Kay Jann

YNIMG Journal 2025 Journal Article

7 tesla multiscale entropy analysis reveals increased resting-state complexity in key regions for fear and anxiety in spider-fearful individuals

• Matthias Grieder
• Niklaus Denier
• Kay Jann
• Werner Strik
• Leila M. Soravia
• Kristina Adorjan
• Marcel Meyer
• Elisabeth Jehli

Resting-state functional connectivity is limited in assessing the temporal dynamics of brain networks and, due to an insufficient signal-to-noise ratio, in detecting subtle changes at 3T MRI. Nonetheless, measures of complexity, which capitalize on temporal dynamics, have revealed alterations for some affective disorders at this field strength. Anxiety disorders have received only scant attention in this regard, despite indications of altered functional brain architecture in spider-fearful participants (SP). To address this gap, we probed resting-state complexity using 7T MRI, comparing 28 adults with SP with 45 healthy controls (HC). We computed multiscale entropy (MSE) on ten scales (1 - 0.1 Hz) for brain regions of the fear and anxiety networks in HC and SP. The MSE scales interacted with group (HC, SP) and brain area, revealing MSE increments in limbic regions in SP (versus HC). Whilst most MSE changes related to SP ranged between 1 and 0.33 Hz, the MSE of the bed nucleus of the stria terminalis (BNST), a nucleus involved in anxiety and the hormonal system, exhibited increases on all scales bar two for SP (i.e., for 0.5 - 0.125, and 0.1 Hz). MSE was also positively associated with SP severity (but not trait anxiety) in the BNST. Altogether, 7T fMRI detected elevated MSE in SP, indicating excessive intra-regional processing in brain regions key to fear and anxiety. The most pronounced effects were found in the BNST, corroborating its central role in the anxiety circuit.

YNIMG Journal 2025 Journal Article

A Test-Retest Study of Single- and Multi-Delay pCASL for Choroid Plexus Perfusion Imaging in Healthy Subjects Aged 19 to 87 Years

• Zixuan Liu
• Qinyang Shou
• Kay Jann
• Chenyang Zhao
• Danny JJ Wang
• Xingfeng Shao

There is a growing interest in the choroid plexus (ChP) due to its critical role in cerebrospinal fluid (CSF) production and its involvement in neurodegenerative and cerebrovascular diseases. However, comprehensive studies comparing the accuracy and reliability of single- and multi-PLD (post-labeling delay) arterial spin labeling (ASL) techniques, specifically in relation to the ChP, remain limited. This study systematically evaluated the test-retest reliability and quantification accuracy of cerebral blood flow (CBF) measurements, focusing on the ChP, using single-delay and multi-delay 3D gradient-and-spin echo (GRASE) pseudo-continuous ASL (pCASL) on 28 subjects (aged 19 to 87 years, 14 males/14 females) at 3.0 tesla. Both single-delay (2 s) and 5-PLD (0.5 - 2.5 s) pCASL scans were repeated approximately one week apart with a spatial resolution of 2.5 × 2.5 × 3 mm³. Voxel-wise and regional CBF and arterial transit time (ATT) measurements were compared to assess test-retest reliability, with a particular focus on ChP perfusion changes with age. In this study, 12.15 % of ChP voxels exhibited ATTs longer than 2 s, potentially leading to a significant underestimation of CBF using single-delay ASL. Multi-delay ASL showed improved accuracy in estimating CBF values for the ChP compared to single-delay ASL when ATT > PLD. Additionally, ChP volume (mean ± std = 1.72± 0.85 ml) increased (p < 0.01) and ChP perfusion (43.07±14.18 mL/100 g/min) decreased (p = 0.04) with age. These findings underscore the robustness of multi-delay ASL with model-fitting quantification in assessing ChP perfusion, making it the preferred method for accurate CBF and ATT estimation, particularly in regions with prolonged transit time such as ChP.

