'Pattern Formation and Dynamics in Nonequilibrium Systems'




 

  Click here for poster presentations in 'Genetics and Neurophysiology of Alcohol Use Disorders'.

 

One of my favorite moments at a poster presentation:

Discussing my results of excitation waves in the Belousov-Zhabotinsky reaction

with Anatol M. Zhabotinsky and Tomohiko Yamaguchi.


A. Ambrose and N. Manz
"Using Matches to Investigate Forest Fire Propagation Along a Slope"
Fall 2017 Meeting of the APS Ohio-Region Section, Oxford, OH, USA, 2017 October 13-14

Abstract:
We experimentally analyzed how slope effects the propagation speed of forest fires. Using a match stick array, we created 3D-printed molds with various angles with specific conditions for the distance between neighboring match heads. We developed three types of models, in which the distance between the match heads are kept constant along the horizontal (x-model), along the vertical (z-model), and along the slope (r-model). For all three models, we determined the slope-speed relationship along the incline for upward and downward propagating fire fronts up to 45 degrees. Each model is best fitted by a different function which will be discussed.

PDF file of the poster on ResearchGate:

C. Fuller and N. Manz
"Effects of advection on the Belousov-Zhabotinsky reaction: standing excitation waves in a quasi-1D system"
Fall 2017 Meeting of the APS Ohio-Region Section, Oxford, OH, USA, 2017 October 13-14

Abstract:
Reaction-diffusion (RD) waves are autocatalytic reaction zones that propagate via molecular diffusion without mass transport. They arise from the interplay of nonlinear reaction kinetics of an activator and an inhibitor species and diffusion-mediated spatial coupling (e.g., action potentials in nerves, forest fires, or stadium waves). Introducing fluid flow in a liquid chemical RD system has a huge effect on the propagation behavior of the wave. By using quasi-1D systems, such as glass capillary tubes, it is possible to create `standing waves' by advecting the liquid solution opposite to the direction of wave propagation. In our experiments, we used the Belousov-Zhabotinsky reaction as the liquid RD system. The solution was restrained in capillaries, with inner diameters of 0.58 mm. This enabled us to study a quasi-1D reaction-diffusion-advection system. After initiating waves on the open end of the capillary, the reaction solution was advected in the opposite direction. The effect of flow rate on the propagation speed and front shape was investigated. Stationary chemical waves were observed under equal-velocity conditions.

PDF file of the poster on ResearchGate:

V. W. H. Hui, J. Lindner, and N. Manz
"The effect of obstacles on the propagation speed of reaction-diffusion waves"
Fall 2017 Meeting of the APS Ohio-Region Section, Oxford, OH, USA, 2017 October 13-14

Abstract:
This project investigates the effect of obstacles within a narrow channel on the propagation speed of reaction-diffusion waves. We used an objective-C program to solve the Tyson-Fife model, with two coupled differential equations, to simulate the behavior of these waves. Values for the activator and inhibitor's diffusion coefficients and the excitability variables were chosen to correspond with the nonlinear chemical Belousov-Zhabotinsky reaction.
We will present the following results: i) The concentration wave slowed down when passing around obstacles, due to the increased curvature of the wave front, then slowly returned to its original speed, while straightening the front again. ii) The average propagation speed, through a defined length of the channel, decreased when the obstacles (rhombuses and ellipses) became larger (size to channel-width ratio) or more vertically oriented (width-to-height radio). iii) The average speed decreased with increasing number of obstacles in the channel. iv) Using a constant number of obstacles, the average speed decreased with more evenly distributed obstacles compared to a dense row of obstacles followed by an uninterrupted channel.

PDF file of the poster on ResearchGate:

A. Gould and N. Manz
"BZ-Reaction diffusion wave speed around obstacles"
Spring 2017 Meeting of the APS Ohio-Region Section, Ypsilanti, MI, USA, 2017 May 5-6

Abstract:
We analyzed the effect of various sized rhombuses and elliptical obstacles on the propagation speed of reaction-diffusion waves. Through numerical simulations with a cellular automaton we found that the obstacle size has an influence on the wave speed of the reaction diffusion waves whereas no difference was found between rhombuses and ellipses of the same size. To create simulations similar to real wave behavior of the chemical model system, the Belousov-Zhabotinsky reaction, required operations with the standard, squared-cell cellular automata method which seemed to be non-physical. Therefore, we introduced a hexagonal structure to produce results which are more physically accurate to be comparable with planed experimental work.

PDF file of the poster on ResearchGate:

R.M.P. Morillo and N. Manz
"A Hill on fire: Using matches, 3D printing, and code as a forest fire analog"
21st Annual Posters on the Hill, Washington, DC, USA, 2017 April 26

Abstract:
The effect that slope has upon forest fire propagation was studied both experimentally and computationally. For the experimental aspect, a forest fire analog was created using matches as model trees inserted into a 3D printed base to produce the desired forest floor geometry. The specific geometry studied was a constant uphill or downhill slope to investigate the effect of the slope angle on the propagation speed. The results are compared to research done by Richard C. Rothermel at the USDA Forest Service. Using a cellular automaton computer simulation, more complex systems were examined, including the formation of spiral waves when treating the forest fire as a reaction-diffusion system.

PDF file of the poster on ResearchGate:

R.M.P. Morillo and N. Manz
"The Ring of Fire: The Effects of Slope upon Pattern Formation in Simulated Forest Fire Systems"
APS March Meeting 2017, New Orleans, LA, USA, 2017 March 13-17

Abstract:
We report about spreading fire fronts under sloped conditions using the general cellular automaton model and data from physical scaled-down experiments. Punckt et al. published experimental and computational results for planar systems [Wildfires in the Lab: Simple Experiment and Models for the Exploration of Excitable Dynamics, J. Chem. Educ. 92(8), 1330-1337, 2015] and our preliminary results confirmed the expected speed-slope dependence of fire fronts propagating up or down the hill with a cut-off slope value above which no fire front can exist. Here we focus on two fascinating structures in reaction-diffusion systems: circular expanding target pattern and rotating spirals. We investigated the behaviors of both structures with varied values for the slope of the forest and the homogeneity of the trees. For both variables, a range of values was found for which target pattern or spiral formation was possible.

PDF file of the poster on ResearchGate:

M.E. Manheim, J.F. Lindner, and N. Manz
"Experimentally modeling black and white hole event horizons via fluid flow"
APS March Meeting 2017, New Orleans, LA, USA, 2017 March 13-17

Abstract:
We will present a scaled down experiment that attempts to hydrodynamically model the interaction between electromagnetic waves and black/white hole event horizons. It has been mathematically proven that gravity waves in water can behave analogously to electromagnetic waves traveling through space-time [Schützhold and Unruh, Gravity Wave Analogues of Black Holes, Phys. Rev. D 66(4), 044019 (2002)]. Such an analogue has already been created in a (30x1.8x1.8) m3 tank [Rousseaux et al., Observation of Negative-frequency Waves in a Water Tank: A Classical Analogue to the Hawking Effect?, New J. Phys. 10(5), 053015 (2008)]. We have reduced the size significantly to be able to perform the experiment under more accessible conditions. In this experiment, gravity waves will be generated in a water tank and propagated in a direction opposed to a flow of varying rate. We observe a noticeable change the wave behavior when traveling through the region of varying flow, with decreased wave speeds and increased curvature.

PDF file of the poster on ResearchGate:

R.M.P. Morillo and N. Manz
"Burning up: The effect of slope upon forest fire propagation"
Dynamics Days 2017, Silver Spring, MD, USA, 2017 January 4-7

Abstract:
We report about experimental and computational results on forest fire propagation under sloped condition. Punckt et al. [Wildfires in the Lab: Simple Experiment and Models for the Exploration of Excitable Dynamics, J. Chem. Educ. 92(8), 1330-1337, 2015] used matchsticks as a lab analogue to investigate the spread of wildfires. We explore the effect of positive and negative slopes on the propagation of fire fronts i) experimentally, using various 3D printed molds with different angles to position the matches and ii) computationally, using a cellular automaton with adjusted diffusion coefficients in up and down direction. In this scaled forest we found a propagation speed dependence on the slope angle with cut-off values for negative slopes at which no waves can spread down the hill and cut-off values for positive slopes at which no clear defined fire front exists in favor of a fire burst. We will also present theoretical results about the slope effect on spiral-like fire fronts.

PDF file of the poster on ResearchGate:

R.M.P. Morillo and N. Manz
"Matchstick Forests: Studying Fire Spread On Hills Using a Scaled Model"
Fall 2016 Meeting of the APS Ohio-Region Section, Bowling Green, OH, USA, 2016 October 7-8

Abstract:
A scaled forest was created using matchsticks attached to an aluminum plate with a flame resistant putty. The setup allowed for one end of the the aluminum plate to be raised, creating a constant positive slope of tan(θ). The use of a 3D-printed grid to align the matchsticks ensured that the matchsticks had a constant spacing and were perpendicular to the ground regardless of the angle of the aluminum plate. By lighting one end of the matchstick grid on fire and recording the flame propagation across the grid, the rate of spread of the fire R was measured. We investigated whether or not this setup could be used to predict the relationship between R and θ and could be scaled up to analyze real forest fires.

