Cortical Midline Regions Research Articles

Neurophysiological Oscillatory Mechanisms Underlying the Effect of Mirror Visual Feedback-Induced Illusion of Hand Movements on Nociception and Cortical Activation.

Mirror Visual Feedback (MVF)-induced illusion of hand movements produces beneficial effects in patients with chronic pain. However, neurophysiological mechanisms underlying these effects are poorly known. In this preliminary study, we test the novel hypothesis that such an MVF-induced movement illusion may exert its effects by changing the activity in midline cortical areas associated with pain processing. Electrical stimuli with individually fixed intensity were applied to the left hand of healthy adults to produce painful and non-painful sensations during unilateral right-hand movements with such an MVF illusion and right and bilateral hand movements without MVF. During these events, electroencephalographic (EEG) activity was recorded from 64 scalp electrodes. Event-related desynchronization (ERD) of EEG alpha rhythms (8-12 Hz) indexed the neurophysiological oscillatory mechanisms inducing cortical activation. Compared to the painful sensations, the non-painful sensations were specifically characterized by (1) lower alpha ERD estimated in the cortical midline, angular gyrus, and lateral parietal regions during the experimental condition with MVF and (2) higher alpha ERD estimated in the lateral prefrontal and parietal regions during the control conditions without MVF. These preliminary results suggest that the MVF-induced movement illusion may affect nociception and neurophysiological oscillatory mechanisms, reducing the activation in cortical limbic and default mode regions.

Menopause Status and Within-Group Differences in Chronological Age Affect the Functional Neural Correlates of Spatial Context Memory in Middle-Aged Females.

Reductions in the ability to encode and retrieve past experiences in rich spatial contextual detail (episodic memory) are apparent by midlife-a time when most females experience spontaneous menopause. Yet, little is known about how menopause status affects episodic memory-related brain activity at encoding and retrieval in middle-aged premenopausal and postmenopausal females, and whether any observed group differences in brain activity and memory performance correlate with chronological age within group. We conducted an event-related task fMRI study of episodic memory for spatial context to address this knowledge gap. Multivariate behavioral partial least squares was used to investigate how chronological age and retrieval accuracy correlated with brain activity in 31 premenopausal females (age range, 39.55-53.30 years; mean age, 44.28 years; SD age, 3.12 years) and 41 postmenopausal females (age range, 46.70-65.14 years; mean age, 57.56 years; SD age, 3.93 years). We found that postmenopausal status, and advanced age within postmenopause, was associated with lower spatial context memory. The fMRI analysis showed that only in postmenopausal females, advanced age was correlated with decreased activity in occipitotemporal, parahippocampal, and inferior parietal cortices during encoding and retrieval, and poorer spatial context memory performance. In contrast, only premenopausal females exhibited an overlap in encoding and retrieval activity in angular gyrus, midline cortical regions, and prefrontal cortex, which correlated with better spatial context retrieval accuracy. These results highlight how menopause status and chronological age, nested within menopause group, affect episodic memory and its neural correlates at midlife.SIGNIFICANCE STATEMENT This is the first fMRI study to examine how premenopause and postmenopause status affect the neural correlates of episodic memory encoding and retrieval, and how chronological age contributes to any observed group similarities and differences. We found that both menopause status (endocrine age) and chronological age affect spatial context memory and its neural correlates. Menopause status directly affected the direction of age-related and performance-related correlations with brain activity in inferior parietal, parahippocampal, and occipitotemporal cortices across encoding and retrieval. Moreover, we found that only premenopausal females exhibited cortical reinstatement of encoding-related activity in midline cortical, prefrontal, and angular gyrus, at retrieval. This suggests that spatial context memory abilities may rely on distinct brain systems at premenopause compared with postmenopause.

