Michael Wagner

YNICL Journal 2021 Journal Article

Association between composite scores of domain-specific cognitive functions and regional patterns of atrophy and functional connectivity in the Alzheimer’s disease spectrum

• Chimezie O. Amaefule
• Martin Dyrba
• Steffen Wolfsgruber
• Alexandra Polcher
• Anja Schneider
• Klaus Fliessbach
• Annika Spottke
• Dix Meiberth

BACKGROUND: Cognitive decline has been found to be associated with gray matter atrophy and disruption of functional neural networks in Alzheimer's disease (AD) in structural and functional imaging (fMRI) studies. Most previous studies have used single test scores of cognitive performance among monocentric cohorts. However, cognitive domain composite scores could be more reliable than single test scores due to the reduction of measurement error. Adopting a multicentric resting state fMRI (rs-fMRI) and cognitive domain approach, we provide a comprehensive description of the structural and functional correlates of the key cognitive domains of AD. METHOD: We analyzed MRI, rs-fMRI and cognitive domain score data of 490 participants from an interim baseline release of the multicenter DELCODE study cohort, including 54 people with AD, 86 with Mild Cognitive Impairment (MCI), 175 with Subjective Cognitive Decline (SCD), and 175 Healthy Controls (HC) in the AD-spectrum. Resulting cognitive domain composite scores (executive, visuo-spatial, memory, working memory and language) from the DELCODE neuropsychological battery (DELCODE-NP), were previously derived using confirmatory factor analysis. Statistical analyses examined the differences between diagnostic groups, and the association of composite scores with regional atrophy and network-specific functional connectivity among the patient subgroup of SCD, MCI and AD. RESULT: Cognitive performance, atrophy patterns and functional connectivity significantly differed between diagnostic groups in the AD-spectrum. Regional gray matter atrophy was positively associated with visuospatial and other cognitive impairments among the patient subgroup in the AD-spectrum. Except for the visual network, patterns of network-specific resting-state functional connectivity were positively associated with distinct cognitive impairments among the patient subgroup in the AD-spectrum. CONCLUSION: Consistent associations between cognitive domain scores and both regional atrophy and network-specific functional connectivity (except for the visual network), support the utility of a multicentric and cognitive domain approach towards explicating the relationship between imaging markers and cognition in the AD-spectrum.

YNICL Journal 2019 Journal Article

Subregional volume reduction of the cholinergic forebrain in subjective cognitive decline (SCD)

• Lukas Scheef
• Michel J. Grothe
• Alexander Koppara
• Marcel Daamen
• Henning Boecker
• Hans Biersack
• Hans H. Schild
• Michael Wagner

Subjective cognitive decline (SCD) patients are considered as a risk population for preclinical Alzheimer's Disease (AD). Supporting this idea, previous studies in SCD populations report subtle alterations in various cognitive and neuroimaging biomarkers that are typically affected during AD progression. To extend these observations, the present study examined whether SCD patients show atrophy of cholinergic basal forebrain nuclei (chBFN), analogous with recent findings in prodromal and clinical AD patients. We assessed volume reductions of the chBFN in 24 SCD subjects compared to 49 matched controls on 3D-T1-weighted MR images based on a postmortem derived atlas. Furthermore, we assessed whether chBFN atrophy was linked with cognitive, structural and metabolic biomarker alterations we previously reported in this SCD cohort: Using correlation analyses we tested for associations between the volumes of the chBFN with the hippocampal gray matter volume, and posterior medial glucose consumption, and the trajectory of verbal memory performance. The SCD cases showed a significant total volume reduction of the chBFN, with largest effect sizes in the Ch1/2 and Ch4p subdivisions of the chBFN. The latter was associated with a reduced glucose metabolism in the precuneus for the SCD group only. These data show an early involvement of the cholinergic basal forebrain nuclei in SCD predominantly in Ch1/2 and Ch4p which supports the conceptual link between SCD and preclinical AD.

YNICL Journal 2018 Journal Article

Neural correlates of working memory deficits and associations to response inhibition in obsessive compulsive disorder

• Stephan Heinzel
• Christian Kaufmann
• Rosa Grützmann
• Robert Hummel
• Julia Klawohn
• Anja Riesel
• Katharina Bey
• Leonhard Lennertz

Previous research in patients with obsessive-compulsive disorder (OCD) has indicated performance decrements in working memory (WM) and response inhibition. However, underlying neural mechanisms of WM deficits are not well understood to date, and empirical evidence for a proposed conceptual link to inhibition deficits is missing. We investigated WM performance in a numeric n-back task with four WM load conditions during functional Magnetic Resonance Imaging (fMRI) in 51 patients with OCD and 49 healthy control participants who were matched for age, sex, and education. Additionally, a stop signal task was performed outside the MRI scanner in a subsample. On the behavioral level, a significant WM load by group interaction was found for both accuracy (p < 0.02) and reaction time measures (p < 0.03), indicating increased reaction times as well as reduced accuracy specifically at high WM load (3-back) in patients with OCD. Whole-brain analyses of fMRI-data identified neural correlates of a load-dependent WM decrement in OCD in the supplementary motor area (SMA) and the inferior parietal lobule (IPL). Within the OCD sample, SMA-activity as well as n-back performance were correlated with stop signal task performance. Results from behavioral and fMRI-analyses indicate a reduced WM load-dependent modulation of neural activity in OCD and suggest a common neural mechanism for inhibitory dysfunction and WM decrements in OCD.

