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Accurate assessment of knee alignment and leg length discrepancy is currently measured manually from standing long-leg radiographs (LLR), a process that is both time consuming and poorly reproducible. The aim was to assess the performance of a commercial available AI software by comparing its outputs with manually performed measurements. The AI was trained on over 15,000 radiographs to measure various clinical angles and lengths from LLRs. We performed a retrospective single-center analysis on 295 LLRs obtained between 2015 and 2020 from male and female patients over 18 years. AI and expert measurements were performed independently. Kellgren-Lawrence score and reading time were assessed. All measurements were compared and non-inferiority, mean-absolute-deviation (sMAD), and intra-class-correlation (ICC) were calculated. A total of 295 LLRs from 284 patients (mean age, 65 years (18; 90); 97 (34.2%) men) were analyzed. The AI model produces outputs on 98.0% of the LLRs. Manually annotations were considered as 100% accurate. For each measurement, its divergence was calculated, resulting in an overall accuracy of 89.2% when comparing the AI outputs to the manually measured. AI vs. mean observer revealed an sMAD between 0.39 and 2.19° for angles and 1.45–5.00 mm for lengths. AI showed good reliability in all lengths and angles (ICC ≥ 0.87). Non-inferiority comparing AI to the mean observer revealed an equivalence-index (γ) between 0.54 and 3.03° for angles and − 0.70–1.95 mm for lengths. On average, AI was 130 s faster than clinicians. Automated measurements of knee alignment and length measurements produced with an AI tool result in reproducible, accurate measures with a time savings compared to manually acquired measurements.

Published online September 6, 2022. 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. Austrian Science Fund (FWF) P35583; P33180; KLI670 Eusko Jaurlaritza (Gobierno Vasco) BERC 2022-2025 Spanish State Research Agency CEX2020-001010-S Spanish Ministry of Science and Innovation IJC2020-042887-I

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.

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.

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.

The neural mechanisms underpinning empathy for pain are still a matter of debate. One of the major questions is whether empathy-related pain responses indicate domain-general vs. pain-specific affective responses. Using fMRI and psychopharmacological experiments, we investigated if placebo analgesia reduces first-hand and empathic experiences of affective touch, and compared them to 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 substantiate the role of shared representations in empathy.

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 steroid hormones such as estradiol and testosterone are known to have organizing, as well as activating effects on neural tissue in animals and humans. This study investigated the effects of transgender hormone replacement therapy on white matter microstructure using diffusion tensor imaging. Female-to-male and male-to-female transgender participants were measured at baseline, four weeks and four months past treatment start and compared to female and male controls. We observed androgenization-related reductions in mean diffusivity and increases in fractional anisotropy. We also observed feminization-related increases in mean diffusivity and reductions in fractional anisotropy. In both transgender participants and controls, hormonal fluctuations were correlated with changes in white matter microstructure. Although the present study does not preclude regression to the mean as a potential contributing factor, the results indicate that sex hormones are - at least in part - responsible for white matter variability in the human brain. Studies investigating the effects of sex hormones on adult human brain structure may be an important route for greater understanding of the psychological differences between females and males.

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 sensory-motor and salience-like networks in placebo but not control participants. Specifically, networks were centered on the bilateral somatosensory cortex, as well as on the brainstem, thalamus, striatal regions, dorsal and rostral anterior cingulate cortex, and the insula, respectively. Across participants, more negative between-network coupling was associated with lower individual pain intensity as assessed during a preceding pain task, but was unrelated to 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 model where placebo analgesia increases activation within a descending pain-modulatory network, segregating it from somatosensory regions that might code for painful experiences.HighlightsPlacebo analgesia affects resting-state connectivity between networks.Salience-related and somatosensory regions are negatively coupled at rest.This coupling is negative following placebo, but not in control participants.More negative between-network coupling is related to lower pain intensity.

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.

