Default Mode Activity Research Articles

Multimodal magnetic resonance imaging: The coordinated use of multiple, mutually informative probes to understand brain structure and function

Differing imaging modalities provide unique channels of information to probe differing aspects of the brain's structural or functional organization. In combination, differing modalities provide complementary and mutually informative data about tissue organization that is more than their sum. We acquired and spatially coregistered data in four MRI modalities--anatomical MRI, functional MRI, diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS)--from 20 healthy adults to understand how interindividual variability in measures from one modality account for variability in measures from other modalities at each voxel of the brain. We detected significant correlations of local volumes with the magnitude of functional activation, suggesting that underlying variation in local volumes contributes to individual variability in functional activation. We also detected significant inverse correlations of NAA (a putative measure of neuronal density and viability) with volumes of white matter in the frontal cortex, with DTI-based measures of tissue organization within the superior longitudinal fasciculus, and with the magnitude of functional activation and default-mode activity during simple visual and motor tasks, indicating that substantial variance in local volumes, white matter organization, and functional activation derives from an underlying variability in the number or density of neurons in those regions. Many of these imaging measures correlated with measures of intellectual ability within differing brain tissues and differing neural systems, demonstrating that the neural determinants of intellectual capacity involve numerous and disparate features of brain tissue organization, a conclusion that could be made with confidence only when imaging the same individuals with multiple MRI modalities.

Mind wandering and attention during focused meditation: A fine-grained temporal analysis of fluctuating cognitive states

Studies have suggested that the default mode network is active during mind wandering, which is often experienced intermittently during sustained attention tasks. Conversely, an anticorrelated task-positive network is thought to subserve various forms of attentional processing. Understanding how these two systems work together is central for understanding many forms of optimal and sub-optimal task performance. Here we present a basic model of naturalistic cognitive fluctuations between mind wandering and attentional states derived from the practice of focused attention meditation. This model proposes four intervals in a cognitive cycle: mind wandering, awareness of mind wandering, shifting of attention, and sustained attention. People who train in this style of meditation cultivate their abilities to monitor cognitive processes related to attention and distraction, making them well suited to report on these mental events. Fourteen meditation practitioners performed breath-focused meditation while undergoing fMRI scanning. When participants realized their mind had wandered, they pressed a button and returned their focus to the breath. The four intervals above were then constructed around these button presses. We hypothesized that periods of mind wandering would be associated with default mode activity, whereas cognitive processes engaged during awareness of mind wandering, shifting of attention and sustained attention would engage attentional subnetworks. Analyses revealed activity in brain regions associated with the default mode during mind wandering, and in salience network regions during awareness of mind wandering. Elements of the executive network were active during shifting and sustained attention. Furthermore, activations during these cognitive phases were modulated by lifetime meditation experience. These findings support and extend theories about cognitive correlates of distributed brain networks.

Representation of somatosensory inputs within the cortical autonomic network

Regions of the cortical autonomic network (CAN) are activated during muscle contraction. However, it is not known to what extent CAN activation patterns reflect muscle sensory inputs, top-down signals from the motor cortex, and/or motor drive to cardiovascular structures. The present study explored the functional representation of somatosensory afferent input within the CAN with an a priori interest in the insula and ventral medial prefrontal cortex (vMPFC) (n=12). Heart rate (HR) and functional MRI data were acquired during 1) 30s periods of electrical stimulation of the wrist flexors at sub-motor (SUB; Type I,II afferents) and 2) motor thresholds (MOT; Type I,II,III afferents), 3) volitional wrist flexion at 5% maximal voluntary contraction (MVC) to match the MOT tension (VOL5%), and 4) volitional handgrip at 35% MVC to elicit tachycardia (VOL35%). Compared with rest, HR did not change during SUB, MOT, or VOL5% but increased during VOL35% (p<0.001). High frequency HR variability was 29.42±18.87ms2 (mean±S.D.) at rest and 39.85±27.60ms2 during SUB (p=0.06). High frequency HR variability was decreased during VOL35% compared to rest (p≤0.005). SUB increased activity in the bilateral posterior insula, vMPFC, subgenual anterior cingulate cortex (ACC), mid-cingulate cortex (MCC), and posterior cingulate cortex. MOT increased activity in the left posterior insula and MCC. During VOL5%, activity increased in the right anterior-mid insula. VOL35% was associated with activity in the bilateral insula as well as vMPFC and subgenual ACC deactivation. These data suggest that the left posterior insula processes sensory input from muscle during passive conditions and specifically that Type I and/or II muscle afferent stimulation during SUB impacts the vMPFC and/or subgenual ACC, regions believed to be involved in brain default mode and parasympathetic activity.

