Different pre‐scanning instructions induce distinct psychological and resting brain states during functional magnetic resonance imaging

Resting‐state functional magnetic resonance imaging (rs‐fMRI) is widely used to investigate functional brain network connectivity during rest or when the subject is not performing an explicit task. In the standard procedure, subjects are instructed to ‘let your mind wander’ or ‘think of nothing’. While these instructions appear appropriate to induce a ‘resting‐state’, they could induce distinct psychological and physiological states during the scan. In this study, we investigated whether different instructions affect mental state and functional connectivity (FC) (i.e. induce distinct ‘resting states’) during rs‐fMRI scanning. Thirty healthy subjects were subjected to two rs‐fMRI scans differing only in pre‐scan instructions: think of nothing (TN) and mind‐wandering (MW) conditions. Self‐reports confirmed that subjects spent the majority of the scanning time in the appropriate mental state. Independent component analysis extracted 19 independent components (ICs) of interest and functional network connectivity analyses indicated several conditional differences in FCs among those ICs, especially characterised by stronger FC in the MW condition than in the TN condition, between default mode network and salience/visual/frontal network. Complementary correlation analysis indicated that some of the network FCs were significantly correlated with their self‐reported data on how often they had the TN condition during the scans. The present results provide evidence that the pre‐scan instruction has a significant influence on resting‐state FC and its relationship with mental activities.     

Cortical electrophysiological evidence for individual‐specific temporal organization of brain functional networks

The human brain has been demonstrated to rapidly and continuously form and dissolve networks on a subsecond timescale, offering effective and essential substrates for cognitive processes. Understanding how the dynamic organization of brain functional networks on a subsecond level varies across individuals is, therefore, of great interest for personalized neuroscience. However, it remains unclear whether features of such rapid network organization are reliably unique and stable in single subjects and, therefore, can be used in characterizing individual networks. Here, we used two sets of 5‐min magnetoencephalography (MEG) resting data from 39 healthy subjects over two consecutive days and modeled the spontaneous brain activity as recurring networks fast shifting between each other in a coordinated manner. MEG cortical maps were obtained through source reconstruction using the beamformer method and subjects' temporal structure of recurring networks was obtained via the Hidden Markov Model. Individual organization of dynamic brain activity was quantified with the features of the network‐switching pattern (i.e., transition probability and mean interval time) and the time‐allocation mode (i.e., fractional occupancy and mean lifetime). Using these features, we were able to identify subjects from the group with significant accuracies (~40% on average in 0.5–48 Hz). Notably, the default mode network displayed a distinguishable pattern, being the least frequently visited network with the longest duration for each visit. Together, we provide initial evidence suggesting that the rapid dynamic temporal organization of brain networks achieved in electrophysiology is intrinsic and subject specific.     

Large‐scale brain networks are distinctly affected in right and left mesial temporal lobe epilepsy

Mesial temporal lobe epilepsy (MTLE) with hippocampus sclerosis (HS) is associated with functional and structural alterations extending beyond the temporal regions and abnormal pattern of brain resting state networks (RSNs) connectivity. We hypothesized that the interaction of large‐scale RSNs is differently affected in patients with right‐ and left‐MTLE with HS compared to controls. We aimed to determine and characterize these alterations through the analysis of 12 RSNs, functionally parceled in 70 regions of interest (ROIs), from resting‐state functional‐MRIs of 99 subjects (52 controls, 26 right‐ and 21 left‐MTLE patients with HS). Image preprocessing and statistical analysis were performed using UF²C‐toolbox, which provided ROI‐wise results for intranetwork and internetwork connectivity. Intranetwork abnormalities were observed in the dorsal default mode network (DMN) in both groups of patients and in the posterior salience network in right‐MTLE. Both groups showed abnormal correlation between the dorsal‐DMN and the posterior salience, as well as between the dorsal‐DMN and the executive‐control network. Patients with left‐MTLE also showed reduced correlation between the dorsal‐DMN and visuospatial network and increased correlation between bilateral thalamus and the posterior salience network. The ipsilateral hippocampus stood out as a central area of abnormalities. Alterations on left‐MTLE expressed a low cluster coefficient, whereas the altered connections on right‐MTLE showed low cluster coefficient in the DMN but high in the posterior salience regions. Both right‐ and left‐MTLE patients with HS have widespread abnormal interactions of large‐scale brain networks; however, all parameters evaluated indicate that left‐MTLE has a more intricate bihemispheric dysfunction compared to right‐MTLE. Hum Brain Mapp 37:3137–3152, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc .     

