Anterior Default Mode Network Research Articles

Sex commonalities and differences in the relationship between resilient personality and the intrinsic connectivity of the salience and default mode networks

Increased resilience is associated with better health outcomes and reduced morbidity in response to injury and homeostatic perturbations. Proper functioning of the salience network (SN) and modulation of the default mode network (DMN) by SN may play a role in adaptively responding to stress. Here, we demonstrate that resilient personality in healthy subjects is associated with SN and DMN connectivity patterns and that these patterns are influenced by sex. While connectivity of SN with several brain regions including right anterior insula was significantly associated with resilient personality in both men and women, results suggest that increased functional integration of anterior DMN preferentially benefits women while increased functional integration of posterior DMN preferentially benefits men in terms of resilience. These findings may relate to previous demonstrations that men and women engage different information processing and behavioral strategies to achieve resilience and highlight the importance of considering sex in resilience research.

Evidence of a dissociation pattern in default mode subnetwork functional connectivity in schizophrenia.

The default mode network (DMN) is suggested to play a pivotal role in schizophrenia; however, the dissociation pattern of functional connectivity of DMN subsystems remains uncharacterized in this disease. In this study, resting-state fMRI data were acquired from 55 schizophrenic patients and 53 matched healthy controls. DMN connectivity was estimated from time courses of independent components. The lateral DMN exhibited decreased connectivity with the unimodal sensorimotor cortex but increased connectivity with the heteromodal association areas in schizophrenics. The increased connectivity between the lateral DMN and right control network was significantly correlated with negative and anergia factor scores in the schizophrenic patients. The anterior and posterior DMNs exhibited increased and decreased connectivity with the right control and lateral visual networks, respectively, in schizophrenics. The altered DMN connectivity may underlie the hallucinations, delusions, thought disturbances, and negative symptoms involved in schizophrenia. Furthermore, DMN connectivity patterns could be used to differentiate patients from controls with 76.9% accuracy. These findings may shed new light on the distinct role of DMN subsystems in schizophrenia, thereby furthering our understanding of the pathophysiology of schizophrenia. Elucidating key disease-related DMN subsystems is critical for identifying treatment targets and aiding in the clinical diagnosis and development of treatment strategies.

Desynchronization and Plasticity of Striato-frontal Connectivity in Major Depressive Disorder.

Major depressive disorder (MDD) is associated with dysfunctional corticolimbic networks, making functional connectivity studies integral for understanding the mechanisms underlying MDD pathophysiology and treatment. Resting-state functional connectivity (RSFC) studies analyze patterns of temporally coherent intrinsic brain activity in "resting-state networks" (RSNs). The default-mode network (DMN) has been of particular interest to depression research; however, a single RSN is unlikely to capture MDD pathophysiology in its entirety, and the DMN itself can be characterized by multiple RSNs. This, coupled with conflicting previous results, underscores the need for further research. Here, we measured RSFC in MDD by targeting RSNs overlapping with corticolimbic regions and further determined whether altered patterns of RSFC were restored with electroconvulsive therapy (ECT). MDD patients exhibited hyperconnectivity between ventral striatum (VS) and the ventral default-mode network (vDMN), while simultaneously demonstrating hypoconnectivity with the anterior DMN (aDMN). ECT influenced this pattern: VS-vDMN hyperconnectivity was significantly reduced while VS-aDMN hypoconnectivity only modestly improved. RSFC between the salience RSN and dorsomedial prefrontal cortex was also reduced in MDD, but was not affected by ECT. Taken together, our results support a model of ventral/dorsal imbalance in MDD and further suggest that the VS is a key structure contributing to this desynchronization.

Intranetwork and internetwork functional connectivity alterations in post-traumatic stress disorder

BackgroundA large number of previous neuroimaging studies have explored the functional alterations of post-traumatic stress disorder (PTSD). However, abnormalities in the functional architecture of resting-state networks in PTSD were rarely elucidated. MethodsThis study used independent component analysis to explore the resting-state intranetwork and internetwork functional connectivity differences between 20 PTSD patients and 20 matched healthy controls (HCs). ResultsSelective alterations of intranetwork and internetwork intrinsic functional connectivities were found in the PTSD patients. Compared with HCs, the PTSD patients exhibited significantly decreased network connectivity within the anterior default mode network, posterior default mode network (pDMN), salience network (SN), sensory-motor network, and auditory network. Furthermore, the PTSD patients exhibited increased internetwork connectivity between SN and pDMN. LimitationsThis study lacked recruitment of trauma-exposed HCs, which limits our ability to determine whether the alterations are caused by PTSD or trauma exposure. ConclusionThe findings suggested that the PTSD patients exhibited abnormal functional connectivity at the brain network level. Notably, the enhanced internetwork connectivity between SN and pDMN in the PTSD patients may be associated with hyperarousal and heightened anxiety in PTSD.

