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Biomedicines Apr 2024The malfunctioning of the brain synucleins is associated with pathogenesis of Parkinson's disease. Synucleins' ability to modulate various pre-synaptic processes...
Disruption of Electroencephalogram Coherence between Cortex/Striatum and Midbrain Dopaminergic Regions in the Knock-Out Mice with Combined Loss of Alpha, Beta, and Gamma Synucleins.
UNLABELLED
The malfunctioning of the brain synucleins is associated with pathogenesis of Parkinson's disease. Synucleins' ability to modulate various pre-synaptic processes suggests their modifying effects on the electroencephalogram (EEG) recorded from different brain structures. Disturbances in interrelations between them are critical for the onset and evolution of neurodegenerative diseases. Recently, we have shown that, in mice lacking several synucleins, differences between the frequency spectra of EEG from different brain structures are correlated with specificity of synucleins' combinations. Given that EEG spectra are indirect characteristics of inter-structural relations, in this study, we analyzed a coherence of instantaneous values for EEGs recorded from different structures as a direct measure of "functional connectivity" between them.
METHODS
EEG data from seven groups of knock-out (KO) mice with combined deletions of alpha, beta, and gamma synucleins versus a group of wild-type (WT) mice were compared. EEG coherence was estimated between the cortex (MC), putamen (Pt), ventral tegmental area (VTA), and substantia nigra (SN) in all combinations.
RESULTS
EEG coherence suppression, predominantly in the beta frequency band, was observed in KO mice versus WT littermates. The suppression was minimal in MC-Pt and VTA-SN interrelations in all KO groups and in all inter-structural relations in mice lacking either all synucleins or only beta synuclein. In other combinations of deleted synucleins, significant EEG coherence suppression in KO mice was dominant in relations with VTA and SN.
CONCLUSION
Deletions of the synucleins produced significant attenuation of intra-cerebral EEG coherence depending on the imbalance of different types of synucleins.
PubMed: 38672235
DOI: 10.3390/biomedicines12040881 -
Brain Sciences Apr 2024Movement and muscle control are crucial for the survival of all free-living organisms. This study aimed to explore differential patterns of cortical and subcortical...
Movement and muscle control are crucial for the survival of all free-living organisms. This study aimed to explore differential patterns of cortical and subcortical activation across different stages of muscle control using functional magnetic resonance imaging (fMRI). An event-related design was employed. In each trial, participants ( = 10) were instructed to gently press a button with their right index finger, hold it naturally for several seconds, and then relax the finger. Neural activation in these temporally separated stages was analyzed using a General Linear Model. Our findings revealed that a widely distributed cortical network, including the supplementary motor area and insula, was implicated not only in the pressing stage, but also in the relaxation stage, while only parts of the network were involved in the steady holding stage. Moreover, supporting the direct/indirect pathway model of the subcortical basal ganglia, their substructures played distinct roles in different stages of muscle control. The caudate nucleus exhibited greater involvement in muscle contraction, whereas the putamen demonstrated a stronger association with muscle relaxation; both structures were implicated in the pressing stage. Furthermore, the subthalamic nucleus was exclusively engaged during the muscle relaxation stage. We conclude that even the control of simple muscle movements involves intricate automatic higher sensory-motor integration at a neural level, particularly when coordinating relative muscle movements, including both muscle contraction and muscle relaxation; the cortical and subcortical regions assume distinct yet coordinated roles across different stages of muscle control.
PubMed: 38672052
DOI: 10.3390/brainsci14040404 -
EJNMMI Physics Apr 2024This study aimed to evaluate the feasibility of C-CFT PET brain imaging in Parkinson's Disease using a total-body PET/CT scanner and explore the optimal scan duration to...
PURPOSE
This study aimed to evaluate the feasibility of C-CFT PET brain imaging in Parkinson's Disease using a total-body PET/CT scanner and explore the optimal scan duration to guide the clinical practice.
METHODS
Thirty-two patients with Parkinson's disease (PD) performing C-CFT PET/CT brain imaging using a total-body PET/CT scanner were retrospectively enrolled. The PET data acquired over a period of 900 s were reconstructed into groups of different durations: 900-s, 720-s, 600-s, 480-s, 300-s, 180-s, 120-s, 60-s, and 30-s (G900 to G30). The subjective image quality analysis was performed using 5-point scales. Semi-quantitative measurements were analyzed by SUVmean and dopamine transporter (DAT) binding of key brain regions implicated in PD, including the caudate nucleus and putamen. The full-time images (G900) were served as reference.
