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Movement Disorders : Official Journal... Apr 2017Spasmodic dysphonia is a focal dystonia characterized by involuntary spasms in the laryngeal muscles that occur selectively during speaking. Although hereditary trends...
BACKGROUND
Spasmodic dysphonia is a focal dystonia characterized by involuntary spasms in the laryngeal muscles that occur selectively during speaking. Although hereditary trends have been reported in up to 16% of patients, the causative etiology of spasmodic dysphonia is unclear, and the influences of various phenotypes and genotypes on disorder pathophysiology are poorly understood. In this study, we examined structural alterations in cortical gray matter and white matter integrity in relationship to different phenotypes and putative genotypes of spasmodic dysphonia to elucidate the structural component of its complex pathophysiology.
METHODS
Eighty-nine patients with spasmodic dysphonia underwent high-resolution magnetic resonance imaging and diffusion-weighted imaging to examine cortical thickness and white matter fractional anisotropy in adductor versus abductor forms (distinct phenotypes) and in sporadic versus familial cases (distinct genotypes).
RESULTS
Phenotype-specific abnormalities were localized in the left sensorimotor cortex and angular gyrus and the white matter bundle of the right superior corona radiata. Genotype-specific alterations were found in the left superior temporal gyrus, supplementary motor area, and the arcuate portion of the left superior longitudinal fasciculus.
CONCLUSIONS
Our findings suggest that phenotypic differences in spasmodic dysphonia arise at the level of the primary and associative areas of motor control, whereas genotype-related pathophysiological mechanisms may be associated with dysfunction of regions regulating phonological and sensory processing. Identification of structural alterations specific to disorder phenotype and putative genotype provides an important step toward future delineation of imaging markers and potential targets for novel therapeutic interventions for spasmodic dysphonia. © 2017 International Parkinson and Movement Disorder Society.
Topics: Adult; Aged; Anisotropy; Apoptosis Regulatory Proteins; Brain Mapping; Cerebral Cortex; DNA-Binding Proteins; Diffusion Tensor Imaging; Dysphonia; Female; GTP-Binding Protein alpha Subunits; Genotype; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Molecular Chaperones; Nuclear Proteins; Phenotype; Severity of Illness Index; Tomography Scanners, X-Ray Computed; Tubulin
PubMed: 28186656
DOI: 10.1002/mds.26920 -
Journal of Cellular Physiology Jan 2015In the adult brain, neural progenitor cells (NPCs) reside in the subventricular zone (SVZ) of the lateral ventricles, the dentate gyrus and the olfactory bulb. Following... (Review)
Review
In the adult brain, neural progenitor cells (NPCs) reside in the subventricular zone (SVZ) of the lateral ventricles, the dentate gyrus and the olfactory bulb. Following CNS insult, NPCs from the SVZ can migrate along the rostral migratory stream (RMS), a migration of NPCs that is directed by proinflammatory cytokines. Cells expressing CXCR4 follow a homing signal that ultimately leads to neuronal integration and CNS repair, although such molecules can also promote NPC quiescence. The ligand, SDF1 alpha (or CXCL12) is one of the chemokines secreted at sites of injury that it is known to attract NSC-derived neuroblasts, cells that express CXCR4. In function of its concentration, CXCL12 can induce different responses, promoting NPC migration at low concentrations while favoring cell adhesion via EGF and the alpha 6 integrin at high CXCL12 concentrations. However, the preclinical effectiveness of chemokines and their relationship with NPC mobilization requires further study, particularly with respect to CNS repair. NPC migration may also be affected by the release of cytokines or chemokines induced by local inflammation, through autocrine or paracrine mechanisms, as well as through erythropoietin (EPO) or nitric oxide (NO) release. CXCL12 activity requires G-coupled proteins and the availability of its ligand may be modulated by its binding to CXCR7, for which it shows a stronger affinity than for CXCR4.
Topics: Brain; Cell Adhesion; Cell Differentiation; Cell Movement; Chemokine CXCL12; Dentate Gyrus; Erythropoietin; Humans; Inflammation; Lateral Ventricles; Neural Stem Cells; Neurogenesis; Nitric Oxide; Olfactory Bulb; Protein Binding; Receptors, CXCR; Receptors, CXCR4; Signal Transduction
PubMed: 24913264
DOI: 10.1002/jcp.24695 -
Neurological Sciences : Official... Jan 2024Our study aimed to explore the functional connectivity alterations between cortical nodes of resting-state networks in Parkinson's disease (PD) patients with wearing-off...
