@article {4459, title = {A somato-cognitive action network alternates with effector regions in motor cortex.}, journal = {Nature}, volume = {617}, year = {2023}, month = {05/2023}, pages = {351-359}, abstract = {

Motor cortex (M1) has been thought to form a continuous somatotopic homunculus extending down~the precentral gyrus from foot to face representations, despite evidence for concentric functional zones and maps of complex actions. Here, using precision functional magnetic resonance imaging (fMRI) methods, we find that the classic homunculus is interrupted by regions with distinct connectivity, structure and function, alternating with effector-specific (foot, hand and mouth) areas. These inter-effector regions exhibit decreased cortical thickness and strong functional connectivity to each other, as well as to the cingulo-opercular network (CON), critical for action and physiological control, arousal, errors and pain. This interdigitation of action control-linked and motor effector regions was verified in the three largest fMRI datasets. Macaque and pediatric (newborn, infant and child) precision fMRI suggested cross-species homologues and developmental precursors of the inter-effector system. A battery of motor and action fMRI tasks documented concentric effector somatotopies, separated by the CON-linked inter-effector regions. The inter-effectors lacked movement specificity and co-activated during action planning (coordination of hands and feet) and axial body movement (such as of the abdomen or eyebrows). These results, together with previous studies demonstrating stimulation-evoked complex actions and connectivity to internal organs such as the adrenal medulla, suggest that M1 is punctuated by a system for whole-body action planning, the somato-cognitive action network (SCAN). In M1, two parallel systems intertwine, forming an integrate-isolate pattern: effector-specific regions (foot, hand and mouth) for isolating fine motor control and the SCAN for integrating goals, physiology and body movement.

}, keywords = {Animals, Brain Mapping, Child, Cognition, Datasets as Topic, Foot, Hand, Humans, Infant, Infant, Newborn, Macaca, Magnetic Resonance Imaging, Motor Cortex, Mouth}, issn = {1476-4687}, doi = {10.1038/s41586-023-05964-2}, author = {Gordon, Evan M and Chauvin, Roselyne J and Van, Andrew N and Rajesh, Aishwarya and Nielsen, Ashley and Newbold, Dillan J and Lynch, Charles J and Seider, Nicole A and Krimmel, Samuel R and Scheidter, Kristen M and Monk, Julia and Miller, Ryland L and Metoki, Athanasia and Montez, David F and Zheng, Annie and Elbau, Immanuel and Madison, Thomas and Nishino, Tomoyuki and Myers, Michael J and Kaplan, Sydney and Badke D{\textquoteright}Andrea, Carolina and Demeter, Damion V and Feigelis, Matthew and Ramirez, Julian S B and Xu, Ting and Barch, Deanna M and Smyser, Christopher D and Rogers, Cynthia E and Zimmermann, Jan and Botteron, Kelly N and Pruett, John R and Willie, Jon T and Brunner, Peter and Shimony, Joshua S and Kay, Benjamin P and Marek, Scott and Norris, Scott A and Gratton, Caterina and Sylvester, Chad M and Power, Jonathan D and Liston, Conor and Greene, Deanna J and Roland, Jarod L and Petersen, Steven E and Raichle, Marcus E and Laumann, Timothy O and Fair, Damien A and Dosenbach, Nico U F} } @article {4453, title = {Heksor: the central nervous system substrate of an adaptive behaviour.}, journal = {J Physiol}, volume = {600}, year = {2022}, month = {08/2022}, pages = {3423-3452}, abstract = {

Over the past half-century, the largely hardwired central nervous system (CNS) of 1970~has become the ubiquitously plastic CNS of today, in which change is the rule not the exception. This transformation complicates a central question in neuroscience: how are adaptive behaviours - behaviours that serve the needs of the individual - acquired and maintained through life? It poses a more basic question: how do many adaptive behaviours share the ubiquitously plastic CNS? This question compels neuroscience to adopt a new paradigm. The core of this paradigm is a CNS entity with unique properties, here given the name heksor from the Greek hexis. A heksor is a distributed network of neurons and synapses that changes itself as needed to maintain the key features of an adaptive behaviour, the features that make the behaviour satisfactory. Through their concurrent changes, the numerous heksors that share the CNS negotiate the properties of the neurons and synapses that they all use. Heksors keep the CNS in a state of negotiated equilibrium that enables each heksor to maintain the key features of its behaviour. The new paradigm based on heksors and the negotiated equilibrium they create is supported by animal and human studies of interactions among new and old adaptive behaviours, explains otherwise inexplicable results, and underlies promising new approaches to restoring behaviours impaired by injury or disease. Furthermore, the paradigm offers new and potentially important answers to extant questions, such as the generation and function of spontaneous neuronal activity, the aetiology of muscle synergies, and the control of homeostatic plasticity.

}, keywords = {Adaptation, Psychological, Animals, central nervous system, Humans, Neuronal Plasticity, Plastics, Synapses}, issn = {1469-7793}, doi = {10.1113/JP283291}, author = {Wolpaw, Jonathan R and Kamesar, Adam} } @article {3390, title = {Locomotor impact of beneficial or nonbeneficial H-reflex conditioning after spinal cord injury.}, journal = {J Neurophysiol}, volume = {111}, year = {2014}, month = {03/2014}, pages = {1249-58}, abstract = {When new motor learning changes neurons and synapses in the spinal cord, it may affect previously learned behaviors that depend on the same spinal neurons and synapses. To explore these effects, we used operant conditioning to strengthen or weaken the right soleus H-reflex pathway in rats in which a right spinal cord contusion had impaired locomotion. When up-conditioning increased the H-reflex, locomotion improved. Steps became longer, and step-cycle asymmetry (i.e., limping) disappeared. In contrast, when down-conditioning decreased the H-reflex, locomotion did not worsen. Steps did not become shorter, and asymmetry did not increase. Electromyographic and kinematic analyses explained how H-reflex increase improved locomotion and why H-reflex decrease did not further impair it. Although the impact of up-conditioning or down-conditioning on the H-reflex pathway was still present during locomotion, only up-conditioning affected the soleus locomotor burst. Additionally, compensatory plasticity apparently prevented the weaker H-reflex pathway caused by down-conditioning from weakening the locomotor burst and further impairing locomotion. The results support the hypothesis that the state of the spinal cord is a "negotiated equilibrium" that serves all the behaviors that depend on it. When new learning changes the spinal cord, old behaviors undergo concurrent relearning that preserves or improves their key features. Thus, if an old behavior has been impaired by trauma or disease, spinal reflex conditioning, by changing a specific pathway and triggering a new negotiation, may enable recovery beyond that achieved simply by practicing the old behavior. Spinal reflex conditioning protocols might complement other neurorehabilitation methods and enhance recovery.}, keywords = {Animals, Conditioning, Operant, Female, H-Reflex, Learning, Locomotion, Male, Rats, Rats, Sprague-Dawley, Spinal Cord Injuries}, issn = {1522-1598}, doi = {10.1152/jn.00756.2013}, url = {http://www.ncbi.nlm.nih.gov/pubmed/24371288}, author = {Yi Chen and Lu Chen and Liu, Rongliang and Wang, Yu and Xiang Yang Chen and Jonathan Wolpaw} } @article {3384, title = {Long-term recording of external urethral sphincter EMG activity in unanesthetized, unrestrained rats.}, journal = {Am J Physiol Renal Physiol}, volume = {307}, year = {2014}, month = {08/2014}, pages = {F485-97}, abstract = {

