Arno Villringer

YNICL Journal 2025 Journal Article

Exploring the effect of multi-modal intervention against cognitive decline on atrophy and small vessel disease imaging markers in the AgeWell.de imaging study

• Frauke Beyer
• Lukas Kleine
• Andrea Zülke
• Melanie Luppa
• Toralf Mildner
• Jochen Gensichen
• Thomas Frese
• David Czock

BACKGROUND: Multimodal lifestyle interventions might help to maintain healthy cognition in older age and to delay onset of dementia. Here, we studied the effects of a multi-modal lifestyle-based intervention, based on the FINGER trial, on magnetic resonance imaging (MRI) markers of hippocampal-limbic atrophy and cerebral small vessel disease in older adults at increased risk for dementia in Germany. METHODS: Leipzig participants of the multicenter AgeWell.de randomized controlled trial underwent neuroimaging before and after a two year intervention at 3 Tesla MRI. We extracted hippocampal volume and entorhinal cortex thickness (ECT), free water fraction (FW), peak width of skeletonized mean diffusivity (PSMD), white matter hyperintensity volume and mean gray matter cerebral blood flow and assessed the effect of the intervention on these imaging markers using linear mixed models. We also tested the effect of the intervention on the hippocampus-dependent Mnemonic Similarity Test and fixel-based white matter microstructure. RESULTS: 56 individuals (mean (sd) age: 68.8 (4.2) years, 26 females, 24/32 intervention/control group) were included at baseline and 41 returned after an average of 28 months for the second assessment. ECT and FW exhibited stronger decline in the intervention compared to the control group in preregistered models but not when adjusted for baseline differences. All other markers progressed similarly across groups, however sample size was smaller than expected. In exploratory analyses, cerebral blood flow increased more in the intervention group and this change was associated with decreases in systolic blood pressure. CONCLUSIONS: In this group of older adults at risk for dementia, we find no conclusive evidence whether a multi-modal lifestyle intervention improves brain imaging markers of neurodegeneration and small vessel disease. Preliminary evidence suggested an association of the intervention, increased cerebral blood flow and systolic blood pressure reductions. ABBREVIATIONS: ECT, entorhinal cortex thickness; FW, free water fraction; WHO, world health organization; AD, Alzheimer's disease; VCI, vascular cognitive impairment; FINGER, Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability; MTL, medial temporal lobe; MIND, Mediterranean-DASH Intervention for Neurodegenerative Delay diet; cSVD, cerebral small vessel disease; WMH, white matter hyperintensities of presumed vascular origin; PSMD, peak width of the mean diffusivity distribution; WW-FINGERS, world wide FINGER studies; CAIDE, Cardiovascular Risk Factors, Aging, and Incidence of Dementia; GPP, general practitioner praxis; MRI, magnetic resonance imaging; MST, Mnemonic Similarity Test; TE, echo time; TR, repetition time; FA, flip angle; FOV, field of view; GRAPPA, GeneRalized Autocalibrating Partial Parallel Acquisition; CMRR, Center for Magnetic Resonance Research; BOLD, blood oxygenation level dependent; pcASL: pseudo-continuous arterial spin labeling; EPI, echo-planar imaging; FLAIR, fluid attenuated inversion recovery; CBF, cerebral blood flow; QA, quality assessment; GM, gray matter; HCV, hippocampal volume; eICV, estimated intracranial volume; DWI, diffusion-weighted imaging; MD, mean diffusivity; FA, fractional anisotropy TBSS: tract-based spatial statistics; CSF, cerebral spinal fluid; ISI, inter-stimulus interval; LDI, lure discrimination index; REC, recognition score; CG, control group; IG, intervention group; MoCA, Montreal Cognitive Assessment; CASMIN, Comparative Analysis of Social Mobility in Industrial Nations; BMI, body mass index; SBP/DBP, systolic/diastolic blood pressure; OSF, open science framework; LMM, linear mixed model; ANOVA, analysis of covariance.

YNICL Journal 2025 Journal Article

Short-term BCI intervention enhances functional brain connectivity associated with motor performance in chronic stroke

• Khosrov A. Grigoryan
• Karsten Mueller
• Matthias Wagner
• Diaa Masri
• Kerrin J. Pine
• Arno Villringer
• Bernhard Sehm

BACKGROUND: Evidence suggests that brain-computer interface (BCI)-based rehabilitation strategies show promise in overcoming the limited recovery potential in the chronic phase of stroke. However, the specific mechanisms driving motor function improvements are not fully understood. OBJECTIVE: We aimed at elucidating the potential functional brain connectivity changes induced by BCI training in participants with chronic stroke. METHODS: A longitudinal crossover design was employed with two groups of participants over the span of 4 weeks to allow for within-subject (n = 21) and cross-group comparisons. Group 1 (n = 11) underwent a 6-day motor imagery-based BCI training during the second week, whereas Group 2 (n = 10) received the same training during the third week. Before and after each week, both groups underwent resting state functional MRI scans (4 for Group 1 and 5 for Group 2) to establish a baseline and monitor the effects of BCI training. RESULTS: Following BCI training, an increased functional connectivity was observed between the medial prefrontal cortex of the default mode network (DMN) and motor-related areas, including the premotor cortex, superior parietal cortex, SMA, and precuneus. Moreover, these changes were correlated with the increased motor function as confirmed with upper-extremity Fugl-Meyer assessment scores, measured before and after the training. CONCLUSIONS: Our findings suggest that BCI training can enhance brain connectivity, underlying the observed improvements in motor function. They provide a basis for developing novel rehabilitation approaches using non-invasive brain stimulation for targeting functionally relevant brain regions, thereby augmenting BCI-induced neuroplasticity and enhancing motor recovery.

YNIMG Journal 2023 Journal Article

Alterations in rhythmic and non‐rhythmic resting‐state EEG activity and their link to cognition in older age

• Elena Cesnaite
• Paul Steinfath
• Mina Jamshidi Idaji
• Tilman Stephani
• Deniz Kumral
• Stefan Haufe
• Christian Sander
• Tilman Hensch

While many structural and biochemical changes in the brain have previously been associated with older age, findings concerning functional properties of neuronal networks, as reflected in their electrophysiological signatures, remain rather controversial. These discrepancies might arise due to several reasons, including diverse factors determining general spectral slowing in the alpha frequency range as well as amplitude mixing between the rhythmic and non-rhythmic parameters. We used a large dataset (N = 1703, mean age 70) to comprehensively investigate age-related alterations in multiple EEG biomarkers taking into account rhythmic and non-rhythmic activity and their individual contributions to cognitive performance. While we found strong evidence for an individual alpha peak frequency (IAF) decline in older age, we did not observe a significant relationship between theta power and age while controlling for IAF. Not only did IAF decline with age, but it was also positively associated with interference resolution in a working memory task primarily in the right and left temporal lobes suggesting its functional role in information sampling. Critically, we did not detect a significant relationship between alpha power and age when controlling for the 1/f spectral slope, while the latter one showed age-related alterations. These findings thus suggest that the entanglement of IAF slowing and power in the theta frequency range, as well as 1/f slope and alpha power measures, might explain inconsistencies reported previously in the literature. Finally, despite the absence of age-related alterations, alpha power was negatively associated with the speed of processing in the right frontal lobe while 1/f slope showed no consistent relationship to cognitive performance. Our results thus demonstrate that multiple electrophysiological features, as well as their interplay, should be considered for the comprehensive assessment of association between age, neuronal activity, and cognitive performance.

YNICL Journal 2023 Journal Article

Multiclass prediction of different dementia syndromes based on multi-centric volumetric MRI imaging

• Leonie Lampe
• Hans-Jürgen Huppertz
• Sarah Anderl-Straub
• Franziska Albrecht
• Tommaso Ballarini
• Sandrine Bisenius
• Karsten Mueller
• Sebastian Niehaus

INTRODUCTION: Dementia syndromes can be difficult to diagnose. We aimed at building a classifier for multiple dementia syndromes using magnetic resonance imaging (MRI). METHODS: Atlas-based volumetry was performed on T1-weighted MRI data of 426 patients and 51 controls from the multi-centric German Research Consortium of Frontotemporal Lobar Degeneration including patients with behavioral variant frontotemporal dementia, Alzheimer's disease, the three subtypes of primary progressive aphasia, i.e., semantic, logopenic and nonfluent-agrammatic variant, and the atypical parkinsonian syndromes progressive supranuclear palsy and corticobasal syndrome. Support vector machine classification was used to classify each patient group against controls (binary classification) and all seven diagnostic groups against each other in a multi-syndrome classifier (multiclass classification). RESULTS: The binary classification models reached high prediction accuracies between 71 and 95% with a chance level of 50%. Feature importance reflected disease-specific atrophy patterns. The multi-syndrome model reached accuracies of more than three times higher than chance level but was far from 100%. Multi-syndrome model performance was not homogenous across dementia syndromes, with better performance in syndromes characterized by regionally specific atrophy patterns. Whereas diseases generally could be classified vs controls more correctly with increasing severity and duration, differentiation between diseases was optimal in disease-specific windows of severity and duration. DISCUSSION: Results suggest that automated methods applied to MR imaging data can support physicians in diagnosis of dementia syndromes. It is particularly relevant for orphan diseases beside frequent syndromes such as Alzheimer's disease.

YNIMG Journal 2023 Journal Article

Rapid volumetric brain changes after acute psychosocial stress

• Marie Uhlig
• Janis D. Reinelt
• Mark E. Lauckner
• Deniz Kumral
• H. Lina Schaare
• Toralf Mildner
• Anahit Babayan
• Harald E. Möller

Stress is an important trigger for brain plasticity: Acute stress can rapidly affect brain activity and functional connectivity, and chronic or pathological stress has been associated with structural brain changes. Measures of structural magnetic resonance imaging (MRI) can be modified by short-term motor learning or visual stimulation, suggesting that they also capture rapid brain changes. Here, we investigated volumetric brain changes (together with changes in T1 relaxation rate and cerebral blood flow) after acute stress in humans as well as their relation to psychophysiological stress measures. Sixty-seven healthy men (25.8±2.7 years) completed a standardized psychosocial laboratory stressor (Trier Social Stress Test) or a control version while blood, saliva, heart rate, and psychometrics were sampled. Structural MRI (T1 mapping / MP2RAGE sequence) at 3T was acquired 45 min before and 90 min after intervention onset. Grey matter volume (GMV) changes were analysed using voxel-based morphometry. Associations with endocrine, autonomic, and subjective stress measures were tested with linear models. We found significant group-by-time interactions in several brain clusters including anterior/mid-cingulate cortices and bilateral insula: GMV was increased in the stress group relative to the control group, in which several clusters showed a GMV decrease. We found a significant group-by-time interaction for cerebral blood flow, and a main effect of time for T1 values (longitudinal relaxation time). In addition, GMV changes were significantly associated with state anxiety and heart rate variability changes. Such rapid GMV changes assessed with VBM may be induced by local tissue adaptations to changes in energy demand following neural activity. Our findings suggest that endogenous brain changes are counteracted by acute psychosocial stress, which emphasizes the importance of considering homeodynamic processes and generally highlights the influence of stress on the brain.

YNIMG Journal 2023 Journal Article

Visuo-motor transformations in the intraparietal sulcus mediate the acquisition of endovascular medical skill

• Katja I. Paul
• Karsten Mueller
• Paul-Noel Rousseau
• Annegret Glathe
• Niels A. Taatgen
• Fokie Cnossen
• Peter Lanzer
• Arno Villringer

Performing endovascular medical interventions safely and efficiently requires a diverse set of skills that need to be practised in dedicated training sessions. Here, we used multimodal magnetic resonance (MR) imaging to determine the structural and functional plasticity and core skills associated with skill acquisition. A training group learned to perform a simulator-based endovascular procedure, while a control group performed a simplified version of the task; multimodal MR images were acquired before and after training. Using a well-controlled interaction design, we found strong multimodal evidence for the role of the intraparietal sulcus (IPS) in endovascular skill acquisition that is in line with previous work implicating the structure in visuospatial transformations including simple visuo-motor and mental rotation tasks. Our results provide a unique window into the multimodal nature of rapid structural and functional plasticity of the human brain while learning a multifaceted and complex clinical skill. Further, our results provide a detailed description of the plasticity process associated with endovascular skill acquisition and highlight specific facets of skills that could enhance current medical pedagogy and be useful to explicitly target during clinical resident training.

