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AIDS (London, England) Jul 2016Little is known about the extent of cortical and subcortical volumetric alterations that may occur within the first year of HIV infection [primary HIV infection (PHI)].
OBJECTIVE
Little is known about the extent of cortical and subcortical volumetric alterations that may occur within the first year of HIV infection [primary HIV infection (PHI)].
DESIGN
We used structural MRI in this prospective cross-sectional neuroimaging study to determine the extent of volumetric changes in early HIV infection.
METHODS
Cerebrospinal fluid, blood, neuropsychological testing, and structural T1 MRI scans were acquired from 18 HIV and 47 PHI age-matched antiretroviral-naïve male participants. Using FreeSurfer 5.1, volumetric measurements were obtained from the caudate, amygdala, corpus callosum, ventricles, putamen, thalamus, cortical white matter, and total gray matter. Regional volumes were compared groupwise and related to biomarkers in cerebrospinal fluid (viral load, neopterin, and neurofilament light chain), blood (viral load, CD4, and CD8 T-cell count), and neuropsychometric tests (digit-symbol, grooved pegboard, finger-tapping, and timed gait).
RESULTS
A trend-level moderate reduction of putamen volume (P = 0.076, adjusted Cohen's d = 0.5 after controlling for age) was observed for PHI compared with HIV-uninfected individuals. Within the PHI group, putamen volume associated with CD4 cell count (P = 0.03), CD4/CD8 ratio (P = 0.045), infection duration (P = 0.009), and worsening psychomotor performance on the digit-symbol (P = 0.028), finger-tapping (P = 0.039), and timed gait (P = 0.009) tests.
CONCLUSION
Our volumetric results suggest that the putamen is preferentially susceptible to early HIV-associated processes. Examining the natural course of early HIV infection longitudinally will allow for mapping of the trajectory of HIV-associated central nervous system changes, enabling creation of improved interventional strategies to potentially stabilize or reverse these observed structural changes.
Topics: Adult; Anthropometry; Cross-Sectional Studies; HIV Infections; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Prospective Studies; Putamen
PubMed: 27045376
DOI: 10.1097/QAD.0000000000001103 -
CNS Neuroscience & Therapeutics Feb 2020Impairment of basal ganglia (BG)-thalamo-cortical circuit causes various symptoms of Parkinson's disease (PD). We investigated the functional connectivity (FC) patterns...
OBJECTIVE
Impairment of basal ganglia (BG)-thalamo-cortical circuit causes various symptoms of Parkinson's disease (PD). We investigated the functional connectivity (FC) patterns of putamen among PD subtypes and healthy control (HC) and explored their clinical significance.
METHODS
A total of 16 patients with tremor-dominant (TD) PD, 23 patients with postural instability and gait difficulty-dominant (PIGD) PD, and 31 HC that underwent functional magnetic resonance imaging were observed. Voxel-wise FC analysis was performed by computing correlation between bilateral putamen and other voxels within the brain. Correlation analysis was performed between FC strength and clinical symptoms.
RESULTS
Compared with PIGD group, TD group showed increased FC between left putamen and right cerebellum lobule VI and cerebellum crus I, then we compared the cerebellum FC difference among the three groups. The cerebellum lobule VI FC difference was mainly involved in motor related cortex, and the cerebellum crus I FC difference was related to cognition areas. While compared with HC, TD and PIGD groups both had significant FC difference brain areas correlated with motor and cognition symptoms. The connectively of putamen and right cerebellum lobules VI and I showed positive correlation with tremor and Montreal Cognitive Assessment degree of scores, respectively. The connectivity of putamen and sensorimotor cortex had negative correlation with PIGD scores.
CONCLUSIONS
The altered connectivity of BG-cortical circuit in patients with PD was related to PIGD symptoms. Motor and cognitive impairments declined slower in patients with TD PD, which may be related to increased functional connectivity between putamen and cerebellum.
