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Motor symptoms and gray matter volume change over time. Greater gray matter volume loss over 4 years was associated with AR but not tremor symptom severity at baseline. SPL superior parietal lobule, PCL paracentral lobule.
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The akinetic/rigid (AR) motor subtype of Parkinson’s Disease is associated with increased rates of motor and cognitive decline. Cross-sectional studies examining the neural correlates of AR have found abnormalities in both subcortical and cortical networks involved in motor planning and execution relative to controls. To better understand how these...
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... volume loss across the 4 years in the paracentral (PCL) and posterior superior parietal lobule (SPL) at the whole brain level (Table 2). Though one participant's rate of PCL decline was more than three standard deviations beyond the mean, the correlations between AR and gray matter decline in PCL remained significant after removing this outlier (Fig. 1) and the strength of the correlation did not change significantly (z = −0.47, p = 0.63). Additionally, a cluster in the motor cortex was prominent, though not meeting the cluster corrected significance threshold (k = 148, p = 0.11) ( Table 2). After removing one outlier, the relationship between AR and gray matter decline in the motor ...
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... of the correlation did not change significantly (z = −0.47, p = 0.63). Additionally, a cluster in the motor cortex was prominent, though not meeting the cluster corrected significance threshold (k = 148, p = 0.11) ( Table 2). After removing one outlier, the relationship between AR and gray matter decline in the motor cortex remained significant (Fig. 1) and the strength of the correlation did not change significantly (z = −0.46, p = 0.64). Surprisingly, no significant relationship between AR scores and putamen volume decline were found, even at a more lenient threshold (p < ...
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... contrast, baseline tremor scores did not show any significant relationship with longitudinal gray matter volume changes in the whole brain analyses. The correlations between tremor and gray matter loss in ROIs defined in the above AR analysis were also not statistically significant (Fig. 1). Critically, we found that the correlations between gray matter decline in the above ROIs and AR symptoms were significantly different from the correlations between decline of these ROIs and tremor symptoms (z's = −1.96 − −4.215, p's = <0.001-0.04) 34,35 ...
Citations
... Akinesia/Bradykinesia Index Index evaluating the loss/slowness of spontaneous voluntary limb movement. It is derived by adding the MDS-UPDRS III scores of items from 3.4 to 3.11, 3.13 and 3.14 [36]. MoCA consists of 16 items assessing different cognitive domains, including visuospatial and executive functions, memory, attention and orientation). ...
Although the 6-Minute Walk Test (6MWT) is among the recommended clinical tools to assess gait impairments in individuals with Parkinson’s disease (PD), its standard clinical outcome consists only of the distance walked in 6 min. Integrating a single Inertial Measurement Unit (IMU) could provide additional quantitative and objective information about gait quality complementing standard clinical outcome. This study aims to evaluate the test–retest reliability, validity and discriminant ability of gait parameters obtained by a single IMU during the 6MWT in subjects with mild PD. Twenty-two people with mild PD and ten healthy persons performed the 6MWT wearing an IMU placed on the lower trunk. Features belonging to rhythm and pace, variability, regularity, jerkiness, intensity, dynamic instability and symmetry domains were computed. Test–retest reliability was evaluated through the Intraclass Correlation Coefficient (ICC), while concurrent validity was determined by Spearman’s coefficient. Mann–Whitney U test and the Area Under the receiver operating characteristic Curve (AUC) were then applied to assess the discriminant ability of reliable and valid parameters. Results showed an overall high reliability (ICC ≥ 0.75) and multiple significant correlations with clinical scales in all domains. Several features exhibited significant alterations compared to healthy controls. Our findings suggested that the 6MWT instrumented with a single IMU can provide reliable and valid information about gait features in individuals with PD. This offers objective details about gait quality and the possibility of being integrated into clinical evaluations to better define walking rehabilitation strategies in a quick and easy way.
... Parkinsonism presents initially in 89% of subjects with rigidity and akinesia, and this is found to be highly correlated with dopamine levels in the basal ganglia . This rigidity can be assessed easily through the activity index, as rigidity causes slowness of movement (hypokinesia) and can lead ultimately to akinesia (Kann et al., 2020). This was evident in PD groups, as the lowest values for the activity index were recorded in these mice; amelioration was proven in mice treated with the M-NE. ...