Engaging in mentalizing, i.e., reflecting on others' thoughts, beliefs and feelings, is known to facilitate later empathy and prosocial behavior. Activation in dorsomedial prefrontal (dmPFC) areas during mentalizing has been shown to predict the extent of prosocial behavior. It is unclear, however, what cognitive process drives these effects: a simulation process in which the own mental states are used as a proxy for those of others (self-projection) or an effortful other-enhancement process in which one's own perspective is overridden. In this fMRI study we examined the effects of mentalizing with similar and dissimilar others on behavioral and brain measures of empathy and prosocial behavior, to assess which cognitive process mediates the facilitative effects of mentalizing. Participants had to mentalize with two fictitious target persons, one of whom was manipulated to have similar thoughts and beliefs as the participant, while the other had dissimilar mental states. We then assessed participants' behavioral and neural responses during an empathy for pain task and a prosocial behavior task. Similarity between participant and target person increased empathy and affiliation ratings, and mentalizing with dissimilar persons evoked increased activation in ventrolateral prefrontal cortex, the extent of which was inversely related with bias towards the similar person in empathy. Responses in two dmPFC regions were also predictive of later variations in subsequent empathy and prosocial behavior, either predicting overall prosociality and empathic concern (lateral dmPFC), or predicting reduced empathic bias towards the similar person and a lower response to self-related stressors in pain matrix areas (medial dmPFC). This pattern of results suggests that generating and enhancing other-related representations while overcoming one's own perspective, rather than enhanced recruitment of self-projection processes, is driving the facilitative effects of mentalizing on later empathic and prosocial responses.

Sex-steroid hormones have repeatedly been shown to influence empathy, which is in turn reflected in resting state functional connectivity (rsFC). Cross-sex hormone treatment in transgender individuals provides the opportunity to examine changes to rsFC over gender transition. We aimed to investigate whether sex-steroid hormones influence rsFC patterns related to unique aspects of empathy, namely emotion recognition and description as well as emotional contagion. RsFC data was acquired with 7Tesla magnetic resonance imaging in 24 male-to-female (MtF) and 33 female-to-male (FtM) transgender individuals before treatment, in addition to 33 male- and 44 female controls. Of the transgender participants, 15 MtF and 20 FtM were additionally assessed after 4 weeks and 4 months of treatment. Empathy scores were acquired at the same time-points. MtF differed at baseline from all other groups and assimilated over the course of gender transition in a rsFC network around the supramarginal gyrus, a region central to interpersonal emotion processing. While changes to sex-steroid hormones did not correlate with rsFC in this network, a sex hormone independent association between empathy scores and rsFC was found. Our results underline that 1) MtF transgender persons demonstrate unique rsFC patterns in a network related to empathy and 2) changes within this network over gender transition are likely related to changes in emotion recognition, -description, and -contagion, and are sex-steroid hormone independent.

Functional MRI enables the acquisition of a retinotopic map that relates regions of the visual field to neural populations in the visual cortex. During such a "population receptive field" (PRF) experiment, stable gaze fixation is of utmost importance in order to correctly link the presented stimulus patterns to stimulated retinal regions and the resulting Blood Oxygen Level Dependent (BOLD) response of the appropriate region within the visual cortex. A method is described that compensates for unstable gaze fixation by recording gaze position via an eyetracker and subsequently modifies the input stimulus underlying the PRF analysis according to the eyetracking measures. Here we show that PRF maps greatly improve when the method is applied to data acquired with either saccadic or smooth eye movements. We conclude that the technique presented herein is useful for studies involving subjects with unstable gaze fixation, particularly elderly patient populations.