RESULTS
The overall G900, G720, and G600 image quality scores were 5.0 ± 0.0, 5.0 ± 0.0, and 4.9 ± 0.3 points, respectively, and there was no significant difference among these groups (P > 0.05). A significant decrease in these scores at durations shorter than 600 s was observed when compared to G900 images (P < 0.05). However, all G300 image quality was clinically acceptable (≥ 3 points). As the scan duration reduced, the SUVmean and DAT binding of caudate nucleus and putamen decreased progressively, while there were no statistically significant variations in the SUVmean of the background among the different groups. Moreover, the changes in the lesion DAT binding (ΔDAT-binding) between the full-time reference G900 image and other reconstructed group G720 to G30 images generally increased along with the reduced scan time.
CONCLUSION
Sufficient image quality and lesion conspicuity could be achieved at 600-s scan duration for C-CFT PET brain imaging in PD assessment using a total-body PET/CT scanner, while the image quality of G300 was acceptable to meet clinical diagnosis, contributing to improve patient compliance and throughput of PET brain imaging.
PubMed: 38662044
DOI: 10.1186/s40658-024-00640-4 -
BMC Psychiatry Apr 2024Distinguishing untreated major depressive disorder without medication (MDD) from schizophrenia with depressed mood (SZDM) poses a clinical challenge. This study aims to...
Differences in fractional amplitude of low-frequency fluctuations (fALFF) and cognitive function between untreated major depressive disorder and schizophrenia with depressive mood patients.
BACKGROUND
Distinguishing untreated major depressive disorder without medication (MDD) from schizophrenia with depressed mood (SZDM) poses a clinical challenge. This study aims to investigate differences in fractional amplitude of low-frequency fluctuations (fALFF) and cognition in untreated MDD and SZDM patients.
METHODS
The study included 42 untreated MDD cases, 30 SZDM patients, and 46 healthy controls (HC). Cognitive assessment utilized the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Resting-state functional magnetic resonance imaging (rs-fMRI) scans were conducted, and data were processed using fALFF in slow-4 and slow-5 bands.
RESULTS
Significant fALFF changes were observed in four brain regions across MDD, SZDM, and HC groups for both slow-4 and slow-5 fALFF. Compared to SZDM, the MDD group showed increased slow-5 fALFF in the right gyrus rectus (RGR). Relative to HC, SZDM exhibited decreased slow-5 fALFF in the left gyrus rectus (LGR) and increased slow-5 fALFF in the right putamen. Changes in slow-5 fALFF in both RGR and LGR were negatively correlated with RBANS scores. No significant correlations were found between remaining fALFF (slow-4 and slow-5 bands) and RBANS scores in MDD or SZDM groups.
CONCLUSIONS
Alterations in slow-5 fALFF in RGR may serve as potential biomarkers for distinguishing MDD from SZDM, providing preliminary insights into the neural mechanisms of cognitive function in schizophrenia.
Topics: Humans; Depressive Disorder, Major; Male; Female; Adult; Schizophrenia; Magnetic Resonance Imaging; Cognition; Brain; Neuropsychological Tests; Middle Aged; Young Adult; Cognitive Dysfunction
PubMed: 38658896
DOI: 10.1186/s12888-024-05777-1 -
Frontiers in Neuroscience 2024Dopamine D3 receptor (D3R) ligands have been studied for the possible treatment of neurological and neuropsychiatric disorders. However, selective D3R radioligands for...
INTRODUCTION
Dopamine D3 receptor (D3R) ligands have been studied for the possible treatment of neurological and neuropsychiatric disorders. However, selective D3R radioligands for binding studies have been challenging to identify due to the high structural similarity between the D2R and D3R. In a prior study, we reported a new conformationally-flexible benzamide scaffold having a high affinity for D3R and excellent selectivity vs. D2R. In the current study, we characterized the binding properties of a new radioiodinated ligand, [I]HY-3-24.
METHODS
binding studies were conducted in cell lines expressing D3 receptors, rat striatal homogenates, and rat and non-human primate (NHP) brain tissues to measure regional brain distribution of this radioligand.
RESULTS
HY-3-24 showed high potency at D3R ( = 0.67 ± 0.11 nM, IC = 1.5 ± 0.58 nM) compared to other D2-like dopamine receptor subtypes (D2R = 86.7 ± 11.9 nM and D4R > 1,000). The (0.34 ± 0.22 nM) and B (38.91 ± 2.39 fmol/mg) values of [I]HY-3-24 were determined. binding studies in rat striatal homogenates using selective D2R and D3R antagonists confirmed the D3R selectivity of [I]HY-3-24. Autoradiography results demonstrated that [I]HY-3-24 specifically binds to D3Rs in the nucleus accumbens, islands of Calleja, and caudate putamen in rat and NHP brain sections.