YNIMG Journal 2022 Journal Article

Harmoni: A method for eliminating spurious interactions due to the harmonic components in neuronal data

• Mina Jamshidi Idaji
• Juanli Zhang
• Tilman Stephani
• Guido Nolte
• Klaus-Robert Müller
• Arno Villringer
• Vadim V. Nikulin

Cross-frequency synchronization (CFS) has been proposed as a mechanism for integrating spatially and spectrally distributed information in the brain. However, investigating CFS in Magneto- and Electroencephalography (MEG/EEG) is hampered by the presence of spurious neuronal interactions due to the non-sinusoidal waveshape of brain oscillations. Such waveshape gives rise to the presence of oscillatory harmonics mimicking genuine neuronal oscillations. Until recently, however, there has been no methodology for removing these harmonics from neuronal data. In order to address this long-standing challenge, we introduce a novel method (called HARMOnic miNImization - Harmoni) that removes the signal components which can be harmonics of a non-sinusoidal signal. Harmoni's working principle is based on the presence of CFS between harmonic components and the fundamental component of a non-sinusoidal signal. We extensively tested Harmoni in realistic EEG simulations. The simulated couplings between the source signals represented genuine and spurious CFS and within-frequency phase synchronization. Using diverse evaluation criteria, including ROC analyses, we showed that the within- and cross-frequency spurious interactions are suppressed significantly, while the genuine activities are not affected. Additionally, we applied Harmoni to real resting-state EEG data revealing intricate remote connectivity patterns which are usually masked by the spurious connections. Given the ubiquity of non-sinusoidal neuronal oscillations in electrophysiological recordings, Harmoni is expected to facilitate novel insights into genuine neuronal interactions in various research fields, and can also serve as a steppingstone towards the development of further signal processing methods aiming at refining within- and cross-frequency synchronization in electrophysiological recordings.

YNIMG Journal 2022 Journal Article

Harmonized-Multinational qEEG norms (HarMNqEEG)

• Min Li
• Ying Wang
• Carlos Lopez-Naranjo
• Shiang Hu
• Ronaldo César García Reyes
• Deirel Paz-Linares
• Ariosky Areces-Gonzalez
• Aini Ismafairus Abd Hamid

This paper extends frequency domain quantitative electroencephalography (qEEG) methods pursuing higher sensitivity to detect Brain Developmental Disorders. Prior qEEG work lacked integration of cross-spectral information omitting important functional connectivity descriptors. Lack of geographical diversity precluded accounting for site-specific variance, increasing qEEG nuisance variance. We ameliorate these weaknesses. (i) Create lifespan Riemannian multinational qEEG norms for cross-spectral tensors. These norms result from the HarMNqEEG project fostered by the Global Brain Consortium. We calculate the norms with data from 9 countries, 12 devices, and 14 studies, including 1564 subjects. Instead of raw data, only anonymized metadata and EEG cross-spectral tensors were shared. After visual and automatic quality control, developmental equations for the mean and standard deviation of qEEG traditional and Riemannian DPs were calculated using additive mixed-effects models. We demonstrate qEEG "batch effects" and provide methods to calculate harmonized z-scores. (ii) We also show that harmonized Riemannian norms produce z-scores with increased diagnostic accuracy predicting brain dysfunction produced by malnutrition in the first year of life and detecting COVID induced brain dysfunction. (iii) We offer open code and data to calculate different individual z-scores from the HarMNqEEG dataset. These results contribute to developing bias-free, low-cost neuroimaging technologies applicable in various health settings.

YNICL Journal 2022 Journal Article

The influence of white matter lesions on the electric field in transcranial electric stimulation

• Benjamin Kalloch
• Konstantin Weise
• Leonie Lampe
• Pierre-Louis Bazin
• Arno Villringer
• Mario Hlawitschka
• Bernhard Sehm

BACKGROUND: Transcranial direct current stimulation (tDCS) is a promising tool to enhance therapeutic efforts, for instance, after a stroke. The achieved stimulation effects exhibit high inter-subject variability, primarily driven by perturbations of the induced electric field (EF). Differences are further elevated in the aging brain due to anatomical changes such as atrophy or lesions. Informing tDCS protocols by computer-based, individualized EF simulations is a suggested measure to mitigate this variability. OBJECTIVE: While brain anatomy in general and specifically atrophy as well as stroke lesions are deemed influential on the EF in simulation studies, the influence of the uncertainty in the change of the electrical properties of the white matter due to white matter lesions (WMLs) has not been quantified yet. METHODS: A group simulation study with 88 subjects assigned into four groups of increasing lesion load was conducted. Due to the lack of information about the electrical conductivity of WMLs, an uncertainty analysis was employed to quantify the variability in the simulation when choosing an arbitrary conductivity value for the lesioned tissue. RESULTS: The contribution of WMLs to the EF variance was on average only one tenth to one thousandth of the contribution of the other modeled tissues. While the contribution of the WMLs significantly increased (p≪.01) in subjects exhibiting a high lesion load compared to low lesion load subjects, typically by a factor of 10 and above, the total variance of the EF didnot change with the lesion load. CONCLUSION: Our results suggest that WMLs do not perturb the EF globally and can thus be omitted when modeling subjects with low to medium lesion load. However, for high lesion load subjects, the omission of WMLs may yield less robust local EF estimations in the vicinity of the lesioned tissue. Our results contribute to the efforts of accurate modeling of tDCS for treatment planning.

YNIMG Journal 2022 Journal Article

Towards the interpretability of deep learning models for multi-modal neuroimaging: Finding structural changes of the ageing brain

• Simon M. Hofmann
• Frauke Beyer
• Sebastian Lapuschkin
• Ole Goltermann
• Markus Loeffler
• Klaus-Robert Müller
• Arno Villringer
• Wojciech Samek

Brain-age (BA) estimates based on deep learning are increasingly used as neuroimaging biomarker for brain health; however, the underlying neural features have remained unclear. We combined ensembles of convolutional neural networks with Layer-wise Relevance Propagation (LRP) to detect which brain features contribute to BA. Trained on magnetic resonance imaging (MRI) data of a population-based study (n = 2637, 18-82 years), our models estimated age accurately based on single and multiple modalities, regionally restricted and whole-brain images (mean absolute errors 3.37-3.86 years). We find that BA estimates capture ageing at both small and large-scale changes, revealing gross enlargements of ventricles and subarachnoid spaces, as well as white matter lesions, and atrophies that appear throughout the brain. Divergence from expected ageing reflected cardiovascular risk factors and accelerated ageing was more pronounced in the frontal lobe. Applying LRP, our study demonstrates how superior deep learning models detect brain-ageing in healthy and at-risk individuals throughout adulthood.

YNIMG Journal 2021 Journal Article

Heartbeat and somatosensory perception

• Esra Al
• Fivos Iliopoulos
• Vadim V. Nikulin
• Arno Villringer

Our perception of the external world is influenced by internal bodily signals. For example, we recently showed that timing of stimulation along the cardiac cycle and spontaneous fluctuations of heartbeat-evoked potential (HEP) amplitudes influence somatosensory perception and the associated neural processing (Al et al., 2020). While cardiac phase affected detection sensitivity and late components of the somatosensory-evoked potentials (SEPs), HEP amplitudes affected detection criterion and both early and late SEP components. In a new EEG study, we investigate whether these results are replicable in a modified paradigm, which includes two succeeding temporal intervals. In one of the intervals, subjects received a weak electrical finger stimulation and reported first whether they detected any stimulation and then allocated the stimulus to one of the two intervals. Our results confirm the previously reported cardiac cycle and prestimulus HEP effects on somatosensory perception and evoked potentials. In addition, we obtained two new findings. Source analyses in this and our original study show that the increased likelihood of conscious perception goes along with HEP fluctuations in parietal and posterior cingulate regions, known to play important roles in interoceptive processes. Furthermore, HEP amplitudes were shown to decrease when subjects engaged in the somatosensory task compared to a resting state condition. Our findings are consistent with the view that HEP amplitudes are a marker of interoceptive (versus exteroceptive) attention and provide a neural underpinning for this view.

YNIMG Journal 2021 Journal Article

Neural correlates of conscious tactile perception: An analysis of BOLD activation patterns and graph metrics

• Martin Grund
• Norman Forschack
• Till Nierhaus
• Arno Villringer

Theories of human consciousness substantially vary in the proposed spatial extent of brain activity associated with conscious perception as well as in the assumed functional alterations within the involved brain regions. Here, we investigate which local and global changes in brain activity accompany conscious somatosensory perception following electrical finger nerve stimulation, and whether there are whole-brain functional network alterations by means of graph metrics. Thirty-eight healthy participants performed a somatosensory detection task and reported their decision confidence during fMRI. For conscious tactile perception in contrast to undetected near-threshold trials (misses), we observed increased BOLD activity in the precuneus, the intraparietal sulcus, the insula, the nucleus accumbens, the inferior frontal gyrus and the contralateral secondary somatosensory cortex. For misses compared to correct rejections, bilateral secondary somatosensory cortices, supplementary motor cortex and insula showed greater activations. The analysis of whole-brain functional network topology for hits, misses and correct rejections, did not result in any significant differences in modularity, participation, clustering or path length, which was supported by Bayes factor statistics. In conclusion, for conscious somatosensory perception, our results are consistent with an involvement of (probably) domain-general brain areas (precuneus, insula, inferior frontal gyrus) in addition to somatosensory regions; our data do not support the notion of specific changes in graph metrics associated with conscious experience. For the employed somatosensory submodality of fine electrical current stimulation, this speaks for a global broadcasting of sensory content across the brain without substantial reconfiguration of the whole-brain functional network resulting in an integrative conscious experience.

YNIMG Journal 2021 Journal Article

Neuronal biomarkers of Parkinson's disease are present in healthy aging

• Juanli Zhang
• Mina Jamshidi Idaji
• Arno Villringer
• Vadim V. Nikulin

The prevalence of Parkinson's disease (PD) increases with aging and both processes share similar cellular mechanisms and alterations in the dopaminergic system. Yet it remains to be investigated whether aging can also demonstrate electrophysiological neuronal signatures typically associated with PD. Previous work has shown that phase-amplitude coupling (PAC) between the phase of beta oscillations and the amplitude of gamma oscillations as well as beta bursts features can serve as electrophysiological biomarkers for PD. Here we hypothesize that these metrics are also present in apparently healthy elderly subjects. Using resting state multichannel EEG measurements, we show that PAC between beta oscillation and broadband gamma activity (50-150 Hz) is elevated in a group of elderly (59-77 years) compared to young volunteers (20-35 years) without PD. Importantly, the increase of PAC is statistically significant even after ruling out confounds relating to changes in spectral power and non-sinusoidal shape of beta oscillation. Moreover, a trend for a higher percentage of longer beta bursts (> 0.2 s) along with the increase in their incidence rate is also observed for elderly subjects. Using inverse modeling, we further show that elevated PAC and longer beta bursts are most pronounced in the sensorimotor areas. Moreover, we show that PAC and longer beta bursts might reflect distinct mechanisms, since their spatial patterns only partially overlap and the correlation between them is weak. Taken together, our findings provide novel evidence that electrophysiological biomarkers of PD may already occur in apparently healthy elderly subjects. We hypothesize that PAC and beta bursts characteristics in aging might reflect a pre-clinical state of PD and suggest their predictive value to be tested in prospective longitudinal studies.

YNIMG Journal 2020 Journal Article

Dissociable neural correlates of stimulation intensity and detection in somatosensation

• Norman Forschack
• Till Nierhaus
• Matthias M. Müller
• Arno Villringer

Somatosensory stimulation intensity and behavioral detection are positively related, and both correlate with neural responses. However, it is still controversial as to what extent stimulus intensity and early somatosensory evoked potentials (SEP) predict detection and how these parameters interact with pre-stimulus brain oscillatory states, which also influence sensory processing. Here we investigated how early SEP components encode stimulation intensity, how pre-stimulus alpha- and beta-band amplitudes interact with SEPs, and which neural markers predict stimulus detection. To this end, we randomly presented electrical finger nerve stimulation with various intensities distributed along the individual psychometric response function (including catch trials) while recording the EEG. Participants reported stimulus presence on a trial-by-trial basis (one-alternative-forced-choice). For the lowest (imperceptible) intensities, participants showed zero (behavioral) sensitivity despite measurable early cortical processing reflected by the P50 component. The P50 amplitude scaled with increasing stimulation intensities but was not predictive of stimulus detection. Instead, detection was associated with the later negative N150 component, as well as with pre-stimulus lowered somatosensory alpha- and increased frontal beta-band amplitudes. Our results give evidence for a serial representation of stimulus intensity and detection, as reflected by the P50 and N150 amplitude, respectively. Furthermore, stimulus detection seems to depend on the current brain state, rendering upcoming stimulation being reportable or not.

