Posterior Regions Of Default Mode Network Research Articles

Circulating PACAP levels are associated with increased amygdala-default mode network resting-state connectivity in posttraumatic stress disorder

The pituitary adenylate cyclase-activating polypeptide (PACAP) system is implicated in posttraumatic stress disorder (PTSD) and related amygdala-mediated arousal and threat reactivity. PTSD is characterized by increased amygdala reactivity to threat and, more recently, aberrant intrinsic connectivity of the amygdala with large-scale resting state networks, specifically the default mode network (DMN). While the influence of PACAP on amygdala reactivity has been described, its association with intrinsic amygdala connectivity remains unknown. To fill this gap, we examined functional connectivity of resting-state functional magnetic resonance imaging (fMRI) in eighty-nine trauma-exposed adults (69 female) screened for PTSD symptoms to examine the association between blood-borne (circulating) PACAP levels and amygdala-DMN connectivity. Higher circulating PACAP levels were associated with increased amygdala connectivity with posterior DMN regions, including the posterior cingulate cortex/precuneus (PCC/Precun) and left angular gyrus (lANG). Consistent with prior work, this effect was seen in female, but not male, participants and the centromedial, but not basolateral, subregions of the amygdala. Clinical association analyses linked amygdala-PCC/Precun connectivity to anxious arousal symptoms, specifically exaggerated startle response. Taken together, our findings converge with previously demonstrated effects of PACAP on amygdala activity in PTSD-related processes and offer novel evidence for an association between PACAP and intrinsic amygdala connectivity patterns in PTSD. Moreover, these data provide preliminary evidence to motivate future work ascertaining the sex- and subregion-specificity of these effects. Such findings may enable novel mechanistic insights into neural circuit dysfunction in PTSD and how the PACAP system confers risk through a disruption of intrinsic resting-state network dynamics.

Effects of Acupuncture at Neiguan in Neural Activity of Related Brain Regions: A Resting-State fMRI Study in Anxiety.

BackgroundAcupuncture of PC6 points has the effects of calming, tranquilizing, regulating qi, and relieving pain and has been clinically found to alleviate anxiety disorders. To explore the mechanism of improvement at the Neiguan point acupuncture in anxiety patients, we used fMRI to observe the changes in brain function in patients with immediate anxiety before and after acupuncture at the Neiguan point.Subjects and MethodsThe experiment followed the principle of randomized, single-blind design. Twenty-four anxiety volunteers (14 males and 10 females, 20–35 years old) were divided randomly into two groups: a group of acupuncture at Neiguan and a group of acupuncture at non-acupoint. Functional magnetic resonance imaging (fMRI) was applied to measure brain activity pre- and post-acupuncture. The amplitude of low-frequency fluctuations (ALFF) and seed-based functional connectivity (FC) was used to analyze the activity and network of brain regions. Statistical analysis was done using SPSS 21.0 and REST 1.8 software.ResultsALFF results revealed that post-acupuncture at Neiguan increased the activity of the left parahippocampal gyrus, fusiform gyrus, and right superior temporal gyrus and decreased the activity of the right middle frontal gyrus, right precuneus, and cuneus. Post-acupuncture at non-acupoint led to a significant ALFF increase in the thalamus and middle frontal gyrus. The ALFF in the left middle frontal gyrus was decreased. Functional connectivity in several anterior default mode network (DMN) regions and vermis cerebelli at left parahippocampal/fusiform gyri was increased, and connectivity in bilateral superior temporal gyri was decreased. FC with posterior DMN regions decreased at the right middle frontal gyrus, right precuneus, and cuneus.ConclusionOur study elucidates that acupuncture at Neiguan modulates anxiety by activating or deactivating these brain anxiety-related regions and provides potential explanations for the application of PC6 acupuncture in mental diseases.