The external urethral sphincter muscle (EUS) plays an important role in urinary function and often contributes to urinary dysfunction. EUS study would benefit from methodology for longitudinal recording of electromyographic activity (EMG) in unanesthetized animals, but this muscle is a poor substrate for chronic intramuscular electrodes, and thus the required methodology has not been available. We describe a method for long-term recording of EUS EMG by implantation of fine wires adjacent to the EUS that are secured to the pubic bone. Wires pass subcutaneously to a skull-mounted plug and connect to the recording apparatus by a flexible cable attached to a commutator. A force transducer-mounted cup under a metabolic cage collected urine, allowing recording of EUS EMG and voided urine weight without anesthesia or restraint. Implant durability permitted EUS EMG recording during repeated (up to 3 times weekly) 24-h sessions for more than 8 wk. EMG and voiding properties were stable over weeks 2-8. The degree of EUS phasic activity (bursting) during voiding was highly variable, with an average of 25\% of voids not exhibiting bursting. Electrode implantation adjacent to the EUS yielded stable EMG recordings over extended periods and eliminated the confounding effects of anesthesia, physical restraint, and the potential for dislodgment of the chronically implanted intramuscular electrodes. These results show that micturition in unanesthetized, unrestrained rats is usually, but not always, associated with EUS bursting. This methodology is applicable to studying EUS behavior during progression of gradually evolving disease and injury models and in response to therapeutic interventions.

}, keywords = {Animals, Electrodes, Implanted, Electromyography, Female, Pubic Bone, Rats, Rats, Sprague-Dawley, Urethra, Urination, Urodynamics}, issn = {1522-1466}, doi = {10.1152/ajprenal.00059.2014}, url = {http://www.ncbi.nlm.nih.gov/pubmed/24990895}, author = {LaPallo, Brandon K and Jonathan Wolpaw and Xiang Yang Chen and Jonathan S. Carp} } @article {3389, title = {The simplest motor skill: mechanisms and applications of reflex operant conditioning.}, journal = {Exerc Sport Sci Rev}, volume = {42}, year = {2014}, month = {04/2014}, pages = {82-90}, abstract = {Operant conditioning protocols can change spinal reflexes gradually, which are the simplest behaviors. This article summarizes the evidence supporting two propositions: that these protocols provide excellent models for defining the substrates of learning and that they can induce and guide plasticity to help restore skills, such as locomotion, that have been impaired by spinal cord injury or other disorders.}, keywords = {Animals, Conditioning, Operant, H-Reflex, Humans, Motor Skills, Muscle, Skeletal, Neuronal Plasticity, Reflex, Spinal Cord, Spinal Cord Injuries}, issn = {1538-3008}, doi = {10.1249/JES.0000000000000010}, url = {http://www.ncbi.nlm.nih.gov/pubmed/24508738}, author = {Thompson, Aiko K and Jonathan Wolpaw} } @article {3377, title = {Novel inter-hemispheric white matter connectivity in the BTBR mouse model of autism.}, journal = {Brain Res}, volume = {1513}, year = {2013}, month = {06/2013}, pages = {26-33}, abstract = {Alterations in the volume, density, connectivity and functional activation of white matter tracts are reported in some individuals with autism and may contribute to their abnormal behaviors. The BTBR (BTBR T+tf/J) inbred strain of mouse, is used to model facets of autism because they develop low social behaviors, stereotypical and immune changes similar to those found in people with autism. Previously, it was thought a total absence of corpus callosal interhemispheric connective tissues in the BTBR mice may underlie their abnormal behaviors. However, postnatal lesions of the corpus callosum do not precipitate social behavioral problems in other strains of mice suggesting a flaw in this theory. In this study we used digital pathological methods to compare subcortical white matter connective tracts in the BTBR strain of mice with those found in the C57Bl/6 mouse and those reported in a standardized mouse brain atlas. We report, for the first time, a novel connective subcortical interhemispheric bridge of tissue in the posterior, but not anterior, cerebrum of the BTBR mouse. These novel connective tissues are comprised of myelinated fibers, with reduced myelin basic protein levels (MBP) compared to levels in the C57Bl/6 mouse. We used electrophysiological analysis and found increased inter-hemispheric connectivity in the posterior hemispheres of the BTBR strain compared with the anterior hemispheres. The conduction velocity was slower than that reported in normal mice. This study shows there is novel abnormal interhemispheric connectivity in the BTBR strain of mice, which may contribute to their behavioral abnormalities.}, keywords = {Analysis of Variance, Animals, Autistic Disorder, Brain, Corpus Callosum, Disease Models, Animal, Electroencephalography, Enzyme-Linked Immunosorbent Assay, Female, Functional Laterality, Image Processing, Computer-Assisted, Male, Mice, Mice, Inbred C57BL, Mice, Neurologic Mutants, Microtubule-Associated Proteins, Myelin Basic Protein, Nerve Fibers, Myelinated, Neuroimaging, Spectrum Analysis}, issn = {1872-6240}, doi = {10.1016/j.brainres.2013.04.001}, url = {http://www.ncbi.nlm.nih.gov/pubmed/23570707}, author = {Miller, V M and Disha Gupta and Neu, N and Cotroneo, A and Chadwick B. Boulay and Seegal, R F} } @article {2149, title = {Silent Communication: toward using brain signals.}, journal = {IEEE Pulse}, volume = {3}, year = {2012}, month = {01/2012}, pages = {43-6}, abstract = {

From the 1980s movie Firefox to the more recent Avatar, popular science fiction has speculated about the possibility of a persons thoughts being read directly from his or her brain. Such braincomputer interfaces (BCIs) might allow people who are paralyzed to communicate with and control their environment, and there might also be applications in military situations wherever silent user-to-user communication is desirable. Previous studies have shown that BCI systems can use brain signals related to movements and movement imagery or attention-based character selection. Although these systems have successfully demonstrated the possibility to control devices using brain function, directly inferring which word a person intends to communicate has been elusive. A BCI using imagined speech might provide such a practical, intuitive device. Toward this goal, our studies to date addressed two scientific questions: (1) Can brain signals accurately characterize different aspects of speech? (2) Is it possible to predict spoken or imagined words or their components using brain signals?

