Mind wandering away from pain dynamically engages antinociceptive and default mode brain networks

Human minds often wander away from their immediate sensory environment. It remains unknown whether such mind wandering is unsystematic or whether it lawfully relates to an individual’s tendency to attend to salient stimuli such as pain and their associated brain structure/function. Studies of pain–cognition interactions typically examine explicit manipulation of attention rather than spontaneous mind wandering. Here we sought to better represent natural fluctuations in pain in daily life, so we assessed behavioral and neural aspects of spontaneous disengagement of attention from pain. We found that an individual’s tendency to attend to pain related to the disruptive effect of pain on his or her cognitive task performance. Next, we linked behavioral findings to neural networks with strikingly convergent evidence from functional magnetic resonance imaging during pain coupled with thought probes of mind wandering, dynamic resting state activity fluctuations, and diffusion MRI. We found that (i) pain-induced default mode network (DMN) deactivations were attenuated during mind wandering away from pain; (ii) functional connectivity fluctuations between the DMN and periaqueductal gray (PAG) dynamically tracked spontaneous attention away from pain; and (iii) across individuals, stronger PAG–DMN structural connectivity and more dynamic resting state PAG–DMN functional connectivity were associated with the tendency to mind wander away from pain. These data demonstrate that individual tendencies to mind wander away from pain, in the absence of explicit manipulation, are subserved by functional and structural connectivity within and between default mode and antinociceptive descending modulation networks.

Increased resting state functional connectivity in the default mode network in recovered anorexia nervosa.

Functional brain imaging studies have shown abnormal neural activity in individuals recovered from anorexia nervosa (AN) during both cognitive and emotional task paradigms. It has been suggested that this abnormal activity which persists into recovery might underpin the neurobiology of the disorder and constitute a neural biomarker for AN. However, no study to date has assessed functional changes in neural networks in the absence of task-induced activity in those recovered from AN. Therefore, the aim of this study was to investigate whole brain resting state functional connectivity in nonmedicated women recovered from anorexia nervosa. Functional magnetic resonance imaging scans were obtained from 16 nonmedicated participants recovered from anorexia nervosa and 15 healthy control participants. Independent component analysis revealed functionally relevant resting state networks. Dual regression analysis revealed increased temporal correlation (coherence) in the default mode network (DMN) which is thought to be involved in self-referential processing. Specifically, compared to healthy control participants the recovered anorexia nervosa participants showed increased temporal coherence between the DMN and the precuneus and the dorsolateral prefrontal cortex/inferior frontal gyrus. The findings support the view that dysfunction in resting state functional connectivity in regions involved in self-referential processing and cognitive control might be a vulnerability marker for the development of anorexia nervosa.

Alterações da default mode network provocadas pela ingestão de Ayahuasca investigadas por Ressonância Magnética Funcional

Ayahuasca is psychotropic beverage that has been used for ages by indigenous populations in South America, notably in the Amazon region, for religious and medicinal purposes. The tea is obtained by the decoction of leaves from the Psychotria viridis with the bark and stalk of a shrub, the Banisteriopsis caapi. The first is rich in N-N-dimethyltryptamine (DMT), which has an important and well-known hallucinogenic effect due to its agonistic action in serotonin receptors, specifically 5-HT2A. On the other hand, β-carbolines present in B. caapi, particularly harmine and harmaline, are potent monoamine oxidase inhibitors (MAOi). In addition, the tetrahydroharmine (THH), also present in B. caapi, acts as mild selective serotonin reuptake inhibitor and a weak MAOi. This unique composition induces a number of affective, sensitive, perceptual and cognitive changes in individuals under the effect of Ayahuasca. On the other hand, there is growing interest in the Default Mode Network (DMN), which has been consistently observed in functional neuroimaging studies. The key components of this network include structures in the brain midline, as the anterior medial frontal cortex, ventral medial frontal cortex, posterior cingulate cortex, precuneus, and some regions within the inferior parietal lobe and middle temporal gyrus. It has been argued that DMN participate in tasks involving self-judgments, autobiographical memory retrieval, mental simulations, thinking in perspective, meditative states, and others. In general, these tasks require an internal focus of attention, hence the conclusion that the DMN is associated with introspective mental activity. Therefore, this study aimed to evaluate by functional magnetic resonance imaging (fMRI) changes in DMN caused via the ingestion of Ayahuasca by 10 healthy subjects while submitted to two fMRI protocols: a verbal fluency task and a resting state acquisition. In general, it was observed that Ayahuasca causes a reduction in the fMRI signal in central nodes of DMN, such as the anterior cingulate cortex, the medial prefrontal cortex, the posterior cingulate cortex, precuneus and inferior parietal lobe. Furthermore, changes in connectivity patterns of the DMN were observed, especially a decrease in the functional connectivity of the precuneus. Together, these findings indicate an association between the altered state of consciousness experienced by individuals under the effect of Ayahuasca, and changes in the stream of spontaneous thoughts leading to an increased introspective mental activity