AIIM Journal 2012 Journal Article

Identifying a small set of marker genes using minimum expected cost of misclassification

• Samuel H. Huang
• Dengyao Mo
• Jarek Meller
• Michael Wagner

Objectives This paper presents a model independent feature selection approach to identify a small subset of marker genes. Methods and material An evaluation measure, minimum expected cost of misclassification (MEMC), is used to estimate the discriminative power of a feature subset without building a model. The MECM measure is combined with sequential forward search for feature selection. This approach was applied to a breast cancer profiling problem, with the goal of identifying a small number of marker genes whose expression can be used to predict cancer molecular subtype (p53 gene status). Furthermore, the method was also applied to find a small set of single-nucleotide polymorphisms (SNPs) that can be used to predict molecular phenotype of a different type, namely alleles (genetic variants) of human leukocyte antigen genes that play an important roles in autoimmunity. Results Two marker genes were identified based on p53 status, which achieved a p-value of 7. 53×10−5 (vs. 6×10−4 with 32 genes identified by previous research) in survival analysis. Six SNP loci were identified that achieved a leave-one-out cross-validation accuracy of 92. 8% (vs. 90. 6% and 89. 5% with 18 SNPs selected using χ 2 statistics and information gain, respectively). Conclusion The MECM-based feature selection approach is capable of identifying a smaller subset of market genes with comparable or even better performance than that obtained using conventional filter methods.

YNIMG Journal 2008 Journal Article

Spatiotemporal dynamics of audiovisual speech processing

• Lynne E. Bernstein
• Edward T. Auer
• Michael Wagner
• Curtis W. Ponton

The cortical processing of auditory-alone, visual-alone, and audiovisual speech information is temporally and spatially distributed, and functional magnetic resonance imaging (fMRI) cannot adequately resolve its temporal dynamics. In order to investigate a hypothesized spatiotemporal organization for audiovisual speech processing circuits, event-related potentials (ERPs) were recorded using electroencephalography (EEG). Stimuli were congruent audiovisual /ba/, incongruent auditory /ba/ synchronized with visual /ga/, auditory-only /ba/, and visual-only /ba/ and /ga/. Current density reconstructions (CDRs) of the ERP data were computed across the latency interval of 50–250 ms. The CDRs demonstrated complex spatiotemporal activation patterns that differed across stimulus conditions. The hypothesized circuit that was investigated here comprised initial integration of audiovisual speech by the middle superior temporal sulcus (STS), followed by recruitment of the intraparietal sulcus (IPS), followed by activation of Broca’s area [Miller, L. M. , d’Esposito, M. , 2005. Perceptual fusion and stimulus coincidence in the cross-modal integration of speech. Journal of Neuroscience 25, 5884–5893]. The importance of spatiotemporally sensitive measures in evaluating processing pathways was demonstrated. Results showed, strikingly, early (<100 ms) and simultaneous activations in areas of the supramarginal and angular gyrus (SMG/AG), the IPS, the inferior frontal gyrus, and the dorsolateral prefrontal cortex. Also, emergent left hemisphere SMG/AG activation, not predicted based on the unisensory stimulus conditions was observed at approximately 160 to 220 ms. The STS was neither the earliest nor most prominent activation site, although it is frequently considered the sine qua non of audiovisual speech integration. As discussed here, the relatively late activity of the SMG/AG solely under audiovisual conditions is a possible candidate audiovisual speech integration response.

YNIMG Journal 2007 Journal Article

Generators of the intracranial P50 response in auditory sensory gating

• Oleg Korzyukov
• Mark E. Pflieger
• Michael Wagner
• Susan M. Bowyer
• T. Rosburg
• Karthik Sundaresan
• Christian Erich Elger
• Nashaat N. Boutros

Clarification of the cortical mechanisms underlying auditory sensory gating may advance our understanding of brain dysfunctions associated with schizophrenia. To this end, data from nine epilepsy patients who participated in an auditory paired-click paradigm during pre-surgical evaluation and had grids of electrodes covering temporal and frontal lobe were analyzed. A distributed source localization approach was applied to the intracranial P50 response and the Gating Difference Wave obtained by subtracting the response to the second stimuli from the response to the first stimuli. Source reconstruction of the P50 showed that the main generators of the response were localized in the temporal lobes. The analysis also suggested that the maximum neuronal activity contributing to the amplitude reduction in the P50 time range (phenomenon of auditory sensory gating) is localized at the frontal lobe. Present findings suggest that while the temporal lobe is the main generator of the P50 component, the frontal lobe seems to be a substantial contributor to the process of sensory gating as observed from scalp recordings.

