02375nas a2200361 4500008004100000022001400041245008900055210006900144260001600213300000900229490000700238520131500245653001001560653001201570653001001582653001801592653002701610653000901637653001501646653001101661653001201672100002101684700002101705700001801726700002201744700002401766700002201790700002001812700001901832700002101851700001901872856012201891 2024 eng d a2045-232200aMotor imagery ability scores are related to cortical activation during gait imagery.0 aMotor imagery ability scores are related to cortical activation  c2024 Mar 03 a52070 v143 a

Motor imagery (MI) is the mental execution of actions without overt movements that depends on the ability to imagine. We explored whether this ability could be related to the cortical activity of the brain areas involved in the MI network. To this goal, brain activity was recorded using high-density electroencephalography in nineteen healthy adults while visually imagining walking on a straight path. We extracted Event-Related Desynchronizations (ERDs) in the θ, α, and β band, and we measured MI ability via (i) the Kinesthetic and Visual Imagery Questionnaire (KVIQ), (ii) the Vividness of Movement Imagery Questionnaire-2 (VMIQ), and (iii) the Imagery Ability (IA) score. We then used Pearson's and Spearman's coefficients to correlate MI ability scores and average ERD power (avgERD). Positive correlations were identified between VMIQ and avgERD of the middle cingulum in the β band and with avgERD of the left insula, right precentral area, and right middle occipital region in the θ band. Stronger activation of the MI network was related to better scores of MI ability evaluations, supporting the importance of testing MI ability during MI protocols. This result will help to understand MI mechanisms and develop personalized MI treatments for patients with neurological dysfunctions.

10aAdult10aAnimals10aBrain10aCell Membrane10aElectroencephalography10aGait10aGastropoda10aHumans10aWalking1 aPutzolu, Martina1 aSamogin, Jessica1 aBonassi, Gaia1 aCosentino, Carola1 aMezzarobba, Susanna1 aBotta, Alessandro1 aAvanzino, Laura1 aMantini, Dante1 aVato, Alessandro1 aPelosin, Elisa uhttps://www.neurotechcenter.org/publications/2024/motor-imagery-ability-scores-are-related-cortical-activation-during03911nas a2200361 4500008004100000022001400041245007800055210006900133260001300202300001400215490000800229520287700237653001203114653001303126653002503139653001003164653002603174653001303200653001303213653000903226653001803235653002403253653000903277653002503286653001603311100001303327700001303340700001303353700002103366700002203387700002403409856011603433 2024 eng d a1469-779300aMotor learning changes the axon initial segment of the spinal motoneuron.0 aMotor learning changes the axon initial segment of the spinal mo c2024 May a2107-21260 v6023 a

We are studying the mechanisms of H-reflex operant conditioning, a simple form of learning. Modelling studies in the literature and our previous data suggested that changes in the axon initial segment (AIS) might contribute. To explore this, we used blinded quantitative histological and immunohistochemical methods to study in adult rats the impact of H-reflex conditioning on the AIS of the spinal motoneuron that produces the reflex. Successful, but not unsuccessful, H-reflex up-conditioning was associated with greater AIS length and distance from soma; greater length correlated with greater H-reflex increase. Modelling studies in the literature suggest that these increases may increase motoneuron excitability, supporting the hypothesis that they may contribute to H-reflex increase. Up-conditioning did not affect AIS ankyrin G (AnkG) immunoreactivity (IR), p-p38 protein kinase IR, or GABAergic terminals. Successful, but not unsuccessful, H-reflex down-conditioning was associated with more GABAergic terminals on the AIS, weaker AnkG-IR, and stronger p-p38-IR. More GABAergic terminals and weaker AnkG-IR correlated with greater H-reflex decrease. These changes might potentially contribute to the positive shift in motoneuron firing threshold underlying H-reflex decrease; they are consistent with modelling suggesting that sodium channel change may be responsible. H-reflex down-conditioning did not affect AIS dimensions. This evidence that AIS plasticity is associated with and might contribute to H-reflex conditioning adds to evidence that motor learning involves both spinal and brain plasticity, and both neuronal and synaptic plasticity. AIS properties of spinal motoneurons are likely to reflect the combined influence of all the motor skills that share these motoneurons. KEY POINTS: Neuronal action potentials normally begin in the axon initial segment (AIS). AIS plasticity affects neuronal excitability in development and disease. Whether it does so in learning is unknown. Operant conditioning of a spinal reflex, a simple learning model, changes the rat spinal motoneuron AIS. Successful, but not unsuccessful, H-reflex up-conditioning is associated with greater AIS length and distance from soma. Successful, but not unsuccessful, down-conditioning is associated with more AIS GABAergic terminals, less ankyrin G, and more p-p38 protein kinase. The associations between AIS plasticity and successful H-reflex conditioning are consistent with those between AIS plasticity and functional changes in development and disease, and with those predicted by modelling studies in the literature. Motor learning changes neurons and synapses in spinal cord and brain. Because spinal motoneurons are the final common pathway for behaviour, their AIS properties probably reflect the combined impact of all the behaviours that use these motoneurons.