Semantic memory involvement in the default mode network: a functional neuroimaging study using independent component analysis

The Default Mode Network (DMN) is a higher order functional neural network that displays activation during passive rest and deactivation during many types of cognitive tasks. Accordingly, the DMN is viewed to represent the neural correlate of internally-generated self-referential cognition. This hypothesis implies that the DMN requires the involvement of cognitive processes, like declarative memory. The present study thus examines the spatial and functional convergence of the DMN and the semantic memory system. Using an active block-design functional Magnetic Resonance Imaging (fMRI) paradigm and Independent Component Analysis (ICA), we trace the DMN and fMRI signal changes evoked by semantic, phonological and perceptual decision tasks upon visually-presented words. Our findings show less deactivation during semantic compared to the two non-semantic tasks for the entire DMN unit and within left-hemispheric DMN regions, i.e., the dorsal medial prefrontal cortex, the anterior cingulate cortex, the retrosplenial cortex, the angular gyrus, the middle temporal gyrus and the anterior temporal region, as well as the right cerebellum. These results demonstrate that well-known semantic regions are spatially and functionally involved in the DMN. The present study further supports the hypothesis of the DMN as an internal mentation system that involves declarative memory functions.

Reduced Cerebral Blood Flow Within the Default-Mode Network and Within Total Gray Matter in Major Depression

The default-mode network (DMN) was shown to have aberrant blood oxygenation-level-dependent (BOLD) activity in major depressive disorder (MDD). While BOLD is a relative measure of neural activity, cerebral blood flow (CBF) is an absolute measure. Resting-state CBF alterations have been reported in MDD. However, the association of baseline CBF and CBF fluctuations is unclear in MDD. Therefore, the aim was to investigate the CBF within the DMN in MDD, applying a strictly data-driven approach. In 22 MDD patients and 22 matched healthy controls, CBF was acquired using arterial spin labeling (ASL) at rest. A concatenated independent component analysis was performed to identify the DMN within the ASL data. The perfusion of the DMN and its nodes was quantified and compared between groups. The DMN was identified in both groups with high spatial similarity. Absolute CBF values within the DMN were reduced in MDD patients (p<0.001). However, after controlling for whole-brain gray matter CBF and age, the group difference vanished. In patients, depression severity was correlated with reduced perfusion in the DMN in the posterior cingulate cortex and the right inferior parietal lobe. Hypoperfusion within the DMN in MDD is not specific to the DMN. Still, depression severity was linked to DMN node perfusion, supporting a role of the DMN in depression pathobiology. The finding has implications for the interpretation of BOLD functional magnetic resonance imaging data in MDD.

BOLD correlates of EEG alpha phase-locking and the fMRI default mode network

Phase locking or synchronization of brain areas is a key concept of information processing in the brain. Synchronous oscillations have been observed and investigated extensively in EEG during the past decades. EEG oscillations occur over a wide frequency range. In EEG, a prominent type of oscillations is alpha-band activity, present typically when a subject is awake, but at rest with closed eyes. The spectral power of alpha rhythms has recently been investigated in simultaneous EEG/fMRI recordings, establishing a wide-range cortico-thalamic network. However, spectral power and synchronization are different measures and little is known about the correlations between BOLD effects and EEG synchronization. Interestingly, the fMRI BOLD signal also displays synchronous oscillations across different brain regions. These oscillations delineate so-called resting state networks (RSNs) that resemble the correlation patterns of simultaneous EEG/fMRI recordings. However, the nature of these BOLD oscillations and their relations to EEG activity is still poorly understood. One hypothesis is that the subunits constituting a specific RSN may be coordinated by different EEG rhythms. In this study we report on evidence for this hypothesis. The BOLD correlates of global EEG synchronization (GFS) in the alpha frequency band are located in brain areas involved in specific RSNs, e.g. the 'default mode network'. Furthermore, our results confirm the hypothesis that specific RSNs are organized by long-range synchronization at least in the alpha frequency band. Finally, we could localize specific areas where the GFS BOLD correlates and the associated RSN overlap. Thus, we claim that not only the spectral dynamics of EEG are important, but also their spatio-temporal organization.

