Vestibular-dependent inter-stimulus interval effects on sound evoked potentials of central origin.

PubMed

Todd, N P M; Govender, S; Colebatch, J G

2016-11-01

Todd et al. (2014ab) have recently demonstrated the presence of vestibular-dependent contributions to auditory evoked potentials (AEPs) when passing through the vestibular threshold as determined by vestibular evoked myogenic potentials (VEMPs), including a particular deflection labeled as an N42/P52 prior to the long-latency AEPs N1 and P2. In this paper we report the results of an experiment to determine the effect of inter-stimulus interval (ISI) and regularity on potentials recorded above and below VEMP threshold. Five healthy, right-handed subjects were recruited and evoked potentials were recorded to binaurally presented sound stimulation, above and below vestibular threshold, at seven stimulus rates with ISIs of 212, 300, 424, 600, 848, 1200 and 1696 ms. The inner five intervals, i.e. 300, 424, 600, 848, 1200 ms, were presented twice in both regular and irregular conditions. ANOVA on the global field power (GFP) were conducted for each of four waves, N42, P52, N1 and P2 with factors of intensity, ISI and regularity. Both N42 and P52 waves showed significant ANOVA effects of intensity but no other main effects or interactions. In contrast both N1 and P2 showed additional effects of ISI, as well as intensity, and evidence of non-linear interactions between ISI and intensity. A source analysis was carried out consistent with prior work suggesting that when above vestibular threshold, in addition to bilateral superior temporal cortex, ocular, cerebellar and cingulate sources are recruited. Further statistical analysis of the source currents indicated that the origin of the interactions with intensity may be the ISI sensitivity of the vestibular-dependent sources. This in turn may reflect a specific vestibular preference for stimulus rates associated with locomotion, i.e. rates close to 2 Hz, or ISIs close to 500 ms, where saccular afferents show increased gain and the corresponding reflexes are most sensitive. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Subvocal articulatory rehearsal during verbal working memory in multiple sclerosis.

PubMed

Sweet, Lawrence H; Vanderhill, Susan D; Jerskey, Beth A; Gordon, Norman M; Paul, Robert H; Cohen, Ronald A

2010-10-01

This study was designed to examine verbal working memory (VWM) components among multiple sclerosis (MS) patients and determine the influence of information processing speed. Of two frequently studied VWM sub-components, subvocal rehearsal was expected to be more affected by MS than short-term memory buffering. Furthermore, worse subvocal rehearsal was predicted to be specifically related to slower cognitive processing. Fifteen MS patients were administered a neuropsychological battery assessing VWM, processing speed, mood, fatigue, and disability. Participants performed a 2-Back VWM task with modified nested conditions designed to increase subvocal rehearsal (via inter-stimulus interval) and short-term memory buffering demands (via phonological similarity). Performance during these 2-Back conditions did not significantly differ and both exhibited strong positive correlations with disability. However, only scores on the subvocal rehearsal 2-Back were significantly related to performance on the remaining test battery, including processing speed and depressive symptoms. Findings suggest that performance during increased subvocal rehearsal demands is specifically influenced by cognitive processing speed and depressive symptoms.

Selective suppression of the incorrect response implementation in choice behavior assessed by transcranial magnetic stimulation.

PubMed

Tandonnet, Christophe; Garry, Michael I; Summers, Jeffery J

2011-04-01

Selecting the adequate alternative in choice situations may involve an inhibition process. Here we assessed response implementation during the reaction time of a between-hand choice task with single- or paired-pulse (3 or 15 ms interstimulus intervals [ISIs]) transcranial magnetic stimulation of the motor cortex. The amplitude of the single-pulse motor evoked potential (MEP) initially increased for both hands. At around 130 ms, the single-pulse MEP kept increasing for the responding hand and decreased for the nonresponding hand. The paired-pulse MEP revealed a similar pattern for both ISIs with no effect on short intracortical inhibition and intracortical facilitation measures. The results suggest that the incorrect response implementation was selectively suppressed before execution of the correct response, preventing errors in choice context. The results favor models assuming that decision making involves an inhibition process. Copyright © 2010 Society for Psychophysiological Research.

Human cerebral potentials evoked by moving dynamic random dot stereograms.

PubMed

Herpers, M J; Caberg, H B; Mol, J M

1981-07-01

In 11 normal healthy human subjects an evoked potential was elicited by moving dynamic random dot stereograms. The random dots were generated by a minicomputer. An average of each of 8 EEG channels of the subjects tested was made. The maximum of the cerebral evoked potentials thus found was localized in the central and parietal region. No response earlier than 130--150 msec after the stimulus could be proved. The influence of fixation, the number of dots provided, an interocular interstimulus interval in the presentation of the dots, and lense accommodation movements on the evoked stereoptic potentials was investigated and discussed. An interocular interstimulus interval (left eye leading) in the presentation of the dots caused an increase in latency of the response much longer than the imposed interstimulus interval itself. It was shown that no accommodation was needed to perceive the depth impression, and to evoke the cerebral response with random dot stereograms. There are indications of an asymmetry between the two hemispheres in the handling of depth perception after 250 msec. The potential distribution of the evoked potentials strongly suggests that they are not generated in the occipital region.

Disruption of trace conditioning of the nictitating membrane response in rabbits by central cholinergic blockade.

PubMed

Kaneko, T; Thompson, R F

1997-05-01

Central muscarinic cholinergic involvement in classical conditioning of eyeblink responses was determined in trace and delay paradigms. Rabbits were trained on a trace procedure in which a 250-ms tone conditioned stimulus (CS) and a 100-ms air-puff unconditioned stimulus (UCS) were presented with a 500-ms trace interval. Each training session day consisted of ten tone alone, ten air-puff alone and 80 paired CS-UCS trials. Scopolamine hydrochloride at doses of 0.03 and 0.1 mg/0.5 ml per kg, s.c. dose-dependently disrupted acquisition of conditioned responses. Rabbits that were treated with scopolamine and failed to learn showed a gradual increase in conditioned responses during an additional training period with saline injections and no transfer from earlier training. Scopolamine methyl bromide, which does not appreciably cross the blood-brain barrier, showed no effects in the trace conditioning paradigm at a dose of 0.1 mg/kg, s.c., indicating central cholinergic blockade is responsible for the suppressive effect of scopolamine. Scopolamine hydrochloride at a dose of 0.1 mg/kg, s.c. did not block acquisition in the delay procedure with a 250-ms inter-stimulus interval, although the rate of acquisition was somewhat reduced by the drug. These data are the first to demonstrate that classical conditioning of the eyeblink response in the trace procedure is highly sensitive to central cholinergic deficits.

Perception of Scenes in Different Sensory Modalities: A Result of Modal Completion.

PubMed

Gruber, Ronald R; Block, Richard A

2017-01-01

Dynamic perception includes amodal and modal completion, along with apparent movement. It fills temporal gaps for single objects. In 2 experiments, using 6 stimulus presentation conditions involving 3 sensory modalities, participants experienced 8-10 sequential stimuli (200 ms each) with interstimulus intervals (ISIs) of 0.25-7.0 s. Experiments focused on spatiotemporal completion (walking), featural completion (object changing), auditory, completion (falling bomb), and haptic changes (insect crawling). After each trial, participants judged whether they experienced the process of "happening " or whether they simply knew that the process must have occurred. The phenomenon was frequency independent, being reported at short ISIs but not at long ISIs. The phenomenon involves dynamic modal completion and possibly also conceptual processes.

The ventral tegmental area modulates intracortical microstimulation (ICMS)-evoked M1 activity in a time-dependent manner.

PubMed

Kunori, Nobuo; Kajiwara, Riichi; Takashima, Ichiro

2016-03-11

Intracortical microstimulation (ICMS)-evoked neural activity combined with ventral tegmental area (VTA) stimulation was studied in rat primary motor cortex (M1). We used voltage-sensitive dye (VSD) imaging to analyze the spatiotemporal dynamics of M1 activity following VTA-M1 paired stimulation. VTA stimulation was preceded by M1 ICMS at inter-stimulus intervals (ISIs) of 15-350ms. VSD imaging showed an excitatory-inhibitory sequence of neural activity after composing VTA stimulus- and ICMS-induced M1 neural activity. To evaluate the net ICMS M1 response, the optical response to unpaired VTA stimulation was subtracted from the VTA-M1 paired response. This revealed that the net ICMS-evoked M1 neural activity was inhibited when the ISI was 30-50ms, but highly facilitated when the ISI was 100-350ms. These results suggest that VTA modulates M1 excitability in the order of tens to hundreds of milliseconds and might directly affect the motor command generation process in the M1. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Character Decomposition and Transposition Processes of Chinese Compound Words in Rapid Serial Visual Presentation.

PubMed

Cao, Hong-Wen; Yang, Ke-Yu; Yan, Hong-Mei

2017-01-01

Character order information is encoded at the initial stage of Chinese word processing, however, its time course remains underspecified. In this study, we assess the exact time course of the character decomposition and transposition processes of two-character Chinese compound words (canonical, transposed, or reversible words) compared with pseudowords using dual-target rapid serial visual presentation (RSVP) of stimuli appearing at 30 ms per character with no inter-stimulus interval. The results indicate that Chinese readers can identify words with character transpositions in rapid succession; however, a transposition cost is involved in identifying transposed words compared to canonical words. In RSVP reading, character order of words is more likely to be reversed during the period from 30 to 180 ms for canonical and reversible words, but the period from 30 to 240 ms for transposed words. Taken together, the findings demonstrate that the holistic representation of the base word is activated, however, the order of the two constituent characters is not strictly processed during the very early stage of visual word processing.

Reduced cortical inhibition in violent offenders: a study with transcranial magnetic stimulation.

PubMed

Philipp-Wiegmann, Florence; Rösler, Michael; Römer, Konstanze D; Schneider, Marc; Baumgart, Sibylle; Retz, Wolfgang

2011-01-01

Aggression and violent behaviour are often regarded as a threat to society. Therefore, understanding violent behaviour has high social relevance. We performed a study with transcranial magnetic stimulation on a sample of violent offenders in order to measure cortical inhibition in the motor neuron system that is part of the frontal cortex. To investigate intracortical inhibition and intracortical facilitation, we conducted paired-pulse stimulation according to the technique of Kujirai and his group (see Method). The investigation sample comprised 62 right-handers: 32 prisoners who had committed severe violent crimes and 30 controls with no history of violence. All subjects were male and matched for age. Using the paired-pulse paradigm with interstimulus intervals (ISI) of 1-15 ms, a reduced cortical inhibition (ISI: 3 ms) was found in the left cortex of violent offenders compared with control subjects. These findings corroborate the hypothesis of inhibition deficits and frontal cortex dysfunction in violent offenders when compared with non-violent control subjects. Copyright © 2011 S. Karger AG, Basel.

Motor cortical hyperexcitability in idiopathic scoliosis: could focal dystonia be a subclinical etiological factor?

PubMed Central

Tormos, José María; Barrios, Carlos; Pascual-Leone, Alvaro

2009-01-01

The aetiology of idiopathic scoliosis (IS) remains unknown; however, there is a growing body of evidence suggesting that the spine deformity could be the expression of a subclinical nervous system disorder. A defective sensory input or an anomalous sensorimotor integration may lead to an abnormal postural tone and therefore the development of a spine deformity. Inhibition of the motor cortico-cortical excitability is abnormal in dystonia. Therefore, the study of cortico-cortical inhibition may shed some insight into the dystonia hypothesis regarding the pathophysiology of IS. Paired pulse transcranial magnetic stimulation was used to study cortico-cortical inhibition and facilitation in nine adolescents with IS, five teenagers with congenital scoliosis (CS) and eight healthy age-matched controls. The effect of a previous conditioning stimulus (80% intensity of resting motor threshold) on the amplitude of the motor-evoked potential induced by the test stimulus (120% of resting motor threshold) was examined at various interstimulus intervals (ISIs) in both abductor pollicis brevis muscles. The results of healthy adolescents and those with CS showed a marked inhibitory effect of the conditioning stimulus on the response to the test stimulus at interstimulus intervals shorter than 6 ms. These findings do not differ from those reported for normal adults. However, children with IS revealed an abnormally reduced cortico-cortical inhibition at the short ISIs. Cortico-cortical inhibition was practically normal on the side of the scoliotic convexity while it was significantly reduced on the side of the scoliotic concavity. In conclusion, these findings support the hypothesis that a dystonic dysfunction underlies in IS. Asymmetrical cortical hyperexcitability may play an important role in the pathogenesis of IS and represents an objective neurophysiological finding that could be used clinically. PMID:20033462

Functional plasticity in the interposito-thalamo-cortical pathway during conditioning. Role of the interstimulus interval.

PubMed

Pananceau, M; Rispal-Padel, L

2000-06-01

In classic conditioning, the interstimulus interval (ISI) between the conditioned (CS) and unconditioned (US) stimulus is a critical parameter. The aim of the present experiment was to assess whether, during conditioning, modification of the CS-US interval could reliably produce changes in the functional properties of the interposito-thalamo-cortical pathways (INTCps). Five cats were prepared for chronic stimulation and recording from several brain regions along this pathway in awake animals. The CS was a weak electric shock applied on the interposed nucleus of the cerebellum in sites that initially elicited forelimb flexion (i.e., alpha motor responses) in three cats, and equal proportions of flexor and extensor responses in two cats. The US was an electric shock applied on the skin that elicited forelimb flexions. The motor and neurobiological effects of synchronous CS-US were compared with pairings in which the CS was applied 100 ms before US. Simultaneous and sequential application of CS and US produced different behavioral outcomes and resulted in different neural processes in the interposito-thalamo-cortical pathways (INTCps). The simultaneous presentation of stimuli only produced a small increase in excitability spreading to all the body representational zones of the primary motor cortex and a weak increase in the amplitude of the alpha motor response. In contrast, the sequential application led to a profound modification of the interposed output to neurons in the forelimb representation of the motor cortex. These robust neuronal correlates of conditioning were accompanied by a large facilitation of the alpha motor response (alpha-MR). There were also changes in the direction of misdirected alpha responses and an emergence of functionally appropriate, long-latency withdrawal forelimb flexion. These data revealed that, during conditioning, plastic changes within the thalamocortical connections are selectively induced by sequential information from central and peripheral afferents. This sequence significantly contributed to neural processes that are responsible for the acquisition, expression, and extinction of anticipatory flexion responses.

Corticospinal activation confounds cerebellar effects of posterior fossa stimuli.

PubMed

Fisher, Karen M; Lai, H Ming; Baker, Mark R; Baker, Stuart N

2009-12-01

To investigate the efficacy of magnetic stimulation over the posterior fossa (PF) as a non-invasive assessment of cerebellar function in man. We replicated a previously reported conditioning-test paradigm in 11 healthy subjects. Transcranial magnetic stimulation (TMS) at varying intensities was applied to the PF and motor cortex with a 3, 5 or 7 ms interstimulus interval (ISI), chosen randomly for each trial. Surface electromyogram (EMG) activity was recorded from two intrinsic hand muscles and two forearm muscles. Responses were averaged and rectified, and MEP amplitudes were compared to assess whether suppression of the motor output occurred as a result of the PF conditioning pulse. Cortical MEPs were suppressed following conditioning-test ISIs of 5 or 7 ms. No suppression occurred with an ISI of 3 ms. PF stimuli alone also produced EMG responses, suggesting direct activation of the corticospinal tract (CST). CST collaterals are known to contact cortical inhibitory interneurones; antidromic CST activation could therefore contribute to the observed suppression of cortical MEPs. PF stimulation probably activates multiple pathways; even at low intensities it should not be regarded as a selective assessment of cerebellar function unless stringent controls can confirm the absence of confounding activity in other pathways.

Transcranial magnetic and electrical stimulation compared: does TES activate intracortical neuronal circuits?

PubMed

Brocke, J; Irlbacher, K; Hauptmann, B; Voss, M; Brandt, S A

2005-12-01

To determine whether, and under which conditions, transcranial electrical stimulation (TES) and transcranial magnetic stimulation (TMS) can activate similar neuronal structures of the human motor cortex, as indicated by electromyographic recordings. Focal TMS was performed on three subjects inducing a postero-anterior directed current (p-a), TES with postero-anteriorly (p-a) and latero-medially (l-m) oriented electrodes. We analyzed the onset latencies and amplitudes (single-pulse) and intracortical inhibition and excitation (paired-pulse). TMS p-a and TES p-a produced muscle responses with the same onset latency, while TES l-m led to 1.4-1.9 ms shorter latencies. Paired-pulse TMS p-a and TES p-a induced inhibition at short inter-stimulus intervals (ISI) (maximum: 2-3 ms) and facilitation at longer ISIs (maximum: 10 ms). No inhibition but a strong facilitation was obtained from paired-pulse TES l-m (ISIs 1-5 ms). Our findings support the hypothesis, that current direction is the most relevant factor in determining the mode of activation for both TMS and TES: TMS p-a and TES p-a are likely to activate the corticospinal neurons indirectly. In contrast, TES l-m may preferentially activate the corticospinal fibres directly, distant of the neuronal body. TES is a suitable tool to induce intracortical inhibition and excitation.

Does temporal contiguity moderate contingency learning in a speeded performance task?

PubMed

Schmidt, James R; De Houwer, Jan

2012-01-01

In four experiments, we varied the time between the onset of distracting nonwords and target colour words in a word-word version of the colour-word contingency learning paradigm. Contingencies were created by pairing a distractor nonword more often with one target colour word than with other colour words. A contingency effect corresponds to faster responses to the target colour word on high-contingency trials (i.e., distractor nonword followed by the target colour word with which it appears most often) than on low-contingency trials (i.e., distractor nonword followed by a target colour word with which it appears only occasionally). Roughly equivalent-sized contingency effects were found at stimulus-onset asynchronies (SOAs) of 50, 250, and 450 ms in Experiment 1, and 50, 500, and 1,000 ms in Experiment 2. In Experiment 3, a contingency effect was observed at SOAs of -50, -200, and -350 ms. In Experiment 4, interstimulus interval (ISI) was varied along with SOA, and learning was equivalent for 200-, 700-, and 1,200-ms SOAs. Together, these experiments suggest that the distracting stimulus does not need to be presented in close temporal contiguity with the response to induce learning. Relations to past research on causal judgement and implications for further contingency learning research are discussed.

Age-related Differences in Pre- and Post-synaptic Motor Cortex Inhibition are Task Dependent.

PubMed

Opie, George M; Ridding, Michael C; Semmler, John G

2015-01-01

Previous research has shown age-related differences in short- (SICI) and long-interval intracortical inhibition (LICI) in both resting and active hand muscles, suggesting that healthy ageing influences post-synaptic motor cortex inhibition. However, it is not known how the ageing process effects the pre-synaptic interaction of SICI by LICI, and how these pre- and post-synaptic intracortical inhibitory circuits are modulated by the performance of different motor tasks in older adults. To examine age-related differences in pre- and post-synaptic motor cortex inhibition at rest, and during index finger abduction and precision grip. In 13 young (22.3 ± 3.8 years) and 15 old (73.7 ± 4.0 years) adults, paired-pulse transcranial magnetic stimulation (TMS) was used to measure SICI (2 ms inter-stimulus interval; ISI) and LICI (100 and 150 ms ISI), whereas triple-pulse TMS was used to investigate SICI when primed by LICI. We found no age-related difference in SICI at rest or during index finger abduction, but significantly greater SICI in older subjects during precision grip. Older adults showed reduced LICI in resting muscle (at an ISI of 150 ms), with no age-related differences in LICI during either task. When SICI was primed by LICI, disinhibition of motor cortex was reduced in older adults at rest (100 ms ISI) and during index finger abduction (150 ms ISI), but not during precision grip. Our results support age-related differences in pre- and post-synaptic motor cortex inhibition, which may contribute to impaired hand function during task performance in older adults. Copyright © 2015 Elsevier Inc. All rights reserved.

Selective attention and the auditory vertex potential. 1: Effects of stimulus delivery rate

NASA Technical Reports Server (NTRS)

Schwent, V. L.; Hillyard, S. A.; Galambos, R.

1975-01-01

Enhancement of the auditory vertex potentials with selective attention to dichotically presented tone pips was found to be critically sensitive to the range of inter-stimulus intervals in use. Only at the shortest intervals was a clear-cut enhancement of the latency component to stimuli observed for the attended ear.

Cortical Plasticity Induction by Pairing Subthalamic Nucleus Deep-Brain Stimulation and Primary Motor Cortical Transcranial Magnetic Stimulation in Parkinson's Disease.

PubMed

Udupa, Kaviraja; Bahl, Nina; Ni, Zhen; Gunraj, Carolyn; Mazzella, Filomena; Moro, Elena; Hodaie, Mojgan; Lozano, Andres M; Lang, Anthony E; Chen, Robert

2016-01-13

Noninvasive brain stimulation studies have shown abnormal motor cortical plasticity in Parkinson's disease (PD). These studies used peripheral nerve stimulation paired with transcranial magnetic stimulation (TMS) to primary motor cortex (M1) at specific intervals to induce plasticity. Induction of cortical plasticity through stimulation of the basal ganglia (BG)-M1 connections has not been studied. In the present study, we used a novel technique of plasticity induction by repeated pairing of deep-brain stimulation (DBS) of the BG with M1 stimulation using TMS. We hypothesize that repeated pairing of subthalamic nucleus (STN)-DBS and M1-TMS at specific time intervals will lead to plasticity in the M1. Ten PD human patients with STN-DBS were studied in the on-medication state with DBS set to 3 Hz. The interstimulus intervals (ISIs) between STN-DBS and TMS that produced cortical facilitation were determined individually for each patient. Three plasticity induction conditions with repeated pairings (180 times) at specific ISIs (∼ 3 and ∼ 23 ms) that produced cortical facilitation and a control ISI of 167 ms were tested in random order. Repeated pairing of STN-DBS and M1-TMS at short (∼ 3 ms) and medium (∼ 23 ms) latencies increased M1 excitability that lasted for at least 45 min, whereas the control condition (fixed ISI of 167 ms) had no effect. There were no specific changes in motor thresholds, intracortical circuits, or recruitment curves. Our results indicate that paired-associative cortical plasticity can be induced by repeated STN and M1 stimulation at specific intervals. These results show that STN-DBS can modulate cortical plasticity. We introduced a new experimental paradigm to test the hypothesis that pairing subthalamic nucleus deep-brain stimulation (STN-DBS) with motor cortical transcranial magnetic stimulation (M1-TMS) at specific times can induce cortical plasticity in patients with Parkinson's disease (PD). We found that repeated pairing of STN-DBS with TMS at short (∼ 3 ms) and medium (∼ 23 ms) intervals increased cortical excitability that lasted for up to 45 min, whereas the control condition (fixed latency of 167 ms) had no effects on cortical excitability. This is the first demonstration of associative plasticity in the STN-M1 circuits in PD patients using this novel technique. The potential therapeutic effects of combining DBS and noninvasive cortical stimulation should be investigated further. Copyright © 2016 the authors 0270-6474/16/360397-09$15.00/0.

Influence of waveform and current direction on short-interval intracortical facilitation: a paired-pulse TMS study.

PubMed

Delvendahl, Igor; Lindemann, Hannes; Jung, Nikolai H; Pechmann, Astrid; Siebner, Hartwig R; Mall, Volker

2014-01-01

Transcranial magnetic stimulation (TMS) of the human primary motor hand area (M1-HAND) can produce multiple descending volleys in fast-conducting corticospinal neurons, especially so-called indirect waves (I-waves) resulting from trans-synaptic excitation. Facilitatory interaction between these I-waves can be studied non-invasively using a paired-pulse paradigm referred to as short-interval intracortical facilitation (SICF). We examined whether SICF depends on waveform and current direction of the TMS pulses. In young healthy volunteers, we applied single- and paired-pulse TMS to M1-HAND. We probed SICF by pairs of monophasic or half-sine pulses at suprathreshold stimulation intensity and inter-stimulus intervals (ISIs) between 1.0 and 5.0 ms. For monophasic paired-pulse stimulation, both pulses had either a posterior-anterior (PA) or anterior-posterior (AP) current direction (AP-AP or PA-PA), whereas current direction was reversed between first and second pulse for half-sine paired-pulse stimulation (PA-AP and AP-PA). Monophasic AP-AP stimulation resulted in stronger early SICF at 1.4 ms relative to late SICF at 2.8 and 4.4 ms, whereas monophasic PA-PA stimulation produced SICF of comparable size at all three peaks. With half-sine stimulation the third SICF peak was reduced for PA-AP current orientation compared with AP-PA. SICF elicited using monophasic as well as half-sine pulses is affected by current direction at clearly suprathreshold intensities. The impact of current orientation is stronger for monophasic compared with half-sine pulses. The direction-specific effect of paired-pulse TMS on the strength of early versus late SICF shows that different cortical circuits mediate early and late SICF. Copyright © 2014 Elsevier Inc. All rights reserved.

Strategy difficulty effects in young and older adults' episodic memory are modulated by inter-stimulus intervals and executive control processes.

PubMed

Burger, Lucile; Uittenhove, Kim; Lemaire, Patrick; Taconnat, Laurence

2017-04-01

Efficient execution of strategies is crucial to memory performance and to age-related differences in this performance. Relative strategy complexity influences memory performance and aging effects on memory. Here, we aimed to further our understanding of the effects of relative strategy complexity by looking at the role of cognitive control functions and the time-course of the effects of relative strategy complexity. Thus, we manipulated inter-stimulus intervals (ISI) and assessed executive functions. Results showed that (a) performance as a function of the relative strategy difficulty of the current and previous trial was modulated by ISI, (b) these effects were modulated by inhibition capacities, and (c) significant age differences were found in the way ISI modulates relative strategy difficulty. These findings have important implications for understanding the relationships between aging, executive control, and strategy execution in episodic memory. Copyright © 2017 Elsevier B.V. All rights reserved.

Influence of cognitive style and interstimulus interval on the hemispheric processing of tactile stimuli.

PubMed

Minagawa, N; Kashu, K

1989-06-01

16 adult subjects performed a tactile recognition task. According to our 1984 study, half of the subjects were classified as having a left hemispheric preference for the processing of visual stimuli, while the other half were classified as having a right hemispheric preference for the processing of visual stimuli. The present task was conducted according to the S1-S2 matching paradigm. The standard stimulus was a readily recognizable object and was presented tactually to either the left or right hand of each subject. The comparison stimulus was an object-picture and was presented visually by slide in a tachistoscope. The interstimulus interval was .05 sec. or 2.5 sec. Analysis indicated that the left-preference group showed right-hand superiority, and the right-preference group showed left-hand superiority. The notion of individual hemisphericity was supported in tactile processing.

An empirical comparison of SPM preprocessing parameters to the analysis of fMRI data.

PubMed

Della-Maggiore, Valeria; Chau, Wilkin; Peres-Neto, Pedro R; McIntosh, Anthony R

2002-09-01

We present the results from two sets of Monte Carlo simulations aimed at evaluating the robustness of some preprocessing parameters of SPM99 for the analysis of functional magnetic resonance imaging (fMRI). Statistical robustness was estimated by implementing parametric and nonparametric simulation approaches based on the images obtained from an event-related fMRI experiment. Simulated datasets were tested for combinations of the following parameters: basis function, global scaling, low-pass filter, high-pass filter and autoregressive modeling of serial autocorrelation. Based on single-subject SPM analysis, we derived the following conclusions that may serve as a guide for initial analysis of fMRI data using SPM99: (1) The canonical hemodynamic response function is a more reliable basis function to model the fMRI time series than HRF with time derivative. (2) Global scaling should be avoided since it may significantly decrease the power depending on the experimental design. (3) The use of a high-pass filter may be beneficial for event-related designs with fixed interstimulus intervals. (4) When dealing with fMRI time series with short interstimulus intervals (<8 s), the use of first-order autoregressive model is recommended over a low-pass filter (HRF) because it reduces the risk of inferential bias while providing a relatively good power. For datasets with interstimulus intervals longer than 8 seconds, temporal smoothing is not recommended since it decreases power. While the generalizability of our results may be limited, the methods we employed can be easily implemented by other scientists to determine the best parameter combination to analyze their data.

Characteristics of temporal summation of second pain sensations elicited by brief contact of glabrous skin by a preheated thermode.

PubMed

Vierck, C J; Cannon, R L; Fry, G; Maixner, W; Whitsel, B L

1997-08-01

Temporal summation of sensory intensity was investigated in normal subjects using novel methods of thermal stimulation. A Peltier thermode was heated and then applied in a series of brief (700 ms) contacts to different sites on the glabrous skin of either hand. Repetitive contacts on the thenar or hypothenar eminence, at interstimulus intervals (ISIs) of 3 s, progressively increased the perceived intensity of a thermal sensation that followed each contact at an onset latency > 2 s. Temporal summation of these delayed (late) sensations was proportional to thermode temperature over a range of 45-53 degrees C, progressing from a nonpainful level (warmth) to painful sensations that could be rated as very strong after 10 contacts. Short-latency pain sensations rarely were evoked by such stimuli and never attained levels substantially above pain threshold for the sequences and temperatures presented. Temporal summation produced by brief contacts was greater in rate and amount than increases in sensory intensity resulting from repetitive ramping to the same temperature by a thermode in constant contact with the skin. Variation of the interval between contacts revealed a dependence of sensory intensity on interstimulus interval that is similar to physiological demonstrations of windup, where increasing frequencies of spike train activity are evoked from spinal neurons by repetitive activation of unmyelinated nociceptors. However, substantial summation at repetition rates of > or = 0.33 Hz was observed for temperatures that produced only late sensations of warmth when presented at frequencies < 0.16 Hz. Measurements of subepidermal skin temperature from anesthetized monkeys revealed different time courses for storage and dissipation of heat by the skin than for temporal summation and decay of sensory intensity for the human subjects. For example, negligible heat loss occurred during a 6-s interval between two trials of 10 contacts at 0.33 Hz, but ratings of sensory magnitude decreased from very strong levels of pain to sensations of warmth during the same interval. Evidence that temporal summation of sensory intensity during series of brief contacts relies on central integration, rather than a sensitization of peripheral receptors, was obtained using two approaches. In the first, a moderate degree of temporal summation was observed during alternating stimulation of adjacent but nonoverlapping skin sites at 0.33 Hz. Second, temporal summation was significantly attenuated by prior administration of dextromethorphan, a N-methyl-D-aspartate receptor antagonist.

The effect of 1/f fluctuation in inter-stimulus intervals on auditory evoked mismatch field.

PubMed

Harada, Nobuyoshi; Masuda, Tadashi; Endo, Hiroshi; Nakamura, Yukihiro; Takeda, Tsunehiro; Tonoike, Mitsuo

2005-05-13

This study focused on the effect of regularity of environmental stimuli on the informational order extracting function of human brain. The regularity of environmental stimuli can be described with the exponent n of the fluctuation 1/f(n). We studied the effect of the exponent of the fluctuation in the inter-stimulus interval (ISI) on the elicitation of auditory evoked mismatch fields (MMF) with two sounds with alternating frequency. ISI times were given by three types of fluctuation, 1/f(0), 1/f(1), 1/f(2), and with a fixed interval (1/f(infinity)). The root mean square (RMS) value of the MMF increased significantly (F(3/9)=4.95, p=0.027) with increases in the exponent of the fluctuation. Increments in the regularity of the fluctuation provoked enhancement of the MMF, which reflected the production of a memory trace, based on the anticipation of the stimulus timing. The gradient of the curve, indicating the ratio of increments between the MMF and the exponent of fluctuation, can express a subject's capability to extract regularity from fluctuating stimuli.

Central nervous system abnormalities in vaginismus.

PubMed

Frasson, Emma; Graziottin, Alessandra; Priori, Alberto; Dall'ora, Elisa; Didonè, Giuseppe; Garbin, Emilio Luigi; Vicentini, Silvana; Bertolasi, Laura

2009-01-01

To investigate possible altered CNS excitability in vaginismus. In 10 patients with primary idiopathic lifelong vaginismus, 10 with vulvar vestibulitis syndrome accompanied by vaginismus and healthy controls we recorded EMG activity from the levator ani (LA) and external anal sphincter (EAS) muscles and tested bulbocavernosus reflex (BCR). Pudendal-nerve somatosensory evoked potentials (SEPs) were tested after a single stimulus. Pudendal-nerve SEP recovery functions were assessed using a paired conditioning-test paradigm at interstimulus intervals (ISIs) of 5, 20 and 40ms. EMG in patients showed muscular hyperactivity at rest and reduced inhibition during straining. The BCR polysynaptic R2 had larger amplitude (p<0.01) and longer duration (p<0.01) in patients from both groups than in controls. In controls, paired-pulse SEPs were suppressed at the 5ms ISI for N35-P40 (p<0.05) and P40-N50 ms (p<0.001) and facilitated at the 20ms ISI for N35-P40 (p<0.05) and P40-N50 (p<0.05). No significant differences were found in the paired-pulse N35-P40 in patients and controls but the cortical P40-N50 at 20 ISI was facilitated in patients (p<0.05). EMG activity is enhanced and the cortical SEP recovery cycle and BCR are hyperexcitable in vaginismus. The neurophysiological abnormalities in patients with vaginismus indicate concomitant CNS changes in this disorder.

