Brain communications最新文献

Brain ageing involves microstructural changes that vary across tissue types and even within regions of those tissues, leading to functional and cognitive alterations. Quantitative MRI (qMRI) offers sensitivity to tissue properties, enabling the identification of differential ageing patterns and distinguishing physiological ageing from pathological changes. In this study, we analysed qMRI data from 293 healthy adults (median age: 52; interquartile range: 36-66; age range: 18-79 years). We applied a multiparametric qMRI approach, including longitudinal relaxation rate (R ₁), apparent transverse relaxation rate (R ₂*) and Quantitative Susceptibility Mapping, to model normal ageing effects on qMRI metrics across regions using second-order polynomial regression, adjusting for sex, education and cognition. Peak ages in turning points derived from quadratic fits were extracted to capture region-specific age-related differences across cortical grey matter, superficial white matter (sWM) and white matter (WM) bundles. According to the results, R ₁ showed the most robust age modelling, whereas R ₂* and susceptibility presented greater regional variability. Peak ages varied substantially across regions, reflecting the heterogeneity of age-related microstructural differences. Based on quadratic fits, we identified a spatial gradient in qMRI ageing patterns, with earlier peak ages in WM bundles, followed by sWM and culminating in cortical GM. This gradient followed a posterior-to-anterior pattern in the cortex and an inferior-to-superior pattern in WM bundles, consistently observed across all three qMRI metrics. Our study presents exploratory mapping of region- and tissue-specific ageing patterns across brain grey and WM using multiparametric qMRI, offering insights to support future normative healthy ageing research.

Migraine is a leading cause of disability worldwide, and triptans, the most widely used acute treatment, act through vasoconstriction and are contraindicated in patients with vascular disease. Rimegepant, a calcitonin gene-related peptide receptor antagonist, is proposed as a non-vasoconstrictive alternative, but its direct vascular effects during spontaneous migraine attacks have not been examined. This was a prospective, longitudinal study conducted at a single academic imaging centre between 12 January 2024 and 10 June 2025. Eighteen women aged 18-40 years with menstrually related migraine without aura were enrolled. Fifteen participants completed high-resolution 3 T magnetic resonance angiography during a spontaneous migraine attack before, and at 30 and 60 min after, administration of a single 75 mg oral dose of rimegepant. The primary outcome was change in arterial circumference of the cerebral artery and meningeal artery. Circumference was measured in millimetre and compared using paired samples t-tests. No significant vasoconstriction was observed in either artery following rimegepant administration. Cerebral artery circumference remained stable (baseline 8.13 ± 0.93 mm; 30 min 8.02 ± 0.84 mm, P = 0.404; 60 min 8.15 ± 0.90 mm, P = 0.918). Meningeal artery circumference showed no significant change (baseline 4.30 ± 0.83 mm; 30 min 4.47 ± 0.68 mm, P = 0.084; 60 min 4.35 ± 0.78 mm, P = 0.688). Rimegepant did not induce measurable constriction of cerebral or meningeal arteries during spontaneous migraine attacks. These findings support its vascular safety and indicate that effective migraine relief with calcitonin gene-related peptide receptor antagonists does not depend on vasoconstriction, in contrast to triptan therapy.

Our editors discuss the importance of fair and constructive peer review while extending thanks to all those who have contributed their expertise in reviewing manuscripts for Brain Communications.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration, with significant clinical and genetic variability. While the role of genetic factors is well-established in ALS pathogenesis, their impact on survival outcomes remains poorly understood, particularly in the Indian population. We performed whole-exome sequencing in 159 ALS patients from North India (familial = 2, sporadic = 157). Clinical parameters, including age at onset, site of onset, sex, family history and survival, were recorded. Males exhibited shorter survival than females, but did not achieve statistical significance (median: 48 versus 60 years, P = 0.05). Bulbar-onset patients developed ALS at a significantly older age (mean: 59.7 versus 54 years, P = 0.007) and experienced poorer survival outcomes than spinal-onset patients (median: 48 versus 60 months, P = 0.03). A small subset of ALS patients (6.3%, n = 10) had very long survival duration of more than 10 years. We identified 102 genetic variants in 92 ALS patients, of which 45 variants were novel. According to American College of Medical Genetics and Genomics guidelines, 13.5% of total variants were pathogenic, 19.8% were likely pathogenic, and 66.7% were variants of uncertain significance. The presence of genetic variations was significantly associated with delayed onset (mean: 53.4 versus 57.1 years, P = 0.049) and diminished life expectancy (median: 48 versus 60 months, P = 0.029). Variations in more than one gene were detected in 16.7% of the patients, supporting the theory of oligogenic basis for ALS. After adjusting for age at onset, increased risk of mortality was associated with males [hazard ratio = 1.740, 95% confidence interval (CI) = 1.105-2.740] and rare genetic variations (hazard ratio = 1.533, 95% CI = 1.001-2.350). Furthermore, bulbar onset (hazard ratio = 1.75, 95% CI = 1.11-2.75) was found to be a negative prognostic factor for survival. Our study provides valuable insights into the genetic complexity and its impact on clinical outcomes in ALS patients of North Indian origin.

