Brain communications最新文献

The glymphatic system may play a central role in cognitive impairment associated with Parkinson's disease, but its relationship with regional cortical atrophy is not fully explored. To explore associations among glymphatic dysfunction, regional cortical degeneration and cognitive impairment in Parkinson's disease participants, we evaluated 51 participants with documented Parkinson's disease (28 men; age, 61.65 ± 8.27 years) and 30 age- and sex-matched normal controls (11 men; age, 59.2 ± 5.90 years) who underwent 3.0-T MRI of the brain, including high-resolution T1-weighted imaging and diffusion-tensor imaging along the perivascular space as a surrogate for glymphatic flow. Cortical grey matter volume was segmented automatically based on three-dimensional T1-weighted sequences. Cognitive function was assessed by Mini-Mental State Examination. The relationship between glymphatic dysfunction, cognitive decline and regional cortical degeneration was explored. The participants with Parkinson's disease revealed lower diffusion-tensor imaging along the perivascular space (1.45 ± 0.17 versus 1.64 ± 0.17, P < 0.0001) as compared with normal controls, indicating disturbed glymphatic flow. Glymphatic dysfunction was associated with cognitive scores (r = 0.54, P = 0.003). Diffusion-tensor imaging along the perivascular space values were positively associated with the volume of specific cortical regions (all P-values <0.05) including the temporal pole, posterior orbital gyrus, orbital part of the inferior frontal gyrus, frontal operculum, central operculum and anterior cingulate gyrus. Mediation analysis within the Parkinson's disease participants indicated that the relationship between glymphatic dysfunction and cognitive scores was partially mediated by the integrity of orbital part of the inferior frontal gyrus and anterior cingulate gyrus. Glymphatic dysfunction is associated with cognitive decline in Parkinson's disease, whereas the distribution of regional cortical degeneration may constitute the link between glymphatic dysfunction and cognitive impairment.

Multiple sclerosis is an inflammatory demyelinating condition of the central nervous system affecting approximately 1 million people in the USA. Although standard structural MRI techniques are now the main imaging modality for multiple sclerosis diagnosis and management, they are yet to provide information regarding the metabolic profile of the disease. Ultra-high field 7T MRI systems have provided gains in signal-to-noise ratio (SNR) and spatial resolution for structural MRI as well as larger chemical shifts leading to improvements in specialized imaging sequences, such as nuclear Overhauser effect (NOE) imaging, that can evaluate macromolecular metabolite composition. In this work, NOE images were acquired on a cohort of multiple sclerosis and healthy control subjects to spatially map differences in their lipid metabolites as a result of NOE effects. NOE image data were acquired on a total of 25 subjects {15 multiple sclerosis subjects [10 females, 5 males (21-70 years)] and 10 healthy controls [5 females, 5 males (23-71 years)]} on a 7T MRI system with a frequency offset range of -5 to 5 ppm. A five-pool Lorentzian line fitting model was utilized to fit and quantitatively compare direct saturation (DS), magnetization transfer (MT), amide proton transfer (APT), amine, and relayed NOE (rNOE) and used as a comparison to conventional T₁ maps. Grey and white matter tissues were segmented using the T₁ maps, while the lesion tissue was segmented manually. Correlations between disease duration and lesion load were performed to investigate any existing relationship to image contrast. The primary findings of this work include statistically significant decreases in the rNOE pool for the normal-appearing white matter (NAWM) (11.4% decrease) and normal-appearing grey matter (NAGM) (10.6% decrease) in multiple sclerosis subjects compared to healthy controls. Additionally, a significant decrease in the amine pool was also observed for NAWM (15.3% decrease) in multiple sclerosis subjects compared to healthy controls. Changes in multiple sclerosis lesion contrast were also observed for several pools (DS, amine, and rNOE). Decreases in both the rNOE and amine pools suggest that in multiple sclerosis, there are diffuse decreases in mobile lipids, such as those found in neuronal cell bodies, as well as a decrease in proteins with amine groups. Furthermore, these measurable contrast changes were not detected in the corresponding T₁ maps. NOE imaging can provide complementary metabolic information to conventional MRI methods. Future studies will focus on utilizing this technique for longitudinal tracking of disease progression and investigating similar demyelinating diseases.