YNIMG Journal 2025 Journal Article

Understanding whole person systems in brain-gut-microbiome research through ultra-high-field MRI imaging

• Tien S. Dong
• Kay Jann
• Danny J.J. Wang
• Arpana Church

The brain-gut-microbiome (BGM) axis regulates interoception, metabolism, and immunity, with dysfunction linked to IBS, obesity, and mood disorders. Ultra-high-field (UHF) MRI advances neural imaging, enhancing resolution of vagal and spinal circuits mediating gut-brain communication. UHF enables real-time tracking of interventions like vagus nerve stimulation and probiotics, linking microbiome shifts to neural adaptations. Despite challenges like signal distortions, innovations in coil design are improving imaging fidelity. Integrating neuroimaging with multi-omic profiling fosters a systems-level approach, advancing personalized therapies for BGM disorders. This commentary underscores UHF MRI's transformative potential in bridging neuroscience, microbiome science, and clinical applications.

YNIMG Journal 2024 Journal Article

Analyzing fractal dimension in electroconvulsive therapy: Unraveling complexity in structural and functional neuroimaging

• Niklaus Denier
• Matthias Grieder
• Kay Jann
• Sigrid Breit
• Nicolas Mertse
• Sebastian Walther
• Leila M. Soravia
• Agnes Meyer

BACKGROUND: Numerous studies show that electroconvulsive therapy (ECT) induces hippocampal neuroplasticity, but findings are inconsistent regarding its clinical relevance. This study aims to investigate ECT-induced plasticity of anterior and posterior hippocampi using mathematical complexity measures in neuroimaging, namely Higuchi's fractal dimension (HFD) for fMRI time series and the fractal dimension of cortical morphology (FD-CM). Furthermore, we explore the potential of these complexity measures to predict ECT treatment response. METHODS: Twenty patients with a current depressive episode (16 with major depressive disorder and 4 with bipolar disorder) underwent MRI-scans before and after an ECT-series. Twenty healthy controls matched for age and sex were also scanned twice for comparison purposes. Resting-state fMRI data were processed, and HFD was computed for anterior and posterior hippocampi. Group-by-time effects for HFD in anterior and posterior hippocampi were calculated and correlations between HFD changes and improvement in depression severity were examined. For FD-CM analyses, we preprocessed structural MRI with CAT12's surface-based methods. We explored group-by-time effects for FD-CM and the predictive value of baseline HFD and FD-CM for treatment outcome. RESULTS: Patients exhibited a significant increase in bilateral hippocampal HFD from baseline to follow-up scans. Right anterior hippocampal HFD increase was associated with reductions in depression severity. We found no group differences and group-by-time effects in FD-CM. After applying a whole-brain regression analysis, we found that baseline FD-CM in the left temporal pole predicted reduction of overall depression severity after ECT. Baseline hippocampal HFD did not predict treatment outcome. CONCLUSION: This study suggests that HFD and FD-CM are promising imaging markers to investigate ECT-induced neuroplasticity associated with treatment response.

YNICL Journal 2024 Journal Article

Cerebral blood flow and white matter alterations in adults with phenylketonuria

• Leonie Steiner
• Raphaela Muri
• Dilmini Wijesinghe
• Kay Jann
• Stephanie Maissen-Abgottspon
• Piotr Radojewski
• Katarzyna Pospieszny
• Roland Kreis

BACKGROUND: Phenylketonuria (PKU) represents a congenital metabolic defect that disrupts the process of converting phenylalanine (Phe) into tyrosine. Earlier investigations have revealed diminished cognitive performance and changes in brain structure and function (including the presence of white matter lesions) among individuals affected by PKU. However, there exists limited understanding regarding cerebral blood flow (CBF) and its potential associations with cognition, white matter lesions, and metabolic parameters in patients with PKU, which we therefore aimed to investigate in this study. METHOD: H spectroscopy, and white matter lesions were rated by two neuroradiologists on T2 weighted images. White matter integrity was examined with diffusion tensor imaging (DTI). For patients only, concurrent plasma Phe levels were assessed after an overnight fasting period. Furthermore, past Phe levels were collected to estimate historical metabolic control. On the day of the MRI, each participant underwent a cognitive assessment measuring IQ and performance in executive functions, attention, and processing speed. RESULTS: No significant group difference was observed in global CBF between patients and controls (F (1, 87) = 3.81, p = 0.054). Investigating CBF on the level of cerebral arterial territories, reduced CBF was observed in the left middle and posterior cerebral artery (MCA and PCA), with the most prominent reduction of CBF in the anterior subdivision of the MCA (F (1, 87) = 6.15, p = 0.015, surviving FDR correction). White matter lesions in patients were associated with cerebral blood flow reduction in the affected structure. Particularly, patients with lesions in the occipital lobe showed significant CBF reductions in the left PCA (U = 352, p = 0.013, surviving FDR correction). Additionally, axial diffusivity measured with DTI was positively associated with CBF in the ACA and PCA (surviving FDR correction). Cerebral blood flow did not correlate with cognitive performance or metabolic parameters. CONCLUSION: The relationship between cerebral blood flow and white matter indicates a complex interplay between vascular health and white matter alterations in patients with PKU. It highlights the importance of considering a multifactorial model when investigating the impact of PKU on the brain.