YNIMG Journal 2020 Journal Article

Nonlinear interaction decomposition (NID): A method for separation of cross-frequency coupled sources in human brain

• Mina Jamshidi Idaji
• Klaus-Robert Müller
• Guido Nolte
• Burkhard Maess
• Arno Villringer
• Vadim V. Nikulin

Cross-frequency coupling (CFC) between neuronal oscillations reflects an integration of spatially and spectrally distributed information in the brain. Here, we propose a novel framework for detecting such interactions in Magneto- and Electroencephalography (MEG/EEG), which we refer to as Nonlinear Interaction Decomposition (NID). In contrast to all previous methods for separation of cross-frequency (CF) sources in the brain, we propose that the extraction of nonlinearly interacting oscillations can be based on the statistical properties of their linear mixtures. The main idea of NID is that nonlinearly coupled brain oscillations can be mixed in such a way that the resulting linear mixture has a non-Gaussian distribution. We evaluate this argument analytically for amplitude-modulated narrow-band oscillations which are either phase-phase or amplitude-amplitude CF coupled. We validated NID extensively with simulated EEG obtained with realistic head modelling. The method extracted nonlinearly interacting components reliably even at SNRs as small as − 15 dB. Additionally, we applied NID to the resting-state EEG of 81 subjects to characterize CF phase-phase coupling between alpha and beta oscillations. The extracted sources were located in temporal, parietal and frontal areas, demonstrating the existence of diverse local and distant nonlinear interactions in resting-state EEG data. All codes are available publicly via GitHub.

YNIMG Journal 2020 Journal Article

Reduction of somatosensory functional connectivity by transcranial alternating current stimulation at endogenous mu-frequency

• Christopher Gundlach
• Matthias M. Müller
• Maike Hoff
• Patrick Ragert
• Till Nierhaus
• Arno Villringer
• Bernhard Sehm

Alpha, the most prominent human brain rhythm, might reflect a mechanism of functional inhibition for gating neural processing. This concept has been derived predominantly from local measures of inhibition, while large-scale network mechanisms to guide information flow are largely unknown. Here, we investigated functional connectivity changes on a whole-brain level by concurrent transcranial alternating current stimulation (tACS) and resting-state functional MRI in humans. We specifically focused on somatosensory alpha-band oscillations by adjusting the tACS frequency to each individual´s somatosensory (mu-) alpha peak frequency (mu-tACS). Potential differences of Eigenvector Centrality of primary somatosensory cortex (S1) as well as on a whole brain level between mu-tACS and sham were analyzed. Our results demonstrate that mu-tACS induces a locally-specific decrease in whole-brain functional connectivity of left S1. An additional exploratory analysis revealed that this effect primarily depends on a decrease in functional connectivity between S1 and a network of regions that are crucially involved in somatosensory processing. Furthermore, the decrease in functional centrality was specific to mu-tACS and was not observed when tACS was applied in the gamma-range in an independent study. Our findings provide evidence that modulated somatosensory (mu-) alpha-activity may affect whole-brain network level activity by decoupling primary sensory areas from other hubs involved in sensory processing.

YNIMG Journal 2019 Journal Article

Acute psychosocial stress alters thalamic network centrality

• Janis Reinelt
• Marie Uhlig
• Karsten Müller
• Mark E. Lauckner
• Deniz Kumral
• H. Lina Schaare
• Blazej M. Baczkowski
• Anahit Babayan

Acute stress triggers a broad psychophysiological response that is adaptive if rapidly activated and terminated. While the brain controls the stress response, it is strongly affected by it. Previous research of stress effects on brain activation and connectivity has mainly focused on pre-defined brain regions or networks, potentially missing changes in the rest of the brain. We here investigated how both stress reactivity and stress recovery are reflected in whole-brain network topology and how changes in functional connectivity relate to other stress measures. Healthy young males (n = 67) completed the Trier Social Stress Test or a control task. From 60 min before until 105 min after stress onset, blocks of resting-state fMRI were acquired. Subjective, autonomic, and endocrine measures of the stress response were assessed throughout the experiment. Whole-brain network topology was quantified using Eigenvector centrality (EC) mapping, which detects central hubs of a network. Stress influenced subjective affect, autonomic activity, and endocrine measures. EC differences between groups as well as before and after stress exposure were found in the thalamus, due to widespread connectivity changes in the brain. Stress-driven EC increases in the thalamus were significantly correlated with subjective stress ratings and showed non-significant trends for a correlation with heart rate variability and saliva cortisol. Furthermore, increases in thalamic EC and in saliva cortisol persisted until 105 min after stress onset. We conclude that thalamic areas are central for information processing after stress exposure and may provide an interface for the stress response in the rest of the body and in the mind.

YNIMG Journal 2019 Journal Article

Power and temporal dynamics of alpha oscillations at rest differentiate cognitive performance involving sustained and phasic cognitive control

• Keyvan Mahjoory
• Elena Cesnaite
• Friederike U. Hohlefeld
• Arno Villringer
• Vadim V. Nikulin

Resting state neuronal activity in EEG/MEG recordings is primarily characterized by the presence of alpha oscillations (approx. 8–12 Hz). However, their functional significance and link to cognitive task performance remains elusive. We investigated resting state neuronal activity and its relation to task performance by assessing traditional measures of alpha activity (power and individual alpha peak frequency) and dynamic properties of the signal measured by long-range temporal correlations (LRTC). Multichannel EEG was recorded at rest in 82 healthy male adults and compared to their cognitive performance, measured by tests involving executive functions, working memory, short- and long-term memory demands. Our results showed that attention-span scores positively correlated with alpha power at rest, with corresponding neuronal sources located primarily in the left-hemispheric anterior cingulate cortex, parietal regions, and bilateral suplementary motor areas. Furthermore, better working memory performance was related to increased LRTC of alpha oscillations at rest in the right hemispheric fronto-parietal, temporal, and occipital regions. Our findings suggest that resting state neuronal activity may reflect properties of brain networks that are functionally relevant for cognitive task performance. While alpha power measured at rest might relate to tasks that employ sustained inhibitory control, LRTC are suggested to reflect the capacity of neuronal networks to perform tasks that require phasic attention and quick adaptation to changing task demands.

YNIMG Journal 2019 Journal Article

Structural connectivity prior to whole-body sensorimotor skill learning associates with changes in resting state functional connectivity

• Nobuaki Mizuguchi
• Tom Maudrich
• Rouven Kenville
• Daniel Carius
• Dennis Maudrich
• Arno Villringer
• Patrick Ragert

Changes in resting state functional connectivity are induced by sensorimotor training and assumed to be concomitant of motor learning, although a potential relationship between functional and structural connectivity associated with sensorimotor sequence learning remains elusive. To investigate whether initial structural connectivity relates to changes in functional connectivity, we evaluated resting state functional connectivity (rs-FC), white matter fibre density (FD), fibre-bundle cross-section (FC), and gray matter volume (GMV) in healthy human participants before and after two days of performing a complex whole-body serial reaction time task (CWB-SRTT). As CWB-SRTT was implicit, participants were not told about the presence of any sequence. Since the lateral prefrontal cortex (PFC) plays an important role in sequence learning, we hypothesized that structural connectivity within the PFC prior to learning is associated with changes in rs-FC involving the lateral PFC. Sequence specific improvements, as assessed by the time difference between the last random and the last sequence blocks, were observed for reaction times, suggesting that sensorimotor sequence memory was acquired. Rs-FC between the right lateral PFC and bilateral striatum increased significantly in the learning group, when compared to a control group who performed only random blocks. This indicated that rs-FC changes are related to sequence memory but not to exercise itself. In addition, changes in rs-FC between the right lateral PFC and the left striatum were correlated with sequence specific improvements in individual reaction times. Furthermore, changes in rs-FC between right lateral PFC and left striatum were positively correlated with FC in the right anterior corona radiata measured before the task. We did not find any structural changes or significant correlations in FD or GMV. These findings suggest that an early phase of sensorimotor sequence learning in complex whole-body movements is associated with an increase in rs-FC between prefrontal and subcortical regions. Furthermore, we provide novel evidence that CWB-SRTT-induced changes in rs-FC were correlated with FC within the PFC.

YNICL Journal 2019 Journal Article

The impact of ischemic stroke on connectivity gradients

• Şeyma Bayrak
• Ahmed A. Khalil
• Kersten Villringer
• Jochen B. Fiebach
• Arno Villringer
• Daniel S. Margulies
• Smadar Ovadia-Caro

The functional organization of the brain can be represented as a low-dimensional space that reflects its macroscale hierarchy. The dimensions of this space, described as connectivity gradients, capture the similarity of areas' connections along a continuous space. Studying how pathological perturbations with known effects on functional connectivity affect these connectivity gradients provides support for their biological relevance. Previous work has shown that localized lesions cause widespread functional connectivity alterations in structurally intact areas, affecting a network of interconnected regions. By using acute stroke as a model of the effects of focal lesions on the connectome, we apply the connectivity gradient framework to depict how functional reorganization occurs throughout the brain, unrestricted by traditional definitions of functional network boundaries. We define a three-dimensional connectivity space template based on functional connectivity data from healthy controls. By projecting lesion locations into this space, we demonstrate that ischemic strokes result in dimension-specific alterations in functional connectivity over the first week after symptom onset. Specifically, changes in functional connectivity were captured along connectivity Gradients 1 and 3. The degree of functional connectivity change was associated with the distance from the lesion along these connectivity gradients (a measure of functional similarity) regardless of the anatomical distance from the lesion. Together, these results provide support for the biological validity of connectivity gradients and suggest a novel framework to characterize connectivity alterations after stroke.

YNIMG Journal 2018 Journal Article

Effects of resveratrol on memory performance, hippocampus connectivity and microstructure in older adults – A randomized controlled trial

• Sebastian Huhn
• Frauke Beyer
• Rui Zhang
• Leonie Lampe
• Jana Grothe
• Jürgen Kratzsch
• Anja Willenberg
• Jana Breitfeld

Introduction The polyphenol resveratrol has been suggested to exert beneficial effects on memory and the aging hippocampus due to calorie-restriction mimicking effects. However, the evidence based on human interventional studies is scarce. We therefore aimed to determine the effects of resveratrol on memory performance, and to identify potential underlying mechanisms using a broad array of blood-based biomarkers as well as hippocampus connectivity and microstructure assessed with ultra-high field magnetic resonance imaging (UHF-MRI). Methods In this double-blind, randomized controlled trial, 60 elderly participants (60–79 years) with a wide body-mass index (BMI) range of 21–37 kg/m2 were randomized to receive either resveratrol (200 mg/day) or placebo for 26 weeks (registered at ClinicalTrials. gov: NCT02621554). Baseline and follow-up assessments included the California Verbal Learning Task (CVLT, main outcome), the ModBent task, anthropometry, markers of glucose and lipid metabolism, inflammation and neurotrophins derived from fasting blood, multimodal neuroimaging at 3 and 7 T, and questionnaires to assess confounding factors. Results Multivariate repeated-measures ANOVA did not detect significant time by group effects for CVLT performance. There was a trend for preserved pattern recognition memory after resveratrol, while performance decreased in the placebo group (n. s. , p = 0. 07). Further exploratory analyses showed increases in both groups over time in body fat, cholesterol, fasting glucose, interleukin 6, high sensitive C-reactive protein, tumor necrosis factor alpha and in mean diffusivity of the subiculum and presubiculum, as well as decreases in physical activity, brain-derived neurotrophic factor and insulin-like growth factor 1 at follow-up, which were partly more pronounced after resveratrol. Discussion This interventional study failed to show significant improvements in verbal memory after 6 months of resveratrol in healthy elderly with a wide BMI range. A non-significant trend emerged for positive effects on pattern recognition memory, while possible confounding effects of unfavorable changes in lifestyle behavior, neurotrophins and inflammatory markers occurred. Our findings also indicate the feasibility to detect (un)healthy aging-related changes in measures of hippocampus microstructure after 6 months using 7T diffusion MRI. More studies incorporating a longer duration and larger sample size are needed to determine if resveratrol enhances memory performance in healthy older adults.

YNIMG Journal 2018 Journal Article

Intermittent compared to continuous real-time fMRI neurofeedback boosts control over amygdala activation

• Lydia Hellrung
• Anja Dietrich
• Maurice Hollmann
• Burkhard Pleger
• Christian Kalberlah
• Elisabeth Roggenhofer
• Arno Villringer
• Annette Horstmann

Real-time fMRI neurofeedback is a feasible tool to learn the volitional regulation of brain activity. So far, most studies provide continuous feedback information that is presented upon every volume acquisition. Although this maximizes the temporal resolution of feedback information, it may be accompanied by some disadvantages. Participants can be distracted from the regulation task due to (1) the intrinsic delay of the hemodynamic response and associated feedback and (2) limited cognitive resources available to simultaneously evaluate feedback information and stay engaged with the task. Here, we systematically investigate differences between groups presented with different variants of feedback (continuous vs. intermittent) and a control group receiving no feedback on their ability to regulate amygdala activity using positive memories and feelings. In contrast to the feedback groups, no learning effect was observed in the group without any feedback presentation. The group receiving intermittent feedback exhibited better amygdala regulation performance when compared with the group receiving continuous feedback. Behavioural measurements show that these effects were reflected in differences in task engagement. Overall, we not only demonstrate that the presentation of feedback is a prerequisite to learn volitional control of amygdala activity but also that intermittent feedback is superior to continuous feedback presentation.

