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Psychiatry Research. Neuroimaging Oct 2023Parkinson's disease (PD), multisystem atrophy (MSA), and progressive supranuclear palsy (PSP) present similarly with bradykinesia, tremor, rigidity, and cognitive...
Striatal and thalamic automatic segmentation, morphology, and clinical correlates in Parkinsonism: Parkinson's disease, multiple system atrophy and progressive supranuclear palsy.
Parkinson's disease (PD), multisystem atrophy (MSA), and progressive supranuclear palsy (PSP) present similarly with bradykinesia, tremor, rigidity, and cognitive impairments. Neuroimaging studies have found differential changes in the nigrostriatal pathway in these disorders, however whether the volume and shape of specific regions within this pathway can distinguish between atypical Parkinsonian disorders remains to be determined. This paper investigates striatal and thalamic volume and morphology as distinguishing biomarkers, and their relationship to neuropsychiatric symptoms. Automatic segmentation to calculate volume and shape analysis of the caudate nucleus, putamen, and thalamus were performed in 18 PD patients, 12 MSA, 15 PSP, and 20 healthy controls, then correlated with clinical measures. PSP bilateral thalami and right putamen were significantly smaller than controls, but not MSA or PD. The left caudate and putamen significantly correlated with the Neuropsychiatric Inventory total score. Bilateral thalamus, caudate, and left putamen had significantly different morphology between groups, driven by differences between PSP and healthy controls. This study demonstrated that PSP patient striatal and thalamic volume and shape are significantly different when compared with controls. Parkinsonian disorders could not be differentiated on volumetry or morphology, however there are trends for volumetric and morphological changes associated with PD, MSA, and PSP.
Topics: Humans; Parkinson Disease; Supranuclear Palsy, Progressive; Multiple System Atrophy; Parkinsonian Disorders; Thalamus
PubMed: 37806261
DOI: 10.1016/j.pscychresns.2023.111719 -
Clinical Parkinsonism & Related... 2023Most commonly, hemichorea associated with nonketotic and ketotic hyperglycemia resolves with normalization of blood glucose. Herein, we present a case of hyperosmolar...
Most commonly, hemichorea associated with nonketotic and ketotic hyperglycemia resolves with normalization of blood glucose. Herein, we present a case of hyperosmolar hyperglycemic left hemichoreoathetosis-hemidystonia that has persisted for over 1 year. The subject presented to the emergency room with dysarthria and manifested left hemichoreoathetosis-hemidystonia within 36 h of admission. Initial computed tomography (CT) showed hyperdensity in the right putamen and left caudate. Magnetic resonance imaging (MRI) showed T1 hyperintensity within the right putamen. Failure to detect these classic imaging abnormalities during hospitalization resulted in a delayed etiologic diagnosis. Modest symptomatic improvement in the severity of hemichoreoathetosis-hemidystonia has been noted with low dose tetrabenazine.
PubMed: 37927362
DOI: 10.1016/j.prdoa.2023.100221 -
Frontiers in Neurology 2021The striatum is unevenly impaired bilaterally in Parkinson's disease (PD). Because the striatum plays a key role in cortico-striatal circuits, we assume that...
The striatum is unevenly impaired bilaterally in Parkinson's disease (PD). Because the striatum plays a key role in cortico-striatal circuits, we assume that lateralization affects cortico-striatal functional connectivity in PD. The present study sought to evaluate the effect of lateralization on various cortico-striatal circuits through resting-state functional magnetic resonance imaging (fMRI). Thirty left-onset Parkinson's disease (LPD) patients, 27 right-onset Parkinson's disease (RPD) patients, and 32 normal controls with satisfactory data were recruited. Their demographic, clinical, and neuropsychological information was collected. Resting-state fMRI was performed, and functional connectivity changes of seven subdivisions of the striatum were explored in the two PD groups. In addition, the associations between altered functional connectivity and various clinical and neuropsychological characteristics were analyzed by Pearson's or Spearman's correlation. Directly comparing the LPD and RPD patients demonstrated that the LPD patients had lower FC between the left dorsal rostral putamen and the left orbitofrontal cortex than the RPD patients. In addition, the LPD patients showed aberrant functional connectivity involving several striatal subdivisions in the right hemisphere. The right dorsal caudate, ventral rostral putamen, and superior ventral striatum had decreased functional connectivity with the cerebellum and parietal and occipital lobes relative to the normal control group. The comparison between RPD patients and the controls did not obtain significant difference in functional connectivity. The functional connectivity between the left dorsal rostral putamen and the left orbitofrontal cortex was associated with contralateral motor symptom severity in PD patients. Our findings provide new insights into the distinct characteristics of cortico-striatal circuits in LPD and RPD patients. Lateralization of motor symptoms is associated with lateralized striatal functional connectivity.
