Biology subjects

Jann, K.

Publications and source records attributed to Jann, K..

13 recordsLinked to original sources

bioRxiv2026

Distinct spatial organization of human hippocampal perfusion and microvascular pulsatility across age

Arterial pulsation can modulate neuronal activity through mechanosensitive pathways in mice, but whether vascular pulsatility is similarly related to neural organization in humans remains unclear. Here, using 7T MRI in 35 young and older adults, we mapped cerebral perfusion and microvascular volumetric pulsatility index (mvPI) across the unfolded hippocampus and integrated these measures with histological, electrophysiological, and transcriptomic reference maps. Perfusion and mvPI exhibited distinct spatial organization and age-related differences. In young adults, perfusion preferentially corresponded to parvalbumin-interneuron density and beta/gamma distribution, whereas mvPI was associated with theta-band distribution. A number of associations detected in young adults were not detected in the older adults maps. Spectral simulations showed qualitative similarity to heartbeat-related phase resetting as one possible explanation for the mvPI-theta relationship, while spatial transcriptomics revealed perivascular enrichment of PIEZO2, a candidate mediator of vascular mechanotransduction. Together, these findings establish perfusion and tissue-level pulsatility as distinct dimensions of human hippocampal vascular organization and provide a framework for investigating their relationships with neural dynamics across aging.

neuroscience↗

bioRxiv2025

Assessing molecular, cellular and transcriptomic bases of laminar perfusion and cytoarchitecture coupling in the human cortex

Understanding how cellular architecture organizes cortical function requires mesoscopic approaches that resolve structure-function coupling in vivo. Here we introduce cerebral blood flow (CBF) and cell-body staining intensity (CSI) similarity index (CCSI), a localized similarity index between the CBF estimates from ultra-high-field 7T arterial spin labeling images and CSI from the BigBrain histology images to serve as a quantitative marker of laminar perfusion-cytoarchitecture coupling. CCSI revealed a reproducible, region- specific alignment between laminar vascular and cellular profiles across the cortex. Going beyond CBF, CCSI selectively tracked mitochondrial respiratory capacity and colocalized with capillary endothelial and mature non-myelination oligodendrocyte populations forming neurovascular interfaces. Transcriptomic enrichment highlighted pathways related to vascular remodeling, oxidative metabolism, and lipid-myelin homeostasis, indicating that CCSI reflects integrated metabolic-structural specialization. At the systems level, CCSI strengthened structure-function gradient correspondence in transmodal cortices, such as the default mode network. Together, these findings establish CCSI as a physiologically grounded, non-invasive marker of perfusion-cytoarchitecture alignment, providing a cross-scale framework linking cortical microstructure, metabolism, and functional organization.

neuroscience↗

bioRxiv2025

Lifespan Trajectories of the Brains Functional Complexity Characterized by Multiscale Sample Entropy

Resting state functional magnetic resonance imaging (rs-fMRI) is a widely used imaging modality that can capture spontaneous neural activity of the brain. The human brain is a complex system, and emerging evidence suggests that the complexity of neural activity may serve as an index of the brains capacity of information processing. In this study we used multiscale sample entropy (MSE) to analyze the complexity of rs-fMRI timeseries of 504 healthy subjects between the age of 6 to 85 years. We constructed the global and regional trajectories of brains functional complexity over the lifespan and analyzed its correlation with executive function. We observed a nonlinear trajectory of fMRI-complexity over the lifespan with a peak age occurring at 23 (95% CI 21.27, 26.38 years) years of age. Males reach the peak age of complexity at 26 years (95% CI 19.95, 33.14 years) whereas females at 23 (95% CI 20.16, 29.18 years). We found significant correlations between complexity and Number-Letter Switching of Trail Making Test in parietal and medial temporal lobes while Inhibition and Inhibition/Switching of Color Word Interference Test also revealed a significant negative correlation with rs-fMRI complexity in lateral and medial frontal cortex. These results help to understand behavior of fMRI-complexity with aging and reveals association with executive function of the brain. As a non-invasive biomarker, fMRI-complexity could provide novel approach to understand information processing capacity in the brain and deficits thereof in illness.

neuroscience↗

bioRxiv2025

Classifying Mild Cognitive Impairment from Normal Cognition: fMRI Complexity Matches Tau PET Performance

