Retinotopic cortical mapping in objective functional monitoring of macular therapy.

BACKGROUND/AIMS: To determine the suitability of functional MRI (fMRI) as an objective measure of macular function following therapeutic intervention; conventional psychophysical measures rely heavily on patient compliance. METHODS: Twenty patients with neovascular age-related macular degeneration (nAMD) were studied with high-resolution fMRI, visual acuity, reading accuracy and speed, contrast sensitivity (CS) and microperimetry (MP) before and after 3 monthly intravitreal injections of ranibizumab. Population-receptive field retinotopic maps calculated from fMRI data were compared with psychophysical measures and optical coherence tomography. RESULTS: Best-corrected visual acuity (BCVA) responders (≥5 letters) showed an increase of 29.5% in activated brain area, while non-responders showed a decrease of 0.8%. Radial histograms over eccentricity allowed quantification of the absolute number of significant voxels and thus differences before and after treatment. Responders showed increases in foveal (α<0.5°) activation, while non-responders did not. Absence of intraretinal fluid and preservation of outer retinal layers was associated with higher numbers of active V1 voxels and better BCVA. Higher voxel numbers were associated with improved reading performance and, less marked, with BCVA, CS and MP. CONCLUSION: The data show that retinotopic mapping using fMRI can successfully be applied objectively to evaluate the therapeutic response in nAMD patients treated with anti-vascular endothelial growth factor therapy. This demonstrates the ability of retinotopic mapping to provide an objective assessment of functional recovery at a cortical level; the technique can therefore be applied, in other degenerative macular diseases, to the assessment of potential therapeutic interventions such as gene therapy or cell replacement therapy.

Chronometric TMS-fMRI of personalized left dorsolateral prefrontal target reveals state-dependency of subgenual anterior cingulate cortex effects.

Transcranial magnetic stimulation (TMS) applied to a left dorsolateral prefrontal cortex (DLPFC) area with a specific connectivity profile to the subgenual anterior cingulate cortex (sgACC) has emerged as a highly effective non-invasive treatment option for depression. However, antidepressant outcomes demonstrate significant variability among therapy plans and individuals. One overlooked contributing factor is the individual brain state at the time of treatment. In this study we used interleaved TMS-fMRI to investigate the influence of brain state on acute TMS effects, both locally and remotely. TMS was performed during rest and during different phases of cognitive task processing. Twenty healthy participants were included in this study. In the first session, imaging data for TMS targeting were acquired, allowing for identification of individualized targets in the left DLPFC based on highest anti-correlation with the sgACC. The second session involved chronometric interleaved TMS-fMRI measurements, with 10 Hz triplets of TMS administered during rest and at distinct timings during an N-back task. Consistent with prior findings, interleaved TMS-fMRI revealed significant BOLD activation changes in the targeted network. The precise timing of TMS relative to the cognitive states during the task demonstrated distinct BOLD response in clinically relevant brain regions, including the sgACC. Employing a standardized timing approach for TMS using a task revealed more consistent modulation of the sgACC at the group level compared to stimulation during rest. In conclusion, our findings strongly suggest that acute local and remote effects of TMS are influenced by brain state during stimulation. This study establishes a basis for considering brain state as a significant factor in designing treatment protocols, possibly improving TMS treatment outcomes.

Concurrent TMS/fMRI reveals individual DLPFC dose-response pattern.