}, keywords = {Animals, Brain, Brain Waves, Humans, Movement, User-Computer Interface}, issn = {2154-2287}, doi = {10.1109/MPUL.2011.2175637}, url = {http://www.ncbi.nlm.nih.gov/pubmed/22344951}, author = {Pei, Xiao-Mei and Jeremy Jeremy Hill and Gerwin Schalk} } @article {3413, title = {Interferon-gamma limits the availability of iron for intramacrophage Salmonella typhimurium.}, journal = {Eur J Immunol}, volume = {38}, year = {2008}, month = {07/2008}, pages = {1923-36}, abstract = {

In stimulating effector functions of mononuclear phagocytes, IFN-gamma is of pivotal importance in host defense against intramacrophage pathogens including salmonellae. As the activity of IFN-gamma is modulated by iron and since a sufficient availability of iron is essential for the growth of pathogens, we investigated the regulatory effects of IFN-gamma on iron homeostasis and immune function in murine macrophages infected with Salmonella typhimurium. In Salmonella-infected phagocytes, IFN-gamma caused a significant reduction of iron uptake via transferrin receptor 1 and resulted in an increased iron efflux caused by an enhanced expression of the iron exporter ferroportin 1. Moreover, the expression of haem oxygenase 1 and of the siderophore-capturing antimicrobial peptide lipocalin 2 was markedly elevated following bacterial invasion, with IFN-gamma exerting a super-inducing effect. This observed regulatory impact of IFN-gamma reduced the intracellular iron pools within infected phagocytes, thus restricting the acquisition of iron by engulfed Salmonella typhimurium while concomitantly promoting NO and TNF-alpha production. Our data suggest that the modulation of crucial pathways of macrophage iron metabolism in response to IFN-gamma concordantly aims at withdrawing iron from intracellular Salmonella and at strengthening macrophage immune response functions. These regulations are thus consistent with the principles of nutritional immunity.

}, keywords = {Acute-Phase Proteins, Animals, Antimicrobial Cationic Peptides, Cation Transport Proteins, Cell Line, Ferritins, Heme Oxygenase (Decyclizing), Hepcidins, Interferon-gamma, Iron, Lipocalins, Macrophages, Mice, Nitric Oxide, Oncogene Proteins, Salmonella typhimurium, Transferrin, Tumor Necrosis Factor-alpha}, issn = {0014-2980}, doi = {10.1002/eji.200738056}, url = {http://www.ncbi.nlm.nih.gov/pubmed/18581323}, author = {Nairz, Manfred and Fritsche, Gernot and Peter Brunner and Talasz, Heribert and Hantke, Klaus and Weiss, G{\"u}nter} } @article {2106, title = {Analysis of the correlation between local field potentials and neuronal firing rate in the motor cortex.}, journal = {Conf Proc IEEE Eng Med Biol Soc}, volume = {1}, year = {2006}, month = {09/2006}, pages = {6185-8}, abstract = {

Neuronal firing rate has been the signal of choice for invasive motor\ brain\ machine\ interfaces\ (BMI). The use of local field potentials (LFP) in BMI experiments may provide additional dendritic information about movement intent and may improve performance. Here we study the time-varying amplitude modulated relationship between local field potentials (LFP) and single unit activity (SUA) in the motor cortex. We record LFP and SUA in the primary motor cortex of rats trained to perform a lever pressing task, and evaluate the correlation between pairs of peri-event time histograms (PETH) and movement evoked local field potentials (mEP) at the same electrode. Three different correlation coefficients were calculated and compared between the neuronal PETH and the magnitude and power of the mEP. Correlation as high as 0.7 for some neurons occurred between the PETH and the mEP magnitude. As expected, the correlations between the single trial LFP and SUV are much lower due to the inherent variability of both signals.

}, keywords = {Action Potentials, Animals, Brain, Brain Mapping, Electric Stimulation, Electrodes, Evoked Potentials, Motor, Male, Models, Statistical, Motor Cortex, Neurons, Rats, Rats, Sprague-Dawley, Signal Processing, Computer-Assisted, Synaptic Transmission}, issn = {1557-170X}, doi = {10.1109/IEMBS.2006.260516}, url = {http://www.ncbi.nlm.nih.gov/pubmed/17946745}, author = {Wang, Yiwen and Sanchez, Justin C and Principe, Jose and Mitzelfelt, Jeremiah D and Gunduz, Aysegul} } @article {2155, title = {Progress of brain-neural function informatics.}, journal = {Zhongguo Yi Liao Qi Xie Za Zhi}, volume = {30}, year = {2006}, month = {11/2006}, pages = {399-406, 462}, abstract = {

Firstly the fundamental concept and research hotspots of\ Brain-Neural Function Informatics (BNFI) are described. Then the main study fields and progresses of BNFI are expounded. Finally the prospects of BNFI research are given. Studies on BNFI not only promote the "Brain\ Science" progress, but also boost the industry of a new kind of medical instruments - function rehabilitation equipment and artificial functional prostheses.

