Elevated blood pressure (BP) in midlife is a well-established risk factor for impaired brain health and cognitive ability in old age. We hypothesized that exposure to elevated BP within the first five decades of life may contribute to this risk through impacts on brain health and/or cognitive ability evident by midlife. Participants (n = 893) were selected from the Dunedin Multidisciplinary Health and Development Study (The Dunedin Study). Exposures were systolic (SBP) and diastolic (DBP) blood pressures measured at ages 7, 11, 18, 26, 32, 38 and 45. Cumulative early-life exposure to blood pressure was also quantified as the area under the curve (AUC). Brain health was assessed at age 45 via imaging measures comprising BrainAGE (difference between chronological age and age predicted from machine-learning models of brain-imaging data), white matter hyperintensity (WMH) burden, and retinal arteriolar calibres (RAC)-a proxy for cerebral small vessel remodelling. Cognitive ability (assessed using IQ) was also measured at age 45, with replication of cognitive findings tested in a larger contemporary cohort, the 1970 British Cohort Study. We found limited evidence for any association between BP in the first four decades of life and brain health or cognitive ability at age 45. Most associations instead emerged for BP from early-midlife onwards. Midlife BP was associated with older BrainAGE (Beta for DBP at age 45 = 0.11 [0.04, 0.19]; P = 0.003) and higher WMH burden (Beta = 0.09 [0.02, 0.17]; P = 0.019). Effect estimates for SBP were similar. For cognitive ability, DBP at ages 38 and 45 showed modest associations with age 45 IQ, which became null after accounting for childhood IQ. These findings were broadly replicated in the 1970 British Cohort Study for age 47 IQ. Only RAC in The Dunedin Study were found to associate with BP from childhood (Beta for age 7 DBP = -0.09 [-0.16, -0.03]; P = 0.006), and the magnitude of these estimates increased during midlife (Beta at age 45 = -0.37 [-0.45, -0.30]; P < 0.001). We found little evidence for any association between BP prior to age 40 and BrainAGE, WMH volume, or cognitive ability in midlife. However, cumulative exposure to elevated BP from childhood was associated with reduced RAC, suggesting a potential link between BP and adverse cerebral small vessel remodelling from childhood.
Photoacoustic tomography as an optical-ultrasound hybrid imaging modality provides rich optical contrast over the extended penetration depth of biological tissues, enabling multiscale multicontrast structural and functional imaging. However, inherent limitations in the state-of-the-art piezoelectric transducer arrays of the photoacoustic tomography, including size-dependent sensitivity, narrow bandwidth, and high material rigidity, compromise the resolution, penetration depth, and functional assessment precision. Here, an arc-shaped fiber ultrasound transducer array with a sheet-like ultrasound focus is demonstrated for photoacoustic computed tomography. At the ultrasound focus, a low detection limit of ~ 5.2 Pa and a dual-frequency response spanning several octaves are achieved. Whole mouse brain imaging with a depth up to ~ 1.2 cm and a spatial resolution of ~ 70 μm in the cerebral cortex region is showcased. The blood oxygen saturation within the entire mouse brain and the brain tumors is visualized, and the assessment precision is improved by leveraging the dual-frequency response of the transducer array. The centimeter-scale imaging depth, fine resolution of the cerebral vessels, and improved precision in the blood oxygenation evaluation make the fiber-array photoacoustic tomography a competitive candidate to the sought-after magnetic resonance imaging and ultrasound localization microscopy for brain functionality study and disease diagnosis.