An evolutionary gap in primate default mode network organization

SUMMARYThe human default mode network (DMN) is engaged at rest and in cognitive states such as self-directed thoughts. Interconnected homologous cortical areas in primates constitute a network considered as the equivalent. Here, based on a cross-species comparison of the DMN between humans and non-hominoid primates (macaques, marmosets, and mouse lemurs), we report major dissimilarities in connectivity profiles. Most importantly, the medial prefrontal cortex (mPFC) of non-hominoid primates is poorly engaged with the posterior cingulate cortex (PCC), though strong correlated activity between the human PCC and the mPFC is a key feature of the human DMN. Instead, a fronto-temporal resting-state network involving the mPFC was detected consistently across non-hominoid primate species. These common functional features shared between non-hominoid primates but not with humans suggest a substantial gap in the organization of the primate’s DMN and its associated cognitive functions.

Interplay Between the Salience and the Default Mode Network in a Social-Cognitive Task Toward a Close Other.

Social cognition relies on two main subsystems to construct the understanding of others, which are sustained by different social brain networks. One of these social networks is the default mode network (DMN) associated with the socio-cognitive subsystem (i.e., mentalizing), and the other is the salience network (SN) associated with the socio-affective route (i.e., empathy). The DMN and the SN are well-known resting state networks that seem to constitute a baseline for the performance of social tasks. We aimed to investigate both networks' functional connectivity (FC) pattern in the transition from resting state to social task performance. A sample of 38 participants involved in a monogamous romantic relationship completed a questionnaire of dyadic empathy and underwent an fMRI protocol that included a resting state acquisition followed by a task in which subjects watched emotional videos of their romantic partner and elaborated on their partner's (Other condition) or on their own experience (Self condition). Independent component and ROI-to-ROI correlation analysis were used to assess alterations in task-independent (Rest condition) and task-dependent (Self and Other conditions) FC. We found that the spatial FC maps of the DMN and SN evidenced the traditional regions associated with these networks in the three conditions. Anterior and posterior DMN regions exhibited increased FC during the social task performance compared to resting state. The Other condition revealed a more limited SN's connectivity in comparison to the Self and Rest conditions. The results revealed an interplay between the main nodes of the DMN and the core regions of the SN, particularly evident in the Self and Other conditions.

Modulation of the brain's core-self network by self-appraisal processes

The ‘core’ regions of the default mode network (DMN) – the medial prefrontal cortex (MPFC), the posterior cingulate cortex (PCC), and inferior parietal lobules (IPL) – show consistent engagement across mental states that involve self-oriented processing. Precisely how these regions interact in support of such processes remains an important unanswered question. In the current functional magnetic resonance imaging (fMRI) study, we examined dynamic interactions of the ‘core-self’ DMN regions during two forms of self-referential cognition: direct self-appraisal (thinking about oneself) and reflected self-appraisal (thinking about oneself from a third-person perspective). One-hundred and eleven participants completed our dual self-appraisal task during fMRI, and general linear models were used to characterize common and distinct neural responses to these conditions. Informed by these results, we then applied dynamic causal modelling to examine causal interactions among the ‘core-self’ regions, and how they were specifically modulated under the influence of direct and reflected self-appraisal. As a primary observation, this network modelling revealed a distinct inhibitory influence of the left IPL on the PCC during reflected compared to direct self-appraisal, which was accompanied by evidence of greater activation in both regions during the reflected self-appraisal condition. We suggest that the greater engagement of posterior DMN regions during reflected self-appraisal is a function of the higher-order processing needed for this form of self-appraisal, with the left IPL supporting abstract self-related processes including episodic memory retrieval and shifts of perspective. Overall, we show that core DMN regions interact in functionally unique ways in support of self-referential processes, even when these processes are inter-related. Further characterization of DMN functional interactions across self-related mental states is likely to inform a deeper understanding of how this brain network orchestrates the self.

Roles of the Default Mode and Multiple-Demand Networks in Naturalistic versus Symbolic Decisions.