BACKGROUND: TMS is a valuable tool in both research and clinical settings, playing a crucial role in understanding brain-behavior relationships and providing treatment for various neurological and psychiatric conditions. Importantly, TMS over left DLPFC is an FDA approved treatment for MDD. Despite its potential, response variability to TMS remains a challenge, with stimulation parameters, particularly the stimulation intensity, being a primary contributor to these differences. OBJECTIVE: The objective of this study was to establish dose-response relationships of TMS stimulation in DLPFC by means of concurrent TMS/fMRI. METHODS: Here, we stimulated 15 subjects at different stimulation intensities of 80, 90, 100 and 110 % relative to the motor threshold during concurrent TMS/fMRI. The experiment comprised two sessions: one session to collect anatomical data in order to perform neuronavigation and one session dedicated to dose-response mapping. We calculated GLMs for each intensity level and each subject, as well as at a group-level per intensity. RESULTS: On a group level, we show that the strongest BOLD-response was at 100 % stimulation. However, investigating individual dose response-relationships showed differences in response patterns across the group: subjects that responded to subthreshold stimulation, subjects that required above threshold stimulation in order to show a significant BOLD-response and atypical responders. CONCLUSIONS: We observed qualitative inter-subject variability in terms of dose-response relationship to TMS over left DLPFC, which hints towards the motor threshold not being directly transferable to the excitability of the DLPFC. Concurrent TMS/fMRI might have the potential to improve response rates to rTMS applications. As such, it may be valuable in the future to consider implementing this approach prior to clinical TMS or validating more cost-effective methods to determine dose and target with respect to changes in clinical symptoms.

Functional connectivity explains how neuronavigated TMS of posterior temporal subregions differentially affect language processing.

BACKGROUND: "Wernicke's area" is most often used to describe the posterior superior temporal gyrus (STG) and refers to a region traditionally thought to support language comprehension. However, the posterior STG additionally plays a critical role in language production. The purpose of the current study was to determine to what extent regions within the posterior STG are selectively recruited during language production. METHODS: 23 healthy right-handed participants completed an auditory fMRI localizer task, resting-state fMRI and underwent neuronavigated TMS language mapping. We applied repetitive TMS bursts during a picture naming paradigm to probe speech disruptions of different categories (anomia, speech arrest, semantic paraphasia and phonological paraphasia). We combined an in-house built high precision stimulation software suite with E-field modeling to map the naming errors to cortical regions and revealed a dissociation of language functions within the temporal gyrus. Resting state fMRI was used to explain how E-field peaks of different categories differentially affected language production. RESULTS: Peaks for phonological and semantic errors were found in the STG while those for anomia and speech arrest were located in the MTG. Seed-based connectivity analysis revealed a local connectivity pattern for phonological and semantic errors, while anomia and speech arrest seeds resulted in a larger network between IFG and posterior MTG. CONCLUSIONS: Our study provides important insights into the functional neuroanatomy of language production and might help to increase the current understanding of specific language production difficulties on a causal level.

Improved brain stimulation targeting by optimising image acquisition parameters.

Functional connectivity analysis from rs-fMRI data has been used for determining cortical targets in therapeutic applications of non-invasive brain stimulation using transcranial magnetic stimulation (TMS). Reliable connectivity measures are therefore essential for every rs-fMRI-based TMS targeting approach. Here, we examine the effect of echo time (TE) on the reproducibility and spatial variability of resting-state connectivity measures. We acquired multiple runs of single-echo fMRI data with either short (TE = 30 ms) or long (TE = 38 ms) echo time to investigate inter-run spatial reproducibility of a clinically relevant functional connectivity map, i.e., originating from the sgACC. We find that connectivity maps obtained from TE = 38 ms rs-fMRI data are significantly more reliable than those obtained from TE = 30 ms data sets. Our results clearly show that optimizing sequence parameters can be beneficial for ensuring high-reliability resting-state acquisition protocols to be used for TMS targeting. The differences between reliability in connectivity measures for different TEs could inform future clinical research in optimising MR sequences.

Comparison of Stimulus Types for Retinotopic Cortical Mapping of Macular Disease.

