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Tyrone D. Cannon

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15 papers
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15

YNICL Journal 2021 Journal Article

Discriminatory experiences predict neuroanatomical changes and anxiety among healthy individuals and those at clinical high risk for psychosis

  • Meghan A. Collins
  • Yoonho Chung
  • Jean Addington
  • Carrie E. Bearden
  • Kristin S. Cadenhead
  • Barbara A. Cornblatt
  • Daniel H. Mathalon
  • Thomas H. McGlashan

Individuals face discrimination based on characteristics including race/ethnicity, gender, age, and disability. Discriminatory experiences (DE) are associated with poor psychological health in the general population and with worse outcomes among individuals at clinical high risk for psychosis (CHR). Though the brain is sensitive to stress, and brain structural change is a well-documented precursor to psychosis, potential relationships between DE and brain structure among CHR or healthy individuals are not known. This report assessed whether lifetime DE are associated with cortical thinning and clinical outcomes across time, after controlling for discrimination-related demographic factors among CHR individuals who ultimately do (N = 57) and do not convert to psychosis (N = 451), and healthy comparison (N = 208) participants in the North American Prodrome Longitudinal Study 2. Results indicate that DE are associated with thinner cortex across time in several cortical areas. Thickness in several right hemisphere regions partially mediates associations between DE and subsequent anxiety symptoms, but not attenuated positive symptoms of psychosis. This report provides the first evidence to date of an association between DE and brain structure in both CHR and healthy comparison individuals. Results also suggest that thinner cortex across time in areas linked with DE may partially explain associations between DE and cross-diagnostic indicators of psychological distress.

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YNIMG Journal 2021 Journal Article

Identifying neural signatures mediating behavioral symptoms and psychosis onset: High-dimensional whole brain functional mediation analysis

  • Oliver Y. Chén
  • Hengyi Cao
  • Huy Phan
  • Guy Nagels
  • Jenna M. Reinen
  • Jiangtao Gou
  • Tianchen Qian
  • Junrui Di

Along the pathway from behavioral symptoms to the development of psychotic disorders sits the multivariate mediating brain. The functional organization and structural topography of large-scale multivariate neural mediators among patients with brain disorders, however, are not well understood. Here, we design a high-dimensional brain-wide functional mediation framework to investigate brain regions that intermediate between baseline behavioral symptoms and future conversion to full psychosis among individuals at clinical high risk (CHR). Using resting-state functional magnetic resonance imaging (fMRI) data from 263 CHR subjects, we extract an α brain atlas and a β brain atlas: the former underlines brain areas associated with prodromal symptoms and the latter highlights brain areas associated with disease onset. In parallel, we identify and separate mediators that potentially positively and negatively mediate symptoms and psychosis, respectively, and quantify the effect of each neural mediator on disease development. Taken together, these results paint a brain-wide picture of neural markers that are potentially mediating behavioral symptoms and the development of psychotic disorders; additionally, they underscore a statistical framework that is useful to uncover large-scale intermediating variables in a regulatory biological system.

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YNICL Journal 2019 Journal Article

Cortical abnormalities in youth at clinical high-risk for psychosis: Findings from the NAPLS2 cohort

  • Yoonho Chung
  • Dana Allswede
  • Jean Addington
  • Carrie E. Bearden
  • Kristin Cadenhead
  • Barbara Cornblatt
  • Daniel H. Mathalon
  • Thomas McGlashan

MRI scans from 378 CHR individuals and 190 healthy controls (HC) from the North American Prodrome Longitudinal Study (NAPLS2) were analyzed. Widespread smaller cortical volume was observed among CHR individuals compared with HC at baseline evaluation, particularly among the younger group (i.e., those who were 12 to 17 years of age). Moreover, the younger CHR individuals who converted or presented worsened clinical symptoms at follow-up (within 2 years) exhibited smaller surface area in rostral anterior cingulate, lateral and medial prefrontal regions, and parahippocampal gyrus relative to the younger CHR individuals who remitted or presented a stable pattern of prodromal symptoms at follow-up. In turn, poorer premorbid functioning in childhood was associated with smaller surface area in medial orbitofrontal, lateral frontal, rostral anterior cingulate, precuneus, and temporal regions. Together with our prior report, these results are consistent with the view that neuroanatomical deviance manifesting in early adolescence marks vulnerability to a form of psychosis presenting with poor premorbid adjustment, an earlier age of onset (generally prior to the age of 18 years), and poor long-term outcome.

