Cholinergic system changes in Parkinson's disease: emerging therapeutic approaches

In patients with Parkinson's disease, heterogeneous cholinergic system changes can occur in different brain regions. These changes correlate with a range of clinical features, both motor and non-motor, that are refractory to dopaminergic therapy, and can be conceptualised within a systems-level framework in which nodal deficits can produce circuit dysfunctions. The topographies of cholinergic changes overlap with neural circuitries involved in sleep and cognitive, motor, visuo-auditory perceptual, and autonomic functions. Cholinergic deficits within cognition network hubs predict cognitive deficits better than do total brain cholinergic changes. Postural instability and gait difficulties are associated with cholinergic system changes in thalamic, caudate, limbic, neocortical, and cerebellar nodes. Cholinergic system deficits can involve also peripheral organs. Hypercholinergic activity of mesopontine cholinergic neurons in people with isolated rapid eye movement (REM) sleep behaviour disorder, as well as in the hippocampi of cognitively normal patients with Parkinson's disease, suggests early compensation during the prodromal and early stages of Parkinson's disease. Novel pharmacological and neurostimulation approaches could target the cholinergic system to treat motor and non-motor features of Parkinson's disease

Diagnosis and Treatment of Parkinson's Disease

Parkinson's disease is diagnosed by history and physical examination and there are no laboratory investigations available to aid the diagnosis of Parkinson's disease. Confirmation of diagnosis of Parkinson's disease thus remains a difficulty. This book brings forth an update of most recent developments made in terms of biomarkers and various imaging techniques with potential use for diagnosing Parkinson's disease. A detailed discussion about the differential diagnosis of Parkinson's disease also follows as Parkinson's disease may be difficult to differentiate from other mimicking conditions at times. As Parkinson's disease affects many systems of human body, a multimodality treatment of this condition is necessary to improve the quality of life of patients. This book provides detailed information on the currently available variety of treatments for Parkinson's disease including pharmacotherapy, physical therapy and surgical treatments of Parkinson's disease. Postoperative care of patients of Parkinson's disease has also been discussed in an organized manner in this text. Clinicians dealing with day to day problems caused by Parkinson's disease as well as other healthcare workers can use beneficial treatment outlines provided in this book

Simultaneous EEG Monitoring During Transcranial Direct Current Stimulation

Transcranial direct current stimulation (tDCS) is a technique that delivers weak electric currents through the scalp. This constant electric current induces shifts in neuronal membrane excitability, resulting in secondary changes in cortical activity. Although tDCS has most of its neuromodulatory effects on the underlying cortex, tDCS effects can also be observed in distant neural networks. Therefore, concomitant EEG monitoring of the effects of tDCS can provide valuable information on the mechanisms of tDCS. In addition, EEG findings can be an important surrogate marker for the effects of tDCS and thus can be used to optimize its parameters. This combined EEG-tDCS system can also be used for preventive treatment of neurological conditions characterized by abnormal peaks of cortical excitability, such as seizures. Such a system would be the basis of a non-invasive closed-loop device. In this article, we present a novel device that is capable of utilizing tDCS and EEG simultaneously. For that, we describe in a step-by-step fashion the main procedures of the application of this device using schematic figures, tables and video demonstrations. Additionally, we provide a literature review on clinical uses of tDCS and its cortical effects measured by EEG techniques

Study of EEG spectral bands from Parkinson's disease patients treated with transcranial magnetic stimulation

