Modern neuroimaging advances in methodology and data modelling allow for brain tissue structure and function to be imaged in increasing detail and specificity. These advances have promise when applied to polycystic ovary syndrome (PCOS), a common multisystem condition associated with psycho-cognitive symptomatology and an increased risk of cerebrovascular disease. This hot-topic review will outline three biological themes that encompass PCOS neurobiology and symptomatology and may benefit from the application of advanced neuroimaging techniques: i) the endocrine system and biorhythms, ii) the cerebrovascular system, and iii) neural structure and function. How modern neuroimaging advances can provide new insights to these areas will be discussed. While knowledge of brain health in PCOS is still an emerging field, advanced neuroimaging offers valuable opportunities to investigate the origins and enduring consequences of PCOS.

The ovarian hormones, oestrogen and progesterone, have vaso- and neuroprotective effects, potentially due to cerebrovascular interactions. This study investigates their neuroendocrine influence on cerebral and retinal baseline vascular metrics across a healthy menstrual cycle. Twenty-six menstruating females completed imaging sessions and assessment of circulating hormone levels during their early follicular, late follicular and mid-luteal phase. Perfusion, arterial arrival time (AAT), global oxygen extraction fraction (OEF), cerebrovascular metabolic rate of oxygen (CMRO2), carotid artery radius and carotid pulsatility index (PI) were measured using 3 T MRI. Retinal vessel density and blood flow resistance were assessed with optical coherence tomography angiography (OCT-A). Assessed with linear models, increased oestradiol was related to increased global perfusion (χ2 (1) = 91.623; p = 1.049 × 10-21) and decreased AAT (χ2 (1) = 106.950; p = 4.575 × 10-25). An independent progesterone increase was also associated with increased global perfusion (χ2 (1) = 19.512; p = 9.998 × 10-6) and decreased AAT (χ2 (1) = 40.062; p = 2.46 × 10-10). A relationship was also found between increased oestradiol and decreased retinal blood flow resistance (χ2 (1) = 5.28; p = 0.0215), primarily driven by centrally localised vessels. This study finds that circulating oestrogen increases blood flow in the eye and brain, while progesterone is associated with brain perfusion increases alone. Both are associated with decreased cortical blood arrival speed. These effects suggest a potential pathway for neuroprotective mechanisms.

The practice of combining neuroimaging data with concurrent physiological data is crucial for interpreting neuroimaging results, yet it is often overlooked. The barriers to collecting and using physiological data often stem from the cost and complexity of the extra equipment needed and, more importantly, from the lack of expertise and knowledge required to collect, assess, analyze, and integrate such data. Consequently, the use of physiological data is still uncommon outside of a few specialized groups or centers. To improve the uptake of concurrent physiological and neuroimaging data collection practice, as well as the quality and consistency of physiological recordings collected within neuroimaging settings, the Physiopy community is compiling and maintaining a live, open-access, collaborative set of community practices describing physiological data acquisition, its processing, and its usage in neuroimaging. We present here the methods used to compile this resource, as well as its aims and its future development.

Previous GWAS of brain’s connectivity have been challenged by the difficulty of best representing the complexity of this phenotype. Here we report the results from a multivariate GWAS approach that allows for a better representation of this complexity, while boosting statistical power. This strategy notably increases the detection of significant signals to 114 independent SNPs, pointing at 315 candidate genes. Our results show a large overlap of the genetic makeup associated with functional connectivity across brain networks but also identify network specific signals, suggesting a potential genetic stratification between cognitive and sensory-motor networks. We also identify a large genetic overlap between functional connectivity and risk for neuropsychiatric disorders, suggesting that regions of the genome important for neuronal communication are enriched for neuropsychiatric risk SNPs. The work presented here expands our understanding of the common allele architecture of brain connectivity, as well as provides novel targets to functional genomics research. This study identified 114 independent SNPs (315 candidate genes) associated with brain’s functional connectivity, showing a large genetic commonality affecting connectivity across different brain networks and with several neuropsychiatric conditions.

