Prefrontal Brain Network Connectivity Indicates Degree of Both Schizophrenia Risk and Cognitive Dysfunction

Unschuld, Paul G.; Buchholz, A; Varvaris, Mark; Zijl, Peter C.M. van; Ross, Christopher A.; Pekar, James J.; Höck, Christoph; Sweeney, John A.; Tamminga, Carol A.; Keshavan, Matcheri S.; Pearlson, Godfrey D.; Thaker, Gunvant K.; Schretlen, David J.

doi:10.1093/schbul/sbt077

Cited by 63 publications

(39 citation statements)

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“…When we restricted the hippocampal seed to anterior hippocampus, dysconnected regions shifted more anteriorly, including anterior cingulate and the medial prefrontal cortex, as well as the superior temporal gyrus, thalamus and precuneus. Results illustrate dysconnectivity patterns with regions that are primarily impacted by previously reported alterations in hippocampal structure and activity (Shergill et al, 2000; Kircher et al, 2001; Shergill et al, 2003; Seiferth et al, 2008; Wolf et al, 2009; Cronenwett and Csernansky, 2010; Preston et al, 2010; Faget-Agius et al, 2012; Arnold et al, 2014; Unschuld et al, 2014; Anticevic et al, 2014; van Tol et al, 2014; Lui et al, 2014; Mathew et al, 2014). These present results lend support to the hypothesis that cerebral dysfunction in psychotic illnesses derives from hippocampal dysfunction.…”

Section: Discussionmentioning

confidence: 59%

Alterations in hippocampal connectivity across the psychosis dimension

Samudra

Ivleva

Hubbard

et al. 2015

Psychiatry Research: Neuroimaging

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Recent evidence demonstrates that hippocampal hyperactivity helps mediate psychosis. Using resting state functional magnetic resonance imaging (rsfMRI), we examined hippocampal connectivity alterations in individuals with psychosis (PS) versus healthy controls (HC). Because of its putative greater involvement in psychiatric disorders, we hypothesized that the anterior hippocampus network would show greater dysconnectivity in psychosis. We tested rsfMRI connectivity in 88 PS (including 21 with schizophrenia; 40 with schizoaffective disorder; 27 with psychotic bipolar I disorder) and 65 HC. Seed-based voxel-wise connectivity analyses were carried out using whole, anterior, and posterior hippocampal seeds. No significant differences in functional hippocampal connectivity were found across the three conventional diagnoses. PS were then contrasted with HC, showing strong reductions in anterior hippocampal connectivity to anterior neocortical regions, including medial frontal and anterior cingulate cortices, as well as superior temporal gyrus, precuneus, thalamus and cerebellum. Posterior hippocampal seeds also demonstrated decreased connectivity in PS, with fewer dysconnected regions and a posterior/cerebellar distribution. Whole hippocampal outcomes were consistent with anterior/posterior hippocampal connectivity changes. Connectivity alterations did not correlate with cognition, clinical symptoms, or medication effect variables. Our results suggest a psychosis network of decreased hippocampal connectivity with limbic and frontal contributions, independent of diagnostic categories.

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Section: Discussionmentioning

confidence: 59%

Alterations in hippocampal connectivity across the psychosis dimension

Samudra

Ivleva

Hubbard

et al. 2015

Psychiatry Research: Neuroimaging

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“…We plan to pursue this approach. In addition, the assumption here is that the correlation trends between the imaging maps and MCCB scores would be similar in both groups, in consistent with (81, 82), whereas our method also allows patients and controls to exhibit opposite correlations between imaging signatures and cognition by separately calculating correlations within each group, as shown in (83). In future studies with more subjects and greater statistical power or with task-related fMRI, we may expect to find such relationships.…”

Section: Discussionmentioning

confidence: 80%

In Search of Multimodal Neuroimaging Biomarkers of Cognitive Deficits in Schizophrenia