Cortical networks for recognition of speech with simultaneous talkers

The relative contributions of superior temporal vs. inferior frontal and parietal networks to recognition of speech in a background of competing speech remain unclear, although the contributions themselves are well established. Here, we use fMRI with spectrotemporal modulation transfer function (ST-MTF) modeling to examine the speech information represented in temporal vs. frontoparietal networks for two speech recognition tasks with and without a competing talker. Specifically, 31 listeners completed two versions of a three-alternative forced choice competing speech task: “Unison” and “Competing”, in which a female (target) and a male (competing) talker uttered identical or different phrases, respectively. Spectrotemporal modulation filtering (i.e., acoustic distortion) was applied to the two-talker mixtures and ST-MTF models were generated to predict brain activation from differences in spectrotemporal-modulation distortion on each trial. Three cortical networks were identified based on differential patterns of ST-MTF predictions and the resultant ST-MTF weights across conditions (Unison, Competing): a bilateral superior temporal (S-T) network, a frontoparietal (F-P) network, and a network distributed across cortical midline regions and the angular gyrus (M-AG). The S-T network and the M-AG network responded primarily to spectrotemporal cues associated with speech intelligibility, regardless of condition, but the S-T network responded to a greater range of temporal modulations suggesting a more acoustically driven response. The F-P network responded to the absence of intelligibility-related cues in both conditions, but also to the absence (presence) of target-talker (competing-talker) vocal pitch in the Competing condition, suggesting a generalized response to signal degradation. Task performance was best predicted by activation in the S-T and F-P networks, but in opposite directions (S-T: more activation = better performance; F-P: vice versa). Moreover, S-T network predictions were entirely ST-MTF mediated while F-P network predictions were ST-MTF mediated only in the Unison condition, suggesting an influence from non-acoustic sources (e.g., informational masking) in the Competing condition. Activation in the M-AG network was weakly positively correlated with performance and this relation was entirely superseded by those in the S-T and F-P networks. Regarding contributions to speech recognition, we conclude: (a) superior temporal regions play a bottom-up, perceptual role that is not qualitatively dependent on the presence of competing speech; (b) frontoparietal regions play a top-down role that is modulated by competing speech and scales with listening effort; and (c) performance ultimately relies on dynamic interactions between these networks, with ancillary contributions from networks not involved in speech processing per se (e.g., the M-AG network).

Efficiency of Heterogenous Functional Connectomes Explains Variance in Callous-Unemotional Traits After Computational Lesioning of Cortical Midline and Salience Regions.

Introduction: Callous-unemotional (CU) traits are a youth antisocial phenotype hypothesized to be a result of differences in the integration of multiple brain systems. However, mechanistic insights into these brain systems are a continued challenge. Where prior work describes activation and connectivity, new mechanistic insights into the brain's functional connectome can be derived by removing nodes and quantifying changes in network properties (hereafter referred to as computational lesioning) to characterize connectome resilience and vulnerability. Methods: Here, we study the resilience of connectome integration in CU traits by estimating changes in efficiency after computationally lesioning individual-level connectomes. From resting-state data of 86 participants (48% female, age 14.52 ± 1.31) drawn from the Nathan Kline institute's Rockland study, individual-level connectomes were estimated using graphical lasso. Computational lesioning was conducted both sequentially and by targeting global and local hubs. Elastic net regression was applied to determine how these changes explained variance in CU traits. Follow-up analyses characterized modeled node hubs, examined moderation, determined impact of targeting, and decoded the brain mask by comparing regions to meta-analytic maps. Results: Elastic net regression revealed that computational lesioning of 23 nodes, network modularity, and Tanner stage explained variance in CU traits. Hub assignment of selected hubs differed at higher CU traits. No evidence for moderation between simulated lesioning and CU traits was found. Targeting global hubs increased efficiency and targeting local hubs had no effect at higher CU traits. Identified brain mask meta-analytically associated with more emotion and cognitive terms. Although reliable patterns were found across participants, adolescent brains were heterogeneous even for those with a similar CU traits score. Conclusion: Adolescent brain response to simulated lesioning revealed a pattern of connectome resiliency and vulnerability that explains variance in CU traits, which can aid prediction of youth at greater risk for higher CU traits.