Development of auditory sensory memory from 2 to 6 years: an MMN study.

PubMed

Glass, Elisabeth; Sachse, Steffi; von Suchodoletz, Waldemar

2008-08-01

Short-term storage of auditory information is thought to be a precondition for cognitive development, and deficits in short-term memory are believed to underlie learning disabilities and specific language disorders. We examined the development of the duration of auditory sensory memory in normally developing children between the ages of 2 and 6 years. To probe the lifetime of auditory sensory memory we elicited the mismatch negativity (MMN), a component of the late auditory evoked potential, with tone stimuli of two different frequencies presented with various interstimulus intervals between 500 and 5,000 ms. Our findings suggest that memory traces for tone characteristics have a duration of 1-2 s in 2- and 3-year-old children, more than 2 s in 4-year-olds and 3-5 s in 6-year-olds. The results provide insights into the maturational processes involved in auditory sensory memory during the sensitive period of cognitive development.

Adaptation to visual or auditory time intervals modulates the perception of visual apparent motion

PubMed Central

Zhang, Huihui; Chen, Lihan; Zhou, Xiaolin

2012-01-01

It is debated whether sub-second timing is subserved by a centralized mechanism or by the intrinsic properties of task-related neural activity in specific modalities (Ivry and Schlerf, 2008). By using a temporal adaptation task, we investigated whether adapting to different time intervals conveyed through stimuli in different modalities (i.e., frames of a visual Ternus display, visual blinking discs, or auditory beeps) would affect the subsequent implicit perception of visual timing, i.e., inter-stimulus interval (ISI) between two frames in a Ternus display. The Ternus display can induce two percepts of apparent motion (AM), depending on the ISI between the two frames: “element motion” for short ISIs, in which the endmost disc is seen as moving back and forth while the middle disc at the overlapping or central position remains stationary; “group motion” for longer ISIs, in which both discs appear to move in a manner of lateral displacement as a whole. In Experiment 1, participants adapted to either the typical “element motion” (ISI = 50 ms) or the typical “group motion” (ISI = 200 ms). In Experiments 2 and 3, participants adapted to a time interval of 50 or 200 ms through observing a series of two paired blinking discs at the center of the screen (Experiment 2) or hearing a sequence of two paired beeps (with pitch 1000 Hz). In Experiment 4, participants adapted to sequences of paired beeps with either low pitches (500 Hz) or high pitches (5000 Hz). After adaptation in each trial, participants were presented with a Ternus probe in which the ISI between the two frames was equal to the transitional threshold of the two types of motions, as determined by a pretest. Results showed that adapting to the short time interval in all the situations led to more reports of “group motion” in the subsequent Ternus probes; adapting to the long time interval, however, caused no aftereffect for visual adaptation but significantly more reports of group motion for auditory adaptation. These findings, suggesting amodal representation for sub-second timing across modalities, are interpreted in the framework of temporal pacemaker model. PMID:23133408

The Duration of Auditory Sensory Memory for Vowel Processing: Neurophysiological and Behavioral Measures.

PubMed

Yu, Yan H; Shafer, Valerie L; Sussman, Elyse S

2018-01-01

Speech perception behavioral research suggests that rates of sensory memory decay are dependent on stimulus properties at more than one level (e.g., acoustic level, phonemic level). The neurophysiology of sensory memory decay rate has rarely been examined in the context of speech processing. In a lexical tone study, we showed that long-term memory representation of lexical tone slows the decay rate of sensory memory for these tones. Here, we tested the hypothesis that long-term memory representation of vowels slows the rate of auditory sensory memory decay in a similar way to that of lexical tone. Event-related potential (ERP) responses were recorded to Mandarin non-words contrasting the vowels /i/ vs. /u/ and /y/ vs. /u/ from first-language (L1) Mandarin and L1 American English participants under short and long interstimulus interval (ISI) conditions (short ISI: an average of 575 ms, long ISI: an average of 2675 ms). Results revealed poorer discrimination of the vowel contrasts for English listeners than Mandarin listeners, but with different patterns for behavioral perception and neural discrimination. As predicted, English listeners showed the poorest discrimination and identification for the vowel contrast /y/ vs. /u/, and poorer performance in the long ISI condition. In contrast to Yu et al. (2017), however, we found no effect of ISI reflected in the neural responses, specifically the mismatch negativity (MMN), P3a and late negativity ERP amplitudes. We did see a language group effect, with Mandarin listeners generally showing larger MMN and English listeners showing larger P3a. The behavioral results revealed that native language experience plays a role in echoic sensory memory trace maintenance, but the failure to find an effect of ISI on the ERP results suggests that vowel and lexical tone memory traces decay at different rates. Highlights : We examined the interaction between auditory sensory memory decay and language experience. We compared MMN, P3a, LN and behavioral responses in short vs. long interstimulus intervals. We found that different from lexical tone contrast, MMN, P3a, and LN changes to vowel contrasts are not influenced by lengthening the ISI to 2.6 s. We also found that the English listeners discriminated the non-native vowel contrast with lower accuracy under the long ISI condition.

Using a Sequence of Earcons to Monitor Multiple Simulated Patients.

PubMed

Hickling, Anna; Brecknell, Birgit; Loeb, Robert G; Sanderson, Penelope

2017-03-01

The aim of this study was to determine whether a sequence of earcons can effectively convey the status of multiple processes, such as the status of multiple patients in a clinical setting. Clinicians often monitor multiple patients. An auditory display that intermittently conveys the status of multiple patients may help. Nonclinician participants listened to sequences of 500-ms earcons that each represented the heart rate (HR) and oxygen saturation (SpO 2 ) levels of a different simulated patient. In each sequence, one, two, or three patients had an abnormal level of HR and/or SpO 2 . In Experiment 1, participants reported which of nine patients in a sequence were abnormal. In Experiment 2, participants identified the vital signs of one, two, or three abnormal patients in sequences of one, five, or nine patients, where the interstimulus interval (ISI) between earcons was 150 ms. Experiment 3 used the five-sequence condition of Experiment 2, but the ISI was either 150 ms or 800 ms. Participants reported which patient(s) were abnormal with median 95% accuracy. Identification accuracy for vital signs decreased as the number of abnormal patients increased from one to three, p < .001, but accuracy was unaffected by number of patients in a sequence. Overall, identification accuracy was significantly higher with an ISI of 800 ms (89%) compared with an ISI of 150 ms (83%), p < .001. A multiple-patient display can be created by cycling through earcons that represent individual patients. The principles underlying the multiple-patient display can be extended to other vital signs, designs, and domains.

Analysis and Synthesis of Adaptive Neural Elements and Assemblies

DTIC Science & Technology

1988-09-22

neuromodulation , has been identified in sensory neurons mediating the gill and tail withdrawal reflexes of Aplysia (Hawkins et al., 1983, Walters and... neuromodulation and predicted a characteristic interstimulus interval (ISI) curve (Gingrich and Byrne, 1987). At the subcellular level, the model’s ISI

Change detection and change blindness in pigeons (Columba livia).

PubMed

Herbranson, Walter T; Trinh, Yvan T; Xi, Patricia M; Arand, Mark P; Barker, Michael S K; Pratt, Theodore H

2014-05-01

Change blindness is a phenomenon in which even obvious details in a visual scene change without being noticed. Although change blindness has been studied extensively in humans, we do not yet know if it is a phenomenon that also occurs in other animals. Thus, investigation of change blindness in a nonhuman species may prove to be valuable by beginning to provide some insight into its ultimate causes. Pigeons learned a change detection task in which pecks to the location of a change in a sequence of stimulus displays were reinforced. They were worse at detecting changes if the stimulus displays were separated by a brief interstimulus interval, during which the display was blank, and this primary result matches the general pattern seen in previous studies of change blindness in humans. A second experiment attempted to identify specific stimulus characteristics that most reliably produced a failure to detect changes. Change detection was more difficult when interstimulus intervals were longer and when the change was iterated fewer times. ©2014 APA, all rights reserved.

Masked Priming Effects in Aphasia: Evidence for Altered Automatic Spreading Activation

PubMed Central

Silkes, JoAnn P.; Rogers, Margaret A.

2015-01-01

Purpose Previous research has suggested that impairments of automatic spreading activation may underlie some aphasic language deficits. This study further investigated the status of automatic spreading activation in individuals with aphasia as compared with typical adults. Method Participants were 21 individuals with aphasia (12 fluent, 9 non-fluent) and 31 typical adults. Reaction time data were collected on a lexical decision task with masked repetition primes, assessed at 11 different interstimulus intervals (ISIs). Masked primes were used to assess automatic spreading activation without the confound of conscious processing. The various ISIs were used to assess the time to onset, and duration, of priming effects. Results The control group showed maximal priming in the 200 ms ISI condition, with significant priming at a range of ISIs surrounding that peak. Participants with both fluent and non-fluent aphasia showed maximal priming effects in the 250 ms ISI condition, and primed across a smaller range of ISIs than the control group. Conclusions Results suggest that individuals with aphasia have slowed automatic spreading activation, and impaired maintenance of activation over time, regardless of fluency classification. These findings have implications for understanding aphasic language impairment and for development of aphasia treatments designed directly address automatic language processes. PMID:22411281

Masked priming effects in aphasia: evidence of altered automatic spreading activation.

PubMed

Silkes, JoAnn P; Rogers, Margaret A

2012-12-01

Previous research has suggested that impairments of automatic spreading activation may underlie some aphasic language deficits. The current study further investigated the status of automatic spreading activation in individuals with aphasia as compared with typical adults. Participants were 21 individuals with aphasia (12 fluent, 9 nonfluent) and 31 typical adults. Reaction time data were collected on a lexical decision task with masked repetition primes, assessed at 11 different interstimulus intervals (ISIs). Masked primes were used to assess automatic spreading activation without the confound of conscious processing. The various ISIs were used to assess the time to onset and duration of priming effects. The control group showed maximal priming in the 200-ms ISI condition, with significant priming at a range of ISIs surrounding that peak. Participants with both fluent and nonfluent aphasia showed maximal priming effects in the 250-ms ISI condition and primed across a smaller range of ISIs than did the control group. Results suggest that individuals with aphasia have slowed automatic spreading activation and impaired maintenance of activation over time, regardless of fluency classification. These findings have implications for understanding aphasic language impairment and for development of aphasia treatments designed to directly address automatic language processes.

Atypical auditory refractory periods in children from lower socio-economic status backgrounds: ERP evidence for a role of selective attention.

PubMed

Stevens, Courtney; Paulsen, David; Yasen, Alia; Neville, Helen

2015-02-01

Previous neuroimaging studies indicate that lower socio-economic status (SES) is associated with reduced effects of selective attention on auditory processing. Here, we investigated whether lower SES is also associated with differences in a stimulus-driven aspect of auditory processing: the neural refractory period, or reduced amplitude response at faster rates of stimulus presentation. Thirty-two children aged 3 to 8 years participated, and were divided into two SES groups based on maternal education. Event-related brain potentials were recorded to probe stimuli presented at interstimulus intervals (ISIs) of 200, 500, or 1000 ms. These probes were superimposed on story narratives when attended and ignored, permitting a simultaneous experimental manipulation of selective attention. Results indicated that group differences in refractory periods differed as a function of attention condition. Children from higher SES backgrounds showed full neural recovery by 500 ms for attended stimuli, but required at least 1000 ms for unattended stimuli. In contrast, children from lower SES backgrounds showed similar refractory effects to attended and unattended stimuli, with full neural recovery by 500 ms. Thus, in higher SES children only, one functional consequence of selective attention is attenuation of the response to unattended stimuli, particularly at rapid ISIs, altering basic properties of the auditory refractory period. Together, these data indicate that differences in selective attention impact basic aspects of auditory processing in children from lower SES backgrounds. Copyright © 2013 Elsevier B.V. All rights reserved.

The influence of iris color on the pupillary light reflex.

PubMed

Bergamin, O; Schoetzau, A; Sugimoto, K; Zulauf, M

1998-08-01

This study was carried out to investigate the effect of iris color on the pupillary light reflex (PLR) in normal healthy volunteers. Pupil perimetry was performed on 50 healthy volunteers with the Octopus 1-2-3 automated perimeter. Within the 30-deg visual field, 33 test locations were investigated four times. Stimulus parameters were Goldmann size V (1.72 degrees), intensity 1632 cd/m2, stimulus time 200 ms, background illumination 0 cd/m2, and interstimulus interval 3 s. Pupillometric parameters studied were initial pupil size, amplitude (magnitude of pupillary contraction), latency time, contraction time, pre-PLR movement, contraction velocity, and redilation velocity. Pupillometric parameters were investigated by analysis of variance by the independent variables blue and brown irides. Iris color (blue vs brown) influenced statistically significantly (P < 0.05) amplitude (0.504 mm vs 0.594 mm), contraction time (401 ms vs 407 ms), contraction velocity (13.75 mm2/s vs 16.01 mm2/s), and redilation velocity (4.80 mm2/s vs 5.66 mm2/s). Iris color did not influence initial pupil size (4.78 mm vs 4.83 mm), latency time (520 mm vs 521 ms), and pre-PLR movement (0.328 mm2/s vs 0.325 mm2/s). Pupillary contraction amplitude and velocity depended on iris color, whereas pupil size and latency time were independent of iris color. Therefore, iris color might be considered when, evaluating pupillary movements in pupil perimetry.

Brainstem Correlates of Temporal Auditory Processing in Children with Specific Language Impairment

ERIC Educational Resources Information Center

Basu, Madhavi; Krishnan, Ananthanarayan; Weber-Fox, Christine

2010-01-01

Deficits in identification and discrimination of sounds with short inter-stimulus intervals or short formant transitions in children with specific language impairment (SLI) have been taken to reflect an underlying temporal auditory processing deficit. Using the sustained frequency following response (FFR) and the onset auditory brainstem responses…

Pitch discrimination as a function of the inter-stimulus interval: Evidence against a simple model of perceptual memory

NASA Astrophysics Data System (ADS)

Demany, Laurent; Montandon, Gaspard; Semal, Catherine

2003-04-01

A listener's ability to compare two sounds separated by a silent time interval T is limited by a sum of ``sensory noise'' and ``memory noise.'' The present work was intended to test a model according to which these two components of internal noise are independent and, for a given sensory continuum, the memory noise depends only on T. In three experiments using brief sounds (<80 ms), pitch discrimination performances were measured in terms of d' as a function of T (0.1-4 s) and a physical parameter affecting the amount of sensory noise (pitch salience). As T increased, d' first increased rapidly and then declined more slowly. According to the tested model, the relative decline of d' beyond the optimal value of T should have been slower when pitch salience was low (large amount of sensory noise) than when pitch salience was high (small amount of sensory noise). However, this prediction was disproved in each of the three experiments. It was also found, when a ``roving'' procedure was used, that the optimal value of T was markedly shorter for very brief tone bursts (6 sine cycles) than for longer tone bursts (30 sine cycles).

Intracortical excitability in patients with relapsing-remitting and secondary progressive multiple sclerosis.

PubMed

Conte, A; Lenzi, D; Frasca, V; Gilio, F; Giacomelli, E; Gabriele, M; Bettolo, C Marini; Iacovelli, E; Pantano, P; Pozzilli, C; Inghilleri, M

2009-06-01

We designed this study to investigate possible correlations between variables measuring primary motor cortex excitability detected by single and paired-pulse transcranial magnetic stimulation (TMS) and the severity of clinical manifestations in patients with multiple sclerosis (MS). Thirty patients with MS in remission, 16 with relapsing-remitting (RR), 14 with secondary progressive disease (SP) and 17 healthy subjects participated in the study. In each subject, the central motor conduction time (CMCT) was calculated, and single-pulse and paired-pulse TMS at 3 and 10 ms interstimulus intervals was delivered over the primary motor cortex of the dominant hemisphere to measure the amplitude of motor-evoked potentials (MEPs), motor threshold (MTh), intracortical inhibition (ICI) and facilitation (ICF). Correlations were determined between the patients' TMS findings and magnetic resonance imaging (MRI) (lesion load) and clinical features (expanded disability status scale, EDSS score). EDSS scores were significantly higher in SPMS than in RRMS patients. The MTh was significantly higher, and the MEP was significantly smaller in SPMS patients than in RRMS patients and control subjects. All patients had longer CMCTs than healthy subjects. In all patients, paired-pulse TMS elicited an inhibited test MEP at the 3-ms ISI and a facilitated test MEP at the 10 ms ISI. Post hoc analysis showed that ICI was significantly lower in SPMS patients than in those with RRMS and healthy subjects. EDSS scores correlated significantly with TMS measures (MEP, ICI, CMCT and MTh), but not with MRI lesion load. It was found that intracortical excitability as measured with TMS differs according to the clinical course of MS; it remains normal in patients with low EDSS scores and is altered in patients with high EDSS scores.

Cross-modal transfer of the conditioned eyeblink response during interstimulus interval discrimination training in young rats

PubMed Central

Brown, Kevin L.; Stanton, Mark E.

2008-01-01

Eyeblink classical conditioning (EBC) was observed across a broad developmental period with tasks utilizing two interstimulus intervals (ISIs). In ISI discrimination, two distinct conditioned stimuli (CSs; light and tone) are reinforced with a periocular shock unconditioned stimulus (US) at two different CS-US intervals. Temporal uncertainty is identical in design with the exception that the same CS is presented at both intervals. Developmental changes in conditioning have been reported in each task beyond ages when single-ISI learning is well developed. The present study sought to replicate and extend these previous findings by testing each task at four separate ages. Consistent with previous findings, younger rats (postnatal day – PD - 23 and 30) trained in ISI discrimination showed evidence of enhanced cross-modal influence of the short CS-US pairing upon long CS conditioning relative to older subjects. ISI discrimination training at PD43-47 yielded outcomes similar to those in adults (PD65-71). Cross-modal transfer effects in this task therefore appear to diminish between PD30 and PD43-47. Comparisons of ISI discrimination with temporal uncertainty indicated that cross-modal transfer in ISI discrimination at the youngest ages did not represent complete generalization across CSs. ISI discrimination undergoes a more protracted developmental emergence than single-cue EBC and may be a more sensitive indicator of developmental disorders involving cerebellar dysfunction. PMID:18726989

Developing a New Quantitative Account of Backward Masking

ERIC Educational Resources Information Center

Francis, Gregory

2003-01-01

A new general explanation for u-shaped backward masking is analyzed and found to predict shifts in the interstimulus interval (ISI) that produces strongest masking. This predicted shift is then compared to six sets of masking data. The resulting comparisons force the general explanation to make certain assumptions to account for the data. In this…

Measuring Children's Attention Span: A Microcomputer Assessment Technique.

ERIC Educational Resources Information Center

Murphy-Berman, Virginia; And Others

1986-01-01

A microcomputer technique was used to measure the attention span of 115 boys and 117 girls in kindergarten through the ninth grade. Attentional ability increased only up through the fifth grade, and both the false alarm rate and the interstimulus interval scores were related to behavioral activity during test sessions. (Author/CB)

Sensory tricks and brain excitability in cervical dystonia: a transcranial magnetic stimulation study.

PubMed

Amadio, Stefano; Houdayer, Elise; Bianchi, Francesca; Tesfaghebriel Tekle, Habtom; Urban, Ivan Pietro; Butera, Calogera; Guerriero, Roberta; Cursi, Marco; Leocani, Letizia; Comi, Giancarlo; Del Carro, Ubaldo

2014-08-01

Sensory tricks such as touching the face with fingertips often improve cervical dystonia [CD]. This study is to determine whether sensory tricks modulate motor cortex excitability, assessed by paired-pulse transcranial magnetic stimulation [p-pTMS]. Eight patients with rotational CD underwent p-pTMS, at rest and when the sensory trick was applied. To test intracortical inhibition [ICI] and facilitation [ICF], the amplitude ratio between conditioned and unconditioned cortical motor evoked potentials was measured at several interstimulus intervals (ISI 1, 3, 15, and 20 ms) and compared with controls mimicking patients' sensory tricks. At rest, a significant ICF enhancement was found at ISIs 15 through 20 in patients compared with controls, whereas no significant ICI changes were observed. Sensory tricks significantly reduced the abnormal ICF in patients and did not induce any change in controls. In our CD patients, sensory tricks seem to improve dystonia through an inhibitory effect on motor cortex excitability. © 2014 International Parkinson and Movement Disorder Society.

Decision making and action implementation: evidence for an early visually triggered motor activation specific to potential actions.

PubMed

Tandonnet, Christophe; Garry, Michael I; Summers, Jeffery J

2013-07-01

To make a decision may rely on accumulating evidence in favor of one alternative until a threshold is reached. Sequential-sampling models differ by the way of accumulating evidence and the link with action implementation. Here, we tested a model's prediction of an early action implementation specific to potential actions. We assessed the dynamics of action implementation in go/no-go and between-hand choice tasks by transcranial magnetic stimulation of the motor cortex (single- or paired-pulse TMS; 3-ms interstimulus interval). Prior to implementation of the selected action, the amplitude of the motor evoked potential first increased whatever the visual stimulus but only for the hand potentially involved in the to-be-produced action. These findings suggest that visual stimuli can trigger an early motor activation specific to potential actions, consistent with race-like models with continuous transmission between decision making and action implementation. Copyright © 2013 Society for Psychophysiological Research.

Selective attention and the auditory vertex potential. I - Effects of stimulus delivery rate. II - Effects of signal intensity and masking noise

NASA Technical Reports Server (NTRS)

Schwent, V. L.; Hillyard, S. A.; Galambos, R.

1976-01-01

The effects of varying the rate of delivery of dichotic tone pip stimuli on selective attention measured by evoked-potential amplitudes and signal detectability scores were studied. The subjects attended to one channel (ear) of tones, ignored the other, and pressed a button whenever occasional targets - tones of a slightly higher pitch were detected in the attended ear. Under separate conditions, randomized interstimulus intervals were short, medium, and long. Another study compared the effects of attention on the N1 component of the auditory evoked potential for tone pips presented alone and when white noise was added to make the tones barely above detectability threshold in a three-channel listening task. Major conclusions are that (1) N1 is enlarged to stimuli in an attended channel only in the short interstimulus interval condition (averaging 350 msec), (2) N1 and P3 are related to different modes of selective attention, and (3) attention selectivity in multichannel listening task is greater when tones are faint and/or difficult to detect.

Increased tissue oxygenation explains the attenuation of hyperemia upon repetitive pneumatic compression of the lower leg.

PubMed

Messere, Alessandro; Ceravolo, Gianluca; Franco, Walter; Maffiodo, Daniela; Ferraresi, Carlo; Roatta, Silvestro

2017-12-01

The rapid hyperemia evoked by muscle compression is short lived and was recently shown to undergo a rapid decrease even in spite of continuing mechanical stimulation. The present study aims at investigating the mechanisms underlying this attenuation, which include local metabolic mechanisms, desensitization of mechanosensitive pathways, and reduced efficacy of the muscle pump. In 10 healthy subjects, short sequences of mechanical compressions ( n = 3-6; 150 mmHg) of the lower leg were delivered at different interstimulus intervals (ranging from 20 to 160 s) through a customized pneumatic device. Hemodynamic monitoring included near-infrared spectroscopy, detecting tissue oxygenation and blood volume in calf muscles, and simultaneous echo-Doppler measurement of arterial (superficial femoral artery) and venous (femoral vein) blood flow. The results indicate that 1 ) a long-lasting (>100 s) increase in local tissue oxygenation follows compression-induced hyperemia, 2 ) compression-induced hyperemia exhibits different patterns of attenuation depending on the interstimulus interval, 3 ) the amplitude of the hyperemia is not correlated with the amount of blood volume displaced by the compression, and 4 ) the extent of attenuation negatively correlates with tissue oxygenation ( r  = -0,78, P < 0.05). Increased tissue oxygenation appears to be the key factor for the attenuation of hyperemia upon repetitive compressive stimulation. Tissue oxygenation monitoring is suggested as a useful integration in medical treatments aimed at improving local circulation by repetitive tissue compression. NEW & NOTEWORTHY This study shows that 1 ) the hyperemia induced by muscle compression produces a long-lasting increase in tissue oxygenation, 2 ) the hyperemia produced by subsequent muscle compressions exhibits different patterns of attenuation at different interstimulus intervals, and 3 ) the extent of attenuation of the compression-induced hyperemia is proportional to the level of oxygenation achieved in the tissue. The results support the concept that tissue oxygenation is a key variable in blood flow regulation. Copyright © 2017 the American Physiological Society.

Dissociating Long and Short-term Memory in Three-Month-Old Infants Using the Mismatch Response to Voice Stimuli

PubMed Central

Zinke, Katharina; Thöne, Leonie; Bolinger, Elaina M.; Born, Jan

2018-01-01

Auditory event-related potentials (ERPs) have been successfully used in adults as well as in newborns to discriminate recall of longer-term and shorter-term memories. Specifically the Mismatch Response (MMR) to deviant stimuli of an oddball paradigm is larger if the deviant stimuli are highly familiar (i.e., retrieved from long-term memory) than if they are unfamiliar, representing an immediate change to the standard stimuli kept in short-term memory. Here, we aimed to extend previous findings indicating a differential MMR to familiar and unfamiliar deviants in newborns (Beauchemin et al., 2011), to 3-month-old infants who are starting to interact more with their social surroundings supposedly based on forming more (social) long-term representations. Using a voice discrimination paradigm, each infant was repeatedly presented with the word “baby” (400 ms, interstimulus interval: 600 ms, 10 min overall duration) pronounced by three different female speakers. One voice that was unfamiliar to the infants served as the frequently presented “standard” stimulus, whereas another unfamiliar voice served as the “unfamiliar deviant” stimulus, and the voice of the infant’s mother served as the “familiar deviant.” Data collection was successful for 31 infants (mean age = 100 days). The MMR was determined by the difference between the ERP to standard stimuli and the ERP to the unfamiliar and familiar deviant, respectively. The MMR to the familiar deviant (mother’s voice) was larger, i.e., more positive, than that to the unfamiliar deviant between 100 and 400 ms post-stimulus over the frontal and central cortex. However, a genuine MMR differentiating, as a positive deflection, between ERPs to familiar deviants and standard stimuli was only found in the 300–400 ms interval. On the other hand, a genuine MMR differentiating, as a negative deflection, between ERPs to unfamiliar deviants from ERPs to standard stimuli was revealed for the 200–300 ms post-stimulus interval. Overall results confirm a differential MMR response to unfamiliar and familiar deviants in 3-month-olds, with the earlier negative MMR to unfamiliar deviants likely reflecting change detection based on comparison processes in short-term memory, and the later positive MMR to familiar deviants reflecting subsequent long-term memory-based processing of stimulus relevance. PMID:29441032

Dissociating Long and Short-term Memory in Three-Month-Old Infants Using the Mismatch Response to Voice Stimuli.

PubMed

Zinke, Katharina; Thöne, Leonie; Bolinger, Elaina M; Born, Jan

2018-01-01

Auditory event-related potentials (ERPs) have been successfully used in adults as well as in newborns to discriminate recall of longer-term and shorter-term memories. Specifically the Mismatch Response (MMR) to deviant stimuli of an oddball paradigm is larger if the deviant stimuli are highly familiar (i.e., retrieved from long-term memory) than if they are unfamiliar, representing an immediate change to the standard stimuli kept in short-term memory. Here, we aimed to extend previous findings indicating a differential MMR to familiar and unfamiliar deviants in newborns (Beauchemin et al., 2011), to 3-month-old infants who are starting to interact more with their social surroundings supposedly based on forming more (social) long-term representations. Using a voice discrimination paradigm, each infant was repeatedly presented with the word "baby" (400 ms, interstimulus interval: 600 ms, 10 min overall duration) pronounced by three different female speakers. One voice that was unfamiliar to the infants served as the frequently presented "standard" stimulus, whereas another unfamiliar voice served as the "unfamiliar deviant" stimulus, and the voice of the infant's mother served as the "familiar deviant." Data collection was successful for 31 infants (mean age = 100 days). The MMR was determined by the difference between the ERP to standard stimuli and the ERP to the unfamiliar and familiar deviant, respectively. The MMR to the familiar deviant (mother's voice) was larger, i.e., more positive, than that to the unfamiliar deviant between 100 and 400 ms post-stimulus over the frontal and central cortex. However, a genuine MMR differentiating, as a positive deflection, between ERPs to familiar deviants and standard stimuli was only found in the 300-400 ms interval. On the other hand, a genuine MMR differentiating, as a negative deflection, between ERPs to unfamiliar deviants from ERPs to standard stimuli was revealed for the 200-300 ms post-stimulus interval. Overall results confirm a differential MMR response to unfamiliar and familiar deviants in 3-month-olds, with the earlier negative MMR to unfamiliar deviants likely reflecting change detection based on comparison processes in short-term memory, and the later positive MMR to familiar deviants reflecting subsequent long-term memory-based processing of stimulus relevance.

The effect of the anodal transcranial direct current stimulation over the cerebellum on the motor cortex excitability.

PubMed

Ates, Mehlika Panpalli; Alaydin, Halil Can; Cengiz, Bulent

2018-04-25

This study was designed to investigate whether the cerebellum has an inhibitory effect on motor cortical excitability. Sixteen healthy adults (age range, 25-50 years, five female) participated in the study. Anodal cerebellar transcranial direct current stimulation (a-cTDCS) was used to modulate cerebellar excitability. A-cTDCS was given for 20 min at 1 mA intensity. The automatic threshold tracking method was used to investigate cortical excitability. Resting motor threshold (RMT), short interval intracortical inhibition (SICI), short interval intracortical facilitation (SICF), intracortical facilitation (ICF), and the input output curve (I-O curve) were motor cortical excitability parameters. a-cTDCS caused a reduction in overall SICI and the reduced SICF for interstimulus intervals (ISIs) to 2.4-4.4 ms. a-cTDCS has no effect on ICF, RMT, and the I-O curve. There were no significant changes in any of these cortical excitability parameters after sham cTDCS. Results of the study indicate that a-cTDCS has a dual (both inhibitory and excitatory) effect on motor cortical excitability, rather than a simple inhibitory effect. The cerebellum modulates both the inhibitory and facilitatory activities of motor cortex (M1) and suggest that cerebello-cerebral motor connectivity is more complex than solely inhibitory or facilitatory connections. Copyright © 2018 Elsevier Inc. All rights reserved.

High-Fidelity Visual Long-Term Memory within an Unattended Blink of an Eye.

PubMed

Kuhbandner, Christof; Rosas-Corona, Elizabeth A; Spachtholz, Philipp

2017-01-01

What is stored in long-term memory from current sensations is a question that has attracted considerable interest. Over time, several prominent theories have consistently proposed that only attended sensory information leaves a durable memory trace whereas unattended information is not stored beyond the current moment, an assumption that seems to be supported by abundant empirical evidence. Here we show, by using a more sensitive memory test than in previous studies, that this is actually not true. Observers viewed a rapid stream of real-world object pictures overlapped by words (presentation duration per stimulus: 500 ms, interstimulus interval: 200 ms), with the instruction to attend to the words and detect word repetitions, without knowing that their memory would be tested later. In a surprise two-alternative forced-choice recognition test, memory for the unattended object pictures was tested. Memory performance was substantially above chance, even when detailed feature knowledge was necessary for correct recognition, even when tested 24 h later, and even although participants reported that they do not have any memories. These findings suggests that humans have the ability to store at high speed detailed copies of current visual stimulations in long-term memory independently of current intentions and the current attentional focus.

Frogs Jump Forward: Semantic Knowledge Influences the Perception of Element Motion in the Ternus Display.

PubMed

Hsu, Patty; Taylor, J Eric T; Pratt, Jay

2015-01-01

The Ternus effect is a robust illusion of motion that produces element motion at short interstimulus intervals (ISIs; < 50 ms) and group motion at longer ISIs (> 50 ms). Previous research has shown that the nature of the stimuli (e.g., similarity, grouping), not just ISI, can influence the likelihood of perceiving element or group motion. We examined if semantic knowledge can also influence what type of illusory motion is perceived. In Experiment I, we used a modified Ternus display with pictures of frogs in a jump-ready pose facing forwards or backwards to the direction of illusory motion. Participants perceived more element motion with the forward-facing frogs and more group motion with the backward-facing frogs. Experiment 2 tested whether this effect would still occur with line drawings of frogs, or if a more life-like image was necessary. Experiment 3 tested whether this effect was due to visual asymmetries inherent in the jumping pose. Experiment 4 tested whether frogs in a "non-jumping," sedentary pose would replicate the original effect. These experiments elucidate the role of semantic knowledge in the Ternus effect. Prior knowledge of the movement of certain animate objects, in this case, frogs can also bias the perception of element or group motion.