There are still some gaps in understanding the role of inflammation in focal lesional epilepsy. Surgical specimens often contain activated leukocytes, usually thought to originate from the systemic circulation. However, the cerebrospinal fluid, meninges, and skull form a distinct brain-specific immune hub that also reacts to local signals. This study assessed immune hub activation adjacent to epileptogenic lesions in children with focal lesional epilepsy using 2-[18F]-fluoro-2-deoxy-D-glucose (FDG)-PET. Children with focal lesional epilepsy who underwent brain FDG-PET for presurgical assessment were compared to age- and sex-matched controls who had total-body FDG-PET for other clinical indications. Spherical regions of interest (ROIs) were placed on the skull, with a cubic ROI on the pons used as a reference. In epilepsy patients, skull ROIs were positioned adjacent to the perilesional hypometabolic defect and contralaterally. In non-epilepsy patients, ROIs mirrored those of epilepsy patients. Metabolic activity was measured as maximum and mean standardized uptake values (SUVmax and SUVmean). Corrected SUV (cSUV), normalized to the pons, and asymmetry index (AI), comparing lesional and contralateral ROIs, were calculated. Twenty-nine epilepsy and 29 non-epilepsy patients (16 boys, 55%) were included. The median age at the time of the scan was 9.0 years (interquartile range, IQR: 3.0-14.0). Across all patients, the median cSUVmax and cSUVmean were 0.36 (IQR: 0.27-0.48) and 0.23 (IQR: 0.16-0.32), respectively. In epilepsy patients, cSUVmax and cSUVmean were 0.33 (IQR: 0.26-0.40) and 0.23 (IQR: 0.18-0.31), and in non-epilepsy patients, 0.44 (IQR: 0.29-0.55) and 0.23 (IQR: 0.13-0.33). Neither cSUVmax nor cSUVmean differed by side (W = 800, P: 0.84; W = 682, P: 0.25), confirming comparability. However, in epilepsy patients, both cSUVmax and cSUVmean were higher on the lesional side than on the contralateral side (W = 43 and W = 49, P < 0.001 for both). In non-epilepsy patients, mirrored ROIs showed no significant difference (W = 142, P: 0.17; W = 154, P: 0.27). AI values for SUVmax and SUVmean were higher in epilepsy than in non-epilepsy patients (t = -4.36 and t = -3.58, both P < 0.001), a difference that remained significant after covariate adjustment, demonstrating metabolic asymmetry relative to the epileptogenic lesion. In children with focal lesional epilepsy, we observed increased metabolic activity in the brain-specific immune hub adjacent to the epileptogenic lesion. This local immune activation likely plays a role in the disease mechanism, which may clarify why immune-modulating treatments can be effective and point the way towards new therapeutic approaches.
Theory of mind (ToM), the ability to infer others' beliefs (cognitive ToM) and emotions (affective ToM), is compromised in behavioural variant frontotemporal dementia (bvFTD). However, its diagnostic and prognostic value in other frontotemporal dementia (FTD) variants remains underexplored due to limited understanding of the underlying neural mechanisms. This study investigated whether ToM deficits are shared across the frontotemporal dementia spectrum and explored the functional connectivity alterations underlying these disturbances using resting-state functional magnetic resonance imaging. Sixty-seven FTD patients [14 non-fluent variant primary progressive aphasia (nfvPPA), 17 semantic variant primary progressive aphasia (svPPA), 23 bvFTD, 13 right temporal variant frontotemporal dementia (rtvFTD); 34 women; mean age 66.5 ± 7.7 years] and two control groups (48 age-matched healthy controls; 50 young healthy controls) underwent clinical, neuropsychological and brain magnetic resonance imaging assessments. ToM was evaluated in patients using the Story-Based Empathy Task (SET), which includes the Story-Based Empathy Task affective subtest (SET-EA) and the Story-Based Empathy Task cognitive subtest (SET-IA). Resting-state functional connectivity networks were obtained in young healthy controls using seed-based analysis centred on the left medial prefrontal cortex for affective ToM and the right supramarginal gyrus for cognitive ToM. In addition, four large-scale functional networks were reconstructed to reflect disease-specific vulnerability. Functional brain connectivity within all networks was quantified using graph analysis and connectomics, and between-group comparisons were performed on both global and seed-based regional metrics. All patient groups showed similar impairments in affective and cognitive ToM performance. Network analyses revealed two dissociable but interconnected ToM systems. Global metrics of network topology indicated increased path length and reduced nodal strength in both ToM networks, particularly in bvFTD and nfvPPA patients (P < 0.05). Direct seed-based connectivity analyses confirmed widespread functional connectivity reductions from key nodes (e.g. left inferior frontal gyrus, anterior cingulate cortex) in these groups. In contrast, svPPA and rtvFTD cases exhibited relatively preserved functional connectivity within ToM circuits. Correlation analyses revealed associations between cognitive ToM network metrics and global ToM performance, and between functional connectivity in the salience network and behavioural dysfunction. Affective and cognitive ToM abilities are comparably impaired across FTD variants, suggesting that socio-cognitive impairments may represent a core and early feature across the FTD spectrum. Such deficits are mirrored by patterns of functional disconnection within dedicated large-scale networks, with bvFTD and nfvPPA showing the most pronounced disruptions. This study underscores the diagnostic relevance of socio-cognitive markers and highlights their potential as clinical and biomarker targets in future therapeutic interventions.