Neural signal variability relates to maladaptive rumination in depression

Rumination is a common feature of depression and predicts the onset and maintenance of depressive episodes. Maladaptive and adaptive subtypes of rumination contribute to distinct outcomes, with brooding worsening negative mood and reflection related to fewer depression symptoms in healthy populations. Neuroimaging studies have implicated several cortical midline and lateral prefrontal brain regions in rumination. Recent research indicates that blood oxygen level-dependent (BOLD) signal variability may be a novel predictor of cognitive flexibility. However, no prior studies have investigated whether brooding and reflection are associated with distinct patterns of BOLD signal variability in depression. We collected resting-state fMRI data for 79 women with different depression histories: no history, past history, and current depression. We examined differences in BOLD signal variability (BOLDSD) related to rumination subtypes for the following regions of interest previously implicated in rumination: amygdala, medial prefrontal, anterior cingulate, posterior cingulate, and dorsolateral prefrontal cortices (dlPFC). Rumination subtype was associated with BOLDSD in the dlPFC, with greater levels of brooding associated with lower BOLDSD in the dlPFC, even after controlling for depression severity. Depression history was related to BOLDSD in the dlPFC, with reduced BOLDSD in those with current depression versus no history of depression. These findings provide a novel demonstration of the neural circuitry associated with maladaptive rumination in depression and implicate decreased prefrontal neural signal variability in the pathophysiology of depression.

Fronto—Parietal Regions Predict Transient Emotional States in Emotion Modulated Response Inhibition via Low Frequency and Beta Oscillations

The current study evaluated the impact of task-relevant emotion on inhibitory control while focusing on midline cortical regions rather than brain asymmetry. Single-trial time-frequency analysis of electroencephalography recordings linked with response execution and response inhibition was done while thirty-four participants performed the emotion modulated stop-signal task. To evaluate individual differences across decision-making processes involved in inhibitory control, a hierarchical drift-diffusion model was used to fit data from Go-trials for each of the 34 participants. Response threshold in the early processing stage for happy and disgust emotions could be distinguished from the later processing stage at the mid-parietal and mid-frontal regions, respectively, by the single-trial power increments in low frequency (delta and theta) bands. Beta desynchronization in the mid-frontal region was specific for differentiating disgust from neutral emotion in the early as well as later processing stages. The findings are interpreted based on the influence of emotional stimuli on early perceptual processing originating as a bottom-up process in the mid-parietal region and later proceeding to the mid-frontal region responsible for cognitive control processing, which resulted in enhanced inhibitory performance. The results show the importance of mid-frontal and mid-parietal regions in single-trial dynamics of inhibitory control processing.

The Reflection of Self-Esteem on the Brain Structure: A Voxel Based Morphometry Study in Healthy Young Adults.

Low self-esteem is a known risk factor for mental illnesses. Neuroimaging studies have identified evidence for a functional association between default mode network (DMN) and self-esteem levels. However, it is not clear whether there is a similar association between trait self-esteem and the structures composing DMN. This study aimed to investigate the relationship between the DMN associated brain structures and trait self-esteem. We obtained 3T structural magnetic resonance imaging (MRI) data of 75 healthy subjects and detected anatomical regions correlated with their Rosenberg Self-Esteem scores via voxel-based morphometry (VBM). We found positive associations between self-esteem and regional grey matter volumes in the right temporoparietal junction/inferior parietal lobule (BA 39), cortical midline regions at precuneus/dorsal cingulate cortex (BA 31), rostral and dorsal anterior cingulate cortices (BA 32). The results of the current study support the fMRI studies suggesting self-esteem levels associated with DMN. Further neuroimaging studies should consider the functional and structural coupling of the default mode network during the execution of the functions related to self-esteem.

Cortical midline structures associated with rumination in women with PTSD

Elevated rumination, characterized by repetitive, negative self-focused cognition, is common in posttraumatic stress disorder (PTSD) and has been shown to predict the onset and maintenance of the disorder. Neuroimaging research has implicated cortical midline brain structures, including the rostral anterior cingulate cortex (rACC), posterior cingulate cortex (PCC), and isthmus cingulate (IsthCing), in rumination in healthy and depressed populations. While past research has revealed dysfunction in cortical midline regions in PTSD, no studies have yet investigated the structural and functional neural mechanisms underlying rumination in women with PTSD. In the current study, we used structural MRI and resting-state fMRI to examine relationships between rumination and brain volume, as well as resting-state functional connectivity (rsFC) of cortical midline structures in women with PTSD due to interpersonal trauma (N = 71). We performed multiple linear regression analyses to relate brain volume in rACC, PCC, and IsthCing regions to self-reported rumination, after controlling for age and total intracranial volume. We also conducted standard seed-based voxelwise rsFC analyses for significant regions identified in the structural analysis. We found a significant relationship between greater rumination and volume in the left IsthCing (p = .025). Results from the rsFC analyses revealed a significant relationship between greater rumination and diminished rsFC between the left IsthCing and left precuneus (pFWE < .05). These findings provide novel support for alterations in the neural substrates of ruminative thought in women with PTSD. More broadly, we discuss clinical implications for targeted interventions to reduce rumination through psychotherapy or non-invasive brain stimulation.