Topics: Aged; Cerebellum; Cognition Disorders; Female; Gait Disorders, Neurologic; Humans; Magnetic Resonance Imaging; Male; Mental Status and Dementia Tests; Middle Aged; Motor Cortex; Neural Pathways; Parkinson Disease; Putamen; Tremor
PubMed: 31730272
DOI: 10.1111/cns.13259 -
Cells Aug 2020Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons from the substantia nigra (SN) that project to the dorsal striatum (caudate-putamen). To...
Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons from the substantia nigra (SN) that project to the dorsal striatum (caudate-putamen). To better understand the molecular mechanisms underlying PD, we performed combined lipid profiling and RNA sequencing of SN and putamen samples from PD patients and age-matched controls. SN lipid analysis pointed to a neuroinflammatory component and included elevated levels of the endosomal lipid Bis (Monoacylglycero)Phosphate 42:8, while two of the three depleted putamen lipids were saturated sphingomyelin species. Remarkably, we observed gender-related differences in the SN and putamen lipid profiles. Transcriptome analysis revealed that the top-enriched pathways among the 354 differentially expressed genes (DEGs) in the SN were "protein folding" and "neurotransmitter transport", and among the 261 DEGs from putamen "synapse organization". Furthermore, we identified pathways, e.g., "glutamate signaling", and genes, encoding, e.g., an angiotensin receptor subtype or a proprotein convertase, that have not been previously linked to PD. The identification of 33 genes that were common among the SN and putamen DEGs, which included the α-synuclein paralog β-synuclein, may contribute to the understanding of general PD mechanisms. Thus, our proof-of-concept data highlights new genes, pathways and lipids that have not been explored before in the context of PD.
Topics: Aged; Aged, 80 and over; Female; Gene Expression Profiling; Humans; Lipids; Male; Parkinson Disease; Putamen; Substantia Nigra
PubMed: 32858884
DOI: 10.3390/cells9091966 -
NeuroImage. Clinical 2022Compulsive behaviors in obsessive-compulsive disorder (OCD) have been suggested to result from an imbalance in cortico-striatal connectivity. However, the nature of this...
BACKGROUND
Compulsive behaviors in obsessive-compulsive disorder (OCD) have been suggested to result from an imbalance in cortico-striatal connectivity. However, the nature of this impairment, the relative involvement of different striatal areas, their imbalance in genetically related but unimpaired individuals, and their relationship with cognitive dysfunction in OCD patients, remain unknown.
METHODS
In the current study, striatal (i.e., caudate and putamen) whole-brain connectivity was computed in a sample of OCD patients (OCD, n = 62), unaffected first-degree relatives (UFDR, n = 53) and healthy controls (HC, n = 73) by ROI-based resting-state functional magnetic resonance imaging (rs-fMRI). A behavioral task switch paradigm outside of the scanner was also performed to measure cognitive flexibility in OCD patients.
RESULTS
There were significantly increased strengths (Z-transformed Pearson correlation coefficient) in caudate connectivity in OCD patients. A significant correlation between the two types of connectivity strengths in the relevant regions was observed only in the OCD patient group. Furthermore, the caudate connectivity of patients was negatively associated with their task-switch performance.
CONCLUSIONS
The imbalance between the caudate and putamen connectivity, arising from the abnormal increase of caudate activity, may serve as a clinical characteristic for obsessive-compulsive disorder.
Topics: Brain Mapping; Corpus Striatum; Humans; Magnetic Resonance Imaging; Neural Pathways; Obsessive-Compulsive Disorder; Putamen
PubMed: 35717885
DOI: 10.1016/j.nicl.2022.103083 -
Parkinsonism & Related Disorders Apr 2021Microstructural integrity of the middle cerebellar peduncle (MCP) and the putamen captured by diffusion-tensor imaging (DTI) is differentially affected in the...
