Medial Temporal Lobe Subsystem Research Articles

Roles of the Default Mode Network in Different Aspects of Self-representation When Remembering Social Autobiographical Memories.

Autobiographical memory (AM) is episodic memory for personally experienced events, in which self-representation is more important than that in laboratory-based memory. Theoretically, self-representation in a social context is categorized as the interpersonal self (IS) referred to in a social interaction with a person or the social-valued self (SS) based on the reputation of the self in the surrounding society. Although functional neuroimaging studies have demonstrated the involvement of the default mode network (DMN) in self-representation, little is known about how the DMN subsystems contribute differentially to IS-related and SS-related AMs. To elucidate this issue, we used fMRI to scan healthy young adults during the recollection of AMs. We performed multivariate pattern analysis (MVPA) and assessed functional connectivity in the DMN subsystems: the midline core, medial temporal lobe (MTL), and dorsomedial pFC (dmPFC) subsystems. The study yielded two main sets of findings. First, MVPA revealed that all DMN subsystems showed significant classification accuracy between IS-related and nonsocial-self-related AMs, and IS-related functional connectivity of the midline core regions with the retrosplenial cortex of the MTL subsystem and the dmPFC of the dmPFC subsystem was significant. Second, MVPA significantly distinguished between SS-related and nonsocial-self-related AMs in the midline core and dmPFC subsystems but not in the MTL subsystem, and SS-related functional connectivity with the midline core regions was significant in the temporal pole and TPJ of the dmPFC subsystem. Thus, dissociable neural mechanisms in the DMN could contribute to different aspects of self-representation in social AMs.

Default mode network connectivity and social dysfunction in children with Attention Deficit/Hyperactivity Disorder

ObjectiveAttention Deficit/Hyperactivity Disorder (ADHD) negatively affects social functioning; however, its neurological underpinnings remain unclear. Altered Default Mode Network (DMN) connectivity may contribute to social dysfunction in ADHD. We investigated whether DMN's dynamic functional connectivity (dFC) alterations were associated with social dysfunction in individuals with ADHD. MethodsResting-state fMRI was used to examine DMN subsystems (dorsal medial prefrontal cortex (dMPFC), medial temporal lobe (MTL)) and the midline core in 40 male ADHD patients (7-10 years) and 45 healthy controls (HCs). Connectivity correlations with symptoms and demographic data were assessed. Group-based analyses compared rsFC between groups with two-sample t-tests and post-hoc analyses. ResultsSocial dysfunction in ADHD patients was related to reduced DMN connectivity, specifically in the MTL subsystem and the midline core. ADHD patients showed decreased dFC between parahippocampal cortex (PHC) and left superior frontal gyrus, and between ventral medial prefrontal cortex (vMPFC) and right middle frontal gyrus compared to HCs (MTL subsystem). Additionally, decreased dFC between posterior cingulate cortex (PCC), anterior medial prefrontal cortex (aMPFC), and right angular gyrus (midline core) was observed in ADHD patients relative to HCs. No abnormal connectivity was found within the dMPFC. ConclusionPreliminary findings suggest that DMN connectional abnormalities may contribute to social dysfunction in ADHD, providing insights into the disorder's neurobiology and pathophysiology.

Subsystem mechanisms of default mode network underlying white matter hyperintensity-related cognitive impairment.

Functional changes of default mode network (DMN) have been proven to be closely associated with white matter hyperintensity (WMH) related cognitive impairment (CI). However, subsystem mechanisms of DMN underlying WMH-related CI remain unclear. The present study recruited WMH patients (n=206) with mild CI and normal cognition, as well as healthy controls (HC, n=102). Static/dynamic functional connectivity (FC) of the DMN's three subsystems were calculated using resting-state functional MRI. K-means clustering analyses were performed to extract distinct dynamic connectivity states. Compared with the WMH-NC group, the WMH-MCI group displayed lower static FC within medial temporal lobe (MTL) and core subsystem, between core-MTL subsystem, as well as between core and dorsal medial prefrontal cortex subsystem. All these static alterations were positively associated with information processing speed (IPS). Regarding dynamic FC, the WMH-MCI group exhibited higher dynamic FC within MTL subsystem than the HC and WMH-NC groups. Altered dynamic FC within MTL subsystem mediated the relationship between WMH and memory span (indirect effect: -0.2251, 95% confidence interval [-0.6295, -0.0267]). Additionally, dynamic FCs of DMN subsystems could be clustered into two recurring states. For dynamic FCs within MTL subsystem, WMH-MCI subjects exhibited longer mean dwell time (MDT) and higher reoccurrence fraction (RF) in a sparsely connected state (State 2). Altered MDT and RF in State 2 were negatively associated with IPS. Taken together, these findings indicated static/dynamic FC of DMN subsystems can provide relevant information on cognitive decline from different aspects, which provides a comprehensive view of subsystem mechanisms of DMN underlying WMH-related CI.