CONCLUSION
These results suggest that [I]HY-3-24 appears to be a novel radioligand that exhibits high affinity binding at D3R, with low binding to other D2-like dopamine receptors. It is anticipated that [I]HY-3-24 can be used as the specific D3R radioligand.
PubMed: 38655111
DOI: 10.3389/fnins.2024.1380009 -
Scientific Reports Apr 2024Sensory impairment and brain atrophy is common among older adults, increasing the risk of dementia. Yet, the degree to which multiple co-occurring sensory impairments...
Sensory impairment and brain atrophy is common among older adults, increasing the risk of dementia. Yet, the degree to which multiple co-occurring sensory impairments (MSI across vision, proprioception, vestibular function, olfactory, and hearing) are associated with brain morphometry remain unexplored. Data were from 208 cognitively unimpaired participants (mean age 72 ± 10 years; 59% women) enrolled in the Baltimore Longitudinal Study of Aging. Multiple linear regression models were used to estimate cross-sectional associations between MSI and regional brain imaging volumes. For each additional sensory impairment, there were associated lower orbitofrontal gyrus and entorhinal cortex volumes but higher caudate and putamen volumes. Participants with MSI had lower mean volumes in the superior frontal gyrus, orbitofrontal gyrus, superior parietal lobe, and precuneus compared to participants with < 2 impairments. While MSI was largely associated with lower brain volumes, our results suggest the possibility that MSI was associated with higher basal ganglia volumes. Longitudinal analyses are needed to evaluate the temporality and directionality of these associations.
Topics: Humans; Female; Aged; Male; Brain; Longitudinal Studies; Cross-Sectional Studies; Aging; Baltimore; Aged, 80 and over; Magnetic Resonance Imaging; Middle Aged; Organ Size; Atrophy
PubMed: 38653745
DOI: 10.1038/s41598-024-59965-w -
Addiction & Health Feb 2024The likelihood of substance dependency in offspring is increased in cases when there is a family history of drug or alcohol use. Mothering is limited by maternal... (Review)
Review
The likelihood of substance dependency in offspring is increased in cases when there is a family history of drug or alcohol use. Mothering is limited by maternal addiction because of the separation. Maternal separation (MS) leads to the development of behavioural and neuropsychiatric issues in the future. Despite the importance of this issue, empirical investigations of the influences of maternal substance use and separation on substance use problems in offspring are limited, and studies that consider both effects are rare. This study aims to review a few studies on the mechanisms, treatments, genetics, epigenetics, molecular and psychological alterations, and neuroanatomical regions involved in the dependence of offspring who underwent maternal addiction and separation. The PubMed database was used. A total of 95 articles were found, including the most related ones in the review. The brain's lateral paragigantocellularis (LPGi), nucleus accumbens (NAc), caudate-putamen (CPu), prefrontal cortex (PFC), and hippocampus, can be affected by MS. Dopamine receptor subtype genes, alcohol biomarker minor allele, and preproenkephalin mRNA may be affected by alcohol or substance use disorders. After early-life adversity, histone acetylation in the hippocampus may be linked to brain-derived neurotrophic factor (BDNF) gene epigenetics and glucocorticoid receptors (GRs). The adverse early-life experiences differ in offspring›s genders and rewire the brain›s dopamine and endocannabinoid circuits, making offspring more susceptible to dependence. Related psychological factors rooted in early-life stress (ELS) and parental substance use disorder (SUD). Treatments include antidepressants, histone deacetylase inhibitors, lamotrigine, ketamine, choline, modafinil, methadone, dopamine, cannabinoid 1 receptor agonists/antagonists, vitamins, oxytocin, tetrahydrocannabinol, SR141716A, and dronabinol. Finally, the study emphasizes the need for multifaceted strategies to prevent these outcomes.
PubMed: 38651025
DOI: 10.34172/ahj.2024.1478 -
Frontiers in Aging Neuroscience 2024Peripheral inflammatory responses are suggested to play a major role in the pathophysiology of Parkinson's disease (PD). The neutrophil-to-lymphocyte ratio (NLR), a new...
INTRODUCTION
Peripheral inflammatory responses are suggested to play a major role in the pathophysiology of Parkinson's disease (PD). The neutrophil-to-lymphocyte ratio (NLR), a new recognized biomarker, can reflect peripheral inflammation in PD. However, the association between the NLR and dopaminergic degeneration in PD remains unclear.