Alzheimer Research Series on the Default Network

The idea of the default mode network, an interconnected set of brain regions that are active when the brain is resting and that power down during focused mental tasks, was first proposed in 2001, but it quickly became a hot topic in cognitive neuroscience and for Alzheimer’s disease (AD) researchers. The seesaw activation and deactivation of the default network and task-related brain regions appears critical for peak performance on memory tasks and deactivation and network connectivity are disrupted early in AD, perhaps as a result of amyloid deposition [1]. AD is not the only disease where network activity suffers. A new study in PNAS reveals that function of the default network, as measured by fMRI, is also altered in people with schizophrenia, and their healthy first-degree relatives [2]. The changes are somewhat different from those seen in AD – network connectivity is strengthened, for one, and overall network activity is increased both at rest and during task. The study, from Susan Whitfield-Gabrieli at MIT, suggests that changes in default mode activity and alterations in the normal balance between activation and deactivation contribute to the symptoms of schizophrenia, and could be part of the genetic risk for the disease. To look at the default network in people with schizophrenia, the researchers performed fMRI scans on subjects while they were idle, and then when they engaged in a simple memory test. That allowed assessment of the basal network activity, and the extent of deactivation that occurred during a task that required concentration. The study compared 13 volunteers with early phase schizophrenia, 13 unaffected first-degree relatives and 13 healthy controls. When subjects performed the test, suppression of the default mode network was most effective in controls, and decreased in both patients and relatives. Overall, the deactivation in the default network and activation of task-related areas were strongly correlated in control subjects, but the seesaw effect was much weaker in patients and relatives. The result was a consistent hyperactivity of the default network. In addition, the patients and relatives showed stronger connectively between the medial prefrontal cortex and the precuneous and the rest of the default network, whether measured at rest or during a task. The strength of connectivity and defect in deactivation correlated with poorer performance in the working memory task and stronger schizophrenia symptoms, suggesting that the default mode network could play an important role in the cognitive and clinical symptoms of schizophrenia. In addition, the observation that unaffected relatives show similar changes suggests that aberrant network activity stems from genetic risk and is causal, rather than just a consequence of the disease, Whitfield-Gabrieli told ARF. “In the future, it may be possible to use these fMRI measures as a way of diagnosing disease, or to figure out how patients are responding to treatment,” she said. In terms of the symptoms of schizophrenia, it is interesting that the default mode network is activated during internal, self-referential thought. Network overactivity could lead to problems integrating the internal and external worlds, the authors speculate. Besides AD and schizophrenia, other diseases where default mode network activity is known to be altered include autism,

Age differences in default mode activity on easy and difficult spatial judgment tasks

The default network is a system of brain areas that are engaged when the mind is not involved in goal-directed activity. Most previous studies of age-related changes in default mode processing have used verbal tasks. We studied non-verbal spatial tasks that vary in difficulty. We presented old and young participants with two spatial judgment tasks: an easy categorical judgment and a more demanding coordinate judgment. We report that (a) Older adults show markedly less default network modulation than young on the demanding spatial task, but there is age equivalence on the easy task; (b) This Age × Task interaction is restricted to the default network: Brain areas that are deactivated by the tasks, but that are outside the default network, show no interaction; (c) Young adults exhibit significantly stronger functional connectivity among posterior regions of the default network compared with older adults, whereas older adults exhibit stronger connectivity between medial prefrontal cortex and other sites; and (d) The relationship of default activity to reaction time performance on the spatial tasks is mediated by age: in old adults, those who deactivate the default network most also perform best, whereas the opposite is true in younger adults. These results extend the findings of age-related changes in default mode processing and connectivity to visuo-spatial tasks and demonstrate that the results are specific to the default network.