}, keywords = {Animals, Biomedical Engineering, Brain, Brain Diseases, Computing Methodologies, Humans, Informatics, Nervous System Physiological Phenomena}, issn = {1671-7104}, url = {http://www.ncbi.nlm.nih.gov/pubmed/17300003}, author = {Zheng, Shi Dong and Pei, Xiao-Mei and Xu, Jin} } @article {2177, title = {The Wadsworth BCI Research and Development Program: At Home with BCI.}, journal = {IEEE Trans Neural Syst Rehabil Eng}, volume = {14}, year = {2006}, month = {06/2006}, pages = {229-33}, abstract = {

The ultimate goal of brain-computer interface (BCI) technology is to provide communication and control capacities to people with severe motor disabilities. BCI research at the Wadsworth Center focuses primarily on noninvasive,\ electroencephalography\ (EEG)-based BCI methods. We have shown that people, including those with severe motor disabilities, can learn to use sensorimotor rhythms (SMRs) to move a cursor rapidly and accurately in one or two dimensions. We have also improved P300-based BCI operation. We are now translating this laboratory-proven BCI technology into a system that can be used by severely disabled people in their homes with minimal ongoing technical oversight. To accomplish this, we have: improved our general-purpose BCI software (BCI2000); improved online adaptation and feature translation for SMR-based BCI operation; improved the accuracy and bandwidth of P300-based BCI operation; reduced the\ complexity\ of system hardware and software and begun to evaluate home system use in appropriate users. These developments have resulted in prototype systems for every day use in people{\textquoteright}s homes.

}, keywords = {Animals, Brain, Electroencephalography, Evoked Potentials, Humans, Neuromuscular Diseases, New York, Research, Switzerland, Therapy, Computer-Assisted, Universities, User-Computer Interface}, issn = {1534-4320}, doi = {10.1109/TNSRE.2006.875577}, url = {http://www.ncbi.nlm.nih.gov/pubmed/16792301}, author = {Theresa M Vaughan and Dennis J. McFarland and Gerwin Schalk and Sarnacki, William A and Krusienski, Dean J and Sellers, Eric W and Jonathan Wolpaw} } @article {3414, title = {Pathways for the regulation of body iron homeostasis in response to experimental iron overload.}, journal = {J Hepatol}, volume = {43}, year = {2005}, month = {10/2005}, pages = {711-9}, abstract = {BACKGROUND/AIMS: Secondary iron overload is a frequent clinical condition found in association with multiple blood transfusions. METHODS: To gain insight into adaptive changes in the expression of iron genes in duodenum, liver and spleen upon experimental iron overload we studied C57BL/6 mice receiving repetitive daily injections of iron-dextran for up to 5 days. RESULTS: Iron initially accumulated in spleen macrophages but with subsequent increase in macrophage ferroportin and ferritin expression its content in the spleen decreased while a progressive storage of iron occurred within hepatocytes which was paralleled by a significant increase in hepcidin and hemojuvelin expression. Under these conditions, iron was still absorbed from the duodenal lumen as divalent metal transporter-1 expressions were high, however, most of the absorbed iron was incorporated into duodenal ferritin, while ferroportin expression drastically decreased and iron transfer to the circulation was reduced. CONCLUSIONS: Experimental iron overload results in iron accumulation in macrophages and later in hepatocytes. In parallel, the transfer of iron from the gut to the circulation is diminished which may be referred to interference of hepcidin with ferroportin mediated iron export, thus preventing body iron accumulation.}, keywords = {Animals, Disease Models, Animal, Disease Progression, DNA Primers, Duodenum, Gene Expression Regulation, Hepatocytes, Homeostasis, Iron, Iron Overload, Macrophages, Mice, Mice, Inbred C57BL, Polymerase Chain Reaction, RNA}, issn = {0168-8278}, doi = {10.1016/j.jhep.2005.03.030}, url = {http://www.sciencedirect.com/science/article/pii/S0168827805003168$\#$}, author = {Theurl, Igor and Ludwiczek, Susanne and Eller, Philipp and Seifert, Markus and Artner, Erika and Peter Brunner and Weiss, G{\"u}nter} } @article {2164, title = {Temporal transformation of multiunit activity improves identification of single motor units.}, journal = {J Neurosci Methods}, volume = {114}, year = {2002}, month = {02/2002}, pages = {87-98}, abstract = {

This report describes a temporally based method for identifying repetitive firing of motor units. This\ approach\ is ideally suited to spike trains with negative serially correlated inter-spike intervals (ISIs). It can also be applied to spike trains in which ISIs exhibit little serial correlation if their coefficient of variation (COV) is sufficiently low. Using a novel application of the Hough transform, this method (i.e. the modified Hough transform (MHT)) maps motor unit action potential (MUAP) firing times into a feature space with ISI and offset (defined as the latency from an arbitrary starting time to the first MUAP in the train) as dimensions. Each MUAP firing time corresponds to a pattern in the feature space that represents all possible MUAP trains with a firing at that time. Trains with stable ISIs produce clusters in the feature space, whereas randomly firing trains do not. The MHT provides a direct estimate of mean firing rate and its variability for the entire data segment, even if several individual MUAPs are obscured by firings from other motor units. Addition of this method to a shape-based classification\ approach\ markedly improved rejection of false positives using simulated data and identified spike trains in whole muscle electromyographic recordings from rats. The relative independence of the MHT from the need to correctly classify individual firings permits a global description of stable repetitive firing behavior that is complementary to shape-based approaches to MUAP classification.

}, keywords = {Action Potentials, Animals, Electromyography, H-Reflex, Motor Neurons, Muscle, Skeletal, Rats, Signal Processing, Computer-Assisted}, issn = {0165-0270}, doi = {10.1016/S0165-0270(01)00517-9}, url = {http://www.ncbi.nlm.nih.gov/pubmed/11850043}, author = {Gerwin Schalk and Jonathan S. Carp and Jonathan Wolpaw} } @article {2117, title = {Visualizing excitation waves inside cardiac muscle using transillumination.}, journal = {Biophys J}, volume = {80}, year = {2001}, month = {01/2001}, pages = {516-30}, abstract = {

Voltage-sensitive fluorescent dyes have become powerful tools for the visualization of excitation propagation in the\ heart. However, until recently they were used exclusively for surface recordings. Here we demonstrate the possibility of visualizing the electrical activity from inside cardiac muscle via fluorescence measurements in the transillumination mode (in which the light source and photodetector are on opposite sides of the preparation). This mode enables the detection of light escaping from layers deep within the tissue. Experiments were conducted in perfused (8 mm thick) slabs of sheep right ventricular wall stained with the voltage-sensitive dye di-4-ANEPPS. Although the amplitude and signal-to-noise ratio recorded in the transillumination mode were significantly smaller than those recorded in the epi-illumination mode, they were sufficient to reliably determine the activation sequence. Penetration depths (spatial decay constants) derived from measurements of light attenuation in cardiac muscle were 0.8 mm for excitation (520 +/- 30 nm) and 1.3 mm for emission wavelengths (640 +/- 50 nm). Estimates of emitted fluorescence based on these attenuation values in 8-mm-thick tissue suggest that 90\% of the transillumination signal originates from a 4-mm-thick layer near the illuminated surface. A 69\% fraction of the recorded signal originates from \> or =1 mm below the surface. Transillumination recordings may be combined with endocardial and epicardial surface recordings to obtain information about three-dimensional propagation in the thickness of the myocardial wall. We show an example in which transillumination reveals an intramural reentry, undetectable in surface recordings.

