Voxel-based morphometry (VBM) is a widely used tool for studying structural patterns of brain plasticity, brain development and disease. The source of the T-1-signal changes is not understood. Most of these changes are discussed to represent loss or possibly gain of brain gray matter and recent publications speculate also about non-structural changes affecting T-1-signal. We investigated the potential of pain stimulation to ultra-short-term alter gray matter signal changes in pain relevant brain regions in healthy volunteers using a longitudinal design. Immediately following regional nociceptive input, we detected significant gray matter volume (GMV) changes in central pain processing areas, i.e. anterior cingulate and insula cortex. However, similar results were observed in a control group using the identical time intervals but without nociceptive painful input. These GMV changes could be reproduced in almost 100 scanning sessions enrolling 72 healthy individuals comprising repetitive magnetization-prepared rapid gradient-echo (MPRAGE) sequences. These data suggest that short-term longitudinal repetitive MPRAGE may produce significant GMV changes without any intervention. Future studies investigating brain plasticity should focus and specifically report a consistent timing at which time-point during the experiment the T-1-weighted scan is conducted. There is a necessity of a control group for longitudinal imaging studies.

OBJECTIVE:The aim of the current study was to identify typical alterations in resting state connectivity within different stages of the migraine cycle and to thus explore task-free mechanisms of headache attack generation in migraineurs.BACKGROUND:Recent evidence in migraine pathophysiology suggests that hours and even days before headache certain changes in brain activity take place, ultimately leading to an attack. Here, we investigate changes before headache onset using resting state functional magnetic resonance imaging (fMRI).METHODS:Nine episodic migraineurs underwent daily resting state functional magnetic resonance imaging for a minimum period of 30 consecutive days, leading to a cumulative number of 282 total days scanned. Thus, data from 15 spontaneous headache attacks were acquired. This allows analysing not only the ictal and the interictal phase of migraine but also the preictal phase. ROI-to-ROI (region of interest) and ROI-to-voxel connectivity was calculated over the migraine cycle.RESULTS:Within the ROI-to-ROI analysis, the right nucleus accumbens showed enhanced functional connectivity to the left amygdala, hippocampus and gyrus parahippocampalis in the preictal phase compared to the interictal phase. ROI-to-voxel connectivity of the right accumbens with the dorsal rostral pons was enhanced during the preictal phase compared to interictally. Regarding custom defined ROIs, the dorsal pons was ictally functionally more strongly coupled to the hypothalamic area than interictally.CONCLUSIONS:This unique data set suggests that particularly connectivity changes in dopaminergic centres and between the dorsal pons and the hypothalamus are important within migraine attack generation and sustainment.

Dopaminergic brain structures like the nucleus accumbens (NAc) are thought to encode the incentive salience of palatable foods motivating appetitive behaviour. Animal studies have identified neural networks mediating the regulation of hedonic feeding that comprise connections of the NAc with the ventral tegmental area (VTA) and the lateral hypothalamus (LH). Here, we investigated how structural connectivity of these pathways relates to individual variability in decisions on sweet food consumption in humans. We therefore combined probabilistic tractography on diffusion imaging data from 45 overnight fasted lean to overweight participants with real decisions about high and low sugar food consumption. Across all individuals, sugar preference and connectivity strength were not directly related, however, multiple regression analysis revealed interaction of mesolimbic structure and sugar preference to depend on individuals’ BMI score. In overweight individuals (BMI: ≥25 kg/m², N = 22) higher sugar preference was thereby specifically related to stronger connectivity within the VTA-NAc pathway while the opposite pattern emerged in participants with normal BMI (BMI: <25 kg/m², N = 23). Our structural results complement previous functional findings on the critical role of the human mesolimbic system for regulating hedonic eating in overweight individuals.

