Tushar Das

Propofol-induced Frontal Cortex Disconnection: a Study of Resting State Networks, Total Brain Connectivity, and Mean BOLD Signal Oscillation Frequencies.

Propofol is one of the most commonly used anesthetics in the world, but much remains unknown about the mechanisms by which it induces loss of consciousness. In this resting-state functional magnetic resonance imaging study, we examined qualitative and quantitative changes of resting-state networks (RSNs), total brain connectivity, and mean oscillation frequencies of the regional blood oxygenation level-dependent (BOLD) signal, associated with propofol-induced mild sedation and loss of responsiveness in healthy subjects. We found that detectability of RSNs diminished significantly with loss of responsiveness, and total brain connectivity decreased strongly in the frontal cortex, which was associated with increased mean oscillation frequencies of the BOLD signal. Our results suggest a pivotal role of the frontal cortex in propofol-induced loss of responsiveness.

Highlighting the Structure-Function Relationship of the Brain with the Ising Model and Graph Theory

With the advent of neuroimaging techniques, it becomes feasible to explore the structure-function relationships in the brain. When the brain is not involved in any cognitive task or stimulated by any external output, it preserves important activities which follow well-defined spatial distribution patterns. Understanding the self-organization of the brain from its anatomical structure, it has been recently suggested to model the observed functional pattern from the structure of white matter fiber bundles. Different models which study synchronization (e.g., the Kuramoto model) or global dynamics (e.g., the Ising model) have shown success in capturing fundamental properties of the brain. In particular, these models can explain the competition between modularity and specialization and the need for integration in the brain. Graphing the functional and structural brain organization supports the model and can also highlight the strategy used to process and organize large amount of information traveling between the different modules. How the flow of information can be prevented or partially destroyed in pathological states, like in severe brain injured patients with disorders of consciousness or by pharmacological induction like in anaesthesia, will also help us to better understand how global or integrated behavior can emerge from local and modular interactions.

Surface magnetic polaritons in ferromagnetic and antiferromagnetic cylindrical tubes

A theory is developed for the localized surface magnetic polaritons in hollow magnetic cylinders or tubes, in the presence of a longitudinal applied field. This involves solving for the dynamical response using the nondiagonal susceptibility tensor for a ferromagnet or antiferromagnet in Maxwell’s equations, with electromagnetic boundary conditions at the inner and outer tube surfaces. Results for wires and antiwires are deduced as limiting cases of this geometry. As the outer radius is increased, the surface polariton branches near the light line are reduced in frequency and the localization properties are modified due to strong retardation effects. Numerical applications are made to yttrium iron garnet and MnF2 materials.

Clinical utility of a short resting-state MRI scan in differentiating bipolar from unipolar depression

Depression in bipolar disorder (BipD) requires a therapeutic approach that is from treating unipolar major depressive disorder (UniD), but to date, no reliable methods could separate these two disorders. The aim of this study was to establish the clinical validity and utility of a non‐invasive functional MRI‐based method to classify BipD from UniD.

Theory of dipole-exchange spin waves in metallic ferromagnetic nanotubes of large aspect ratio

A macroscopic continuum theory is presented for the dipole-exchange spin waves in nanometer-sized cylindrical tubes with a large length-to-diameter aspect ratio. The magnetization and applied magnetic field are taken parallel to the cylinder axis, and the properties of the hybridized surface and bulk magnetic excitations are studied in relation to the inner and outer interfaces of the nanotubes. The calculations describe the radial and angular quantization of the different modes for both unpinned and effective pinned cases. The results for tube geometries are found to be in contrast with the limiting (single-interface) special cases of wires and antiwires. Numerical examples are presented mainly for Ni materials.

A method for independent component graph analysis of resting-state fMRI.

Independent component analysis (ICA) has been extensively used for reducing task‐free BOLD fMRI recordings into spatial maps and their associated time‐courses. The spatially identified independent components can be considered as intrinsic connectivity networks (ICNs) of non‐contiguous regions. To date, the spatial patterns of the networks have been analyzed with techniques developed for volumetric data.