YNICL Journal 2024 Journal Article

Effect of a four-week oral Phe administration on neural activation and cerebral blood flow in adults with early-treated phenylketonuria

• Stephanie Maissen-Abgottspon
• Leonie Steiner
• Raphaela Muri
• Dilmini Wijesinghe
• Kay Jann
• Yosuke Morishima
• Michel Hochuli
• Roland Kreis

BACKGROUND: Phenylketonuria (PKU) is a rare inborn error of metabolism characterized by impaired catabolism of the amino acid phenylalanine (Phe) into tyrosine. Cross-sectional studies suggest slight alterations in cognitive performance and neural activation in adults with early-treated PKU. The influence of high Phe levels on brain function in adulthood, however, remains insufficiently studied. Therefore, we aimed to explore the effect of a four-week period of oral Phe administration - simulating a controlled discontinuation of Phe restriction and raising Phe to an off-diet scenario - on working memory-related neural activation and cerebral blood flow (CBF). METHODS: H-MR spectroscopy. RESULTS: Plasma Phe and cerebral Phe were significantly increased after the Phe intervention. However, no significant effect of Phe compared to placebo was found on neural activation and CBF. Regarding fMRI task performance, a significant impact of the Phe intervention on 1-back reaction time was observed with slower reaction times following the Phe intervention, whereas 3-back reaction time and accuracy did not differ following the Phe intervention compared to the placebo intervention. CONCLUSION: Results from this present trial simulating a four-week discontinuation of the Phe-restricted diet showed that a high Phe load did not uniformly affect neural markers and cognition in a statistically significant manner. These results further contribute to the discussion on safe Phe levels during adulthood and suggest that a four-week discontinuation of Phe-restricted diet does not demonstrate significant changes in brain function.

YNIMG Journal 2024 Journal Article

Vessel density mapping of small cerebral vessels on 3D high resolution black blood MRI

• Mona Sharifi Sarabi
• Samantha J. Ma
• Kay Jann
• John M. Ringman
• Danny J.J. Wang
• Yonggang Shi

Small cerebral blood 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 small cerebral blood 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. 5 mm spatial resolution (interpolated from 0. 51×0. 51×0. 64 mm3) 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. Small cerebral blood vessels including small artery, arterioles, small veins, and venules 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 small cerebral blood 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.

YNIMG Journal 2022 Journal Article

Corrigendum to “Laminar perfusion imaging with zoomed arterial spin labeling at 7 Tesla” [NeuroImage volume 245, 2021, 118724]

• Xingfeng Shao
• Fanhua Guo
• Qinyang Shou
• Kai Wang
• Kay Jann
• Lirong Yan
• Arthur W. Toga
• Peng Zhang

YNIMG Journal 2021 Journal Article

Laminar perfusion imaging with zoomed arterial spin labeling at 7 Tesla

• Xingfeng Shao
• Fanhua Guo
• Qinyang Shou
• Kai Wang
• Kay Jann
• Lirong Yan
• Arthur W. Toga
• Peng Zhang

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 (pCASL) technique at 7T that offers the 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 ms shorter than in middle/deep layers revealing the time course 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). This observation is highly consistent with reported laminar profiles of CBV activation on M1. We further demonstrated that visuospatial 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 stimulus driven activity peaked in the middle layers (feedforward thalamic input). With the capability for quantitative CBF measurements both at baseline and during task activation, high-resolution ASL perfusion fMRI at 7T provides an important tool for in vivo assessment of neurovascular function and metabolic activities of neural circuits across cortical layers.

