1,117 results on '"Putamen pathology"'
Search Results
2. Chemoarchitectural signatures of subcortical shape alterations in generalized epilepsy.
- Author
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Meng Y, Xiao J, Yang S, Li J, Xu Q, Zhang Q, Lu G, Chen H, Zhang Z, and Liao W
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- Humans, Female, Male, Adult, Young Adult, Magnetic Resonance Imaging, Thalamus pathology, Thalamus diagnostic imaging, Thalamus metabolism, Brain pathology, Brain diagnostic imaging, Adolescent, Putamen pathology, Putamen diagnostic imaging, Putamen metabolism, Case-Control Studies, Hippocampus pathology, Epilepsy, Generalized pathology, Epilepsy, Generalized physiopathology
- Abstract
Genetic generalized epilepsies (GGE) exhibit widespread morphometric alterations in the subcortical structures. Subcortical structures are essential for understanding GGE pathophysiology, but their fine-grained morphological diversity has yet to be comprehensively investigated. Furthermore, the relationships between macroscale morphological disturbances and microscale molecular chemoarchitectures are unclear. High-resolution structural images were acquired from patients with GGE (n = 97) and sex- and age-matched healthy controls (HCs, n = 184). Individual measurements of surface shape features (thickness and surface area) of seven bilateral subcortical structures were quantified. The patients and HCs were then compared vertex-wise, and shape anomalies were co-located with brain neurotransmitter profiles. We found widespread morphological alterations in GGE and prominent disruptions in the thalamus, putamen, and hippocampus. Shape area dilations were observed in the bilateral ventral, medial, and right dorsal thalamus, as well as the bilateral lateral putamen. We found that the shape area deviation pattern was spatially correlated with the norepinephrine transporter and nicotinic acetylcholine (Ach) receptor (α
4 β2 ) profiles, but a distinct association was seen in the muscarinic Ach receptor (M1 ). The findings provided a comprehensive picture of subcortical morphological disruptions in GGE, and further characterized the associated molecular mechanisms. This information may increase our understanding of the pathophysiology of GGE., (© 2024. The Author(s).)- Published
- 2024
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3. The neurostructural consequences of glaucoma and their overlap with disorders exhibiting emotional dysregulations: A voxel-based meta-analysis and tripartite system model.
- Author
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Klugah-Brown B, Bore MC, Liu X, Gan X, Biswal BB, Kendrick KM, Chang DHF, Zhou B, and Becker B
- Subjects
- Humans, Magnetic Resonance Imaging, Brain pathology, Brain diagnostic imaging, Emotional Regulation physiology, Case-Control Studies, Putamen pathology, Putamen diagnostic imaging, Glaucoma pathology, Glaucoma physiopathology, Gray Matter pathology, Gray Matter diagnostic imaging, Anxiety Disorders pathology, Anxiety Disorders diagnostic imaging, Depressive Disorder, Major pathology, Depressive Disorder, Major diagnostic imaging
- Abstract
Background: Glaucoma, a progressive neurodegenerative disorder leading to irreversible blindness, is associated with heightened rates of generalized anxiety and depression. This study aims to comprehensively investigate brain morphological changes in glaucoma patients, extending beyond visual processing areas, and explores overlaps with morphological alterations observed in anxiety and depression., Methods: A comparative meta-analysis was conducted, using case-control studies of brain structural integrity in glaucoma patients. We aimed to identify regions with gray matter volume (GMV) changes, examine their role within distinct large-scale networks, and assess overlap with alterations in generalized anxiety disorder (GAD) and major depressive disorder (MDD)., Results: Glaucoma patients exhibited significant GMV reductions in visual processing regions (lingual gyrus, thalamus). Notably, volumetric reductions extended beyond visual systems, encompassing the left putamen and insula. Behavioral and functional network decoding revealed distinct large-scale networks, implicating visual, motivational, and affective domains. The insular region, linked to pain and affective processes, displayed reductions overlapping with alterations observed in GAD., Limitations: While the study identified significant morphological alterations, the number of studies from both the glaucoma and GAD cohorts remains limited due to the lack of independent studies meeting our inclusion criteria., Conclusion: The study proposes a tripartite brain model for glaucoma, with visual processing changes related to the lingual gyrus and additional alterations in the putamen and insular regions tied to emotional or motivational functions. These neuroanatomical changes extend beyond the visual system, implying broader implications for brain structure and potential pathological developments, providing insights into the overall neurological consequences of glaucoma., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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4. Persistent fatigue in post-acute COVID syndrome is associated with altered T1 MRI texture in subcortical structures: a preliminary investigation.
- Author
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Churchill NW, Roudaia E, Chen JJ, Sekuler A, Gao F, Masellis M, Lam B, Cheng I, Heyn C, Black SE, MacIntosh BJ, Graham SJ, and Schweizer TA
- Subjects
- Humans, Male, Female, Middle Aged, Adult, Brain diagnostic imaging, Brain pathology, Thalamus diagnostic imaging, Thalamus pathology, Aged, Putamen diagnostic imaging, Putamen pathology, SARS-CoV-2, Post-Acute COVID-19 Syndrome, COVID-19 complications, COVID-19 diagnostic imaging, Magnetic Resonance Imaging, Fatigue diagnostic imaging, Fatigue etiology, Fatigue pathology, Brain Stem diagnostic imaging, Brain Stem pathology
- Abstract
Post-acute COVID syndrome (PACS) is a global health concern and is often associated with debilitating symptoms. Post-COVID fatigue is a particularly frequent and troubling issue, and its underlying mechanisms remain incompletely understood. One potential contributor is micropathological injury of subcortical and brainstem structures, as has been identified in other patient populations. Texture-based analysis (TA) may be used to measure such changes in anatomical MRI data. The present study develops a methodology of voxel-wise TA mapping in subcortical and brainstem regions, which is then applied to T1-weighted MRI data from a cohort of 48 individuals who had PACS (32 with and 16 without ongoing fatigue symptoms) and 15 controls who had cold and flu-like symptoms but tested negative for COVID-19. Both groups were assessed an average of 4-5 months post-infection. There were no significant differences between PACS and control groups, but significant differences were observed within the PACS groups, between those with and without fatigue symptoms. This included reduced texture energy and increased entropy, along with reduced texture correlation, cluster shade and profile in the putamen, pallidum, thalamus and brainstem. These findings provide new insights into the neurophysiological mechanisms that underlie PACS, with altered tissue texture as a potential biomarker of this debilitating condition., Competing Interests: Declaration of Competing Interest The authors report no disclosures relevant to the manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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5. Is the Caudate, Putamen, and Globus Pallidus the Delusional Disorder's Trio? A Texture Analysis Study.
- Author
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Baykara M and Baykara S
- Subjects
- Humans, Female, Male, Middle Aged, Adult, Case-Control Studies, Neuroimaging methods, Putamen diagnostic imaging, Putamen pathology, Globus Pallidus diagnostic imaging, Globus Pallidus pathology, Magnetic Resonance Imaging, Caudate Nucleus diagnostic imaging, Caudate Nucleus pathology, Schizophrenia, Paranoid diagnostic imaging, Schizophrenia, Paranoid pathology
- Abstract
Background: The neurobiological basis of delusional disorder is less explored through neuroimaging techniques than in other psychotic disorders. This study aims to provide information about the neural origins of delusional disorder (DD) by examining the neuroanatomical features of some basal nuclei with magnetic resonance imaging (MRI) texture analysis., Materials and Methods: Twenty DD patients and 20 healthy individuals were included in the study. Globus pallidus, putamen, and caudate nuclei were selected individually with a region of interest (ROI) on the axial MRI images. The entire texture analysis algorithm applied to all selected ROIs was done with an in-house software. Nuclei on both sides were taken as separate samples., Results: There were no significant differences between groups in terms of age and gender. The average "mean, median and maximum" values of all three nuclei were decreased in DD patients. The small putamen area and the differences detected in different tissue parameters for all three nuclei in delusional disorder patients indicate that they differ in delusional disorder from normal controls (p < 0.05)., Conclusion: The differences detected in the texture parameters for all three nuclei indicate that there is something different in the DD from in the normal controls. Neuroimaging studies with larger samples and different techniques in the future may shed light on the etiology of delusional disorder.
- Published
- 2024
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6. White Matter Microstructural Underpinnings of Mild Behavioral Impairment in Parkinson's Disease.
- Author
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Monchi O, Pinilla-Monsalve GD, Almgren H, Ghahremani M, Kibreab M, Maarouf N, Kathol I, Boré A, Rheault F, Descoteaux M, and Ismail Z
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Neuropsychological Tests, Diffusion Magnetic Resonance Imaging methods, Amygdala pathology, Amygdala diagnostic imaging, Diffusion Tensor Imaging methods, Putamen diagnostic imaging, Putamen pathology, Parkinson Disease pathology, Parkinson Disease diagnostic imaging, Parkinson Disease complications, White Matter diagnostic imaging, White Matter pathology, Cognitive Dysfunction pathology, Cognitive Dysfunction diagnostic imaging, Cognitive Dysfunction etiology
- Abstract
Background: Patients with Parkinson's disease (PD) experience changes in behavior, personality, and cognition that can manifest even in the initial stages of the disease. Previous studies have suggested that mild behavioral impairment (MBI) should be considered an early marker of cognitive decline. However, the precise neurostructural underpinnings of MBI in early- to mid-stage PD remain poorly understood., Objective: The aim was to explore the changes in white matter microstructure linked to MBI and mild cognitive impairment (MCI) in early- to mid-stage PD using diffusion magnetic resonance imaging (dMRI)., Methods: A total of 91 PD patients and 36 healthy participants were recruited and underwent anatomical MRI and dMRI, a comprehensive neuropsychological battery, and the completion of the Mild Behavioral Impairment-Checklist. Metrics of white matter integrity included tissue fractional anisotropy (FAt) and radial diffusivity (RDt), free water (FW), and fixel-based apparent fiber density (AFD)., Results: The connection between the left amygdala and the putamen was disrupted when comparing PD patients with MBI (PD-MBI) to PD-non-MBI, as evidenced by increased RDt (η
2 = 0.09, P = 0.004) and both decreased AFD (η2 = 0.05, P = 0.048) and FAt (η2 = 0.12, P = 0.014). Compared to controls, PD patients with both MBI and MCI demonstrated increased FW for the connection between the left orbitofrontal gyrus (OrG) and the hippocampus (η2 = 0.22, P = 0.008), augmented RDt between the right OrG and the amygdala (η2 = 0.14, P = 0.008), and increased RDt (η2 = 0.25, P = 0.028) with decreased AFD (η2 = 0.10, P = 0.046) between the right OrG and the caudate nucleus., Conclusion: MBI is associated with abnormal microstructure of connections involving the orbitofrontal cortex, putamen, and amygdala. To our knowledge, this is the first assessment of the white matter microstructure in PD-MBI using dMRI. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)- Published
- 2024
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7. Putaminal hypointensity on T2-weighted MRI mimicking multiple system atrophy in amyotrophic lateral sclerosis: An autopsy case report.
- Author
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Ishikawa A, Takeda T, Kokubun S, Saito Y, Isose S, Ito K, Arai K, Sugiyama A, Kuwabara S, and Honda K
- Subjects
- Humans, Putamen diagnostic imaging, Putamen pathology, Male, Diagnosis, Differential, Middle Aged, Aged, Female, Amyotrophic Lateral Sclerosis diagnostic imaging, Amyotrophic Lateral Sclerosis pathology, Multiple System Atrophy diagnostic imaging, Multiple System Atrophy pathology, Magnetic Resonance Imaging, Autopsy
- Abstract
Competing Interests: Declaration of competing interest The authors declare no financial or other conflicts of interest.
- Published
- 2024
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8. The longitudinal volumetric and shape changes of subcortical nuclei in Parkinson's disease.