This scientific commentary refers to 'Retinal microstructure and microvasculature in association with brain amyloid burden', by Egle et al. (https://doi.org/10.1093/braincomms/fcaf013).

Transcranial direct current stimulation shows promise as a non-invasive therapeutic method for patients with focal drug-resistant epilepsy. However, there is considerable variability in individual responses to transcranial direct current stimulation, and the factors influencing treatment effectiveness in targeted regions are not well understood. We aimed to assess how the extent and depth of the epileptogenic zone and associated networks impact patient responses to transcranial direct current stimulation therapy. We conducted a retrospective analysis of stereoelectroencephalography data from 23 patients participating in a personalized multichannel transcranial direct current stimulation protocol. We evaluated the extent and depth of the epileptogenic zone network, propagation zone network, and the combined network of the entire epileptogenic and propagation zones, correlating these factors with clinical response measured by the reduction in seizure frequency following repeated transcranial direct current stimulation sessions. Among the patients, 10 (43.5%) were classified as responders (R), experiencing a significant (>50%) decrease in seizure frequency, while 13 were non-responders, showing minimal improvement or increased seizure frequency. Importantly, we found a significant positive correlation between the extent of the epileptogenic zone network and changes in seizure frequency. A smaller epileptogenic zone network extent was associated with better transcranial direct current stimulation efficacy, with responders demonstrating a significantly smaller epileptogenic and propagation zones compared with non-responders. Additionally, non-responders tended to have a significantly deeper epileptogenic zone network compared with responders. Our results highlight the significant impact of the extent and depth of the epileptogenic zone network on transcranial direct current stimulation efficacy in patients with refractory focal epilepsy. Responders typically exhibited a smaller and shallower epileptogenic zone network compared with non-responders. These findings suggest that utilizing individualized epileptogenic zone network characteristics could help refine patient selection for personalized transcranial direct current stimulation protocols, potentially improving therapeutic outcomes.

Cortical amyloid burden is associated with neuronal and vascular abnormalities. The retina shares significant structural and physiological similarities with the brain. This study assessed the association of retinal microstructural and microvascular signs with cortical amyloid burden in the prospective Atherosclerosis Risk in Communities-Positron Emission Tomography study. One hundred and twenty-four participants without a diagnosis of dementia underwent florbetapir PET (2011-13) and optical coherence tomography and optical coherence tomography angiography imaging (2017-19). Retinal nerve fibre thickness, total macular thickness and the ganglion cell-inner plexiform layer thickness were derived from the optical coherence tomography scan. Vessel density and the foveal avascular zone were measured on the 3 × 3 mm² optical coherence tomography angiography scan. Amyloid burden, defined by global cortical standardized uptake value ratio, was treated as a dichotomous (standardized uptake value ratio > 1.2) and continuous outcome measure in logistic and robust linear regression models, respectively. Only lower intermediate capillary plexus vessel density [β (95% confidence interval) = -0.05 (-0.12, -0.01)] was significantly associated with increased continuous amyloid standardized uptake value ratio but not elevated dichotomous amyloid burden independently of demographic, genetic and vascular risk factors. No other retinal measure showed a significant association. Microvascular signs may accompany greater amyloid burden in late life in individuals without dementia.

Soluble urokinase plasminogen activator receptor (suPAR) has garnered attention as a potential blood-based biomarker for low-grade chronic inflammation. However, its specific association with migraine, including its subtypes, remains to be elucidated. We sought to examine the association of plasma suPAR levels with migraine and its subtypes. In this single-centre, cross-sectional study, plasma was collected at a single time point in adults with migraine and sex-matched healthy controls from October 2020 to June 2022. The quantification of plasma suPAR levels was performed in a blinded fashion using a validated enzyme-linked immunosorbent assay. Plasma suPAR levels were compared between participants with migraine (including subgroups) and healthy controls. Plasma samples were analysed from 634 eligible participants with migraine [mean (SD) age, 44.0 (12.2) years; 568 (89.6%) females] and 154 healthy controls [mean (SD), 41.3 (11.8%) years; 132 (86%) females]. Plasma suPAR levels were 6.7% higher (95% CI: 0.1-13.6%; P = 0.045, adjusted for age, sex, body mass index and smoking) in participants with migraine with aura, when compared with healthy controls. Further analysis revealed no difference in plasma suPAR levels between the overall migraine group and healthy controls (3.7%; 95% CI: -0.7-8.2%; P = 0.097), as well as between participants with migraine without aura and healthy controls (2.5%; 95% CI: -2.9-8.3%; P = 0.81). Similarly, plasma suPAR levels did not differ across participants with episodic migraine, chronic migraine and healthy controls. Finally, we found no difference when comparing participants with migraine at time of blood sampling with participants with non-migraine headache (1.0%; 95% CI: -5.7-8.2; P > 0.99), participants without headache (1.2%; 95% CI: -4.2-7.0%; P > 0.99) or healthy controls (4.5%; 95% CI: -1.9-11.3%; P = 0.39). Elevated plasma suPAR levels in migraine with aura indicate the presence of low-grade chronic inflammation. Future research should explore the role of suPAR in the neurobiologic underpinnings of migraine with aura.

