Reliability of task-based fMRI in the dorsal horn of the human spinal cord.

The application of functional magnetic resonance imaging (fMRI) to the human spinal cord is still a relatively small field of research and faces many challenges. Here we aimed to probe the limitations of task-based spinal fMRI at 3T by investigating the reliability of spinal cord blood oxygen level dependent (BOLD) responses to repeated nociceptive stimulation across two consecutive days in 40 healthy volunteers. We assessed the test-retest reliability of subjective ratings, autonomic responses, and spinal cord BOLD responses to short heat pain stimuli (1s duration) using the intraclass correlation coefficient (ICC). At the group level, we observed robust autonomic responses as well as spatially specific spinal cord BOLD responses at the expected location, but no spatial overlap in BOLD response patterns across days. While autonomic indicators of pain processing showed good-to-excellent reliability, both ß-estimates and z-scores of task-related BOLD responses showed poor reliability across days in the target region (gray matter of the ipsilateral dorsal horn). When taking into account the sensitivity of gradient-echo echo planar imaging (GE-EPI) to draining vein signals by including the venous plexus in the analysis, we observed BOLD responses with good reliability across days. Taken together, these results demonstrate that heat pain stimuli as short as one second are able to evoke a robust and spatially specific BOLD response, which is however strongly variable within participants across time, resulting in low reliability in the dorsal horn gray matter. Further improvements in data acquisition and analysis techniques are thus necessary before event-related spinal cord fMRI as used here can be reliably employed in longitudinal designs or clinical settings.

Multi-echo investigations of positive and negative CBF and concomitant BOLD changes.

Unlike the positive blood oxygenation level-dependent (BOLD) response (PBR), commonly taken as an indication of an 'activated' brain region, the physiological origin of negative BOLD signal changes (i.e. a negative BOLD response, NBR), also referred to as 'deactivation' is still being debated. In this work, an attempt was made to gain a better understanding of the underlying mechanism by obtaining a comprehensive measure of the contributing cerebral blood flow (CBF) and its relationship to the NBR in the human visual cortex, in comparison to a simultaneously induced PBR in surrounding visual regions. To overcome the low signal-to-noise ratio (SNR) of CBF measurements, a newly developed multi-echo version of a center-out echo planar-imaging (EPI) readout was employed with pseudo-continuous arterial spin labeling (pCASL). It achieved very short echo and inter-echo times and facilitated a simultaneous detection of functional CBF and BOLD changes at 3 T with improved sensitivity. Evaluations of the absolute and relative changes of CBF and the effective transverse relaxation rate, R2*, the coupling ratios, and their dependence on CBF at rest, CBFrest, indicated differences between activated and deactivated regions. Analysis of the shape of the respective functional responses also revealed faster negative responses with more pronounced post-stimulus transients. Resulting differences in the flow-metabolism coupling ratios were further examined for potential distinctions in the underlying neuronal contributions.

Distributed networks for auditory memory differentially contribute to recall precision.

Re-directing attention to objects in working memory can enhance their representational fidelity. However, how this attentional enhancement of memory representations is implemented across distinct, sensory and cognitive-control brain network is unspecified. The present fMRI experiment leverages psychophysical modelling and multivariate auditory-pattern decoding as behavioral and neural proxies of mnemonic fidelity. Listeners performed an auditory syllable pitch-discrimination task and received retro-active cues to selectively attend to a to-be-probed syllable in memory. Accompanied by increased neural activation in fronto-parietal and cingulo-opercular networks, valid retro-cues yielded faster and more perceptually sensitive responses in recalling acoustic detail of memorized syllables. Information about the cued auditory object was decodable from hemodynamic response patterns in superior temporal sulcus (STS), fronto-parietal, and sensorimotor regions. However, among these regions retaining auditory memory objects, neural fidelity in the left STS and its enhancement through attention-to-memory best predicted individuals' gain in auditory memory recall precision. Our results demonstrate how functionally discrete brain regions differentially contribute to the attentional enhancement of memory representations.

Alexithymia and automatic processing of facial emotions: behavioral and neural findings.