10aAnimals10aAnkyrins10aAxon Initial Segment10aAxons10aConditioning, Operant10aH-Reflex10aLearning10aMale10aMotor Neurons10aNeuronal Plasticity10aRats10aRats, Sprague-Dawley10aSpinal Cord1 aWang, Yu1 aChen, Yi1 aChen, Lu1 aHerron, Bruce, J1 aChen, Xiang, Yang1 aWolpaw, Jonathan, R uhttps://www.neurotechcenter.org/publications/2024/motor-learning-changes-axon-initial-segment-spinal-motoneuron04323nas a2200877 4500008004100000022001400041245008800055210006900143260001200212300001200224490000800236520184100244653001202085653001802097653001002115653001402125653002202139653000902161653000902170653001102179653001102190653002002201653001102221653003102232653001702263653001002280100002002290700002502310700001902335700002202354700002002376700002302396700002202419700002202441700002302463700002602486700001602512700002202528700002202550700002102572700001702593700002002610700002002630700002202650700002202672700001902694700003002713700002302743700002202766700002502788700001302813700002102826700002702847700002302874700002002897700002302917700002002940700001902960700001902979700002302998700002103021700001703042700002103059700002203080700002303102700002303125700001803148700002203166700002103188700002403209700002303233700002403256700002003280700002503300856012003325 2023 eng d a1476-468700aA somato-cognitive action network alternates with effector regions in motor cortex.0 asomatocognitive action network alternates with effector regions  c05/2023 a351-3590 v6173 a

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.

10aAnimals10aBrain Mapping10aChild10aCognition10aDatasets as Topic10aFoot10aHand10aHumans10aInfant10aInfant, Newborn10aMacaca10aMagnetic Resonance Imaging10aMotor Cortex10aMouth1 aGordon, Evan, M1 aChauvin, Roselyne, J1 aVan, Andrew, N1 aRajesh, Aishwarya1 aNielsen, Ashley1 aNewbold, Dillan, J1 aLynch, Charles, J1 aSeider, Nicole, A1 aKrimmel, Samuel, R1 aScheidter, Kristen, M1 aMonk, Julia1 aMiller, Ryland, L1 aMetoki, Athanasia1 aMontez, David, F1 aZheng, Annie1 aElbau, Immanuel1 aMadison, Thomas1 aNishino, Tomoyuki1 aMyers, Michael, J1 aKaplan, Sydney1 aD'Andrea, Carolina, Badke1 aDemeter, Damion, V1 aFeigelis, Matthew1 aRamirez, Julian, S B1 aXu, Ting1 aBarch, Deanna, M1 aSmyser, Christopher, D1 aRogers, Cynthia, E1 aZimmermann, Jan1 aBotteron, Kelly, N1 aPruett, John, R1 aWillie, Jon, T1 aBrunner, Peter1 aShimony, Joshua, S1 aKay, Benjamin, P1 aMarek, Scott1 aNorris, Scott, A1 aGratton, Caterina1 aSylvester, Chad, M1 aPower, Jonathan, D1 aListon, Conor1 aGreene, Deanna, J1 aRoland, Jarod, L1 aPetersen, Steven, E1 aRaichle, Marcus, E1 aLaumann, Timothy, O1 aFair, Damien, A1 aDosenbach, Nico, U F uhttps://www.neurotechcenter.org/publications/2023/somato-cognitive-action-network-alternates-effector-regions-motor02437nas a2200241 4500008004100000022001400041245007500055210006900130260001200199300001400211490000800225520167700233653003001910653001201940653002701952653001101979653002401990653001302014653001302027100002402040700001802064856011302082 2022 eng d a1469-779300aHeksor: the central nervous system substrate of an adaptive behaviour.0 aHeksor the central nervous system substrate of an adaptive behav c08/2022 a3423-34520 v6003 a