This special communications piece responds to previous calls from the field of physical medicine and rehabilitation to incorporate methodological diversity in our work, specifically community-based participatory research (CBPR). Our team reports on our CBPR efforts and use of Human-Centered Design (HCD) within the context of executing a multidisciplinary Department of Defense-funded award on improving access to care for those with traumatic brain injury (TBI). First, we situate the context for our program, "Improving Health Care Access and Engagement for Veterans and Service Members with TBI Morbidity". Second, we review the use of CBPR and HCD methods to interact with project partners, including persons with lived-experience, professional society representatives, clinicians, and policymakers. Third, we conclude with practical recommendations to support CBPR and HCD efforts in this context. Given the complexity of eliciting and understanding community perspectives across lived experiences (eg, patients, clinicians, care partners), the primary contributions of this piece are: (1) the provision of exemplar adaptive HCD activities; and (2) the identification of practices that foster both HCD and CBPR, and (3) strengthen community partnerships and authentic engagement through a tailored approach, specifically with persons with TBI lived experience.
[This corrects the article DOI: 10.1093/braincomms/fcaf315.].
In the present study, using the novel quantitative susceptibility mapping technique, we aimed to systematically investigate brain iron alterations in a large group of sporadic early-stage amyotrophic lateral sclerosis patients and their correlation with clinical disability. In this study, amyotrophic lateral sclerosis patients at King's stage 1 were defined as early-stage amyotrophic lateral sclerosis patients, and 53 newly diagnosed early-stage amyotrophic lateral sclerosis patients and 50 healthy controls were included. Voxel-based whole-brain quantitative susceptibility mapping analysis was used to explore brain iron alterations. Voxel-based morphometry analysis was also performed. Longitudinal follow-up was performed in amyotrophic lateral sclerosis patients, and the follow-up progression rate was calculated. We found that, compared with healthy controls, early-stage amyotrophic lateral sclerosis patients presented significantly increased susceptibility values, mainly in the motor cortex, prefrontal cortex, hippocampus and cerebellar regions, while volumetric alterations were not detected. Moreover, motor and extra-motor cortex susceptibility values were significantly correlated with upper motor neuron scores and follow-up progression rate (r = 0.452-0.504, P < 0.01) in early-stage amyotrophic lateral sclerosis patients. We demonstrated a clear profile of early motor and extra-motor iron depositions and their important roles in early-stage amyotrophic lateral sclerosis patients. We suggest that quantitative susceptibility mapping is likely a promising neuroimaging approach for assessing early upper motor neuron damage and detecting early extra-motor alterations in amyotrophic lateral sclerosis patients.
Quantitative susceptibility mapping is a novel, non-invasive MRI technique that measures tissue magnetic susceptibility, offering insights into brain iron, calcium and myelin distribution. Here, we used quantitative susceptibility mapping to assess whole-brain long-term susceptibility changes in adult rats following endothelin-1-induced mild focal stroke in the right motor cortex over 48 weeks. No significant differences in susceptibility trajectories were found between stroke and sham groups in either hemisphere. However, both groups exhibited shared regional susceptibility changes, likely age-related, reflecting variations in iron, calcium, or white matter myelination over time. These findings provide a new perspective on ageing effects on brain metal accumulation and structural integrity, highlighting the need for further histological validation to clarify underlying mechanisms.
