The diagnostic yield of magnetic resonance imaging (MRI) postprocessing using 7‑T data for patients with nonlesional epilepsy has been rarely evaluated, but has shown acceptable diagnostic outcomes. However, to date there have been no prospective clinical studies comparing MP2RAGE sequences in 3‑T and 7‑T MRI in parallel using the same protocol for morphometric analysis. We present a study protocol developed to address the hypothesis that application of 7‑T structural MRI increases the rate of detection of structural lesions with morphometric analysis when compared with parallel coherent study protocols in 3‑T MRI. The 7‑T MRI study protocol is designed to supply data showing the clinical practicability and proof of principle for increasing the detection rate of subtle epileptogenic lesions.

Objectives Major Depression (MDD) and anxiety disorders are stress-related disorders that share pathophysiological mechanisms. There is evidence for alterations of glutamate-glutamine, N-acetylaspartate (NAA) and GABA in the anterior cingulate cortex (ACC), a stress-sensitive region affected by hypothalamic-pituitary-adrenal axis (HPA). The aim was to investigate metabolic alterations in the ACC and whether hair cortisol, current stress or early life adversity predict them. Methods We investigated 22 patients with MDD and comorbid anxiety disorder and 23 healthy controls. Proton magnetic resonance spectroscopy was performed with voxels placed in pregenual (pg) and dorsal (d) ACC in 3 T. Analysis of hair cortisol was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results The N-acetylaspartate/Creatin ratio (NAA/Cr) was reduced in patients in both pgACC (p = .040) and dACC (p = .016). A significant interactive effect of diagnosis and cortisol on both pg-NAA/Cr (F = 5.00, p = .033) and d-NAA/Cr (F = 7.86, p = .009) was detected, whereby in controls cortisol was positively correlated with d-NAA/Cr (r = 0.61, p = .004). Conclusions Our results suggest a relationship between NAA metabolism in ACC and HPA axis activity as represented by long-term cortisol output.

BACKGROUND:Childhood trauma (CT) increases vulnerability for the development of major depressive disorder (MDD). Alterations in resting-state functional connectivity (RSFC) have frequently been reported for MDD. These alterations may be much more prominent in depressive patients with a history of CT. The present study aims to compare RSFC in different brain networks of patients with MDD and CT (MDD+CT) vs. MDD and no CT compared to healthy controls.METHODS:45 patients (22 with CT) were compared to 23 age-and-gender-matched healthy control subjects. Demographic parameters, severity of MDD, severity of CT and comorbid anxiety disorders were assessed. For assessment of RSFC alterations, a seed-based approach within five well-established RSFC networks was used.RESULTS:CT in MDD patients predicts severity of comorbid anxiety. A significant decrease in in-between network RSFC-values of MDD patients compared to controls was found in the network pairs of default mode network (DMN) - dorsal attention network (DAN), ventral attention network (VAN) - DMN and DAN - affective network (AN). MDD+CT patients presented more aberrant RSFC than MDD-CT patients. MDD scores predicted the decrease in RSFC for MDD patients. Higher Childhood Trauma Questionnaire (CTQ) scores are linked to reduced functional connectivity (FC) between DMN - DAN.CONCLUSIONS:Our study shows reduced RSFC in MDD patients for DMN - DAN, VAN - DMN, DAN - AN and MDD+CT patients presented more aberrant RSFC so that we suspect CT to be a considerable factor in the etiology of MDD. Through dysregulated neural circuits, CT is likely to contribute to a distinct MDD pathophysiology.

Learning the spatial layout of a novel environment is associated with dynamic activity changes in the hippocampus and in medial parietal areas. With advancing age, the ability to learn spatial environments deteriorates substantially but the underlying neural mechanisms are not well understood. Here, we report findings from a behavioral and a fMRI experiment where healthy human older and younger adults of either sex performed a spatial learning task in a photorealistic virtual environment (VE). We modeled individual learning states using a Bayesian state-space model and found that activity in retrosplenial cortex (RSC)/parieto-occipital sulcus (POS) and anterior hippocampus did not change systematically as a function learning in older compared with younger adults across repeated episodes in the environment. Moreover, effective connectivity analyses revealed that the age-related learning deficits were linked to an increase in hippocampal excitability. Together, these results provide novel insights into how human aging affects computations in the brain?s navigation system, highlighting the critical role of the hippocampus.