YNIMG Journal 2021 Journal Article

Multi-vendor and multisite evaluation of cerebrovascular reactivity mapping using hypercapnia challenge

• Peiying Liu
• Dengrong Jiang
• Marilyn Albert
• Christopher E. Bauer
• Arvind Caprihan
• Brian T. Gold
• Steven M. Greenberg
• Karl G. Helmer

Cerebrovascular reactivity (CVR), which measures the ability of cerebral blood vessels to dilate or constrict in response to vasoactive stimuli such as CO2 inhalation, is an important index of the brain's vascular health. Quantification of CVR using BOLD MRI with hypercapnia challenge has shown great promises in research and clinical studies. However, in order for it to be used as a potential imaging biomarker in large-scale and multi-site studies, the reliability of CO2-CVR quantification across different MRI acquisition platforms and researchers/raters must be examined. The goal of this report from the MarkVCID small vessel disease biomarkers consortium is to evaluate the reliability of CO2-CVR quantification in three studies. First, the inter-rater reliability of CO2-CVR data processing was evaluated by having raters from 5 MarkVCID sites process the same 30 CVR datasets using a cloud-based CVR data processing pipeline. Second, the inter-scanner reproducibility of CO2-CVR quantification was assessed in 10 young subjects across two scanners of different vendors. Third, test-retest repeatability was evaluated in 20 elderly subjects from 4 sites with a scan interval of less than 2 weeks. In all studies, the CO2 CVR measurements were performed using the fixed inspiration method, where the subjects wore a nose clip and a mouthpiece and breathed room air and 5% CO2 air contained in a Douglas bag alternatively through their mouth. The results showed that the inter-rater CoV of CVR processing was 0.08 ± 0.08% for whole-brain CVR values and ranged from 0.16% to 0.88% in major brain regions, with ICC of absolute agreement above 0.9959 for all brain regions. Inter-scanner CoV was found to be 6.90 ± 5.08% for whole-brain CVR values, and ranged from 4.69% to 12.71% in major brain regions, which are comparable to intra-session CoVs obtained from the same scanners on the same day. ICC of consistency between the two scanners was 0.8498 for whole-brain CVR and ranged from 0.8052 to 0.9185 across major brain regions. In the test-retest evaluation, test-retest CoV across different days was found to be 18.29 ± 17.12% for whole-brain CVR values, and ranged from 16.58% to 19.52% in major brain regions, with ICC of absolute agreement ranged from 0.6480 to 0.7785. These results demonstrated good inter-rater, inter-scanner, and test-retest reliability in healthy volunteers, and suggested that CO2-CVR has suitable instrumental properties for use as an imaging biomarker of cerebrovascular function in multi-site and longitudinal observational studies and clinical trials.

YNIMG Journal 2019 Journal Article

Characterization of lenticulostriate arteries with high resolution black-blood T1-weighted turbo spin echo with variable flip angles at 3 and 7 Tesla

• Samantha J. Ma
• Mona Sharifi Sarabi
• Lirong Yan
• Xingfeng Shao
• Yue Chen
• Qi Yang
• Kay Jann
• Arthur W. Toga

Objectives The lenticulostriate arteries (LSAs) with small diameters of a few hundred microns take origin directly from the high flow middle cerebral artery (MCA), making them especially susceptible to damage (e. g. by hypertension). This study aims to present high resolution (isotropic ∼0. 5 mm), black blood MRI for the visualization and characterization of LSAs at both 3 T and 7 T. Materials and methods T1-weighted 3D turbo spin-echo with variable flip angles (T1w TSE-VFA) sequences were optimized for the visualization of LSAs by performing extended phase graph (EPG) simulations. Twenty healthy volunteers (15 under 35 years old, 5 over 60 years old) were imaged with the T1w TSE-VFA sequences at both 3 T and 7 T. Contrast-to-noise ratio (CNR) was quantified, and LSAs were manually segmented using ITK-SNAP. Automated Reeb graph shape analysis was performed to extract features including vessel length and tortuosity. All quantitative metrics were compared between the two field strengths and two age groups using ANOVA. Results LSAs can be clearly delineated using optimized 3D T1w TSE-VFA at 3 T and 7 T, and a greater number of LSA branches can be detected compared to those by time-of-flight MR angiography (TOF MRA) at 7 T. The CNR of LSAs was comparable between 7 T and 3 T. T1w TSE-VFA showed significantly higher CNR than TOF MRA at the stem portion of the LSAs branching off the medial middle cerebral artery. The mean vessel length and tortuosity were greater on TOF MRA compared to TSE-VFA. The number of detected LSAs by both TSE-VFA and TOF MRA was significantly reduced in aged subjects, while the mean vessel length measured on 7 T TSE-VFA showed significant difference between the two age groups. Conclusion The high-resolution black-blood 3D T1w TSE-VFA sequence offers a new method for the visualization and quantification of LSAs at both 3 T and 7 T, which may be applied for a number of pathological conditions related to the damage of LSAs.