FMRI default mode connectivity in vegetative state and locked-in syndrome patients

The aim of this study is to assess fMRI resting-state cerebral connectivity in vegetative state and locked-in syndrome patients by means of a user-independent method. Resting baseline (or default mode) activity is thought to be related to awareness of the internal world (that is, mind wandering, and so forth) and encompasses posterior cingulate/precuneal, anterior cingulate/mesiofrontal and posterior lateral parietal cortices.

Hypnotic induction decreases anterior default mode activity

The ‘default mode’ network refers to cortical areas that are active in the absence of goal-directed activity. In previous studies, decreased activity in the ‘default mode’ has always been associated with increased activation in task-relevant areas. We show that the induction of hypnosis can reduce anterior default mode activity during rest without increasing activity in other cortical regions. We assessed brain activation patterns of high and low suggestible people while resting in the fMRI scanner and while engaged in visual tasks, in and out of hypnosis. High suggestible participants in hypnosis showed decreased brain activity in the anterior parts of the default mode circuit. In low suggestible people, hypnotic induction produced no detectable changes in these regions, but instead deactivated areas involved in alertness. The findings indicate that hypnotic induction creates a distinctive and unique pattern of brain activation in highly suggestible subjects.

An fMRI Study of the Effects of Psychostimulants on Default-Mode Processing During Stroop Task Performance in Youths With ADHD

The authors examined the effect of psychostimulants on brain activity in children and adolescents with ADHD performing the Stroop Color and Word Test. The authors acquired 52 functional MRI scans in 16 youths with ADHD who were known responders to stimulant medication and 20 healthy comparison youths. Participants with ADHD were scanned on and off medication in a counterbalanced design, and comparison subjects were scanned once without medication. Stimulant medication significantly improved suppression of default-mode activity in the ventral anterior cingulate cortex in the ADHD group. When off medication, youths with ADHD were unable to suppress default-mode activity to the same degree as comparison subjects, whereas when on medication, they suppressed this activity to comparison group levels. Greater activation of the lateral prefrontal cortex when off medication predicted a greater reduction in ADHD symptoms when on medication. Granger causality analyses demonstrated that activity in the lateral prefrontal and ventral anterior cingulate cortices mutually influenced one another but that the influence of the ventral anterior cingulate cortex on the lateral prefrontal cortex was significantly reduced in youths with ADHD off medication relative to comparison subjects and increased significantly to normal levels when ADHD youths were on medication. Psychostimulants in youths with ADHD improved suppression of default-mode activity in the ventral anterior cingulate and posterior cingulate cortices, components of a circuit in which activity has been shown to correlate with the degree of mind-wandering during attentional tasks. Stimulants seem to improve symptoms in youths with ADHD by normalizing activity within this circuit and improving its functional interactions with the lateral prefrontal cortex.

Interrater and intermethod reliability of default mode network selection.

There has been a growing interest in the neuroimaging community regarding resting state data (i.e., passive mental activity) and the subsequent activation of the so-called default mode network (DMN). Although this network was originally characterized by a pattern of deactivation during active cognitive states, more recent applications of data-driven techniques such as independent component analysis (ICA) have permitted the analysis of brain activation during extended periods of truly passive mental activity. However, ICA requires the resultant components to be evaluated for "goodness of fit" via either human raters or more automated techniques. To our knowledge, an investigation on the reliability of either technique in determining the component that best corresponds to default-mode activity has not been performed. Moreover, it is not clear how automated techniques, which are necessarily dependent upon a template mask, are affected by the structures used to compose the mask. The current study investigated both interrater (human-human) reliability and intermethod (human-machine) reliability for determining DMN activation in 42 healthy controls. Results indicated that near perfect interrater reliability was achieved, whereas intermethod reliability was only within the moderate range. The latter was significantly improved via a weighted combination of the anterior and posterior cingulate nodes of the DMN. Implications for fully automating the component selection process are discussed.