International audience; People often spontaneously engage in copying each other's postures and mannerisms, a phenomenon referred to as behavioral mimicry. Social psychology experiments indicate that mimicry denotes an implicit affiliative signal flexibly regulated in response to social requirements. Yet, the mediating processes and neural underpinnings of such regulation are largely unexplored. The present functional magnetic resonance imaging (fMRI) study examined mimicry regulation by combining an automatic imitation task with facial stimuli, varied on two social-affective dimensions: emotional expression (angry vs happy) and ethnic group membership (in-vs out-group). Behavioral data revealed increased mimicry when happy and when out-group faces were shown. Imaging results revealed that mimicry regulation in response to happy faces was associated with increased activation in the right temporo-parietal junction (TPJ), right dorsal premotor cortex (dPMC), and right superior parietal lobule (SPL). Mimicry regulation in response to out-group faces was related to increased activation in the left ventral premotor cortex (vPMC) and inferior pa-rietal lobule (IPL), bilateral anterior insula, and mid-cingulate cortex (MCC). We suggest that mimicry in response to happy and to out-group faces is driven by distinct affiliative goals, and that mimicry regulation to attain these goals is mediated by distinct neuro-cognitive processes. Higher mimicry in response to happy faces seems to denote reciprocation of an affiliative signal. Higher mimicry in response to out-group faces, reflects an appeasement attempt towards an interaction partner perceived as threatening (an interpretation supported by implicit measures showing that out-group members are more strongly associated with threat). Our findings show that subtle social cues can result in the implicit regulation of mimicry. This regulation serves to achieve distinct affiliative goals, is mediated by different regulatory processes, and relies on distinct parts of an overarching network of task-related brain areas. Our findings shed new light on the neural mechanisms underlying the interplay between implicit action control and social cognition.

Recent technological progress enables MRI recordings at ultra-high fields of 7 T and above leading to brain images of higher resolution and increased signal-to-noise ratio. Despite these benefits, imaging at 7 T exhibits distinct challenges due to B1 field inhomogeneities, causing decreased image quality and problems in data analysis. Although several strategies have been proposed, a systematic investigation of bias-corrected 7 T data for voxel-based morphometry (VBM) is still missing and it is an ongoing matter of debate if VBM at 7 T can be carried out properly. Here, an optimized VBM study was conducted, evaluating the impact of field strength (3T vs. 7 T) and pulse sequence (MPRAGE vs. MP2RAGE) on gray matter volume (GMV) estimates. More specifically, twenty-two participants were measured under the conditions 3T MPRAGE, 7 T MPRAGE and 7 T MP2RAGE. Due to the fact that 7 T MPRAGE data exhibited strong intensity inhomogeneities, an alternative preprocessing pipeline was proposed and applied for that data. VBM analysis revealed higher GMV estimates for 7 T predominantly in superior cortical areas, caudate nucleus, cingulate cortex and the hippocampus. On the other hand, 3T yielded higher estimates especially in inferior cortical areas of the brain, cerebellum, thalamus and putamen compared to 7 T. Besides minor exceptions, these results were observed for 7 T MPRAGE as well for the 7 T MP2RAGE measurements. Results gained in the inferior parts of the brain should be taken with caution, as native GM segmentations displayed misclassifications in these regions for both 7 T sequences. This was supported by the test-retest measurements showing highest variability in these inferior regions of the brain for 7 T and also for the advanced MP2RAGE sequence. Hence, our data support the use of 7 T MRI for VBM analysis in cortical areas, but direct comparison between field strengths and sequences requires careful assessment. Similarly, analysis of the inferior cortical regions, cerebellum and subcortical regions still remains challenging at 7 T even if the advanced MP2RAGE sequence is used.

Citalopram and Escitalopram are gold standard pharmaceutical treatment options for affective, anxiety, and other psychiatric disorders. However, their neurophysiologic function on cortico-limbic circuits is incompletely characterized. Here we studied the neuropharmacological influence of Citalopram and Escitalopram on cortico-limbic regulatory processes by assessing the effective connectivity between orbitofrontal cortex (OFC) and amygdala using dynamic causal modeling (DCM) applied to functional MRI data. We investigated a cohort of 15 healthy subjects in a randomized, crossover, double-blind design after 10days of Escitalopram (10mg/d (S)-citalopram), Citalopram (10mg/d (S)-citalopram and 10mg/d (R)-citalopram), or placebo. Subjects performed an emotional face discrimination task, while undergoing functional magnetic resonance imaging (fMRI) scanning at 3 Tesla. As hypothesized, the OFC, in the context of the emotional face discrimination task, exhibited a down-regulatory effect on amygdala activation. This modulatory effect was significantly increased by (S)-citalopram, but not (R)-citalopram. For the first time, this study shows that (1) the differential effects of the two enantiomers (S)- and (R)-citalopram on cortico-limbic connections can be demonstrated by modeling effective connectivity methods, and (2) one of their mechanisms can be linked to an increased inhibition of amygdala activation by the orbitofrontal cortex.

