Age-associated network controllability changes in first episode drug-naïve schizophrenia

Abstract Background Recent neuroimaging studies revealed dysregulated neurodevelopmental, or/and neurodegenerative trajectories of both structural and functional connections in schizophrenia. However, how the alterations in the brain’s structural connectivity lead to dynamic function changes in schizophrenia with age remains poorly understood. Methods Combining structural magnetic resonance imaging and a network control theory approach, the white matter network controllability metric (average controllability) was mapped from age 16 to 60 years in 175 drug-naïve schizophrenia patients and 155 matched healthy controls. Results Compared with controls, the schizophrenia patients demonstrated the lack of age-related decrease on average controllability of default mode network (DMN), as well as the right precuneus (a hub region of DMN), suggesting abnormal maturational development process in schizophrenia. Interestingly, the schizophrenia patients demonstrated an accelerated age-related decline of average controllability in the subcortical network, supporting the neurodegenerative model. In addition, compared with controls, the lack of age-related increase on average controllability of the left inferior parietal gyrus in schizophrenia patients also suggested a different pathway of brain development. Conclusions By applying the control theory approach, the present study revealed age-related changes in the ability of white matter pathways to control functional activity states in schizophrenia. The findings supported both the developmental and degenerative hypotheses of schizophrenia, and suggested a particularly high vulnerability of the DMN and subcortical network possibly reflecting an illness-related early marker for the disorder.

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Network controllability in transmodal cortex predicts psychosis spectrum symptoms

10.1101/2020.10.01.20205336 ◽

2020 ◽

Cited By ~ 1

Author(s):

Linden Parkes ◽

Tyler M. Moore ◽

Monica E. Calkins ◽

Matthew Cieslak ◽

David R. Roalf ◽

...

Keyword(s):

Control Theory ◽

Structural Connectivity ◽

Prediction Performance ◽

Network Control ◽

Association Cortex ◽

Out Of Sample ◽

Sample Testing ◽

Functional Hierarchy ◽

Structural Connections ◽

Network Controllability

ABSTRACTBackgroundThe psychosis spectrum is associated with structural dysconnectivity concentrated in transmodal association cortex. However, understanding of this pathophysiology has been limited by an exclusive focus on the direct connections to a region. Using Network Control Theory, we measured variation in both direct and indirect structural connections to a region to gain new insights into the pathophysiology of the psychosis spectrum.MethodsWe used psychosis symptom data and structural connectivity in 1,068 youths aged 8 to 22 years from the Philadelphia Neurodevelopmental Cohort. Applying a Network Control Theory metric called average controllability, we estimated each brain region’s capacity to leverage its direct and indirect structural connections to control linear brain dynamics. Next, using non-linear regression, we determined the accuracy with which average controllability could predict negative and positive psychosis spectrum symptoms in out-of-sample testing. We also compared prediction performance for average controllability versus strength, which indexes only direct connections to a region. Finally, we assessed how the prediction performance for psychosis spectrum symptoms varied over the functional hierarchy spanning unimodal to transmodal cortex.ResultsAverage controllability outperformed strength at predicting positive psychosis spectrum symptoms, demonstrating that indexing indirect structural connections to a region improved prediction performance. Critically, improved prediction was concentrated in association cortex for average controllability, whereas prediction performance for strength was uniform across the cortex, suggesting that indexing indirect connections is crucial in association cortex.ConclusionsExamining inter-individual variation in direct and indirect structural connections to association cortex is crucial for accurate prediction of positive psychosis spectrum symptoms.

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A Computational Network Control Theory Analysis of Depression Symptoms

Personality Neuroscience ◽

10.1017/pen.2018.15 ◽

2018 ◽

Vol 1 ◽

Cited By ~ 2

Author(s):

Yoed N. Kenett ◽

Roger E. Beaty ◽

John D. Medaglia

Keyword(s):