}, keywords = {Animals, Biophysical Phenomena, Biophysics, Electrophysiology, Endocardium, Fluorescent Dyes, Heart, Models, Cardiovascular, Myocardium, Optics and Photonics, Perfusion, Pericardium, Pyridinium Compounds, Sheep}, issn = {0006-3495}, doi = {10.1016/S0006-3495(01)76034-1}, url = {http://www.ncbi.nlm.nih.gov/pubmed/11159422}, author = {Baxter, Bill and Mironov, S F and Zaitsev, A V and Jalife, J and Pertsov, A V} } @article {2119, title = {Quantification of effects of global ischemia on dynamics of ventricular fibrillation in isolated rabbit heart.}, journal = {Circulation}, volume = {98}, year = {1998}, month = {10/1998}, pages = {1688-96}, abstract = {

BACKGROUND:\ 

Ventricular fibrillation (VF) leads to global ischemia of the heart. After 1 to 2 minutes of onset, the VF rate decreases and appears more organized. The objectives of this study were to determine the effects of no-flow global ischemia on nonlinear wave dynamics and establish the mechanism of ischemia-induced slowing of the VF rate.

METHODS AND RESULTS:\ 

Activation patterns of VF in the Langendorff-perfused rabbit heart were studied with the use of 2 protocols: (1) 15 minutes of no-flow global ischemia followed by reperfusion (n=7) and (2) decreased excitability induced by perfusion with 5 micromol/L of tetrodotoxin (TTX) followed by washout (n=3). Video imaging ( approximately 7500 pixels per frame; 240 frames per second) with a voltage-sensitive dye, ECG, and signal processing (fast Fourier transform) were used for analysis. The dominant frequency of VF decreased from 13.5+/-1.3 during control to 9.3+/-1.4 Hz at 5 minutes of global ischemia (P\<0.02). The dominant frequency decreased from 13.9+/-1.1 during control to 7.0+/-0.3 Hz at 2 minutes of TTX infusion (P\<0.001). The rotation period of rotors on the epicardial surface (n=27) strongly correlated with the inverse dominant frequency of the corresponding episode of VF (R2=0. 93). The core area, measured for 27 transiently appearing rotors, was 5.3+/-0.7 mm2 during control. A remarkable increase in core area was observed both during global ischemia (13.6+/-1.7 mm2; P\<0.001) and TTX perfusion (16.8+/-3.6 mm2; P\<0.001). Density of wave fronts decreased during both global ischemia (P\<0.002) and TTX perfusion (P\<0.002) compared with control.

CONCLUSIONS:\ 

This study suggests that rotating spiral waves are most likely the underlying mechanism of VF and contribute to its frequency content. Ischemia-induced decrease in the VF rate results from an increase in the rotation period of spiral waves that occurs secondary to an increase in their core area. Remarkably, similar findings in the TTX protocol suggest that reduced excitability during ischemia is an important underlying mechanism for the changes seen.

}, keywords = {Animals, Electrocardiography, Linear Models, Myocardial Ischemia, Rabbits, Rotation, Sodium Channel Blockers, Tetrodotoxin, Ventricular Fibrillation, Video Recording}, issn = {0009-7322}, doi = {10.1161/01.CIR.98.16.1688}, url = {http://www.ncbi.nlm.nih.gov/pubmed/9778336}, author = {Mandapati, R and Asano, Y and Baxter, Bill and Gray, R A and Davidenko, J M and Jalife, J} } @article {2120, title = {Optical mapping of drug-induced polymorphic arrhythmias and torsade de pointes in the isolated rabbit heart.}, journal = {J Am Coll Cardiol}, volume = {29}, year = {1997}, month = {03/1997}, pages = {831-42}, abstract = {

OBJECTIVES:\ 

This study sought to 1) test the hypothesis that in the setting of bradycardia and drug-induced action potential prolongation, multiple foci of early afterdepolarizations (EADs) result in beat to beat changes in the origin and direction of the excitation wave front and are responsible for polymorphic arrhythmias; and 2) determine whether EADs may initiate nonstationary reentry, giving rise to the typical torsade de pointes (TDP) pattern.

BACKGROUND:\ 

In the past, it has been difficult to associate EADs or reentry with the undulating electrocardiographic (ECG) patterns of TDP.

METHODS:\ 

A voltage-sensitive dye was used for high resolution\ videoimaging\ of electrical waves on the\ epicardial\ and endocardial\ surface\ of the Langendorff-perfused\ rabbitheart. ECG and monophasic action potentials from the right septal region were also recorded. Bradycardia was induced by ablation of the atrioventricular node.

RESULTS:\ 

Perfusion of low potassium chloride Tyrode solution plus quinidine led to prolongation of the action potential and the QT interval. Eventually, EADs and triggered activity ensued, giving rise to intermittent episodes of polymorphic arrhythmia. In one experiment, triggered activity was followed by a long episode of vortex-like reentry with an ECG pattern characteristic of TDP. However, in most experiments, focal activity of varying origins and propagation patterns was observed. Triggered responses also showed varying degrees of local block. Similar results were obtained with E-4031. Burst pacing both at control conditions and in the presence of quinidine consistently led to vortex-like reentry whose ECG pattern resembled TDP. However, the cycle length of the arrhythmia with quinidine was longer than that for control ([mean +/- SEM] 194 +/- 12 vs. 132 +/- 8 ms, p \< 0.03).

CONCLUSIONS:\ 

Drug-induced polymorphic ventricular arrhythmias may result from beat to beat changes in wave propagation patterns initiated by EADs or EAD-induced nonstationary reentrant activity. In contrast, burst pacing-induced polymorphic tachycardia in the presence or absence of drugs is the result of nonstationary reentrant activity.