Prestimulus default mode activity influences depth of processing and recognition in an emotional memory task

Low self-referential thoughts are associated with better concentration, which leads to deeper encoding and increases learning and subsequent retrieval. There is evidence that being engaged in externally rather than internally focused tasks is related to low neural activity in the default mode network (DMN) promoting open mind and the deep elaboration of new information. Thus, reduced DMN activity should lead to enhanced concentration, comprehensive stimulus evaluation including emotional categorization, deeper stimulus processing, and better long-term retention over one whole week. In this fMRI study, we investigated brain activation preceding and during incidental encoding of emotional pictures and on subsequent recognition performance. During fMRI, 24 subjects were exposed to 80 pictures of different emotional valence and subsequently asked to complete an online recognition task one week later. Results indicate that neural activity within the medial temporal lobes during encoding predicts subsequent memory performance. Moreover, a low activity of the default mode network preceding incidental encoding leads to slightly better recognition performance independent of the emotional perception of a picture. The findings indicate that the suppression of internally-oriented thoughts leads to a more comprehensive and thorough evaluation of a stimulus and its emotional valence. Reduced activation of the DMN prior to stimulus onset is associated with deeper encoding and enhanced consolidation and retrieval performance even one week later. Even small prestimulus lapses of attention influence consolidation and subsequent recognition performance. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.

The default mode network is functionally and structurally disrupted in amnestic mild cognitive impairment — a bimodal MEG–DTI study

Over the past years, several studies on Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD) have reported Default Mode Network (DMN) deficits. This network is attracting increasing interest in the AD community, as it seems to play an important role in cognitive functioning and in beta amyloid deposition. Attention has been particularly drawn to how different DMN regions are connected using functional or structural connectivity. To this end, most studies have used functional Magnetic Resonance Imaging (fMRI), Positron Emission Tomography (PET) or Diffusion Tensor Imaging (DTI). In this study we evaluated (1) functional connectivity from resting state magnetoencephalography (MEG) and (2) structural connectivity from DTI in 26 MCI patients and 31 age-matched controls. Compared to controls, the DMN in the MCI group was functionally disrupted in the alpha band, while no differences were found for delta, theta, beta and gamma frequency bands. In addition, structural disconnection could be assessed through a decreased fractional anisotropy along tracts connecting different DMN regions. This suggests that the DMN functional and anatomical disconnection could represent a core feature of MCI.

Medial prefrontal cortex and self-referential mental activity: Relation to a default mode of brain function

Medial prefrontal cortex (MPFC) is among those brain regions having the highest baseline metabolic activity at rest and one that exhibits decreases from this baseline across a wide variety of goal-directed behaviors in functional imaging studies. This high metabolic rate and this behavior suggest the existence of an organized mode of default brain function, elements of which may be either attenuated or enhanced. Extant data suggest that these MPFC regions may contribute to the neural instantiation of aspects of the multifaceted “self.” We explore this important concept by targeting and manipulating elements of MPFC default state activity. In this functional magnetic resonance imaging (fMRI) study, subjects made two judgments, one self-referential, the other not, in response to affectively normed pictures: pleasant vs. unpleasant (an internally cued condition, ICC) and indoors vs. outdoors (an externally cued condition, ECC). The ICC was preferentially associated with activity increases along the dorsal MPFC. These increases were accompanied by decreases in both active task conditions in ventral MPFC. These results support the view that dorsal and ventral MPFC are differentially influenced by attentiondemanding tasks and explicitly self-referential tasks. The presence of self-referential mental activity appears to be associated with increases from the baseline in dorsal MPFC. Reductions in ventral MPFC occurred consistent with the fact that attention-demanding tasks attenuate emotional processing. We posit that both self-referential mental activity and emotional processing represent elements of the default state as represented by activity in MPFC. We suggest that a useful way to explore the neurobiology of the self is to explore the nature of default state activity.

