Proton Magnetic Resonance Spectroscopy for the Early Diagnosis of Parkinson Disease in the Substantia Nigra and Globus Pallidus: A Meta-Analysis With Trial Sequential Analysis.
Ontology highlight
ABSTRACT: Systematic review registration
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=125731, registration number: CRD42019125731.
SUBMITTER: Gu W
PROVIDER: S-EPMC9244590 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The indirect pathway of the basal ganglia, including the subthalamic nucleus (STN) and globus pallidus external segment (GPe), is believed to play a crucial role in suppressing involuntary movements. However, recent evidence suggests the STN and GPe also facilitate voluntary movements. This study hypothesized that excitatory inputs from the STN to the GPe contribute to this facilitation, and that excitatory projections to the substantia nigra pars reticulata (SNr) are involved in the inhibition. To disrupt the STN-GPe or STN-SNr projections in monkeys during choice and fixation tasks, glutamate receptor inhibitors were injected into the GPe or SNr, which induced delayed saccade latencies toward good choices in the choice task (GPe) and caused frequent reflexive saccades to objects in the fixation task (SNr). Our findings suggest excitatory inputs to the GPe and SNr work in opposing manners, providing new insights that redefine our understanding of the functions of basal ganglia pathways.HighlightsSTN and GPe neuronal activity increased when good objects were chosenSNr activity increased when rejecting bad objects and decreased when accepting good objectsExcitatory inputs inactivation in the GPe caused delayed saccade to good objectsExcitatory projection inhibition to the SNr suppressed involuntary saccade control.
| S-EPMC10402021 | biostudies-literature
Project description:To characterize changes in the magnetic resonance (MR) relaxation properties of progressive supranuclear palsy (PSP) and tissue from neurologically normal brains by using high-resolution (21.1-T, 900-MHz) MR microscopy of postmortem human midbrain and basal ganglia.This HIPAA-compliant study was approved by the institutional review board at the Mayo Clinic and informed consent was obtained. Postmortem tissue from age-matched PSP (n = 6) and control (n = 3) brains was imaged by using three-dimensional fast low-angle shot MR imaging with isotropic resolution of 50 μm. Relaxation times and parametric relaxation maps were generated from spin-echo and gradient-recalled-echo sequences. MR findings were correlated with histologic features by evaluating the presence of iron by using Prussian blue and ferritin and microglia burden as determined by a custom-designed color deconvolution algorithm. T2 and T2*, signal intensities, percent pixels (that could not be fitted in a pixel-by-pixel regression analysis due to severe hypointensity), and histologic data (total iron, ferritin, and microglia burden) were statistically analyzed by using independent sample t tests (P < .05).PSP specimens showed higher iron burden in the cerebral peduncles and substantia nigra than did controls. However, only the putamen was significantly different, and it correlated with a decrease of T2* compared with controls (-48%; P = .043). Similarly, substantia nigra showed a significant decrease of T2* signal in PSP compared with controls (-57%; P = .028). Compared with controls, cerebral peduncles showed increased T2 (38%; P = .026) and T2* (34%; P = .014), as well as higher T2 signal intensity (57%; P = .049). Ferritin immunoreactivity was the opposite from iron burden and was significantly lower compared with controls in the putamen (-74%; P = .025), red nucleus (-61%; P = .018), and entire basal ganglia section (-63%; P = .016).High-field-strength MR microscopy yielded pronounced differences in substantia nigra and globus pallidus of PSP compared with control brains. Histologic data also suggested that the predominant iron in PSP is hemosiderin, not ferritin. Iron in the brain is a contrast enhancer and potential biomarker for PSP.