- Author
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Yang W, Bai X, Guan X, Zhou C, Guo T, Wu J, Xu X, Zhang M, Zhang B, Pu J, and Tian J
- Subjects
- Humans, Magnetic Resonance Imaging, Brain pathology, Putamen pathology, Disease Progression, Atrophy pathology, Parkinson Disease pathology
- Abstract
Brain structural changes in Parkinson's disease (PD) are progressive throughout the disease course. Changes in surface morphology with disease progression remain unclear. This study aimed to assess the volumetric and shape changes of the subcortical nuclei during disease progression and explore their association with clinical symptoms. Thirty-four patients and 32 healthy controls were enrolled. The global volume and shape of the subcortical nuclei were compared between patients and controls at baseline. The volume and shape changes of the subcortical nuclei were also explored between baseline and 2 years of follow-up. Association analysis was performed between the volume of subcortical structures and clinical symptoms. In patients with PD, there were significantly atrophied areas in the left pallidum and left putamen, while in healthy controls, the right putamen was dilated compared to baseline. The local morphology of the left pallidum was correlated with Mini Mental State Examination scores. The left putamen shape variation was negatively correlated with changes in Unified Parkinson's Disease Rating Scale PART III scores. Local morphological atrophy of the putamen and pallidum is an important pathophysiological change in the development of PD, and is associated with motor symptoms and cognitive status in patients with PD., (© 2024. The Author(s).)
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- 2024
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9. Evaluation of putamen area and cerebral peduncle with surrounding cistern in patients with Parkinson's disease: is there a difference from controls in cranial MRI?
- Author
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Say B, Bayar Muluk N, İnal M, Göncüoğlu A, Yörübulut S, and Ergün U
- Subjects
- Humans, Putamen diagnostic imaging, Putamen pathology, Retrospective Studies, Magnetic Resonance Imaging methods, Substantia Nigra pathology, Parkinson Disease diagnosis, Cerebral Peduncle pathology
- Abstract
Objectives: Nigrostriatal dopaminergic neuron loss is essential in pathogenesis of Parkinson's disease (PD). The purpose of this study was to evaluate nigrostriatal structures including the putamen, cerebral peduncle, widths of interpeduncular cistern, and ambient cistern around the midbrain with conventional cranial magnetic resonance images (MRI) in patients with PD., Methods: The MRI of 56 subjects was included, which was selected from the radiological data system for this retrospective study. The 29 patients with idiopathic PD were included and their disease duration, Hoehn&Yahr stage, and Levodopa equivalent dose (LED) were recorded. The 27 controls had a normal neurologic examination and cranial MRI. All subjects in the patient and control groups had right-hand dominance. Putamen and cerebral peduncle areas and widths of interpeduncular and ambient cisterns were measured in T2 sequences of MRI. Further statistical analysis was applied to exclude gender and age effect on areas., Results: The areas of putamen and cerebral peduncles were significantly reduced in patients with PD compared to the control bilaterally ( p < 0.001). Enlargement of interpeduncular and ambient cisterns in patients was higher than in controls, and it was significant ( p < 0.001). A correlation was not observed between measurement results and clinical characteristics of patients with PD. Only the cerebral peduncle area/ambient cistern width ratio was significantly correlated with disease duration positively (right r = 0.46 p = 0.012, left r = 0.389 p = 0.037)., Conclusion: Clinicians should be careful with conventional MRIs of patients with idiopathic PD in practice. It may be different from controls without any neurological disorder, particularly putamen, cerebral peduncles, interpeduncular, and ambient cisterns.
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- 2024
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10. 18 F-FP-DTBZ PET/CT detectable associations between monoaminergic depletion in the putamen with rigidity and the pallidus with tremor in Parkinson's disease.
- Author
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Huang AQ, Liu SY, Barret O, Qiao HW, Tamagnan GD, Liu XL, Fan CC, Li Z, Lu J, Chan P, and Xu EH
- Subjects
- Humans, Tremor etiology, Tremor complications, Positron Emission Tomography Computed Tomography adverse effects, Putamen diagnostic imaging, Putamen pathology, Brain pathology, Dopamine, Parkinson Disease complications, Parkinson Disease diagnostic imaging
- Abstract
Introduction: The motor subtypes of Parkinson's disease (PD) are widely accepted and implemented. However, the motor subtypes have been thought to represent different stages of PD recently because some patients experience tremor-dominant (TD) conversion to the non-tremor-dominant subtype, such as postural instability-gait difficulty (PIGD). In this study, we explore the monoaminergic denervation features of the striatal and extra-striatal areas in patients with different subtypes of PD with
18 F-9-fluoropropyl-(+)-dihydrotetrabenazine (18 F-FP-DTBZ) PET/CT., Methods: Sixty-five patients diagnosed with PD were included and classified as TD (n = 25) and PIGD (n = 40). We evaluated the difference of monoaminergic features of each subregion of brain between motor subtypes of PD, as well as associations between these features and Parkinsonian motor symptoms., Results: The striatal standardized uptake value ratios (SUVR) showed that dopaminergic disruption of patients with PIGD was more symmetrical in the posterior ventral putamen (p < 0.001) and more severe in the ipsilateral posterior dorsal putamen (p < 0.001 corrected) compared with that of patients with TD. The severity of PIGD scores was associated with striatal dopaminergic depletion, while tremor was associated with monoaminergic changes in extra-striatal areas, including pallidus, thalamus, and raphe nuclie., Conclusion: These results indicate that patients with different motor subtypes may have different underlying mechanisms of PD pathogenesis. Therefore, accurate diagnosis of PD subtypes can aid prognosis evaluation and treatment decision-making., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)- Published
- 2024
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11. Magnetic Resonance T1w/T2w Ratio in the Putamen and Cerebellum as a Marker of Cognitive Impairment in MSA: a Longitudinal Study.
- Author
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Cuoco S, Ponticorvo S, Bisogno R, Manara R, Esposito F, Di Salle G, Di Salle F, Amboni M, Erro R, Picillo M, Barone P, and Pellecchia MT
- Subjects
- Humans, Putamen diagnostic imaging, Putamen pathology, Longitudinal Studies, Magnetic Resonance Imaging methods, Cerebellum diagnostic imaging, Cerebellum pathology, Magnetic Resonance Spectroscopy, Multiple System Atrophy complications, Multiple System Atrophy diagnostic imaging, Cognitive Dysfunction diagnostic imaging, Cognitive Dysfunction pathology
- Abstract
The exact pathophysiology of cognitive impairment in multiple system atrophy (MSA) is unclear. In our longitudinal study, we aimed to analyze (I) the relationships between cognitive functions and some subcortical structures, such as putamen and cerebellum assessed by voxel-based morphometry (VBM) and T1-weighted/T2-weighted (T1w/T2w) ratio, and (II) the neuroimaging predictors of the progression of cognitive deficits. Twenty-six patients with MSA underwent a comprehensive neuropsychological battery, motor examination, and brain MRI at baseline (T
0 ) and 1-year follow-up (T1 ). Patients were then divided according to cognitive status into MSA with normal cognition (MSA-NC) and MSA with mild cognitive impairment (MCI). At T1 , we divided the sample according to worsening/non worsening of cognitive status compared to baseline evaluation. Logistic regression analysis showed that age (β = - 9.45, p = .02) and T1w/T2w value in the left putamen (β = 230.64, p = .01) were significant predictors of global cognitive status at T0 , explaining 65% of the variance. Logistic regression analysis showed that ∆-values of WM density in the cerebellum/brainstem (β = 2188.70, p = .02) significantly predicted cognitive worsening at T1 , explaining 64% of the variance. Our results suggest a role for the putamen and cerebellum in the cognitive changes of MSA, probably due to their connections with the cortex. The putaminal T1w/T2w ratio may deserve further studies as a marker of cognitive impairment in MSA., (© 2022. The Author(s).)- Published
- 2023
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12. Putative neurochemical and cell type contributions to hemodynamic activity in the rodent caudate putamen.
- Author
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Katz BM, Walton LR, Houston KM, Cerri DH, and Shih YI
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- Animals, Brain blood supply, Magnetic Resonance Imaging methods, Hemodynamics physiology, Putamen diagnostic imaging, Putamen pathology, Rodentia
- Abstract
Functional magnetic resonance imaging (fMRI) is widely used by researchers to noninvasively monitor brain-wide activity. The traditional assumption of a uniform relationship between neuronal and hemodynamic activity throughout the brain has been increasingly challenged. This relationship is now believed to be impacted by heterogeneously distributed cell types and neurochemical signaling. To date, most cell-type- and neurotransmitter-specific influences on hemodynamics have been examined within the cortex and hippocampus of rodent models, where glutamatergic signaling is prominent. However, neurochemical influences on hemodynamics are relatively unknown in largely GABAergic brain regions such as the rodent caudate putamen (CPu). Given the extensive contribution of CPu function and dysfunction to behavior, and the increasing focus on this region in fMRI studies, improved understanding of CPu hemodynamics could have broad impacts. Here we discuss existing findings on neurochemical contributions to hemodynamics as they may relate to the CPu with special consideration for how these contributions could originate from various cell types and circuits. We hope this review can help inform the direction of future studies as well as interpretation of fMRI findings in the CPu.
- Published
- 2023
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13. Putamen Structure and Function in Familial Risk for Depression: A Multimodal Imaging Study.
- Author
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Talati A, van Dijk MT, Pan L, Hao X, Wang Z, Gameroff M, Dong Z, Kayser J, Shankman S, Wickramaratne PJ, Posner J, and Weissman MM
- Subjects
- Humans, Creatine, Depression, Genetic Predisposition to Disease, Prospective Studies, Magnetic Resonance Imaging methods, Multimodal Imaging, Putamen diagnostic imaging, Putamen pathology, Depressive Disorder, Major
- Abstract
Background: The putamen has been implicated in depressive disorders, but how its structure and function increase depression risk is not clearly understood. Here, we examined how putamen volume, neuronal density, and mood-modulated functional activity relate to family history and prospective course of depression., Methods: The study includes 115 second- and third-generation offspring at high or low risk for depression based on the presence or absence of major depressive disorder in the first generation. Offspring were followed longitudinally using semistructured clinical interviews blinded to their familial risk; putamen structure, neuronal integrity, and functional activation were indexed by structural magnetic resonance imaging (MRI), proton magnetic resonance spectroscopy (N-acetylaspartate/creatine ratio), and functional MRI activity modulated by valence and arousal components of a mood induction task, respectively., Results: After adjusting for covariates, the high-risk individuals had lower putamen volume (standardized betas, β-
left = -0.17, β-right = -0.15, ps = .002), N-acetylaspartate/creatine ratio (β-left = -0.40, β-right = -0.37, ps < .0001), and activation modulated by valence (β-left = -0.22, β-right = -0.27, ps < .05) than low-risk individuals. Volume differences were greater at younger ages, and N-acetylaspartate/creatine ratio differences were greater at older ages. Lower putamen volume also predicted major depressive disorder episodes up to 8 years after the scan (β-left = -0.72, p = .013; β-right = -0.83, p = .037). Magnetic resonance spectroscopy and task functional MRI measures were modestly correlated (0.27 ≤ r ≤ 0.33)., Conclusions: Findings demonstrate abnormalities in putamen structure and function in individuals at high risk for major depressive disorder. Future studies should focus on this region as a potential biomarker for depressive illness, noting meanwhile that differences attributable to family history may peak at different ages based on which MRI modality is being used to assay them., (Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
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14. Importance of Susceptibility-weighted-imaging in Methanol Toxicity.
- Author
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Altintas F, Kaya A, Cesme DH, and Alkan A
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- Humans, Male, Putamen diagnostic imaging, Putamen pathology, Necrosis pathology, Methanol, Magnetic Resonance Imaging methods
- Abstract
Methanol poisoning is a rare but potentially lethal condition. Haemorrhagic necrosis of bilateral basal ganglia, particularly of the putamen, is one of the distinctive features of this entity. One of the proposed responsible mechanisms for putaminal haemorrhagic necrosis due to methanol toxicity is inadequate venous drainage of this region. Advanced imaging modalities are used to guide diagnosis and patient management. Here, we report a 61-year man who had a fulminant acute methanol toxicity due to accidental ingestion. Susceptibility-weighted-imaging (SWI) showed marked bilateral basal ganglia and brainstem haemorrhage. Also, congested and dilated venous structures were detected in SWI, which may be an indirect sign of inadequate venous drainage of this region. We intend to present the cerebral SWI features of a patient with fulminant methanol toxicity in order to clarify the underlying physiopathology of the brain damage, which has not yet been presented in the literature to the best of our knowledge. Key Words: Methanol, Toxic encephalopathy, Magnetic resonance imaging, Cerebral haemorrhage.