Naturalistic learning scenarios are characterized by infrequent experience of external feedback to guide behavior. Higher-order learning mechanisms like second-order conditioning (SOC) may allow stimuli that were never experienced together with reinforcement to acquire motivational value. Despite its explanatory potential for real-world learning, surprisingly little is known about the neural mechanism underlying such associative transfer of value in SOC. Here, we used multivariate cross-session, cross-modality searchlight classification on functional magnetic resonance imaging data obtained from humans during SOC. We show that visual first-order conditioned stimuli (CS) reinstate cortical patterns representing previously paired gustatory outcomes in the lateral orbitofrontal cortex (OFC). During SOC, this OFC region showed increased functional covariation with amygdala, where neural pattern similarity between second-order CS and outcomes increased from early to late stages of SOC. Our data suggest a mechanism by which motivational value is conferred to stimuli that were never paired with reinforcement.

Current initiatives to restore vision emphasize the need for objective assessments of visual field (VF) defects as pursued with functional magnetic resonance imaging (fMRI) approaches. Here, we compared population receptive field (pRF) mapping-based VF reconstructions to an fMRI method that uses more robust visual stimulation (on-off block design) in combination with individualized anatomy-driven retinotopic atlas-information (atlas-based VF). We investigated participants with sizable peripheral VF-deficits due to advanced glaucoma (n = 4) or retinitis pigmentosa (RP; n = 2) and controls (n = 6) with simulated scotoma. We obtained (1) standard automated perimetry (SAP) data as reference VFs and 3T fMRI data for (2) pRF-mapping [8-direction bar stimulus, fixation color change task] and (3) block-design full-field stimulation [8-direction drifting contrast patterns during (a) passive viewing (PV) and (b) one-back-task (OBT; reporting successions of identical motion directions) to probe the impact of previously reported task-related unspecific visual cortex activations]. Correspondence measures between the SAP and fMRI-based VFs were accuracy, assisted by sensitivity and specificity. We found an accuracy of pRF-based VF from V1 in patients [median: 0.62] that was similar to previous reports and increased by adding V2 and V3 to the analysis [0.74]. In comparison to the pRF-based VF, equivalent accuracies were obtained for the atlas-based VF for both PV [0.67] and, unexpectedly, the OBT [0.59], where, however, unspecific cortical activations were reflected by a reduction in sensitivity [0.71 (PV) and 0.35 (OBT)]. In conclusion, in patients with peripheral VF-defects, we demonstrate that previous fMRI procedures to obtain VF-estimates might be enhanced by: (1) pooling V1-V3 to enhance accuracy; (2) reporting sensitivity and specificity measures to increase transparency of the VF-reconstruction metric; (3) applying atlas-based procedures, if pRF-based VFs are not available or difficult to obtain; and (4) giving, counter-intuitively, preference to PV. These findings are expected to provide guidance to overcome current limitations of translating fMRI-based methods to a clinical work-up.

Zusammenfassung Wir berichten über einen 30-jährigen Patienten, der mit 21 Jahren an einer fokalen Epilepsie mit epigastrischen Auren und nicht bewusst erlebten Anfällen sowie selten bilateralen tonisch-klonischen Anfällen mit Hippocampussklerose erkrankte. Dem Patienten wurde das resektive Standardverfahren (vordere Temporallappenresektion) sowie alternativ das neu in Europa zugelassene Verfahren der stereotaktischen Laserthermoablation angeboten. Der Patient entschied sich aufgrund der geringeren Invasivität für letzteres Verfahren. Im Folgenden werden der klinische Verlauf mit einer postoperativen Nachbeobachtungszeit von 9 Monaten berichtet. Zudem wird die Methode und die Ergebnisse einer funktionellen Gedächtnis-MRT Untersuchung beschrieben.

