Brain communications最新文献

Hydrocephalus and Dandy-Walker malformation are amongst the most common congenital brain anomalies. We identified three consanguineous families with both obstructive hydrocephalus and Dandy-Walker malformation. To understand the molecular basis of these anomalies, we conducted genome-wide sequencing in these families. We identified three homozygous truncating variants in the PLAT gene in the four affected family members. All of them showed tetraventricular hydrocephalus. In two individuals, a membrane at the inferior aspect of the fourth ventricle was likely the cause of their hydrocephalus. Three cases exhibited Dandy-Walker malformation, whereas the two oldest individuals displayed intellectual disability. PLAT encodes the tissue-type plasminogen activator, a serine protease whose main function is to cleave the proenzyme plasminogen to produce active plasmin. Interestingly, plasminogen deficiency has also been shown to cause obstructive hydrocephalus and Dandy-Walker malformation, suggesting that loss of PLAT causes these defects by disrupting plasmin production. In summary, we describe a recessive disorder characterized by obstructive hydrocephalus, Dandy-Walker malformation and intellectual disability in individuals with loss-of-function variants in PLAT. This discovery further strengthens the involvement of the plasminogen pathway in the pathogenesis of these developmental disorders.

The outcome prediction of acute anterior circulation non-lacunar infarction (AACNLI) is important for the precise clinical treatment of this disease. However, the accuracy of prognosis prediction is still limited. This study aims to develop and compare machine learning models based on MRI radiomics of multiple ischaemic-related areas for prognostic prediction in AACNLI. This retrospective multicentre study consecutively included 372 AACNLI patients receiving MRI examinations and conventional therapy between October 2020 and February 2023. These were grouped into training set, internal test set and external test set. MRI radiomics features were extracted from the mask diffusion-weighted imaging, mask apparent diffusion coefficient (ADC) and mask ADC620 by AACNLI segmentations. Grid search parameter tuning was performed on 12 feature selection and 9 machine learning algorithms, and algorithm combinations with the smallest rank-sum of area under the curve (AUC) was selected for model construction. The performances of all models were evaluated in the internal and external test sets. The AUC of radiomics model was larger than that of non-radiomics model with the same machine learning algorithm in the three mask types. The radiomics model using least absolute shrinkage and selection operator-random forest algorithm combination gained the smallest AUC rank-sum among all the algorithm combinations. The AUC of the model with ADC620 was 0.98 in the internal test set and 0.91 in the external test set, and the weighted average AUC in the three sets was 0.96, the largest among three mask types. The Shapley additive explanations values of the maximum of National Institute of Health Stroke Scale score within 7 days from onset (7-d NIHSS_max), stroke-associated pneumonia and admission Glasgow coma scale score ranked top three among the features in AACNLI outcome prediction. In conclusion, the random forest model with mask ADC620 can accurately predict the AACNLI outcome and reveal the risk factors leading to the poor prognosis.