INTRODUCTION
Microstructural integrity of the middle cerebellar peduncle (MCP) and the putamen captured by diffusion-tensor imaging (DTI) is differentially affected in the parkinsonian and cerebellar variants of multiple system atrophy (MSA-P, MSA-C) compared to Parkinson's disease (PD). The current study applied DTI and tractography in order to 1) characterize the distribution of DTI metrics along the tracts of the MCP and from the putamen in MSA variants, and 2) evaluate the usefulness of combining these measures for the differential diagnosis of MSA-P against PD in the clinical setting.
METHODS
Twenty-nine MSA patients (MSA-C, n = 10; MSA-P, n = 19), with a mean disease duration of 2.8 ± 1.7 years, 19 PD patients, and 27 healthy controls (HC) were included in the study. Automatized tractography with a masking procedure was employed to isolate the MCP tracts. DTI measures along the tracts of the MCP and within the putamen were acquired and jointly used to classify MSA vs. PD, and MSA-P vs. PD. Putamen volume was additionally tested as classification feature in post hoc analyses.
RESULTS
DTI measures within the MCP and putamen showed significant alterations in MSA variants compared to HC and PD. Classification accuracy for MSA vs. PD and MSA-P vs PD using diffusion measures was 91.7% and 89.5%, respectively. When replacing the putaminal DTI measure by a normalized measure of putamen volume classification accuracy improved to 95.8% and 94.7%, respectively.
CONCLUSION
Multimodal information from MCP tractography and putamen volume yields excellent diagnostic accuracy to discriminate between early-to-moderately advanced patients with MSA and PD.
Topics: Aged; Diagnosis, Differential; Diffusion Tensor Imaging; Female; Humans; Male; Middle Aged; Middle Cerebellar Peduncle; Multiple System Atrophy; Parkinson Disease; Putamen; Sensitivity and Specificity
PubMed: 33713904
DOI: 10.1016/j.parkreldis.2021.02.027 -
BMC Neurology Mar 2021To explore the correlation between the volume of putamen and brain cognitive impairment in patients with HIV and to predict the feasibility of early-stage HIV brain...
BACKGROUND
To explore the correlation between the volume of putamen and brain cognitive impairment in patients with HIV and to predict the feasibility of early-stage HIV brain cognitive impairment through radiomics.
METHOD
Retrospective selection of 90 patients with HIV infection, including 36 asymptomatic neurocognitive impairment (ANI) patients and 54 pre-clinical ANI patients in Beijing YouAn Hospital. All patients received comprehensive neuropsychological assessment and MRI scanning. 3D Slicer software was used to acquire volume of interest (VOI) and radiomics features. Clinical variables and volume of putamen were compared between patients with ANI and pre-clinical ANI. The Kruskal Wallis test was used to analysis multiple comparisons between groups. The relationship between cognitive scores and VOI was compared using linear regression. For radiomics, principal component analysis (PCA) was used to reduce model overfitting and calculations and then a support vector machine (SVM) was used to build a binary classification model. For model performance evaluation, we used an accuracy, sensitivity, specificity and receiver operating characteristic curve (ROC).
RESULT
There were no significant differences in clinical variables between ANI group and pre-clinical-ANI group (P>0.05). The volume of bilateral putamen was significantly different between AHI group and pre-clinical group (P<0.05), but there was only a trend in the left putamen between ANI-treatment group and pre-clinical treatment group(P = 0.063). Reduced cognitive scores in Verbal Fluency, Attention/Working Memory, Executive Functioning, memory and Speed of Information Processing were negatively correlated with the increased VOI (P<0.05), but the correlation was relatively low. In diagnosing the ANI from pre-clinical ANI, the mean area under the ROC curves (AUC) were 0.85 ± 0.22, the mean sensitivity and specificity were 63.12 ± 5.51 and 94.25% ± 3.08%.