YNIMG Journal 2018 Journal Article

White matter microstructural variability mediates the relation between obesity and cognition in healthy adults

• Rui Zhang
• Frauke Beyer
• Leonie Lampe
• Tobias Luck
• Steffi G. Riedel-Heller
• Markus Loeffler
• Matthias L. Schroeter
• Michael Stumvoll

Obesity has been linked with structural and functional brain changes. However, the impact of obesity on brain and cognition in aging remains debatable, especially for white matter. We therefore aimed to determine the effects of obesity on white matter microstructure and potential implications for cognition in a well-characterized large cohort of healthy adults. In total, 1255 participants (50% females, 19–80 years, BMI 16. 8–50. 2 kg/m2) with diffusion-weighted magnetic resonance imaging at 3T were analysed. Tract-based spatial statistics (TBSS) probed whether body mass index (BMI) and waist-to-hip ratio (WHR) were related to fractional anisotropy (FA). We conducted partial correlations and mediation analyses to explore whether obesity or regional FA were related to cognitive performance. Analyses were adjusted for demographic, genetic, and obesity-associated confounders. Results showed that higher BMI and higher WHR were associated with lower FA in multiple white matter tracts (p < 0. 05, FWE-corrected). Mediation analyses provided evidence for indirect negative effects of higher BMI and higher WHR on executive functions and processing speed through lower FA in fiber tracts connecting (pre)frontal, visual, and associative areas (indirect paths, |ß| ≥ 0. 01; 99% |CI| > 0). This large cross-sectional study showed that obesity is correlated with lower FA in multiple white matter tracts in otherwise healthy adults, independent of confounders. Moreover, although effect sizes were small, mediation results indicated that visceral obesity was linked to poorer executive functions and lower processing speed through lower FA in callosal and associative fiber tracts. Longitudinal studies are needed to support this hypothesis.

YNIMG Journal 2017 Journal Article

In need of constraint: Understanding the role of the cingulate cortex in the impulsive mind

• Johannes Golchert
• Jonathan Smallwood
• Elizabeth Jefferies
• Franziskus Liem
• Julia M. Huntenburg
• Marcel Falkiewicz
• Mark E. Lauckner
• Sabine Oligschläger

Impulsive behavior often occurs without forethought and can be driven by strong emotions or sudden impulses, leading to problems in cognition and behavior across a wide range of situations. Although neuroimaging studies have explored the neurocognitive indicators of impulsivity, the large-scale functional networks that contribute to different aspects of impulsive cognition remain unclear. In particular, we lack a coherent account of why impulsivity is associated with such a broad range of different psychological features. Here, we use resting state functional connectivity, acquired in two independent samples, to investigate the neural substrates underlying different aspects of self-reported impulsivity. Based on the involvement of the anterior cingulate cortex (ACC) in cognitive but also affective processes, five seed regions were placed along the caudal to rostral gradient of the ACC. We found that positive urgency was related to functional connectivity between subgenual ACC and bilateral parietal regions such as retrosplenial cortex potentially highlighting this connection as being important in the modulation of the non-prospective, hastiness – related aspects of impulsivity. Further, two impulsivity dimensions were associated with significant alterations in functional connectivity of the supragenual ACC: (i) lack of perseverance was positively correlated to connectivity with the bilateral dorsolateral prefrontal cortex and right inferior frontal gyrus and (ii) lack of premeditation was inversely associated with functional connectivity with clusters within bilateral occipital cortex. Further analysis revealed that these connectivity patterns overlapped with bilateral dorsolateral prefrontal and bilateral occipital regions of the multiple demand network, a large-scale neural system implicated in the general control of thought and action. Together these results demonstrate that different forms of impulsivity have different neural correlates, which are linked to the functional connectivity of a region of anterior cingulate cortex. This suggests that poor perseveration and premeditation might be linked to dysfunctions in how the rostral zone of the ACC interacts with the multiple demand network that allows cognition to proceed in a controlled way.

YNIMG Journal 2017 Journal Article

Individual variation in intentionality in the mind-wandering state is reflected in the integration of the default-mode, fronto-parietal, and limbic networks

• Johannes Golchert
• Jonathan Smallwood
• Elizabeth Jefferies
• Paul Seli
• Julia M. Huntenburg
• Franziskus Liem
• Mark E. Lauckner
• Sabine Oligschläger

Mind-wandering has a controversial relationship with cognitive control. Existing psychological evidence supports the hypothesis that episodes of mind-wandering reflect a failure to constrain thinking to task-relevant material, as well the apparently alternative view that control can facilitate the expression of self-generated mental content. We assessed whether this apparent contradiction arises because of a failure to consider differences in the types of thoughts that occur during mind-wandering, and in particular, the associated level of intentionality. Using multi-modal magnetic resonance imaging (MRI) analysis, we examined the cortical organisation that underlies inter-individual differences in descriptions of the spontaneous or deliberate nature of mind-wandering. Cortical thickness, as well as functional connectivity analyses, implicated regions relevant to cognitive control and regions of the default-mode network for individuals who reported high rates of deliberate mind-wandering. In contrast, higher reports of spontaneous mind-wandering were associated with cortical thinning in parietal and posterior temporal regions in the left hemisphere (which are important in the control of cognition and attention) as well as heightened connectivity between the intraparietal sulcus and a region that spanned limbic and default-mode regions in the ventral inferior frontal gyrus. Finally, we observed a dissociation in the thickness of the retrosplenial cortex/lingual gyrus, with higher reports of spontaneous mind-wandering being associated with thickening in the left hemisphere, and higher repots of deliberate mind-wandering with thinning in the right hemisphere. These results suggest that the intentionality of the mind-wandering state depends on integration between the control and default-mode networks, with more deliberation being associated with greater integration between these systems. We conclude that one reason why mind-wandering has a controversial relationship with control is because it depends on whether the thoughts emerge in a deliberate or spontaneous fashion.

YNIMG Journal 2017 Journal Article

Predicting brain-age from multimodal imaging data captures cognitive impairment

• Franziskus Liem
• Gaël Varoquaux
• Jana Kynast
• Frauke Beyer
• Shahrzad Kharabian Masouleh
• Julia M. Huntenburg
• Leonie Lampe
• Mehdi Rahim

The disparity between the chronological age of an individual and their brain-age measured based on biological information has the potential to offer clinically relevant biomarkers of neurological syndromes that emerge late in the lifespan. While prior brain-age prediction studies have relied exclusively on either structural or functional brain data, here we investigate how multimodal brain-imaging data improves age prediction. Using cortical anatomy and whole-brain functional connectivity on a large adult lifespan sample (N=2354, age 19–82), we found that multimodal data improves brain-based age prediction, resulting in a mean absolute prediction error of 4. 29 years. Furthermore, we found that the discrepancy between predicted age and chronological age captures cognitive impairment. Importantly, the brain-age measure was robust to confounding effects: head motion did not drive brain-based age prediction and our models generalized reasonably to an independent dataset acquired at a different site (N=475). Generalization performance was increased by training models on a larger and more heterogeneous dataset. The robustness of multimodal brain-age prediction to confounds, generalizability across sites, and sensitivity to clinically-relevant impairments, suggests promising future application to the early prediction of neurocognitive disorders.

YNIMG Journal 2016 Journal Article

Advanced MRI techniques to improve our understanding of experience-induced neuroplasticity

• Christine Lucas Tardif
• Claudine Joëlle Gauthier
• Christopher John Steele
• Pierre-Louis Bazin
• Andreas Schäfer
• Alexander Schaefer
• Robert Turner
• Arno Villringer

Over the last two decades, numerous human MRI studies of neuroplasticity have shown compelling evidence for extensive and rapid experience-induced brain plasticity in vivo. To date, most of these studies have consisted of simply detecting a difference in structural or functional images with little concern for their lack of biological specificity. Recent reviews and public debates have stressed the need for advanced imaging techniques to gain a better understanding of the nature of these differences – characterizing their extent in time and space, their underlying biological and network dynamics. The purpose of this article is to give an overview of advanced imaging techniques for an audience of cognitive neuroscientists that can assist them in the design and interpretation of future MRI studies of neuroplasticity. The review encompasses MRI methods that probe the morphology, microstructure, function, and connectivity of the brain with improved specificity. We underline the possible physiological underpinnings of these techniques and their recent applications within the framework of learning- and experience-induced plasticity in healthy adults. Finally, we discuss the advantages of a multi-modal approach to gain a more nuanced and comprehensive description of the process of learning.

YNIMG Journal 2016 Journal Article

Baseline oxygenation in the brain: Correlation between respiratory-calibration and susceptibility methods

• Audrey P. Fan
• Andreas Schäfer
• Laurentius Huber
• Leonie Lampe
• Steffen von Smuda
• Harald E. Möller
• Arno Villringer
• Claudine J. Gauthier

New MRI methods for noninvasive imaging of baseline oxygen extraction fraction (OEF) in the brain show great promise. Quantitative O2 imaging (QUO2) applies a biophysical model to measure OEF in tissue from BOLD, cerebral blood flow (CBF), and end-tidal O2 (ETO2) signals acquired during two or more gas manipulations. Alternatively, quantitative susceptibility mapping (QSM) maps baseline OEF along cerebral vessels based on the deoxyhemoblogin (dHb) susceptibility shift between veins and water. However, these approaches have not been carefully compared to each other or to known physiological signals. The aims of this study were to compare OEF values by QUO2 and QSM; and to see if baseline OEF relates to BOLD and CBF changes during a visual task. Simultaneous BOLD and arterial spin labeling (ASL) scans were acquired at 7T in 11 healthy subjects continuously during hypercapnia (5% CO2, 21% O2), hyperoxia (100% O2), and carbogen (5% CO2, 95% O2) for QUO2 analysis. Separate BOLD-ASL scans were acquired during a checkerboard stimulus to identify functional changes in the visual cortex. Gradient echo phase images were also collected at rest for QSM reconstruction of OEF along cerebral veins draining the visual cortex. Mean baseline OEF was (43. 5±14)% for QUO2 with two gases, (42. 3±17)% for QUO2 with three gases, and (29. 4±3)% for QSM across volunteers. Three-gas QUO2 values of OEF correlated with QSM values of OEF (P =0. 03). However, Bland–Altman analysis revealed that QUO2 tended to measure higher baseline OEF with respect to QSM, which likely results from underestimation of the hyperoxic BOLD signal and low signal-to-noise ratio of the ASL acquisitions. Across subjects, the percent CBF change during the visual task correlated with OEF measured by 3-gas QUO2 (P <0. 04); and by QSM (P =0. 035), providing evidence that the new methods measure true variations in brain physiology across subjects.

YNIMG Journal 2016 Journal Article

Open Science CBS Neuroimaging Repository: Sharing ultra-high-field MR images of the brain

• Christine Lucas Tardif
• Andreas Schäfer
• Robert Trampel
• Arno Villringer
• Robert Turner
• Pierre-Louis Bazin

Magnetic resonance imaging at ultra high field opens the door to quantitative brain imaging at sub-millimeter isotropic resolutions. However, novel image processing tools to analyze these new rich datasets are lacking. In this article, we introduce the Open Science CBS Neuroimaging Repository: a unique repository of high-resolution and quantitative images acquired at 7T. The motivation for this project is to increase interest for high-resolution and quantitative imaging and stimulate the development of image processing tools developed specifically for high-field data. Our growing repository currently includes datasets from MP2RAGE and multi-echo FLASH sequences from 28 and 20 healthy subjects respectively. These datasets represent the current state-of-the-art in in-vivo relaxometry at 7T, and are now fully available to the entire neuroimaging community.

YNIMG Journal 2016 Journal Article

Rapid and specific gray matter changes in M1 induced by balance training

• Marco Taubert
• Jan Mehnert
• Burkhard Pleger
• Arno Villringer

Training-induced changes in cortical structure can be observed non-invasively with magnetic resonance imaging (MRI). While macroscopic changes were found mainly after weeks to several months of training in humans, imaging of motor cortical networks in animals revealed rapid microstructural alterations after a few hours of training. We used MRI to test the hypothesis of immediate and specific training-induced alterations in motor cortical gray matter in humans. We found localized increases in motor cortical thickness after 1h of practice in a complex balancing task. These changes were specific to motor cortical effector representations primarily responsible for balance control in our task (lower limb and trunk) and these effects could be confirmed in a replication study. Cortical thickness changes (i) linearly increased across the training session, (ii) occurred independent of alterations in resting cerebral blood flow and (iii) were not triggered by repetitive use of the lower limbs. Our findings show that motor learning triggers rapid and specific gray matter changes in M1.

