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Scientific Reports Jun 2024Structural brain network topology can be altered in case of a brain tumor, due to both the tumor itself and its treatment. In this study, we explored the role of...
Structural brain network topology can be altered in case of a brain tumor, due to both the tumor itself and its treatment. In this study, we explored the role of structural whole-brain and nodal network metrics and their association with cognitive functioning. Fifty WHO grade 2-3 adult glioma survivors (> 1-year post-therapy) and 50 matched healthy controls underwent a cognitive assessment, covering six cognitive domains. Raw cognitive assessment scores were transformed into w-scores, corrected for age and education. Furthermore, based on multi-shell diffusion-weighted MRI, whole-brain tractography was performed to create weighted graphs and to estimate whole-brain and nodal graph metrics. Hubs were defined based on nodal strength, betweenness centrality, clustering coefficient and shortest path length in healthy controls. Significant differences in these metrics between patients and controls were tested for the hub nodes (i.e. n = 12) and non-hub nodes (i.e. n = 30) in two mixed-design ANOVAs. Group differences in whole-brain graph measures were explored using Mann-Whitney U tests. Graph metrics that significantly differed were ultimately correlated with the cognitive domain-specific w-scores. Bonferroni correction was applied to correct for multiple testing. In survivors, the bilateral putamen were significantly less frequently observed as a hub (p < 0.001). These nodes' assortativity values were positively correlated with attention (r(90) > 0.573, p < 0.001), and proxy IQ (r(90) > 0.794, p < 0.001). Attention and proxy IQ were significantly more often correlated with assortativity of hubs compared to non-hubs (p < 0.001). Finally, the whole-brain graph measures of clustering coefficient (r = 0.685), global (r = 0.570) and local efficiency (r = 0.500) only correlated with proxy IQ (p < 0.001). This study demonstrated potential reorganization of hubs in glioma survivors. Assortativity of these hubs was specifically associated with cognitive functioning, which could be important to consider in future modeling of cognitive outcomes and risk classification in glioma survivors.
Topics: Humans; Glioma; Female; Male; Adult; Middle Aged; Cognition; Brain Neoplasms; Cancer Survivors; Brain; Nerve Net; Case-Control Studies; Diffusion Tensor Imaging; Diffusion Magnetic Resonance Imaging
PubMed: 38834633
DOI: 10.1038/s41598-024-63716-2 -
International Journal of Medical... 2024Citicoline can be used to reduce acute ischemic stroke injury via venous infusion, however, its protective effects in the brain extracellular space remain largely...
Citicoline can be used to reduce acute ischemic stroke injury via venous infusion, however, its protective effects in the brain extracellular space remain largely unknown. Herein, we investigated the brain protective effects of citicoline administered via the brain extracellular space and sought precise effective dosage range that can protect against ischemic injury after experimental ischemic stroke in rats. : Fifty-six Sprague-Dawley rats were randomly divided into control, intraperitoneal (IP), caudate-putamen (CPu)-25, CPu-40, CPu-50, CPu-60 and CPu-75 groups based on the infusion site and concentration of citicoline. Two hours after the administration of citicoline, the rats were subjected to a permanent middle cerebral artery occlusion to mimic acute ischemic stroke. Then, the brain infarct volume in rats after stroke was measured and their neurological deficiency was evaluated to explain the protective effects and effective dosage range of citicoline. Compared to the control and IP groups, brain infarct volume of rats in CPu-40, CPu-50, and CPu-60 groups is significant smaller. Furthermore, the brain infarct volume of rats in CPu-50 is the least. Here, we showed that citicoline can decrease the brain infarct volume, thus protecting the brain from acute ischemic stroke injury. We also found that the appropriate effective citicoline dose delivered via the brain extracellular space is 50 mM. Our study provides novel insights into the precise treatment of acute ischemic stroke by citicoline via the brain extracellular space, further guiding the treatment of brain disease.
