Sleep disturbances are highly prevalent among patients with Parkinson's disease (PD) and often appear from the early-phase disease or prodromal stages. In this chapter, we will discuss the current evidence addressing the...Sleep disturbances are highly prevalent among patients with Parkinson's disease (PD) and often appear from the early-phase disease or prodromal stages. In this chapter, we will discuss the current evidence addressing the links between sleep dysfunctions in PD, focusing most closely on those data from animal and mathematical/computational models, as well as in human-based studies that explore the electrophysiological and molecular mechanisms by which PD and sleep may be intertwined, whether as predictors or consequences of the disease. It is possible to clearly state that leucine-rich repeat kinase 2 gene (LRRK2) is significantly related to alterations in sleep architecture, particularly affecting rapid eye movement (REM) sleep and non-REM sleep, thus impacting sleep quality. Also, decreases in gamma power, observed after dopaminergic lesions, correlates negatively with the degree of injury, which brings other levels of understanding the impacts of the disease. Besides, abnormal synchronized oscillations among basal ganglia nuclei can be detrimental for information processing considering both motor and sleep-related processes. Altogether, despite clear advances in the field, it is still difficult to definitely establish a comprehensive understanding of causality among all the sleep dysfunctions with the disease itself. Although, certainly, the search for biomarkers is helping in shortening this road towards a better and faster diagnosis, as well as looking for more efficient treatments.
With the advent of novel advanced therapy medicinal products (ATMPs) for neurodegenerative diseases, their pathway to clinical trials and the therapeutic landscape has highlighted some new challenges, many of which are o...With the advent of novel advanced therapy medicinal products (ATMPs) for neurodegenerative diseases, their pathway to clinical trials and the therapeutic landscape has highlighted some new challenges, many of which are outlined in other chapters of this volume. The practical considerations of all these aspects from basic research and animal models through to clinical trials and eventual clinical implementation are significant. By and large, the major voices surrounding these challenges are the scientists and clinical teams who both develop the interventions and design and deliver the clinical trials to test these novel ATMPs. Their expertise is of course essential, but there is a key voice that can add considerable benefit to the pipeline, that of the lived experience of the disease being treated and the new intervention being considered. While still in their relative infancy in neurodegenerative disease, some ATMPs are already in clinical application in other disease areas, mainly cancer and inherited disorders. This more advanced status has raised some interesting questions about the role of the patient voice across all aspects of the therapeutic research and clinical delivery pipeline. This chapter highlights what has been learnt from the patient voice in their understanding and perspectives of ATMPs and in their experiences of clinical trials in neurodegenerative diseases to date. We discuss when, and how, including people living with neurodegenerative disease is of value in the development and implementation of ATMPs and the questions this collaborative effort can allow us to answer.
A crucial question in placebo research is related to which conditions and physiological functions are affected by placebos. Here we present evidence that critical life functions, like ventilation, oxygenation, circulatio...A crucial question in placebo research is related to which conditions and physiological functions are affected by placebos. Here we present evidence that critical life functions, like ventilation, oxygenation, circulation, and perfusion, can be sensitive to placebo treatments in some circumstances. Indeed, we have investigated the role of placebo effects at an altitude of 3500m, where oxygen pressure is 64% compared to the sea level. In these extreme conditions, hypoxia triggers several compensatory responses, such as hyperventilation, increased cardiac output, and increased brain perfusion. A conditioned placebo procedure was found to mimic the effects of oxygen on these compensatory responses, and these effects are still present at altitudes as high as 4500 and 5500m, where oxygen pressure is only 57% and 50%, respectively, compared to the sea level. Thus, placebo effects also take place for those functions that are critical for life and whereby oxygen is the key element.
Communication changes are an important feature of Parkinson's and include both motor and nonmotor features. This chapter will cover briefly the motor features affecting speech production and voice function before focusin...Communication changes are an important feature of Parkinson's and include both motor and nonmotor features. This chapter will cover briefly the motor features affecting speech production and voice function before focusing on the nonmotor aspects. A description of the difficulties experienced by people with Parkinson's when trying to communicate effectively is presented along with some of the assessment tools and therapists' treatment options. The idea of clinical heterogeneity of PD and subtyping patients with different communication problems is explored and suggestions are made on how this may influence clinicians' treatment methods and choices so as to provide personalized therapy programmes. The importance of encouraging and supporting people to maintain social networks, employment, and leisure activities is stated as the key to achieving sustainability. Finally looking into the future, the emergence of new technologies is seen as providing further possibilities to support therapists in the goal of helping people with Parkinson's to maintain good communication skills throughout the course of the disease.
Humans have coevolved over time to not only tolerate but also rely on trillions of microbes that aid in the development of our immune system, provide nutrients, break down potentially noxious substances, and act as a bar...Humans have coevolved over time to not only tolerate but also rely on trillions of microbes that aid in the development of our immune system, provide nutrients, break down potentially noxious substances, and act as a barrier against potentially pathogenic organisms. These microbes, collectively known as the microbiota, live in relatively stable communities on mucosal surfaces such as the respiratory tract and gastrointestinal tract. Changes to the microbiota are often transient, due to changes in diet, antibiotic exposure, and psychological stressor exposure. This chapter will discuss how psychological stressors can shape the intestinal microbial community and how these perturbations can contribute to stressor-induced changes in immune function, neurodevelopment, and behavioral deficits.
The aim of the present study was to investigate the involvement of basal ganglia in altering respiration. The experiments were carried out on cats using the electrical stimulation techniques. The electrical stimulation o...The aim of the present study was to investigate the involvement of basal ganglia in altering respiration. The experiments were carried out on cats using the electrical stimulation techniques. The electrical stimulation of the basal ganglia caused locus-dependent changes both in the tidal volume and the rate of respiration. The most frequent effect of stimulation was hyperpnea and decrease in the tidal volume in awake, freely moving cats. An increase in the tidal volume appeared only as rebound-like aftereffect. The stimulation that caused hyperpnea in awake cats elicited smaller changes under chloralose or ketamine-induced anaesthesia, and, in certain cases, the stimulation produced apnea. After locally applied neurotoxic damage, the electrical stimulation failed to induce significant respiratory changes. It is suggested that the fast, small amplitude ventilation is, probably, produced by high excitation that shifts the respiratory rhythm generator towards the upper limits of its regulatory range. The slowing of ventilation might be produced by an inhibitory mechanism, which is able to cause even apnea under anaesthesia.
The intracranial electrical self-stimulation (ICSS) from the substantia nigra (SN) was reduced by simultaneous stimulation of the nucleus of the solitary tract (NTS) in cats. This effect varied with the current intensity...The intracranial electrical self-stimulation (ICSS) from the substantia nigra (SN) was reduced by simultaneous stimulation of the nucleus of the solitary tract (NTS) in cats. This effect varied with the current intensity and the sequence of NTS stimulation paired with the rewarding SN stimulation. Namely, NTS stimulation preceding the SN stimulation was more effective in lessening ICSS than that following the SN stimulation. Both SN and NTS stimulations produced significant cardiorespiratory effects, when they were applied separately. However, the cardiorespiratory responses to NTS stimulation have no substantial role in altering ICSS, because vagotomy abolished the heart rate effects of NTS stimulation but caused no change in its reducing effect on ICSS. Moreover, no statistically significant correlation was found between the blood pressure changes and the decrease in response rate. These data are interpreted as suggesting that the NTS stimulation may reduce centrally the rewarding value ordinarily derived from ICSS at the SN.