Functional disconnection between subsystems of the default mode network in bipolar disorder

BackgroundDisruption in connectivity between default mode network (DMN) regions has previously been reported in bipolar disorder (BD). The current study aimed to investigate the dysfunction of the DMN subsystem in patients with BD during manic and depressive episodes and to explore its relationship with the symptoms of BD. MethodsFifty-two patients with bipolar disorder and 39 healthy controls were recruited. Eleven seed points were selected from three DMN subsystems. We performed seed-based resting-state functional connectivity (FC) analysis and obtained individual DMN FC matrices by computing the spatial correlations between pairs of FC maps. The strength of the connections within and between the three DMN subsystems, including the core subsystem, dorsal medial prefrontal cortex subsystem, and medial temporal lobe (MTL) subsystem, was used for group analyses. ResultsCompared with healthy controls, reduced FC between the core and MTL subsystem was observed in BD patients, especially in those with depressive episodes, but not in those with manic episodes. There were significant differences in core-MTL connectivity strength between the two patient groups during manic and depressive episodes. Moreover, core-MTL subsystem connectivity was negatively correlated with the depression scale. The FC within the core subsystem was negatively correlated with anxiety and negatively correlated with depression. ConclusionThis study provides evidence for an abnormal default network subsystem connection in bipolar disorder during manic and depressive episodes, revealing the neuropathological mechanism of the disease from the perspective of brain functional connectivity.

Functional connectivity of the default mode network subsystems in patients with major depressive episodes with mixed features

BackgroundThe neuroimaging mechanism of major depressive episodes with mixed features (MMF) is not clear.AimsThis study aimed to investigate the functional connectivity of the default mode network (DMN) subsystems among patients...

Abnormal topological parameters in the default mode network in patients with impaired cognition undergoing maintenance hemodialysis.

ObjectiveThe role of the default mode network (DMN) in the cognitive impairment experienced by patients with end-stage renal disease (ESRD) undergoing maintenance hemodialysis (MHD) remains unknown. This study tested the hypothesis that the topological architecture of the DMN plays a key role in ESRD-related cognitive impairment.MethodsFor this study, 43 ERSD patients receiving MHD and 41 healthy control (HC) volunteers matched for gender, age and education underwent resting-state functional magnetic resonance imaging examinations. DMN architecture was depicted by 20 selected DMN subregions. Graph theory approaches were applied to investigate multiple topological parameters within the DMN in resting state at the global, local and edge levels.ResultsGlobally, the MHD group exhibited topological irregularities as indicated by reduced values for the clustering coeffcient (Cp), normalized Cp (γ), world-index (σ), and local effciency (Eloc) compared with the HC group. Locally, the MHD group showed greater nodal betweenness in the left retrosplenial cortex (RC) compared with the HC group. At the edge level, the MHD group exhibited disconnected resting-state functional connections (RSFCs) in the medial temporal lobe (MTL) subsystem including the ventral medial prefrontal cortex (VMPC)–left posterior inferior parietal lobule, VMPC–right parahippocampal cortex (PC), and right RC–left PC RSFCs. Additionally, the VMPC–right PC RSFC was positively correlated with the Digit Span Test score and Eloc, and the right RC–left PC RSFC was positively correlated with the Montreal Cognitive Assessment score and Eloc in the MHD group.ConclusionsESRD patients undergoing MHD showed local inefficiency, abnormal nodal centralities, and hypoconnectivity within the DMN, implying that the functional differentiation and local information transmission efficiency of the DMN are disturbed in ESRD. The disconnected RSFCs in the MTL subsystem likely facilitated topological reconfiguration in the DMN of ESRD patients, leading to impairments of multidomain neurocognition including memory and emotion regulation.