PurposeThe present study describes retinotopic mapping of the primary visual cortex using functional MRI (fMRI) in patients with retinal disease. It addresses the relationship between fMRI data and data obtained by conventional assessment including microperimetry (MP) and structural imaging.MethodsInitial testing involved eight patients with central retinal disease (Stargardt disease, STGD) and eight with peripheral retinal disease (retinitis pigmentosa, RP), who were examined using fMRI and MP (Nidek MP-1). All had a secure clinical diagnosis supported by electrophysiological data. fMRI used population-receptive field (pRF) mapping to provide retinotopic data that were then compared with the results of MP, optical coherence tomography and fundus autofluorescence imaging.ResultsFull analysis, following assessment of fMRI data reliability criteria, was performed in five patients with STGD and seven patients with RP; unstable fixation was responsible for unreliable pRF measurements in three patients excluded from final analysis. The macular regions in patients with STGD with central visual field defects and outer retinal atrophy (ORA) at the macula correlated well with pRF coverage maps showing reduced density of activated voxels at the occipital pole. Patients with RP exhibited peripheral ORA and concentric visual field defects both on MP and pRF mapping. Anterior V1 voxels, corresponding to peripheral regions, showed no significant activation. Correspondence between MP and pRF mapping was quantified by calculating the simple matching coefficient.ConclusionRetinotopic maps acquired by fMRI provide a valuable adjunct in the assessment of retinal dysfunction. The addition of microperimetric data to pRF maps allowed better assessment of macular function than MP alone. Unlike MP, pRF mapping provides objective data independent of psychophysical perception from the patient.

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.

Recent behavioral investigations suggest that acute stress can increase prosocial behavior. Here, we investigated whether increased empathy represents a potential mechanism for this finding. Using functional magnetic resonance imaging, we assessed the effects of acute stress on neural responses related to automatic and regulatory components of empathy for pain as well as subsequent prosocial behavior. Stress increased activation in brain areas associated with the automatic sharing of others’ pain, such as the anterior insula, the anterior midcingulate cortex, and the primary somatosensory cortex. In addition, we found increased prosocial behavior under stress. Furthermore, activation in the anterior midcingulate cortex mediated the effects of stress on prosocial behavior. However, stressed participants also displayed stronger and inappropriate other-related responses in situations which required them to take the perspective of another person, and to regulate their automatic affective responses. Thus, while acute stress may increase prosocial behavior by intensifying the sharing of others’ emotions, this comes at the cost of reduced cognitive appraisal abilities. Depending on the contextual constraints, stress may therefore affect empathy in ways that are either beneficial or detrimental.

Question Transcranial magnetic stimulation (TMS) has become a promising therapeutic treatment and neuroscientific research tool, yet how it works is not fully understood. We developed a dedicated MR coil array positioned beneath the TMS coil that allows for concurrent stimulation and imaging and flexible positioning while ensuring TMS efficiency, high MR sensitivity and the use of parallel/multiband imaging sequences. Here we aimed to explain acute effects of TMS over left DLPFC using a new online TMS/fMRI setup in combination with advanced imaging and neuronavigation methods. Resting State functional connectivity and DTI Tractography shall further explain resulting activation patterns at a network level. Methods The study was performed on a 3T Tim Trio scanner (Siemens, Erlangen, Germany). The TMS system used included a MagProX100 stimulator and MRi-B91 MR-compatible TMS coil (Magventure, Farum, Denmark). Five right-handed female subjects (age: 28.6 ± 4.3 years) were examined. Functional images were acquired using EPI (echo-planar imaging) sequence with TR/TE = 1000/33 ms, 28 slices, 1.5 × 1.5 × 3mm3. The experimental procedure is depicted in Fig. 1. FMRI data analyses were performed using SPM12. The design matrix comprised four regressors representing different stimulation amplitudes. DTI tractography was performed using DSI Studio. Figure options Download full-size image Download high-quality image (729 K) Download as PowerPoint slide Results TMS led to intensity-dependent activation increase in the left DLPFC and the contralateral DLPFC ( Figure options Download full-size image Download high-quality image (874 K) Download as PowerPoint slide Fig. 2): Higher stimulation intensities evoked higher bilateral activation. ACC showed a more complex response pattern. Resting-state functional connectivity maps using the stimulation target as seed-voxel showed a network very similar to the TMS-derived activation pattern (Fig. 2). DTI tractography provided additional information about the axonal connection between the left DLPFC stimulation site and the right DLPFC activation cluster. Conclusion This is the first study to assess the acute influence of TMS over DLPFC at an individual level, made possible by a dedicated concurrent TMS/fMRI coil array. Here we show a dose-dependent increase in activity not only underneath the stimulation site but also on the contralateral homologous area and apparent mediating responses in the ACC. This network is confirmed by additional resting-state and tractography data.

