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.

Effects of dopamine and opioid receptor antagonism on the neural processing of social and nonsocial rewards.

Rewards are a broad category of stimuli inducing approach behavior to aid survival. Extensive evidence from animal research has shown that wanting (the motivation to pursue a reward) and liking (the pleasure associated with its consumption) are mostly regulated by dopaminergic and opioidergic activity in dedicated brain areas. However, less is known about the neuroanatomy of dopaminergic and opioidergic regulation of reward processing in humans, especially when considering different types of rewards (i.e., social and nonsocial). To fill this gap of knowledge, we combined dopaminergic and opioidergic antagonism (via amisulpride and naltrexone administration) with functional neuroimaging to investigate the neurochemical and neuroanatomical bases of wanting and liking of matched nonsocial (food) and social (interpersonal touch) rewards, using a randomized, between-subject, placebo-controlled, double-blind design. While no drug effect was observed at the behavioral level, brain activity was modulated by the administered compounds. In particular, opioid antagonism, compared to placebo, reduced activity in the medial orbitofrontal cortex during consumption of the most valued social and nonsocial rewards. Dopamine antagonism, however, had no clear effects on brain activity in response to reward anticipation. These findings provide insights into the neurobiology of human reward processing and suggest a similar opioidergic regulation of the neural responses to social and nonsocial reward consumption.

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.

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.

Beyond Sharing Unpleasant Affect-Evidence for Pain-Specific Opioidergic Modulation of Empathy for Pain.

It is not known how specific the neural mechanisms underpinning empathy for different domains are. In the present study, we set out to test whether shared neural representations between first-hand pain and empathy for pain are pain-specific or extend to empathy for unpleasant affective touch as well. Using functional magnetic resonance imaging and psychopharmacological experiments, we investigated if placebo analgesia reduces first-hand and empathic experiences of affective touch, and compared them with the effects on pain. Placebo analgesia also affected the first-hand and empathic experience of unpleasant touch, implicating domain-general effects. However, and in contrast to pain and pain empathy, administering an opioid antagonist did not block these effects. Moreover, placebo analgesia reduced neural activity related to both modalities in the bilateral insular cortex, while it specifically modulated activity in the anterior midcingulate cortex for pain and pain empathy. These findings provide causal evidence that one of the major neurochemical systems for pain regulation is involved in pain empathy, and crucially substantiates the role of shared representations in empathy.

Test-retest reliability of emotion regulation networks using fMRI at ultra-high magnetic field.

Given the importance of emotion regulation in affective disorders, emotion regulation is at the focus of attempts to identify brain biomarkers of disease risk, treatment response, and brain development. However, to be useful as an indicator for individual characteristics of brain functions - particularly as a biomarker in a clinical context - ensuring reliability is a key challenge. Here, we systematically evaluated test-retest reliability of task-based functional magnetic resonance imaging (fMRI) activity within neural networks associated with emotion generation and regulation across three sessions. Acquiring fMRI data at ultra-high field (7T), we examined region- and voxel-wise test-retest reliability of brain activity in response to a well-established emotion regulation task for predefined region-of-interests (ROIs) implicated in four neural networks. Test-retest reliability varied considerably across the emotion regulation networks and respective ROIs. However, core emotion regulation regions, including the ventrolateral and dorsolateral prefrontal cortex (vlPFC and dlPFC) as well as the middle temporal gyrus (MTG) showed high reliability. Our findings thus support the role of these prefrontal and temporal regions as promising candidates for the study of individual differences in emotion regulation as well as for neurobiological biomarkers in clinical neuroscience research.

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.

Sex Matters: A Multivariate Pattern Analysis of Sex- and Gender-Related Neuroanatomical Differences in Cis- and Transgender Individuals Using Structural Magnetic Resonance Imaging.

Univariate analyses of structural neuroimaging data have produced heterogeneous results regarding anatomical sex- and gender-related differences. The current study aimed at delineating and cross-validating brain volumetric surrogates of sex and gender by comparing the structural magnetic resonance imaging data of cis- and transgender subjects using multivariate pattern analysis. Gray matter (GM) tissue maps of 29 transgender men, 23 transgender women, 35 cisgender women, and 34 cisgender men were created using voxel-based morphometry and analyzed using support vector classification. Generalizability of the models was estimated using repeated nested cross-validation. For external validation, significant models were applied to hormone-treated transgender subjects (n = 32) and individuals diagnosed with depression (n = 27). Sex was identified with a balanced accuracy (BAC) of 82.6% (false discovery rate [pFDR] < 0.001) in cisgender, but only with 67.5% (pFDR = 0.04) in transgender participants indicating differences in the neuroanatomical patterns associated with sex in transgender despite the major effect of sex on GM volume irrespective of the self-identification as a woman or man. Gender identity and gender incongruence could not be reliably identified (all pFDR > 0.05). The neuroanatomical signature of sex in cisgender did not interact with depressive features (BAC = 74.7%) but was affected by hormone therapy when applied in transgender women (P < 0.001).

Placebo-induced pain reduction is associated with negative coupling between brain networks at rest.