CONCLUSION
The volumes of putamen in patients with ANI may be larger than patients with pre-clinical ANI, the change of the volume of the putamen may have a certain process; there is a relationship between putamen and cognitive impairment, but the exact mechanism is unclear. Radiomics may be a useful tool for predicting early stage HAND in patients with HIV.
Topics: AIDS Dementia Complex; Adult; Brain; Cognitive Dysfunction; Female; Humans; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Putamen; Radiographic Image Interpretation, Computer-Assisted; Retrospective Studies
PubMed: 33750319
DOI: 10.1186/s12883-021-02114-x -
American Journal of Medical Genetics.... Jun 2020Individuals with attention deficit hyperactivity disorder (ADHD) show gray matter volume (GMV) reduction in the putamen. KTN1 variants may regulate kinectin 1 expression...
Individuals with attention deficit hyperactivity disorder (ADHD) show gray matter volume (GMV) reduction in the putamen. KTN1 variants may regulate kinectin 1 expression in the putamen and influence putamen structure and function. We aim to test the hypothesis that the KTN1 variants may represent a genetic risk factor of ADHD. Two independent family-based Caucasian samples were analyzed, including 922 parent-child trios (a total of 2,757 subjects with 924 ADHD children) and 735 parent-child trios (a total of 1,383 subjects with 613 ADHD children). The association between ADHD and a total of 143 KTN1 SNPs was analyzed in the first sample, and the nominally-significant (p < .05) risk SNPs were classified into independent haplotype blocks. All SNPs, including imputed SNPs within these blocks, and haplotypes across each block, were explored for replication of associations in both samples. The potential biological functions of all risk SNPs were predicted using a series of bioinformatics analyses, their regulatory effects on the putamen volumes were tested, and the KTN1 mRNA expression was examined in three independent human putamen tissue samples. We found that fifteen SNPs were nominally associated with ADHD (p < .05) in the first sample, and three of them remained significant even after correction for multiple testing (1.3 × 10 ≤ p ≤ 1.2 × 10 ; α = 2.5 × 10 ). These 15 risk SNPs were located in five haplotype blocks, and 13 SNPs within four of these blocks were associated with ADHD in the second sample. Six haplotypes within these blocks were also significantly (1.2 × 10 ≤ p ≤ .009) associated with ADHD in these samples. These risk variants were located in disease-related transposons and/or transcription-related functional regions. Major alleles of these risk variants significantly increased putamen volumes. Finally, KTN1 mRNA was significantly expressed in putamen across three independent cohorts. We concluded that the KTN1 variants were significantly associated with ADHD. KTN1 may play a functional role in the development of ADHD.
Topics: Adolescent; Alleles; Attention Deficit Disorder with Hyperactivity; Child; Computational Biology; Family Health; Female; Genetic Predisposition to Disease; Genetic Variation; Genotype; Gray Matter; Haplotypes; Humans; Male; Membrane Proteins; Polymorphism, Single Nucleotide; Putamen; Risk
PubMed: 32190980
DOI: 10.1002/ajmg.b.32782 -
Ugeskrift For Laeger Jan 2017Tourette's syndrome is characterized by involuntary tics. First choice of treatment has been pharmacological, but recently, behavioural therapy teaching patients to... (Review)
Review
Tourette's syndrome is characterized by involuntary tics. First choice of treatment has been pharmacological, but recently, behavioural therapy teaching patients to suppress their tics has been introduced. Neuroimaging studies have shown an increased activity in the prefrontal cortex, temporal lobes and caudate nucleus, and a decreased activity in globus pallidus and putamen during inhibition of tics. The activity in the frontal lobes changes with age, probably caused by a lack of compensatory hypertrophy. In order to fully understand the mechanism behind behavioural therapy further studies are needed.