Introduction: Parkinson’s disease (PD) is a neurologic condition exhibiting motor
dysfunction that affects old people. Marula oil (M-Oil) has been used longley in
cosmetics and curing skin disorders. M-Oil is particularly stable due to its high
concentration of monounsaturated fatty acids and natural antioxidants. The
current study formulated M-Oil in an o/w nanoemulsion (M-NE) preparations
and tested its anti-inflammatory and antioxidant actions against experimental
parkinsonism.
Methods: Four experimental groups of male albino mice were used and assigned
as vehicle, PD, PD + M-Oil and PD + M-NE. Locomotor function was evaluated
using the open field test and the cylinder test. Striatal samples were used to
measure inflammatory and oxidative stress markers.
Results: The results indicated poor motor performance of the mice in PD control
group then, improvements were recorded after treatment with crude M-Oil or MNE.
In addition, we found high expression and protein of inflammatory markers
and malondialdehyde levels in PD group which were downregulated by using
doses of crude M-Oil or M-NE. Hence, formulating M-Oil in form of M-NE
enhanced its physical characters.
... Comparing connections patterns revealed that nodes or regions contributed differently to AR and tremor negative networks and only three connections overlapped. Most of the connections in the negative network of AR come from cortical regions, mostly motor strip, which was consistent with previous studies demonstrating a correlation between motor strip dysfunction and worsening AR. 44,51 As for the tremor negative network, most were located in the temporal lobe, while connections from other cortical regions were less prevalent. In previous studies, it was found that patients domained with tremors had lower neural activity in the temporal lobe as compared to other patients. ...
Aims
To detect functional connectomes of akinetic‐rigid (AR) and tremor and compare their connection pattern.
Methods
Resting‐state functional MRI data of 78 drug‐naïve PD patients were enrolled to construct connectomes of AR and tremor via connectome‐based predictive modeling (CPM). The connectomes were further validated with 17 drug‐naïve patients to verify their replication.
Results
The connectomes related to AR and tremor were identified via CPM method and successfully validated in the independent set. Additional regional‐based CPM demonstrated neither AR nor tremor could be simplified to functional changes within a single brain region. Computational lesion version of CPM revealed that parietal lobe and limbic system were the most important regions among AR‐related connectome, and motor strip and cerebellum were the most important regions among tremor‐related connectome. Comparing two connectomes found that the patterns of connection between them were largely distinct, with only four overlapped connections identified.
Conclusion
AR and tremor were found to be associated with functional changes in multiple brain regions. Distinct connection patterns of AR‐related and tremor‐related connectomes suggest different neural mechanisms underlying the two symptoms.
... Frontiers in Neurology 09 frontiersin.org the akinetic/rigid motor subtype patients had reduced activation and greater gray matter loss than that of TD patients (31,32). Similarly, we found that FC between the left Stha and the right SFGdl in TD patients was significantly higher than that in PIGD patients and HCs. ...
Objective
The thalamus is an integrative hub of motor circuits in Parkinson’s disease (PD). This study aimed to investigate the alterations of structure and functional connectivity (FC) of the thalamic subregions in the tremor-dominant (TD) subtype and the postural instability and gait difficulty (PIGD) subtype in PD.
Methods
A total of 59 drug-naïve patients (24 TD and 35 PIGD) and 37 healthy controls were recruited. The volumes of the thalamus and the thalamic subregions were calculated using FreeSurfer. Functional connectivity (FC) analysis of the resting-state functional MRI (rsfMRI) was conducted on the thalamic subregions. Finally, the altered structure and FC were used for correlation analysis with clinical motor scores and for further motor subtypes differentiation.
Results
The volumes of the left posterior parietal thalamus (PPtha) in TD patients were significantly lower than those of PIGD patients. Compared with PIGD patients, TD patients exhibited higher FC between the thalamic subregions, the left middle temporal gyrus (MTG), the right dorsolateral superior frontal gyrus (SFGdl), the left middle occipital gyrus (MOG), and the right superior temporal gyrus (STG). Compared with HCs, TD patients showed higher FC between the thalamic subregions and the right SFGdl, as well as the left MOG. Compared with HCs, PIGD patients showed lower FC between the thalamic subregions and the left MTG. In addition, the altered FC was closely related to clinical symptoms and performed high-discriminative power in differentiating the motor subtypes.