}, keywords = {Action Potentials, Animals, Anti-Arrhythmia Agents, Arrhythmias, Cardiac, Electrocardiography, Heart, Heart Conduction System, Image Processing, Computer-Assisted, Models, Cardiovascular, Organ Culture Techniques, Perfusion, Piperidines, Pyridines, Quinidine, Rabbits, Torsades de Pointes}, issn = {0735-1097}, doi = {10.1016/S0735-1097(96)00588-8}, url = {http://www.ncbi.nlm.nih.gov/pubmed/9091531}, author = {Asano, Y and Davidenko, J M and Baxter, Bill and Gray, R A and Jalife, J} } @article {2118, title = {Technical features of a CCD video camera system to record cardiac fluorescence data.}, journal = {Ann Biomed Eng}, volume = {25}, year = {1997}, month = {07/1997}, pages = {713-25}, abstract = {

A charge-coupled device (CCD) camera was used to acquire movies of transmembrane activity from thin slices of sheep ventricular\ epicardial\ muscle stained with a voltage-sensitive dye. Compared with photodiodes, CCDs have high spatial resolution, but low temporal resolution. Spatial resolution in our system ranged from 0.04 to 0.14 mm/pixel; the acquisition rate was 60, 120, or 240 frames/sec. Propagating waves were readily visualized after subtraction of a background image. The optical signal had an amplitude of 1 to 6 gray levels, with signal-to-noise ratios between 1.5 and 4.4. Because CCD cameras integrate light over the frame interval, moving objects, including propagating waves, are blurred in the resulting movies. A computer model of such an integrating\ imaging\ system was developed to study the effects of blur, noise, filtering, and quantization on the ability to measure conduction velocity and action potential duration (APD). The model indicated that blurring, filtering, and quantization do not affect the ability to localize wave fronts in the optical data (i.e., no systematic error in determining spatial position), but noise does increase the uncertainty of the measurements. The model also showed that the low frame rates of the CCD camera introduced a systematic error in the calculation of APD: for cutoff levels \> 50\%, the APD was erroneously long. Both noise and quantization increased the uncertainty in the APD measurements. The optical measures of conduction velocity were not significantly different from those measured simultaneously with microelectrodes. Optical APDs, however, were longer than the electrically recorded APDs. This APD error could be reduced by using the 50\% cutoff level and the fastest frame rate possible.

}, keywords = {Action Potentials, Algorithms, Animals, Body Surface Potential Mapping, Calibration, Computer Simulation, Electric Conductivity, Fluorescent Dyes, Image Processing, Computer-Assisted, Models, Cardiovascular, Sheep, Ventricular Function, Video Recording}, issn = {0090-6964}, doi = {10.1007/BF02684848}, url = {http://www.ncbi.nlm.nih.gov/pubmed/9236983}, author = {Baxter, Bill and Davidenko, J M and Loew, L M and Wuskell, J P and Jalife, J} } @article {2121, title = {Vortex shedding as a precursor of turbulent electrical activity in cardiac muscle.}, journal = {Biophys J}, volume = {70}, year = {1996}, month = {03/1996}, pages = {1105-11}, abstract = {

In cardiac tissue, during partial blockade of the membrane sodium channels, or at high frequencies of excitation, inexcitable obstacles with sharp edges may destabilize the propagation of electrical excitation waves, causing the formation of self-sustained vortices and turbulent cardiac electrical activity. The formation of such vortices, which visually resembles vortex shedding in hydrodynamic turbulent flows, was observed in sheep epicardial tissue using voltage-sensitive dyes in combination with video-imaging techniques. Vortex shedding is a potential mechanism leading to the spontaneous initiation of uncontrolled high-frequency excitation of the heart.

}, keywords = {Animals, Biophysical Phenomena, Biophysics, Cell Membrane, Computer Simulation, Electric Stimulation, Electrochemistry, Electrophysiology, Heart, Models, Cardiovascular, Myocardial Contraction, Myocardium, Sheep, Sodium Channels}, issn = {0006-3495}, doi = {10.1016/S0006-3495(96)79691-1}, url = {http://www.ncbi.nlm.nih.gov/pubmed/8785270}, author = {Cabo, C and Pertsov, A V and Davidenko, J M and Baxter, Bill and Gray, R A and Jalife, J} } @article {2122, title = {Effects of pacing on stationary reentrant activity. Theoretical and experimental study.}, journal = {Circ Res}, volume = {77}, year = {1995}, month = {12/1995}, pages = {1166-79}, abstract = {

It is well known that electrical pacing may either terminate or change the rate and/or ECG appearance of reentrant ventricular tachycardia. However, the dynamics of interaction of reentrant waves with waves initiated by external pacing are poorly understood. Prevailing concepts are based on simplistic models in which propagation occurs in one-dimensional rings of cardiac tissue. Since reentrant activation in the ventricles occurs in two or three dimensions, such concepts might be insufficient to explain the mechanisms of pacing-induced effects. We used numerical and biological models of cardiac excitation to explore the phenomena, which may take place as a result of electrical pacing during functionally determined reentry. Computer simulations of a two-dimensional array of electrically coupled FitzHugh-Nagumo cells were used to predict the response patterns expected from thin slices of sheep ventricular epicardial muscle, in which self-sustaining reentrant activity in the form of spiral waves was consistently initiated by premature stimulation and monitored by means of video mapping techniques. The results show that depending on their timing and shape, externally induced waves may collide with the self-sustaining spiral and result in one of three possible outcomes: (1) direct annihilation of the spiral, (2) multiplication of the spiral, or (3) shift of the spiral center (ie, core). Multiplication and shift of the spiral core were attended by changes in rate and morphology of the arrhythmia as seen by "pseudo-ECGs." Furthermore, delayed termination (ie, termination of the activity one to three cycles after the stimulus) occurred after both multiplication and shift of the spiral center. Both numerical predictions and experimental results support the hypothesis that whether a pacing stimulus will terminate a reentrant arrhythmia or modify its ECG appearance depends on whether the interactions between the externally induced wave and the spiral wave result in the de novo formation of one or more "wavebreaks." The final outcome depends on the stimulus parameters (ie, position and size of the electrodes and timing of the stimulus) as well as on the position of the newly formed wavebreak(s) in relation to that of the original wave.