Mapping the artistic brain: Common and distinct neural activations associated with musical,drawing, and literary creativity

Whether creativity is a domain‐general or domain‐specific ability has been a topic of intense speculation. Although previous studies have examined domain‐specific mechanisms of creative performance, little is known about commonalities and distinctions in neural correlates across different domains. We applied activation likelihood estimation (ALE) meta‐analysis to identify the brain activation of domain‐mechanisms by synthesizing functional neuroimaging studies across three forms of artistic creativity: music improvisation, drawing, and literary creativity. ALE meta‐analysis yielded a domain‐general pattern across three artistic forms, with overlapping clusters in the presupplementary motor area (pre‐SMA), left dorsolateral prefrontal cortex, and right inferior frontal gyrus (IFG). Regarding domain‐specificity, musical creativity was associated with recruitment of the SMA‐proper, bilateral IFG, left precentral gyrus, and left middle frontal gyrus (MFG) compared to the other two artistic forms; drawing creativity recruited the left fusiform gyrus, left precuneus, right parahippocampal gyrus, and right MFG compared to musical creativity; and literary creativity recruited the left angular gyrus and right lingual gyrus compared to musical creativity. Contrasting drawing and literary creativity revealed no significant differences in neural activation, suggesting that these domains may rely on a common neurocognitive system. Overall, these findings reveal a central, domain‐general system for artistic creativity, but with each domain relying to some degree on domain‐specific neural circuits.     

The bright side and dark side of daydreaming predict creativity together through brain functional connectivity

Daydreaming and creativity have similar cognitive processes and neural basis. However, few empirical studies have examined the relationship between daydreaming and creativity using cognitive neuroscience methods. The present study explored the relationship between different types of daydreaming and creativity and their common neural basis. The behavioral results revealed that positive constructive daydreaming is positively related to creativity, while poor attentional control is negatively related to it. Machine learning framework was adopted to examine the predictive effect of daydreaming‐related brain functional connectivity (FC) on creativity. The results demonstrated that task FCs related to positive constructive daydreaming and task FCs related to poor attentional control both predicted an individual''s creativity score successfully. In addition, task FCs combining the positive constructive daydreaming and poor attentional control also had significant predictive effect on creativity score. Furthermore, predictive analysis based on resting‐state FCs showed similar patterns. Both of the subscale‐related FCs and combined FCs had significant predictive effect on creativity score. Further analysis showed the task and the resting‐state FCs both mainly located in the default mode network, central executive network, salience network, and attention network. These results showed that daydreaming was closely related to creativity, as they shared common FC basis.     

Competition between frontoparietal control and default networks supports social working memory and empathy

An extensive body of literature has indicated that there is increased activity in the frontoparietal control network (FPC) and decreased activity in the default mode network (DMN) during working memory (WM) tasks. The FPC and DMN operate in a competitive relationship during tasks requiring externally directed attention. However, the association between this FPC-DMN competition and performance in social WM tasks has rarely been reported in previous studies. To investigate this question, we measured FPC-DMN connectivity during resting state and two emotional face recognition WM tasks using the 2-back paradigm. Thirty-four individuals were instructed to perform the tasks based on either the expression [emotion (EMO)] or the identity (ID) of the same set of face stimuli. Consistent with previous studies, an increased anti-correlation between the FPC and DMN was observed during both tasks relative to the resting state. Specifically, this anti-correlation during the EMO task was stronger than during the ID task, as the former has a higher social load. Intriguingly, individual differences in self-reported empathy were significantly correlated with the FPC-DMN anti-correlation in the EMO task. These results indicate that the top-down signals from the FPC suppress the DMN to support social WM and empathy.     