The ability to maintain information for a short period of time (i.e. working memory, WM) tends to decrease across the life span with large inter-individual variability; the underlying neuronal bases, however, remain unclear. To address this issue, we used a multimodal imaging approach (voxel-based morphometry, diffusion-tensor imaging, electroencephalography) to test the contribution of brain structures and neural oscillations in an elderly population. Thirty-one healthy elderly participants performed a change-detection task with different load conditions. As expected, accuracy decreased with increasing WM load, reflected by power modulations in the theta-alpha band (5–12 Hz). Importantly, these power changes were directly related to the tract strength between parahippocampus and parietal cortex. Furthermore, between-subject variance in gray matter volume of the parahippocampus and dorsal striatum predicted WM accuracy. Together, our findings provide new evidence that WM performance critically depends on parahippocampal and striatal integrity, while theta-alpha oscillations may provide a mechanism to bind the nodes within the WM network.

Sleep loss is associated with increased obesity risk, as demonstrated by correlations between sleep duration and change in body mass index or body fat percentage. Whereas previous studies linked this weight gain to disturbed endocrine parameters after sleep deprivation (SD) or restriction, neuroimaging studies revealed up-regulated neural processing of food rewards after sleep loss in reward-processing areas such as the anterior cingulate cortex, ventral striatum and insula. To tackle this ongoing debate between homeostatic versus hedonic factors underlying sleep loss-associated weight gain, we rigorously tested the association between SD and food cue processing using high-resolution fMRI and assessment of hormones. After taking blood samples from thirty-two lean, healthy men, they underwent fMRI while performing a neuroeconomic, value-based decision making task with snack food and trinket rewards following a full night of habitual sleep (HS) and a night of SD in a repeated-measures cross-over design. We found that des-acyl ghrelin concentrations were increased after SD compared with HS. Despite similar hunger ratings due to fasting in both conditions, participants were willing to spend more money on food items only after SD. Furthermore, fMRI data paralleled this behavioral finding, revealing a food reward-specific up-regulation of hypothalamic valuation signals and amygdala-hypothalamic coupling after a single night of SD. Behavioral and fMRI results were not significantly correlated with changes in acyl, des-acyl or total ghrelin concentrations. Our results indicate that increased food valuation after sleep loss is due to hedonic rather than hormonal mechanisms.

The so-called ‘replicability crisis’ has sparked methodological discussions in many areas of science in general, and in psychology in particular. This has led to recent endeavours to promote the transparency, rigour, and ultimately, replicability of research. Originating from this zeitgeist, the challenge to discuss critical issues on terminology, design, methods, and analysis considerations in fear conditioning research is taken up by this work, which involved representatives from fourteen of the major human fear conditioning laboratories in Europe. This compendium is intended to provide a basis for the development of a common procedural and terminology framework for the field of human fear conditioning. Whenever possible, we give general recommendations. When this is not feasible, we provide evidence-based guidance for methodological decisions on study design, outcome measures, and analyses. Importantly, this work is also intended to raise awareness and initiate discussions on crucial questions with respect to data collection, processing, statistical analyses, the impact of subtle procedural changes, and data reporting specifically tailored to the research on fear conditioning.

It has been shown repeatedly that perceiving itch-related pictures or listening to a lecture on itch can enhance itch sensation and scratching behaviour (Niemeier and Gieler, 2000; Holle et al., 2012; Lloyd et al., 2013), indicating that itch is strongly influenced by expectations. Using fMRI, we investigated the neural correlates of the itch-related nocebo effect in healthy male and female human subjects. Itch sensation on the left forearm was induced by cutaneous histamine application and thermally modulated, with cooling leading to higher itch. Nocebo-induced aggravation of histaminergic itch was achieved by ostensibly treating volunteers with "transcutaneous electrical nerve stimulation (TENS)" about which subjects were instructed that it would increase itch. During a conditioning phase subjects indeed experienced stronger itch due to slightly altered cooling and histamine concentrations, but attributed it to the alleged "TENS stimulation". Importantly, in the subsequent test phase where no "TENS" or electrical stimulation was applied, volunteers significantly reported stronger itch during the nocebo as compared to the control condition. Comparing BOLD responses during nocebo in contrast to control, we observed increased activity in contralateral (right) rolandic operculum. Opercular involvement was repeatedly reported in studies related to the expectation of stimulus intensification and might thus represent an early area integrating expectation information with somatosensory information. Finally, functional coupling between the insula and the periaqueductal gray (PAG) was enhanced specifically in the nocebo condition. This cortex-PAG interaction indicates that context-dependent top-down modulation during itch might represent a shared mechanism with other modalities such as pain.