Sui

Pearlson

et al. 2015

Biological Psychiatry

168

122

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BACKGROUND The cognitive deficits of schizophrenia are largely resistant to current treatments, thus are a life-long illness burden. The MATRICS Consensus Cognitive Battery (MCCB) provides a reliable and valid assessment of cognition across major cognitive domains; however, the multimodal brain alterations specifically associated with MCCB in schizophrenia have not been examined. METHODS The interrelationships between MCCB and the abnormalities seen in three types of neuroimaging-derived maps—fractional amplitude of low frequency fluctuations (fALFF) from resting-state functional magnetic resonance imaging (MRI), grey matter density (GM) from structural MRI and fractional anisotropy (FA) from diffusion MRI, were investigated by using multi-set canonical correlation analysis in data from 47 schizophrenia patients treated with antipsychotic medications and 50 age-matched healthy controls. RESULTS One multimodal component (CV8) was identified as both group-differentiating and significantly correlated with the MCCB composite. It demonstrated: 1) Increased cognitive performance associated with higher fALFF (intensity of regional spontaneous brain activity) and higher GM volumes in thalamus, striatum, hippocampus, and the mid-occipital region, with co-occurring FA changes in superior longitudinal fascicules, anterior thalamic radiation and forceps major. 2) Higher fALFF but lower GM volume in dorsolateral prefrontal cortex related to worse cognition in schizophrenia. 3) Distinct domains of MCCB might exhibit dissociable multimodal signatures, e.g., increased fALFF in inferior parietal lobule particularly correlated with decreased social cognition. Medication dose did not relate to these findings in schizophrenia. CONCLUSIONS Our results suggest linked functional and structural deficits in distributed cortico-striato-thalamic circuits may be closely related to MCCB-measured cognitive impairments in schizophrenia.

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“…In particular, SZ patients showed more severe and pervasive cognitive deficits while BD patients present a milder and more confined impairment. Prior B-SNIP analysis showed that the excessive connectivity within brain networks coupled to the dlPFC and medial PFC was associated with cognitive deficits in persons at risk for SZ (Unschuld et al, 2014). We found a modest association between brain signal randomness in the dorsal or ventral PFC and the BACS digit span.…”

Section: Discussionmentioning

confidence: 99%

Neural complexity as a potential translational biomarker for psychosis

Hager

Yang

Brady

et al. 2017

Journal of Affective Disorders

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Background The adaptability of the human brain to the constantly changing environment is reduced in patients with psychotic disorders, leading to impaired cognitive functions. Brain signal complexity, which may reflect adaptability, can be readily quantified via resting-state functional magnetic resonance imaging (fMRI) signals. We hypothesized that resting-state brain signal complexity is altered in psychotic disorders, and is correlated with cognitive impairment. Methods We assessed 156 healthy controls (HC) and 330 probands, including 125 patients with psychotic bipolar disorder (BP), 107 patients with schizophrenia (SZ), 98 patients with schizoaffective disorder (SAD) and 230 of their unaffected first-degree relatives (76 BPR, 79 SADR, and 75 SZR) from four sites of the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium. Using multi-scale entropy analysis, we determined whether patients and/or relatives had pathologic differences in complexity of resting-state fMRI signals toward regularity (reduced entropy in all time scales), or toward uncorrelated randomness (increased entropy in fine time scales that decays as the time scale increases) and how these complexity differences might be associated with cognitive impairment. Results Compared to HC subjects, proband groups showed either decreased complexity toward regularity or toward randomness. SZ probands showed decreased complexity toward regular signal in hypothalamus, and BP probands in left inferior occipital, right precentral and left superior parietal regions, whereas no brain region with decreased complexity toward regularity was found in SAD probands. All proband groups showed significantly increased brain signal randomness in dorsal and ventral prefrontal cortex (PFC), and unaffected relatives showed no complexity differences in PFC regions. SZ had the largest area of involvement in both dorsal and ventral PFC. BP and SAD probands shared increased brain signal randomness in ventral medial PFC, BP and SZ probands shared increased brain signal randomness in ventral lateral PFC, whereas SAD and SZ probands shared increased brain signal randomness in dorsal medial PFC. Only SZ showed increased brain signal randomness in dorsal lateral PFC. The increased brain signal randomness in dorsal or ventral PFC was weakly associated with reduced cognitive performance in psychotic probands. Conclusion These observations support the loss of brain complexity hypothesis in psychotic probands. Furthermore, we found significant differences as well as overlaps of pathologic brain signal complexity between psychotic probands by DSM diagnoses, thus suggesting a biological approach to categorizing psychosis based on functional neuroimaging data.

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Prefrontal Brain Network Connectivity Indicates Degree of Both Schizophrenia Risk and Cognitive Dysfunction

Cited by 63 publications

References 100 publications

Alterations in hippocampal connectivity across the psychosis dimension

Alterations in hippocampal connectivity across the psychosis dimension

In Search of Multimodal Neuroimaging Biomarkers of Cognitive Deficits in Schizophrenia

Neural complexity as a potential translational biomarker for psychosis

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