The amnestic mild cognitive impairment progression to probable Alzheimer's disease is a continuous phenomenon. Here we conduct a cohort study and apply machine learning to generate a model of predicting episodic memory development for individual amnestic mild cognitive impairment patient that incorporates whole-brain functional connectivity. Fifty amnestic mild cognitive impairment patients completed baseline and 3-year follow-up visits including episodic memory assessments (e.g. Rey Auditory Verbal Learning Test Delayed Recall) and resting-state functional MRI scanning. Using a multivariate analytical method known as relevance vector regression, we found that the baseline whole-brain functional connectivity features failed to predict the baseline Rey Auditory Verbal Learning Test Delayed Recall scores (r = 0.17, P = 0.082). Nonetheless, the baseline whole-brain functional connectivity pattern could predict the longitudinal Rey Auditory Verbal Learning Test Delayed Recall score with statistically significant accuracy (r = 0.50, P < 0.001). The connectivity that contributed most to the prediction (i.e. the top 1% connectivity) included within-default mode connections, within-limbic connections and the connections between default mode and limbic systems. More importantly, these connections with the highest absolute contribution weight mainly displayed long anatomical distances (i.e. Euclidean distance >75 mm). These 'neural fingerprints' may be appropriate biomarkers for amnestic mild cognitive impairment patients to optimize individual patient management and longitudinal evaluation in a timely fashion.

This cross-sectional study examined associations between multiple fluid biomarkers of neuronal and glial dysfunction (plasma neurofilament light chain, CSF growth-associated protein 43 and CSF soluble triggering receptor expressed on myeloid cells 2), total white matter hyperintensity volume and episodic memory and executive function performance in the context of Alzheimer's disease biomarker status. A total of 563 participants (mean age = 71.9 years, standard deviation = 7.2) from the Alzheimer's Disease Neuroimaging Initiative were classified by the amyloid-β/tau/neurodegeneration framework into no Alzheimer's disease pathology (n = 176), suspected non-Alzheimer's disease pathophysiology (n = 87) or Alzheimer's disease continuum (n = 300) groups. Participants completed baseline neuropsychological assessment, plasma/CSF biomarker collection and MRI. Analyses explored the relative contributions of biomarkers to episodic memory and executive function performance and whether relationships varied by amyloid-β/tau/neurodegeneration group status. Across all participants, neurofilament light chain ( $\hat{\beta }$ = -0.14, P < 0.001) and growth-associated protein 43 ( $\hat{\beta }$ = -0.13, P < 0.001) were the strongest biomarkers associated with episodic memory performance, such that greater levels were associated with worse episodic memory. There was a group by growth-associated protein 43 interaction with episodic memory: greater growth-associated protein 43 was associated with lower episodic memory performance in participants classified as Alzheimer's disease continuum relative to the no Alzheimer's disease pathology group ( $\hat{\beta }$ = -0.26, P < 0.001). No robust associations between biomarkers and executive function performance or between soluble triggering receptor expressed on myeloid cells 2, white matter hyperintensity volume and cognition were observed. Biomarkers of neuro-axonal injury and synaptic dysfunction may independently contribute to episodic memory performance across participants with differing amyloid-β/tau/neurodegeneration profiles. Growth-associated protein 43 may predict worse episodic memory performance in participants with greater Alzheimer's disease pathology. These biomarkers of neuronal dysfunction may serve as domain-specific cognitive correlates in the context of Alzheimer's disease biomarker status.