Conclusion
Increased FC between the thalamic subregions and the sensory cortices in TD patients may indicate a better compensatory capacity for impairment of sensory information integration than that in PIGD patients. The altered FC between the thalamus and the MTG was a potential biomarker for the distinction of the PD motor subtypes.
... Patients with PD can be divided into tremor-dominant (TD) and postural instability/gait difficulty dominant (PIGD) subtypes based on their predominant motor symptoms (Nutt 2016). Non-motor dysfunctions and prognosis in patients with PD are heterogeneous, with the PIGD subtype being associated with rapid progression and increased risk of dementia compared to the TD subtype (Kann et al. 2020). ...
Cerebellar dysfunction may substantially contribute to the clinical symptoms of Parkinson’s disease (PD). The role of cerebellar subregions in tremors and gait disturbances in PD remains unknown. To investigate alterations in cerebellar subregion volumes and functional connectivity (FC), as well as FC between the dentate nucleus (DN) and ventral lateral posterior nucleus (VLp) of the thalamus, which are potentially involved in different PD motor subtypes. We conducted morphometric and resting-state functional connectivity analyses in various cerebellar subregions in 22 tremor-dominant (TD)-PD and 35 postural instability gait difficulty dominant (PIGD)-PD patients and 38 sex- and age-matched healthy controls (HCs). The volume and FC alterations in various cerebellar subregions and the neural correlates of these changes with the clinical severity scores were investigated. The PIGD-PD group showed greater FC between the right motor cerebellum (CBMm) and left postcentral gyrus than the HC group, and a higher FC was associated with less severe PIGD symptoms. In contrast, the TD-PD group had decreased FC between the right DN and left VLp compared with the PIGD-PD and HC groups, and lower FC was associated with worse TD symptoms. Furthermore, the PIGD-PD group had higher FC between the left DN and left inferior temporal gyrus than the TD-PD group. Morphometric analysis revealed that the TD-PD group showed a significantly higher volume of left CBMm than the HC group. Our findings point to differential alteration patterns in cerebellar subregions and offer a new perspective on the pathophysiology of motor subtypes of PD.
... Compared with HCs, patients with the AR subtype showed significantly decreased cortical surface area in the left superior parietal gyrus, the left paracentral lobule, and bilateral superior frontal gyrus in the AR subtype. These results are consistent with a previous study showing significant AR-related gray matter volume reduction and functional connectivity alterations in similar regions in PD patients 16 . The superior parietal gyrus has been involved in the integration of sensory and motor-planning processes as its anterior and posterior subregions are respectively connected with regions critically involved in sensory processing and executive functions 17,18 . ...
Parkinson’s disease (PD) can be classified into an akinetic-rigid (AR) and a tremor-dominant (TD) subtype based on predominant motor symptoms. Patients with different motor subtypes often show divergent clinical manifestations; however, the underlying neural mechanisms remain unclear. This study aimed to characterize the cortical and subcortical morphological alterations in motor subtypes of PD. T1-weighted MRI images were obtained for 90 patients with PD (64 with the AR subtype and 26 with the TD subtype) and 56 healthy controls (HCs). Cortical surface area, sulcal depth (measured by Freesurfer’s Sulc index), and subcortical volume were computed to identify the cortical and subcortical morphological alterations in the two motor subtypes. Compared with HCs, we found widespread surface area reductions in the AR subtype yet sparse surface area reductions in the TD subtype. We found no significant Sulc change in the AR subtype yet increased Sulc in the right supramarginal gyrus in the TD subtype. The hippocampal volumes in both subtypes were lower than those of HCs. In PD patients, the surface area of left posterior cingulate cortex was positively correlated with Mini-Mental State Examination (MMSE) score, while the Sulc value of right middle frontal gyrus was positively correlated with severity of motor impairments. Additionally, the hippocampal volumes were positively correlated with MMSE and Montreal Cognitive Assessment scores and negatively correlated with severity of motor impairments and Hoehn & Yahr scores. Taken together, these findings may contribute to a better understanding of the neural substrates underlying the distinct symptom profiles in the two PD subtypes.