Loss of functional connectivity is greater outside the default mode network in nonfamilial early-onset Alzheimer's disease variants

The common and specific involvement of brain networks in clinical variants of Alzheimer's disease (AD) is not well understood. We performed task-free (“resting-state”) functional imaging in 60 nonfamilial AD patients, including 20 early-onset AD (age at onset <65 years, amnestic/dysexecutive deficits), 24 logopenic aphasia (language deficits), and 16 posterior cortical atrophy patients (visual deficits), as well as 60 healthy controls. Seed-based connectivity analyses were conducted to assess differences between groups in 3 default mode network (DMN) components (anterior, posterior, and ventral) and 4 additional non-DMN networks: left and right executive-control, language, and higher visual networks. Significant decreases in connectivity were found across AD variants compared with controls in the non-DMN networks. Within the DMN components, patients showed higher connectivity in the anterior DMN, in particular in logopenic aphasia. No significant differences were found for the posterior and ventral DMN. Our findings suggest that loss of functional connectivity is greatest in networks outside the DMN in early-onset and nonamnestic AD variants and may thus be a better biomarker in these patients.

Increased connectivity between sensorimotor and attentional areas in Parkinson's disease.

Our study is using Independent Component Analysis (ICA) to evaluate functional connectivity changes in Parkinson's disease (PD) in an unbiased manner. Resting-state functional magnetic resonance imaging (rs-fMRI) data was collected for 27 PD patients and 16 healthy subjects. Differences for intra- and inter-network connectivity between healthy subjects and patients were investigated using FMRIB Software Library (FSL) tools (Melodic ICA, dual regression, FSLNets). Twenty-three ICA maps were identified as components of neuronal origin. For intra-network connectivity changes, eight components showed a significant connectivity increase in patients (p < 0.05); these were correlated with clinical scores and were largest for (sensori)motor networks. For inter-network connectivity changes, we found higher connectivity between the sensorimotor network and the spatial attention network (p = 0.0098) and lower connectivity between anterior and posterior default mode networks (DMN) (p = 0.024), anterior DMN and visual recognition networks (p = 0.026), as well as between visual attention and main dorsal attention networks (p = 0.03), for patients as compared to healthy subjects. The area under the Receiver Operating Characteristics (ROC) curve for the best predictor (partial correlation between sensorimotor and spatial attention networks) was 0.772. These functional alterations were not associated with any gray or white matter structural changes. Our results show higher connectivity between sensorimotor and spatial attention areas in patients that may be related to the reduced movement automaticity in PD.

Abnormally reduced anti-correlation between resting-state default mode and fronto-parietal networks is associated with memory impairment in MCI

Impaired deactivations of the Default Mode Network (DMN) during tasks have been associated with cognitive impairment in Alzheimer's disease. However, it remains unclear whether the functional connectivity (FC) between brain networks is also altered at rest. Here, we examined whether the FC between the task-negative DMN and the task-positive frontoparietal attention network (FPAN) is altered at rest and whether that predicts cognitive performance in non-demented elderlies with Mild Cognitive Impairment (MCI). We examined 93 subjects with MCI, recruited at our memory clinic in Munich. For cross-validation, 78 MCI subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were used. Subjects underwent resting-state fMRI and episodic memory testing using standard neuropsychological tests (word list learning). Via Independent Component Analysis, we identified 4 networks of interest (NOI): an anterior and posterior DMN component (a-DMN, p-DMN) and a left and right lateralized FPAN component (l-FPAN, r-FPAN). The average time course was extracted for each NOI and the between-NOI functional connectivity (FC) was computed via pair-wise Pearson moment correlations. Linear regression analyses were conducted, with between-NOI FC values as a regressor of memory scores, controlling for age, gender, and cognitive reserve. The between-NOI FC values ranged from -0.41 to +0.80 in the Munich sample, and from -0.44 to +0.78 in the ADNI sample. More positive between-NOI FC between a-DMN and l-FPAN predicted lower word list learning scores in both the Munich (β=-0.24, p=0.008) and the ADNI sample (β=-0.28, p=0.009). More positive between-NOI FC between a-DMN and r-FPAN predicted lower verbal learning scores (β=-0.18, p=0.046) in the Munich sample (for an example, see figure 1). The between NOI FC is plotted against the word list learning raw score. The fitted regression line plus β-weight and p-value are indicated. Our results indicate, that weaker inverse correlations between the DMN and FPAN are associated with memory impairment in MCI. This suggests, that impaired anti-correlation of task-activated and task-deactivated networks even when assessed during rest might be predictive of memory impairment in MCI.