The brain’s default state interacts with working memory processes in a complex and load-dependent manner

Recently, many studies about a network active during rest and deactivated during tasks emerged in the literature: the default mode network (DMN). Spatial and temporal DMN features are important markers for psychiatric diseases. Another prominent indicator of cognitive functioning, yielding information about the mental condition in health and disease, is working memory (WM) processing. In EEG studies, frontal-midline theta power has been shown to increase with load during WM retention in healthy subjects. From these findings, the conclusion can be drawn that an increase in resting state DMN activity may go along with an increase in theta power in high-load WM conditions. We followed this hypothesis in a study on 17 healthy subjects performing a visual Sternberg WM task. The DMN was obtained by a BOLD-ICA approach and its dynamics represented by the percent-strength during pre-stimulus periods. DMN dynamics were temporally correlated with EEG theta spectral power from retention intervals. This so-called covariance mapping yielded the spatial distribution of the theta EEG fluctuations associated with the dynamics of the DMN. In line with previous findings, theta power was increased at frontal-midline electrodes in high- versus low-load conditions during early WM retention. However, load-dependent correlations of DMN with theta power resulted in primarily positive correlations in low-load conditions, while during high-load conditions negative correlations of DMN activity and theta power were observed at frontal-midline electrodes. This DMN-dependent load effect reached significance during later retention. Our results show a complex and load-dependent interaction of pre-stimulus DMN activity and theta power during retention, varying over the course of the retention period. Since both, WM performance and DMN activity, are markers of mental health, our results could be important for further investigations of psychiatric populations.

The brain’s pre-stimulus default state interacts with working memory in a load-dependent manner

Recently, multiple studies showed that spatial and temporal features of a task-negative default mode network (DMN) (Greicius et al., 2003) are important markers for psychiatric diseases (Balsters et al., 2013). Another prominent indicator of cognitive functioning, yielding information about the mental condition in health and disease, is working memory (WM) processing. In EEG and MEG studies, frontal-midline theta power has been shown to increase with load during WM retention in healthy subjects (Brookes et al., 2011). Negative correlations between DMN activity and theta amplitude have been found during resting state (Jann et al., 2010) as well as during WM (Michels et al., 2010). Likewise, WM training resulted in higher resting state theta power as well as increased small-worldness of the resting brain (Langer et al., 2013). Further, increased fMRI connectivity between nodes of the DMN correlated with better WM performance (Hampson et al., 2006). Hence, the brain’s default state might influence it’s functioning during task. We therefore hypothesized correlations between pre-stimulus DMN activity and EEG-theta power during WM maintenance, depending on the WM load. 17 healthy subjects performed a Sternberg WM task while being measured simultaneously with EEG and fMRI. Data was recorded within a multicenter-study: 12 subjects were measured in Zurich with a 64-channels MR-compatible system (Brain Products) in a 3T Philips scanner, 5 subjects with a 96-channel MR-compatible system (Brain Products) in a 3T Siemens Scanner in Bern. The DMN components was obtained by a group BOLD-ICA approach over the full task duration (figure 1). The subject-wise dynamics were obtained by back-reconstructed onto each subject’s fMRI data and normalized to percent signal change values. The single trial pre-stimulus-DMN activation was then temporally correlated with the single trial EEG-theta (3-8 Hz) spectral power during retention intervals. This so-called covariance mapping (Jann et al., 2010) yielded the spatial distribution of the theta EEG fluctuations during retention associated with the dynamics of the pre-stimulus DMN. In line with previous findings, theta power was increased at frontal-midline electrodes in high- versus low-load conditions during early WM retention (figure 2). However, correlations of DMN with theta power resulted in primarily positive correlations in low-load conditions, while during high-load conditions negative correlations of DMN activity and theta power were observed at frontal-midline electrodes. This DMN-dependent load effect reached significance in the middle of the retention period (TANOVA, p<0.05) (figure 3). Our results show a complex and load-dependent interaction of pre-stimulus DMN activity and theta power during retention, varying over time. While at a more global, load-independent view pre-stimulus DMN activity correlated positively with theta power during retention, the correlation was inversed during certain time windows in high-load trials, meaning that in trials with enhanced pre-stimulus DMN activity theta power decreases during retention. Since both WM performance and DMN activity are markers of mental health our results could be important for further investigations of psychiatric populations.