BackgroundTau protein accumulation is closely linked to synaptic and neuronal loss in Alzheimers disease (AD), resulting in progressive cognitive decline. Although tau-PET imaging is a direct biomarker of tau pathology, it is costly, carries radiation risks, and is not widely accessible. Resting-state functional MRI (rs-fMRI) complexity--an entropy-based measure of BOLD signal variation--has been proposed as a non-invasive surrogate biomarker of early neuronal dysfunction associated with tau pathology. ObjectivesTo determine whether fMRI-based brain complexity (sample entropy and multiscale entropy) can match or exceed tau-PET in classifying cognitively normal (CN) versus cognitively impaired (MCI/AD) individuals. And to investigate and compare the most influential network regions-of-interest (ROIs) for classification between fMRI complexity and tau-PET, thereby identifying key neuroanatomical correlates of AD-related changes. DesignA cross-sectional study employing 3D convolutional neural network (CNN) classification with five-fold cross-validation and leave-one-network-out analysis. SettingData from the Alzheimers Disease Neuroimaging Initiative (ADNI) database. ParticipantsOne hundred forty-seven older adults (age 72.5 {+/-} 7.5 years), including 95 CN, 45 MCI, and 7 AD. MeasurementsWe created whole-brain complexity maps from rs-fMRI and standardized uptake value ratio (SUVR) maps from tau-PET. Each modality was separately fed into CNN classifiers. Region-based analyses (leave-one-network-out) were performed to identify critical ROIs for classification. ResultsfMRI complexity showed classification accuracy comparable to tau-PET yet surpassed it in F1-score (0.64 vs. 0.61) and area under the curve (AUC; 0.73 vs. 0.67). Salience and dorsal attention networks contributed most to fMRI-based classification, and a dorsal attention network contributed most to tau-PET-based classification. ConclusionsfMRI complexity performs similarly to tau-PET in detecting cognitive impairment related to AD and identifies partially distinct critical ROIs, suggesting an alternative, radiation- free imaging biomarker for earlier detection and broader clinical application.

neuroscience↗

bioRxiv2024

Age-Related Decline in BBB Function is More Pronounced in Males than Females

The blood-brain barrier (BBB) plays a pivotal role in protecting the central nervous system (CNS), shielding it from potential harmful entities. A natural decline of BBB function with aging has been reported in both animal and human studies, which may contribute to cognitive decline and neurodegenerative disorders. Limited data also suggest that being female may be associated with protective effects on BBB function. Here we investigated age and sex-dependent trajectories of perfusion and BBB water exchange rate (kw) across the lifespan in 186 cognitively normal participants spanning the ages of 8 to 92 years old, using a non-invasive diffusion prepared pseudo-continuous arterial spin labeling (DP-pCASL) MRI technique. We found that the pattern of BBB kw decline with aging varies across brain regions. Moreover, results from our DP-pCASL technique revealed a remarkable decline in BBB kw beginning in the early 60s, which was more pronounced in males. In addition, we observed sex differences in parietal and temporal regions. Our findings provide in vivo results demonstrating sex differences in the decline of BBB function with aging, which may serve as a foundation for future investigations into perfusion and BBB function in neurodegenerative and other brain disorders. Significance statementThe blood-brain barrier (BBB) serves as a critical protection mechanism for the CNS. A natural decline of BBB function with aging has been reported in both animal and human studies, with possible differences in BBB function by sex. Using our MRI technique, DP-pCASL that measures water exchange rate (kw) without contrast in 186 participants from diverse race and age groups, we identified age and sex-specific patterns in BBB kw especially in parietal and temporal regions. We observed of a decline in kw beginning in the early 60s, especially in males. Our study unveils the dynamic spatiotemporal pattern of kw differences with age and sex, which serve as a foundation for understanding aberrations of BBB function in neurodegenerative and other brain disorders.

neuroscience↗

bioRxiv2023

A window to the brain: ultrasound imaging of human neural activity through a permanent acoustic window

Recording human brain activity is crucial for understanding normal and aberrant brain function. However, available recording methods are either highly invasive or have relatively low sensitivity. Functional ultrasound imaging (fUSI) is an emerging technique that offers sensitive, large-scale, high-resolution neural imaging. However, fUSI cannot be performed through adult human skull. Here, we use a polymeric skull replacement material to create an acoustic window allowing ultrasound to monitor brain activity in fully intact adult humans. We design the window through experiments in phantoms and rodents, then implement it in a participant undergoing reconstructive skull surgery. Subsequently, we demonstrate fully non-invasive mapping and decoding of cortical responses to finger movement, marking the first instance of high-resolution (200 m) and large-scale (50 mmx38 mm) brain imaging through a permanent acoustic window.

