Portraying the unique contribution of the default mode network to internally driven mnemonic processes

NREM sleep stages specifically alter dynamical integration of large-scale brain networks.

Alpha (8-12 Hz) oscillations and default mode network (DMN) activity dominate the brain's intrinsic activity in the temporal and spatial domains, respectively. They are thought to play crucial roles in the spatiotemporal organization of the complex brain system. Relatedly, both have been implicated, often concurrently, in diverse neuropsychiatric disorders, with accruing electroencephalogram/magnetoencephalogram (EEG/MEG) and functional magnetic resonance imaging (fMRI) data linking these two neural activities both at rest and during key cognitive operations. Prominent theories and extant findings thus converge to suggest a mechanistic relationship between alpha oscillations and the DMN. Here, we leveraged simultaneous EEG-fMRI data acquired before and after alpha-frequency transcranial alternating current stimulation (α-tACS) and observed that α-tACS tightened the dynamic coupling between spontaneous fluctuations in alpha power and DMN connectivity (especially, in the posterior DMN, between the posterior cingulate cortex and the bilateral angular gyrus). In comparison, no significant changes were observed for temporal correlations between power in other oscillatory frequencies and connectivity in other major networks. These results thus suggest an inherent coupling between alpha and DMN activity in humans. Importantly, these findings highlight the efficacy of α-tACS in regulating the DMN, a clinically significant network that is challenging to target directly with non-invasive methods.Significance Statement Alpha (8-12 Hz) oscillations and the default mode network (DMN) represent two major intrinsic activities of the brain. Prominent theories and extant findings converge to suggest a mechanistic relationship between alpha oscillations and the DMN. Combining simultaneous electroencephalogram-functional-magnetic-resonance imaging (EEG-fMRI) with alpha-frequency transcranial alternating current stimulation (α-tACS), we demonstrated tightened coupling between alpha oscillations and DMN connectivity. These results lend credence to an inherent alpha-DMN link. Given DMN dysfunctions in multiple major neuropsychiatric conditions, the findings also highlight potential utility of α-tACS in clinical interventions by regulating the DMN.

An evolutionary gap in primate default mode network organization

SPECIALTY GRAND CHALLENGE article Front. Psychiatry, 23 March 2012Sec. Child and Adolescent Psychiatry Volume 3 - 2012 | https://doi.org/10.3389/fpsyt.2012.00027

Alpha (8–12 Hz) oscillations and default mode network (DMN) activity dominate the brain’s intrinsic activity in the temporal and spatial domains, respectively. They are thought to play crucial roles in the spatiotemporal organization of the complex brain system. Relatedly, both have been implicated, often concurrently, in diverse neuropsychiatric disorders, with accruing electroencephalogram/magnetoencephalogram (EEG/MEG) and functional magnetic resonance imaging (fMRI) data linking these two neural activities both at rest and during key cognitive operations. Prominent theories and extant findings thus converge to suggest a mechanistic relationship between alpha oscillations and the DMN. Here, we leveraged simultaneous EEG-fMRI data acquired before and after alpha-frequency transcranial alternating current stimulation (α-tACS) and observed that α-tACS tightened the dynamic coupling between spontaneous fluctuations in alpha power and DMN connectivity (especially, in the posterior DMN, between the posterior cingulate cortex and the bilateral angular gyrus). In comparison, no significant changes were observed for temporal correlations between power in other oscillatory frequencies and connectivity in other major networks. These results thus suggest an inherent coupling between alpha and DMN activity in humans. Importantly, these findings highlight the efficacy of α-tACS in regulating the DMN, a clinically significant network that is challenging to target directly with non-invasive methods.