| S-EPMC3528969 | biostudies-other
Project description:The basal ganglia are a subcortical assembly of nuclei involved in many aspects of behavior. Three of the nuclei have high firing rates and inhibitory influences: the substantia nigra pars reticulata (SNr), globus pallidus interna (GPi), and globus pallidus externa (GPe). The SNr contains a wide range of visual, cognitive, and motor signals that have been shown to contribute to saccadic eye movements. Our hypothesis was that GPe and GPi neurons carry similarly diverse signals during saccadic behavior. We recorded from GPe, GPi, and SNr neurons in monkeys that made memory-guided saccades and found that neurons in all three structures had increases or decreases in activity synchronized with saccade generation, visual stimulation, or reward. Comparing GPe neurons with GPi neurons, we found relatively more visual-related activity in GPe and more reward-related activity in GPi. Comparing both pallidal samples with the SNr, we found a greater resemblance between GPe and SNr neurons than that between GPi and SNr neurons. As expected from a known inhibitory projection from GPe to SNr, there was a general reversal of sign in activity modulations between the structures: bursts of activity were relatively more common in GPe and pauses more common in SNr. We analyzed the response fields of neurons in all three structures and found relatively narrow and lateralized fields early in trials (during visual and saccadic events) followed by a broadening later in trials (during reward). Our data reinforce an emerging, new consensus that the GPe and GPi, in addition to the SNr, contribute to oculomotor behavior.
| S-EPMC2853273 | biostudies-literature
Project description:IntroductionThe subthalamic nucleus, substantia nigra, and globus pallidus, three nuclei of the human basal ganglia, play an important role in motor, associative, and limbic processing. The network of the basal ganglia is generally characterized by a direct, indirect, and hyperdirect pathway. This study aims to investigate the mesoscopic nature of these connections between the subthalamic nucleus, substantia nigra, and globus pallidus and their surrounding structures.MethodsA human post mortem brain specimen including the substantia nigra, subthalamic nucleus, and globus pallidus was scanned on a 7 T MRI scanner. High resolution diffusion weighted images were used to reconstruct the fibers intersecting the substantia nigra, subthalamic nucleus, and globus pallidus. The course and density of these tracks was analyzed.ResultsMost of the commonly established projections of the subthalamic nucleus, substantia nigra, and globus pallidus were successfully reconstructed. However, some of the reconstructed fiber tracks such as the connections of the substantia nigra pars compacta to the other included nuclei and the connections with the anterior commissure have not been shown previously. In addition, the quantitative tractography approach showed a typical degree of connectivity previously not documented. An example is the relatively larger projections of the subthalamic nucleus to the substantia nigra pars reticulata when compared to the projections to the globus pallidus internus.DiscussionThis study shows that ultra-high field post mortem tractography allows for detailed 3D reconstruction of the projections of deep brain structures in humans. Although the results should be interpreted carefully, the newly identified connections contribute to our understanding of the basal ganglia.
| S-EPMC4909758 | biostudies-literature
Project description:ObjectiveMutations in the glucocerebrosidase gene (GBA) represent a significant risk factor for developing Parkinson disease (PD). We investigated the enzymatic activity of glucocerebrosidase (GCase) in PD brains carrying heterozygote GBA mutations (PD+GBA) and sporadic PD brains.MethodsGCase activity was measured using a fluorescent assay in cerebellum, frontal cortex, putamen, amygdala, and substantia nigra of PD+GBA (n = 9-14) and sporadic PD brains (n = 12-14). Protein expression of GCase and other lysosomal proteins was determined by western blotting. The relation between GCase, ?-synuclein, and mitochondria function was also investigated in vitro.ResultsA significant decrease in GCase activity was observed in all PD+GBA brain areas except the frontal cortex. The greatest deficiency was in the substantia nigra (58% decrease; p < 0.01). GCase activity was also significantly decreased in the substantia nigra (33% decrease; p < 0.05) and cerebellum (24% decrease; p < 0.05) of sporadic PD brains. GCase protein expression was lower in PD+GBA and PD brains, whereas increased C/EBP homologous protein and binding immunoglobulin protein levels indicated that the unfolded protein response was activated. Elevated ?-synuclein levels or PTEN-induced putative kinase 1 deficiency in cultured cells had a significant effect on GCase protein levels.InterpretationGCase deficiency in PD brains with GBA mutations is a combination of decreased catalytic activity and reduced protein levels. This is most pronounced in the substantia nigra. Biochemical changes involved in PD pathogenesis affect wild-type GCase protein expression in vitro, and these could be contributing factors to the GCase deficiency observed in sporadic PD brains.