neuroscience↗

bioRxiv2023

Vessel Density Mapping of Cerebral Small Vessels on 3D High Resolution Black Blood MRI

Cerebral small vessels are largely inaccessible to existing clinical in vivo imaging technologies. This study aims to present a novel analysis pipeline for vessel density mapping of cerebral small vessels from high-resolution 3D black-blood MRI at 3T. Twenty-eight subjects (10 under 35 years old, 18 over 60 years old) were imaged with the T1-weighted turbo spin-echo with variable flip angles (T1w TSE-VFA) sequence optimized for black-blood small vessel imaging with iso-0.5mm spatial resolution at 3T. Hessian-based vessel segmentation methods (Jerman, Frangi and Sato filter) were evaluated by vessel landmarks and manual annotation of lenticulostriate arteries (LSAs). Using optimized vessel segmentation, large vessel pruning and non-linear registration, a semiautomatic pipeline was proposed for quantification of small vessel density across brain regions and further for localized detection of small vessel changes across populations. Voxel-level statistics was performed to compare vessel density between two age groups. Additionally, local vessel density of aged subjects was correlated with their corresponding gross cognitive and executive function (EF) scores using Montreal Cognitive Assessment (MoCA) and EF composite scores compiled with Item Response Theory (IRT). Jerman filter showed better performance for vessel segmentation than Frangi and Sato filter which was employed in our pipeline. Cerebral small vessels on the order of a few hundred microns can be delineated using the proposed analysis pipeline on 3D black-blood MRI at 3T. The mean vessel density across brain regions was significantly higher in young subjects compared to aged subjects. In the aged subjects, localized vessel density was positively correlated with MoCA and IRT EF scores. The proposed pipeline is able to segment, quantify, and detect localized differences in vessel density of cerebral small vessels based on 3D high-resolution black-blood MRI. This framework may serve as a tool for localized detection of small vessel density changes in normal aging and cerebral small vessel disease.

neuroscience↗

bioRxiv2022

FMRI complexity correlates with tau-PET in Late-Onset and Autosomal Dominant Alzheimer's Disease

Neurofibrillary tangle pathology detected with tau-PET correlates closely with neuronal injury and cognitive symptoms in Alzheimers disease (AD). Complexity of rs-fMRI time-series, measured by entropy values, have recently been reported to decrease with aging, APOE {varepsilon}4 genotype and cognitive decline in AD. Here we hypothesize that the complexity of BOLD signals provides an index for tau-related neuronal injury and cognitive decline in the AD process. Data were obtained from the Alzheimers Disease Neuroimaging Initiative phase 3 (ADNI3) and the Estudio de la Enfermedad de Alzheimer en Jalisciences (EEAJ) study, including cognitively normal elderly controls, persons with late onset AD (LOAD) and early onset autosomal dominant AD (ADAD) patients and their relatives. Our cohort consisted of a sample of 147 subjects from ADNI3 and 41 subjects from EEAJ with T1 structural, tau-PET (tracer: 18F-AV1451) and fMRI scans. Correlations between SUVR tau-PET and multi-scale entropy (MSE) were calculated voxelwise as well as for standard automated anatomical labeling (AAL) atlas regions while accounting for age, gender, and regional gray matter volume. Potential pathways relating MSE to cognitive function mediated through tau-PET were assessed by path analysis. We found significant negative correlations between low frequency MSE and tau-PET measures in medial temporal lobe, in both ADNI3 and EEAJ cohorts. Furthermore, low frequency MSE showed significant associations with the Clinical Dementia Rating (CDR) scale and the Mini-Mental State Status Exam (MMSE) scores in both ADNI3 and EEAJ cohorts, which were largely mediated through the tau-PET signal. Correlations of MSE with tau-PET in temporal lobes support our hypothesis that the complexity of rs-fMRI is associated with regional tau protein accumulation. Furthermore, the association of MSE with CDR and MMSE, mediated by tau-PET, in disease relevant areas suggests that a reduction in MSE is indicative of decreased information processing capacity and cognitive decline in AD processes.

neuroscience↗

bioRxiv2021

Aberrant Functional Connectivity between Reward and Inhibitory Control Networks in Pre-Adolescent Binge Eating Disorder