Topics: Caudate Nucleus; Globus Pallidus; Gyrus Cinguli; Humans; Inhibition, Psychological; Models, Psychological; Neuroimaging; Parietal Lobe; Prefrontal Cortex; Putamen; Temporal Lobe; Thalamus; Tics; Tourette Syndrome
PubMed: 28074769
DOI: No ID Found -
Brain Pathology (Zurich, Switzerland) Sep 2021Prion-like spreading of abnormal proteins is proposed to occur in neurodegenerative diseases, and the progression of α-synuclein (α-syn) deposits has been reported in...
Prion-like spreading of abnormal proteins is proposed to occur in neurodegenerative diseases, and the progression of α-synuclein (α-syn) deposits has been reported in the brains of animal models injected with synthetic α-syn fibrils or pathological α-syn prepared from patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). However, α-syn transmission in nonhuman primates, which are more similar to humans, has not been fully clarified. Here, we injected synthetic human α-syn fibrils into the left striatum of a macaque monkey (Macaca fuscata). At 3 months after the injection, we examined neurodegeneration and α-syn pathology in the brain using α-syn epitope-specific antibodies, antiphosphorylated α-syn antibodies (pSyn#64 and pSer129), anti-ubiquitin antibodies, and anti-p62 antibodies. Immunohistochemical examination with pSyn#64, pSer129, and α-syn epitope-specific antibodies revealed Lewy bodies, massive α-syn-positive neuronal intracytoplasmic inclusions (NCIs), and neurites in the left putamen. These inclusions were also positive for ubiquitin and p62. LB509, a human-specific α-syn antibody targeting amino acid residues 115-122, showed limited immunoreactivity around the injection site. The left substantia nigra (SN) and the bilateral frontal cortex also contained some NCIs and neurites. The left hemisphere, including parietal/temporal cortex presented sparse α-syn pathology, and no immunoreactivity was seen in olfactory nerves, amygdala, hippocampus, or right parietal/temporal cortex. Neuronal loss and gliosis in regions with α-syn pathology were mild, except for the left striatum and SN. Our results indicate that abnormal α-syn fibrils propagate throughout the brain of M. fuscata via projection, association, and commissural fibers, though the progression of α-syn pathology is limited.
Topics: Animals; Brain; Inclusion Bodies; Lewy Bodies; Macaca fuscata; Male; Parkinson Disease; Putamen; Substantia Nigra; Synucleinopathies; alpha-Synuclein
PubMed: 33754430
DOI: 10.1111/bpa.12952 -
Social Cognitive and Affective... Jun 2017Psychometric research has identified stable traits that predict inter-individual differences in appetitive motivation and approach behavior. Behavioral Inhibition...
Psychometric research has identified stable traits that predict inter-individual differences in appetitive motivation and approach behavior. Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) scales have been developed to quantitatively assess these traits. However, neural mechanisms corresponding to the proposed constructs reflected in BIS/BAS are still poorly defined. The ventral striatum (VS) and orbitofrontal cortex (OFC) are implicated in subserving reward-related functions that are also associated with the BAS. In this study, we examined whether functional connectivity between these regions predicts components of these scales. We employed resting-state functional connectivity and BIS/BAS scores assessed by a personality questionnaire. Participants completed a resting state run and the Behavioral Inhibition and Activation Systems (BIS/BAS) Questionnaire. Using resting-state BOLD, we assessed correlations between two basal ganglia ROIs (caudate and putamen) and bilateral OFC ROIs, establishing single subject connectivity summary scores. Summary scores were correlated with components of BIS/BAS scores. Results demonstrate a novel correlation between BAS-fun seeking and resting-state connectivity between middle OFC and putamen, implying that spontaneous synchrony between reward-processing regions may play a role in defining personality characteristics related to impulsivity.
Topics: Adolescent; Adult; Caudate Nucleus; Female; Humans; Impulsive Behavior; Inhibition, Psychological; Linear Models; Magnetic Resonance Imaging; Male; Neural Pathways; Oxygen; Personality; Prefrontal Cortex; Putamen; Reward; Ventral Striatum; Young Adult
PubMed: 28402539
DOI: 10.1093/scan/nsx031