Decision-making is guided by memories of option values. However, retrieving items from memory renders them malleable. Here, we show that merely retrieving values from memory and making a choice between options is sufficient both to induce changes to stimulus-reward associations in the hippocampus and to bias future decision-making. After allowing participants to make repeated choices between reward-conditioned stimuli, in the absence of any outcome, we observe that participants prefer stimuli they have previously chosen, and neglect previously unchosen stimuli, over otherwise identical-valued options. Using functional brain imaging, we show that decisions induce changes to hippocampal representations of stimulus-outcome associations. These changes are correlated with future decision biases. Our results indicate that choice-induced preference changes are partially driven by choice-induced modification of memory representations and suggest that merely making a choice - even without experiencing any outcomes - induces associative plasticity.

Background: Diagnosis of immune-mediated neuropathies and their differentiation from amyotrophic lateral sclerosis (ALS) can be challenging, especially at early disease stages. Accurate diagnosis is, however, important due to the different prognosis and available treatment options. We present one patient with a left-sided dorsal flexor paresis and initial suspicion of ALS and another with multifocal sensory deficits. In both, peripheral nerve imaging was the key for diagnosis. Methods: We performed high-resolution nerve ultrasound (HRUS) and 7T or 3T magnetic resonance neurography (MRN). Results: In both patients, HRUS revealed mild to severe, segmental or inhomogeneous, nerve enlargement at multiple sites, as well as an area increase of isolated fascicles. MRN depicted T2 hyperintense nerves with additional contrast-enhancement. Discussion: Peripheral nerve imaging was compatible with the respective diagnosis of an immune-mediated neuropathy, i.e., multifocal motor neuropathy (MMN) in patient 1 and multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) in patient 2. Peripheral nerve imaging, especially HRUS, should play an important role in the diagnostic work-up for immune-mediated neuropathies and their differentiation from ALS.

Taste processing is an essential ability in all animals signaling potential harm or benefit of ingestive behavior. However, current evidence for cortical taste representations remains contradictory. To address this issue, high-resolution functional MRI (fMRI) and multivariate pattern analysis were used to characterize taste-related informational content in human insular cortex, which contains primary gustatory cortex. Human participants judged pleasantness and intensity of low- and high-concentration tastes (salty, sweet, sour, and bitter) in two fMRI experiments on two different days to test for task- and concentration-invariant taste representations. We observed patterns of fMRI activity within insular cortex narrowly tuned to specific tastants consistently across tasks in all participants. Fewer patterns responded to more than one taste category. Importantly, changes in taste concentration altered the spatial layout of putative taste-specific patterns with distinct, almost nonoverlapping patterns for each taste category at different concentration levels. Together, our results point at macroscopic representations in human insular cortex as a complex function of taste category and concentration rather than representations based solely on taste identity.

Zusammenfassung: Wir berichten uber einen 30-jahrigen Patienten, der mit 21 Jahren an einer fokalen Epilepsie mit epigastrischen Auren und nicht bewusst erlebten Anfallen sowie selten bilateralen tonisch-klonischen Anfallen mit Hippocampussklerose erkrankte. Dem Patienten wurde das resektive Standardverfahren (vordere Temporallappenresektion) sowie alternativ das neu in Europa zugelassene Verfahren der stereotaktischen Laserthermoablation angeboten. Der Patient entschied sich aufgrund der geringeren Invasivitat fur letzteres Verfahren. Im Folgenden werden der klinische Verlauf mit einer postoperativen Nachbeobachtungszeit von 9 Monaten berichtet. Zudem wird die Methode und die Ergebnisse einer funktionellen Gedachtnis-MRT Untersuchung beschrieben. / Abstract: This article reports about a 30-year-old male patient who had suffered from a focal epilepsy with epigastric auras, unaware seizures and rarely bilateral tonic clonic seizures due to hippocampal sclerosis since the age of 21 years. The patient was offered the standard anterior temporal lobe resection and alternatively stereotactic laser thermal ablation, which recently received approval with the European CE mark. The patient opted for stereotactic laser ablation because of its less invasive nature compared to standard craniotomy and resection. This article reports the clinical course over a 9-month follow-up period. Additionally, the method and the results of a functional magnetic resonance imaging (fMRI) memory examination are summarized.

