Brain communications最新文献

Lewy body diseases, including Parkinson's disease and dementia with Lewy bodies, often involve mild cognitive impairment at diagnosis (mild cognitive impairment with Lewy bodies (MCI-LB). Language dysfunction in MCI-LB patients is often unrecognized. This study aimed to assess syntactic comprehension deficits in MCI-LB patients and to explore their neural correlates. A total of 25 MCI-LB patients (mean ± sd: 72 ± 5.6 years old, 10 women) and 25 healthy controls (HC, mean ± sd: 66 ± 4.0 years old, 12 women) performed task functional MRI Test of Sentence Comprehension (ToSC). Functional connectivity was analysed using psychophysiological interaction (PPI) method, focusing on the striatum and language networks. MCI-LB patients had lower ToSC scores than HC (MCI-LB: 74.7 ± 15.7, HC: 88.5 ± 9.0, P < 0.001) and their PPI analysis revealed decreased connectivity from the striatum to the cuneus, precuneus, and left supramarginal gyrus, and reduced connectivity particularly in the dorsal pathway during noncanonical (syntactically more complex) sentence processing. Taken together, in this cross-sectional study MCI-LB patients showed impaired sentence comprehension related to decreased subcortical-cortical and dorsal language network connectivity. Specific changes in frontotemporal connectivity in MCI-LB might be a promising indicator of language related cognitive impairment in these a-synucleinopathies.

[This corrects the article DOI: 10.1093/braincomms/fcaf323.].

Although the classifications of 'past,' 'present,' and 'future' are considered abstract concepts, we naturally understand them. Those classifications were named 'A-series' time by McTaggart in 1908. Alzheimer's disease (AD) is the most common type of dementia, with initial symptoms generally including temporal disorientation. This study aims to (1) elucidate the impairment process of temporal cognition in AD by administering A-series temporal tasks to individuals with AD, mild cognitive impairment (MCI), and healthy controls, and (2) clarify the relationship between temporal cognition at each stage of impairment and cerebral blood flow (CBF). A diagnosis of AD (n = 37), MCI (n = 10), and no dementia (ND) (n = 10) took part. The 'A-series' task consisted of eleven short sentences that were grammatically correct using seven-time qualifiers (last week, yesterday, today, now, tomorrow, this week, or next week). The participants were required to respond when the events in the sentences happened or would happen in nine stages. We compared the pattern of their responses, the scores of the Japanese version of the Mini-Mental State Examination (MMSE-J), and the regional CBFs performed by ^99mTc-ethyl cysteinate dimer Single Photon Emission Computed Tomography. We found that ND was intact in the ability to distinguish between the past, present, and future, on the other hand, AD and MCI showed a diminished ability in temporal orientation when we sorted the 11 sentences in the ascending order of the mean response scores among the ND participants, they were generally ordered according to the time represented by adverbs of time. We also found that the participants could be best classified into three clusters. All ND participants (10/10) and half of the MCI participants (5/10) belonged to Cluster 1, whereas only 19% of the AD participants belonged to the cluster (7/37). Cluster 2 was contributed by three MCI participants (3/10) and 30% of the AD participants (11/37). Finally, most of the AD participants (51%) belonged to cluster 3 (19/37) with a few MCI participants (2/10). We compared CBFs across the three clusters and found the CBF in the pairs of the left and the right pericallosal region could predict whether a participant belonged to either cluster at the largest hit rate of 75%. Our findings suggest that the bilateral pericallosal region, including the posterior cingulate gyrus and precuneus cortex, is associated with temporal orientation.

The treatment of chronic pain represents a widespread clinical challenge. Current approaches to network-based mapping of the cerebral cortex have the potential to localize chronic pain in the brain. In an effort to further characterize the dynamical brain networks, or the 'dynome' in the setting of chronic pain, we performed a Coordinate-Based Meta-Analysis of resting-state functional Magnetic Resonance Imaging studies on chronic pain to create a multinetwork dynome of chronic pain. A cluster-level analysis generated seven statistically significant activation likelihood estimates (ALEs): one for chronic pain as a whole dynome, three for chronic pain conditions, and three for chronic pain mechanisms. Chronic pain is a complex disease process involving tripartite network dysfunction encompassing the Default Mode Network, Central Executive Network and Salience Network. Chronic visceral pain was distinct from chronic headache and chronic musculoskeletal pain, and chronic pain mechanisms have the potential to share common cortical network rearrangements with their respective chronic pain conditions. Collectively, this work represents the first anatomically specific network-based cortical map of chronic pain, with representation of disease-specific and mechanism-specific disruptions in cortical function.

