Neural markers of negative symptom outcomes in distributed working memory brain activity of antipsychotic-naive schizophrenia patients

Abstract Since working memory deficits in schizophrenia have been linked to negative symptoms, we tested whether features of the one could predict the treatment outcome in the other. Specifically, we hypothesized that working memory-related functional connectivity at pre-treatment can predict improvement of negative symptoms in antipsychotic-treated patients. Fourteen antipsychotic-naive patients with first-episode schizophrenia were clinically assessed before and after 7 months of quetiapine monotherapy. At baseline, patients underwent functional magnetic resonance imaging while performing a verbal n-back task. Spatial independent component analysis identified task-modulated brain networks. A linear support vector machine was trained with these components to discriminate six patients who showed improvement in negative symptoms from eight non-improvers. Classification accuracy and significance was estimated by leave-one-out cross-validation and permutation tests, respectively. Two frontoparietal and one default mode network components predicted negative symptom improvement with a classification accuracy of 79% (p = 0.003). Discriminating features were found in the frontoparietal networks but not the default mode network. These preliminary data suggest that functional patterns at baseline can predict negative symptom treatment–response in schizophrenia. This information may be used to stratify patients into subgroups thereby facilitating personalized treatment.

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Dissociation of anatomical and functional alterations of the default-mode network in first-episode, drug-naive schizophrenia

Clinical Neurophysiology ◽

10.1016/j.clinph.2015.01.025 ◽

2015 ◽

Vol 126 (12) ◽

pp. 2276-2281 ◽

Cited By ~ 5

Author(s):

Wenbin Guo ◽

Feng Liu ◽

Changqing Xiao ◽

Zhikun Zhang ◽

Miaoyu Yu ◽

...

Keyword(s):

Default Mode Network ◽

First Episode ◽

Default Mode ◽

Drug Naïve

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Patterns of Brain Activity Supporting Autobiographical Memory, Prospection, and Theory of Mind, and Their Relationship to the Default Mode Network

Journal of Cognitive Neuroscience ◽

10.1162/jocn.2009.21282 ◽

2010 ◽

Vol 22 (6) ◽

pp. 1112-1123 ◽

Cited By ~ 511

Author(s):

R. Nathan Spreng ◽

Cheryl L. Grady

Keyword(s):

Theory Of Mind ◽

Default Mode Network ◽

Brain Activity ◽

Brain Structures ◽

Neural Activation ◽

Default Mode ◽

Cognitive Behaviors ◽

Core Set ◽

Multiple Processes ◽

Human Feature

The ability to rise above the present environment and reflect upon the past, the future, and the minds of others is a fundamentally defining human feature. It has been proposed that these three self-referential processes involve a highly interconnected core set of brain structures known as the default mode network (DMN). The DMN appears to be active when individuals are engaged in stimulus-independent thought. This network is a likely candidate for supporting multiple processes, but this idea has not been tested directly. We used fMRI to examine brain activity during autobiographical remembering, prospection, and theory-of-mind reasoning. Using multivariate analyses, we found a common pattern of neural activation underlying all three processes in the DMN. In addition, autobiographical remembering and prospection engaged midline DMN structures to a greater degree and theory-of-mind reasoning engaged lateral DMN areas. A functional connectivity analysis revealed that activity of a critical node in the DMN, medial prefrontal cortex, was correlated with activity in other regions in the DMN during all three tasks. We conclude that the DMN supports common aspects of these cognitive behaviors involved in simulating an internalized experience.

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Parietal memory network and default mode network in first‐episode drug‐naïve schizophrenia: Associations with auditory hallucination

Human Brain Mapping ◽

10.1002/hbm.24923 ◽

2020 ◽

Vol 41 (8) ◽

pp. 1973-1984

Author(s):

Qian Guo ◽

Yang Hu ◽

Botao Zeng ◽

Yingying Tang ◽

Guanjun Li ◽

...

Keyword(s):

Default Mode Network ◽

Auditory Hallucination ◽

First Episode ◽

Default Mode ◽

Drug Naïve ◽

Memory Network

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The efficacy of cariprazine in negative symptoms of schizophrenia: Post hoc analyses of PANSS individual items and PANSS-derived factors

European Psychiatry ◽

10.1016/j.eurpsy.2019.01.015 ◽

2019 ◽

Vol 58 ◽

pp. 1-9 ◽

Cited By ~ 14

Author(s):

Wolfgang Fleischhacker ◽

Silvana Galderisi ◽

István Laszlovszky ◽

Balázs Szatmári ◽

Ágota Barabássy ◽

...

