Analysis of Brain Activity Changes in Patients with Parkinson’s Disease Based on Resting-State Functional Magnetic Resonance Imaging

This paper uses resting-state functional magnetic resonance imaging to observe the changes in local consistency of brain activity in patients with Parkinson’s disease (PD). Both healthy volunteers and Parkinson’s disease patients were scanned for resting brain functional imaging, and the collected raw data were processed using resting functional magnetic resonance data processing toolkit software. This study adopted the use of Regional Homogeneity (ReHo). The postprocessing method of RS-fMRI is to study the spontaneous brain activity changes of patients with Parkinson’s disease and cognitive impairment and to explore the changes in the function of their brain regions in the hope of providing help for the treatment of Parkinson’s disease cognitive impairment. The results showed that, compared with the normal control group, the brain regions with increased ReHo values in the PD group were the right central anterior gyrus, the right lingual gyrus, the left middle occipital gyrus, and the bilateral anterior cuneiform lobes. The results show that PD patients have abnormal brain nerve activities in the resting state, and these abnormal brain nerve activities may be related to PD cognitive and behavioral dysfunction.

Neurexins in serotonergic neurons regulate serotonin transmission and complex mouse behaviors

Extensive serotonin (5-HT) innervation throughout the brain corroborates 5-HT’s modulatory role in numerous cognitive activities. Volume transmission is the major mode for 5-HT transmission but mechanisms underlying 5-HT signaling are still largely unknown. Abnormal brain 5-HT levels and function have been implicated in autism spectrum disorder (ASD). Neurexin (Nrxn) genes encode presynaptic cell adhesion molecules important for the regulation of synaptic neurotransmitter release, notably glutamatergic and GABAergic transmission. Mutations in Nrxn genes are associated with neurodevelopmental disorders including ASD. However, the role of Nrxn genes in the 5-HT system is poorly understood. Here, we generated a mouse model with all three Nrxn genes disrupted specifically in 5-HT neurons to study how Nrxns affect 5-HT transmission. Loss of Nrxns in 5-HT neurons impaired 5-HT release in the dorsal raphe nucleus and dorsal hippocampus and decreased serotonin transporter distribution in specific brain areas. Furthermore, 5-HT neuron-specific Nrxn knockout reduced sociability and increased depressive-like behavior. Our results highlight functional roles for Nrxns in 5-HT neurotransmission and the execution of complex behaviors.

Abnormal brain development of monoamine oxidase mutant zebrafish and impaired social interaction of heterozygous fish

Monoamine oxidase (MAO) deficiency and imbalanced levels of brain monoamines have been associated with developmental delay, neuropsychiatric disorders and aggressive behavior. Animal models are valuable tools to gain mechanistic insight into outcomes associated with MAO deficiency. Here we report a novel genetic model to study the effects of mao-loss-of-function in zebrafish. Quantitative PCR, in situ hybridization and immunocytochemistry were used to study neurotransmitter systems, and expression of relevant genes for brain development in zebrafish mao mutants. Larval and adult fish behavior was evaluated through different tests. A stronger serotonin immunoreactivity was detected in both mao+/- and mao−/- larvae when compared with mao+/+ siblings. Mao−/- larvae were hypoactive, presented decreased reactions to visual and acoustic stimuli. They also had impaired histaminergic and dopaminergic systems, abnormal expression of developmental markers, and they died within 20 days post-fertilization. Mao+/- fish were viable, grew until adulthood and demonstrated anxiety-like behavior and impaired social interactions when compared with adult mao+/+ siblings. Our results indicate that mao−/- and mao+/- mutants could be promising tools to study the roles of MAO in brain development and behavior.