YNICL Journal 2018 Journal Article

Regional association of pCASL-MRI with FDG-PET and PiB-PET in people at risk for autosomal dominant Alzheimer's disease

• Lirong Yan
• Collin Y. Liu
• Koon-Pong Wong
• Sung-Cheng Huang
• Wendy J. Mack
• Kay Jann
• Giovanni Coppola
• John M. Ringman

Autosomal dominant Alzheimer's disease (ADAD) is a small subset of Alzheimer's disease that is genetically determined with 100% penetrance. It provides a valuable window into studying the course of pathologic processes that leads to dementia. Arterial spin labeling (ASL) MRI is a potential AD imaging marker that non-invasively measures cerebral perfusion. In this study, we investigated the relationship of cerebral blood flow measured by pseudo-continuous ASL (pCASL) MRI with measures of cerebral metabolism (FDG PET) and amyloid deposition (Pittsburgh Compound B (PiB) PET). Thirty-one participants at risk for ADAD (age 39 ± 13 years, 19 females) were recruited into this study, and 21 of them received both MRI and FDG and PiB PET scans. Considerable variability was observed in regional correlations between ASL-CBF and FDG across subjects. Both regional hypo-perfusion and hypo-metabolism were associated with amyloid deposition. Cross-sectional analyses of each biomarker as a function of the estimated years to expected dementia diagnosis indicated an inverse relationship of both perfusion and glucose metabolism with amyloid deposition during AD development. These findings indicate that neurovascular dysfunction is associated with amyloid pathology, and also indicate that ASL CBF may serve as a sensitive early biomarker for AD. The direct comparison among the three biomarkers provides complementary information for understanding the pathophysiological process of AD.

YNIMG Journal 2016 Journal Article

Developmental trajectories of cerebral blood flow and oxidative metabolism at baseline and during working memory tasks

• Mayank A. Jog
• Lirong Yan
• Emily Kilroy
• Kate Krasileva
• Kay Jann
• Holly LeClair
• David Elashoff
• Danny J.J. Wang

The neurobiological interpretation of developmental BOLD fMRI findings remains difficult due to the confounding issues of potentially varied baseline of brain function and varied strength of neurovascular coupling across age groups. The central theme of the present research is to study the development of brain function and neuronal activity through in vivo assessments of cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) both at baseline and during the performance of a working memory task in a cohort of typically developing children aged 7 to 18years. Using a suite of 4 emerging MRI technologies including MR blood oximetry, phase-contrast MRI, pseudo-continuous arterial spin labeling (pCASL) perfusion MRI and concurrent CBF/BOLD fMRI, we found: 1) At baseline, both global CBF and CMRO2 showed an age related decline while global OEF was stable across the age group; 2) During the working memory task, neither BOLD nor CBF responses showed significant variations with age in the activated fronto-parietal brain regions. Nevertheless, detailed voxel-wise analyses revealed sub-regions within the activated fronto-parietal regions that show significant decline of fractional CMRO2 responses with age. These findings suggest that the brain may become more “energy efficient” with age during development.