Fornix alterations induce the disruption of default mode network in patients with adamantinomatous craniopharyngiomas

Adamantinomatous craniopharyngioma (ACPs) are rare embryonic tumors and often involve the hypothalamus. The underlying neural substrate of the hypothalamic involvement (HI)-related cognitive decline in patients with ACP is still unclear. We aimed to combine the multi-modal neuroimaging and histological characteristics of the ACP to explore the potential neural substrate of the HI-related cognitive decline. 45 patients with primary ACPs (invasive, 23; noninvasive, 22) and 52 healthy control subjects (HCs) were admitted to the cross-sectional study. No significant difference in cognitive domains was observed between HCs and patients with noninvasive ACPs (NACP). Patients with invasive ACPs (IACP) showed significantly lower working memory performance (WM, p = 0.002) than patients with NACP. The WM decline was correlated with the disruption of the medial temporal lobe (MTL) subsystem in the default mode network (DMN) (r = 0.45, p = 0.004). The increased radial diffusivity of the fornix, indicating demyelinating process, was correlated with the disruption of the MTL subsystem (r = -0.48, p = 0.002). Our study demonstrated that the fornix alterations link DMN disruption to HI-related cognitive decline in patients with ACPs. ACPs that invade the hypothalamus can provide a natural disease model to investigate the potential neural substrate of HI-related cognitive decline.

The passive recipient: Neural correlates of negative self‐view in depression

IntrodctionPrevious studies have argued that people tend to isolate themselves from negative information. This tendency is modulated by the individual's role in social interaction, that is, as an initiative actor (e.g., “I hit Tom”) or a passive recipient (e.g., “Paul hits me”). Depressed patients tend to focus on negative aspects of themselves and cope with situations passively. It is still an open question how the actor/recipient role affects the behavioral and neural responses to self in depression.MethodsThe present study adopted functional magnetic resonance imaging (fMRI) technology to investigate behavioral and neural responses to self (as an actor/recipient) in depressed patients and the matched healthy controls when attributing negative events.ResultsCompared with healthy controls, depressed patients showed more self‐attribution for negative events. Depressed patients showed increased brain activity in the dorsal medial prefrontal cortex (dmPFC) subsystem of the default mode network (DMN) when they played recipient role in self‐related negative events. Activity of the dmPFC subsystem was negatively correlated with depressed patients’ self‐attribution for negative events in recipient condition. While decreased brain activity in the medial temporal lobe (MTL) subsystem was observed in depressed patients when they played the actor or recipient role in self‐related negative events. Activity of the MTL subsystem was negatively correlated with depressed patients’ reaction time when they played recipient role in selfrelated negative events.ConclusionThese results implicated that depressed patients manifested the negative self‐view. Actor/recipient role affected their activation patterns in the DMN which were different from the healthy controls. The correlation between the abnormal brain activations of the DMN and the behavioral performances might manifest more easily when depressed patients played recipient role in negative events.

Difference in default mode network subsystems in autism across childhood and adolescence.

Differences in the default mode network are among the most replicated brain-level findings in autistic individuals. Furthermore, subregions within the default mode network are associated with cognitive functions such as mentalising that are immediately relevant to cognitive theories of autism. Recent evidence suggests that the default mode network comprises partially independent subsystems that are tied to dissociable cognitive processes, specifically a medial temporal lobe subsystem involved in memory retrieval, a dorsal medial prefrontal cortex subsystem involved in social processing and a posterior cingulate cortex – anterior medial prefrontal cortex system that ties the other subsystems together. This modular organisation is thought to arise in childhood development. The current analysis investigated differences in default mode network subsystems in 193 autistic boys and young men (5–18 years) and in a group of 208 age-matched boys and young men without a diagnosis using resting-state functional magnetic resonance imaging from the data repository of the Autism Brain Imaging Data Exchange. The results indicated a developmental trend towards greater modularisation of the default mode network across childhood and adolescence in autism, mostly driven by reduced between-subnetwork connection strength. In contrast, default mode network subnetwork organisation was relatively stable in the comparison group. We suggest that these differences reflect delayed maturation of the default mode network in autism.Lay abstractNeuroimaging research has identified a network of brain regions that are more active when we daydream compared to when we are engaged in a task. This network has been named the default mode network. Furthermore, differences in the default mode network are the most consistent findings in neuroimaging research in autism. Recent studies suggest that the default mode network is composed of subnetworks that are tied to different functions, namely memory and understanding others’ minds. In this study, we investigated if default mode network differences in autism are related to specific subnetworks of the default mode network and if these differences change across childhood and adolescence. Our results suggest that the subnetworks of the default mode network are less differentiated in autism in middle childhood compared to neurotypicals. By late adolescence, the default mode network subnetwork organisation was similar in the autistic and neurotypical groups. These findings provide a foundation for future studies to investigate if this developmental pattern relates to improvements in the integration of memory and social understanding as autistic children grow up.