Control Theory ◽

Diffusion Tensor ◽

Brain Regions ◽

Brain Network ◽

Network Control ◽

Depression Symptoms ◽

Theory Approach ◽

Imaging Data ◽

The Brain ◽

Subclinical Depression

AbstractRumination and impaired inhibition are considered core characteristics of depression. However, the neurocognitive mechanisms that contribute to these atypical cognitive processes remain unclear. To address this question, we apply a computational network control theory approach to structural brain imaging data acquired via diffusion tensor imaging in a large sample of participants, to examine how network control theory relates to individual differences in subclinical depression. Recent application of this theory at the neural level is built on a model of brain dynamics, which mathematically models patterns of inter-region activity propagated along the structure of an underlying network. The strength of this approach is its ability to characterize the potential role of each brain region in regulating whole-brain network function based on its anatomical fingerprint and a simplified model of node dynamics. We find that subclinical depression is negatively related to higher integration abilities in the right anterior insula, replicating and extending previous studies implicating atypical switching between the default mode and Executive Control Networks in depression. We also find that subclinical depression is related to the ability to “drive” the brain system into easy to reach neural states in several brain regions, including the bilateral lingual gyrus and lateral occipital gyrus. These findings highlight brain regions less known in their role in depression, and clarify their roles in driving the brain into different neural states related to depression symptoms.

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Escitalopram Increased Gray Matter and White Matter in a First-Episode Drug-Naïve Panic Disorder Patient Within 6 Weeks

Journal of Neuropsychiatry ◽

10.1176/appi.neuropsych.11060135 ◽

2012 ◽

Vol 24 (2) ◽

pp. E23-E24 ◽

Cited By ~ 2

Author(s):

Chien-Han Lai

Keyword(s):

White Matter ◽

Panic Disorder ◽

Gray Matter ◽

First Episode ◽

Disorder Patient ◽

Drug Naïve

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Risperidone-induced topological alterations of anatomical brain network in first-episode drug-naive schizophrenia patients: a longitudinal diffusion tensor imaging study

Psychological Medicine ◽

10.1017/s0033291716001380 ◽

2016 ◽

Vol 46 (12) ◽

pp. 2549-2560 ◽

Cited By ~ 7

Author(s):

M. Hu ◽

X. Zong ◽

J. Zheng ◽

J. J. Mann ◽

Z. Li ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

White Matter ◽

Negative Symptoms ◽

Diffusion Tensor ◽

Imaging Study ◽

First Episode ◽

Longitudinal Diffusion ◽

Before And After ◽

Drug Naïve ◽

Diffusion Tensor Imaging Study

BackgroundIt remains unclear whether the topological deficits of the white matter network documented in cross-sectional studies of chronic schizophrenia patients are due to chronic illness or to other factors such as antipsychotic treatment effects. To answer this question, we evaluated the white matter network in medication-naive first-episode schizophrenia patients (FESP) before and after a course of treatment.MethodWe performed a longitudinal diffusion tensor imaging study in 42 drug-naive FESP at baseline and then after 8 weeks of risperidone monotherapy, and compared them with 38 healthy volunteers. Graph theory was utilized to calculate the topological characteristics of brain anatomical network. Patients’ clinical state was evaluated using the Positive and Negative Syndrome Scale (PANSS) before and after treatment.ResultsPretreatment, patients had relatively intact overall topological organizations, and deficient nodal topological properties primarily in prefrontal gyrus and limbic system components such as the bilateral anterior and posterior cingulate. Treatment with risperidone normalized topological parameters in the limbic system, and the enhancement positively correlated with the reduction in PANSS-positive symptoms. Prefrontal topological impairments persisted following treatment and negative symptoms did not improve.ConclusionsDuring the early phase of antipsychotic medication treatment there are region-specific alterations in white matter topological measures. Limbic white matter topological dysfunction improves with positive symptom reduction. Prefrontal deficits and negative symptoms are unresponsive to medication intervention, and prefrontal deficits are potential trait biomarkers and targets for negative symptom treatment development.

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White-matter microstructure in previously drug-naive patients with schizophrenia after 6 weeks of treatment

Psychological Medicine ◽

10.1017/s0033291713000238 ◽

2013 ◽

Vol 43 (11) ◽

pp. 2301-2309 ◽

Cited By ~ 55

Author(s):

Q. Wang ◽

C. Cheung ◽

W. Deng ◽

M. Li ◽

C. Huang ◽

...