L-dopa modulates functional connectivity in striatal cognitive and motor networks: A double-blind placebo-controlled study

Functional connectivity (FC) analyses of resting-state fMRI data allow for the mapping of large-scale functional networks, and provide a novel means of examining the impact of dopaminergic challenge. Here, using a double-blind, placebo-controlled design, we examined the effect of L-dopa, a dopamine precursor, on striatal resting-state FC in 19 healthy young adults.Weexamined the FC of 6 striatal regions of interest (ROIs) previously shown to elicit networks known to be associated with motivational, cognitive and motor subdivisions of the caudate and putamen (Di Martino et al., 2008). In addition to replicating the previously demonstrated patterns of striatal FC, we observed robust effects of L-dopa. Specifically, L-dopa increased FC in motor pathways connecting the putamen ROIs with the cerebellum and brainstem. Although L-dopa also increased FC between the inferior ventral striatum and ventrolateral prefrontal cortex, it disrupted ventral striatal and dorsal caudate FC with the default mode network. These alterations in FC are consistent with studies that have demonstrated dopaminergic modulation of cognitive and motor striatal networks in healthy participants. Recent studies have demonstrated altered resting state FC in several conditions believed to be characterized by abnormal dopaminergic neurotransmission. Our findings suggest that the application of similar experimental pharmacological manipulations in such populations may further our understanding of the role of dopaminergic neurotransmission in those conditions.

A novel brain partition highlights the modular skeleton shared by structure and function

Elucidating the intricate relationship between brain structure and function, both in healthy and pathological conditions, is a key challenge for modern neuroscience. Recent progress in neuroimaging has helped advance our understanding of this important issue, with diffusion images providing information about structural connectivity (SC) and functional magnetic resonance imaging shedding light on resting state functional connectivity (rsFC). Here, we adopt a systems approach, relying on modular hierarchical clustering, to study together SC and rsFC datasets gathered independently from healthy human subjects. Our novel approach allows us to find a common skeleton shared by structure and function from which a new, optimal, brain partition can be extracted. We describe the emerging common structure-function modules (SFMs) in detail and compare them with commonly employed anatomical or functional parcellations. Our results underline the strong correspondence between brain structure and resting-state dynamics as well as the emerging coherent organization of the human brain.

High-field FMRI reveals brain activation patterns underlying saccade execution in the human superior colliculus.

BACKGROUND: The superior colliculus (SC) has been shown to play a crucial role in the initiation and coordination of eye- and head-movements. The knowledge about the function of this structure is mainly based on single-unit recordings in animals with relatively few neuroimaging studies investigating eye-movement related brain activity in humans. METHODOLOGY/PRINCIPAL FINDINGS: The present study employed high-field (7 Tesla) functional magnetic resonance imaging (fMRI) to investigate SC responses during endogenously cued saccades in humans. In response to centrally presented instructional cues, subjects either performed saccades away from (centrifugal) or towards (centripetal) the center of straight gaze or maintained fixation at the center position. Compared to central fixation, the execution of saccades elicited hemodynamic activity within a network of cortical and subcortical areas that included the SC, lateral geniculate nucleus (LGN), occipital cortex, striatum, and the pulvinar. CONCLUSIONS/SIGNIFICANCE: Activity in the SC was enhanced contralateral to the direction of the saccade (i.e., greater activity in the right as compared to left SC during leftward saccades and vice versa) during both centrifugal and centripetal saccades, thereby demonstrating that the contralateral predominance for saccade execution that has been shown to exist in animals is also present in the human SC. In addition, centrifugal saccades elicited greater activity in the SC than did centripetal saccades, while also being accompanied by an enhanced deactivation within the prefrontal default-mode network. This pattern of brain activity might reflect the reduced processing effort required to move the eyes toward as compared to away from the center of straight gaze, a position that might serve as a spatial baseline in which the retinotopic and craniotopic reference frames are aligned.

The use of cues for attention in ancient Greek art: aspects that influence concentration in the work of art and its elements

The goal of this study is to identify cues for the cognitive process of attention in ancient Greek art, aiming to find confirmation of its possible use by ancient Greek audiences and artists. Evidence of cues that trigger attention’s psychological dispositions was searched through content analysis of image reproductions of ancient Greek sculpture and fine vase painting from the archaic to the Hellenistic period - ca. 7th -1st cent. BC. Through this analysis, it was possible to observe the presence of cues that trigger orientation to the work of art (i.e. amplification, contrast, emotional salience, simplification, symmetry), of a cue that triggers a disseminate attention to the parts of the work (i.e. distribution of elements) and of cues that activate selective attention to specific elements in the work of art (i.e. contrast of elements, salient color, central positioning of elements, composition regarding the flow of elements and significant objects). Results support the universality of those dispositions, probably connected with basic competencies that are hard-wired in the nervous system and in the cognitive processes.