The default mode network (DMN) is often associated with representing semantic, social, and situational content of contexts and episodes. The DMN may therefore be important for contextual decision-making, through representing situational constraints and simulating common courses of events. Most decision-making paradigms, however, use symbolic stimuli and instead implicate cognitive control regions, such as the multiple demand (MD) system. This fMRI study aimed to contrast the brain mechanisms underlying decision-making based on rich naturalistic contexts or symbolic cues. While performing an ongoing task, 40 human participants (25 female) responded to different sounds. For one sound, the stimulus-response mapping was fixed; responses for the other sounds depended on the visual context: either lifelike scenes or letter symbols, varying across participants. Despite minimal behavioral differences between the groups, posterior DMN regions showed increased activity during context-dependent decision-making using the naturalistic scenes only, compared with symbolic cues. More anterior temporal and frontal DMN regions showed a different pattern, with sensitivity to the need for contextual control, but not to the type of context. Furthermore, in the scenes group, widespread DMN regions showed stronger representation of not just the context but also the sound whose significance it modulated. In comparison, the MD system showed strong univariate activity for every decision, but, intriguingly, somewhat reduced activity in the case of a scene-based but demanding context-dependent decision. Depending on context, we suggest, either DMN or MD regions may play a prominent role in selection and control of appropriate behavior.SIGNIFICANCE STATEMENT Contextual knowledge is widely believed to be important for guiding real-world goal-directed behavior. Much remains to be understood, however, regarding the underlying brain mechanisms. Using a novel paradigm to contrast decisions based on richly meaningful naturalistic scenes with decisions based on symbolic cues, we find that both multiple demand regions and default mode regions may contribute to the cognitive control of behavior. Rich semantic context enhances representation not just of the context itself, but also of the contents of the decision that it controls. Dependence of a decision on naturalistic context can also reverse the common pattern of multiple demand regions responding more, and default mode regions responding less, to more difficult decisions.

Preterm birth leads to impaired rich-club organization and fronto-paralimbic/limbic structural connectivity in newborns

Prematurity disrupts brain development during a critical period of brain growth and organization and is known to be associated with an increased risk of neurodevelopmental impairments. Investigating whole-brain structural connectivity alterations accompanying preterm birth may provide a better comprehension of the neurobiological mechanisms related to the later neurocognitive deficits observed in this population.Using a connectome approach, we aimed to study the impact of prematurity on neonatal whole-brain structural network organization at term-equivalent age. In this cohort study, twenty-four very preterm infants at term-equivalent age (VPT-TEA) and fourteen full-term (FT) newborns underwent a brain MRI exam at term age, comprising T2-weighted imaging and diffusion MRI, used to reconstruct brain connectomes by applying probabilistic constrained spherical deconvolution whole-brain tractography. The topological properties of brain networks were quantified through a graph-theoretical approach. Furthermore, edge-wise connectivity strength was compared between groups.Overall, VPT-TEA infants’ brain networks evidenced increased segregation and decreased integration capacity, revealed by an increased clustering coefficient, increased modularity, increased characteristic path length, decreased global efficiency and diminished rich-club coefficient. Furthermore, in comparison to FT, VPT-TEA infants had decreased connectivity strength in various cortico-cortical, cortico-subcortical and intra-subcortical networks, the majority of them being intra-hemispheric fronto-paralimbic and fronto-limbic. Inter-hemispheric connectivity was also decreased in VPT-TEA infants, namely through connections linking to the left precuneus or left dorsal cingulate gyrus – two regions that were found to be hubs in FT but not in VPT-TEA infants. Moreover, posterior regions from Default-Mode-Network (DMN), namely precuneus and posterior cingulate gyrus, had decreased structural connectivity in VPT-TEA group.Our finding that VPT-TEA infants’ brain networks displayed increased modularity, weakened rich-club connectivity and diminished global efficiency compared to FT infants suggests a delayed transition from a local architecture, focused on short-range connections, to a more distributed architecture with efficient long-range connections in those infants. The disruption of connectivity in fronto-paralimbic/limbic and posterior DMN regions might underlie the behavioral and social cognition difficulties previously reported in the preterm population.

S164. HIPPOCAMPAL CONNECTIVITY IN YOUTH WITH SCHIZOPHRENIA: COMPARISON WITH PATIENTS WITH NMDA RECEPTOR ENCEPHALITIS AND HEALTHY VOLUNTEERS