Changes in the neural correlates of self-blame following mindfulness-based cognitive therapy in remitted depressed participants

Mindfulness-Based-Cognitive-Therapy (MBCT) reduces vulnerability for relapse into depression by helping individuals to counter tendencies to engage in maladaptive repetitive patterns of thinking and respond more compassionately to negative self-judgment. However, little is known about the neural correlates underlying these effects. To elucidate these correlates, we investigated fMRI brain activation during a task eliciting feelings of blaming oneself or others. Sixteen participants in remission from major depressive disorder (MDD) completed fMRI assessments before and after MBCT, alongside self-reported levels of self-compassion, mindfulness, and depression symptoms. Analyses of self-blame versus other-blame contrasts showed a reduction in activation in the bilateral dorsal anterior cingulate/medial superior frontal gyrus after MBCT compared to baseline. Further, exploratory analyses showed that increases in self-kindness after MBCT correlated with reduced activation in the posterior cingulate cortex (PCC)/precuneus in self-blame versus rest contrasts. These findings suggest that MBCT is associated with a reduction in activations in cortical midline regions to self-blame which may be mediated by increasing self-kindness. However, this is a small, uncontrolled study with 16 participants and therefore our results will need confirmation in a controlled study.

Effective connectivity during autobiographical memory search.

IntroductionWe used dynamic causal modeling (DCM) to examine effective connectivity during cued autobiographical memory (AM) search in a left‐hemispheric network consisting of six major regions within the large network of brain regions recruited during memory retrieval processes.MethodsFunctional MRI data were acquired while participants were shown verbal cues describing common life events and requested to search for a personal memory associated with the cue. We examined directed couplings between the ventromedial (vmPFC), dorsomedial (dmPFC), and dorsolateral prefrontal cortices (dlPFC), hippocampus, angular gyrus, and the posterior midline cortex (RSC/PCC/Prec).ResultsDuring AM search, the vmPFC, dlPFC, and RSC/PCC/Prec acted as primary drivers of activity in the rest of the network. Moreover, when AM search completed successfully (Hits), the effective connectivity of the hippocampus on the vmPFC and angular gyrus was up‐modulated. Likewise, there was an increase in the influence of the RSC/PCC/Prec in the activity of the dlPFC and dmPFC. Further analysis indicated that the modulation observed during Hits is primarily a distributed phenomenon that relies on the interplay between different brain regions.ConclusionThese results suggest that prefrontal and posterior midline cortical regions together with the dlPFC largely coordinate the processes underlying AM search, setting up the conditions on which the angular gyrus and the hippocampus may act upon when the outcome of the search is successful.

M49. BEHAVIOURAL SOCIAL COGNITION IN SCHIZOPHRENIA SPECTRUM DISORDERS IN COMPARISON TO AUTISM SPECTRUM DISORDER: A SYSTEMATIC REVIEW AND META-ANALYSIS