Keyword(s):

Negative Symptom ◽

Repeated Measures ◽

Negative Symptoms ◽

Social Withdrawal ◽

Partial Agonist ◽

Factor Models ◽

Symptom Improvement ◽

Symptom Dimensions ◽

Intent To Treat ◽

Post Hoc

AbstractBackground:Negative symptoms in schizophrenia are heterogeneous and multidimensional; effective treatments are lacking. Cariprazine, a dopamine D3-preferring D3/D2 receptor partial agonist and serotonin 5-HT1A receptor partial agonist, was significantly more effective than risperidone in treating negative symptoms in a prospectively designed trial in patients with schizophrenia and persistent, predominant negative symptoms.Methods:Using post hoc analyses, we evaluated change from baseline at week 26 in individual items of the Positive and Negative Syndrome Scale (PANSS) and PANSS-derived factor models using a mixed-effects model for repeated measures (MMRM) in the intent-to-treat (ITT) population (cariprazine = 227; risperidone = 227).Results:Change from baseline was significantly different in favor of cariprazine versus risperidone on PANSS items N1-N5 (blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking) (P <.05), but not on N6 (lack of spontaneity/flow of conversation) or N7 (stereotyped thinking). On all PANSS-derived negative symptom factor models evaluated (PANSS-Factor Score for Negative Symptoms, Liemburg factors, Khan factors, Pentagonal Structure Model Negative Symptom factor), statistically significant improvement was demonstrated for cariprazine versus risperidone (P <.01). Small and similar changes in positive/depressive/EPS symptoms suggested that negative symptom improvement was not pseudospecific. Change from baseline was significantly different for cariprazine versus risperidone on PANSS-based factors evaluating other relevant symptom domains (disorganized thoughts, prosocial function, cognition; P <.05).Conclusions:Since items representing different negative symptom dimensions may represent different fundamental pathophysiological mechanisms, significant improvement versus risperidone on most PANSS Negative Subscale items and across all PANSS-derived factors suggests broad-spectrum efficacy for cariprazine in treating negative symptoms of schizophrenia.

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Spontaneous Brain Activity in the Default Mode Network Is Sensitive to Different Resting-State Conditions with Limited Cognitive Load

PLoS ONE ◽

10.1371/journal.pone.0005743 ◽

2009 ◽

Vol 4 (5) ◽

pp. e5743 ◽

Cited By ~ 212

Author(s):

Chaogan Yan ◽

Dongqiang Liu ◽

Yong He ◽

Qihong Zou ◽

Chaozhe Zhu ◽

...

Keyword(s):

Cognitive Load ◽

Default Mode Network ◽

Resting State ◽

Brain Activity ◽

Default Mode ◽

Spontaneous Brain Activity

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Working memory as a predictor of negative symptoms and functional outcome in first episode psychosis

Psychiatry Research ◽

10.1016/j.psychres.2012.08.025 ◽

2013 ◽

Vol 206 (1) ◽

pp. 8-16 ◽

Cited By ~ 33

Author(s):

Itxaso González-Ortega ◽

Vanesa de los Mozos ◽

Enrique Echeburúa ◽

Maria Mezo ◽

Ariadna Besga ◽

...

Keyword(s):

Working Memory ◽

Functional Outcome ◽

Negative Symptoms ◽

First Episode Psychosis ◽

First Episode ◽

Episode Psychosis

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Resting-state hyperconnectivity within the default mode network impedes the ability to initiate cognitive performance in first-episode schizophrenia patients

Progress in Neuro-Psychopharmacology and Biological Psychiatry ◽

10.1016/j.pnpbp.2020.109959 ◽

2020 ◽

Vol 102 ◽

pp. 109959 ◽

Cited By ~ 2

Author(s):

Paweł Krukow ◽

Kamil Jonak ◽

Cezary Grochowski ◽

Małgorzata Plechawska-Wójcik ◽

Hanna Karakuła-Juchnowicz

Keyword(s):

Cognitive Performance ◽

Default Mode Network ◽

Resting State ◽

First Episode ◽

Default Mode ◽

First Episode Schizophrenia

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Temporal circuit of macroscale dynamic brain activity supports human consciousness

Science Advances ◽

10.1126/sciadv.aaz0087 ◽

2020 ◽

Vol 6 (11) ◽

pp. eaaz0087 ◽

Cited By ~ 11

Author(s):

Zirui Huang ◽

Jun Zhang ◽

Jinsong Wu ◽

George A. Mashour ◽

Anthony G. Hudetz

Keyword(s):

Default Mode Network ◽

Functional Role ◽

Brain Activity ◽

Human Consciousness ◽

Attention Network ◽

Attention Networks ◽

Default Mode ◽

Dorsal Attention Network ◽

Brain States

The ongoing stream of human consciousness relies on two distinct cortical systems, the default mode network and the dorsal attention network, which alternate their activity in an anticorrelated manner. We examined how the two systems are regulated in the conscious brain and how they are disrupted when consciousness is diminished. We provide evidence for a “temporal circuit” characterized by a set of trajectories along which dynamic brain activity occurs. We demonstrate that the transitions between default mode and dorsal attention networks are embedded in this temporal circuit, in which a balanced reciprocal accessibility of brain states is characteristic of consciousness. Conversely, isolation of the default mode and dorsal attention networks from the temporal circuit is associated with unresponsiveness of diverse etiologies. These findings advance the foundational understanding of the functional role of anticorrelated systems in consciousness.

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

Cerebral Cortex ◽

10.1093/cercor/bhaa166 ◽

2020 ◽

Vol 30 (11) ◽

pp. 5915-5929 ◽

Cited By ~ 1

Author(s):

Tanya Wen ◽

Daniel J Mitchell ◽

John Duncan

Keyword(s):

Default Mode Network ◽

Medial Temporal Lobe ◽

Brain Activity ◽

Activity Patterns ◽

Univariate Analysis ◽

Moral Dilemmas ◽

Default Mode ◽

Multiple Components ◽

Common Activity ◽

Rest Condition

Abstract 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.

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