- Published
- 2022
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15. Modulation effect of substantia nigra iron deposition and functional connectivity on putamen glucose metabolism in Parkinson's disease.
- Author
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Zang Z, Song T, Li J, Yan S, Nie B, Mei S, Ma J, Yang Y, Shan B, Zhang Y, and Lu J
- Subjects
- Cross-Sectional Studies, Fluorodeoxyglucose F18 metabolism, Glucose metabolism, Humans, Iron metabolism, Magnetic Resonance Imaging, Substantia Nigra metabolism, Parkinson Disease metabolism, Putamen pathology
- Abstract
Neurodegeneration of the substantia nigra affects putamen activity in Parkinson's disease (PD), yet in vivo evidence of how the substantia nigra modulates putamen glucose metabolism in humans is missing. We aimed to investigate how substantia nigra modulates the putamen glucose metabolism using a cross-sectional design. Resting-state fMRI, susceptibility-weighted imaging, and [
18 F]-fluorodeoxyglucose-PET (FDG-PET) data were acquired. Forty-two PD patients and 25 healthy controls (HCs) were recruited for simultaneous PET/MRI scanning. The main measurements of the current study were R 2 * images representing iron deposition (28 PD and 25 HCs), standardized uptake value ratio (SUVr) images representing FDG-uptake (33 PD and 25 HCs), and resting state functional connectivity maps from resting state fMRI (34 PD and 25 HCs). An interaction term based on the general linear model was used to investigate the joint modulation effect of nigral iron deposition and nigral-putamen functional connectivity on putamen FDG-uptake. Compared with HCs, we found increased iron deposition in the substantia nigra (p = .007), increased FDG-uptake in the putamen (left: PFWE < 0.001; right: PFWE < 0.001), and decreased functional connectivity between the substantia nigra and the anterior putamen (left PFWE < 0.001, right: PFWE = 0.007). We then identified significant interaction effect of nigral iron deposition and nigral-putamen connectivity on FDG-uptake in the putamen (p = .004). The current study demonstrated joint modulation effect of the substantia nigra iron deposition and nigral-putamen functional connectivity on putamen glucose metabolic distribution, thereby revealing in vivo pathological mechanism of nigrostriatal neurodegeneration of PD., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)- Published
- 2022
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16. Reduced brain subcortical volumes in patients with glaucoma: a pilot neuroimaging study using the region-of-interest-based approach.
- Author
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Ha YW, Jang H, Koh SB, Noh Y, Lee SK, Seo SW, Cho J, and Kim C
- Subjects
- Brain diagnostic imaging, Brain pathology, Humans, Magnetic Resonance Imaging methods, Putamen pathology, Glaucoma diagnostic imaging, Glaucoma pathology, Neuroimaging
- Abstract
Background: While numerous neuroimaging studies have demonstrated that glaucoma is associated with smaller volumes of the visual cortices in the brain, only a few studies have linked glaucoma with brain structures beyond the visual cortices. Therefore, the objective of this study was to compare brain imaging markers and neuropsychological performance between individuals with and without glaucoma., Methods: We identified 64 individuals with glaucoma and randomly selected 128 age-, sex-, and education level-matched individuals without glaucoma from a community-based cohort. The study participants underwent 3 T brain magnetic resonance imaging and neuropsychological assessment battery. Regional cortical thickness and subcortical volume were estimated from the brain images of the participants. We used a linear mixed model after adjusting for potential confounding variables., Results: Cortical thickness in the occipital lobe was significantly smaller in individuals with glaucoma than in the matched individuals (β = - 0.04 mm, P = 0.014). This did not remain significant after adjusting for cardiovascular risk factors (β = - 0.02 mm, P = 0.67). Individuals with glaucoma had smaller volumes of the thalamus (β = - 212.8 mm
3 , P = 0.028), caudate (β = - 170.0 mm3 , P = 0.029), putamen (β = - 151.4 mm3 , P = 0.051), pallidum (β = - 103.6 mm3 , P = 0.007), hippocampus (β = - 141.4 mm3 , P = 0.026), and amygdala (β = - 87.9 mm3 , P = 0.018) compared with those without glaucoma. Among neuropsychological battery tests, only the Stroop color reading test score was significantly lower in individuals with glaucoma compared with those without glaucoma (β = - 0.44, P = 0.038)., Conclusions: We found that glaucoma was associated with smaller volumes of the thalamus, caudate, putamen, pallidum, amygdala, and hippocampus., (© 2022. The Author(s).)- Published
- 2022
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17. Phospholipid Profiles Are Selectively Altered in the Putamen and White Frontal Cortex of Huntington's Disease.
- Author
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Phillips GR, Hancock SE, Jenner AM, McLean C, Newell KA, and Mitchell TW
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- Adult, Esters, Frontal Lobe metabolism, Humans, Phospholipids metabolism, Putamen metabolism, Putamen pathology, Huntington Disease genetics
- Abstract
Huntington's disease (HD) is a genetic, neurodegenerative illness that onsets in late adulthood as a series of progressive and terminal cognitive, motor, and psychiatric deficits. The disease is caused by a polyQ mutation in the Huntingtin gene ( HTT ), producing a polyglutamine expansion in the Huntingtin protein (HTT). HTT interacts with phospholipids in vitro; however, its interactions are changed when the protein is mutated in HD. Emerging evidence suggests that the susceptibility of brain regions to pathological stimuli is influenced by lipid composition. This study aimed to identify where and how phospholipids are changed in human HD brain tissue. Phospholipids were extracted using a modified MTBE method from the post-mortem brain of 13 advanced-stage HD patients and 13 age- and sex-matched controls. Targeted precursor ion scanning mass spectrometry was used to detect phospholipid species. In the white cortex of HD patients, there was a significantly lower abundance of phosphatidylcholine (PC) and phosphatidylserine (PS), but no difference in phosphatidylethanolamine (PE). In HD putamen, ester-linked 22:6 was lower in all phospholipid classes promoting a decrease in the relative abundance of ester polyunsaturated fatty acids in PE. No differences in phospholipid composition were identified in the caudate, grey cortex or cerebellum. Ether-linked PE fatty acids appear protected in the HD brain, as no changes were identified. The nature of phospholipid alterations in the HD brain is dependent on the lipid (subclass, species, and bond type) and the location.
- Published
- 2022
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18. Bihemispheric developmental alterations in basal ganglia volumes following unilateral perinatal stroke.
- Author
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Hassett J, Carlson H, Babwani A, and Kirton A
- Subjects
- Basal Ganglia, Child, Female, Hand, Humans, Magnetic Resonance Imaging methods, Pregnancy, Putamen pathology, Stroke complications
- Abstract
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., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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19. Predicting alcohol dependence from multi-site brain structural measures.
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Hahn S, Mackey S, Cousijn J, Foxe JJ, Heinz A, Hester R, Hutchinson K, Kiefer F, Korucuoglu O, Lett T, Li CR, London E, Lorenzetti V, Maartje L, Momenan R, Orr C, Paulus M, Schmaal L, Sinha R, Sjoerds Z, Stein DJ, Stein E, van Holst RJ, Veltman D, Walter H, Wiers RW, Yucel M, Thompson PM, Conrod P, Allgaier N, and Garavan H
- Subjects
- Cerebral Cortex pathology, Humans, Putamen pathology, Reproducibility of Results, Alcoholism diagnostic imaging, Cerebral Cortex diagnostic imaging, Machine Learning, Magnetic Resonance Imaging methods, Magnetic Resonance Imaging standards, Multicenter Studies as Topic methods, Multicenter Studies as Topic standards, Neuroimaging methods, Neuroimaging standards, Putamen diagnostic imaging
- Abstract
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., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)
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- 2022
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20. Therapeutic potential of iron modulating drugs in a mouse model of multiple system atrophy.
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Shukla JJ, Stefanova N, Bush AI, McColl G, Finkelstein DI, and McAllum EJ
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- Animals, Brain metabolism, Brain pathology, Cerebellum drug effects, Cerebellum metabolism, Cerebellum pathology, Ceruloplasmin pharmacology, Copper metabolism, Deferiprone pharmacology, Disease Models, Animal, Ferritins drug effects, Ferritins metabolism, Iron Chelating Agents pharmacology, Mice, Mice, Transgenic, Multiple System Atrophy genetics, Multiple System Atrophy pathology, Multiple System Atrophy physiopathology, Prefrontal Cortex drug effects, Prefrontal Cortex metabolism, Prefrontal Cortex pathology, Putamen drug effects, Putamen metabolism, Putamen pathology, Substantia Nigra drug effects, Substantia Nigra metabolism, Substantia Nigra pathology, alpha-Synuclein genetics, Brain drug effects, Iron metabolism, Multiple System Atrophy metabolism
- Abstract
Multiple System Atrophy (MSA) is a rare neurodegenerative synucleinopathy which leads to severe disability followed by death within 6-9 years of symptom onset. There is compelling evidence suggesting that biological trace metals like iron and copper play an important role in synucleinopathies like Parkinson's disease and removing excess brain iron using chelators could slow down the disease progression. In human MSA, there is evidence of increased iron in affected brain regions, but role of iron and therapeutic efficacy of iron-lowering drugs in pre-clinical models of MSA have not been studied. We studied age-related changes in iron metabolism in different brain regions of the PLP-αsyn mice and tested whether iron-lowering drugs could alleviate disease phenotype in aged PLP-αsyn mice. Iron content, iron-ferritin association, ferritin protein levels and copper-ceruloplasmin association were measured in prefrontal cortex, putamen, substantia nigra and cerebellum of 3, 8, and 20-month-old PLP-αsyn and age-matched non-transgenic mice. Moreover, 12-month-old PLP-αsyn mice were administered deferiprone or ceruloplasmin or vehicle for 2 months. At the end of treatment period, motor testing and stereological analyses were performed. We found iron accumulation and perturbed iron-ferritin interaction in substantia nigra, putamen and cerebellum of aged PLP-αsyn mice. Furthermore, we found significant reduction in ceruloplasmin-bound copper in substantia nigra and cerebellum of the PLP-αsyn mice. Both deferiprone and ceruloplasmin prevented decline in motor performance in aged PLP-αsyn mice and were associated with higher neuronal survival and reduced density of α-synuclein aggregates in substantia nigra. This is the first study to report brain iron accumulation in a mouse model of MSA. Our results indicate that elevated iron in MSA mice may result from ceruloplasmin dysfunction and provide evidence that targeting iron in MSA could be a viable therapeutic option., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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21. Persistent dependent behaviour is accompanied by dynamic switching between the ventral and dorsal striatal connections in internet gaming disorder.
