Acute modulation of brain connectivity in Parkinson disease after automatic mechanical peripheral stimulation: A pilot study

The present study shows the results of a double-blind sham-controlled pilot trial to test whether measurable stimulus-specific functional connectivity changes exist after Automatic Mechanical Peripheral Stimulation (AMPS) in patients with idiopathic Parkinson Disease.Eleven patients (6 women and 5 men) with idiopathic Parkinson Disease underwent brain fMRI immediately before and after sham or effective AMPS. Resting state Functional Connectivity (RSFC) was assessed using the seed-ROI based analysis. Seed ROIs were positioned on basal ganglia, on primary sensory-motor cortices, on the supplementary motor areas and on the cerebellum. Individual differences for pre- and post-effective AMPS and pre- and post-sham condition were obtained and first entered in respective one-sample t-test analyses, to evaluate the mean effect of condition.Effective AMPS, but not sham stimulation, induced increase of RSFC of the sensory motor cortex, nucleus striatum and cerebellum. Secondly, individual differences for both conditions were entered into paired group t-test analysis to rule out sub-threshold effects of sham stimulation, which showed stronger connectivity of the striatum nucleus with the right lateral occipital cortex and the cuneal cortex (max Z score 3.12) and with the right anterior temporal lobe (max Z score 3.42) and of the cerebellum with the right lateral occipital cortex and the right cerebellar cortex (max Z score 3.79).Our results suggest that effective AMPS acutely increases RSFC of brain regions involved in visuo-spatial and sensory-motor integration.This study provides Class II evidence that automatic mechanical peripheral stimulation is effective in modulating brain functional connectivity of patients with Parkinson Disease at rest.Clinical Trials.gov NCT01815281

The role of high-field magnetic resonance imaging in parkinsonian disorders:Pushing the boundaries forward

Historically, magnetic resonance imaging (MRI) has contributed little to the study of Parkinson's disease (PD), but modern MRI approaches have unveiled several complementary markers that are useful for research and clinical applications. Iron- and neuromelanin-sensitive MRI detect qualitative changes in the substantia nigra. Quantitative MRI markers can be derived from diffusion weighted and iron-sensitive imaging or volumetry. Functional brain alterations at rest or during task performance have been captured with functional and arterial spin labeling perfusion MRI. These markers are useful for the diagnosis of PD and atypical parkinsonism, to track disease progression from the premotor stages of these diseases and to better understand the neurobiological basis of clinical deficits. A current research goal using MRI is to generate time-dependent models of the evolution of PD biomarkers that can help understand neurodegeneration and provide reliable markers for therapeutic trials. This article reviews recent advances in MRI biomarker research at high-field (3T) and ultra high field-imaging (7T) in PD and atypical parkinsonism. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

Apathy in Mild Parkinson's Disease: Neuropsychological and Neuroimaging Evidence.

BACKGROUND: Apathy is one of the most common neuropsychiatric symptoms in Parkinson's disease (PD). Few studies have investigated the cognitive and neuroanatomical correlates of apathy in PD, and those which have done so have not controlled for the presence of other neuropsychiatric comorbidities. OBJECTIVE: To explore the cognitive and neuroanatomical correlates of apathy in PD at a mild disease stage. METHODS: Sixty-five PD patients and 24 healthy controls participated in this study. Patients underwent extensive neuropsychological screening, neuropsychiatric assessment using the Neuropsychiatric Inventory, structural MRI scanning, and neurological examination. A voxel-based multiple regression analysis was used to assess the relationship between grey matter volumes and apathy scores. RESULTS: Higher apathy scores correlated with lower grey matter volume in several brain areas including the left insula, left inferior/middle/medial frontal gyrus, right anterior cingulate, and the left superior temporal gyrus. Significant impairments were found in tests assessing executive functions, and a trend-level significant difference was observed in long term memory tests in patients with apathy, when compared with patients without apathy. CONCLUSIONS: Apathy was associated with greater levels of atrophy in the frontal and temporal cortex, and anterior cingulate, as well as overall lower level of cognitive performance, particularly in executive function and memory skills. Apathy appears to be associated with cognitive impairments in PD, therefore, treatment of this symptom might mitigate its effects on cognitive performance in this clinical population

Parkinson\u27s disease-related spatial covariance pattern identified with resting-state functional MRI

In this study, we sought to identify a disease-related spatial covariance pattern of spontaneous neural activity in Parkinson\u27s disease using resting-state functional magnetic resonance imaging (MRI). Time-series data were acquired in 58 patients with early to moderate stage Parkinson\u27s disease and 54 healthy controls, and analyzed by Scaled Subprofile Model Principal Component Analysis toolbox. A split-sample analysis was also performed in a derivation sample of 28 patients and 28 control subjects and validated in a prospective testing sample of 30 patients and 26 control subjects. The topographic pattern of neural activity in Parkinson\u27s disease was characterized by decreased activity in the striatum, supplementary motor area, middle frontal gyrus, and occipital cortex, and increased activity in the thalamus, cerebellum, precuneus, superior parietal lobule, and temporal cortex. Pattern expression was elevated in the patients compared with the controls, with a high accuracy (90%) to discriminate the patients from the controls. The split-sample analysis produced a similar pattern but with a lower accuracy for group discrimination in both the derivation (80%) and the validation (73%) samples. Our results showed that resting-state functional MRI can be potentially useful for identification of Parkinson\u27s disease-related spatial covariance patterns, and for differentiation of Parkinson\u27s disease patients from healthy controls at an individual level.Journal of Cerebral Blood Flow & Metabolism advance online publication, 3 June 2015; doi:10.1038/jcbfm.2015.118