Stability of Default-Mode Network Activity in the Aging Brain

Activity attributed to the default-mode occurs during the resting state and is thought to represent self-referential and other intrinsic processes. Although activity in default-associated regions changes across the lifespan, little is known about the stability of default-mode activity in the healthy aging brain. We investigated changes in rest-specific activity across an 8 year period in older participants in the Baltimore Longitudinal Study of Aging (BLSA) neuroimaging study. Comparison of resting-state and recognition memory PET regional cerebral blood flow conditions from baseline and 8-year follow-up shows relative stability of rest-specific activity over time in medial frontal/anterior cingulate, hippocampal and posterior cingulate regions commonly associated with the default-mode. In contrast, prefrontal, parahippocampal and occipital cortical regions, which are not typically associated with default-mode activity, show changes over time Overall, activity in the major components of the default-mode network remains stable in healthy older individuals, a finding which may assist in identifying factors that discriminate between normal and pathological aging.

P03-215 Default mode and temporal lobe networks activity during a working memory performance in schizophrenia

Background:Temporal correlations in the blood oxygen level-dependent (BOLD) signal oscillations of widely separated brain regions are presumed to reflect intrinsic functional connectivity and have been demonstrated across several distinct networks serving different functions. Impaired connectivity or disturbed integration of neural activity, as seen in brain networks in schizophrenia, might influence the symptoms of the disorder and biologically implicates in temporal and spatial alterations in BOLD signal fluctuations.The objective of this study is to examine the activity of a temporal lobe and default modes during working memory task in schizophrenic patients. These two networks were selected because both have been previously studied.Methods:Patients with schizophrenia and healthy comparison subjects undergo functional magnetic resonance imaging (fMRI) scanning while performing a verbal working memory “n-back” task. All subjects receive identical training in task performance prior to scanning. Independent component analysis will be used to identify the default mode and temporal lobe component. Spatial and temporal aspects of the networks will be examined in patients versus healthy control subjects.Results:Data collection and statistical evaluation will proceed until October 2008.Conclusions:Identifying specific activation patterns for the temporal lobe and default mode components may contribute to the identification of a trait-related marker for schizophrenia and improve diagnostic sensitivity and specificity.

Application of amplitude of low-frequency fluctuation to the temporal lobe epilepsy with bilateral hippocampal sclerosis: an fMRI study

To study the changes of amplitude of low-frequency fluctuation (ALFF) of the resting-fMRI in the mesial temporal lobe epilepsy (mTLE) with bilateral hippocampal sclerosis (HS), and discussed its underlying neuro-pathophysiological mechanism. The resting-fMRI data of 20 TLE patients with HS and 20 normal volunteers were performed ALFF analysis. The amplitude of the blood oxygenation level-dependent activation of the resting-state brain was investigated. The brain structures showing increased and decreased ALFF in TLE patients were demonstrated by comparing to normal subjects with 2-sample t-test with threshold of P < 0.01. By comparison with that of normal subjects, the regions showing increased and decreased ALFF in TLE patients were distributed in the brain symmetrically and bilaterally. The regions showing increased ALFF were distributed with center of limbic system, such as parahippocampal gyri, amygdala, hypothalamus, dorsal anterior cingulate gyrus and part of posterior insular lobe, as well as the neocortices such as primary sensorimotor cortices, occipital cortices, inferior temporal gyri, orbital gyri, and the subcortical structures of verbal brainstem and mesial cerebellum. The point with maximal increased ALFF (T = 6.02) located in the right precentral gyru (15, - 12.51). While the regions showing decreased ALFF covered the areas of default mode, such as posterior cingulate cortex/ precuneus and medial prefrontal cortex /ventral anterior cingulate cortex, as well as other structures such as dorsal lateral prefrontal cortices, superior temporal gyri, caudate heads, dorsal brain stem and the posterior cerebellum (3, -78, -21) with the maximal decreased ALFF (T = -4.42). The method of ALFF allows the direct observation to the epileptic activation in TLE. The increased ALFF is considered the facilitation such as the epileptic activity generation and propagation; while the ALFF decrease is considered the function inhibition in these regions, especially implies the suspension in the default mode activity.

