fMRI-based spatio-temporal parcellations of the human brain.

PURPOSE OF REVIEW: Human brain parcellation based on functional magnetic resonance imaging (fMRI) plays an essential role in neuroscience research. By segmenting vast and intricate fMRI data into functionally similar units, researchers can better decipher the brain's structure in both healthy and diseased states. This article reviews current methodologies and ideas in this field, while also outlining the obstacles and directions for future research. RECENT FINDINGS: Traditional brain parcellation techniques, which often rely on cytoarchitectonic criteria, overlook the functional and temporal information accessible through fMRI. The adoption of machine learning techniques, notably deep learning, offers the potential to harness both spatial and temporal information for more nuanced brain segmentation. However, the search for a one-size-fits-all solution to brain segmentation is impractical, with the choice between group-level or individual-level models and the intended downstream analysis influencing the optimal parcellation strategy. Additionally, evaluating these models is complicated by our incomplete understanding of brain function and the absence of a definitive "ground truth". SUMMARY: While recent methodological advancements have significantly enhanced our grasp of the brain's spatial and temporal dynamics, challenges persist in advancing fMRI-based spatio-temporal representations. Future efforts will likely focus on refining model evaluation and selection as well as developing methods that offer clear interpretability for clinical usage, thereby facilitating further breakthroughs in our comprehension of the brain.

Investigating the efficacy and importance of mobile-based assessments for Parkinson's disease: uncovering the potential of novel digital tests.

This study introduces PDMotion, a mobile application comprising 11 digital tests, including those adapted from the MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III and novel assessments, for remote Parkinson's Disease (PD) motor symptoms evaluation. Employing machine learning techniques on data from 50 PD patients and 29 healthy controls, PDMotion achieves accuracies of 0.878 for PD status prediction and 0.715 for severity assessment. A post-hoc explanation model is employed to assess the importance of features and tasks in diagnosis and severity evaluation. Notably, novel tasks that are not adapted from MDS-UPDRS Part III like the circle drawing, coordination test, and alternative tapping test are found to be highly important, suggesting digital assessments for PD can go beyond digitizing existing tests. The alternative tapping test emerges as the most significant task. Using its features alone achieves prediction accuracies comparable to the full task set, underscoring its potential as an independent screening tool. This study addresses a notable research gap by digitalizing a wide array of tests, including novel ones, and conducting a comparative analysis of their feature and task importance. These insights provide guidance for task selection and future development in PD mobile assessments, a field previously lacking such comparative studies.

Artificial intelligence-based video monitoring of movement disorders in the elderly: a review on current and future landscapes.

ABSTRACT: Due to global ageing, the burden of chronic movement and neurological disorders (Parkinson's disease and essential tremor) is rapidly increasing. Current diagnosis and monitoring of these disorders rely largely on face-to-face assessments utilising clinical rating scales, which are semi-subjective and time-consuming. To address these challenges, the utilisation of artificial intelligence (AI) has emerged. This review explores the advantages and challenges associated with using AI-driven video monitoring to care for elderly patients with movement disorders. The AI-based video monitoring systems offer improved efficiency and objectivity in remote patient monitoring, enabling real-time analysis of data, more uniform outcomes and augmented support for clinical trials. However, challenges, such as video quality, privacy compliance and noisy training labels, during development need to be addressed. Ultimately, the advancement of video monitoring for movement disorders is expected to evolve towards discreet, home-based evaluations during routine daily activities. This progression must incorporate data security, ethical considerations and adherence to regulatory standards.

Apathy scores in Parkinson's disease relate to EEG components in an incentivized motor task.