}, keywords = {Acceleration, Animals, Cardiac Pacing, Artificial, Computer Simulation, Deceleration, Electrocardiography, Models, Cardiovascular, Sheep, Tachycardia, Ventricular}, issn = {0009-7330}, doi = {10.1161/01.RES.77.6.1166}, url = {http://www.ncbi.nlm.nih.gov/pubmed/7586230}, author = {Davidenko, J M and Salomonsz, R and Pertsov, A V and Baxter, Bill and Jalife, J} } @article {2123, title = {Mechanisms of cardiac fibrillation.}, journal = {Science}, volume = {270}, year = {1995}, month = {11/1995}, pages = {1222-3; author reply 1224-5}, keywords = {Animals, Computer Simulation, Electrocardiography, Heart Ventricles, Models, Cardiovascular, Rabbits, Ventricular Fibrillation}, issn = {0036-8075}, doi = {10.1126/science.270.5239.1222}, url = {http://www.ncbi.nlm.nih.gov/pubmed/7502055}, author = {Gray, R A and Jalife, J and Panfilov, A and Baxter, Bill and Cabo, C and Davidenko, J M and Pertsov, A V} } @article {2124, title = {Nonstationary vortexlike reentrant activity as a mechanism of polymorphic ventricular tachycardia in the isolated rabbit heart.}, journal = {Circulation}, volume = {91}, year = {1995}, month = {05/1995 }, pages = {2454-69}, abstract = {

BACKGROUND:\ 

Ventricular tachycardia may result from vortexlike reentrant excitation of the myocardium. Our general hypothesis is that in the structurally normal heart, these arrhythmias are the result of one or two nonstationary three-dimensional electrical scroll waves activating the heart muscle at very high frequencies.

METHODS AND RESULTS:\ 

We used a combination of high-resolution video imaging, electrocardiography, and image processing in the isolated rabbit heart, together with mathematical modeling. We characterized the dynamics of changes in transmembrane potential patterns on the epicardial surface of the ventricles using optical mapping. Image processing techniques were used to identify the surface manifestation of the reentrant organizing centers, and the location of these centers was used to determine the movement of the reentrant pathway. We also used numerical simulations incorporating Fitzhugh-Nagumo kinetics and realistic heart geometry to study how stationary and nonstationary scroll waves are manifest on the epicardial surface and in the simulated ECG. We present epicardial surface manifestations (reentrant spiral waves) and ECG patterns of nonstationary reentrant activity that are consistent with those generated by scroll waves established at the right and left ventricles. We identified the organizing centers of the reentrant circuits on the epicardial surface during polymorphic tachycardia, and these centers moved during the episodes. In addition, the arrhythmias that showed the greatest movement of the reentrant centers displayed the largest changes in QRS morphology. The numerical simulations showed that stationary scroll waves give rise to monomorphic ECG signals, but nonstationary meandering scroll waves give rise to undulating ECGs characteristic of torsade de pointes.

CONCLUSIONS:\ 

Polymorphic ventricular tachycardia in the healthy, isolated rabbit heart is the result of either a single or paired ("figure-of-eight") nonstationary scroll waves. The extent of the scroll wave movement corresponds to the degree of polymorphism in the ECG. These results are consistent with our numerical simulations that showed monomorphic ECG patterns of activity for stationary scroll waves but polymorphic patterns for scroll waves that were nonstationary.

}, keywords = {Animals, Electrocardiography, Heart, Image Processing, Computer-Assisted, Models, Cardiovascular, Perfusion, Rabbits, Tachycardia, Ventricular}, issn = {0009-7322}, doi = {10.1161/01.CIR.91.9.2454}, url = {http://www.ncbi.nlm.nih.gov/pubmed/7729033}, author = {Gray, R A and Jalife, J and Panfilov, A and Baxter, Bill and Cabo, C and Davidenko, J M and Pertsov, A V} } @article {2125, title = {Wave-front curvature as a cause of slow conduction and block in isolated cardiac muscle.}, journal = {Circ Res}, volume = {75}, year = {1994}, month = {12/1994}, pages = {1014-28}, abstract = {

We have investigated the role of wave-front curvature on propagation by following the wave front that was diffracted through a narrow isthmus created in a two-dimensional ionic model (Luo-Rudy) of ventricular muscle and in a thin (0.5-mm) sheet of sheep ventricular epicardial muscle. The electrical activity in the experimental preparations was imaged by using a high-resolution video camera that monitored the changes in fluorescence of the potentiometric dye di-4-ANEPPS on the surface of the tissue. Isthmuses were created both parallel and perpendicular to the fiber orientation. In both numerical and biological experiments, when a planar wave front reached the isthmus, it was diffracted to an elliptical wave front whose pronounced curvature was very similar to that of a wave front initiated by point stimulation. In addition, the velocity of propagation was reduced in relation to that of the original planar wave. Furthermore, as shown by the numerical results, wave-front curvature changed as a function of the distance from the isthmus. Such changes in local curvature were accompanied by corresponding changes in velocity of propagation. In the model, the critical isthmus width was 200 microns for longitudinal propagation and 600 microns for transverse propagation of a single planar wave initiated proximal to the isthmus. In the experiments, propagation depended on the width of the isthmus for a fixed stimulation frequency. Propagation through an isthmus of fixed width was rate dependent both along and across fibers. Thus, the critical isthmus width for propagation was estimated in both directions for different frequencies of stimulation. In the longitudinal direction, for cycle lengths between 200 and 500 milliseconds, the critical width was \< 1 mm; for 150 milliseconds, it was estimated to be between 1.3 and 2 mm; and for the maximum frequency of stimulation (117 +/- 15 milliseconds), it was \> 2.5 mm. In the transverse direction, critical width was between 1.78 and 2.32 mm for a basic cycle length of 200 milliseconds. It increased to values between 2.46 and 3.53 mm for a basic cycle length of 150 milliseconds. The overall results demonstrate that the curvature of the wave front plays an important role in propagation in two-dimensional cardiac muscle and that changes in curvature may cause slow conduction or block.

}, keywords = {Animals, Computer Simulation, Electric Conductivity, Heart, Heart Block, Heart Conduction System, Humans, Models, Cardiovascular, Motion Pictures as Topic, Sheep, Staining and Labeling}, issn = {0009-7330}, url = {http://www.ncbi.nlm.nih.gov/pubmed/7525101}, author = {Cabo, C and Pertsov, A V and Baxter, Bill and Davidenko, J M and Gray, R A and Jalife, J} } @article {2126, title = {Spiral waves of excitation underlie reentrant activity in isolated cardiac muscle.}, journal = {Circ Res}, volume = {72}, year = {1993}, month = {03/1993 }, pages = {631-50}, abstract = {