Freshwater plants, or macrophytes, make up only 1-2% of all plant species on Earth but play a crucial role in aquatic ecosystems. They are key to primary production, provide habitat and food for various organisms, and influence water quality. Despite their importance, freshwater plants face significant threats from global changes, which necessitates research at broader scales. Historically, freshwater plants have been less studied than terrestrial plants, partly due to a lack of global data and a focus on local scales by ecologists. Unlike terrestrial plants, freshwater plants do not always follow the same ecological patterns. In this text, we summarise current knowledge on three well-known macroecological patterns and how they differ between freshwater and terrestrial plants: latitude-species richness gradient, Rapoport’s rule and species replacement vs. species richness differences of beta diversity. For example, terrestrial plants follow the latitudinal diversity gradient hypothesis, whereas species richness peaks in the sub-tropics for freshwater plants. Although findings on Rapoport’s rule are less clear, research on terrestrial plants in North America shows that turnover (i.e., species replacing each other) is more significant in areas with high species richness and environmental stability, whereas nestedness (i.e., species composition at one site is a subset of a richer site) is more common in species-poor areas with high environmental variability. For freshwater plants, beta diversity patterns vary with latitude, but species replacement generally dominates over nestedness. Overall, freshwater plants exhibit unique macroecological patterns that differ from terrestrial plants, highlighting the need for more extensive research to understand their biodiversity and ecological roles. This can be achieved with more harmonized data sets and equal research efforts in both realms. Better knowledge of macroecological patterns and their drivers for freshwater plants is crucial for conservation efforts and policy-making aimed at preserving plant species diversity and sustaining ecosystem services in freshwater environments.

Background Cystic fibrosis (CF) is a progressive inherited disorder that primarily affects the lungs. With recent breakthroughs in effective treatments for CF that increase life-expectancy, a higher prevalence of age-related comorbidities has been reported including cardiovascular disease, stroke and cognitive decline. Despite the known relationship between cardiovascular health and cerebrovascular function, very little is known about brain blood flow and oxygen metabolism in people with CF (PwCF). Methods In 14 PwCF and 56 healthy age / sex matched controls, we used pseudo-continuous arterial spin labelling (pCASL) to quantify cerebral perfusion in grey-matter and T2-Relaxation-Under-Spin-Tagging (TRUST) to estimate global oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen consumption (CMRO2). Results Compared to healthy controls, PwCF showed elevated CMRO2 (p =0.015). There were no significant between-group differences in grey-matter CBF (p =0.342), or whole brain OEF (p =0.091). However, regional analysis showed certain areas with higher CBF in PwCF (p < .05, FDR). Conclusions Our results show increased CMRO2 and regional CBF in PwCF, which could be explained by potential differences in PaO2/PaCO2 and/or endothelial cell function. Our findings highlight the need for further investment in brain research in PwCF to reduce the risk of early cerebrovascular breakdown that leads to premature cognitive decline.

Velocity-selective arterial spin labelling (VSASL) MRI is insensitive to prolonged arterial transit time. This is an advantage over other arterial spin labelling schemes, where long arterial transit times can lead to bias. Therefore, VSASL can be used with greater confidence to study perfusion in the presence of long arterial transit times, such as in the ageing brain, in vascular pathologies, and cancer, or where arterial transit time changes, such as during measurement of cerebrovascular reactivity (CVR). However, when calculating perfusion (cerebral blood flow, CBF, in the brain) from VSASL signal, it is assumed that a vascular crushing module, defining the duration of the bolus, is applied before the arrival of the trailing edge. The early arrival of the trailing edge of the labelled bolus of blood will cause an underestimation of perfusion. Here, we measure bolus duration in adult, healthy human brains, both at rest and during elevated CBF during CO2 breathing (5% inspired CO2). Grey matter bolus duration was of 2.20 ± 0.35 s/2.22 ± 0.53 s/2.05 ± 0.34 s (2/3/4 cm/s vcutoff) at rest, in close agreement with a prior investigation. However, we observed a significant decrease in bolus duration during hypercapnia, and a matched reduction in CVR above a labelling delay of approximately 1.2 s. The reduction in CVR and bolus duration was spatially heterogenous, with shorter hypercapnic bolus durations observed in the frontal lobe (1.31 ± 0.54 s) and temporal lobes (1.36 ± 0.24 s), compared to the occipital lobe (1.50 ± 0.26 s). We place these results in the context of recommendations from a recent consensus paper, which recommends imaging 1.4 s after the label, which could lead to CBF underestimation in conditions with fast flow or during CVR measurements. These results can be used to inform the experimental design of future VSASL studies, to avoid underestimating perfusion by imaging after the arrival of the trailing edge of the labelled bolus.

The aim of this chapter is to describe issues related to the choice of an optimal design for fMRI experiments. More specifically, it describes how the psychological process of interest is isolated and contrasted using fMRI, and how principal fMRI designs divide into block, event-related, and participant-response dependent designs. The topic of data analysis, with particular emphasis on optimizing and isolating the signal in activated brain regions, is illustrated. Finally, a number of practical matters related to study design are addressed, including optimal sample sizes and trial durations.