BACKGROUND: Alexithymia is a personality trait characterized by difficulties identifying and describing feelings, an externally oriented style of thinking, and a reduced inclination to imagination. Previous research has shown deficits in the recognition of emotional facial expressions in alexithymia and reductions of brain responsivity to emotional stimuli. Using an affective priming paradigm, we investigated automatic perception of facial emotions as a function of alexithymia at the behavioral and neural level. In addition to self-report scales, we applied an interview to assess alexithymic tendencies. RESULTS: During 3 T fMRI scanning, 49 healthy individuals judged valence of neutral faces preceded by briefly shown happy, angry, fearful, and neutral facial expressions. Alexithymia was assessed using the 20-Item Toronto Alexithymia Scale (TAS-20), the Bermond-Vorst Alexithymia Questionnaire (BVAQ) and the Toronto Structured Interview for Alexithymia (TSIA). As expected, only negative correlations were found between alexithymic features and affective priming. The global level of self-reported alexithymia (as assessed by the TAS-20 and the BVAQ) was found to be related to less affective priming owing to angry faces. At the facet level, difficulties identifying feelings, difficulties analyzing feelings, and impoverished fantasy (as measured by the BVAQ) were correlated with reduced affective priming due to angry faces. Difficulties identifying feelings (BVAQ) correlated also with reduced affective priming due to fearful faces and reduced imagination (TSIA) was related to decreased affective priming due to happy faces. There was only one significant correlation between alexithymia dimensions and automatic brain response to masked facial emotions: TAS-20 alexithymia correlated with heightened brain response to masked happy faces in superior and medial frontal areas. CONCLUSIONS: Our behavioral results provide evidence that alexithymic features are related in particular to less sensitivity for covert facial expressions of anger. The perceptual alterations could reflect impaired automatic recognition or integration of social anger signals into judgemental processes and might contribute to the problems in interpersonal relationships associated with alexithymia. Our findings suggest that self-report measures of alexithymia may have an advantage over interview-based tests as research tools in the field of emotion perception at least in samples of healthy individuals characterized by rather low levels of alexithymia.

Brain networks underlying aesthetic appreciation as modulated by interaction of the spectral and temporal organisations of music.

Music is organised both spectrally and temporally, determining musical structures such as musical scale, harmony, and sequential rules in chord progressions. A number of human neuroimaging studies investigated neural processes associated with emotional responses to music investigating the influence of musical valence (pleasantness/unpleasantness) comparing the response to music and unpleasantly manipulated counterparts where harmony and sequential rules were varied. Interactions between the previously applied alterations to harmony and sequential rules of the music in terms of emotional experience and corresponding neural activities have not been systematically studied although such interactions are at the core of how music affects the listener. The current study investigates the interaction between such alterations in harmony and sequential rules by using data sets from two functional magnetic resonance imaging (fMRI) experiments. While replicating the previous findings, we found a significant interaction between the spectral and temporal alterations in the fronto-limbic system, including the ventromedial prefrontal cortex (vmPFC), nucleus accumbens, caudate nucleus, and putamen. We further revealed that the functional connectivity between the vmPFC and the right inferior frontal gyrus (IFG) was reduced when listening to excerpts with alterations in both domains compared to the original music. As it has been suggested that the vmPFC operates as a pivotal point that mediates between the limbic system and the frontal cortex in reward-related processing, we propose that this fronto-limbic interaction might be related to the involvement of cognitive processes in the emotional appreciation of music.

WOME: Theory-Based Working Memory Training - A Placebo-Controlled, Double-Blind Evaluation in Older Adults.

Background: Scientifically evaluated cognitive intervention programs are essential to meet the demands of our increasingly aging society. Currently, one of the "hottest" topics in the field is the improvement of working memory function and its potential impact on overall cognition. The present study evaluated the efficacy of WOME (WOrking MEmory), a theory-based working memory training program, in a double-blind, placebo-controlled, and randomized controlled trial (www.drks.de, DRKS00013162). Methods:N = 60 healthy older adults were allocated to (1) the WOME intervention, (2) an active low-level intervention, or (3) a passive control group. Overall, the intervention groups practiced twelve sessions of 45 min within 4 weeks of their respective training. Transfer effects were measured via an extensive battery of neuropsychological tests and questionnaires both pre-/post-training and at a 3-month follow-up. Results:WOME led to a significant improvement in working memory function, demonstrated on a non-trained near transfer task and on two different composite scores with moderate to large effect sizes. In addition, we found some indication of relevant impact on everyday life. The effects were short-term rather than stable, being substantially diminished at follow-up with only little evidence suggesting long-term maintenance. No transfer effects on other cognitive functions were observed. Conclusion:WOME is an appropriate and efficient intervention specifically targeting the working memory system in healthy older adults. Trial Registration: German Clinical Trials Register (DRKS), Identifier: DRKS00013162.