BackgroundBehavioral features of binge eating disorder (BED) suggest abnormalities in reward and inhibitory control. Studies of adult populations suggest functional abnormalities in reward and inhibitory control networks. Despite behavioral markers often developing in children, the neurobiology of pediatric BED remains unstudied. Methods58 pre-adolescent children (aged 9-10-years) with BED and 66 age, BMI and developmentally-matched control children were extracted from the 3.0 baseline (Year 0) release of the Adolescent Brain Cognitive Development (ABCD) Study. We investigated group differences in resting-state functional MRI (rs-fMRI) functional connectivity (FC) within and between reward and inhibitory control networks. A seed-based approach was employed to assess nodes in the reward (orbitofrontal cortex, nucleus accumbens, amygdala) and inhibitory control (dorsolateral prefrontal cortex, anterior cingulate cortex) networks via hypothesis-driven seed-to- seed analyses, and secondary seed-to-voxel analyses. ResultsOur findings revealed reduced FC between the dlPFC and amygdala, and between the anterior cingulate cortex and orbitofrontal cortex in pre-adolescent children with BED, relative to age, gender, BMI and developmentally matched controls. These findings indicating aberrant connectivity between nodes of inhibitory control and reward networks were corroborated by the whole-brain FC analyses. ConclusionsEarly-onset BED may be characterized by diffuse abnormalities in the functional synergy between reward and cognitive control networks, without perturbations within reward and inhibitory control networks, respectively. The decreased capacity to regulate a reward-driven pursuit of hedonic foods, which is characteristic of BED, may in part, rest on this dysconnectivity between reward and inhibitory control networks.

neuroscience↗

bioRxiv2021

FGF21 Response Varies by Sugar Type and is Associated with Body Weight, Dietary Added Sugar, and Neural Signaling in Humans

Fibroblast growth factor 21 (FGF21) is a liver-derived hormone that regulates energy homeostasis. In humans, few studies have investigated whether FGF21 may act to suppress sugar intake and influence eating behavior, and the effects of adiposity on post-ingestive FGF21 regulation of appetite are unknown. Here, we demonstrate among two cohorts of healthy, young adults that acute oral fructose and sucrose compared to glucose lead to greater circulating FGF21. Moreover, high compared to low dietary added sugar intake is associated with greater sucrose-stimulated FGF21 among participants with healthy weight but attenuated in people with overweight and obesity. In addition, our study is the first to demonstrate associations between circulating FGF21 and neural signaling following an acute sucrose load among humans with healthy weight. Collectively, our results suggest that these potential compensatory relationships between sucrose-stimulated circulating FGF21, habitual sugar intake, and post-ingestive brain responses may be altered among adults with overweight and obesity. Significance StatementAnimal models have established FGF21 as an autoregulator of sweet consumption, but few studies have examined post-ingestive FGF21 effects in humans. In this report, we demonstrate a compensatory relationship between sucrose-stimulated FGF21 and high dietary added sugar intake through a potential liver-to-brain negative-feedback cycle among healthy, young adults. Notably, our findings also suggest that humans with overweight and obesity may have altered FGF21 neuroendocrine signaling.

physiology↗

bioRxiv2021

Laminar perfusion imaging with zoomed arterial spin labeling at 7 Tesla

Laminar fMRI based on BOLD and CBV contrast at ultrahigh magnetic fields has been applied for studying the dynamics of mesoscopic brain networks. However, the quantitative interpretations of BOLD/CBV fMRI results are confounded by different baseline physiology across cortical layers. Here we introduce a novel 3D zoomed pseudo-continuous arterial spin labeling technique at 7T that offers the unique capability for quantitative measurements of laminar cerebral blood flow (CBF) both at rest and during task activation with high spatial specificity and sensitivity. We found arterial transit time in superficial layers is [~]100 msec shorter than in middle/deep layers revealing the dynamics of labeled blood flowing from pial arteries to downstream microvasculature. Resting state CBF peaked in the middle layers which is highly consistent with microvascular density measured from human cortex specimens. Finger tapping induced a robust two-peak laminar profile of CBF increases in the superficial (somatosensory and premotor input) and deep (spinal output) layers of M1, while finger brushing task induced a weaker CBF increase in superficial layers (somatosensory input). We further demonstrated that top-down attention induced a predominant CBF increase in deep layers and a smaller CBF increase on top of the lower baseline CBF in superficial layers of V1 (feedback cortical input), while bottom-up stimulus driven activity peaked in the middle layers (feedforward thalamic input). These quantitative laminar profiles of perfusion activity suggest an important role of M1 superficial layers for the computation of finger movements, and that visual attention may amplify deep layer output to the subcortex. Significance StatementCBF or microvascular perfusion measured by arterial spin labeling (ASL) is a key parameter for in vivo assessment of neurovascular function. Compared to BOLD or VASO fMRI, ASL perfusion contrast offers the unique capability for quantitative CBF measurements both at baseline and during task activation, which is critical for quantitative estimation of metabolic activities tightly related to neuronal activation. We proposed a zoomed 3D ASL technique at 7T for laminar perfusion imaging with high spatial specificity and sensitivity. This technique is able to differentiate and quantify the input/output and feedforward/feedback activities of human motor and visual cortex, thereby providing an important tool for quantitative assessment of neurovascular function and metabolic activities of neural circuits across cortical layers.