BackgroundThe N-methyl-D-aspartate receptor (NMDAR) hypofunction model of schizophrenia suggests that dysfunction of these receptors could underlie the brain functional abnormalities characterising these patients. In NMDAR encephalitis (NMDARE), which holds clinical similarities with schizophrenia, autoantibodies target NMDARs, predominantly located in the hippocampal region, leading to disrupted glutamatergic transmission. One study so far has described abnormal connectivity between the medial temporal lobe and posterior default mode network regions in patients with NMDARE (Peer et al., 2017), however no study so far has examined brain functional correlates of schizophrenia and NMDARE comparatively.MethodsPatients with schizophrenia (N=16) and with NMDARE shortly after clinical stabilisation (N=15) were recruited within a tertiary setting, and compared with age and sex-matched healthy volunteers (N=20). All individuals were scanned with a 3T Siemens scanner including a functional resting state sequence, during which individuals were instructed to view a fixation cross. A seed-based analysis was performed using a spherical seed of 4mm located in the left hippocampus (MNI coordinates x =-32, y=-24, x=-14). Only grey matter voxels were considered to obtain the seed average signal. BOLD signal was preprocessed including slice timing, motion correction, spatial smoothing, and frequency filtering, and regressed taken into account movement parameters (rigid transformation, frame displacement, and DVARS). Statistics was performed between the correlation maps including age and sex as covariates. Family-wise error (FWE) was used to correct for multiple comparisons.ResultsSeed to voxel analyses revealed connectivity between the seed and the bilateral thalamus, parahippocampus, precuneus, posterior cingulate, right hippocampus and lateral temporal regions (threshold Fisher’s z > 0.28). We first examined differences in connectivity between both patient groups combined and healthy volunteers, which revealed greater connectivity in patients than in controls between the left hippocampus and the left inferior parietal, postcentral and posterior cingulate gyri (pFWE< 0.05). When examining patient groups individually, patients with schizophrenia continued to exhibit significantly greater connectivity between the left hippocampus and left inferior parietal and postcentral region (pFWE< 0.05) and at near trend level in the posterior cingulate (pFWE= 0.15). NMDARE patients also presented near trend level increased connectivity in the posterior cingulate and postcentral gyri (pFWE= 0.10). There were no differences in functional connectivity of the left hippocampus between patients with schizophrenia and with NMDARE.DiscussionTo our knowledge, this is the first study to compare patients with schizophrenia with patients with NMDARE using measures of brain function. We found that, for both conditions, the left hippocampus showed greater connectivity with areas belonging to the posterior default mode network. Connectivity between these regions has been associated with psychotic symptoms in schizophrenia (Lefebvre et al., 2016). Our findings suggest that this alteration could also underlie neuropsychiatric symptoms in NMDARE, and provides further evidence that NMDAR dysfunction may underpin the pathophysiology of schizophrenia.

Abstract 19: Default Mode Network Alterations in Cerebral Amyloid Angiopathy: A Resting State FMRI Study

Introduction: Cerebral amyloid angiopathy (CAA) is an established cause of intracerebral hemorrhage and vascular dysfunction leading to ischemia. Functional connectivity analysis using MRI is becoming an important tool to analyze the brain activity during resting state, the default mode network (DMN) representing the prototypical set of connections. As CAA pathology has a posterior predominance, we sought to characterize the functional connectivity of the posterior DMN at resting state in patients with CAA. Methods: Patients with probable CAA diagnosed using Boston Criteria and healthy controls (HC) were prospectively enrolled and received high resolution 3T MRI scans including dedicated resting-state fMRI sequences. Functional seed-to-seed analyses were done using the default processing pipeline in the CONN Toolbox. Correlation maps between the established DMN and specific regions of the posterior DMN, the precuneus and posterior cingulate, were averaged within groups and compared in an ANCOVA model. Results: Study participants consisted of 60 patients with probable CAA and 20 healthy controls [aged 69 ± 7.5 vs 72.3 ± 8 years, P = 0.108]. Seed-to-seed analysis revealed a significantly lower strength of DMN connectivity in CAA when compared to controls in the precuneus [ P = 0.009] and posterior cingulate [ P = 0.003] adjusted for age and sex (Fig 1). Conclusion: Patients with CAA exhibited significant loss of connectivity in the posterior regions of the DMN when compared to controls. The precuneus and posterior cingulate are core regions of the DMN with reportedly high metabolic rates at rest. Disruption of these posterior DMN regions might occur due to vascular amyloid pathology that shows a predominantly posterior distribution.

Differential tDCS and tACS Effects on Working Memory-Related Neural Activity and Resting-State Connectivity.