Apathy is one of the most prevalent non-motor symptoms of Parkinson's disease and is characterized by decreased goal-directed behaviour due to a lack of motivation and/or impaired emotional reactivity. Despite its high prevalence, the neurophysiological mechanisms underlying apathy in Parkinson's disease, which may guide neuromodulation interventions, are poorly understood. Here, we investigated the neural oscillatory characteristics of apathy in Parkinson's disease using EEG data recorded during an incentivized motor task. Thirteen Parkinson's disease patients with apathy and 13 Parkinson's disease patients without apathy as well as 12 healthy controls were instructed to squeeze a hand grip device to earn a monetary reward proportional to the grip force they used. Event-related spectral perturbations during the presentation of a reward cue and squeezing were analysed using multiset canonical correlation analysis to detect different orthogonal components of temporally consistent event-related spectral perturbations across trials and participants. The first component, predominantly located over parietal regions, demonstrated suppression of low-beta (12-20 Hz) power (i.e. beta desynchronization) during reward cue presentation that was significantly smaller in Parkinson's disease patients with apathy compared with healthy controls. Unlike traditional event-related spectral perturbation analysis, the beta desynchronization in this component was significantly correlated with clinical apathy scores. Higher monetary rewards resulted in larger beta desynchronization in healthy controls but not Parkinson's disease patients. The second component contained gamma and theta frequencies and demonstrated exaggerated theta (4-8 Hz) power in Parkinson's disease patients with apathy during the reward cue and squeezing compared with healthy controls (HCs), and this was positively correlated with Montreal Cognitive Assessment scores. The third component, over central regions, demonstrated significantly different beta power across groups, with apathetic groups having the lowest beta power. Our results emphasize that altered low-beta and low-theta oscillations are critical for reward processing and motor planning in Parkinson's disease patients with apathy and these may provide a target for non-invasive neuromodulation.

Clinically Informed Automated Assessment of Finger Tapping Videos in Parkinson's Disease.

The utilization of Artificial Intelligence (AI) for assessing motor performance in Parkinson's Disease (PD) offers substantial potential, particularly if the results can be integrated into clinical decision-making processes. However, the precise quantification of PD symptoms remains a persistent challenge. The current standard Unified Parkinson's Disease Rating Scale (UPDRS) and its variations serve as the primary clinical tools for evaluating motor symptoms in PD, but are time-intensive and prone to inter-rater variability. Recent work has applied data-driven machine learning techniques to analyze videos of PD patients performing motor tasks, such as finger tapping, a UPDRS task to assess bradykinesia. However, these methods often use abstract features that are not closely related to clinical experience. In this paper, we introduce a customized machine learning approach for the automated scoring of UPDRS bradykinesia using single-view RGB videos of finger tapping, based on the extraction of detailed features that rigorously conform to the established UPDRS guidelines. We applied the method to 75 videos from 50 PD patients collected in both a laboratory and a realistic clinic environment. The classification performance agreed well with expert assessors, and the features selected by the Decision Tree aligned with clinical knowledge. Our proposed framework was designed to remain relevant amid ongoing patient recruitment and technological progress. The proposed approach incorporates features that closely resonate with clinical reasoning and shows promise for clinical implementation in the foreseeable future.

Multi-Level Ethical Considerations of Artificial Intelligence Health Monitoring for People Living with Parkinson's Disease.

Artificial intelligence (AI) has garnered tremendous attention in health care, and many hope that AI can enhance our health system's ability to care for people with chronic and degenerative conditions, including Parkinson's Disease (PD). This paper reports the themes and lessons derived from a qualitative study with people living with PD, family caregivers, and health care providers regarding the ethical dimensions of using AI to monitor, assess, and predict PD symptoms and progression. Thematic analysis identified ethical concerns at four intersecting levels: personal, interpersonal, professional/institutional, and societal levels. Reflecting on potential benefits of predictive algorithms that can continuously collect and process longitudinal data, participants expressed a desire for more timely, ongoing, and accurate information that could enhance management of day-to-day fluctuations and facilitate clinical and personal care as their disease progresses. Nonetheless, they voiced concerns about intersecting ethical questions around evolving illness identities, familial and professional care relationships, privacy, and data ownership/governance. The multi-layer analysis provides a helpful way to understand the ethics of using AI in monitoring and managing PD and other chronic/degenerative conditions.

