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Frontiers in Aging Neuroscience 2023Deep gray nuclear pathology relates to motor deterioration in idiopathic Parkinson's disease (PD). Inconsistent deep nuclear diffusion tensor imaging (DTI) findings in...
BACKGROUND
Deep gray nuclear pathology relates to motor deterioration in idiopathic Parkinson's disease (PD). Inconsistent deep nuclear diffusion tensor imaging (DTI) findings in cross-sectional or short-term longitudinal studies have been reported. Long-term studies in PD are clinically challenging; decade-long deep nuclear DTI data are nonexistent. We investigated serial DTI changes and clinical utility in a case-control PD cohort of 149 subjects (72 patients/77 controls) over 12 years.
METHODS
Participating subjects underwent brain MRI at 1.5T; DTI metrics from segmented masks of caudate, putamen, globus pallidus and thalamus were extracted from three timepoints with 6-year gaps. Patients underwent clinical assessment, including Unified Parkinson Disease Rating Scale Part 3 (UPDRS-III) and Hoehn and Yahr (H&Y) staging. A multivariate linear mixed-effects regression model with adjustments for age and gender was used to assess between-group differences in DTI metrics at each timepoint. Partial Pearson correlation analysis was used to correlate clinical motor scores with DTI metrics over time.
RESULTS
MD progressively increased over time and was higher in the putamen ( < 0.001) and globus pallidus ( = 0.002). FA increased ( < 0.05) in the thalamus at year six, and decreased in the putamen and globus pallidus at year 12. Putaminal ( = 0.0210), pallidal ( = 0.0066) and caudate MD ( < 0.0001) correlated with disease duration. Caudate MD ( < 0.05) also correlated with UPDRS-III and H&Y scores.
CONCLUSION
Pallido-putaminal MD showed differential neurodegeneration in PD over 12 years on longitudinal DTI; putaminal and thalamic FA changes were complex. Caudate MD could serve as a surrogate marker to track late PD progression.
PubMed: 37409008
DOI: 10.3389/fnagi.2023.1169254 -
Brain Communications 2020Therapeutic trials of disease-modifying agents in neurodegenerative disease typically require several hundred participants and long durations for clinical endpoints....
Therapeutic trials of disease-modifying agents in neurodegenerative disease typically require several hundred participants and long durations for clinical endpoints. Trials of this size are not feasible for prion diseases, rare dementia disorders associated with misfolding of prion protein. In this situation, biomarkers are particularly helpful. On diagnostic imaging, prion diseases demonstrate characteristic brain signal abnormalities on diffusion-weighted MRI. The aim of this study was to determine whether cerebral water diffusivity could be a quantitative imaging biomarker of disease severity. We hypothesized that the basal ganglia were most likely to demonstrate functionally relevant changes in diffusivity. Seventy-one subjects (37 patients and 34 controls) of whom 47 underwent serial scanning (23 patients and 24 controls) were recruited as part of the UK National Prion Monitoring Cohort. All patients underwent neurological assessment with the Medical Research Council Scale, a functionally orientated measure of prion disease severity, and diffusion tensor imaging. Voxel-based morphometry, voxel-based analysis of diffusion tensor imaging and regions of interest analyses were performed. A significant voxel-wise correlation of decreased Medical Research Council Scale score and decreased mean, radial and axial diffusivities in the putamen bilaterally was observed ( < 0.01). Significant decrease in putamen mean, radial and axial diffusivities over time was observed for patients compared with controls ( = 0.01), and there was a significant correlation between monthly decrease in putamen mean, radial and axial diffusivities and monthly decrease in Medical Research Council Scale ( < 0.001). Step-wise linear regression analysis, with dependent variable decline in Medical Research Council Scale, and covariates age and disease duration, showed the rate of decrease in putamen radial diffusivity to be the strongest predictor of rate of decrease in Medical Research Council Scale ( < 0.001). Sample size calculations estimated that, for an intervention study, 83 randomized patients would be required to provide 80% power to detect a 75% amelioration of decline in putamen radial diffusivity. Putamen radial diffusivity has potential as a secondary outcome measure biomarker in future therapeutic trials in human prion diseases.