Understanding and interpreting how words are organized in a sentence to convey distinct meanings is a cornerstone of human communication. The neural underpinnings of this ability, known as syntactic comprehension, are far from agreed upon in current neurocognitive models of language comprehension. Traditionally, left frontal regions (e.g. left posterior inferior frontal gyrus) were considered critical, while more recently, left temporal regions (most prominently, left posterior middle temporal gyrus) have been identified as more indispensable to syntactic comprehension. Syntactic processing has been investigated by using different types of non-canonical sentences i.e. those that do not follow prototypical word order and are considered more syntactically complex. However, non-canonical sentences can be complex for different linguistic reasons, and thus, their comprehension might rely on different neural underpinnings. In this cross-sectional study, we explored the neural correlates of syntactic comprehension by investigating the roles of left hemisphere brain regions and white matter pathways in processing sentences with different levels of syntactic complexity. Participants were assessed at a single point in time using structural MRI and behavioural tests. Employing lesion-symptom mapping and indirect structural disconnection mapping in a cohort of 131 left hemisphere stroke survivors, our analysis revealed the following left temporal regions and underlying white matter pathways as crucial for general sentence comprehension: the left mid-posterior superior temporal gyrus, middle temporal gyrus and superior temporal sulcus and the inferior longitudinal fasciculus, the inferior fronto-occipital fasciculus, the middle longitudinal fasciculus, the uncinate fasciculus and the tracts crossing the most posterior part of the corpus callosum. We further found significant involvement of different white matter tracts connecting the left temporal and frontal lobes for different sentence types. Spared connections between the left temporal and frontal regions were critical for the comprehension of non-canonical sentences requiring long-distance retrieval (spared superior longitudinal fasciculus for both subject and object extraction and spared arcuate fasciculus for object extraction) but not for comprehension of non-canonical passive sentences and canonical declarative sentences. Our results challenge traditional language models that emphasize the primary role of the left frontal regions, such as Broca's area, in basic sentence structure comprehension. Our findings suggest a gradient of syntactic complexity, rather than a clear-cut dichotomy between canonical and non-canonical sentence structures. Our findings contribute to a more nuanced understanding of the neural architecture of language comprehension and highlight potential directions for future research.

Neuromuscular disorders affect almost 20 million people worldwide. Advances in molecular diagnosis have provided valuable insights into neuromuscular disorders, allowing for improved standards of care and targeted therapeutic approaches. Despite this progress, access to genomic diagnosis remains scarce and inconsistent in middle-income countries such as Brazil. The lack of public health policies to enable feasible genetic diagnosis and the shortage of neuromuscular disorders specialists are the main reasons in this process. We report our experience in a transcontinental genomic consortium for neuromuscular disorders highlighting how collaborative efforts have helped overcome various obstacles in diagnosing our patients. We describe several challenging cases categorized into three major themes, underlining significant gaps in genetic diagnosis: (i) reverse phenotyping and variant validation, (ii) deep phenotyping and identifying a bespoke molecular approach, and (iii) exploring the use of genomic tests beyond whole exome sequencing. We applied a qualitative case-based approach to exemplify common pitfalls in genomic diagnosis in a middle-income country. Our experience has shown that establishing a virtual transcontinental partnership is viable, offering effective exchange of scientific experiences, providing both guidance for rational decision-making and specialized training on a local level and access to diverse molecular diagnosis strategies and functional analyses. Collaborative efforts such as these have the potential to overcome local obstacles, strengthen scientific capabilities, foster diverse multi-ethnic cohorts, and ultimately provide improved care for patients.

Concussion, or mild traumatic brain injury, is caused by sudden mechanical forces impacting the brain either directly or through inertial loading. This can lead to physical, behavioural and cognitive impairments. Despite concussion being a significant health issue, our understanding of the relationship between initial impact force and the subsequent neurological consequences is not well understood. Previously, we established a model of concussion in zebrafish larvae. Here, we further investigate concussions of varying severities in zebrafish larvae using linear deceleration. Using an acoustic assay to monitor the larval sensorimotor behaviour, we found that different parameters of the resulting escape behaviour are modulated by the impact force of the preceding concussive insult. To investigate the relative contributions of habituation performance and fatigue on the escape response behaviour, we constructed a neurocomputational model. Our findings suggest that a concussive impact initially affects habituation performance at first and, as the impact force increases, fatigue is induced. Fatigue then alters the escape response behaviour in an opposing manner.

In the cerebral cortex, establishing the precise relationship between functional areas and the macroscopic anatomy of gyri and sulci has a paramount importance for the field of neuroimaging and neurosurgical interventions. The anatomical orientation should start with the identification of anatomical landmarks to set the anatomo-functional boundaries. The human central sulcus region stands out as a well-defined structural and functional unit housing the primary motor and sensory cortices and is considered as key region to be identified during brain surgery. While useful anatomical landmarks have been discovered, especially in the axial plane, the identification of this region in the sagittal plane remains sometimes difficult. Using cadaveric whole brains and multi-modal analysis of MRI brain scans, we systematically observed a tuning fork-shaped sulco-gyral configuration centred around the gyral continuum bridging the pre-central gyrus with the middle frontal gyrus. We provide evidence that this 'Fork sign' is a consistent morphological feature visible on the lateral surface of the brain and a reliable radioanatomical landmark for identifying central sulcus region structures on sagittal MRI images, including the motor hand area.