Electrophysiological evidence for attenuated auditory recovery cycles in children with specific language impairment

PubMed Central

Stevens, Courtney; Paulsen, David; Yasen, Alia; Mitsunaga, Leila; Neville, Helen

2012-01-01

Previous research indicates that at least some children with specific language impairment (SLI) show a reduced neural response when non-linguistic tones were presented at rapid rates. However, this past research has examined older children, and it is unclear whether such deficits emerge earlier in development. It is also unclear whether atypical refractory effects differ for linguistic versus non-linguistic stimuli or can be explained by deficits in selective auditory attention reported among children with SLI. In the present study, auditory refractory periods were compared in a group of 24 young children with SLI (age 3–8 years) and 24 matched control children. Event-related brain potentials (ERPs) were recorded and compared to 100 ms linguistic and non-linguistic probe stimuli presented at inter-stimulus intervals (ISIs) of 200, 500, or 1000 ms. These probes were superimposed on story narratives when attended and ignored, permitting an experimental manipulation of selective attention within the same paradigm. Across participants, clear refractory effects were observed with this paradigm, evidenced as a reduced amplitude response from 100 to 200 ms at shorter ISIs. Children with SLI showed reduced amplitude ERPs relative to the typically-developing group at only the shortest, 200 ms, ISI and this difference was over the left-hemisphere for linguistic probes and over the right-hemisphere for non-linguistic probes. None of these effects was influenced by the direction of selective attention. Taken together, these findings suggest that deficits in the neural representation of rapidly presented auditory stimuli may be one risk factor for atypical language development. PMID:22265331

The Crossmodal Facilitation of Visual Object Representations by Sound: Evidence from the Backward Masking Paradigm

ERIC Educational Resources Information Center

Chen, Yi-Chuan; Spence, Charles

2011-01-01

We report a series of experiments designed to demonstrate that the presentation of a sound can facilitate the identification of a concomitantly presented visual target letter in the backward masking paradigm. Two visual letters, serving as the target and its mask, were presented successively at various interstimulus intervals (ISIs). The results…

Induction of motor associative plasticity in the posterior parietal cortex-primary motor network.

PubMed

Chao, Chi-Chao; Karabanov, Anke Ninija; Paine, Rainer; Carolina de Campos, Ana; Kukke, Sahana N; Wu, Tianxia; Wang, Han; Hallett, Mark

2015-02-01

There is anatomical and functional connectivity between the primary motor cortex (M1) and posterior parietal cortex (PPC) that plays a role in sensorimotor integration. In this study, we applied corticocortical paired-associative stimuli to ipsilateral PPC and M1 (parietal ccPAS) in healthy right-handed subjects to test if this procedure could modulate M1 excitability and PPC-M1 connectivity. One hundred and eighty paired transcranial magnetic stimuli to the PPC and M1 at an interstimulus interval (ISI) of 8 ms were delivered at 0.2 Hz. We found that parietal ccPAS in the left hemisphere increased the excitability of conditioned left M1 assessed by motor evoked potentials (MEPs) and the input-output curve. Motor behavior assessed by the Purdue pegboard task was unchanged compared with controls. At baseline, conditioning stimuli over the left PPC potentiated MEPs from left M1 when ISI was 8 ms. This interaction significantly attenuated at 60 min after left parietal ccPAS. Additional experiments showed that parietal ccPAS induced plasticity was timing-dependent, was absent if ISI was 100 ms, and could also be seen in the right hemisphere. Our results suggest that parietal ccPAS can modulate M1 excitability and PPC-M1 connectivity and is a new approach to modify motor excitability and sensorimotor interaction. Published by Oxford University Press 2013. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Both trace and delay conditioned eyeblink responding can be dissociated from outcome expectancy.

PubMed

Weidemann, Gabrielle; Broderick, Joshua; Lovibond, Peter F; Mitchell, Christopher J

2012-01-01

Squire and colleagues have proposed that trace and delay eyeblink conditioning are fundamentally different kinds of learning: trace conditioning requires acquisition of a conscious declarative memory for the stimulus contingencies whereas delay conditioning does not. Declarative memory in trace conditioning is thought to generate conditioned responding through the activation of a conscious expectancy for when the unconditioned stimulus (US) is going to occur. Perruchet (1985) has previously shown that in a 50% partial reinforcement design it is possible to dissociate single cue delay eyeblink conditioning from conscious expectancy for the US by examining performance over runs of reinforced and nonreinforced trials. Clark, Manns, and Squire (2001) claim that this dissociation does not occur in trace eyeblink conditioning. In the present experiment we examined the Perruchet effect for short, moderate, and long trace intervals (600, 1000, and 1400 ms) and for the equivalent interstimulus intervals (ISIs) in a delay conditioning procedure. We found evidence for a dissociation of eyeblink CRs and US expectancy over runs regardless of whether there was a delay or a trace arrangement of cues. The reasons for the Perruchet effect are still unclear, but the present data suggest that it does not depend on a separate nondeclarative system of the type proposed by Squire and colleagues. (c) 2012 APA, all rights reserved.

A relationship between bruxism and orofacial-dystonia? A trigeminal electrophysiological approach in a case report of pineal cavernoma.

PubMed

Frisardi, Gianni; Iani, Cesare; Sau, Gianfranco; Frisardi, Flavio; Leornadis, Carlo; Lumbau, Aurea; Enrico, Paolo; Sirca, Donatella; Staderini, Enrico Maria; Chessa, Giacomo

2013-10-28

In some clinical cases, bruxism may be correlated to central nervous system hyperexcitability, suggesting that bruxism may represent a subclinical form of dystonia. To examine this hypothesis, we performed an electrophysiological evaluation of the excitability of the trigeminal nervous system in a patient affected by pineal cavernoma with pain symptoms in the orofacial region and pronounced bruxism. Electrophysiological studies included bilateral electrical transcranial stimulation of the trigeminal roots, analysis of the jaw jerk reflex, recovery cycle of masseter inhibitory reflex, and a magnetic resonance imaging study of the brain. The neuromuscular responses of the left- and right-side bilateral trigeminal motor potentials showed a high degree of symmetry in latency (1.92 ms and 1.96 ms, respectively) and amplitude (11 mV and 11.4 mV, respectively), whereas the jaw jerk reflex amplitude of the right and left masseters was 5.1 mV and 8.9 mV, respectively. The test stimulus for the recovery cycle of masseter inhibitory reflex evoked both silent periods at an interstimulus interval of 150 ms. The duration of the second silent period evoked by the test stimulus was 61 ms and 54 ms on the right and left masseters, respectively, which was greater than that evoked by the conditioning stimulus (39 ms and 35 ms, respectively). We found evidence of activation and peripheral sensitization of the nociceptive fibers, the primary and secondary nociceptive neurons in the central nervous system, and the endogenous pain control systems (including both the inhibitory and facilitatory processes), in the tested subject. These data suggest that bruxism and central orofacial pain can coexist, but are two independent symptoms, which may explain why numerous experimental and clinical studies fail to reach unequivocal conclusions.

A relationship between bruxism and orofacial-dystonia? A trigeminal electrophysiological approach in a case report of pineal cavernoma

PubMed Central

2013-01-01

Background In some clinical cases, bruxism may be correlated to central nervous system hyperexcitability, suggesting that bruxism may represent a subclinical form of dystonia. To examine this hypothesis, we performed an electrophysiological evaluation of the excitability of the trigeminal nervous system in a patient affected by pineal cavernoma with pain symptoms in the orofacial region and pronounced bruxism. Methods Electrophysiological studies included bilateral electrical transcranial stimulation of the trigeminal roots, analysis of the jaw jerk reflex, recovery cycle of masseter inhibitory reflex, and a magnetic resonance imaging study of the brain. Results The neuromuscular responses of the left- and right-side bilateral trigeminal motor potentials showed a high degree of symmetry in latency (1.92 ms and 1.96 ms, respectively) and amplitude (11 mV and 11.4 mV, respectively), whereas the jaw jerk reflex amplitude of the right and left masseters was 5.1 mV and 8.9 mV, respectively. The test stimulus for the recovery cycle of masseter inhibitory reflex evoked both silent periods at an interstimulus interval of 150 ms. The duration of the second silent period evoked by the test stimulus was 61 ms and 54 ms on the right and left masseters, respectively, which was greater than that evoked by the conditioning stimulus (39 ms and 35 ms, respectively). Conclusions We found evidence of activation and peripheral sensitization of the nociceptive fibers, the primary and secondary nociceptive neurons in the central nervous system, and the endogenous pain control systems (including both the inhibitory and facilitatory processes), in the tested subject. These data suggest that bruxism and central orofacial pain can coexist, but are two independent symptoms, which may explain why numerous experimental and clinical studies fail to reach unequivocal conclusions. PMID:24165294

Auditory Attentional Capture during Serial Recall: Violations at Encoding of an Algorithm-Based Neural Model?

ERIC Educational Resources Information Center

Hughes, Robert W.; Vachon, Francois; Jones, Dylan M.

2005-01-01

A novel attentional capture effect is reported in which visual-verbal serial recall was disrupted if a single deviation in the interstimulus interval occurred within otherwise regularly presented task-irrelevant spoken items. The degree of disruption was the same whether the temporal deviant was embedded in a sequence made up of a repeating item…

Local inhibition of GABA affects precedence effect in the inferior colliculus

PubMed Central

Wang, Yanjun; Wang, Ningyu; Wang, Dan; Jia, Jun; Liu, Jinfeng; Xie, Yan; Wen, Xiaohui; Li, Xiaoting

2014-01-01

The precedence effect is a prerequisite for faithful sound localization in a complex auditory environment, and is a physiological phenomenon in which the auditory system selectively suppresses the directional information from echoes. Here we investigated how neurons in the inferior colliculus respond to the paired sounds that produce precedence-effect illusions, and whether their firing behavior can be modulated through inhibition with gamma-aminobutyric acid (GABA). We recorded extracellularly from 36 neurons in rat inferior colliculus under three conditions: no injection, injection with saline, and injection with gamma-aminobutyric acid. The paired sounds that produced precedence effects were two identical 4-ms noise bursts, which were delivered contralaterally or ipsilaterally to the recording site. The normalized neural responses were measured as a function of different inter-stimulus delays and half-maximal interstimulus delays were acquired. Neuronal responses to the lagging sounds were weak when the inter-stimulus delay was short, but increased gradually as the delay was lengthened. Saline injection produced no changes in neural responses, but after local gamma-aminobutyric acid application, responses to the lagging stimulus were suppressed. Application of gamma-aminobutyric acid affected the normalized response to lagging sounds, independently of whether they or the paired sounds were contralateral or ipsilateral to the recording site. These observations suggest that local inhibition by gamma-aminobutyric acid in the rat inferior colliculus shapes the neural responses to lagging sounds, and modulates the precedence effect. PMID:25206830

Timing in Trace Conditioning of the Nictitating Membrane Response of the Rabbit ("Oryctolagus Cuniculus"): Scalar, Nonscalar, and Adaptive Features

ERIC Educational Resources Information Center

Kehoe, E. James; Ludvig, Elliot A.; Sutton, Richard S.

2010-01-01

Using interstimulus intervals (ISIs) of 125, 250, and 500 msec in trace conditioning of the rabbit nictitating membrane response, the offset times and durations of conditioned responses (CRs) were collected along with onset and peak latencies. All measures were proportional to the ISI, but only onset and peak latencies conformed to the criterion…

Increased Inhibition in Non-Primary Motor Areas of String-Instrument Players: A Preliminary Study with Paired-Pulse Transcranial Magnetic Stimulation

PubMed Central

Vaalto, Selja; Julkunen, Petro; Säïsänen, Laura; Könönen, Mervi; Määttä, Sara; Karhu, Jari

2016-01-01

Background: The muscle representations in non-primary motor area (NPMA) are located in the dorsal premotor area (PMd) and in the border region between the premotor area and the supplementary motor area (SMA). Objective: We characterized the plasticity of intracortical inhibitory and excitatory circuits in muscle representations in primary motor cortex (M1) and in NPMA related to acquired fine motor skills. We compared local cortical inhibition and facilitation balance in M1 and in NPMA between control subjects (n = 6) and right-handed string-instrument players (n = 5). Methods: Navigated transcranial magnetic stimulation (TMS) was used to compare motor thresholds (MTs), motor evoked potentials (MEPs), short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) in non-dominant hand muscle representations in M1 and NPMA. Results: String-instrument players showed reduced SICI in M1 in the actively used left hand abductor digiti minimi (ADM) muscle representation at 3 ms inter-stimulus interval (ISI) with a conditioning stimulus (CS) intensity of 80% of MT and increased SICI in NPMA in ADM representation at 2 ms ISI and CS intensity of 50% of MT in comparison with controls. No differences between string-instrument players and controls were found for the SICI in the left hand opponens pollicis (OP) muscle representation, which is a muscle not intensively trained in string-instrument players. Conclusions: These preliminary results indicate that the stronger inhibition in motor representations outside M1 in string-instrument players may be crucial when accurate movements of single muscles must be performed. In contrast, weaker inhibition in M1 in string-instrument players may benefit the performance of fast finger movements. PMID:29765844

22q11.2 Deletion Syndrome Is Associated With Impaired Auditory Steady-State Gamma Response

PubMed Central

Pellegrino, Giovanni; Birknow, Michelle Rosgaard; Kjær, Trine Nørgaard; Baaré, William Frans Christiaan; Didriksen, Michael; Olsen, Line; Werge, Thomas; Mørup, Morten; Siebner, Hartwig Roman

2018-01-01

Abstract Background The 22q11.2 deletion syndrome confers a markedly increased risk for schizophrenia. 22q11.2 deletion carriers without manifest psychotic disorder offer the possibility to identify functional abnormalities that precede clinical onset. Since schizophrenia is associated with a reduced cortical gamma response to auditory stimulation at 40 Hz, we hypothesized that the 40 Hz auditory steady-state response (ASSR) may be attenuated in nonpsychotic individuals with a 22q11.2 deletion. Methods Eighteen young nonpsychotic 22q11.2 deletion carriers and a control group of 27 noncarriers with comparable age range (12–25 years) and sex ratio underwent 128-channel EEG. We recorded the cortical ASSR to a 40 Hz train of clicks, given either at a regular inter-stimulus interval of 25 ms or at irregular intervals jittered between 11 and 37 ms. Results Healthy noncarriers expressed a stable ASSR to regular but not in the irregular 40 Hz click stimulation. Both gamma power and inter-trial phase coherence of the ASSR were markedly reduced in the 22q11.2 deletion group. The ability to phase lock cortical gamma activity to regular auditory 40 Hz stimulation correlated with the individual expression of negative symptoms in deletion carriers (ρ = −0.487, P = .041). Conclusions Nonpsychotic 22q11.2 deletion carriers lack efficient phase locking of evoked gamma activity to regular 40 Hz auditory stimulation. This abnormality indicates a dysfunction of fast intracortical oscillatory processing in the gamma-band. Since ASSR was attenuated in nonpsychotic deletion carriers, ASSR deficiency may constitute a premorbid risk marker of schizophrenia. PMID:28521049

Effects of linguistic experience on early levels of perceptual tone processing

NASA Astrophysics Data System (ADS)

Huang, Tsan; Johnson, Keith

2005-04-01

This study investigated the phenomenon of language-specificity in Mandarin Chinese tone perception. The main question was whether linguistic experience affects the earliest levels of perceptual processing of tones. Chinese and American English listeners participated in four perception experiments, which involved short inter-stimulus intervals (300 ms or 100 ms) and an AX discrimination or AX degree-of-difference rating task. Three experiments used natural speech monosyllabic tone stimuli and one experiment used time-varying sinusoidal simulations of Mandarin tones. AE listeners showed psychoacoustic listening in all experiments, paying much attention to onset and offset pitch. Chinese listeners showed language-specific patterns in all experiments to various degrees, where tonal neutralization rules reduced perceptual distance between two otherwise contrastive tones for Chinese listeners. Since these experiments employed procedures hypothesized to tap the auditory trace mode (Pisoni, Percept. Psychophys. 13, 253-260 (1973)], language-specificity found in this study seems to support the proposal of an auditory cortical map [Guenther et al., J. Acoust. Soc. Am. 23, 213-221 (1999)]. But the model needs refining to account for different degrees of language-specificity, which are better handled by Johnsons (2004, TLS03:26-41) lexical distance model, although the latter model is too rigid in assuming that linguistic experience does not affect low-level perceptual tasks such as AX discrimination with short ISIs.

Temporal masking of multidimensional tactual stimuli

NASA Astrophysics Data System (ADS)

Tan, Hong Z.; Reed, Charlotte M.; Delhorne, Lorraine A.; Durlach, Nathaniel I.; Wan, Natasha

2003-12-01

Experiments were performed to examine the temporal masking properties of multidimensional tactual stimulation patterns delivered to the left index finger. The stimuli consisted of fixed-frequency sinusoidal motions in the kinesthetic (2 or 4 Hz), midfrequency (30 Hz), and cutaneous (300 Hz) frequency ranges. Seven stimuli composed of one, two, or three spectral components were constructed at each of two signal durations (125 or 250 ms). Subjects identified target signals under three different masking paradigms: forward masking, backward masking, and sandwiched masking (in which the target is presented between two maskers). Target identification was studied as a function of interstimulus interval (ISI) in the range 0 to 640 ms. For both signal durations, percent-correct scores increased with ISI for each of the three masking paradigms. Scores with forward and backward masking were similar and significantly higher than scores obtained with sandwiched masking. Analyses of error trials revealed that subjects showed a tendency to respond, more often than chance, with the masker, the composite of the masker and target, or the combination of the target and a component of the masker. The current results are compared to those obtained in previous studies of tactual recognition masking with brief cutaneous spatial patterns. The results are also discussed in terms of estimates of information transfer (IT) and IT rate, are compared to previous studies with multidimensional tactual signals, and are related to research on the development of tactual aids for the deaf.

Two forms of persistence in visual information processing.

PubMed

Di Lollo, Vincent; Dixon, Peter

1988-11-01

Iconic memory, which was initially regarded as a unitary phenomenon, has since been subdivided into several components. In the present work we examined the joint effects of two such components (visible persistence and the visual analog representation) on performance in a partial report task. The display consisted of 15 alphabetic characters arranged around the perimeter of an imaginary circle on the face of an oscilloscope. The observer named the character singled out by a bar-probe. Two factors were varied: exposure duration of the array (10, 50, 100, 150, 200, 300, 400 or 500 ms) and duration of blank period (interstimulus interval, ISI) between the termination of the array and the onset of the probe (0, 50, 100, 150, or 200 ms). Performance was progressively impaired as both exposure duration and ISI were increased. The results were explained in terms of a probabilistic combinatorial model in which the timecourses of visible persistence and of the visual analog representation are regarded as time-locked to the onset and to the end of stimulation, respectively. The impairing effect of exposure duration was attributed to the relatively high spatial demands of the task that could be met optimally by information in visible persistence (which declines as a function of exposure duration), but less adequately by information in the visual analog representation. A second experiment, employing a task with lesser spatial demands, confirmed this interpretation.

The adaptive pattern of the auditory N1 peak revealed by standardized low-resolution brain electromagnetic tomography

PubMed Central

Zhang, Fawen; Deshpande, Aniruddha; Benson, Chelsea; Smith, Mathew; Eliassen, James; Fu, Qian-Jie

2011-01-01

The N1 peak in the late auditory evoked potential (LAEP) decreases in amplitude following stimulus repetition, displaying an adaptive pattern. The present study explored the functional neural substrates that may underlie the N1 adaptive pattern using standardized Low Resolution Electromagnetic Tomography (sLORETA). Fourteen young normal hearing (NH) listeners participated in the study. Tone bursts (80 dB SPL) were binaurally presented via insert earphones in trains of ten; the inter-stimulus interval was 0.7 s and the inter-train interval was 15 s. Current source density analysis was performed for the N1 evoked by the 1st, 2nd and 10th stimuli (S1, S2 and S10) at three different timeframes that corresponded to the latency ranges of the N1 waveform subcomponents (70–100, 100–130 and 130–160 ms). The data showed that S1 activated broad regions in different cortical lobes and the activation was much smaller for S2 and S10. Response differences in the LAEP waveform and sLORETA were observed between S1 and S2, but not between the S2 and S10. The sLORETA comparison map between S1 and S2 response showed the activation was located in the parietal lobe for the 70–100 ms timeframe, the frontal and limbic lobes for the 100–130 ms timeframe, and the frontal lobe for the 130–160 ms timeframe. These sLORETA comparison results suggest a parieto-frontal network that might help to sensitize the brain to novel stimuli by filtering out repetitive and irrelevant stimuli. This study demonstrates that sLORETA may be useful for identifying generators of scalp-recorded event related potentials and for examining the physiological features of these generators. This technique could be especially useful for cortical source localization in individuals who cannot be examined with functional magnetic resonance imaging or magnetoencephalography (e.g., cochlear implant users). PMID:21658681

The adaptive pattern of the auditory N1 peak revealed by standardized low-resolution brain electromagnetic tomography.

PubMed

Zhang, Fawen; Deshpande, Aniruddha; Benson, Chelsea; Smith, Mathew; Eliassen, James; Fu, Qian-Jie

2011-07-11

The N1 peak in the late auditory evoked potential (LAEP) decreases in amplitude following stimulus repetition, displaying an adaptive pattern. The present study explored the functional neural substrates that may underlie the N1 adaptive pattern using standardized Low Resolution Electromagnetic Tomography (sLORETA). Fourteen young normal hearing (NH) listeners participated in the study. Tone bursts (80 dB SPL) were binaurally presented via insert earphones in trains of 10; the inter-stimulus interval was 0.7s and the inter-train interval was 15s. Current source density analysis was performed for the N1 evoked by the 1st, 2nd and 10th stimuli (S(1), S(2) and S(10)) at 3 different timeframes that corresponded to the latency ranges of the N1 waveform subcomponents (70-100, 100-130 and 130-160 ms). The data showed that S(1) activated broad regions in different cortical lobes and the activation was much smaller for S(2) and S(10). Response differences in the LAEP waveform and sLORETA were observed between S(1) and S(2), but not between the S(2) and S(10). The sLORETA comparison map between S(1) and S(2) responses showed that the activation was located in the parietal lobe for the 70-100 ms timeframe, the frontal and limbic lobes for the 100-130 ms timeframe, and the frontal lobe for the 130-160 ms timeframe. These sLORETA comparison results suggest a parieto-frontal network that might help to sensitize the brain to novel stimuli by filtering out repetitive and irrelevant stimuli. This study demonstrates that sLORETA may be useful for identifying generators of scalp-recorded event related potentials and for examining the physiological features of these generators. This technique could be especially useful for cortical source localization in individuals who cannot be examined with functional magnetic resonance imaging or magnetoencephalography (e.g., cochlear implant users). Copyright © 2011 Elsevier B.V. All rights reserved.

The impulse response of S-cone pathways in detection of increments and decrements

PubMed Central

Shinomori, Keizo; Werner, John S.

2008-01-01

Impulse response functions (IRFs) were obtained from two-pulse detection thresholds using isoluminant stimuli that produced increments or decrements in S-cone excitation. The pulses were chromatically modulated at constant luminance (based on 18 Hz heterochromatic flicker photometry). Chromatic stimuli were presented as a Gaussian patch (±1 SD = 2.3°) in one of four quadrants around a central fixation cross on a CRT screen. Each of the two pulses (6.67 ms) was separated by an inter-stimulus interval (ISI) from 20 to 360 ms. Chromaticity of the pulses was changed from the equal-energy white of the background to a bluish or yellowish color along individually determined tritan lines (based on color matching under strong S-cone adaptation from a 420 nm background superimposed in Maxwellian view). Chromatic detection thresholds were determined by a four-alternative forced-choice method with staircases for each ISI interleaved in each session. Measurements were repeated in at least four sessions for each observer. IRFs were calculated by varying four parameters of an exponentially-damped sinewave. Both S-cone increment and decrement IRFs are characterized by a single excitatory phase and a much longer time course compared with IRFs derived for luminance modulation using the same apparatus and observers. S-cone increment IRFs are faster than S-cone decrement IRFs; the time to peak amplitude of S-cone increment and decrement IRFs is 50–70 and 100–120 ms, respectively. These results were used to derive the temporal contrast sensitivity for human observers of putative ON- and OFF-channels carrying signals from S-cones. PMID:18321402

The effects of combined exposure to the pyrethroids deltamethrin and S-bioallethrin on hippocampal inhibition and skeletal muscle hyperexcitability in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ray, David E.; Burr, Steven A.; Lister, Timothy

2006-10-15

The default assumption that different pyrethroid insecticides, sharing a common mode of action, will show additivity of toxicity has not always been supported by in vitro measures, some of which have indicated antagonism. Our intention was to see whether the antagonism between pyrethroids of different classes seen in vitro could be reproduced in vivo. We therefore investigated the effects of single and combined exposures to two commonly used pyrethroids, deltamethrin (type II) and S-bioallethrin (type I) given intravenously to anaesthetised rats. We used two quantitative measures that are responsive to pyrethroids: the duration of prolongation of hippocampal dentate granule cellmore » inhibition and the amplitude of the abnormal electromyogram discharge. At equi-toxic doses, S-bioallethrin extended the inter-stimulus interval evoking 50% inhibition in the hippocampus by 30 {+-} 2.2 ms, and deltamethrin extended it by 199 {+-} 21 ms. Combined administration of the same doses of deltamethrin and S-bioallethrin extended hippocampal inhibition by 164 {+-} 14 ms, which did not differ significantly from the effect of deltamethrin alone. S-bioallethrin was without any effect on the electromyogram, and produced no significant change in the amplitude of the abnormal muscle discharges evoked by deltamethrin. The increase in arterial blood pressure evoked by the combination was significantly less than that evoked by either pyrethroid alone (p < 0.001). In summary, although our electrophysiological indices provide no support for functional antagonism between these two pyrethroids, they also fail to indicate any summation of effect.« less

The 3-Second Rule in Hereditary Pure Cerebellar Ataxia: A Synchronized Tapping Study

PubMed Central

Matsuda, Shunichi; Matsumoto, Hideyuki; Furubayashi, Toshiaki; Hanajima, Ritsuko; Tsuji, Shoji; Ugawa, Yoshikazu; Terao, Yasuo

2015-01-01

The ‘3-second rule’ has been proposed based on miscellaneous observations that a time period of around 3 seconds constitutes the fundamental unit of time related to the neuro-cognitive machinery in normal humans. The aim of paper was to investigate the temporal processing in patients with spinocerebellar ataxia type 6 (SCA6) and SCA31, pure cerebellar types of spinocerebellar degeneration, using a synchronized tapping task. Seventeen SCA patients (11 SCA6, 6 SCA31) and 17 normal age-matched volunteers participated. The task required subjects to tap a keyboard in synchrony with sequences of auditory stimuli presented at fixed interstimulus intervals (ISIs) between 200 and 4800 ms. In this task, the subjects required non-motor components to estimate the time of forthcoming tone in addition to motor components to tap. Normal subjects synchronized their taps to the presented tones at shorter ISIs, whereas as the ISI became longer, the normal subjects displayed greater latency between the tone and the tapping (transition zone). After the transition zone, normal subjects pressed the button delayed relative to the tone. On the other hand, SCA patients could not synchronize their tapping with the tone even at shorter ISIs, although they pressed the button delayed relative to the tone earlier than normal subjects did. The earliest time of delayed tapping appearance after the transition zone was 4800 ms in normal subjects but 1800 ms in SCA patients. The span of temporal integration in SCA patients is shortened compared to that in normal subjects. This could represent non-motor cerebellar dysfunction in SCA patients. PMID:25706752

The stability of M(max) and H (max) amplitude over time.

PubMed

McNulty, Penelope A; Shiner, Christine T; Thayaparan, Ganesha K; Burke, David

2012-05-01

The stability of the maximal muscle response (M(max)) is critical to H reflex methodology. It has previously been reported that the amplitude of M(max) declines over time. If reproducible, this finding would have implications for all experimental studies that normalise the output of the motoneurone pool against the M wave. We investigated the effect of time on changes in M(max) and the maximal H reflex (H(max)) evoked at 4-s intervals over 60 min. To identify an influence of homosynaptic depression, we extended the interstimulus interval to 10 s and the time to 100 min. Two recording montages over soleus were used to ensure that interelectrode distance was not a critical factor. The soleus M(max) and H reflex were evoked by stimulation of the tibial nerve in the popliteal fossa in 7 subjects who sat with the knee flexed to 30° and the ankle plantar flexed by ~30°. We found no change in the pooled data for M(max), H(max), a reflex 50% of maximal, or the current required to produce it. However, one subject had a statistically significant increase in M(max) and a concurrent decrease in H(max) regardless of the interstimulus interval. On average, there was no change in the H(max)/M(max) ratio over time. While both M(max) and H(max) may change in response to many factors, these results suggest that, typically, time is not one of them.

Complementary fMRI and EEG evidence for more efficient neural processing of rhythmic vs. unpredictably timed sounds

PubMed Central

van Atteveldt, Nienke; Musacchia, Gabriella; Zion-Golumbic, Elana; Sehatpour, Pejman; Javitt, Daniel C.; Schroeder, Charles

2015-01-01

The brain’s fascinating ability to adapt its internal neural dynamics to the temporal structure of the sensory environment is becoming increasingly clear. It is thought to be metabolically beneficial to align ongoing oscillatory activity to the relevant inputs in a predictable stream, so that they will enter at optimal processing phases of the spontaneously occurring rhythmic excitability fluctuations. However, some contexts have a more predictable temporal structure than others. Here, we tested the hypothesis that the processing of rhythmic sounds is more efficient than the processing of irregularly timed sounds. To do this, we simultaneously measured functional magnetic resonance imaging (fMRI) and electro-encephalograms (EEG) while participants detected oddball target sounds in alternating blocks of rhythmic (e.g., with equal inter-stimulus intervals) or random (e.g., with randomly varied inter-stimulus intervals) tone sequences. Behaviorally, participants detected target sounds faster and more accurately when embedded in rhythmic streams. The fMRI response in the auditory cortex was stronger during random compared to random tone sequence processing. Simultaneously recorded N1 responses showed larger peak amplitudes and longer latencies for tones in the random (vs. the rhythmic) streams. These results reveal complementary evidence for more efficient neural and perceptual processing during temporally predictable sensory contexts. PMID:26579044

Effect of duration and inter-stimulus interval on auditory temporal order discrimination in young normal-hearing and elderly hearing-impaired listeners

NASA Astrophysics Data System (ADS)

Narendran, Mini M.; Humes, Larry E.

2003-04-01

Increasing the rate of presentation can have a deleterious effect on auditory processing, especially among the elderly. Rate can be manipulated by changing the duration of individual components of a sequence of sounds, by changing the inter-stimulus interval (ISI) between components, or both. Consequently, when age-related deficits in performance appear to be attributable to rate of stimulus presentation, it is often the case that alternative explanations in terms of the effects of stimulus duration or ISI are also possible. In this study, the independent effects of duration and ISI on the discrimination of temporal order for four-tone sequences were investigated in a group of young normal-hearing and elderly hearing-impaired listeners. It was found that discrimination performance was driven by the rate of presentation, rather than stimulus duration or ISI alone, for both groups of listeners. The performance of the two groups of listeners differed significantly for the fastest presentation rates, but was similar for the slower rates. Slowing the rate of presentation seemed to improve performance, regardless of whether this was done by increasing stimulus duration or increasing ISI, and this was observed for both groups of listeners. [Work supported, in part, by NIA.

Influence of inter-stimulus interval of spinal cord stimulation in patients with disorders of consciousness: A preliminary functional near-infrared spectroscopy study.

PubMed

Zhang, Yujin; Yang, Yi; Si, Juanning; Xia, Xiaoyu; He, Jianghong; Jiang, Tianzi

2018-01-01

Spinal cord stimulation (SCS) is a promising treatment for disorders of consciousness (DOC), but the underlying mechanism and most effective procedures remain uncertain. To optimize the protocol, previous studies evaluated the frequency-specific effects of SCS on neurophysiological activities. However, whether and how the inter-stimulus interval (ISI) parameter affects the SCS neuromodulation in DOC remains unknown. We enrolled nine DOC patients who had implanted SCS devices and conducted three different durations of ISIs. Using functional near-infrared spectroscopy (fNIRS), we monitored the blood volume fluctuations in the prefrontal and occipital cortices during the SCS. The results showed that short stimuli (30 s) induced significant cerebral blood volume changes, especially in the prefrontal cortex, an important area in the consciousness system. By comparing the mean value of the responses from the first and the last block in each session, a shorter ISI was found to improve the blood volume in the prefrontal cortex. This phenomenon was more significant for the subgroup of patients with a favorable prognosis. These preliminary results imply that the ISI may be an important factor for SCS. The research paradigm proposed here also provides insights for further quantitative evaluations of the therapeutic effects of neuromodulation.

Cortical processing of tactile stimuli applied in quick succession across the fingertips: temporal evolution of dipole sources revealed by magnetoencephalography.