... 35 Multiple studies have found that PD patients show abnormal structure and function of the precentral gyrus relative to healthy controls. 36,37 Kann et al. 38 reported that PD patients with more severe akinetic rigid symptoms also showed greater loss of gray matter in the motor cortex and superior parietal and paracentral lobules. Cortical thickness in the precentral gyrus is significantly decreased in PD patients with and without freezing of gait. ...
... 39,40 Prior studies have also shown significant changes in the patterns of connections between the precentral gyrus and other brain regions in PD patients. 38,41 Therefore, we hypothesize that progression of PD symptoms is related to structural damage and functional deterioration of the motor cortex. Luo et al. used the amplitude of low-frequency fluctuation method to analyze brain activity in PD patients before and after DBS surgery. ...
OBJECTIVE
After deep brain stimulation (DBS), patients with Parkinson’s disease (PD) show improved motor symptoms and decreased verbal fluency, an effect that occurs before the initiation of DBS in the subthalamic nucleus. However, the underlying mechanism remains unclear. This study aimed to evaluate the effects of DBS on whole-brain degree centrality (DC) and seed-based functional connectivity (FC) in PD patients.
METHODS
The authors obtained resting-state functional MRI data of 28 PD patients before and after DBS surgery. All patients underwent MRI scans in the off-stimulation state. The DC method was used to evaluate the effects of DBS on whole-brain FC at the voxel level. Seed-based FC analysis was used to examine network function changes after DBS.
RESULTS
After DBS surgery, PD patients showed significantly weaker DC values in the left middle temporal gyrus, left supramarginal gyrus, and left middle frontal gyrus, but significantly stronger DC values in the midbrain, left precuneus, and right precentral gyrus. FC analysis revealed decreased FC values within the default mode network (DMN).
CONCLUSIONS
This study demonstrated that the DC of DMN-related brain regions decreased in PD patients after DBS surgery, whereas the DC of the motor cortex increased. These findings provide new evidence for the neural effects of DBS on voxel-based whole-brain networks in PD patients.
... Since the PPMI cohort used in our analysis were drug-naive, de novo PD patients at baseline, our findings suggest that microstructural changes in the CC may play a role in early signs of AR and disease progression. Indeed, we have previously found that AR, but not tremor severity, was related to altered functional connectivity between the cortical motor areas in a similar cohort of early-stage PD subjects 38 . ...
... Given the anatomy, it is possible that these callosal sections may play a crucial role in connecting the frontal and parietal motor areas across the hemispheres, and disruption to these connections may worsen akinetic-rigid symptoms, as previous research has shown that interhemispheric communication between the motor and supplementary cortices are crucial for initiation and planning of voluntary movement 39 . Further, the current findings of these callosoal microstructure changes provide an anatomical underpinning to our previous findings of worse AR symptoms in association with altered functional connectivity between the pre-SMA and paracentral lobule, and between the anterior portions of the superior parietal lobule 38 . These findings together suggest that alterations of callosal microstructure may underlie altered functional connectivity, and these changes may have implications for understanding PD subtype development. ...
Previous diffusion tensor imaging (DTI) studies of Parkinson’s disease (PD) show reduced microstructural integrity of the corpus callosum (CC) relative to controls, although the characteristics of such callosal degradation remain poorly understood. Here, we utilized a longitudinal approach to identify microstructural decline in the entire volume of the CC and its functional subdivisions over 2 years and related the callosal changes to motor symptoms in early-stage PD. The study sample included 61 PD subjects (N = 61, aged 45–82, 38 M & 23 F, H&Y ≤ 2) from the Parkinson’s Progressive Markers Initiative database (PPMI). Whole-brain voxel-wise results revealed significant fractional anisotropy (FA) and mean diffusivity (MD) changes in the CC, especially in the genu and splenium. Using individually drawn CC regions of interest (ROI), our analysis further revealed that almost all subdivisions of the CC show significant decline in FA to certain extents over the two-year timeframe. Additionally, FA seemed lower in the right hemisphere of the CC at both time-points, and callosal FA decline was associated with FA and MD decline in widespread cortical and subcortical areas. Notably, multiple regression analysis revealed that across-subject akinetic-rigid severity was negatively associated with callosal FA at baseline and 24 months follow-up, and the effect was strongest in the anterior portion of the CC. These results suggest that callosal microstructure alterations in the anterior CC may serve as a viable biomarker for akinetic-rigid symptomology and disease progression, even in early PD.