PDF file of the poster on ResearchGate:

J. Pachar and N. Manz
"Effects of Advection on Reaction-Diffusion Waves"
Fall 2016 Meeting of the APS Ohio-Region Section, Bowling Green, OH, USA, 2016 October 7-8

Abstract:
A quasi-one-dimensional reaction-diffusion advection system is created by placing BZ solution in a capillary that is attached to a syringe filled with more solution. As the reaction occurs and waves propagate in the capillary, solution in the syringe is pushed into the capillary against the waves. At varying the velocity of the fluid being pushed, it is observed that the speed of advection will directly impact the speed of the propagating waves and that quasione-dimensional standing waves can be created under certain conditions.

PDF file of the poster on ResearchGate:

N. Manz, R. J. Field, and K. Kiprijanov
"Illustrative timeline of Boris P. Belousov and Anatol M. Zhabotinsky"
Gordon Research Conference on Oscillations and Dynamic Instabilities in Chemical Systems, Stowe, VT, USA, 2016 July 17-23

Abstract:
We present a selection of images of our project “The Belousov-­Zhabotinsky reaction: chronological and illustrated”, a visual and chronological approach to the history of the Belousov-­Zhabotinsky reaction. We hope to inspire other scientists to provide interesting images and/or background information.

PDF file of the poster on ResearchGate:

S. L. Kirn and N. Manz
"Light-sensitive reaction-diffusion waves in a checkerboard-like illumination system"
47th Central Regional Meeting of the American Chemical Society, Covington, KY, USA, 2016 May 18-21
Spring 2016 Meeting of the APS Ohio-Region Section, Dayton, OH, USA, 2016 April 8-9

Abstract:
We will report about a set-up to experimentally investigate the propagation behavior of excitation waves traveling through an inhomogeneously illuminated reaction-diffusion medium, including preliminary results. This work was inspired by the theoretical work done by Schebesch and Engel [Schebesch, I. and Engel, H., Wave propagationin heterogeneous excitable media, Phys. Rev. E, 57(4), 3905-3910, 1998], who numerically simulated the propagation behavior of light-sensitive excitation waves in a pure checkerboard-like illuminated system. We are using the model system of excitable meda, the chemical Belousov-Zhabotinsky (BZ) reaction, to verify their one-dimensional and two dimensional results.

PDF file of the poster on ResearchGate:

N. Manz, B. T. Ginn, and O. Steinbock
"Complex wave dynamics in the 1,4-cyclohexanedione Belousov-Zhabotinsky reaction"
International Chemical Congress of Pacific Basin Societies Sponsors, Honolulu, HI, USA, 2005 December 15-20

Abstract:
We report experimental and theoretical analyses of an excitable reaction-diffusion system with anomalous velocity-wavelength dependencies. In the 1,4-cyclohexanedione Belousov-Zhabotinsky system various novel dynamics (tracking, merging, and stacking) can be observed. In the tracking regime, wave patterns increase their size through repeated annihilation events of the frontier pulse that allow the succeeding pulses to advance farther. Merging dynamics involve a stable but slow frontier pulse that annihilates trailing waves in front-to-back collisions. We present quantitative measurements concerning wave merging and wave tracking. In particular, we describe unusual propagation failures and firing sequences that are characteristic for conditions between merging and tracking. Experimental observations are modeled and complemented by numerical simulations using simple, three-variable reaction-diffusion equations.

PDF file of the poster on ResearchGate:

N. Manz, B. T. Ginn, and O. Steinbock
"Excitable systems with an anomalous dispersion relations"
Gordon Research Conference on Oscillations and Dynamic Instabilities in Chemical Systems, Bates College, Lewiston, ME, USA, 2004 July 18-23

Abstract:
Propagating excitation waves exist in numerous biological, chemical, and physical systems. The wave velocity c and the period T of consecutive fronts are related through the dispersion relation. Most of these reaction-diffusion (RD) systems show a monotonically increasing dispersion relation c(T) that converges to the velocity of a solitary pulse for very large periods.
Exceptions from this normal behavior can be found in a few systems with a non-monotonic dispersion relation (e.g., non-unique rotation periods of spiral waves and different velocities for the same wavelength). We report about stacking, merging, and tracking behaviors during the wave propagation in the 1,4-cyclohexanedione Belousov-Zhabotinsky (CHD-BZ) reaction. It involves the oxidation of CHD by bromate in an acidic medium. Its main nonlinearity stems from the autocatalytic production of bromous acid. We use [Fe{batho(SO3)2}3]4-/3- as the redox catalyst to increase the contrast between the oxidized and the reduced state of the solution.
The CHD-BZ reaction is a valuable model system for experimental and numerical investigations of anomalous dispersion relations. Our observations reveal in the tracking regime an unexpected low-frequency limit for pulse trains that gives rise to a tracking-like evolution of wave patterns. The experimental results are reproduced by a simple, three-species RD model. In two-dimensional systems we identified a novel nucleation mechanism of spiral waves in a system with merging dynamics and observed a tracking-induced spiral drift along the “imaginary” frontier line of the excited domain. Two counter-rotating spirals, drifting along the boundary of an excited island.

PDF file of the poster on ResearchGate:

B. T. Ginn, N. Manz, and O. Steinbock
"Quantized spiral tip motion in a reaction-diffusion system with periodic heterogeneities"
Gordon Research Conference on Oscillations and Dynamic Instabilities in Chemical Systems, Bates College, Lewiston, ME, USA, 2004 July 18-23

Abstract:
The Belousov–Zhabotinsky (BZ) reaction involves the oxidation of an organic substrate by bromate in acidic solution and shows autocatalytic oxidation waves that are easily observed using a charged–coupled–device (CCD) camera. The significance of this reaction lies in its model character for the study of temporal and spatio–temporal self–organization. The reaction exhibits for example oscillations and traveling waves as a result of its nonlinear dynamics. Here, the classic organic substrate (malonic acid) is replaced by 1,4–cyclohexanedione (CHD). Soft Lithography combined with microfluidcs allows the creation of small, patterned reaction devices for chemical systems. These devices can be used to create devices with periodic heterogeneities for the study of reaction–diffusion system dynamics such as the BZ reaction.

PDF file of the poster on ResearchGate:

N. Manz, B. T. Ginn, and O. Steinbock
"Excitation wave dynamics in a chemical system with an anomalous dispersion relation"
American Physical Society, Montréal, Québec, Canada, 2004 March 22-26

Abstract:
We report about different propagation dynamics in the 1,4-cyclohexanedione (CHD) Belousov-Zhabotinsky system. Using CHD instead of malonic acid as its organic compound causes the appearance of at least one unstable branch in the dispersion relation with a negative slope. Depending on the initial concentration of sodium bromate in the reaction media one can find stacking and merging behavior [1,2,3] or the recently observed tracking regime. In this system we also found a new kind of spiral drift. The experimental results are explained in the framework of a three-variable reaction-diffusion model.
[1] N. Manz, S. C. Müller, and O. Steinbock, J. Phys. Chem. A 104 (2000), 5895.
[2] C. T. Hamik, N. Manz, and O. Steinbock, J. Phys. Chem. A 105 (2001), 6144.
[3] O. Steinbock, Phys. Rev. Lett. 88 (2002), 228302.

PDF file of the poster on ResearchGate:

N. Manz and S.C. Müller
"Erregungswellen in quasi-zweidimensionalen, gekrümmten Reaktions-Diffusions-Systemen"
Spring meeting of the German Physical Society, Regensburg, Germany, 2004 March 8-12

Abstract:
Die chemische Belousov-Zhabotinsky-Reaktion stellt ein ideales System zur Untersuchung der Dynamik von Reaktions-Diffusions Mustern dar, die in den unterschiedlichsten biologischen, chemischen und physikalischen Systemen zu beobachten sind. Obwohl diese propagierenden Strukturen auch in gekrümmten Medien wie der Herzoberfläche oder der Retina vorkommen, befaßten sich die experimentellen Untersuchungen überwiegend mit planaren raumzeitlichen Strukturen.
Wir stellen ein Verfahren zur Herstellung quasi-zweidimensionaler, nichtebener Medien vor [1]. Mit Hilfe dieser gleichmäßig bzw. nichtgleichmäßig gekrümmten Systemen werden propagierende Wellen und Spiralen in verschiedenen nichtebenen Systemen untersucht. Die experimentellen Ergebnisse werden im Rahmen der kinematischen Theorie der Ausbreitung von Reaktions-Diffusions-Wellen erörtert.
[1] N. Manz and S.C. Müller, Fabrication of quasi-two-dimensional, heterogeneously curved Belousov-Zhabotinsky systems, Rev. Sci. Instrum. 74(12) (2003), in print.

PDF file of the poster on ResearchGate:

N. Manz, B. T. Ginn, and O. Steinbock
"Front propagation in the 1,4-cyclohexanedione Belousov-Zhabotinsky system: meandering spiral waves"
Gordon Research Conference on Nonlinear Science, Tilton School, Tilton, NH, USA, 2003 August 3-8

Abstract:
We report meandering spiral waves in the 1,4-cyclohexanedione (CHD) Belousov-Zhabotinsky (BZ) system. Increasing the malonic acid concentration in the classical BZ system leads to the transition from small circular cores to hypocycles, prolate cycloids, epicycles, and large circular cores. Until now the malonic acid BZ system is the only known reaction-diffusion system with a large variety of spiral dynamics in addition to rigid rotation. In the CHD-BZ system we found a phase space only with hypocyles and without the boundaries to circular spiral cores. Instead of this, the transition to linear spiral cores are observed at very low CHD concentration with a long refractory phase which is only known from experiments in anisotropic cardiac tissue but generally predicted using different mathematical models of excitable media.