Sex, myelin, and clinical characteristics of Parkinson's disease.

Objective: To determine if there are sex differences in myelin in Parkinson's disease, and whether these explain some of the previously-described sex differences in clinical presentation. Methods: Thirty-three subjects (23 males, 10 females) with Parkinson's disease underwent myelin water fraction (MWF) imaging, an MRI scanning technique of in vivo myelin content. MWF of 20 white matter regions of interest (ROIs) were assessed. Motor symptoms were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS). Principal component analysis, logistic and multiple linear regressions, and t-tests were used to determine which white matter ROIs differed between sexes, the clinical features associated with these myelin changes, and if overall MWF and MWF laterality differed between males and females. Results: Consistent with prior reports, tremor and bradykinesia were more likely seen in females, whereas rigidity and axial symptoms were more likely seen in males in our cohort. MWF of the thalamic radiation, cingulum, cingulum hippocampus, inferior fronto-occipital fasciculi, inferior longitudinal fasciculi, and uncinate were significant in predicting sex. Overall MWF and asymmetry of MWF was greater in males. MWF differences between sexes were associated with tremor symptomatology and asymmetry of motor performance. Conclusion: Sex differences in myelin are associated with tremor and asymmetry of motor presentation. While preliminary, our results suggest that further investigation of the role of biological sex in myelin pathology and clinical presentation in Parkinson's disease is warranted.

Automatic labeling of Parkinson's Disease gait videos with weak supervision.

Motor dysfunction in Parkinson's Disease (PD) patients is typically assessed by clinicians employing the Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Such comprehensive clinical assessments are time-consuming, expensive, semi-subjective, and may potentially result in conflicting labels across different raters. To address this problem, we propose an automatic, objective, and weakly-supervised method for labeling PD patients' gait videos. The proposed method accepts videos of patients and classifies their gait scores as normal (Gait score in MDS-UPDRS = 0) or PD (MDS-UPDRS ≥ 1). Unlike previous work, the proposed method does not require a priori MDS-UPDRS ratings for training, utilizing only domain-specific knowledge obtained from neurologists. We propose several labeling functions that classify patients' gait and use a generative model to learn the accuracy of each labeling function in a self-supervised manner. Since results depended upon the estimated values of the patients' 3D poses, and existing pre-trained 3D pose estimators did not yield accurate results, we propose a weakly-supervised 3D human pose estimation method for fine-tuning pre-trained models in a clinical setting. Using leave-one-out evaluations, the proposed method obtains an accuracy of 89% on a dataset of 29 PD subjects - a significant improvement compared to previous work by 7%-10% depending upon the dataset. The method obtained state-of-the-art results on the Human3.6M dataset. Our results suggest that the use of labeling functions may provide a robust means to interpret and classify patient-oriented videos involving motor tasks.

An Individualized Multi-Modal Approach for Detection of Medication "Off" Episodes in Parkinson's Disease via Wearable Sensors.

The primary treatment for Parkinson's disease (PD) is supplementation of levodopa (L-dopa). With disease progression, people may experience motor and non-motor fluctuations, whereby the PD symptoms return before the next dose of medication. Paradoxically, in order to prevent wearing-off, one must take the next dose while still feeling well, as the upcoming off episodes can be unpredictable. Waiting until feeling wearing-off and then taking the next dose of medication is a sub-optimal strategy, as the medication can take up to an hour to be absorbed. Ultimately, early detection of wearing-off before people are consciously aware would be ideal. Towards this goal, we examined whether or not a wearable sensor recording autonomic nervous system (ANS) activity could be used to predict wearing-off in people on L-dopa. We had PD subjects on L-dopa record a diary of their on/off status over 24 hours while wearing a wearable sensor (E4 wristband®) that recorded ANS dynamics, including electrodermal activity (EDA), heart rate (HR), blood volume pulse (BVP), and skin temperature (TEMP). A joint empirical mode decomposition (EMD) / regression analysis was used to predict wearing-off (WO) time. When we used individually specific models assessed with cross-validation, we obtained > 90% correlation between the original OFF state logged by the patients and the reconstructed signal. However, a pooled model using the same combination of ASR measures across subjects was not statistically significant. This proof-of-principle study suggests that ANS dynamics can be used to assess the on/off phenomenon in people with PD taking L-dopa, but must be individually calibrated. More work is required to determine if individual wearing-off detection can take place before people become consciously aware of it.