Biomarkers of brain insulin resistance and neuroimaging correlates in early Alzheimer's disease

Insulin resistance (IR) and type 2 diabetes are risk factors for Alzheimer's disease (AD). Exosomes are endosome-derived vesicles containing macromolecules reflecting their cellular source. Using a methodology for enriching blood exosomes for neuronal origin, we recently identified differentially phosphorylated forms of Insulin Receptor Substrate-1 (IRS-1), as in vivo biomarkers of brain-specific IR in AD (Kapogiannis et al., FASEB J, 2014). Here, we assess their cognitive, functional connectivity, and brain structure correlates in AD. In 26 patients with early AD (Global CDR 0.5 or 1), we isolated blood exosomes and enriched for neuronal origin by immunoabsorption with anti-L1CAM antibody. We measured concentrations of total IRS-1, total phosphorylated tyrosine (pY-), and phosphorylated Ser312 (pS312-) IRS-1. T1-weighted MPRAGE images were acquired and gray matter (GM) images were segmented using the VBM8 toolbox; voxel-based morphometry analysis against exosomal biomarkers was conducted in SPM8. The Allen Human Brain Atlas was used to create a GM mask of IRS-1 gene microarray expression values, which was used for Biological Parametric Mapping. Independent component analysis (ICA) with the GIFT toolbox was used to derive ventral, anterior and posterior default mode networks (DMNs) from resting EPI images (Fig.2A). Associations between DMNs and exosomal biomarkers were examined with the MANCOVAN toolbox. Higher pY-IRS-1 predicted worse global cognition, and immediate and delayed verbal memory. Higher pY-IRS-1 and pS312-IRS-1 were associated with less GM in lateral and medial temporal cortex, precuneus and medial prefrontal DMN nodes, before and after adjusting for IRS-1 expression (Fig.1). Higher pS312-IRS-1 was associated with lower low- to medium-frequency spectral power of anterior DMN (Fig.2.B.C.). Higher pY-IRS-1 was associated with higher low-frequency spectral power of anterior DMN, higher medium- to high-frequency spectral power of posterior and ventral DMN, and spatially restricted posterior DMN (Fig.2.D.E.F.G).

Increased short-range and long-range functional connectivity in first-episode, medication-naive schizophrenia at rest

ObjectiveSchizophrenia is conceived as a disconnection syndrome and anatomical distance may affect functional connectivity (FC) in schizophrenia patients. However, whether and how anatomical distance affects FC remains unclear in first-episode, medication-naive schizophrenia at rest. MethodsForty-nine schizophrenia patients and 50 age-, sex-, and education-matched healthy controls underwent resting-state functional magnetic resonance imaging scanning. Regional FC strength was computed for each voxel in the brain, which was further divided into short-range and long-range FC strength. ResultsThe patients exhibited increased short-range positive FC strength in the left superior medial frontal gyrus, and increased long-range positive FC strength in the right angular gyrus and bilateral posterior cingulate cortex (PCC)/precuneus compared with the controls. Further seed-based FC analysis showed that the left superior medial frontal gyrus had increased short-range FC with the right inferior frontal gyrus, while the right angular gyrus and bilateral PCC/precuneus had increased long-range FC with the prefrontal gyrus. No significant correlation was observed between abnormal FC strength and clinical variables in the patient group. ConclusionsThe findings reveal a pattern of increased anatomical distance affecting FC in the patients, with the results of increased short-range positive FC strength in the anterior default-mode network (DMN) and increased long-range positive FC strength in the posterior DMN in schizophrenia, and highlight the importance of the DMN in the neurobiology of schizophrenia.