IC-P-071: The effect of APOE-4 on fMRI deactivation in older controls, MCI subjects and AD patients

The epsilon 4 allele of apolipoprotein E (APOE–4) is a known risk factor for Alzheimer's disease (AD). PET studies of non–demented APOE–4 carriers have revealed hypometabolism of posterior association cortices, particularly in posterior cingulate and parietal regions, similar to the pattern of metabolic abnormalities seen in AD patients. A similar set of regions have shown alterations in deactivation, or “default mode activity,” in fMRI studies of AD patients. We wanted to investigate the effect of APOE–4 on fMRI deactivation pattern in aging, MCI and early AD. A total of 82 older subjects underwent fMRI during a face–name associative encoding paradigm. At least one APOE–4 allele was present in 8/29 (28%) of older controls (OC), in 13/38 (34%) of subjects with mild cognitive impairment (MCI, defined here as CDR 0.5), and in 9/15 (60%) of patients with early AD. FMRI was performed using a 3.0T scanner, oblique coronal acquisition, and spatial resolution of 3.125x3.125x6 mm. Data were analyzed using FEAT5.43 software contrasting the passive fixation baseline to the encoding novel and repeated face–name pairs; peak z–values and corresponding uncorrected p–values for the within and between–group comparisons are reported. The OC group demonstrated significant deactivation in posterior cingulate/retrosplenial, and precuneal regions (corresponding to Brodmann areas 23/29/30/31; z=4.83, p<0.0001). OC APOE–4 carriers showed less deactivation in both regions compared to OC non–carriers (z=3.55, p<0.0001). The deactivation pattern of MCI subjects was heterogeneous varying both according to their level of impairment and APOE–4 status. AD patients showed significantly less deactivation than OC in medial parietal and cingulate/retrosplenial cortices (z=5.32, p<0.0001). Comparing OC and AD subgroups, we found evidence of a hierarchy of deactivation decreasing in the following order: OC APOE–4 non–carriers > OC APOE–4 carriers > AD APOE–4 non–carriers > AD APOE–4 carriers. The present study demonstrates that the pattern of task–related fMRI deactivation is remarkably disrupted in AD patients, particularly in AD APOE–4 carriers. Furthermore, consistent with PET findings, APOE–4 was associated with impaired parietal and posterior cingulate deactivation even in cognitively intact older individuals at risk for AD.

IC-101-05: fMRI alterations in medial temporal and default mode activity in MCI and AD

IC-101-05: fMRI alterations in medial temporal and default mode activity in MCI and AD

Default-Mode Activity during a Passive Sensory Task: Uncoupled from Deactivation but Impacting Activation

Deactivation refers to increased neural activity during low-demand tasks or rest compared with high-demand tasks. Several groups have reported that a particular set of brain regions, including the posterior cingulate cortex and the medial prefrontal cortex, among others, is consistently deactivated. Taken together, these typically deactivated brain regions appear to constitute a default-mode network of brain activity that predominates in the absence of a demanding external task. Examining a passive, block-design sensory task with a standard deactivation analysis (rest epochs vs. stimulus epochs), we demonstrate that the default-mode network is undetectable in one run and only partially detectable in a second run. Using independent component analysis, however, we were able to detect the full default-mode network in both runs and to demonstrate that, in the majority of subjects, it persisted across both rest and stimulus epochs, uncoupled from the task waveform, and so mostly undetectable as deactivation. We also replicate an earlier finding that the default-mode network includes the hippocampus suggesting that episodic memory is incorporated in default-mode cognitive processing. Furthermore, we show that the more a subject's default-mode activity was correlated with the rest epochs (and "deactivated" during stimulus epochs), the greater that subject's activation to the visual and auditory stimuli. We conclude that activity in the default-mode network may persist through both experimental and rest epochs if the experiment is not sufficiently challenging. Time-series analysis of default-mode activity provides a measure of the degree to which a task engages a subject and whether it is sufficient to interrupt the processes--presumably cognitive, internally generated, and involving episodic memory--mediated by the default-mode network.