Background We present one patient with an initial diagnosis of Guillain-Barre syndrome (GBS) and one with Charcot-Marie-Tooth disease (CMT) type 1A. Methods Both patients underwent ankle tibial nerve fusion-imaging of high-resolution ultrasound (HRUS) with 7T MR neurography (MRN). Results In GBS, the nerve was enlarged, T2-hyperintense, and showed increased vascularization 21 months after symptom onset. In CMT1A, the enlarged nerve was T2-isointense with normal endoneurial blood flow. Conclusions We demonstrate the utility of 7T-MRN-HRUS-fusion-imaging. In GBS, there was evidence of ongoing inflammation resulting in a changed diagnosis to acute-onset chronic demyelinating polyradiculoneuropathy and maintenance of immunotherapy. By MRN-HRUS-fusion, patients with presumed peripheral axonal degeneration could be shown to display imaging markers associated with peripheral nervous system inflammation. Thus, more accurate identification of a treatable inflammatory component may become possible.

fMRI studies in macular degeneration (MD) and retinitis pigmentosa (RP) demonstrated that responses in the lesion projection zones (LPZ) of V1 are task related, indicating significant limits of bottom-up visual system plasticity in MD and RP. In advanced glaucoma (GL), a prevalent eye disease and leading cause of blindness, the scope of visual system plasticity is currently unknown. We performed 3T fMRI in patients with extensive visual field defects due to GL (n=5), RP (n=2) and healthy controls (n=7; with simulated defects). Participants viewed contrast patterns drifting in 8 directions alternating with uniform gray and performed 3 tasks: (1) passive viewing (PV), (2) one-back task (OBT) and (3) fixation-dot task (FDT). During PV, they passively viewed the stimulus with central fixation, during OBT they reported the succession of the same two motion directions, and during FDT a change in the fixation color. In GL, LPZ responses of the early visual cortex (V1, V2 and V3) shifted from negative during PV to positive for OBT [p (corrected): V1(0.006); V2(0.04); V3(0.008)], while they were negative in the controls’ simulated LPZ for all stimulation conditions. For RP a similar pattern as for GL was observed. Consequently, activity in the de-afferented visual cortex in glaucoma is, similar to MD and RP, task-related. In conclusion, the lack of bottom-up plasticity appears to be a general feature of the human visual system. These insights are of importance for the development of treatment and rehabilitation schemes in glaucoma.Highlights 1. Functional dynamics of early visual cortex LPZ depend on task demands in glaucoma2. Brain activity in deprived visual cortex suggests absence of large-scale remapping3. Limited scope of bottom-up plasticity is a general feature of human visual system4. Visual system stability and plasticity is of relevance for therapeutic advances### Competing Interest StatementThe authors have declared no competing interest.

Expectancy shapes our perception of impending events. Although such an interplay between cognitive and affective processes is often impaired in mental disorders, it is not well understood how top-down expectancy signals modulate future affect. We therefore track the information flow in the brain during cognitive and affective processing segregated in time using task-specific cross-correlations. Participants in two independent fMRI studies (N 1 = 37 & N 2 = 55) were instructed to imagine a situation with affective content as indicated by a cue, which was then followed by an emotional picture congruent with expectancy. To correct for intrinsic covariance of brain function, we calculate resting-state cross-correlations analogous to the task. First, using factorial modeling of delta cross-correlations (task-rest) of the first study, we find that the magnitude of expectancy signals in the anterior insula cortex (AIC) modulates the BOLD response to emotional pictures in the anterior cingulate and dorsomedial prefrontal cortex in opposite directions. Second, using hierarchical linear modeling of lagged connectivity, we demonstrate that expectancy signals in the AIC indeed foreshadow this opposing pattern in the prefrontal cortex. Third, we replicate the results in the second study using a higher temporal resolution, showing that our task-specific cross-correlation approach robustly uncovers the dynamics of information flow. We conclude that the AIC arbitrates the recruitment of distinct prefrontal networks during cued picture processing according to triggered expectations. Taken together, our study provides new insights into neuronal pathways channeling cognition and affect within well-defined brain networks. Better understanding of such dynamics could lead to new applications tracking aberrant information processing in mental disorders.