ObjectiveThis study aimed to evaluate whether somatic symptoms in adolescents with attention deficit hyperactivity disorder (ADHD) are associated with a dissociative pattern of functional connectivity (FC) within the default mode network (DMN) and whether methylphenidate administration can improve clinical and somatic symptoms. We also evaluated whether the improvement of somatic symptoms is associated with increased FC within the DMN in response to methylphenidate treatment.MethodsFifteen male adolescents with somatic symptoms of ADHD and 15 male adolescents with ADHD without somatic symptoms were included. At baseline and after 6 months of methylphenidate treatment, all adolescents were asked to complete questionnaires for the Korean version of the Dupaul’s ADHD rating scale, the symptom checklist-90- revised-somatization subscales, the Beck Depression Inventory, and the Beck Anxiety Inventory. Additionally, a resting-state functional magnetic resonance imaging scan was conducted.ResultsMethylphenidate treatment improved clinical and somatic symptoms in adolescents with ADHD. In addition, it increased brain FC within the DMN from the posterior cingulate cortex (posterior DMN) to the middle prefrontal cortex (anterior DMN). The improvement of somatic symptoms was associated with FC within the DMN from the posterior cingulate cortex to the middle prefrontal cortex in ADHD adolescents with somatic symptoms.ConclusionMethylphenidate increased brain FC between the anterior and posterior DMN. The improvement of somatic symptoms in adolescents with ADHD was associated with FC within the DMN. The DMN in adolescents with ADHD seems to be associated with the severity of the clinical and somatic symptoms of ADHD.

The default mode network (DMN) could be divided into subsystems, the functional connectivity of which are different across the Alzheimer's disease (AD) spectrum. However, the functional connectivity patterns within the subsystems are unknown in presymptomatic autosomal dominant AD (ADAD). To investigate functional connectivity patterns within the subsystems of the DMN in presymptomatic subjects carrying PSEN1, PSEN2, or APP gene mutations. Twenty-six presymptomatic mutation carriers (PMC) and twenty-nine cognitively normal non-carriers as normal controls (NC) from the same families underwent resting state functional MRI and structural MRI. Seed-based analyses were done to obtain functional connectivity of posterior and anterior DMN. For the regions that showed significant connectivity difference between PMC and NC, volumes were extracted and compared between the two groups. Connectivity measures were then correlated with cognitive tests scores. The posterior DMN showed connectivity decrease in the PMC group as compared with the NC group, which was primarily the connectivity of left precuneus with right precuneus and superior frontal gyrus; the anterior DMN showed significant connectivity decrease in the PMC group, which was the connectivity of medial frontal gyrus with middle frontal gyrus. In the brain regions showing connectivity changes in the PMC group, there was no group difference in volume. A positive correlation was observed between the precuneus connectivity value and Mini-Mental State Examination total score. Functional connectivity within both posterior and anterior DMN were disrupted in the presymptomatic stage of ADAD. Connectivity disruption within the posterior DMN may be useful for early identification of general cognitive decline and a potential imaging biomarker for early diagnosis.

BackgroundDeclines in response inhibition are observed both typical and atypical aging, i.e., mild cognitive impairment (MCI). Increased functional activation in frontoparietal regions during response inhibition has been interpreted to represent the emergence of a compensatory mechanism in older adulthood. While electrophysiology studies suggest the decline in response inhibition in MCI reflects a similar but amplified process as seen in normal aging this has not been examined thoroughly using functional MRI (fMRI).Method31 cognitively normal older adults (M age = 73.6, 9 male) and 22 adult patients with MCI (M age = 67.2, 14 male) performed a Go/NoGo task during an fMRI scan. Group differences in accuracy and reaction time were examined for Go and NoGo trials. Individual BOLD signal change during task fMRI was examined, then voxel‐wise group comparison was conducted for MCI vs. HC groups, using age, gender, education, and gray matter density as covariates. Permutation‐estimated cluster size at alpha <.05 was defined to correct for errors of multiple comparisons.ResultBehaviorally, the MCI group made significantly more errors during NoGo and Go trials (p<.001, p = .032, respectively), however, average reaction time did not differ significantly between groups. During NoGo trials, greater activation in the anterior default mode network (DMN), right dorsolateral prefrontal cortex (DLPFC), and motor areas was observed for MCI vs. HC, while during go trials, there was greater activation in DMN and right insula (corrected p<0.05). However, when Go vs. NoGo trials were examined, MCI showed more activation in right insula and DLPFC, but less activation in the motor area at trend level (p<0.05, uncorrected). While, there were no significant task performance differences between MCI subtypes (amnestic vs. non‐amnestic), amnestic MCI (aMCI) showed more activation in posterior DMN and dorsal attention area during NoGo trials (corrected p<0.05).ConclusionMCI demonstrated significantly greater activation during both Go and NoGo trials and made significantly more errors in performance during both trial types as well. While the MCI subtypes did not exhibit differences in performance on the task, the aMCI exhibited significantly greater activation in multiple regions. Our findings suggested inefficient DMN suppression during task performance in the MCI cohort, especially in the aMCI subgroup.