BackgroundSchizophrenia spectrum disorders (SSDs) and autism spectrum disorder (ASD) both feature social cognitive deficits, which are highly debilitating. These include lower-level processes (e.g. emotion recognition), thought to be subserved by a frontoparietal mirroring network, and higher-level mentalizing processes (e.g. theory of mind), involving cortical midline and lateral temporal brain regions. Across both disorders, impairments in social cognition persist over time, drive disability, and predict functional outcome. Overlapping symptoms in SSDs and ASD have long been recognized, particularly in the realm of social deficits. However, despite some studies including both individuals with SSDs and ASD showing similar levels of social cognitive impairment, including lower-level and higher-level deficits, results are mixed. Thus, our objective was to determine based on the extant literature how deficits in social cognition diverge or overlap between individuals with SSDs and ASD by conducting a systematic review and meta-analysis of studies directly comparing these groups on behavioural social cognitive measures.MethodsLiterature searches were conducted in MEDLINE, Embase, PsycINFO, and Web of Science to identify articles that utilized behavioural measures to assess social cognition in both SSD and ASD samples. Of 3682 articles identified, 28 met all inclusion criteria. Across the accepted articles, lower-level (e.g. facial and/or context-embedded emotion recognition) and higher-level (e.g. intention understanding, perspective taking) social cognitive measures were identified, and random-effects meta-analyses were conducted for each category. A separate meta-analysis was also conducted for the Reading the Mind in the Eyes test given that it was the most commonly used social cognitive metric. Effect sizes were estimated using Hedges’ g. Homogeneity of effects and publication bias were also assessed for each meta-analysis.ResultsA significant difference in lower-level social cognitive performance was found between individuals with SSDs and ASD, with the SSD group performing better than the ASD group (Hedges’ g = 0.30, 95% CI [0.05, 0.56], p = .018). In contrast, there was no significant difference in higher-level social cognitive performance between SSD and ASD groups (Hedges’ g = -0.14, 95% CI [-0.52, 0.24], p = .46). Similarly, the Reading the Mind in the Eyes test meta-analysis revealed no significant difference in effect sizes between disorders (Hedges’ g = 0.24, 95% CI [-0.07, 0.55], p = .14). Effect size distributions were significantly heterogeneous in all three cases (all p < .001).DiscussionBased on meta-analyses of the extant literature, both shared and differential social cognitive deficits may be present between individuals with SSDs and ASD. Though no differences were detected between SSD and ASD groups on higher-level social cognitive tasks or the Reading the Mind in the Eyes test, lower-level social cognitive deficits were found to be more severe in individuals with ASD than SSDs. Notably, the majority of studies included in the meta-analyses had small sample sizes, and heterogeneity of effect sizes was apparent. Thus, studies including larger sample sizes and validated measures of social cognition in conjunction with other methodologies are needed to substantiate these results, and better understand the shared and unique behavioural underpinnings and associated neural circuit abnormalities underlying social cognitive deficits in SSDs and ASD.

Functional neural correlates of psychopathy: a meta-analysis of MRI data

Neuroimaging studies over the last two decades have begun to specify the neurobiological correlates of psychopathy, a personality disorder that is strongly related to criminal offending and recidivism. Despite the accumulation of neuroimaging studies of psychopathy, a clear and comprehensive picture of the disorder’s neural correlates has yet to emerge. The current study is a meta-analysis of functional MRI studies of psychopathy. Multilevel kernel density analysis was used to identify consistent findings across 25 studies (460 foci) of task-related brain activity. Psychopathy was associated with increased task-related activity predominantly in midline cortical regions overlapping with the default mode network (dorsomedial prefrontal cortex, posterior cingulate, and precuneus) as well as medial temporal lobe (including amygdala). Psychopathy was related to decreased task-related activity in a region of the dorsal anterior cingulate cortex overlapping with the salience network. These findings challenge predominant theories of amygdala hypoactivity and highlight the potential role of hyperactivity in medial default mode network regions and hypoactivity in a key node of the salience network during task performance in psychopathy.

Strong health messages increase audience brain coupling

Mass media messaging is central for health communication. The success of these efforts, however, depends on whether health messages resonate with their target audiences. Here, we used electroencephalography (EEG) to capture brain responses of young adults - an important target group for alcohol prevention - while they viewed real-life video messages of varying perceived message effectiveness about risky alcohol use. We found that strong messages, which were rated to be more effective, prompted enhanced inter-subject correlation (ISC). In further analyses, we linked ISC to subsequent drinking behavior change and used time-resolved EEG-ISC to model functional neuroimaging data (fMRI) of an independent audience. The EEG measure was not only related to sensory-perceptual brain regions, but also to regions previously related to successful messaging, i.e., cortical midline regions and the insula. The findings suggest EEG-ISC as a marker for audience engagement and effectiveness of naturalistic health messages, which could quantify the impact of mass communication within the brains of small target audiences.

Clarifying the neural substrates of threat and safety reversal learning in humans