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YNICL Journal 2018 Journal Article

Connectivity-enhanced diffusion analysis reveals white matter density disruptions in first episode and chronic schizophrenia

  • Rachael G. Grazioplene
  • Carrie E. Bearden
  • Kenneth L. Subotnik
  • Joseph Ventura
  • Kristen Haut
  • Keith H. Nuechterlein
  • Tyrone D. Cannon

Reduced fractional anisotropy (FA) is a well-established correlate of schizophrenia, but it remains unclear whether these tensor-based differences are the result of axon damage and/or organizational changes and whether the changes are progressive in the adult course of illness. Diffusion MRI data were collected in 81 schizophrenia patients (54 first episode and 27 chronic) and 64 controls. Analysis of FA was combined with “fixel-based” analysis, the latter of which leverages connectivity and crossing-fiber information to assess both fiber bundle density and organizational complexity (i. e. , presence and magnitude of off-axis diffusion signal). Compared with controls, patients with schizophrenia displayed clusters of significantly lower FA in the bilateral frontal lobes, right dorsal centrum semiovale, and the left anterior limb of the internal capsule. All FA-based group differences overlapped substantially with regions containing complex fiber architecture. FA within these clusters was positively correlated with principal axis fiber density, but inversely correlated with both secondary/tertiary axis fiber density and voxel-wise fiber complexity. Crossing fiber complexity had the strongest (inverse) association with FA (r = −0. 82). When crossing fiber structure was modeled in the MRtrix fixel-based analysis pipeline, patients exhibited significantly lower fiber density compared to controls in the dorsal and posterior corpus callosum (central, postcentral, and forceps major). Findings of lower FA in patients with schizophrenia likely reflect two inversely related signals: reduced density of principal axis fiber tracts and increased off-axis diffusion sources. Whereas the former confirms at least some regions where myelin and or/axon count are lower in schizophrenia, the latter indicates that the FA signal from principal axis fiber coherence is broadly contaminated by macrostructural complexity, and therefore does not necessarily reflect microstructural group differences. These results underline the need to move beyond tensor-based models in favor of acquisition and analysis techniques that can help disambiguate different sources of white matter disruptions associated with schizophrenia.

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YNIMG Journal 2017 Journal Article

Multisite reliability of MR-based functional connectivity

  • Stephanie Noble
  • Dustin Scheinost
  • Emily S. Finn
  • Xilin Shen
  • Xenophon Papademetris
  • Sarah C. McEwen
  • Carrie E. Bearden
  • Jean Addington

Recent years have witnessed an increasing number of multisite MRI functional connectivity (fcMRI) studies. While multisite studies provide an efficient way to accelerate data collection and increase sample sizes, especially for rare clinical populations, any effects of site or MRI scanner could ultimately limit power and weaken results. Little data exists on the stability of functional connectivity measurements across sites and sessions. In this study, we assess the influence of site and session on resting state functional connectivity measurements in a healthy cohort of traveling subjects (8 subjects scanned twice at each of 8 sites) scanned as part of the North American Prodrome Longitudinal Study (NAPLS). Reliability was investigated in three types of connectivity analyses: (1) seed-based connectivity with posterior cingulate cortex (PCC), right motor cortex (RMC), and left thalamus (LT) as seeds; (2) the intrinsic connectivity distribution (ICD), a voxel-wise connectivity measure; and (3) matrix connectivity, a whole-brain, atlas-based approach to assessing connectivity between nodes. Contributions to variability in connectivity due to subject, site, and day-of-scan were quantified and used to assess between-session (test-retest) reliability in accordance with Generalizability Theory. Overall, no major site, scanner manufacturer, or day-of-scan effects were found for the univariate connectivity analyses; instead, subject effects dominated relative to the other measured factors. However, summaries of voxel-wise connectivity were found to be sensitive to site and scanner manufacturer effects. For all connectivity measures, although subject variance was three times the site variance, the residual represented 60–80% of the variance, indicating that connectivity differed greatly from scan to scan independent of any of the measured factors (i. e. , subject, site, and day-of-scan). Thus, for a single 5min scan, reliability across connectivity measures was poor (ICC=0. 07–0. 17), but increased with increasing scan duration (ICC=0. 21–0. 36 at 25min). The limited effects of site and scanner manufacturer support the use of multisite studies, such as NAPLS, as a viable means of collecting data on rare populations and increasing power in univariate functional connectivity studies. However, the results indicate that aggregation of fcMRI data across longer scan durations is necessary to increase the reliability of connectivity estimates at the single-subject level.