Question While the precise mechanism of action is still unclear, rTMS is an effective FDA-approved treatment in depression and shows beneficial behavioral effects in a range of pathologies. A better understanding could improve treatment success and reduce the number of non-treatment responders. This study is the first to investigate effectiveness and specificity of rTMS over left DLPFC using a large-scale (n = 60) sham-controlled cross-over design and an unbiased resting-state (RS) approach. Methods 60 healthy subjects (age: 25.01 ± 4.6 years, f/m: 31/29) underwent rTMS DLPFC and sham stimulation (see Fig. 1) Download : Download high-res image (493KB) Download : Download full-size image . Resting state (rs) fMRI scans were acquired before and twice after stimulation. We investigated BOLD signal changes in functional connectivity (fc) following 10 Hz rTMS (24 × 5 s trains, ITI 20s, 1200 pulses @ 90%MT) during a classic resting state paradigm. We examined rsfc changes using an unbiased approach based on a set of 20 well-established resting state networks derived from multicenter-data independent component analysis by Biswal et al. (2010a, http://fcon_1000.projects.nitrc.org ). Results Comparisons between pre and post stimulation revealed that 19 out of a total of 20 IC networks remained unchanged, i.e. showed no statistically significant differences before and after rTMS irrespective of real/sham stimulation (Fig. 2 A, blue) Download : Download high-res image (1MB) Download : Download full-size image . Only one network (IC17, red dashed) which includes the ACC and PFC showed DLPFC rTMS-related connectivity changes (while staying stable throughout the whole procedure in sham session, Fig. 2 B): The ACC had increased connection strength in the post-rTMS scan within this network, particularly with the DLPFC (stimulation site), bilateral insula and striatum. Conclusion For the first time this study shows in a model-free approach that rTMS over left DLPFC modulates functional connectivity within a specific network while other networks stay stable. This network is typically associated with attention, mood, reward processing and psychiatric conditions that are linked to maladaptive changes in these domains. This could have further implications on treatment, screening and treatment response monitoring of psychiatric conditions.

Although previous investigations of transsexual people have focused on regional brain alterations, evaluations on a network level, especially those structural in nature, are largely missing. Therefore, we investigated the structural connectome of 23 female-to-male (FtM) and 21 male-to-female (MtF) transgender patients before hormone therapy as compared with 25 female and 25 male healthy controls. Graph theoretical analysis of whole-brain probabilistic tractography networks (adjusted for differences in intracranial volume) showed decreased hemispheric connectivity ratios of subcortical/limbic areas for both transgender groups. Subsequent analysis revealed that this finding was driven by increased interhemispheric lobar connectivity weights (LCWs) in MtF transsexuals and decreased intrahemispheric LCWs in FtM patients. This was further reflected on a regional level, where the MtF group showed mostly increased local efficiencies and FtM patients decreased values. Importantly, these parameters separated each patient group from the remaining subjects for the majority of significant findings. This work complements previously established regional alterations with important findings of structural connectivity. Specifically, our data suggest that network parameters may reflect unique characteristics of transgender patients, whereas local physiological aspects have been shown to represent the transition from the biological sex to the actual gender identity.