Altered functional connectivity among default, attention, and control networks in idiopathic generalized epilepsy

Numerous resting-state fMRI studies have demonstrated altered functional connectivity within canonical intrinsic connectivity networks (ICNs) in patients with idiopathic generalized epilepsy (IGE). It is possible that the widespread ICN abnormalities on electroencephalography in IGE derive from abnormal functional interactions between ICNs. To test this possibility, we explored the functional connectivity between the subnetworks of the default mode network (DMN), attention network (ATN), and frontoparietal control network (FPN) using independent component analysis of resting-state fMRI data collected from 27 patients with IGE characterized by generalized tonic–clonic seizures (GTCS) and 29 matched healthy controls. It was observed that the left FPN exhibited increased connectivity with the anterior DMN and ventral ATN, while the right FPN exhibited increased connectivity with the anterior and posterior DMNs in the patients with IGE–GTCS. Furthermore, the functional connectivity between the anterior DMN and ventral ATN was negative in healthy controls but positive in the patients with IGE–GTCS. In addition, the anterior DMN exhibited increased intranetwork functional connectivity in the right frontal pole in IGE–GTCS. These findings suggest that IGE–GTCS is likely associated with a disrupted brain organization probably derived from abnormal functional interactions among ICNs. Furthermore, the alterations in the functional architecture of the ICNs may be related to deficits in mentation and attention in IGE–GTCS, providing informative evidence for the understanding of the pathophysiology of IGE–GTCS.

Multimodal functional and structural neuroimaging investigation of major depressive disorder following treatment with duloxetine.

BackgroundLongitudinal neuroimaging studies of major depressive disorder (MDD) have most commonly assessed the effects of antidepressants from the serotonin reuptake inhibitor class and usually reporting a single measure. Multimodal neuroimaging assessments were acquired from MDD patients during an acute depressive episode with serial measures during a 12-week treatment with the serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine.MethodsParticipants were medication-free MDD patients (n = 32; mean age 40.2 years) in an acute depressive episode and healthy controls matched for age, gender, and IQ (n = 25; mean age 38.8 years). MDD patients received treatment with duloxetine 60 mg daily for 12 weeks with an optional dose increase to 120 mg daily after 8 weeks. All participants had serial imaging at weeks 0, 1, 8, and 12 on a 3 Tesla magnetic resonance imaging (MRI) scanner. Neuroimaging tasks included emotional facial processing, negative attentional bias (emotional Stroop), resting state functional MRI and structural MRI.ResultsA significant group by time interaction was identified in the anterior default mode network in which MDD patients showed increased connectivity with treatment, while there were no significant changes in healthy participants. In the emotional Stroop task, increased posterior cingulate activation in MDD patients normalized following treatment. No significant group by time effects were observed for happy or sad facial processing, including in amygdala responsiveness, or in regional cerebral volumes. Reduced baseline resting state connectivity within the orbitofrontal component of the default mode network was predictive of clinical response. An early increase in hippocampal volume was predictive of clinical response.ConclusionsBaseline resting state functional connectivity was predictive of subsequent clinical response. Complementary effects of treatment were observed from the functional neuroimaging correlates of affective facial expressions, negative attentional bias, and resting state. No significant effects were observed in affective facial processing, while the interaction effect in negative attentional bias and individual group effects in resting state connectivity could be related to the SNRI class of antidepressant medication. The specificity of the observed effects to SNRI pharmacological treatments requires further investigation.Trial registrationRegistered at clinicaltrials.gov (NCT01051466).Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-015-0457-2) contains supplementary material, which is available to authorized users.

Resting-state functional connectivity of antero-medial prefrontal cortex sub-regions in major depression and relationship to emotional intelligence.