Neonatal brain injuries, such as stroke, cause focal ischaemic lesions that often result in lifelong neurological disabilities, yet effective treatments remain limited. Early-phase therapeutic screening requires models that can reliably reproduce injury severity while minimising confounding variables, including prolonged or variable anaesthesia, surgical stress, and invasive procedures that themselves affect injury progression. Existing models of neonatal focal ischaemia often exhibit high mortality, technical complexity, and substantial variability in lesion location and volume. As a result, there is a critical need for a rapid, ethically refined, and scalable neonatal model that produces consistent cortical injury suitable for screening neuroprotective, biomaterial-based, and regenerative therapies. We established a minimally invasive photothrombotic ischaemia model in postnatal day 10 rats by administering intraperitoneal Rose Bengal (25, 40, or 60 mg/kg) and activating it with a fixed 10-minute exposure to 565-nm light through the intact scalp and skull. This incision-free protocol allowed a total procedure duration of 19 min. We characterized dose-dependent effects on infarct volume and anatomical distribution, cortical atrophy, ventricular enlargement, apoptosis (cleaved caspase-3), astrocytic and microglial reactivity (glial fibrillary acidic protein, GFAP; ionized calcium-binding adapter molecule 1, Iba1), and sensorimotor outcomes (wire hang, cylinder rearing, adhesive tape removal) at 1, 7, and 14 days after injury. Additional analyses assessed the reproducibility of lesion size across litters and explored sex-specific differences. A 25 mg/kg dose induced a reliable and well-localized motor cortex infarct with no mortality. Higher doses of Rose Bengal produced proportionally larger infarcts with greater subcortical involvement and more pronounced secondary atrophy. Across all groups, apoptotic signalling and glial reactivity remained elevated through 14 days, indicating persistent tissue injury. Sensorimotor impairments were robust at all stages, with deficits in forepaw use, endurance, and tactile response correlating with lesion volumes in the 25 mg/kg group. No significant sex differences were observed for any histological or behavioural outcomes. This refined neonatal photothrombotic model provides a reproducible, simple, scalable, and ethically optimized platform for inducing severe focal cortical injury. The model's stable injury territory, short, standardized procedure, and consistent functional readouts fill a major gap in current research tools and provide a practical foundation for early-phase testing of neuroprotective and regenerative interventions.
The perception of hostility in online contexts is closely associated with the occurrence of online aggression. Compared to traditional methods that rely on self-report or behavioral analysis, ERP allows for real-time, objective capture of neural responses to emotional stimuli, making it especially suited to reveal the immediate processing of hostility expectation violations. By creating distinct social contexts, we examined participants' brain responses to violations of hostility expectations in text-based communications, both with and without emojis. The results indicated that in the absence of emojis, violations of hostility expectations triggered a significant negative deflection in the N400 waveform, reflecting a heightened neural response to perceived hostility. In contrast, when emojis were present, this negative neural response was substantially reduced, suggesting that emojis play a key role in mitigating hostile attributions and fostering positive social interactions. These findings not only highlight the important function of emojis in online communication from a neuroscience perspective, demonstrating their ability to effectively reduce hostility attribution and potential conflicts in digital interactions, but also provide new empirical evidence for understanding the emotional regulation mechanisms of nonverbal cues in digital environments and improving the quality of online interactions.
Spatial transcriptomics analysis is a powerful approach for dissecting the structure of tissue microenvironment and uncovering the mechanism of cell-cell communications. However, existing technologies are limited by either spatial resolution or gene coverage. Most single-cell-resolution technologies target only a few hundred preselected genes, whose choice plays an important role in the overall analysis. It remains a challenge to optimally design a gene panel to maximize the utility of spatial transcriptomics profiling. To fill this gap, we introduce a novel method, named ReconST, to automatically design optimal gene panels for spatial transcriptomics profiling. ReconST leverages information from existing scRNA-seq data and identifies the optimal subset of genes by using a gated autoencoder. By using a high-coverage mouse brain MERFISH dataset and a fetal lung dataset as the reference benchmarks, we showed that ReconST outperforms existing methods in terms of reconstruction accuracy, spatial pattern preservation, and computing efficiency. As such, ReconST provides a useful and generally applicable tool for optimal gene panel design, which in turn can significantly enhance the utility of spatial transcriptomics profiling in a wide range of biomedical investigations.
This paper presents an ultra-compact millimetre-wave antenna designed to support 28 GHz and 38 GHz 5G smartphone applications. To ensure safe and reliable integration, a comprehensive specific absorption rate (SAR) evaluation was carried out using three anatomically realistic head phantoms: a full-head, a skeletal skull, and an isolated brain model. The fabricated prototype demonstrated robust dual-band performance with close agreement between simulated and measured results. Importantly, SAR levels remained well below international safety limits, confirming both compliance and user safety. These results highlight the antenna's strong potential for enabling next-generation high-data-rate communications in compact mobile devices.