PubMed

Karageorgiou, Elissaios; Koutlas, Ioannis G; Alonso, Aurelio A; Leuthold, Arthur C; Lewis, Scott M; Georgopoulos, Apostolos P

2008-08-01

We used magnetoencephalography (MEG) in 10 healthy human subjects to study cortical responses to tactile stimuli applied to the fingertips of digits 2-5 of the right hand. Each stimulus lasted 50 ms and was produced by air-driven elastic membranes. Four-hundred stimuli were delivered on each finger in three temporal patterns (conditions). In the "Discrete" condition, stimuli were applied to each finger repetitively with an interstimulus interval (ISI) of 1-2 s. In the "Continuous" condition, stimuli were applied to the fingers sequentially as four-stimulus trains with zero ISI and 1-2 s intervening between trains. Finally, in the "Gap" condition, stimuli were applied as in the Continuous condition but with an ISI of 50 ms. A sensation of tactile motion across fingers (digit 2 --> digit 5) was reported by all subjects in the Continuous and Gap conditions. Cortical responses were extracted as single equivalent current dipoles over a period of 1 s following stimulus onset. In all three conditions, initial responses in left primary somatosensory cortex (SI) were observed ~20 to 50 ms after stimulus onset and were followed by additional left SI responses and bilateral responses in the secondary somatosensory cortex (SII). In addition, in the Continuous and Gap conditions, there was an activation of the precentral gyrus, the temporal aspects of which depended on the temporal relation of the administered stimuli, as follows. An ISI of 0 ms led to activation of the precentral gyrus shortly after the second stimulation, whereas an ISI of 50 ms led to activation of the precentral gyrus after the third stimulation. The current findings support results from previous studies on temporal activity patterns in SI and SII, verify the participation of the precentral gyrus during tactile motion perception and, in addition, reveal aspects of integration of sequential sensory stimulations over nonadjacent areas as well as temporal activity patterns in the postcentral and precentral gyri.

Differing Presynaptic Contributions to LTP and Associative Learning in Behaving Mice

PubMed Central

Madroñal, Noelia; Gruart, Agnès; Delgado-García, José M.

2009-01-01

The hippocampal CA3-CA1 synapse is an excellent experimental model for studying the interactions between short- and long-term plastic changes taking place following high-frequency stimulation (HFS) of Schaffer collaterals and during the acquisition and extinction of a classical eyeblink conditioning in behaving mice. Input/output curves and a full-range paired-pulse study enabled determining the optimal intensities and inter-stimulus intervals for evoking paired-pulse facilitation (PPF) or depression (PPD) at the CA3-CA1 synapse. Long-term potentiation (LTP) induced by HFS lasted ≈10 days. HFS-induced LTP evoked an initial depression of basal PPF. Recovery of PPF baseline values was a steady and progressive process lasting ≈20 days, i.e., longer than the total duration of the LTP. In a subsequent series of experiments, we checked whether PPF was affected similarly during activity-dependent synaptic changes. Animals were conditioned using a trace paradigm, with a tone as a conditioned stimulus (CS) and an electrical shock to the trigeminal nerve as an unconditioned stimulus (US). A pair of pulses (40 ms interval) was presented to the Schaffer collateral-commissural pathway to evoke field EPSPs (fEPSPs) during the CS-US interval. Basal PPF decreased steadily across conditioning sessions (i.e., in the opposite direction to that during LTP), reaching a minimum value during the 10th conditioning session. Thus, LTP and classical eyeblink conditioning share some presynaptic mechanisms, but with an opposite evolution. Furthermore, PPF and PPD might play a homeostatic role during long-term plastic changes at the CA3-CA1 synapse. PMID:19636387

Concurrent functional magnetic resonance imaging and electroencephalography assessment of sensory gating in schizophrenia

PubMed Central

Bak, Nikolaj; Rostrup, Egill; Larsson, Henrik BW; Glenthøj, Birte Y; Oranje, Bob

2014-01-01

Schizophrenia is frequently accompanied by deficits in basic information processing, such as sensory gating. The sources behind deficient sensory gating in schizophrenia patients are, however, still largely unclear. The aim of the current study was to identify the brain structures involved in deficient sensory gating in schizophrenia patients. Twenty healthy male volunteers and 23 male schizophrenia patients were initially assessed in a somatosensory P50 suppression paradigm using concurrent electroencephalography (EEG)/functional magnetic resonance imaging (fMRI) methodology. The trials consisted of single stimuli or pairs of identical stimuli with either 500 ms or 1,000 ms interstimulus intervals. Not all subjects showed a P50 waveform as a result of the somatosensory stimuli: It was detected in 13 schizophrenia patients and 15 control subjects. Significant P50 suppression was found in the 500 ms trials in controls only. Region of interest analyses were performed for a priori chosen regions. Significant negative correlations between P50 ratios and the BOLD response were found bilaterally in the hippocampus, thalamus, anterior and posterior superior temporal gyrus (STG), and in the left inferior frontal gyrus pars opercularis. However, significant group differences were found in the hippocampus and the thalamus only. This is the first study in which P50 suppression was assessed in schizophrenia patients with concurrent fMRI/EEG methodology. The data support that the STG, thalamus, inferior frontal gyrus, and the hippocampus are involved in P50 suppression. However, of these structures only the hippocampus and thalamus appeared involved in the altered sensory processing found in schizophrenia. Hum Brain Mapp 35:3578–3587, 2014. © 2013 Wiley Periodicals, Inc. PMID:24375687

Hemispheric asymmetries in processing L1 and L2 idioms: effects of salience and context.

PubMed

Cieślicka, Anna B; Heredia, Roberto R

2011-03-01

This study investigates the contribution of the left and right hemispheres to the comprehension of bilingual figurative language and the joint effects of salience and context on the differential cerebral involvement in idiom processing. The divided visual field and the lexical decision priming paradigms were employed to examine the activation of salient and nonsalient ambiguous idiom interpretations (i.e., literal vs. non-literal) in the two hemispheres. Literally plausible ambiguous idioms, L1 (Polish) and L2 (English), were embedded in unconstraining ambiguous (e.g., I knew he kept an ace up his sleeve) or constraining unambiguous context clearly favoring their conventional idiomatic interpretation (e.g., The debating president kept an ace up his sleeve). Idioms were presented centrally, followed by laterally presented targets related to the figurative (e.g., GAIN) or literal (e.g., SHIRT) meaning of the idiom and displayed at Interstimulus Intervals (ISIs) of 0 ms (Experiment 1), 300 ms (Experiment 2), and 800 ms (Experiment 3). Results indicate that context and salience effects are significantly modulated by the language (native vs. nonnative) of the stimulus materials being presented to each hemisphere. Literal facilitation was found for L2 idioms in all three ISI conditions, which supports the notion of the special status that literal meanings of L2 idioms enjoy in the course of their processing by nonnative language users. No significant differences were found between the right and left hemispheres in regards to their sensitivity to contextual constraints. Results are discussed in terms of the Graded Salience Hypothesis and the Fine/Coarse Coding Theory. Copyright © 2010 Elsevier Inc. All rights reserved.

Promoting Motor Cortical Plasticity with Acute Aerobic Exercise: A Role for Cerebellar Circuits

PubMed Central

Mang, Cameron S.; Brown, Katlyn E.; Neva, Jason L.; Snow, Nicholas J.; Campbell, Kristin L.; Boyd, Lara A.

2016-01-01

Acute aerobic exercise facilitated long-term potentiation-like plasticity in the human primary motor cortex (M1). Here, we investigated the effect of acute aerobic exercise on cerebellar circuits, and their potential contribution to altered M1 plasticity in healthy individuals (age: 24.8 ± 4.1 years). In Experiment   1, acute aerobic exercise reduced cerebellar inhibition (CBI) (n = 10, p = 0.01), elicited by dual-coil paired-pulse transcranial magnetic stimulation. In Experiment   2, we evaluated the facilitatory effects of aerobic exercise on responses to paired associative stimulation, delivered with a 25 ms (PAS25) or 21 ms (PAS21) interstimulus interval (n = 16 per group). Increased M1 excitability evoked by PAS25, but not PAS21, relies on trans-cerebellar sensory pathways. The magnitude of the aerobic exercise effect on PAS response was not significantly different between PAS protocols (interaction effect: p = 0.30); however, planned comparisons indicated that, relative to a period of rest, acute aerobic exercise enhanced the excitatory response to PAS25 (p = 0.02), but not PAS21 (p = 0.30). Thus, the results of these planned comparisons indirectly provide modest evidence that modulation of cerebellar circuits may contribute to exercise-induced increases in M1 plasticity. The findings have implications for developing aerobic exercise strategies to “prime” M1 plasticity for enhanced motor skill learning in applied settings. PMID:27127659

Effect of gap detection threshold on consistency of speech in children with speech sound disorder.

PubMed

Sayyahi, Fateme; Soleymani, Zahra; Akbari, Mohammad; Bijankhan, Mahmood; Dolatshahi, Behrooz

2017-02-01

The present study examined the relationship between gap detection threshold and speech error consistency in children with speech sound disorder. The participants were children five to six years of age who were categorized into three groups of typical speech, consistent speech disorder (CSD) and inconsistent speech disorder (ISD).The phonetic gap detection threshold test was used for this study, which is a valid test comprised six syllables with inter-stimulus intervals between 20-300ms. The participants were asked to listen to the recorded stimuli three times and indicate whether they heard one or two sounds. There was no significant difference between the typical and CSD groups (p=0.55), but there were significant differences in performance between the ISD and CSD groups and the ISD and typical groups (p=0.00). The ISD group discriminated between speech sounds at a higher threshold. Children with inconsistent speech errors could not distinguish speech sounds during time-limited phonetic discrimination. It is suggested that inconsistency in speech is a representation of inconsistency in auditory perception, which causes by high gap detection threshold. Copyright © 2016 Elsevier Ltd. All rights reserved.

A compact electroencephalogram recording device with integrated audio stimulation system.

PubMed

Paukkunen, Antti K O; Kurttio, Anttu A; Leminen, Miika M; Sepponen, Raimo E

2010-06-01

A compact (96 x 128 x 32 mm(3), 374 g), battery-powered, eight-channel electroencephalogram recording device with an integrated audio stimulation system and a wireless interface is presented. The recording device is capable of producing high-quality data, while the operating time is also reasonable for evoked potential studies. The effective measurement resolution is about 4 nV at 200 Hz sample rate, typical noise level is below 0.7 microV(rms) at 0.16-70 Hz, and the estimated operating time is 1.5 h. An embedded audio decoder circuit reads and plays wave sound files stored on a memory card. The activities are controlled by an 8 bit main control unit which allows accurate timing of the stimuli. The interstimulus interval jitter measured is less than 1 ms. Wireless communication is made through bluetooth and the data recorded are transmitted to an external personal computer (PC) interface in real time. The PC interface is implemented with LABVIEW and in addition to data acquisition it also allows online signal processing, data storage, and control of measurement activities such as contact impedance measurement, for example. The practical application of the device is demonstrated in mismatch negativity experiment with three test subjects.

A compact electroencephalogram recording device with integrated audio stimulation system

NASA Astrophysics Data System (ADS)

Paukkunen, Antti K. O.; Kurttio, Anttu A.; Leminen, Miika M.; Sepponen, Raimo E.

2010-06-01

A compact (96×128×32 mm3, 374 g), battery-powered, eight-channel electroencephalogram recording device with an integrated audio stimulation system and a wireless interface is presented. The recording device is capable of producing high-quality data, while the operating time is also reasonable for evoked potential studies. The effective measurement resolution is about 4 nV at 200 Hz sample rate, typical noise level is below 0.7 μVrms at 0.16-70 Hz, and the estimated operating time is 1.5 h. An embedded audio decoder circuit reads and plays wave sound files stored on a memory card. The activities are controlled by an 8 bit main control unit which allows accurate timing of the stimuli. The interstimulus interval jitter measured is less than 1 ms. Wireless communication is made through bluetooth and the data recorded are transmitted to an external personal computer (PC) interface in real time. The PC interface is implemented with LABVIEW® and in addition to data acquisition it also allows online signal processing, data storage, and control of measurement activities such as contact impedance measurement, for example. The practical application of the device is demonstrated in mismatch negativity experiment with three test subjects.

Generalizing Over Conditions by Combining the Multitrait Multimethod Matrix and the Representative Design of Experiments,

DTIC Science & Technology

1986-01-01

by Anderson (1985) was reported in an article by Posner (1969) in which the difference in reaction time to an 1 "identity match" and a "name match...shorter reaction time) for the identity match but after a two-second [inter-stimulus) interval this * * advantage has almost completely disappeared. This...of critical sentences in a story. It is similar, however, in that reaction time was also used to evaluate differences between response categories that

Impaired induction of long-term potentiation-like plasticity in patients with high-functioning autism and Asperger syndrome.

PubMed

Jung, Nikolai H; Janzarik, Wibke G; Delvendahl, Igor; Münchau, Alexander; Biscaldi, Monica; Mainberger, Florian; Bäumer, Tobias; Rauh, Reinhold; Mall, Volker

2013-01-01

We aimed to investigate the induction of long-term potentiation (LTP)-like plasticity by paired associative stimulation (PAS) in patients with high-functioning autism and Asperger syndrome (HFA/AS). PAS with an interstimulus interval between electrical and transcranial magnetic stimulation of 25 ms (PAS(25)) was performed in patients with HFA/AS (n=9; eight males, one female; mean age 17 y 11 mo, SD 4 y 5 mo) and in typically developing age-matched volunteers (n=9; five males, four females; mean age 22 y 4 mo, SD 5 y 2 mo). The amplitude of motor-evoked potentials was measured before PAS(25), immediately after stimulation, and 30 minutes and 60 minutes later. A PAS protocol adapted to individual N20 latency (PAS(N20+2)) was performed in six additional patients with HFA/AS. Short-interval intracortical inhibition was measured using paired-pulse stimulation. In contrast to the typically developing participants, the patients with HFA/AS did not show a significant increase in motor-evoked potentials after PAS(25). This finding could also be demonstrated after adaptation for N20 latency. Short-interval intracortical inhibition of patients with HFA/AS was normal compared with the comparison group and did not correlate with PAS effect. Our results show a significant impairment of LTP-like plasticity induced by PAS in individuals with HFA/AS compared with typically developing participants. This finding is in accordance with results from animal studies as well as human studies. Impaired LTP-like plasticity in patients with HFA/AS points towards reduced excitatory synaptic connectivity and deficits in sensory-motor integration in these patients. © The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.

Age-related change in fast adaptation mechanisms measured with the scotopic full-field ERG.

PubMed

Tillman, Megan A; Panorgias, Athanasios; Werner, John S

2016-06-01

To quantify the response dynamics of fast adaptation mechanisms of the scotopic ERG in younger and older adults using full-field m-sequence flash stimulation. Scotopic ERGs were measured for a series of flashes separated by 65 ms over a range of 260 ms in 16 younger (20-26, 22.2 ± 2.1; range mean ±1 SD) and 16 older (65-85, 71.2 ± 7) observers without retinal pathology. A short-wavelength (λ peak = 442 nm) LED was used for scotopic stimulation, and the flashes ranged from 0.0001 to 0.01 cd s m(-2). The complete binary kernel series was derived from the responses to the m-sequence flash stimulation, and the first- and second-order kernel responses were analyzed. The first-order kernel represented the response to a single, isolated flash, while the second-order kernels reflected the adapted flash responses that followed a single flash by one or more base intervals. B-wave amplitudes of the adapted flash responses were measured and plotted as a function of interstimulus interval to describe the recovery of the scotopic ERG. A linear function was fitted to the linear portion of the recovery curve, and the slope of the line was used to estimate the rate of fast adaptation recovery. The amplitudes of the isolated flash responses and rates of scotopic fast adaptation recovery were compared between the younger and older participants using a two-way ANOVA. The isolated flash responses and rates of recovery were found to be significantly lower in the older adults. However, there was no difference between the two age groups in response amplitude or recovery rate after correcting for age-related changes in the density of the ocular media. These results demonstrated that the rate of scotopic fast adaptation recovery of normal younger and older adults is similar when stimuli are equated for retinal illuminance.

Intracortical inhibition in the human trigeminal motor system.

PubMed

Jaberzadeh, Shapour; Pearce, Sophie L; Miles, Timothy S; Türker, Kemal S; Nordstrom, Michael A

2007-08-01

To investigate the presence and features of short-interval intracortical inhibition (SICI) in the human trigeminal motor system. Surface electromyogram (EMG) was recorded from left and right digastric muscles in 7 subjects, along with additional experiments with intramuscular EMG in 2 subjects. Focal transcranial magnetic stimulation (TMS) was used to activate the motor cortex of one hemisphere and elicit motor evoked potentials (MEPs) in digastric muscles on each side, at rest and while subjects activated the muscles at 10% maximal EMG. Paired or single TMS pulses were delivered in blocks of trials, while conditioning TMS intensity and interstimulus interval (ISI) were varied. At rest, paired TMS (3-ms ISI) with conditioning intensities 0.8-0.9x active motor threshold (TA) reduced the digastric MEP amplitude to a similar extent bilaterally. Conditioning at 0.5-0.7TA did not significantly reduce the MEP. MEP amplitude was reduced to a similar extent in both digastric muscles by ISIs between 1 and 4 ms (0.8TA). Voluntary bilateral activation of digastric muscles reduced the effectiveness of conditioning TMS compared to the resting state, with no differences between sides. The similarity of the responses in both digastric muscles was not due to EMG cross-talk (estimated to be approximately 10% in surface records and approximately 2% in intramuscular records), as the intramuscular records showed the same pattern as the surface records. The effects of paired-pulse TMS on digastric are similar to those reported for contralateral hand muscles, and are consistent with activation of SICI circuits in M1 by conditioning TMS. Our evidence further suggests that the corticomotor representations of left and right digastric muscles in M1 of a single hemisphere receive analogous inhibitory modulation from SICI circuits. SICI has been demonstrated in the face area of motor cortex controlling the trigeminal motor system in normal subjects. This method can be used to investigate abnormalities of SICI in movement disorders affecting the masticatory muscles in humans.

Functional difference in short- and long-latency interhemispheric inhibitions from active to resting hemisphere during a unilateral muscle contraction.

PubMed

Uehara, Kazumasa; Morishita, Takuya; Kubota, Shinji; Hirano, Masato; Funase, Kozo

2014-01-01

The aim of the present study was to investigate whether there is a functional difference in short-latency (SIHI) and long-latency (LIHI) interhemispheric inhibition from the active to the resting primary motor cortex (M1) with paired-pulse transcranial magnetic stimulation during a unilateral muscle contraction. In nine healthy right-handed participants, IHI was tested from the dominant to the nondominant M1 and vice versa under resting conditions or during performance of a sustained unilateral muscle contraction with the right or left first dorsal interosseous muscle at 10% and 30% maximum voluntary contraction. To obtain measurements of SIHI and LIHI, a conditioning stimulus (CS) was applied over the M1 contralateral to the muscle contraction, followed by a test stimulus over the M1 ipsilateral to the muscle contraction at short (10 ms) and long (40 ms) interstimulus intervals. We used four CS intensities to investigate SIHI and LIHI from the active to the resting M1 systematically. The amount of IHI during the unilateral muscle contractions showed a significant difference between SIHI and LIHI, but the amount of IHI during the resting condition did not. In particular, SIHI during the muscle contractions, but not LIHI, significantly increased with increase in CS intensity compared with the resting condition. Laterality of IHI was not detected in any of the experimental conditions. The present study provides novel evidence that a functional difference between SIHI and LIHI from the active to the resting M1 exists during unilateral muscle contractions.

Perception of non-verbal auditory stimuli in Italian dyslexic children.

PubMed

Cantiani, Chiara; Lorusso, Maria Luisa; Valnegri, Camilla; Molteni, Massimo

2010-01-01

Auditory temporal processing deficits have been proposed as the underlying cause of phonological difficulties in Developmental Dyslexia. The hypothesis was tested in a sample of 20 Italian dyslexic children aged 8-14, and 20 matched control children. Three tasks of auditory processing of non-verbal stimuli, involving discrimination and reproduction of sequences of rapidly presented short sounds were expressly created. Dyslexic subjects performed more poorly than control children, suggesting the presence of a deficit only partially influenced by the duration of the stimuli and of inter-stimulus intervals (ISIs).

Modeling phoneme perception. II: A model of stop consonant discrimination.

PubMed

van Hessen, A J; Schouten, M E

1992-10-01

Combining elements from two existing theories of speech sound discrimination, dual process theory (DPT) and trace context theory (TCT), a new theory, called phoneme perception theory, is proposed, consisting of a long-term phoneme memory, a context-coding memory, and a trace memory, each with its own time constants. This theory is tested by means of stop-consonant discrimination data in which interstimulus interval (ISI; values of 100, 300, and 2000 ms) is an important variable. It is shown that discrimination in which labeling plays an important part (2IFC and AX between category) benefits from increased ISI, whereas discrimination in which only sensory traces are compared (AX within category), decreases with increasing ISI. The theory is also tested on speech discrimination data from the literature in which ISI is a variable [Pisoni, J. Acoust. Soc. Am. 36, 277-282 (1964); Cowan and Morse, J. Acoust. Soc. Am. 79, 500-507 (1986)]. It is concluded that the number of parameters in trace context theory is not sufficient to account for most speech-sound discrimination data and that a few additional assumptions are needed, such as a form of sublabeling, in which subjects encode the quality of a stimulus as a member of a category, and which requires processing time.

Augmentation of the Sympathetic Skin Response after Electrical Train Stimuli

PubMed Central

Emmer, A.; Mangalo, S.; Kornhuber, M. E.

2012-01-01

It is well known that the size of the sympathetic skin response (SSR) depends on the stimulus strength. In the present investigation train stimuli (TS) were employed to study the behavior of the SSR when recruited above the usual level. The SSR was obtained in healthy human subjects over the palm of the hand after supramaximal single stimuli (SS) and trains of three (TS; interstimulus interval 3 ms) over the ipsilateral superficial radial nerve in 15 healthy volunteers. Ipsilateral to the stimulus site SSR amplitudes were 5.7 ± 5.3 (SS) and 7.7 ± 5.9 mV (TS; p < 0.001), and contralateral 6.3 ± 6.3 (SS) and 7.2 ± 4.9 mV (TS; not significant). The relative gain in amplitude after TS vs. SS was negatively correlated with the SSR amplitude after SS ipsilateral (p < 0.0005) and contralateral to the stimulus site (p < 0.01). The increase in SSR amplitudes after TS compared with SS is in line with temporal summation of the excitatory synaptic input in neurons generating the SSR. Driving the SSR with TS is of possible relevance for the investigation of disorders of the peripheral or central autonomic nervous system. PMID:23115555

flexTMS--a novel repetitive transcranial magnetic stimulation device with freely programmable stimulus currents.

PubMed

Gattinger, Norbert; Moessnang, Georg; Gleich, Bernhard

2012-07-01

Transcranial magnetic stimulation (TMS) is able to noninvasively excite neuronal populations due to brief magnetic field pulses. The efficiency and the characteristics of stimulation pulse shapes influence the physiological effect of TMS. However, commercial devices allow only a minimum of control of different pulse shapes. Basically, just sinusoidal and monophasic pulse shapes with fixed pulse widths are available. Only few research groups work on TMS devices with controllable pulse parameters such as pulse shape or pulse width. We describe a novel TMS device with a full-bridge circuit topology incorporating four insulated-gate bipolar transistor (IGBT) modules and one energy storage capacitor to generate arbitrary waveforms. This flexible TMS (flexTMS ) device can generate magnetic pulses which can be adjusted with respect to pulse width, polarity, and intensity. Furthermore, the equipment allows us to set paired pulses with a variable interstimulus interval (ISI) from 0 to 20 ms with a step size of 10  μs. All user-defined pulses can be applied continually with repetition rates up to 30 pulses per second (pps) or, respectively, up to 100 pps in theta burst mode. Offering this variety of flexibility, flexTMS will allow the enhancement of existing TMS paradigms and novel research applications.

Transformations of visual memory induced by implied motions of pattern elements.

PubMed

Finke, R A; Freyd, J J

1985-10-01

Four experiments measured distortions in short-term visual memory induced by displays depicting independent translations of the elements of a pattern. In each experiment, observers saw a sequence of 4 dot patterns and were instructed to remember the third pattern and to compare it with the fourth. The first three patterns depicted translations of the dots in consistent, but separate directions. Error rates and reaction times for rejecting the fourth pattern as different from the third were substantially higher when the dots in that pattern were displaced slightly forward, in the same directions as the implied motions, compared with when the dots were displaced in the opposite, backward directions. These effects showed little variation across interstimulus intervals ranging from 250 to 2,000 ms, and did not depend on whether the displays gave rise to visual apparent motion. However, they were eliminated when the dots in the fourth pattern were displaced by larger amounts in each direction, corresponding to the dot positions in the next and previous patterns in the same inducing sequence. These findings extend our initial report of the phenomenon of "representational momentum" (Freyd & Finke, 1984a), and help to rule out alternatives to the proposal that visual memories tend to undergo, at least to some extent, the transformations implied by a prior sequence of observed events.

Blink reflex recovery cycle to differentiate Progressive Supranuclear Palsy from Cortico-basal syndrome.

PubMed

Sciacca, Giorgia; Nicoletti, Alessandra; Mostile, Giovanni; Luca, Antonina; Raciti, Loredana; Dibilio, Valeria; Drago, Filippo; Salomone, Salvatore; Zappia, Mario

2018-05-13

Progressive Supranuclear Palsy (PSP) and Cortico-basal syndrome (CBS) may share similar clinical findings and peculiar tests to distinguish between the two disorders could be useful. We evaluated Blink Reflex (BR) and R2 Blink Reflex Recovery Cycle (R2BRRC), determining diagnostic sensitivity, specificity, positive and negative predictive value of R2BRRC in differentiating PSP from CBS patients. This was a prospective data collection study investigating BR and R2BRRC at interstimulus intervals (ISIs) of 100, 150, 200, 300, 400, 500, 750 ms in 12 PSP patients, 8 CBS patients, and 10 controls. Patients with PSP have earlier recruitment of R2BRRC as compared to patients with CBS (ISI 100: p=0.002; ISI 150: p<0.001; ISI 200: p<0.001; ISI 300: p=0.02) and controls (ISI 100: p<0.001; ISI 150: p<0.001; ISI 200: p<0.001; ISI 300: p=0.004). The presence of an early recovery of the R2 differentiated PSP from CBS with specificity and sensitivity of 87.5% and 91.7% respectively. R2BRRC curve might be considered a useful tool in differentiating PSP from CBS patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The influence of prior experience and expected timing on vibrotactile discrimination

PubMed Central

Karim, Muhsin; Harris, Justin A.; Langdon, Angela; Breakspear, Michael

2013-01-01

Vibrotactile discrimination tasks involve perceptual judgements on stimulus pairs separated by a brief interstimulus interval (ISI). Despite their apparent simplicity, decision making during these tasks is biased by prior experience in a manner that is not well understood. A striking example is when participants perform well on trials where the first stimulus is closer to the mean of the stimulus-set than the second stimulus, and perform comparatively poorly when the first stimulus is further from the stimulus mean. This “time-order effect” suggests that participants implicitly encode the mean of the stimulus-set and use this internal standard to bias decisions on any given trial. For relatively short ISIs, the magnitude of the time-order effect typically increases with the distance of the first stimulus from the global mean. Working from the premise that the time-order effect reflects the loss of precision in working memory representations, we predicted that the influence of the time-order effect, and this superimposed “distance” effect, would monotonically increase for trials with longer ISIs. However, by varying the ISI across four intervals (300, 600, 1200, and 2400 ms) we instead found a complex, non-linear dependence of the time-order effect on both the ISI and the distance, with the time-order effect being paradoxically stronger at short ISIs. We also found that this relationship depended strongly on participants' prior experience of the ISI (from previous task titration). The time-order effect not only depends on participants' expectations concerning the distribution of stimuli, but also on the expected timing of the trials. PMID:24399927

Modulation of somatosensory evoked potentials during wake-sleep states and spike-wave discharges in the rat.

PubMed

Shaw, Fu-Zen; Lee, Su-Ying; Chiu, Ted H

2006-03-01

To clarify the cortical evoked responses in the primary somatosensory cortex of the rat under states of waking, slow-wave sleep (SWS), paradoxical sleep (PS), and spike-wave discharges (SWDs), which are associated with absence seizure. Somatosensory evoked potentials (SEPs) in response to single- and paired-pulse stimulations under waking, SWS, PS, and SWDs were compared. SEPs to a single-pulse stimulus with regard to cortical spikes of sleep spindles and SWDs were also evaluated. Twenty Long Evans rats. Single- and paired-pulse innocuous electrical stimulations were applied to the tail of rats with chronically implanted electrodes in the primary somatosensory cortex and neck muscle under waking, SWS, PS, and SWDs. SEPs displayed distinct patterns under waking/PS and SWS/SWDs. The short-latency P1-N1 wave of the SEP was severely impeded during SWDs but not in other states. Reduction of the P1-N1 magnitude to the second stimulus of the paired-pulse stimulus for interstimulus intervals of < or = 300 milliseconds appeared in waking and PS states, but the decrease occurred only at particular interstimulus intervals under SWS. Interestingly, augmentation was found under SWDs. Moreover, cyclic augmentation of the P1-N1 magnitude was associated with spindle spikes, but cyclic reduction was observed with SWD spikes. Changes in SEPs are not only behavior dependent, but also phase locked onto ongoing brain activity. Distinct short-term plasticity of SEPs during sleep spindles or SWDs may merit further studies for seizure control and tactile information processing.

Paired-pulse flash-visual evoked potentials: new methods revive an old test.

PubMed

Cantello, Roberto; Strigaro, Gionata; Prandi, Paolo; Varrasi, Claudia; Mula, Marco; Monaco, Francesco

2011-08-01

We aimed at reviving with modern technology the paired flash-visual evoked potential (F-VEP) testing of the visual system excitability. In the 1960s, methodological problems hindered this test, which was expected to provide important physiologic information. We studied 22 consenting healthy subjects (10 men). We recorded F-VEPs from electrodes over occipital and central brain regions. We delivered single flashes, mixed at random to flash pairs at the interstimulus interval (ISI) of 333, 125, 62.5, 50, 33, and 16.5 ms, (i.e. an internal frequency (IF) of 3, 8, 16, 20, 30, and 60 Hz). Recordings were performed with the subject's eyes closed and opened. The F-VEP was split into a "main complex" and an "afterdischarge", which we analyzed statistically in relation to the eye state (closed or open) and to the changes due to paired stimulation. The eye state affected the single F-VEP size, latency and shape significantly (p<0.05). On paired stimulation, the test (second) F-VEP exhibited significant (p<0.05), ISI-dependent size changes, such as a progressive decrease for ISIs from 62.5 to 16.5 ms (IFs of 16-60 Hz), whose timing/amount varied significantly (p<0.05) according to the eye state and to the F-VEP epoch considered. Suppression of the test F-VEP was never complete, even for the shortest ISI (ISI=16.5 ms, IF=60 Hz). The eye state (closed or open) must be considered meticulously when studying F-VEPs. F-VEP changes on paired stimulation express neural inhibition within the visual system, which can be depicted as ISI-dependent curves. Modern equipment and simplified measures render this an easy test, with statistical validity, providing specific information on the excitability properties of the visual system. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

TMS activation of interhemispheric pathways between the posterior parietal cortex and the contralateral motor cortex

PubMed Central

Koch, Giacomo; Ruge, Diane; Cheeran, Binith; Fernandez Del Olmo, Miguel; Pecchioli, Cristiano; Marconi, Barbara; Versace, Viviana; Lo Gerfo, Emanuele; Torriero, Sara; Oliveri, Massimiliano; Caltagirone, Carlo; Rothwell, John C

2009-01-01

Using a twin coil transcranial magnetic stimulation (tc-TMS) approach we have previously demonstrated that facilitation may be detected in the primary motor cortex (M1) following stimulation over the ipsilateral caudal intraparietal sulcus (cIPS). Here we tested the interhemispheric interactions between the IPS and the contralateral motor cortex (M1). We found that conditioning the right cIPS facilitated contralateral M1 when the conditioning stimulus had an intensity of 90% resting motor threshold (RMT) but not at 70% or 110% RMT. Facilitation was maximal when the interstimulus interval (ISI) between cIPS and M1 was 6 or 12 ms. These facilitatory effects were mediated by interactions with specific groups of interneurons in the contralateral M1. In fact, short intracortical inhibition (SICI) was reduced following cIPS stimulation. Moreover, additional comparison of facilitation of responses evoked by anterior–posterior versus posterior–anterior stimulation of M1 suggested that facilitation was more effective on early I1/I2 circuits than on I3 circuits. In contrast to these effects, stimulation of anterior IPS (aIPS) at 90% RMT induced inhibition, instead of facilitation, of contralateral M1 at ISIs of 10–12 ms. Finally, we found similar facilitation between left cIPS and right M1 although the conditioning stimuli had to have a higher intensity compared with stimulation of right cIPS (110% instead of 90% RMT). These findings demonstrate that different subregions of the posterior parietal cortex (PPC) in humans exert both facilitatory and inhibitory effects towards the contralateral primary motor cortex. These corticocortical projections could contribute to a variety of motor tasks such as bilateral manual coordination, movement planning in space and grasping. PMID:19622612

Cortico-cortical and motor evoked potentials to single and paired-pulse stimuli: An exploratory transcranial magnetic and intracranial electric brain stimulation study.