Alterations to brain macrostructure, assessed via T1-weighted magnetic resonance imaging are observed in preclinical models of Alzheimer’s disease (AD), reflecting susceptibility, prodromal stages of AD or correlates of early AD pathophysiology. While changes in cingulate and medial temporal lobe structures may be functionally implicated in cognitive decline, little is known about the viability of brain-based biomarkers that support autonomic functions implicated in preclinical AD risk such as the brainstem. In a series of multiple linear regressions, we assess the volume of the brainstem in two asymptomatic at-AD-risk samples, assessed via the presence of either mild cognitive impairment (MCI, N = 148), or extremely high polygenic risk (N = 13) with matched demographics (mean age = 67 [range 58–76], in both cases). We further determine the strength of the association, compared to 150 other structural MRI features. We observed brainstem volume reductions (MCI: b = -0.29, P = 0.018; Genetic risk: b = -1.29, P = 0.002) in both samples. The magnitude of each preclinical AD marker (MCI / AD-polygenic risk)– brainstem association was empirically larger (Z > 2.3, P < 0.05, in both cases) than 150 frequently segmented MRI features. We further replicate the negative AD-polygenic risk score– brainstem association in UK Biobank (N = 31968; b = -0.002, P = 0.03), with weaker evidence that the association was larger than all other MRI features (Z = 1.622; P = 0.052). These observations suggest that AD risk, assessed via the presence of MCI or extremely high AD-polygenic risk score is linked to reduced brainstem volume before most typically observed morphological brain alterations. This conforms with evidence implicating the brainstem as one of the earliest sites of morphological neurodegeneration and provides a plausible biological mechanism linking prodromal autonomic symptoms to AD risk in later life. These observations warrant future investigation into the molecular correlates of AD-linked brainstem dysfunction, assessment as a candidate biomarker, and the exploration of brainstem mediated treatment strategies in AD prevention.

Human cerebrovasculature is finely tuned to enable local changes in blood flow to meet the brain's demands, whilst protecting the brain from systemic changes in blood pressure, both acutely during a heartbeat and chronically over time. This review summarises cerebrovascular structure and function, their role in disease and neurodegeneration and the part MRI measurements can play in probing them. MRI methods to measure various aspects of cerebrovascular physiology are described and placed in context of applications studying cerebrovascular health. The role of the cardiovascular system linking the cardiac pulse wave to cerebrovascular disease and gaps in mechanistic knowledge are highlighted.

OBJECTIVE:Despite an increased cerebrovascular disease risk, the impact of Polycystic Ovary Syndrome (PCOS) on cerebrovascular haemodynamics and function is unknown. This study characterised cerebrovascular haemodynamics and function in women with PCOS versus healthy controls. DESIGN:Case-control study. PATIENTS:Fifteen women with PCOS (age: 31 ± 6 years; body mass index (BMI): 31.8 ± 5.7 kg/m2) and 16 controls (age: 30 ± 7 years; BMI: 29.9 ± 5.5 kg/m2). MEASUREMENTS:Resting global cerebral blood (CBF) was assessed by 3T MRI. Middle- and posterior cerebral artery blood velocities (MCAv, PCAv) were measured by Doppler ultrasound and pulsatility index (MCAPI, PCAPI) calculated. Neurovascular coupling (NVC), internal carotid artery cerebrovascular reactivity (CVRCO2) and dynamic cerebral autoregulation (dCA) directional sensitivity were assessed using a visual stimulus, 6% fixed-inspired CO2 and repeated squat-stand manoeuvres, respectively. RESULTS:Resting CBF (PCOS: 57.2 ± 7.5 ml/100 g/min; controls: 61.6 ± 11.6 ml/100 g/min, p = 0.25) and MCAv, PCAv, MCAPI and PCAPI (all p > 0.05) were similar between groups. NVC (14 ± 4.9% vs. 13 ± 3.4%, p = 0.45), CVRCO2 (5.1 ± 1.9% vs. 6.5 ± 2.9%, p = 0.20) and dCA directional sensitivity were similar between groups. However, women with PCOS had elevated relative PCAPI during NVC (PCOS: 12.0 ± 5.6% vs. controls: 7.0 ± 3.8%, p = 0.04), and impaired vasodilation of the internal carotid artery during CVRCO2 (PCOS: -0.10 ± 0.22 mm vs. controls: 0.18 ± 0.24 mm, p < 0.01). CONCLUSIONS:Cerebrovascular function is largely preserved in women with PCOS, although elevated arterial pulsatility and impaired vasodilatory response to carbon dioxide may indicate early endothelial dysfunction in the cerebral vasculature. Larger studies are needed to confirm this in view of our limited study power.