Default mode network subsystem alterations in bipolar disorder during major depressive episode

BackgroundDefault mode network (DMN) has been widely reported to be altered in bipolar disorder during major depressive episode (BDD). Recent studies supported the idea that DMN is not an unitary system, but composed of smaller and distinct functional subsystems. The current study aimed to investigate the abnormal functional connectivity (FC) patterns of DMN subsystems in BDD. MethodsSeed-based FC method was applied to extract 11 DMN components in resting-state functional magnetic resonance imaging data acquired from 40 patients with BDD and 63 demographically matched healthy controls. ResultsPatients showed reduced FC between precuneus and all three DMN subsystems. Additionally, in the midline core, patients revealed increased FC between posterior cingutate cortex (PCC) seed and lateral orbitofrontal cortex. In the dorsomedial prefrontal cortex and medial temporal lobe subsystems, patients demonstrated increased FC with sensorimotor, visual, and salience network regions. Furthermore, the abnormal FC between the PCC seed and precuneus was correlated with high pessimism. LimitationsOur sample size is relatively small, limiting the power to detect subtle group differences and significant correlations between brain connectivity and clinical variables. In addition, most of our patients have been treated with medications. ConclusionOur findings revealed the abnormal FC patterns of DMN subdivision circuits and highlighted these abnormalities were associated the pathological mechanisms in BDD.

Primarily Disrupted Default Subsystems Cause Impairments in Inter-system Interactions and a Higher Regulatory Burden in Alzheimer's Disease.

Background: Intrinsically organized large-scale brain networks and their interactions support complex cognitive function. Investigations suggest that the default network (DN) is the earliest disrupted network and that the frontoparietal control network (FPCN) and dorsal attention network (DAN) are subsequently impaired in Alzheimer's disease (AD). These large-scale networks comprise different subsystems (DN: medial temporal lobe (MTL), dorsomedial prefrontal cortex (DM) subsystems and a Core; FPCN: FPCNA and FPCNB). Our previous research has indicated that different DN subsystems are not equally damaged in AD. However, changes in the patterns of interactions among these large-scale network subsystems and the underlying cause of the alterations in AD remain unclear. We hypothesized that disrupted DN subsystems cause specific impairments in inter-system interactions and a higher regulatory burden for the FPCNA.Method: To test this hypothesis, Granger causality analysis (GCA) was performed to explore effective functional connectivity (FC) pattern of these networks. The regional information flow strength (IFS) was calculated and compared across groups to explore changes in the subsystems and their inter-system interactions and the relationship between them. To investigate specific inter-system changes, we summed the inter-system IFS and performed correlation analyses of the bidirectional inter-system IFS, which was compared across groups. Additionally, correlation analyses of dynamic effective FC patterns were performed to reveal alterations in the temporal co-evolution of sets of inter-subsystem interactions. Furthermore, we used partial correlation analysis to quantify the FPCN's regulatory effects. Finally, we applied a support vector machine (SVM) linear classifier to probe which network most effectively discriminated patients from controls.Results: Compared with controls, AD patients showed a decreased intra-DN regional IFS, which was significantly related to the inter-network's IFS. The IFS between the DN subsystems and FPCN subsystems/DAN decreased. Critically, the correlation values of the decreased bidirectional IFS between the DN subsystems and FPCNA diminished. Additionally, the Core and DM play pivotal roles in disordered temporal co-evolution. Furthermore, the FPCNA showed enhanced regulation of the Core. Finally, the MTL subsystem and Core were effective at discriminating patients from controls.Conclusion: The predominantly disrupted DN subsystems caused impaired inter-system interactions and created a higher regulatory burden for the FPCNA.