BackgroundDeclines in response inhibition are observed both typical and atypical aging, i.e., mild cognitive impairment (MCI). Increased functional activation in frontoparietal regions during response inhibition has been interpreted to represent the emergence of a compensatory mechanism in older adulthood. While electrophysiology studies suggest the decline in response inhibition in MCI reflects a similar but amplified process as seen in normal aging this has not been examined thoroughly using functional MRI (fMRI).Methods31 cognitively normal older adults (M age = 73.6, 9 male) and 22 adult patients with MCI (M age = 67.2, 14 male) performed a Go/NoGo task during an fMRI scan. Group differences in accuracy and reaction time were examined for Go and NoGo trials. Individual BOLD signal change during task fMRI was examined, then voxel‐wise group comparison was conducted for MCI vs. HC groups, using age, gender, education, and gray matter density as covariates. Permutation‐estimated cluster size at alpha <.05 was defined to correct for errors of multiple comparisons.ResultsBehaviorally, the MCI group made significantly more errors during NoGo and Go trials (p<.001, p = .032, respectively), however, average reaction time did not differ significantly between groups. During NoGo trials, greater activation in the anterior default mode network (DMN), right dorsolateral prefrontal cortex (DLPFC), and motor areas was observed for MCI vs. HC, while during go trials, there was greater activation in DMN and right insula (corrected p<0.05). However, when Go vs. NoGo trials were examined, MCI showed more activation in right insula and DLPFC, but less activation in the motor area at trend level (p<0.05, uncorrected). While, there were no significant task performance differences between MCI subtypes (amnestic vs. non‐amnestic), amnestic MCI (aMCI) showed more activation in posterior DMN and dorsal attention area during NoGo trials (corrected p<0.05).ConclusionMCI demonstrated significantly greater activation during both Go and NoGo trials and made significantly more errors in performance during both trial types as well. While the MCI subtypes did not exhibit differences in performance on the task, the aMCI exhibited significantly greater activation in multiple regions. Our findings suggested inefficient DMN suppression during task performance in the MCI cohort, especially in the aMCI subgroup.

Meditation can exert a profound impact on our mental life, with proficient practitioners often reporting an experience free of boundaries between a separate self and the environment, suggesting an explicit experience of “nondual awareness.” What are the neural correlates of such experiences and how do they relate to the idea of nondual awareness itself? In order to unravel the effects that meditation has on the brain’s spatial topography, we review functional magnetic resonance imaging brain findings from studies specific to an array of meditation types and meditator experience levels. We also review findings from studies that directly probe the interaction between meditation and the experience of the self. The main results are (i) decreased posterior default mode network (DMN) activity, (ii) increased central executive network (CEN) activity, (iii) decreased connectivity within posterior DMN as well as between posterior and anterior DMN, (iv) increased connectivity within the anterior DMN and CEN, and (v) significantly impacted connectivity between the DMN and CEN (likely a nonlinear phenomenon). Together, these suggest a profound organizational shift of the brain’s spatial topography in advanced meditators—we therefore propose a topographic reorganization model of meditation (TRoM). One core component of the TRoM is that the topographic reorganization of DMN and CEN is related to a decrease in the mental-self-processing along with a synchronization with the more nondual layers of self-processing, notably interoceptive and exteroceptive-self-processing. This reorganization of the functionality of both brain and self-processing can result in the explicit experience of nondual awareness. In conclusion, this review provides insight into the profound neural effects of advanced meditation and proposes a result-driven unifying model (TRoM) aimed at identifying the inextricably tied objective (neural) and subjective (experiential) effects of meditation.

A supplementary functional connectivity microstate attached to the default mode network in depression revealed by resting-state magnetoencephalography