| S-EPMC3638323 | biostudies-literature
Project description:Increased somatic mitochondrial DNA (mtDNA) mutagenesis causes premature aging in mice, and mtDNA damage accumulates in the human brain with aging and neurodegenerative disorders such as Parkinson disease (PD). Here, we study the complete spectrum of mtDNA changes, including deletions, copy-number variation and point mutations, in single neurons from the dopaminergic substantia nigra and other brain areas of individuals with Parkinson disease and neurologically healthy controls. We show that in dopaminergic substantia nigra neurons of healthy individuals, mtDNA copy number increases with age, maintaining the pool of wild-type mtDNA population in spite of accumulating deletions. This upregulation fails to occur in individuals with Parkinson disease, however, resulting in depletion of the wild-type mtDNA population. By contrast, neuronal mtDNA point mutational load is not increased in Parkinson disease. Our findings suggest that dysregulation of mtDNA homeostasis is a key process in the pathogenesis of neuronal loss in Parkinson disease.
| S-EPMC5121427 | biostudies-other
Project description:To test the hypothesis that degeneration of the substantia nigra pars compacta (SNc) precedes that of the cholinergic basal forebrain (BF) in Parkinson disease (PD) using new multispectral structural magnetic resonance (MR) imaging tools to measure the volumes of the SNc and BF.Matched case-control study.The Athinoula A. Martinos Imaging Center at the McGovern Institute for Brain Research, Massachusetts Institute of Technology (MIT), and the Massachusetts General Hospital/MIT Morris Udall Center of Excellence in Parkinson Disease Research.Participants included 29 patients with PD (Hoehn and Yahr [H&Y] stages 1-3) and 27 matched healthy control subjects.We acquired multiecho T1-weighted, multiecho proton density, T2-weighted, and T2-weighted fluid-attenuated inversion recovery (FLAIR) sequences from each participant. For the SNc, we created a weighted mean of the multiple echoes, yielding a single volume with a high ratio of contrast to noise. We visualized the BF using T2-weighted FLAIR images. For each participant, we manually labeled the 2 structures and calculated their volumes.Relative to the controls, 13 patients with H&Y stage 1 PD had significantly decreased SNc volumes. Sixteen patients with H&Y stage 2 or 3 PD showed little additional volume loss. In contrast, the BF volume loss occurred later in the disease, with a significant decrease apparent in patients having H&Y stage 2 or 3 PD compared with the controls and the patients having H&Y stage 1 PD. The latter group did not differ significantly from the controls.Our results support the proposed neuropathological trajectory in PD and establish novel multispectral methods as MR imaging biomarkers for tracking the degeneration of the SNc and BF.