YNIMG Journal 2015 Journal Article

Discovering frequency sensitive thalamic nuclei from EEG microstate informed resting state fMRI

• Simon Schwab
• Thomas Koenig
• Yosuke Morishima
• Thomas Dierks
• Andrea Federspiel
• Kay Jann

Microstates (MS), the fingerprints of the momentarily and time-varying states of the brain derived from electroencephalography (EEG), are associated with the resting state networks (RSNs). However, using MS fluctuations along different EEG frequency bands to model the functional MRI (fMRI) signal has not been investigated so far, or elucidated the role of the thalamus as a fundamental gateway and a putative key structure in cortical functional networks. Therefore, in the current study, we used MS predictors in standard frequency bands to predict blood oxygenation level dependent (BOLD) signal fluctuations. We discovered that multivariate modeling of BOLD-fMRI using six EEG-MS classes in eight frequency bands strongly correlated with thalamic areas and large-scale cortical networks. Thalamic nuclei exhibited distinct patterns of correlations for individual MS that were associated with specific EEG frequency bands. Anterior and ventral thalamic nuclei were sensitive to the beta frequency band, medial nuclei were sensitive to both alpha and beta frequency bands, and posterior nuclei such as the pulvinar were sensitive to delta and theta frequency bands. These results demonstrate that EEG-MS informed fMRI can elucidate thalamic activity not directly observable by EEG, which may be highly relevant to understand the rapid formation of thalamocortical networks.

YNIMG Journal 2015 Journal Article

Functional connectivity in BOLD and CBF data: Similarity and reliability of resting brain networks

• Kay Jann
• Dylan G. Gee
• Emily Kilroy
• Simon Schwab
• Robert X. Smith
• Tyrone D. Cannon
• Danny J.J. Wang

Resting-state functional connectivity (FC) fMRI (rs-fcMRI) offers an appealing approach to mapping the brain's intrinsic functional organization. Blood oxygen level dependent (BOLD) and arterial spin labeling (ASL) are the two main rs-fcMRI approaches to assess alterations in brain networks associated with individual differences, behavior and psychopathology. While the BOLD signal is stronger with a higher temporal resolution, ASL provides quantitative, direct measures of the physiology and metabolism of specific networks. This study systematically investigated the similarity and reliability of resting brain networks (RBNs) in BOLD and ASL. A 2×2×2 factorial design was employed where each subject underwent repeated BOLD and ASL rs-fcMRI scans on two occasions on two MRI scanners respectively. Both independent and joint FC analyses revealed common RBNs in ASL and BOLD rs-fcMRI with a moderate to high level of spatial overlap, verified by Dice Similarity Coefficients. Test–retest analyses indicated more reliable spatial network patterns in BOLD (average modal Intraclass Correlation Coefficients: 0. 905±0. 033 between-sessions; 0. 885±0. 052 between-scanners) than ASL (0. 545±0. 048; 0. 575±0. 059). Nevertheless, ASL provided highly reproducible (0. 955±0. 021; 0. 970±0. 011) network-specific CBF measurements. Moreover, we observed positive correlations between regional CBF and FC in core areas of all RBNs indicating a relationship between network connectivity and its baseline metabolism. Taken together, the combination of ASL and BOLD rs-fcMRI provides a powerful tool for characterizing the spatiotemporal and quantitative properties of RBNs. These findings pave the way for future BOLD and ASL rs-fcMRI studies in clinical populations that are carried out across time and scanners.

YNIMG Journal 2015 Journal Article

Rivalry of homeostatic and sensory-evoked emotions: Dehydration attenuates olfactory disgust and its neural correlates

• Lea Meier
• Hergen Friedrich
• Andrea Federspiel
• Kay Jann
• Yosuke Morishima
• Basile Nicolas Landis
• Roland Wiest
• Werner Strik

Neural correlates have been described for emotions evoked by states of homeostatic imbalance (e. g. thirst, hunger, and breathlessness) and for emotions induced by external sensory stimulation (such as fear and disgust). However, the neurobiological mechanisms of their interaction, when they are experienced simultaneously, are still unknown. We investigated the interaction on the neurobiological and the perceptional level using subjective ratings, serum parameters, and functional magnetic resonance imaging (fMRI) in a situation of emotional rivalry, when both a homeostatic and a sensory-evoked emotion were experienced at the same time. Twenty highly dehydrated male subjects rated a disgusting odor as significantly less repulsive when they were thirsty. On the neurobiological level, we found that this reduction in subjective disgust during thirst was accompanied by a significantly reduced neural activity in the insular cortex, a brain area known to be considerably involved in processing of disgust. Furthermore, during the experience of disgust in the satiated condition, we observed a significant functional connectivity between brain areas responding to the disgusting odor, which was absent during the stimulation in the thirsty condition. These results suggest interference of conflicting emotions: an acute homeostatic imbalance can attenuate the experience of another emotion evoked by the sensory perception of a potentially harmful external agent. This finding offers novel insights with regard to the behavioral relevance of biologically different types of emotions, indicating that some types of emotions are more imperative for behavior than others. As a general principle, this modulatory effect during the conflict of homeostatic and sensory-evoked emotions may function to safeguard survival.