Keyword(s):

White Matter ◽

Early Phase ◽

Clinical Symptoms ◽

Diffusion Tensor ◽

Disease Process ◽

Anterior Cingulate ◽

First Episode ◽

Drug Naïve ◽

The Right ◽

First Episode Schizophrenia

BackgroundIt is not clear whether the progressive changes in brain microstructural deficits documented in previous longitudinal magnetic resonance imaging (MRI) studies might be due to the disease process or to other factors such as medication. It is important to explore the longitudinal alterations in white-matter (WM) microstructure in antipsychotic-naive patients with first-episode schizophrenia during the very early phase of treatment when relatively ‘free’ from chronicity.MethodThirty-five patients with first-episode schizophrenia and 22 healthy volunteers were recruited. High-resolution diffusion tensor imaging (DTI) was obtained from participants at baseline and after 6 weeks of treatment. A ‘difference map’ for each individual was calculated from the 6-week follow-up fractional anisotropy (FA) of DTI minus the baseline FA. Differences in Positive and Negative Syndrome Scale (PANSS) scores and Global Assessment of Functioning (GAF) scores between baseline and 6 weeks were also evaluated and expressed as a 6-week/baseline ratio.ResultsCompared to healthy controls, there was a significant decrease in absolute FA of WM around the bilateral anterior cingulate gyrus and the right anterior corona radiata of the frontal lobe in first-episode drug-naive patients with schizophrenia following 6 weeks of treatment. Clinical symptoms improved during this period but the change in FA did not correlate with the changes in clinical symptoms or the dose of antipsychotic medication.ConclusionsDuring the early phase of treatment, there is an acute reduction in WM FA that may be due to the effects of antipsychotic medications. However, it is not possible to entirely exclude the effects of underlying progression of illness.

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A diffusion tensor imaging study of structural dysconnectivity in never-medicated, first-episode schizophrenia

Psychological Medicine ◽

10.1017/s0033291707001808 ◽

2007 ◽

Vol 38 (6) ◽

pp. 877-885 ◽

Cited By ~ 143

Author(s):

V. Cheung ◽

C. Cheung ◽

G. M. McAlonan ◽

Y. Deng ◽

J. G. Wong ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

White Matter ◽

Corpus Callosum ◽

Diffusion Tensor ◽

Structural Connectivity ◽

First Episode ◽

Cerebral Peduncle ◽

Healthy Controls ◽

Subcortical Region ◽

First Episode Schizophrenia

BackgroundDiffusion tensor imaging (DTI) can be used to investigate cerebral structural connectivity in never-medicated individuals with first-episode schizophrenia.MethodSubjects with first-episode schizophrenia according to DSM-IV-R who had never been exposed to antipsychotic medication (n=25) and healthy controls (n=26) were recruited. Groups were matched for age, gender, best parental socio-economic status and ethnicity. All subjects underwent DTI and structural magnetic resonance imaging (MRI) scans. Voxel-based analysis was performed to investigate brain regions where fractional anisotropy (FA) values differed significantly between groups. A confirmatory region-of-interest (ROI) analysis of FA scores was performed in which regions were placed blind to group membership.ResultsIn patients, FA values significantly lower than those in healthy controls were located in the left fronto-occipital fasciculus, left inferior longitudinal fasciculus, white matter adjacent to right precuneus, splenium of corpus callosum, right posterior limb of internal capsule, white matter adjacent to right substantia nigra, and left cerebral peduncle. ROI analysis of the corpus callosum confirmed that the patient group had significantly lower mean FA values than the controls in the splenium but not in the genu. The intra-class correlation coefficient (ICC) for independent ROI measurements was 0.90 (genu) and 0.90 (splenium). There were no regions where FA values were significantly higher in the patients than in the healthy controls.ConclusionsWidespread structural dysconnectivity, including the subcortical region, is already present in neuroleptic-naive patients in their first episode of illness.

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Glucose disturbances, cognitive deficits and white matter abnormalities in first-episode drug-naive schizophrenia

Molecular Psychiatry ◽

10.1038/s41380-019-0478-1 ◽

2019 ◽

Vol 25 (12) ◽

pp. 3220-3230 ◽

Cited By ~ 4

Author(s):

Xiangyang Zhang ◽

Mi Yang ◽

Xiangdong Du ◽

Wei Liao ◽

Dachun Chen ◽

...