BACKGROUND Pulmonary arteriovenous malformations (PAVMs) are rare structural vascular abnormalities that create communications between pulmonary arteries and veins, resulting in right-to-left shunts. PAVMs are often asymptomatic; however, patients may exhibit a range of clinical symptoms, including dyspnea, hemoptysis, chest pain, and cyanosis. Common serious complications include cerebrovascular events (eg, paradoxical embolism resulting in stroke or transient ischemic attack) and infectious complications (eg, brain abscess). PAVMs do not always require treatment; management should be guided by factors such as feeding artery size and patient symptoms. When intervention is indicated, percutaneous transcatheter embolization is the primary treatment and demonstrates efficacy in most cases. This report describes a case of recurrent cerebral embolism attributed to an undiagnosed PAVM, which was treated with percutaneous transcatheter embolization. CASE REPORT A 67-year-old man lacking prior medical history or medication use experienced recurrent cerebral embolism within 3 months despite therapeutic anticoagulation. The paradoxical embolism was attributed to a PAVM diagnosed by contrast-enhanced chest computed tomography. Subsequent transcatheter embolization of the PAVM was successfully performed. No recurrence was observed at the 4-year follow-up. CONCLUSIONS In cases of unexplained cerebral embolism, PAVMs should be considered a potential underlying etiology. Hemorrhagic transformation requires careful risk assessment but is not an absolute contraindication to percutaneous transcatheter embolization. Timely diagnosis and embolization are essential to prevent disabling recurrent events.
Astrocytes communicate bidirectionally with neurons by releasing various signaling molecules. This astrocyte-neuron "dialogue" is essential for long-term processes in the nervous system, and its disruption correlates with various neuropathologies, including Alzheimer's disease (AD). Neurogenetic approaches including opto- and chemogenetics allow targeted modulation of astrocyte functioning. Our study investigated how chemogenetic activation of the Gq-coupled pathway in hippocampal astrocytes modulates synaptic plasticity and gene expression in both healthy state and AD pathology. To selectively manipulate astrocytic Gq signaling, we expressed DREADD receptors hM3Dq in hippocampal astrocytes of both wild-type (WT) and transgenic 5xFAD mice, a model of familial Alzheimer's disease, using adeno-associated viruses. In the acute brain slices, we assessed the amplitude of field excitatory postsynaptic potentials (fEPSPs) and expression of immediate early genes following activation of DREADD receptors hM3Dq via application of specific agonist Compound-21 (C21), both under resting conditions and during the induction of long-term potentiation (LTP) via theta-burst stimulation (TBS). High concentrations of C21 (2-10 µM) non-specifically increased fEPSPs amplitude even in slices lacking DREADD expression, indicating significant off-target effects. At a lower concentration (1 µM), C21 did not alter baseline synaptic transmission in mice of both genotypes. In healthy animals, chemogenetic astrocyte stimulation with C21 (1 µM) can robustly enhance activity-dependent plasticity without altering the transcription of immediate early genes. In contrast, in 5xFAD slices, the fEPSPs amplitudes were already potentiated following TBS stimulation. On this background, chemogenetic astrocyte stimulation with C21 (1 µM) elicited no further increase in LTP. Our work highlights a common pitfall in chemogenetic studies by demonstrating that excessive DREADD agonist concentrations (more than 1 µM) produce significant off-target effects. We further show that stimulation of astrocytic Gq signaling with low agonist concentration exerts a facilitation of long-term hippocampal plasticity in slices from healthy animals. However, the efficacy of targeted astrocytic Gq-mediated modulation appears limited in advanced-stage AD. LTP was enhanced and C21 did not facilitate it further, likely due to a significant reorganization of neuroglial communications.
[This corrects the article DOI: 10.1093/braincomms/fcag087.].