YNIMG Journal 2012 Journal Article

The link between visual exploration and neuronal activity: A multi-modal study combining eye tracking, functional magnetic resonance imaging and transcranial magnetic stimulation

• Silvia Chaves
• Patrizia Vannini
• Kay Jann
• Pascal Wurtz
• Andrea Federspiel
• Thomas Nyffeler
• Mathias Luethi
• Daniela Hubl

In the present multi-modal study we aimed to investigate the role of visual exploration in relation to the neuronal activity and performance during visuospatial processing. To this end, event related functional magnetic resonance imaging er-fMRI was combined with simultaneous eye tracking recording and transcranial magnetic stimulation (TMS). Two groups of twenty healthy subjects each performed an angle discrimination task with different levels of difficulty during er-fMRI. The number of fixations as a measure of visual exploration effort was chosen to predict blood oxygen level-dependent (BOLD) signal changes using the general linear model (GLM). Without TMS, a positive linear relationship between the visual exploration effort and the BOLD signal was found in a bilateral fronto-parietal cortical network, indicating that these regions reflect the increased number of fixations and the higher brain activity due to higher task demands. Furthermore, the relationship found between the number of fixations and the performance demonstrates the relevance of visual exploration for visuospatial task solving. In the TMS group, offline theta bursts TMS (TBS) was applied over the right posterior parietal cortex (PPC) before the fMRI experiment started. Compared to controls, TBS led to a reduced correlation between visual exploration and BOLD signal change in regions of the fronto-parietal network of the right hemisphere, indicating a disruption of the network. In contrast, an increased correlation was found in regions of the left hemisphere, suggesting an intent to compensate functionality of the disturbed areas. TBS led to fewer fixations and faster response time while keeping accuracy at the same level, indicating that subjects explored more than actually needed.

YNIMG Journal 2012 Journal Article

Theta burst TMS increases cerebral blood flow in the primary motor cortex during motor performance as assessed by arterial spin labeling (ASL)

• Ariane Orosz
• Kay Jann
• Miranka Wirth
• Roland Wiest
• Thomas Dierks
• Andrea Federspiel

Theta burst stimulation (TBS) is a novel variant of repetitive transcranial magnetic stimulation (rTMS), which induces changes in neuronal excitability persisting up to 1h. When elicited in the primary motor cortex, such physiological modulations might also have an impact on motor behavior. In the present study, we applied TBS in combination with pseudo continuous arterial spin labeling (pCASL) in order to address the question of whether TBS effects are measurable by means of changes in physiological parameters such as cerebral blood flow (CBF) and if TBS-induced plasticity can modify motor behavior. Twelve right-handed healthy subjects were stimulated using an inhibitory TBS protocol at subthreshold stimulation intensity targeted over the right motor cortex. The control condition consisted of within-subject Sham treatment in a crossover design. PCASL was performed before (pre TBS/pre Sham) and immediately after treatment (post TBS/post Sham). During the pCASL runs, the subjects performed a sequential fingertapping task with the left hand at individual maximum speed. There was a significant increase of CBF in the primary motor cortex after TBS, but not after Sham. It is assumed that inhibitory TBS induced a “local virtual lesion” which leads to the mobilization of more neuronal resources. There was no TBS-specific modulation in motor behavior, which might indicate that acute changes in brain plasticity caused by TBS are immediately compensated. This compensatory reaction seems to be observable at the metabolic, but not at the behavioral level.