PubMed: 32954290
DOI: 10.1093/braincomms/fcaa032 -
Human Brain Mapping Jan 2022To identify neuroimaging biomarkers of alcohol dependence (AD) from structural magnetic resonance imaging, it may be useful to develop classification models that are... (Meta-Analysis)
Meta-Analysis
To identify neuroimaging biomarkers of alcohol dependence (AD) from structural magnetic resonance imaging, it may be useful to develop classification models that are explicitly generalizable to unseen sites and populations. This problem was explored in a mega-analysis of previously published datasets from 2,034 AD and comparison participants spanning 27 sites curated by the ENIGMA Addiction Working Group. Data were grouped into a training set used for internal validation including 1,652 participants (692 AD, 24 sites), and a test set used for external validation with 382 participants (146 AD, 3 sites). An exploratory data analysis was first conducted, followed by an evolutionary search based feature selection to site generalizable and high performing subsets of brain measurements. Exploratory data analysis revealed that inclusion of case- and control-only sites led to the inadvertent learning of site-effects. Cross validation methods that do not properly account for site can drastically overestimate results. Evolutionary-based feature selection leveraging leave-one-site-out cross-validation, to combat unintentional learning, identified cortical thickness in the left superior frontal gyrus and right lateral orbitofrontal cortex, cortical surface area in the right transverse temporal gyrus, and left putamen volume as final features. Ridge regression restricted to these features yielded a test-set area under the receiver operating characteristic curve of 0.768. These findings evaluate strategies for handling multi-site data with varied underlying class distributions and identify potential biomarkers for individuals with current AD.
Topics: Alcoholism; Cerebral Cortex; Humans; Machine Learning; Magnetic Resonance Imaging; Multicenter Studies as Topic; Neuroimaging; Putamen; Reproducibility of Results
PubMed: 33064342
DOI: 10.1002/hbm.25248 -
Minerva Medica Dec 2023
Topics: Humans; Putamen; Punctures
PubMed: 37293891
DOI: 10.23736/S0026-4806.23.08662-7 -
Frontiers in Aging Neuroscience 2022F-FP-DTBZ has been proven as a biomarker for quantifying the concentration of presynaptic vesicular monoamine transporter 2 (VMAT2). However, its clinical application is...
BACKGROUND
F-FP-DTBZ has been proven as a biomarker for quantifying the concentration of presynaptic vesicular monoamine transporter 2 (VMAT2). However, its clinical application is still limited.
OBJECTIVES
To evaluate the difference in dopaminergic integrity between patients with Parkinson's disease (PD) and healthy controls (HC) using F-FP-DTBZ PET and to determine the diagnostic value of standardized uptake value ratios (SUVRs) using the Receiver Operating Characteristic (ROC) curve.
METHODS
A total of 34 PD and 31 HC participants were enrolled in the PET/MR derivation cohort, while 89 PD and 18 HC participants were recruited in the PET/CT validation cohort. The Hoehn-Yahr Scale and the third part of the MDS-Unified Parkinson's Disease Rating Scale (MDSUPDRS-III) were used to evaluate the disease staging and severity. All assessments and PET scanning were performed in drug-off states. The striatum was segmented into five subregions as follows: caudate, anterior dorsal putamen (ADP), anterior ventral putamen (AVP), posterior dorsal putamen (PDP), and posterior ventral putamen (PVP) using automatic pipeline built with the PMOD software (version 4.105). The SUVRs of the targeted subregions were calculated using the bilateral occipital cortex as the reference region.