Preferentially Disrupted Core Hubs Within the Default-Mode Network in Patients With End-Stage Renal Disease: A Resting-State Functional Magnetic Resonance Imaging Study.

Neuroimaging evidence implies that cognitive impairment in patients with end-stage renal disease (ESRD) is related to the disruption of the default-mode network (DMN). The DMN can be divided into three functionally independent subsystems, which include the cortical hub subsystem [consisting of the posterior cingulate cortex (PCC) and the anterior medial prefrontal cortex (aMPFC)], the dorsal medial prefrontal cortex (dMPFC) subsystem, and the medial temporal lobe (MTL) subsystem. However, it is unknown how the functional connectivity (FC) in DMN subsystems is differentially impaired in ESRD. This prospective study was carried out at the Affiliated Hospital of Qingdao University, China, between August 2018 and July 2020. Thirty-two ESRD patients and forty-five healthy controls (HCs) were recruited for this study and received resting-state functional magnetic resonance imaging (rs-fMRI) scanning, and FCs on predefined regions of interest (ROIs) were individually calculated in three DMN subsystems using both ROI- and seed-based FC analyses to examine FC alterations within and between DMN subsystems. The two-sample t-test was used for the comparisons between groups. We also tested the associations between FC changes and clinical information using Pearson's correlation analysis. The results demonstrated that ESRD patients, compared with HCs, exhibit reduced FC specifically within the cortical hubs and between the DMN hubs and two subsystems (the dMPFC and MTL subsystems). Moreover, the FC values between the aMPFC and PCC were positively correlated with creatinine and urea levels in the ESRD patients. Our results suggest that the cortical hubs (PCC and aMPFC) are preferentially disrupted and that other subsystems may be progressively damaged to a certain degree as the disease develops.

The subsystem mechanism of default mode network underlying rumination: A reproducible neuroimaging study

Rumination is a repetitive self-referential thinking style that is often interpreted as an expression of abnormalities of the default mode network (DMN) observed during “resting-state” in major depressive disorder (MDD). Recent evidence has demonstrated that the DMN is not unitary but can be further divided into 3 functionally heterogenous subsystems, although the subsystem mechanistically underlying rumination remains unclear. Due to the unconstrained and indirect correlational nature of previous resting-state fMRI studies on rumination's network underpinnings, a paradigm allowing direct investigation of network interactions during active rumination is needed. Here, with a modified continuous state-like paradigm, we induced healthy participants to ruminate or imagine objective scenarios (distraction, as a control condition) on 3 different MRI scanners. We compared functional connectivities (FC) of the DMN and its 3 subsystems between rumination and distraction states. Results yielded a highly reproducible and dissociated pattern. During rumination, within-DMN FC was generally decreased as compared to the distraction state. At the subsystem level, we found increased FC between the core and medial temporal lobe (MTL) subsystem as well as decreased FC between the core and dorsal medial prefrontal cortex (DMPFC) subsystem and within the MTL subsystem. Finally, subjects’ behavioral measures of rumination and brooding were negatively correlated with FC between the core and DMPFC subsystems. These results suggest active rumination involves enhanced constraint by the core subsystem on the MTL subsystem and decreased coupling between the core and DMPFC subsystem, allowing for more information exchange among those involved DMN components. Furthermore, the reproducibility of our findings provides a rigorous evaluation of their validity and significance.

The Functional Convergence and Heterogeneity of Social, Episodic, and Self-Referential Thought in the Default Mode Network.

The default mode network (DMN) is engaged in a variety of cognitive settings, including social, semantic, temporal, spatial, and self-related tasks. Andrews-Hanna et al. (2010; Andrews-Hanna 2012) proposed that the DMN consists of three distinct functional–anatomical subsystems—a dorsal medial prefrontal cortex (dMPFC) subsystem that supports social cognition; a medial temporal lobe (MTL) subsystem that contributes to memory-based scene construction; and a set of midline core hubs that are especially involved in processing self-referential information. We examined activity in the DMN subsystems during six different tasks: 1) theory of mind, 2) moral dilemmas, 3) autobiographical memory, 4) spatial navigation, 5) self/other adjective judgment, and 6) a rest condition. At a broad level, we observed similar whole-brain activity maps for the six contrasts, and some response to every contrast in each of the three subsystems. In more detail, both univariate analysis and multivariate activity patterns showed partial functional separation, especially between dMPFC and MTL subsystems, though with less support for common activity across the midline core. Integrating social, spatial, self-related, and other aspects of a cognitive situation or episode, multiple components of the DMN may work closely together to provide the broad context for current mental activity.