PA-Tran: Learning to Estimate 3D Hand Pose with Partial Annotation.

This paper tackles a novel and challenging problem-3D hand pose estimation (HPE) from a single RGB image using partial annotation. Most HPE methods ignore the fact that the keypoints could be partially visible (e.g., under occlusions). In contrast, we propose a deep-learning framework, PA-Tran, that jointly estimates the keypoints status and 3D hand pose from a single RGB image with two dependent branches. The regression branch consists of a Transformer encoder which is trained to predict a set of target keypoints, given an input set of status, position, and visual features embedding from a convolutional neural network (CNN); the classification branch adopts a CNN for estimating the keypoints status. One key idea of PA-Tran is a selective mask training (SMT) objective that uses a binary encoding scheme to represent the status of the keypoints as observed or unobserved during training. In addition, by explicitly encoding the label status (observed/unobserved), the proposed PA-Tran can efficiently handle the condition when only partial annotation is available. Investigating the annotation percentage ranging from 50-100%, we show that training with partial annotation is more efficient (e.g., achieving the best 6.0 PA-MPJPE when using about 85% annotations). Moreover, we provide two new datasets. APDM-Hand, is for synthetic hands with APDM sensor accessories, which is designed for a specific hand task. PD-APDM-Hand, is a real hand dataset collected from Parkinson's Disease (PD) patients with partial annotation. The proposed PA-Tran can achieve higher estimation accuracy when evaluated on both proposed datasets and a more general hand dataset.

Connectivity-Based Brain Parcellation for Parkinson's Disease.

Connectivity-based parcellation (CBP) studies for exploring cerebral topographic organization have emerged rapidly, likely due to the joint developments of non-invasive imaging technologies and advances in computing science. CBP studies have extended our understanding of human brain development and many brain-related disorders such as Parkinson's Disease (PD), and have provided promising approaches to guide electrode placement during the planning of deep brain stimulation (DBS) surgery. This work reviews prevalent CBP methods, summarizing the methodological advantages and limitations of each. As PD is the second most common neurodegenerative disorder, we particularly focus on data-driven parcellation studies in this disease, providing researchers with a comprehensive overview of PD-specific atlases and their applications. We show that, while many advances have been achieved, heterogeneity in the PD population still provides an ongoing challenge to find a robust consensus on regional representation. Although some parcellation-driven studies exhibit encouraging achievements, these PD-specific parcellations are still limited and most approaches depend on a single modality. We discuss the future directions of parcellation-driven PD exploration and surgical planning, with the aim to inspire future investigation into connectivity-based parcellation for PD.

Spatiotemporal patterns of putaminal dopamine processing in Parkinson's disease: A multi-tracer positron emission tomography study.

Alterations in different aspects of dopamine processing may exhibit different progressive behaviours throughout the course of Parkinson's disease. We used a novel data-driven multivariate approach to quantify and compare spatiotemporal patterns related to different aspects of dopamine processing from cross-sectional Parkinson's subjects obtained with: 1) 69 [11C]±dihydrotetrabenazine (DTBZ) scans, most closely related to dopaminergic denervation; 2) 73 [11C]d-threo-methylphenidate (MP) scans, marker of dopamine transporter density; 3) 50 6-[18F]fluoro-l-DOPA (FD) scans, marker of dopamine synthesis and storage. The anterior-posterior gradient in the putamen was identified as the most salient feature associated with disease progression, however the temporal progression of the spatial gradient was different for the three tracers. The expression of the anterior-posterior gradient was the highest for FD at disease onset compared to that of DTBZ and MP (P = 0.018 and P = 0.047 respectively), but decreased faster (P = 0.006) compared to that of DTBZ. The gradient expression for MP was initially similar but decreased faster (P = 0.015) compared to that for DTBZ. These results reflected unique temporal behaviours of regulatory mechanisms related to dopamine synthesis (FD) and reuptake (MP). While the relative early disease upregulation of dopamine synthesis in the anterior putamen prevalent likely extends to approximately 10 years after symptom onset, the presumed downregulation of dopamine transporter density may play a compensatory role in the prodromal/earliest disease stages only.

