroma-taste integration. [Copyright &y& Elsevier]

fter more than 40 years of clinical use, levodopa (LD) still remains the gold standard for symptomatic efficacy in Parkinson's disease (PD). However, long-term treatment with LD is often complicated by the development of various types of motor response oscillations as well as drug-induced dyskinesias. These treatment-related motor complications evolve in approximately one-third of patients after only 2 years of LD exposure and, once established, they are difficult to treat and significantly contribute to overall disability and disease burden. Although first described soon after the introduction of LD, the pathophysiology of motor complications is still not completely understood. In fact, it is most likely that non-physiological pulsatile stimulation of dopamine receptors, which is followed by various downstream alterations, plays a key role in the development of LD-induced motor response oscillations and dyskinesias. This review outlines the various types of motor complications and will also address underlying mechanisms, treatment options, as well as impact on clinical disability and quality of life (QoL). [ABSTRACT FROM AUTHOR]

In the parkinsonian patient, the striatal levels of dopamine strictly depend on peripheral levodopa levels; short half-life of levodopa is responsible for plasmatic level fluctuations, which are consistent with a pulsatile receptor stimulation of the striatal system. This sort of non-physiologic stimulation induces a change of the condition of post-synaptic neurons, which is considered responsible for the fluctuations of clinical response. In this respect, apomorphine administration, via infusion pump, may be a good therapeutic option, aimed at obtaining continuous receptor stimulation, assisting in the management of motor fluctuations in the advanced phase of the disease. [ABSTRACT FROM AUTHOR]

• Inhomogeneous distribution of sucrose can increase sweetness perception by >30%. • Sweetness increase depends on the spatial arrangement as well as sucrose gradient. • 3D printing can create more complex objects to perform structure – sensory research. • With complex structural designs, pulsatile stimulation could be applied to solids. The development of sugar-reduced food products is a strategy to reduce the high sugar intake, which is a leading cause of global health concerns. Replacement and/or reduction of sucrose often leads to reduced sweetness perception with the consequence of decreased consumer acceptance. The aim of this work is to implement sensory modulation principles in a model confectionery system with the goal of enhancing sweetness perception. By using 3D-printing, confectionary samples were meso-structured by inhomogenous distribution of sucrose concentrations and assessed with a trained panel regarding sweetness. All samples were made up of a high and low sucrose phase and compared to a homogeneous reference sample. The overall sugar content was kept constant at 22.8% in all samples and sweetness perception was compared. A significant increase of sweetness perception by over 30% was found for samples consisting of a sweet outer shell and an inner less sweet core with a high sucrose gradient between the two phases. Whilst textural effects on sweetness perception could not be fully excluded, results can be seen as a strong indication that sweetness modulation by inhomogenious distribution has a potential to be applied directly in solid food products. [ABSTRACT FROM AUTHOR]