PDF file of the poster on ResearchGate:

B. T. Ginn, N. Manz, and O. Steinbock
"Microfluidic Systems for the Belousov-Zhabotinsky Reaction"
Gordon Research Conference on Nonlinear Science, Tilton School, Tilton, NH, USA, 2003 August 3-8

Abstract:
We present results on reaction-diffusion systems in geometrical arrays. The arrays are fabricated using soft lithography methodologies and poly(dimethylsiloxane) as the matrix material. Each micro-reactor contains a microliter volume of Belousov-Zhabotinsky solution. Spiral waves are observed for various concentrations and demonstrate a dynamic behavior influenced by the micro-reactor geometry.

PDF file of the poster on ResearchGate:

N. Manz and S. C. Müller
"Spiral Waves on Curved Surfaces"
Gordon Research Conference on Oscillations and Dynamic Instabilities in Chemical Systems, Queen's College, Oxford, UK, 2002 July 28 - August 2

Abstract:
Rotating spiral waves have been observed in numerous physical, chemical, and biological systems. Many investigations were done in the chemical Belousov-Zhabotinsky (BZ) reaction which can be seen as a model system for excitable media. Most of the theoretical and experimental studies of two-dimensional excitable systems were done in planar geometries. In natural systems, however, many excitable reactions occur on curved surfaces, e.g., on the heart muscle or in the phenomenon of spreading depression waves in chicken retina. To understand the behaviour of spiral waves on curved surfaces one can use the BZ reaction as an model system for other nonplanar media.
In the framework of kinematic approach Brazhnik et al. and Zykov showed that the angular velocity of spiral waves depends on the curvature of the spherical system. For small radii (large curvature) the dependence is inverse linear [1]. For large radii (small curvature) one obtains an inverse quadratic relation [2].
The results of the theoretical consideration are compared with experimental data obtained with a BZ system as hemispherical shells.
[1] P. K. Brazhnik, V. A. Davydov, and A. S. Mikhailov, Theor. Math. Phys. 74 (1988), 300-306.
[2] V. S. Zykov and S. C. Müller, Physica D 97 (1996), 322-332.

PDF file of the poster on ResearchGate:

C. T. Hamik, N. Manz, S. C. Müller, and O. Steinbock
"Anomalous Dispersion in the 1,4-Cyclohexanedione Belousov-Zhabotinsky Reaction"
101th Meeting of the German Bunsen Society for Physical Chemistry 2002, Potsdam, Germany, 2002 May 9-11

Abstract:
We report about anomalous dispersion in a homogeneously catalyzed reaction-diffusion system. In this Belousov-Zhabotinsky reaction, the classical organic substrate malonic acid is replaced by 1,4-cyclohexanedione (1,4-CHD). Furthermore the sulfuric acid concentration is about 4-5 times higher. Changing the concentration of 1,4-CHD and bromate generates different wave interactions. We found attractive interactions between propagating wave fronts such as merging and stacking [1]. Beyond it one can observe the formation of stable bound wave packets through bunching events [2]. We show experimental results to prove the anomalous behavior and exclude the possibility of hydrodynamical effects and buoyancy-driven convection. Besides, we present a phase diagram in the bromate-1,4-CHD concentration plane with five different wave dynamics.
[1] N. Manz, S. C. Müller, and O. Steinbock, Anomalous Dispersion of Chemical Waves in a Homogeneously Catalyzed Reaction System, J. Phys. Chem. A 104(25) (2000), 5895-5896.
[2] C. T. Hamik, N. Manz, and O. Steinbock, Anomalous Dispersion and Attractive Pulse Interaction in the 1,4-Cyclohexanedione Belousov-Zhabotinsky Reaction, J. Phys. Chem. A  105(25) (2001), 6144-6153.

PDF file of the poster on ResearchGate:

N. Manz, V. S. Zykov und S. C. Müller
"Erregungswellen in einem modulierten BZ-System"
Spring meeting of the German Physical Society, Hamburg, Germany, 2001 March 26-30

Abstract:
Wie schon in [1] experimentell und theoretisch gezeigt wurde, kann die Ausbreitung von Erregungswellen auf einer periodisch gekrümmten Oberfläche zu Oszillationen der Geschwindigkeiten und somit zu neuartigen Wellenmustern führen. Der Einsatz des lichtsensitiven Ru(bpy)32+ statt des Ferroins ermöglicht es, die gekrümmte Oberfläche durch eine Lichtmaske zu simulieren. Die nun erhaltenen Wellenmuster werden mit den in [1] erhaltenen Gleichungen verglichen und entsprechend der Vorhersage diskutiert.
[1] V. A. Davydov, N. Manz, O. Steinbock, V. S. Zykov and S. C. Müller, Excitation Fronts on a Periodically Modulated Curved Surface, Phys. Rev. Lett. 85(4) (2000), 868-871.

PDF file of the poster on ResearchGate:

N. Manz, V. A. Davydov, O. Steinbock, V. S. Zykov, and S. C. Müller
"Excitation Fronts on a Periodically Modulated Curved Surface"
Gordon Research Conference on Oscillations and Dynamic Instabilities in Chemical Systems, Roger Williams University, Bristol, RI, USA, 2000 August 20-25

Abstract:
The evolution of an excitation front propagating on a nonuniformly curved surface is considered within the framework of a kinematical model of its motion. For the case of a surface with a periodically modulated curvature an exact solution of the front shape is obtained under the assumption of sufficiently small surface deformation. The results of the theoretical consideration are compared with the experimental data obtained with a modified Belousov-Zhabotinsky reaction in a thin nonuniformly curved layer.

PDF file of the poster on ResearchGate:

N. Manz, O. Steinbock, V. S. Zykov und S. C. Müller
"Spiraldynamik und Propagation von Erregungswellen in einem nichtgleichmäßig gekrümmten Belousov-Zhabotinsky System"
99th Meeting of the German Bunsen Society for Physical Chemistry, Würzburg, Germany, 2000 June 1-3

Abstract:
The Belousov-Zhabotinsky (BZ) reaction is a well-studied model system for the investigation of reaction-diffusion patterns. Thin layers of this reaction medium show wave structures such as target patterns or rotating spirals. Theoretical analyses predict that the propagation velocity of excitation waves depends on the local curvature of the medium and that the center of spiral waves can migrate in systems with non-zero curvature gradients. We present first experimental results on wave propagation on undulated surfaces. The reaction medium is embedded in a gel system which is supported by curved plastic molds with custom-made geometries.

PDF file of the poster on ResearchGate:

N. Manz, S. C. Müller, and O. Steinbock
"Pattern formation on curved surfaces"
218th American Chemical Society National Meeting, New Orleans, LA, USA, 1999 August 22-26

Abstract:
The Belousov-Zhabotinsky (BZ) reaction is a well-studied model system for the investigation of reaction-diffusion patterns. Thin layers of this reaction medium show wave structures such as target patterns or rotating spirals. Theoretical analysis predict that the propagation velocity of excitation waves depends on the local curvature of the medium and that the center of spiral waves can migrate in systems with non-zero curvature gradients. We present first experimental results on wave propagation on undulated surfaces. The reaction medium is embedded in a gel system which is supported by curved plastic molds with custom-made geometries.

N. Manz, S. C. Müller, and O. Steinbock
"Wave propagation on curved surface"
Florida Section of the American Chemical Society Annual Meeting and Exposition, Orlando, FL, USA, 1999 May 7-8

Abstract:
The Belousov-Zhabotinsky (BZ) reaction is a well-studied model system for the investigation of reaction-diffusion patterns. Thin layers of this reaction medium show wave structures such as target patterns or rotating spirals. Theoretical analyses predict that the propagation velocity of excitation waves depends on the local curvature of the medium and that the center of spiral waves can migrate in systems with non-zero curvature gradients. We present first experimental results on wave propagation on undulated surfaces. The reaction medium is embedded in a gel system which is supported by curved plastic molds with custom-made geometries.




Poster presentations in 'Genetics and Neurophysiology of Alcohol Use Disorders':

 


C. Kamarajan, A.K. Pandey, D.B. Chorlian, N. Manz, COGA collaborators, and B. Porjesz
"Genotypic variations in a single nucleotide polymorphism of the KCNJ6 gene affect theta oscillations during reward processing"
Annual Scientific Meeting of the Research Society of Alcoholism, San Antonio, TX, USA, 2015 June 20-24

Abstract:
Event-related oscillations (EROs) have served as a powerful tool to measure neurocognitive processing in normal and clinical populations including those with Alcohol Use Disorders (AUDs). Studies have reported reduced theta EROs during reward processing in alcoholics and individuals at risk for AUDs. Theta EROs to targets during a visual oddball task have been found to be significantly associated with several single nucleotide polymorphisms (SNPs) in KCNJ6 at genomewide significant levels in a family genomewide association study (GWAS). The KCNJ6 gene encodes GIRK2, a G-protein inward rectifying potassium channel that is important in regulating the excitability of neuronal networks, and has been shown to be involved in the pharmacokinetics of alcohol. The goal of the present study is to examine the effects of a synonymous KCNJ6 SNP (rs702859) on theta EROs during reward processing in a monetary gambling task. The sample included 1,601 individuals (800 males and 801 females) between 17 and 25 years of age from the prospective study of the Collaborative Study on the Genetics of Alcoholism (COGA) from the high dense alcoholism families and from the community control families. Results showed that theta ERO power (3.5-7.5 Hz, 300-500 ms poststimulus) varied significantly across rs702859 SNP genotypes in accordance with an additive effect. This pattern was seen in each gender and family type for both loss and gain conditions. Evidence of anterior-posterior topographic differences of theta power across genotypes was also observed. These findings suggest that specific SNP genotypes in the KCNJ6 gene affect neural oscillations that underlie vulnerability for alcoholism.