... Previous studies have shown a relationship between predominantly rigid-akinetic phenotypes of PD and a higher prevalence of apathy [26,27]. In this sense, it could be considered that patients with more rigid-akinetic symptomatology and who therefore score higher on bradykinesia-hypokinesia will have not only more severe hypomimia but also more severe apathy. ...
Background and purpose:
Reduced facial expression of emotions is a very frequent symptom of Parkinson's disease (PD) and has been considered part of the motor features of the disease. However, the neural correlates of hypomimia and the relationship between hypomimia and other non-motor symptoms of PD are poorly understood.
Methods:
The clinical and structural brain correlates of hypomimia were studied. For this purpose, cross-sectional data from the COPPADIS study database were used. Age, disease duration, levodopa equivalent daily dose, Unified Parkinson's Disease Rating Scale part III (UPDRS-III), severity of apathy and depression and global cognitive status were collected. At the imaging level, analyses based on gray matter volume and cortical thickness were used.
Results:
After controlling for multiple confounding variables such as age or disease duration, the severity of hypomimia was shown to be indissociable from the UPDRS-III speech and bradykinesia items and was significantly related to the severity of apathy (β = 0.595; p < 0.0001). At the level of neural correlates, hypomimia was related to motor regions brodmann area 8 (BA 8) and to multiple fronto-temporo-parietal regions involved in the decoding, recognition and production of facial expression of emotions.
Conclusion:
Reduced facial expressivity in PD is related to the severity of symptoms of apathy and is mediated by the dysfunction of brain systems involved in motor control and in the recognition, integration and expression of emotions. Therefore, hypomimia in PD may be conceptualized not exclusively as a motor symptom but as a consequence of a multidimensional deficit leading to a symptom where motor and non-motor aspects converge.
... In other words, better clinical outcomes could be linked to treatmentinduced decreased regional low frequency activity in these regions. This supports the notion that distributed cortical networks might be the key for ameliorating parkinsonian features rather than frontostriatal circuits only 40,41 . Many of these cortical regions have also been previously recognized as functional brain hubs, such as the posterior cingulate cortex, superior frontal gyrus, fusiform gyrus, and middle temporal gyrus 31,42 . ...
Subthalamotomy using transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) is a novel and promising treatment for Parkinson’s Disease (PD). In this study, we investigate if baseline brain imaging features can be early predictors of tcMRgFUS-subthalamotomy efficacy, as well as which are the post-treatment brain changes associated with the clinical outcomes. Towards this aim, functional and structural neuroimaging and extensive clinical data from thirty-five PD patients enrolled in a double-blind tcMRgFUS-subthalamotomy clinical trial were analyzed. A multivariate cross-correlation analysis revealed that the baseline multimodal imaging data significantly explain (P < 0.005, FWE-corrected) the inter-individual variability in response to treatment. Most predictive features at baseline included neural fluctuations in distributed cortical regions and structural integrity in the putamen and parietal regions. Additionally, a similar multivariate analysis showed that the population variance in clinical improvements is significantly explained (P < 0.001, FWE-corrected) by a distributed network of concurrent functional and structural brain changes in frontotemporal, parietal, occipital, and cerebellar regions, as opposed to local changes in very specific brain regions. Overall, our findings reveal specific quantitative brain signatures highly predictive of tcMRgFUS-subthalamotomy responsiveness in PD. The unanticipated weight of a cortical-subcortical-cerebellar subnetwork in defining clinical outcome extends the current biological understanding of the mechanisms associated with clinical benefits.