PubMed: 34054684
DOI: 10.3389/fneur.2021.619631 -
Neurobiology of Disease Jul 2024Iron overload is observed in neurodegenerative diseases, especially Alzheimer's disease (AD) and Parkinson's disease (PD). Homozygotes for the iron-overload... (Observational Study)
Observational Study
BACKGROUND
Iron overload is observed in neurodegenerative diseases, especially Alzheimer's disease (AD) and Parkinson's disease (PD). Homozygotes for the iron-overload (haemochromatosis) causing HFE p.C282Y variant have increased risk of dementia and PD. Whether brain iron deposition is causal or secondary to the neurodegenerative processes in the general population is unclear.
METHODS
We analysed 39,533 UK Biobank participants of European genetic ancestry with brain MRI data. We studied brain iron estimated by R2* and quantitative susceptibility mapping (QSM) in 8 subcortical regions: accumbens, amygdala, caudate, hippocampus, pallidum, putamen, substantia nigra, and thalamus. We performed genome-wide associations studies (GWAS) and used Mendelian Randomization (MR) methods to estimate the causal effect of brain iron on grey matter volume, and risk of AD, non-AD and PD. We also used MR to test whether genetic liability to AD or PD causally increased brain iron (R2* and QSM).
FINDINGS
In GWAS of R2* and QSM we replicated 83% of previously reported genetic loci and identified 174 further loci across all eight brain regions. Higher genetically predicted brain iron, using both R2* and QSM, was associated with lower grey matter volumes in the caudate, putamen and thalamus (e.g., Beta-putamenQSM: -0.37, p = 2*10-46). Higher genetically predicted thalamus R2* was associated with increased risk of non-AD dementia (OR 1.36(1.16;1.60), p = 2*10-4) but not AD (p > 0.05). In males, genetically predicted putamen R2* increased non-AD dementia risk, but not in females. Higher genetically predicted iron in the caudate, putamen, and substantia nigra was associated with an increased risk of PD (Odds Ratio QSM ∼ substantia-nigra 1.21(1.07;1.37), p = 0.003). Genetic liability to AD or PD was not associated with R2* or QSM in the dementia or PD-associated regions.
INTERPRETATION
Our genetic analysis supports a causal effect of higher iron deposition in specific subcortical brain regions for Parkinson's disease, grey matter volume, and non-Alzheimer's dementia.
Topics: Humans; Parkinson Disease; Magnetic Resonance Imaging; Male; Dementia; Female; Iron; Gray Matter; United Kingdom; Aged; Genome-Wide Association Study; Middle Aged; Cohort Studies; Biological Specimen Banks; Brain; UK Biobank
PubMed: 38789058
DOI: 10.1016/j.nbd.2024.106539 -
Neuroscience Apr 2020We aimed to clarify the mechanisms of neural plasticity involved in language. We hypothesized that alterations which occur in bilinguals could reflect the mechanisms of...
We aimed to clarify the mechanisms of neural plasticity involved in language. We hypothesized that alterations which occur in bilinguals could reflect the mechanisms of acquisition of a second language and simulate neural plasticity related to language. We compared spatial characteristics of story listening-related hemodynamic modulations and subcortical fiber networks between monolinguals and bilinguals. Participants were Japanese monolinguals and Japanese-English bilinguals whose first language was Japanese. We divided bilinguals into early and late bilinguals depending on whether the age of acquisition was before after 7 years of age. We applied intergroup analysis to investigate the following: (1) blood oxygen level-dependent response (BOLD) responses during story listening by block-based fMRI; (2) number of fibers (NOFs) between specific edges by DTI. Both bilingual samples showed larger BOLD responses (BRs) in the right putamen and bilateral superior temporal gyri compared to the Japanese monolinguals in fMRI. Late bilinguals demonstrated bigger BRs in the right anterior temporal lobe and left medial parietal lobe than early bilinguals. Early bilinguals showed a higher NOFs between the right putamen and precentral gyrus than monolinguals and late bilinguals in DTI. Late bilinguals showed a lower NOFs between the left superior temporal gyrus and supramarginal gyrus than monolinguals and early bilinguals. Early bilinguals reinforce the subcortical fiber network between the right putamen and precentral gyrus, and activate the right putamen to gain alternative language function. We conclude that these key cerebral regions and subcortical fiber networks could contribute to the neural plasticity of language.