OBJECTIVE
Our study aimed to explore the functional connectivity alterations between cortical nodes of resting-state networks in Parkinson's disease (PD) patients with wearing-off (WO) at different levels.
METHODS
Resting-state functional magnetic resonance imaging was performed on 36 PD patients without wearing-off (PD-nWO), 30 PD patients with wearing-off (PD-WO), and 35 healthy controls (HCs) to extract functional networks. Integrity, network, and edge levels were calculated for comparison between groups. UPDRS-III, MMSE, MOCA, HAMA, and HAMD scores were collected for further regression analysis.
RESULTS
We observed significantly reduced connectivity strength in the dorsal attention network and limbic network in the PD-WO group compared with the HC group. The PD-WO group showed a decreased degree of functional connectivity at 12 nodes, including the bilateral orbital part of the superior frontal gyrus, right olfactory cortex, left medial orbital part of the superior frontal gyrus, bilateral gyrus rectus, right parahippocampal gyrus, right thalamus, left Heschl's gyrus, right superior temporal gyrus part of the temporal pole, left middle temporal gyrus part of the temporal pole, and right inferior temporal gyrus. Furthermore, the PD-WO group showed a significantly lower degree of functional connectivity in the left orbital part of the superior frontal gyrus and right gyrus rectus than the PD-nWO group. Internetwork analysis indicated reduced functional connectivity in five pairs of resting-state networks.
CONCLUSION
Our results demonstrated altered intra- and internetwork connections in PD patients with WO. These findings will facilitate a better understanding of the distinction between the network changes in PD pathophysiology.
Topics: Humans; Brain Mapping; Magnetic Resonance Imaging; Parkinson Disease; Prefrontal Cortex; Temporal Lobe
PubMed: 37578631
DOI: 10.1007/s10072-023-07005-2 -
Frontiers in Neuroscience 2022To investigate the alteration of cerebral blood flow (CBF) and its connectivity patterns in olfactory-related regions of type 2 diabetes mellitus (T2DM) patients using...
To investigate the alteration of cerebral blood flow (CBF) and its connectivity patterns in olfactory-related regions of type 2 diabetes mellitus (T2DM) patients using arterial spin labeling (ASL). Sixty-nine patients with T2DM and 63 healthy controls (HCs) underwent ASL scanning using 3.0T magnetic resonance imaging. We compared the CBF values of the olfactory-related brain regions between the two groups and analyzed the correlation between their changes and clinical variables. We also used these regions as seeds to explore the differences in CBF connectivity patterns in olfactory-related brain regions between the T2DM patients and HCs. Compared with the HC group, the CBF of the right orbital part of the inferior frontal gyrus (OIFG), right insula, and bilateral olfactory cortex was decreased in the T2DM patients. Moreover, the duration of the patients was negatively correlated with the CBF changes in the right OIFG, right insula, and right olfactory cortex. The CBF changes in the right OIFG were positively correlated with the Self-Rating Depression Scale scores, those in the right insula were negatively correlated with the max blood glucose of continuous glucose, and those in the right olfactory cortex were negatively correlated with the mean blood glucose of continuous glucose. In addition, the T2DM patients also showed decreased CBF connectivity between the right OIFG and the left temporal pole of the middle temporal gyrus and increased CBF connectivity between the right medial orbital part of the superior frontal gyrus and the right orbital part of the superior frontal gyrus and between the right olfactory cortex and the bilateral caudate and the left putamen. Patients with T2DM have decreased CBF and altered CBF connectivity in multiple olfactory-related brain regions. These changes may help explain why olfactory dysfunction occurs in patients with T2DM, thus providing insights into the neuropathological mechanism of olfactory dysfunction and cognitive decline in T2DM patients.
PubMed: 35898415
DOI: 10.3389/fnins.2022.904468 -
Neurology(R) Neuroimmunology &... Mar 2022This [F]fluorodeoxyglucose (FDG) PET study evaluates the accuracy of semiquantitative measurement of putaminal hypermetabolism in identifying anti-leucine-rich,...