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.

10aAdaptation, Psychological10aAnimals10acentral nervous system10aHumans10aNeuronal Plasticity10aPlastics10aSynapses1 aWolpaw, Jonathan, R1 aKamesar, Adam uhttps://www.neurotechcenter.org/publications/2022/heksor-central-nervous-system-substrate-adaptive-behaviour02675nas a2200325 4500008004100000022001400041245010000055210006900155260001200224300001200236490000800248520178700256653001202043653002602055653001102081653001302092653001302105653001502118653000902133653000902142653002502151653002502176100001302201700001302214700001902227700001302246700002102259700002102280856004802301 2014 eng d a1522-159800aLocomotor impact of beneficial or nonbeneficial H-reflex conditioning after spinal cord injury.0 aLocomotor impact of beneficial or nonbeneficial Hreflex conditio c03/2014 a1249-580 v1113 aWhen 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.10aAnimals10aConditioning, Operant10aFemale10aH-Reflex10aLearning10aLocomotion10aMale10aRats10aRats, Sprague-Dawley10aSpinal Cord Injuries1 aChen, Yi1 aChen, Lu1 aLiu, Rongliang1 aWang, Yu1 aChen, Xiang Yang1 aWolpaw, Jonathan uhttp://www.ncbi.nlm.nih.gov/pubmed/2437128802577nas a2200301 4500008004100000022001400041245010600055210006900161260001200230300001200242490000800254520171500262653001201977653002601989653002102015653001102036653001502047653000902062653002502071653001202096653001402108653001602122100002402138700002102162700002102183700002302204856004802227 2014 eng d a1522-146600aLong-term recording of external urethral sphincter EMG activity in unanesthetized, unrestrained rats.0 aLongterm recording of external urethral sphincter EMG activity i c08/2014 aF485-970 v3073 a

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.