In Vitro Recapitulation of Neuropsychiatric Disorders with Pluripotent Stem Cells-Derived Brain Organoids

Adolescent neuropsychiatric disorders have been recently increasing due to genetic and environmental influences. Abnormal brain development before and after birth contribute to the pathology of neuropsychiatric disorders. However, it is difficult to experimentally investigate because of the complexity of brain and ethical constraints. Recently generated human brain organoids from pluripotent stem cells are considered as a promising in vitro model to recapitulate brain development and diseases. To better understand how brain organoids could be applied to investigate neuropsychiatric disorders, we analyzed the key consideration points, including how to generate brain organoids from pluripotent stem cells, the current application of brain organoids in recapitulating neuropsychiatric disorders and the future perspectives. This review covered what have been achieved on modeling the cellular and neural circuit deficits of neuropsychiatric disorders and those challenges yet to be solved. Together, this review aims to provide a fundamental understanding of how to generate brain organoids to model neuropsychiatric disorders, which will be helpful in improving the mental health of adolescents.

Predicting factors for abnormal brain computed tomography in children with minor head trauma

Background Deciding whether a cranial Computed Tomography (CT) scan in a patient with minor head trauma (MHT) is necessary or not has always been challenging. Diagnosing Traumatic Brain Injury (TBI) is a fundamental part of MHT managing especially in children who are more vulnerable in terms of brain CT radiation consequences and TBI. Defining some indications to timely and efficiently predict the likelihood of TBI is necessary. Thus, we aimed to determine the impact of clinical findings to predict the need for brain CT in children with MHT. Methods In a prospective cohort study, 200 children (2 to 14 years) with MHT were included from 2019 to 2020. The data of MHT-related clinical findings were gathered. The primary and secondary outcomes were defined as a positive brain CT and any TBI requiring neurosurgery intervention, respectively. In statistical analysis, we performed Binary Logistic regression analysis, Fisher’s exact test and independent samples t-test using SPSS V.26. Results The mean age of participants was 6.5 ± 3.06 years. Ninety patients underwent brain CT. The most common clinical finding and injury mechanism were headache and falling from height, respectively. The results of brain CTs were positive in seven patients (3.5%). We identified three predicting factors for an abnormal brain CT including headache, decreased level of consciousness, and vomiting. Conclusion We showed that repetitive vomiting (≥2), headache, and decreased level of consciousness are predicting factors for an abnormal brain CT in children with MHT.

Abnormal Brain Functional Network Dynamics in Acute CO Poisoning

Aims: Carbon monoxide poisoning is a common condition that can cause severe neurological sequelae. Previous studies have revealed that functional connectivity in carbon monoxide poisoning is abnormal under the assumption that it is resting during scanning and have focused on studying delayed encephalopathy in carbon monoxide poisoning. However, studies of functional connectivity dynamics in the acute phase of carbon monoxide poisoning may provide a more insightful perspective for understanding the neural mechanisms underlying carbon monoxide poisoning. To our knowledge, this is the first study that explores abnormal brain network dynamics in the acute phase of carbon monoxide poisoning.Methods: Combining the sliding window method and k-means algorithm, we identified four recurrent dynamic functional cognitive impairment states from resting-state functional magnetic resonance imaging data from 29 patients in the acute phase of carbon monoxide poisoning and 29 healthy controls. We calculated between-group differences in the temporal properties and intensity of dFC states, and we also performed subgroup analyses to separately explore the brain network dynamics characteristics of adult vs. child carbon monoxide poisoning groups. Finally, these differences were correlated with patients’ cognitive performance in the acute phase of carbon monoxide poisoning and coma duration.Results: We identified four morphological patterns of brain functional network connectivity. During the acute phase of carbon monoxide poisoning, patients spent more time in State 2, which is characterized by positive correlation between SMN and CEN, and negative correlation between DMN and SMN. In addition, the fractional window and mean dwell time of State 2 were positively correlated with coma duration. The subgroup analysis results demonstrated that the acute phase of childhood carbon monoxide poisoning had greater dFNC time variability than adult carbon monoxide poisoning.Conclusion: Our findings reveal that patients in the acute phase of carbon monoxide poisoning exhibit dynamic functional abnormalities. Furthermore, children have greater dFNC instability following carbon monoxide poisoning than adults. This advances our understanding of the pathophysiological mechanisms underlying acute carbon monoxide poisoning.