PDF file of the poster on ResearchGate:

A. Gogne, C. Kamarajan, A.K. Pandey, D. Chorlian, N. Manz, COGA collaborators, and B. Porjesz
"Reduced P3 amplitude in adolescents at high risk for alcoholism"
SUNY Downstate Medical Center Annual Research Day, Brooklyn, NY, USA, 2015 April 2

Abstract:
Objective: Alcoholism has been considered to be part of a spectrum of disinhibitory disorders, with impulsivity being an important characteristic. Event-related potentials (ERPs) have been used as effective tools to study cognitive deficits related alcoholism and risk. Previous studies have reported low P3 amplitudes of the ERP and high impulsivity in alcoholics as well as in offspring who are at high risk (HR) to develop alcoholism. Our objective in the present study was to investigate the P3 component of the ERP as well as impulsivity in high risk subjects with a heavy loading of family history of alcoholism using an auditory oddball paradigm. Current source density (CSD) was also computed in each group to examine brain topography of P3 in these risk groups.
Methods: Offspring in an adolescent age range (12-17 years) from HR families (N = 396) from the multi-site Collaborative Study on the Genetics of Alcoholism (COGA) and offspring from low risk (LR) control families (N = 79) were assessed with an Auditory Oddball Paradigm; P3 amplitudes to target stimuli were measured at midline frontal (Fz), central (Cz), parietal (Pz) and occipital (Oz) regions. Barratt Impulsiveness Scale (BIS) was used to evaluate impulsivity in subjects in both groups. Subjects were further grouped for gender within this age group.
Results: HR subjects in both gender groups showed statistically significant lower P3 amplitudes in the posterior region (p = 0.007) than LR subjects. Further, HR subjects showed increased impulsivity in motor, attentional, and total BIS scores in both gender groups. HR and LR subjects manifested differences in both intensity and topography of CSD activation. The differences in CSD activation across risk groups were stronger in males as compared to females.

Conclusions: Our results demonstrate significant cognitive deficits as reflected by lower P3 amplitudes and differential CSD profiles in subjects from HR COGA families, i.e., families that have a high density of alcoholism. Higher impulsivity in HR subjects further establishes the view that impulsivity and/or underlying neurocognitive disinhibition may contribute to vulnerability to develop alcoholism.

PDF file of the poster on ResearchGate:

C. Kamarajan, B.A. Ardekani, A.K. Pandey, D.B. Chorlian, N. Manz, S.J. Kang, and B. Porjesz
"Neural Circuitry During Reward Processing in Alcoholics: A Study of EEG Synchrony and fMRI Connectivity"
Annual Scientific Meeting of the Research Society of Alcoholism, Belleview, WA, USA, 2014 June 21-25

Abstract:
Background: Individuals with Alcohol Use Disorders (AUDs) have been found to show a variety of neurocognitive deficits, including deficits during reward processing. Connectivity measures such as EEG-based synchrony (EEG-Synch) and fMRI based functional connectivity (fMRI-FC) have proven useful to identify brain regions that are coupled together. This study has two aims: 1) to examine the EEG-Synch between alcoholics and controls during reward processing; and 2) to elucidate possible relationship between EEG-Synch and fMRI-FC in order to identify key brain regions of the resting state networks that may be involved during reward processing.
Method: The sample consisted of 25 alcoholic and 21 control subjects of both genders. EEG data was collected during a Monetary Gambling Task (MGT), where the subjects bet either 50¢ or 10¢ during each trial and received feedback of a loss or a gain. EEG-Synch was computed as a measure of instantaneous phase consistency across trials in each condition averaged across the time window in 77 electrode pairs representing all regions. Synchrony values at 200-500 ms after the onset of feedback stimulus were extracted for delta (1-4 Hz), low theta (4-5 Hz), and high theta (6-7 Hz) bands and compared between alcoholics and controls. Resting state fMRI-FC analysis was done between eight preselected seed regions and the rest of the brain areas. A correlation analysis was performed between the fMRI-FC values for each significant region and the EEG-Synch values.
Results: Alcoholics showed increased synchrony in delta band during loss (p<0.05) and in theta bands during both loss (p<0.05) and gain (p<0.01) conditions. More electrode pairs were significant for the theta bands during gain conditions. fMRI-FC analysis elicited nine significant connectivity representing left (L), right (R) and bilateral (b) brain areas between the seed and another region: 1) L. anterior prefrontal cortex (APFC) with L. precentral gyrus (preCG); 2) L. APFC with R. preCG; 3) R. APFC with R. preCG; 4) R. APFC with L. postcentral gyrus (postCG); 5) R. orbital frontal insula (ROFI) with B. postCG; 6) R. orbital frontal insula (ROFI) with R. frontal pole; 7) Posterior cingulate cortex (PCC) with L. Precuneous; 8) PCC with L. middle frontal gyrus; and 9) B. nucleus accumbens with R. superior parietal lobule. EEG-synch showed significant positive correlations with first six fMRI-FC networks (p<0.01) as well as negative correlations with last 3 three fMRI-FC networks (p<0.01). Further, the topographic patterns of significant electrode pairs for these correlations were different between controls and alcoholics.
Conclusion: Increased synchrony in alcoholics during reward processing may suggest a possible imbalance between neural excitation and inhibition. Correlations between reward-based EEG-synch and resting state fMRI-FC suggest that some of the key structures of the resting state networks may be related to or involved in reward processing. Differential activation patterns in alcoholics as elicited by the topographic differences in the correlations between fMRI-FC values and the EEG-Synch may explain the reward processing abnormalities in alcoholics. Further studies are necessary to confirm these findings.

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A. Gogne, C. Kamarajan, A.K. Pandey, D. Chorlian, N. Manz, S.J. Kang, COGA collaborators, and B. Porjesz
"Reduced P300 amplitude in individuals at high risk for alcoholism"
SUNY Downstate Medical Center Annual Research Day, Brooklyn, NY, USA, 2014 April 2

Abstract:
Objective: Alcoholism has been considered to be part of a spectrum of disinhibitory disorders, with impulsivity being an important characteristic. Previous studies have shown a correlation between impulsivity and cognitive deficits in alcoholics and in offspring who are at high risk (HR) to develop alcoholism. Event- related potentials (ERPs) have been used as an effective tool to study cognitive deficits in these populations. Our objective in the present study was to investigate the P300 component of the ERP as well as impulsivity in high risk subjects with a heavy loading of family history of alcoholism using an auditory oddball paradigm.
Methods: Offspring from HR families (N=1785) from the multi-site Collaborative Study on the Genetics of Alcoholism (COGA) and offspring of low risk (LR) control families (N=152) were assessed with an Auditory Oddball Paradigm; P3 amplitudes to target stimuli were measured at midline frontal (Fz), central (Cz), parietal (Pz) and occipital (Oz) regions. Barratt Impulsiveness Scale (BIS) was used to evaluate impulsivity in subjects in both groups. Subjects were further grouped for gender and age (12-15 and 16-25 years).
Conclusions: Younger HR subjects showed statistically significant lower P3 amplitudes in the posterior (Oz) region (p=0.042), while the older HR group had lower amplitudes in the central (CZ) region (p=0.033). Females showed higher P3 amplitude than males. Further, HR subjects showed increased impulsivity in all subscales (Non planning, Motor impulsivity, Attentional impulsivity) and total BIS scores. Our results demonstrate significant cognitive deficits as reflected by lower auditory P3 amplitudes in subjects from HR COGA families, i.e., families that have a high density of alcoholism. The finding of higher P3 amplitudes in females compared to males is consistent with previous research in this area. Higher impulsivity and lower P3 amplitude in HR subjects further supports the view that a vulnerability to alcoholism may be due underlying neurocognitive disinhibition/hyperexcitability in those at risk.