Topics: Animals; Cytidine Diphosphate Choline; Rats; Ischemic Stroke; Disease Models, Animal; Extracellular Space; Male; Rats, Sprague-Dawley; Brain; Neuroprotective Agents; Humans; Infarction, Middle Cerebral Artery; Brain Ischemia
PubMed: 38818467
DOI: 10.7150/ijms.93482 -
Indian Journal of Nuclear Medicine :... 2024Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra. SPECT imaging using technetium-99m [Tc] labeled trodat is...
BACKGROUND
Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra. SPECT imaging using technetium-99m [Tc] labeled trodat is the choice of imaging to differentiate PD from its other forms like drug-induced PD.
AIMS AND OBJECTIVES
The main objective of our study was to prepare in-house sterile formulation of [Tc]Tc-trodat and use in clinics.
MATERIALS AND METHODS
The labeling of trodat was standardized using glucoheptonate sodium salt (GHA), stannous chloride dihydrate (in 0.05 N HCl), and ethylenediaminetetraacetic acid (Na-EDTA). The preparation was mixed and autoclaved at 15 psi for 15 min. The standardised formulation was stored at 4°C, -20°C and -80°C and labeling with Tc was tested for up to 6 days. The radiochemical purity, chemical impurities, and endotoxin levels were tested. The frozen formulation was tested in swiss mice (n = 3) for biodistribution studies at 4 h. Around 18 ± 2 mCi was injected intravenously in each patient (n = 5) and the image was acquired at 4 h post-injection.
RESULTS
The radiochemical purity of the preparation was 98.3 ± 1.4% with a retention time of 16.8 ± 1.5 min as compared to 4.0 ± 0.5 min for free Tc. Animal distribution showed highest uptake in liver and dual excretion via hepatobiliary and renal system. [Tc]Tc-trodat imaging was able to differentiate both caudate and putamen.
CONCLUSIONS
In-house frozen preparation was advantageous, as it has decreased the chance of manual error as compared to daily make up formulations and economical as compared to commercially available kits.
PubMed: 38817725
DOI: 10.4103/ijnm.ijnm_104_23 -
Turkish Journal of Medical Sciences 2023The cause and treatment of electrical status epilepticus during sleep (ESES), one of the epileptic encephalopathies of childhood, is unclear. The aim of this study was...
BACKGROUND/AIM
The cause and treatment of electrical status epilepticus during sleep (ESES), one of the epileptic encephalopathies of childhood, is unclear. The aim of this study was to evaluate possible microstructural abnormalities in the brain using advanced magnetic resonance imaging (MRI) techniques in ESES patients with and without genetic mutations.
MATERIALS AND METHODS
This research comprised 12 ESES patients without structural thalamic lesions (6 with genetic abnormalities and 6 without) and 12 healthy children. Whole-exome sequencing was used for the genetic mutation analysis. Brain MRI data were evaluated using tractus-based spatial statistics, voxel-based morphometry, a local gyrification index, subcortical shape analysis, FreeSurfer volume, and cortical thickness. The data of the groups were compared.
RESULTS
The mean age in the control group was 9.05 ± 1.85 years, whereas that in the ESES group was 9.45 ± 2.72 years. Compared to the control group, the ESES patients showed higher mean thalamus diffusivity (p < 0.05). ESES patients with genetic mutations had lower axial diffusivity in the superior longitudinal fasciculus and gray matter volume in the entorhinal region, accumbens area, caudate, putamen, cerebral white matter, and outer cerebellar areas. The superior and middle temporal cortical thickness increased in the ESES patients.
CONCLUSION
This study is important in terms of presenting the microstructural evaluation of the brain in ESES patients with advanced MRI analysis methods as well as comparing patients with and without genetic mutations. These findings may be associated with corticostriatal transmission, ictogenesis, epileptogenesis, neuropsychiatric symptoms, cognitive impairment, and cerebellar involvement in ESES. Expanded case-group studies may help to understand the physiology of the corticothalamic circuitry in its etiopathogenesis and develop secondary therapeutic targets for ESES.