Keyword(s):

White Matter ◽

Cognitive Deficits ◽

First Episode ◽

White Matter Abnormalities ◽

Drug Naïve

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Fornix Microstructure and Memory Performance Is Associated with Altered Neural Connectivity during Episodic Recognition

Journal of the International Neuropsychological Society ◽

10.1017/s1355617715001216 ◽

2016 ◽

Vol 22 (2) ◽

pp. 191-204 ◽

Cited By ~ 10

Author(s):

Martina Ly ◽

Nagesh Adluru ◽

Daniel J. Destiche ◽

Sharon Y. Lu ◽

Jennifer M. Oh ◽

...

Keyword(s):

White Matter ◽

Diffusion Tensor ◽

Negative Impact ◽

Interaction Analysis ◽

Memory Performance ◽

Structural Connectivity ◽

Middle Frontal Gyrus ◽

Age Related ◽

White Matter Microstructure ◽

Psychophysiological Interaction

AbstractObjectives: The purpose of this study was to assess whether age-related differences in white matter microstructure are associated with altered task-related connectivity during episodic recognition. Methods: Using functional magnetic resonance imaging and diffusion tensor imaging from 282 cognitively healthy middle-to-late aged adults enrolled in the Wisconsin Registry for Alzheimer’s Prevention, we investigated whether fractional anisotropy (FA) within white matter regions known to decline with age was associated with task-related connectivity within the recognition network. Results: There was a positive relationship between fornix FA and memory performance, both of which negatively correlated with age. Psychophysiological interaction analyses revealed that higher fornix FA was associated with increased task-related connectivity amongst the hippocampus, caudate, precuneus, middle occipital gyrus, and middle frontal gyrus. In addition, better task performance was associated with increased task-related connectivity between the posterior cingulate gyrus, middle frontal gyrus, cuneus, and hippocampus. Conclusions: The findings indicate that age has a negative effect on white matter microstructure, which in turn has a negative impact on memory performance. However, fornix microstructure did not significantly mediate the effect of age on performance. Of interest, dynamic functional connectivity was associated with better memory performance. The results of the psychophysiological interaction analysis further revealed that alterations in fornix microstructure explain–at least in part–connectivity among cortical regions in the recognition memory network. Our results may further elucidate the relationship between structural connectivity, neural function, and cognition. (JINS, 2016, 22, 191–204)

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Positive symptoms and white matter microstructure in never-medicated first episode schizophrenia

Psychological Medicine ◽

10.1017/s003329171000156x ◽

2010 ◽

Vol 41 (8) ◽

pp. 1709-1719 ◽

Cited By ~ 66

Author(s):

V. Cheung ◽

C. P. Y. Chiu ◽

C. W. Law ◽

C. Cheung ◽

C. L. M. Hui ◽

...

Keyword(s):

White Matter ◽

Negative Symptoms ◽

Diffusion Tensor ◽

Structural Connectivity ◽

Anterior Cingulate ◽

Middle Temporal Gyrus ◽

First Episode ◽

Positive Symptoms ◽

Cingulate Gyrus ◽

First Episode Schizophrenia

BackgroundWe investigated cerebral structural connectivity and its relationship to symptoms in never-medicated individuals with first-onset schizophrenia using diffusion tensor imaging (DTI).MethodWe recruited subjects with first episode DSM-IV schizophrenia who had never been exposed to antipsychotic medication (n=34) and age-matched healthy volunteers (n=32). All subjects received DTI and structural magnetic resonance imaging scans. Patients' symptoms were assessed on the Positive and Negative Syndrome Scale. Voxel-based analysis was performed to investigate brain regions where fractional anisotropy (FA) values significantly correlated with symptom scores.ResultsIn patients with first-episode schizophrenia, positive symptoms correlated positively with FA scores in white matter associated with the right frontal lobe, left anterior cingulate gyrus, left superior temporal gyrus, right middle temporal gyrus, right middle cingulate gyrus, and left cuneus. Importantly, FA in each of these regions was lower in patients than controls, but patients with more positive symptoms had FA values closer to controls. We found no significant correlations between FA and negative symptoms.ConclusionsThe newly-diagnosed, neuroleptic-naive patients had lower FA scores in the brain compared with controls. There was positive correlation between FA scores and positive symptoms scores in frontotemporal tracts, including left fronto-occipital fasciculus and left inferior longitudinal fasciculus. This implies that white matter dysintegrity is already present in the pre-treatment phase and that FA is likely to decrease after clinical treatment or symptom remission.

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