Responding flexibly to sources of threat and safety is critical to the adaptive regulation of emotions, including fear. At a neural systems level, such flexibility is thought to rely on an extended neural circuitry involving the dorsal anterior cingulate cortex (dACC) and ventromedial prefrontal cortices (vmPFC), although precisely how this occurs remains unclear. Using a novel fear reversal task and functional magnetic resonance imaging (fMRI), we examined the neural correlates of threat and safety reversal learning and their associations with individual differences in anxious responding in a large sample of healthy adolescents and young adults. Overall, participants demonstrated successful threat and safety reversal learning, as indexed by subjective ratings. At a whole-brain level, threat reversal was associated with significant activation of the bilateral anterior insular cortex and dACC, in particular its rostral subregion. Conversely, safety reversal led to significant activation of the anterior vmPFC, together with posterior mid-line regions. Further analyses of regional responses suggested a more selective role for the rostral dACC in threat signal updating, as well as a direct association of its activity with participants’ change in subjective anxious arousal to the reversed threat. Taken together, our findings complement existing neurocircuitry models of human fear regulation, particularly regarding the importance of midline cortical regions, and provide further insights into their specific contribution to flexible threat-safety signal processing. In particular, our results suggest that rostral dACC function may be more centrally involved in regulating levels of anxious arousal when flexibility is required. They also raise important questions regarding the vmPFC’s role in safety learning, particularly involving its hypothesized subregional contributions to response inhibitory versus stimulus value processing functions.

Structure/function interrelationships in patients with schizophrenia who have persistent auditory verbal hallucinations: A multimodal MRI study using parallel ICA

There is accumulating neuroimaging evidence for both structural and functional abnormalities in schizophrenia patients with persistent auditory verbal hallucinations (AVH). So far, the direct interrelationships between altered structural and functional changes underlying AVH are unknown. Recently, it has become possible to reveal hidden patterns of neural dysfunction not sufficiently captured by separate analysis of these two modalities. A data-driven fusion method called parallel independent component analysis (p-ICA) is able to identify maximally independent components of each imaging modality as well as the link between them. In the present study, we utilized p-ICA to study covarying components among gray matter volume maps computed from structural MRI (sMRI) and fractional amplitude of low-frequency fluctuations (fALFF) maps computed from resting-state functional MRI (rs-fMRI) data of 15 schizophrenia patients with AVH, 16 non-hallucinating schizophrenia patients (nAVH), and 19 healthy controls (HC). We found a significant correlation (r = 0.548, n = 50, p < .001) between a sMRI component and a rs-fMRI component, which was significantly different between the AVH and non AVH group (nAVH). The rs-fMRI component comprised temporal cortex and cortical midline regions, the sMRI component included predominantly fronto-temporo-parietal regions. Distinct clinical features, as measured by the Psychotic Symptoms Rating Scale (PSYRATS), were associated with two different modality specific rs-fMRI components. There was a significant correlation between a predominantly parietal resting-state network and the physical dimension of PSYRATS and the posterior cingulate/temporal cortex network and the emotional dimension of PSYRATS. These data suggest AVH-specific interrelationships between intrinsic network activity and GMV, together with modality-specific associations with distinct symptom dimensions of AVH.

The Threatful Self: Midbrain Functional Connectivity to Cortical Midline and Parietal Regions During Subliminal Trauma-Related Processing in PTSD

Background The innate alarm system consists of a subcortical network of interconnected midbrain, lower brainstem, and thalamic nuclei, which together mediate the detection of evolutionarily-relevant stimuli. The periaqueductal gray is a midbrain structure innervated by the innate alarm system that coordinates the expression of defensive states following threat detection. In participants with post-traumatic stress disorder, the periaqueductal gray displays overactivation during the subliminal presentation of trauma-related stimuli as well as altered resting-state functional connectivity. Aberrant functional connectivity is also reported in post-traumatic stress disorder for the default-mode network, a large-scale brain network recruited during self-referential processing and autobiographical memory. Here, research lacks investigation on the extent to which functional interactions are displayed between the midbrain and the large-scale cortical networks in post-traumatic stress disorder. Methods Using a subliminal threat presentation paradigm, we investigated psycho-physiological interactions during functional neuroimaging in participants with post-traumatic stress disorder (n = 26) and healthy control subjects (n = 20). Functional connectivity of the periaqueductal gray was investigated across the whole-brain of each participant during subliminal exposure to trauma-related and neutral word stimuli. Results As compared to controls during subliminal threat presentation, the post-traumatic stress disorder group showed significantly greater periaqueductal gray functional connectivity with regions of the default-mode network (i.e., angular gyrus, precuneus, superior frontal gyrus). Moreover, multiple regression analyses revealed that the functional connectivity between the periaqueductal gray and the regions of the default-mode network correlated positively to symptoms of avoidance and state dissociation in post-traumatic stress disorder. Conclusion Given that the periaqueductal gray engages the expression of defensive states, stronger midbrain functional coupling with the default-mode network may have clinical implications to self-referential and trauma-related processing in participants with post-traumatic stress disorder.