Structural Neural Correlates of Physiological Mirror Activity During Isometric Contractions of Non-Dominant Hand Muscles.

Mirror Activity (MA) describes involuntarily occurring muscular activity in contralateral homologous limbs during unilateral movements. This phenomenon has not only been reported in patients with neurological disorders (i.e. Mirror Movements) but has also been observed in healthy adults referred to as physiological Mirror Activity (pMA). However, despite recent hypotheses, the underlying neural mechanisms and structural correlates of pMA still remain insufficiently described. We investigated the structural correlates of pMA during isometric contractions of hand muscles with increasing force demands on a whole-brain level by means of voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS). We found significant negative correlations between individual tendencies to display pMA and grey matter volume (GMV) in the right anterior cingulate cortex (ACC) as well as fractional anisotropy (FA) of white matter (WM) tracts of left precuneus (PrC) during left (non-dominant) hand contractions. No significant structural associations for contractions of the right hand were found. Here we extend previously reported functional associations between ACC/PrC and the inhibtion of intrinsically favoured mirror-symmetrical movement tendencies to an underlying structural level. We provide novel evidence that the individual structural state of higher order motor/executive areas upstream of primary/secondary motor areas might contribute to the phenomen of pMA.

Mirror Electromyografic Activity in the Upper and Lower Extremity: A Comparison between Endurance Athletes and Non-Athletes.

During unimanual motor tasks, muscle activity may not be restricted to the contracting muscle, but rather occurs involuntarily in the contralateral resting limb, even in healthy individuals. This phenomenon has been referred to as mirror electromyographic activity (MEMG). To date, the physiological (non-pathological) form of MEMG has been observed predominately in upper extremities (UE), while remaining sparsely described in lower extremities (LE). Accordingly, evidence regarding the underlying mechanisms and modulation capability of MEMG, i.e., the extent of MEMG in dependency of exerted force during unilateral isometric contractions are insufficiently investigated in terms of LE. Furthermore, it still remains elusive if and how MEMG is affected by long-term exercise training. Here, we provide novel quantitative evidence for physiological MEMG in homologous muscles of LE (tibialis anterior (TA), rectus femoris (RF)) during submaximal unilateral dorsiflexion in healthy young adults. Furthermore, endurance athletes (EA, n = 11) show a higher extent of MEMG in LE compared to non-athletes (NA, n = 11) at high force demands (80% MVC, maximum voluntary contraction). While the underlying neurophysiological mechanisms of MEMG still remain elusive, our study indicates, at least indirectly, that sport-related long-term training might affect the amount of MEMG during strong isometric contractions specifically in trained limbs. To support this assumption of exercise-induced limb-specific MEMG modulation, future studies including different sports disciplines with contrasting movement patterns and parameters should additionally be performed.

Dissonance encoding in human inferior colliculus covaries with individual differences in dislike of dissonant music.

Harmony is one of the most fundamental elements of music that evokes emotional response. The inferior colliculus (IC) has been known to detect poor agreement of harmonics of sound, that is, dissonance. Electrophysiological evidence has implicated a relationship between a sustained auditory response mainly from the brainstem and unpleasant emotion induced by dissonant harmony. Interestingly, an individual's dislike of dissonant harmony of an individual correlated with a reduced sustained auditory response. In the current paper, we report novel evidence based on functional magnetic resonance imaging (fMRI) for such a relationship between individual variability in dislike of dissonance and the IC activation. Furthermore, for the first time, we show how dissonant harmony modulates functional connectivity of the IC and its association with behaviourally reported unpleasantness. The current findings support important contributions of low level auditory processing and corticofugal interaction in musical harmony preference.