RESULTS
Regarding the diagnostic value, ROC curve and blind validation showed that the contralateral PDP (SUVR = 3.43) had the best diagnostic accuracy (AUC = 0.973; < 0.05), with a sensitivity of 97.1% (95% CI: 82.9-99.8%), specificity of 100% (95% CI: 86.3-100%), positive predictive value (PPV) of 100% (95% CI: 87.0-100%), negative predictive value (NPV) of 96.9% (95% CI: 82.0-99.8%), and an accuracy of 98.5% for the diagnosis of PD in the derivation cohort. Blind validation of F-FP-DTBZ PET imaging diagnosis was done using the PET/CT cohort, where participants with a SUVR of the PDP <3.43 were defined as PD. Kappa test showed a consistency of 0.933 ( < 0.05) between clinical diagnosis and imaging diagnosis, with a sensitivity of 98.9% (95% CI: 93.0-99.9%), specificity of 94.4% (95% CI: 70.6-99.7%), PPV of 98.9% (95% CI: 93.0-99.9%), NPV of 94.4% (95% CI: 70.6-99.7%), and a diagnostic accuracy of 98.1%.
CONCLUSIONS
Our results showed that an SUVR threshold of 3.43 in the PDP could effectively distinguish patients with PD from HC.
PubMed: 35936768
DOI: 10.3389/fnagi.2022.931015 -
CNS Neuroscience & Therapeutics May 2023Periventricular nodular heterotopia (PNH) is a common type of heterotopia usually characterized by epilepsy. Previous studies have identified alterations in structural...
OBJECTIVE
Periventricular nodular heterotopia (PNH) is a common type of heterotopia usually characterized by epilepsy. Previous studies have identified alterations in structural and functional connectivity related to this disorder, but its local functional neural basis has received less attention. The purpose of this study was to combine univariate analysis and a Gaussian process classifier (GPC) to assess local activity and further explore neuropathological mechanisms in PNH-related epilepsy.
METHODS
We used a 3.0-T scanner to acquire resting-state data and measure local regional homogeneity (ReHo) alterations in 38 patients with PNH-related epilepsy and 38 healthy controls (HCs). We first assessed ReHo alterations by comparing the PNH group to the HC group using traditional univariate analysis. Next, we applied a GPC to explore whether ReHo could be used to differentiate PNH patients from healthy patients at an individual level.
RESULTS
Compared to HCs, PNH-related epilepsy patients exhibited lower ReHo in the left insula extending to the putamen as well as in the subgenual anterior cingulate cortex (sgACC) extending to the orbitofrontal cortex (OFC) [p < 0.05, family-wise error corrected]. Both of these regions were also correlated with epilepsy duration. Furthermore, the ReHo GPC classification yielded a 76.32% accuracy (sensitivity = 71.05% and specificity = 81.58%) with p < 0.001 after permutation testing.
INTERPRETATION
Using the resting-state approach, we identified localized activity alterations in the left insula extending to the putamen and the sgACC extending to the OFC, providing pathophysiological evidence of PNH. These local connectivity patterns may provide a means to differentiate PNH patients from HCs.
Topics: Humans; Magnetic Resonance Imaging; Periventricular Nodular Heterotopia; Epilepsy; Insular Cortex; Putamen
PubMed: 36740260
DOI: 10.1111/cns.14104 -
Frontiers in Aging Neuroscience 2019In an increasingly aging society, it is of great importance to consider trajectories of subcortical volumes at different ages for understanding biological markers of...
PURPOSE
In an increasingly aging society, it is of great importance to consider trajectories of subcortical volumes at different ages for understanding biological markers of aging. Thus, we investigated sex, age, and their interactions on subcortical volumes, including the basal ganglia (caudate, putamen, accumbens, and pallidum), thalamus, hippocampus, and amygdala.
METHODS
We analyzed the adult lifespan trajectory of subcortical volumes and asymmetries in 563 healthy subjects aged from 19 to 86 using magnetic resonance imaging (MRI) data from the publicly available 7IXI data set.
