To investigate the reliability of a scoring system to differentiate movement severity by observing the signals and transforms of instrumentation to identify the position in space of the extremities of people with Parkinson's disease (PD)
Abstract Neuroinflammation through enhanced innate immunity is thought play a role in the pathogenesis of Parkinson’s disease (PD). Methods for monitoring neuroinflammation in living patients with PD are currently limited to positron emission tomography (PET) ligands that lack specificity in labeling immune cells in the nervous system. The colony stimulating factor 1 receptor (CSF1R) plays a crucial role in microglial function, an important cellular contributor to the nervous system’s innate immune response. Using immunologic methods, we show that CSF1R in human brain is colocalized with the microglial marker, ionized calcium binding adaptor molecule 1 (Iba1). In PD, CSF1R immunoreactivity is significantly increased in PD across multiple brain regions, with the largest differences in the midbrain versus controls. Autoradiography revealed significantly increased [ 3 H]JHU11761 binding in the inferior parietal cortex of PD patients. PET imaging demonstrated that higher [ 11 C]CPPC binding in the striatum was associated with greater motor disability in PD. Furthermore, increased [ 11 C]CPPC binding in various regions correlated with more severe motor disability and poorer verbal fluency. This study finds that CSF1R expression is elevated in PD and that [ 11 C]CPPC-PET imaging of CSF1R is indicative of motor and cognitive impairments in the early stages of the disease. Moreover, the study underscores the significance of CSF1R as a promising biomarker for neuroinflammation in Parkinson’s disease, suggesting its potential use for non-invasive assessment of disease progression and severity, leading to earlier diagnosis and targeted interventions. Significance Statement This study demonstrates that the Colony Stimulating Factor 1 Receptor (CSF1R) colocalizes with microglial markers in the human brain, and the research establishes elevated CSF1R expression in PD autopsy tissues. Employing [ 11 C]CPPC-PET imaging, the study unveils a correlation between increased CSF1R binding and both motor disability and cognitive decline in PD patients. These findings highlight the potential of CSF1R as a novel biomarker for neuroinflammation in PD, offering a non-invasive means to assess disease progression and severity, ultimately contributing to earlier diagnosis and targeted interventions.
Transcranial direct current stimulation (tDCS) is an emerging method, used for non-invasively stimulating the brain in normal healthy subjects and in patients with neurological disorders. However, the pattern of the spatial distribution of the current intensity induced by tDCS is poorly understood. In this study, we directly measured the spatial characteristics of the current intensity induced by tDCS using an intracranial strip electrode array implanted over the motor cortex in patients with Parkinson's disease undergoing deep brain stimulation lead placement surgery. We used a bilateral stimulation configuration for the tDCS electrode placement and measured the amount of electric current passing through the contacts along the implanted strip electrode contacts. Our results showed significant changes of the current flow induced by the tDCS in some of the contacts during stimulation with respect to baseline activities. These results may provide vital information regarding the biophysical effects of tDCS stimulation and might be potentially useful for developing more effective stimulation strategies.
ABSTRACT Objective To investigate hemispheric effects of directional versus ring subthalamic nucleus (STN) deep brain stimulation (DBS) surgery on cognitive function in patients with advanced Parkinson’s disease (PD). Methods We examined 31 PD patients (Left STN n = 17; Right STN n = 14) who underwent unilateral subthalamic nucleus (STN) DBS as part of a NIH-sponsored randomized, cross-over, double-blind (ring vs directional) clinical trial. Outcome measures were tests of verbal fluency, auditory-verbal memory, and response inhibition. First, all participants were pooled together to study the effects of directional versus ring stimulation. Then, we stratified the groups by surgery hemisphere and studied the longitudinal changes in cognition post-unilateral STN DBS. Results Relative to pre-DBS cognitive baseline performances, there were no group changes in cognition following unilateral DBS for either directional or ring stimulation. However, assessment of unilateral DBS by hemisphere revealed a different pattern. The left STN DBS group had lower verbal fluency than the right STN group ( t (20.66 = -2.50, p = 0.02). Over a period of eight months post-DBS, verbal fluency declined in the left STN DBS group ( p = 0.013) and improved in the right STN DBS group over time ( p < .001). Similarly, response inhibition improved following right STN DBS ( p = 0.031). Immediate recall did not significantly differ over time, nor was it affected by implant hemisphere, but delayed recall equivalently declined over time for both left and right STN DBS groups (left STN DBS p = 0.001, right STN DBS differ from left STN DBS p = 0.794). Conclusions Directional and ring DBS did not differentially or adversely affect cognition over time. Regarding hemisphere effects, verbal fluency decline was observed in those who received left STN DBS, along with the left and right STN DBS declines in delayed memory. The left STN DBS verbal fluency decrement is consistent with prior bilateral DBS research, likely reflecting disruption of the basal-ganglia-thalamocortical network connecting STN and inferior frontal gyrus. Interestingly, we found an improvement in verbal fluency and response inhibition following right STN DBS. It is possible that unilateral STN DBS, particularly in the right hemisphere, may mitigate cognitive decline.
A low-cost quantitative structured office measurement of movements in the extremities of people with Parkinson’s disease [1,2] was performed on participants with Parkinson’s disease and multiple system atrophy as well as age- and sex-matched healthy participants with typical development. Participants underwent twelve videotaped procedures rated by a trainer examiner while connected to four accelerometers [1,2] generating a trace of the three location dimensions expressed as spreadsheets [3,4]. The signals of the five repetitive motion items (3.4 Finger tapping, 3.5 Hand movements, 3.6 Pronation-supination movements of hands, 3.7 Toe tapping, and 3.8 Leg agility) [1] underwent processing to fast Fourier [5] and continuous wavelet transforms [6-13]. Images of the signals and their transforms [4,5] of the five repetitive tasks of each participant were randomly expressed as panels on an electronic framework for rating by 35 trained examiners who did not know the source of the original output [14]. The team of international raters completed ratings of the signals and their transforms independently using criteria like the scoring systems for live assessments of movements in human participants [1,2]. The raters scored signals and transforms for deficits in the sustained performance of rhythmic movements (interruptions, slowing, and amplitude decrements) [15-20]. Raters were first presented the images of the signals and transforms of a man with multiple system atrophy as a test and a retest in a different random order. After the raters completed the assessments of the man with multiple system atrophy, they were presented random test and retest panels of the images of signals and transforms of ten participants with Parkinson’s disease who completed a single rating session. After the raters completed the assessments of the participants with Parkinson’s disease who completed one set of ratings, they were presented random test and retest panels of the images of signals and transforms of ten participants with Parkinson’s disease and eight age- and sex-match healthy participants with typical development who completed two rating session separated by a month or more [15-20]. The data provide a framework for further analysis of the acquired information. Additionally, the data provide a template for the construction of electronic frameworks for the remote analysis by trained raters of signals and transforms of rhythmic processes to verify that the systems are operating smoothly without interruptions or changes in frequency and amplitude. Thus, the data provide the foundations to construct electronic frameworks for the virtual quality assurance of a vast spectrum of rhythmic processes.
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