Search

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 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.

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.

Objectives: Anticipatory processes prepare the organism for upcoming experiences. The aim of this study was to investigate neural responses related to anticipation and processing of painful stimuli occurring with different levels of uncertainty. Experimental design: Twenty-five participants (13 females) took part in an electroencephalography and functional magnetic resonance imaging (fMRI) experiment at separate times. A visual cue announced the occurrence of an electrical painful or nonpainful stimulus, delivered with certainty or uncertainty (50% chance), at some point during the following 15 s. Principal observations: During the first 2 s of the anticipation phase, a strong effect of uncertainty was reflected in a pronounced frontal stimulus-preceding negativity (SPN) and increased fMRI activation in higher visual processing areas. In the last 2 s before stimulus delivery, we observed stimulus-specific preparatory processes indicated by a centroparietal SPN and posterior insula activation that was most pronounced for the certain pain condition. Uncertain anticipation was associated with attentional control processes. During stimulation, the results revealed that unexpected painful stimuli produced the strongest activation in the affective pain processing network and a more pronounced offset-P2. Conclusions: Our results reflect that during early anticipation uncertainty is strongly associated with affective mechanisms and seems to be a more salient event compared to certain anticipation. During the last 2 s before stimulation, attentional control mechanisms are initiated related to the increased salience of uncertainty. Furthermore, stimulus-specific preparatory mechanisms during certain anticipation also shaped the response to stimulation, underlining the adaptive value of stimulus-targeted preparatory activity which is less likely when facing an uncertain event. Hum Brain Mapp 36:744–755, 2015. © 2014 Wiley Periodicals, Inc.

The anticipation of favourable or unfavourable events is a key component in our daily life. However, the temporal dynamics of anticipation processes in relation to brain activation are still not fully understood. A modified version of the monetary incentive delay task was administered during separate functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG) sessions in the same 25 participants to assess anticipatory processes with a multi-modal neuroimaging set-up. During fMRI, gain and loss anticipation were both associated with heightened activation in ventral striatum and reward-related areas. EEG revealed most pronounced P300 amplitudes for gain anticipation, whereas CNV amplitudes distinguished neutral from gain and loss anticipation. Importantly, P300, but not CNV amplitudes, were correlated to neural activation in the ventral striatum for both gain and loss anticipation. Larger P300 amplitudes indicated higher ventral striatum blood oxygen level dependent (BOLD) response. Early stimulus evaluation processes indexed by EEG seem to be positively related to higher activation levels in the ventral striatum, indexed by fMRI, which are usually associated with reward processing. The current results, however, point towards a more general motivational mechanism processing salient stimuli during anticipation., Highlights • Monetary incentive delay task was assessed in separate EEG and fMRI sessions. • Both gain and loss anticipation activated well known reward-related areas. • P300 amplitude differentiated reward cue from non-reward cues. • P300 amplitudes positively correlated with BOLD response in the ventral striatum. • Ventral striatum activation associated with general motivational processes.

Progressing from 3T to 7 T functional MRI enables marked improvements of human brain imaging in vivo. Although direct comparisons demonstrated advantages concerning blood oxygen level dependent (BOLD) signal response and spatial specificity, these mostly focused on single brain regions with rather simple tasks. Considering that physiological noise also increases with higher field strength, it is not entirely clear whether the advantages of 7T translate equally to the entire brain during tasks which elicit more complex neuronal processing. Therefore, we investigated the difference between 3T and 7 T in response to transcutaneous electrical painful and non-painful stimulation in 22 healthy subjects. For painful stimuli vs. baseline, stronger activations were observed at 7 T in several brain regions including the insula and supplementary motor area, but not the secondary somatosensory cortex (p

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.

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.