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Wang M, Zheng H, Zhou W, Jiang Q, and Dong GH
- Subjects
- Brain Mapping, Gambling diagnostic imaging, Humans, Image Processing, Computer-Assisted, Internet Addiction Disorder diagnostic imaging, Magnetic Resonance Imaging, Male, Nucleus Accumbens diagnostic imaging, Nucleus Accumbens pathology, Putamen diagnostic imaging, Support Vector Machine, Ventral Striatum diagnostic imaging, Young Adult, Gambling pathology, Internet Addiction Disorder pathology, Putamen pathology, Ventral Striatum pathology
- Abstract
Cross-sectional studies have suggested that functional heterogeneity within the striatum in individuals with addictive behaviours may involve the transition from ventral to dorsal partitions; however, due to limitations of the cross-sectional design, whether the contribution of this transition to addiction was confused by individual differences remains unclear, especially for internet gaming disorder (IGD). Longitudinal functional magnetic resonance imaging (fMRI) data from 22 IGD subjects and 18 healthy controls were collected at baseline and more than 6 months later. We examined the connectivity features of subregions within the striatum between these two scans. Based on the results, we further performed dynamic causal modelling to explore the directional effect between regions and used these key features for data classification in machine learning to test the replicability of the results. Compared with controls, IGD subjects exhibited decreased functional connectivity between the left dorsal striatum (putamen) and the left insula, whereas connectivity between the right ventral striatum (nucleus accumbens [Nacc]) and the left insula was relatively stable over time. An inhibitory effective connectivity from the left putamen to the right Nacc was found in IGD subjects during the follow-up scan. Using the above features, the classification accuracy of the training model developed with the follow-up was better than that of the model based on the initial scan. Persistent IGD status was accompanied by a switch in the locus of control within the striatum, which provided new insights into association between IGD and drug addiction., (© 2021 Society for the Study of Addiction.)
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- 2021
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22. GABA B receptor signaling in the caudate putamen is involved in binge-like consumption during a high fat diet in mice.
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Sun R, Tsunekawa T, Hirose T, Yaginuma H, Taki K, Mizoguchi A, Miyata T, Kobayashi T, Sugiyama M, Onoue T, Takagi H, Hagiwara D, Ito Y, Iwama S, Suga H, Banno R, Bettler B, and Arima H
- Subjects
- Animals, Baclofen administration & dosage, Bulimia drug therapy, Bulimia genetics, Bulimia pathology, Diet, High-Fat adverse effects, Disease Models, Animal, Dopaminergic Neurons metabolism, Female, GABA-B Receptor Agonists administration & dosage, Humans, Male, Mice, Mice, Knockout, Mice, Transgenic, Nucleus Accumbens cytology, Nucleus Accumbens metabolism, Nucleus Accumbens pathology, Obesity etiology, Obesity prevention & control, Putamen cytology, Putamen metabolism, Putamen pathology, Receptors, Dopamine D1 metabolism, Receptors, G-Protein-Coupled genetics, Receptors, GABA-B genetics, Signal Transduction drug effects, Signal Transduction genetics, Bulimia physiopathology, Obesity physiopathology, Putamen physiopathology, Receptors, GABA-B metabolism
- Abstract
Previous studies suggest that signaling by the gamma-aminobutyric acid (GABA) type B receptor (GABA
B R) is involved in the regulation of binge eating, a disorder which might contribute to the development of obesity. Here, we show that intermittent access to a high fat diet (HFD) induced binge-like eating behavior with activation of dopamine receptor d1 (drd1)-expressing neurons in the caudate putamen (CPu) and nucleus accumbens (NAc) in wild-type (WT) mice. The activation of drd1-expressing neurons during binge-like eating was substantially increased in the CPu, but not in the NAc, in corticostriatal neuron-specific GABAB R-deficient knockout (KO) mice compared to WT mice. Treatment with the GABAB R agonist, baclofen, suppressed binge-like eating behavior in WT mice, but not in KO mice, as reported previously. Baclofen also suppressed the activation of drd1-expressing neurons in the CPu, but not in the NAc, during binge-like eating in WT mice. Thus, our data suggest that GABAB R signaling in CPu neurons expressing drd1 suppresses binge-like consumption during a HFD in mice., (© 2021. The Author(s).)- Published
- 2021
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23. Resting-State Correlations of Fatigue Following Military Deployment.
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Lewis JD, Knutson KM, Gotts SJ, Tierney M, Ramage A, Tate DF, Clauw D, Williams DA, Robin DA, and Wassermann EM
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- Adult, Female, Humans, Magnetic Resonance Imaging, Male, Prefrontal Cortex pathology, Putamen pathology, Self Report, Surveys and Questionnaires statistics & numerical data, Basal Ganglia pathology, Brain pathology, Brain Concussion complications, Fatigue etiology, Military Deployment psychology
- Abstract
Objective: Persistent fatigue is common among military servicemembers returning from deployment, especially those with a history of mild traumatic brain injury (mTBI). The purpose of this study was to characterize fatigue following deployment using the Multidimensional Fatigue Inventory (MFI), a multidimensional self-report instrument. The study was developed to test the hypothesis that if fatigue involves disrupted effort/reward processing, this should manifest as altered basal ganglia functional connectivity as observed in other amotivational states., Methods: Twenty-eight current and former servicemembers were recruited and completed the MFI. All 28 participants had a history of at least one mTBI during deployment. Twenty-six participants underwent resting-state functional MRI. To test the hypothesis that fatigue was associated with basal ganglia functional connectivity, the investigators measured correlations between MFI subscale scores and the functional connectivity of the left and right caudate, the putamen, and the globus pallidus with the rest of the brain, adjusting for the presence of depression., Results: The investigators found a significant correlation between functional connectivity of the left putamen and bilateral superior frontal gyri and mental fatigue scores. No correlations with the other MFI subscales survived multiple comparisons correction., Conclusions: This exploratory study suggests that mental fatigue in military servicemembers with a history of deployment with at least one mTBI may be related to increased striatal-prefrontal functional connectivity, independent of depression. A finding of effort/reward mismatch may guide future treatment approaches.
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- 2021
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24. The stimulator of interferon genes (STING) pathway is upregulated in striatal astrocytes of patients with multiple system atrophy.
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Inoue Y, Ayaki T, Ishimoto T, Yamakado H, Maki T, Matsuzawa S, Sawamoto N, and Takahashi R
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- Aged, Aged, 80 and over, Case-Control Studies, Glial Fibrillary Acidic Protein analysis, Glial Fibrillary Acidic Protein metabolism, Humans, Male, Membrane Proteins analysis, Middle Aged, Multiple System Atrophy pathology, Putamen cytology, Putamen immunology, Signal Transduction immunology, Substantia Nigra cytology, Substantia Nigra immunology, Up-Regulation immunology, Astrocytes metabolism, Membrane Proteins metabolism, Multiple System Atrophy immunology, Putamen pathology, Substantia Nigra pathology
- Abstract
Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by the accumulation of pathogenic phosphorylated α-synuclein in oligodendrocytes. In brains affected by MSA, severe astrogliosis is also observed, but its precise role in MSA pathogenesis remains largely unknown. Recently, the stimulator of interferon genes (STING) pathway and type I interferons, its downstream molecules, have been reported to be involved in the neurodegenerative process and to be activated in astrocytes. This study aimed to investigate the role of the STING pathway in the pathogenesis of MSA using postmortem brains. Samples used for immunohistochemical analysis included 6 cases of MSA parkinsonism type (MSA-P), 6 cases of MSA cerebellar type (MSA-C), and 7 age-matched controls. In MSA-P cases, astrocytes immunopositive for STING and TANK-binding kinase 1 (TBK1), its downstream molecule, were abundantly observed in the putamen and the substantia nigra. Moreover, these molecules colocalized with glial fibrillary acidic protein (GFAP) in reactive astrocytes, and the density of STING-positive astrocytes correlated with that of GFAP-positive reactive astrocytes in the brains of patients with MSA-P. These results suggest that the upregulated expression of STING pathway-related proteins in astrocytes and the subsequent inflammation may contribute to the pathogenesis in MSA-P and could provide novel therapeutic targets for the treatment of MSA., (Copyright © 2021. Published by Elsevier B.V.)
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- 2021
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25. Targeting the mitochondrial permeability transition pore for neuroprotection in a piglet model of neonatal hypoxic-ischemic encephalopathy.
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Chen MW, Santos P, Kulikowicz E, Koehler RC, Lee JK, and Martin LJ
- Subjects
- Animals, Animals, Newborn, Cell Death, Heart Arrest, Male, Putamen pathology, Somatosensory Cortex pathology, Swine, Asphyxia Neonatorum prevention & control, Hypoxia-Ischemia, Brain prevention & control, Mitochondrial Permeability Transition Pore, Neuroprotective Agents therapeutic use
- Abstract
Neonatal hypoxic-ischemic encephalopathy (HIE) causes significant morbidity despite treatment with therapeutic hypothermia. Mitochondrial dysfunction may drive the mechanisms underlying neuronal cell death, thereby making mitochondria prime targets for neuroprotection. The mitochondrial permeability transition pore (mPTP) is one such target within mitochondria. In adult animal models, mPTP inhibition is neuroprotective. However, evidence for mPTP inhibition in neonatal models of neurologic disease is less certain. We tested the therapeutic efficacy of the mPTP small molecule inhibitor GNX-4728 and examined the developmental presence of brain mPTP proteins for drug targeting in a neonatal piglet model of hypoxic-ischemic brain injury. Male neonatal piglets were randomized to hypoxia-ischemia (HI) or sham procedure with GNX-4728 (15 mg/kg, IV) or vehicle (saline/cyclodextrin/DMSO, IV). GNX-4728 was administered as a single dose within 5 min after resuscitation from bradycardic arrest. Normal, ischemic, and injured neurons were counted in putamen and somatosensory cortex using hematoxylin and eosin staining. In separate neonatal and juvenile pigs, western blots of putamen mitochondrial-enriched fractions were used to evaluate mitochondrial integrity and the presence of mPTP proteins. We found that a single dose of GNX-4728 did not protect putamen and cortical neurons from cell death after HI. However, loss of mitochondrial matrix integrity occurred within 6h after HI, and while mPTP components are present in the neonatal brain their levels were significantly different compared to that of a mature juvenile brain. Thus, the neonatal brain mPTP may not be a good target for current neurotherapeutic drugs that are developed based on adult mitochondria., (© 2021 Wiley Periodicals LLC.)
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- 2021
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26. Neural correlates of fat preference in frontotemporal dementia: translating insights from the obesity literature.
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Ahmed RM, Tse NY, Chen Y, Henning E, Hodges JR, Kiernan MC, Irish M, Farooqi IS, and Piguet O
- Subjects
- Aged, Amygdala diagnostic imaging, Amygdala pathology, Atrophy pathology, Cerebral Cortex diagnostic imaging, Cerebral Cortex pathology, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Nerve Net diagnostic imaging, Patient Acuity, Putamen diagnostic imaging, Putamen pathology, Alzheimer Disease pathology, Alzheimer Disease physiopathology, Dietary Fats, Food Preferences physiology, Frontotemporal Dementia pathology, Frontotemporal Dementia physiopathology, Nerve Net pathology, Obesity
- Abstract
Objective: Alterations in eating behaviour are one of the diagnostic features of behavioural variant frontotemporal dementia (bvFTD). It is hypothesised that underlying brain network disturbances and atrophy to key structures may affect macronutrient preference in bvFTD. We aimed to establish whether a preference for dietary fat exists in bvFTD, its association with cognitive symptoms and the underlying neural mechanisms driving these changes., Methods: Using a test meal paradigm, adapted from the obesity literature, with variable fat content (low 20%, medium 40% and high 60%), preference for fat in 20 bvFTD was compared to 16 Alzheimer's disease (AD) and 13 control participants. MRI brain scans were analysed to determine the neural correlates of fat preference., Results: Behavioural variant FTD patients preferred the high-fat meal compared to both AD (U = 61.5; p = 0.001) and controls (U = 41.5; p = 0.001), with 85% of bvFTD participants consistently rating the high-fat content meal as their preferred option. This increased preference for the high-fat meal was associated with total behavioural change (Cambridge Behavioural Inventory: r
s = 0.462; p = 0.001), as well as overall functional decline (Frontotemporal Dementia Rating Scale: rs = -0.420; p = 0.03). A preference for high-fat content in bvFTD was associated with atrophy in an extended brain network including frontopolar, anterior cingulate, insular cortices, putamen and amygdala extending into lateral temporal, posteromedial parietal and occipital cortices., Conclusions: Increased preference for fat content is associated with many of the canonical features of bvFTD. These findings offer new insights into markers of disease progression and pathogenesis, providing potential treatment targets., (© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)- Published
- 2021
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27. Genetic underpinnings of risky behaviour relate to altered neuroanatomy.