Transcranial direct and alternating current stimulation (tDCS and tACS, respectively) entail capability to modulate human brain dynamics and cognition. However, the comparability of these approaches at the level of large-scale functional networks has not been thoroughly investigated. In this study, 44 subjects were randomly assigned to receive sham (N = 15), tDCS (N = 15), or tACS (N = 14). The first electrode (anode in tDCS) was positioned over the left dorsolateral prefrontal cortex, the target area, and the second electrode (cathode in tDCS) was placed over the right supraorbital region. tDCS was delivered with a constant current of 2 mA. tACS was fixed to 2 mA peak-to-peak with 6 Hz frequency. Stimulation was applied concurrently with functional magnetic resonance imaging (fMRI) acquisitions, both at rest and during the performance of a verbal working memory (WM) task. After stimulation, subjects repeated the fMRI WM task. Our results indicated that at rest, tDCS increased functional connectivity particularly within the default-mode network (DMN), while tACS decreased it. When comparing both fMRI WM tasks, it was observed that tDCS displayed decreased brain activity post-stimulation as compared to online. Conversely, tACS effects were driven by neural increases online as compared to post-stimulation. Interestingly, both effects primarily occurred within DMN-related areas. Regarding the differences in each fMRI WM task, during the online fMRI WM task, tACS engaged distributed neural resources which did not overlap with the WM-dependent activity pattern, but with some posterior DMN regions. In contrast, during the post-stimulation fMRI WM task, tDCS strengthened prefrontal DMN deactivations, being these activity reductions associated with faster responses. Furthermore, it was observed that tDCS neural responses presented certain consistency across distinct fMRI modalities, while tACS did not. In sum, tDCS and tACS modulate fMRI-derived network dynamics differently. However, both effects seem to focus on DMN regions and the WM network-DMN shift, which are highly affected in aging and disease. Thus, albeit exploratory and needing further replication with larger samples, our results might provide a refined understanding of how the DMN functioning can be externally modulated through commonly used non-invasive brain stimulation techniques, which may be of eventual clinical relevance.

Intrinsic functional connectivity in social anxiety disorder with and without comorbid attention deficit hyperactivity disorder

Neuroimaging research about social anxiety disorder (SAD) points to hyperactivity in the fear circuit and altered connectivity between the fear circuit and the intrinsic connectivity networks that modulate it. We investigated intrinsic functional connectivity changes in SAD patients by taking into consideration the commonly overlooked comorbidity of attention deficit hyperactivity disorder (ADHD). We compared intrinsic functional connectivity alterations in 16 patients with pure SAD, 18 patients with SAD and comorbid ADHD and 21 healthy controls using seed-to-voxel functional connectivity analyses. Hypoconnectivity of the right fusiform gyrus with the left lingual gyrus was the unique difference between whole SAD group and healthy controls, while in the pure SAD group the fusiform gyrus displayed hypoconnectivity with the posterior default mode network (DMN) regions. In contrast, ADHD comorbidity was associated with hyperconnectivities of the salience network (SN) with the fusiform cortex and the posterior DMN regions, and hyperconnectivities of the posterior DMN with visual, somatosensory and motor cortices. The dichotomic dissociation of the SAD related functional connectivity changes into hypoconnectivities in the pure SAD group vs hyperconnectivities in the SAD-ADHD group leads also to the question, whether ADHD treatment can be considered an alternative for selected SAD cases.

Functional connectivity changes associated with fMRI neurofeedback of right inferior frontal cortex in adolescents with ADHD