A doença de Parkinson é uma condição degenerativa do Sistema Nervoso Central, relacionado com a perda de um neurotransmissor, a Dopamina. Os principais sintomas presentes são: os tremores nos membros assim como, o maxilar e a face; a instabilidade postural e a afectação do equilíbrio e coordenação. Em Portugal a doença de Parkinson afecta cerca de vinte mil de pessoas, enquanto na Finlândia são cerca de dez mil pessoas. Estes doentes são normalmente sujeitos a medicações que reduzem parte dos sintomas, como o caso da Levodopa (L-dopa), e também é comum estes doentes apresentarem problemas na marcha. Com este estudo é pretendido ver se a técnica Estimulação Magnética Transcraniana pode ser um tratamento alternativo para os doentes de Parkinson. Estas pessoas detêm uma actividade da banda de frequência Beta superior ao normal, e pretende-se que esta diminua após o tratamento. Para tal foram adquiridos dados de electroencefalograma (EEG) de 26 pacientes previamente divididos em dois grupos, um dos quais receberia a estimulação e o outro seria o seu controlo. Este estudo baseia-se num protocolo duplamente cego, onde os pacientes foram distribuídos aleatoriamente, e nem os médicos ou técnicos têm conhecimento dos grupos. Os doentes de Parkinson seleccionados tinham idades compreendidas entre 40-80 anos, classificados de acordo com os parâmetros de UK-PD-Brain-Bank-criteria Hoehn –Yahrstage (escala: 2-4), eram medicados com 300mg ou mais de Levodopa ou semelhante; e apresentavam dificuldades no andar (demorando 6 segundos ou mais a percorrer 10 metros). A técnica intermittent Theta Burst Stimulation (iTBS) foi aplicada no Córtex Motor e no Córtex Dorsolateral Prefrontal (DLPFC) dos pacientes pertencentes ao grupo experimental. Como tratamento dos dados de EEG foi usada a Análise de Componentes Independentes, assim como Fast Fourier Transform para o cálculo da Potência no domínio das frequências. No entanto a hipótese não foi confirmada, uma vez que os resultados obtidos não mostraram as diferenças significativas desejadas entre o grupo controlo e o grupo que sofreu a estimulação no que concerne a actividade da frequência Beta.Parkinson’s disease (PD) is a degenerative condition of the Central Nervous System, that is related with the loss of the neurotransmitter, Dopamine. The main symptoms are: tremors especially on limbs, jaw and face; the postural instability and loss of control of coordination and balance. In Portugal there are twenty thousand people that suffer from Parkinson’s disease, and ten thousand in Finland. Usually these people take medication to reduce the symptoms, such as Levodopa (L-dopa) and they also have problems walking. The study intended to verify if the technique Transcranial Magnetic Stimulation (TMS) may be an alternative treatment for Parkinson's disease patients. These patients have the activity of beta band higher than normal, and it is supposed to be lower after treatment. For that, electroencephalogram (EEG) data of 26 patients were acquired and divided into two groups: one that would receive the stimulation and the other would be its control. The study was designed to be a random, double-blind study. The PD patients included 40-80 years old, were classified according to UK-PD-Brain-Bank-criteria, Hoehn-Yahr-stage 2 to 4; also, these patients were medicated with a total dose of Levodopa or other Dopamine agonist agents of equal or more than 300 mg or more revealed problems with walking (taking 6 or more seconds to walk a 10 meter distance). Standard tests were performed before and during this study, to test walking capacity of patients. The intermittent Theta Burst Stimulation (iTBS) was applied to the Motor Cortex and Dorsolateral Prefrontal Cortex (DLPFC) of patients belonging to the experimental group. While processing the EEG data, the Independent Component Analysis (ICA), as well as Fast Fourier Transform (FFT) were used to calculate the band power in the frequency domain. However the hypothesis was not fully confirmed, since the results showed no significant differences between the sham group and the group that received stimulation as for the activity of Beta band was concerned

Understanding the temporal dynamics of visual hallucinations in Parkinson's Disease with dementia

