Michael Woletz

Stability of low-frequency fluctuation amplitudes in prolonged resting-state fMRI

The (fractional) amplitudes of low-frequency fluctuations (f)ALFF are popular measures for the magnitude of low-frequency oscillations in resting-state fMRI (R-fMRI) data. Both measures can be directly derived from the spectral power of R-fMRI time courses. Numerous studies suggest that ALFF and fALFF might be used as biomarkers for a variety of diseases including schizophrenia, major depressive disorder, and obsessive-compulsive disorder. However, the temporal stability of (f)ALFF values, which is of great importance for the application of (f)ALFF both as a biomarker and scaling parameter, has not been studied in detail yet. Here, we quantify the temporal stability, robustness and reproducibility of both ALFF and fALFF maps obtained from R-fMRI data by performing statistical analyses over 55 minute resting-state scans which included a period of NaCl infusion. We also examine the differences of using either raw or standardised (f)ALFF maps. Our analyses show that no significant changes of (f)ALFF values over the 55minute period occur for both raw and standardised (f)ALFF maps. In addition, we demonstrate that raw (f)ALFF maps across subjects are correlated with head motion as quantified via frame-wise displacement, whereas no such correlation is present in standardised (f)ALFF maps. In conclusion, the results of our study show that both ALFF and fALFF qualify as potential biomarkers due to their high temporal stability.

A novel coil array for combined TMS/fMRI experiments at 3 T

To overcome current limitations in combined transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) studies by employing a dedicated coil array design for 3 Tesla.

Subcortical gray matter changes in transgender subjects after long-term cross-sex hormone administration

Sex-steroid hormones are primarily involved in sexual differentiation and development and are thought to underlie processes related to cognition and emotion. However, divergent results have been reported concerning the effects of hormone administration on brain structure including side effects like brain atrophy and dementia. Cross-sex hormone therapy in transgender subjects offers a unique model for studying the effects of sex hormones on the living human brain. In this study, 25 Female-to-Male (FtM) and 14 Male-to-Female (MtF) subjects underwent MRI examinations at baseline and after a period of at least 4-months of continuous cross-sex hormone administration. While MtFs received estradiol and anti-androgens, FtM subjects underwent high-dose testosterone treatment. The longitudinal processing stream of the FreeSurfer software suite was used for the automated assessment and delineation of brain volumes to assess the structural changes over the treatment period of cross-sex hormone administration. Most prominent results were found for MtFs receiving estradiol and anti-androgens in the form of significant decreases in the hippocampal region. Further analysis revealed that these decreases were reflected by increases in the ventricles. Additionally, changes in progesterone levels correlated with changes in gray matter structures in MtF subjects. In line with prior studies, our results indicate hormonal influences on subcortical structures related to memory and emotional processing. Additionally, this study adds valuable knowledge that progesterone may play an important role in this process.

Default mode network deactivation during emotion processing predicts early antidepressant response

Several previous functional magnetic resonance imaging (fMRI) studies have demonstrated the predictive value of brain activity during emotion processing for antidepressant response, with a focus on clinical outcome after 6–8 weeks. However, longitudinal studies emphasize the paramount importance of early symptom improvement for the course of disease in major depressive disorder (MDD). We therefore aimed to assess whether neural activity during the emotion discrimination task (EDT) predicts early antidepressant effects, and how these predictive measures relate to more sustained response. Twenty-three MDD patients were investigated once with ultrahigh-field 7T fMRI and the EDT. Following fMRI, patients received Escitalopram in a flexible dose schema and were assessed with the Hamilton Depression Rating Scale (HAMD) before, and after 2 and 4 weeks of treatment. Deactivation of the precuneus and posterior cingulate cortex (PCC) during the EDT predicted change in HAMD scores after 2 weeks of treatment. Baseline EDT activity was not predictive of HAMD change after 4 weeks of treatment. The precuneus and PCC are integral components of the default mode network (DMN). We show that patients who exhibit stronger DMN suppression during emotion processing are more likely to show antidepressant response after 2 weeks. This is, to our knowledge, the first study to show that DMN activity predicts early antidepressant effects. However, DMN deactivation did not predict response at 4 weeks, suggesting that our finding is representative of early, likely treatment-related, yet unspecific symptom improvement. Regardless, early effects may be harnessed for optimization of treatment regimens and patient care.

Unsmoothed functional MRI of the human amygdala and bed nucleus of the stria terminalis during processing of emotional faces.

ABSTRACT Functional neuroimaging of the human amygdala has been of great interest to uncover the neural underpinnings of emotions, mood, motivation, social cognition, and decision making, as well as their dysfunction in psychiatric disorders. Yet, several factors limit in vivo imaging of amygdalar function, most importantly its location deep within the temporal lobe adjacent to air‐filled cavities that cause magnetic field inhomogeneities entailing signal dropouts. Additionally, the amygdala and the extended amygdalar region consist of several substructures, which have been assigned different functions and have important implications for functional and effective connectivity studies. Here we show that high‐resolution ultra‐high field fMRI at 7 T can be used to overcome these fundamental challenges for acquisition and can meet some of the demands posed by the complex neuroanatomy and ‐physiology in this region. Utilizing the inherently high SNR, we use an optimized preprocessing and data analysis strategy to demonstrate that imaging of the (extended) amygdala is highly reliable and robust. Using unsmoothed single‐subject data allowed us to differentiate brain activation during processing of emotional faces in the central and basolateral amygdala and, for the first time, in the bed nucleus of the stria terminalis (BNST), which is critically involved in the neural mechanisms of anxiety and threat monitoring. We also provide a quantitative assessment of single subject sensitivity, which is relevant for connectivity studies that rely on time course extraction of functionally‐defined volumes of interest. HIGHLIGHTS7 Tesla functional MRI of emotional face discrimination task in 38 healthy subjects.Unsmoothed single‐subject data applicable for whole‐brain group analysis.Differentiation of activation in central and basolateral amygdala.Significant effects in bed nucleus of stria terminalis, a key region for anxiety.Robust effects also on single‐subject level, relevant for connectivity analyses.

