Project description:Behavioral studies indicate that persons with Parkinson's disease have complexity dependent problems with the discrimination of auditory rhythms. Furthermore, neuroimaging studies show that rhythm processing activates many brain areas that overlap with areas affected by Parkinson's disease (PD). This study sought to investigate the neural correlates of rhythm processing in PD and healthy controls, with a particular focus on rhythmic complexity. We further aimed to investigate differences in brain activation during initial phases of rhythm processing. Functional magnetic resonance imaging was used to scan 15 persons with Parkinson's disease and 15 healthy controls while they listened to musical rhythms with two different levels of complexity. Rhythmic complexity had no significant effect on brain activations, but patients and controls showed differences in areas related to temporal auditory processing, notably bilateral planum temporale and inferior parietal lobule. We found indications of a particular sequential or phasic activation pattern of brain activity, where activity in caudate nucleus in the basal ganglia was time-displaced by activation in the saliency network-comprised of anterior cingulate cortex and bilateral anterior insula-and cortical and subcortical motor areas, during the initial phases of listening to rhythms. We relate our findings to core PD pathology, and discuss the overall, rhythm processing related hyperactivity in PD as a possible dysfunction in specific basal ganglia mechanisms, and the phasic activation pattern in PD as a reflection of a lack of preparatory activation of task-relevant brain networks for rhythm processing in PD.
Project description:Gait abnormalities, such as shuffling steps, start hesitation, and freezing, are common and often incapacitating symptoms of Parkinson's disease (PD) and other parkinsonian disorders. Pharmacological and surgical approaches have only limited efficacy in treating these gait disorders. Rhythmic auditory stimulation (RAS), such as playing marching music and dance therapy, has been shown to be a safe, inexpensive, and an effective method in improving gait in PD patients. However, RAS that adapts to patients' movements may be more effective than rigid, fixed-tempo RAS used in most studies. In addition to auditory cueing, immersive virtual reality technologies that utilize interactive computer-generated systems through wearable devices are increasingly used for improving brain-body interaction and sensory-motor integration. Using multisensory cues, these therapies may be particularly suitable for the treatment of parkinsonian freezing and other gait disorders. In this review, we examine the affected neurological circuits underlying gait and temporal processing in PD patients and summarize the current studies demonstrating the effects of RAS on improving these gait deficits.
Project description:Parkinson's disease (PD) is a chronic progressive neurodegenerative disease that is clinically manifested by a triad of cardinal motor symptoms - rigidity, bradykinesia and tremor - due to loss of dopaminergic neurons. The motor symptoms of PD become progressively worse as the disease advances. PD is also a heterogeneous disease since rigidity and bradykinesia are the major complaints in some patients whereas tremor is predominant in others. In recent years, many studies have investigated the progression of the hallmark symptoms over time, and the cardinal motor symptoms have different rates of progression, with the disease usually progressing faster in patients with rigidity and bradykinesia than in those with predominant tremor. The current treatment regime of dopamine-replacement therapy improves motor symptoms and alleviates disability. Increasing the dosage of dopaminergic medication is commonly used to combat the worsening symptoms. However, the drug-induced involuntary body movements and motor complications can significantly contribute to overall disability. Further, none of the currently-available therapies can slow or halt the disease progression. Significant research efforts have been directed towards developing neuroprotective or disease-modifying agents that are intended to slow the progression. In this article, the most recent clinical studies investigating disease progression and current progress on the development of disease-modifying drug trials are reviewed.
Project description:Rhythm and motor function are intrinsically linked to each other and to music, but the rhythm-motor interplay during music training, and the corresponding brain mechanisms, are underexplored. In a longitudinal training study with children, we examined the role of rhythm predisposition in the fine motor improvements arising from music training, and which brain regions would be implicated. Fifty-seven 8-year-olds were assigned to either a 6-month music training (n = 21), sports training (n = 18), or a control group (n = 18). They performed rhythm and motor tasks, and structural brain scans before and after training were collected. Better ability to perceive rhythm before training was related to less gray matter volume in regions of the cerebellum, fusiform gyrus, supramarginal gyrus, ventral diencephalon, amygdala, and inferior/middle temporal gyri. Music training improved motor performance, and greater improvements correlated with better pre-training rhythm discrimination. Music training also induced a loss of gray matter volume in the left cerebellum and fusiform gyrus, and volume loss correlated with higher motor gains. No such effects were found in the sports and control groups. In summary, children with finer-tuned rhythm perception abilities were prone to finer motor improvements through music training, and this rhythm-motor link was to some extent subserved by the left cerebellum and fusiform gyrus. These findings have implications for models on music-related plasticity and rhythm cognition, and for programs targeting motor function.