Topics: Child; Connectome; Humans; Japan; Language; Magnetic Resonance Imaging; Multilingualism
PubMed: 32027993
DOI: 10.1016/j.neuroscience.2020.01.030 -
Life (Basel, Switzerland) Dec 2022The objective of this study was to analyze the neurostructural abnormalities of brain areas responsible for the acquisition and maintenance of fear in small animal...
The objective of this study was to analyze the neurostructural abnormalities of brain areas responsible for the acquisition and maintenance of fear in small animal phobia by comparing gray matter volume (GMV) in individuals with phobia and non-fearful controls. Structural magnetic resonance imaging was obtained from 62 adults (79% female) assigned to one of two groups: 31 were diagnosed with small animal phobia and 31 were non-fearful controls. To investigate structural alterations, a whole-brain voxel-based morphometry analysis was conducted to compare the GMV of the brain areas involved in fear between both groups. The results indicated that individuals with a small animal specific phobia showed smaller GMV in cortical regions, such as the orbitofrontal (OFC) and medial frontal cortex, and greater GMV in the putamen than non-fearful controls. These brain areas are responsible for avoidant behavior (putamen) and emotional regulation processes or inhibitory control (prefrontal cortex (PFC)), which might suggest a greater vulnerability of phobic individuals to acquiring non-adaptive conditioned responses and emotional dysregulation. The findings provide preliminary support for the involvement of structural deficits in OFC and medial frontal cortex in phobia, contributing to clarify the neurobiological substrates for phobias.
PubMed: 36676068
DOI: 10.3390/life13010119 -
Frontiers in Neuroscience 2021Neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH) are biomarkers for neuroaxonal damage. We assessed whether NfL and other biomarker...
Neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH) are biomarkers for neuroaxonal damage. We assessed whether NfL and other biomarker levels in the CSF are correlated to the loss of presynaptic dopamine transporters in neurons as detected with dopamine transporter SPECT (DaTscan). We retrospectively identified 47 patients (17 Alzheimer's dementia, 10 idiopathic Parkinson's disease, 7 Lewy body dementia, 13 progressive supranuclear palsy or corticobasal degeneration) who received a DaTscan and a lumbar puncture. DaTscan imaging was performed according to current guidelines, and z-scores indicating the decrease in uptake were software based calculated for the nucleus caudatus and putamen. The CSF biomarkers progranulin, total-tau, alpha-synuclein, NfL, and pNfH were correlated with the z-scores. DaTscan results in AD patients did not correlate with any biomarker. Subsuming every movement disorder with nigrostriatal neurodegeneration resulted in a strong correlation between putamen/nucleus caudatus and NfL (nucleus caudatus right < 0.01, putamen right < 0.05, left < 0.05) and between pNfH and putamen (right < 0.05; left < 0.042). Subdividing in disease cohorts did not reveal significant correlations. Progranulin, alpha-synuclein, and total-tau did not correlate with DaTscan results. We show a strong correlation of NfL and pNfH with pathological changes in presynaptic dopamine transporter density in the putamen concomitant to nigrostriatal degeneration. This correlation might explain the reported correlation of impaired motor functions in PD and NfL as seen before, despite the pathological heterogeneity of these diseases.
PubMed: 34924923
DOI: 10.3389/fnins.2021.690013 -
Human Brain Mapping Apr 2023Temporal lobe epilepsy (TLE) is the most common type of intractable epilepsy in adults. Although brain myelination alterations have been observed in TLE, it remains...
Temporal lobe epilepsy (TLE) is the most common type of intractable epilepsy in adults. Although brain myelination alterations have been observed in TLE, it remains unclear how the myelination network changes in TLE. This study developed a novel method in characterization of myelination structural covariance network (mSCN) by T1-weighted and T2-weighted magnetic resonance imaging (MRI). The mSCNs were estimated in 42 left TLE (LTLE), 42 right TLE (RTLE) patients, and 41 healthy controls (HCs). The topology of mSCN was analyzed by graph theory. Voxel-wise comparisons of myelination laterality were also examined among the three groups. Compared to HC, both patient groups showed decreased myelination in frontotemporal regions, amygdala, and thalamus; however, the LTLE showed lower myelination in left medial temporal regions than RTLE. Moreover, the LTLE exhibited decreased global efficiency compared with HC and more increased connections than RTLE. The laterality in putamen was differently altered between the two patient groups: higher laterality at posterior putamen in LTLE and higher laterality at anterior putamen in RTLE. The putamen may play a transfer station role in damage spreading induced by epileptic seizures from the hippocampus. This study provided a novel workflow by combination of T1-weighted and T2-weighted MRI to investigate in vivo the myelin-related microstructural feature in epileptic patients first time. Disconnections of mSCN implicate that TLE is a system disorder with widespread disruptions at regional and network levels.