Atlas-guided parcellation: Individualized functionally-homogenous parcellation in cerebral cortex.

Resting-state Magnetic resonance imaging-based parcellation aims to group the voxels/vertices non-invasively based on their connectivity profiles, which has achieved great success in understanding the fundamental organizational principles of the human brain. Given the substantial inter-individual variability, the increasing number of studies focus on individual parcellation. However, current methods perform individual parcellations independently or are based on the group prior, requiring expensive computational costs, precise parcel alignment, and extra group information. In this work, an efficient and flexible parcellation framework of individual cerebral cortex was proposed based on a region growing algorithm by merging the unassigned and neighbor vertex with the highest-correlated parcel iteratively. It considered both consistency with prior atlases and individualized functional homogeneity of parcels, which can be applied to a single individual without parcel alignment and group information. The proposed framework was leveraged to 100 unrelated subjects for functional homogeneity comparison and individual identification, and 186 patients with Parkison's disease for symptom prediction. Results demonstrated our framework outperformed other methods in functional homogeneity, and the generated parcellations provided 100% individual identification accuracy. Moreover, the default mode network (DMN) exhibited higher functional homogeneity, intra-subject parcel reproducibility and fingerprinting accuracy, while the sensorimotor network did the opposite, reflecting that the DMN is the most representative, stable, and individual-identifiable network in the resting state. The correlation analysis showed that the severity of the disease symptoms was related negatively to the similarity of individual parcellation and the atlases of healthy populations. The disease severity can be correctly predicted using machine learning models based on individual topographic features such as parcel similarity and parcel size. In summary, the proposed framework not only significantly improves the functional homogeneity but also captures individualized and disease-related brain topography, serving as a potential tool to explore brain function and disease in the future.

Home EEG sleep assessment shows reduced slow-wave sleep in mild-moderate Alzheimer's disease.

Introduction: Sleep disturbances are common in Alzheimer's disease (AD), with estimates of prevalence as high as 65%. Recent work suggests that specific sleep stages, such as slow-wave sleep (SWS) and rapid eye movement (REM), may directly impact AD pathophysiology. A major limitation to sleep staging is the requirement for clinical polysomnography (PSG), which is often not well tolerated in patients with dementia. We have recently developed a deep learning model to reliably analyze lower quality electroencephalogram (EEG) data obtained from a simple, two-lead EEG headband. Here we assessed whether this methodology would allow for home EEG sleep staging in patients with mild-moderate AD. Methods: A total of 26 mild-moderate AD patients and 24 age-matched, healthy control participants underwent home EEG sleep recordings as well as actigraphy and subjective sleep measures through the Pittsburgh Sleep Quality Index (PSQI). Each participant wore the EEG headband for up to three nights. Sleep was staged using a deep learning model previously developed by our group, and sleep stages were correlated with actigraphy measures as well as PSQI scores. Results: We show that home EEG with a headband is feasible and well tolerated in patients with AD. Patients with mild-moderate AD were found to spend less time in SWS compared to healthy control participants. Other sleep stages were not different between the two groups. Actigraphy or the PSQI were not found to predict home EEG sleep stages. Discussion: Our data show that home EEG is well tolerated, and can ascertain reduced SWS in patients with mild-moderate AD. Similar findings have previously been reported, but using clinical PSG not suitable for the home environment. Home EEG will be particularly useful in future clinical trials assessing potential interventions that may target specific sleep stages to alter the pathogenesis of AD. Highlights: Home electroencephalogram (EEG) sleep assessments are important for measuring sleep in patients with dementia because polysomnography is a limited resource not well tolerated in this patient population.Simplified at-home EEG for sleep assessment is feasible in patients with mild-moderate Alzheimer's disease (AD).Patients with mild-moderate AD exhibit less time spent in slow-wave sleep in the home environment, compared to healthy control participants.Compared to healthy control participants, patients with mild-moderate AD spend more time in bed, with decreased sleep efficiency, and more awakenings as measured by actigraphy, but these measures do not correlate with EEG sleep stages.