PhD ThesisBackground Integrative models of visual hallucinations (VH) posit that the symptom requires disruptions to both bottom-up and top-down visual processing. Although many lines of evidence point to a mixture of aberrant processing and disconnection between key nodes in the visual system, in particular the dorsal and ventral attention networks, there have been no attempts to understand the dynamic behaviour of these systems in Parkinson’s disease with dementia (PDD) with VH. Aims The primary aim of this thesis was to explore the correlates of synaptic communication in the visual system and how spatio-temporal dynamics of the early visual system are altered in relation to the severity of VH. The secondary aim was to help understand the balance between the contributions of bottom-up and top-down processing for the experience of VH in PDD. Methods An assortment of investigative approaches, including resting state electroencephalography (EEG), visual evoked potentials (VEPs), and concurrent EEG and transcranial magnetic stimulation (TMS) were applied in a group of PDD patients with a range of VH severities (n = 26) and contrasted with a group of age matched healthy controls (n = 17). Results Latency of the N1 component was similar between groups, suggesting intact transfer between the retina and the cortex. However, PDD patients had an inherent reduction in the amplitude of the VEP components and displayed a pattern of declining P1 latencies in association with more frequent and severe VH. Evoked potentials arising from TMS of the striate cortex were similar in amplitude and latency for each of the components between PDD and controls. However, inter-component activity at several stages was altered in the PDD group, whilst the frequency and severity of VH was positively associated with the amplitudes of several components in the occipital and parietal regions. Finally, attentional modulation as measured by the alpha-band reactivity was also compromised in PDD patients. iv Conclusions These data provide neurophysiological evidence that both early bottom-up and top-down dysfunctions of the visual system occur in PDD patients who hallucinate, thus supporting integrative models of VH.National Institute for Health Research (NIHR) Biomedical Research Unit (BRU)

Disorders of Sleep and Motor Control During the Impaired Cholinergic Innervation in Rat – Relevance to Parkinson’s Disease

The medical profession has been generally very slow to acknowledge the importance of sleep medicine and sleep research. Disorders of sleep are related to anxiety, many mental and neurodegenerative diseases, cardiovascular and respiratory disorders, and obesity

Brain stimulation techniques as novel treatment options for insomnia: A systematic review.

Despite the success of cognitive behavioural therapy for insomnia and recent advances in pharmacotherapy, many patients with insomnia do not sufficiently respond to available treatments. This systematic review aims to present the state of science regarding the use of brain stimulation approaches in treating insomnia. To this end, we searched MEDLINE, Embase and PsycINFO from inception to 24 March 2023. We evaluated studies that compared conditions of active stimulation with a control condition or group. Outcome measures included standardized insomnia questionnaires and/or polysomnography in adults with a clinical diagnosis of insomnia. Our search identified 17 controlled trials that met inclusion criteria, and assessed a total of 967 participants using repetitive transcranial magnetic stimulation, transcranial electric stimulation, transcutaneous auricular vagus nerve stimulation or forehead cooling. No trials using other techniques such as deep brain stimulation, vestibular stimulation or auditory stimulation met the inclusion criteria. While several studies report improvements of subjective and objective sleep parameters for different repetitive transcranial magnetic stimulation and transcranial electric stimulation protocols, important methodological limitations and risk of bias limit their interpretability. A forehead cooling study found no significant group differences in the primary endpoints, but better sleep initiation in the active condition. Two transcutaneous auricular vagus nerve stimulation trials found no superiority of active stimulation for most outcome measures. Although modulating sleep through brain stimulation appears feasible, gaps in the prevailing models of sleep physiology and insomnia pathophysiology remain to be filled. Optimized stimulation protocols and proof of superiority over reliable sham conditions are indispensable before brain stimulation becomes a viable treatment option for insomnia

Spinocerebellar Ataxia Type 2

1. Introduction: The autosomal dominant cerebellar ataxias (ADCA) are a clinically, pathologically and genetically heterogeneous group of neurodegenerative disorders caused by degeneration of cerebellum and its afferent and efferent connections. The degenerative process may additionally involves the ponto- medullar systems, pyramidal tracts, basal ganglia, cerebral cortex, peripheral nerves (ADCA I) and the retina (ADCA II), or can be limited to the cerebellum (ADCA III) (Harding et al., 1993). The most common of these dominantly inherited autosomal ataxias, ADCA I, includes many Spinocerebellar Ataxias (SCA) subtypes, some of which are caused by pathological CAG trinucleotide repeat expansion in the coding region on the mutated gene. Such is the case for SCA1, SCA2, SCA3/MJD, SCA6, SCA7, SCA17 and Dentatorubral-pallidoluysian atrophy (DRPLA) (Matilla et al., 2006). Among the almost 30 SCAs, the variant SCA2 is the second most prevalent subtype worldwide, only surpassed by SCA3 (Schöls et al., 2004; Matilla et al., 2006; Auburger, 2011)..