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YNIMG Journal 2017 Journal Article

Reliability of functional magnetic resonance imaging activation during working memory in a multisite study: Clarification and implications for statistical power

  • Tyrone D. Cannon
  • Hengyi Cao
  • Daniel H. Mathalon
  • Jennifer Forsyth

In this technical note, we clarify the meaning of the generalizability-theory based coefficients reported in our multisite reliability study of fMRI measures of regional brain activation during working memory processing (Forsyth et al. , Neuroimage 2014; 97: 51-52). While the original paper reported generalizability and dependability coefficients based on the design of our traveling subjects study (in which each subject was scanned twice at each of eight sites), those coefficients are of limited applicability outside of the reliability study context. Here we report generalizability and dependability coefficients that represent the reliability one can expect for a multisite study in which a given subject is scanned once on a scanner drawn randomly from the pool of available scanners (i. e. , analogous to the more typical multisite study design). We also characterize the implications of a multisite versus single site study design for statistical power, including a figure that shows sample size requirements to detect activation in two key nodes of the working memory circuitry given observed differences in reliability of measurement between single and multisite designs.

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YNIMG Journal 2017 Journal Article

Using neuroimaging to help predict the onset of psychosis

  • George Gifford
  • Nicolas Crossley
  • Paolo Fusar-Poli
  • Hugo G. Schnack
  • René S. Kahn
  • Nikolaos Koutsouleris
  • Tyrone D. Cannon
  • Philip McGuire

The aim of this review is to assess the potential for neuroimaging measures to facilitate prediction of the onset of psychosis. Research in this field has mainly involved people at ‘ultra-high risk’ (UHR) of psychosis, who have a very high risk of developing a psychotic disorder within a few years of presentation to mental health services. The review details the key findings and developments in this area to date and examines the methodological and logistical challenges associated with making predictions in an individual subject in a clinical setting.

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YNIMG Journal 2015 Journal Article

Functional connectivity in BOLD and CBF data: Similarity and reliability of resting brain networks

  • Kay Jann
  • Dylan G. Gee
  • Emily Kilroy
  • Simon Schwab
  • Robert X. Smith
  • Tyrone D. Cannon
  • Danny J.J. Wang

Resting-state functional connectivity (FC) fMRI (rs-fcMRI) offers an appealing approach to mapping the brain's intrinsic functional organization. Blood oxygen level dependent (BOLD) and arterial spin labeling (ASL) are the two main rs-fcMRI approaches to assess alterations in brain networks associated with individual differences, behavior and psychopathology. While the BOLD signal is stronger with a higher temporal resolution, ASL provides quantitative, direct measures of the physiology and metabolism of specific networks. This study systematically investigated the similarity and reliability of resting brain networks (RBNs) in BOLD and ASL. A 2×2×2 factorial design was employed where each subject underwent repeated BOLD and ASL rs-fcMRI scans on two occasions on two MRI scanners respectively. Both independent and joint FC analyses revealed common RBNs in ASL and BOLD rs-fcMRI with a moderate to high level of spatial overlap, verified by Dice Similarity Coefficients. Test–retest analyses indicated more reliable spatial network patterns in BOLD (average modal Intraclass Correlation Coefficients: 0. 905±0. 033 between-sessions; 0. 885±0. 052 between-scanners) than ASL (0. 545±0. 048; 0. 575±0. 059). Nevertheless, ASL provided highly reproducible (0. 955±0. 021; 0. 970±0. 011) network-specific CBF measurements. Moreover, we observed positive correlations between regional CBF and FC in core areas of all RBNs indicating a relationship between network connectivity and its baseline metabolism. Taken together, the combination of ASL and BOLD rs-fcMRI provides a powerful tool for characterizing the spatiotemporal and quantitative properties of RBNs. These findings pave the way for future BOLD and ASL rs-fcMRI studies in clinical populations that are carried out across time and scanners.