YNIMG Journal 2015 Journal Article

Comparison of variants of canonical correlation analysis and partial least squares for combined analysis of MRI and genetic data

• Claudia Grellmann
• Sebastian Bitzer
• Jane Neumann
• Lars T. Westlye
• Ole A. Andreassen
• Arno Villringer
• Annette Horstmann

The standard analysis approach in neuroimaging genetics studies is the mass-univariate linear modeling (MULM) approach. From a statistical view, however, this approach is disadvantageous, as it is computationally intensive, cannot account for complex multivariate relationships, and has to be corrected for multiple testing. In contrast, multivariate methods offer the opportunity to include combined information from multiple variants to discover meaningful associations between genetic and brain imaging data. We assessed three multivariate techniques, partial least squares correlation (PLSC), sparse canonical correlation analysis (sparse CCA) and Bayesian inter-battery factor analysis (Bayesian IBFA), with respect to their ability to detect multivariate genotype–phenotype associations. Our goal was to systematically compare these three approaches with respect to their performance and to assess their suitability for high-dimensional and multi-collinearly dependent data as is the case in neuroimaging genetics studies. In a series of simulations using both linearly independent and multi-collinear data, we show that sparse CCA and PLSC are suitable even for very high-dimensional collinear imaging data sets. Among those two, the predictive power was higher for sparse CCA when voxel numbers were below 400 times sample size and candidate SNPs were considered. Accordingly, we recommend Sparse CCA for candidate phenotype, candidate SNP studies. When voxel numbers exceeded 500 times sample size, the predictive power was the highest for PLSC. Therefore, PLSC can be considered a promising technique for multivariate modeling of high-dimensional brain–SNP-associations. In contrast, Bayesian IBFA cannot be recommended, since additional post-processing steps were necessary to detect causal relations. To verify the applicability of sparse CCA and PLSC, we applied them to an experimental imaging genetics data set provided for us. Most importantly, application of both methods replicated the findings of this data set.

YNIMG Journal 2014 Journal Article

Response inhibition and its relation to multidimensional impulsivity

• Tilmann Wilbertz
• Lorenz Deserno
• Annette Horstmann
• Jane Neumann
• Arno Villringer
• Hans-Jochen Heinze
• Carsten N. Boehler
• Florian Schlagenhauf

Impulsivity is a multidimensional construct that has been suggested as a vulnerability factor for several psychiatric disorders, especially addiction disorders. Poor response inhibition may constitute one facet of impulsivity. Trait impulsivity can be assessed by self-report questionnaires such as the widely used Barratt Impulsiveness Scale (BIS-11). However, regarding the multidimensionality of impulsivity different concepts have been proposed, in particular the UPPS self-report questionnaire (‘Urgency’, ‘Lack of Premeditation’, ‘Lack of Perseverance’, ‘Sensation Seeking’) that is based on a factor analytic approach. The question as to which aspects of trait impulsivity map on individual differences of the behavioral and neural correlates of response inhibition so far remains unclear. In the present study, we investigated 52 healthy individuals that scored either very high or low on the BIS-11 and underwent a reward-modulated Stop-signal task during fMRI. Neither behavioral nor neural differences were observed with respect to high- and low-BIS groups. In contrast, UPPS subdomain Urgency best explained inter-individual variability in SSRT scores and was further negatively correlated to right IFG/aI activation in 'Stop>Go’ trials — a key region for response inhibition. Successful response inhibition in rewarded compared to nonrewarded stop trials yielded ventral striatal (VS) activation which might represent a feedback signal. Interestingly, only participants with low Urgency scores were able to use this VS feedback signal for better response inhibition. Our findings indicate that the relationship of impulsivity and response inhibition has to be treated carefully. We propose Urgency as an important subdomain that might be linked to response inhibition as well as to the use of reward-based neural signals. Based on the present results, further studies examining the influence of impulsivity on psychiatric disorders should take into account Urgency as an important modulator of behavioral adaptation.

YNIMG Journal 2013 Journal Article

Dynamic causal modeling suggests serial processing of tactile vibratory stimuli in the human somatosensory cortex—An fMRI study

• Christian Kalberlah
• Arno Villringer
• Burkhard Pleger

Sensitivity to location and frequency of tactile stimuli is a characterizing feature of human primary (S1), and secondary (S2) somatosensory cortices. Recent evidence suggests that S1 is predominantly receptive to stimulus location, while S2 is attuned to stimulus frequency. Although it is well established in humans that tactile frequency information is relayed serially from S1 to S2, a recent study, using functional magnetic resonance imaging (fMRI) in combination with dynamic causal modeling (DCM), suggested that somatosensory inputs are processed in parallel in S1 and S2. In the present fMRI/DCM study, we revisited this controversy and investigated the specialization of the human somatosensory cortical areas with regard to tactile stimulus representations, as well as their effective connectivity. During brain imaging, 14 participants performed a somatosensory discrimination task on vibrotactile stimuli. Importantly, the model space for DCM was chosen to allow for direct inference on the question of interest by systematically varying the information transmission from pure parallel to pure serial implementations. Bayesian model comparison on the level of model families strongly favors a serial, instead of a parallel processing route for tactile stimulus information along the somatosensory pathway. Our fMRI/DCM data thus support previous suggestions of a sequential information transmission from S1 to S2 in humans.

YNIMG Journal 2013 Journal Article

Internal ventilation system of MR scanners induces specific EEG artifact during simultaneous EEG-fMRI

• Till Nierhaus
• Christopher Gundlach
• Dominique Goltz
• Sabrina D. Thiel
• Burkhard Pleger
• Arno Villringer

During simultaneous EEG-fMRI acquisition, the EEG signal suffers from tremendous artifacts caused by the scanner “environment”. Particularly, gradient artifacts and the ballistocardiogram have been well characterized, along with methods to eliminate them. Here, we describe another systematic artifact in the EEG signal, which is induced by the internal ventilation system of Siemens TRIO and VERIO MR scanners. A ventilation-level dependent vibration induces specific peaks in the frequency spectrum of the EEG. These frequency peaks are in the range of physiologically relevant brain rhythms (gamma frequency range), and thus interfere with their reliable acquisition. This ventilation dependent artifact was most prominent on the electrodes placed directly on the subject's head, so it is not sufficient to simply place the EEG's amplifier outside the scanner tube. Instead, the ventilator must be switched off to fully eliminate the ventilator's artificial manipulation of EEG recordings. Without the internal ventilator system being on, the temperature within the scanner tube may rise, thus requiring shorter scanning sessions or an additional external ventilation system.

YNIMG Journal 2013 Journal Article

Overlapping and parallel cerebello-cerebral networks contributing to sensorimotor control: An intrinsic functional connectivity study

• Judy A. Kipping
• Wolfgang Grodd
• Vinod Kumar
• Marco Taubert
• Arno Villringer
• Daniel S. Margulies

In concert with sensorimotor control areas of the cerebrum, the cerebellum shows differential activation patterns during a variety of sensorimotor-related tasks. However, the spatial details and extent of the complex and heterogeneous cerebello-cerebral systems involved in action control remain uncertain. In this study, we use intrinsic functional connectivity (iFC) to examine cerebello-cerebral networks of five cerebellar lobules (I–IV, V, VI, and VIIIa/b) that have been empirically identified to form the functional basis of sensorimotor processes. A refined cerebellar seed-region selection allowed us to identify a network of primary sensorimotor and supplementary motor areas (I–V), a network of prefrontal, premotor, occipito-temporal and inferior-parietal regions (VI), and two largely overlapping networks involving premotor and superior parietal regions, the temporo-parietal junction as well as occipito-temporal regions (VIIIa/b). All networks involved the medial prefrontal/cingulate cortex. These cerebral clusters were used in a partial correlation analysis to systematically map cerebral connectivity throughout the entire cerebellum. We discuss these findings in the framework of affective and cognitive control, sensorimotor, multisensory systems, and executive/language systems. Within the cerebellum we found that cerebro-cerebellar systems seem to run in parallel, as indicated by distinct sublobular functional topography of prefrontal, parietal, sensorimotor, cingulate, and occipito-temporal regions. However, all areas showed overlapping connectivity to various degrees in both hemispheres. The results of both analyses demonstrate that different sublobular parts of the cerebellar lobules may dominate in different aspects of primary or higher-order sensorimotor processing. This systems-level cerebellar organization provides a more detailed structure for cerebello-cerebral interaction which contributes to our understanding of complex motor behavior.

YNICL Journal 2013 Journal Article

Relationship between imaging biomarkers, age, progression and symptom severity in Alzheimer's disease

• Juergen Dukart
• Karsten Mueller
• Arno Villringer
• Ferath Kherif
• Bogdan Draganski
• Richard Frackowiak
• Matthias L. Schroeter

The early diagnostic value of glucose hypometabolism and atrophy as potential neuroimaging biomarkers of mild cognitive impairment (MCI) and Alzheimer's disease (AD) have been extensively explored using [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) and structural magnetic resonance imaging (MRI). The vast majority of previous imaging studies neglected the effects of single factors, such as age, symptom severity or time to conversion in MCI thus limiting generalisability of results across studies. Here, we investigated the impact of these factors on metabolic and structural differences. FDG-PET and MRI data from AD patients (n = 80), MCI converters (n = 65) and MCI non-converters (n = 64) were compared to data of healthy subjects (n = 79). All patient groups were split into subgroups by age, time to conversion (for MCI), or symptom severity and compared to the control group. AD patients showed a strongly age-dependent pattern, with younger patients showing significantly more extensive reductions in gray matter volume and glucose utilisation. In the MCI converter group, the amount of glucose utilisation reduction was linked to the time to conversion but not to atrophy. Our findings indicate that FDG-PET might be more closely linked to future cognitive decline whilst MRI being more closely related to the current cognitive state reflects potentially irreversible damage.

YNIMG Journal 2012 Journal Article

Cortical thickness in primary sensorimotor cortex influences the effectiveness of paired associative stimulation

• Virginia Conde
• Henning Vollmann
• Bernhard Sehm
• Marco Taubert
• Arno Villringer
• Patrick Ragert

Non-invasive brain stimulation protocols in general and paired associative stimulation (PAS) in particular seem to alter corticospinal excitability and thereby to influence behaviour with a high degree of inter-subject variability. The cause of this variability is multidimensional and to some extent still unknown. Here, we tested the hypothesis that individual variations in cortical thickness can explain some of the variability of PAS-induced excitability changes. Ten minutes of a facilitatory PAS protocol (PASLTP) rapidly increased corticospinal excitability in the majority of the subjects (14/19 subjects) while others showed no such effect (5/19 subjects). A whole brain correlation analysis based on high resolution T1-weighted images revealed a significant positive relationship of PASLTP-induced excitability changes with cortical thickness of the underlying left sensorimotor cortex (SM1) only. Cortical thickness alone, among other potential influencing factors, explained about half of the PASLTP variance, indicating that subjects with a strong after-effect were those with thicker gray matter in this region. Based on these findings, we provide novel evidence that local brain structure influences the individual amount of functional plasticity induced by PASLTP. While the underlying neurophysiological and/or anatomical reasons for this effect still remain elusive at this point, we conclude that cortical thickness should be considered as an important and until now not recognized modulating factor in studies employing non-invasive brain stimulation techniques.

YNIMG Journal 2012 Journal Article

Enhanced performance by a hybrid NIRS–EEG brain computer interface

• Siamac Fazli
• Jan Mehnert
• Jens Steinbrink
• Gabriel Curio
• Arno Villringer
• Klaus-Robert Müller
• Benjamin Blankertz

Noninvasive Brain Computer Interfaces (BCI) have been promoted to be used for neuroprosthetics. However, reports on applications with electroencephalography (EEG) show a demand for a better accuracy and stability. Here we investigate whether near-infrared spectroscopy (NIRS) can be used to enhance the EEG approach. In our study both methods were applied simultaneously in a real-time Sensory Motor Rhythm (SMR)-based BCI paradigm, involving executed movements as well as motor imagery. We tested how the classification of NIRS data can complement ongoing real-time EEG classification. Our results show that simultaneous measurements of NIRS and EEG can significantly improve the classification accuracy of motor imagery in over 90% of considered subjects and increases performance by 5% on average (p<0: 01). However, the long time delay of the hemodynamic response may hinder an overall increase of bit-rates. Furthermore we find that EEG and NIRS complement each other in terms of information content and are thus a viable multimodal imaging technique, suitable for BCI.

YNIMG Journal 2012 Journal Article

Morphometric gray matter differences of the medial frontal cortex influence the social Simon effect

• Thomas Dolk
• Roman Liepelt
• Arno Villringer
• Wolfgang Prinz
• Patrick Ragert

Interacting with others plays a fundamental role in human life. Although several brain regions have recently been associated with complex cognitive control processes, surprisingly little is known about the structural correlates underlying cognitive control processes involved in social interactions. In the present study we used gray matter voxel-based morphometry (VBM) to investigate structural brain correlates of individual performance differences in a social Simon task. Here, two people share a Simon task, which requires each participant to respond to only one of two possible stimuli, rendering the paradigm a go-nogo task, so that a Simon effect – known as the Social Simon Effect (SSE) – is observable across both participants. Using a whole brain approach, we found that inter-individual differences in the SSE are negatively correlated with gray matter (GM) volume of the medial frontal cortex (MFC). The present data indicate that individuals with larger MFC GM volume were those with better conflict resolution in a social Simon task and vice versa. This brain-behavior relationship between cognitive control processes and individual GM volume differences might help to improve our understanding of social interactions in joint task performance.