Training of verbal creativity modulates brain activity in regions associated with language‐ and memory‐related demands

This functional magnetic resonance (fMRI) study was designed to investigate changes in functional patterns of brain activity during creative ideation as a result of a computerized, 3‐week verbal creativity training. The training was composed of various verbal divergent thinking exercises requiring participants to train approximately 20 min per day. Fifty‐three participants were tested three times (psychometric tests and fMRI assessment) with an intertest‐interval of 4 weeks each. Participants were randomly assigned to two different training groups, which received the training time‐delayed: The first training group was trained between the first and the second test, while the second group accomplished the training between the second and the third test session. At the behavioral level, only one training group showed improvements in different facets of verbal creativity right after the training. Yet, functional patterns of brain activity during creative ideation were strikingly similar across both training groups. Whole‐brain voxel‐wise analyses (along with supplementary region of interest analyses) revealed that the training was associated with activity changes in well‐known creativity‐related brain regions such as the left inferior parietal cortex and the left middle temporal gyrus, which have been shown as being particularly sensitive to the originality facet of creativity in previous research. Taken together, this study demonstrates that continuous engagement in a specific complex cognitive task like divergent thinking is associated with reliable changes of activity patterns in relevant brain areas, suggesting more effective search, retrieval, and integration from internal memory representations as a result of the training. Hum Brain Mapp 36:4104–4115, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.     

Disrupted connectivity within visual,attentional and salience networks in the visual snow syndrome

Here we investigate brain functional connectivity in patients with visual snow syndrome (VSS). Our main objective was to understand more about the underlying pathophysiology of this neurological syndrome. Twenty‐four patients with VSS and an equal number of gender and age‐matched healthy volunteers attended MRI sessions in which whole‐brain maps of functional connectivity were acquired under two conditions: at rest while watching a blank screen and during a visual paradigm consisting of a visual‐snow like stimulus. Eight unilateral seed regions were selected a priori based on previous observations and hypotheses; four seeds were placed in key anatomical areas of the visual pathways and the remaining were derived from a pre‐existing functional analysis. The between‐group analysis showed that patients with VSS had hyper and hypoconnectivity between key visual areas and the rest of the brain, both in the resting state and during a visual stimulation, compared with controls. We found altered connectivity internally within the visual network; between the thalamus/basal ganglia and the lingual gyrus; between the visual motion network and both the default mode and attentional networks. Further, patients with VSS presented decreased connectivity during external sensory input within the salience network, and between V5 and precuneus. Our results suggest that VSS is characterised by a widespread disturbance in the functional connectivity of several brain systems. This dysfunction involves the pre‐cortical and cortical visual pathways, the visual motion network, the attentional networks and finally the salience network; further, it represents evidence of ongoing alterations both at rest and during visual stimulus processing.     

Brain networks underlying mental imagery of auditory and visual information

Mental imagery is a complex cognitive process that resembles the experience of perceiving an object when this object is not physically present to the senses. It has been shown that, depending on the sensory nature of the object, mental imagery also involves correspondent sensory neural mechanisms. However, it remains unclear which areas of the brain subserve supramodal imagery processes that are independent of the object modality, and which brain areas are involved in modality‐specific imagery processes. Here, we conducted a functional magnetic resonance imaging study to reveal supramodal and modality‐specific networks of mental imagery for auditory and visual information. A common supramodal brain network independent of imagery modality, two separate modality‐specific networks for imagery of auditory and visual information, and a common deactivation network were identified. The supramodal network included brain areas related to attention, memory retrieval, motor preparation and semantic processing, as well as areas considered to be part of the default‐mode network and multisensory integration areas. The modality‐specific networks comprised brain areas involved in processing of respective modality‐specific sensory information. Interestingly, we found that imagery of auditory information led to a relative deactivation within the modality‐specific areas for visual imagery, and vice versa. In addition, mental imagery of both auditory and visual information widely suppressed the activity of primary sensory and motor areas, for example deactivation network. These findings have important implications for understanding the mechanisms that are involved in generation of mental imagery.     