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Aydogan G, Daviet R, Karlsson Linnér R, Hare TA, Kable JW, Kranzler HR, Wetherill RR, Ruff CC, Koellinger PD, and Nave G
- Subjects
- Adult, Aged, Amygdala diagnostic imaging, Amygdala pathology, Female, Genome-Wide Association Study, Gray Matter pathology, Humans, Hypothalamus diagnostic imaging, Hypothalamus pathology, Male, Middle Aged, Multifactorial Inheritance, Prefrontal Cortex diagnostic imaging, Prefrontal Cortex pathology, Putamen diagnostic imaging, Putamen pathology, United Kingdom, Ventral Striatum diagnostic imaging, Ventral Striatum pathology, Alcohol Drinking, Automobile Driving, Gray Matter diagnostic imaging, Organ Size genetics, Risk-Taking, Sexual Behavior, Smoking
- Abstract
Previous research points to the heritability of risk-taking behaviour. However, evidence on how genetic dispositions are translated into risky behaviour is scarce. Here, we report a genetically informed neuroimaging study of real-world risky behaviour across the domains of drinking, smoking, driving and sexual behaviour in a European sample from the UK Biobank (N = 12,675). We find negative associations between risky behaviour and grey-matter volume in distinct brain regions, including amygdala, ventral striatum, hypothalamus and dorsolateral prefrontal cortex (dlPFC). These effects are replicated in an independent sample recruited from the same population (N = 13,004). Polygenic risk scores for risky behaviour, derived from a genome-wide association study in an independent sample (N = 297,025), are inversely associated with grey-matter volume in dlPFC, putamen and hypothalamus. This relation mediates roughly 2.2% of the association between genes and behaviour. Our results highlight distinct heritable neuroanatomical features as manifestations of the genetic propensity for risk taking.
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- 2021
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28. Characterization and diagnostic potential of diffusion tractography in multiple system atrophy.
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Beliveau V, Krismer F, Skalla E, Schocke MM, Gizewski ER, Wenning GK, Poewe W, Seppi K, and Scherfler C
- Subjects
- Aged, Diagnosis, Differential, Female, Humans, Male, Middle Aged, Middle Cerebellar Peduncle pathology, Multiple System Atrophy pathology, Parkinson Disease pathology, Putamen pathology, Sensitivity and Specificity, Diffusion Tensor Imaging standards, Middle Cerebellar Peduncle diagnostic imaging, Multiple System Atrophy diagnostic imaging, Parkinson Disease diagnostic imaging, Putamen diagnostic imaging
- Abstract
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., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2021
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29. Early prediction of putamen imaging features in HIV-associated neurocognitive impairment syndrome.
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Qi Y, Xu M, Wang W, Wang YY, Liu JJ, Ren HX, Liu MM, Li RL, and Li HJ
- Subjects
- Adult, Brain diagnostic imaging, Brain pathology, Cognitive Dysfunction, Female, Humans, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Radiographic Image Interpretation, Computer-Assisted, Retrospective Studies, AIDS Dementia Complex diagnostic imaging, AIDS Dementia Complex pathology, AIDS Dementia Complex physiopathology, Putamen diagnostic imaging, Putamen pathology
- Abstract
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.
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- 2021
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30. Significant, replicable, and functional associations between KTN1 variants and alcohol and drug codependence.
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Luo X, Guo X, Luo X, Tan Y, Zhang P, Yang K, Xie T, Shi J, Zhang Y, Xu J, Zuo L, and Li CR
- Subjects
- Alcoholism epidemiology, Alcoholism genetics, Alleles, Australia, Comorbidity, Female, Genetic Predisposition to Disease, Gray Matter pathology, Humans, Male, Marijuana Abuse epidemiology, Marijuana Abuse genetics, Polymorphism, Single Nucleotide, RNA, Messenger biosynthesis, Tobacco Use Disorder epidemiology, Tobacco Use Disorder genetics, White People, Membrane Proteins genetics, Putamen pathology, Substance-Related Disorders epidemiology, Substance-Related Disorders genetics
- Abstract
The gray matter volume (GMV) of the putamen has been reported to be regulated by kinectin 1 gene (KTN1). As a hub of the dopaminergic circuit, the putamen is widely implicated in the etiological processes of substance use disorders (SUD). Here, we aimed to identify robust and reliable associations between KTN1 SNPs and SUD across multiple samples. We examined the associations between SUD and KTN1 SNPs in four independent population-based or family-based samples (n = 10,209). The potential regulatory effects of the risk alleles on the putamen GMVs, the effects of alcohol, nicotine, marijuana and cocaine on KTN1 mRNA expression, and the relationship between KTN1 mRNA expression and SUD were explored. We found that a total of 23 SNPs were associated with SUD across at least two independent samples (1.4 × 10
-4 ≤ p ≤ 0.049), including one SNP (rs12895072) across three samples (8.8 × 10-3 ≤ p ≤ 0.049). Four other SNPs were significantly or suggestively associated with SUD only in European-Australians (4.8 × 10-4 ≤ p ≤ 0.058). All of the SUD-risk alleles of these 27 SNPs increased (β > 0) the putamen GMVs and represented major alleles (f > 0.5) in Europeans. Twenty-two SNPs were potentially biologically functional. Alcohol, nicotine and cocaine significantly affected the KTN1 mRNA expression, and the KTN1 mRNA was differentially expressed between nicotine or cocaine dependent and control subjects. We concluded that there was a replicable and robust relationship among the KTN1 variants, KTN1 mRNA expression, putamen GMVs, molecular effects of substances, and SUD, suggesting that some risk KTN1 alleles might increase kinectin 1 expression in the putamen, altering putamen structures and functions, and leading to SUD., (© 2020 Society for the Study of Addiction.)- Published
- 2021
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31. Association of Dilated Perivascular Spaces and Disease Severity in Patients With Huntington Disease.
- Author
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Chan ST, Mercaldo ND, Ravina B, Hersch SM, and Rosas HD
- Subjects
- Adult, Cross-Sectional Studies, Female, Glymphatic System diagnostic imaging, Humans, Huntington Disease diagnostic imaging, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Putamen diagnostic imaging, Severity of Illness Index, White Matter diagnostic imaging, Glymphatic System pathology, Huntington Disease pathology, Huntington Disease physiopathology, Putamen pathology, White Matter pathology
- Abstract
Objective: To quantify the percent volume of dilated perivascular space (PVS) in the subcortical forebrain in patients with early Huntington disease (HD) and to explore the relationship between PVS and disease severity., Methods: MRI scans were performed on 25 patients with HD and 23 healthy age-matched controls at Massachusetts General Hospital. The imaging data were analyzed with a novel algorithm to determine regional PVS volume. A fractional logistic regression analysis was used to quantify the association between regional percent PVS volume and (1) disease designation (HD or control) and (2) disease severity as assessed by normalized caudate volume., Results: Patients with HD had the greatest percent volume of dilated PVS in the putamen (left putamen: odds ratio 2.06 [95% confidence interval (CI) 1.62-2.62], HD 3.27% [95% CI 2.83-3.78] vs controls 1.62% [95% CI 1.32-1.97], p
fdr < 0.001; right putamen: odds ratio 1.66 [95% CI 1.33-2.08], HD 3.43% [95% CI 2.94-4.01] vs controls 2.09% [95% CI 1.79-2.45], pfdr < 0.001) and several subcortical white matter regions compared to controls. Dilated PVS increased with disease severity., Conclusions: The objective quantification of dilated PVS suggests that PVS burden is high, is associated with disease severity, and may affect the distribution and success of treatments administered either intrathecally such as antisense oligonucleotides or by intraparenchymal administration such as cell and gene therapies., Classification of Evidence: This study provides Class II evidence that increased dilated PVS is associated with worse HD severity. The study is rated Class II because of the cross-sectional design., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)- Published
- 2021
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32. White Matter Microstructural Abnormalities in the Broca's-Wernicke's-Putamen "Hoffman Hallucination Circuit" and Auditory Transcallosal Fibers in First-Episode Psychosis With Auditory Hallucinations.
- Author
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Salisbury DF, Wang Y, Yeh FC, and Coffman BA
- Subjects
- Adolescent, Adult, Affective Disorders, Psychotic diagnostic imaging, Broca Area diagnostic imaging, Corpus Callosum diagnostic imaging, Diffusion Magnetic Resonance Imaging, Female, Hallucinations diagnostic imaging, Humans, Male, Neural Pathways diagnostic imaging, Neural Pathways pathology, Psychotic Disorders diagnostic imaging, Putamen diagnostic imaging, Schizophrenia diagnostic imaging, Wernicke Area diagnostic imaging, White Matter diagnostic imaging, Young Adult, Affective Disorders, Psychotic pathology, Auditory Perception, Broca Area pathology, Corpus Callosum pathology, Hallucinations pathology, Psychotic Disorders pathology, Putamen pathology, Schizophrenia pathology, Wernicke Area pathology, White Matter pathology
- Abstract
Background: Functional connectivity abnormalities between Broca's and Wernicke's areas and the putamen revealed by functional magnetic resonance imaging (fMRI) are related to auditory hallucinations (AH). In long-term schizophrenia, reduced white matter structural integrity revealed by diffusion imaging in left arcuate fasciculus (connecting Broca's and Wernicke's areas) is likely related to AH. The structural integrity of connections with putamen and their relation to AH are unknown. Little is known about this relationship in first-episode psychosis (FEP), although auditory transcallosal connections were reported to play a role. White matter in the Broca's-Wernicke's-putamen language-related circuit and auditory transcallosal fibers was examined to investigate associations with AH in FEP., Methods: White matter connectivity was measured in 40 FEP and 32 matched HC using generalized fractional anisotropy (gFA) derived from diffusion spectrum imaging (DSI)., Results: FEP and HC did not differ in gFA in any fiber bundle. In FEP, AH severity was significantly inversely related to gFA in auditory transcallosal fibers and left arcuate fasciculus. Although the right hemisphere arcuate fasciculus-AH association did not attain significance, the left and right arcuate fasciculus associations were not significantly different., Conclusions: Despite overall normal gFA in FEP, AH severity was significantly related to gFA in transcallosal auditory fibers and the left hemisphere connection between Broca's and Wernicke's areas. Other bilateral tracts' gFA were weakly associated with AH. At the first psychotic episode, AH are more robustly associated with left hemisphere arcuate fasciculus and interhemispheric auditory fibers microstructural deficits, likely reflecting mistiming of information flow between language-related cortical centers., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2021
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33. A link between synaptic plasticity and reorganization of brain activity in Parkinson's disease.