Project description:Background and objectiveSex plays a role in Parkinson's disease (PD) mechanisms. We analyzed sex difference manifestations among Spanish patients with PD.Patients and methodsPD patients who were recruited from the Spanish cohort COPPADIS from January 2016 to November 2017 were included. A cross-sectional and a two-year follow-up analysis were conducted. Univariate analyses and general linear model repeated measure were used.ResultsAt baseline, data from 681 PD patients (mean age 62.54 ± 8.93) fit the criteria for analysis. Of them, 410 (60.2%) were males and 271 (39.8%) females. There were no differences between the groups in mean age (62.36 ± 8.73 vs. 62.8 ± 9.24; p = 0.297) or in the time from symptoms onset (5.66 ± 4.65 vs. 5.21 ± 4.11; p = 0.259). Symptoms such as depression (p < 0.0001), fatigue (p < 0.0001), and pain (p < 0.00001) were more frequent and/or severe in females, whereas other symptoms such as hypomimia (p < 0.0001), speech problems (p < 0.0001), rigidity (p < 0.0001), and hypersexuality (p < 0.0001) were more noted in males. Women received a lower levodopa equivalent daily dose (p = 0.002). Perception of quality of life was generally worse in females (PDQ-39, p = 0.002; EUROHIS-QOL8, p = 0.009). After the two-year follow-up, the NMS burden (Non-Motor Symptoms Scale total score) increased more significantly in males (p = 0.012) but the functional capacity (Schwab and England Activities of Daily Living Scale) was more impaired in females (p = 0.001).ConclusionThe present study demonstrates that there are important sex differences in PD. Long-term prospective comparative studies are needed.
Project description:It is commonly agreed that vision is more sensitive to spatial information, while audition is more sensitive to temporal information. When both visual and auditory information are available simultaneously, the modality appropriateness hypothesis predicts that, depending on the task, the most appropriate (i.e., reliable) modality dominates perception. While previous research mainly focused on discrepant information from different sensory inputs to scrutinize the modality appropriateness hypothesis, the current study aimed at investigating the modality appropriateness hypothesis when multimodal information was provided in a nondiscrepant and simultaneous manner. To this end, participants performed a temporal rhythm reproduction task for which the auditory modality is known to be the most appropriate. The experiment comprised an auditory (i.e., beeps), a visual (i.e., flashing dots), and an audiovisual condition (i.e., beeps and dots simultaneously). Moreover, constant as well as variable interstimulus intervals were implemented. Results revealed higher accuracy and lower variability in the auditory condition for both interstimulus interval types when compared to the visual condition. More importantly, there were no differences between the auditory and the audiovisual condition across both interstimulus interval types. This indicates that the auditory modality dominated multimodal perception in the task, whereas the visual modality was disregarded and hence did not add to reproduction performance.
Project description:Non-motor symptoms (NMS) including sleep disorders, anxiety, depression, fatigue, and cognitive decline can significantly impact quality of life in people with PD. Qigong exercise is a mind-body exercise that shows a wide range of benefits in various medical conditions. The purpose of this study was to investigate the effect of Qigong exercise on NMS with a focus on sleep quality. Seventeen participants completed a 12-week intervention of Qigong (n = 8) or sham Qigong (n = 9). Disease severity, anxiety and depression levels, fatigue, cognition, quality of life, and other NMS of the participants were evaluated prior to the intervention and at the end of the 12-week intervention. After the intervention, both Qigong and sham-Qigong group showed significant improvement in sleep quality (p < 0.05) and overall NMS (p < 0.05). No significant difference was found between groups. Qigong exercise has the potential as a rehabilitation method for people with PD, specifically alleviating NMS in PD. However, this finding needs to be carefully considered due to the small sample size and potentially low intervention fidelity of this study.
