Dost Öngür

YNIMG Journal 2023 Journal Article

Exploring the influence of functional architecture on cortical thickness networks in early psychosis – A longitudinal study

• Kristina M. Holton
• Shi Yu Chan
• Austin J. Brockmeier
• Dost Öngür
• Mei-Hua Hall

Cortical thickness reductions differ between individuals with psychotic disorders and comparison subjects even in early stages of illness. Whether these reductions covary as expected by functional network membership or simply by spatial proximity has not been fully elucidated. Through orthonormal projective non-negative matrix factorization, cortical thickness measurements in functionally-annotated regions from MRI scans of early-stage psychosis and matched healthy controls were reduced in dimensionality into features capturing positive covariance. Rather than matching the functional networks, the covarying regions in each feature displayed a more localized spatial organization. With Bayesian belief networks, the covarying regions per feature were arranged into a network topology to visualize the dependency structure and identify key driving regions. The features demonstrated diagnosis-specific differences in cortical thickness distributions per feature, identifying reduction-vulnerable spatial regions. Differences in key cortical thickness features between psychosis and control groups were delineated, as well as those between affective and non-affective psychosis. Clustering of the participants, stratified by diagnosis and clinical variables, characterized the clinical traits that define the cortical thickness patterns. Longitudinal follow-up revealed that in select clusters with low baseline cortical thickness, clinical traits improved over time. Our study represents a novel effort to characterize brain structure in relation to functional networks in healthy and clinical populations and to map patterns of cortical thickness alterations among ESP patients onto clinical variables for a better understanding of brain pathophysiology.

YNICL Journal 2021 Journal Article

Auditory hallucinations across the psychosis spectrum: Evidence of dysconnectivity involving cerebellar and temporal lobe regions

• Melissa Hwang
• Youkyung S. Roh
• Jessica Talero
• Bruce M. Cohen
• Justin T. Baker
• Roscoe O. Brady
• Dost Öngür
• Ann K. Shinn

BACKGROUND: Auditory hallucinations (AH) are typically associated with schizophrenia (SZ), but they are also prevalent in bipolar disorder (BD). Despite the large body of research on the neural correlates of AH in SZ, the pathophysiology underlying AH remains unclear. Few studies have examined the neural substrates associated with propensity for AH in BD. Investigating AH across the psychosis spectrum has the potential to inform about the neural signature associated with the trait of AH, irrespective of psychiatric diagnosis. METHODS: We compared resting state functional magnetic resonance imaging data in psychosis patients with (n = 90 AH; 68 SZ, 22 BD) and without (n = 55 NAH; 16 SZ, 39 BD) lifetime AH. We performed region of interest (ROI)-to-ROI functional connectivity (FC) analysis using 91 cortical, 15 subcortical, and 26 cerebellar atlas-defined regions. The primary aim was to identify FC differences between patients with and without lifetime AH. We secondarily examined differences between AH and NAH within each diagnosis. RESULTS: Compared to the NAH group, patients with AH showed higher FC between cerebellum and frontal (left precentral gyrus), temporal [right middle temporal gyrus (MTG), left inferior temporal gyrus (ITG), left temporal fusiform gyrus)], parietal (bilateral superior parietal lobules), and subcortical (left accumbens, left palldium) brain areas. AH also showed lower FC between temporal lobe regions (between right ITG and right MTG and bilateral superior temporal gyri) relative to NAH. CONCLUSIONS: Our findings suggest that dysconnectivity involving the cerebellum and temporal lobe regions may be common neurofunctional elements associated with AH propensity across the psychosis spectrum. We also found dysconnectivity patterns that were unique to lifetime AH within SZ or bipolar psychosis, suggesting both common and distinct mechanisms underlying AH pathophysiology in these disorders.

YNICL Journal 2019 Journal Article

Decreased peak alpha frequency and impaired visual evoked potentials in first episode psychosis

• Michael Murphy
• Dost Öngür

Abnormal spontaneous and evoked oscillations have been reported in several studies of patients with psychotic disorders. Resting alpha power and peak alpha frequency may be decreased in patients with psychosis. We used high-density EEG (hd-EEG) to record resting-state data and steady-state visual evoked potentials (SSVEPs) in patients with first episode psychosis (FEP) and healthy controls to compare brain resonances across multiple frequencies. We recorded hd-EEG (128 channels) from 22 FEP patients and 22 healthy controls during eyes-closed resting state and eyes-closed photic stimulation at 1 Hz, 4 Hz, 10 Hz, 20 Hz, and 40 Hz. Alpha power, peak alpha frequency, and SSVEP amplitude were analyzed using ANOVA and statistical non-parametric mapping. We found that FEP patients had lower peak alpha frequencies (9. 72 Hz vs 10. 40 Hz, p =. 02, Cohen's d = 0. 73) and this decrease was driven by slowing over the central and posterior scalp. There was no difference in alpha power. Alpha waves propagated primarily from anterior to posterior and that propagation was slowed in patients. During SSVEP, patients had smaller increases in EEG power in the stimulation band (F(1, 184) = 5. 3, p =. 02). Patients had attenuated responses to SSVEP stimulation at alpha, beta and gamma frequencies. The gamma response was partially preserved in patients who also had depressive symptoms. We conclude that even in early stages of illness, psychotic disorders are associated with decreased alpha peak frequency and impaired evoked resonances. These findings implicate multiple patterns of dysconnectivity in cortico-cortico and cortico-thalamic networks in FEP.