| S-EPMC5751707 | biostudies-literature
Project description:Maintaining and manipulating sequences online is essential for daily activities such as scheduling a day. In Parkinson's disease (PD), sequential working memory deficits have been associated with altered regional activation and functional connectivity in the basal ganglia. This study demonstrates that the substantia nigra (SN) integrity correlated with basal ganglia function and sequencing performance in 29 patients with PD (17 women) and 29 healthy controls (HC, 18 women). In neuromelanin-sensitive structural MRI, PD patients showed smaller SN than HC. In a digit ordering task with functional MRI, participants either recalled sequential digits in the original order ('pure recall') or rearranged the digits and recalled the new sequence ('reorder & recall'). PD patients performed less accurately than HC, accompanied by the caudate and pallidal hypo-activation, subthalamic hyper-activation, and weakened functional connectivity between the bilateral SN and all three basal ganglia regions. PD patients with larger SN tended to exhibit smaller ordering-related accuracy costs ('reorder & recall' versus 'pure recall'). This effect was fully mediated by the ordering-related caudate activation. Unlike HC, the ordering-related accuracy cost correlated with the ordering-related caudate activation but not subthalamic activation in PD. Moreover, the ordering-related caudate activation correlated with the SN area but not the daily dose of D2/3 receptor agonists. In PD, the daily dose of D2/3 receptor agonists correlated with the ordering-related subthalamic activation, which was not related to the accuracy cost. The findings suggest that damage to the SN may lead to sequential working memory deficits in PD, mediated by basal ganglia dysfunction.SIGNIFICANCELiu et al. demonstrate that damage to the substantia nigra (SN) correlates with basal ganglia dysfunction and poor sequencing performance in Parkinson's disease (PD). In neuromelanin-sensitive MRI, PD showed smaller SN than healthy controls. In a digit ordering task with functional MRI, PD's lower task accuracy was accompanied by the caudate and pallidal hypo-activation, subthalamic hyper-activation, and weakened functional connectivity between the SN and basal ganglia. PD with larger SN exhibited greater ordering-related caudate activation and lower ordering-related accuracy cost when sequencing digits. PD with more daily exposure to D2/3 receptor agonists exhibited greater ordering-related subthalamic activation, which did not reduce accuracy cost. It suggests that the SN may affect sequencing performance by regulating the task-dependent caudate activation in PD.
| S-EPMC8287987 | biostudies-literature
Project description:In an effort to account for deficiencies in axonal transport that limit the effectiveness of neurotrophic factors, this study tested the safety and feasibility, in moderately advanced Parkinson disease (PD), of bilaterally administering the gene therapy vector AAV2-neurturin (CERE-120) to the putamen plus substantia nigra (SN, a relatively small structure deep within the midbrain, in proximity to critical neuronal and vascular structures).After planning and minimizing risks of stereotactically targeting the SN, an open-label, dose-escalation safety trial was initiated in 6 subjects with PD who received bilateral stereotactic injections of CERE-120 into the SN and putamen.Two-year safety data for all subjects suggest the procedures were well-tolerated, with no serious adverse events. All adverse events and complications were expected for patients with PD undergoing stereotactic brain surgery.Bilateral stereotactic administration of CERE-120 to the SN plus putamen in PD is feasible and this evaluation provides initial empirical support that it is safe and well-tolerated.This study provides Class IV evidence that bilateral neurturin gene delivery (CERE-120) to the SN plus putamen in patients with moderately advanced PD is feasible and safe.
| S-EPMC3716474 | biostudies-literature
Project description:BackgroundBecause dopamine neurons signal a mismatch between expected and actual reward called prediction error (PE), aberrant PE signals in schizophrenia have been attributed to known dopaminergic abnormalities. However, dysfunction of N-methyl-D-aspartate receptors on cortical γ-aminobutyric acid neurons, as hypothesized in schizophrenia, could lead to excess glutamate release in the substantia nigra (SN) and affect reward processing.AimsThe aim of this study was to investigate the contribution of SN glutamate to PE signals in healthy controls (HC) and patients with schizophrenia (SZ).MethodsWe recruited 22 medicated SZ and 19 HC. We obtained (1) functional magnetic resonance imaging during a probabilistic monetary reward task to assess PE-related blood oxygen level-dependent (BOLD) signal and (2) magnetic resonance spectroscopy to measure Glx (glutamate+glutamine) in the SN. To identify group differences in regions where the BOLD signal varies as a function of PE, we analyzed PEs generated during the task as parametric modulators of reward delivery. Finally, we examined the correlation of PE-related BOLD signal and SN Glx in each group.ResultsRelative to HC, PE-related BOLD signals in SZ were significantly different in the midbrain/SN and ventral striatum. In SZ, SN Glx was significantly elevated. In HC, but not in SZ, PE-related BOLD signal in SN was positively correlated with SN Glx.ConclusionsThese results suggest a role of glutamate in the neural coding of PE in controls. They indicate that glutamatergic dysfunction might contribute to abnormal PE coding in schizophrenia, suggesting the use of glutamate-targeted approaches to improve these deficits.
| S-EPMC4752128 | biostudies-literature