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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 -
BioRxiv : the Preprint Server For... Apr 2024Early psychosis (EP) is a critical period in the course of psychotic disorders during which the brain is thought to undergo rapid and significant functional and...
INTRODUCTION
Early psychosis (EP) is a critical period in the course of psychotic disorders during which the brain is thought to undergo rapid and significant functional and structural changes . Growing evidence suggests that the advent of psychotic disorders is early alterations in the brain's functional connectivity and structure, leading to aberrant neural network organization. The Human Connectome Project (HCP) is a global effort to map the human brain's connectivity in healthy and disease populations; within HCP, there is a specific dataset that focuses on the EP subjects (i.e., those within five years of the initial psychotic episode) (HCP-EP), which is the focus of our study. Given the critically important role of the midbrain function and structure in psychotic disorders (cite), and EP in particular (cite), we specifically focused on the midbrain macro- and micro-structural alterations and their association with clinical outcomes in HCP-EP.
METHODS
We examined macro- and micro-structural brain alterations in the HCP-EP sample (n=179: EP, n=123, Controls, n=56) as well as their associations with behavioral measures (i.e., symptoms severity) using a stepwise approach, incorporating a multimodal MRI analysis procedure. First, Deformation Based Morphometry (DBM) was carried out on the whole brain 3 Tesla T1w images to examine gross brain anatomy (i.e., seed-based and voxel-based volumes). Second, we extracted Fractional Anisotropy (FA), Axial Diffusivity (AD), and Mean Diffusivity (MD) indices from the Diffusion Tensor Imaging (DTI) data; a midbrain mask was created based on FreeSurfer v.6.0 atlas. Third, we employed Tract-Based Spatial Statistics (TBSS) to determine microstructural alterations in white matter tracts within the midbrain and broader regions. Finally, we conducted correlation analyses to examine associations between the DBM-, DTI- and TBSS-based outcomes and the Positive and Negative Syndrome Scale (PANSS) scores.
RESULTS
DBM analysis showed alterations in the hippocampus, midbrain, and caudate/putamen. A DTI voxel-based analysis shows midbrain reductions in FA and AD and increases in MD; meanwhile, the hippocampus shows an increase in FA and a decrease in AD and MD. Several key brain regions also show alterations in DTI indices (e.g., insula, caudate, prefrontal cortex). A seed-based analysis centered around a midbrain region of interest obtained from freesurfer segmentation confirms the voxel-based analysis of DTI indices. TBSS successfully captured structural differences within the midbrain and complementary alterations in other main white matter tracts, such as the corticospinal tract and cingulum, suggesting early altered brain connectivity in EP. Correlations between these quantities in the EP group and behavioral scores (i.e., PANSS and CAINS tests) were explored. It was found that midbrain volume noticeably correlates with the Cognitive score of PA and all DTI metrics. FA correlates with the several dimensions of the PANSS, while AD and MD do not show many associations with PANSS or CAINS.
CONCLUSIONS
Our findings contribute to understanding the midbrain-focused circuitry involvement in EP and complimentary alteration in EP. Our work provides a path for future investigations to inform specific brain-based biomarkers of EP and their relationships to clinical manifestations of the psychosis course.
PubMed: 38645197
DOI: 10.1101/2024.04.10.588901 -
MedRxiv : the Preprint Server For... Apr 2024Dystonia is a movement disorder defined by involuntary muscle contractions leading to abnormal postures or twisting and repetitive movements. Classically dystonia has...
OBJECTIVE
Dystonia is a movement disorder defined by involuntary muscle contractions leading to abnormal postures or twisting and repetitive movements. Classically dystonia has been thought of as a disorder of the basal ganglia, but newer results in idiopathic dystonia and lesion-induced dystonia in adults point to broader motor network dysfunction spanning the basal ganglia, cerebellum, premotor cortex, sensorimotor, and frontoparietal regions. It is unclear whether a similar network is shared between different etiologies of pediatric lesion-induced dystonia.
METHODS
Three cohorts of pediatric patients with lesion-induced dystonia were identified. The lesion etiologies included hypoxia, kernicterus, and stroke versus comparison subjects with acquired lesions not associated with dystonia. Multivariate lesion-symptom mapping and lesion network mapping were used to evaluate the anatomy and networks associated with dystonia.
RESULTS
Multivariate lesion-symptom mapping showed that lesions of the putamen (stroke: r = 0.50, p <0.01; hypoxia, r = 0.64, p <0.001) and globus pallidus (kernicterus, r = 0.61, p <0.01) were associated with dystonia. Lesion network mapping using normative connectome data from healthy children demonstrated that these regional findings occurred within a common brain-wide network that involves the basal ganglia, anterior and medial cerebellum, and cortical regions that overlap the cingulo-opercular and somato-cognitive-action networks.
INTERPRETATION
We interpret these findings as novel evidence for a unified dystonia brain network that involves the somato-cognitive-action network, which is involved in higher order coordination of movement. Elucidation of this network gives insight into the functional origins of dystonia and provides novel targets to investigate for therapeutic intervention.
PubMed: 38645071
DOI: 10.1101/2024.04.06.24305421 -
CNS Neuroscience & Therapeutics Apr 2024Motor abnormalities have been identified as one common symptom in patients with generalized tonic-clonic seizures (GTCS) inspiring us to explore the disease in a motor...
AIMS
Motor abnormalities have been identified as one common symptom in patients with generalized tonic-clonic seizures (GTCS) inspiring us to explore the disease in a motor execution condition, which might provide novel insight into the pathomechanism.
METHODS
Resting-state and motor-task fMRI data were collected from 50 patients with GTCS, including 18 patients newly diagnosed without antiepileptic drugs (ND_GTCS) and 32 patients receiving antiepileptic drugs (AEDs_GTCS). Motor activation and its association with head motion and cerebral gradients were assessed. Whole-brain network connectivity across resting and motor states was further calculated and compared between groups.
RESULTS
All patients showed over-activation in the postcentral gyrus and the ND_GTCS showed decreased activation in putamen. Specifically, activation maps of ND_GTCS showed an abnormal correlation with head motion and cerebral gradient. Moreover, we detected altered functional network connectivity in patients within states and across resting and motor states by using repeated-measures analysis of variance. Patients did not show abnormal connectivity in the resting state, while distributed abnormal connectivity in the motor-task state. Decreased across-state network connectivity was also found in all patients.
CONCLUSION
Convergent findings suggested the over-response of activation and connection of the brain to motor execution in GTCS, providing new clues to uncover motor susceptibility underlying the disease.
Topics: Humans; Male; Female; Magnetic Resonance Imaging; Adult; Brain; Rest; Young Adult; Seizures; Middle Aged; Brain Mapping; Neural Pathways; Anticonvulsants; Adolescent; Motor Activity
PubMed: 38644561
DOI: 10.1111/cns.14672