RESULTS
The sex made strong contributions to the trajectories of subcortical volumes with aging, including the right putamen, right pallidum, bilateral thalamus, hippocampus, and amygdala. The volume of the right putamen, right pallidum, and right thalamus decreased more rapidly in males than in females, and the volume of the left thalamus, bilateral hippocampus, and amygdala in males followed a quadratic model, while those in females followed a linear decline model. The asymmetries in the caudate and hippocampus showed a linear decline, and a sex and age interaction was found in the hippocampus; that is, the asymmetry in the hippocampus decreased only in the males and not in the females. Changes in the accumbens and pallidum fit quadratic trajectories, in which females increased until 39.26 years old in the accumbens asymmetry and then began to rapidly decline, and males showed a linear decline. The asymmetry in the pallidum in males and females showed a slow decreasing period until almost 45 years of age and then increased.
CONCLUSION
The results suggest that compared with females, males have a faster decline in the volume of the right putamen, right pallidum, and right thalamus, while aging occurred later but also faster in the left thalamus, bilateral hippocampus, and amygdala. Interestingly, we found the inflection point in the thalamus, bilateral hippocampus, and amygdala volume in the quadratic model, and after this point, the volume change accelerated with aging, which may have resulted from the stronger work pressure in the middle-aged men and the low levels of testosterone in the older adults. The interaction of age and sex on individual subcortical structures provides evidence to support the impact of sex on psychopathologies associated with degenerative brain disorders in the elderly. The findings may be significant to investigate the occurrence and prevalence of degenerative brain disorders in males and females. Future studies can focus on the functional and behavioral relations with subcortical structures for preventive measures of related disorders.
PubMed: 31616285
DOI: 10.3389/fnagi.2019.00259 -
Cerebral Cortex (New York, N.Y. : 1991) Jun 2022The striatum and cerebral cortex are interconnected via multiple recurrent loops that play a major role in many neuropsychiatric conditions. Primate corticostriatal...
The striatum and cerebral cortex are interconnected via multiple recurrent loops that play a major role in many neuropsychiatric conditions. Primate corticostriatal connections can be precisely mapped using invasive tract-tracing. However, noninvasive human research has not mapped these connections with anatomical precision, limited in part by the practice of averaging neuroimaging data across individuals. Here we utilized highly sampled resting-state functional connectivity MRI for individual-specific precision functional mapping (PFM) of corticostriatal connections. We identified ten individual-specific subnetworks linking cortex-predominately frontal cortex-to striatum, most of which converged with nonhuman primate tract-tracing work. These included separable connections between nucleus accumbens core/shell and orbitofrontal/medial frontal gyrus; between anterior striatum and dorsomedial prefrontal cortex; between dorsal caudate and lateral prefrontal cortex; and between middle/posterior putamen and supplementary motor/primary motor cortex. Two subnetworks that did not converge with nonhuman primates were connected to cortical regions associated with human language function. Thus, precision subnetworks identify detailed, individual-specific, neurobiologically plausible corticostriatal connectivity that includes human-specific language networks.
Topics: Animals; Brain Mapping; Corpus Striatum; Frontal Lobe; Humans; Magnetic Resonance Imaging; Motor Cortex; Neural Pathways; Nucleus Accumbens; Prefrontal Cortex; Putamen
PubMed: 34718460
DOI: 10.1093/cercor/bhab387 -
NeuroImage. Clinical 2022Growing evidence points towards dysfunction of the ventral striatum as a neural substrate of motivational impairments in schizophrenia. Ventral striatal activity during...
BACKGROUND
Growing evidence points towards dysfunction of the ventral striatum as a neural substrate of motivational impairments in schizophrenia. Ventral striatal activity during reward anticipation is generally reduced in patients with schizophrenia and specifically correlates with apathy. However, little is known about the cortico-striatal functional connectivity in patients with schizophrenia during reward anticipation and its relation to negative symptoms.
OBJECTIVES
The aim of this study was to identify categorical group differences in ventral striatal functional connectivity during reward anticipation between patients with schizophrenia and healthy controls, and dimensional associations between cortico-striatal functional connectivity and negative symptom severity.