BACKGROUND AND OBJECTIVES
This [F]fluorodeoxyglucose (FDG) PET study evaluates the accuracy of semiquantitative measurement of putaminal hypermetabolism in identifying anti-leucine-rich, glioma-inactivated-1 (LGI1) protein autoimmune encephalitis (AE). In addition, the extent of brain dysmetabolism, their association with clinical outcomes, and longitudinal metabolic changes after immunotherapy in LGI1-AE are examined.
METHODS
FDG-PET scans from 49 age-matched and sex-matched subjects (13 in LGI1-AE group, 15 in non-LGI1-AE group, 11 with Alzheimer disease [AD], and 10 negative controls [NCs]) and follow-up scans from 8 patients with LGI1 AE on a median 6 months after immunotherapy were analyzed. Putaminal standardized uptake value ratios (SUVRs) normalized to global brain (P-SUVRg), thalamus (P/Th), and midbrain (P/Mi) were evaluated for diagnostic accuracy. SUVRg was applied for all other analyses.
RESULTS
P-SUVRg, P/Th, and P/Mi were higher in LGI1-AE group than in non-LGI1-AE group, AD group, and NCs (all < 0.05). P/Mi and P-SUVRg differentiated LGI1-AE group robustly from other groups (areas under the curve 0.84-0.99). Mediotemporal lobe (MTL) SUVRg was increased in both LGI1-AE and non-LGI1-AE groups when compared with NCs (both < 0.05). SUVRg was decreased in several frontoparietal regions and increased in pallidum, caudate, pons, olfactory, and inferior occipital gyrus in LGI1-AE group when compared with that in NCs (all < 0.05). In LGI1-AE group, both MTL and putaminal hypermetabolism were reduced after immunotherapy. Normalization of regional cortical dysmetabolism associated with clinical improvement at the 6- and 20-month follow-up.
DISCUSSION
Semiquantitative measurement of putaminal hypermetabolism with FDG-PET may be used to distinguish LGI1-AE from other pathologies. Metabolic abnormalities in LGI1-AE extend beyond putamen and MTL into other subcortical and cortical regions. FDG-PET may be used in evaluating disease evolution in LGI1-AE.
CLASSIFICATION OF EVIDENCE
This study provides Class II evidence that semiquantitative measures of putaminal metabolism on PET can differentiate patients with LGI1-AE from patients without LGI1-AE, patients with AD, or NCs.
Topics: Adolescent; Adult; Aged; Alzheimer Disease; Autoantibodies; Cerebral Cortex; Demyelinating Autoimmune Diseases, CNS; Electroencephalography; Encephalitis; Female; Follow-Up Studies; Humans; Intracellular Signaling Peptides and Proteins; Magnetic Resonance Imaging; Male; Mesencephalon; Middle Aged; Positron-Emission Tomography; Putamen; Retrospective Studies; Young Adult
PubMed: 35091466
DOI: 10.1212/NXI.0000000000001136 -
Frontiers in Behavioral Neuroscience 2018Aversive odors are highly salient stimuli that serve a protective function. Thus, emotional reactions elicited by negative odors may be hardly influenceable. We aim to...
Aversive odors are highly salient stimuli that serve a protective function. Thus, emotional reactions elicited by negative odors may be hardly influenceable. We aim to elucidate if negative mood induced by negative odors can be modulated automatically by positively valenced stimuli. We included 32 healthy participants (16 men) in an fMRI design combining aversive and neutral olfactory stimuli with positive and neutral auditory stimuli to test the influence of aversive olfactory stimuli on subjective emotional state and brain activation when combined with positive and neutral auditory stimuli. The behavioral results show an interaction of negative olfactory stimuli on ratings of disgust, perceived valence of music, and subjective affective state, while positive auditory stimulation did not show this interaction. On a neuronal level, we observed main effects for auditory and olfactory stimulation, which are largely congruent with previous literature. However, the pairing of both stimuli was associated with attenuated brain activity in a set of brain areas (supplementary motor area, temporal pole, superior frontal gyrus) which overlaps with multisensory processing areas and pave the way for automatic emotion regulation. Our behavioral results and the integrated neural patterns provide evidence of predominance of olfaction in processing of affective rivalry from multiple sensory modalities.