METHODS
In this retrospective study, 101 enrolled PD patients were categorized into early-stage and advanced-stage PD based on the Hoehn and Yahr (HY) scale. We evaluated the clinical characteristics, peripheral immune profile, and 11C-CFT striatal dopamine transporter (DAT) binding levels. Linear regression analyses were employed to assess the associations between NLR and striatal DAT levels at different stages in PD patients.
RESULTS
Covariate-controlled regression analysis revealed that higher NLR was significantly associated with lower DAT levels in the caudate (β = -0.27, = 0.003) and the putamen (β = -0.27, = 0.011). Moreover, in the early-stage PD subgroup, a similar association was observed (caudate: β = -0.37, = 0.013; putamen: β = -0.45, = 0.005). The lymphocytes count was correlated positively with the striatal DAT levels in the Spearman correlation analysis whether in total patients (caudate: ρ = 0.25, = 0.013; putamen: ρ = 0.22, = 0.026) or in the early-stage subgroup (caudate: ρ = 0.31, = 0.023, putamen: ρ = 0.34, = 0.011).
CONCLUSION
Dopaminergic degeneration is associated with peripheral inflammation in PD. The NLR, a widely used inflammatory marker, may have the potential to reflect the degree of dopaminergic degeneration in individuals with early-stage PD.
PubMed: 38650864
DOI: 10.3389/fnagi.2024.1377994 -
Scientific Reports Apr 2024A crucial step in the clinical adaptation of an AI-based tool is an external, independent validation. The aim of this study was to investigate brain atrophy in patients...
A crucial step in the clinical adaptation of an AI-based tool is an external, independent validation. The aim of this study was to investigate brain atrophy in patients with confirmed, progressed Huntington's disease using a certified software for automated volumetry and to compare the results with the manual measurement methods used in clinical practice as well as volume calculations of the caudate nuclei based on manual segmentations. Twenty-two patients were included retrospectively, consisting of eleven patients with Huntington's disease and caudate nucleus atrophy and an age- and sex-matched control group. To quantify caudate head atrophy, the frontal horn width to intercaudate distance ratio and the intercaudate distance to inner table width ratio were obtained. The software mdbrain was used for automated volumetry. Manually measured ratios and automatically measured volumes of the groups were compared using two-sample t-tests. Pearson correlation analyses were performed. The relative difference between automatically and manually determined volumes of the caudate nuclei was calculated. Both ratios were significantly different between the groups. The automatically and manually determined volumes of the caudate nuclei showed a high level of agreement with a mean relative discrepancy of - 2.3 ± 5.5%. The Huntington's disease group showed significantly lower volumes in a variety of supratentorial brain structures. The highest degree of atrophy was shown for the caudate nucleus, putamen, and pallidum (all p < .0001). The caudate nucleus volume and the ratios were found to be strongly correlated in both groups. In conclusion, in patients with progressed Huntington's disease, it was shown that the automatically determined caudate nucleus volume correlates strongly with measured ratios commonly used in clinical practice. Both methods allowed clear differentiation between groups in this collective. The software additionally allows radiologists to more objectively assess the involvement of a variety of brain structures that are less accessible to standard semiquantitative methods.
Topics: Humans; Huntington Disease; Male; Female; Middle Aged; Deep Learning; Caudate Nucleus; Retrospective Studies; Brain; Atrophy; Magnetic Resonance Imaging; Adult; Aged; Software; Organ Size; Image Processing, Computer-Assisted
PubMed: 38649395
DOI: 10.1038/s41598-024-59590-7 -
NeuroImage Apr 2024Transcranial alternating current stimulation (tACS) is an efficient neuromodulation technique that enhances cognitive function in a non-invasive manner. Using functional...
Transcranial alternating current stimulation (tACS) is an efficient neuromodulation technique that enhances cognitive function in a non-invasive manner. Using functional magnetic resonance imaging, we investigated whether tACS with different phase lags (0° and 180°) between the dorsal anterior cingulate and left dorsolateral prefrontal cortices modulated inhibitory control performance during the Stroop task. We found out-of-phase tACS mediated improvements in task performance, which was neurodynamically reflected as putamen, dorsolateral prefrontal, and primary motor cortical activation as well as prefrontal-based top-down functional connectivity. Our observations uncover the neurophysiological bases of tACS-phase-dependent neuromodulation and provide a feasible non-invasive approach to effectively modulate inhibitory control.
Topics: Humans; Transcranial Direct Current Stimulation; Male; Female; Magnetic Resonance Imaging; Adult; Young Adult; Inhibition, Psychological; Stroop Test; Gyrus Cinguli; Dorsolateral Prefrontal Cortex; Executive Function; Brain Mapping; Motor Cortex
PubMed: 38648868
DOI: 10.1016/j.neuroimage.2024.120612