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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 -
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 -
NeuroImage. Clinical 2022Perinatal stroke affects millions of children and results in lifelong disability. Two forms prevail: arterial ischemic stroke (AIS), and periventricular venous...
INTRODUCTION
Perinatal stroke affects millions of children and results in lifelong disability. Two forms prevail: arterial ischemic stroke (AIS), and periventricular venous infarction (PVI). With such focal damage early in life, neural structures may reorganize during development to determine clinical function, particularly in the contralesional hemisphere. Such processes are increasingly understood in the motor system, however, the role of the basal ganglia, a group of subcortical nuclei that are critical to movement, behaviour, and learning, remain relatively unexplored. Perinatal strokes that directly damage the basal ganglia have been associated with worse motor outcomes, but how developmental plasticity affects bilateral basal ganglia structure is unknown. We hypothesized that children with perinatal stroke have alterations in bilateral basal ganglia volumes, the degree of which correlates with clinical motor function.
METHODS
Children with AIS or PVI, and controls, aged 6-19 years, were recruited from a population-based cohort. MRIs were acquired on a 3 T GE MR750w scanner. High-resolution T1-weighted images (166 slices, 1 mm isotropic voxels) underwent manual segmentations of bilateral caudate and putamen. Extracted volumes were corrected for total intracranial volume. A structure volume ratio quantified hemispheric asymmetry of caudate and putamen (non-dominant/dominant hemisphere structure volume) with ratios closer to 1 reflecting a greater degree of symmetry between structures. Participants were additionally dichotomized by volume ratios into two groups, those with values above the group mean (0.8) and those below. Motor function was assessed using the Assisting Hand Assessment (AHA) and the Box and Blocks test in affected (BBTA) and unaffected (BBTU) hands. Group differences in volumes were explored using Kruskal-Wallis tests, and interhemispheric differences using Wilcoxon. Partial Spearman correlations explored associations between volumes and motor function (factoring out age, and whole-brain white matter volume, a proxy for lesion extent).
RESULTS
In the dominant (non-lesioned) hemisphere, volumes were larger in AIS compared to PVI for both the caudate (p < 0.05) and putamen (p < 0.01) but comparable between stroke groups and controls. Non-dominant (lesioned) hemisphere volumes were larger for controls than AIS for the putamen (p < 0.05), and for the caudate in PVI (p = 0.001). Interhemispheric differences showed greater dominant hemisphere volumes for the putamen in controls (p < 0.01), for both the caudate (p < 0.01) and putamen (p < 0.001) in AIS, and for the caudate (p = 0.01) in PVI. Motor scores did not differ between AIS and PVI thus groups were combined to increase statistical power. Better motor scores were associated with larger non-dominant putamen volumes (BBTA: r = 0.40, p = 0.011), and larger putamen volume ratios (BBTA: r = 0.52, p < 0.001, AHA: r = 0.43, p < 0.01). For those with relatively symmetrical putamen volume ratios (ratio > group mean of 0.8), age was positively correlated with BBTA (r = 0.54, p < 0.01) and BBTU (r = 0.69, p < 0.001). For those with more asymmetrical putamen volume ratios, associations with motor function and age were not seen (BBTA: r = 0.21, p = 0.40, BBTU: r = 0.37, p = 0.13).
CONCLUSION
Specific perinatal stroke lesions affect different elements of basal ganglia development. PVI primarily affected the caudate, while AIS primarily affected the putamen. Putamen volumes in the lesioned hemisphere are associated with clinical motor function. The basal ganglia should be included in evolving models of developmental plasticity after perinatal stroke.
Topics: Basal Ganglia; Child; Female; Hand; Humans; Magnetic Resonance Imaging; Pregnancy; Putamen; Stroke
PubMed: 36002972
DOI: 10.1016/j.nicl.2022.103143 -
Addiction Biology Jan 2018The putamen has been shown to play a key role in inhibitory control and addiction, and consists of distinct subregions associated with distinct functions. The anterior...
The putamen has been shown to play a key role in inhibitory control and addiction, and consists of distinct subregions associated with distinct functions. The anterior putamen is thought to be specialized in goal-directed control or response-monitoring in connection with frontal regions, whereas the posterior part is specialized in habitual or automatic responding in connection with sensorimotor regions. The present study is the first to delineate functional networks of the anterior and posterior putamen in a Go-NoGo response inhibition task, and to examine differences between smokers (n = 25) and non-smokers (n = 23) within these networks. Functional connectivity analyses were conducted on fMRI data from a Go-NoGo study, using the generalized form of psychophysiological interaction with anterior and posterior putamen seed regions. In the context of inhibition, the anterior putamen exhibited connectivity with the anterior cingulate cortex (ACC) and precuneus (p < .05), which was in line with previous literature. Conversely, the posterior putamen showed connectivity with regions implicated in sensorimotor processing. When we compared smokers to non-smokers, we did not observe the expected weaker connectivity between the anterior putamen and ACC during inhibition in smokers. Instead, our study revealed stronger inhibition-related connectivity between the anterior putamen and right insula in smokers. This finding highlights the involvement of putamen - insula interactions in addiction and impulse control.