Project description:The aim of this study was to summarize recent studies on nondopaminergic options for the treatment of motor symptoms in Parkinson's disease (PD).Papers in English published in PubMed, Cochrane, and Ovid Nursing databases between January 1988 and November 2016 were searched using the following keywords: PD, nondopaminergic therapy, adenosine, glutamatergic, adrenergic, serotoninergic, histaminic, and iron chelator. We also reviewed the ongoing clinical trials in the website of clinicaltrials.gov.Articles related to the nondopaminergic treatment of motor symptoms in PD were selected for this review.PD is conventionally treated with dopamine replacement strategies, which are effective in the early stages of PD. Long-term use of levodopa could result in motor complications. Recent studies revealed that nondopaminergic systems such as adenosine, glutamatergic, adrenergic, serotoninergic, histaminic, and iron chelator pathways could include potential therapeutic targets for motor symptoms, including motor fluctuations, levodopa-induced dyskinesia, and gait disorders. Some nondopaminergic drugs, such as istradefylline and amantadine, are currently used clinically, while most such drugs are in preclinical testing stages. Transitioning of these agents into clinically beneficial strategies requires reliable evaluation since several agents have failed to show consistent results despite positive findings at the preclinical level.Targeting nondopaminergic transmission could improve some motor symptoms in PD, especially the discomfort of dyskinesia. Although nondopaminergic treatments show great potential in PD treatment as an adjunct therapy to levodopa, further investigation is required to ensure their success.
Project description:Background: Non-motor symptoms (NMS), including neuropsychiatric, sleep, autonomic, and sensory domains, are an integral aspect of the clinical presentation of Parkinson disease (PD) and affect neurocognitive functioning as well as patients' and caregivers' well-being. Objective: To describe the occurrence of NMS in PD patients with motor fluctuations in real-life condition. Methods: The present study is a secondary analysis of a previous multinational, multicenter, retrospective-prospective cohort observational study (SYNAPSES). Patients with PD diagnosis and motor fluctuations aged ≥18 years were included. Data collected at the baseline visit were used for this study, and descriptive analyzes were conducted to describe the distribution of NMS in motor-fluctuating PD patients distributed according to different clinical characteristics. Results: Of the 1,610 patients enrolled, 1,589 were included for the analysis (978 males and 611 females), with a mean age of 68.4 (SD = 9.6). Most patients had at least one NMS (88.5%). Sleep problems and psychiatric symptoms were the most prevalent NMS in motor fluctuating PD patients in all H and Y stages. Psychiatric disorders were more frequent in older patients and in patients with a larger number of years of PD diagnosis, while sleep problems were more preeminent in younger patients and with inferior disease duration. Conclusions: The present findings further support the high prevalence of NMS in PD patients with motor fluctuations, thus reinforcing the need for assessing them for diagnostic accuracy and for delivering holistic care.
Project description:The risk factors of mild cognitive impairment (MCI) in patients with de novo Parkinson's disease (PD) remain unclear. Therefore, the objective of this study was to compare motor and non-motor symptoms between de novo patients with PD with and without MCI. Moreover, detailed relationships between each cognitive deficit and other clinical characteristics in de novo patients with PD were investigated. Consecutive patients with de novo PD were retrospectively enrolled in this study. Motor symptoms were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) part-III and the Hoehn and Yahr (HY) stage. Non-motor symptoms including depression, anxiety, fatigue, and autonomic dysfunction were measured using representative questionnaires. Motor symptoms, depression, and dysautonomia were associated with MCI in de novo patients with PD. Compared with the non-MCI group with PD, the MCI group with PD had higher scores of UPDRS-III, HY stage, depression, and dysautonomia, but not fatigue or anxiety. Both UPDRS-III and HY stage were significantly linked to all cognitive deficits except attention. Logistic regression analysis showed that depression was associated with memory, visuospatial, and executive impairment, and dysautonomia was related to visuospatial and executive impairment. The results of this study suggest that cognitive impairment in PD might have a different relationship pattern to the motor and some non-motor symptoms.