YNIMG Journal 2012 Journal Article

The intravascular susceptibility effect and the underlying physiology of fMRI

• Arno Villringer

In this article, I will first give a brief account of my work at MGH on characterizing the intravascular susceptibility effect. Then I will describe studies into the underlying physiology of BOLD-fMRI which has become of interest to my group in the following decade. I will touch issues such as signal source of BOLD fMRI, capillary recruitment, the elusive initial dip and others.

YNIMG Journal 2011 Journal Article

Long-term effects of motor training on resting-state networks and underlying brain structure

• Marco Taubert
• Gabriele Lohmann
• Daniel S. Margulies
• Arno Villringer
• Patrick Ragert

Acquired motor skills are coded in fronto-parietal brain networks, but how these networks evolve through motor training is unclear. On the one hand, increased functional connectivity has been shown immediately after a training session; on the other hand, training-induced structural changes are visible only after several weeks. Based on known associations between functional and structural network development during human ontogeny, we hypothesised that learning a challenging motor task leads to long-lasting changes in functional resting-state networks and the corresponding cortical and sub-cortical brain structures. Using longitudinal functional and structural MRI at multiple time points, we demonstrate increased fronto-parietal network connectivity one week after two brief motor training sessions in a dynamic balancing task, although subjects were engaged in their regular daily activities during the week. Repeated training sessions over six consecutive weeks progressively modulate these changes in accordance with individual performance improvements. Multimodal correlation analyses showed an association between structural grey matter alterations and functional connectivity changes in prefrontal and supplementary-motor areas. These coincident changes were most prominent in the first three weeks of training. In contrast, changes in fronto-parietal functional connectivity and the underlying white matter fibre structure developed gradually during the six weeks. Our results demonstrate a tight correlation between training-induced functional and structural brain plasticity on the systems level and suggest a functional relevance of intrinsic brain activity for morphological adaptation in the human brain.

YNIMG Journal 2010 Journal Article

Differential effects of global and cerebellar normalization on detection and differentiation of dementia in FDG-PET studies

• Juergen Dukart
• Karsten Mueller
• Annette Horstmann
• Barbara Vogt
• Stefan Frisch
• Henryk Barthel
• Georg Becker
• Harald E. Möller

FDG-PET ([18F]fluorodeoxyglucose positron emission tomography) is frequently used to improve the differential diagnosis of dementia. However, a fundamental methodological issue of the reference area for the intensity normalization procedure is still unsolved. Here, we systematically compared the two most commonly used normalization methods to the cerebral and to the cerebellar metabolic rate for glucose with regard to detection and differentiation of dementia syndromes. FDG-PET imaging was performed on 19 subjects with early Alzheimer's disease, 13 subjects with early frontotemporal lobar degeneration and 10 subjects complaining of memory impairment, which had not been confirmed by comprehensive clinical testing. Images were normalized to either the cerebral or the cerebellar metabolic rate for glucose. Differences in relative regional glucose metabolism were assessed by voxelwise comparison. Analysis using the two normalization procedures revealed remarkable differential effects. Whereas cerebellar normalization was superior in identifying dementia patients in comparison to control subjects, cerebral normalization showed better results for differential diagnosis between types of dementia. These effects were shown for both, Alzheimer's disease and frontotemporal lobar degeneration. Relative hypermetabolism in comparison to the control group was only detected in both kinds of dementia using global normalization. The results indicate that normalization has a decisive impact on diagnostic accuracy in dementia. While cerebellar normalization seems to be more sensitive for early diagnosis, cerebral global normalization might be superior for differential diagnostic purposes in dementia syndromes.

YNIMG Journal 2009 Journal Article

Ultrahigh-frequency EEG during fMRI: Pushing the limits of imaging-artifact correction

• Frank Freyer
• Robert Becker
• Kimitaka Anami
• Gabriel Curio
• Arno Villringer
• Petra Ritter

Although solutions for imaging-artifact correction in simultaneous EEG–fMRI are improving, residual artifacts after correction still considerably affect the EEG spectrum in the ultrafast frequency band above 100 Hz. Yet this band contains subtle but valuable physiological signatures such as fast gamma oscillations or evoked high-frequency (600 Hz) bursts related to spiking of thalamocortical and cortical neurons. Here we introduce a simultaneous EEG–fMRI approach that integrates hard and software modifications for continuous acquisition of ultrafast EEG oscillations during fMRI. Our approach is based upon and extends the established method of averaged artifact subtraction (AAS). Particularly for recovery of ultrahigh-frequency EEG signatures, AAS requires invariantly sampled and constant imaging-artifact waveforms to achieve optimal imaging-artifact correction. Consequently, we adjusted our acquisition setup such that both physiological ultrahigh-frequency EEG and invariantly sampled imaging artifacts were captured. In addition, we extended the AAS algorithm to cope with other, non-sampling related sources of imaging-artifact variations such as subject movements. A cascaded principal component analysis finally removed remaining imaging-artifact residuals. We provide a detailed evaluation of averaged ultrahigh-frequency signals and unaveraged broadband EEG spectra up to 1 kHz. Evoked nanovolt-sized high-frequency bursts were successfully recovered during periods of MR data acquisition afflicted by imaging artifacts in the millivolt range. Compared to periods without imaging artifacts they exhibited the same mean amplitudes, latencies and waveforms and a signal-to-noise ratio of 72%. Furthermore we identified consistent dipole sources. In conclusion, ultrafast EEG oscillations can be continuously monitored during fMRI using the proposed approach.

YNIMG Journal 2008 Journal Article

High-frequency (600 Hz) population spikes in human EEG delineate thalamic and cortical fMRI activation sites

• Petra Ritter
• Frank Freyer
• Gabriel Curio
• Arno Villringer

Functional magnetic resonance imaging (fMRI) measures neural activity indirectly via its slow vascular/metabolic consequences. At a temporal resolution on the order of seconds, fMRI does not reveal the real ‘language of neurons’, spelt out by fast electrical discharges (‘spikes’) which occur on a time scale of milliseconds. In animal studies, these limitations have been addressed by adding invasive electrode measurements to fMRI. Here, we propose to circumvent this ‘inverse problem of fMRI’ by deriving a noninvasive spike measure from recordings of ultrafast electroencephalography (EEG) signals during fMRI. We demonstrate how in response to median nerve stimulation 600 Hz oscillatory EEG signals can be measured reliably during fMRI. These high-frequency bursts (HFBs) are supposed to reflect population spikes in the thalamus and the somatosensory cortex, respectively. We show that distinct fMRI activations in these two generator structures can be attributed to spontaneous HFB fluctuations. Thus, our approach allowed the noninvasive identification of neural processes along the thalamocortical pathway unfolding at a millisecond time scale.

YNIMG Journal 2008 Journal Article

Influence of ongoing alpha rhythm on the visual evoked potential

• Robert Becker
• Petra Ritter
• Arno Villringer

The relationship between ongoing occipital alpha rhythm (8–12 Hz) and the generation of visual evoked potentials (VEPs) has been discussed controversially. While the “evoked theory” sees no interaction between VEP generation and the alpha rhythm, the “oscillatory theory” (also known as “phase-reset theory”) postulates VEP generation to be based on alpha rhythm phase resetting. Previous experimental results are contradictory, rendering a straightforward interpretation difficult. Our approach was to theoretically model the implications of the evoked and oscillatory theory also incorporating stimulus-induced alpha-rhythm desynchronization. As a result, the model based on the oscillatory theory predicts alpha-band dependent VEP amplitudes but constant phase locking. The model based on the evoked theory predicts unaffected VEP amplitudes but alpha-band dependent phase locking. Subsequently, we analyzed experimental data in which VEPs were assessed in an “eyes open” and “eyes closed” condition in 17 subjects. For early components of the VEP, findings are in agreement with the evoked theory, i. e. VEP amplitudes remain unaffected and phase locking decreases during periods of high alpha activity. Late VEP component amplitudes (>175 ms), however, are dependent on pre-stimulus alpha amplitudes. This interaction is contradictory to the oscillatory theory since this VEP amplitude difference is not paralleled by a corresponding difference in alpha-band amplitude in the affected time window. In summary, by using a model-based approach we identified early VEPs to be compatible with the evoked theory, while results of late VEPs support a modulatory but not causative role – the latter implied by the oscillatory theory – of alpha activity for EP generation.

YNIMG Journal 2008 Journal Article

Inhibitory impact of subliminal electrical finger stimulation on SI representation and perceptual sensitivity of an adjacent finger

• Birol Taskin
• Susanne Holtze
• Thomas Krause
• Arno Villringer

Simultaneous stimulation of two adjacent fingers above sensory perception threshold (supraliminal stimulation) leads to an inhibitory interaction effect on responses in primary somatosensory cortex (SI). Moreover, during electrical finger stimulation closely below threshold for conscious perception (subliminal stimulation) inhibitory interneurons in cortical layer 4 are assumed to be activated preferentially as compared to excitatory interneurons. Using fMRI in humans, here we show that interspersed subliminal electrical stimulation of an adjacent finger reduces the response to target finger stimulation in contralateral SI. This effect was shown in a complementary study to be associated behaviorally with a diminished detectability of test pulses on the target finger. We propose the mechanism underlying this lateral inhibitory effect to be related to a representational overlap of inhibitory interneurons in SI based on the divergence of thalamocortical feedforward projections, or to intracortical lateral inhibitory projections targeting juxtaposed receptive fields, or both.

YNIMG Journal 2008 Journal Article

Proprioceptive head posture-related processing in human polysensory cortical areas

• Oliver Fasold
• Johanna Heinau
• Maja U. Trenner
• Arno Villringer
• Rüdiger Wenzel

Besides visual input and vestibular afferents, proprioceptive input from muscle spindle receptors of the neck region contributes to the perception of egocentric space. Using fMRI we performed a neck muscle vibration paradigm in humans in order to detect brain areas involved in processing changes of the head position in relation to the rest of the body. We identified a network of primary and secondary cortical areas: (I) regions that presumably receive direct proprioceptive thalamic input such as areas 3a, 2, S2 and the parieto-insular vestibular cortex (PIVC), (II) foci in the intraparietal sulcus, motor and premotor areas, and the frontal eye field (FEF). Activation of the former reflect early stages of proprioceptive processing, nevertheless these areas contain polysensory subdivisions such as area 3aNv, which also receives vestibular afferents. Together with area PIVC and the vestibular field in area 2 (2v), area 3aNv constitutes the inner vestibular circuit, an interconnected cortical triangle of polysensory areas that project to the posterior parietal cortex (PPC), which is known to be involved in polysensory integration. With respect to possible analogies in the monkey, we speculate that the activation we observed in the PPC is closely related to the LIP and VIP regions of the macaque.

YNIMG Journal 2006 Journal Article

A neural network reflecting individual differences in cognitive processing of emotions during perceptual decision making

• Katja Mériau
• Isabell Wartenburger
• Philipp Kazzer
• Kristin Prehn
• Claas-Hinrich Lammers
• Elke van der Meer
• Arno Villringer
• Hauke R. Heekeren

Even simple perceptual decisions are influenced by the emotional content of a stimulus. Recent neuroimaging studies provide evidence about the neural mechanisms of perceptual decision making on emotional stimuli. However, the effect of individual differences in cognitive processing of emotions on perceptual decision making remains poorly understood. Here, we investigated how changes in the fMRI signal during perceptual decision making on facial stimuli covaried with individual differences in the ability to identify and communicate one’s emotional state. Although this personality trait covaried with changes in activity in the dorsal anterior cingulate cortex (dACC) during gender decisions on facial expressions, there was no correlation during emotion decisions. Further, we investigated whether individual differences in the ability to cognitively process emotions depend on differences in the functional integration of emotional and cognitive brain regions. We therefore compared task-dependent changes in effective connectivity of dACC in individuals with good and with poor ability to cognitively process emotions using a psychophysiological interaction analysis. We found greater coupling of dACC with prefrontal regions in individuals with good ability to identify and communicate their emotional state. Conversely, individuals with poor ability in this domain showed greater coupling of dACC with the amygdala. Our data indicate that individual differences in the ability to identify and communicate one’s emotional state are reflected by altered effective connectivity of the dACC with prefrontal and limbic regions. Thus, we provide neurophysiological evidence for a theoretical model that posits that a discommunication between limbic areas and the neocortex impairs cognitive processing of emotions.