Resting State Functional Connectivity of the Supplementary Motor Area and the Caudate Nucleus in Prodromal Huntington\u27s Disease

Huntington’s disease (HD) is a fatal neurodegenerative genetic disease that causes motor difficulties, mood impairment, and cognitive dysfunction. Prodromal Huntington’s disease (PrHD) refers to people who carry the mutated huntingtin (htt) gene, but do not yet fit the criteria needed for a full diagnosis. Changes in mood typically begin in the prodromal phase, and apathy is a particularly devastating change that progresses in severity throughout the course of the disease. We investigated neural connectivity changes that could be associated with apathy severity within this population. We performed a seed-based connectivity analysis on resting state scans of 89 (PrHD) patients, with the supplementary motor area, bilateral caudate and caudate head as our regions of interest. We found that apathy severity was significantly correlated with increased connectivity between the caudate head and the supplementary motor area (p = 0.03). Further analyses are needed to establish the extent of the effect of caudate atrophy on this relationship, which we would predict would be highly related due to the degenerative nature of the disease

Cognitive and neuroanatomical correlates of neuropsychiatric symptoms in Parkinson's disease: A systematic review

Introduction Neuropsychiatric symptoms are one of the most common non-motor symptoms in Parkinson's disease (PD). These symptoms have a negative impact on daily living activities and cognitive abilities. This review will be centred on published articles which focused on clarifying the cognitive and neuroanatomical features associated with the appearance of specific neuropsychiatric symptoms in this disease. Methods All articles indexed in the Web of Science and PubMed databases were reviewed for potential inclusion in October 2014. In the first stage of the review, we identified 41 articles that investigated neuropsychiatric symptoms and cognitive impairments in PD. In the second stage, there were 26 published articles on the neural bases of neuropsychiatric symptoms in PD. Results The main findings revealed that executive dysfunctions were common in patients with depression, apathy, visual hallucinations (VH), impulse control disorders (ICDs) and anxiety, whereas, memory deficits were associated mainly with depression and VH. Imaging studies have shown that frontal lobe atrophy was frequently observed in patients with depression, apathy, VH and ICDs. Conclusion This review gives a snapshot of those cognitive and neural correlates of neuropsychiatric symptoms in PD. Methodological shortcoming in the available studies were identified, however, of which the most critical appeared neglecting the presence of multiple neuropsychiatric symptoms in some of the patients included in studies of specific individual symptoms. Additionally, in most studies only patients in the moderate to severe stages were included which limits possible inferences to the early stage of the disease

The role of high-field magnetic resonance imaging in parkinsonian disorders: Pushing the boundaries forward

Historically, magnetic resonance imaging (MRI) has contributed little to the study of Parkinson's disease (PD), but modern MRI approaches have unveiled several complementary markers that are useful for research and clinical applications. Iron- and neuromelanin-sensitive MRI detect qualitative changes in the substantia nigra. Quantitative MRI markers can be derived from diffusion weighted and iron-sensitive imaging or volumetry. Functional brain alterations at rest or during task performance have been captured with functional and arterial spin labeling perfusion MRI. These markers are useful for the diagnosis of PD and atypical parkinsonism, to track disease progression from the premotor stages of these diseases and to better understand the neurobiological basis of clinical deficits. A current research goal using MRI is to generate time-dependent models of the evolution of PD biomarkers that can help understand neurodegeneration and provide reliable markers for therapeutic trials. This article reviews recent advances in MRI biomarker research at high-field (3T) and ultra high field-imaging (7T) in PD and atypical parkinsonism.For information regarding funding, please visit the publisher's website

The Effects of SNCA rs894278 on Resting-State Brain Activity in Parkinson’s Disease

The pathogenesis of Parkinson’s disease (PD) is not well established. The rs894278 polymorphism of SNCA has been associated with PD. We performed this study to investigate the relationship between rs894278 and PD status on resting-state brain activity, by analyzing the amplitude of low-frequency fluctuation (ALFF). A total of 81 PD patients and 64 healthy controls were recruited. Disease severity and PD stage were evaluated in PD patients using the unified Parkinson’s disease rating scale (UPDRS) and the Hoehn and Yahr (HY) scale, while the cognitive function of all participants was assessed using the mini-mental state examination (MMSE). All participants were genotyped for the rs894278 SNP and underwent a resting state functional magnetic resonance imaging scan. We found that the ALFF values of PD patients in the lingual gyrus and left caudate were lower than those of HCs; and the ALFF values for the right fusiform of participants with G allele were lower than those of participants without G allele. And we further revealed higher ALFF values in bilateral fusiform in rs894278-G carriers than in rs894278-G non-carriers in the PD group and lower ALFF values in bilateral fusiform in rs894278-G carriers than in rs894278-G non-carriers in the HC group. Our findings show that rs894278 and PD status interactively affect the brain activity of PD patients and HCs, and changes in the brain connectomes may play a key role in the pathogenesis of PD. Thus, our work sheds light on the mechanism underlying PD pathogenesis

Biomarkers for Dementia, Fatigue, and Depression in Parkinson's Disease

Parkinson's disease is a common multisystem neurodegenerative disorder characterized by typical motor and non-motor symptoms. There is an urgent need for biomarkers for assessment of disease severity, complications and prognosis. In addition, biomarkers reporting the underlying pathophysiology assist in understanding the disease and developing neuroprotective therapies. Ultimately, biomarkers could be used to develop a more efficient personalized approach for clinical trials and treatment strategies. With the goal to improve quality of life in Parkinson's disease it is essential to understand and objectively monitor non-motor symptoms. This narrative review provides an overview of recent developments of biomarkers (biofluid samples and imaging) for three common neuropsychological syndromes in Parkinson's disease: dementia, fatigue, and depression