Although effects of deafness on the brain have been reported, little is known about the differential impact of genetic versus acquired etiologies. Our purpose was to assess cortical volumetric differences and hemispheric asymmetry in children with gap junction protein beta-2 (GJB2)- and congenital cytomegalovirus (cCMV)-related hearing loss compared with age- and sex-matched controls. In this retrospective study, 3D T1-weighted sequences of children with cCMV-related hearing loss, GJB2-related hearing loss, and normal hearing were analyzed using FreeSurfer volumetric segmentation. Cortical volumes of Heschl gyrus (HG), planum polare (PP), planum temporale (PT), lateral aspect of superior temporal gyrus (LSTG), primary visual cortex, and cuneus were assessed. We performed a linear mixed model analysis to investigate cortical volumetric differences between 1:3 case:control-matched groups, adjusting for age, sex, and field strength. The laterality index was calculated to assess hemispheric asymmetry, and a 2-tailed 1-sample t test was used to compare the distribution of values against zero. Statistical significance was determined at a threshold of P < .05. Twenty-two children with cCMV-related hearing loss, 7 children with GJB2-related hearing loss, and 87 age- and sex-matched children with normal hearing were included. Significant differences were observed between the cortical volumes in the right (P = .03), left (P = .03), and total cuneus (P = .02) between GJB2-related hearing loss and controls; HG (P = .02) and PT (P < .001) on the right; LSTG (P = .002) on the left; and the total HG (P = .02) and PT (P < .001) between cCMV-related hearing loss and controls. HG was significantly larger on the left in GJB2-related SNHL (P = .01), and the HG, PT, and LSTG were significantly larger on the left with a significantly larger right cuneus in both cCMV-related hearing loss and controls (P < .01). GJB2-related hearing loss is associated with volumetric alterations in the visual cortices, and alterations in the auditory cortical regions occur in cCMV-related hearing loss. Particular auditory areas showed significant leftward asymmetry in GJB2- and cCMV-related hearing loss and controls. In contrast, the visual areas showed significant rightward asymmetry in both CMV-related hearing loss and controls.
Music engages brain regions involved in perceptual, socio-emotional and cognitive functions that may be relatively preserved in individuals with Alzheimer's disease but seem affected early in behavioural variant frontotemporal dementia. The effects of music in dementia are often assessed through observational studies, leaving the neurophysiological underpinnings of music processing in these dementia types unclear. Improved understanding of these mechanisms is relevant because the effectiveness of music therapy may depend on dementia types. In this study we investigated whether patients with behavioural variant frontotemporal dementia and Alzheimer's disease differ in music processing compared with healthy controls. We studied 60 participants (n = 35 female; aged 52-81), including 13 patients with behavioural variant frontotemporal dementia, 22 patients Alzheimer's disease, and 25 healthy controls. We designed a novel functional MRI paradigm based on passive listening to self-selected favourite music and experimenter-selected unfamiliar musical pieces using a sparse-sampling design. Activation patterns of favourite music listening (favourite > silence), unfamiliar music listening (unfamiliar > silence), and favourite music more than unfamiliar music (favourite > unfamiliar) were determined for each participant. Next, we compared activation patterns across groups for each contrast. Finally, associations between activation patterns and disease severity were investigated in behavioural variant frontotemporal dementia and Alzheimer's disease separately. The patient groups exhibited typical neuropsychological, socio-emotional and structural anatomical changes associated with Alzheimer's disease and behavioural variant frontotemporal dementia. Patients with behavioural variant frontotemporal dementia showed overall less activation during favourite music listening compared with Alzheimer's disease and healthy controls. When contrasting favourite and unfamiliar music, we found that patients with behavioural variant frontotemporal dementia showed reduced activation in the supplementary motor area, a region that has previously been implicated as an important region for semantic musical memory. Increased connectivity of the auditory cortices was observed in behavioural variant frontotemporal dementia compared with controls, potentially indicating network immaturity. Only patients with Alzheimer's disease exhibited activation in the caudate nucleus during unfamiliar music, a region associated with musical reward processing. Disease severity in Alzheimer's disease and behavioural variant frontotemporal dementia were associated with distinct patterns of functional activation. Our results confirm and expand the observation that music is processed differently in patients with behavioural variant frontotemporal dementia and Alzheimer's disease. The reduced activation in the supplementary motor area may explain altered music processing in behavioural variant frontotemporal dementia. These differences in music processing could have clinical implications in the selection of music therapy.
Spontaneous neural activity shapes brain states, which are associated with various behaviors, yet its organization in the teleost telencephalon is poorly understood. We characterized intrinsic neural activity dynamics in medaka (Oryzias latipes) by recording 32-site local field potentials in the lateral (Dl) and medial (Dm) dorsal telencephalon under anesthesia. We segmented delta-band (1-4 Hz) signals into 3-s episodes and computed pairwise correlation matrices for each episode. We embedded them via principal component analysis and identified brain states from the correlation patterns using k-means. State occupancy was biased rather than uniform, and temporal dynamics were structured; the episode-to-episode distances were shorter than those for shuffled surrogates, and the transitions preferentially recurred within the same state. These results indicate that, even under reduced sensory drive, the medaka telencephalon self-organizes into stable and preferred network configurations with structured propagation, echoing conserved principles of spontaneous activity across vertebrates. Our framework advances understanding of intrinsic brain function in teleosts and provides a platform for future studies in conscious animals.