10aAnimals10aElectrodes, Implanted10aElectromyography10aFemale10aPubic Bone10aRats10aRats, Sprague-Dawley10aUrethra10aUrination10aUrodynamics1 aLaPallo, Brandon, K1 aWolpaw, Jonathan1 aChen, Xiang Yang1 aCarp, Jonathan, S. uhttp://www.ncbi.nlm.nih.gov/pubmed/2499089501203nas a2200277 4500008004100000022001400041245009000055210006900145260001200214300001000226490000700236520041500243653001200658653002600670653001300696653001100709653001700720653002100737653002400758653001100782653001600793653002500809100002200834700002100856856004800877 2014 eng d a1538-300800aThe simplest motor skill: mechanisms and applications of reflex operant conditioning.0 asimplest motor skill mechanisms and applications of reflex opera c04/2014 a82-900 v423 aOperant 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.10aAnimals10aConditioning, Operant10aH-Reflex10aHumans10aMotor Skills10aMuscle, Skeletal10aNeuronal Plasticity10aReflex10aSpinal Cord10aSpinal Cord Injuries1 aThompson, Aiko, K1 aWolpaw, Jonathan uhttp://www.ncbi.nlm.nih.gov/pubmed/2450873802948nas a2200445 4500008004100000022001400041245008900055210006900144260001200213300001000225490000900235520165000244653002501894653001201919653002201931653001001953653002001963653002701983653002702010653003802037653001102075653002602086653004002112653000902152653000902161653002302170653002902193653003602222653002502258653002902283653001702312653002202329100001702351700001702368700001102385700001602396700002502412700001702437856004802454 2013 eng d a1872-624000aNovel inter-hemispheric white matter connectivity in the BTBR mouse model of autism.0 aNovel interhemispheric white matter connectivity in the BTBR mou c06/2013 a26-330 v15133 aAlterations 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.10aAnalysis of Variance10aAnimals10aAutistic Disorder10aBrain10aCorpus Callosum10aDisease Models, Animal10aElectroencephalography10aEnzyme-Linked Immunosorbent Assay10aFemale10aFunctional Laterality10aImage Processing, Computer-Assisted10aMale10aMice10aMice, Inbred C57BL10aMice, Neurologic Mutants10aMicrotubule-Associated Proteins10aMyelin Basic Protein10aNerve Fibers, Myelinated10aNeuroimaging10aSpectrum Analysis1 aMiller, V, M1 aGupta, Disha1 aNeu, N1 aCotroneo, A1 aBoulay, Chadwick, B.1 aSeegal, R, F uhttp://www.ncbi.nlm.nih.gov/pubmed/2357070701835nas a2200241 4500008004100000022001400041245005400055210005200109260001200161300000900173490000600182520120500188653001201393653001001405653001601415653001101431653001301442653002801455100001801483700002501501700001901526856004801545 2012 eng d a2154-228700aSilent Communication: toward using brain signals.0 aSilent Communication toward using brain signals c01/2012 a43-60 v33 a

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?

10aAnimals10aBrain10aBrain Waves10aHumans10aMovement10aUser-Computer Interface1 aPei, Xiao-Mei1 aHill, Jeremy, Jeremy1 aSchalk, Gerwin uhttp://www.ncbi.nlm.nih.gov/pubmed/2234495102677nas a2200421 4500008004100000022001400041245009700055210006900152260001200221300001200233490000700245520147600252653002501728653001201753653003601765653003001801653001401831653001401845653003301859653001401892653002101906653000901927653001501936653001601951653000901967653001701976653002201993653002702015653001602042653003202058100001902090700002102109700001902130700002102149700001802170700001902188856004802207 2008 eng d a0014-298000aInterferon-gamma limits the availability of iron for intramacrophage Salmonella typhimurium.0 aInterferongamma limits the availability of iron for intramacroph c07/2008 a1923-360 v383 a

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.

10aAcute-Phase Proteins10aAnimals10aAntimicrobial Cationic Peptides10aCation Transport Proteins10aCell Line10aFerritins10aHeme Oxygenase (Decyclizing)10aHepcidins10aInterferon-gamma10aIron10aLipocalins10aMacrophages10aMice10aNitric Oxide10aOncogene Proteins10aSalmonella typhimurium10aTransferrin10aTumor Necrosis Factor-alpha1 aNairz, Manfred1 aFritsche, Gernot1 aBrunner, Peter1 aTalasz, Heribert1 aHantke, Klaus1 aWeiss, Günter uhttp://www.ncbi.nlm.nih.gov/pubmed/1858132302708nas a2200373 4500008004100000022001400041245010900055210006900164260001200233300001100245490000600256520162400262653002201886653001201908653001001920653001801930653002501948653001501973653002901988653000902017653002402026653001702050653001202067653000902079653002502088653004102113653002602154100001602180700002302196700001902219700002802238700002002266856004802286 2006 eng d a1557-170X00aAnalysis of the correlation between local field potentials and neuronal firing rate in the motor cortex.0 aAnalysis of the correlation between local field potentials and n c09/2006 a6185-80 v13 a

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.