The mechanism of reentrant ventricular tachycardia was studied in computer simulations and in thin (approximately 20 x 20 x 0.5-mm) slices of dog and sheep ventricular epicardial muscle. A two-dimensional matrix consisting of 96 x 96 electrically coupled cells modeled by the FitzHugh-Nagumo equations was used to analyze the dynamics of self-sustaining reentrant activity in the form of elliptical spiral waves induced by premature stimulation. In homogeneous anisotropic media, spirals are stationary and may last indefinitely. However, the presence of small parameter gradients may lead to drifting and eventual termination of the spiral at the boundary of the medium. On the other hand, spirals may anchor and rotate around small discontinuities within the matrix. Similar results were obtained experimentally in 10 preparations whose electrical activity was monitored by means of a potentiometric dye and high-resolution optical mapping techniques; premature stimulation triggered reproducible episodes of sustained or nonsustained reentrant tachycardia in the form of spiral waves. As a rule, the spirals were elongated, with the major hemiaxis parallel to the longitudinal axis of the cells. The period of rotation (183 +/- 68 msec [mean +/- SD]) was longer than the refractory period (131 +/- 38 msec) and appeared to be determined by the size of the spiral{\textquoteright}s core, which was measured using a newly devised "frame-stack" plot. Drifting of spiral waves was also observed experimentally. Drift velocity was 9.8\% of the velocity of wave propagation. In some cases, the core became stationary by anchoring to small arteries or other heterogeneities, and the spiral rotated rhythmically for prolonged periods of time. Yet, when drift occurred, spatiotemporal variations in the excitation period were manifested as a result of a Doppler effect, with the excitation period ahead of the core being 20 +/- 6\% shorter than the excitation period behind the core. As a result of these coexisting frequencies, a pseudoelectrocardiogram of the activity in the presence of a drifting spiral wave exhibited "QRS complexes" with an undulating axis, which resembled those observed in patients with torsade de pointes. The overall results show that spiral wave activity is a property of cardiac muscle and suggest that such activity may be the common mechanism of a number of monomorphic and polymorphic tachycardias.

}, keywords = {Animals, Computer Simulation, Disease Models, Animal, Dogs, Electrophysiology, Sheep, Tachycardia, Atrioventricular Nodal Reentry, Torsades de Pointes}, issn = {0009-7330}, doi = {10.1161/01.RES.72.3.631}, url = {http://www.ncbi.nlm.nih.gov/pubmed/8431989}, author = {Pertsov, A V and Davidenko, J M and Salomonsz, R and Baxter, Bill and Jalife, J} } @article {2127, title = {Spatiotemporal irregularities of spiral wave activity in isolated ventricular muscle.}, journal = {J Electrocardiol}, volume = {24 Suppl}, year = {1992}, month = {1992}, pages = {113-22}, abstract = {

Voltage-sensitive dyes and high resolution optical mapping were used to analyze the characteristics of spiral waves of excitation in isolated ventricular myocardium. In addition, analytical techniques, which have been previously used in the study of the characteristics of spiral waves in chemical reactions, were applied to determine the voltage structure of the center of the rotating activity (ie, the core). During stable spiral wave activity local activation occurs in a periodic fashion (ie, 1:1 stimulus: response activation ratio) throughout the preparation, except at the core, which is a small elongated area where the activity is of low voltage and the activation ratio is 1:0. The voltage amplitude increases gradually from the center of the core to the periphery. In some cases, however, regular activation patterns at the periphery may coexist with irregular local activation patterns near the core. Such a spatiotemporal irregularity is attended by variations in the core size and shape and results from changes in the core position. The authors conclude that functionally determined reentrant activity in the heart may be the result of spiral waves of propagation and that local spatiotemporal irregularities in the activation pattern are the result of changes in the core position.

}, keywords = {Animals, Cardiac Pacing, Artificial, Fluorescent Dyes, Heart Conduction System, Membrane Potentials, Optics and Photonics, Pericardium, Signal Processing, Computer-Assisted, Tachycardia, Ventricular Function}, issn = {0022-0736}, doi = {10.1016/s0022-0736(10)80029-9}, url = {http://www.ncbi.nlm.nih.gov/pubmed/1552240}, author = {Davidenko, J M and Pertsov, A V and Salomonsz, R and Baxter, Bill and Jalife, J} } @article {2128, title = {Stationary and drifting spiral waves of excitation in isolated cardiac muscle.}, journal = {Nature}, volume = {355}, year = {1992}, month = {01/1992}, pages = {349-51}, abstract = {

Excitable media can support spiral waves rotating around an organizing centre. Spiral waves have been discovered in different types of autocatalytic chemical reactions and in biological systems. The so-called {\textquoteright}re-entrant excitation{\textquoteright} of myocardial cells, causing the most dangerous cardiac arrhythmias, including ventricular tachycardia and fibrillation, could be the result of spiral waves. Here we use a potentiometric dye in combination with CCD (charge-coupled device) imaging technology to demonstrate spiral waves in the heart muscle. The spirals were elongated and the rotation period, Ts, was about 180 ms (3-5 times faster than normal heart rate). In most episodes, the spiral was anchored to small arteries or bands of connective tissue, and gave rise to stationary rotations. In some cases, the core drifted away from its site of origin and dissipated at a tissue border. Drift was associated with a Doppler shift in the local excitation period, T, with T ahead of the core being about 20\% shorter than T behind the core.

}, keywords = {Animals, Dogs, Heart, Mathematics, Membrane Potentials, Models, Biological, Myocardial Contraction, Sheep}, issn = {0028-0836}, doi = {10.1038/355349a0}, url = {http://www.ncbi.nlm.nih.gov/pubmed/1731248}, author = {Davidenko, J M and Pertsov, A V and Salomonsz, R and Baxter, Bill and Jalife, J} } @article {2129, title = {Horizontal organization of orientation-sensitive cells in primate visual cortex.}, journal = {Biol Cybern}, volume = {61}, year = {1989}, month = {07/1989}, pages = {171-82}, abstract = {

In the visual cortex of the monkey the horizontal organization of the preferred orientations of orientation-selective cells follows two opposing rules: (1) neighbors tend to have similar orientation preferences, and (2) many different orientations are observed in a local region. We have described a classification for orientation maps based on the types of topological singularities and the spacing of these singularities relative to the cytochrome oxidase blobs. Using the orientation drift rate as a measure we have compared simulated orientation maps to published records of horizontal electrode recordings.

}, keywords = {Animals, Electron Transport Complex IV, Form Perception, Models, Neurological, Pattern Recognition, Visual, Visual Cortex}, issn = {0340-1200}, doi = {10.1007/BF00198764}, url = {http://www.ncbi.nlm.nih.gov/pubmed/2548628}, author = {Baxter, Bill and Dow, B M} }