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S. J. Kang, M. Rangaswamy, D. B. Chorlian, N. Manz, COGA collaborators, and B. Porjesz
"Family-based Genome-wide Association Study of EEG Identifies UROC1 and PAH"
63th Annual Meeting of the American Society of Human Genetics 2013, Boston, MA, USA, 2013 October, 22-26

XXII World Congress of Abstract:
Introduction: Electroencephalography (EEG) measures are highly heritable neuroelectrical correlates of resting brain state, and contribute several markers of risk for alcoholism and related disorders. Increased beta power has been found to be a hallmark of alcoholism and related disorders and also a marker of those at risk, and is an index of neural hyperexcitability. To identify genetic variants associated with EEG, we performed a family-based genome-wide association study (GWAS) using extended multiplex families densely affected by alcohol dependence. An advantage of the design of this study is robustness against population substructure.
Methods: High beta power (20-28 Hz) of the three frontal-central bipolar electrode pairs (F3-C3, Fz-Cz, F4-C4) were calculated using standard Fourier transform methods. Samples from the Collaborative Study on the Genetics of Alcoholism (COGA) were genotyped using the Illumina Human OmniExpress array on 118 families, densely affected by alcohol use disorder. Phenotype data was derived from multivariate linear regression models which were constructed from log transformed high beta power EEGs, controlling for log-transformed age and stratified by gender. After quality control procedures, association testing was done on 1,564 samples assuming an additive model using the generalized disequilibrium test (GDT). Pathway analysis was performed using ALIGATOR (Association List Go Annotator) to study groups of genes by testing for overrepresentation of members of those groups within lists of genes containing significantly associated SNPs from the GWAS.
Results: We found that a SNP in UROC1 (rs1687482) was significantly associated with F3-C3 high beta power EEG at a genome-wide significant level (p = 4.8 × 10−8). We also confirmed that SNPs in GABRA2 were significantly associated with this phenotype (p = 9.8 × 10−3). The most significant individual GO category from the pathway analysis is a neurotransmitter biosynthetic process with significantly associated SNPs in PAH (p = 1.2 × 10−5). These results suggest PAH accounts for some of the variations in high beta power EEG. PAH catalyzes the conversion of phenylalanine to tyrosine, shares physical, structural and catalytic properties with tyrosine hydroxylase and tryptophan hydroxylase that catalyze the rate-limiting steps in the biosynthesis of the neurotransmitters dopamine, noradrenaline and serotonin.
Discussion: These findings underscore the utility of using EEG phenotypes to identify meaningful genetic correlates of resting brain state with pathophysiology of neuropsychiatric conditions.

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S. J. Kang, M. Rangaswamy, D. B. Chorlian, N. Manz, COGA collaborators, and B. Porjesz
"Family-based Genome-wide Association Study of EEG Identifies UROC1 and PAH"
Psychiatric Genetics 2013, Boston, MA, USA, 2013 October 17-21

Abstract:
Introduction: Electroencephalography (EEG) measures are highly heritable neuroelectrical correlates of resting brain state, and contribute several markers of risk for alcoholism and related disorders. Increased beta power has been found to be a hallmark of alcoholism and related disorders and also a marker of those at risk, and is an index of neural hyperexcitability. To identify genetic variants associated with EEG, we performed a family-based genome-wide association study (GWAS) using extended multiplex families densely affected by alcohol dependence. An advantage of the design of this study is robustness against population substructure.
Methods: High beta power (20-28 Hz) of the three frontal-central bipolar electrode pairs (F3-C3, Fz-Cz, F4-C4) were calculated using standard Fourier transform methods. Samples from the Collaborative Study on the Genetics of Alcoholism (COGA) were genotyped using the Illumina Human OmniExpress array on 118 families, densely affected by alcohol use disorder. Phenotype data was derived from multivariate linear regression models which were constructed from log transformed high beta power EEGs, controlling for log-transformed age and stratified by gender. After quality control procedures, association testing was done on 1,564 samples assuming an additive model using the generalized disequilibrium test (GDT). Pathway analysis was performed using ALIGATOR (Association List Go Annotator) to study groups of genes by testing for overrepresentation of members of those groups within lists of genes containing significantly associated SNPs from the GWAS.
Results: We found that a SNP in UROC1 (rs1687482) was significantly associated with F3-C3 high beta power EEG at a genome-wide significant level (p = 4.8 × 10−8). We also confirmed that SNPs in GABRA2 were significantly associated with this phenotype (p = 9.8 × 10−3). The most significant individual GO category from the pathway analysis is a neurotransmitter biosynthetic process with significantly associated SNPs in PAH (p = 1.2 × 10−5). These results suggest PAH accounts for some of the variations in high beta power EEG. PAH catalyzes the conversion of phenylalanine to tyrosine, shares physical, structural and catalytic properties with tyrosine hydroxylase and tryptophan hydroxylase that catalyze the rate-limiting steps in the biosynthesis of the neurotransmitters dopamine, noradrenaline and serotonin.
Discussion: These findings underscore the utility of using EEG phenotypes to identify meaningful genetic correlates of resting brain state with pathophysiology of neuropsychiatric conditions.

PDF file of the poster on ResearchGate:

N. Manz, M. Rangaswamy, D. B. Chorlian, S. J. Kang, A. Goate, K. K. Bucholz, J. Wang, J. P. Rice, L. Almasy, J. A. Tischfield, M. Schuckit, J. Kramer, S. Kuperman, H. J. Edenberg, L. J. Bierut, and B. Porjesz
"Association of event-related theta band oscillations and SNPs in the cholinergic nicotinic receptor gene locus (CHRNA6-CHRNB3) on chromosome 8"
Annual Scientific Meeting of the Research Society of Alcoholism, Orlando, FL, USA, 2013 June 22-27

Abstract:
Introduction: Event-related oscillations (ERO) in theta (4-7 Hz) band are elevated during target detection and have been instrumental in gene identification as they are associated with a predisposition to develop alcohol dependence and related disorders. A strong association between smoking and alcohol behaviors and nicotinic cholinergic receptor genes in the CHRNB3-CHRNA6 locus has been reported. Evidence indicates that the receptor nAChR α6 subunit is not widely expressed but abundant in midbrain dopaminergic (DA) regions associated with reward and mood control; β3 subunit coexpression promotes function of α6 containing nAChR. DA neurons switch between tonic (1-5 Hz) and phasic firing (20–100 Hz), and a frequency-dependent function relates DA neuron activity and DA release. α6 nAChRs have a role in visual salience, and mediate cholinergic sensitization of brain pathways important for recognizing and responding to unexpected and important sensory experiences, which may be impacted in addictive disorders.
Methodology: The study comprised 3082 adolescents and young adults (12-25 years) from 1103 alcoholic and control families in the Collaborative Study on the Genetics of Alcoholism (COGA). Overlapping subgroups of 1088 subjects with EEG recordings and 2938 with clinical variables were analyzed. ERO power in high theta (6.0-7.5 Hz, 200-500 ms) was calculated from EEG recordings during a visual oddball task. Analyses of theta EROs at the three midline leads (Fz, Cz, and Pz) and single nucleotide polymorphisms (SNPs) in the CHRNB3-CHRNA6 cluster were performed using a linear regression model for a case-control study (798 cases and 290 controls) with age and gender as covariates. A discrete time survival analysis (DTSA) model evaluated association between SNPs and onset of regular use of alcohol, cannabis, and illicit drugs in a subgroup of 2938 subjects.
Results: With this candidate gene approach, we find evidence for several SNPs in the CHRNA6-CHRNB3 locus to be significantly associated (p = 7.89×10-3 – 6.58×10-4) with high theta EROs (6.0-7.5 Hz, 200-500 ms) at the Pz electrode for European subjects in response to the target stimulus. The DTSA analysis showed significant risk associated with CHRNB3 SNPs for early age of onset of illicit drug use and late age of onset of alcohol and cannabis regular use.
Conclusions: These findings support a role for the cholinergic nicotinic receptor genes on chromosome 8 (CHRNB3 and CHRNA6) in modulating theta oscillations in the context of alcoholism and related disorders.

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C. Kamarajan, M. Rangaswamy, A. K. Pandey, D. B. Chorlian, N. Manz, S. Kang, L. Bauer, M. Schuckit, V. Hesselbrock, and B. Porjesz
"Dysfunctional Reward Processing in Individuals at Risk for Alcoholism"
Annual Scientific Meeting of the Research Society of Alcoholism, Orlando, FL, USA, 2013 June 22-27

Abstract:
Background: Electrophysiological anomalies in individuals at risk for alcoholism have been previously reported using several tasks, including gambling paradigms. Studies have also identified reward processing as a key cognitive component in alcoholism and risk prediction. While reward processing deficits in alcoholics have been reported earlier, such anomalies in high-risk individuals have not yet been ascertained. This is the first study to report dysfunctional activation in frontal regions during reward processing in subjects at high risk for alcoholism.
Method: The sample comprised both male and female offspring from families in the Collaborative Study on the Genetics of Alcoholism (COGA) within the age range of 12-25 years; 742 high risk (HR) subjects who had at least one parent who was alcohol dependent and 428 low risk (LR) individuals without any parental history of alcohol dependence were included. Subjects performed a single outcome gambling task where they bet either 50¢ or 10¢ during each trial and received a feedback of a win or loss. Electrophysiological responses recorded during gain/loss feedback were evaluated with the standardized low resolution brain electromagnetic tomography (sLORETA) to identify cortical sources. Trial averaged data corresponding to the P3 peak (340-360 milliseconds post-stimulus) during loss and gain conditions were compared between HR and LR groups using statistical non-parametric mapping (SnPM) with 5000 permutations.
Results: HR subjects showed decreased current density in anterior cingulate cortex (ACC, BA 24) and in right Interior frontal gyrus (IFG, BA 45) compared to LR subjects during the loss condition. During the gain condition, HR subjects show decreased current density in the middle cingulate region (BA 24) compared to LR subjects. The maximum current density activations during loss and gain conditions also varied between HR and LR groups.
Conclusion: The results suggest that individuals at high risk for alcoholism may have less activation in frontal lobe regions, perhaps contributing to reward processing deficits. Differential activations during loss and gain outcomes further indicate that HR subjects may have dysfunctional brain circuitries subserving the reward/outcome processing.