Neural Correlates of Mirror Visual Feedback-Induced Performance Improvements: A Resting-State fMRI Study.

Mirror visual feedback (MVF) is a promising approach to enhance motor performance without training in healthy adults as well as in patients with focal brain lesions. There is preliminary evidence that a functional modulation within and between primary motor cortices as assessed with transcranial magnetic stimulation (TMS) might be one candidate mechanism mediating the observed behavioral effects. Recently, studies using task-based functional magnetic resonance imaging (fMRI) have indicated that MVF-induced functional changes might not be restricted to the primary motor cortex (M1) but also include higher order regions responsible for perceptual-motor coordination and visual attention. However, aside from these instantaneous task-induced brain changes, little is known about learning-related neuroplasticity induced by MVF. Thus, in the present study, we assessed MVF-induced functional network plasticity with resting-state fMRI (rs-fMRI). We performed rs-fMRI of 35 right-handed, healthy adults before and after performing a complex ball-rotation task. The primary outcome measure was the performance improvement of the untrained left hand (LH) before and after right hand (RH) training with MVF (mirror group [MG], n = 17) or without MVF (control group [CG], n = 18). Behaviorally, the MG showed superior performance improvements of the untrained LH. In resting-state functional connectivity (rs-FC), an interaction analysis between groups showed changes in left visual cortex (V1, V2) revealing an increase of centrality in the MG. Within group comparisons showed further functional alterations in bilateral primary sensorimotor cortex (SM1), left V4 and left anterior intraparietal sulcus (aIP) in the MG, only. Importantly, a correlation analysis revealed a linear positive relationship between MVF-induced improvements of the untrained LH and functional alterations in left SM1. Our results suggest that MVF-induced performance improvements are associated with functional learning-related brain plasticity and have identified additional target regions for non-invasive brain stimulation techniques, a finding of potential interest for neurorehabilitation.

"Eyes Open - Eyes Closed" EEG/fMRI data set including dedicated "Carbon Wire Loop" motion detection channels.

This data set contains electroencephalography (EEG) data as well as simultaneous EEG with functional magnetic resonance imaging (EEG/fMRI) data. During EEG/fMRI, the EEG cap was outfitted with a hardware-based add-on consisting of carbon-wire loops (CWL). These yielded six extra׳CWL׳ signals related to Faraday induction of these loops in the main magnetic field "Measurement and reduction of motion and ballistocardiogram artefacts from simultaneous EEG and fMRI recordings" (Masterton et al., 2007) [1]. In this data set, the CWL data make it possible to do a direct regression approach to deal with the BCG and specifically He artifact. The CWL-EEG/fMRI data in this paper has been recorded on two MRI scanners with different Helium pump systems (4 subjects on a 3 T TIM Trio and 4 subjects on a 3T VERIO). Separate EEG/fMRI data sets have been recorded for the helium pump ON as well as the helium pump OFF conditions. The EEG-only data (same subjects) has been recorded for a motion artifact-free reference EEG signal outside of the scanner. This paper also links to an EEGlab "EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis" (Delorme and Makeig, 2004) [2] plugin to perform a CWL regression approach to deal with the He pump artifact, as published in the main paper "Carbon-wire loop based artifact correction outperforms post-processing EEG/fMRI corrections-A validation of a real-time simultaneous EEG/fMRI correction method" (van der Meer et al., 2016) [3].

Prior probability modulates anticipatory activity in category-specific areas.

Bayesian models are currently a dominant framework for describing human information processing. However, it is not clear yet how major tenets of this framework can be translated to brain processes. In this study, we addressed the neural underpinning of prior probability and its effect on anticipatory activity in category-specific areas. Before fMRI scanning, participants were trained in two behavioral sessions to learn the prior probability and correct order of visual events within a sequence. The events of each sequence included two different presentations of a geometric shape and one picture of either a house or a face, which appeared with either a high or a low likelihood. Each sequence was preceded by a cue that gave participants probabilistic information about which items to expect next. This allowed examining cue-related anticipatory modulation of activity as a function of prior probability in category-specific areas (fusiform face area and parahippocampal place area). Our findings show that activity in the fusiform face area was higher when faces had a higher prior probability. The finding of a difference between levels of expectations is consistent with graded, probabilistically modulated activity, but the data do not rule out the alternative explanation of a categorical neural response. Importantly, these differences were only visible during anticipation, and vanished at the time of stimulus presentation, calling for a functional distinction when considering the effects of prior probability. Finally, there were no anticipatory effects for houses in the parahippocampal place area, suggesting sensitivity to stimulus material when looking at effects of prediction.