PubMed: 30618666
DOI: 10.3389/fnbeh.2018.00313 -
BMC Neuroscience Apr 2021Brain radiation exposure, in particular, radiotherapy, can induce cognitive impairment in patients, with significant effects persisting for the rest of their life....
BACKGROUND
Brain radiation exposure, in particular, radiotherapy, can induce cognitive impairment in patients, with significant effects persisting for the rest of their life. However, the main mechanisms leading to this adverse event remain largely unknown. A study of radiation-induced injury to multiple brain regions, focused on the hippocampus, may shed light on neuroanatomic bases of neurocognitive impairments in patients. Hence, we irradiated BALB/c mice (male and female) at postnatal day 3 (P3), day 10 (P10), and day 21 (P21) and investigated the long-term radiation effect on brain MRI changes and hippocampal neurogenesis.
RESULTS
We found characteristic brain volume reductions in the hippocampus, olfactory bulbs, the cerebellar hemisphere, cerebellar white matter (WM) and cerebellar vermis WM, cingulate, occipital and frontal cortices, cerebellar flocculonodular WM, parietal region, endopiriform claustrum, and entorhinal cortex after irradiation with 5 Gy at P3. Irradiation at P10 induced significant volume reduction in the cerebellum, parietal region, cingulate region, and olfactory bulbs, whereas the reduction of the volume in the entorhinal, parietal, insular, and frontal cortices was demonstrated after irradiation at P21. Immunohistochemical study with cell division marker Ki67 and immature marker doublecortin (DCX) indicated the reduced cell division and genesis of new neurons in the subgranular zone of the dentate gyrus in the hippocampus after irradiation at all three postnatal days, but the reduction of total granule cells in the stratum granulosun was found after irradiation at P3 and P10.
CONCLUSIONS
The early life radiation exposure during different developmental stages induces varied brain pathophysiological changes which may be related to the development of neurological and neuropsychological disorders later in life.
Topics: Animals; Animals, Newborn; Brain; Cranial Irradiation; Female; Male; Mice; Mice, Inbred BALB C; Neurogenesis
PubMed: 33882822
DOI: 10.1186/s12868-021-00635-2 -
Pharmacological Research Mar 2024Neuronal death is one of the key pathologies in Alzheimer's disease (AD). How neuronal death begins in AD is far from clear, so clarifying this process may help develop...
Neuronal death is one of the key pathologies in Alzheimer's disease (AD). How neuronal death begins in AD is far from clear, so clarifying this process may help develop effective therapies. This study collected single-cell RNA sequencing data of 85 AD samples and 83 control samples, covering the prefrontal cortex, internal olfactory cortex, superior parietal lobe, superior frontal gyrus, caudal internal olfactory cortex, somatosensory cortex, hippocampus, superior frontal cortex and peripheral blood mononuclear cells. Additionally, spatial transcriptomic data of coronal sections from 6 App AD mice and 6 control C57Bl/6 J mice were acquired. The main single-cell and spatial transcriptomics results were experimentally validated in wild type and 5 × FAD mice. We found that the microglia subpopulation Mic_PTPRG can communicate with specific types of neurons (especially excitatory ExNeu_PRKN_VIRMA and inhibitory InNeu_PRKN_VIRMA neuronal subpopulations) and cause them to express PTPRG during AD progression. Within neurons, PTPRG binds and upregulates the mA methyltransferase VIRMA, thus inhibiting translation of PRKN mRNA to prevent the clearance of damaged mitochondria in neurons through suppressing mitophagy. As the disease progresses, the energy and nutrient metabolic pathways in neurons are reprogrammed, leading to their death. Consistently, we determined that PTPTRG can physically interact with VIRMA in mouse brains and PRKN is significantly upregulated in 5 × FAD mouse brain. Altogether, our findings demonstrate that PTPRG activates the mA methyltransferase VIRMA to block mitophagy-mediated neuronal death in AD, which is a potential pathway, through which microglia and neuronal PTPRG modify neuronal connections in the brain during AD progression.
Topics: Animals; Mice; Alzheimer Disease; Leukocytes, Mononuclear; Mitophagy; Gene Expression Profiling; Methyltransferases; Mice, Inbred C57BL
PubMed: 38325728
DOI: 10.1016/j.phrs.2024.107098 -
Frontiers in Aging Neuroscience 2021To compare gray matter microstructural characteristics of higher-order olfactory regions among older adults with and without hyposmia. Data from the Brief Smell...