The effect of jet lag on the human brain: A neuroimaging study.

Jet lag is commonly experienced when travelers cross multiple time zones, leaving the wake–sleep cycle and intrinsic biological “clocks” out of synchrony with the current environment. The effect of jet lag on intrinsic cortical function remains unclear. Twenty‐two healthy individuals experiencing west‐to‐east jet lag flight were recruited. Brain structural and functional magnetic resonance studies, as well as psychological and neurohormonal tests, were carried out when participants returned from travel over six time zones and 50 days later when their jet lag symptoms had resolved. During jet lag, the functional brain network exhibited a small‐world topology that was shifted toward regularity. Alterations during jet lag relative to recovery included decreased basal ganglia‐thalamocortical network connections and increased functional connectivity between the medial temporal lobe subsystem and medial visual cortex. The lower melatonin and higher thyroid hormone levels during jet lag showed the same trend as brain activity in the right lingual gyrus. Although there was no significant difference between cortisol measurements during and after jet lag, cortisol levels were associated with temporal lobe activity in the jet lag condition. Brain and neuroendocrine changes during jet lag were related to jet lag symptoms. Further prospective studies are needed to explore the time course over which jet lag acts on the human brain.

Age-Related Decreases in Interhemispheric Resting-State Functional Connectivity and Their Relationship With Executive Function.

Age-related alterations of functional brain networks contribute to cognitive decline. Current theories indicate that age-related intrinsic brain functional reorganization may be a critical marker of cognitive aging. Yet, little is known about how intrinsic interhemispheric functional connectivity changes with age in adults, and how this relates to critical executive functions. To address this, we examined voxel-mirrored homotopic connectivity (VMHC), a metric that quantifies interhemispheric communication, in 93 healthy volunteers (age range: 19–85) with executive function assessment using the Delis-Kaplan Executive Function System (D-KEFS) scales. Resting functional MRI data were analyzed to assess VMHC, and then a multiple linear regression model was employed to evaluate the relationship between age and the whole-brain VMHC. We observed age-related reductions in VMHC of ventromedial prefrontal cortex (vmPFC) and hippocampus in the medial temporal lobe subsystem, dorsal anterior cingulate cortex and insula in salience network, and inferior parietal lobule in frontoparietal control network. Performance on the color-word inhibition task was associated with VMHC of vmPFC and insula, and VMHC of vmPFC mediated the relationship between age and CWIT inhibition reaction times. The percent ratio of correct design scores in design fluency test correlated positively with VMHC of the inferior parietal lobule. The current study suggests that brain interhemispheric functional alterations may be a promising new avenue for understanding age-related cognitive decline.

Human hippocampal CA3 damage disrupts both recent and remote episodic memories.

Neocortical-hippocampal interactions support new episodic (event) memories, but there is conflicting evidence about the dependence of remote episodic memories on the hippocampus. In line with systems consolidation and computational theories of episodic memory, evidence from model organisms suggests that the cornu ammonis 3 (CA3) hippocampal subfield supports recent, but not remote, episodic retrieval. In this study, we demonstrated that recent and remote memories were susceptible to a loss of episodic detail in human participants with focal bilateral damage to CA3. Graph theoretic analyses of 7.0-Tesla resting-state fMRI data revealed that CA3 damage disrupted functional integration across the medial temporal lobe (MTL) subsystem of the default network. The loss of functional integration in MTL subsystem regions was predictive of autobiographical episodic retrieval performance. We conclude that human CA3 is necessary for the retrieval of episodic memories long after their initial acquisition and functional integration of the default network is important for autobiographical episodic memory performance.