YNIMG Journal 2006 Journal Article

Is the movement-evoked potential mandatory for movement execution? A high-resolution EEG study in a deafferented patient

• Rumyana Kristeva
• Vihren Chakarov
• Michael Wagner
• Jürgen Schulte-Mönting
• M.-C. Hepp-Reymond

During simple self-paced index finger flexion with and without visual feedback of the finger, we compared the movement-evoked potentials of the completely deafferented patient GL with those of 7 age-matched healthy subjects. EEG was recorded from 58 scalp positions, together with the electromyogram (EMG) from the first dorsal interosseous muscle and the movement trace. We analyzed the movement parameters and the contralateral movement-evoked potential and its source. The patient performed the voluntary movements almost as well as the controls in spite of her lack of sensory information from the periphery. In contrast, the movement-evoked potential was observed only in the controls and not in the patient. These findings clearly demonstrate that the movement-evoked potential reflects cutaneous and proprioceptive feedback from the moving part of the body. They also indicate that in absence of sensory peripheral input the motor control switches from an internal “sensory feedback-driven” to a “feedforward” mode. The role of the sensory feedback in updating the internal models and of the movement-evoked potential as a possible cortical correlate of motor awareness is discussed.

JMLR Journal 2005 Journal Article

What's Strange About Recent Events (WSARE): An Algorithm for the Early Detection of Disease Outbreaks

• Weng-Keen Wong
• Andrew Moore
• Gregory Cooper
• Michael Wagner

Traditional biosurveillance algorithms detect disease outbreaks by looking for peaks in a univariate time series of health-care data. Current health-care surveillance data, however, are no longer simply univariate data streams. Instead, a wealth of spatial, temporal, demographic and symptomatic information is available. We present an early disease outbreak detection algorithm called What's Strange About Recent Events (WSARE), which uses a multivariate approach to improve its timeliness of detection. WSARE employs a rule-based technique that compares recent health-care data against data from a baseline distribution and finds subgroups of the recent data whose proportions have changed the most from the baseline data. In addition, health-care data also pose difficulties for surveillance algorithms because of inherent temporal trends such as seasonal effects and day of week variations. WSARE approaches this problem using a Bayesian network to produce a baseline distribution that accounts for these temporal trends. The algorithm itself incorporates a wide range of ideas, including association rules, Bayesian networks, hypothesis testing and permutation tests to produce a detection algorithm that is careful to evaluate the significance of the alarms that it raises. [abs] [ pdf ][ bib ] &copy JMLR 2005. ( edit, beta )

YNIMG Journal 2001 Journal Article

A standard BEM head model for EEG source reconstruction

• Manfred Fuchs
• Michael Wagner
• Jörn Kastner

YNIMG Journal 2001 Journal Article

The role of the right inferior parietal lobule in the calculation of saccade amplitude: An fMRI study

• Klaus Hoenig
• Frank Jessen
• Dirk Granath
• Nikolaus Freymann
• Jürgen Reul
• Reinhard Heun
• Michael Wagner

YNIMG Journal 2000 Journal Article

Subcortical correlates of craving in early abstinent alcoholic patients

• Frank Schneider
• Ute Habel
• Petra Franke
• Michael Wagner
• Jasmin B. Salloum
• Klaus Honig
• Christian Sulzbach
• Karl Zilles

YNIMG Journal 1999 Journal Article

The Role of Higher-Order Motor Areas in Voluntary Movement as Revealed by High-Resolution EEG and fMRI

• Tonio Ball
• Axel Schreiber
• Bernd Feige
• Michael Wagner
• Carl Hermann Lücking
• Rumyana Kristeva-Feige

In the human motor cortex structural and functional differences separate motor areas related to motor output from areas essentially involved in higher-order motor control. Little is known about the function of these higher-order motor areas during simple voluntary movement. We examined a simple finger flexion movement in six healthy subjects using a novel brainimaging approach, integrating high-resolution EEG with the individual structural and functional MRI. Electrical source reconstruction was performed in respect to the individual brain morphology from MRI. Highly converging results from EEG and fMRI were obtained for both executive and higher-order motor areas. All subjects showed activation of the primary motor area (MI) and of the frontal medial wall motor areas. Two different types of medial wall activation were observed with both methods: Four of the subjects showed an anterior type of activation, and two of the subjects a posterior type of activation. In the former, activity started in the anterior cingulate motor area (CMA) and subsequently shifted its focus to the intermediate supplementary motor area (SMA). Approximately 120 ms before the movement started, the intermediate SMA showed a drop of source strength, and simultaneously MI showed an increase of source strength. In the posterior type, activation was restricted to the posterior SMA. Further, three of the subjects investigated showed activation in the inferior parietal lobe (IPL) starting during early movement preparation. In all subjects showing activation of higher-order motor areas (anterior CMA, intermediate SMA, IPL) these areas became active before the executive motor areas (MI and posterior SMA). We suggest that the early activation of the anterior CMA and the IPL may be related to attentional functions of these areas. Further, we argue that the intermediate part of the SMA triggers the actual motor act via the release of inhibition of the primary motor area. Our results demonstrate that a noninvasive, multimodal brain imaging technique can reveal individual cortical brain activity with high temporal and spatial resolution, independent of a priori physiological assumptions.