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A. K. Pandey, C. Kamarajan, N. Manz, S. J. Kang, D. B. Chorlian, M. Rangaswamy, and B. Porjesz
"Reduced Power in Slow Frequencies Reflects Impaired Frontal Inhibitory Control in Alcoholics: EROs During an Equal Probability Go/NoGo Task"
Annual Scientific Meeting of the Research Society of Alcoholism, Orlando, FL, USA, 2013 June 22-27

Abstract:
Purpose: A variety of neurocognitive functional deficits/dysfunctions involving impairments in different brain regions and/or neural circuits have been associated with chronic alcoholism. Electrophysiological techniques provide opportunities to study neurocognitive functions due to their high time resolution. Several studies using event-related potentials (ERPs) have reported reduced amplitudes in alcoholics of ERP components, such as P3 and N2. Time and frequency specific components occurring in different brain regions during task-based sensory and cognitive events can be analyzed using event-related oscillations (EROs). EROs can provide greater specificity in understanding brain function than traditional ERPs. Different frequency bands within EROs have been attributed to underlie various task-specific cognitive processes. Delta oscillations are thought to mediate signal detection and decision making, while theta frequencies are linked with different cognitive processes, such as conscious awareness, recognition memory, episodic retrieval, and frontal inhibitory control. The present study attempts to examine time-frequency aspects of brain signals that reflect neurocognitive impairments in alcoholics during an equal probability Go/NoGo task.
Method: The S-Transform was used to analyze time-frequency components of event-related brain signals in 15 abstinent male participants with a diagnosis of alcohol dependence and 15 age-matched male control participants (age rage 18-35 years.). The resultant power values of various frequency bands were extracted based on event-relevant time ranges and were subjected to statistical analysis. The mixed-linear model from PROC MIXED procedure of SAS was used for the statistical analysis.
Results: The alcoholics were found to produce significantly reduced total delta (1.0-3.5 Hz) power compared to controls at the parietal region under the Go condition (p<0.05) and at the frontal region (p<0.0001) under the NoGo condition. They also produced significantly reduced low NoGo theta (4.0-5.5 Hz) power compared to controls at the central region (p<0.01). However, there were no statistically significant differences in either total theta (4.0-7.5 Hz) or total high theta (6.0-7.5 Hz) power.
Conclusion: The results suggest deficient processing of frontal inhibitory control and decision making in alcoholics.

PDF file of the poster on ResearchGate:

N. Manz, M. Rangaswamy, S. J. Kang, L. Wetherill, A. Goate, K. K. Bucholz, J. Wang, J. P. Rice, L. Almasy, J. A. Tisch eld, M. Schuckit, J. Kramer, H. J. Edenberg, L. Bierut, and B. Porjesz
"Replication of clinical trait and electrophysiological phenotypes associated with an event-related delta band oscillation"
XIX World Congress of Psychiatric Genetics 2011, Washington, DC, USA, 2011 September 10-14

Abstract:
Introduction: Brain electrical activity recorded using non-invasive electroencephalography (EEG) provide sensitive measures of brain function with exquisite temporal resolution during cognitive tasks. Extensive existing literature indicates that the P3 component of the event-related potential (ERP) is reduced in abstinent alcoholics and in offspring at risk. More recently it has been reported that the theta and delta event-related oscillations (EROs) underlying P3 are also reduced in alcoholics and their offspring; theta has a frontal topography and is related to attention, while delta has a posterior topography and is related to decision making processes. These ERO endophenotypes are highly heritable and more proximal to gene function than diagnosis, providing a powerful strategy in searching for genes in psychiatric disorders, such as alcoholism. In the Collaborative Study on the Genetics of Alcoholism (COGA) we have found that these ERO phenotypes have been useful in gene identification associated with a predisposition to develop alcohol dependence and related disorders. There is evidence in the literature that nicotinic receptor genes in the CHRNA6-CHRNB3 locus are associated with smoking and alcohol behaviors.
Methodology: EROs in the delta band (1-3 Hz) were calculated from EEG recordings during a visual oddball task in 988 adolescents and young adults (12-25 years) from COGA alcoholic and control families (643 European-American, 247 African-American, 98 Others) along with drinking and smoking variables. Analyses of delta EROs at the midline posterior lead where they are maximum and single nucleotide polymorphisms (SNPs) in the cholinergic nicotinic receptor gene cluster CHRNA6-CHRNB3 was performed using a linear regression model for a case-control study with 263 subjects from families affected with alcoholism and 725 subjects from control families.
Results: We find evidence for several SNPs in the CHRNA6-CHRNB3 locus on chromosome 8 to be significantly associated (FDR corrected p=0.02-0.004) with delta EROs at the posterior midline electrode (Pz) in response to the target stimulus.
Conclusions: These findings support a role for the cholinergic nicotinic receptor genes on chromosome 8 (CHRNA6 and CHRNB3) in the genetic predisposition towards alcoholism, and underscore the utility of brain oscillations and the endophenotype approach in understanding complex psychiatric disorders.

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S. J. Kang, N. Manz, M. Rangaswamy, J. Kramer, L. Almasy, V. Hesselbrock, S. Kuperman, J. Nurnberger Jr, H. Edenberg, J. Tischfeld, and B. Porjesz
"Multivariate Genome-Wide Association Analyses of Neurophysiological Phenotypes in Alcoholism"
XIX World Congress of Psychiatric Genetics 2011, Washington, DC, USA, 2011 September 10-14

Abstract:
Introduction: Event-related oscillations (EROs) represent highly heritable neuroelectrical correlates of human perception and cognitive performance, and some are markers of risk for alcoholism. To identify genetic variants associated with EROs, we performed a genome-wide association study (GWAS). While statistical methods used for GWAS data analyses have been largely univariate (single phenotypes), multivariate analyses have advantages over univariate analysis whether or not there is correlation between phenotypes. To investigate the advantages of information from correlated phenotypes, we conducted multivariate GWAS for delta and theta ERO and P3 amplitude.
Methods: All neurophysiological phenotype values were extracted from the target case of the Visual Oddball experiment. The two EROs were calculated at the parietal midline channel (Pz) for the delta band (1-3 Hz) and the frontal midline channel (Fz) for the theta band (3-7 Hz). The extracted measures were derived from a 300-700 ms post stimulus window, bounding the visual P3 event. P3 amplitude was measured as the voltage difference between the pre-stimulus baseline (100 ms prestimulus) and the largest positive going peak in the latency window 300-600 ms after stimulus onset at the parietal midline electrode (Pz). Illumina HumanHap 1M chips in 1399 unrelated European Americans drawn from the Collaborative Study on the Genetics of Alcoholism (COGA) were used for analysis. After quality control procedures, we regressed theta and delta ERO and P3 amplitude phenotypes on age for each gender.
Results: We compared the p values of univariate and multivariate analyses results for the SNPs in genes previously found to be associated with alcohol dependence or neurophysiological phenotypes. SNPs in SNCA, ADH4, TACR3, NPY2R, ACN9, GRM8, CHRM2, OPRK1, PENK, GABRG3, CHRNA7, PDYN, CDH13 and PRKG2 genes that showed no significant association with the neurophysiological phenotypes in univariate analysis were significantly associated with the phenotypes in multivariate analysis. For example, univariate analysis p values for rs1316749 in NPY2R are greater than 0.1 for all three phenotypes, whereas multivariate analysis p value for this SNP is less than 0.008. Another example is rs7656323 in PRKG2. The univariate p values for theta, delta, and P3 are 2×10-4, 0.99, and 0.02, respectively. In contrast, the bivariate p value for theta and P3 is 4×10-7 while the multivariate p value for theta, delta, and P3 is 2×10-6.
Conclusions: These results underscore the advantage of using multivariate over univariate GWAS by utilizing the correlated phenotypic information to prioritize significant genes.

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D. Zaveri, B. Porjesz, N. Manz, J. Nurnberger Jr, J. Kramer, COGA collaborators, and M. Rangaswamy
"A comparison of the P300 amplitude changes across alcoholism and depression spectrum"
American Psychiatric Association Annual Meeting 2011, Honolulu, HI, USA, 2011 May 14-18

Abstract:
The P300 component of the Event-Related Potential (ERP) is the time-locked electrical activity that occurs between 300-700 ms after the stimulus, irrespective of stimulus type (e.g., visual, auditory, olfactory). P300 is obtained to rare target and novel stimuli, not to non-target stimuli. It is related to the “significance” of the stimulus and not to its physical features and represents a measure of CNS information processing (attention resource allocation, context updating and context closure).
Females have slightly higher P300 amplitudes than their male counterparts.
P300 amplitude is reduced in alcoholics and does not improve with prolonged abstinence. Reduced P300 amplitude in high-risk offspring predates the development of alcoholism. Decreases in P300 amplitude in female alcoholic probands is not to the same extent as males. P300 has proved to be a significant endophenotype in psychiatric genetics.
There is some evidence of reduced amplitude of P300 in Major Depressive Disorder (MDD), but these results are not consistent.
Depression is frequently co-morbid with alcohol/substance dependence, presenting both before and as a sequel of substance dependence. Patients having a dual diagnosis of MDD with alcohol use disorders report more adverse environmental influences. The alcohol use disorder is earlier in onset, more severe, and more likely to be accompanied by lifetime aggression, impulsivity and hostility. The results of studies of P300 changes in patients with dual diagnosis are not consistent.
Genetic studies have demonstrated an association of CHRM2 gene to brain oscillations underlying P300 in a visual oddball task, and to a comorbid phenotype of Alcoholism and Major Depressive Disorder (MDD).