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Rebelo D, Oliveira F, Abrunhosa A, Januário C, Lemos J, and Castelo-Branco M
- Subjects
- Aged, Brain Mapping, Case-Control Studies, Caudate Nucleus diagnostic imaging, Caudate Nucleus drug effects, Caudate Nucleus pathology, Dopamine metabolism, Dopamine Antagonists therapeutic use, Female, Frontal Lobe diagnostic imaging, Frontal Lobe drug effects, Frontal Lobe pathology, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neurons drug effects, Neurons metabolism, Neurons pathology, Oxygen blood, Parietal Lobe diagnostic imaging, Parietal Lobe drug effects, Parietal Lobe pathology, Parkinson Disease diagnostic imaging, Parkinson Disease drug therapy, Parkinson Disease pathology, Positron-Emission Tomography, Putamen diagnostic imaging, Putamen drug effects, Putamen pathology, Raclopride therapeutic use, Saccades physiology, Synapses drug effects, Synapses metabolism, Synapses pathology, Caudate Nucleus metabolism, Frontal Lobe metabolism, Neuronal Plasticity drug effects, Parietal Lobe metabolism, Parkinson Disease metabolism, Putamen metabolism, Receptors, Dopamine D2 metabolism
- Abstract
The link between synaptic plasticity and reorganization of brain activity in health and disease remains a scientific challenge. We examined this question in Parkinson's disease (PD) where functional up-regulation of postsynaptic D
2 receptors has been documented while its significance at the neural activity level has never been identified. We investigated cortico-subcortical plasticity in PD using the oculomotor system as a model to study reorganization of dopaminergic networks. This model is ideal because this system reorganizes due to frontal-to-parietal shifts in blood oxygen level-dependent (BOLD) activity. We tested the prediction that functional activation plasticity is associated with postsynaptic dopaminergic modifications by combining positron emission tomography/functional magnetic resonance imaging to investigate striatal postsynaptic reorganization of dopamine D2 receptors (using11 C-raclopride) and neural activation in PD. We used covariance (connectivity) statistics at molecular and functional levels to probe striato-cortical reorganization in PD in on/off medication states to show that functional and molecular forms of reorganization are related. D2 binding across regions defined by prosaccades showed increased molecular connectivity between both caudate/putamen and hyperactive parietal eye fields in PD in contrast with frontal eye fields in controls, in line with the shift model. Concerning antisaccades, parietal-striatal connectivity dominated in again in PD, unlike frontal regions. Concerning molecular-BOLD covariance, a striking sign reversal was observed: PD patients showed negative frontal-putamen functional-molecular associations, consistent with the reorganization shift, in contrast with the positive correlations observed in controls. Follow-up analysis in off-medication PD patients confirmed the negative BOLD-molecular correlation. These results provide a link among BOLD responses, striato-cortical synaptic reorganization, and neural plasticity in PD., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)- Published
- 2021
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34. Viral-based rodent and nonhuman primate models of multiple system atrophy: Fidelity to the human disease.
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Marmion DJ, Rutkowski AA, Chatterjee D, Hiller BM, Werner MH, Bezard E, Kirik D, McCown T, Gray SJ, and Kordower JH
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- Animals, Dependovirus, Genetic Vectors, Humans, Macaca fascicularis, Multiple System Atrophy metabolism, Multiple System Atrophy pathology, Oligodendroglia metabolism, Rats, Stereotaxic Techniques, alpha-Synuclein metabolism, Disease Models, Animal, Multiple System Atrophy genetics, Neostriatum pathology, Neurons pathology, Oligodendroglia pathology, Putamen pathology, alpha-Synuclein genetics
- Abstract
Multiple system atrophy (MSA) is a rare and extremely debilitating progressive neurodegenerative disease characterized by variable combinations of parkinsonism, cerebellar ataxia, dysautonomia, and pyramidal dysfunction. MSA is a unique synucleinopathy, in which alpha synuclein-rich aggregates are present in the cytoplasm of oligodendroglia. The precise origin of the alpha synuclein (aSyn) found in the glial cytoplasmic inclusions (GCIs) as well the mechanisms of neurodegeneration in MSA remain unclear. Despite this fact, cell and animal models of MSA rely on oligodendroglial overexpression of aSyn. In the present study, we utilized a novel oligotrophic AAV, Olig001, to overexpress aSyn specifically in striatal oligodendrocytes of rats and nonhuman primates in an effort to further characterize our novel viral vector-mediated MSA animal models. Using two cohorts of animals with 10-fold differences in Olig001 vector titers, we show a dose-dependent formation of MSA-like pathology in rats. High titer of Olig001-aSyn in these animals were required to produce the formation of pS129+ and proteinase K resistant aSyn-rich GCIs, demyelination, and neurodegeneration. Using this knowledge, we injected high titer Olig001 in the putamen of cynomolgus macaques. After six months, histological analysis showed that oligodendroglial overexpression of aSyn resulted in the formation of hallmark GCIs throughout the putamen, demyelination, a 44% reduction of striatal neurons and a 12% loss of nigral neurons. Furthermore, a robust inflammatory response similar to MSA was produced in Olig001-aSyn NHPs, including microglial activation, astrogliosis, and a robust infiltration of T cells into the CNS. Taken together, oligodendroglial-specific viral vector-mediated overexpression of aSyn in rats and nonhuman primates faithfully reproduces many of the pathological disease hallmarks found in MSA. Future studies utilizing these large animal models of MSA would prove extremely valuable as a pre-clinical platform to test novel therapeutics that are so desperately needed for MSA., (Copyright © 2020. Published by Elsevier Inc.)
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- 2021
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35. Sydenham Chorea: Putaminal Enlargement.
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Karalok ZS, Öztürk Z, Gunes A, and Gurkas E
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- Adolescent, Child, Female, Humans, Male, Retrospective Studies, Turkey, Chorea diagnostic imaging, Chorea pathology, Magnetic Resonance Imaging methods, Putamen diagnostic imaging, Putamen pathology
- Abstract
Background: Our aim in this study was to evaluate the efficacy of magnetic resonance imaging (MRI) studies in the detection of brain regions effected by Sydenham chorea and to determine whether they provided data regarding the pathogenesis of Sydenham chorea. To this end, we assessed basal ganglia structures in Sydenham chorea patients and control group by quantitative MRI volumetric analysis., Methods: Patients with a recent onset of chorea and control subjects matched for age and gender were included in the study. Medical history, laboratory tests, and physical and neurologic examinations were reviewed. All MRIs were considered within normal limits. High-resolution T1-weighted 3D magnetization-prepared rapid acquisition of gradient echo scans were used for quantitative volumetric assessment of the brain via the "volBrain" method., Results: Twenty-four subjects with Sydenham chorea (16 girls and 8 boys, aged between 7 and 16 years) and 35 control subjects were evaluated. Mean age was 11.25 ± 2.89 years for Sydenham chorea patients and 10.58 ± 2.53 years for the controls. No significant difference was found relative to globus pallidus, caudate, and thalamic volumes between patients with Sydenham chorea and controls. The relative mean total, left, and right putamen volumes were significantly larger in patients with Sydenham chorea compared to controls ( P = .003, P = .018, P = .001, respectively)., Conclusion: Selective neuroanatomic differences in putamen among other basal ganglia structures and significant increases in size are consistent with a hypothesis of a cross-reactive antibody-mediated inflammation of the putamen as being the pathophysiologic mechanism for this disorder.
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- 2021
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36. Cholesteryl ester levels are elevated in the caudate and putamen of Huntington's disease patients.
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Phillips GR, Hancock SE, Brown SHJ, Jenner AM, Kreilaus F, Newell KA, and Mitchell TW
- Subjects
- Acetyl-CoA C-Acetyltransferase analysis, Acetyl-CoA C-Acetyltransferase metabolism, Aged, Aged, 80 and over, Animals, Case-Control Studies, Caudate Nucleus pathology, Cerebellum metabolism, Cerebellum pathology, Cholesterol Esters metabolism, Female, Humans, Male, Mass Spectrometry, Mice, Middle Aged, Putamen pathology, Caudate Nucleus chemistry, Cholesterol Esters analysis, Huntington Disease pathology, Putamen chemistry
- Abstract
Huntington's disease (HD) is an autosomal dominant neurodegenerative illness caused by a mutation in the huntingtin gene (HTT) and subsequent protein (mhtt), to which the brain shows a region-specific vulnerability. Disturbances in neural cholesterol metabolism are established in HD human, murine and cell studies; however, cholesteryl esters (CE), which store and transport cholesterol in the brain, have not been investigated in human studies. This study aimed to identify region-specific alterations in the concentrations of CE in HD. The Victorian Brain Bank provided post-mortem tissue from 13 HD subjects and 13 age and sex-matched controls. Lipids were extracted from the caudate, putamen and cerebellum, and CE were quantified using targeted mass spectrometry. ACAT 1 protein expression was measured by western blot. CE concentrations were elevated in HD caudate and putamen compared to controls, with the elevation more pronounced in the caudate. No differences in the expression of ACAT1 were identified in the striatum. No remarkable differences in CE were detected in HD cerebellum. The striatal region-specific differences in CE profiles indicate functional subareas of lipid disturbance in HD. The increased CE concentration may have been induced as a compensatory mechanism to reduce cholesterol accumulation.
- Published
- 2020
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37. Neurologic effects of short-term treatment with a soluble epoxide hydrolase inhibitor after cardiac arrest in pediatric swine.
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O'Brien CE, Santos PT, Kulikowicz E, Lee JK, Koehler RC, and Martin LJ
- Subjects
- Animals, Asphyxia pathology, Cell Death, Endoplasmic Reticulum Stress, Male, Motor Cortex pathology, Neurons pathology, Phenylurea Compounds therapeutic use, Piperidines therapeutic use, Putamen pathology, Swine, Treatment Outcome, Enzyme Inhibitors therapeutic use, Epoxide Hydrolases antagonists & inhibitors, Heart Arrest complications, Nervous System Diseases drug therapy, Nervous System Diseases etiology
- Abstract
Background: Cardiac arrest (CA) is the most common cause of acute neurologic insult in children. Many survivors have significant neurocognitive deficits at 1 year of recovery. Epoxyeicosatrienoic acids (EETs) are multifunctional endogenous lipid signaling molecules that are involved in brain pathobiology and may be therapeutically relevant. However, EETs are rapidly metabolized to less active dihydroxyeicosatrienoic acids by soluble epoxide hydrolase (sEH), limiting their bioavailability. We hypothesized that sEH inhibition would improve outcomes after CA in an infant swine model. Male piglets (3-4 kg, 2 weeks old) underwent hypoxic-asphyxic CA. After resuscitation, they were randomized to intravenous treatment with an sEH inhibitor (TPPU, 1 mg/kg; n = 8) or vehicle (10% poly(ethylene glycol); n = 9) administered at 30 min and 24 h after return of spontaneous circulation. Two sham-operated groups received either TPPU (n = 9) or vehicle (n = 8). Neurons were counted in hematoxylin- and eosin-stained sections from putamen and motor cortex in 4-day survivors., Results: Piglets in the CA + vehicle groups had fewer neurons than sham animals in both putamen and motor cortex. However, the number of neurons after CA did not differ between vehicle- and TPPU-treated groups in either anatomic area. Further, 20% of putamen neurons in the Sham + TPPU group had abnormal morphology, with cell body attrition and nuclear condensation. TPPU treatment also did not reduce neurologic deficits., Conclusion: Treatment with an sEH inhibitor at 30 min and 24 h after resuscitation from asphyxic CA does not protect neurons or improve acute neurologic outcomes in piglets.
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- 2020
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38. Early putamen hypertrophy and ongoing hippocampus atrophy predict cognitive performance in the first ten years of relapsing-remitting multiple sclerosis.
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Morelli ME, Baldini S, Sartori A, D'Acunto L, Dinoto A, Bosco A, Bratina A, and Manganotti P
- Subjects
- Atrophy pathology, Cognition, Hippocampus diagnostic imaging, Hippocampus pathology, Humans, Hypertrophy diagnostic imaging, Hypertrophy pathology, Magnetic Resonance Imaging, Neuropsychological Tests, Putamen pathology, Cognition Disorders diagnostic imaging, Cognition Disorders etiology, Cognition Disorders pathology, Multiple Sclerosis pathology, Multiple Sclerosis, Relapsing-Remitting complications, Multiple Sclerosis, Relapsing-Remitting diagnostic imaging
- Abstract
Background: The first years of relapsing-remitting multiple sclerosis (RRMS) constitute the most vulnerable phase for the progression of cognitive impairment (CImp), due to a gradual decrease of compensatory mechanisms. In the first 10 years of RRMS, the temporal volumetric changes of deep gray matter structures must be clarified, since they could constitute reliable cognitive biomarkers for diagnostic, prognostic, and therapeutic purposes., Methods: Forty-five cognitively asymptomatic patients with RRMS lasting ≤ 10 years, and with a brain MRI performed in a year from the neuropsychological evaluation (Te-MRI), were included. They performed the Brief International Cognitive Assessment battery for MS. Thirty-one brain MRIs performed in the year of diagnosis (Td-MRI) and 13 brain MRIs of age- and sex-matched healthy controls (HCs) were also included in the study. The relationships between clinical features, cognitive performances, and Te- and Td-MRI volumes were statistically analyzed., Results: Cognitively preserved (CP) patients had significantly increased Td-L-putamen (P = 0.035) and Td-R-putamen volume (P = 0.027) with respect to cognitively impaired (CI) ones. CI patients had significantly reduced Te-L-hippocampus (P = 0.019) and Te-R-hippocampus volume (P = 0.042) compared, respectively, with Td-L-hippocampus and Td-R-hippocampus volume. Td-L-putamen volume (P = 0.011) and Te-L-hippocampus volume (P = 0.023) were independent predictors of the Symbol Digit Modalities Test score in all patients (r2 = 0.31, F = 6.175, P = 0.001)., Conclusion: In the first years of RRMS, putamen hypertrophy and hippocampus atrophy could represent promising indices of cognitive performance and reserve, and become potentially useful tools for diagnostic, prognostic, and therapeutic purposes.