Disorganized Gyrification Network Properties During the Transition to Psychosis

Importance There is urgent need to improve the limited prognostic accuracy of clinical instruments to predict psychosis onset in individuals at clinical high risk (CHR) for psychosis. As yet, no reliable biological marker has been established to delineate CHR individuals who will develop psychosis from those who will not. Objectives To investigate abnormalities in a graph-based gyrification connectome in the early stages of psychosis and to test the accuracy of this systems-based approach to predict a transition to psychosis among CHR individuals. Design, Setting, and Participants This investigation was a cross-sectional magnetic resonance imaging (MRI) study with follow-up assessment to determine the transition status of CHR individuals. Participants were recruited from a specialized clinic for the early detection of psychosis at the Department of Psychiatry (Universitäre Psychiatrische Kliniken [UPK]), University of Basel, Basel, Switzerland. Participants included individuals in the following 4 study groups: 44 healthy controls (HC group), 63 at-risk mental state (ARMS) individuals without later transition to psychosis (ARMS-NT group), 16 ARMS individuals with later transition to psychosis (ARMS-T group), and 38 antipsychotic-free patients with first-episode psychosis (FEP group). The study dates were November 2008 to November 2014. The dates of analysis were March to November 2017. Main Outcomes and Measures Gyrification-based structural covariance networks (connectomes) were constructed to quantify global integration, segregation, and small-worldness. Group differences in network measures were assessed using functional data analysis across a range of network densities. The extremely randomized trees algorithm with repeated 5-fold cross-validation was used to delineate ARMS-T individuals from ARMS-NT individuals. Permutation tests were conducted to assess the significance of classification performance measures. Results The 4 study groups comprised 161 participants with mean (SD) ages ranging from 24.0 (4.7) to 25.9 (5.7) years. Small-worldness was reduced in the ARMS-T and FEP groups and was associated with decreased integration and increased segregation in both groups (Hedges g range, 0.666-1.050). Using the connectome properties as features, a good classification performance was obtained (accuracy, 90.49%; balanced accuracy, 81.34%; positive predictive value, 84.47%; negative predictive value, 92.18%; sensitivity, 66.11%; specificity, 96.58%; and area under the curve, 88.30%). Conclusions and Relevance These findings suggest that there is poor integration in the coordinated development of cortical folding in patients who develop psychosis. These results further suggest that gyrification-based connectomes might be a promising means to generate systems-based measures from anatomical data to improve individual prediction of a transition to psychosis in CHR individuals.

Coupled Dipolar Spin Waves of Magnetic Multilayer Systems With Cylindrical Geometries

A theory is developed for the dipolar spin waves in cylindrical multilayer systems consisting of a core surrounded by any arbitrary number of concentric layers (or tubes). Each layer may be magnetic (either ferromagnetic or antiferromagnetic) or a nonmagnetic spacer. The long-range dipolar fields provide coupling between magnetic layers across the spacer regions, resulting in a coupling between the dipolar modes of the system. A transfer matrix approach is employed to calculate the dispersion relations for the mode frequencies in terms of a longitudinal wave number. Numerical applications are made to multilayer systems that include several layers of the ferromagnet Ni, or the uniaxial antiferromagnet GdAlO3, or both. Particular attention is given to the localized interface modes, which are shown to be strongly modified (for example, in their frequency and wave number cutoff) by the multilayer structure, compared to the behavior found in single magnetic wires and tubes.