Purpose: Retinotopic maps acquired using functional magnetic resonance imaging (fMRI) provide a valuable adjunct in the assessment of macular function at the level of the visual cortex. The present study quantitatively assessed the performance of different visual stimulation approaches for mapping visual field coverage. Methods: Twelve patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) were examined using high-resolution ultra-high field fMRI (Siemens Magnetom 7T) and microperimetry (MP; Nidek MP-3). The population receptive field (pRF)-based coverage maps obtained with two different stimulus techniques (moving bars, and rotating wedges and expanding rings) were compared with the results of MP. Correspondence between MP and pRF mapping was quantified by calculating the simple matching coefficient (SMC). Results: Stimulus choice is shown to bias the spatial distribution of pRF centers and eccentricity values with pRF sizes obtained from wedge/ring or bar stimulation showing systematic differences. Wedge/ring stimulation results show a higher number of pRF centers in foveal areas and strongly reduced pRF sizes compared to bar stimulation runs. A statistical comparison shows significantly higher pRF center numbers in the foveal 2.5 degrees region of the visual field for wedge/ring compared to bar stimuli. However, these differences do not significantly influence SMC values when compared to MP (bar <2.5 degrees: 0.88 ± 0.13; bar >2.5 degrees: 0.88 ± 0.11; wedge/ring <2.5 degrees: 0.89 ± 0.12 wedge/ring; >2.5 degrees: 0.86 ± 0.10) for the peripheral visual field. Conclusions: Both visual stimulation designs examined can be applied successfully in patients with GA. Although the two designs show systematic differences in the distribution of pRF center locations, this variability has minimal impact on the SMC when compared to the MP outcome.

Intrasession and Intersession Reproducibility of Artificial Scotoma pRF Mapping Results at Ultra-High Fields.

Functional magnetic resonance imaging (fMRI) combined with population receptive field (pRF) mapping allows for associating positions on the visual cortex to areas on the visual field. Apart from applications in healthy subjects, this method can also be used to examine dysfunctions in patients suffering from partial visual field losses. While such objective measurement of visual deficits (scotoma) is of great importance for, e.g., longitudinal studies addressing treatment effects, it requires a thorough assessment of accuracy and reproducibility of the results obtained. In this study, we quantified the reproducibility of pRF mapping results within and across sessions in case of central visual field loss in a group of 15 human subjects. We simulated scotoma by masking a central area of 2° radius from stimulation to establish ground-truth conditions. This study was performed on a 7T ultra-high field MRI scanner for increased sensitivity. We found excellent intrasession and intersession reproducibility for the pRF center position (Spearman correlation coefficients for x, y: >0.95; eccentricity: >0.87; polar angle: >0.98), but only modest reproducibility for pRF size (Spearman correlation coefficients around 0.4). We further examined the scotoma detection performance using an automated method based on a reference dataset acquired with full-field stimulation. For the 2° artificial scotoma, the group-averaged scotoma sizes were estimated at between 1.92° and 2.19° for different sessions. We conclude that pRF mapping of visual field losses yields robust, reproducible measures of retinal function and suggest the use of pRF mapping as an objective method for monitoring visual deficits during therapeutic interventions or disease progression.

Combining stimulus types for improved coverage in population receptive field mapping.

Retinotopy experiments using population receptive field (pRF) mapping are ideal for assigning regions in the visual field to cortical brain areas. While various designs for visual stimulation were suggested in the literature, all have specific shortcomings regarding visual field coverage. Here we acquired high-resolution 7 Tesla fMRI data to compare pRF-based coverage maps obtained with the two most commonly used stimulus variants: moving bars; rotating wedges and expanding rings. We find that stimulus selection biases the spatial distribution of pRF centres. In addition, eccentricity values and pRF sizes obtained from wedge/ring or bar stimulation runs show systematic differences. Wedge/ring stimulation results show lower eccentricity values and strongly reduced pRF sizes compared to bar stimulation runs. Statistical comparison shows significantly higher pRF centre numbers in the foveal 2° region of the visual field for wedge/ring compared to bar stimuli. We suggest and evaluate approaches for combining pRF data from different visual stimulus patterns to obtain improved mapping results.

Detached empathic experience of others' pain in remitted states of depression - An fMRI study.