10aAction Potentials10aAnimals10aBrain10aBrain Mapping10aElectric Stimulation10aElectrodes10aEvoked Potentials, Motor10aMale10aModels, Statistical10aMotor Cortex10aNeurons10aRats10aRats, Sprague-Dawley10aSignal Processing, Computer-Assisted10aSynaptic Transmission1 aWang, Yiwen1 aSanchez, Justin, C1 aPrincipe, Jose1 aMitzelfelt, Jeremiah, D1 aGunduz, Aysegul uhttp://www.ncbi.nlm.nih.gov/pubmed/1794674501743nas a2200265 4500008004100000022001400041245005100055210004900106260001200155300001700167490000700184520102200191653001201213653002701225653001001252653001901262653002801281653001101309653001601320653004301336100002001379700001801399700001201417856004801429 2006 eng d a1671-710400aProgress of brain-neural function informatics.0 aProgress of brainneural function informatics c11/2006 a399-406, 4620 v303 a

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.

10aAnimals10aBiomedical Engineering10aBrain10aBrain Diseases10aComputing Methodologies10aHumans10aInformatics10aNervous System Physiological Phenomena1 aZheng, Shi Dong1 aPei, Xiao-Mei1 aXu, Jin uhttp://www.ncbi.nlm.nih.gov/pubmed/1730000302977nas a2200361 4500008004100000022001400041245007400055210006800129260001200197300001100209490000700220520195300227653001202180653001002192653002702202653002202229653001102251653002702262653001302289653001302302653001602315653003102331653001702362653002802379100002402407700002602431700001902457700002502476700002402501700002102525700002102546856004802567 2006 eng d a1534-432000aThe Wadsworth BCI Research and Development Program: At Home with BCI.0 aWadsworth BCI Research and Development Program At Home with BCI c06/2006 a229-330 v143 a

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's homes.

10aAnimals10aBrain10aElectroencephalography10aEvoked Potentials10aHumans10aNeuromuscular Diseases10aNew York10aResearch10aSwitzerland10aTherapy, Computer-Assisted10aUniversities10aUser-Computer Interface1 aVaughan, Theresa, M1 aMcFarland, Dennis, J.1 aSchalk, Gerwin1 aSarnacki, William, A1 aKrusienski, Dean, J1 aSellers, Eric, W1 aWolpaw, Jonathan uhttp://www.ncbi.nlm.nih.gov/pubmed/1679230102450nas a2200397 4500008004100000022001400041245010000055210006900155260001200224300001000236490000700246520132400253653001201577653002701589653002401616653001601640653001301656653003101669653001601700653001601716653000901732653001801741653001601759653000901775653002301784653003001807653000801837100001701845700002301862700001901885700002001904700001801924700001901942700001901961856007201980 2005 eng d a0168-827800aPathways for the regulation of body iron homeostasis in response to experimental iron overload.0 aPathways for the regulation of body iron homeostasis in response c10/2005 a711-90 v433 aBACKGROUND/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.10aAnimals10aDisease Models, Animal10aDisease Progression10aDNA Primers10aDuodenum10aGene Expression Regulation10aHepatocytes10aHomeostasis10aIron10aIron Overload10aMacrophages10aMice10aMice, Inbred C57BL10aPolymerase Chain Reaction10aRNA1 aTheurl, Igor1 aLudwiczek, Susanne1 aEller, Philipp1 aSeifert, Markus1 aArtner, Erika1 aBrunner, Peter1 aWeiss, Günter uhttp://www.sciencedirect.com/science/article/pii/S0168827805003168#02917nas a2200265 4500008004100000022001400041245009700055210006900152260001200221300001000233490000800243520213200251653002202383653001202405653002102417653001302438653001802451653002102469653000902490653004102499100001902540700002302559700002102582856004802603 2002 eng d a0165-027000aTemporal transformation of multiunit activity improves identification of single motor units.0 aTemporal transformation of multiunit activity improves identific c02/2002 a87-980 v1143 a

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.

10aAction Potentials10aAnimals10aElectromyography10aH-Reflex10aMotor Neurons10aMuscle, Skeletal10aRats10aSignal Processing, Computer-Assisted1 aSchalk, Gerwin1 aCarp, Jonathan, S.1 aWolpaw, Jonathan uhttp://www.ncbi.nlm.nih.gov/pubmed/1185004303049nas a2200361 4500008004100000022001400041245008000055210006900135260001200204300001100216490000700227520206900234653001202303653002602315653001502341653002202356653001602378653002102394653001002415653002702425653001502452653002502467653001402492653001602506653002502522653001002547100001702557700001702574700001702591700001402608700001702622856004802639 2001 eng d a0006-349500aVisualizing excitation waves inside cardiac muscle using transillumination.0 aVisualizing excitation waves inside cardiac muscle using transil c01/2001 a516-300 v803 a

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.