S123. TREATMENT RESISTANT SCHIZOPHRENIA AND GYRIFICATION-BASED CONNECTOME

Abstract Background Treatment-resistant schizophrenia (TRS) is a major cause of disability and functional impairment worldwide. Approximately 30% of patients with schizophrenia will develop TRS at some point during their illness course. Despite the staggering financial and emotional costs associated with TRS, this severe disorder is poorly understood. The pathophysiological basis of TRS is posited in part to have neurodevelopmental roots. If early brain development (<2 years of age) influences TRS, then cortical gyrification, which is often complete by 2 years of life, could be abnormal in TRS when compared to non-TRS subjects. Subtle but diffuse pathological changes that occur during early development are postulated to disrupt the maturational relationship (covariance) among brain regions, even if no localised morphological changes are seen in adult life. The disrupted structural covariance resulting from diffuse developmental dyscoordination in early life can be quantified using gyrification-based connectomes obtained using graph theory. We applied this method to baseline MRI data collected during first contact with mental health services for psychosis to predict the emergence of TRS in the next 5 years. Methods 70 patients with first episode schizophrenia spectrum disorder who presented to mental health services between 2005 and 2010 were followed up for 5 years using electronic case notes. Psychopathology was assessed at baseline with the Positive and Negative Syndrome Scale (PANSS) and symptom dimensions were derived using Wallwork’s model. TRS was defined according to Health and Clinical Excellence guidelines. Structural MRI images were obtained at baseline, with minimal exposure to antipsychotics (<3 months). Local gyrification indices were computed using Schaer’s method for 68 contiguous cortical regions (34 in each hemisphere) using Freesurfer’s Desikan atlas. After adjusting for age, gender and intracranial volume, group-based structural covariance was estimated (68x68 correlation indices) and each subject’s contribution to the covariance was quantified using a jack-knife procedure, providing one distance matrix for each subject. These matrices were used to construct distance-based gyrification connectomes using Graph Analysis Toolbox. We used a functional data analysis approach across a range of cost-thresholds to reduce multiple testing when comparing TRS and non-TRS groups. Results 17 (24.3%) of patients with first episode schizophrenia spectrum disorder met criteria for TRS at the end of the 5 years of follow up; 53 (75.7%) were non-TRS. TRS subjects had a significant reduction in small-worldness compared to non-TRS group (Hedges’s g=2.09, p<0.001) and reduced clustering coefficient (Hedges’s g=1.07, p<0.001) with increased path length (Hedges’s g=-2.17, p<0.001).The positive symptoms were positively correlated (after adjusting for age, gender and TRS status) with higher small-worldness (r=0.414, p=0.001) suggesting that a predominantly hyperdopaminergic status that induces positive symptoms may relate to preserved small-worldness seen in non-TRS individuals, while subtle developmental changes resulting in reduced small-worldness may underlie TRS. Discussion These changes suggest that in the presence of TRS, the cortex-wide covariance in folding patterns become less organized, with reduced regional segregation as well as reduced overall integration of the morphological connectome. Such an effect may result from weakening of the tensions that arise from inter-regional connectivity in the neonatal brain. The emergence of TRS may be characterised by a neurodevelopmentally driven abnormality in structural organisation of the human cortex in those who develop schizophrenia.

O6.3. PATTERNS OF GRAY MATTER ABNORMALITIES IN PATIENTS WITH FIRST-EPISODE AND TREATMENT-NAïVE SCHIZOPHRENIA

Abstract Background To detect schizophrenia-related anatomical changes that are not confounded by antipsychotic treatment and to establish clinically identifiable subgroups that differ in underlying neuroanatomical patterns. Methods This case-control study was conducted at West China hospital in China, and analysis was undertaken in Robarts Research Institute, London, Canada. 206 patients with schizophreniform psychosis and schizophrenia and 170 healthy controls were scanned on a Signa 3.0-T MR scanner; 137 patients with schizophreniform psychosis and schizophrenia and 172 healthy controls were scanned on a 3.0 T MR scanner. All the patients were first-episode and treatment-naïve. Source based morphometry (SBM) performed to analyze the gray matter (GM) concentration. Latent class analysis used to identify clinical subtypes of patients using the scores of symptom dimensions. GMC component-based connectomes were constructed to study the graphic organization of structural brain network of subtypes of schizophrenia. Results Patients showed prominent reduction in GM in two components; one including anterior insula, inferior frontal gyrus, anterior cingulate and another with superior temporal gyrus, and precuneus, inferior/superior parietal lobule, cuneus, and lingual gyrus. Increased GM was seen in one component of cerebellar tonsil and inferior semi-lunar lobule, and the other component of middle temporal gyrus, superior temporal gyrus, middle frontal gyrus and putamen. Greater GM of latter component was associated with less severe positive symptoms and better performance on cognitive tests. Reduced global efficiency only existed in a subgroup of patients with severe negative and disorganization symptoms. Discussion These findings delineate a common pattern of gray matter changes in schizophrenia, and a subgroup of patients with robust cortical reorganization suggestive of compensatory plasticity after first episode.