BACKGROUND: Major depressive disorder is strongly associated with impairments and difficulties in social interactions. Deficits in empathy, a vital skill for social interactions, have been identified as a risk factor for relapse. However, research on empathy in remitted states of depression is scarce. We chose a social neuroscience approach to investigate potentially altered neural processes involved in sub-components of empathy in remitted states of depression. We expected aberrations in cognitive components of empathy, based on previous reports regarding their role as risk factors for relapse. METHODS: Employing functional magnetic resonance imaging and a pain empathy task (video clips of painful medical treatments), we compared behavioral and neural empathic responses of unmedicated remitted depressive patients (N = 32) to those of untreated acutely depressed patients (N = 29) and healthy controls (N = 35). Self-report ratings of pain evaluation and affect-sharing were obtained. RESULTS: Compared to controls and acutely depressed patients, remitted depressive patients reported higher pain evaluation and showed increased activity in the right temporo-parietal junction. This region, which is central to self-other distinction and which has been linked to adopting a detached perspective, also exhibited reduced connectivity to the anterior insula. Furthermore, we observed reduced activity in regions involved in emotion processing (amygdala) and perception of affective facial expressions (fusiform face area, posterior superior temporal sulcus). CONCLUSIONS: Remitted states of depression are associated with a detached empathic style in response to others' pain, characterized by increased self-other distinction, lowered affective processing, and reduced connectivity between empathy-related brain regions. Although this may prevent emotional harm in specific situations, it may reduce opportunities for positive experiences in social interactions in the long run.

Technical Note: Human tissue-equivalent MRI phantom preparation for 3 and 7 Tesla.

PURPOSE: While test objects (phantoms) in magnetic resonance imaging (MRI) are crucial for sequence development, protocol validation, and quality control, studies on the preparation of phantoms have been scarce, particularly at fields exceeding 3 Tesla. Here, we present a framework for the preparation of phantoms with well-defined T1 and T2 times at 3 and 7 Tesla. METHODS: Phantoms with varying concentrations of agarose and Gd-DTPA were prepared and measured at 3 and 7 Tesla using T1 and T2 mapping techniques. An empirical, polynomial model was constructed that best represents the data at both field strengths, enabling the preparation of new phantoms with specified combinations of both T1 and T2 . Instructions for three different tissue types (brain gray matter, brain white matter, and renal cortex) are presented and validated. RESULTS: T1 times in the samples ranged from 698 to 2820 ms and from 695 to 2906 ms, whereas T2 times ranged from 39 to 227 ms and from 34 to 235 ms for 3 and 7 Tesla scans, respectively. Models for both relaxation times used six parameters to represent the data with an adjusted R² of 0.998 and 0.997 for T1 and T2 , respectively. CONCLUSION: Based on the equations derived from the current study, it is now possible to obtain accurate weight specifications for a test object with desired T1 and T2 relaxation times. This will spare researchers the laborious task of trail-and-error approaches in test object preparation attempts.

Reproducibility of amygdala activation in facial emotion processing at 7T.

Despite its importance as the prime method for non-invasive assessment of human brain function, functional MRI (fMRI) was repeatedly challenged with regards to the validity of the fMRI-derived brain activation maps. Amygdala fMRI was particularly targeted, as the amygdala's anatomical position in the ventral brain combined with strong magnetic field inhomogeneities and proximity to large vessels pose considerable obstacles for robust activation mapping. In this high-resolution study performed at ultra-high field (7T) fMRI, we aimed at (1) investigating systematic replicability of amygdala group-level activation in response to an established emotion processing task by varying task instruction and acquisition parameters and (2) testing for intra- and intersession reliability. At group-level, our results show statistically significant activation in bilateral amygdala and fusiform gyrus for each of the runs acquired. In addition, while fusiform gyrus activations are consistent across runs and sessions, amygdala activation levels show habituation effects across runs. This amygdala habituation effect is replicated in a session repeated two weeks later. Varying task instruction between matching emotions and matching persons does not change amygdala activation strength. Also, comparing two acquisition protocols with repetition times of either 700 â€‹ms or 1400 â€‹ms did not result in statistically significant differences of activation levels. Regarding within-subject reliability of amygdala activation, despite considerable variance in individual habituation patterns, we report fair to good inter-session reliability for the first run and excellent reliability for averages over runs. We conclude that high-resolution fMRI at 7T allows for robust mapping of amygdala activation in a broad range of variations. Our results of amygdala 7T fMRI are suitable to inform methodology and may encourage future studies to continue using emotion discrimination paradigms in clinical and non-clinical applications.