Neural sensitization can cause neuroinflammation, which is a type of inflammation that occurs in both the peripheral nervous system and central nervous system. The purpose of this study was to investigate the effect of dimethyl itaconate (DMI) on the expression of NGFI-A and NGFI-B and inflammatory cytokines in the spinal cord in the formalin test. The rats were divided into five groups: control, formalin, DMI 10 mg/kg + formalin, DMI 20 mg/kg + formalin and diclofenac sodium 10 mg/kg + formalin. We evaluated the impact of DMI on the spinal cords NGFI-A and NGFI-B expressions and inflammatory and anti-inflammatory cytokines [interleukin-1 beta (IL-1β), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10)]. The findings indicate that DMI 10, DMI 20 and diclofenac sodium 10 mg/kg can relieve pain in rats during the formalin test. In addition, these substances were found to reduce the expression of NGFI-A and NGFI-B in the spinal cord. Moreover, DMI 10, DMI 20 and diclofenac sodium 10 mg/kg were observed to increase the expression of IL-10 while decreasing IL-1β, TNF-α and IL-6 in the spinal cord when compared with the formalin group. We have found that administering DMI can alleviate pain in rats during formalin test. Through our research, we have observed that DMI decreases the expression of NGFI-A and NGFI-B in the spinal cord. Furthermore, DMI has been shown to increase the levels of IL-10 while decreasing IL-1β, TNF-α and IL-6 in the spinal cord.

Astrocytes are fundamental in neural functioning and homeostasis in the central nervous system. These cells respond to injuries and pathological conditions through astrogliosis, a reactive process associated with neurodegenerative diseases such as Alzheimer's disease. This process is thought to begin in the early stages of these conditions. Glial fibrillary acidic protein (GFAP), a type III intermediate filament protein predominantly expressed in astrocytes, has emerged as a key biomarker for monitoring this response. During astrogliosis, GFAP is released into biofluids, making it a candidate for non-invasive diagnosis and tracking of neurodegenerative diseases. Growing evidence positions GFAP as a biomarker for Alzheimer's disease with specificity and disease-correlation characteristics comparable to established clinical markers, such as Aβ peptides and phosphorylated tau protein. To improve diagnostic accuracy, particularly in the presence of confounders and comorbidities, incorporating a panel of biomarkers may be advantageous. This review will explore the potential of GFAP within such a panel, examining its role in early diagnosis, disease progression monitoring and its integration into clinical practice for Alzheimer's disease management.

Neural underpinnings of Parkinson's disease psychosis remain unclear to this day with relatively few studies and reviews available. Using a systematic review approach, here, we aimed to qualitatively synthesize evidence from studies investigating Parkinson's psychosis-specific alterations in brain structure, function or chemistry using different neuroimaging modalities. PubMed, Web of Science and Embase databases were searched for functional MRI (task-based and resting state), diffusion tensor imaging, PET and single-photon emission computed tomography studies comparing Parkinson's disease psychosis patients with Parkinson's patients without psychosis. We report findings from 29 studies (514 Parkinson's psychosis patients, mean age ± SD = 67.92 ± 4.37 years; 51.36% males; 853 Parkinson's patients, mean age ± SD = 66.75 ± 4.19 years; 55.81% males). Qualitative synthesis revealed widespread patterns of altered brain function across task-based and resting-state functional MRI studies in Parkinson's psychosis patients compared with Parkinson's patients without psychosis. Similarly, white matter abnormalities were reported in parietal, temporal and occipital regions. Hypo-metabolism and reduced dopamine transporter binding were also reported whole brain and in sub-cortical areas. This suggests extensive alterations affecting regions involved in high-order visual processing and attentional networks.