10aAnimals10aBiophysical Phenomena10aBiophysics10aElectrophysiology10aEndocardium10aFluorescent Dyes10aHeart10aModels, Cardiovascular10aMyocardium10aOptics and Photonics10aPerfusion10aPericardium10aPyridinium Compounds10aSheep1 aBaxter, Bill1 aMironov, S F1 aZaitsev, A V1 aJalife, J1 aPertsov, A V uhttp://www.ncbi.nlm.nih.gov/pubmed/1115942203960nas a2200325 4500008004100000022001400041245011500055210006900170260001200239300001200251490000700263520302600270653001203296653002403308653001803332653002403350653001203374653001303386653002803399653001703427653002903444653002003473100001703493700001303510700001703523700001403540700001903554700001403573856004703587 1998 eng d a0009-732200aQuantification of effects of global ischemia on dynamics of ventricular fibrillation in isolated rabbit heart.0 aQuantification of effects of global ischemia on dynamics of vent c10/1998 a1688-960 v983 a

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.

10aAnimals10aElectrocardiography10aLinear Models10aMyocardial Ischemia10aRabbits10aRotation10aSodium Channel Blockers10aTetrodotoxin10aVentricular Fibrillation10aVideo Recording1 aMandapati, R1 aAsano, Y1 aBaxter, Bill1 aGray, R A1 aDavidenko, J M1 aJalife, J uhttp://www.ncbi.nlm.nih.gov/pubmed/977833605025nas a2200385 4500008004100000022001400041245011300055210006900168260001200237300001100249490000700260520391000267653002204177653001204199653002704211653002504238653002404263653001004287653002804297653004004325653002704365653002904392653001404421653001604435653001404451653001404465653001204479653002404491100001304515700001904528700001704547700001404564700001404578856004704592 1997 eng d a0735-109700aOptical mapping of drug-induced polymorphic arrhythmias and torsade de pointes in the isolated rabbit heart.0 aOptical mapping of druginduced polymorphic arrhythmias and torsa c03/1997 a831-420 v293 a

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 video imaging of electrical waves on the epicardial and endocardial surface of the Langendorff-perfused rabbit heart. 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.

10aAction Potentials10aAnimals10aAnti-Arrhythmia Agents10aArrhythmias, Cardiac10aElectrocardiography10aHeart10aHeart Conduction System10aImage Processing, Computer-Assisted10aModels, Cardiovascular10aOrgan Culture Techniques10aPerfusion10aPiperidines10aPyridines10aQuinidine10aRabbits10aTorsades de Pointes1 aAsano, Y1 aDavidenko, J M1 aBaxter, Bill1 aGray, R A1 aJalife, J uhttp://www.ncbi.nlm.nih.gov/pubmed/909153103382nas a2200349 4500008004100000022001400041245008900055210006900144260001200213300001100225490000700236520236800243653002202611653001502633653001202648653003502660653001602695653002402711653002602735653002102761653004002782653002702822653001002849653002502859653002002884100001702904700001902921700001402940700001702954700001402971856004702985 1997 eng d a0090-696400aTechnical features of a CCD video camera system to record cardiac fluorescence data.0 aTechnical features of a CCD video camera system to record cardia c07/1997 a713-250 v253 a

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.