YNIMG Journal 2011 Journal Article

Semantic memory involvement in the default mode network: A functional neuroimaging study using independent component analysis

• Miranka Wirth
• Kay Jann
• Thomas Dierks
• Andrea Federspiel
• Roland Wiest
• Helge Horn

The Default Mode Network (DMN) is a higher order functional neural network that displays activation during passive rest and deactivation during many types of cognitive tasks. Accordingly, the DMN is viewed to represent the neural correlate of internally-generated self-referential cognition. This hypothesis implies that the DMN requires the involvement of cognitive processes, like declarative memory. The present study thus examines the spatial and functional convergence of the DMN and the semantic memory system. Using an active block-design functional Magnetic Resonance Imaging (fMRI) paradigm and Independent Component Analysis (ICA), we trace the DMN and fMRI signal changes evoked by semantic, phonological and perceptual decision tasks upon visually-presented words. Our findings show less deactivation during semantic compared to the two non-semantic tasks for the entire DMN unit and within left-hemispheric DMN regions, i. e. , the dorsal medial prefrontal cortex, the anterior cingulate cortex, the retrosplenial cortex, the angular gyrus, the middle temporal gyrus and the anterior temporal region, as well as the right cerebellum. These results demonstrate that well-known semantic regions are spatially and functionally involved in the DMN. The present study further supports the hypothesis of the DMN as an internal mentation system that involves declarative memory functions.

YNIMG Journal 2010 Journal Article

Association of individual resting state EEG alpha frequency and cerebral blood flow

• Kay Jann
• Thomas Koenig
• Thomas Dierks
• Chris Boesch
• Andrea Federspiel

Cognitive task performance differs considerably between individuals. Besides cognitive capacities, attention might be a source of such differences. The individual's EEG alpha frequency (IAF) is a putative marker of the subject's state of arousal and attention, and was found to be associated with task performance and cognitive capacities. However, little is known about the metabolic substrate (i. e. the network) underlying IAF. Here we aimed to identify this network. Correlation of IAF with regional Cerebral Blood Flow (rCBF) in fifteen young healthy subjects revealed a network of brain areas that are associated with the modulation of attention and preparedness for external input, which are relevant for task execution. We hypothesize that subjects with higher IAF have pre-activated task-relevant networks and thus are both more efficient in the task-execution, and show a reduced fMRI-BOLD response to the stimulus, not because the absolute amount of activation is smaller, but because the additional activation by processing of external input is limited due to the higher baseline.

YNIMG Journal 2008 Journal Article

BOLD correlates of continuously fluctuating epileptic activity isolated by independent component analysis

• Kay Jann
• Roland Wiest
• Martinus Hauf
• Klaus Meyer
• Chris Boesch
• Johannes Mathis
• Gerhard Schroth
• Thomas Dierks

Combined EEG/fMRI recordings offer a promising opportunity to detect brain areas with altered BOLD signal during interictal epileptic discharges (IEDs). These areas are likely to represent the irritative zone, which is itself a reflection of the epileptogenic zone. This paper reports on the imaging findings using independent component analysis (ICA) to continuously quantify epileptiform activity in simultaneously acquired EEG and fMRI. Using ICA derived factors coding for the epileptic activity takes into account that epileptic activity is continuously fluctuating with each spike differing in amplitude, duration and maybe topography, including subthreshold epileptic activity besides clear IEDs and may thus increase the sensitivity and statistical power of combined EEG/fMRI in epilepsy. Twenty patients with different types of focal and generalized epilepsy syndromes were investigated. ICA separated epileptiform activity from normal physiological brain activity and artifacts. In 16/20 patients, BOLD correlates of epileptic activity matched the EEG sources, the clinical semiology, and, if present, the structural lesions. In clinically equivocal cases, the BOLD correlates aided to attribute proper diagnosis of the underlying epilepsy syndrome. Furthermore, in one patient with temporal lobe epilepsy, BOLD correlates of rhythmic delta activity could be employed to delineate the affected hippocampus. Compared to BOLD correlates of manually identified IEDs, the sensitivity was improved from 50% (10/20) to 80%. The ICA EEG/fMRI approach is a safe, non-invasive and easily applicable technique, which can be used to identify regions with altered hemodynamic effects related to IEDs as well as intermittent rhythmic discharges in different types of epilepsy.