PubMed

Boulogne, Sébastien; Andre-Obadia, Nathalie; Kimiskidis, Vasilios K; Ryvlin, Philippe; Rheims, Sylvain

2016-11-01

Paired-pulse (PP) paradigms are commonly employed to assess in vivo cortical excitability using transcranial magnetic stimulation (TMS) to stimulate the primary motor cortex and modulate the induced motor evoked potential (MEP). Single-pulse cortical direct electrical stimulation (DES) during intracerebral EEG monitoring allows the investigation of brain connectivity by eliciting cortico-cortical evoked potentials (CCEPs). However, PP paradigm using intracerebral DES has rarely been reported and has never been previously compared with TMS. The work was intended (i) to verify that the well-established modulations of MEPs following PP TMS remain similar using DES in the motor cortex, and (ii) to evaluate if a similar pattern could be observed in distant cortico-cortical connections through modulations of CCEP. Three patients undergoing intracerebral EEG monitoring with electrodes implanted in the central region were studied. Single-pulse DES (1-3 mA, 1 ms, 0.2 Hz) and PP DES using six interstimulus intervals (5, 15, 30, 50, 100, and 200 ms) in the motor cortex with concomitant recording of CCEPs and MEPs in contralateral muscles were performed. Finally, a navigated PP TMS session targeted the intracranial stimulation site to record TMS-induced MEPs in two patients. MEP modulations elicited by PP intracerebral DES proved similar among the three patients and to those obtained by PP TMS. CCEP modulations elicited by PP intracerebral DES usually showed a pattern comparable to that of MEP, although a different pattern could be observed occasionally. PP intracerebral DES seems to involve excitatory and inhibitory mechanisms similar to PP TMS and allows the recording of intracortical inhibition and facilitation modulation on cortico-cortical connections. Hum Brain Mapp 37:3767-3778, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Modulation of motor cortex excitability by paired peripheral and transcranial magnetic stimulation.

PubMed

Kumru, Hatice; Albu, Sergiu; Rothwell, John; Leon, Daniel; Flores, Cecilia; Opisso, Eloy; Tormos, Josep Maria; Valls-Sole, Josep

2017-10-01

Repetitive application of peripheral electrical stimuli paired with transcranial magnetic stimulation (rTMS) of M1 cortex at low frequency, known as paired associative stimulation (PAS), is an effective method to induce motor cortex plasticity in humans. Here we investigated the effects of repetitive peripheral magnetic stimulation (rPMS) combined with low frequency rTMS ('magnetic-PAS') on intracortical and corticospinal excitability and whether those changes were widespread or circumscribed to the cortical area controlling the stimulated muscle. Eleven healthy subjects underwent three 10min stimulation sessions: 10HzrPMS alone, applied in trains of 5 stimuli every 10s (60 trains) on the extensor carpi radialis (ECR) muscle; rTMS alone at an intensity 120% of ECR threshold, applied over motor cortex of ECR and at a frequency of 0.1Hz (60 stimuli) and magnetic PAS, i.e., paired rPMS and rTMS. We recorded motor evoked potentials (MEPs) from ECR and first dorsal interosseous (FDI) muscles. We measured resting motor threshold, motor evoked potentials (MEP) amplitude at 120% of RMT, short intracortical inhibition (SICI) at interstimulus interval (ISI) of 2ms and intracortical facilitation (ICF) at an ISI of 15ms before and immediately after each intervention. Magnetic-PAS , but not rTMS or rPMS applied separately, increased MEP amplitude and reduced short intracortical inhibition in ECR but not in FDI muscle. Magnetic-PAS can increase corticospinal excitability and reduce intracortical inhibition. The effects may be specific for the area of cortical representation of the stimulated muscle. Application of magnetic-PAS might be relevant for motor rehabilitation. Copyright © 2017 International Federation of Clinical Neurophysiology. All rights reserved.

The influence of expertise and of physical complexity on visual short-term memory consolidation.

PubMed

Sun, Huiming; Zimmer, Hubert D; Fu, Xiaolan

2011-04-01

We investigated whether the expertise of a perceiver and the physical complexity of a stimulus influence consolidation of visual short-term memory (VSTM) in a S1-S2 (Stimulus 1-Stimulus 2) change detection task. Consolidation is assumed to make transient perceptual representations in VSTM more durable, and it is investigated by postexposure of a mask shortly after offset of the perceived stimulus (S1; 17 to 483 ms). We presented colours, Chinese characters, pseudocharacters, and novel symbols to novices (Germans) or experts of Chinese language (Chinese readers). Physical complexity was manipulated by the number of strokes. Unfamiliar material was remembered worse than familiar material (Experiments 1, 2, and 3). For novices the absolute VSTM performance was better for physically simple than for complex material, whereas for experts the complexity did not matter-Chinese readers memorized Chinese characters (Experiment 3). Articulatory suppression did not change these effects (Experiment 2). We always observed a strong effect of SOA, but this effect was influenced neither by physical complexity nor by expertise; only the length of the interstimulus interval between S1 and the mask was relevant. This was observed even with short stimulus onset asynchrony (SOA) of 100 ms (Experiment 2) and in comparing colours and characters (Experiment 5). However, masks impaired memory if they were presented at the locations of the to-be-memorized items, but not beside them-that is, interference was location-based (Experiment 6). We explain the effect of SOA by the assumption that it takes time to stop encoding of information presented at item locations with the offset of S1. The increasing resistance against interference by irrelevant material appears as consolidation of S1.

Early ERP Signature of Hearing Impairment in Visual Rhyme Judgment

PubMed Central

Classon, Elisabet; Rudner, Mary; Johansson, Mikael; Rönnberg, Jerker

2013-01-01

Postlingually acquired hearing impairment (HI) is associated with changes in the representation of sound in semantic long-term memory. An indication of this is the lower performance on visual rhyme judgment tasks in conditions where phonological and orthographic cues mismatch, requiring high reliance on phonological representations. In this study, event-related potentials (ERPs) were used for the first time to investigate the neural correlates of phonological processing in visual rhyme judgments in participants with acquired HI and normal hearing (NH). Rhyme task word pairs rhymed or not and had matching or mismatching orthography. In addition, the inter-stimulus interval (ISI) was manipulated to be either long (800 ms) or short (50 ms). Long ISIs allow for engagement of explicit, top-down processes, while short ISIs limit the involvement of such mechanisms. We hypothesized lower behavioral performance and N400 and N2 deviations in HI in the mismatching rhyme judgment conditions, particularly in short ISI. However, the results showed a different pattern. As expected, behavioral performance in the mismatch conditions was lower in HI than in NH in short ISI, but ERPs did not differ across groups. In contrast, HI performed on a par with NH in long ISI. Further, HI, but not NH, showed an amplified N2-like response in the non-rhyming, orthographically mismatching condition in long ISI. This was also the rhyme condition in which participants in both groups benefited the most from the possibility to engage top-down processes afforded with the longer ISI. Taken together, these results indicate an early ERP signature of HI in this challenging phonological task, likely reflecting use of a compensatory strategy. This strategy is suggested to involve increased reliance on explicit mechanisms such as articulatory recoding and grapheme-to-phoneme conversion. PMID:23653613

Neurophysiological and Behavioral Responses of Mandarin Lexical Tone Processing

PubMed Central

Yu, Yan H.; Shafer, Valerie L.; Sussman, Elyse S.

2017-01-01

Language experience enhances discrimination of speech contrasts at a behavioral- perceptual level, as well as at a pre-attentive level, as indexed by event-related potential (ERP) mismatch negativity (MMN) responses. The enhanced sensitivity could be the result of changes in acoustic resolution and/or long-term memory representations of the relevant information in the auditory cortex. To examine these possibilities, we used a short (ca. 600 ms) vs. long (ca. 2,600 ms) interstimulus interval (ISI) in a passive, oddball discrimination task while obtaining ERPs. These ISI differences were used to test whether cross-linguistic differences in processing Mandarin lexical tone are a function of differences in acoustic resolution and/or differences in long-term memory representations. Bisyllabic nonword tokens that differed in lexical tone categories were presented using a passive listening multiple oddball paradigm. Behavioral discrimination and identification data were also collected. The ERP results revealed robust MMNs to both easy and difficult lexical tone differences for both groups at short ISIs. At long ISIs, there was either no change or an enhanced MMN amplitude for the Mandarin group, but reduced MMN amplitude for the English group. In addition, the Mandarin listeners showed a larger late negativity (LN) discriminative response than the English listeners for lexical tone contrasts in the long ISI condition. Mandarin speakers outperformed English speakers in the behavioral tasks, especially under the long ISI conditions with the more similar lexical tone pair. These results suggest that the acoustic correlates of lexical tone are fairly robust and easily discriminated at short ISIs, when the auditory sensory memory trace is strong. At longer ISIs beyond 2.5 s language-specific experience is necessary for robust discrimination. PMID:28321179

Oscillatory support for rapid frequency change processing in infants.

PubMed

Musacchia, Gabriella; Choudhury, Naseem A; Ortiz-Mantilla, Silvia; Realpe-Bonilla, Teresa; Roesler, Cynthia P; Benasich, April A

2013-11-01

Rapid auditory processing and auditory change detection abilities are crucial aspects of speech and language development, particularly in the first year of life. Animal models and adult studies suggest that oscillatory synchrony, and in particular low-frequency oscillations play key roles in this process. We hypothesize that infant perception of rapid pitch and timing changes is mediated, at least in part, by oscillatory mechanisms. Using event-related potentials (ERPs), source localization and time-frequency analysis of event-related oscillations (EROs), we examined the neural substrates of rapid auditory processing in 4-month-olds. During a standard oddball paradigm, infants listened to tone pairs with invariant standard (STD, 800-800 Hz) and variant deviant (DEV, 800-1200 Hz) pitch. STD and DEV tone pairs were first presented in a block with a short inter-stimulus interval (ISI) (Rapid Rate: 70 ms ISI), followed by a block of stimuli with a longer ISI (Control Rate: 300 ms ISI). Results showed greater ERP peak amplitude in response to the DEV tone in both conditions and later and larger peaks during Rapid Rate presentation, compared to the Control condition. Sources of neural activity, localized to right and left auditory regions, showed larger and faster activation in the right hemisphere for both rate conditions. Time-frequency analysis of the source activity revealed clusters of theta band enhancement to the DEV tone in right auditory cortex for both conditions. Left auditory activity was enhanced only during Rapid Rate presentation. These data suggest that local low-frequency oscillatory synchrony underlies rapid processing and can robustly index auditory perception in young infants. Furthermore, left hemisphere recruitment during rapid frequency change discrimination suggests a difference in the spectral and temporal resolution of right and left hemispheres at a very young age. © 2013 Elsevier Ltd. All rights reserved.

The Amount of Time Dilation for Visual Flickers Corresponds to the Amount of Neural Entrainments Measured by EEG.

PubMed

Hashimoto, Yuki; Yotsumoto, Yuko

2018-01-01

The neural basis of time perception has long attracted the interests of researchers. Recently, a conceptual model consisting of neural oscillators was proposed and validated by behavioral experiments that measured the dilated duration in perception of a flickering stimulus (Hashimoto and Yotsumoto, 2015). The model proposed that flickering stimuli cause neural entrainment of oscillators, resulting in dilated time perception. In this study, we examined the oscillator-based model of time perception, by collecting electroencephalography (EEG) data during an interval-timing task. Initially, subjects observed a stimulus, either flickering at 10-Hz or constantly illuminated. The subjects then reproduced the duration of the stimulus by pressing a button. As reported in previous studies, the subjects reproduced 1.22 times longer durations for flickering stimuli than for continuously illuminated stimuli. The event-related potential (ERP) during the observation of a flicker oscillated at 10 Hz, reflecting the 10-Hz neural activity phase-locked to the flicker. Importantly, the longer reproduced duration was associated with a larger amplitude of the 10-Hz ERP component during the inter-stimulus interval, as well as during the presentation of the flicker. The correlation between the reproduced duration and the 10-Hz oscillation during the inter-stimulus interval suggested that the flicker-induced neural entrainment affected time dilation. While the 10-Hz flickering stimuli induced phase-locked entrainments at 10 Hz, we also observed event-related desynchronizations of spontaneous neural oscillations in the alpha-frequency range. These could be attributed to the activation of excitatory neurons while observing the flicker stimuli. In addition, neural activity at approximately the alpha frequency increased during the reproduction phase, indicating that flicker-induced neural entrainment persisted even after the offset of the flicker. In summary, our results suggest that the duration perception is mediated by neural oscillations, and that time dilation induced by flickering visual stimuli can be attributed to neural entrainment.

The role of interstimulus interval and "Stimulus-type" in prepotent response inhibition abilities in people with ASD: A quantitative and qualitative review.

PubMed

Kuiper, Marieke W M; Verhoeven, Elisabeth W M; Geurts, Hilde M

2016-11-01

Autism spectrum disorders (ASD) are associated with prepotent response inhibition difficulties. However, the large variation between studies suggests that understudied factors, such as interstimulus interval (ISI) and "stimulus-type" (both hypothesized proxies of stressors influencing arousal), might influence the inhibitory abilities of people with ASD. Using meta-analysis, we tested whether differences in prepotent response inhibition between people with and without ASD was influenced by ISI. There was not enough variation in "stimulus-type" between the studies to include it as a moderator. Thirty-seven studies met inclusion criteria, with a combined sample size of 950 people with ASD and 966 typically developing controls. Additionally, a qualitative review including studies comparing a neutral and an arousing condition in one experiment was performed to examine whether fast ISI or specific arousing stimuli directly influence prepotent response inhibition. The meta-analysis indicated that ISI was not a relevant moderator. The qualitative review showed that ISI and "stimulus-type" had the same effect for both groups. Although all studies regarding ISI indicated that fast ISI worsened performance, different types of stimuli had either a positive or a negative influence. This could suggest that distinctive stimuli might affect arousal differently. While we replicated the inhibition difficulties in people with ASD (g = .51), our results do not show strong ASD-specific effects of ISI or "stimulus-type" on inhibition. Nonetheless, ISI and "stimulus-type" do seem to influence performance. Future research focusing on potential underlying factors (e.g., baseline physiological arousal) is needed to examine why this is the case. Autism Res 2016, 9: 1124-1141. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

SLOWLY REPEATED EVOKED PAIN (SREP) AS A MARKER OF CENTRAL SENSITIZATION IN FIBROMYALGIA: DIAGNOSTIC ACCURACY AND RELIABILITY IN COMPARISON WITH TEMPORAL SUMMATION OF PAIN.

PubMed

de la Coba, Pablo; Bruehl, Stephen; Gálvez-Sánchez, Carmen María; Reyes Del Paso, Gustavo A

2018-05-01

This study examined the diagnostic accuracy and test-retest reliability of a novel dynamic evoked pain protocol (slowly repeated evoked pain; SREP) compared to temporal summation of pain (TSP), a standard index of central sensitization. Thirty-five fibromyalgia (FM) and 30 rheumatoid arthritis (RA) patients completed, in pseudorandomized order, a standard mechanical TSP protocol (10 stimuli of 1s duration at the thenar eminence using a 300g monofilament with 1s interstimulus interval) and the SREP protocol (9 suprathreshold pressure stimuli of 5s duration applied to the fingernail with a 30s interstimulus interval). In order to evaluate reliability for both protocols, they were repeated in a second session 4-7 days later. Evidence for significant pain sensitization over trials (increasing pain intensity ratings) was observed for SREP in FM (p<.001) but not in RA (p=.35), whereas significant sensitization was observed in both diagnostic groups for the TSP protocol (p's<.008). Compared to TSP, SREP demonstrated higher overall diagnostic accuracy (87.7% vs. 64.6%), greater sensitivity (0.89 vs. 0.57), and greater specificity (0.87 vs. 0.73) in discriminating between FM and RA patients. Test-retest reliability of SREP sensitization was good in FM (ICCs: 0.80), and moderate in RA (ICC: 0.68). SREP seems to be a dynamic evoked pain index tapping into pain sensitization that allows for greater diagnostic accuracy in identifying FM patients compared to a standard TSP protocol. Further research is needed to study mechanisms underlying SREP and the potential utility of adding SREP to standard pain evaluation protocols.

Modulation of soleus corticospinal excitability during Achilles tendon vibration.

PubMed

Lapole, Thomas; Temesi, John; Arnal, Pierrick J; Gimenez, Philippe; Petitjean, Michel; Millet, Guillaume Y

2015-09-01

Soleus (SOL) corticospinal excitability has been reported to increase during Achilles tendon vibration. The aim of the present study was to further investigate SOL corticospinal excitability and elucidate the changes to intracortical mechanisms during Achilles tendon vibration. Motor-evoked potentials (MEPs) were elicited in the SOL by transcranial magnetic stimulation (TMS) of the corresponding motor cortical area of the leg with and without 50-Hz Achilles tendon vibration. SOL input-output curves were determined. Paired-pulse protocols were also performed to investigate short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) by conditioning test TMS pulses with sub-threshold TMS pulses at inter-stimulus intervals of 3 and 13 ms, respectively. During Achilles tendon vibration, motor threshold was lower than in the control condition (43 ± 13 vs. 49 ± 11 % of maximal stimulator output; p = 0.008). Input-output curves were also influenced by vibration, i.e. there was increased maximal MEP amplitude (0.694 ± 0.347 vs. 0.268 ± 0.167 mV; p < 0.001), decreased TMS intensity to elicit a MEP of half the maximal MEP amplitude (100 ± 13 vs. 109 ± 9 % motor threshold; p = 0.009) and a strong tendency for decreased slope constant (0.076 ± 0.04 vs. 0.117 ± 0.04; p = 0.068). Vibration reduced ICF (98 ± 61 vs. 170 ± 105 % of test MEP amplitude; p = 0.05), but had no effect on SICI (53 ± 26 vs. 48 ± 22 % of test MEP amplitude; p = 0.68). The present results further document the increased vibration-induced corticospinal excitability in the soleus muscle and suggest that this increase is not mediated by changes in SICI or ICF.

Normalization of sensorimotor integration by repetitive transcranial magnetic stimulation in cervical dystonia.

PubMed

Zittel, S; Helmich, R C; Demiralay, C; Münchau, A; Bäumer, T

2015-08-01

Previous studies indicated that sensorimotor integration and plasticity of the sensorimotor system are impaired in dystonia patients. We investigated motor evoked potential amplitudes and short latency afferent inhibition to examine corticospinal excitability and cortical sensorimotor integration, before and after inhibitory 1 Hz repetitive transcranial magnetic stimulation over primary sensory and primary motor cortex in patients with cervical dystonia (n = 12). Motor evoked potentials were recorded from the right first dorsal interosseous muscle after application of unconditioned transcranial magnetic test stimuli and after previous conditioning electrical stimulation of the right index finger at short interstimulus intervals of 25, 30 and 40 ms. Results were compared to a group of healthy age-matched controls. At baseline, motor evoked potential amplitudes did not differ between groups. Short latency afferent inhibition was reduced in cervical dystonia patients compared to healthy controls. Inhibitory 1 Hz sensory cortex repetitive transcranial magnetic stimulation but not motor cortex repetitive transcranial magnetic stimulation increased motor evoked potential amplitudes in cervical dystonia patients. Additionally, both 1 Hz repetitive transcranial magnetic stimulation over primary sensory and primary motor cortex normalized short latency afferent inhibition in these patients. In healthy subjects, sensory repetitive transcranial magnetic stimulation had no influence on motor evoked potential amplitudes and short latency afferent inhibition. Plasticity of sensorimotor circuits is altered in cervical dystonia patients.

Abnormal experimentally- and behaviorally-induced LTP-like plasticity in focal hand dystonia.

PubMed

Belvisi, Daniele; Suppa, Antonio; Marsili, Luca; Di Stasio, Flavio; Parvez, Ahmad Khandker; Agostino, Rocco; Fabbrini, Giovanni; Berardelli, Alfredo

2013-02-01

Idiopathic focal hand dystonia (FHD) arises from abnormal plasticity in the primary motor cortex (M1) possibly reflecting abnormal sensori-motor integration processes. In this transcranial magnetic stimulation (TMS) study in FHD, we evaluated changes in motor evoked potentials (MEPs) after intermittent theta burst stimulation (iTBS) and paired associative stimulation (PAS), techniques that elicit different forms of experimentally-induced long-term potentiation (LTP)-like plasticity in M1. We also examined behaviorally-induced LTP-like plasticity as reflected by early motor learning of a simple motor task. We studied 14 patients with FHD and 14 healthy subjects. MEPs were recorded before and after iTBS and PAS at the 25 ms interstimulus interval (PAS(25)) in separate sessions. Subjects did a simple motor task entailing repetitive index finger abductions. To measure early motor learning we tested practice-related improvement in peak velocity and peak acceleration. In FHD patients iTBS failed to elicit the expected MEP changes and PAS(25) induced abnormally increased MEPs in target and non-target muscles. In the experiment testing early motor learning, patients lacked the expected practice-related changes in kinematic variables. In FHD, the degree of early motor learning correlated with patients' clinical features. We conclude that experimentally-induced (iTBS and PAS) and behaviorally-induced LTP-like plasticity are both altered in FHD. Copyright © 2012 Elsevier Inc. All rights reserved.

Different SEP recovery cycle in adolescent migraineurs with exploding or imploding pain.

PubMed

Iacovelli, Elisa; Tarantino, Samuela; Capuano, Alessandro; De Luca, Massimiliano; De Ranieri, Cristiana; Vigevano, Federico; Arendt-Nielsen, Lars; Valeriani, Massimiliano

2013-01-01

Our aim was to investigate whether migraine adolescents with pain directed inside (imploding pain--IP) and outside (exploding pain--EP) the head may have different levels of cortical excitability underlying their migraineous syndrome. Ten migraine children referring prevalent EP (mean age 14.5 ± 1.4 years, 3 girls, 7 boys), 10 patients with IP (mean age 14.1 ± 2.2 years, 4 girls, 6 boys), and 13 control subjects (mean age 13 ± 1.8 years, 6 males, 7 females) participated to the study. The recovery cycle of the somatosensory evoked potentials to electrical median nerve stimuli at interstimulus intervals of 5, 20, and 40 ms was measured. Anger expression, anxiety, and somatic concerns were investigated in migraine patients. Overall, SEP recovery cycle was shorter in migraineurs than in healthy controls. The recovery cycle of the frontal N30 SEP component was significantly shorter in IP than in EP patients. While among the EP patients those with faster N30 recovery cycle had higher Trait-Anger score, the opposite was found among the IP patients. Our results suggest that the inhibitory mechanisms within the somatosensory cortex are more impaired in IP than in EP migraine adolescents. The pathophysiological difference between IP and EP migraineurs was strengthened also by the opposite correlations between the brain excitability and the anger expression. Copyright © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Subliminal words durably affect neuronal activity.

PubMed

Gaillard, Raphaël; Cohen, Laurent; Adam, Claude; Clemenceau, Stéphane; Hasboun, Dominique; Baulac, Michel; Willer, Jean-Claude; Dehaene, Stanislas; Naccache, Lionel

2007-10-08

Unconscious mental representations elicited by subliminal stimuli are marked by their fleeting lifetimes, usually below 1 s. Can such evanescent subliminal stimuli, nevertheless, lead to long-lasting learning? To date, evidence suggesting a long-term influence of briefly perceived stimuli on behaviour or brain activity is scarce and questionable. In this study, we used intracranial recordings to provide the first direct demonstration that unconsciously perceived subliminal words could exert long-lasting effects on neuronal signals. When repeating subliminal words over long interstimulus intervals, we observed electrophysiological repetition effects. These unconscious repetition effects suggest that the single presentation of a masked word can durably affect neural architecture.

Retention interval affects visual short-term memory encoding.

PubMed

Bankó, Eva M; Vidnyánszky, Zoltán

2010-03-01

Humans can efficiently store fine-detailed facial emotional information in visual short-term memory for several seconds. However, an unresolved question is whether the same neural mechanisms underlie high-fidelity short-term memory for emotional expressions at different retention intervals. Here we show that retention interval affects the neural processes of short-term memory encoding using a delayed facial emotion discrimination task. The early sensory P100 component of the event-related potentials (ERP) was larger in the 1-s interstimulus interval (ISI) condition than in the 6-s ISI condition, whereas the face-specific N170 component was larger in the longer ISI condition. Furthermore, the memory-related late P3b component of the ERP responses was also modulated by retention interval: it was reduced in the 1-s ISI as compared with the 6-s condition. The present findings cannot be explained based on differences in sensory processing demands or overall task difficulty because there was no difference in the stimulus information and subjects' performance between the two different ISI conditions. These results reveal that encoding processes underlying high-precision short-term memory for facial emotional expressions are modulated depending on whether information has to be stored for one or for several seconds.

Out of sight but not out of mind: the neurophysiology of iconic memory in the superior temporal sulcus.

PubMed

Keysers, C; Xiao, D-K; Foldiak, P; Perrett, D I

2005-05-01

Iconic memory, the short-lasting visual memory of a briefly flashed stimulus, is an important component of most models of visual perception. Here we investigate what physiological mechanisms underlie this capacity by showing rapid serial visual presentation (RSVP) sequences with and without interstimulus gaps to human observers and macaque monkeys. For gaps of up to 93 ms between consecutive images, human observers and neurones in the temporal cortex of macaque monkeys were found to continue processing a stimulus as if it was still present on the screen. The continued firing of neurones in temporal cortex may therefore underlie iconic memory. Based on these findings, a neurophysiological vision of iconic memory is presented.

Writing and overwriting short-term memory

PubMed Central

Killeen, Peter R.

2008-01-01

An integrative account of short-term memory is based on data from pigeons trained to report the majority color in a sequence of lights. Performance showed strong recency effects, was invariant over changes in the interstimulus interval, and improved with increases in the intertrial interval. A compound model of binomial variance around geometrically decreasing memory described the data; a logit transformation rendered it isomorphic with other memory models. The model was generalized for variance in the parameters, where it was shown that averaging exponential and power functions from individuals or items with different decay rates generates new functions that are hyperbolic in time and in log time, respectively. The compound model provides a unified treatment of both the accrual and the dissipation of memory and is consistent with data from various experiments, including the choose-short bias in delayed recall, multielement stimuli, and Rubin and Wenzel’s (1996) meta-analyses of forgetting. PMID:11340865

Adaptive flexibility of the within-hand attentional gradient in touch: An MEG study.

PubMed

Kida, Tetsuo; Tanaka, Emi; Kakigi, Ryusuke

2018-06-21

Previous studies have demonstrated the cortical mechanisms for the gradient of spatial attention in vision and audition, whereas those for touch have yet to be elucidated in detail. In order to examine the within-hand gradient of tactile spatial attention in the cerebral cortex, we used magnetoencephalography (MEG) to record cortical responses to an electrocutaneous stimulation presented randomly to any of the five fingers of the right hand at a random interstimulus interval (750-1250 ms). Participants attended to the index finger, ring finger, or both to detect a rare target stimulus in a sequence of frequent standard stimuli presented to the attended finger(s) by silent counting. Neuromagnetic responses around the contralateral primary and secondary somatosensory cortices (SIc and SIIc) at 50-70 ms and 80-100 ms, respectively, for the stimulation of the index or ring finger were stronger when that finger was attended than when the distant finger was attended or at rest. The amplitude of the SIIc response was also intermediate when the index and ring fingers were simultaneously attended. The SIIc response to the task-irrelevant stimulation of the thumb or little finger increased when the index or ring finger was attended, respectively, suggesting an across-finger gradient of tactile attention. Simultaneous attention to the index and ring fingers decreased the SIIc response to the task-irrelevant stimulation of the intervening middle finger more than that with attention to either one of the two fingers. The earliest attentional sign was observed for the SI M40c response, with the amplitude increasing with the stimulation of the unattended finger. Furthermore, late responses in the temporo-parietal junction (TPJ) and prefrontal cortex (PFC) were stronger with the stimulation of the unattended finger than with that of the attended finger. Thus, the present study provides cortical evidence for the adaptive control of the within-hand, across-finger gradient of tactile attention that depends on whether attention is focused on a single finger or divided into non-adjacent different fingers. Copyright © 2018. Published by Elsevier Inc.

Speeded Probed Recall Is Affected by Grouping.

PubMed

Morra, Sergio; Epidendio, Valentina

2015-01-01

Most of the evidence from previous studies on speeded probed recall supported primacy-gradient models of serial order representation. Two experiments investigated the effect of grouping on speeded probed recall. Six-word lists, followed by a number between 1 and 6, were presented for speeded recall of the word in the position indicated by the number. Grouping was manipulated through interstimulus intervals. In both experiments, a significant Position × Grouping interaction was found in RT. It is concluded that the results are not consistent with models of order representation only based on a primacy gradient. Possible alternative representations of serial order are also discussed; a case is made for a holistic order representation.

Spectral mechanisms of spatially induced blackness: data and quantitative model.

PubMed

Shinomori, K; Schefrin, B E; Werner, J S

1997-02-01

Spectral efficiency functions and tests of additivity were obtained with three observers to identify possible chromatic contributions to spatially induced blackness. Stimuli consisted of a series of monochromatic (400-700 nm; 10-nm steps), 52-arcmin circular test lights surrounded by broadband (x = 0.31, y = 0.37), 63-138-arcmin annuli of fixed retinal illuminance. The stimuli were imaged on the fovea in Maxwellian view as 500-ms flashes with 10-s interstimulus intervals. Observers decreased the intensity of the test center until it was first perceived as completely black. Action spectra determined for two surround levels [2.5 and 3.5 log trolands] had three sensitivity peaks (at approximately 440, 540, and 600 nm), However, when monochromatic surrounds were adjusted to induce blackness in a broadband center, action spectra were unimodal and identical to functions obtained by heterochromatic flicker photometry. Tests of additivity revealed that when blackness is induced by broadband surround into a bichromatic center, there is an additivity failure of the cancellation type. This additivity failure indicates that blackness induction is influenced, in part, by signals from opponent-chromatic pathways. A quantitative model is presented to account for these data. This model assumes that blackness induction is determined by the ratio of responses to the stimulus center and the annulus, and while signals form the annulus are based only on achromatic information, responses from the center are based on both chromatic and achromatic properties of the stimulus.

Anodal Direct Current Stimulation of the Cerebellum Reduces Cerebellar Brain Inhibition but Does Not Influence Afferent Input from the Hand or Face in Healthy Adults.

PubMed

Doeltgen, Sebastian H; Young, Jessica; Bradnam, Lynley V

2016-08-01

The cerebellum controls descending motor commands by outputs to primary motor cortex (M1) and the brainstem in response to sensory feedback. The cerebellum may also modulate afferent input en route to M1 and the brainstem. The objective of this study is to determine if anodal transcranial direct current stimulation (tDCS) to the cerebellum influences cerebellar brain inhibition (CBI), short afferent inhibition (SAI) and trigeminal reflexes (TRs) in healthy adults. Data from two studies evaluating effects of cerebellar anodal and sham tDCS are presented. The first study used a twin coil transcranial magnetic stimulation (TMS) protocol to investigate CBI and combined TMS and cutaneous stimulation of the digit to assess SAI. The second study evaluated effects on trigemino-cervical and trigemino-masseter reflexes using peripheral nerve stimulation of the face. Fourteen right-handed healthy adults participated in experiment 1. CBI was observed at baseline and was reduced by anodal cerebellar DCS only (P < 0.01). There was SAI at interstimulus intervals of 25 and 30 ms at baseline (both P < 0.0001), but cerebellar tDCS had no effect. Thirteen right-handed healthy adults participated in experiment 2. Inhibitory reflexes were evoked in the ipsilateral masseter and sternocleidomastoid muscles. There was no effect of cerebellar DCS on either reflex. Anodal DCS reduced CBI but did not change SAI or TRs in healthy adults. These results require confirmation in individuals with neurological impairment.

Effects of acute alcohol intoxication on automated processing: evidence from the double-step paradigm.

PubMed

Vorstius, Christian; Radach, Ralph; Lang, Alan R

2012-02-01

Reflexive and voluntary levels of processing have been studied extensively with respect to possible impairments due to alcohol intoxication. This study examined alcohol effects at the 'automated' level of processing essential to many complex visual processing tasks (e.g., reading, visual search) that involve ongoing modifications or reprogramming of well-practiced routines. Data from 30 participants (16 male) were collected in two counterbalanced sessions (alcohol vs. no-alcohol control; mean breath alcohol concentration = 68 mg/dL vs. 0 mg/dL). Eye movements were recorded during a double-step task where 75% of trials involved two target stimuli in rapid succession (inter-stimulus interval [ISI]=40, 70, or 100 ms) so that they could elicit two distinct saccades or eye movements (double steps). On 25% of trials a single target appeared. Results indicated that saccade latencies were longer under alcohol. In addition, the proportion of single-step responses and the mean saccade amplitude (length) of primary saccades decreased significantly with increasing ISI. The key novel finding, however, was that the reprogramming time needed to cancel the first saccade and adjust saccade amplitude was extended significantly by alcohol. The additional time made available by prolonged latencies due to alcohol was not utilized by the saccade programming system to decrease the number of two-step responses. These results represent the first demonstration of specific alcohol-induced programming deficits at the automated level of oculomotor processing.