YNIMG Journal 2006 Journal Article

Dysfunction of ventral striatal reward prediction in schizophrenia

• Georg Juckel
• Florian Schlagenhauf
• Michael Koslowski
• Torsten Wüstenberg
• Arno Villringer
• Brian Knutson
• Jana Wrase
• Andreas Heinz

Background: Negative symptoms may be associated with dysfunction of the brain reward system in schizophrenia. We used functional magnetic resonance imaging (fMRI) to assess the BOLD response in the ventral striatum of unmedicated schizophrenics during presentation of reward-indicating and loss-indicating stimuli. Methods: A total of 10 schizophrenic men (7 never medicated, 3 unmedicated for at least 2 years) and 10 age-matched healthy male volunteers participated in an incentive monetary delay task, in which visual cues predicted that a rapid response to a subsequent target stimulus would result either in monetary gain or loss or would have no consequence. Results: Compared to healthy controls, unmedicated schizophrenics showed reduced ventral striatal activation during the presentation of reward-indicating cues. Decreased activation of the left ventral striatum was inversely correlated with the severity of negative (and trendwise positive) symptoms. Discussion: Reduced activation in one of the central areas of the brain reward system, the ventral striatum, was correlated with the severity of negative symptoms in medication-free schizophrenics. In unmedicated schizophrenic patients, a high striatal dopamine turnover may increase the “noise” in the reward system, thus interfering with the neuronal processing of reward-predicting cues by phasic dopamine release. This, in turn, may contribute to negative symptoms as such as anhedonia, apathy, and loss of drive and motivation.

YNIMG Journal 2005 Journal Article

Influence of bodily harm on neural correlates of semantic and moral decision-making

• Hauke R. Heekeren
• Isabell Wartenburger
• Helge Schmidt
• Kristin Prehn
• Hans-Peter Schwintowski
• Arno Villringer

Moral decision-making is central to everyday social life because the evaluation of the actions of another agent or our own actions made with respect to the norms and values guides our behavior in a community. There is previous evidence that the presence of bodily harm—even if irrelevant for a decision—may affect the decision-making process. While recent neuroimaging studies found a common neural substrate of moral decision-making, the role of bodily harm has not been systematically studied so far. Here we used event-related functional magnetic resonance imaging (fMRI) to investigate how behavioral and neural correlates of semantic and moral decision-making processes are modulated by the presence of direct bodily harm or violence in the stimuli. Twelve participants made moral and semantic decisions about sentences describing actions of agents that either contained bodily harm or not and that could easily be judged as being good or bad or correct/incorrect, respectively. During moral and semantic decision-making, the presence of bodily harm resulted in faster response times (RT) and weaker activity in the temporal poles relative to trials devoid of bodily harm/violence, indicating a processing advantage and reduced processing depth for violence-related linguistic stimuli. Notably, there was no increase in activity in the amygdala and the posterior cingulate cortex (PCC) in response to trials containing bodily harm. These findings might be a correlate of limited generation of the semantic and emotional context in the anterior temporal poles during the evaluation of actions of another agent related to violence that is made with respect to the norms and values guiding our behavior in a community.

YNIMG Journal 2005 Journal Article

The fast optical signal—Robust or elusive when non-invasively measured in the human adult?

• Jens Steinbrink
• Florian C.D. Kempf
• Arno Villringer
• Hellmuth Obrig

Near infrared spectroscopy (NIRS) can detect vascular changes in cerebral cortical tissue elicited by functional stimulation. For some 10 years, another optical signal has been reported to be accessible by NIRS. This signal has been reported to correlate to the electrophysiological response rendering NIRS an exquisite non-invasive approach to investigate neurovascular coupling in the human adult. Due to their typical latency of up to hundreds of milliseconds, these signals have been termed ‘fast’ optical signals and have been postulated to stem from scatter changes in neuronal tissue, as a fingerprint of the electrophysiological response. Here, we utter a less optimistic view on the non-invasive detectability of these changes in the human, motivated by an upper limit signal size estimation, predicting a signal size by orders of magnitude smaller than those previously reported. Also, we discuss the influence of small stimulus correlated movement artifacts potentially mimicking a fast optical signal. Based on invasive studies, we perform an upper limit estimation for changes in intensity and mean time of flight, which can be expected assuming a scatter change in the cerebral cortex while measuring on the surface of the head of an adult subject. Since the resulting numbers are far below those previously reported, we constructed a simple system, which minimizes technical noise. The system allows us to detect rather small intensity changes (2 × 10−3%) when averaging over approximately 3000 stimuli. Despite this outstandingly low noise level of the system, we find a reliable change in response to a sub-motor-threshold steady state median nerve stimulation in just one single subject (8 subjects examined, 4 subjects twice). Exceeding the motor threshold leads to large stimulus related artifacts, on a similar time scale and with comparable amplitude as previously reported signals. To check for potential modality specific problems, we next performed a visual stimulation study, avoiding potential motor artifacts. For the steady state visually evoked response, no subject yielded a reliable result (11 subjects examined, 4 subjects twice). The paper discusses these findings by a review of the literature on fast optical signals and their being accessible in the adult human.

YNIMG Journal 2004 Journal Article

Cytochrome-c-oxidase redox changes during visual stimulation measured by near-infrared spectroscopy cannot be explained by a mere cross talk artefact

• Kâmil Uludağ
• Jens Steinbrink
• Matthias Kohl-Bareis
• Rüdiger Wenzel
• Arno Villringer
• Hellmuth Obrig

The detection of redox changes in cytochrome-c-oxidase ([Cyt-ox]) in response to cerebral activation by non-invasive NIRS is hampered by methodological spectroscopic issues related to the modification of the Beer–Lambert law. Also, the question whether a change in the enzyme's redox-state is elicited by functional stimulation is unresolved. In a previous study, we found physiological evidence in favour of an activation-induced increase in oxidation of the enzyme [J. Cereb. Blood Flow Metab. 19 (1999) 592], while in a second study on spectroscopic cross talk, we found that the [Cyt-ox] changes to potentially be an artefact of the spectroscopic approach [J. Biomed. Opt. 7 (2002) 51]. Here, we use two different stimuli which differentially activate areas either rich or poor in [Cyt-ox] content (blob/interblob in visual cortex V1 and pale/thin stripes in V2) to further clarify this apparent discrepancy. In a first experiment, two stimuli were presented in an alternating fashion for 20 s and all stimulation periods were separated by resting periods of 40 s. We observed similar changes in [Cyt-ox] for both stimuli. To become more sensitive to the potentially very small optical changes related to changes in [Cyt-ox], we tried to minimise global haemodynamic and metabolic effects in a second experiment by omitting the resting periods. Our hypothesis was that [Cyt-ox] changes could be fully explained by cross talk as it is predicted from our last study [J. Biomed. Opt. 7 (2002) 51]. However, in more than half of the experiments, we were not able to model the changes in Cyt-ox calculated from measured attenuation spectra as a cross talk artefact. We interpret this finding as an argument in favour of the existence of [Cyt-ox] changes in response to functional stimulation. This finding, however, does not lessen the liability of the [Cyt-ox] changes to cross talk and calls for great caution when [Cyt-ox] changes are derived from NIRS measurements based on the modified Beer–Lambert approach. Further (invasive) validation studies are required.

YNIMG Journal 2004 Journal Article

Separability and cross talk: optimizing dual wavelength combinations for near-infrared spectroscopy of the adult head

• Kâmil Uludağ
• Jens Steinbrink
• Arno Villringer
• Hellmuth Obrig

By means of noninvasive near-infrared spectroscopy (NIRS), cerebral concentration changes in oxygenated and deoxygenated hemoglobin ([oxy-Hb] and [deoxy-Hb]) can be determined. The quality of the concentration changes' assessment critically depends on the wavelength combination used. Trying to optimize this combination, two spectroscopic effects must be taken into account: cross talk and separability. Cross talk between [oxy-Hb] and [deoxy-Hb] occurs because the assumption made in the analysis—that there is a homogeneous concentration change—does not hold true for the adult human head. Separability—to be introduced in this paper—is a measure for the degree of physical noise of the measurement that will influence the noise of the concentration changes' assessment. In other words, high separability corresponds to a low noise with respect to the concentration changes assessed. Here, we present analytical expressions for both measures and provide model-based estimates of cross talk and separability for any combination of two wavelengths between 610 and 920 nm. These theoretical considerations allow for two predictions: (a) if both wavelengths used are greater than approximately 780 nm, cross talk is high and separability is low resulting in erroneous and noisy concentration data. (b) If one wavelength is chosen below 720 nm while the other is greater than 730 nm, cross talk is low and separability is high resulting in accurate concentration changes. We show the relevance of these theoretical results for noninvasive NIRS by testing the predictions on experimental data obtained in adults undergoing visual stimulation.

YNIMG Journal 2004 Journal Article

Towards a standard analysis for functional near-infrared imaging

• Matthias L Schroeter
• Markus M Bücheler
• Karsten Müller
• Kâmil Uludağ
• Hellmuth Obrig
• Gabriele Lohmann
• Marc Tittgemeyer
• Arno Villringer

Functional near-infrared spectroscopy (fNIRS) allows the ability to monitor brain activation by measuring changes in the concentration of oxy- and deoxy-hemoglobin. Until now no standardized approach for fNIRS data analysis has been established, although this has to be regarded as a precondition for future application. Hence, we applied the well-established general linear model to optical imaging data. Further, fNIRS data were analyzed in the frequency domain. Two visual tasks were investigated with optical imaging: a checkerboard paradigm supposed to activate the primary and secondary visual cortex, and a paradigm consisting of moving colored stimuli (rotating ‘L’s) additionally involving the motion area V5. Analysis with the general linear model detected the activation focus in the primary and secondary visual cortex during the first paradigm. For the second paradigm, a second laterally localized activated brain region was found, most likely representing V5. Spatially resolved spectral analysis confirmed the results by showing maxima of power spectral density and coherence in the same respective brain regions. Moreover, it demonstrated a delay of the hemodynamic response in the motion area. In summary, the present study suggests that the general linear model and spatially resolved spectral analysis can be used as standard statistical approaches for optical imaging data, particularly because they are almost independent of the assumed differential path length factors.

YNIMG Journal 2003 Journal Article

Correlates of alpha rhythm in functional magnetic resonance imaging and near infrared spectroscopy

• Matthias Moosmann
• Petra Ritter
• Ina Krastel
• Andrea Brink
• Sebastian Thees
• Felix Blankenburg
• Birol Taskin
• Hellmuth Obrig

We used simultaneous electroencephalogram-functional magnetic resonance imaging (EEG-fMRI) and EEG-near infrared spectroscopy (NIRS) to investigate whether changes of the posterior EEG alpha rhythm are correlated with changes in local cerebral blood oxygenation. Cross-correlation analysis of slowly fluctuating, spontaneous rhythms in the EEG and the fMRI signal revealed an inverse relationship between alpha activity and the fMRI-blood oxygen level dependent signal in the occipital cortex. The NIRS-EEG measurements demonstrated a positive cross-correlation in occipital cortex between alpha activity and concentration changes of deoxygenated hemoglobin, which peaked at a relative shift of about 8 s. Our data suggest that alpha activity in the occipital cortex is associated with metabolic deactivation. Mapping of spontaneously synchronizing distributed neuronal networks is thus shown to be feasible.

YNIMG Journal 2003 Journal Article

The functional neuroanatomy of visual conjunction search: a parametric fMRI study

• Notger G Müller
• Tobias H Donner
• Oliver A Bartelt
• Stephan A Brandt
• Arno Villringer
• Andreas Kleinschmidt

Visual conjunction search is proposed to be a multicomponent process which involves scaling and successive shifts of attention in space as well as object identification. Here, we first mapped brain areas sustaining the proposed attentional subprocesses and then tested whether their activity was modulated by search load, i. e. , the number of shifts, as predicted by serial search models. Search load was manipulated indirectly by precueing a varying number of locations at which relevant objects were shown. Multiple subregions within the intraparietal sulcus (IPS) and the prefrontal cortex were activated after cueing. Activity in the right posterior IPS was modulated by the distance of attention shifts and in the left posterior IPS by “zooming out” to cover a large region of the visual field. More anterior subregions of the left IPS responded to object identification irrespective of the need for serial scanning. Corresponding regions in the right IPS were modulated parametrically with respect to search load, along with the right temporoparietal junction. These results support a functional segregation of subregions of the IPS. The posterior regions participate in large-scale shifts and scaling of the attentional focus and the anterior regions in object identification and rapid serial shifts during search. The sustained activation in the frontal eye fields after cueing suggests a role in maintaining attention in the periphery. Together with the findings in early visual areas from this experiment (Müller et al. , 2003) the current observations are best accounted for by hybrid models of visual conjunction search, where parallel processing in visual and temporoparietal regions and serial scanning controlled by the right IPS cooperate.