10aAction Potentials10aAlgorithms10aAnimals10aBody Surface Potential Mapping10aCalibration10aComputer Simulation10aElectric Conductivity10aFluorescent Dyes10aImage Processing, Computer-Assisted10aModels, Cardiovascular10aSheep10aVentricular Function10aVideo Recording1 aBaxter, Bill1 aDavidenko, J M1 aLoew, L M1 aWuskell, J P1 aJalife, J uhttp://www.ncbi.nlm.nih.gov/pubmed/923698301811nas a2200373 4500008004100000022001400041245008700055210006900142260001200211300001200223490000700235520078300242653001201025653002601037653001501063653001801078653002401096653002501120653002101145653002201166653001001188653002701198653002701225653001501252653001001267653002001277100001201297700001701309700001901326700001701345700001401362700001401376856004701390 1996 eng d a0006-349500aVortex shedding as a precursor of turbulent electrical activity in cardiac muscle.0 aVortex shedding as a precursor of turbulent electrical activity  c03/1996 a1105-110 v703 a

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.

10aAnimals10aBiophysical Phenomena10aBiophysics10aCell Membrane10aComputer Simulation10aElectric Stimulation10aElectrochemistry10aElectrophysiology10aHeart10aModels, Cardiovascular10aMyocardial Contraction10aMyocardium10aSheep10aSodium Channels1 aCabo, C1 aPertsov, A V1 aDavidenko, J M1 aBaxter, Bill1 aGray, R A1 aJalife, J uhttp://www.ncbi.nlm.nih.gov/pubmed/878527003253nas a2200301 4500008004100000022001400041245009200055210006900147260001200216300001200228490000700240520238200247653001702629653001202646653003102658653002402689653001702713653002402730653002702754653001002781653002902791100001902820700001702839700001702856700001702873700001402890856004702904 1995 eng d a0009-733000aEffects of pacing on stationary reentrant activity. Theoretical and experimental study.0 aEffects of pacing on stationary reentrant activity Theoretical a c12/1995 a1166-790 v773 a

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.

10aAcceleration10aAnimals10aCardiac Pacing, Artificial10aComputer Simulation10aDeceleration10aElectrocardiography10aModels, Cardiovascular10aSheep10aTachycardia, Ventricular1 aDavidenko, J M1 aSalomonsz, R1 aPertsov, A V1 aBaxter, Bill1 aJalife, J uhttp://www.ncbi.nlm.nih.gov/pubmed/758623000781nas a2200289 4500008004100000022001400041245004000055210003900095260001200134300003200146490000800178653001200186653002400198653002400222653002100246653002700267653001200294653002900306100001400335700001400349700001600363700001700379700001200396700001900408700001700427856004700444 1995 eng d a0036-807500aMechanisms of cardiac fibrillation.0 aMechanisms of cardiac fibrillation c11/1995 a1222-3; author reply 1224-50 v27010aAnimals10aComputer Simulation10aElectrocardiography10aHeart Ventricles10aModels, Cardiovascular10aRabbits10aVentricular Fibrillation1 aGray, R A1 aJalife, J1 aPanfilov, A1 aBaxter, Bill1 aCabo, C1 aDavidenko, J M1 aPertsov, A V uhttp://www.ncbi.nlm.nih.gov/pubmed/750205504137nas a2200313 4500008004100000022001400041245013200055210006900187260001300256300001200269490000700281520321100288653001203499653002403511653001003535653004003545653002703585653001403612653001203626653002903638100001403667700001403681700001603695700001703711700001203728700001903740700001703759856004703776 1995 eng d a0009-732200aNonstationary vortexlike reentrant activity as a mechanism of polymorphic ventricular tachycardia in the isolated rabbit heart.0 aNonstationary vortexlike reentrant activity as a mechanism of po c05/1995  a2454-690 v913 a

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.

10aAnimals10aElectrocardiography10aHeart10aImage Processing, Computer-Assisted10aModels, Cardiovascular10aPerfusion10aRabbits10aTachycardia, Ventricular1 aGray, R A1 aJalife, J1 aPanfilov, A1 aBaxter, Bill1 aCabo, C1 aDavidenko, J M1 aPertsov, A V uhttp://www.ncbi.nlm.nih.gov/pubmed/772903303423nas a2200337 4500008004100000022001400041245009300055210006900148260001200217300001200229490000700241520247800248653001202726653002402738653002602762653001002788653001602798653002802814653001102842653002702853653002902880653001002909653002602919100001202945700001702957700001702974700001902991700001403010700001403024856004703038 1994 eng d a0009-733000aWave-front curvature as a cause of slow conduction and block in isolated cardiac muscle.0 aWavefront curvature as a cause of slow conduction and block in i c12/1994 a1014-280 v753 a

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.

