Brain communications最新文献

Alcohol use disorder (AUD) is a complex condition including affective, cognitive and motivational dimensions. Although AUD is known to induce diffuse brain damage, including grey matter shrinkage and ventricular enlargement, the microstructural changes it induces in white matter remain incompletely understood. This study leverages multi-shell diffusion MRI and multi-fixel models to (i) undertake whole-brain and tract-specific analyses to investigate the microstructure of white matter (WM) tracts affected by AUD, (ii) evaluate whether these differences persist in early abstinence, and (iii) correlate these results with clinical measures evaluated by validated psychological questionnaires. We recruited a final cohort of 37 AUD patients, admitted for alcohol withdrawal and selected for their ongoing alcohol consumption at the time of admission, and a demographically matched control group of 19 healthy subjects. Both groups underwent MRI scans at baseline and 18 days later, with assessments of depression, obsession-compulsion, and anxiety conducted in both sessions for the AUD patients and once for the control group. The imaging results confirmed the presence in AUD participants of clusters microstructural alterations in the fornix, corpus callosum, cingulum, uncinate fasciculus and anterior thalamic radiations. These white matter tracts presented global and localized microstructural changes in axial diffusivity and fractional anisotropy, which are linked to axonal damage and inflammation. There was no significant improvement in the diffusion metrics after almost three weeks of abstinence, although clinical measures did improve significantly. Depression scores were significantly elevated in the patients at admission and decreased with time. Depression scores before withdrawal showed correlations with microstructural metrics across the right anterior thalamic radiations, the isthmus of the corpus callosum, and the right uncinate fasciculus. Lower fractional anisotropy and higher radial diffusivity were predictive of higher depression scores. Overall, these findings highlight the long-term vulnerability of WM tracts affected by AUD and the link between tract microstructure, brain function and behaviour.

The relationship between functional language lateralization and diffusion MRI-based white matter metrics remains a subject of considerable interest and complexity. This systematic review aims to synthesize existing diffusion MRI studies examining white matter correlates of functional language dominance. Twenty-five studies were identified through searches of Web of Science, Scopus and Ovid MEDLINE (search period: inception to 16th May 2023), involving adults with epilepsy, tumours or healthy controls. The results suggest that while the arcuate fasciculus and corpus callosum are commonly associated with language lateralization in clinical populations, the findings in healthy individuals are more variable, often influenced by factors such as handedness. Other white matter tracts, such as uncinate fasciculus, showed less consistent associations with language dominance across studies. Interestingly, temporal lobe regions, especially those involved in semantic processing, exhibited stronger correlations with diffusion measures compared to frontal areas associated with phonological tasks. Methodological inconsistencies, such as variability in sample selection, task design and analytical techniques, were identified as significant challenges in comparing findings across studies. Future research should aim for larger, more diverse sample sizes, whole-brain approaches and a wider range of functional MRI tasks to better elucidate the role of white matter in language lateralization. If regions of interest-based studies are utilized, a more standardized approach to tract segmentation should be adopted to ensure consistency and improve comparability across studies.

There is a pressing unmet clinical and health economic need for effective drugs to treat cognitive impairment that occurs in neurodegenerative diseases. JAK4D is a first-in-class thyrotropin releasing hormone (TRH) analogue that overcomes the pharmacological limitations of thyrotropin releasing hormone and enables delivery of the long-recognized multifactorial neurotherapeutic actions of thyrotropin releasing hormone without inducing endocrine side effects. JAK4D is demonstrated to be neuroprotective and significantly reduce excitotoxic-induced hippocampal-dependent memory deficits in rat. In the present study, we used the scopolamine challenge test coupled with the novel object recognition test to evaluate the effect of JAK4D on scopolamine-induced recognition memory deficits in the male, Lister-Hooded rat. Scopolamine administration has been shown by others to mimic cholinergic and brain network disruption in neurodegenerative diseases. Although the scopolamine challenge test does not fully replicate the pathophysiology of neurodegenerative disease, such as Alzheimer's disease, it is a well-recognized acute pharmacological model for assessing the ability of pharmacological interventions to counteract memory deficits relevant to neurodegenerative diseases. In this model of cholinergic dysfunction, we also assessed the effects of thyrotropin releasing hormone, taltirelin (a degradation-stabilized thyrotropin releasing hormone analogue) and the acetylcholinesterase inhibitor, donepezil, as a positive reference compound. The discrimination (d2) index was used as the primary measure to assess the effect of treatment on scopolamine-induced performance deficit in the novel object recognition test. d2 is a standard well-recognized measure of discrimination between a novel and familiar object in the novel object recognition test, which advantageously takes into account individual differences in exploration levels. Across all investigations, JAK4D (1 mg/kg i.p.) significantly reversed scopolamine-induced recognition memory impairment (P = 0.0274, P = 0.0002, P < 0.0001). The degree of reversal of scopolamine-induced memory deficits by JAK4D (1 mg/kg i.p.) was indistinguishable from that observed for donepezil (0.1 mg/kg p.o.) (P = 0.026). Subcutaneously administered JAK4D (0.3-10.0 mg/kg) also significantly reversed this deficit (P = 0.0432-0.0021). Furthermore, similar pro-cognitive effects were exerted by thyrotropin releasing hormone (5 mg/kg i.p., P = 0.0055) and taltirelin (10 mg/kg p.o., P = 0.0002). Together, these results underscore the relevance of the central thyrotropin releasing hormone signalling system for the treatment of memory impairment. Data from the current study provide further evidence in support of the potential of JAK4D as a novel therapeutic for cognitive deficits in neurodegenerative diseases.

Imagining a movement without executing it has measurable effects on physical performance, learning, and rehabilitation. However, these effects rely on our ability to imagine performing actions, a complex, covert skill that is difficult to quantify. While movement imagery ability can be assessed by behavioural methods or measuring its neural correlates, the relationship between these measures is uncertain. This Registered Report will determine the association between three key behavioural processes during movement imagery - generation, maintenance and manipulation - and well-established neurophysiological measures of corticospinal excitability and intracortical inhibition during imagery, obtained via Transcranial Magnetic Stimulation. A behavioural battery including a questionnaire, a 'mental chronometry' task, and a hand rotation task will be collected alongside the amplitude of Motor Evoked Potentials and the change in Short Interval Cortical Inhibition during imagery. Bayesian correlations will assess the association between these measures to provide a comprehensive evaluation of the neuro-behavioural correlates of movement imagery.

Alzheimer's disease (AD) is a significant global health issue, impacting 50 million individuals with dementia worldwide, a number projected to triple by 2050. Although research has been conducted for decades, there is no effective prevention, treatment, or early diagnostic method for AD. Research on AD in Latin America (LatAm) faces unique challenges compared to developed countries due to socioeconomic, cultural, and infrastructural factors. While the prevalence of dementia is rapidly increasing in LatAm due to demographic shifts, the region is underrepresented in research, diagnostics and care. The informed consent process, a critical aspect of research, becomes particularly complex with individuals who have cognitive impairments. It requires a balance between protecting vulnerable individuals and advancing research for their benefit. By developing and implementing best practices, ethical research can be conducted with this population, ensuring they receive appropriate care. This review provides an update on informed consent for AD research in Chile.

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.