Background:Major depressive disorder has been associated with abnormal resting-state functional connectivity (FC), especially in cognitive processing and emotional regulation networks. Although studies have found abnormal FC in regions of the default mode network (DMN), no study has investigated the FC of specific regions within the anterior DMN based on cytoarchitectonic subdivisions of the antero-medial pre-frontal cortex (PFC). Studies from different areas in the field have shown regions within the anterior DMN to be involved in emotional intelligence. Although abnormalities in this region have been observed in depression, the relationship between the ventromedial PFC (vmPFC) function and emotional intelligence has yet to be investigated in depressed individuals.Methods:Twenty-one medication-free, non–treatment resistant, depressed patients and 21 healthy controls underwent a resting state functional magnetic resonance imaging session. The participants also completed an ability-based measure of emotional intelligence: the Mayer-Salovey-Caruso Emotional Intelligence Test. FC maps of Brodmann areas (BA) 25, 10m, 10r, and 10p were created and compared between the two groups.Results:Mixed-effects analyses showed that the more anterior seeds encompassed larger areas of the DMN. Compared to healthy controls, depressed patients had significantly lower connectivity between BA10p and the right insula and between BA25 and the perigenual anterior cingulate cortex. Exploratory analyses showed an association between vmPFC connectivity and emotional intelligence.Conclusions:These results suggest that individuals with depression have reduced FC between antero-medial PFC regions and regions involved in emotional regulation compared to control subjects. Moreover, vmPFC functional connectivity appears linked to emotional intelligence.

Decreased Resting-State Connectivity between Neurocognitive Networks in Treatment Resistant Depression.

Approximately one-third of patients with major depressive disorder (MDD) do not achieve remission after various treatment options and develop treatment resistant depression (TRD). So far, little is known about the pathophysiology of TRD. Studies in MDD patients showed aberrant functional connectivity (FC) of three “core” neurocognitive networks: the salience network (SN), cognitive control network (CCN), and default mode network (DMN). We used a cross-sectional design and performed resting-state FC MRI to assess connectivity of the SN, CCN, and both anterior and posterior DMN in 17 severe TRD, 18 non-TRD, and 18 healthy control (HC) subjects. Relative to both non-TRD and HC subjects, TRD patients showed decreased FC between the dorsolateral prefrontal cortex and angular gyrus, which suggests reduced FC between the CCN and DMN, and reduced FC between the medial prefrontal cortex and precuneus/cuneus, which suggests reduced FC between the anterior and posterior DMN. No significant differences in SN FC were observed. Our results suggest that TRD is characterized by a disturbance in neurocognitive networks relative to non-TRD and HC.

Chronology and chronicity of altered resting-state functional connectivity after traumatic brain injury.

Whereas traumatic brain injury (TBI) results in widespread disruption of neural networks, changes in regional resting-state functional connectivity patterns after insult remain unclear. Specifically, little is known about the chronology of emergent connectivity alterations and whether they persist after a critical recovery window. We used resting-state functional magnetic resonance imaging and seed-voxel correlational analyses in both cross-sectional and longitudinal designs to probe intrinsic connectivity patterns involving the posterior cingulate cortex (PCC) and hippocampi, regions shown to be important in the default mode network (DMN) and vulnerable to neuropathology. A total of 22 participants in the chronic stage of moderate-to-severe TBI and 18 healthy controls were included for cross-sectional study. Longitudinal analyses included 13 individuals in the TBI group for whom data approximately 3 months after injury (subacute) were available. Overall, results indicated dissociable connectivity trajectories of the PCC and hippocampi during recovery from TBI, with PCC alterations characterized by early hypersynchrony with the anterior DMN that is gradually reduced, and hippocampal changes marked by increasing synchrony with proximal cortex and subcortex. The PCC also showed increasing antiphase synchrony with posterior attentional regions, and the hippocampi showed decreasing antiphase synchrony with frontal attentional regions. Antiphase synchrony of the hippocampus and dorsolateral prefrontal cortex at the subacute stage of TBI was positively associated with attentional performance on neuropsychological tests at both the subacute and chronic stages. Our findings highlight the heterogeneity of regional whole-brain connectivity changes after TBI, and suggest that residual connectivity alterations exist in the clinically stable phase of TBI. Parallels between the chronicity of the observed effects and findings in neurodegenerative disease are discussed in the context of potential long-term outcomes of TBI.

Structural and functional correlates of hypnotic depth and suggestibility

This study explores whether self-reported depth of hypnosis and hypnotic suggestibility are associated with individual differences in neuroanatomy and/or levels of functional connectivity. Twenty-nine people varying in suggestibility were recruited and underwent structural, and after a hypnotic induction, functional magnetic resonance imaging at rest. We used voxel-based morphometry to assess the correlation of grey matter (GM) and white matter (WM) against the independent variables: depth of hypnosis, level of relaxation and hypnotic suggestibility. Functional networks identified with independent components analysis were regressed with the independent variables. Hypnotic depth ratings were positively correlated with GM volume in the frontal cortex and the anterior cingulate cortex (ACC). Hypnotic suggestibility was positively correlated with GM volume in the left temporal-occipital cortex. Relaxation ratings did not correlate significantly with GM volume and none of the independent variables correlated with regional WM volume measures. Self-reported deeper levels of hypnosis were associated with less connectivity within the anterior default mode network. Taken together, the results suggest that the greater GM volume in the medial frontal cortex and ACC, and lower connectivity in the DMN during hypnosis facilitate experiences of greater hypnotic depth. The patterns of results suggest that hypnotic depth and hypnotic suggestibility should not be considered synonyms.