Functional fractionation of default mode network in first episode schizophrenia

A disruption in the connectivity between brain regions may underlie the core pathology in schizophrenia. One of the most consistent observations in human functional imaging is a network of brain regions referred to as the default network (DMN) that contains core subsystem, the dorsomedial prefrontal cortex (dMPFC) subsystem and the medial temporal lobe (MTL) subsystem, with differential contributions. The goal of this study was to examine abnormalities of different DMN subsystems in first episode schizophrenia and associations between these abnormalities and individual psychopathology. We recruited 203 patients and 131 healthy controls. A seed-based resting-state functional connectivity (RSFC) analysis on the 2D surface was conducted. Individual DMN functional connectivity matrices were then obtained by calculating spatial correlations between pairs of RSFC maps, characterizing the functional fractionation of the DMN. Patients showed patterns similar to controls but markedly reduced strength of DMN fractionation, with the degree centrality of the MTL subsystem significantly reduced, including the posterior inferior parietal lobule (pIPL), parahippocampal cortex (PHC) and lateral temporal cortex (LTC). Patients also exhibited hypo-connectivity within the MTL subsystem and between the MTL and dMPFC subsystems. Clinical symptoms were negatively correlated with degree centrality of LTC, pIPL and PHC in patients. Hyper-fractionation of different DMN components implied that communication and coordination throughout the dissociated components of the DMN are functionally over-segregated in schizophrenia. The associations between the hyper-fractionation with clinical symptoms suggest a role of the high fractionation in the DMN in the abnormal neuropathology observed in schizophrenia.

A role for the medial temporal lobe subsystem in guiding prosociality: the effect of episodic processes on willingness to help others.

Why are we willing to help others? Recent behavioral work on episodic processes (i.e. the ability to represent an event that is specific in time and place) suggests that imagining and remembering scenes of helping a person in need increases intentions to help. Here, we provide insight into the cognitive and neural mechanisms that enhance prosocial intentions via episodic simulation and memory. In Experiment 1, we scanned participants using functional neuroimaging as they imagined and remembered helping episodes, and completed non-episodic control conditions accounting for exposure to the story of need and conceptual priming of helping. Analyses revealed that activity in the medial temporal lobe (MTL) subsystem, as well as the right temporoparietal junction (RTPJ) predicted the effect of conditions on the strength of prosocial intentions. In Experiment 2, we used transcranial magnetic stimulation to disrupt activity in the RTPJ, and better isolate the contribution of MTL subsystem to prosocial intentions. The effect of conditions on willingness to help remained even when activity in the RTPJ was disrupted, suggesting that activity in the MTL subsystem may primarily support this prosocial effect. It seems our willingness to help may be guided, in part, by how easily we can construct imagined and remembered helping episodes.

Functional connectivity of the default mode network is associated with prospection in schizophrenia patients and individuals with social anhedonia

BackgroundProspection, which is closely related to negative symptoms in patients with schizophrenia, is mainly associated with the Default Mode Network (DMN). Although abnormalities of the DMN have been reported in schizophrenia patients and at-risk individuals, little is known about the relationship between functional connectivity of the DMN and prospection in these clinical and subclinical populations. MethodStudy 1 recruited 40 schizophrenia patients and 29 healthy controls, while 31 individuals with social anhedonia (SocAhn) and 28 controls participated in Study 2. Participants in both studies were asked to complete a prospection task and underwent resting-state functional MRI scans. Eleven regions of interest (ROIs) in the DMN were defined. Functional connectivity between each ROI and whole brain voxels were calculated and compared between groups (schizophrenia vs. control and SocAhn vs. control). Correlation analysis was conducted between altered functional connectivity and prospection variables in the schizophrenia and SocAhn groups. ResultsSchizophrenia patients showed both hyper-connectivity and hypo-connectivity at the medial temporal lobe (MTL) subsystem of the DMN. Decreased connectivity between the ventral medial prefrontal cortex (vMPFC) and the right superior temporal gyrus (rSTG) was correlated with poor thought/emotion details in prospection. In individuals with SocAhn, decreased connectivity between the retrosplenial cortex (Rsp), a region of the MTL subsystem, and the right fusiform gyrus, was found and this was correlated with their prospection performance. ConclusionAltered functional connectivity of the key nodes of the MTL subsystem was found in both patients with schizophrenia and individuals with SocAhn. Moreover, hypo-connectivity of the vMPFC was found to be correlated with prospection impairments in schizophrenia patients.