A Joint Constrained CCA Model for Network-Dependent Brain Subregion Parcellation.

Connectivity-based brain region parcellation from functional magnetic resonance imaging (fMRI) data is complicated by heterogeneity among aged and diseased subjects, particularly when the data are spatially transformed to a common space. Here, we propose a group-guided functional brain region parcellation model capable of obtaining subregions from a target region with consistent connectivity profiles across multiple subjects, even when the fMRI signals are kept in their native spaces. The model is based on a joint constrained canonical correlation analysis (JC-CCA) method that achieves group-guided parcellation while allowing the data dimension of the parcellated regions for each subject to vary. We performed extensive experiments on synthetic and real data to demonstrate the superiority of the proposed model compared to other classical methods. When applied to fMRI data of subjects with and without Parkinson's disease (PD) to estimate the subregions in the Putamen, significant between-group differences were found in the derived subregions and the connectivity patterns. Superior classification and regression results were obtained, demonstrating its potential in clinical practice.

Walking exercise alters pedunculopontine nucleus connectivity in Parkinson's disease in a dose-dependent manner.

Background: Gait disturbances are critical motor symptoms in Parkinson's disease (PD). The mechanisms of gait impairment in PD are not entirely understood but likely involve changes in the Pedunculopontine Nucleus (PPN), a critical locomotion center, and its associated connections. Exercise is universally accepted as helpful in PD, but the extent and intensity of exercise required for plastic changes are unclear. Methods: Twenty-seven PD subjects participated in a 3-month gait training intervention. Clinical assessments and resting-state functional magnetic resonance imaging were performed at baseline and 3 months after exercise. Functional connectivity of PPN was assessed by combining the methods of partial least squares, conditional dependence and partial correlation. In addition, paired t-tests were used to examine the effect of exercise on PPN functional connectivity and clinical measures, and Pearson's correlation was used to assess the association between altered PPN functional connectivity and clinical measures. Results: Exercise significantly improved Unified Parkinson's Disease Rating Scale-III (UPDRS-III). A significant increase in right PPN functional connectivity was observed after exercise, which did not correlate with motor improvement. However, the decrease in left PPN functional connectivity significantly correlated with the improvement in UPDRS-III and was linearly related to both number of walks and the duration of walks. In addition, exercise induced a significant increase in the laterality of PPN connectivity strength, which correlated with motor improvement. Conclusion: PPN functional connectivity is modifiable by walking exercise in both a dose-independent (right PPN and laterality of PPN connectivity strength) and dose-dependent (left PPN) manner. The PPN may contribute to pathological and compensatory processes in PD gait control. The observed gait improvement by walking exercise is most likely due to the reversal of the maladaptive compensatory mechanism. Altered PPN functional connectivity can be a marker for exercise-induced motor improvement in PD.

Preservation of Eye Movements in Parkinson's Disease Is Stimulus- and Task-Specific.