In rodents, cells in the medial entorhinal cortex (EC) and subiculum code for the allocentric direction to environment boundaries, which is an important prerequisite for accurate positional coding. Although in humans boundary-related signals have been reported, there is no evidence that they contain allocentric direction information. Furthermore, it has not been possible to separate boundary versus goal direction signals in the EC/subiculum. Here, to address these questions, we had participants learn a virtual environment containing four unique boundaries. Participants then underwent fMRI scanning where they made judgements about the allocentric direction of a cue object. Using multivariate decoding, we found information regarding allocentric boundary direction in posterior EC and subiculum, whereas allocentric goal direction was decodable from anterior EC and subiculum. These data provide the first evidence of allocentric boundary coding in humans, and are consistent with recent conceptualisations of a division of labour within the EC.

Previously published results indicate that the accuracy of decoding visual orientation from 7 Tesla fMRI data of V1 peaks at spatial acquisition resolutions that are routinely accessible with more conventional 3 Tesla scanners. This study directly compares the decoding performance between a 3 Tesla and a 7 Tesla dataset that were acquired using the same stimulation paradigm by applying an identical analysis procedure. The results indicate that decoding models built on 3 Tesla data are comparatively impaired. Moreover, we found no evidence for a strong coupling of BOLD signal change magnitude or temporal signal to noise ratio (tSNR) with decoding performance. Direct enhancement of tSNR via multiband fMRI acquisition at the same resolution did not translate into improved decoding performance. Additional voxel selection can boost 3 Tesla decoding performance to the 7 Tesla level only at a 3 mm acquisition resolution. In both datasets the BOLD signal available for orientation decoding is spatially broadband, but, consistent with the size of the BOLD point-spread-function, decoding models at 3 Tesla utilize spatially coarser image components.

Real-time fMRI neurofeedback allows to learn control over activity in a localized brain region. However, with fMRI, physiological factors such as the cardiac cycle and respiration interfere with the measurement of brain activation. In conventional fMRI studies this is usually mitigated by inclusion of motion parameters and/or physiological parameters as nuisance regressors at the analysis stage, allowing to correct for and filter out such confounders. In real-time fMRI, however, such an approach is not routinely feasible due to the necessity to process all signals during the runtime of an experiment. The absence of runtime correction can therefore compromise real-time fMRI study outcomes reporting volitional self-regulation capability as BOLD signal changes. This is especially true for BOLD signal changes in subcortical regions situated close to blood vessels or air vavities, such as the amygdala. We therefore aimed to establish the effects of motion, heart rate, heart rate variability, and respiratory volume on learning effects, which means here an increase in BOLD signal change over NF training, in an amygdala neurofeedback experiment. Specifically, we investigate motion parameters from two emotion regulation studies - performed at 3T and 7T scanners - and additionally acquired physiological variance for the latter one. Our results revealed differences in these parameters between groups and especially between regulation and resting periods within each participant. However, strictly considering these parameters as nuisance regressors in data analysis revealed that the learning of volitional self-regulation of the amygdala is not driven by motion and physiological changes. As validation of our real-time findings, we compare them to the gold standard of assessment of motion and physiology from the Human Connectome Project. Based on this, we recommend to carefully report neurofeedback study results including physiological nuisance regression. To our knowledge, this is the first study investigating the effects of motion and physiological noise correction on neurofeedback BOLD effects.