Functional connectivity and neuronal variability of resting state activity in bipolar disorder--reduction and decoupling in anterior cortical midline structures.

The cortical midline structures seem to be involved in the modulation of different resting state networks, such as the default mode network (DMN) and salience network (SN). Alterations in these systems, in particular in the perigenual anterior cingulate cortex (PACC), seem to play a central role in bipolar disorder (BD). However, the exact role of the PACC, and its functional connections to other midline regions (within and outside DMN) still remains unclear in BD. We investigated functional connectivity (FC), standard deviation (SD, as a measure of neuronal variability) and their correlation in bipolar patients (n = 40) versus healthy controls (n = 40), in the PACC and in its connections in different frequency bands (standard: 0.01-0.10 Hz; Slow-5: 0.01-0.027 Hz; Slow-4: 0.027-0.073 Hz). Finally, we studied the correlations between FC alterations and clinical-neuropsychological parameters and we explored whether subgroups of patients in different phases of the illness present different patterns of FC abnormalities. We found in BD decreased FC (especially in Slow-5) from the PACC to other regions located predominantly in the posterior DMN (such as the posterior cingulate cortex (PCC) and inferior temporal gyrus) and in the SN (such as the supragenual anterior cingulate cortex and ventrolateral prefrontal cortex). Second, we found in BD a decoupling between PACC-based FC and variability in the various target regions (without alteration in variability itself). Finally, in our subgroups explorative analysis, we found a decrease in FC between the PACC and supragenual ACC (in depressive phase) and between the PACC and PCC (in manic phase). These findings suggest that in BD the communication, that is, information transfer, between the different cortical midline regions within the cingulate gyrus does not seem to work properly. This may result in dysbalance between different resting state networks like the DMN and SN. A deficit in the anterior DMN-SN connectivity could lead to an abnormal shifting toward the DMN, while a deficit in the anterior DMN-posterior DMN connectivity could lead to an abnormal shifting toward the SN, resulting in excessive focusing on internal contents and reduced transition from idea to action or in excessive focusing on external contents and increased transition from idea to action, respectively, which could represent central dimensions of depression and mania. If confirmed, they could represent diagnostic markers in BD.

Modulatory interactions between the default mode network and task positive networks in resting-state.

The two major brain networks, i.e., the default mode network (DMN) and the task positive network, typically reveal negative and variable connectivity in resting-state. In the present study, we examined whether the connectivity between the DMN and different components of the task positive network were modulated by other brain regions by using physiophysiological interaction (PPI) on resting-state functional magnetic resonance imaging data. Spatial independent component analysis was first conducted to identify components that represented networks of interest, including the anterior and posterior DMNs, salience, dorsal attention, left and right executive networks. PPI analysis was conducted between pairs of these networks to identify networks or regions that showed modulatory interactions with the two networks. Both network-wise and voxel-wise analyses revealed reciprocal positive modulatory interactions between the DMN, salience, and executive networks. Together with the anatomical properties of the salience network regions, the results suggest that the salience network may modulate the relationship between the DMN and executive networks. In addition, voxel-wise analysis demonstrated that the basal ganglia and thalamus positively interacted with the salience network and the dorsal attention network, and negatively interacted with the salience network and the DMN. The results demonstrated complex modulatory interactions among the DMNs and task positive networks in resting-state, and suggested that communications between these networks may be modulated by some critical brain structures such as the salience network, basal ganglia, and thalamus.