Attention Deficit Hyperactivity Disorder (ADHD) is associated with poor self-control, underpinned by inferior fronto-striatal deficits. We showed previously that 18 ADHD adolescents over 11 runs of 8.5 min of real-time functional magnetic resonance neurofeedback of the right inferior frontal cortex (rIFC) progressively increased activation in 2 regions of the rIFC which was associated with clinical symptom improvement. In this study, we used functional connectivity analyses to investigate whether fMRI-Neurofeedback of rIFC resulted in dynamic functional connectivity changes in underlying neural networks.Whole-brain seed-based functional connectivity analyses were conducted using the two clusters showing progressively increased activation in rIFC as seed regions to test for changes in functional connectivity before and after 11 fMRI-Neurofeedback runs. Furthermore, we tested whether the resulting functional connectivity changes were associated with clinical symptom improvements and whether they were specific to fMRI-Neurofeedback of rIFC when compared to a control group who had to self-regulate another region.rIFC showed increased positive functional connectivity after relative to before fMRI-Neurofeedback with dorsal caudate and anterior cingulate and increased negative functional connectivity with regions of the default mode network (DMN) such as posterior cingulate and precuneus. Furthermore, the functional connectivity changes were correlated with clinical improvements and the functional connectivity and correlation findings were specific to the rIFC-Neurofeedback group.The findings show for the first time that fMRI-Neurofeedback of a typically dysfunctional frontal region in ADHD adolescents leads to strengthening within fronto-cingulo-striatal networks and to weakening of functional connectivity with posterior DMN regions and that this may be underlying clinical improvement.

Regional Prefrontal Resting-State Functional Connectivity in Posttraumatic Stress Disorder

BackgroundPrefrontal subregions, including the ventromedial prefrontal cortex (PFC), dorsomedial PFC, and dorsolateral PFC (DLPFC), are differentially implicated in the pathophysiology of posttraumatic stress disorder (PTSD), though few existing studies have examined subregional differences in resting-state functional connectivity (rsFC). We hypothesized that PTSD would involve weaker positive rsFC between ventromedial PFC, dorsomedial PFC, and other default mode network regions and increased negative rsFC between DLPFC and posterior default mode network regions. Additionally, we hypothesized that prefrontal regions exhibiting group differences in rsFC would be characterized by alterations in cortical thickness. MethodsParticipants included 36 healthy control subjects, 30 trauma-exposed control subjects, and 21 individuals with current DSM-IV PTSD resulting from community-acquired trauma. Participants completed the Clinician Administered PTSD Scale, questionnaires (Childhood Trauma Questionnaire, Adverse Childhood Events, Life Events Checklist, Beck Depression Inventory), structural neuroimaging, and resting-state functional magnetic resonance imaging. rsFC of DLPFC, ventromedial PFC, and dorsomedial PFC seeds was evaluated in SPM12 and CONN. Cortical thickness for regions with significant rsFC findings was assessed using FreeSurfer. ResultsRelative to both healthy control and trauma-exposed control subjects, individuals with PTSD showed increased negative rsFC between the DLPFC and a region of precuneus. This finding was associated with increased overall symptom severity but not with trauma load or childhood trauma exposure. Greater negative DLPFC-precuneus connectivity was associated with greater bilateral precuneus thickness. ConclusionsGiven participation of precuneus subregions in the central executive network, increased anticorrelation between right DLPFC and precuneus in this sample may reflect increased opposition between anterior and posterior central executive network hubs in PTSD.

Posterior cingulate cross-hemispheric functional connectivity predicts the level of consciousness in traumatic brain injury

Previous studies have demonstrated that altered states of consciousness are related to changes in resting state activity in the default-mode network (DMN). Anatomically, the DMN can be divided into anterior and posterior regions. The anterior DMN includes the perigenual anterior cingulate cortex and other medial prefrontal cortical regions, whereas the posterior DMN includes regions such as the posterior cingulate cortex (PCC) and the temporal parietal junction (TPJ). Although differential roles have been attributed to the anterior and posterior DMN regions, their exact contributions to consciousness levels remain unclear. To investigate the specific role of the posterior DMN in consciousness levels, we investigated 20 healthy controls (7 females, mean age = 33.6 years old) and 20 traumatic brain injury (TBI) patients (5 females, mean age = 43 years old) whose brain lesions were mainly restricted to the bilateral frontal cortex but retained a well-preserved posterior DMN (e.g., the PCC and the TPJ) and who exhibited varying levels of consciousness. We investigated the intra- and cross-functional connectivity strengths (FCSs) between the right/left PCC and the right/left TPJ and their correlation with consciousness levels. Significant reductions in both the intra- and cross-hemispheric FCSs were observed in patients compared with controls. A significant correlation with consciousness levels was observed only for the cross-hemispheric PCC-TPJ FCS but not for the intra-hemispheric PCC-TPJ FCS. Taken together, our results show that the cross-hemispheric posterior DMN is related to consciousness levels in a specific group of patients without posterior structural lesions. We therefore propose that the PCC may be central in maintaining consciousness through its cross-hemispheric FC with the TPJ.