Paired-pulse facilitation and depression at unitary synapses in rat hippocampus: quantal fluctuation affects subsequent release.

PubMed Central

Debanne, D; Guérineau, N C; Gähwiler, B H; Thompson, S M

1996-01-01

1. Excitatory synaptic transmission between pairs of monosynaptically coupled pyramidal cells was examined in rat hippocampal slice cultures. Action potentials were elicited in single CA3 pyramidal cells impaled with microelectrodes and unitary excitatory postsynaptic currents (EPSCs) were recorded in whole-cell voltage-clamped CA1 or CA3 cells. 2. The amplitude of successive unitary EPSCs in response to single action potentials varied. The amplitude of EPSCs was altered by adenosine or changes in the [Mg2+]/[CA2+] ratio. We conclude that single action potentials triggered the release of multiple quanta of glutamate. 3. When two action potentials were elicited in the presynaptic cell, the amplitude of the second EPSC was inversely related to the amplitude of the first. Paired-pulse facilitation (PPF) was observed when the first EPSC was small, i.e. the second EPSC was larger than the first, whereas paired-pulse depression (PPD) was observed when the first EPSC was large. 4. The number of trials displaying PPD was greater when release probability was increased, and smaller when release probability was decreased. 5. PPD was not postsynaptically mediated because it was unaffected by decreasing ionic flux with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or receptor desensitization with aniracetam. 6. PPF was maximal at an interstimulus interval of 70 ms and recovered within 500 ms. Recovery from PPD occurred within 5 s. 7. We propose that multiple release sites are formed by the axon of a CA3 pyramidal cell and a single postsynaptic CA1 or CA3 cell. PPF is observed if the first action potential fails to release transmitter at most release sites. PPD is observed if the first action potential successfully triggers release at most release sites. 8. Our observations of PPF are consistent with the residual calcium hypothesis. We conclude that PPD results from a decrease in quantal content, perhaps due to short-term depletion of readily releasable vesicles. PMID:9011608

Short-term memory in zebrafish (Danio rerio).

PubMed

Jia, Jason; Fernandes, Yohaan; Gerlai, Robert

2014-08-15

Learning and memory represent perhaps the most complex behavioral phenomena. Although their underlying mechanisms have been extensively analyzed, only a fraction of the potential molecular components have been identified. The zebrafish has been proposed as a screening tool with which mechanisms of complex brain functions may be systematically uncovered. However, as a relative newcomer in behavioral neuroscience, the zebrafish has not been well characterized for its cognitive and mnemonic features, thus learning and/or memory screens with adults have not been feasible. Here we study short-term memory of adult zebrafish. We show animated images of conspecifics (the stimulus) to the experimental subject during 1 min intervals on ten occasions separated by different (2, 4, 8 or 16 min long) inter-stimulus intervals (ISI), a between subject experimental design. We quantify the distance of the subject from the image presentation screen during each stimulus presentation interval, during each of the 1-min post-stimulus intervals immediately following the stimulus presentations and during each of the 1-min intervals furthest away from the last stimulus presentation interval and just before the next interval (pre-stimulus interval), respectively. Our results demonstrate significant retention of short-term memory even in the longest ISI group but suggest no acquisition of reference memory. Because in the employed paradigm both stimulus presentation and behavioral response quantification is computer automated, we argue that high-throughput screening for drugs or mutations that alter short-term memory performance of adult zebrafish is now becoming feasible. Copyright © 2014 Elsevier B.V. All rights reserved.

Somatosensory Temporal Discrimination Threshold Involves Inhibitory Mechanisms in the Primary Somatosensory Area.

PubMed

Rocchi, Lorenzo; Casula, Elias; Tocco, Pierluigi; Berardelli, Alfredo; Rothwell, John

2016-01-13

Somatosensory temporal discrimination threshold (STDT) is defined as the shortest time interval necessary for a pair of tactile stimuli to be perceived as separate. Although STDT is altered in several neurological disorders, its neural bases are not entirely clear. We used continuous theta burst stimulation (cTBS) to condition the excitability of the primary somatosensory cortex in healthy humans to examine its possible contribution to STDT. Excitability was assessed using the recovery cycle of the N20 component of somatosensory evoked potentials (SEP) and the area of high-frequency oscillations (HFO). cTBS increased STDT and reduced inhibition in the N20 recovery cycle at an interstimulus interval of 5 ms. It also reduced the amplitude of late HFO. All three effects were correlated. There was no effect of cTBS over the secondary somatosensory cortex on STDT, although it reduced the N120 component of the SEP. STDT is assessed conventionally with a simple ascending method. To increase insight into the effect of cTBS, we measured temporal discrimination with a psychophysical method. cTBS reduced the slope of the discrimination curve, consistent with a reduction of the quality of sensory information caused by an increase in noise. We hypothesize that cTBS reduces the effectiveness of inhibitory interactions normally used to sharpen temporal processing of sensory inputs. This reduction in discriminability of sensory input is equivalent to adding neural noise to the signal. Precise timing of sensory information is crucial for nearly every aspect of human perception and behavior. One way to assess the ability to analyze temporal information in the somatosensory domain is to measure the somatosensory temporal discrimination threshold (STDT), defined as the shortest time interval necessary for a pair of tactile stimuli to be perceived as separate. In this study, we found that STDT depends on inhibitory mechanisms within the primary somatosensory area (S1). This finding helps interpret the sensory processing deficits in neurological diseases, such as focal dystonia and Parkinson's disease, and possibly prompts future studies using neurostimulation techniques over S1 for therapeutic purposes in dystonic patients. Copyright © 2016 the authors 0270-6474/16/360325-11$15.00/0.

Fast transfer of crossmodal time interval training.

PubMed

Chen, Lihan; Zhou, Xiaolin

2014-06-01

Sub-second time perception is essential for many important sensory and perceptual tasks including speech perception, motion perception, motor coordination, and crossmodal interaction. This study investigates to what extent the ability to discriminate sub-second time intervals acquired in one sensory modality can be transferred to another modality. To this end, we used perceptual classification of visual Ternus display (Ternus in Psychol Forsch 7:81-136, 1926) to implicitly measure participants' interval perception in pre- and posttests and implemented an intra- or crossmodal sub-second interval discrimination training protocol in between the tests. The Ternus display elicited either an "element motion" or a "group motion" percept, depending on the inter-stimulus interval between the two visual frames. The training protocol required participants to explicitly compare the interval length between a pair of visual, auditory, or tactile stimuli with a standard interval or to implicitly perceive the length of visual, auditory, or tactile intervals by completing a non-temporal task (discrimination of auditory pitch or tactile intensity). Results showed that after fast explicit training of interval discrimination (about 15 min), participants improved their ability to categorize the visual apparent motion in Ternus displays, although the training benefits were mild for visual timing training. However, the benefits were absent for implicit interval training protocols. This finding suggests that the timing ability in one modality can be rapidly acquired and used to improve timing-related performance in another modality and that there may exist a central clock for sub-second temporal processing, although modality-specific perceptual properties may constrain the functioning of this clock.

Effects of inter-stimulus interval and intensity on the perceived urgency of tactile patterns.

PubMed

White, Timothy L; Krausman, Andrea S

2015-05-01

This research examines the feasibility of coding urgency into tactile patterns. Four tactile patterns were presented at either, 12 or 23.5 dB above mean threshold, with an ISI of either 0 (no interval) or 500 msec. Measures included pattern identification and urgency rating on a scale of 1 (least urgent) to 10 (most urgent). Two studies were conducted, a laboratory study and a field study. In the laboratory study, participants received the tactile patterns while seated in front of a computer. For the field study, participants performed dismounted Soldier maneuvers while receiving the tactile patterns. Higher identification rates were found for the 23.5 dB intensity. Patterns presented at the 23.5 dB intensity and no ISI were rated most urgent. No differences in urgency ratings were found for 12 dB based on ISI. Findings support the notion of coding urgency into tactile patterns as a way of augmenting tactile communication. Published by Elsevier Ltd.

Jitter Reduces Response-Time Variability in ADHD: An Ex-Gaussian Analysis.

PubMed

Lee, Ryan W Y; Jacobson, Lisa A; Pritchard, Alison E; Ryan, Matthew S; Yu, Qilu; Denckla, Martha B; Mostofsky, Stewart; Mahone, E Mark

2015-09-01

"Jitter" involves randomization of intervals between stimulus events. Compared with controls, individuals with ADHD demonstrate greater intrasubject variability (ISV) performing tasks with fixed interstimulus intervals (ISIs). Because Gaussian curves mask the effect of extremely slow or fast response times (RTs), ex-Gaussian approaches have been applied to study ISV. This study applied ex-Gaussian analysis to examine the effects of jitter on RT variability in children with and without ADHD. A total of 75 children, aged 9 to 14 years (44 ADHD, 31 controls), completed a go/no-go test with two conditions: fixed ISI and jittered ISI. ADHD children showed greater variability, driven by elevations in exponential (tau), but not normal (sigma) components of the RT distribution. Jitter decreased tau in ADHD to levels not statistically different than controls, reducing lapses in performance characteristic of impaired response control. Jitter may provide a nonpharmacologic mechanism to facilitate readiness to respond and reduce lapses from sustained (controlled) performance. © 2012 SAGE Publications.

Time perception, attention, and memory: a selective review.

PubMed

Block, Richard A; Gruber, Ronald P

2014-06-01

This article provides a selective review of time perception research, mainly focusing on the authors' research. Aspects of psychological time include simultaneity, successiveness, temporal order, and duration judgments. In contrast to findings at interstimulus intervals or durations less than 3.0-5.0 s, there is little evidence for an "across-senses" effect of perceptual modality (visual vs. auditory) at longer intervals or durations. In addition, the flow of time (events) is a pervasive perceptual illusion, and we review evidence on that. Some temporal information is encoded All rights reserved. relatively automatically into memory: People can judge time-related attributes such as recency, frequency, temporal order, and duration of events. Duration judgments in prospective and retrospective paradigms reveal differences between them, as well as variables that moderate the processes involved. An attentional-gate model is needed to account for prospective judgments, and a contextual-change model is needed to account for retrospective judgments. Copyright © 2013 Elsevier B.V. All rights reserved.

Articulatory rehearsal is more than refreshing memory traces.

PubMed

Nishiyama, Ryoji; Ukita, Jun

2013-01-01

This study examined whether additional articulatory rehearsal induced temporary durability of phonological representations, using a 10-s delayed nonword free recall task. Three experiments demonstrated that cumulative rehearsal between the offset of the last study item and the start of the filled delay (Experiments 1 and 3) and a fixed rehearsal of the immediate item during the subsequent interstimulus interval (Experiments 2 and 3) improved free recall performance. These results suggest that an additional rehearsal helps to stabilize phonological representations for a short period. Furthermore, the analyses of serial position curves suggested that the frequency of the articulation affected the durability of the phonological representation. The significance of these findings as clues of the mechanism maintaining verbal information (i.e., verbal working memory) is discussed.

Attention Modulates Spatio-temporal Grouping

PubMed Central

Aydın, Murat; Herzog, Michael H.; Öğmen, Haluk

2011-01-01

Dynamic stimuli are ubiquitous in natural viewing conditions implying that grouping operations need to operate, not only in space, but also jointly in space and time. Moreover, in natural viewing, attention plays an important role in controlling how resources are allocated. We investigated how attention interacts with spatiotemporal perceptual grouping by using a bistable stimulus, called the Ternus-Pikler display. Ternus-Pikler displays can give rise to two different motion percepts, called Element Motion (EM) and Group Motion (GM), the former dominating at short Inter-Stimulus Intervals (ISIs) and the latter at long ISIs. Our results indicate that GM grouping requires more attentional resources than EM grouping. Different theoretical accounts of perceptual grouping and attention are discussed and evaluated in the light of the current results. PMID:21266181

Logical metonymy resolution in a words-as-cues framework: evidence from self-paced reading and probe recognition.

PubMed

Zarcone, Alessandra; Padó, Sebastian; Lenci, Alessandro

2014-06-01

Logical metonymy resolution (begin a book → begin reading a book or begin writing a book) has traditionally been explained either through complex lexical entries (qualia structures) or through the integration of the implicit event via post-lexical access to world knowledge. We propose that recent work within the words-as-cues paradigm can provide a more dynamic model of logical metonymy, accounting for early and dynamic integration of complex event information depending on previous contextual cues (agent and patient). We first present a self-paced reading experiment on German subordinate sentences, where metonymic sentences and their paraphrased version differ only in the presence or absence of the clause-final target verb (Der Konditor begann die Glasur → Der Konditor begann, die Glasur aufzutragen/The baker began the icing → The baker began spreading the icing). Longer reading times at the target verb position in a high-typicality condition (baker + icing → spread ) compared to a low-typicality (but still plausible) condition (child + icing → spread) suggest that we make use of knowledge activated by lexical cues to build expectations about events. The early and dynamic integration of event knowledge in metonymy interpretation is bolstered by further evidence from a second experiment using the probe recognition paradigm. Presenting covert events as probes following a high-typicality or a low-typicality metonymic sentence (Der Konditor begann die Glasur → AUFTRAGEN/The baker began the icing → SPREAD), we obtain an analogous effect of typicality at 100 ms interstimulus interval. © 2014 Cognitive Science Society, Inc.

Self-face Captures, Holds, and Biases Attention.

PubMed

Wójcik, Michał J; Nowicka, Maria M; Kotlewska, Ilona; Nowicka, Anna

2017-01-01

The implicit self-recognition process may take place already in the pre-attentive stages of perception. After a silent stimulus has captured attention, it is passed on to the attentive stage where it can affect decision making and responding. Numerous studies show that the presence of self-referential information affects almost every cognitive level. These effects may share a common and fundamental basis in an attentional mechanism, conceptualized as attentional bias: the exaggerated deployment of attentional resources to a salient stimulus. A gold standard in attentional bias research is the dot-probe paradigm. In this task, a prominent stimulus (cue) and a neutral stimulus are presented in different spatial locations, followed by the presentation of a target. In the current study we aimed at investigating whether the self-face captures, holds and biases attention when presented as a task-irrelevant stimulus. In two dot-probe experiments coupled with the event-related potential (ERP) technique we analyzed the following relevant ERPs components: N2pc and SPCN which reflect attentional shifts and the maintenance of attention, respectively. An inter-stimulus interval separating face-cues and probes (800 ms) was introduced only in the first experiment. In line with our predictions, in Experiment 1 the self-face elicited the N2pc and the SPCN component. In Experiment 2 in addition to N2pc, an attentional bias was observed. Our results indicate that unintentional self-face processing disables the top-down control setting to filter out distractors, thus leading to the engagement of attentional resources and visual short-term memory.

Unconscious Processing of Facial Emotional Valence Relation: Behavioral Evidence of Integration between Subliminally Perceived Stimuli.

PubMed

Liu, Chengzhen; Sun, Zhiyi; Jou, Jerwen; Cui, Qian; Zhao, Guang; Qiu, Jiang; Tu, Shen

2016-01-01

Although a few studies have investigated the integration between some types of unconscious stimuli, no research has yet explored the integration between unconscious emotional stimuli. This study was designed to provide behavioral evidence for the integration between unconsciously perceived emotional faces (same or different valence relation) using a modified priming paradigm. In two experiments, participants were asked to decide whether two faces in the target, which followed two subliminally presented faces of same or different emotional expressions, were of the same or different emotional valence. The interstimulus interval (ISI) between the prime and the target was manipulated (0, 53, 163 ms). In Experiment 1, prime visibility was assessed post-experiment. In Experiment 2, it was assessed on each trial. Interestingly, in both experiments, unconsciously processed valence relation of the two faces in the prime generated a negative priming effect in the response to the supraliminally presented target, independent of the length of ISI. Further analyses suggested that the negative priming was probably caused by a motor response incongruent relation between the subliminally perceived prime and the supraliminally perceived target. The visual feature incongruent relation across the prime and target was not found to play a role in the negative priming. Because the negative priming was found at short ISI, an attention mechanism as well as a motor inhibition mechanism were proposed in the generation of the negative priming effect. Overall, this study indicated that the subliminal valence relation was processed, and that integration between different unconsciously perceived stimuli could occur.

Impairment of sensory-motor plasticity in mild Alzheimer's disease.

PubMed

Terranova, Carmen; Carmen, Terranova; SantAngelo, Antonino; Antonino, Sant'Angelo; Morgante, Francesca; Francesca, Morgante; Rizzo, Vincenzo; Vincenzo, Rizzo; Allegra, Roberta; Roberta, Allegra; Arena, Maria Grazia; Grazia, Arena Maria; Ricciardi, Lucia; Lucia, Ricciardi; Ghilardi, Marie Felice; Felice, Ghilardi Maria; Girlanda, Paolo; Paolo, Girlanda; Quartarone, Angelo; Angelo, Quartarone

2013-01-01

Primary motor cortex (M1) is relatively spared in the early stages of Alzheimer's disease (AD). Aim of the present study was to investigate whether abnormal M1 synaptic plasticity is present at an early stage of AD. We employed an electrophysiological protocol, named rapid paired associative stimulation (rPAS), involving repetitive transcranial magnetic stimulation (rTMS) paired with electrical stimulation of the contralateral median nerve, that modifies corticospinal excitability and short latency afferent inhibition (SAI). We studied 10 patients with a diagnosis of probable mild AD according to the Mini Mental State Examination score (minimum 21) and 14 age-matched control subjects. Motor evoked potentials (MEP) amplitudes and short-afferent inhibition (SAI) were measured at baseline before and for up to 60 min after 5Hz-rPAS in abductor pollicis brevis (APB). rPAS consisted of 600 pairs of transcranial magnetic stimuli, at a rate of 5 Hz for 2 min, coupled with electrical median nerve stimulation preceding TMS over the contralateral M1 at an inter-stimulus interval of 25 ms. Baseline SAI was significantly reduced in AD patients. In the control subjects rPAS induced a significant increase in MEP amplitudes and a decrease of SAI in the APB muscle persistently for up to 1 h. Conversely 5Hz-rPAS did not induce any significant changes in MEP amplitudes and SAI in mild AD patients. Sensory-motor plasticity is impaired in the motor cortex of AD at an early stage of the disease. Copyright © 2013 Elsevier Inc. All rights reserved.

Upper-limb muscle responses to epidural, subdural and intraspinal stimulation of the cervical spinal cord

NASA Astrophysics Data System (ADS)

Sharpe, Abigail N.; Jackson, Andrew

2014-02-01

Objective. Electrical stimulation of the spinal cord has potential applications following spinal cord injury for reanimating paralysed limbs and promoting neuroplastic changes that may facilitate motor rehabilitation. Here we systematically compare the efficacy, selectivity and frequency-dependence of different stimulation methods in the cervical enlargement of anaesthetized monkeys. Approach. Stimulating electrodes were positioned at multiple epidural and subdural sites on both dorsal and ventral surfaces, as well as at different depths within the spinal cord. Motor responses were recorded from arm, forearm and hand muscles. Main results. Stimulation efficacy increased from dorsal to ventral stimulation sites, with the exception of ventral epidural electrodes which had the highest recruitment thresholds. Compared to epidural and intraspinal methods, responses to subdural stimulation were more selective but also more similar between adjacent sites. Trains of stimuli delivered to ventral sites elicited consistent responses at all frequencies whereas from dorsal sites we observed a mixture of short-latency facilitation and long-latency suppression. Finally, paired stimuli delivered to dorsal surface and intraspinal sites exhibited symmetric facilitatory interactions at interstimulus intervals between 2-5 ms whereas on the ventral side interactions tended to be suppressive for near-simultaneous stimuli. Significance. We interpret these results in the context of differential activation of afferent and efferent roots and intraspinal circuit elements. In particular, we propose that distinct direct and indirect actions of spinal cord stimulation on motoneurons may be advantageous for different applications, and this should be taken into consideration when designing neuroprostheses for upper-limb function.

Unconscious Processing of Facial Emotional Valence Relation: Behavioral Evidence of Integration between Subliminally Perceived Stimuli

PubMed Central

Jou, Jerwen; Cui, Qian; Zhao, Guang; Qiu, Jiang; Tu, Shen

2016-01-01

Although a few studies have investigated the integration between some types of unconscious stimuli, no research has yet explored the integration between unconscious emotional stimuli. This study was designed to provide behavioral evidence for the integration between unconsciously perceived emotional faces (same or different valence relation) using a modified priming paradigm. In two experiments, participants were asked to decide whether two faces in the target, which followed two subliminally presented faces of same or different emotional expressions, were of the same or different emotional valence. The interstimulus interval (ISI) between the prime and the target was manipulated (0, 53, 163 ms). In Experiment 1, prime visibility was assessed post-experiment. In Experiment 2, it was assessed on each trial. Interestingly, in both experiments, unconsciously processed valence relation of the two faces in the prime generated a negative priming effect in the response to the supraliminally presented target, independent of the length of ISI. Further analyses suggested that the negative priming was probably caused by a motor response incongruent relation between the subliminally perceived prime and the supraliminally perceived target. The visual feature incongruent relation across the prime and target was not found to play a role in the negative priming. Because the negative priming was found at short ISI, an attention mechanism as well as a motor inhibition mechanism were proposed in the generation of the negative priming effect. Overall, this study indicated that the subliminal valence relation was processed, and that integration between different unconsciously perceived stimuli could occur. PMID:27622600

Time frequency analysis of olfactory induced EEG-power change.

PubMed

Schriever, Valentin Alexander; Han, Pengfei; Weise, Stefanie; Hösel, Franziska; Pellegrino, Robert; Hummel, Thomas

2017-01-01

The objective of the present study was to investigate the usefulness of time-frequency analysis (TFA) of olfactory-induced EEG change with a low-cost, portable olfactometer in the clinical investigation of smell function. A total of 78 volunteers participated. The study was composed of three parts where olfactory stimuli were presented using a custom-built olfactometer. Part I was designed to optimize the stimulus as well as the recording conditions. In part II EEG-power changes after olfactory/trigeminal stimulation were compared between healthy participants and patients with olfactory impairment. In Part III the test-retest reliability of the method was evaluated in healthy subjects. Part I indicated that the most effective paradigm for stimulus presentation was cued stimulus, with an interstimulus interval of 18-20s at a stimulus duration of 1000ms with each stimulus quality presented 60 times in blocks of 20 stimuli each. In Part II we found that central processing of olfactory stimuli analyzed by TFA differed significantly between healthy controls and patients even when controlling for age. It was possible to reliably distinguish patients with olfactory impairment from healthy individuals at a high degree of accuracy (healthy controls vs anosmic patients: sensitivity 75%; specificity 89%). In addition we could show a good test-retest reliability of TFA of chemosensory induced EEG-power changes in Part III. Central processing of olfactory stimuli analyzed by TFA reliably distinguishes patients with olfactory impairment from healthy individuals at a high degree of accuracy. Importantly this can be achieved with a simple olfactometer.

Determination of inadvertent atrial capture during para-Hisian pacing.

PubMed

Obeyesekere, Manoj; Leong-Sit, Peter; Skanes, Allan; Krahn, Andrew; Yee, Raymond; Gula, Lorne J; Bennett, Matthew; Klein, George J

2011-08-01

Inadvertent capture of the atrium will lead to spurious results during para-Hisian pacing. We sought to establish whether the stimulation-to-atrial electrogram interval at the proximal coronary sinus (stim-PCS) or high right atrium (stim-HRA) could signal inadvertent atrial capture. Para-Hisian pacing with and without intentional atrial capture was performed in 31 patients. Stim-HRA and stim-PCS intervals were measured with atrial capture, His plus para-Hisian ventricular (H+V) capture, and para-Hisian ventricular (V) capture alone. The mean stim-HRA interval was significantly shorter with atrial capture (66 ± 18 ms) than with H+V (121 ± 27 ms, P < 0.001) or V capture alone (174 ± 38 ms, P < 0.001). The mean stim-PCS interval was significantly shorter with atrial capture (51 ± 16 ms) than with H+V (92 ± 22 ms, P<0.001) or V capture alone (146 ± 33 ms, P < 0.001). A stim-PCS < 60 ms (stim-HRA < 70 ms) was observed only with atrial capture. A stim-PCS >90 ms (stim-HRA >100 ms) was observed only in the absence of atrial capture. A stim-HRA of < 85 ms was highly specific and stim-PCS of < 85 ms highly sensitive at identifying atrial capture. Stim-HRA intervals of 75 to 97 ms and stim-PCS intervals of 65 to 88 ms were observed with either atrial, His, or para-Hisian ventricular capture without atrial capture. In this overlap zone, all patients demonstrated a stim-PCS or stim-HRA interval prolongation of at least 20 ms when the catheter was advanced to avoid deliberate atrial pacing. The QRS morphology was of limited value in distinguishing atrial capture due to concurrent ventricular or H+V capture, as observed in 20 of 31 (65%) patients. Stim-PCS and stim-HRA intervals can be used to monitor for inadvertent atrial capture during para-Hisian pacing. A stim-PCS < 60 ms (or stim-HRA < 70 ms) and stim-PCS > 90 ms (or stim-HRA > 100 ms) were observed only with and without atrial capture, respectively, but there was significant overlap between these values. Deliberate atrial capture and loss of capture reliably identifies atrial capture regardless of intervals.

ECG parameters predict left ventricular conduction delay in patients with left ventricular dysfunction.

PubMed

Pastore, Gianni; Maines, Massimiliano; Marcantoni, Lina; Zanon, Francesco; Noventa, Franco; Corbucci, Giorgio; Baracca, Enrico; Aggio, Silvio; Picariello, Claudio; Lanza, Daniela; Rigatelli, Gianluca; Carraro, Mauro; Roncon, Loris; Barold, S Serge

2016-12-01

Estimating left ventricular electrical delay (Q-LV) from a 12-lead ECG may be important in evaluating cardiac resynchronization therapy (CRT). The purpose of this study was to assess the impact of Q-LV interval on ECG configuration. One hundred ninety-two consecutive patients undergoing CRT implantation were divided electrocardiographically into 3 groups: left bundle branch block (LBBB), right bundle branch block (RBBB), and nonspecific intraventricular conduction delay (IVCD). The IVCD group was further subdivided into 81 patients with left (L)-IVCD and 15 patients with right (R)-IVCD (resembling RBBB, but without S wave in leads I and aVL). The Q-LV interval in the different groups and the relationship between ECG parameters and the maximum Q-LV interval were analyzed. Patients with LBBB presented a long Q-LV interval (147.7 ± 14.6 ms, all exceeding cutoff value of 110 ms), whereas RBBB patients presented a very short Q-LV interval (75.2 ± 16.3 ms, all <110 ms). Patients with an IVCD displayed a wide range of Q-LV intervals. In L-IVCD, mid-QRS notching/slurring showed the strongest correlation with a longer Q-LV interval, followed, in decreasing order, by QRS duration >150 ms and intrinsicoid deflection >60 ms. Isolated mid-QRS notching/slurring predicted Q-LV interval >110 ms in 68% of patients. The R-IVCD group presented an unexpectedly longer Q-LV interval (127.0 ± 12.5 ms; 13/15 patients had Q-LV >110 ms). Patients with LBBB have a very prolonged Q-LV interval. Mid-QRS notching in lateral leads strongly predicts a longer Q-LV interval in L-IVCD patients. Patients with R-IVCD constitute a subgroup of patients with a long Q-LV interval. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Language performance and auditory evoked fields in 2- to 5-year-old children.

PubMed

Yoshimura, Yuko; Kikuchi, Mitsuru; Shitamichi, Kiyomi; Ueno, Sanae; Remijn, Gerard B; Haruta, Yasuhiro; Oi, Manabu; Munesue, Toshio; Tsubokawa, Tsunehisa; Higashida, Haruhiro; Minabe, Yoshio

2012-02-01

Language development progresses at a dramatic rate in preschool children. As rapid temporal processing of speech signals is important in daily colloquial environments, we performed magnetoencephalography (MEG) to investigate the linkage between speech-evoked responses during rapid-rate stimulus presentation (interstimulus interval < 1 s) and language performance in 2- to 5-year-old children (n = 59). Our results indicated that syllables with this short stimulus interval evoked detectable P50m, but not N100m, in most participants, indicating a marked influence of longer neuronal refractory period for stimulation. The results of equivalent dipole estimation showed that the intensity of the P50m component in the left hemisphere was positively correlated with language performance (conceptual inference ability). The observed positive correlations were suggested to reflect the maturation of synaptic organisation or axonal maturation and myelination underlying the acquisition of linguistic abilities. The present study is among the first to use MEG to study brain maturation pertaining to language abilities in preschool children. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Effect of inter-train interval on the induction of repetition suppression of motor-evoked potentials using transcranial magnetic stimulation.

PubMed

Pitkänen, Minna; Kallioniemi, Elisa; Julkunen, Petro

2017-01-01

Repetition suppression (RS) is evident as a weakened response to repeated stimuli after the initial response. RS has been demonstrated in motor-evoked potentials (MEPs) induced with transcranial magnetic stimulation (TMS). Here, we investigated the effect of inter-train interval (ITI) on the induction of RS of MEPs with the attempt to optimize the investigative protocols. Trains of TMS pulses, targeted to the primary motor cortex by neuronavigation, were applied at a stimulation intensity of 120% of the resting motor threshold. The stimulus trains included either four or twenty pulses with an inter-stimulus interval (ISI) of 1 s. The ITI was here defined as the interval between the last pulse in a train and the first pulse in the next train; the ITIs used here were 1, 3, 4, 6, 7, 12, and 17 s. RS was observed with all ITIs except with the ITI of 1 s, in which the ITI was equal to ISI. RS was more pronounced with longer ITIs. Shorter ITIs may not allow sufficient time for a return to baseline. RS may reflect a startle-like response to the first pulse of a train followed by habituation. Longer ITIs may allow more recovery time and in turn demonstrate greater RS. Our results indicate that RS can be studied with confidence at relatively short ITIs of 6 s and above.

Neonatal ethanol exposure results in dose-dependent impairments in the acquisition and timing of the conditioned eyeblink response and altered cerebellar interpositus nucleus and hippocampal CA1 unit activity in adult rats.

PubMed

Lindquist, Derick H; Sokoloff, Greta; Milner, Eric; Steinmetz, Joseph E

2013-09-01

Exposure to ethanol in neonatal rats results in reduced neuronal numbers in the cerebellar cortex and deep nuclei of juvenile and adult animals. This reduction in cell numbers is correlated with impaired delay eyeblink conditioning (EBC), a simple motor learning task in which a neutral conditioned stimulus (CS; tone) is repeatedly paired with a co-terminating unconditioned stimulus (US; periorbital shock). Across training, cell populations in the interpositus (IP) nucleus model the temporal form of the eyeblink-conditioned response (CR). The hippocampus, though not required for delay EBC, also shows learning-dependent increases in CA1 and CA3 unit activity. In the present study, rat pups were exposed to 0, 3, 4, or 5 mg/kg/day of ethanol during postnatal days (PD) 4-9. As adults, CR acquisition and timing were assessed during 6 training sessions of delay EBC with a short (280 ms) interstimulus interval (ISI; time from CS onset to US onset) followed by another 6 sessions with a long (880 ms) ISI. Neuronal activity was recorded in the IP and area CA1 during all 12 sessions. The high-dose rats learned the most slowly and, with the moderate-dose rats, produced the longest CR peak latencies over training to the short ISI. The low dose of alcohol impaired CR performance to the long ISI only. The 3E (3 mg/kg/day of ethanol) and 5E (5 mg/kg/day of ethanol) rats also showed slower-than-normal increases in learning-dependent excitatory unit activity in the IP and CA1. The 4E (4 mg/kg/day of ethanol) rats showed a higher rate of CR production to the long ISI and enhanced IP and CA1 activation when compared to the 3E and 5E rats. The results indicate that binge-like ethanol exposure in neonatal rats induces long-lasting, dose-dependent deficits in CR acquisition and timing and diminishes conditioning-related neuronal excitation in both the cerebellum and hippocampus. Published by Elsevier Inc.

Influence of sound source location on the behavior and physiology of the precedence effect in cats.

PubMed

Dent, Micheal L; Tollin, Daniel J; Yin, Tom C T

2009-08-01

Psychophysical experiments on the precedence effect (PE) in cats have shown that they localize pairs of auditory stimuli presented from different locations in space based on the spatial position of the stimuli and the interstimulus delay (ISD) between the stimuli in a manner similar to humans. Cats exhibit localization dominance for pairs of transient stimuli with |ISDs| from approximately 0.4 to 10 ms, summing localization for |ISDs| < 0.4 ms and breakdown of fusion for |ISDs| > 10 ms, which is the approximate echo threshold. The neural correlates to the PE have been described in both anesthetized and unanesthetized animals at many levels from auditory nerve to cortex. Single-unit recordings from the inferior colliculus (IC) and auditory cortex of cats demonstrate that neurons respond to both lead and lag sounds at ISDs above behavioral echo thresholds, but the response to the lag is reduced at shorter ISDs, consistent with localization dominance. Here the influence of the relative locations of the leading and lagging sources on the PE was measured behaviorally in a psychophysical task and physiologically in the IC of awake behaving cats. At all configurations of lead-lag stimulus locations, the cats behaviorally exhibited summing localization, localization dominance, and breakdown of fusion. Recordings from the IC of awake behaving cats show neural responses paralleling behavioral measurements. Both behavioral and physiological results suggest systematically shorter echo thresholds when stimuli are further apart in space.