Biological causes underpinning the well known gender dimorphisms in human behavior, cognition, and emotion have received increased attention in recent years. The advent of diffusion-weighted magnetic resonance imaging has permitted the investigation of the white matter microstructure in unprecedented detail. Here, we aimed to study the potential influences of biological sex, gender identity, sex hormones, and sexual orientation on white matter microstructure by investigating transsexuals and healthy controls using diffusion tensor imaging (DTI). Twenty-three female-to-male (FtM) and 21 male-to-female (MtF) transsexuals, as well as 23 female (FC) and 22 male (MC) controls underwent DTI at 3 tesla. Fractional anisotropy, axial, radial, and mean diffusivity were calculated using tract-based spatial statistics (TBSS) and fiber tractography. Results showed widespread significant differences in mean diffusivity between groups in almost all white matter tracts. FCs had highest mean diffusivities, followed by FtM transsexuals with lower values, MtF transsexuals with further reduced values, and MCs with lowest values. Investigating axial and radial diffusivities showed that a transition in axial diffusivity accounted for mean diffusivity results. No significant differences in fractional anisotropy maps were found between groups. Plasma testosterone levels were strongly correlated with mean, axial, and radial diffusivities. However, controlling for individual estradiol, testosterone, or progesterone plasma levels or for subjects' sexual orientation did not change group differences. Our data harmonize with the hypothesis that fiber tract development is influenced by the hormonal environment during late prenatal and early postnatal brain development.

Objectives: Anticipatory processes prepare the organism for upcoming experiences. The aim of this study was to investigate neural responses related to anticipation and processing of painful stimuli occurring with different levels of uncertainty. Experimental design: Twenty‐five participants (13 females) took part in an electroencephalography and functional magnetic resonance imaging (fMRI) experiment at separate times. A visual cue announced the occurrence of an electrical painful or nonpainful stimulus, delivered with certainty or uncertainty (50% chance), at some point during the following 15 s. Principal observations: During the first 2 s of the anticipation phase, a strong effect of uncertainty was reflected in a pronounced frontal stimulus‐preceding negativity (SPN) and increased fMRI activation in higher visual processing areas. In the last 2 s before stimulus delivery, we observed stimulus‐specific preparatory processes indicated by a centroparietal SPN and posterior insula activation that was most pronounced for the certain pain condition. Uncertain anticipation was associated with attentional control processes. During stimulation, the results revealed that unexpected painful stimuli produced the strongest activation in the affective pain processing network and a more pronounced offset‐P2. Conclusions: Our results reflect that during early anticipation uncertainty is strongly associated with affective mechanisms and seems to be a more salient event compared to certain anticipation. During the last 2 s before stimulation, attentional control mechanisms are initiated related to the increased salience of uncertainty. Furthermore, stimulus‐specific preparatory mechanisms during certain anticipation also shaped the response to stimulation, underlining the adaptive value of stimulus‐targeted preparatory activity which is less likely when facing an uncertain event. Hum Brain Mapp 36:744–755, 2015. © 2014 Wiley Periodicals, Inc.

IntroductionSeveral fMRI and resting-state connectivity studies have demonstrated alterations in the limbic system and frontal areas in social anxiety disorder (SAD).AimsHere we used high-resolution whole-brain diffusion tensor imaging (DTI) to examine differences in anatomical connectivity between patients and controls in the white matter.MethodsWe examined 14 SAD patients (age 26.3 ± 9.0y) and 15 healthy controls (age 25.6 ± 3.3y) using DTI on a 3T Trio MRI scanner (Siemens, Germany). DTI acquisition with 1.6 mm isotropic resolution was performed in 30 directions and a maximum b-value of 800. Fractional anisotropy (FA) maps were obtained using FSL. Group analysis was performed in SPM8 (two sample t-test).ResultsThe figure shows a coronal slice through the uncinate fasciculus. Arrows point to areas where SAD patients show decreased FA-values compared to controls (p < 0.05). Note that these areas are limited to the uncinate fasciculus and are found bilaterally.ConclusionReduced FA-values indicate a reduction in anatomical connectivity strength. Our study thus clearly shows reduced connectivity strength in the uncinate fasciculus connecting frontal regions with limbic areas as the amygdalae and hippocampus. This reduced structural connectivity supports functional data demonstrating alterations of brain activation in the amygdala and prefrontal regions in social phobia.