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YNIMG Journal 2014 Journal Article

Reliability of functional magnetic resonance imaging activation during working memory in a multi-site study: Analysis from the North American Prodrome Longitudinal Study

  • Jennifer K. Forsyth
  • Sarah C. McEwen
  • Dylan G. Gee
  • Carrie E. Bearden
  • Jean Addington
  • Brad Goodyear
  • Kristin S. Cadenhead
  • Heline Mirzakhanian

Multi-site neuroimaging studies offer an efficient means to study brain functioning in large samples of individuals with rare conditions; however, they present new challenges given that aggregating data across sites introduces additional variability into measures of interest. Assessing the reliability of brain activation across study sites and comparing statistical methods for pooling functional data are critical to ensuring the validity of aggregating data across sites. The current study used two samples of healthy individuals to assess the feasibility and reliability of aggregating multi-site functional magnetic resonance imaging (fMRI) data from a Sternberg-style verbal working memory task. Participants were recruited as part of the North American Prodrome Longitudinal Study (NAPLS), which comprises eight fMRI scanning sites across the United States and Canada. In the first study sample (n =8), one participant from each home site traveled to each of the sites and was scanned while completing the task on two consecutive days. Reliability was examined using generalizability theory. Results indicated that blood oxygen level-dependent (BOLD) signal was reproducible across sites and was highly reliable, or generalizable, across scanning sites and testing days for core working memory ROIs (generalizability ICCs=0. 81 for left dorsolateral prefrontal cortex, 0. 95 for left superior parietal cortex). In the second study sample (n =154), two statistical methods for aggregating fMRI data across sites for all healthy individuals recruited as control participants in the NAPLS study were compared. Control participants were scanned on one occasion at the site from which they were recruited. Results from the image-based meta-analysis (IBMA) method and mixed effects model with site covariance method both showed robust activation in expected regions (i. e. dorsolateral prefrontal cortex, anterior cingulate cortex, supplementary motor cortex, superior parietal cortex, inferior temporal cortex, cerebellum, thalamus, basal ganglia). Quantification of the similarity of group maps from these methods confirmed a very high (96%) degree of spatial overlap in results. Thus, brain activation during working memory function was reliable across the NAPLS sites and both the IBMA and mixed effects model with site covariance methods appear to be valid approaches for aggregating data across sites. These findings indicate that multi-site functional neuroimaging can offer a reliable means to increase power and generalizability of results when investigating brain function in rare populations and support the multi-site investigation of working memory function in the NAPLS study, in particular.

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YNIMG Journal 2012 Journal Article

Structural and functional neuroimaging phenotypes in dysbindin mutant mice

  • Evan Lutkenhoff
  • Katherine H. Karlsgodt
  • Boris Gutman
  • Jason L. Stein
  • Paul M. Thompson
  • Tyrone D. Cannon
  • J. David Jentsch

Schizophrenia is a highly heritable psychiatric disorder that is associated with a number of structural and functional neurophenotypes. DTNBP1, the gene encoding dysbindin-1, is a promising candidate gene for schizophrenia. Use of a mouse model carrying a large genomic deletion exclusively within the dysbindin gene permits a direct investigation of the gene in isolation. Here, we use manganese-enhanced magnetic resonance imaging (MEMRI) to explore the regional alterations in brain structure and function caused by loss of the gene encoding dysbindin-1. We report novel findings that uniquely inform our understanding of the relationship of dysbindin-1 to known schizophrenia phenotypes. First, in mutant mice, analysis of the rate of manganese uptake into the brain over a 24-hour period, putatively indexing basal cellular activity, revealed differences in dopamine rich brain regions, as well as in CA1 and dentate subregions of the hippocampus formation. Finally, novel tensor-based morphometry techniques were applied to the mouse MRI data, providing evidence for structural volume deficits in cortical regions, subiculum and dentate gyrus, and the striatum of dysbindin mutant mice. The affected cortical regions were primarily localized to the sensory cortices in particular the auditory cortex. This work represents the first application of manganese-enhanced small animal imaging to a mouse model of schizophrenia endophenotypes, and a novel combination of functional and structural measures. It revealed both hypothesized and novel structural and functional neural alterations related to dysbindin-1.