Sleep has a profound impact on memory consolidation. In this study, human participants underwent Pavlovian conditioning and extinction before we manipulated nocturnal memory consolidation by a split-night protocol with 80 healthy male participants in four groups. Recall after a second (recovery) night of sleep revealed that sleeping the first half of the night, which is dominated by slow-wave sleep, did not improve recall. Conversely, sleeping the second half of the night, which is dominated by rapid eye movement (REM) sleep, led to better discrimination between fear-relevant and neutral stimuli in behavioral and autonomic measures. Meanwhile, staying awake in the second half of the night led to an increase of discrimination between extinguished and neutral stimuli, which was paralleled by an activation of the ventromedial prefrontal cortex and amygdala. We conclude that sleep, especially REM sleep, is causal to successful consolidation of dangerous and safety stimuli and reduces return of fear after extinction. SIGNIFICANCE STATEMENT We use a split-night protocol to investigate the influence of different sleep phases on successful consolidation of conditioned fear and extinction. Such a protocol uses the fact that in humans the first half of the night is dominated by slow-wave sleep, whereas during the second half, rapid eye movement (REM) sleep is more predominant. Our data show that only REM-rich sleep during the second half of the night promoted good discrimination between fear-relevant and neutral stimuli during recall, while staying awake led to a recovery of discrimination between extinguished and neutral stimuli. This suggests that sleep following extinction contributes independently to successful extinction memory consolidation.

The concept of affordances indicates "action possibilities" as characterized by object properties the environment provides to interacting organisms. Affordances relate to both perception and action and refer to sensory-motor processes emerging from goal-directed object interaction. In contrast to stable properties, affordances may vary with environmental context. A sub-classification into stable and variable affordances was proposed in the framework of the ROSSI project (Borghi et al., 2010; Borghi and Riggio, 2015, 2009). Here, we present a coordinate-based meta-analysis of functional imaging studies on object interaction targeting consistent anatomical correlates of these different types of affordances. Our review revealed the existence of two parallel (but to some extent overlapping) functional pathways. The network for stable affordances consists of predominantly left inferior parietal and frontal cortices in the ventro-dorsal stream, whereas the network for variable affordances is localized preferentially in the dorso-dorsal stream. This is in line with the proposal of differentiated affordances: stable affordances are characterized by the knowledge of invariant object features, whereas variable affordances underlie adaptation to changing object properties.

Resting-state connectivity has become an increasingly important measure in characterizing the functional integrity of brain circuits in neuro-psychiatric conditions. One approach that has recently gained prominence in this regard-and which we use in this study-is to investigate how resting-state connectivity depends on the integrity of certain neuromodulator systems. Here, we use a pharmacological challenge in combination with functional magnetic resonance imaging to investigate the impact of dopaminergic receptor blockade on whole brain functional connectivity in twenty healthy human subjects. Administration of the D2-receptor antagonist haloperidol led to a profound change in functional integration in network nodes linked to the amygdala. Compared to placebo and baseline measurements, network-based statistics and pairwise connectivity analyses revealed reduced connectivity and decreased link strength between the amygdala and the bilateral posterior cingulate cortex and other cortical areas. This was complemented by less extensive but very circumscribed enhanced connectivity between the amygdala and the right putamen during D2-receptor blockade. It will be interesting to investigate whether these pharmacologically induced shifts in resting-state connectivity will similarly be evident in clinical conditions that involve a dysfunction of the dopaminergic system. Our findings might also aid in interpreting alterations in more complex states, such as those seen psychiatric conditions and their treatment. Hum Brain Mapp 37:4148-4157, 2016. © 2016 Wiley Periodicals, Inc.