Our Guest Editor, Jon Stone, introduces a special collection of articles focusing on functional neurological disorder.

Diffusion Tensor Image Analysis ALong the Perivascular Space (DTI-ALPS) was originally proposed to quantify glymphatic functioning. Although a direct interpretation is now questioned, cross-sectional studies show associations with disability in people with multiple sclerosis (pwMS). Regardless, serial DTI-ALPS studies are largely lacking in MS. In a longitudinal study, we investigated DTI-ALPS with respect to confirmed disability progression (CDP) and progression independent of relapse activity (PIRA) in people with relapsing-remitting MS (pwRRMS) and progressive MS (pwPMS). This study included 72 pwRRMS, 27 pwPMS, and 23 healthy controls (HC) imaged with 3T MRI and again after 5 years. The DTI-ALPS index was calculated using an automated pipeline using template-defined regions of interest (ROIs) in the superior longitudinal fasciculus and superior corona radiata. Areas corresponding to T2 hyperintensities were removed to avoid the influence of overt pathology. CDP and PIRA were assessed after 5 years and in 64 pwRRMS/17 pwPMS after 10 years. Comparisons between those with and without follow-up CDP or PIRA were assessed using analysis of covariance and repeated including normal appearing white matter (NAWM) mean diffusivity (MD) as an additional covariate. Multivariable binary logistic regression was used to explore whether DTI-ALPS offers independent value beyond general disease burden. Although significantly lower in pwMS compared with HCs (1.347 ± 0.178 versus 1.437 ± 0.132, P = 0.034, partial η ² = 0.021), the difference was no longer so after controlling for NAWM MD (P = 0.094, partial η ² = 0.024). DTI-ALPS decreases over 5 years were similar between HC and pwMS (P = 0.188, partial η ² = 0.021). In pwRRMS, baseline DTI-ALPS was lower in those who developed CDP or PIRA at 5- and 10 years of follow-up (all P ≤ 0.019, partial η ² > 0.080, except for PIRA at 5 years, P = 0.051, partial η ² = 0.055). When controlling for NAWM MD, results were in line with original findings. Baseline T2-LV was the only retained imaging predictor of CDP and PIRA over 5 years while only baseline DTI-ALPS was selected for in 10 year models. No associations were found in the pwPMS group. Changes in DTI-ALPS over 5 years did not relate to CDP nor PIRA in neither group. In conclusion, although DTI-ALPS values were not significantly different compared with HCs after considering NAWM MD, decreased baseline DTI-ALPS is associated with disability progression in pwRRMS. The lack of associations in pwPMS suggests that DTI-ALPS may be less informative with more advanced disease.

Emerging evidence suggests that hallucinations may arise because of an over-reliance on prior knowledge during perception. While best established in psychosis-spectrum illness, data also support the presence of this abnormality in other hallucination-prone neuropsychiatric illnesses that vary in their association with disruption of sensory circuits. In this piece, we ask whether an over-weighting of expectations may be conceived of as a compensatory response to degraded incoming sensory information. We make the case that visual hallucinogenesis across a wide array of neuropsychiatric disorders can be captured within a common Bayesian computational framework, as a compensatory response to sensory signal disruptions at different levels of the visual processing hierarchy. We focus on three specific disorders (Charles Bonnet syndrome, dementia with Lewy Bodies and psychosis) with prominent visual hallucinations and highlight the fact that these disorders describe a spectrum of visual impairment where the overtness and localization of the visual processing disruption is reflected in the characteristics of the emergent visual hallucinations. We examine how discrete sensory disruptions in Charles Bonnet syndrome translate to hallucinations via known circuits, and then how different disruptions in dementia with Lewy Bodies and Schizophrenia may lead to hallucinations with distinct phenomenology, comorbidities and circuit involvement. Finally, we appeal to emerging computational theories to unite these observations under a common conceptual umbrella. Taken together, this work presents a means of understanding how sensory disruptions could interact with other aspects of cognitive and neural architecture to produce hallucinations across neuropsychiatric disease. It is our hope that this framework will help in efforts to identify pathophysiologically distinct patient subgroups and new pharmacological and circuit-based interventions.