neuroscience↗

bioRxiv2019

Embodiment improves performance on an immersive brain computer interface in head-mounted virtual reality

Brain computer interfaces (BCI) can be used to provide individuals with neurofeedback of their own brain activity and train them to learn how to control their brain activity. Neurofeedback-based BCIs used for motor rehabilitation aim to close the loop between attempted motor commands and sensory feedback by providing supplemental sensory information when individuals successfully establish specific brain patterns. Existing neurofeedback-based BCIs have used a variety of displays to provide feedback, ranging from devices that provide a more immersive and compelling experience (e.g., head-mounted virtual reality (HMD-VR) or CAVE systems) to devices that are considered less immersive (e.g., computer screens). However, it is not clear whether more immersive systems (i.e., HMD-VR) improve neurofeedback performance compared to computer screens, and whether there are individual performance differences in HMD-VR versus screen-based neurofeedback. In this pilot experiment, we compared neurofeedback performance in HMD-VR versus on a computer screen in twelve healthy individuals. We also examined whether individual differences in presence or embodiment correlated with neurofeedback performance in either environment. Participants were asked to control a virtual right arm by imagining right hand movements. Real-time brain activity indicating motor imagery, which was measured via electroencephalography (EEG) as desynchronized sensorimotor rhythms (SMR; 8-24 Hz) in the left motor cortex, drove the movement of the virtual arm towards (increased SMR desynchronization) or away from (decreased SMR desynchronization) targets. Participants performed two blocks of 30 trials, one for each condition (Screen, HMD-VR), with the order of conditions counterbalanced across participants. After completing each block, participants were asked questions relating to their sense of presence and embodiment in each environment. We found that, while participants performance on the neurofeedback-based BCI task was similar between conditions, the participants reported levels of embodiment was significantly different between conditions. Specifically, participants experienced higher levels of embodiment in HMD-VR compared to the computer screen. We further found that reported levels of embodiment positively correlated with neurofeedback performance only in the HMD-VR condition. Overall, these preliminary results suggest that embodiment may improve performance on a neurofeedback-based BCI and that HMD-VR may increase embodiment during a neurofeedback-based BCI task compared to a standard computer screen.

neuroscience↗

bioRxiv2018

High-definition transcranial direct current stimulation over the dorsal premotor cortex reliably modulates motor network excitability

The effectiveness of transcranial direct current stimulation (tDCS) placed over the motor hotspot (thought to represent the primary motor cortex (M1)) to modulate motor network excitability is highly variable. The premotor cortex--particularly the dorsal premotor cortex (PMd)--may be a promising alternative target to more effectively modulate motor excitability, as it influences motor control across multiple pathways, one independent of M1 and one with direct, modulating connections to M1. This double-blind, placebo-controlled study aimed to differentially excite motor and premotor regions using high-definition tDCS (HD-tDCS) with concurrent functional magnetic resonance imaging (fMRI). HD-tDCS applied over either the motor hotspot or the premotor cortex demonstrated high inter-individual variability in changes on cortical motor excitability. However, HD-tDCS over the premotor cortex led to a higher number of responders and greater changes in local fMRI-based complexity than HD-tDCS over the motor hotspot. Furthermore, an analysis of individual motor hotspot anatomical locations revealed that, in more than half of the participants, the motor hotspot is not located over anatomical M1 boundaries, despite using a canonical definition of the motor hotspot. This heterogeneity in stimulation site may contribute to the variability of tDCS results. Altogether, these findings provide new considerations to enhance tDCS reliability.

neuroscience↗