The efficacy of current treatments for anxiety disorders is limited by high relapse rates. Relapse of anxiety disorders and addiction can be triggered by exposure to life adversity, but the underlying mechanisms remain unexplored. Seventy-six healthy adults were a priori selected for the presence or absence of adverse experiences during childhood (CA) and recent past (RA; that is, past 12 months). Participants underwent fear conditioning (day 1) and fear extinction and experimental return-of-fear (ROF) induction through reinstatement (a model for adversity-induced relapse; day 2). Ratings, autonomic (skin conductance response) and neuronal activation measures (functional magnetic resonance imaging (fMRI)) were acquired. Individuals exposed to RA showed a generalized (that is, not CS- specific) fear recall and ROF, whereas unexposed individuals showed differential (that is, CS+ specific) fear recall and ROF on an autonomic level despite no group differences during fear acquisition and extinction learning. These group differences in ROF were accompanied by corresponding activation differences in brain areas known to be involved in fear processing and differentiability/generalization of ROF (that is, hippocampus). In addition, dimensional measures of RA, CA and lifetime adversity were negatively correlated with differential skin conductance responses (SCRs) during ROF and hippocampal activation. As discriminating signals of danger and safety, as well as a tendency for overgeneralization, are core features in clinically anxious populations, these deficits may specifically contribute to relapse risk following exposure to adversity, in particular to recent adversity. Hence, our results may provide first and novel insights into the possible mechanisms mediating enhanced relapse risk following exposure to (recent) adversity, which may guide the development of effective pre- and intervention programs.

Background: Impaired fear inhibition has been described as a hallmark of pathological anxiety. We aimed at further characterizing the relation between fear inhibition and anxiety by extending previous work to contextual safety stimuli as well as to dimensional scores of trait anxiety in a large sample.Methods: We employed a validated paradigm for context-dependent fear acquisition/extinction (day 1) and retrieval/expression (day 2) in 377 healthy individuals. This large sample size allowed the employment of a dimensional rather than binary approach with respect to individual differences in trait anxiety.Results: We observed a positive correlation on day 1 between trait anxiety with all CSs that possess an inherent inhibitory component, conveyed either by reliable non-reinforcement of a specific CS in a dangerous context (safe cue) or by the context itself (i.e., safe context). No correlation however was observed for a CS that possesses excitatory (threatening) properties only. These results were observed during fear learning (day 1) for US expectancy and fear ratings but not for SCRs. No such pattern was evident during fear and extinction retrieval/expression (day 2).Conclusion: We provide further evidence that high trait anxiety is associated with the inability to take immediate advantage of environmental safety cues (cued and contextual), which might represent a promising trans-diagnostic marker for different anxiety disorders. Consequently, the incorporation of methods to optimize inhibitory learning in current cognitive behavioral therapy (CBT) treatments might open up a promising avenue for precision medicine in anxiety disorders.Limitations: We did not include patients diagnosed with anxiety disorders. (C) 2015 Published by Elsevier B.V.

Background Individual differences in pain perception to a standardized nociceptive input are a well-known phenomenon within pain research. Brain structures known to play a crucial role in pain modulatory processes are the rostral/subgenual anterior cingulate cortex (sACC) as well as the periaqueductal gray (PAG), which belong to the endogenous antinociceptive system. However, the exact mechanisms possibly leading to this high level of variance in pain perception are still a matter of debate. Methods Pain perception within the trigemino-vascular system was investigated in 37 healthy volunteers using functional magnetic resonance imaging. Results Behavioral results show high levels of variance being inversely correlated to mean pain ratings as well as to an increase in BOLD signal intensity within the sACC. In addition, higher sACC activation was coupled with activation in the PAG the lower the level of intra-individual variance. Conclusion This study gives first indications that coupled BOLD response within brain structures of the antinociceptive system seems to rather not code pain intensity within the trigemino-nociceptive system but the stability of volunteers’ pain ratings. Intrinsic mechanisms may modulate the pain perception in the trigemino-vascular system, which is highly involved in headache disorders.