Background: Temporal dynamics may importantly modulate sensory perception, including taste. For example, enhanced perceived taste intensity is often observed when tastant concentration is fluctuating in pulses. The perceived intensity is higher than that of the solutions with a same averaged, but constant concentrations. Meanwhile, taste intensity often decreases with increase of tastant viscosity, despite no changes to the stimuli concentration. The mechanisms to these phenomena are not well understood, in part due to the complicated transport process of tastant through papillae, taste pores, etc. to reach the taste receptors, a cascade of events that are difficult to quantify., Method: We computationally modeled the human tongue surface as a porous micro-fiber medium, extending a previous study and exposed it to pulsatile tastant solution (0.2 and 0.4Hz) with various added viscosity (~0.0011-~0.09 Pa⋅s)., Results: Our simulation revealed that the stimuli concentration within the papillae structure increase with pulsed stimulation, especially those with a longer period (16% increase at 0.4Hz and 23% at 0.2Hz compared to continuous stimuli) and decrease (-6%) with added viscosity. The trend matched well with measured taste perception to sucrose added apple juice in the literature (R 2  > 0.97 for both low and high viscosity stimuli series). Decreased diffusivity due to the increase in viscosity, however, was not a major factor underlying this process., Conclusion: This study re-affirms the validity and accuracy of modeling human tongue surface as a porous medium to investigate taste stimuli transport processes and such peripheral transport dynamics may have significant effects on taste perception., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Two important signalling pathways of NF-κB and ERK transmit merely 1 bit of information about the level of extracellular stimulation. It is thus unclear how such systems can coordinate complex cell responses to external cues. We analyse information transmission in the MAPK/ERK pathway that converts both constant and pulsatile EGF stimulation into pulses of ERK activity. Based on an experimentally verified computational model, we demonstrate that, when input consists of sequences of EGF pulses, transmitted information increases nearly linearly with time. Thus, pulse-interval transcoding allows more information to be relayed than the amplitude-amplitude transcoding considered previously for the ERK and NF-κB pathways. Moreover, the information channel capacity C, or simply bitrate, is not limited by the bandwidth B = 1/ τ, where τ ≈ 1 h is the relaxation time. Specifically, when the input is provided in the form of sequences of short binary EGF pulses separated by intervals that are multiples of τ/ n (but not shorter than τ), then for n = 2, C ≈ 1.39 bit h -1 ; and for n = 4, C ≈ 1.86 bit h -1 . The capability to respond to random sequences of EGF pulses enables cells to propagate spontaneous ERK activity waves across tissue.

Parkinson's disease treatment is characterized by the nearly inevitable development of motor complications, including fluctuations and dyskinesias, in which the duration of benefit of a dose of medication is offset by involuntary movements that can be more disabling than the Parkinsonian features themselves. While levodopa remains the gold standard of therapy, it is the most likely to be associated with these complications. The concept of continuous dopaminergic stimulation has gained increasing acceptance as a potential mechanism by which to avoid or delay the development of motor complications, or to minimize their impact once they have already occurred. This article will explore existing and novel formulations of levodopa to identify their role in the spectrum of Parkinson's disease therapeutics.

This paper investigates the efficacy of high frequency switched-mode neural stimulation. Instead of using a constant stimulation amplitude, the stimulus is switched on and off repeatedly with a high frequency (up to 100 kHz) duty cycled signal. By means of tissue modeling that includes the dynamic properties of both the tissue material as well as the axon membrane, it is first shown that switched-mode stimulation depolarizes the cell membrane in a similar way as classical constant amplitude stimulation. These findings are subsequently verified using in vitro experiments in which the response of a Purkinje cell is measured due to a stimulation signal in the molecular layer of the cerebellum of a mouse. For this purpose a stimulator circuit is developed that is able to produce a monophasic high frequency switched-mode stimulation signal. The results confirm the modeling by showing that switched-mode stimulation is able to induce similar responses in the Purkinje cell as classical stimulation using a constant current source. This conclusion opens up possibilities for novel stimulation designs that can improve the performance of the stimulator circuitry. Care has to be taken to avoid losses in the system due to the higher operating frequency.

The electrical stimulation of neuronal structures is used as a treatment for many neurological disorders, e.g., for the treatment of Parkinson's disease via deep brain stimulation (DBS). To reduce side effects, to avoid tissue or electrode damage, and to increase battery lifetimes, an effective but gentle electrical stimulation is of prime importance. We studied different modified pulse shapes for application in DBS with respect to their efficiency to initiate neuronal activity. Numerical simulations of two mathematical neuron models were performed to investigate the effectiveness of different modified pulse shapes. According to our results, the pulse shapes considered showed a considerably increased efficiency in terms of both activation and entrainment of neural activity. We found that the introduction of a gap with a specific and optimized duration in a biphasic pulse and the reversal of the standard pulse phase order yielded stimulation protocols that could increase the efficiency and therefore reduce the energy consumption of stimulation. The improvements were achieved by simple modifications of existing stimulation techniques. The modification of the pulse shapes resulted in an improvement of up to 50% for both the activation of resting neurons and the entrainment of bursting neurons.