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M. Zlojutro, M. Rangaswamy, N. Manz, J. Derringer, H. J. Edenberg, J. Kramer, R. Krueger, J. Nurnberger Jr, M. A. Schuckit, L. Bierut, B. Porjesz, and L. Almasy
"Identification of Genes Influencing Alcohol Dependence via Electrophysiological Mechanisms using GWAS Scoring and Pathway-Oriented Analysis"
XVIII World Congress of Psychiatric Genetics 2010, Athens, Greece, 2010 October 3-7

Abstract:
Brain oscillations represent important correlates of human information processing and cognition, and have been used to characterize clinical conditions, including alcohol dependence (AD). These oscillations are highly heritable traits that are less complex and more proximate to gene function than diagnostic labels, providing a powerful strategy for identifying susceptibility genes of psychiatric disorders. In this study, we examined three neuroelectrical measurements – beta power band for resting electroencephalogram (EEG), P300 amplitude of event-related potentials and its underlying theta band event-related oscillation (ERO) – in African-American (AA; n=285) and European-American (EA; n=799) case-control samples for AD and conducted pathway-oriented analysis on the results of genome-wide association (GWA) tests for the Illumina HumanHap 1M SNP microarray.
With the exception of beta band EEG in AAs, all three of the neuroelectrical measures exhibit significant or near significant deficits among AD cases relative to controls for both populations. These results are concordant with previous electrophysiological research performed on subjects of mostly European ancestry and thus indicate that oscillatory traits represent endophenotypes for alcoholism in AA populations. GWA tests produced one genome-wide significant SNP from the AA beta EEG data, rs6936632 (Bonferroni-corrected P=0.0293), located within scaffolding protein gene CD2AP. Pathway analysis of the top GWA results (P<0.001) via Fisher’s exact test revealed enriched pathways common to both populations and for all three measures, with the most significant ones involving antidiuretic hormone vasopressin, adrenergic neurotransmitters and tachykinin neuropeptides. These results provide insight into the biological basis of brain oscillation activity and the potential genetic underpinnings of alcohol dependence.

PDF file of the poster on ResearchGate:

M. Rangaswamy, N. Manz, L. Wetherill, X. Xuei, J. Tischfield, S. Kuperman, COGA collaborators, L. Almasy, T. Foroud, V. Hesselbrock, H. J. Edenberg, B. Porjesz
"Event-Related Delta Oscillation (A Trait Marker Of Alcoholism) is Associated with a Glutamatergic Candidate Gene - GRID2"
33rd Annual Scientific Meeting of the Research Society on Alcoholism, San Antonio, TX, USA, 2010 June 26-30

Abstract:
Introduction: Event related oscillations (EROs) provide sensitive measures of brain function. Oscillations provide windows of opportunity for transient cognitive networks to synchronize andlor co-operate to generate effective performance. Quantitative neurophysiological endophenotypes offer a powerful tool to study genetics of complex psychiatric disorders. Reduced power in Delta (1 to 2.5 Hz) and Theta (4 to 7 Hz) EROs during target detection in a visual oddball task have been shown to be robust trait markers of alcoholism risk. Delta oscillations are believed to mediate signal detection and decision-making. Earlier work has highlighted the involvement of glutamatergic systems in alcoholism and cognitive deficits associated with risk. This study aims to explore this further and also to replicate the findings from the family sample in an independent case-control sample.
Methods: The EROs were recorded during a visual oddball task in 1,312 individuals from 251 multiplex alcoholic families in the Collaborative Study on the Genetics of Alcoholism (COGA) sample. Linkage analysis on microsatellite marker data was computed in SOLAR. A candidate gene under the best linkage peak was identified and association analyses were conducted on the European American population subset for 83 single nucleotide polymorphisms (SNPs), using the UNPHASED suite. Genotype data from the genome-wide association study (GWAS) from an independent genetically unrelated case-control sample from COGA was used to replicate the delta ERO association with SNPs in GRID2. The genotype data was based on the lllumina 1 million SNP array and the analysis was performed in PLlNK using a linear regression model.
Results: Significant linkage (LOD = 4.04) on chromosome 4 at 139 cM was observed for the delta ERO power phenotype. The candidate gene GRID2 revealed significant association with 27 SNPs in introns l and 2. The human glutamate receptor gene GRID2 on chromosome 4 is a member of the glutamate receptor family, expressed selectively in cerebellar Purkinje cells. In the case-control sample SNPs in the same genomic region of the human glutamate receptor gene GRID2 were found to be significantly associated with delta ERO. The most significant SNP was associated at 1.8 x 10-3.
Conclusion: These findings from both the family based and case-control studies underscore the involvement of the glutamatergic pathways associated with cognitive dysfunction underlying alcoholism.
Supported by: UlO AA008401.

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M. Zlojutro, N. Manz, M. Rangaswamy, X. Xuei, L. Flury-Wetherill, D. Koller, L. J. Bierut, A. Goate, V. Hesselbrock, S. Kuperman, J. Nurnberger Jr, J. P. Rice, M. A. Schuckit, T. Foroud, H. J. Edenberg, B. Porjesz, and L. Almasy M. Zlojutro, N. Manz, M. Rangaswamy, X. Xuei, L. Flury-Wetherill, D. Koller, L. J. Bierut, A. Goate, V. Hesselbrock, S. Kuperman, J. Nurnberger Jr, J. P. Rice, M. A. Schuckit, T. Foroud, H. J. Edenberg, B. Porjesz, and L. Almasy
"GWAS scoring and pathway-oriented analysis of P300 neuroelectrical measurements for African- and European-American case-control subjects with alcohol dependence"
Annual Meeting of the Human Biology Association 2010, Albuquerque, NM, USA, 2010 April 14-15

Abstract:
Brain oscillations represent important correlates of human information processing and cognition, and have been used to characterize clinical conditions, including alcohol dependence (AD). These oscillations are highly heritable traits that are less complex and more proximate to gene function than diagnostic labels, providing a powerful strategy for identifying susceptibility genes of psychiatric disorders. In this study, we examined three neuroelectrical measurements - beta power band for resting electroencephalogram (EEG), P300 amplitude of event-related potentials and its underlying theta band event-related oscillation (ERO) - in African-American (AA; n=285) and European-American (EA; n=799) case-control samples for AD and conducted pathway-oriented analysis on the results of genome-wide association (GWA) tests for the Illumina HumanHap 1M SNP microarray. With the exception of beta band EEG in AAs, all three of the neuroelectrical measures exhibit significant or near significant deficits among AD cases relative to controls for both populations. These results are concordant with previous electrophysiological research performed on subjects of mostly European ancestry and thus indicate that oscillatory traits represent endophenotypes for alcoholism in AA populations. GWA tests produced one genome-wide significant SNP from the AA beta EEG data, rs6936632 (Bonferroni-corrected P=0.0293), located within scaffolding protein gene CD2AP. Pathway analysis of the top GWA results (P<0.001) via Fisher's exact test revealed enriched pathways common to both populations and for all three measures, with the most significant ones involving antidiuretic hormone vasopressin, adrenergic neurotransmitters and tachykinin neuropeptides. These results provide insight into the biological basis of brain oscillation activity and the potential genetic underpinnings of alcohol dependence. T his study was supported by NIH Grant U10AA008401.

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N. Manz, M. Rangaswamy, D. B. Chorlian, L. Almasy, H. J. Edenberg, T. Foroud, B. Porjesz, and COGA Collaborators
"Exploring a Novel EEG Phenotype in a Genome-Wide Association Study"
XVII World Congress of Psychiatric Genetics 2009, San Diego, CA, USA, 2009 November 4-8

Abstract:
Brain electrical activity recorded using non-invasive electroencephalography (EEG) are sensitive measures of brain function and developmental change. These EEG endophenotypes are highly heritable, less complex and more proximal to gene function than diagnosis or traditional cognitive measures, providing a powerful strategy in searching for genes in psychiatric disorders. In the Collaborative Study on the Genetics of Alcoholism (COGA) we have found that these EEG phenotypes have been useful in gene identification that was associated with a predisposition to develop alcohol dependence and related externalizing disorders. For example, we have previously shown a strong linkage and association of one EEG phenotype (beta power) with GABRA2 (Porjesz et al. 2002; Edenberg et al.2004). This gene is also associated with alcohol dependence, drug dependence and conduct disorder. Here we report on analyses of EEG phenotypes from a genome-wide association study (GWAS) based on the Illumina 1 million SNPchip platform in 1184 unrelated case-control samples ascertained from the COGA study. EEG phenotypes include power and synchrony estimates, and novel factors derived using the trilinear methodology. Studies have strongly implicated specific profiles of these phenotypes in several externalizing disorders such as alcohol and substance dependence, conduct disorder, ADHD and others. We find evidence for several genes and genomic regions that appear to be involved in EEG phenotypes that are also involved in the development of externalizing psychopathology.