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YNIMG Journal 2005 Journal Article

Hippocampal activations during encoding and retrieval in a verbal working memory paradigm

  • Katherine H. Karlsgodt
  • David Shirinyan
  • Theo G.M. van Erp
  • Mark S. Cohen
  • Tyrone D. Cannon

Though the hippocampus has been associated with encoding and retrieval processes in episodic memory, the precise nature of its involvement in working memory has yet to be determined. This functional magnetic resonance imaging (fMRI) study employed a verbal working memory paradigm that allows for the within-subject comparison of functional activations during encoding, maintenance, and retrieval. In each trial, participants were shown 5 target words and, after an 8 s delay, a series of probe words. Probe words consisted of target matches, phonetically or semantically related foils, or foils unrelated to the target words. Both the left and right hippocampi showed higher mean activation amplitudes during encoding than maintenance. In contrast, the right dorsolateral prefrontal cortex (DLPFC) showed greater activation during maintenance than encoding. Both hippocampal and DLPFC regions were more active during retrieval than maintenance. Furthermore, an analysis of retrieval activation separated by probe type showed a trend toward greater bilateral hippocampal activation for probes related (both semantically and phonetically) to the target than for unrelated probes and still greater activation for target matches. This pattern suggests that there may be roles for the hippocampus and DLPFC in working memory that change as function of information processing stage. Additionally, the trend towards increased involvement of the hippocampus with the increase in relatedness of the probe stimuli to the information maintained is interpreted to be consistent with the role of the hippocampus in recollection-based retrieval in long-term memory and may indicate that this role extends to working memory processes.

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YNIMG Journal 2004 Journal Article

Mapping cortical change in Alzheimer's disease, brain development, and schizophrenia

  • Paul M. Thompson
  • Kiralee M. Hayashi
  • Elizabeth R. Sowell
  • Nitin Gogtay
  • Jay N. Giedd
  • Judith L. Rapoport
  • Greig I. de Zubicaray
  • Andrew L. Janke

This paper describes algorithms that can identify patterns of brain structure and function associated with Alzheimer's disease, schizophrenia, normal aging, and abnormal brain development based on imaging data collected in large human populations. Extraordinary information can be discovered with these techniques: dynamic brain maps reveal how the brain grows in childhood, how it changes in disease, and how it responds to medication. Genetic brain maps can reveal genetic influences on brain structure, shedding light on the nature–nurture debate, and the mechanisms underlying inherited neurobehavioral disorders. Recently, we created time-lapse movies of brain structure for a variety of diseases. These identify complex, shifting patterns of brain structural deficits, revealing where, and at what rate, the path of brain deterioration in illness deviates from normal. Statistical criteria can then identify situations in which these changes are abnormally accelerated, or when medication or other interventions slow them. In this paper, we focus on describing our approaches to map structural changes in the cortex. These methods have already been used to reveal the profile of brain anomalies in studies of dementia, epilepsy, depression, childhood- and adult-onset schizophrenia, bipolar disorder, attention-deficit/hyperactivity disorder, fetal alcohol syndrome, Tourette syndrome, Williams syndrome, and in methamphetamine abusers. Specifically, we describe an image analysis pipeline known as cortical pattern matching that helps compare and pool cortical data over time and across subjects. Statistics are then defined to identify brain structural differences between groups, including localized alterations in cortical thickness, gray matter density (GMD), and asymmetries in cortical organization. Subtle features, not seen in individual brain scans, often emerge when population-based brain data are averaged in this way. Illustrative examples are presented to show the profound effects of development and various diseases on the human cortex. Dynamically spreading waves of gray matter loss are tracked in dementia and schizophrenia, and these sequences are related to normally occurring changes in healthy subjects of various ages.

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v2026.09.13