Influence of Sound Source Location on the Behavior and Physiology of the Precedence Effect in Cats

PubMed Central

Dent, Micheal L.; Tollin, Daniel J.; Yin, Tom C. T.

2009-01-01

Psychophysical experiments on the precedence effect (PE) in cats have shown that they localize pairs of auditory stimuli presented from different locations in space based on the spatial position of the stimuli and the interstimulus delay (ISD) between the stimuli in a manner similar to humans. Cats exhibit localization dominance for pairs of transient stimuli with |ISDs| from ∼0.4 to 10 ms, summing localization for |ISDs| < 0.4 ms and breakdown of fusion for |ISDs| > 10 ms, which is the approximate echo threshold. The neural correlates to the PE have been described in both anesthetized and unanesthetized animals at many levels from auditory nerve to cortex. Single-unit recordings from the inferior colliculus (IC) and auditory cortex of cats demonstrate that neurons respond to both lead and lag sounds at ISDs above behavioral echo thresholds, but the response to the lag is reduced at shorter ISDs, consistent with localization dominance. Here the influence of the relative locations of the leading and lagging sources on the PE was measured behaviorally in a psychophysical task and physiologically in the IC of awake behaving cats. At all configurations of lead-lag stimulus locations, the cats behaviorally exhibited summing localization, localization dominance, and breakdown of fusion. Recordings from the IC of awake behaving cats show neural responses paralleling behavioral measurements. Both behavioral and physiological results suggest systematically shorter echo thresholds when stimuli are further apart in space. PMID:19439668

Lateral masking in cycling displays: the relative importance of separation, flanker duration, and interstimulus interval for object-mediated updating.

PubMed

Hein, Elisabeth; Moore, Cathleen M

2010-01-01

A central bar repeatedly presented in alternation with two flanking bars can lead to the disappearance of the central bar. Recently it has been suggested that this masking effect could be explained by object-mediated updating: the information from the central bar is integrated into the representation of the flankers, leading not only to the disappearance of the central bar as a separate object, but also to the perception of the flankers in apparent motion between their real position and the position of the central bar. This account suggests that the visibility of the central bar should depend on the same factors as those that influence the construction and maintenance of object representations. Therefore separation between central bar and flankers should not influence visibility as long as the time interval between them is adequate to make an interpretation of the scene in terms of one object moving from one location to the other possible location. We found that if the time interval between the central bar and the flankers is neither too short nor too long, the central bar becomes invisible even at large separations. These findings are inconsistent with traditional accounts of the cycling lateral masking displays in terms of local inhibitory mechanisms.

Selective attention and the auditory vertex potential. 2: Effects of signal intensity and masking noise

NASA Technical Reports Server (NTRS)

Schwent, V. L.; Hillyard, S. A.; Galambos, R.

1975-01-01

A randomized sequence of tone bursts was delivered to subjects at short inter-stimulus intervals with the tones originating from one of three spatially and frequency specific channels. The subject's task was to count the tones in one of the three channels at a time, ignoring the other two, and press a button after each tenth tone. In different conditions, tones were given at high and low intensities and with or without a background white noise to mask the tones. The N sub 1 component of the auditory vertex potential was found to be larger in response to attended channel tones in relation to unattended tones. This selective enhancement of N sub 1 was minimal for loud tones presented without noise and increased markedly for the lower tone intensity and in noise added conditions.

Auditory attentional capture during serial recall: violations at encoding of an algorithm-based neural model?

PubMed

Hughes, Robert W; Vachon, François; Jones, Dylan M

2005-07-01

A novel attentional capture effect is reported in which visual-verbal serial recall was disrupted if a single deviation in the interstimulus interval occurred within otherwise regularly presented task-irrelevant spoken items. The degree of disruption was the same whether the temporal deviant was embedded in a sequence made up of a repeating item or a sequence of changing items. Moreover, the effect was evident during the presentation of the to-be-remembered sequence but not during rehearsal just prior to recall, suggesting that the encoding of sequences is particularly susceptible. The results suggest that attentional capture is due to a violation of an algorithm rather than an aggregate-based neural model and further undermine an attentional capture-based account of the classical changing-state irrelevant sound effect. ((c) 2005 APA, all rights reserved).

Temporal discrimination threshold with healthy aging.

PubMed

Ramos, Vesper Fe Marie Llaneza; Esquenazi, Alina; Villegas, Monica Anne Faye; Wu, Tianxia; Hallett, Mark

2016-07-01

The temporal discrimination threshold (TDT) is the shortest interstimulus interval at which a subject can perceive successive stimuli as separate. To investigate the effects of aging on TDT, we studied tactile TDT using the method of limits with 120% of sensory threshold in each hand for each of 100 healthy volunteers, equally divided among men and women, across 10 age groups, from 18 to 79 years. Linear regression analysis showed that age was significantly related to left-hand mean, right-hand mean, and mean of 2 hands with R-square equal to 0.08, 0.164, and 0.132, respectively. Reliability analysis indicated that the 3 measures had fair-to-good reliability (intraclass correlation coefficient: 0.4-0.8). We conclude that TDT is affected by age and has fair-to-good reproducibility using our technique. Published by Elsevier Inc.

The prevalence and significance of a short QT interval in 18,825 low-risk individuals including athletes.

PubMed

Dhutia, Harshil; Malhotra, Aneil; Parpia, Sameer; Gabus, Vincent; Finocchiaro, Gherardo; Mellor, Greg; Merghani, Ahmed; Millar, Lynne; Narain, Rajay; Sheikh, Nabeel; Behr, Elijah R; Papadakis, Michael; Sharma, Sanjay

2016-01-01

The short QT syndrome is a cardiac channelopathy characterised by accelerated repolarisation which manifests as a short QT interval on the ECG. The definition of a short QT interval is debated, ranging from <390 to ≤320 ms, and its clinical significance in healthy young individuals is unknown. We assessed the prevalence and medium-term significance of an isolated short QT interval in a diverse young British population. Between 2005 and 2013, 18 825 apparently healthy people aged 14-35 years underwent cardiovascular evaluation with history, physical examination and ECG. QT intervals were measured by cardiologists using 4 recommended guidelines (Seattle 2013, Heart Rhythm Society 2013, European Society of Cardiology 2010 and American Heart Association 2009). The prevalence of a short QT interval was 0.1% (26 patients, ≤320 ms), 0.2% (44 patients, ≤330 ms), 7.9% (1478 patients, <380 ms), 15.8% (2973 patients, <390 ms). Male gender and Afro-Caribbean ethnicity had the strongest association with short QT intervals. Athletes had shorter QT intervals than non-athletes but athletic status did not predict short QT intervals. Individuals with short QT intervals ≤320 ms did not report syncope or a sinister family history, and during a follow-up period of 5.3±1.2 years, there were no deaths in this group. The prevalence of a short QT interval depends on the recommended cut-off value. Even at values ≤320 ms, there was an excellent medium-term prognosis among 14 people followed. We conclude that a definition of ≤320 ms is realistic to prevent overdiagnosis and excessive investigations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Ethanol modulates cortical activity: direct evidence with combined TMS and EEG.

PubMed

Kähkönen, S; Kesäniemi, M; Nikouline, V V; Karhu, J; Ollikainen, M; Holi, M; Ilmoniemi, R J

2001-08-01

The motor cortex of 10 healthy subjects was stimulated by transcranial magnetic stimulation (TMS) before and after ethanol challenge (0.8 g/kg resulting in blood concentration of 0.77 +/- 0.14 ml/liter). The electrical brain activity resulting from the brief electromagnetic pulse was recorded with high-resolution electroencephalography (EEG) and located using inversion algorithms. Focal magnetic pulses to the left motor cortex were delivered with a figure-of-eight coil at the random interstimulus interval of 1.5-2.5 s. The stimulation intensity was adjusted to the motor threshold of abductor digiti minimi. Two conditions before and after ethanol ingestion (30 min) were applied: (1) real TMS, with the coil pressed against the scalp; and (2) control condition, with the coil separated from the scalp by a 2-cm-thick piece of plastic. A separate EMG control recording of one subject during TMS was made with two bipolar platinum needle electrodes inserted to the left temporal muscle. In each condition, 120 pulses were delivered. The EEG was recorded from 60 scalp electrodes. A peak in the EEG signals was observed at 43 ms after the TMS pulse in the real-TMS condition but not in the control condition or in the control scalp EMG. Potential maps before and after ethanol ingestion were significantly different from each other (P = 0.01), but no differences were found in the control condition. Ethanol changed the TMS-evoked potentials over right frontal and left parietal areas, the underlying effect appearing to be largest in the right prefrontal area. Our findings suggest that ethanol may have changed the functional connectivity between prefrontal and motor cortices. This new noninvasive method provides direct evidence about the modulation of cortical connectivity after ethanol challenge. Copyright 2001 Academic Press.

Neural mechanisms of phonemic restoration for speech comprehension revealed by magnetoencephalography.

PubMed

Sunami, Kishiko; Ishii, Akira; Takano, Sakurako; Yamamoto, Hidefumi; Sakashita, Tetsushi; Tanaka, Masaaki; Watanabe, Yasuyoshi; Yamane, Hideo

2013-11-06

In daily communication, we can usually still hear the spoken words as if they had not been masked and can comprehend the speech when spoken words are masked by background noise. This phenomenon is known as phonemic restoration. Since little is known about the neural mechanisms underlying phonemic restoration for speech comprehension, we aimed to identify the neural mechanisms using magnetoencephalography (MEG). Twelve healthy male volunteers with normal hearing participated in the study. Participants were requested to carefully listen to and understand recorded spoken Japanese stories, which were either played forward (forward condition) or in reverse (reverse condition), with their eyes closed. Several syllables of spoken words were replaced by 300-ms white-noise stimuli with an inter-stimulus interval of 1.6-20.3s. We compared MEG responses to white-noise stimuli during the forward condition with those during the reverse condition using time-frequency analyses. Increased 3-5 Hz band power in the forward condition compared with the reverse condition was continuously observed in the left inferior frontal gyrus [Brodmann's areas (BAs) 45, 46, and 47] and decreased 18-22 Hz band powers caused by white-noise stimuli were seen in the left transverse temporal gyrus (BA 42) and superior temporal gyrus (BA 22). These results suggest that the left inferior frontal gyrus and left transverse and superior temporal gyri are involved in phonemic restoration for speech comprehension. Our findings may help clarify the neural mechanisms of phonemic restoration as well as develop innovative treatment methods for individuals suffering from impaired speech comprehension, particularly in noisy environments. © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Coffee, alcohol, smoking, physical activity and QT interval duration: results from the Third National Health and Nutrition Examination Survey.

PubMed

Zhang, Yiyi; Post, Wendy S; Dalal, Darshan; Blasco-Colmenares, Elena; Tomaselli, Gordon F; Guallar, Eliseo

2011-02-28

Abnormalities in the electrocardiographic QT interval duration have been associated with an increased risk of ventricular arrhythmias and sudden cardiac death. However, there is substantial uncertainty about the effect of modifiable factors such as coffee intake, cigarette smoking, alcohol consumption, and physical activity on QT interval duration. We studied 7795 men and women from the Third National Health and Nutrition Survey (NHANES III, 1988-1994). Baseline QT interval was measured from the standard 12-lead electrocardiogram. Coffee and tea intake, alcohol consumption, leisure-time physical activities over the past month, and lifetime smoking habits were determined using validated questionnaires during the home interview. In the fully adjusted model, the average differences in QT interval comparing participants drinking ≥6 cups/day to those who did not drink any were -1.2 ms (95% CI -4.4 to 2.0) for coffee, and -2.0 ms (-11.2 to 7.3) for tea, respectively. The average differences in QT interval duration comparing current to never smokers was 1.2 ms (-0.6 to 2.9) while the average difference in QT interval duration comparing participants drinking ≥7 drinks/week to non-drinkers was 1.8 ms (-0.5 to 4.0). The age, race/ethnicity, and RR-interval adjusted differences in average QT interval duration comparing men with binge drinking episodes to non-drinkers or drinkers without binge drinking were 2.8 ms (0.4 to 5.3) and 4.0 ms (1.6 to 6.4), respectively. The corresponding differences in women were 1.1 (-2.9 to 5.2) and 1.7 ms (-2.3 to 5.7). Finally, the average differences in QT interval comparing the highest vs. the lowest categories of total physical activity was -0.8 ms (-3.0 to 1.4). Binge drinking was associated with longer QT interval in men but not in women. QT interval duration was not associated with other modifiable factors including coffee and tea intake, smoking, and physical activity.

Coffee, Alcohol, Smoking, Physical Activity and QT Interval Duration: Results from the Third National Health and Nutrition Examination Survey

PubMed Central

Zhang, Yiyi; Post, Wendy S.; Dalal, Darshan; Blasco-Colmenares, Elena; Tomaselli, Gordon F.; Guallar, Eliseo

2011-01-01

Background Abnormalities in the electrocardiographic QT interval duration have been associated with an increased risk of ventricular arrhythmias and sudden cardiac death. However, there is substantial uncertainty about the effect of modifiable factors such as coffee intake, cigarette smoking, alcohol consumption, and physical activity on QT interval duration. Methods We studied 7795 men and women from the Third National Health and Nutrition Survey (NHANES III, 1988–1994). Baseline QT interval was measured from the standard 12-lead electrocardiogram. Coffee and tea intake, alcohol consumption, leisure-time physical activities over the past month, and lifetime smoking habits were determined using validated questionnaires during the home interview. Results In the fully adjusted model, the average differences in QT interval comparing participants drinking ≥6 cups/day to those who did not drink any were −1.2 ms (95% CI −4.4 to 2.0) for coffee, and −2.0 ms (−11.2 to 7.3) for tea, respectively. The average differences in QT interval duration comparing current to never smokers was 1.2 ms (−0.6 to 2.9) while the average difference in QT interval duration comparing participants drinking ≥7 drinks/week to non-drinkers was 1.8 ms (−0.5 to 4.0). The age, race/ethnicity, and RR-interval adjusted differences in average QT interval duration comparing men with binge drinking episodes to non-drinkers or drinkers without binge drinking were 2.8 ms (0.4 to 5.3) and 4.0 ms (1.6 to 6.4), respectively. The corresponding differences in women were 1.1 (−2.9 to 5.2) and 1.7 ms (−2.3 to 5.7). Finally, the average differences in QT interval comparing the highest vs. the lowest categories of total physical activity was −0.8 ms (−3.0 to 1.4). Conclusion Binge drinking was associated with longer QT interval in men but not in women. QT interval duration was not associated with other modifiable factors including coffee and tea intake, smoking, and physical activity. PMID:21386989

Cueing listeners to attend to a target talker progressively improves word report as the duration of the cue-target interval lengthens to 2,000 ms.

PubMed

Holmes, Emma; Kitterick, Padraig T; Summerfield, A Quentin

2018-04-25

Endogenous attention is typically studied by presenting instructive cues in advance of a target stimulus array. For endogenous visual attention, task performance improves as the duration of the cue-target interval increases up to 800 ms. Less is known about how endogenous auditory attention unfolds over time or the mechanisms by which an instructive cue presented in advance of an auditory array improves performance. The current experiment used five cue-target intervals (0, 250, 500, 1,000, and 2,000 ms) to compare four hypotheses for how preparatory attention develops over time in a multi-talker listening task. Young adults were cued to attend to a target talker who spoke in a mixture of three talkers. Visual cues indicated the target talker's spatial location or their gender. Participants directed attention to location and gender simultaneously ("objects") at all cue-target intervals. Participants were consistently faster and more accurate at reporting words spoken by the target talker when the cue-target interval was 2,000 ms than 0 ms. In addition, the latency of correct responses progressively shortened as the duration of the cue-target interval increased from 0 to 2,000 ms. These findings suggest that the mechanisms involved in preparatory auditory attention develop gradually over time, taking at least 2,000 ms to reach optimal configuration, yet providing cumulative improvements in speech intelligibility as the duration of the cue-target interval increases from 0 to 2,000 ms. These results demonstrate an improvement in performance for cue-target intervals longer than those that have been reported previously in the visual or auditory modalities.

A Variable Oscillator Underlies the Measurement of Time Intervals in the Rostral Medial Prefrontal Cortex during Classical Eyeblink Conditioning in Rabbits.

PubMed

Caro-Martín, C Rocío; Leal-Campanario, Rocío; Sánchez-Campusano, Raudel; Delgado-García, José M; Gruart, Agnès

2015-11-04

We were interested in determining whether rostral medial prefrontal cortex (rmPFC) neurons participate in the measurement of conditioned stimulus-unconditioned stimulus (CS-US) time intervals during classical eyeblink conditioning. Rabbits were conditioned with a delay paradigm consisting of a tone as CS. The CS started 50, 250, 500, 1000, or 2000 ms before and coterminated with an air puff (100 ms) directed at the cornea as the US. Eyelid movements were recorded with the magnetic search coil technique and the EMG activity of the orbicularis oculi muscle. Firing activities of rmPFC neurons were recorded across conditioning sessions. Reflex and conditioned eyelid responses presented a dominant oscillatory frequency of ≈12 Hz. The firing rate of each recorded neuron presented a single peak of activity with a frequency dependent on the CS-US interval (i.e., ≈12 Hz for 250 ms, ≈6 Hz for 500 ms, and≈3 Hz for 1000 ms). Interestingly, rmPFC neurons presented their dominant firing peaks at three precise times evenly distributed with respect to CS start and also depending on the duration of the CS-US interval (only for intervals of 250, 500, and 1000 ms). No significant neural responses were recorded at very short (50 ms) or long (2000 ms) CS-US intervals. rmPFC neurons seem not to encode the oscillatory properties characterizing conditioned eyelid responses in rabbits, but are probably involved in the determination of CS-US intervals of an intermediate range (250-1000 ms). We propose that a variable oscillator underlies the generation of working memories in rabbits. The way in which brains generate working memories (those used for the transient processing and storage of newly acquired information) is still an intriguing question. Here, we report that the firing activities of neurons located in the rostromedial prefrontal cortex recorded in alert behaving rabbits are controlled by a dynamic oscillator. This oscillator generated firing frequencies in a variable band of 3-12 Hz depending on the conditioned stimulus-unconditioned stimulus intervals (1 s, 500 ms, 250 ms) selected for classical eyeblink conditioning of behaving rabbits. Shorter (50 ms) and longer (2 s) intervals failed to activate the oscillator and prevented the acquisition of conditioned eyelid responses. This is an unexpected mechanism to generate sustained firing activities in neural circuits generating working memories. Copyright © 2015 the authors 0270-6474/15/3514809-13$15.00/0.

Accessing long-term memory representations during visual change detection.

PubMed

Beck, Melissa R; van Lamsweerde, Amanda E

2011-04-01

In visual change detection tasks, providing a cue to the change location concurrent with the test image (post-cue) can improve performance, suggesting that, without a cue, not all encoded representations are automatically accessed. Our studies examined the possibility that post-cues can encourage the retrieval of representations stored in long-term memory (LTM). Participants detected changes in images composed of familiar objects. Performance was better when the cue directed attention to the post-change object. Supporting the role of LTM in the cue effect, the effect was similar regardless of whether the cue was presented during the inter-stimulus interval, concurrent with the onset of the test image, or after the onset of the test image. Furthermore, the post-cue effect and LTM performance were similarly influenced by encoding time. These findings demonstrate that monitoring the visual world for changes does not automatically engage LTM retrieval.

The emotional memory effect: differential processing or item distinctiveness?

PubMed

Schmidt, Stephen R; Saari, Bonnie

2007-12-01

A color-naming task was followed by incidental free recall to investigate how emotional words affect attention and memory. We compared taboo, nonthreatening negative-affect, and neutral words across three experiments. As compared with neutral words, taboo words led to longer color-naming times and better memory in both within- and between-subjects designs. Color naming of negative-emotion nontaboo words was slower than color naming of neutral words only during block presentation and at relatively short interstimulus intervals (ISIs). The nontaboo emotion words were remembered better than neutral words following blocked and random presentation and at both long and short ISIs, but only in mixed-list designs. Our results support multifactor theories of the effects of emotion on attention and memory. As compared with neutral words, threatening stimuli received increased attention, poststimulus elaboration, and benefit from item distinctiveness, whereas nonthreatening emotional stimuli benefited only from increased item distinctiveness.

The color-vision approach to emotional space: cortical evoked potential data.

PubMed

Boucsein, W; Schaefer, F; Sokolov, E N; Schröder, C; Furedy, J J

2001-01-01

A framework for accounting for emotional phenomena proposed by Sokolov and Boucsein (2000) employs conceptual dimensions that parallel those of hue, brightness, and saturation in color vision. The approach that employs the concepts of emotional quality. intensity, and saturation has been supported by psychophysical emotional scaling data gathered from a few trained observers. We report cortical evoked potential data obtained during the change between different emotions expressed in schematic faces. Twenty-five subjects (13 male, 12 female) were presented with a positive, a negative, and a neutral computer-generated face with random interstimulus intervals in a within-subjects design, together with four meaningful and four meaningless control stimuli made up from the same elements. Frontal, central, parietal, and temporal ERPs were recorded from each hemisphere. Statistically significant outcomes in the P300 and N200 range support the potential fruitfulness of the proposed color-vision-model-based approach to human emotional space.

Dispersion of the corrected QT interval in the electrocardiogram of the ex-prisoners of war.

PubMed

Corović, Naima; Duraković, Zijad; Misigoj-Duraković, Marjeta

2003-04-01

The study of electrocardiograms (ECGs) was performed in a subgroup of 181 men, ex-prisoners of war with mean age 35.8+/-11.0 years and mean duration of imprisonment 164.5+/-87.1 days, chosen at random from the total sample of released prisoners (N=1458). The control group was pair-matched. The analysis of ECGs was done according to the Minnesota code, and Bazett's formula gave the values of the corrected QT interval (QT(c)). The dispersion of the QT(c) interval is determined by the difference between the longest and the shortest measured QT(c) interval in each ECG lead. The results of descriptive statistics in the group of ex-prisoners showed the range of QT(c) dispersion of 8.0-122.0 ms (mean 52.4+/-21.6 ms), while in the control group the range was 6.0-72.0 ms (mean 30.4+/-13.8 ms) (df=360, t=11.536; P<0.001). The QT(c) interval from 422.0 to 480.0 ms had 60.2% ex-prisoners and 30.4% controls, while a QT(c) interval over 480.0 ms had 19.3% ex-prisoners and 1.10% controls (P<0.0001). In the ex-prisoners group, the QT(c) dispersion over 50 ms was present in 51.4%; of those, a dispersion of 95 ms and more was found in 3.9%, while in the controls a QT(c) dispersion over 50 ms was found in 8.3%, but a dispersion of 95 ms and more was not recorded (P<0.0001). The odds ratio estimated for the prolonged QT(c) interval was 8.467 and for enlarged QT(c) dispersion it was 11.695 in the ex-prisoners versus controls (P<0.001). In conclusion, persons exposed to long-term maltreatment in detention camps have significantly greater QT(c) dispersion, as well as a higher relative risk of prolonged QT(c) interval and greater QT(c) dispersion than a control group.

The effects of aging on lifetime of auditory sensory memory in humans.

PubMed

Cheng, Chia-Hsiung; Lin, Yung-Yang

2012-02-01

The amplitude change of cortical responses to repeated stimulation with respect to different interstimulus intervals (ISIs) is considered as an index of sensory memory. To determine the effect of aging on lifetime of auditory sensory memory, N100m responses were recorded in young, middle-aged, and elderly healthy volunteers (n=15 for each group). Trains of 5 successive tones were presented with an inter-train interval of 10 s. In separate sessions, the within-train ISIs were 0.5, 1, 2, 4, and 8 s. The amplitude ratio between N100m responses to the first and fifth stimuli (S5/S1 N100m ratio) within each ISI condition was obtained to reflect the recovery cycle profile. The recovery function time constant (τ) was smaller in the elderly (1.06±0.26 s, p<0.001) and middle-aged (1.70±0.25 s, p=0.009) groups compared with the young group (2.77±0.25 s). In conclusion, the present study suggests an aging-related decrease in lifetime of auditory sensory memory. Copyright © 2011 Elsevier B.V. All rights reserved.

Active versus passive maintenance of visual nonverbal memory.

PubMed

McKeown, Denis; Holt, Jessica; Delvenne, Jean-Francois; Smith, Amy; Griffiths, Benjamin

2014-08-01

Forgetting over the short term has challenged researchers for more than a century, largely because of the difficulty of controlling what goes on within the memory retention interval. But the "recent-negative-probe" procedure offers a valuable paradigm, by examining the influences of (presumably) unattended memoranda from prior trials. Here we used a recent-probe task to investigate forgetting for visual nonverbal short-term memory. The target stimuli (two visually presented abstract shapes) on a trial were followed after a retention interval by a probe, and participants indicated whether the probe matched one of the target items. Proactive interference, and hence memory for old trial probes, was observed, whereby participants were slowed in rejecting a nonmatching probe on the current trial that nevertheless matched a target item on the previous trial (a recent-negative probe). The attraction of the paradigm is that, by uncovering proactive influences of past-trial probe stimuli, it can be argued that active maintenance in memory of those probes is unlikely. In two experiments, we recorded such proactive interference of prior-trial items over a range of interstimulus (ISI) and intertrial (ITI) intervals (between 1 and 6 s, respectively). Consistent with a proposed two-process memory conception (the active-passive memory model, or APM), actively maintained memories on current trials decayed, but passively "maintained," or unattended, visual memories of stimuli on past trials did not.

Neural network architecture for form and motion perception (Abstract Only)

NASA Astrophysics Data System (ADS)

Grossberg, Stephen

1991-08-01

Evidence is given for a new neural network theory of biological motion perception, a motion boundary contour system. This theory clarifies why parallel streams V1 yields V2 and V1 yields MT exist for static form and motion form processing among the areas V1, V2, and MT of visual cortex. The motion boundary contour system consists of several parallel copies, such that each copy is activated by a different range of receptive field sizes. Each copy is further subdivided into two hierarchically organized subsystems: a motion oriented contrast (MOC) filter, for preprocessing moving images; and a cooperative-competitive feedback (CC) loop, for generating emergent boundary segmentations of the filtered signals. The present work uses the MOC filter to explain a variety of classical and recent data about short-range and long- range apparent motion percepts that have not yet been explained by alternative models. These data include split motion; reverse-contrast gamma motion; delta motion; visual inertia; group motion in response to a reverse-contrast Ternus display at short interstimulus intervals; speed- up of motion velocity as interflash distance increases or flash duration decreases; dependence of the transition from element motion to group motion on stimulus duration and size; various classical dependencies between flash duration, spatial separation, interstimulus interval, and motion threshold known as Korte''s Laws; and dependence of motion strength on stimulus orientation and spatial frequency. These results supplement earlier explanations by the model of apparent motion data that other models have not explained; a recent proposed solution of the global aperture problem including explanations of motion capture and induced motion; an explanation of how parallel cortical systems for static form perception and motion form perception may develop, including a demonstration that these parallel systems are variations on a common cortical design; an explanation of why the geometries of static form and motion form differ, in particular why opposite orientations differ by 90 degree(s), whereas opposite directions differ by 180 degree(s), and why a cortical stream V1 yields V2 yields MT is needed; and a summary of how the main properties of other motion perception models can be assimilated into different parts of the motion boundary contour system design.

Left ventricular epicardial activation increases transmural dispersion of repolarization in healthy, long QT, and dilated cardiomyopathy dogs.

PubMed

Bai, Rong; Lü, Jiagao; Pu, Jun; Liu, Nian; Zhou, Qiang; Ruan, Yanfei; Niu, Huiyan; Zhang, Cuntai; Wang, Lin; Kam, Ruth

2005-10-01

Benefits of cardiac resynchronization therapy (CRT) are well established. However, less is understood concerning its effects on myocardial repolarization and the potential proarrhythmic risk. Healthy dogs (n = 8) were compared to a long QT interval (LQT) model (n = 8, induced by cesium chloride, CsCl) and a dilated cardiomyopathy with congestive heart failure (DCM-CHF, induced by rapid ventricular pacing, n = 5). Monophasic action potential (MAP) recordings were obtained from the subendocardium, midmyocardium, subepicardium, and the transmural dispersion of repolarization (TDR) was calculated. The QT interval and the interval from the peak to the end of the T wave (T(p-e)) were measured. All these characteristics were compared during left ventricular epicardial (LV-Epi), right ventricular endocardial (RV-Endo), and biventricular (Bi-V) pacing. In healthy dogs, TDR prolonged to 37.54 ms for Bi-V pacing and to 47.16 ms for LV-Epi pacing as compared to 26.75 ms for RV-Endo pacing (P < 0.001), which was parallel to an augmentation in T(p-e) interval (Bi-V pacing, 64.29 ms; LV-Epi pacing, 57.89 ms; RV-Endo pacing, 50.29 ms; P < 0.01). During CsCl exposure, Bi-V and LV-Epi pacing prolonged MAPD, TDR, and T(p-e) interval as compared to RV-Endo pacing. The midmyocardial MAPD (276.30 ms vs 257.35 ms, P < 0.0001) and TDR (33.80 ms vs 27.58 ms, P=0.002) were significantly longer in DCM-CHF dogs than those in healthy dogs. LV-Epi and Bi-V pacing further prolonged the MAPD and TDR in this model. LV-Epi and Bi-V pacing result in prolongation of ventricular repolarization time, and increase of TDR accounted for a parallel augmentation of the T(p-e) interval, which provides evidence that T(p-e) interval accurately represents TDR. These effects are magnified in the LQT and DCM-CHF canine models in addition to their intrinsic transmural heterogeneity in the intact heart. This mechanism may contribute to the development of malignant ventricular arrhythmias, such as torsades de pointes (TdP) in congestive heart failure (CHF) patients treated with CRT.

The prognostic value of the QT interval and QT interval dispersion in all-cause and cardiac mortality and morbidity in a population of Danish citizens.

PubMed

Elming, H; Holm, E; Jun, L; Torp-Pedersen, C; Køber, L; Kircshoff, M; Malik, M; Camm, J

1998-09-01

To evaluate the prognostic value of the QT interval and QT interval dispersion in total and in cardiovascular mortality, as well as in cardiac morbidity, in a general population. The QT interval was measured in all leads from a standard 12-lead ECG in a random sample of 1658 women and 1797 men aged 30-60 years. QT interval dispersion was calculated from the maximal difference between QT intervals in any two leads. All cause mortality over 13 years, and cardiovascular mortality as well as cardiac morbidity over 11 years, were the main outcome parameters. Subjects with a prolonged QT interval (430 ms or more) or prolonged QT interval dispersion (80 ms or more) were at higher risk of cardiovascular death and cardiac morbidity than subjects whose QT interval was less than 360 ms, or whose QT interval dispersion was less than 30 ms. Cardiovascular death relative risk ratios, adjusted for age, gender, myocardial infarct, angina pectoris, diabetes mellitus, arterial hypertension, smoking habits, serum cholesterol level, and heart rate were 2.9 for the QT interval (95% confidence interval 1.1-7.8) and 4.4 for QT interval dispersion (95% confidence interval 1.0-19-1). Fatal and non-fatal cardiac morbidity relative risk ratios were similar, at 2.7 (95% confidence interval 1.4-5.5) for the QT interval and 2.2 (95% confidence interval 1.1-4.0) for QT interval dispersion. Prolongation of the QT interval and QT interval dispersion independently affected the prognosis of cardiovascular mortality and cardiac fatal and non-fatal morbidity in a general population over 11 years.

Electrophysiological markers predicting impeding AV-block during ablation of atrioventricular nodal reentry tachycardia.