Placebos can reduce pain by inducing beliefs in the effectiveness of an actually inert treatment. Such top-down effects on pain typically engage lateral and medial prefrontal regions, the insula, somatosensory cortex, as well as the thalamus and brainstem during pain anticipation or perception. Considering the level of large-scale brain networks, these regions spatially align with fronto-parietal/executive control, salience, and sensory-motor networks, but it is unclear if and how placebos alter interactions between them during rest. Here, we investigated how placebo analgesia affected intrinsic network coupling. Ninety-nine human participants were randomly assigned to a placebo or control group and underwent resting-state fMRI after pain processing. Results revealed inverse coupling between two resting-state networks in placebo but not control participants. Specifically, networks comprised the bilateral somatosensory cortex and posterior insula, as well as the brainstem, thalamus, striatal regions, dorsal and rostral anterior cingulate cortex, and the anterior insula, respectively. Across participants, more negative between-network coupling was associated with lower individual pain intensity as assessed during a preceding pain task, and there was no significant relation with expectations of medication effectiveness in the placebo group. Altogether, these findings provide initial evidence that placebo analgesia affects the intrinsic communication between large-scale brain networks, even in the absence of pain. We suggest a theoretical model where placebo analgesia might affect processing within a descending pain-modulatory network, potentially segregating it from somatosensory regions that may code for painful experiences.

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.

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.

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.

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%.

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.

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.

Probing the association between serotonin-1A autoreceptor binding and amygdala reactivity in healthy volunteers.

INTRODUCTION: The serotonergic system modulates affect and is a target in the treatment of mood disorders. 5-HT1A autoreceptors in the raphe control serotonin release by means of negative feedback inhibition. Hence, 5-HT1A autoreceptor function should influence the serotonergic regulation of emotional reactivity in limbic regions. Previous findings suggest an inverse relationship between 5-HT1A autoreceptor binding and amygdala reactivity to facial emotional expressions. The aim of the current multimodal neuroimaging study was to replicate the previous finding in a larger cohort. METHODS: 31 healthy participants underwent fMRI as well as PET using the radioligand [carbonyl-11C]WAY-100635 to quantify 5-HT1A autoreceptor binding in the dorsal raphe. The binding potential (BPND) was quantified using the multilinear reference tissue model (MRTM2) and cerebellar white matter as reference tissue. Functional MRI was done at 3T using a well-established facial emotion discrimination task (EDT). Here, participants had to match the emotional valence of facial expressions, while in a control condition they had to match geometric shapes. Effects of 5-HT1A autoreceptor binding on amygdala reactivity were investigated using linear regression analysis with SPM8. RESULTS: Regression analysis between 5-HT1A autoreceptor binding and mean amygdala reactivity revealed no statistically significant associations. Investigating amygdala reactivity in a voxel-wise approach revealed a positive association in the right amygdala (peak-T = 3.64, p < .05 FWE corrected for the amygdala volume) which was however conditional on the omission of age and sex as covariates in the model. CONCLUSION: Despite highly significant amygdala reactivity to facial emotional expressions, we were unable to replicate the inverse relationship between 5-HT1A autoreceptor binding in the DRN and amygdala reactivity. Our results oppose previous multimodal imaging studies but seem to be in line with recent animal research. Deviation in results may be explained by methodological differences between our and previous multimodal studies.

Ultra-high-field fMRI insights on insight: Neural correlates of the Aha!-moment.

Finding creative solutions to difficult problems is a fundamental aspect of human culture and a skill highly needed. However, the exact neural processes underlying creative problem solving remain unclear. Insightful problem solving tasks were shown to be a valid method for investigating one subcomponent of creativity: the Aha!-moment. Finding insightful solutions during a remote associates task (RAT) was found to elicit specific cortical activity changes. Considering the strong affective components of Aha!-moments, as manifested in the subjectively experienced feeling of relief following the sudden emergence of the solution of the problem without any conscious forewarning, we hypothesized the subcortical dopaminergic reward network to be critically engaged during Aha. To investigate those subcortical contributions to insight, we employed ultra-high-field 7 T fMRI during a German Version of the RAT. During this task, subjects were exposed to word triplets and instructed to find a solution word being associated with all the three given words. They were supposed to press a button as soon as they felt confident about their solution without further revision, allowing us to capture the exact event of Aha!-moment. Besides the finding on cortical involvement of the left anterior middle temporal gyrus (aMTG), here we showed for the first time robust subcortical activity changes related to insightful problem solving in the bilateral thalamus, hippocampus, and the dopaminergic midbrain comprising ventral tegmental area (VTA), nucleus accumbens (NAcc), and caudate nucleus. These results shed new light on the affective neural mechanisms underlying insightful problem solving.

Placebo analgesia and its opioidergic regulation suggest that empathy for pain is grounded in self pain.

Empathy for pain activates brain areas partially overlapping with those underpinning the first-hand experience of pain. It remains unclear, however, whether such shared activations imply that pain empathy engages similar neural functions as first-hand pain experiences. To overcome the limitations of previous neuroimaging research, we pursued a conceptually novel approach: we used the phenomenon of placebo analgesia to experimentally reduce the first-hand experience of pain, and assessed whether this results in a concomitant reduction of empathy for pain. We first carried out a functional MRI experiment (n = 102) that yielded results in the expected direction: participants experiencing placebo analgesia also reported decreased empathy for pain, and this was associated with reduced engagement of anterior insular and midcingulate cortex: that is, areas previously associated with shared activations in pain and empathy for pain. In a second step, we used a psychopharmacological manipulation (n = 50) to determine whether these effects can be blocked via an opioid antagonist. The administration of the opioid antagonist naltrexone blocked placebo analgesia and also resulted in a corresponding "normalization" of empathy for pain. Taken together, these findings suggest that pain empathy may be associated with neural responses and neurotransmitter activity engaged during first-hand pain, and thus might indeed be grounded in our own pain experiences.

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.