Does Generalized Linear Model Support Functional Default Mode Network Studies.

A growing body of research has emerged on the resting state and the default mode of the brain. Functional connectivity studies, which lately dominate this research area, have confirmed that regions such as the cortical mid-line structures, as well as parietal-temporal regions are tightly interconnected within the default mode network (DMN). However, little is known about the activity patterns of resting state related brain regions detected in fMRI studies using the generalized linear model (GLM) in a whole brain analysis. The aim of the current study was to investigate the activity changes among brain regions identified through GLM during the transition from task to rest and the prolongation of rest. A picture imagination task, as a controlled thought content task, was used in order to minimize confounding factors such as a visual stimulus or a motor response. The present study revealed a consistent fluctuating activation pattern of the dorsal anterior cingulate cortex (dACC), the posterior cingulate cortex (PCC), thalamus, primer motor area (PMA), insula, brain stem and bilateral putamen during the transition from task to the early phase of the resting state and the prolongation of the resting state. All regions showed increased activation during the detachment from task. However, this increased activation was not sustained during the extension of rest, replaced with a decreased activation at the late phase of rest. The increased activation of resting state regions might help with the detachment from the current task. Among these regions dACC, insula and putamen were correlated in all conditions. These findings underline the importance of the activation increase of the cortical mid-line regions and insula in the transition from task to the resting state.

S245. LOWER- AND HIGHER-LEVEL SOCIAL COGNITIVE FACTORS ACROSS INDIVIDUALS WITH SCHIZOPHRENIA SPECTRUM DISORDERS AND HEALTHY CONTROLS: RELATIONSHIP WITH NEUROCOGNITION AND FUNCTIONAL OUTCOME

BackgroundIndividuals with schizophrenia spectrum disorders (SSDs) often suffer social cognitive deficits, which are associated with functional outcome. These include lower-level “simulation” processes (emotion recognition), thought to be subserved by a frontoparietal circuit, and higher-level “mentalizing” processes (theory of mind), involving cortical midline and lateral temporal regions. Despite evidence supporting the distinction of these constructs, little work has focused on the factor structure of social cognition. In schizophrenia, factor analytic results have been inconsistent, likely due to task and analytic approach variability, and inadequate sample sizes. Further, confirmatory factor analysis (CFA) has not been used to compare multiple models across people with SSDs and healthy controls. Thus, our objective was to elucidate the factor structure of social cognition across a large group of people with SSDs and healthy controls. We hypothesized that a two-factor model, including simulation and mentalizing factors, would demonstrate the best fit across participants. We also expected social cognitive and neurocognitive factors to load on separate respective higher-order factors, and social cognition to mediate the relationship between neurocognition and clinical and functional outcome measures.MethodsBehavioural data was collected from 164 participants with SSDs and 102 healthy controls across three sites. Participants completed four tasks including measures of social cognition, ranging from basic emotion recognition to complex mental state inference. Participants also completed measures of functional outcome, symptom ratings, and the MATRICS Consensus Cognitive Battery. CFAs were conducted to test social cognitive models, as well as models of social cognition and neurocognition, and multi-group CFA was used to test measurement invariance between patients and controls.ResultsAs predicted, a two-factor (simulation, mentalizing) model fit the social cognitive data well across participants with SSDs and healthy controls (RMSEA = .010, CFI = 1.00). This model also fit significantly better than a one-factor model (p < .001). Further, measurement invariance testing revealed factor structure invariance, loading invariance, and partial intercept invariance between groups, allowing for between-group comparisons. Participants with SSDs showed lower scores than controls for both simulation and mentalizing factors (p < .001), and scores on both factors correlated significantly with symptom ratings and functional outcome measures. Including neurocognitive data, a higher-order two-factor (social cognition, neurocognition) model fit the data well (RMSEA = .047, CFI = .971), and showed significantly better fit than a one- or two-factor model (p < .001). Lastly, social cognition was found to mediate the relationship between neurocognition and negative symptoms, as well as social functioning and quality of life measures (p < .05).DiscussionOur results provide evidence that social cognition includes lower- and higher-level dimensions across both individuals with SSDs and healthy controls. They also suggest that both aspects are associated with clinical and functional outcome indices, and act as a mediator between neurocognition and these measures. This provides support for distinguishing lower- and higher-level social cognition between and across people with SSDs and healthy controls, and suggests that they may indeed have partially distinct underlying mechanisms. Further, results confirm the importance of social cognition as it relates to clinical and functional outcomes, and thereby as a potential treatment target for patients with SSDs.