Task-dependent modulation of amygdala connectivity in social anxiety disorder

Increased amygdala activation is consistently found in patients suffering from social anxiety disorder (SAD), a psychiatric condition characterized by an intense fear of social situations and scrutiny. Disruptions in the amygdalar-frontal network in SAD may explain the inability of frontal regions to appropriately down-regulate amygdalar hyper-activation. In this study, we measured 15 SAD patients and 15 healthy controls during an affective counting Stroop task with emotional faces to assess the interaction of affective stimuli with a cognitive task in SAD, as well as to investigate the causal interactions between the amygdala and the medial orbitofrontal cortex (OFC) using dynamic causal modeling (DCM). Here we show for the first time that differences in OFC-amygdala effective connectivity between SAD patients and healthy controls are influenced by cognitive load during task processing. In SAD patients relative to controls dysfunctional amygdala regulation was observed during passive viewing of harsh faces This could be linked to ongoing self-initiated cognitive processes (such as rumination and anticipation of negative events) that hinder successful amygdala regulation. However, between-group differences diminished during cognitive processing, suggesting that attentional load interfered with emotional processing in both patients and controls.

High-sensitivity TMS/fMRI of the Human Motor Cortex Using a Dedicated Multichannel MR Coil

Purpose To validate a novel setup for concurrent TMS/fMRI in the human motor cortex based on a dedicated, ultra‐thin, multichannel receive MR coil positioned between scalp and TMS system providing greatly enhanced sensitivity compared to the standard birdcage coil setting. Methods A combined TMS/fMRI design was applied over the primary motor cortex based on 1 Hz stimulation with stimulation levels of 80%, 90%, 100%, and 110% of the individual active motor threshold, respectively. Due to the use of a multichannel receive coil we were able to use multiband‐accelerated (MB=2) EPI sequences for the acquisition of functional images. Data were analysed with SPM12 and BOLD‐weighted signal intensity time courses were extracted in each subject from two local maxima (individual functional finger tapping localiser, fixed MNI coordinate of the hand knob) next to the hand area of the primary motor cortex (M1) and from the global maximum. Results We report excellent image quality without noticeable signal dropouts or image distortions. Parameter estimates in the three peak voxels showed monotonically ascending activation levels over increasing stimulation intensities. Across all subjects, mean BOLD signal changes for 80%, 90%, 100%, 110% of the individual active motor threshold were 0.43%, 0.63%, 1.01%, 2.01% next to the individual functional finger tapping maximum, 0.73%, 0.91%, 1.34%, 2.21% next to the MNI‐defined hand knob and 0.88%, 1.09%, 1.65%, 2.77% for the global maximum, respectively. Conclusion Our results show that the new setup for concurrent TMS/fMRI experiments using a dedicated MR coil array allows for high‐sensitivity fMRI particularly at the site of stimulation. Contrary to the standard birdcage approach, the results also demonstrate that the new coil can be successfully used for multiband‐accelerated EPI acquisition. The gain in flexibility due to the new coil can be easily combined with neuronavigation within the MR scanner to allow for accurate targeting in TMS/fMRI experiments.

Artificial scotoma estimation based on population receptive field mapping

ABSTRACT Population receptive field (pRF) mapping based on functional magnetic resonance imaging (fMRI) is an ideal method for obtaining detailed retinotopic information. One particularly promising application of pRF mapping is the estimation and quantification of visual field effects, for example scotomata in patients suffering from macular dysfunction or degeneration (MD) or hemianopic defects in patients with intracranial dysfunction. However, pRF mapping performance is influenced by a number of factors including spatial and temporal resolution, distribution of dural venous sinuses and patient performance. This study addresses the ability of current pRF methodology to assess the size of simulated scotomata in healthy individuals. The data demonstrate that central scotomata down to a radius of 2.35° (4.7° diameter) visual angle can be reliably estimated in single subjects using high spatial resolution protocols and multi‐channel receive array coils. HighlightsCentral scotomata size assessment by population Receptive Field (pRF) mapping using fMRI.Scotomata size can be reliably estimated down to radius of 2.35° in single subjects.The method could complement microperimetry examinations in patients suffering from macular dysfunction.

Correction to: The pulvinar nucleus and antidepressant treatment: dynamic modeling of antidepressant response and remission with ultra-high field functional MRI

The author list was presented as last name, first name. The names should have been listed as:Christoph Kraus, Manfred Klöbl, Martin Tik, Bastian Auer, Thomas Vanicek, Nicole Geissberger, Daniela M. Pfabigan, Andreas Hahn, Michael Woletz, Katharina Paul, Arkadiusz Komorowski, Siegfried Kasper, Christian Windischberger, Claus Lamm, Rupert Lanzenberger.