Carbon-wire loop based artifact correction outperforms post-processing EEG/fMRI corrections--A validation of a real-time simultaneous EEG/fMRI correction method.

Simultaneous EEG-fMRI combines two powerful neuroimaging techniques, but the EEG signal suffers from severe artifacts in the MRI environment that are difficult to remove. These are the MR scanning artifact and the blood-pulsation artifact--strategies to remove them are a topic of ongoing research. Additionally large, unsystematic artifacts are produced across the full frequency spectrum by the magnet's helium pump (and ventilator) systems which are notoriously hard to remove. As a consequence, experimenters routinely deactivate the helium pump during simultaneous EEG-fMRI acquisitions which potentially risks damaging the MRI system and necessitates more frequent and expensive helium refills. We present a novel correction method addressing both helium pump and ballisto-cardiac (BCG) artifacts, consisting of carbon-wire loops (CWL) as additional sensors to accurately track unpredictable artifacts related to subtle movements in the scanner, and an EEGLAB plugin to perform artifact correction. We compare signal-to-noise metrics of EEG data, corrected with CWL and three conventional correction methods, for helium pump off and on measurements. Because the CWL setup records signals in real-time, it fits requirements of applications where immediate correction is necessary, such as neuro-feedback applications or stimulation time-locked to specific sleep oscillations. The comparison metrics in this paper relate to: (1) the EEG signal itself, (2) the "eyes open vs. eyes closed" effect, and (3) an assessment of how the artifact corrections impacts the ability to perform meaningful correlations between EEG alpha power and the BOLD signal. Results show that the CWL correction corrects for He pump artifact and also produces EEG data more comparable to EEG obtained outside the magnet than conventional post-processing methods.

Physical exercise in overweight to obese individuals induces metabolic- and neurotrophic-related structural brain plasticity.

Previous cross-sectional studies on body-weight-related alterations in brain structure revealed profound changes in the gray matter (GM) and white matter (WM) that resemble findings obtained from individuals with advancing age. This suggests that obesity may lead to structural brain changes that are comparable with brain aging. Here, we asked whether weight-loss-dependent improved metabolic and neurotrophic functioning parallels the reversal of obesity-related alterations in brain structure. To this end we applied magnetic resonance imaging (MRI) together with voxel-based morphometry and diffusion-tensor imaging in overweight to obese individuals who participated in a fitness course with intensive physical training twice a week over a period of 3 months. After the fitness course, participants presented, with inter-individual heterogeneity, a reduced body mass index (BMI), reduced serum leptin concentrations, elevated high-density lipoprotein-cholesterol (HDL-C), and alterations of serum brain-derived neurotrophic factor (BDNF) concentrations suggesting changes of metabolic and neurotrophic function. Exercise-dependent changes in BMI and serum concentration of BDNF, leptin, and HDL-C were related to an increase in GM density in the left hippocampus, the insular cortex, and the left cerebellar lobule. We also observed exercise-dependent changes of diffusivity parameters in surrounding WM structures as well as in the corpus callosum. These findings suggest that weight-loss due to physical exercise in overweight to obese participants induces profound structural brain plasticity, not primarily of sensorimotor brain regions involved in physical exercise, but of regions previously reported to be structurally affected by an increased body weight and functionally implemented in gustation and cognitive processing.

Investigating the dynamics of the brain response to music: A central role of the ventral striatum/nucleus accumbens.