There is growing evidence of cognitive deficits in spinocerebellar ataxias, with the Cerebellar Cognitive Affective Syndrome Scale (CCAS-S) an increasingly common measure of this dysfunction. There remain ongoing questions as to how Cerebellar Cognitive Affective Syndrome Scale performance relates to day-to-day cognitive function, non-motor and motor features of spinocerebellar ataxias and demographic factors. Via an online study, we evaluated Cerebellar Cognitive Affective Syndrome Scale performance amongst individuals with spinocerebellar ataxia Type 1 (n = 14), Type 2 (n = 16), Type 3 (n = 18), and Type 6 (n = 26) relative to demographically-matched control groups. Furthermore, amongst individuals with spinocerebellar ataxia, we examined associations between performance and (i) age and education, (ii) ataxia motor severity, (iii) psychomotor function measured by computerized finger tapping and reaction time tasks and (iv) self-rated cognition, depression, emotional regulation, psychosocial function and fatigue. Cerebellar Cognitive Affective Syndrome Scale performance was significantly reduced in spinocerebellar ataxia Types 2, 3, and 6 compared to controls, although substantial inter-individual variability in performance was observed in the spinocerebellar ataxia cohort (43.2%/24.3%/21.6%/10.8% met criteria for Definite, Probable, Possible, and No CCAS). Performance in individuals with spinocerebellar ataxias correlated significantly with self-reported ataxia motor severity, fine motor speed, psychomotor trial-by-trial variability, and one of two measures of day-to-day cognitive function. Significant correlations were not observed against age, education, age at disease onset, disease duration, psychomotor reaction time, depression, emotional regulation, psychosocial function, or fatigue. We present evidence that motor function and psychomotor variability are more important correlates of inter-individual variability in cognitive performance amongst people with spinocerebellar ataxia Types 1, 2, 3 and 6, compared to demographic factors, fatigue, or emotional function. Importantly, formalized cognitive testing using the Cerebellar Cognitive Affective Syndrome Scale correlates with self-reported cognitive functioning. This study highlights cognitive dysfunction as a functionally impactful feature of certain spinocerebellar ataxias, and motivates further investigation into the disease- and individual-specific profiles of cognitive impairment in this population.

Genetic deletion of the complement C3a anaphylatoxin chemotactic receptor (C3ar1), a key component of the innate immune response, is reported to induce behavioural phenotypes resembling anxiety and hyperactivity in mice, suggesting a neurodevelopmental role for this gene in health. However, it is not currently clear when and where C3ar1 is needed in the brain, which is further complicated by the fact that C3ar1 is expressed predominantly by microglia and therefore does not localize to specific brain regions, warranting exploratory and brain-wide assessment through neuroimaging. Resolving when and where C3ar1 is needed are questions of significant translational importance because, as a G-protein-coupled receptor, human C3AR1 serves as a potential therapeutic target for disorders associated with complement upregulation, such as schizophrenia. To provide a brain-wide assessment of developmental C3ar1 activity, we used longitudinal MRI in male and female adolescent and adult mice (N = 34 C3ar1^{tm1Cge/tm1Cge} and N = 35 C3ar1^+/+ ) to estimate regional brain volume using tensor based morphometry, white matter microstructure using fractional anisotropy from diffusion-weighted MRI, and functional connectivity from blood oxygen-level dependent MRI, with behavioural assessment in adulthood. We repeated structural MRI measures in this cohort ex vivo to achieve higher resolution. We further repeated in vivo structural assessment preceded by behavioural testing in adulthood in a second cohort of mice (N  = 20 C3ar1^{tm1Cge/tm1Cge} and N  = 19 C3ar1^+/+ ) to improve confidence in our findings. We achieved low regional brain volume variability, allowing us to resolve previously reported sexually dimorphic effects. We were further able to confirm a well-known developmental increase in fractional anisotropy. Despite being able to detect these established effects, we did not find a robust C3ar1-dependent phenotype in any of the measures we tested, including behaviour, which may be attributed to our study being the first behavioural study in C3ar1-deficient mice to include littermate controls. Therefore, our data do not support neurodevelopmental hypotheses for C3ar1, which is encouraging for therapeutic strategies targeting this receptor since interventions are unlikely to disrupt brain development.