Topics: Humans; Status Epilepticus; Male; Child; Female; Magnetic Resonance Imaging; Brain; Sleep; Adolescent; Case-Control Studies; Thalamus
PubMed: 38813507
DOI: 10.55730/1300-0144.5754 -
Turkish Journal of Medical Sciences 2023There are reports stating that deteriorations in metal homeostasis in neurodegenerative diseases promote abnormal protein accumulation. In this study, the serum metal...
BACKGROUND/AIM
There are reports stating that deteriorations in metal homeostasis in neurodegenerative diseases promote abnormal protein accumulation. In this study, the serum metal levels in Alzheimer's disease (AD) and Parkinson's disease (PD) and its relationship with the cortical regions of the brain were investigated.
MATERIALS AND METHODS
The patients were divided into 3 groups consisting of the AD group, PD group, and healthy control group (n = 15 for each). The volumes of specific brain regions were measured over the participants' 3dimensional magnetic resonance images, and they were compared across the groups. Copper, zinc, iron, and ferritin levels in the serums were determined, and their correlations with the brain region volumes were examined.
RESULTS
The volumes of left hippocampus and right substantia nigra were lower in the AD and PD groups, while the volume of the left nucleus caudatus (CdN) and bilateral insula were lower in the AD group compared to the control group. Serum zinc levels were lower in the AD and PD groups, while the iron level was lower in the PD group in comparison to the control group. In addition, the serum ferritin level was higher in the AD group than in the control group. Serum zinc and copper levels in the AD group were positively correlated with the volumes of the right entorhinal cortex, thalamus, CdN, and insula. Serum zinc and copper levels in the PD group showed a negative correlation with the left nucleus accumbens (NAc), right putamen, and right insula volumes. While the serum ferritin level in the PD group displayed a positive correlation with the bilateral CdN, putamen, and NAc, as well as the right hippocampus and insula volumes, no area was detected that showed a correlation with the serum ferritin level in the AD group.
CONCLUSION
A relationship was determined between the serum metal levels in the AD and PD groups and certain brain cortical regions that showed volumetric changes, which can be important for the early diagnosis of neurodegenerative diseases.
Topics: Humans; Male; Female; Aged; Alzheimer Disease; Zinc; Iron; Magnetic Resonance Imaging; Parkinson Disease; Middle Aged; Ferritins; Brain; Copper; Neurodegenerative Diseases; Case-Control Studies; Metals
PubMed: 38812995
DOI: 10.55730/1300-0144.5714 -
NeuroImage Aug 2024The complexity of fMRI signals quantifies temporal dynamics of spontaneous neural activity, which has been increasingly recognized as providing important insights into...
The complexity of fMRI signals quantifies temporal dynamics of spontaneous neural activity, which has been increasingly recognized as providing important insights into cognitive functions and psychiatric disorders. However, its heritability and structural underpinnings are not well understood. Here, we utilize multi-scale sample entropy to extract resting-state fMRI complexity in a large healthy adult sample from the Human Connectome Project. We show that fMRI complexity at multiple time scales is heritable in broad brain regions. Heritability estimates are modest and regionally variable. We relate fMRI complexity to brain structure including surface area, cortical myelination, cortical thickness, subcortical volumes, and total brain volume. We find that surface area is negatively correlated with fine-scale complexity and positively correlated with coarse-scale complexity in most cortical regions, especially the association cortex. Most of these correlations are related to common genetic and environmental effects. We also find positive correlations between cortical myelination and fMRI complexity at fine scales and negative correlations at coarse scales in the prefrontal cortex, lateral temporal lobe, precuneus, lateral parietal cortex, and cingulate cortex, with these correlations mainly attributed to common environmental effects. We detect few significant associations between fMRI complexity and cortical thickness. Despite the non-significant association with total brain volume, fMRI complexity exhibits significant correlations with subcortical volumes in the hippocampus, cerebellum, putamen, and pallidum at certain scales. Collectively, our work establishes the genetic basis and structural correlates of resting-state fMRI complexity across multiple scales, supporting its potential application as an endophenotype for psychiatric disorders.