The cognitive and neural representation of abstract words is still an open question for theories of embodied cognition. Generally, it is proposed that abstract words are grounded in the activation of sensorimotor or at least experiential properties, exactly as concrete words. Further behavioral theories propose multiple representations evoked by abstract and concrete words. We conducted a functional magnetic resonance imaging (fMRI) study to investigate the neural correlates of concrete and abstract multi-word expressions in an action context. Participants were required to read simple sentences which combined each concrete noun with an adequate concrete verb and an adequate abstract verb, as well as an adequate abstract noun with either kind of verbs previously used. Thus, our experimental design included a continuum from pure concreteness to mere abstractness. As expected, comprehension of both concrete and abstract language content activated the core areas of the sensorimotor neural network namely the left lateral (precentral gyrus) and medial (supplementary motor area) premotor cortex. While the purely concrete multi-word expressions elicited activations within the left inferior frontal gyrus (pars triangularis) and two foci within the left inferior parietal cortex, the purely abstract multi-word expressions were represented in the anterior part of left middle temporal gyrus that is part of the language processing system. Although the sensorimotor neural network is engaged in both concrete and abstract language contents, the present findings show that concrete multi-word processing relies more on the sensorimotor system, and abstract multi-word processing relies more on the linguistic system.

Binkofski, F., Buxbaum, L.J. (2012). Two action systems in the human brain. Brain and language, in press. Borghi, A.M., Riggio, L. (2009). Sentence comprehension and simulation of object temporary, canonical and stable affordances. Brain Research, vol. 1253, pp. 117-128 Eickhoff, S. B., Stephan, K. E., Mohlberg, H., Grefkes, C., Fink, G. R., Amunts, K., Zilles, K. (2005), A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data. NeuroImage, vol. 25, no. 4, pp. 1325-1335. Eickhoff, S.B., Laird, A.R., Grefkes, C., Wang, L.E., Zilles, K., Fox, P.T. (2009), Coordinate‐based activation likelihood estimation meta‐analysis of neuroimaging data: a random‐effects approach based on empirical estimates of spatial uncertainty. Human Brain Mapping, vol. 30, no. 9, pp. 2907‐2926. Gibson, J.J. (1979), The ecological approach to visual perception. Houghton Mifflin, Boston. Laird, A.R., Eickhoff, S.B., Kurth, F., Fox, P.M., Uecker, A.M., Turner, J.A., Robinson, J.L., Lancaster, J.L., Fox, P.T. (2009a), ALE meta-analysis workflows via the brainmap database: progress towards a probabilistic functional brain atlas. Frontiers in neuroinformatics, vol. 3, no. 23. Pisella, L., Binkofski, F., Lasek, K., Toni, I., Rossetti, Y. (2006), No double-dissociation between optic ataxia and visual agnosia: multiple sub-streams for multiple visuo-manual integrations. Neuropsychologia, vol. 44, no. 13, pp. 2734-2748. Rizzolatti, G., Luppino, G., Matelli, M. (1998), The organisation of the cortical motor system: new concepts. Electroencephalography and Clinical Neurophysiology, vol. 106, pp. 283–296. Rizzolatti, G., Matelli, M. (2003), Two different streams form the dorsal visual system: anatomy and functions. Experimental brain research, vol. 153, no. 2, pp.146-157. Thill, S., Caligiore, D., Borghi, A.M., Ziemke, T., Baldassarre, G. (2013), Theories and computational models of affordance and mirror systems: an integrative review. Neuroscience and Biobehavioral Reviews, vol. 37, no. 3, pp. 491-521. Turkeltaub, P.E., Eickhoff, S.B., Laird, A.R., Fox, M., Wiener, M., Fox, P. (2012), Minimizing within-experiment and within-group effects in activation likelihood estimation meta-analyses. Human Brain Mapping, vol. 33, pp. 1-13. Young, G. (2006), Are different affordances subserved by different neural pathways? Brain and Cognition, vol. 62, pp. 134–142. 1 • The concept of affordances was first introduced by the ecological psychologist James J. Gibson (1979) to indicate properties the environment provides to acting organisms which are relevant for a goal.