The Qinghai-Tibet Plateau is one of the regions with the highest prevalence of cerebral echinococcosis worldwide. Investigating the risk factors for cerebral echinococcosis in Ganzi and developing an effective clinical risk prediction model is crucial for enhancing disease prevention and control in the region. Study participants were selected from the People's Hospital of Ganzi Tibetan Autonomous Prefecture between January 2016 and December 2023. In this subject, 152 cases were diagnosed with cerebral echinococcosis (case group), while 580 cases were diagnosed with non-Echinococcus infection (control group). The chi-square test revealed significant differences in the component ratios for occupation, residential altitude, presence or absence of comorbidities with other sites of echinococcal infections, hypoproteinaemia, and tuberculosis (all P < 0.001). Logistic regression identified five variables-occupation, residential altitude, tuberculosis, hypovitaminosis, and combined infection in other sites-as risk factors for cerebral echinococcosis (P < 0.005). The predictive nomogram assigned the following scores: farmers (0), public officials or students (5.81), and herdsmen (60.624). The scores for the presence or absence of infections in other sites were 100 and 0, respectively. The scores for the presence or absence of hypoproteinaemia were 58.99 and 0, respectively. The scores for the presence or absence of tuberculosis were 54.65 and 0, respectively. The scores for altitudes ≤3000 m and >3000 m were 53.32 and 0, respectively. Internal validation of the nomogram's receiver operating characteristic curve using the Bootstrap method with 500 repeated samples showed the area under the curve was 0.920 (95% confidence intervals: 0.887-0.952). A confusion matrix was constructed using the true infection values, revealing a maximum Youden index of 0.76, sensitivity of 0.763, and specificity of 0.887. Internal validation using the Bootstrap method with 500 repeated samples showed that the calibration curve closely approximated the ideal curve, indicating that the model was well-calibrated. The Hosmer-Lemeshow goodness-of-fit test showed that χ² = 10.234, P > 0.05, further confirming that the model was well-calibrated. The decision curve analysis indicated that the model's best applicability for cerebral echinococcosis infection thresholds lies between 0.02 and 0.99. The nomogram model developed in this study for human brain echinococcosis infection demonstrated strong identification and predictive capabilities. The receiver operating characteristic curves and calibration plots confirmed the model's high accuracy and consistency, further supporting its effectiveness. By identifying high-risk groups and protective factors for cerebral echinococcosis, the model offers a solid scientific foundation for the development of targeted prevention and control strategies.

Neuromyelitis optica spectrum disorder associated with aquaporin-4-antibodies (AQP4-NMOSD) is an autoimmune disease of the CNS with a high risk of visual, motor and sensory disability secondary to optic neuritis (ON) and transverse myelitis (TM) attacks. The degree of recovery is difficult to predict and may be affected by the extent of ensuing neurodegeneration. While neurodegeneration in AQP4-NMOSD is reported in the visual system after ON, its occurrence in patients with TM remains largely unknown. The aim of this study was to use advanced MRI to cross-sectionally examine the sensory and motor pathways in 18 AQP4-NMOSD patients with a history of TM and 20 healthy controls. The results showed that AQP4-NMOSD patients had decreased cross-sectional area (mean 63.62 versus 70.75, P = 0.016) and reduced fractional anisotropy (mean 0.60 versus 0.65, P = 0.014) in the cervical spinal cord, and changes in the sensory, but not motor, cerebral pathway as evidenced by higher isotropic volume fraction in the ventral posterolateral (VPL) nuclei (mean 0.06 versus 0.05, P = 0.03), reduced neurite density in the right superior thalamic radiation and lower T1 relaxation rates in the primary somatosensory cortex (mean 0.72 versus 0.74, P = 0.04) when compared with healthy controls. Neurite density in the VPL nuclei significantly correlated with the Expanded Disability Status Scale (r = -0.469, P < 0.05). In conclusion, AQP4-NMOSD patients who had TM display features of anterograde and trans-synaptic neurodegeneration in the sensory pathway, which correlate with clinical outcomes. Further studies will clarify the temporal dynamics of such changes and their potential utility as clinical trial outcomes.

Multiple sclerosis is a chronic inflammatory disease affecting the central nervous system. While treatment made huge advances, progression remains a challenge. Eomesodermin⁺ Th cells are associated with cytotoxicity, neuroinflammation and disease progression in secondary progressive multiple sclerosis. We performed a prospective longitudinal study over one year to investigate the role of Eomesodermin⁺ T cells in multiple sclerosis progression and neurodegeneration. Patients underwent detailed clinical assessment and immunophenotyping. In a subcohort of patients, cross-sectional magnetic resonance imaging using voxel-based morphometry was performed. Frequencies of Eomesodermin⁺ Th cells could differentiate between patients with secondary and primary progressive multiple sclerosis and correlated with B-cells in secondary progressive multiple sclerosis. Secondary progressive patients experiencing a subjective worsening of disease activity showed higher baseline frequencies of Eomesodermin⁺ Th cells. Higher baseline frequencies of Eomesodermin⁺ Th cells predicted prospective one-year disability progression in a small group of secondary progressive patients. Conclusively, voxel-based morphometry analysis revealed pronounced infratentorial brain atrophy in a sub-cohort of patients with higher Eomesodermin⁺ Th frequencies. In summary, Eomesodermin⁺ Th cells may shape a dysregulated and proinflammatory immune milieu, driving disease progression and neurodegeneration in secondary progressive multiple sclerosis with potential as both biomarker and therapeutic target.