Thalamocortical interactions underlying visual fear conditioning in humans

Despite a strong focus on the role of the amygdala in fear conditioning, recent works point to a more distributed network supporting fear conditioning. We aimed to elucidate interactions between subcortical and cortical regions in fear conditioning in humans. To do this, we used two fearful faces as conditioned stimuli (CS) and an electrical stimulation at the left hand, paired with one of the CS, as unconditioned stimulus (US). The luminance of the CS was rhythmically modulated leading to “entrainment” of brain oscillations at a predefined modulation frequency. Steady‐state responses (SSR) were recorded by MEG. In addition to occipital regions, spectral analysis of SSR revealed increased power during fear conditioning particularly for thalamus and cerebellum contralateral to the upcoming US. Using thalamus and amygdala as seed‐regions, directed functional connectivity was calculated to capture the modulation of interactions that underlie fear conditioning. Importantly, this analysis showed that the thalamus drives the fusiform area during fear conditioning, while amygdala captures the more general effect of fearful faces perception. This study confirms ideas from the animal literature, and demonstrates for the first time the central role of the thalamus in fear conditioning in humans. Hum Brain Mapp 36:4592–4603, 2015. © 2015 Wiley Periodicals, Inc.     

Vulnerability of multiple large‐scale brain networks in dementia with Lewy bodies

Aberrations of large‐scale brain networks are found in the majority of neurodegenerative disorders. The brain connectivity alterations underlying dementia with Lewy bodies (DLB) remain, however, still elusive, with contrasting results possibly due to the pathological and clinical heterogeneity characterizing this disorder. Here, we provide a molecular assessment of brain network alterations, based on cerebral metabolic measurements as proxies of synaptic activity and density, in a large cohort of DLB patients (N = 72). We applied a seed‐based interregional correlation analysis approach (p < .01, false discovery rate corrected) to evaluate large‐scale resting‐state networks' integrity and their interactions. We found both local and long‐distance metabolic connectivity alterations, affecting the posterior cortical networks, that is, primary visual and the posterior default mode network, as well as the limbic and attention networks, suggesting a widespread derangement of the brain connectome. Notably, patients with the lowest visual and attention cognitive scores showed the most severe connectivity derangement in regions of the primary visual network. In addition, network‐level alterations were differentially associated with the core clinical manifestations, namely, hallucinations with more severe metabolic dysfunction of the attention and visual networks, and rapid eye movement sleep behavior disorder with alterations of connectivity of attention and subcortical networks. These multiple network‐level vulnerabilities may modulate the core clinical and cognitive features of DLB and suggest that DLB should be considered as a complex multinetwork disorder.     

Modulation of steady state functional connectivity in the default mode and working memory networks by cognitive load

Interregional correlations between blood oxygen level dependent (BOLD) magnetic resonance imaging (fMRI) signals in the resting state have been interpreted as measures of connectivity across the brain. Here we investigate whether such connectivity in the working memory and default mode networks is modulated by changes in cognitive load. Functional connectivity was measured in a steady-state verbal identity N-back task for three different conditions (N = 1, 2, and 3) as well as in the resting state. We found that as cognitive load increases, the functional connectivity within both the working memory the default mode network increases. To test whether functional connectivity between the working memory and the default mode networks changed, we constructed maps of functional connectivity to the working memory network as a whole and found that increasingly negative correlations emerged in a dorsal region of the posterior cingulate cortex. These results provide further evidence that low frequency fluctuations in BOLD signals reflect variations in neural activity and suggests interaction between the default mode network and other cognitive networks.     

Auditory and visual connectivity gradients in frontoparietal cortex

A frontoparietal network of brain regions is often implicated in both auditory and visual information processing. Although it is possible that the same set of multimodal regions subserves both modalities, there is increasing evidence that there is a differentiation of sensory function within frontoparietal cortex. Magnetic resonance imaging (MRI) in humans was used to investigate whether different frontoparietal regions showed intrinsic biases in connectivity with visual or auditory modalities. Structural connectivity was assessed with diffusion tractography and functional connectivity was tested using functional MRI. A dorsal–ventral gradient of function was observed, where connectivity with visual cortex dominates dorsal frontal and parietal connections, while connectivity with auditory cortex dominates ventral frontal and parietal regions. A gradient was also observed along the posterior–anterior axis, although in opposite directions in prefrontal and parietal cortices. The results suggest that the location of neural activity within frontoparietal cortex may be influenced by these intrinsic biases toward visual and auditory processing. Thus, the location of activity in frontoparietal cortex may be influenced as much by stimulus modality as the cognitive demands of a task. It was concluded that stimulus modality was spatially encoded throughout frontal and parietal cortices, and was speculated that such an arrangement allows for top–down modulation of modality‐specific information to occur within higher‐order cortex. This could provide a potentially faster and more efficient pathway by which top–down selection between sensory modalities could occur, by constraining modulations to within frontal and parietal regions, rather than long‐range connections to sensory cortices. Hum Brain Mapp 38:255–270, 2017. © 2016 Wiley Periodicals, Inc.     