Topics: Adult; Humans; Epilepsy, Temporal Lobe; Myelin Sheath; Brain Mapping; Temporal Lobe; Magnetic Resonance Imaging; Functional Laterality
PubMed: 36692056
DOI: 10.1002/hbm.26212 -
Aging Cell Jul 2023Age is a major risk factor for neurodegenerative diseases. Shortening of leucocyte telomeres with advancing age, arguably a measure of "biological" age, is a known...
Age is a major risk factor for neurodegenerative diseases. Shortening of leucocyte telomeres with advancing age, arguably a measure of "biological" age, is a known phenomenon and epidemiologically correlated with age-related disease. The main mechanism of telomere shortening is cell division, rendering telomere length in post-mitotic cells presumably stable. Longitudinal measurement of human brain telomere length is not feasible, and cross-sectional cortical brain samples so far indicated no attrition with age. Hence, age-related changes in telomere length in the brain and the association between telomere length and neurodegenerative diseases remain unknown. Here, we demonstrate that mean telomere length in the putamen, a part of the basal ganglia, physiologically shortens with age, like leukocyte telomeres. This was achieved by using matched brain and leukocyte-rich spleen samples from 98 post-mortem healthy human donors. Using spleen telomeres as a reference, we further found that mean telomere length was brain region-specific, as telomeres in the putamen were significantly shorter than in the cerebellum. Expression analyses of genes involved in telomere length regulation and oxidative phosphorylation revealed that both region- and age-dependent expression pattern corresponded with region-dependent telomere length dynamics. Collectively, our results indicate that mean telomere length in the human putamen physiologically shortens with advancing age and that both local and temporal gene expression dynamics correlate with this, pointing at a potential mechanism for the selective, age-related vulnerability of the nigro-striatal network.
Topics: Humans; Putamen; Cross-Sectional Studies; Telomere Shortening; Risk Factors; Telomere
PubMed: 37129365
DOI: 10.1111/acel.13861 -
EJNMMI Physics Dec 2022Molecular imaging of the dopamine transporters (DAT) provides valuable information about neurodegenerative diseases, such as Parkinson's. This study assessed the...
BACKGROUND AND AIMS
Molecular imaging of the dopamine transporters (DAT) provides valuable information about neurodegenerative diseases, such as Parkinson's. This study assessed the accuracy and precision of DAT-SPECT quantification methods.
METHODS
Twenty-three DAT-SPECT images of a striatal phantom were acquired. The specific (caudate and putamen) and the non-specific (background activity) chambers were filled with [Tc]Tc. Different specific-to-non-specific activity ratios (10, 9, 8, 7, 6, 5, 4, 3 and 2 to 1) and the specific binding ratio (SBR) were calculated. Five methods using ROIs were assessed: (a) Manual ROIs on SPECT images; (b) TwoBox and (c) ThreeBox methods and Volume of Interest (VOI) using structural images; (d) MRI and (e) CT. Accuracy was evaluated by the concordance correlation coefficient (CCC) and precision by Pearson's coefficient and linear regression.
RESULTS
The SBR quantified in the specific and striatal chambers resulted in a CCC increase with a decrease in the nominal values. For lower SBR, MRI and CT showed higher CCCs when caudate ([Formula: see text] = 0.89 e [Formula: see text] = 0.84) and putamen ([Formula: see text] = 0.86 e [Formula: see text] = 0.82) were evaluated. For striatal assessments, the TwoBox method was the most accurate ([Formula: see text] = 0.95). High Pearson's coefficients were found in the correlations between all methods.
CONCLUSIONS
All five methods showed high precision even when applied to images with different activities. MRI and CT were the most accurate for assessing the caudate or putamen. To assess the striatal chamber and in the absence of structural information, the TwoBox method is advisable.
PubMed: 36577862
DOI: 10.1186/s40658-022-00519-2