Topics: Humans; Magnetic Resonance Imaging; Male; Female; Adult; Connectome; Brain; Young Adult; Rest
PubMed: 38810892
DOI: 10.1016/j.neuroimage.2024.120657 -
Translational Psychiatry May 2024Heavy maternal alcohol drinking during pregnancy has been associated with altered neurodevelopment in the child but the effects of low-dose alcohol drinking are less...
Heavy maternal alcohol drinking during pregnancy has been associated with altered neurodevelopment in the child but the effects of low-dose alcohol drinking are less clear and any potential safe level of alcohol use during pregnancy is not known. We evaluated the effects of prenatal alcohol on reward-related behavior and substance use in young adulthood and the potential sex differences therein. Participants were members of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) prenatal birth cohort who participated in its neuroimaging follow-up in young adulthood. A total of 191 participants (28-30 years; 51% men) had complete data on prenatal exposure to alcohol, current substance use, and fMRI data from young adulthood. Maternal alcohol drinking was assessed during mid-pregnancy and pre-conception. Brain response to reward anticipation and reward feedback was measured using the Monetary Incentive Delay task and substance use in young adulthood was assessed using a self-report questionnaire. We showed that even a moderate exposure to alcohol in mid-pregnancy but not pre-conception was associated with robust effects on brain response to reward feedback (six frontal, one parietal, one temporal, and one occipital cluster) and with greater cannabis use in both men and women 30 years later. Moreover, mid-pregnancy but not pre-conception exposure to alcohol was associated with greater cannabis use in young adulthood and these effects were independent of maternal education and maternal depression during pregnancy. Further, the extent of cannabis use in the late 20 s was predicted by the brain response to reward feedback in three out of the nine prenatal alcohol-related clusters and these effects were independent of current alcohol use. Sex differences in the brain response to reward outcome emerged only during the no loss vs. loss contrast. Young adult men exposed to alcohol prenatally had significantly larger brain response to no loss vs. loss in the putamen and occipital region than women exposed to prenatal alcohol. Therefore, we conclude that even moderate exposure to alcohol prenatally has long-lasting effects on brain function during reward processing and risk of cannabis use in young adulthood.
Topics: Humans; Female; Reward; Pregnancy; Prenatal Exposure Delayed Effects; Male; Adult; Magnetic Resonance Imaging; Alcohol Drinking; Longitudinal Studies; Brain; Sex Factors
PubMed: 38806472
DOI: 10.1038/s41398-024-02941-9 -
Frontiers in Endocrinology 2024Vasopressin and oxytocin are well known and evolutionarily ancient modulators of social behavior. The distribution and relative densities of vasopressin and oxytocin... (Comparative Study)
Comparative Study
Vasopressin and oxytocin are well known and evolutionarily ancient modulators of social behavior. The distribution and relative densities of vasopressin and oxytocin receptors are known to modulate the sensitivity to these signaling molecules. Comparative work is needed to determine which neural networks have been conserved and modified over evolutionary time, and which social behaviors are commonly modulated by nonapeptide signaling. To this end, we used receptor autoradiography to determine the distribution of vasopressin 1a and oxytocin receptors in the Southern giant pouched rat () brain, and to assess the relative densities of these receptors in specific brain regions. We then compared the relative receptor pattern to 23 other species of rodents using a multivariate ANOVA. Pouched rat receptor patterns were strikingly similar to hamsters and voles overall, despite the variation in social organization among species. Uniquely, the pouched rat had dense vasopressin 1a receptor binding in the caudate-putamen (i.e., striatum), an area that might impact affiliative behavior in this species. In contrast, the pouched rat had relatively little oxytocin receptor binding in much of the anterior forebrain. Notably, however, oxytocin receptor binding demonstrated extremely dense binding in the bed nucleus of the stria terminalis, which is associated with the modulation of several social behaviors and a central hub of the social decision-making network. Examination of the nonapeptide system has the potential to reveal insights into species-specific behaviors and general themes in the modulation of social behavior.