- Published
- 2020
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39. Lexical-semantic search related to side of onset and putamen volume in Parkinson's disease.
- Author
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Wagner D, Eslinger PJ, Sterling NW, Du G, Lee EY, Styner M, Lewis MM, and Huang X
- Subjects
- Age Factors, Aged, Case-Control Studies, Corpus Striatum pathology, Female, Humans, Language Development, Language Disorders etiology, Language Disorders physiopathology, Magnetic Resonance Imaging, Male, Middle Aged, Organ Size, Parkinson Disease physiopathology, Parkinson Disease psychology, Functional Laterality physiology, Language Disorders pathology, Parkinson Disease pathology, Putamen pathology, Semantics
- Abstract
Parkinson's disease (PD) is characterized by dopaminergic cell loss and reduced striatal volume. Prior studies have demonstrated striatal involvement in access to lexical-semantic knowledge and damage to this structure may be evident in the lexical properties of responses. Semantic fluency task responses from early stage, non-demented PD participants with right (PD-R) or left (PD-L) lateralizing symptoms were compared to matched controls on lexical properties (word frequency, age of acquisition) and correlated with striatal volumes segmented from T1-weighted brain MR images. PD-R participants produced semantic fluency responses of a lower age of acquisition than PD-L and control participants (p < 0.05). PD-R age of acquisition responses correlated positively with putamen volume (p < 0.05), while age of acquisition of responses correlated negatively with caudate volume in controls (p < 0.05). Findings provide evidence for a role of the striatum in lexical-semantic access and qualitative changes in lexical access in select PD patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Inc.)
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- 2020
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40. Remodeling microglia to a protective phenotype in Parkinson's disease?
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Awogbindin IO, Ishola IO, St-Pierre MK, Carrier M, Savage JC, Di Paolo T, and Tremblay MÈ
- Subjects
- Animals, Humans, Phenotype, Microglia pathology, Parkinson Disease pathology, Pars Compacta pathology, Putamen pathology
- Abstract
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., (Copyright © 2020 Elsevier B.V. All rights reserved.)
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- 2020
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41. Older, non-demented apolipoprotein ε 4 carrier males show hyperactivation and structural differences in odor memory regions: a blood-oxygen-level-dependent and structural magnetic resonance imaging study.
- Author
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Kapoulea EA and Murphy C
- Subjects
- Age Factors, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Organ Size, Putamen pathology, Apolipoprotein E4, Heterozygote, Magnetic Resonance Imaging, Memory physiology, Odorants, Oxygen Consumption physiology, Putamen diagnostic imaging, Putamen physiology, Sex Characteristics, Smell genetics, Smell physiology
- Abstract
The current study sought to examine the interaction of sex and Apolipoprotein ε
4 status on olfactory recognition memory within non-demented, older individuals. We separated 39 participants into groups based on ε4 status and sex. Each participant completed an olfactory memory recognition task during 2 functional magnetic resonance imaging scans and 1 structural scan. The ε4 carriers had greater functional recruitment of memory regions during false positives relative to ε4 non-carriers. During hits, the male ε4 carriers showed greater functional recruitment compared to female ε4 carriers. The ε4 carriers had larger bilateral putamen volumes relative to ε4 non-carriers. Neuroimaging data were significantly associated with Dementia Rating Scale scores solely in males. Results suggest differential olfactory memory processing in relation to sex and ε4 status. Male ε4 carriers in particular, demonstrated hyperactivation during recognition memory, which we suspect reflects neuronal compensation to maintain functional performance. Future studies should consider examining underlying mechanisms that contribute to these sex differences within ε4 carriers., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2020
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42. Discrete changes in brain volume after deep brain stimulation in patients with Parkinson's disease.
- Author
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Kern DS, Uy D, Rhoades R, Ojemann S, Abosch A, and Thompson JA
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- Atrophy pathology, Deep Brain Stimulation adverse effects, Deep Brain Stimulation methods, Female, Globus Pallidus physiology, Humans, Male, Middle Aged, Subthalamic Nucleus physiology, Time Factors, Caudate Nucleus pathology, Globus Pallidus pathology, Parkinson Disease therapy, Putamen pathology, Thalamus pathology
- Abstract
Objectives: Deep brain stimulation (DBS), targeting the subthalamic nucleus (STN) and globus pallidus interna, is a surgical therapy with class 1 evidence for Parkinson's disease (PD). Bilateral DBS electrodes may be implanted within a single operation or in separate staged surgeries with an interval of time that varies patient by patient. In this study, we used the variation in the timing of implantation from the first to the second implantation allowing for examination of potential volumetric changes of the basal ganglia in patients with PD who underwent staged STN DBS., Methods: Thirty-two patients with a mean time interval between implantations of 141.8 (±209.1; range: 7-700) days and mean duration of unilateral stimulation of 244.7 (±227.7; range: 20-672) days were included in this study. Using volumetric analysis of whole hemisphere and subcortical structures, we observed whether implantation or stimulation affected structural volume., Results: We observed that DBS implantation, but not the duration of stimulation, induced a significant reduction of volume in the caudate, pallidum, putamen and thalamus ipsilateral to the implanted hemisphere. These findings were not dependent on the trajectory of the implanted electrode nor on first surgery pneumocephalus (0.07%: %Δ for intracranial volume between first and second surgery). In addition, unique regional atrophy differences were evident in each of the structures., Conclusion: Our results demonstrate that DBS implantation surgery may affect hemisphere volume at the level of subcortical structures connected to the surgical target., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2020
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43. Faciobrachial dystonic seizures secondary to basal ganglia involvement in anti-LGI1 encephalitis.
- Author
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Gupta D, Mehta A, Pradeep R, Javali M, Acharya PT, and Srinivasa R
- Subjects
- Electroencephalography, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Putamen diagnostic imaging, Putamen pathology, Putamen physiopathology, Autoimmune Diseases of the Nervous System complications, Autoimmune Diseases of the Nervous System diagnosis, Basal Ganglia Diseases complications, Basal Ganglia Diseases diagnosis, Basal Ganglia Diseases pathology, Basal Ganglia Diseases physiopathology, Dystonia diagnosis, Dystonia etiology, Dystonia physiopathology, Encephalitis complications, Encephalitis diagnosis, Intracellular Signaling Peptides and Proteins immunology, Seizures diagnosis, Seizures etiology, Seizures physiopathology
- Published
- 2020
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44. Para-limbic Structural Abnormalities Are Associated With Internalizing Symptoms in Children With Prenatal Alcohol Exposure.
- Author
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Krueger AM, Roediger DJ, Mueller BA, Boys CA, Hendrickson TJ, Schumacher MJ, Mattson SN, Jones KL, Riley EP, Lim KO, and Wozniak JR
- Subjects
- Adolescent, Anxiety psychology, Caudate Nucleus pathology, Child, Depression psychology, Female, Hippocampus pathology, Humans, Limbic System diagnostic imaging, Limbic System pathology, Magnetic Resonance Imaging, Male, Organ Size, Pregnancy, Prenatal Exposure Delayed Effects chemically induced, Prenatal Exposure Delayed Effects psychology, Putamen pathology, Anxiety diagnostic imaging, Caudate Nucleus diagnostic imaging, Central Nervous System Depressants adverse effects, Depression diagnostic imaging, Ethanol adverse effects, Hippocampus diagnostic imaging, Prenatal Exposure Delayed Effects diagnostic imaging, Putamen diagnostic imaging
- Abstract
Background: Prenatal alcohol exposure (PAE) is associated with a variety of structural abnormalities in the brain, including several within the para-limbic system. Children with PAE have higher rates of internalizing disorders, including depression and anxiety, which may be related to underlying limbic system anomalies., Methods: Children aged 8 to 16 with PAE (n = 41) or without PAE (n = 36) underwent an magnetic resonance imaging of the brain and parents completed behavioral questionnaires about their children. Semi-automated procedures (FreeSurfer) were used to derive para-limbic volumes from T1-weighted anatomical images., Results: There were significant group differences (PAE vs. nonexposed controls) in the caudate, hippocampus, and the putamen; children with PAE had smaller volumes in these regions even after controlling for total intracranial volume. A trend-level association was seen between caudate volume and internalizing symptoms in children with PAE; smaller caudate volumes (presumably reflecting less optimal neurodevelopment) were associated with higher levels of anxiety and depression symptoms in these children., Conclusions: Caudate structure may be disproportionately affected by PAE and may be associated with the later development of internalizing symptoms in those affected by PAE., (© 2020 Research Society on Alcoholism.)
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- 2020
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45. Synaptic RTP801 contributes to motor-learning dysfunction in Huntington's disease.
- Author
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Martín-Flores N, Pérez-Sisqués L, Creus-Muncunill J, Masana M, Ginés S, Alberch J, Pérez-Navarro E, and Malagelada C
- Subjects
- Animals, Cells, Cultured, Cerebral Cortex pathology, Corpus Striatum metabolism, Dendritic Spines metabolism, Disease Models, Animal, Gene Knockdown Techniques, Humans, Huntingtin Protein metabolism, Mice, Mice, Transgenic, Models, Biological, Mutant Proteins metabolism, Neurons metabolism, Phosphorylation, Phosphoserine metabolism, Putamen metabolism, Putamen pathology, Rats, Sprague-Dawley, Adaptor Proteins, Signal Transducing metabolism, Huntington Disease metabolism, Huntington Disease physiopathology, Learning, Motor Activity, Synapses metabolism, Transcription Factors metabolism
- Abstract
RTP801/REDD1 is a stress-responsive protein that mediates mutant huntingtin (mhtt) toxicity in cellular models and is up regulated in Huntington's disease (HD) patients' putamen. Here, we investigated whether RTP801 is involved in motor impairment in HD by affecting striatal synaptic plasticity. To explore this hypothesis, ectopic mhtt was over expressed in cultured rat primary neurons. Moreover, the protein levels of RTP801 were assessed in homogenates and crude synaptic fractions from human postmortem HD brains and mouse models of HD. Finally, striatal RTP801 expression was knocked down with adeno-associated viral particles containing a shRNA in the R6/1 mouse model of HD and motor learning was then tested. Ectopic mhtt elevated RTP801 in synapses of cultured neurons. RTP801 was also up regulated in striatal synapses from HD patients and mouse models. Knocking down RTP801 in the R6/1 mouse striatum prevented motor-learning impairment. RTP801 silencing normalized the Ser473 Akt hyperphosphorylation by downregulating Rictor and it induced synaptic elevation of calcium permeable GluA1 subunit and TrkB receptor levels, suggesting an enhancement in synaptic plasticity. These results indicate that mhtt-induced RTP801 mediates motor dysfunction in a HD murine model, revealing a potential role in the human disease. These findings open a new therapeutic framework focused on the RTP801/Akt/mTOR axis.
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- 2020
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46. A pilot study of brain morphometry following donepezil treatment in mild cognitive impairment: volume changes of cortical/subcortical regions and hippocampal subfields.