Context Most aquatic macrophytes are ecozone-endemic species, and approximately two-thirds of them have rare occurrence at global scale. These small-range plants are seriously under-studied at macroecological scale, despite their marked vulnerability to extinction through habitat loss and climate change. Aims To identify global hotspots of endemism and rarity of aquatic macrophytes and examine the factors that resulted in speciation hotspots of macrophytes in some areas of the planet. Methods We analysed a database of 3499 macrophyte species to locate speciation hotspots and assess the biogeographic and environmental drivers that maintain ecozone-endemic, and globally rare species within their current limited global areas of occupancy. Key results Ecozone-endemic and globally rare macrophyte species hotspots across the planet showed similar occurrence patterns and drivers among ecozones. Ecozone environmental conditions, particularly harsh environments, influenced macrophyte phylogenetic diversity and structure. Most macrophyte species diversification is recent (<10 million years ago). A negative association with bird-mediated zoochory was seen for endemicity and rarity hotspots. Conclusions This study identified hotspots of endemicity and rarity, and potential cradle and museum speciation areas. Implications Our findings could inform global action to conserve the macrophyte diversity of wetlands, and other inland aquatic habitats, across the world.

The ovarian hormones, oestrogen and progesterone, have vaso- and neuroprotective effects, likely due to interactions with the cerebrovascular system. This study investigates their neuroendocrine influence on a range of cerebral and retinal vascular functions across a healthy menstrual cycle. Twenty-six healthy, menstruating females completed imaging sessions and assessment of circulating hormone levels during their early follicular, late follicular, and mid-luteal phase (1-4, 10-12 and 20-22 days after menses onset). Cerebral blood flow (CBF), arterial arrival time (AAT), global oxygen extraction fraction (OEF), cerebrovascular metabolic rate of oxygen (CMRO2), carotid artery radius and carotid pulsatility index (PI) were measured using 3T MRI. Retinal vessel density and blood flow resistance were assessed with optical coherence tomography angiography (OCT-A). Assessed with linear models, increased oestradiol was related to increased global CBF (Chi2(1)=35.05; p=3.2x10-9) and increased AAT (Chi2(1)=5.87; p=0.015). Increased progesterone was associated with increased global CBF (Chi2(1)=13.00; p=0.0003). In the retina, a relationship was found between oestradiol and decreased retinal blood flow resistance (Chi2(1)=5.28; p=0.0215), which was primarily driven by centrally localised vessels. This study finds that circulating oestrogen increases blood flow in the eye and brain, while progesterone significantly impacts the brain alone. These effects suggest a potential pathway for neuroprotective mechanisms. ### Competing Interest Statement The authors have declared no competing interest.

Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy regarding treatment approaches, especially related to the behavioral sequelae, we have hypothesized in other published work that it is characterized by the rapid onset of Reward Deficiency Syndrome (RDS) in children. We propose utilizing a multi-systems biological approach involving the coupling of genetic addiction risk testing and pro-dopamine regulation (KB220/POLYGEN®) to help induce "dopamine homeostasis" in patients with PANDAS, especially those with known DNA-induced hypodopaminergia. This case study examines a 12-year-old Caucasian male with no prior psychiatric issues who presented with a sudden onset of severe anxiety, depression, emotional liability, and suicidal ideation. The patient underwent genotyping and the genetic addiction risk score (GARS) testing, which revealed risk polymorphisms in the dopamine D2 (-DRD2/ANKK (Taq1A), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) genes. These polymorphisms have been linked to hypodopaminergia. The patient was subsequently placed on research ID-KB220ZPBMPOLY (POLYGEN®), and albeit the possibility of bias, based upon self and parental assessment, a marked rapid improvement in psychiatric symptoms was observed. In the second phase of treatment (102 days utilizing KB220), the patient received standard antibody testing, which was positive for Lyme. Antibacterial therapy started immediately, and KB220z was discontinued to provide a wash-out period. A monotonic trend analysis was performed on each outcome measure, and a consistently decreasing trend was observed utilizing antibacterial therapy. Our recommendation, albeit only one case, is to utilize and further research a combined therapeutic approach, involving precision-guided DNA testing and pro-dopamine regulation along with antibacterial therapy, as well as glutathione to address offensive enhanced cytokines, in patients with suspected PANDAS/CANS.