Alzheimer's disease is defined by the abnormal accumulation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles, the two hallmark proteinopathies detectable via molecular imaging. Aβ deposition typically begins in neocortical regions and is hypothesized to constitute a permissive condition for the subsequent spread of tau. Tau pathology is known to spread systematically through select brain regions, typically described as Braak stages (I-VI), reflecting the spatiotemporal trajectory of tau distribution with disease progression. Evaluating the associations between regional Aβ accumulation and the spatial distribution of tau remains an important question in understanding disease progression. This study examined the associations between regional Aβ and tau burden, measured by positron emission tomography (PET), in 192 participants without dementia (178 cognitively unimpaired, 14 with mild cognitive impairment [MCI],) in the Biomarkers of Cognitive Decline Among Normal Individuals (BIOCARD) cohort (age range: 32-88 years; mean age: 68 years; 58% female), of whom 52 were Aβ positive. Aβ burden was assessed using standardized uptake value ratios (SUVR) obtained from several cortical areas [the medial orbitofrontal cortex (OFC), lateral OFC, precuneus, posterior cingulate, anterior cingulate, parietal, temporal, and superior frontal regions], using 11C-PIB PET. Tau burden was quantified using 18F-MK6240 PET, within regions of interest defined as Braak stages I-VI. Elastic net regression was employed to delineate the association of regional Aβ burden and tau PET accumulation across Braak stages, covarying for age, sex, education, and apolipoprotein E (APOE) ɛ4 carrier status. Aβ burden in the medial OFC showed the strongest association with tau burden in Braak stages I-II. For Braak stage III, tau deposition was most strongly associated with Aβ burden in both the medial OFC and precuneus, while in later Braak stages (IV-V), the precuneus showed the strongest association with tau deposition. These region-specific associations remained robust in sensitivity analyses excluding participants with MCI, underscoring the consistency of these findings. Together, these results show regional differences in Aβ-tau associations, with medial OFC Aβ burden being strongly associated with early tau pathology accumulation, while precuneus Aβ burden is associated with tau in later stages. These findings suggest that localized amyloid burden measures may enhance early detection of clinically significant amyloid changes and show utility in understanding Aβ-tau dynamics.
Brain magnetic resonance imaging (MRI) abnormalities are an important finding in the evaluation of patients with suspected autoimmune encephalitis (AE). There have been few studies evaluating the frequency and prognostic significance of MRI abnormalities, especially hippocampal swelling, in anti-N-methyl-D-aspartate receptor (NMDAR) and anti-leucine-rich glioma-inactivated 1 (LGI1) Ab-mediated encephalitides. We conducted a multi-centre, retrospective study involving adult patients with confirmed antibody-mediated encephalitis and at least one MRI scan from 10 Australian hospitals (n = 139). MRI scans were evaluated by a neuroradiologist blinded to the specific autoimmune encephalitis diagnosis. We evaluated associations between acute MRI abnormalities (e.g. hippocampal swelling) with 12-month function (modified Rankin scale, mRS ≥2 = worse outcome) and radiological findings. In patients with anti-LGI1 Ab-mediated encephalitis, we identified hippocampal swelling on initial MRI to be associated with worse function at 12 months (OR 0.03; 95% CI 0.003, 0.34; P = 0.005). We found initial AE-associated T2/fluid attenuated inversion recovery (FLAIR) hyperintensities were not associated with 12-month mRS in either the anti-NMDAR (OR 0.39; 95% CI 0.04, 3.97; P = 0.42) or anti-LGI1 Ab-mediated encephalitis groups (OR 0.34; 95% CI 0.07, 1.57; P = 0.17). In anti-LGI1 Ab-mediated encephalitis, both hippocampal swelling (OR 5.76; 95% CI 1.14, 29.02; P = 0.03) and T2/FLAIR hyperintensity (OR 6.81; 95% CI 1.28, 36.22; P = 0.03) were related to the development of mesial temporal atrophy and hippocampal sclerosis. Acute hippocampal swelling is associated with worse outcomes in anti-LGI1 Ab-mediated encephalitis and, alongside initial T2/FLAIR hyperintensity, is associated with the development of both mesial temporal atrophy and hippocampal sclerosis.