Deactivations, Global Signal, and the Default Mode of Brain Function

The concept of deactivation in functional MRI (fMRI) has recently gained greater acceptance as a physiological process rather than an artifact of image analyses or shunting of blood flow. It is likely that recent studies demonstrating decreases in the rate of oxygen metabolism (Shmuel, Yacoub, et al., 2002) and local field potentials (Shmuel, Augath, et al., 2003) in regions of deactivation have contributed to this greater acceptance. However, the signal change in fMRI is relative, and the concept of a deactivation suggests that there is some state that can be used as a standard baseline (Newman, Twieg, & Carpenter, 2001; Raichle et al., 2001; Stark & Squire, 2001). Deactivations are BOLD signal decreases that occur during a task relative to this standard baseline. Several recent studies have identified specific brain regions (inferior parietal, posterior cingulate, medial temporal/parahippocampal, and medial prefrontal cortices) that are active while subjects rest quietly and are deactivated during attention-demanding tasks (McKiernan, Kaufman, Kucera-Thompson, & Binder, 2003; Gusnard & Raichle, 2001; Raichle et al., 2001; Binder et al., 1999). The article published in this issue of the Journal of Cognitive Neuroscience by Michael D. Greicius and Vinod Menon (Default-Mode Activity during a Passive Sensory Task: Uncoupled from Deactivation but Impacting Activation) uses independent component analyses (ICA) to investigate this ‘‘default mode’’ of brain function in a dataset from the fMRI Data Center archive (Laurienti et al., 2002). The primary hypothesis presented in the manuscript is that the default-mode network will not be deactivated during passive stimulation. This hypothesis is based on the idea that passive sensory stimulation does not demand attentional resources and will not suppress activity in this network. The investigators suggest that it will be possible to identify the default-mode network even in the absence of stimulus-induced deactivation using ICA. The data clearly demonstrate that the analysis methodology is able to identify a predefined network of brain regions providing further evidence that there is, in fact, a default-mode brain network. In addition to the main findings, this study again raises the important issue of global normalization that often surrounds studies evaluating deactivations (Macey, Macey, Kumar, & Harper, 2004; Gavrilescu et al., 2002; Desjardins, Kiehl, & Liddle, 2001; Aguirre, Zarahn, & D’Esposito, 1998). The process of global normalization is designed to remove whole-brain signal changes that can act as confounds in studies designed to evaluate regional signal changes (Aguirre et al., 1998). There have been several methods developed to remove unwanted global signal changes (Macey et al., 2004; Gavrilescu et al., 2002; Andersson, Ashburner, & Friston, 2001; Desjardins et al., 2001; Andersson, 1997). If the global signal is correlated with the time course of the stimulation paradigm, artifacts can occur when commonly used normalization procedures, such as proportional scaling, are used. Specifically, if the global signal is positively correlated with the stimulus time course, the global normalization procedure can induce extensive regions of artifactual deactivations (Gavrilescu et al., 2002; Desjardins et al., 2001; Aguirre et al., 1998) and can include white matter, as noted by Greicius and Menon in their article. It is important to recognize that although the global normalization procedure can induce artifacts in the results, the global signal change that is correlated with the paradigm may not be an artifact itself. It has been reasoned that global signal changes can be an ‘‘artifact’’ when the whole-brain mean signal increases due to large regional signal increases (Aguirre et al., 1998). Such large ‘‘regional’’ increases in signal can elevate the ‘‘global’’ signal even if increases were localized to the activated brain areas. In such a case, the global normalization procedure will artificially decrease the signal (artifactual deactivations) in regions that exhibit no correlation with the stimulation paradigm, including the white matter. However, it is also possible that there are true global signal changes where the total brain blood flow changes in concert with the stimulation paradigm. In fact, it has been shown that the global cerebral blood flow (CBF) can actually decrease during painful stimulation (Coghill, Sang, Berman, Bennett, & Iadarola, 1998. This finding of global CBF decreases in the presence of significant activity increases suggests that large regional areas of activity may not account for the global signal change in all studies. It is interesting to note that when global signal is negatively correlated with the stimulation time course, the global normalization Wake Forest University School of Medicine, Winston-Salem, NC