To compare gray matter microstructural characteristics of higher-order olfactory regions among older adults with and without hyposmia. Data from the Brief Smell Identification Test (BSIT) were obtained in 1998-99 for 265 dementia-free adults from the Health, Aging, and Body Composition study (age at BSIT: 74.9 ± 2.7; 62% White; 43% male) who received 3T diffusion tensor imaging in 2006-08 [Interval of time: mean (SD): 8.01 years (0.50)], Apolipoprotein (ApoEε4) genotypes, and repeated 3MS assessments until 2011-12. Cognitive status (mild cognitive impairment, dementia, normal cognition) was adjudicated in 2011-12. Hyposmia was defined as BSIT ≤ 8. Microstructural integrity was quantified by mean diffusivity (MD) in regions of the primary olfactory cortex amygdala, orbitofrontal cortex (including olfactory cortex, gyrus rectus, the orbital parts of the superior, middle, and inferior frontal gyri, medial orbital part of the superior frontal gyrus), and hippocampus. Multivariable regression models were adjusted for total brain atrophy, demographics, cognitive status, and ApoEε4 genotype. Hyposmia in 1998-99 ( = 57, 21.59%) was significantly associated with greater MD in 2006-08, specifically in the orbital part of the middle frontal gyrus, and amygdala, on the right [adjusted beta (p value): 0.414 (); 0.527 (); respectively]. Older adults with higher mean diffusivity in regions important for olfaction are more likely to have hyposmia up to ten years prior. Future studies should address whether hyposmia can serve as an early biomarker of brain microstructural abnormalities for older adults with a range of cognitive functions, including those with normal cognition.
PubMed: 34744681
DOI: 10.3389/fnagi.2021.648598 -
NeuroImage. Clinical 2022Subjective cognitive decline (SCD), one of the important clinical indicators for preclinical Alzheimer's disease (AD), is primarily defined as self-perceived cognitive...
BACKGROUNDS
Subjective cognitive decline (SCD), one of the important clinical indicators for preclinical Alzheimer's disease (AD), is primarily defined as self-perceived cognitive decline without objective evidence for cognitive impairment. However, the accuracy of their self-evaluation of cognition is unclear. This study sought to investigate the capacity for self-evaluation of own cognitive performance in SCD by applying an objective metamemory paradigm.
METHODS
147 individuals with SCD were classified into four subgroups by their subjective feeling of worse performance than peers or not (P+/-) and whether they have objectively slight cognitive impairment compared to normative data (S+/-). Metamemory scores, the amplitude of the low-frequency fluctuation (ALFF), fractional low-frequency fluctuation amplitude (fALFF), and cortical thickness were compared among four subgroups. Partial correlations between neuropsychological scores and neuroimaging measures were examined, controlling for age, sex, and education years.
RESULTS
SCD S+P- showed the worst performance in short-term delayed recall and the worst metamemory performance, indicated by the highest value in the degree of confidence of short-term delayed recall (DOC-N4) and long-term cued recall (DOC-N6) and the worst value in relative accuracy of judgments of short-term delayed recall (ROJ-N4). ALFF values in the bilateral superior medial frontal and olfactory cortices and the left superior orbitofrontal gyrus cortex were significantly higher in SCD P- compared with SCD P+ groups (all P < 0.05, FWE-corrected, cluster-wise level). A significant S × P interaction effect in the left hippocampus and middle cingulate cortex was found for the fALFF signals (all P < 0.05, FWE-corrected, cluster-wise level). Significant interaction and main effects on cortical thickness were reported. The parahippocampal and posterior cingulate cortices were significantly decreased in SCD S+P- (all P < 0.05).
CONCLUSION
SCD S+P- showed the worst episodic memory performance, altered metamemory capacity (overconfidence and less accuracy of judgment), and altered neuroimaging measures, though they had feelings of similar performance with peers. Our results indicate that metamemory capacity is affected in a subtype of SCD with reduced cortical thickness and intensity of regional spontaneous activity in key areas for metamemory processing.
Topics: Humans; Neuropsychological Tests; Magnetic Resonance Imaging; Cognitive Dysfunction; Cognition; Metacognition
PubMed: 36451360
DOI: 10.1016/j.nicl.2022.103255