Common and distinct brain networks underlying explicit emotional evaluation: a meta-analytic study

Brain mechanisms underlying explicit evaluation of emotion have been explored using different tasks including ‘stimulus-focused evaluation’, ‘evaluation of one''s own emotion’ and ‘evaluation of others’ emotions’. Yet the extent to which similar brain mechanisms underlie different evaluation tasks is unclear. A meta-analysis of published neuroimaging studies of explicit emotional evaluation was conducted to examine common and distinct regions underlying these different evaluation tasks. This study revealed regions common to all three tasks: The amygdala and LPFC as common regions may be involved in emotion–cognition interactions, and the DMPFC may possibly play integrative roles in explicit emotional evaluation. Distinct regions were also identified: (i) the sensory cortex and VLPFC were specifically associated with ‘stimulus evaluation’, possibly involved in perceptual and conceptual processing; (ii) the insula and rACC were specifically associated with ‘evaluation of one''s own emotion’, potentially associated with interoceptive and experiential processing; and (iii) the STS and TPJ were specifically associated with ‘evaluation of others’ emotions’, potentially reflecting their roles in TOM and empathy. These findings suggest that different types of explicit emotional evaluation may involve common and distinct networks and provide new insights on multiple mechanisms underlying explicit emotional evaluation.     

A Gradient of Sharpening Effects by Perceptual Prior across the Human Cortical Hierarchy

Prior knowledge profoundly influences perceptual processing. Previous studies have revealed consistent suppression of predicted stimulus information in sensory areas, but how prior knowledge modulates processing higher up in the cortical hierarchy remains poorly understood. In addition, the mechanism leading to suppression of predicted sensory information remains unclear, and studies thus far have revealed a mixed pattern of results in support of either the “sharpening” or “dampening” model. Here, using 7T fMRI in humans (both sexes), we observed that prior knowledge acquired from fast, one-shot perceptual learning sharpens neural representation throughout the ventral visual stream, generating suppressed sensory responses. In contrast, the frontoparietal and default mode networks exhibit similar sharpening of content-specific neural representation, but in the context of unchanged and enhanced activity magnitudes, respectively: a pattern we refer to as “selective enhancement.” Together, these results reveal a heretofore unknown macroscopic gradient of prior knowledge''s sharpening effect on neural representations across the cortical hierarchy.SIGNIFICANCE STATEMENT A fundamental question in neuroscience is how prior knowledge shapes perceptual processing. Perception is constantly informed by internal priors in the brain acquired from past experiences, but the neural mechanisms underlying this process are poorly understood. To date, research on this question has focused on early visual regions, reporting a consistent downregulation when predicted stimuli are encountered. Here, using a dramatic one-shot perceptual learning paradigm, we observed that prior knowledge results in sharper neural representations across the cortical hierarchy of the human brain through a gradient of mechanisms. In visual regions, neural responses tuned away from internal predictions are suppressed. In frontoparietal regions, neural activity consistent with priors is selectively enhanced. These results deepen our understanding of how prior knowledge informs perception.     

Parietal memory network and default mode network in first‐episode drug‐naïve schizophrenia: Associations with auditory hallucination