Antidepressant treatment, not depression, leads to reductions in behavioral and neural responses to pain empathy.

Major depressive disorder (MDD) has been hypothesized to lead to impairments in empathy. Previous cross-sectional studies did not disentangle effects of MDD itself and antidepressant treatment. In this first longitudinal neuroimaging study on empathy in depression, 29 patients with MDD participated in two functional magnetic resonance imaging (fMRI) sessions before and after 3 months of antidepressant therapy. We compared their responses to an empathy for pain task to a group of healthy controls (N = 35). All participants provided self-report ratings targeting cognitive (perspective taking) and affective (unpleasant affect) aspects of empathy. To control for general effects on processing of negative affective states, participants additionally underwent an electrical pain task. Before treatment, we found no differences in empathic responses between controls and patients with MDD. After treatment, patients showed significant decreases in both affective empathy and activity of three a priori selected brain regions associated with empathy for pain. Decreases in affective empathy were moreover correlated with symptom improvement. Moreover, functional connectivity during the empathy task between areas associated with affective (anterior insula) and cognitive (precuneus) empathy decreased between sessions in the MDD group. Neither cognitive empathy nor responses to painful electrical shocks were changed after treatment. These findings contradict previous cross-sectional reports of empathy deficits in acute MDD. Rather, they suggest that antidepressant treatment reduces the aversive responses triggered by exposure to the suffering of others. Importantly, this cannot be explained by a general blunting of negative affect, as treatment did not change self-experienced pain.

Hippocampal Subfields in Acute and Remitted Depression-an Ultra-High Field Magnetic Resonance Imaging Study.

BACKGROUND: Studies investigating hippocampal volume changes after treatment with serotonergic antidepressants in patients with major depressive disorder yielded inconsistent results, and effects on hippocampal subfields are unclear. METHODS: To detail treatment effects on total hippocampal and subfield volumes, we conducted an open-label study with escitalopram followed by venlafaxine upon nonresponse in 20 unmedicated patients with major depressive disorder. Before and after 12 weeks treatment, we measured total hippocampal formation volumes and subfield volumes with ultra-high field (7 Tesla), T1-weighted, structural magnetic resonance imaging, and FreeSurfer. Twenty-eight remitted patients and 22 healthy subjects were included as controls. We hypothesized to detect increased volumes after treatment in major depressive disorder. RESULTS: We did not detect treatment-related changes of total hippocampal or subfield volumes in patients with major depressive disorder. Secondary results indicated that the control group of untreated, stable remitted patients, compared with healthy controls, had larger volumes of the right hippocampal-amygdaloid transition area and right fissure at both measurement time points. Depressed patients exhibited larger volumes of the right subiculum compared with healthy controls at MRI-2. Exploratory data analyses indicated lower baseline volumes in the subgroup of remitting (n = 10) vs nonremitting (n = 10) acute patients. CONCLUSIONS: The results demonstrate that monoaminergic antidepressant treatment in major depressive disorder patients was not associated with volume changes in hippocampal subfields. Studies with larger sample sizes to detect smaller effects as well as other imaging modalities are needed to further assess the impact of antidepressant treatment on hippocampal subfields.

Modulations in resting state networks of subcortical structures linked to creativity.