- Author
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Kim GW, Kim BC, Park KS, and Jeong GW
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- Aged, Aged, 80 and over, Alzheimer Disease pathology, Brain diagnostic imaging, Brain pathology, Cerebral Cortex diagnostic imaging, Cerebral Cortex drug effects, Cerebral Cortex pathology, Cognitive Dysfunction diagnostic imaging, Cognitive Dysfunction pathology, Disease Progression, Donepezil therapeutic use, Female, Globus Pallidus diagnostic imaging, Globus Pallidus drug effects, Globus Pallidus pathology, Hippocampus diagnostic imaging, Hippocampus drug effects, Hippocampus pathology, Humans, Male, Mental Status and Dementia Tests, Middle Aged, Nootropic Agents therapeutic use, Organ Size drug effects, Pilot Projects, Prodromal Symptoms, Putamen diagnostic imaging, Putamen drug effects, Putamen pathology, Brain drug effects, Cognitive Dysfunction drug therapy, Donepezil pharmacology, Magnetic Resonance Imaging, Neuroimaging, Nootropic Agents pharmacology
- Abstract
The efficacy of donepezil is well known for improving the cognitive performance in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Most of the recent neuroimaging studies focusing on the brain morphometry have dealt with the targeted brain structures, and thus it remains unknown how donepezil treatment influences the volume change over the whole brain areas including the cortical and subcortical regions and hippocampal subfields in particular. This study aimed to evaluate overall gray matter (GM) volume changes after donepezil treatment in MCI, which is a prodromal phase of AD, using voxel-based morphometry. Patients with MCI underwent the magnetic resonance imaging (MRI) before and after 6-month donepezil treatment. The cognitive function for MCI was evaluated using the questionnaires of the Korean version of the mini-mental state examination (K-MMSE) and Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog). Compared with healthy controls, patients with MCI showed significantly lower GM volumes in the hippocampus and its subfields, specifically in the right subiculum and left cornu ammonis (CA3). The average scores of K-MMSE in patients with MCI improved by 8% after donepezil treatment. Treated patients showed significantly higher GM volumes in the putamen, globus pailldus, and inferior frontal gyrus after donepezil treatment (p < 0.001). However, whole hippocampal volume in the patients decreased by 0.6% after 6-month treatment, and the rate of volume change in the left hippocampus was negatively correlated with the period of treatment. These findings will be useful for screening and tracking MCI, as well as understanding of the pathogenesis of MCI in connection with brain morphometric change.
- Published
- 2020
- Full Text
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47. Sleep Onset Problems and Subcortical Development in Infants Later Diagnosed With Autism Spectrum Disorder.
- Author
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MacDuffie KE, Shen MD, Dager SR, Styner MA, Kim SH, Paterson S, Pandey J, St John T, Elison JT, Wolff JJ, Swanson MR, Botteron KN, Zwaigenbaum L, Piven J, and Estes AM
- Subjects
- Amygdala diagnostic imaging, Amygdala pathology, Autism Spectrum Disorder diagnostic imaging, Brain diagnostic imaging, Brain pathology, Caudate Nucleus diagnostic imaging, Caudate Nucleus pathology, Child, Preschool, Female, Globus Pallidus diagnostic imaging, Globus Pallidus pathology, Humans, Hypothalamus pathology, Infant, Magnetic Resonance Imaging, Male, Organ Size, Putamen diagnostic imaging, Putamen pathology, Sleep Initiation and Maintenance Disorders diagnostic imaging, Sleep Initiation and Maintenance Disorders physiopathology, Sleep Latency, Thalamus diagnostic imaging, Thalamus pathology, Autism Spectrum Disorder epidemiology, Hypothalamus diagnostic imaging, Sleep Initiation and Maintenance Disorders epidemiology
- Abstract
Objective: Sleep patterns in children with autism spectrum disorder (ASD) appear to diverge from typical development in the second or third year of life. Little is known, however, about the occurrence of sleep problems in infants who later develop ASD and possible effects on early brain development. In a longitudinal neuroimaging study of infants at familial high or low risk for ASD, parent-reported sleep onset problems were examined in relation to subcortical brain volumes in the first 2 years of life., Methods: A total of 432 infants were included across three study groups: infants at high risk who developed ASD (N=71), infants at high risk who did not develop ASD (N=234), and infants at low risk (N=127). Sleep onset problem scores (derived from an infant temperament measure) were evaluated in relation to longitudinal high-resolution T
1 and T2 structural imaging data acquired at 6, 12, and 24 months of age., Results: Sleep onset problems were more common at 6-12 months among infants who later developed ASD. Infant sleep onset problems were related to hippocampal volume trajectories from 6 to 24 months only for infants at high risk who developed ASD. Brain-sleep relationships were specific to the hippocampus; no significant relationships were found with volume trajectories of other subcortical structures examined (the amygdala, caudate, globus pallidus, putamen, and thalamus)., Conclusions: These findings provide initial evidence that sleep onset problems in the first year of life precede ASD diagnosis and are associated with altered neurodevelopmental trajectories in infants at high familial risk who go on to develop ASD. If replicated, these findings could provide new insights into a potential role of sleep difficulties in the development of ASD.- Published
- 2020
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48. 123 I-FP-CIT SPECT validation of nigro-putaminal MRI tractography in dementia with Lewy bodies.
- Author
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Pardini M, Nobili F, Arnaldi D, Morbelli S, Bauckneht M, Rissotto R, Serrati C, Serafini G, Lapucci C, Ghio L, Amore M, Massucco D, Sassos D, Bonzano L, Mancardi GL, and Roccatagliata L
- Subjects
- Aged, Diagnosis, Differential, Female, Humans, Iodine Radioisotopes, Male, Putamen pathology, Substantia Nigra pathology, Tropanes, Diffusion Tensor Imaging methods, Lewy Body Disease diagnostic imaging, Putamen diagnostic imaging, Substantia Nigra diagnostic imaging, Tomography, Emission-Computed, Single-Photon methods
- Abstract
Background: Assessment of nigrostriatal degeneration is a key element to discriminate between dementia with Lewy bodies (DLB) and Alzheimer disease (AD), and it is often evaluated using ioflupane (
123 I-FP-CIT) single-photon emission computed tomography (SPECT). Given the limited availability of123 I-FP-CIT SPECT, we evaluated if a mask-based approach to nigroputaminal magnetic resonance imaging (MRI) diffusion-weighted tractography could be able to capture microstructural changes reflecting nigroputaminal degeneration in DLB., Methods: A nigroputaminal bundle mask was delineated on 12 healthy volunteers (HV) and applied to MRI diffusion-weighted data of 18 subjects with DLB, 21 subjects with AD and another group of 12 HV. The correlation between nigroputaminal fractional anisotropy (FA) values and123 I-FP-CIT SPECT findings was investigated. Shapiro-Wilk, ANOVA, ANCOVA, and parametric correlation statistics as well as receiver operating characteristic (ROC) analysis were used., Results: DLB patients showed a higher nigroputaminal FA values compared with both AD and HV-controls groups (p = 0.001 for both comparisons), while no difference was observed between HV-controls and AD groups (p = 0.450); at ROC analysis, the area under the curve for the discriminating DLB and AD subjects was 0.820; FA values correlated with123 I-FP-CIT values (on the left, r = -0.670; on the right, r = -720). No significant differences were observed for the FA of the corticospinal tract across the three groups (p = 0.740)., Conclusions: In DLB, nigroputaminal degeneration could be reliably assessed on MRI diffusion scans using a mask of nigroputaminal bundle trajectory. Nigroputaminal FA in DLB patients correlated with123 I-FP-CIT values data may allow to differentiate these patients from AD patients and HV-controls.- Published
- 2020
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49. Modality-specific overlaps in brain structure and function in obsessive-compulsive disorder: Multimodal meta-analysis of case-control MRI studies.
- Author
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Picó-Pérez M, Moreira PS, de Melo Ferreira V, Radua J, Mataix-Cols D, Sousa N, Soriano-Mas C, and Morgado P
- Subjects
- Case-Control Studies, Humans, Magnetic Resonance Imaging, Emotions physiology, Executive Function physiology, Obsessive-Compulsive Disorder diagnostic imaging, Obsessive-Compulsive Disorder pathology, Obsessive-Compulsive Disorder physiopathology, Prefrontal Cortex diagnostic imaging, Prefrontal Cortex pathology, Prefrontal Cortex physiopathology, Putamen diagnostic imaging, Putamen pathology, Putamen physiopathology
- Abstract
Neuroimaging research has shown that patients with obsessive-compulsive disorder (OCD) may present brain structural and functional alterations, but the results across imaging modalities and task paradigms are difficult to reconcile. Are the same brain systems that are structurally different in OCD patients also involved in executive function and emotional processing? To answer this, we conducted separate meta-analyses of voxel-based morphometry studies, executive function functional magnetic resonance imaging (fMRI) studies, and emotional processing fMRI studies. Next, with a multimodal approach (conjunction analysis), we identified the common alterations across meta-analyses. Patients presented increased gray matter volume and hyperactivation in the putamen, but the putamen subregions affected differed depending on the psychological process. Left posterior/dorsal putamen showed hyperactivation during executive processing tasks, while predominantly right anterior/ventral putamen showed hyperactivation during emotional processing tasks. Interestingly, age was significantly associated with increased right putamen volume. Finally, the left dorsolateral prefrontal cortex was hyperactive in both functional domains. Our findings highlight task-specific correlates of brain structure and function in OCD and help integrate a growing literature., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
50. Brain Volume Changes in Patients with Acute Brain Dysfunction Due to Sepsis.
- Author
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Orhun G, Tüzün E, Bilgiç B, Ergin Özcan P, Sencer S, Barburoğlu M, and Esen F
- Subjects
- Amygdala diagnostic imaging, Amygdala pathology, Atrophy, Brain pathology, Case-Control Studies, Caudate Nucleus diagnostic imaging, Caudate Nucleus pathology, Cerebellar Cortex diagnostic imaging, Cerebellar Cortex pathology, Cerebellum diagnostic imaging, Cerebellum pathology, Cerebral Cortex diagnostic imaging, Cerebral Cortex pathology, Cerebral Infarction diagnostic imaging, Coma etiology, Coma physiopathology, Female, Gray Matter diagnostic imaging, Gray Matter pathology, Hippocampus diagnostic imaging, Hippocampus pathology, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Organ Size, Posterior Leukoencephalopathy Syndrome diagnostic imaging, Putamen diagnostic imaging, Putamen pathology, Sepsis complications, Sepsis-Associated Encephalopathy etiology, Sepsis-Associated Encephalopathy physiopathology, Thalamus diagnostic imaging, Thalamus pathology, White Matter diagnostic imaging, White Matter pathology, Brain diagnostic imaging, Coma diagnostic imaging, Sepsis physiopathology, Sepsis-Associated Encephalopathy diagnostic imaging
- Abstract
Background: Sepsis-induced brain dysfunction (SIBD) is often encountered in sepsis patients and is related to increased morbidity. No specific tests are available for SIBD, and neuroimaging findings are often normal. In this study, our aim was to analyze the diagnostic value of volumetric analysis of the brain structures and to find out its significance as a prognostic measure., Methods: In this prospective observational study, brain magnetic resonance imaging (MRI) sections of 25 consecutively enrolled SIBD patients (17 with encephalopathy and 8 with coma) and 22 healthy controls underwent volumetric evaluation by an automated segmentation method., Results: Ten SIBD patients had normal MRI, and 15 patients showed brain lesions or atrophy. The most prominent volume reduction was found in cerebral and cerebellar white matter, cerebral cortex, hippocampus, and amygdala, whereas deep gray matter regions and cerebellar cortex were relatively less affected. SIBD patients with normal MRI showed significantly reduced volumes in hippocampus and cerebral white matter. Caudate nuclei, putamen, and thalamus showed lower volume values in non-survivor SIBD patients, and left putamen and right thalamus showed a more pronounced volume reduction in coma patients., Conclusions: Volumetric analysis of the brain appears to be a sensitive measure of volumetric changes in SIBD. Volume reduction in specific deep gray matter regions might be an indicator of unfavorable outcome.
- Published
- 2020
- Full Text
- View/download PDF
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