The default mode network (DMN) comprises a set of brain regions with "increased" activity during rest relative to cognitive processing. Activity in the DMN is associated with functional connections with the striatum and dopamine (DA) levels in this brain region. A functional single-nucleotide polymorphism within the dopamine D2 receptor gene (DRD2, rs1076560 G > T) shifts splicing of the 2 D2 isoforms, D2 short and D2 long, and has been associated with striatal DA signaling as well as with cognitive processing. However, the effects of this polymorphism on DMN have not been explored. The aim of this study was to evaluate the effects of rs1076560 on DMN and striatal connectivity and on their relationship with striatal DA signaling. Twenty-eight subjects genotyped for rs1076560 underwent functional magnetic resonance imaging during a working memory task and 123 55 I-Fluoropropyl-2-beta-carbomethoxy-3-beta(4-iodophenyl) nortropan Single Photon Emission Computed Tomography ([(123)I]-FP-CIT SPECT) imaging (a measure of dopamine transporter [DAT] binding). Spatial group-independent component (IC) analysis was used to identify DMN and striatal ICs. Within the anterior DMN IC, GG subjects had relatively greater connectivity in medial prefrontal cortex (MPFC), which was directly correlated with striatal DAT binding. Within the posterior DMN IC, GG subjects had reduced connectivity in posterior cingulate relative to T carriers. Additionally, rs1076560 genotype predicted connectivity differences within a striatal network, and these changes were correlated with connectivity in MPFC and posterior cingulate within the DMN. These results suggest that genetically determined D2 receptor signaling is associated with DMN connectivity and that these changes are correlated with striatal function and presynaptic DA signaling.

The default mode network normally decreases in activity during externally directed tasks. Although default mode network connectivity is disrupted in numerous brain pathologies, default mode network deactivation has not been studied in patients with brain tumors. We investigated default mode network deactivation with language task-based fMRI by measuring the anticorrelation of a critical default mode network node, the posterior cingulate cortex, in patients with gliomas and controls; furthermore, we examined default mode network functional connectivity in these patients with task-based and resting-state fMRI. In 10 healthy controls and 30 patients with gliomas, the posterior cingulate cortex was identified on task-based fMRI and was used as an ROI to create connectivity maps from task-based and resting-state fMRI data. We compared the average correlation in each default mode network region between patients and controls for each correlation map and stratified patients by tumor location, hemisphere, and grade. Patients with gliomas (P = .001) and, in particular, patients with tumors near the posterior default mode network (P < .001) showed less posterior cingulate cortex anticorrelation in task-based fMRI than controls. Patients with both left- and right-hemisphere tumors, as well as those with grade IV tumors, showed significantly lower posterior cingulate cortex anticorrelation than controls (P = .02, .03, and <.001, respectively). Functional connectivity in each default mode network region was not significantly different between task-based and resting-state maps. Task-based fMRI showed impaired deactivation of the default mode network in patients with gliomas. The functional connectivity of the default mode network in both task-based and resting-state fMRI in patients with gliomas using the posterior cingulate cortex identified in task-based fMRI as an ROI for seed-based correlation analysis has strong overlap.

Delirium is an acute brain failure related to uncertain problems in neural connectivity, including aberrant functional interactions between remote cortical regions. This study aimed to elucidate the underlying neural mechanisms of delirium by clarifying the changes in resting-state functional connectivity induced by postoperative delirium using imaging data scanned before and after surgery. Fifty-eight patients with a femoral neck fracture were preoperatively scanned using resting-state functional magnetic resonance imaging. Twenty-five patients developed postoperative delirium, and 14 of those had follow-up scans during delirium. Eighteen patients without delirium completed follow-up scans 5 or 6 days after surgery. We assessed group differences in voxel-based connectivity, in which the seeds were the posterior cingulate cortex, medial prefrontal cortex and 11 subcortical regions. Connections between the subcortical regions were also examined. The results showed four major findings during delirium. Both the posterior cingulate cortex and medial prefrontal cortex were strongly connected to the dorsolateral prefrontal cortex. The posterior cingulate cortex had hyperconnectivity with the inferior parietal lobule, whereas the medial prefrontal cortex had hyperconnectivity with the frontopolar cortex and hypoconnectivity with the superior frontal gyrus. Connectivity of the striatum with the anterior cingulate cortex and insula was increased. Disconnections were found between the lower subcortical regions including the neurotransmitter origins and the striatum/thalamus in the upper level. Our findings suggest that cortical dysfunction during delirium is characterized by a diminution of the anticorrelation between the default mode network and task-positive regions, excessive internal connections in the posterior default mode network and a complex imbalance of internal connectivity in the anterior default mode network. These dysfunctions can be attributed to the loss of reciprocity between the default mode network and central executive network associated with defective function in the salience network, which might be closely linked to aberrant subcortical neurotransmission-related connectivity and striato-cortical connectivity.

Electrophysiological scarring in remitted depressed patients: Elevated EEG functional connectivity between the posterior cingulate cortex and the subgenual prefrontal cortex as a neural marker for rumination