The Self-Pleasantness Judgment Modulates the Encoding Performance and the Default Mode Network Activity.

In this functional magnetic resonance imaging (fMRI) study, we evaluated the effect of self-relevance on cerebral activity and behavioral performance during an incidental encoding task. Recent findings suggest that pleasantness judgments reliably induce self-oriented (internal) thoughts and increase default mode network (DMN) activity. We hypothesized that this increase in DMN activity would relate to increased memory recognition for pleasantly-judged stimuli (which depend on internally-oriented attention) but decreased recognition for unpleasantly-judged items (which depend on externally-oriented attention). To test this hypothesis, brain activity was recorded from 21 healthy participants while they performed a pleasantness judgment requiring them to rate visual stimuli as pleasant or unpleasant. One hour later, participants performed a surprise memory recognition test outside of the scanner. Thus, we were able to evaluate the effects of pleasant and unpleasant judgments on cerebral activity and incidental encoding. The behavioral results showed that memory recognition was better for items rated as pleasant than items rated as unpleasant. The whole brain analysis indicated that successful encoding (SE) activates the inferior frontal and lateral temporal cortices, whereas unsuccessful encoding (UE) recruits two key medial posterior DMN regions, the posterior cingulate cortex (PCC) and precuneus (PCU). A region of interest (ROI) analysis including classic DMN areas, revealed significantly greater involvement of the medial prefrontal cortex (mPFC) in pleasant compared to unpleasant judgments, suggesting this region’s involvement in self-referential (i.e., internal) processing. This area may be responsible for the greater recognition performance seen for pleasant stimuli. Furthermore, a significant interaction between the encoding performance (successful vs. unsuccessful) and pleasantness was observed for the PCC, PCU and inferior frontal gyrus (IFG). Overall, our results suggest the involvement of medial frontal and parietal DMN regions during the evaluation of self-referential pleasantness. We discuss these results in terms of the introspective referential of pleasantness judgments and the differential brain modulation based on internally- vs. externally-oriented attention during encoding.

Longitudinal assessment of default-mode brain function in aging

Age-related changes in the default-mode network (DMN) have been identified in prior cross-sectional functional magnetic resonance imaging studies. Here, we investigated longitudinal change in DMN activity and connectivity. Cognitively intact participants (aged 49–79 years at baseline) were scanned twice, with a 6-year interval, while performing an episodic memory task interleaved with a passive control condition. Longitudinal analyses showed that the DMN (control condition > memory task) could be reliably identified at both baseline and follow-up. Differences in the magnitude of task-induced deactivation in posterior DMN regions were observed between baseline and follow-up indicating reduced deactivation in these regions with increasing age. Although no overall longitudinal changes in within-network connectivity were found across the whole sample, individual differences in memory change correlated with change in connectivity. Thus, our results show stability of whole-brain DMN topology and functional connectivity over time in healthy older adults, whereas within-region DMN analyses show reduced deactivation between baseline and follow-up. The current findings provide novel insights into DMN functioning that may assist in identifying brain changes in patient populations, as well as characterizing factors that distinguish between normal and pathologic aging.

Investigating brain community structure abnormalities in bipolar disorder using path length associated community estimation

In this article, we present path length associated community estimation (PLACE), a comprehensive framework for studying node-level community structure. Instead of the well-known Q modularity metric, PLACE utilizes a novel metric, Ψ(PL), which measures the difference between intercommunity versus intracommunity path lengths. We compared community structures in human healthy brain networks generated using these two metrics and argued that Ψ(PL) may have theoretical advantages. PLACE consists of the following: (1) extracting community structure using top-down hierarchical binary trees, where a branch at each bifurcation denotes a collection of nodes that form a community at that level, (2) constructing and assessing mean group community structure, and (3) detecting node-level changes in community between groups. We applied PLACE and investigated the structural brain networks obtained from a sample of 25 euthymic bipolar I subjects versus 25 gender- and age-matched healthy controls. Results showed community structural differences in posterior default mode network regions, with the bipolar group exhibiting left-right decoupling.