A progressive loss of navigational abilities in old age has been observed in numerous studies, but we have only limited understanding of the neural mechanisms underlying this decline [1]. A central component of the brain's navigation circuit are grid cells in entorhinal cortex [2], largely thought to support intrinsic self-motion-related computations, such as path integration (i.e., keeping track of one's position by integrating self-motion cues) [3-6]. Given that entorhinal cortex is particularly vulnerable to neurodegenerative processes during aging and Alzheimer's disease [7-14], deficits in grid cell function could be a key mechanism to explain age-related navigational decline. To test this hypothesis, we conducted two experiments in healthy young and older adults. First, in an fMRI experiment, we found significantly reduced grid-cell-like representations in entorhinal cortex of older adults. Second, in a behavioral path integration experiment, older adults showed deficits in computations of self-position during path integration based on body-based or visual self-motion cues. Most strikingly, we found that these path integration deficits in older adults could be explained by their individual magnitudes of grid-cell-like representations, as reduced grid-cell-like representations were associated with larger path integration errors. Together, these results show that grid-cell-like representations in entorhinal cortex are compromised in healthy aging. Furthermore, the association between grid-cell-like representations and path integration performance in old age supports the notion that grid cells underlie path integration processes. We therefore conclude that impaired grid cell function may play a key role in age-related decline of specific higher-order cognitive functions, such as spatial navigation.

Cross-modal recalibration allows the brain to maintain coherent sensory representations of the world. Using functional magnetic resonance imaging (fMRI), the present study aimed at identifying the neural mechanisms underlying recalibration in an audiovisual ventriloquism aftereffect paradigm. Participants performed a unimodal sound localization task, before and after they were exposed to adaptation blocks, in which sounds were paired with spatially disparate visual stimuli offset by 14° to the right. Behavioral results showed a significant rightward shift in sound localization following adaptation, indicating a ventriloquism aftereffect. Regarding fMRI results, left and right planum temporale (lPT/rPT) were found to respond more to contralateral sounds than to central sounds at pretest. Contrasting posttest with pretest blocks revealed significantly enhanced fMRI-signals in space-sensitive lPT after adaptation, matching the behavioral rightward shift in sound localization. Moreover, a region-of-interest analysis in lPT/rPT revealed that the lPT activity correlated positively with the localization shift for right-side sounds, whereas rPT activity correlated negatively with the localization shift for left-side and central sounds. Finally, using functional connectivity analysis, we observed enhanced coupling of the lPT with left and right inferior parietal areas as well as left motor regions following adaptation and a decoupling of lPT/rPT with contralateral auditory cortex, which scaled with participants' degree of adaptation. Together, the fMRI results suggest that cross-modal spatial recalibration is accomplished by an adjustment of unisensory representations in low-level auditory cortex. Such persistent adjustments of low-level sensory representations seem to be mediated by the interplay with higher-level spatial representations in parietal cortex.

Several previous imaging studies have aimed at identifying the neural basis of visual food cue processing in humans. However, there is little consistency of the functional magnetic resonance imaging (fMRI) results across studies. Here, we tested the hypothesis that this variability across studies might – at least in part – be caused by the different tasks employed. In particular, we assessed directly the influence of task set on brain responses to food stimuli with fMRI using two tasks (colour vs. edibility judgement, between‐subjects design). When participants judged colour, the left insula, the left inferior parietal lobule, occipital areas, the left orbitofrontal cortex and other frontal areas expressed enhanced fMRI responses to food relative to non‐food pictures. However, when judging edibility, enhanced fMRI responses to food pictures were observed in the superior and middle frontal gyrus and in medial frontal areas including the pregenual anterior cingulate cortex and ventromedial prefrontal cortex. This pattern of results indicates that task sets can significantly alter the neural underpinnings of food cue processing. We propose that judging low‐level visual stimulus characteristics – such as colour – triggers stimulus‐related representations in the visual and even in gustatory cortex (insula), whereas discriminating abstract stimulus categories activates higher order representations in both the anterior cingulate and prefrontal cortex. Hum Brain Mapp 38:2897–2912, 2017 . © 2017 Wiley Periodicals, Inc.