Spatially Distributed Effects of Mental Exhaustion on Resting-State FMRI Networks

Brain activity during rest is spatially coherent over functional connectivity networks called resting-state networks. In resting-state functional magnetic resonance imaging, independent component analysis yields spatially distributed network representations reflecting distinct mental processes, such as intrinsic (default) or extrinsic (executive) attention, and sensory inhibition or excitation. These aspects can be related to different treatments or subjective experiences. Among these, exhaustion is a common psychological state induced by prolonged mental performance. Using repeated functional magnetic resonance imaging sessions and spatial independent component analysis, we explored the effect of several hours of sustained cognitive performances on the resting human brain. Resting-state functional magnetic resonance imaging was performed on the same healthy volunteers in two days, with and without, and before, during and after, an intensive psychological treatment (skill training and sustained practice with a flight simulator). After each scan, subjects rated their level of exhaustion and performed an N-back task to evaluate eventual decrease in cognitive performance. Spatial maps of selected resting-state network components were statistically evaluated across time points to detect possible changes induced by the sustained mental performance. The intensive treatment had a significant effect on exhaustion and effort ratings, but no effects on N-back performances. Significant changes in the most exhausted state were observed in the early visual processing and the anterior default mode networks (enhancement) and in the fronto-parietal executive networks (suppression), suggesting that mental exhaustion is associated with a more idling brain state and that internal attention processes are facilitated to the detriment of more extrinsic processes. The described application may inspire future indicators of the level of fatigue in the neural attention system.

Unlearning chronic pain: A randomized controlled trial to investigate changes in intrinsic brain connectivity following Cognitive Behavioral Therapy.

Chronic pain is a complex physiological and psychological phenomenon. Implicit learning mechanisms contribute to the development of chronic pain and to persistent changes in the central nervous system. We hypothesized that these central abnormalities can be remedied with Cognitive Behavioral Therapy (CBT). Specifically, since regions of the anterior Default Mode Network (DMN) are centrally involved in emotional regulation via connections with limbic regions, such as the amygdala, remediation of maladaptive behavioral and cognitive patterns as a result of CBT for chronic pain would manifest itself as a change in the intrinsic functional connectivity (iFC) between these prefrontal and limbic regions. Resting-state functional neuroimaging was performed in patients with chronic pain before and after 11-week CBT (n = 19), as well as a matched (ages 19–59, both sexes) active control group of patients who received educational materials (n = 19). Participants were randomized prior to the intervention. To investigate the differential impact of treatment on intrinsic functional connectivity (iFC), we compared pre–post differences in iFC between groups. In addition, we performed exploratory whole brain analyses of changes in fractional amplitude of low frequency fluctuations (fALFF). The course of CBT led to significant improvements in clinical measures of pain and self-efficacy for coping with chronic pain. Significant group differences in pre–post changes in both iFC and fALFF were correlated with clinical outcomes. Compared to control patients, iFC between the anterior DMN and the amygdala/periaqueductal gray decreased following CBT, whereas iFC between the basal ganglia network and the right secondary somatosensory cortex increased following CBT. CBT patients also had increased post-therapy fALFF in the bilateral posterior cingulate and the cerebellum. By delineating neuroplasticity associated with CBT-related improvements, these results add to mounting evidence that CBT is a valuable treatment option for chronic pain.

Functional and structural brain changes in anti–N‐methyl‐D‐aspartate receptor encephalitis

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune encephalitis with a characteristic neuropsychiatric syndrome and severe and prolonged clinical courses. In contrast, standard clinical magnetic resonance imaging (MRI) remains normal in the majority of patients. Here, we investigated structural and functional brain changes in a cohort of patients with anti-NMDAR encephalitis. Twenty-four patients with established diagnosis of anti-NMDAR encephalitis and age- and gender-matched controls underwent neuropsychological testing and multimodal MRI, including T1w/T2w structural imaging, analysis of resting state functional connectivity, analysis of white matter using diffusion tensor imaging, and analysis of gray matter using voxel-based morphometry. Patients showed significantly reduced functional connectivity of the left and right hippocampus with the anterior default mode network. Connectivity of both hippocampi predicted memory performance in patients. Diffusion tensor imaging revealed extensive white matter changes, which were most prominent in the cingulum and which correlated with disease severity. In contrast, no differences in T1w/T2w structural imaging and gray matter morphology were observed between patients and controls. Anti-NMDAR encephalitis is associated with characteristic alterations of functional connectivity and widespread changes of white matter integrity despite normal findings in routine clinical MRI. These results may help to explain the clinicoradiological paradox in anti-NMDAR encephalitis and advance the pathophysiological understanding of the disease. Correlation of imaging abnormalities with disease symptoms and severity suggests that these changes play an important role in the symptomatology of anti-NMDAR encephalitis.