Repetitive T1 Imaging Influences Gray Matter Volume Estimations in Structural Brain Imaging.

Voxel-based morphometry (VBM) is a widely used tool for studying structural patterns of brain plasticity, brain development and disease. The source of the T1-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 T1-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 T1-weighted scan is conducted. There is a necessity of a control group for longitudinal imaging studies.

The migraineur's brain networks: Continuous resting state fMRI over 30 days.

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.

Mesolimbic white matter connectivity mediates the preference for sweet food.

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.

Working memory performance in the elderly relates to theta-alpha oscillations and is predicted by parahippocampal and striatal integrity.

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 Deprivation Selectively Upregulates an Amygdala-Hypothalamic Circuit Involved in Food Reward.

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 or restriction, neuroimaging studies revealed upregulated neural processing of food rewards after sleep loss in reward-processing areas such as the anterior cingulate cortex, ventral striatum, and insula. To address this ongoing debate between hormonal versus hedonic factors underlying sleep-loss-associated weight gain, we rigorously tested the association between sleep deprivation and food cue processing using high-resolution fMRI and assessment of hormones. After taking blood samples from 32 lean, healthy, human male participants, 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 and a night of sleep deprivation in a repeated-measures crossover design. We found that des-acyl ghrelin concentrations were increased after sleep deprivation compared with habitual sleep. Despite similar hunger ratings due to fasting in both conditions, participants were willing to spend more money on food items only after sleep deprivation. Furthermore, fMRI data paralleled this behavioral finding, revealing a food-reward-specific upregulation of hypothalamic valuation signals and amygdala-hypothalamic coupling after a single night of sleep deprivation. Behavioral and fMRI results were not significantly correlated with changes in acyl, des-acyl, or total ghrelin concentrations. Our results suggest that increased food valuation after sleep loss might be due to hedonic rather than hormonal mechanisms.SIGNIFICANCE STATEMENT Epidemiological studies suggest an association between overweight and reduced nocturnal sleep, but the relative contributions of hedonic and hormonal factors to overeating after sleep loss are a matter of ongoing controversy. Here, we tested the association between sleep deprivation and food cue processing in a repeated-measures crossover design using fMRI. We found that willingness to pay increased for food items only after sleep deprivation. fMRI data paralleled this behavioral finding, revealing a food-reward-specific upregulation of hypothalamic valuation signals and amygdala-hypothalamic coupling after a single night of sleep deprivation. However, there was no evidence for hormonal modulations of behavioral or fMRI findings. Our results suggest that increased food valuation after sleep loss is due to hedonic rather than hormonal mechanisms.

Nocebo-induced modulation of cerebral itch processing - An fMRI study.

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.

Don't fear 'fear conditioning': Methodological considerations for the design and analysis of studies on human fear acquisition, extinction, and return of fear.

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.

Affordance processing in segregated parieto-frontal dorsal stream sub-pathways.

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.

Dopaminergic receptor blockade changes a functional connectivity network centred on the amygdala.

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.

REM Sleep Is Causal to Successful Consolidation of Dangerous and Safety Stimuli and Reduces Return of Fear after Extinction.

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.

Dissociating the neural mechanisms of pain consistency and pain intensity in the trigemino-nociceptive system.

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.

Are abstract action words embodied? An fMRI investigation at the interface between language and motor cognition.

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.

Multisensory interactions between auditory and haptic object recognition.

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.

Sleep deprivation is associated with attenuated parametric valuation and control signals in the midbrain during value-based decision making.

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.

The left fusiform gyrus hosts trisensory representations of manipulable objects.

During object manipulation the brain integrates the visual, auditory, and haptic experience of an object into a unified percept. Previous brain imaging studies have implicated for instance the dorsal part of the lateral occipital complex in visuo-tactile and the posterior superior temporal sulcus in audio-visual integration of object-related inputs (Amedi et al., 2005). Yet it is still unclear which brain regions represent object-specific information of all three sensory modalities. To address this question, we performed two complementary functional magnetic resonance imaging experiments. In the first experiment, we identified brain regions which were consistently activated by unimodal visual, auditory, and haptic processing of manipulable objects relative to non-object control stimuli presented in the same modality. In the second experiment, we assessed regional brain activations when participants had to match object-related information that was presented simultaneously in two or all three modalities. Only a well-defined region in left fusiform gyrus (FG) showed an object-specific activation during unisensory processing in the visual, auditory, and tactile modalities. The same region was also consistently activated during multisensory matching of object-related information across all three senses. Taken together, our results suggest that this region is central to the recognition of manipulable objects. A putative role of this FG region is to unify object-specific information provided by the visual, auditory, and tactile modalities into trisensory object representations.

Grasping language--a short story on embodiment.

The new concept of embodied cognition theories has been enthusiastically studied by the cognitive sciences, by as well as such disparate disciplines as philosophy, anthropology, neuroscience, and robotics. Embodiment theory provides the framework for ongoing discussions on the linkage between "low" cognitive processes as perception and "high" cognition as language processing and comprehension, respectively. This review gives an overview along the lines of argumentation in the ongoing debate on the embodiment of language and employs an ALE meta-analysis to illustrate and weigh previous findings.The collected evidence on the somatotopic activation of motor areas, abstract and concrete word processing, as well as from reported patient and timing studies emphasizes the important role of sensorimotor areas in language processing and supports the hypothesis that the motor system is activated during language comprehension.