Creativity is a sine qua non ability for almost all aspects of everyday life. Although very profound behavioural models were provided by 21st century psychologists, the neural correlates of these personality features associated with creativity are largely unknown. Recent models suggest strong relationships between dopamine release and various creative skills. Herein, we employed functional connectivity analyses of resting-state functional magnetic imaging data in order to shed light on these neural underpinnings of creative aspects. For improved sensitivity, we performed the study at ultra-high magnetic field (7 T). Seed regions were defined based on subcortical (ventral tegmental area/substantia nigra, nucleus caudatus) activation foci of a remote associates task (RAT). In addition, bilateral PCC was used as seed region to examine the default-mode network. Network strength across subjects was regressed against a battery of psychological variables related to creativity. Dopaminergic network variations turned out to be indicative for individual differences in creative traits. In this regard, the caudate network showed stronger connectivity in individuals with higher extraversion measures, while connectivity with the midbrain network was found increased with higher ideational behaviour and emotional stability.

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

Functional magnetic resonance imaging (fMRI) successfully disentangled neuronal pathophysiology of major depression (MD), but only a few fMRI studies have investigated correlates and predictors of remission. Moreover, most studies have used clinical outcome parameters from two time points, which do not optimally depict differential response times. Therefore, we aimed to detect neuronal correlates of response and remission in an antidepressant treatment study with 7 T fMRI, potentially harnessing advances in detection power and spatial specificity. Moreover, we modeled outcome parameters from multiple study visits during a 12-week antidepressant fMRI study in 26 acute (aMD) patients compared to 36 stable remitted (rMD) patients and 33 healthy control subjects (HC). During an electrical painful stimulation task, significantly higher baseline activity in aMD compared to HC and rMD in the medial thalamic nuclei of the pulvinar was detected (p = 0.004, FWE-corrected), which was reduced by treatment. Moreover, clinical response followed a sigmoid function with a plateau phase in the beginning, a rapid decline and a further plateau at treatment end. By modeling the dynamic speed of response with fMRI-data, perigenual anterior cingulate activity after treatment was significantly associated with antidepressant response (p < 0.001, FWE-corrected). Temporoparietal junction (TPJ) baseline activity significantly predicted non-remission after 2 antidepressant trials (p = 0.005, FWE-corrected). The results underline the importance of the medial thalamus, attention networks in MD and antidepressant treatment. Moreover, by using a sigmoid model, this study provides a novel method to analyze the dynamic nature of response and remission for future trials.

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.

Beware detrending: Optimal preprocessing pipeline for low-frequency fluctuation analysis.

Resting-state functional magnetic resonance imaging (rs-fMRI) offers the possibility to assess brain function independent of explicit tasks and individual performance. This absence of explicit stimuli in rs-fMRI makes analyses more susceptible to nonneural signal fluctuations than task-based fMRI. Data preprocessing is a critical procedure to minimise contamination by artefacts related to motion and physiology. We herein investigate the effects of different preprocessing strategies on the amplitude of low-frequency fluctuations (ALFFs) and its fractional counterpart, fractional ALFF (fALFF). Sixteen artefact reduction schemes based on nuisance regression are applied to data from 82 subjects acquired at 1.5 T, 30 subjects at 3 T, and 23 subjects at 7 T, respectively. In addition, we examine test-retest variance and effects of bias correction. In total, 569 data sets are included in this study. Our results show that full artefact reduction reduced test-retest variance by up to 50%. Polynomial detrending of rs-fMRI data has a positive effect on group-level t-values for ALFF but, importantly, a negative effect for fALFF. We show that the normalisation process intrinsic to fALFF calculation causes the observed reduction and introduce a novel measure for low-frequency fluctuations denoted as high-frequency ALFF (hfALFF). We demonstrate that hfALFF values are not affected by the negative detrending effects seen in fALFF data. Still, highest grey matter (GM) group-level t-values were obtained for fALFF data without detrending, even when compared to an exploratory detrending approach based on autocorrelation measures. From our results, we recommend the use of full nuisance regression including polynomial detrending in ALFF data, but to refrain from using polynomial detrending in fALFF data. Such optimised preprocessing increases GM group-level t-values by up to 60%.

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

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 7T 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.

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 1Hz 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.

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.