10aAnimals10aComputer Simulation10aElectric Conductivity10aHeart10aHeart Block10aHeart Conduction System10aHumans10aModels, Cardiovascular10aMotion Pictures as Topic10aSheep10aStaining and Labeling1 aCabo, C1 aPertsov, A V1 aBaxter, Bill1 aDavidenko, J M1 aGray, R A1 aJalife, J uhttp://www.ncbi.nlm.nih.gov/pubmed/752510103364nas a2200289 4500008004100000022001400041245008700055210006900142260001300211300001100224490000700235520252500242653001202767653002402779653002702803653000902830653002202839653001002861653004802871653002402919100001702943700001902960700001702979700001702996700001403013856004703027 1993 eng d a0009-733000aSpiral waves of excitation underlie reentrant activity in isolated cardiac muscle.0 aSpiral waves of excitation underlie reentrant activity in isolat c03/1993  a631-500 v723 a

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'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.

10aAnimals10aComputer Simulation10aDisease Models, Animal10aDogs10aElectrophysiology10aSheep10aTachycardia, Atrioventricular Nodal Reentry10aTorsades de Pointes1 aPertsov, A V1 aDavidenko, J M1 aSalomonsz, R1 aBaxter, Bill1 aJalife, J uhttp://www.ncbi.nlm.nih.gov/pubmed/843198902348nas a2200313 4500008004100000022001400041245009000055210006900145260000900214300001100223490001300234520141700247653001201664653003101676653002101707653002801728653002401756653002501780653001601805653004101821653001601862653002501878100001901903700001701922700001701939700001701956700001401973856004701987 1992 eng d a0022-073600aSpatiotemporal irregularities of spiral wave activity in isolated ventricular muscle.0 aSpatiotemporal irregularities of spiral wave activity in isolate c1992 a113-220 v24 Suppl3 a

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.

10aAnimals10aCardiac Pacing, Artificial10aFluorescent Dyes10aHeart Conduction System10aMembrane Potentials10aOptics and Photonics10aPericardium10aSignal Processing, Computer-Assisted10aTachycardia10aVentricular Function1 aDavidenko, J M1 aPertsov, A V1 aSalomonsz, R1 aBaxter, Bill1 aJalife, J uhttp://www.ncbi.nlm.nih.gov/pubmed/155224001940nas a2200289 4500008004100000022001400041245008300055210006900138260001200207300001100219490000800230520115000238653001201388653000901400653001001409653001601419653002401435653002301459653002701482653001001509100001901519700001701538700001701555700001701572700001401589856004701603 1992 eng d a0028-083600aStationary and drifting spiral waves of excitation in isolated cardiac muscle.0 aStationary and drifting spiral waves of excitation in isolated c c01/1992 a349-510 v3553 a

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 're-entrant excitation' 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.

10aAnimals10aDogs10aHeart10aMathematics10aMembrane Potentials10aModels, Biological10aMyocardial Contraction10aSheep1 aDavidenko, J M1 aPertsov, A V1 aSalomonsz, R1 aBaxter, Bill1 aJalife, J uhttp://www.ncbi.nlm.nih.gov/pubmed/173124801417nas a2200229 4500008004100000022001400041245008500055210006900140260001200209300001100221490000700232520073000239653001200969653003400981653002001015653002501035653003201060653001801092100001701110700001301127856004701140 1989 eng d a0340-120000aHorizontal organization of orientation-sensitive cells in primate visual cortex.0 aHorizontal organization of orientationsensitive cells in primate c07/1989 a171-820 v613 a

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.

10aAnimals10aElectron Transport Complex IV10aForm Perception10aModels, Neurological10aPattern Recognition, Visual10aVisual Cortex1 aBaxter, Bill1 aDow, B M uhttp://www.ncbi.nlm.nih.gov/pubmed/2548628