METHOD
A total of 40 patients with schizophrenia (10 females) and 33 healthy controls (8 females) were included from two previously published studies. All participants performed a variant of the Monetary Incentive Delay Task while undergoing event-related fMRI. Functional connectivity was assessed using psychophysical interactions (PPI) with the left and right ventral striatum as seeds and the contrast [High Reward Anticipation - No Reward Anticipation]. Negative symptoms were assessed using the Brief Negative Symptom Scale.
RESULTS
Compared to controls, patients with schizophrenia showed increased functional connectivity between the left ventral striatum and the left precuneus and right parahippocampal gyrus, two hubs of the default mode network (cluster-level threshold: FWE, p < .05). In addition, we found a negative association between apathy scores on the BNSS and increased functional connectivity between the left ventral striatum and the left ventral anterior insula / putamen and the left inferior frontal gyrus / dorsal anterior insula (cluster-level threshold: FWE, p < .05).
CONCLUSIONS
Our results indicate that the patterns of increased functional connectivity between the ventral striatum and the dorsal default mode network during reward anticipation could act as a compensatory mechanism to regulate the activity of the ventral striatum. Our results also showed that functional connectivity patterns from the ventral striatum, much like its local activity, is specifically related to apathy, and not diminished expression.
Topics: Anticipation, Psychological; Female; Humans; Magnetic Resonance Imaging; Motivation; Putamen; Reward; Schizophrenia; Ventral Striatum
PubMed: 35078045
DOI: 10.1016/j.nicl.2022.102944 -
BMC Neurology May 2020Neuropathological data and nuclear medicine imaging show extensive serotonergic impairment in Parkinson's disease (PD). We undertook a case-controlled analysis of...
BACKGROUND
Neuropathological data and nuclear medicine imaging show extensive serotonergic impairment in Parkinson's disease (PD). We undertook a case-controlled analysis of I-FP-CIT SPECT images to measure extrastriatal serotonergic transporters (SERT) in PD using the Parkinson's Progression Markers Initiative (PPMI) cohort.
METHODS
We included all PD (n = 154) and Control subjects (n = 62) with available I-FP-CIT SPECT imaging and high-resolution T1-weighted MRI for coregistration (PD: mean age 61.6 years, 62% male, disease duration 26 months, MDS-UPDRS III score 22). I-FP-CIT SPECT images were processed with PETPVE12 using an exploratory voxel-wise analysis including partial-volume effect correction. Linear regressions were performed in the PD group to assess correlations between region of interest I-FP-CIT uptake and clinical motor and non-motor impairment.
RESULTS
Compared to Controls, PD exhibited an uptake reduction in bilateral caudate nucleus, putamen, insula, amygdala and right pallidum (family-wise error (FWE)-corrected p < 0.05). While lower putaminal uptake on the contralateral side to clinically more affected side was associated with higher MDS-UPDRS III score (p = 0.022), we found a trend association between higher geriatric depression scale and lower pallidum uptake (p = 0.09). Higher SCOPA-AUT gastrointestinal subscore was associated with lower uptake in mean putamen and caudate nucleus (p = 0.01 to 0.03), whereas urological subscore was inversely correlated with mean caudate nucleus, putamen, and pallidum uptake (p = 0.002 to 0.03). REM sleep behaviour disorder screening questionnaire was associated with lower I-FP-CIT binding in caudate nucleus, putamen and pallidum (all p < 0.05). No significant association was found for Montreal Cognitive Assessment (all p > 0.45) or excessive daytime sleepiness (all p > 0.29).
CONCLUSIONS
In addition to the well-established striatal deficit, this study provides evidence of a major extrastriatal I-FP-CIT impairment, and therefore of an altered serotonergic transmission in early PD.
Topics: Adult; Aged; Brain; Case-Control Studies; Cohort Studies; Disease Progression; Female; Humans; Image Interpretation, Computer-Assisted; Iodine Radioisotopes; Male; Middle Aged; Parkinson Disease; Serotonin Plasma Membrane Transport Proteins; Tomography, Emission-Computed, Single-Photon; Tropanes
PubMed: 32416724
DOI: 10.1186/s12883-020-01777-2