YNIMG Journal 2019 Journal Article

Individual variation in brain network topology is linked to emotional intelligence

• George Ling
• Ivy Lee
• Synthia Guimond
• Olivia Lutz
• Neeraj Tandon
• Uzma Nawaz
• Dost Öngür
• Shaun Eack

Background Social cognitive ability is a significant determinant of functional outcome, and deficits in social cognition are a disabling symptom of psychotic disorders. The neurobiological underpinnings of social cognition are not well understood, hampering our ability to ameliorate these deficits. Objective Using ‘resting state’ functional magnetic resonance imaging (rsfMRI) and a trans-diagnostic, data-driven analytic strategy, we sought to identify the brain network basis of emotional intelligence, a key domain of social cognition. Methods The study included 60 participants with a diagnosis of schizophrenia or schizoaffective disorder and 45 healthy controls. All participants underwent a rsfMRI scan. Emotional Intelligence was measured using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). A connectome-wide analysis examined how each individual brain voxel's connectivity correlated with emotional intelligence using multivariate distance matrix regression (MDMR). Results We identified a region in the left superior parietal lobule (SPL) where individual network topology is linked to emotional intelligence. Specifically, in high scoring individuals, this region is a node of the Default Mode Network and in low scoring individuals, it is a node of the Dorsal Attention Network. This relationship was observed in both schizophrenia and healthy comparison participants. Conclusion Prior studies have demonstrated individual variance in the topology of canonical resting state networks but the cognitive or behavioral relevance of these differences has largely been undetermined. We observe that the left SPL, a region of high individual variance at the cytoarchitectonic level, also demonstrates individual variance in its association with large scale resting-state networks and that network topology is linked to emotional intelligence.

YNIMG Journal 2015 Journal Article

Frontal P3 event-related potential is related to brain glutamine/glutamate ratio measured in vivo

• Mei-Hua Hall
• J. Eric Jensen
• Fei Du
• Jordan W. Smoller
• Lauren O’Connor
• Kevin M. Spencer
• Dost Öngür

Background The auditory P3 event-related potential (ERP) is thought to index cognitive processing relevant to attention and working memory processes. Drug challenge studies suggest that glutamate neurotransmission plays an important role in modulating P3 ERP. However, while direct links between glutamate activity and P3 ERP response in humans are suspected, mechanistic details remain largely unknown. We investigated here the relationships between P3 ERP and indices of glutamatergic processing measured in vivo with proton magnetic resonance spectroscopy (1H MRS). We hypothesized that a higher index of glutamatergic processing (glutamine/glutamate ratio; abbreviated Gln/Glu) in the anterior cingulate (ACC) and in the parietal–occipital (POC) cortices would associate with larger frontal P3a and parietal P3b amplitudes, respectively. Methods Frontal P3a (Fz) and parietal P3b (Pz) were collected from 32 healthy participants who performed an auditory oddball task. Resting glutamate (Glu), glutamine (Gln), and Gln/Glu (an index of glutamatergic processing) measures were obtained on a 4T MR scanner using J-resolved MR spectroscopy. Linear regression and partial correlations were used for statistical analysis. Results Significant positive correlations were found between frontal P3a amplitude and ACC Gln/Glu ratio (partial R =0. 57; P =0. 001) and between frontal P3a amplitude and ACC Gln concentration (partial R =0. 43; P =0. 02). Relationships between parietal P3b and the glutamate indices in the POC were not significant. Conclusions These results indicate a specific connection between an index of glutamate neurotransmitter function in ACC and frontal P3 ERP, providing a novel insight into the neurochemistry underlying scalp recorded EEG response. Abnormalities in glutamate neurotransmission have been observed in schizophrenia and other psychiatric conditions and may underlie illness related deficits of P3 ERP.

YNIMG Journal 2012 Journal Article

Anticorrelations in resting state networks without global signal regression

• Xiaoqian J. Chai
• Alfonso Nieto Castañón
• Dost Öngür
• Susan Whitfield-Gabrieli

Anticorrelated relationships in spontaneous signal fluctuation have been previously observed in resting-state functional magnetic resonance imaging (fMRI). In particular, it was proposed that there exists two systems in the brain that are intrinsically organized into anticorrelated networks, the default mode network, which usually exhibits task-related deactivations, and the task-positive network, which usually exhibits task-related activations during tasks that demands external attention. However, it is currently under debate whether the anticorrelations observed in resting state fMRI were valid or were instead artificially introduced by global signal regression, a common preprocessing technique to remove physiological and other noise in resting-state fMRI signal. We examined positive and negative correlations in resting-state connectivity using two different preprocessing methods: a component base noise reduction method (CompCor, Behzadi et al. , 2007), in which principal components from noise regions-of-interest were removed, and the global signal regression method. Robust anticorrelations between a default mode network seed region in the medial prefrontal cortex and regions of the task-positive network were observed under both methods. Specificity of the anticorrelations was similar between the two methods. Specificity and sensitivity for positive correlations were higher under CompCor compared to the global regression method. Our results suggest that anticorrelations observed in resting-state connectivity are not an artifact introduced by global signal regression and might have biological origins, and that the CompCor method can be used to examine valid anticorrelations during rest.

YNIMG Journal 1998 Journal Article

Volumetric Studies of the Amygdala in Mood Disorders

• Dost Öngür
• Wayne C. Drevets
• Joseph L. Price