Got it! Understanding the concept of a tool.

Understanding the function of a tool is an essential step in learning to use a tool. This aspect of interaction with tools has hitherto been neglected. Unlike acquiring the expertise in handling a new tool, which involves practice, understanding its function usually only requires a single observation of the tool being used. The present study uncovers the neural areas involved in this transient understanding effect as a left-lateralized pattern involving prefrontal and mediotemporal areas. We suggest that activation in this network reflects the conceptual encoding of the function of new tools as it is independent from the well-known tool-related networks. We demonstrate that understanding the function of a new tool does not rely on known semantic or motor networks involved in processing tool use.

Auditory working memory load impairs visual ventral stream processing: toward a unified model of attentional load.

Attentional interference between tasks performed in parallel is known to have strong and often undesired effects. As yet, however, the mechanisms by which interference operates remain elusive. A better knowledge of these processes may facilitate our understanding of the effects of attention on human performance and the debilitating consequences that disruptions to attention can have. According to the load theory of cognitive control, processing of task-irrelevant stimuli is increased by attending in parallel to a relevant task with high cognitive demands. This is due to the relevant task engaging cognitive control resources that are, hence, unavailable to inhibit the processing of task-irrelevant stimuli. However, it has also been demonstrated that a variety of types of load (perceptual and emotional) can result in a reduction of the processing of task-irrelevant stimuli, suggesting a uniform effect of increased load irrespective of the type of load. In the present study, we concurrently presented a relevant auditory matching task [n-back working memory (WM)] of low or high cognitive load (1-back or 2-back WM) and task-irrelevant images at one of three object visibility levels (0%, 50%, or 100%). fMRI activation during the processing of the task-irrelevant visual stimuli was measured in the lateral occipital cortex and found to be reduced under high, compared to low, WM load. In combination with previous findings, this result is suggestive of a more generalized load theory, whereby cognitive load, as well as other types of load (e.g., perceptual), can result in a reduction of the processing of task-irrelevant stimuli, in line with a uniform effect of increased load irrespective of the type of load.

Dissociating networks of imitation.

The investigation of imitation, which consists of observation and later reproduction of voluntary actions, promises insights into the complex processes of human actions. Although several aspects concerning the component neural processes necessary for action execution are known, our current understanding of the neural networks underlying these remains sparse. The present study applies independent component analysis (ICA) to functional magnetic resonance imaging (fMRI) data acquired during imitation of abstract gestures and object-related actions. This enables identification of neural networks underlying the production of these imitations. The explorative approach of ICA is complemented by an analysis of time courses from the maxima of each component. Four independent networks were active during delayed imitation. These can be assigned to the aspects of (1) action perception, (2) motor preparation and action execution, (3) encoding and retrieval into and from working memory, as well as (4) the dynamic integration of object affordances into the action. At least two of these networks participate in action preparation, one contains areas involved with motor working memory and one includes areas which are connected to the true action execution. The fourth network only shows activity shortly before an object-related action is imitated. This indicates a late integration of object affordances into the movement as the time course of activity in this network pertains to action rather than perception of the object.

Neural dynamics of learning sound-action associations.

A motor component is pre-requisite to any communicative act as one must inherently move to communicate. To learn to make a communicative act, the brain must be able to dynamically associate arbitrary percepts to the neural substrate underlying the pre-requisite motor activity. We aimed to investigate whether brain regions involved in complex gestures (ventral pre-motor cortex, Brodmann Area 44) were involved in mediating association between novel abstract auditory stimuli and novel gestural movements. In a functional resonance imaging (fMRI) study we asked participants to learn associations between previously unrelated novel sounds and meaningless gestures inside the scanner. We use functional connectivity analysis to eliminate the often present confound of 'strategic covert naming' when dealing with BA44 and to rule out effects of non-specific reductions in signal. Brodmann Area 44, a region incorporating Broca's region showed strong, bilateral, negative correlation of BOLD (blood oxygen level dependent) response with learning of sound-action associations during data acquisition. Left-inferior-parietal-lobule (l-IPL) and bilateral loci in and around visual area V5, right-orbital-frontal-gyrus, right-hippocampus, left-para-hippocampus, right-head-of-caudate, right-insula and left-lingual-gyrus also showed decreases in BOLD response with learning. Concurrent with these decreases in BOLD response, an increasing connectivity between areas of the imaged network as well as the right-middle-frontal-gyrus with rising learning performance was revealed by a psychophysiological interaction (PPI) analysis. The increasing connectivity therefore occurs within an increasingly energy efficient network as learning proceeds. Strongest learning related connectivity between regions was found when analysing BA44 and l-IPL seeds. The results clearly show that BA44 and l-IPL is dynamically involved in linking gesture and sound and therefore provides evidence that one of the mechanisms required for the evolution of human communication is found within these motor regions.