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M. Rangaswamy, N. Manz, L. Wetherill, T. Foroud, H. J. Edenberg, B. Porjesz, and COGA Collaborators
"Association of Event-Related Delta Oscillations and a Glutamatergic Candidate Gene - GRID2"
XVII World Congress of Psychiatric Genetics 2009, San Diego, CA, USA, 2009 November 4-8

Abstract:
Brain oscillations provide sensitive measures of brain function with exquisite temporal resolution during cognitive tasks. These quantitative neurophysiological endophenotypes offer a powerful tool to study genetics of complex psychiatric disorders. Event related brain oscillations (EROs) - delta (1-3 Hz) and theta (4-7 Hz) - were recorded during a visual oddball task from 1312 individuals from 251 multiplex alcoholic families in the Collaborative Study on the Genetics of Alcoholism (COGA) sample. Significant linkage (LOD = 3.97) and linkage disequilibrium on chromosome 4 at 139 cM was detected. Association analyses with a glutamatergic gene (GRID2) under this linkage peak revealed strong association with a large number of single nucleotide polymorphisms (SNPs). The human glutamate receptor gene GRID2 on chromosome 4, is a member of the glutamate receptor family which are the predominant excitatory neurotransmitter receptors in the central nervous system. In a genome-wide association study (GWAS) based on the Illumina 1 million SNP array, we analyzed EROs in response to the target stimulus with the same paradigm in 1064 genetically unrelated case-control subjects from the COGA study. SNPs in several glutamatergic genomic regions were found to be significantly associated using a linear regression model for a case-control study. These findings from both the family based and case-control studies highlight the involvement of the glutamatergic pathways associated with cognitive dysfunction underlying alcoholism.

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M. Zlojutro, B. Porjesz, M. Rangaswamy, N. Manz, H. Edenberg, T. Foroud, X. Xuei, J. Nurnberger Jr., J. Rice, R. Cloninger, A. Goate, S. Kuperman, M. Schuckit, and L. Almasy
"Multi-stage genome-wide association study uncovers genetic factors influencing the P300 event-related brain potential"
59th Annual Meeting of the American Society of Human Genetics 2009, Honolulu, HI, USA, 2009 October 20-24

Abstract:
Event-related brain potentials (ERPs) are measurements of neuroelectric activity that are altered in patients with various psychiatric disorders and may serve as quantitative correlates of disease liability. In particular, alcoholic subjects and their offspring exhibit a reduction in the amplitude of the P300 component, a positive oscillatory wave, occurring approximately 300-500 milliseconds after a target stimulus during a cognitive task. Results of a genome-wide association study (GWAS) based on the Illumina HumanHap 1 million SNP array are presented for the P300 component at the Pz scalp position for 1,123 unrelated case-control subjects ascertained from the Collaborative Study on the Genetics of Alcoholism (COGA). Although the most statistically significant SNPs did not achieve genome-wide significant association after adjustment for multiple-testing (smallest P = 2.82 x 10-6 for rs12043526), several new genomic regions not previously identified through linkage analyses were implicated, with 50 top-ranking SNPs selected for follow-up genotyping in 1,374 family-based COGA samples. The most compelling association obtained in the follow-up data was for marker rs2148682, located within the evolutionary conserved gene DNAJC6, a regulator of molecular chaperone activity on chromosome 1p31, producing a P-value of 1.73 x 10-4 (Bonferroni corrected P = 8.65 x 10-3). Other convincing associations were discovered for markers in the forkhead box transcription factor FOXP4 on chromosome 6p21 (two-stage combined P = 3.00 x 10-6) and in FRMD4A on chromosome 10p13 (combined P = 3.67 x 10-5). This large-scale GWAS highlights previously unknown biological pathways contributing to the P300 brain potential in individuals with alcohol dependence.

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C. Kamarajan, D. Chorlian, A. K. Pandey, R. B. Nagaraj, N. Manz, R. Saunders, M. Rangaswamy, and B. Porjesz
"Functional Connectivity During Reward Processing: Theta Coherence in a Gambling Task"
3rd Annual meeting of the Social & Affective Neuroscience Society, New York, NY, USA, 2009 October 9-11

Abstract:
The outcome related negativity (ORN), an event-related potential (ERP) component around 200-250 ms, has been suggested to be an electrophysiological brain signature for the processing of loss and gain. This component has been suggested to involve theta band oscillations as a primary feature. The aim of the current study is to examine oscillatory activity and functional connectivity between frontal and parietal regions during the processing of monetary loss and gain. The sample consisted of 36 healthy individuals with the age range of 18-35 years. A 64-channel EEG was recorded continuously while the subjects were performing a gambling task that prompted the subject to select one of two amounts, 10 and 50. Loss (-50) and Gain (+50) conditions were analyzed using a Wavelet coherence method for frontal (FZ) and parietal (PZ) regions. Time-Frequency representation and Power and Coherence were plotted and compared between loss and gain conditions. Loss condition had more power at FZ while the gain condition had maximum power at PZ. Wavelet coherence values were different between loss and gain in several frequencies at different time interval. High coherence between frontal and parietal sites are reflected in both low and high frequencies during both loss and gain conditions. The results tend confirm the view that loss- and gain-related processing are mediated by separate and distinct cortical circuits.

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N. Manz, M. Rangaswamy, C. Kamarajan, D. B. Chorlian, and B. Porjesz
"Early evoked gamma band responses in the visual oddball task of healthy male adult subjects"
Cognitive Neuroscience Society 2007 Annual Meeting, New York, NY, USA, 2007 May 5-8

Abstract:
We report new results of early evoked gamma band activity during a visual oddball task with target, non-target, and novel stimuli with a focus on the latter case. The sample consisted of 104 healthy, right-handed, substance-abuse free males with an age range of 20-40 years (24.91 ± 4.59 yr). Gamma rhythms are important functional building blocks of brain electrical activity. In humans, gamma band activity has been observed in a variety of cognitive tasks. Event related oscillations in the gamma band can be found as phase-locked (evoked) or non-phase locked (induced) responses to the onset of the experimental stimuli. Studies with novel stimuli have shown that they evoke frontal responses. Using S-Transform analysis, a time-frequency representation method was applied to EEG data and was analyzed in order to obtain stimulus related early evoked gamma band activity (29-45 Hz) and was analyzed within the first 150 ms after stimulus. Target and novel stimuli evoke significantly higher gamma responses than the non-target. The topography of these case differences will be demonstrated. The findings will be discussed in the context of early cognitive and attentional processes.

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C. Kamarajan, D. Chorlian, R. Saunders, M. Rangaswamy, Y. Tang, N. Roopesh, N. Manz, A. Stimus, and B. Porjesz
"Neurocognitive Correlates of Impulsivity and Alcoholism: Theta Oscillations During a Gambling Task"
Cognitive Neuroscience Society 2007 Annual Meeting, New York, NY, USA, 2007 May 5-8

Abstract:
Neurocognitive correlates of impulsivity have been thought to underlie several of externalizing/disinhibitory disorders including alcoholism. The current study examines the aspects of impulsivity in terms of behavioral measures as well as event-related oscillations (EROs) while performing a gambling task that involves monetary gain and loss. Behavioral measures of impulsivity were analyzed and brain oscillations were decomposed into time-frequency-amplitude data using the S-Transform algorithm. The mean amplitude in the outcome-related negativity (ORN) time window (225-275 ms) in each frequency band was statistically analyzed in both groups across four outcomes that involved valence (loss or gain) and magnitude (50 or 10 cents). Alcoholics showed higher impulsivity as measured in Barratt Impulsivity Scale (BIS) and in other task-related impulsivity responses. Further, alcoholics showed significantly decreased amplitude in delta (1-3 Hz) and theta (4-7 Hz) band during the ORN time window. The frontal theta activity was markedly suppressed in alcoholics during all the outcomes. These results are discussed in the light of possible frontal lobe dysfunctions that may mediate high impulsivity and neurocognitive deficits in alcoholics.

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A. K. Pandey, B. Porjesz, C. Kamarajan, M. Rangaswamy, Y. Tang, D. B. Chorlian, B. N. Roopesh, N. Manz, A. Stimus, and H. Begleiter
"Response Inhibition and Production in Alcoholics: An ERP Analysis of N2 Component in a Go/No-Go Task"
Cognitive Neuroscience Society 2007 Annual Meeting, New York, NY, USA, 2007 May 5-8

Abstract:
Studies on neurocognitive impairments in alcoholism are abundant. The objective of the present study is to elucidate the possible brain dysfunctions related to response inhibition and production using a Go/No-Go task. The sample consisted of 78 alcoholic males with an age range between 21-50 years and 58 healthy controls aged between 18 and 25 years. The N2 component of the event-related potentials (ERPs) was compared across task conditions and groups. Alcoholics produced significantly reduced N2 amplitude and weaker current density in the anterior regions. Behaviorally, the alcoholic group was slower in executing a motor (GO) response. Additional analysis using LORETA (Low Resolution Electromagnetic Tomography) indicated that alcoholic group had lesser activation in the frontal regions. These findings suggest that alcoholics have deficits in effortful processing during response inhibition and execution as well as possible frontal lobe dysfunctions.

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Last changed on 2016-10-03