Topics: Animals; Receptors, Oxytocin; Receptors, Vasopressin; Male; Brain; Rodentia; Rats; Species Specificity; Autoradiography; Arvicolinae; Oxytocin; Cricetinae; Social Behavior; Female
PubMed: 38803478
DOI: 10.3389/fendo.2024.1390203 -
BioRxiv : the Preprint Server For... May 2024The functional connectome changes with aging. We systematically evaluated aging related alterations in the functional connectome using a whole-brain connectome network...
The functional connectome changes with aging. We systematically evaluated aging related alterations in the functional connectome using a whole-brain connectome network analysis in 39,675 participants in UK Biobank project. We used adaptive dense network discovery tools to identify networks directly associated with aging from resting-state fMRI data. We replicated our findings in 499 participants from the Lifespan Human Connectome Project in Aging study. The results consistently revealed two motor-related subnetworks (both permutation test p-values <0.001) that showed a decline in resting-state functional connectivity (rsFC) with increasing age. The first network primarily comprises sensorimotor and dorsal/ventral attention regions from precentral gyrus, postcentral gyrus, superior temporal gyrus, and insular gyrus, while the second network is exclusively composed of basal ganglia regions, namely the caudate, putamen, and globus pallidus. Path analysis indicates that white matter fractional anisotropy mediates 19.6% (p<0.001, 95% CI [7.6% 36.0%]) and 11.5% (p<0.001, 95% CI [6.3% 17.0%]) of the age-related decrease in both networks, respectively. The total volume of white matter hyperintensity mediates 32.1% (p<0.001, 95% CI [16.8% 53.0%]) of the aging-related effect on rsFC in the first subnetwork.
PubMed: 38798606
DOI: 10.1101/2024.05.17.594743 -
Brain : a Journal of Neurology Jun 2024Stuttering affects approximately 1 in 100 adults and can result in significant communication problems and social anxiety. It most often occurs as a developmental...
Stuttering affects approximately 1 in 100 adults and can result in significant communication problems and social anxiety. It most often occurs as a developmental disorder but can also be caused by focal brain damage. These latter cases may lend unique insight into the brain regions causing stuttering. Here, we investigated the neuroanatomical substrate of stuttering using three independent datasets: (i) case reports from the published literature of acquired neurogenic stuttering following stroke (n = 20, 14 males/six females, 16-77 years); (ii) a clinical single study cohort with acquired neurogenic stuttering following stroke (n = 20, 13 males/seven females, 45-87 years); and (iii) adults with persistent developmental stuttering (n = 20, 14 males/six females, 18-43 years). We used the first two datasets and lesion network mapping to test whether lesions causing acquired stuttering map to a common brain network. We then used the third dataset to test whether this lesion-based network was relevant to developmental stuttering. In our literature dataset, we found that lesions causing stuttering occurred in multiple heterogeneous brain regions, but these lesion locations were all functionally connected to a common network centred around the left putamen, including the claustrum, amygdalostriatal transition area and other adjacent areas. This finding was shown to be specific for stuttering (PFWE < 0.05) and reproducible in our independent clinical cohort of patients with stroke-induced stuttering (PFWE < 0.05), resulting in a common acquired stuttering network across both stroke datasets. Within the common acquired stuttering network, we found a significant association between grey matter volume and stuttering impact for adults with persistent developmental stuttering in the left posteroventral putamen, extending into the adjacent claustrum and amygdalostriatal transition area (PFWE < 0.05). We conclude that lesions causing acquired neurogenic stuttering map to a common brain network, centred to the left putamen, claustrum and amygdalostriatal transition area. The association of this lesion-based network with symptom severity in developmental stuttering suggests a shared neuroanatomy across aetiologies.
Topics: Humans; Stuttering; Male; Female; Middle Aged; Adult; Adolescent; Aged; Aged, 80 and over; Young Adult; Brain; Stroke; Magnetic Resonance Imaging; Brain Mapping
PubMed: 38797521
DOI: 10.1093/brain/awae059