Sleep, in particular REM sleep, has been shown to improve the consolidation of emotional memories. Here, we investigated the role of sleep and sleep deprivation on the consolidation of fear memories and underlying neuronal mechanisms. We employed a Pavlovian fear conditioning paradigm either followed by a night of polysomnographically monitored sleep, or wakefulness in forty healthy participants. Recall of learned fear was better after sleep, as indicated by stronger explicitly perceived anxiety and autonomous nervous responses. These effects were positively correlated with the preceding time spent in REM sleep and paralleled by activation of the basolateral amygdala. These findings suggest REM sleep-associated consolidation of fear memory in the human amygdala. In view of the critical participation of fear learning mechanisms in the etiology of anxiety and post-traumatic stress disorder, deprivation of REM sleep after exposure to distressing events is an interesting target for further investigation.

Sleep deprivation (SD) has detrimental effects on cognition, but the affected psychological processes and underlying neural mechanisms are still essentially unclear. Here we combined functional magnetic resonance imaging and computational modeling to examine how SD alters neural representation of specific choice variables (subjective value and decision conflict) during reward-related decision making. Twenty-two human subjects underwent two functional neuroimaging sessions in counterbalanced order, once during rested wakefulness and once after 24 h of SD. Behaviorally, SD attenuated conflict-dependent slowing of response times, which was reflected in an attenuated conflict-induced decrease in drift rates in the drift diffusion model. Furthermore, SD increased overall choice stochasticity during risky choice. Model-based functional neuroimaging revealed attenuated parametric subjective value signals in the midbrain, parietal cortex, and ventromedial prefrontal cortex after SD. Conflict-related midbrain signals showed a similar downregulation. Findings are discussed with respect to changes in dopaminergic signaling associated with the sleep-deprived state.

Object manipulation produces characteristic sounds and causes specific haptic sensations that facilitate the recognition of the manipulated object. To identify the neural correlates of audio-haptic binding of object features, healthy volunteers underwent functional magnetic resonance imaging while they matched a target object to a sample object within and across audition and touch. By introducing a delay between the presentation of sample and target stimuli, it was possible to dissociate haptic-to-auditory and auditory-to-haptic matching. We hypothesized that only semantically coherent auditory and haptic object features activate cortical regions that host unified conceptual object representations. The left fusiform gyrus (FG) and posterior superior temporal sulcus (pSTS) showed increased activation during crossmodal matching of semantically congruent but not incongruent object stimuli. In the FG, this effect was found for haptic-to-auditory and auditory-to-haptic matching, whereas the pSTS only displayed a crossmodal matching effect for congruent auditory targets. Auditory and somatosensory association cortices showed increased activity during crossmodal object matching which was, however, independent of semantic congruency. Together, the results show multisensory interactions at different hierarchical stages of auditory and haptic object processing. Object-specific crossmodal interactions culminate in the left FG, which may provide a higher order convergence zone for conceptual object knowledge.

Objective: Adolescents are particularly vulnerable to addiction, and in the case of smoking, this often leads to long-lasting nicotine dependence. The authors investigated a possible neural mechanism underlying this vulnerability. Method: Functional MRI was performed during reward anticipation in 43 adolescent smokers and 43 subjects matched on age, gender, and IQ. The authors also assessed group differences in novelty seeking, impulsivity, and reward delay discounting. Results: In relation to the comparison subjects, the adolescent smokers showed greater reward delay discounting and higher scores for novelty seeking. Neural responses in the ventral striatum during reward anticipation were significantly lower in the smokers than in the comparison subjects, and in the smokers this response was correlated with smoking frequency. Notably, the lower response to reward anticipation in the ventral striatum was also observed in smokers (N=14) who had smoked on fewer than 10 occasions. Conclusions: The present findings suggest that a lower response to reward anticipation in the ventral striatum may be a vulnerability factor for the development of early nicotine use.