Atypical spontaneous activities in resting‐state networks may play a role in auditory hallucinations (AHs), but networks relevant to AHs are not apparent. Given the debating role of the default mode network (DMN) in AHs, a parietal memory network (PMN) may better echo cognitive theories of AHs in schizophrenia, because PMN is spatially adjacent to the DMN and more relevant to memory processing or information integration. To examine whether PMN is more relevant to AHs than DMN, we characterized these intrinsic networks in AHs with 59 first‐episode, drug‐naïve schizophrenics (26 AH+ and 33 AH?) and 60 healthy participants in resting‐state fMRI. We separated the PMN, DMN, and auditory network (AN) using independent component analysis, and compared their functional connectivity across the three groups. We found that only AH+ patients displayed dysconnectivity in PMN, both AH+ and AH? patients exhibited dysfunctions of AN, but neither patient group showed abnormal connectivity within DMN. The connectivity of PMN significantly correlated with memory performance of the patients. Further region‐of‐interest analyses confirmed that the connectivity between the core regions of PMN, the left posterior cingulate gyrus and the left precuneus, was significantly lower only in the AH+ group. In exploratory correlation analysis, this functional connectivity metric significantly correlated with the severity of AH symptoms. The results implicate that compared to the DMN, the PMN is more relevant to the AH symptoms in schizophrenia, and further provides a more precise potential brain modulation target for the intervention of AH symptoms.     

Metaphors and verbal creativity: The role of the right hemisphere

Ample research suggests that the right cerebral hemisphere plays a central role in verbal creativity as well as in novel metaphor comprehension. The aim of the present study was to directly examine the relation between verbal creativity and right hemisphere involvement during novel metaphor comprehension. Thus 30 healthy adults were asked to fill in the Hebrew version of the Remote Association Test to assess their level of creativity. In addition, reaction times and error rates were measured while these participants performed a semantic judgement task on two word expressions presented in a divided visual field paradigm. The word pairs comprised four types of semantic relations: novel metaphors, conventional metaphors, literal word pairs, and meaningless word pairs. Correlations were conducted to assess the relation between level of creativity and processing of the four pair types in the two cerebral hemispheres. The main finding was of a significant negative correlation between degree of creativity and reaction times to novel metaphor processing in the right hemisphere, thus supporting the involvement of this cerebral hemisphere in both tasks. Results are discussed in light of linguistic theories and recent neuroscientific evidence regarding relative hemispheric involvement during semantic processing.     

Individual and sex‐related differences in pain and relief responsiveness are associated with differences in resting‐state functional networks in healthy volunteers

Pain processing is associated with neural activity in a number of widespread brain regions. Here, we investigated whether functional connectivity at rest between these brain regions is associated with individual and sex‐related differences in thermal pain and relief responsiveness. Twenty healthy volunteers (ten females) were scanned with functional magnetic resonance imaging in resting conditions. Half an hour after scanning, we administered thermal pain on the back of their right hand and collected pain and relief ratings in two separate runs of twelve stimuli each. Across the whole group, mean pain ratings were associated with decreased connectivity at rest between brain regions belonging to the default mode and the visual resting‐state network. In men, pain measures correlated with increased connectivity within the visual resting‐state network. In women, in contrast, decreased connectivity between this network and parietal and prefrontal brain regions implicated in affective cognitive control were associated with both pain and relief ratings. Our findings indicate that the well documented individual variability and sex differences in pain sensitivity may be explained, at least in part, by network dynamics at rest in these brain regions.     

The neural correlates of the awe experience: Reduced default mode network activity during feelings of awe

In the present fMRI study, we aimed to obtain insight into the key brain networks involved in the experience of awe—a complex emotion that is typically elicited by perceptually vast stimuli. Participants were presented with awe‐eliciting, positive and neutral videos, while they were instructed to get fully absorbed in the scenery or to count the number of perspective changes. By using a whole‐brain analysis we found that several brain regions that are considered part of the default mode network (DMN), including the frontal pole, the angular gyrus, and the posterior cingulate cortex, were more strongly activated in the absorption condition. But this was less the case when participants were watching awe videos. We suggest that while watching awe videos, participants were deeply immersed in the videos and that levels of self‐reflective thought were as much reduced during the awe videos, as during the perspective counting condition. In contrast, key regions of the fronto‐parietal network (FPN), including the supramarginal gyrus, the medial frontal gyrus, and the insula, were most strongly activated in the analytical condition when participants were watching awe compared to positive and neutral videos. This finding underlines the captivating, immersive, and attention‐grabbing nature of awe stimuli that is considered to be responsible for reductions in self‐reflective thought. Together these findings suggest that a key feature of the experience of awe is a reduced engagement in self‐referential processing, in line with the subjective self‐report measures (i.e., participants perceived their self to be smaller).