Ventral striatal activity has been previously shown to correspond well to reward value mediated by music. Here, we investigate the dynamic brain response to music and manipulated counterparts using functional magnetic resonance imaging (fMRI). Counterparts of musical excerpts were produced by either manipulating the consonance/dissonance of the musical fragments or playing them backwards (or both). Results show a greater involvement of the ventral striatum/nucleus accumbens both when contrasting listening to music that is perceived as pleasant and listening to a manipulated version perceived as unpleasant (backward dissonant), as well as in a parametric analysis for increasing pleasantness. Notably, both analyses yielded a ventral striatal response that was strongest during an early phase of stimulus presentation. A hippocampal response to the musical stimuli was also observed, and was largely mediated by processing differences between listening to forward and backward music. This hippocampal involvement was again strongest during the early response to the music. Auditory cortex activity was more strongly evoked by the original (pleasant) music compared to its manipulated counterparts, but did not display a similar decline of activation over time as subcortical activity. These findings rather suggest that the ventral striatal/nucleus accumbens response during music listening is strongest in the first seconds and then declines.

Automatic emotion processing as a function of trait emotional awareness: an fMRI study.

It is unclear whether reflective awareness of emotions is related to extent and intensity of implicit affective reactions. This study is the first to investigate automatic brain reactivity to emotional stimuli as a function of trait emotional awareness. To assess emotional awareness the Levels of Emotional Awareness Scale (LEAS) was administered. During scanning, masked happy, angry, fearful and neutral facial expressions were presented to 46 healthy subjects, who had to rate the fit between artificial and emotional words. The rating procedure allowed assessment of shifts in implicit affectivity due to emotion faces. Trait emotional awareness was associated with increased activation in the primary somatosensory cortex, inferior parietal lobule, anterior cingulate gyrus, middle frontal and cerebellar areas, thalamus, putamen and amygdala in response to masked happy faces. LEAS correlated positively with shifts in implicit affect caused by masked happy faces. According to our findings, people with high emotional awareness show stronger affective reactivity and more activation in brain areas involved in emotion processing and simulation during the perception of masked happy facial expression than people with low emotional awareness. High emotional awareness appears to be characterized by an enhanced positive affective resonance to others at an automatic processing level.

Obesity Associated Cerebral Gray and White Matter Alterations Are Interrelated in the Female Brain.

Obesity is known to affect the brain's gray matter (GM) and white matter (WM) structure but the interrelationship of such changes remains unclear. Here we used T1-weighted magnetic resonance imaging (MRI) in combination with voxel-based morphometry (VBM) and diffusion-tensor imaging (DTI) with tract-based spatial statistics (TBSS) to assess the relationship between obesity-associated alterations of gray matter density (GMD) and anisotropic water diffusion in WM, respectively. In a small cohort of lean to obese women, we confirmed previous reports of obesity-associated alterations of GMD in brain regions involved in executive control (i.e., dorsolateral prefrontal cortex, DLPFC) and habit learning (i.e., dorsal striatum). Gray matter density alterations of the DLPFC were negatively correlated with radial diffusivity in the entire corpus callosum. Within the genu of the corpus callosum we found a positive correlation with axial diffusivity. In posterior region and inferior areas of the body of the corpus callosum, axial diffusivity correlated negatively with altered GMD in the dorsal striatum. These findings suggest that, in women, obesity-related alterations of GMD in brain regions involved in executive control and habit learning might relate to alterations of associated WM fiber bundles within the corpus callosum.

Alexithymic features and the labeling of brief emotional facial expressions - An fMRI study.

The ability to recognize subtle facial expressions can be valuable in social interaction to infer emotions and intentions of others. Research has shown that the personality trait of alexithymia is linked to difficulties labeling facial expressions especially when these are presented with temporal constraints. The present study investigates the neural mechanisms underlying this deficit. 50 young healthy volunteers had to label briefly presented (≤100ms) emotional (happy, angry, fearful) facial expressions masked by a neutral expression while undergoing functional magnetic resonance imaging (fMRI). A multi-method approach (20-Item Toronto Alexithymia Scale and Toronto Structured Interview for Alexithymia) was administered to assess alexithymic tendencies. Behavioral results point to a global deficit of alexithymic individuals in labeling brief facial expressions. Alexithymia was related to decreased response of the ventral striatum to negative facial expressions. Moreover, alexithymia was associated with lowered activation in frontal, temporal and occipital cortices. Our data suggest that alexithymic individuals have difficulties in creating appropriate representations of the emotional state of other persons under temporal constraints. These deficiencies could lead to problems in labeling other people׳s facial emotions.