Topics: Brain; Case-Control Studies; Cerebral Cortex; Cigarette Smoking; Female; Gyrus Cinguli; Humans; Inhibition, Psychological; Male; Neural Pathways; Non-Smokers; Parietal Lobe; Putamen; Smokers; Task Performance and Analysis; Young Adult
PubMed: 27917562
DOI: 10.1111/adb.12482 -
Neuroscience Letters Sep 2020Parkinson's disease (PD) is the most widespread movement disorder with a prevalence of 1 in 1000 individuals above 60 years of age. Until now, understanding the... (Review)
Review
Parkinson's disease (PD) is the most widespread movement disorder with a prevalence of 1 in 1000 individuals above 60 years of age. Until now, understanding the pathological mechanisms of PD to translate them into therapy has remained a high research priority. In this review, we highlight evidence describing the involvement of microglial dysfunction in PD. Thereafter, we provide current knowledge suggesting that the substantia nigra pars compacta and putamen, compared to other brain regions, show a reduced microglial density, as well as altered morphological and functional properties in homeostatic conditions, while presenting dystrophic features associated with aging. Further, we describe that this defective microglial programing emerges as early as the second postnatal week, persists until adulthood and impacts negatively on their transcriptional pattern and provision of local trophic support. We emphasize the role of α-synuclein oligomers as a major dysfunctional signal underlining microglial-mediated phenotypic switch and adaptive response contributing to neurodegeneration. Moreover, we explore available avenues should microglia be considered as target for neuroprotective or restorative strategies including preventing the aggregation of α-synuclein protofibrils formation. However, we provide a note of caution regarding the success of microglial-targeted PD strategies, using minocycline as an example. In conclusion, we discuss putative neuroprotective agents that were unsuccessful in previous trials but could be reconsidered by focusing on the stage of microglial-dependent pathogenic events during PD in suitable cohorts of patients.
Topics: Animals; Humans; Microglia; Parkinson Disease; Pars Compacta; Phenotype; Putamen
PubMed: 32561452
DOI: 10.1016/j.neulet.2020.135164 -
Movement Disorders : Official Journal... Jan 2022Dopamine transporter single photon-emission computed tomography (DAT-SPECT) is the strongest risk factor for phenoconversion in patients with idiopathic rapid eye...
BACKGROUND
Dopamine transporter single photon-emission computed tomography (DAT-SPECT) is the strongest risk factor for phenoconversion in patients with idiopathic rapid eye movement (REM)-sleep behavior disorder (iRBD). However, it might be used as a second-line stratification tool in clinical trials, because it is expensive and mini-invasive.
OBJECTIVE
Aim of the study is to investigate whether other cost-effective and non-invasive biomarkers may be proposed as first-line stratification tools.
METHODS
Forty-seven consecutive iRBD patients (68.53 ± 7.16 years, 40 males) underwent baseline clinical and neuropsychological assessment, olfaction test, resting electroencephalogram (EEG), and DAT-SPECT. All patients underwent 6 month-based clinical follow-up to investigate the emergence of parkinsonism and/or dementia. Survival analysis and Cox regression were used to estimate conversion risk.
RESULTS
Seventeen patients developed an overt synucleinopathy (eight Parkinsonism and nine dementia) 32.8 ± 22 months after diagnosis. The strongest risk factors were putamen specific to non-displaceable binding ratio (SBR) (hazard ratio [HR], 7.3), attention/working memory cognitive function (NPS-AT/WM) (HR, 5.9), EEG occipital mean frequency (HR, 2.7) and clinical motor assessment (HR, 2.3). On multivariate Cox-regression analysis, only putamen SBR and NPS-AT/WM significantly contributed to the model (HR, 6.2, 95% confidence interval [CI], 1.9-19.8). At post-hoc analysis, the trail-making test B (TMT-B) was the single most efficient first-line stratification tool that allowed to reduce the number of eligible subjects to 76.6% (sensitivity 1, specificity 0.37). Combining TMT-B and DAT-SPECT further reduced the sample to 66% (sensitivity 0.88, specificity 0.47).
CONCLUSION
The TMT-B seems to be a cost-effective and efficient first-line screening tool, to be used to select patients that deserve DAT-SPECT as second-line screening tool for disease-modifying clinical trials. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Aged; Female; Humans; Male; Middle Aged; Parkinsonian Disorders; Putamen; REM Sleep Behavior Disorder; Synucleinopathies; Tomography, Emission-Computed, Single-Photon
PubMed: 34533239
DOI: 10.1002/mds.28785