The neural signature of self-concept development in adolescence: The role of domain and valence distinctions

Neuroimaging studies in adults showed that cortical midline regions including medial prefrontal cortex (mPFC) and posterior parietal cortex (PPC) are important in self-evaluations. The goals of this study were to investigate the contribution of these regions to self-evaluations in late childhood, adolescence, and early adulthood, and to examine whether these differed per domain (academic, physical and prosocial) and valence (positive versus negative). Also, we tested whether this activation changes across adolescence. For this purpose, participants between ages 11–21-years (N = 150) evaluated themselves on trait sentences in an fMRI session. Behaviorally, adolescents rated their academic traits less positively than children and young adults. The neural analyses showed that evaluating self-traits versus a control condition was associated with increased activity in mPFC (domain-general effect), and positive traits were associated with increased activity in ventral mPFC (valence effect). Self-related mPFC activation increased linearly with age, but only for evaluating physical traits. Furthermore, an adolescent-specific decrease in striatum activation for positive self traits was found. Finally, we found domain-specific neural activity for evaluating traits in physical (dorsolateral PFC, dorsal mPFC) and academic (PPC) domains. Together, these results highlight the importance of domain distinctions when studying self-concept development in late childhood, adolescence, and early adulthood.

ASSOCIATIONS BETWEEN MEASURES OF MEDIAL TEMPORAL LOBE NEURODEGENERATION AND ANOSOGNOSIA FOR MEMORY DEFICITS

Loss of insight of memory deficits, anosognosia, is a common feature of Alzheimer's disease (AD). The basis of this metacognitive disturbance remains elusive, although evidence points to compromised brain regions critical for self-referential processing (e.g., cortical midline regions) and recently also medial temporal lobe (MTL) structures such as the hippocampus (Perrotin et al., 2015, Vannini et al., submitted). Here we aimed to further our understanding of the relationship between memory awareness and neurodegeneration in the MTL region. Thus, using a multimodal approach we examined the associations among in vivo measures of MTL tau deposition, tissue volume in six hippocampal subfields (HCsf: CA1, CA2/3, CA4, DG, subiculum and presubiculum) and memory awareness in a cohort of cognitively normal to mildly memory-impaired individuals. 94 older individuals (76.3yrs, SD=6.9, CDR 0=76, CDR≥0.5=18) participated in the study. HCsf volumes (FreeSurfer6) were corrected for intracranial volume. Flortaucipir (FTP) binding in the entorhinal cortex (EC) was expressed in SUVR and cerebellar gray was used as reference (partial volume corrected). Memory-awareness was assessed by regressing each person's memory performance on their subjective memory ratings. Age, gender, education and depression scores were controlled for in each statistical model. Increased EC Tau was associated with significantly lower volumes in all HCsf except for CA2/3 where it was trending (p=.075). Increased EC Tau was also associated with decreased memory awareness r=-0.5, p<.001. Of the HCsf only the subiculum (r=0.4, p<.001) and CA1 (r=0.3, p=.004) demonstrated a significant association, such that lower volume was associated with decreased memory awareness. Last, subiculum volume was found to partially mediate the relationship between EC Tau and memory awareness (bias-bootstrapping 95% BCI, [-0.63,-0.02]), Sobel test t=-2.1, p=.036 (Fig.1). None of the other HCsf showed a significant mediation effect. A) Schematic representation of the direct effect. B) The subiculum partially mediates the relationship between entorhinal Tau binding and memory awareness. Standardized regression coefficients are presented: a=the association between EC Tau and subiculum volume, b=the association between subiculum volume and memory awareness adjusted for the effect of EC Tau on memory awareness, c'= the association between EC Tau and memory awareness adjusting for subiculum volume, and c=the direct association between EC Tau and memory awareness. Standardized regression coefficients are also presented for the mediation (a*b) effects. All analyses are corrected for age, education, gender and depression score. *p=0.05, ***p=0.001. Abbreviations: BCI=bias-corrected confidence interval (bootstrapped), EC = entorhinal cortex.