YNIMG Journal 2002 Journal Article

Habituation of the Visually Evoked Potential and Its Vascular Response: Implications for Neurovascular Coupling in the Healthy Adult

• Hellmuth Obrig
• Heike Israel
• Matthias Kohl-Bareis
• Kamil Uludag
• Rüdiger Wenzel
• Bianca Müller
• Guy Arnold
• Arno Villringer

In the human, visually evoked potentials (VEP) and cerebral oxygenation changes, as measured by near-infrared spectroscopy (NIRS), are assessed to elucidate the relation between electrophysiological and vascular responses to a checkerboard stimulus reversing at 3 Hz. Habituation of either response is analysed on two time scales. Within the 1-min stimulation period we find a decrease in P100N135-component amplitude, closely coupled to a decrease in the amplitude of the oxygenation parameters (concentration changes in oxygenated and deoxygenated haemoglobin, [oxy-Hb] and [deoxy-Hb]). The N75P100-component amplitude exhibits a different behaviour along the 1-min stimulation period. An initial increase is overridden by an overall decrease, the latter not reaching statistical significance. The analysis across the 13 successive stimulation blocks separated by resting periods of equal duration yields a trend for an decrease in the VEP-components' amplitude, not reflected in the vascular response. When calculating a ratio between the amplitude of the P100N135-component and the concentration changes in the haemoglobins a “coupling index” of a 0. 2 μM decrease in [deoxy-Hb] and an increase of 0. 6 μM in [oxy-Hb] is found per 1 μV increase in VEP-component amplitude. The ratio is the same irrespective of its assessment from the difference stimulation/rest or from the habituation effect, i. e. , the difference between the amplitudes at the beginning and towards the end of the stimulation period. Although supporting the notion that the coupling between neuronal activation and the vascular response exhibits linear aspects, our findings cannot be taken as a proof of such a linearity across all brain regions and activation types. On the contrary, tentatively calculating a coupling index for the data assessed in the visual system, we intend to stress the necessity to assess both neuronal and vascular response to allow for a comparison between different systems and conditions in whom neurovascular coupling is expected to be altered (Miller et al. , 2001; Mechelli et al. , 2001).

YNIMG Journal 2002 Journal Article

Human Vestibular Cortex as Identified with Caloric Stimulation in Functional Magnetic Resonance Imaging

• Oliver Fasold
• Michael von Brevern
• Marc Kuhberg
• Christoph J. Ploner
• Arno Villringer
• Thomas Lempert
• Rüdiger Wenzel

Anatomic and electrophysiological studies in monkeys have yielded a detailed map of cortex areas receiving vestibular afferents. In contrast, comparatively little is known about the cortical representation of the human vestibular system. In this study we applied caloric stimulation and fMRI to further characterize human cortical vestibular areas and to test for hemispheric dominance of vestibular information processing. For caloric vestibular stimulation we used cold nitrogen to avoid susceptibility artifacts induced by water calorics. Right and left side vestibular stimulation was repetitively performed inducing a nystagmus for at least 90 s after the end of the stimulation in all subjects. Only the first 60 s of this nystagmus period was included for statistical analysis and compared with the baseline condition. Activation maps revealed a cortical network with right hemispheric dominance, which in all subjects comprised the temporoparietal junction extending into the posterior insula and, furthermore, the anterior insula, pre- and postcentral gyrus, areas in the parietal lobe, the ventrolateral portion of the occipital lobe, and the inferior frontal gyrus extending into the inferior part of the precentral sulcus. In conclusion, caloric stimulation in fMRI reveals a widespread cortical network involved in vestibular signal processing corresponding to the findings from animal experiments and previous functional imaging studies in humans. Furthermore, this study demonstrates a strong right hemispheric dominance of vestibular cortex areas regardless of the stimulated side, consistent with the current view of a rightward asymmetrical cortical network for spatial orientation.

YNIMG Journal 2002 Journal Article

Visual Feature and Conjunction Searches of Equal Difficulty Engage Only Partially Overlapping Frontoparietal Networks

• Tobias H. Donner
• Andreas Kettermann
• Eugen Diesch
• Florian Ostendorf
• Arno Villringer
• Stephan A. Brandt

According to a classical view of visual object recognition, targets are detected “preattentively” if they carry unique features, whereas attention has to be deployed serially to object locations for feature binding if the targets can be distinguished from distracters only in terms of their feature conjunctions. Consistent with this view, recent reports suggest a contribution of the posterior parietal cortex (PPC; one major region controlling spatial attention) to conjunction search as opposed to feature search. However, PPC engagement in conjunction search might also reflect feature-based attention or the difficulty of target selection. The present fMRI study compared regions and amplitudes of cortical activity reflecting the attention mechanisms of a conjunction and a feature search of equal difficulty performed during maintenance of fixation. Attention-related activity was assessed by comparing each hard feature and conjunction search with an easy feature search. Hard feature and conjunction search activated overlapping regions in multiple PPC areas and in the frontal eye field (FEF). Most consistent PPC overlaps were located in the anterior and posterior intraparietal sulcus (IPS). The response amplitude of posterior IPS did not differ between both search tasks. However, the IPS junction with the transverse occipital sulcus and the FEF responded at a higher amplitude during conjunction search. Moreover, regions of the prefrontal cortex and the PPC were activated only during either hard feature or conjunction search. These findings suggest that equally difficult visual searches for features and conjunctions are controlled by overlapping frontoparietal networks, but also that both search types involve specific mechanisms.

YNIMG Journal 2001 Journal Article

Assessment of cortical activation by multi channel topography

• Cathleen Buckow
• Matthias Kohl
• Harald Zank
• Hellmuth Obrig
• Kamil Uludag
• Jens Steinbrink
• Heike Israel
• Arno Villringer

YNIMG Journal 2001 Journal Article

Cortical representation of the human vestibular system

• Marc Kuhberg
• Ruediger Wenzel
• Oliver Fasold
• Michael von Brevern
• Christoph Ploner
• Hellmuth Obrig
• Thomas Lempert
• Arno Villringer

YNIMG Journal 2001 Journal Article

Functional assessment of broca's area using near infrared spectroscopy in humans

• Andrew F. Cannestra
• I. Wartenburger
• Arno Villringer
• Arthur W. Toga

YNIMG Journal 2001 Journal Article

Is neuro-vascular coupling altered in interictal migraineurs? A combined visually evoked potential (VEP) and near-infrared-spectroscopy (NIRS) approach

• Heike Israel
• Hellmuth Obrig
• Matthias Kohl
• Kamil Uludag
• Bianca Müller
• Rüdiger Wenzel
• Cathleen Buckow
• Guy Arnold

YNIMG Journal 2001 Journal Article

Linear Aspects of Changes in Deoxygenated Hemoglobin Concentration and Cytochrome Oxidase Oxidation during Brain Activation

• Petra Wobst
• Rüdiger Wenzel
• Matthias Kohl
• Hellmuth Obrig
• Arno Villringer

We used near infrared spectroscopy (NIRS) to investigate the vascular and metabolic response to brain activation in human primary and adjacent secondary visual cortex. NIRS is able to measure concentration changes in deoxygenated hemoglobin ([deoxy-Hb]) (which mainly contribute to the blood oxygenation level-dependent (BOLD) signal in functional magnetic resonance imaging (fMRI)) as well as concentration changes of oxygenated hemoglobin ([oxy-Hb]) and corpuscular blood volume ([total-Hb] = [oxy-Hb] + [deoxy-Hb]) and changes in the redox status of the cytochrome c oxidase ([Cyt-Ox]), a putative parameter for cellular oxygenation. A sound understanding of the transfer functions between stimulus parameters, neuronal activity, and vascular/metabolic parameters is important for interpretation of data acquired with indirect neuroimaging techniques like fMRI, especially in event-related design studies. In the present study we tested whether the vascular/metabolic response to stimulation can be described as a linear and time invariant system. Since linearity is a property attributed to systems that satisfy the scaling and superposition properties, as a first simple test, superposition of the responses obtained from short duration visual stimuli was used to predict the responses of longer duration stimuli. Our results showed that the predictions of [deoxy-Hb] and [Cyt-Ox] responses to stimuli of 6- to 24-s duration were satisfactory whereas predictions of [oxy-Hb] and [total-Hb] were insufficient. In a second step, a calculated convolution function of an assumed impulse response function and the stimulus function was fitted with the measured [deoxy-Hb] and [Cyt-Ox] curves to obtain amplitude, time delay, and time constant parameters. We show that predictions of cellular and vascular oxygenation responses to visual stimulation are good for 6- to 24-s stimuli duration under the assumption of a linear transfer characteristic. This model is not valid for corpuscular volume changes which affect mainly the [oxy-Hb] response. Noninvasive NIRS is shown to be a suitable method to get more direct information about neuronal-activity-associated changes in cerebral parameters which are partly reflected in BOLD signal but are not fully understood yet.

YNIMG Journal 2001 Journal Article

Mirror-representation of the right hand in human primary sensory cortex — An fMRI study

• Robert Meyer
• Felix Blankenburg
• Jan Ruben
• Jessica Schwiemann
• Sebastian Thees
• Ralf Kurth
• Gabriel Curio
• Kersten Villringer

YNIMG Journal 2001 Journal Article

No Evidence for Early Decrease in Blood Oxygenation in Rat Whisker Cortex in Response to Functional Activation

• Ute Lindauer
• Georg Royl
• Christoph Leithner
• Marc Kühl
• Lorenz Gold
• Jörn Gethmann
• Matthias Kohl-Bareis
• Arno Villringer

Using optical methods through a closed cranial window over the rat primary sensory cortex in chloralose/urethane-anesthetized rats we evaluated the time course of oxygen delivery and consumption in response to a physiological stimulus (whisker deflection). Independent methodological approaches (optical imaging spectroscopy, single fiber spectroscopy, oxygen-dependent phosphorescence quenching) were applied to different modes of whisker deflection (single whisker, full whisker pad). Spectroscopic data were evaluated using different algorithms (constant pathlength, differential pathlength correction). We found that whisker deflection is accompanied by a significant increase of oxygenated hemoglobin (oxy-Hb), followed by an undershoot. An early increase in deoxygenated hemoglobin (deoxy-Hb) proceeded hyperoxygenation when spectroscopic data were analyzed by constant pathlength analysis. However, correcting for the wavelength dependence of photon pathlength in brain tissue (differential pathlength correction) completely eliminated the increase in deoxy-Hb. Oxygen-dependent phosphorescence quenching did not reproducibly detect early deoxygenation. Together with recent fMRI data, our results argue against significant early deoxygenation as a universal phenomenon in functionally activated mammalian brain. Interpreted with a diffusion-limited model of oxygen delivery to brain tissue our results are compatible with coupling between neuronal activity and cerebral blood flow throughout stimulation, as postulated 110 years ago by C. Roy and C. Sherrington (1890, J. Physiol. 11: 85–108).

YNIMG Journal 2001 Journal Article

Simultaneous 32-channel-EEG based ERP and fMRI: Spatial correlation of dipole source localization and fMRI activations

• Sebastian Thees
• Felix Blankenburg
• Arno Villringer

YNIMG Journal 2000 Journal Article

Spontaneous Low Frequency Oscillations of Cerebral Hemodynamics and Metabolism in Human Adults

• Hellmuth Obrig
• Markus Neufang
• Rüdiger Wenzel
• Matthias Kohl
• Jens Steinbrink
• Karl Einhäupl
• Arno Villringer

We investigated slow spontaneous oscillations in cerebral oxygenation in the human adult's visual cortex. The rationale was (1) to demonstrate their detectability by near infrared spectroscopy (NIRS); (2) to analyze the spectral power of as well as the phase relationship between the different NIRS parameters (oxygenated and deoxygenated hemoglobin and cytochrome-oxidase; oxy-Hb/deoxy-Hb/Cyt-ox). Also (3) influences of functional stimulation and hypercapnia on power and phase shifts were investigated. The results show that—in line with the literature—low frequency oscillations (LFO) centred around 0. 1 s−1 and even slower oscillations at about 0. 04 s−1 (very low frequency, VLFO) can be distinguished. Their respective power differs between oxy-Hb, deoxy-Hb, and Cyt-ox. Either frequency (LFO and VLFO) is altered in magnitude by functional stimulation of the cortical area examined. Also we find a change of the phase shift between the vascular parameters (oxy-Hb, tot-Hb) and the metabolic parameter (Cyt-ox) evoked by the stimulation. It is shown that hypercapnia attenuates the LFO in oxy-Hb and deoxy-Hb. Conclusions: (1) spontaneous vascular and metabolic LFO and VLFO can be reproducibly detected by NIRS in the human adult. (2) Their spectral characteristics and their response to hypercapnia are in line with those described in exposed cortex (for review see (Hudetz et al. , 1998)) and correspond to findings with transcranial doppler sonography (TCD) (Diehl et al. , 1995) and fMRI (Biswal et al. , 1997). (3) The magnitude of and phase relation between NIRS-parameters at the LFO may allow for a local noninvasive assessment of autoregulatory mechanisms in the adult brain.