Parkinson's disease (PD) is a neurodegenerative disease that includes motor impairments, such as tremor, bradykinesia, and postural instability. Although eye movement deficits are commonly found in saccade and pursuit tasks, preservation of oculomotor function has also been reported. Here we investigate specific task and stimulus conditions under which oculomotor function in PD is preserved. Sixteen PD patients and 18 healthy, age-matched controls completed a battery of movement tasks that included stationary or moving targets eliciting reactive or deliberate eye movements: pro-saccades, anti-saccades, visually guided pursuit, and rapid go/no-go manual interception. Compared with controls, patients demonstrated systematic impairments in tasks with stationary targets: pro-saccades were hypometric and anti-saccades were incorrectly initiated toward the cued target in ∼35% of trials compared with 14% errors in controls. In patients, task errors were linked to short latency saccades, indicating abnormalities in inhibitory control. However, patients' eye movements in response to dynamic targets were relatively preserved. PD patients were able to track and predict a disappearing moving target and make quick go/no-go decisions as accurately as controls. Patients' interceptive hand movements were slower on average but initiated earlier, indicating adaptive processes to compensate for motor slowing. We conclude that PD patients demonstrate stimulus and task dependency of oculomotor impairments, and we propose that preservation of eye and hand movement function in PD is linked to a separate functional pathway through the superior colliculus-brainstem loop that bypasses the fronto-basal ganglia network. Our results demonstrate that studying oculomotor and hand movement function in PD can support disease diagnosis and further our understanding of disease progression and dynamics.SIGNIFICANCE STATEMENT Eye movements are a promising clinical tool to aid in the diagnosis of movement disorders and to monitor disease progression. Although Parkinson's disease (PD) patients show some oculomotor abnormalities, it is not clear whether previously described eye movement impairments are task-specific. We assessed eye movements in PD under different visual (stationary vs moving targets) and movement (reactive vs deliberate) conditions. We demonstrate that PD patients are able to accurately track moving objects but make inaccurate eye movements toward stationary targets. The preservation of eye movements toward dynamic stimuli might enable patients to accurately act on the predicted motion path of the moving target. These results can inform the development of tools for the rehabilitation or maintenance of functional performance.

A Multi-sequence MRI Study in Parkinson's Disease: Association Between Rigidity and Myelin.

BACKGROUND: The pathophysiology of rigidity in Parkinson's disease (PD) is poorly understood. Multi-sequence functional and structural brain MRI may further clarify the origin of this clinical characteristic. PURPOSE: To examine both joint and unique relationships of MRI-based functional and structural imaging modalities to rigidity and other clinical features of PD. STUDY TYPE: Retrospective cross-sectional study. POPULATION: 31 PD subjects (aged 68.0 ± 5.9 years, 21 males) with average disease duration 9.3 ± 5.4 years. FIELD STRENGTH/SEQUENCE: Multi-echo GRASE, diffusion-weighted echo planar imaging (EPI), and blood oxygen level dependent contrast EPI T2*-weighted sequences on a 3T scanner. ASSESSMENT: Myelin water fraction (MWF) and fractional anisotropy (FA) of 20 white-matter regions of interest (ROIs), and functional connectivity derived from resting-state fMRI among 56 ROIs were assessed. The Unified Parkinson's Disease Rating Scale-Part III, Montreal Cognitive Assessment, Beck Depression Index, and Apathy Rating Scales were used to assess motor and non-motor symptoms. STATISTICAL TESTS: Multiset canonical correlation analysis (MCCA) and canonical correlation analysis (CCA) were utilized to examine the joint and unique relationships of multiple imaging measures with clinical symptoms of PD. A permutation test was used to determine statistical significance (P < 0.05). RESULTS: MCCA revealed a single significant component jointly linking MWF, FA, and functional connectivity to age, bradykinesia, and leg agility, non-motor symptoms of cognition, depression, and apathy, but not rigidity (P = 0.77), tremor (P = 0.50 and 0.67 on the left and right side), or sex (P = 0.54). After controlling for this joint component, CCA found a unique significant association between MWF and rigidity, but no other associations were detected, including with FA (P = 0.87). DATA CONCLUSION: MWF, FA, and functional connectivity can serve as multi-sequence imaging markers to characterize many PD symptoms. However, rigidity in PD is additionally associated with widespread myelin changes. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 3.