PubMed

Fragakis, Nikolaos; Krexi, Lydia; Kyriakou, Panagiota; Sotiriadou, Melani; Lazaridis, Charalambos; Karamanolis, Athanasios; Dalampyras, Panagiotis; Tsakiroglou, Stelios; Skeberis, Vassilios; Tsalikakis, Dimitrios; Vassilikos, Vassilios

2018-01-01

Radiofrequency (RF) ablation of the slow pathway (SP) in atrioventricular nodal reentry tachycardia (AVNRT) is occasionally complicated with atrioventricular block (AVB) often predicted by junctional beats (JB) with loss of ventriculo-atrial (VA) conduction. We analyzed retrospectively 153 patients undergoing ablation of SP for typical AVNRT. Patients were divided into two age groups: 127 ≤ 70 years and 26 > 70 years. We analyzed the interval between the atrial electrogram in the His-bundle position and the distal ablation catheter [A(H)-A(RFd)] and between the distal ablation catheter and the proximal coronary sinus catheter [A(RFd)-A(CS)] before RF applications with and without JB. We evaluated if these intervals can be used as predictors of JB incidence and also of JB with loss of VA conduction. We also assessed if age influences the risk of loss of VA conduction. The A(H)-A(RFd) and A(RFd)-A(CS) intervals were significantly shorter in RF applications causing JB than those without JB (33 ± 11 ms vs 39 ± 9 ms, P < 0.001, 14 ± 9 ms vs 20 ± 7 ms, P < 0.001, respectively). The A(H)-A(RFd) and A(RFd)-A(CS) intervals were also significantly shorter in RFs causing JB with VA block than those with VA conduction (29 ± 11 ms vs 35 ± 11 ms, P < 0.001, 8 ± 8 ms vs 17 ± 8 ms, P < 0.001, respectively). Patients > 70 years had shorter intervals (36 ± 11 ms vs 29 ± 8 ms, P  =  0.012, 17 ± 8 ms vs 13 ± 7 ms, P  =  0.027, respectively), while VA block was more common in this age group. The A(H)-A(RFd) and A(RFd)-A(CS) intervals can be used as markers for predicting JB occurrence as well as impending AVB. JB with loss of VA conduction occur more often in older patients possibly due to a higher position of SP. © 2017 Wiley Periodicals, Inc.

Dried blood spot testing for seven steroids using liquid chromatography-tandem mass spectrometry with reference interval determination in the Korean population.

PubMed

Kim, Borahm; Lee, Mi Na; Park, Hyung Doo; Kim, Jong Won; Chang, Yun Sil; Park, Won Soon; Lee, Soo Youn

2015-11-01

Conventional screening for congenital adrenal hyperplasia (CAH) using immunoassays generates a large number of false-positive results. A more specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been introduced to minimize unnecessary follow-ups. However, because of limited data on its use in the Korean population, LC-MS/MS has not yet been incorporated into newborn screening programs in this region. The present study aims to develop and validate an LC-MS/MS method for the simultaneous determination of seven steroids in dried blood spots (DBS) for CAH screening, and to define age-specific reference intervals in the Korean population. We developed and validated an LC-MS/MS method to determine the reference intervals of cortisol, 17-hydroxyprogesterone, 11-deoxycortisol, 21-deoxycortisol, androstenedione, corticosterone, and 11-deoxycorticosterone simultaneously in 453 DBS samples. The samples were from Korean subjects stratified by age group (78 full-term neonates, 76 premature neonates, 89 children, and 100 adults). The accuracy, precision, matrix effects, and extraction recovery were satisfactory for all the steroids at three concentrations; values of intra- and inter-day precision coefficients of variance, bias, and recovery were 0.7-7.7%, -1.5-9.8%, and 49.3-97.5%, respectively. The linearity range was 1-100 ng/mL for cortisol and 0.5-50 ng/mL for other steroids (R²>0.99). The reference intervals were in agreement with the previous reports. This LC-MS/MS method and the reference intervals validated in the Korean population can be successfully applied to analyze seven steroids in DBS for the diagnosis of CAH.

Pediatric Reference Intervals for Free Thyroxine and Free Triiodothyronine

PubMed Central

Jang, Megan; Guo, Tiedong; Soldin, Steven J.

2009-01-01

Background The clinical value of free thyroxine (FT4) and free triiodothyronine (FT3) analysis depends on the reference intervals with which they are compared. We determined age- and sex-specific reference intervals for neonates, infants, and children 0–18 years of age for FT4 and FT3 using tandem mass spectrometry. Methods Reference intervals were calculated for serum FT4 (n = 1426) and FT3 (n = 1107) obtained from healthy children between January 1, 2008, and June 30, 2008, from Children's National Medical Center and Georgetown University Medical Center Bioanalytical Core Laboratory, Washington, DC. Serum samples were analyzed using isotope dilution liquid chromatography tandem mass spectrometry (LC/MS/MS) with deuterium-labeled internal standards. Results FT4 reference intervals were very similar for males and females of all ages and ranged between 1.3 and 2.4 ng/dL for children 1 to 18 years old. FT4 reference intervals for 1- to 12-month-old infants were 1.3–2.8 ng/dL. These 2.5 to 97.5 percentile intervals were much tighter than reference intervals obtained using immunoassay platforms 0.48–2.78 ng/dL for males and 0.85–2.09 ng/dL for females. Similarly, FT3 intervals were consistent and similar for males and females and for all ages, ranging between 1.5 pg/mL and approximately 6.0 pg/mL for children 1 month of age to 18 years old. Conclusions This is the first study to provide pediatric reference intervals of FT4 and FT3 for children from birth to 18 years of age using LC/MS/MS. Analysis using LC/MS/MS provides more specific quantification of thyroid hormones. A comparison of the ultrafiltration tandem mass spectrometric method with equilibrium dialysis showed very good correlation. PMID:19583487

Systematic review of serum steroid reference intervals developed using mass spectrometry.

PubMed

Tavita, Nevada; Greaves, Ronda F

2017-12-01

The aim of this study was to perform a systematic review of the published literature to determine the available serum/plasma steroid reference intervals generated by mass spectrometry (MS) methods across all age groups in healthy subjects and to suggest recommendations to achieve common MS based reference intervals for serum steroids. MEDLINE, EMBASE and PubMed databases were used to conduct a comprehensive search for English language, MS-based reference interval studies for serum/plasma steroids. Selection of steroids to include was based on those listed in the Royal College of Pathologists of Australasia Quality Assurance Programs, Chemical Pathology, Endocrine Program. This methodology has been registered onto the PROSPERO International prospective register of systematic reviews (ID number: CRD42015029637). After accounting for duplicates, a total of 60 manuscripts were identified through the search strategy. Following critical evaluation, a total of 16 studies were selected. Of the 16 studies, 12 reported reference intervals for testosterone, 11 for 17 hydroxy-progesterone, nine for androstenedione, six for cortisol, three for progesterone, two for dihydrotestosterone and only one for aldosterone and dehydroepiandrosterone sulphate. No studies established MS-based reference intervals for oestradiol. As far as we are aware, this report provides the first comparison of the peer reviewed literature for serum/plasma steroid reference intervals generated by MS-based methods. The reference intervals based on these published studies can be used to inform the process to develop common reference intervals, and agreed reporting units for mass spectrometry based steroid methods. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Influence of Pacing by Periodic Auditory Stimuli on Movement Continuation: Comparison with Self-regulated Periodic Movement

PubMed Central

Ito, Masanori; Kado, Naoki; Suzuki, Toshiaki; Ando, Hiroshi

2013-01-01

[Purpose] The purpose of this study was to investigate the influence of external pacing with periodic auditory stimuli on the control of periodic movement. [Subjects and Methods] Eighteen healthy subjects performed self-paced, synchronization-continuation, and syncopation-continuation tapping. Inter-onset intervals were 1,000, 2,000 and 5,000 ms. The variability of inter-tap intervals was compared between the different pacing conditions and between self-paced tapping and each continuation phase. [Results] There were no significant differences in the mean and standard deviation of the inter-tap interval between pacing conditions. For the 1,000 and 5,000 ms tasks, there were significant differences in the mean inter-tap interval following auditory pacing compared with self-pacing. For the 2,000 ms syncopation condition and 5,000 ms task, there were significant differences from self-pacing in the standard deviation of the inter-tap interval following auditory pacing. [Conclusion] These results suggest that the accuracy of periodic movement with intervals of 1,000 and 5,000 ms can be improved by the use of auditory pacing. However, the consistency of periodic movement is mainly dependent on the inherent skill of the individual; thus, improvement of consistency based on pacing is unlikely. PMID:24259932

The truth will out: interrogative polygraphy ("lie detection") with event-related brain potentials.

PubMed

Farwell, L A; Donchin, E

1991-09-01

The feasibility of using Event Related Brain Potentials (ERPs) in Interrogative Polygraphy ("Lie Detection") was tested by examining the effectiveness of the Guilty Knowledge Test designed by Farwell and Donchin (1986, 1988). The subject is assigned an arbitrary task requiring discrimination between experimenter-designated targets and other, irrelevant stimuli. A group of diagnostic items ("probes"), which to the unwitting are indistinguishable from the irrelevant items, are embedded among the irrelevant. For subjects who possess "guilty knowledge" these probes are distinct from the irrelevants and are likely to elicit a P300, thus revealing their possessing the special knowledge that allows them to differentiate the probes from the irrelevants. We report two experiments in which this paradigm was tested. In Experiment 1, 20 subjects participated in one of two mock espionage scenarios and were tested for their knowledge of both scenarios. All stimuli consisted of short phrases presented for 300 ms each at an interstimulus interval of 1550 ms. A set of items were designated as "targets" and appeared on 17% of the trials. Probes related to the scenarios also appeared on 17% of the trials. The rest of the items were irrelevants. Subjects responded by pressing one switch following targets, and the other following irrelevants (and, of course, probes). ERPs were recorded from FZ, CZ, and PZ. As predicted, targets elicited large P300s in all subjects. Probes associated with a given scenario elicited a P300 in subjects who participated in that scenario. A bootstrapping method was used to assess the quality of the decision for each subject. The algorithm declared the decision indeterminate in 12.5% of the cases. In all other cases a decision was made. There were no false positives and no false negatives: whenever a determination was made it was accurate. The second experiment was virtually identical to the first, with identical results, except that this time 4 subjects were tested, each of which had a minor brush with the law. Subjects were tested to determine whether they possessed information on their own "crimes." The results were as expected; the Guilty Knowledge Test determined correctly which subject possessed which information. The implications of these data both for the practice of Interrogative Polygraphy and the interpretation of the P300 are discussed.

Xenon does not increase heart rate-corrected cardiac QT interval in volunteers and in patients free of cardiovascular disease.

PubMed

Neukirchen, Martin; Schaefer, Maximilian S; Kern, Carolin; Brett, Sarah; Werdehausen, Robert; Rellecke, Philipp; Reyle-Hahn, Matthias; Kienbaum, Peter

2015-09-01

Impaired cardiac repolarization, indicated by prolonged QT interval, may cause critical ventricular arrhythmias. Many anesthetics increase the QT interval by blockade of rapidly acting potassium rectifier channels. Although xenon does not affect these channels in isolated cardiomyocytes, the authors hypothesized that xenon increases the QT interval by direct and/or indirect sympathomimetic effects. Thus, the authors tested the hypothesis that xenon alters the heart rate-corrected cardiac QT (QTc) interval in anesthetic concentrations. The effect of xenon on the QTc interval was evaluated in eight healthy volunteers and in 35 patients undergoing abdominal or trauma surgery. The QTc interval was recorded on subjects in awake state, after their denitrogenation, and during xenon monoanesthesia (FetXe > 0.65). In patients, the QTc interval was recorded while awake, after anesthesia induction with propofol and remifentanil, and during steady state of xenon/remifentanil anesthesia (FetXe > 0.65). The QTc interval was determined from three consecutive cardiac intervals on electrocardiogram printouts in a blinded manner and corrected with Bazett formula. In healthy volunteers, xenon did not alter the QTc interval (mean difference: +0.11 ms [95% CI, -22.4 to 22.7]). In patients, after anesthesia induction with propofol/remifentanil, no alteration of QTc interval was noted. After propofol was replaced with xenon, the QTc interval remained unaffected (417 ± 32 ms vs. awake: 414 ± 25 ms) with a mean difference of 4.4 ms (95% CI, -4.6 to 13.5). Xenon monoanesthesia in healthy volunteers and xenon/remifentanil anesthesia in patients without clinically relevant cardiovascular disease do not increase QTc interval.

Dynamic QT Interval Changes from Supine to Standing in Healthy Children.

PubMed

Dionne, Audrey; Fournier, Anne; Dahdah, Nagib; Abrams, Dominic; Khairy, Paul; Abadir, Sylvia

2018-01-01

QT-interval variations in response to exercise-induced increases in heart rate have been reported in children and adults in the diagnosis of long QT syndrome (LQTS). A quick standing challenge has been proposed as an alternative provocative test in adults, with no pediatric data yet available. A standing test was performed in 100 healthy children (mean age, 9.7 ± 3.1 years) after 10 minutes in a supine position with continuous electrocardiographic recording. QT intervals were measured at baseline, at maximal heart rate, at maximal QT, and at each minute of a 5-minute recovery while standing. Measurements were taken in leads II/V 5 and were corrected for heart rate (QTc). On standing, the heart rate increased by 29 ± 10 beats per minute (bpm). The QT interval was similar at baseline and on standing (394 ± 34 ms vs 394 ± 34 ms; P = 1.0). However, QTc increased from 426 ± 21 to 509 ± 41 ms (P < 0.001). The 95th percentile for QTc at baseline and maximal heart rate was 457 ms and 563 ms, respectively. At 1 minute of recovery, the QT interval was shorter (375 ± 31 ms) compared with baseline (394 ± 34 ms; P < 0.001) and standing (394 ± 34 ms; P < 0.001). QTc reached baseline values after 1 minute of recovery and remained stable thereafter (423 ± 23 ms at 1 minute; 426 ± 22 ms at 5 minutes; P = 1.0). This first characterization of QTc changes on standing in children shows substantial alterations, which are greater than those seen in adults. Two-thirds of the children would have been misclassified as having LQTS by adult criteria, indicating the need to create child-specific standards. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Lacosamide cardiac safety: a thorough QT/QTc trial in healthy volunteers.

PubMed

Kropeit, D; Johnson, M; Cawello, W; Rudd, G D; Horstmann, R

2015-11-01

To determine whether lacosamide prolongs the corrected QT interval (QTc). In this randomized, double-blind, positive- and placebo-controlled, parallel-design trial, healthy volunteers were randomized to lacosamide 400 mg/day (maximum-recommended daily dose, 6 days), lacosamide 800 mg/day (supratherapeutic dose, 6 days), placebo (6 days), or moxifloxacin 400 mg/day (3 days). Variables included maximum time-matched change from baseline in QT interval individually corrected for heart rate ([HR] QTcI), other ECG parameters, pharmacokinetics (PK), and safety/tolerability. The QTcI mean maximum difference from placebo was -4.3 ms and -6.3 ms for lacosamide 400 and 800 mg/day; upper limits of the 2-sided 90% confidence interval were below the 10 ms non-inferiority margin (-0.5 and -2.5 ms, respectively). Placebo-corrected QTcI for moxifloxacin was +10.4 ms (lower 90% confidence bound >0 [6.6 ms]), which established assay sensitivity for this trial. As lacosamide did not increase QTcI, the trial is considered a negative QTc trial. There was no dose-related or clinically relevant effect on QRS duration. HR increased from baseline by ~5 bpm with lacosamide 800 mg/day versus placebo. Placebo-subtracted mean increases in PR interval at tmax were 7.3 ms (400 mg/day) and 11.9 ms (800 mg/day). There were no findings of second-degree or higher atrioventricular block. Adverse events (AEs) were dose related and most commonly involved the nervous and gastrointestinal systems. Lacosamide (≤ 800 mg/day) did not prolong the QTc interval. Lacosamide caused a small, dose-related increase in mean PR interval that was not associated with AEs. Cardiac, overall safety, and PK profiles for lacosamide in healthy volunteers were consistent with those observed in patients with partial-onset seizures. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Influence of double stimulation on sound-localization behavior in barn owls.

PubMed

Kettler, Lutz; Wagner, Hermann

2014-12-01

Barn owls do not immediately approach a source after they hear a sound, but wait for a second sound before they strike. This represents a gain in striking behavior by avoiding responses to random incidents. However, the first stimulus is also expected to change the threshold for perceiving the subsequent second sound, thus possibly introducing some costs. We mimicked this situation in a behavioral double-stimulus paradigm utilizing saccadic head turns of owls. The first stimulus served as an adapter, was presented in frontal space, and did not elicit a head turn. The second stimulus, emitted from a peripheral source, elicited the head turn. The time interval between both stimuli was varied. Data obtained with double stimulation were compared with data collected with a single stimulus from the same positions as the second stimulus in the double-stimulus paradigm. Sound-localization performance was quantified by the response latency, accuracy, and precision of the head turns. Response latency was increased with double stimuli, while accuracy and precision were decreased. The effect depended on the inter-stimulus interval. These results suggest that waiting for a second stimulus may indeed impose costs on sound localization by adaptation and this reduces the gain obtained by waiting for a second stimulus.

Is there a prognostic relevance of electrophysiological studies in bundle branch block patients?

PubMed

Bogossian, Harilaos; Frommeyer, Gerrit; Göbbert, Kornelius; Hasan, Fuad; Nguyen, Quy Suu; Ninios, Ilias; Mijic, Dejan; Bandorski, Dirk; Hoeltgen, Reinhard; Seyfarth, Melchior; Lemke, Bernd; Eckardt, Lars; Zarse, Markus

2017-08-01

The present European guidelines suggest a diagnostic electrophysiological (EP) study to determine indication for cardiac pacing in patients with bundle branch block and unexplained syncope. We evaluated the prognostic relevance of an EP study for mortality and the development of permanent complete atrioventricular (AV) block in patients with symptomatic bifascicular block and first-degree AV block. The HV interval is a poor prognostic marker to predict the development of permanent AV block in patients with symptomatic bifascicular block (BFB) and AV block I°. Thirty consecutive patients (mean age, 74.8 ± 8.6 years; 25 males) with symptomatic BFB and first-degree AV block underwent an EP study before device implantation, according to current guidelines. For 53 ± 31 months, patients underwent yearly follow-up screening for syncope or higher-degree AV block. Thirty patients presented with prolonged HV interval during the EP study (mean, 82.2 ± 20.1 ms; range, 57-142 ms), classified into 3 groups: group 1, <70 ms (mean, 62 ± 4 ms; range, 57-67 ms; n = 7), group 2, >70 to ≤100 ms (mean, 80 ± 8 ms; range, 70-97 ms; n = 18), and group 3, >100 ms (mean, 119 ± 14 ms; range, 107-142 ms; n = 5). According to the guidelines, patients in groups 2 and 3 received a pacemaker. The length of the HV interval was not associated with the later development of third-degree AV block or with increased mortality. Our present study suggests that an indication for pacemaker implantation based solely on a diagnostic EP study with prolongation of the HV interval is not justified. © 2017 Wiley Periodicals, Inc.

Tp-Te interval predicts heart rate reduction after fingolimod administration in patients with multiple sclerosis.

PubMed

Tocci, Giuliano; Giuliani, Manuela; Canichella, Flaminia; Timpano, Jacopo; Presta, Vivianne; Francia, Pietro; Musumeci, Maria Beatrice; Fubelli, Federica; Pozzilli, Carlo; Volpe, Massimo; Ferrucci, Andrea

2016-10-15

FTY720 (Fingolimod) is an immunosuppressive drug, which provides favourable effects in patients with multiple sclerosis (MS), albeit it induces heart rate (HR) and blood pressure (BP) reductions. Therefore, we tested potential factors able to predict HR response in MS patients treated with fingolimod. We analysed patients with MS followed at our Neurology Outpatient Clinic from May 2013 to June 2015. All patients underwent BP measurements and 12-lead ECG before and 6-h after drug administration. At these time intervals, conventional and new ECG indexes for cardiac damage, including Tp-Te interval, were measured. Univariate and multivariate analyses were performed to test the outcome of HR reduction more than median difference between baseline and final observations. 69 outpatients with MS (46 males, age 35.1±9.4years, BP 119.0±12.7/73.0±9.3mmHg, HR 73.5±11.4bpm) were included. No relevant adverse reactions were reported. Fingolimod induced progressive systolic (P=0.024) and diastolic (P<0.001) BP, as well as HR (P<0.001) reductions compared to baseline. Prolonged PQ (150.4±19.5 vs. 157.0±19.5ms; P<0.001), QT (374.9±27.0 vs. 400.0±25.8ms; P<0.001), Tp-Te (1.8±0.3 vs. 1.9±0.3mm; P=0.021), and reduced QTc (414.4±24.4 vs. 404.5±24.5ms; P<0.001) intervals were also recorded at final observation. Baseline HR, QT and Tp-Te intervals provided prognostic information at univariate analysis, although Tp-Te interval resulted the best independent predictor for HR reduction at multivariate analysis [0.057 (0.005-0.660); P=0.022]. This study firstly demonstrates that prolonged Tp-Te interval may identify those MS patients treated with fingolimod at higher risk of having significant, asymptomatic HR reduction during clinical observation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Circadian rhythm in QT interval is preserved in mice deficient of potassium channel interacting protein 2.

PubMed

Gottlieb, Lisa A; Lubberding, Anniek; Larsen, Anders Peter; Thomsen, Morten B

2017-01-01

Potassium Channel Interacting Protein 2 (KChIP2) is suggested to be responsible for the circadian rhythm in repolarization duration, ventricular arrhythmias, and sudden cardiac death. We investigated the hypothesis that there is no circadian rhythm in QT interval in the absence of KChIP2. Implanted telemetric devices recorded electrocardiogram continuously for 5 days in conscious wild-type mice (WT, n = 9) and KChIP2 -/- mice (n = 9) in light:dark periods and in complete darkness. QT intervals were determined from all RR intervals and corrected for heart rate (QT 100 = QT/(RR/100) 1/2 ). Moreover, QT intervals were determined from complexes within the RR range of mean-RR ± 1% in the individual mouse (QT mean-RR ). We find that RR intervals are 125 ± 5 ms in WT and 123 ± 4 ms in KChIP2 -/- (p = 0.81), and QT intervals are 52 ± 1 and 52 ± 1 ms, respectively(p = 0.89). No ventricular arrhythmias or sudden cardiac deaths were observed. We find similar diurnal (light:dark) and circadian (darkness) rhythms of RR intervals in WT and KChIP2 -/- mice. Circadian rhythms in QT 100 intervals are present in both groups, but at physiological small amplitudes: 1.6 ± 0.2 and 1.0 ± 0.3 ms in WT and KChIP2 -/- , respectively (p = 0.15). A diurnal rhythm in QT 100 intervals was only found in WT mice. QT mean-RR intervals display clear diurnal and circadian rhythms in both WT and KChIP2 -/- . The amplitude of the circadian rhythm in QT mean-RR is 4.0 ± 0.3 and 3.1 ± 0.5 ms in WT and KChIP2 -/- , respectively (p = 0.16). In conclusion, KChIP2 expression does not appear to underlie the circadian rhythm in repolarization duration.

Association of low-moderate urine arsenic and QT interval: Cross-sectional and longitudinal evidence from the Strong Heart Study.

PubMed

Moon, Katherine A; Zhang, Yiyi; Guallar, Eliseo; Francesconi, Kevin A; Goessler, Walter; Umans, Jason G; Best, Lyle G; Howard, Barbara V; Devereux, Richard B; Okin, Peter M; Navas-Acien, Ana

2018-05-21

Epidemiologic studies suggest that chronic exposure to arsenic is related to cardiovascular disease (CVD), but the pathophysiological link remains uncertain. We evaluated the association of chronic low-moderate arsenic exposure and arsenic metabolism with baseline difference and annual change in ECG measures (QT interval, JT interval, PR interval, QRS duration, and QT dispersion) using linear mixed models in the Strong Heart Study main cohort (N = 1174, median age 55 years) and family study (N = 1695 diabetes-free, median age 36 years). At baseline, arsenic exposure was measured as the sum of inorganic and methylated species in urine (ΣAs) and arsenic metabolism was measured as the relative percentage of arsenic species. Median ΣAs and Bazett heart rate-corrected QT interval (QTc) were 8.6 μg/g creatinine and 424 ms in the main cohort and 4.3 μg/g and 414 ms in the family study, respectively. In the main cohort, a comparison of the highest to lowest ΣAs quartile (>14.4 vs. <5.2 μg/g creatinine) was associated with a 5.3 (95% CI: 1.2, 9.5) ms higher mean baseline QTc interval but no difference in annual change in QTc interval. In the family study, a comparison of the highest to lowest quartile (>7.1 vs. <2.9 μg/g creatinine) was associated with a 3.2 (95% CI: 0.6, 5.7) ms higher baseline QTc interval and a 0.6 (95% CI: 0.04, 1.2) ms larger annual increase in QTc interval. Associations with JTc interval were similar but stronger in magnitude compared to QTc interval. Arsenic exposure was largely not associated with PR interval, QRS duration or QT dispersion. Similar to arsenic exposure, a pattern of lower %MMA and higher %DMA was associated with longer baseline QTc interval in both cohorts and with a larger annual change in QTc interval in the family study. Chronic low-moderate arsenic exposure and arsenic metabolism were associated with prolonged ventricular repolarization. Copyright © 2018 Elsevier Ltd. All rights reserved.

Stability of auditory discrimination and novelty processing in physiological aging.

PubMed

Raggi, Alberto; Tasca, Domenica; Rundo, Francesco; Ferri, Raffaele

2013-01-01

Complex higher-order cognitive functions and their possible changes with aging are mandatory objectives of cognitive neuroscience. Event-related potentials (ERPs) allow investigators to probe the earliest stages of information processing. N100, Mismatch negativity (MMN) and P3a are auditory ERP components that reflect automatic sensory discrimination. The aim of the present study was to determine if N100, MMN and P3a parameters are stable in healthy aged subjects, compared to those of normal young adults. Normal young adults and older participants were assessed using standardized cognitive functional instruments and their ERPs were obtained with an auditory stimulation at two different interstimulus intervals, during a passive paradigm. All individuals were within the normal range on cognitive tests. No significant differences were found for any ERP parameters obtained from the two age groups. This study shows that aging is characterized by a stability of the auditory discrimination and novelty processing. This is important for the arrangement of normative for the detection of subtle preclinical changes due to abnormal brain aging.

New objects do not capture attention without a sensory transient.

PubMed

Hollingworth, Andrew; Simons, Daniel J; Franconeri, Steven L

2010-07-01

Attention capture occurs when a stimulus event involuntarily recruits attention. The abrupt appearance of a new object is perhaps the most well-studied attention-capturing event, yet there is debate over the root cause of this capture. Does a new object capture attention because it involves the creation of a new object representation or because its appearance creates a characteristic luminance transient? The present study sought to resolve this question by introducing a new object into a search display, either with or without a unique luminance transient. Contrary to the results of a recent study (Davoli, Suszko, & Abrams, 2007), when the new object's transient was masked by a brief interstimulus interval introduced between the placeholder and search arrays, a new object did not capture attention. Moreover, when a new object's transient was masked, participants could not locate a new object efficiently even when that was their explicit goal. Together, these data suggest that luminance transient signals are necessary for attention capture by new objects.

A Novel Stimulus Artifact Removal Technique for High-Rate Electrical Stimulation

PubMed Central

Heffer, Leon F; Fallon, James B

2008-01-01

Electrical stimulus artifact corrupting electrophysiological recordings often make the subsequent analysis of the underlying neural response difficult. This is particularly evident when investigating short-latency neural activity in response to high-rate electrical stimulation. We developed and evaluated an off-line technique for the removal of stimulus artifact from electrophysiological recordings. Pulsatile electrical stimulation was presented at rates of up to 5000 pulses/s during extracellular recordings of guinea pig auditory nerve fibers. Stimulus artifact was removed by replacing the sample points at each stimulus artifact event with values interpolated along a straight line, computed from neighbouring sample points. This technique required only that artifact events be identifiable and that the artifact duration remained less than both the inter-stimulus interval and the time course of the action potential. We have demonstrated that this computationally efficient sample-and-interpolate technique removes the stimulus artifact with minimal distortion of the action potential waveform. We suggest that this technique may have potential applications in a range of electrophysiological recording systems. PMID:18339428

Effects of verbal and nonverbal interference on spatial and object visual working memory.

PubMed

Postle, Bradley R; Desposito, Mark; Corkin, Suzanne

2005-03-01

We tested the hypothesis that a verbal coding mechanism is necessarily engaged by object, but not spatial, visual working memory tasks. We employed a dual-task procedure that paired n-back working memory tasks with domain-specific distractor trials inserted into each interstimulus interval of the n-back tasks. In two experiments, object n-back performance demonstrated greater sensitivity to verbal distraction, whereas spatial n-back performance demonstrated greater sensitivity to motion distraction. Visual object and spatial working memory may differ fundamentally in that the mnemonic representation of featural characteristics of objects incorporates a verbal (perhaps semantic) code, whereas the mnemonic representation of the location of objects does not. Thus, the processes supporting working memory for these two types of information may differ in more ways than those dictated by the "what/where" organization of the visual system, a fact more easily reconciled with a component process than a memory systems account of working memory function.

Spaced Learning Enhances Subsequent Recognition Memory by Reducing Neural Repetition Suppression

PubMed Central

Xue, Gui; Mei, Leilei; Chen, Chuansheng; Lu, Zhong-Lin; Poldrack, Russell; Dong, Qi

2012-01-01

Spaced learning usually leads to better recognition memory as compared with massed learning, yet the underlying neural mechanisms remain elusive. One open question is whether the spacing effect is achieved by reducing neural repetition suppression. In this fMRI study, participants were scanned while intentionally memorizing 120 novel faces, half under the massed learning condition (i.e., four consecutive repetitions with jittered interstimulus interval) and the other half under the spaced learning condition (i.e., the four repetitions were interleaved). Recognition memory tests afterward revealed a significant spacing effect: Participants recognized more items learned under the spaced learning condition than under the massed learning condition. Successful face memory encoding was associated with stronger activation in the bilateral fusiform gyrus, which showed a significant repetition suppression effect modulated by subsequent memory status and spaced learning. Specifically, remembered faces showed smaller repetition suppression than forgotten faces under both learning conditions, and spaced learning significantly reduced repetition suppression. These results suggest that spaced learning enhances recognition memory by reducing neural repetition suppression. PMID:20617892

Spaced learning enhances subsequent recognition memory by reducing neural repetition suppression.

PubMed

Xue, Gui; Mei, Leilei; Chen, Chuansheng; Lu, Zhong-Lin; Poldrack, Russell; Dong, Qi

2011-07-01

Spaced learning usually leads to better recognition memory as compared with massed learning, yet the underlying neural mechanisms remain elusive. One open question is whether the spacing effect is achieved by reducing neural repetition suppression. In this fMRI study, participants were scanned while intentionally memorizing 120 novel faces, half under the massed learning condition (i.e., four consecutive repetitions with jittered interstimulus interval) and the other half under the spaced learning condition (i.e., the four repetitions were interleaved). Recognition memory tests afterward revealed a significant spacing effect: Participants recognized more items learned under the spaced learning condition than under the massed learning condition. Successful face memory encoding was associated with stronger activation in the bilateral fusiform gyrus, which showed a significant repetition suppression effect modulated by subsequent memory status and spaced learning. Specifically, remembered faces showed smaller repetition suppression than forgotten faces under both learning conditions, and spaced learning significantly reduced repetition suppression. These results suggest that spaced learning enhances recognition memory by reducing neural repetition suppression.

Effects of verbal and nonverbal interference on spatial and object visual working memory

PubMed Central

POSTLE, BRADLEY R.; D’ESPOSITO, MARK; CORKIN, SUZANNE

2005-01-01

We tested the hypothesis that a verbal coding mechanism is necessarily engaged by object, but not spatial, visual working memory tasks. We employed a dual-task procedure that paired n-back working memory tasks with domain-specific distractor trials inserted into each interstimulus interval of the n-back tasks. In two experiments, object n-back performance demonstrated greater sensitivity to verbal distraction, whereas spatial n-back performance demonstrated greater sensitivity to motion distraction. Visual object and spatial working memory may differ fundamentally in that the mnemonic representation of featural characteristics of objects incorporates a verbal (perhaps semantic) code, whereas the mnemonic representation of the location of objects does not. Thus, the processes supporting working memory for these two types of information may differ in more ways than those dictated by the “what/where” organization of the visual system, a fact more easily reconciled with a component process than a memory systems account of working memory function. PMID:16028575

Does sensitivity in binary choice tasks depend on response modality?

PubMed

Szumska, Izabela; van der Lubbe, Rob H J; Grzeczkowski, Lukasz; Herzog, Michael H

2016-07-01

In most models of vision, a stimulus is processed in a series of dedicated visual areas, leading to categorization of this stimulus, and possible decision, which subsequently may be mapped onto a motor-response. In these models, stimulus processing is thought to be independent of the response modality. However, in theories of event coding, common coding, and sensorimotor contingency, stimuli may be very specifically mapped onto certain motor-responses. Here, we compared performance in a shape localization task and used three different response modalities: manual, saccadic, and verbal. Meta-contrast masking was employed at various inter-stimulus intervals (ISI) to manipulate target visibility. Although we found major differences in reaction times for the three response modalities, accuracy remained at the same level for each response modality (and all ISIs). Our results support the view that stimulus-response (S-R) associations exist only for specific instances, such as reflexes or skills, but not for arbitrary S-R pairings. Copyright © 2016 Elsevier Inc. All rights reserved.

Influence of motion on face recognition.

PubMed

Bonfiglio, Natale S; Manfredi, Valentina; Pessa, Eliano

2012-02-01

The influence of motion information and temporal associations on recognition of non-familiar faces was investigated using two groups which performed a face recognition task. One group was presented with regular temporal sequences of face views designed to produce the impression of motion of the face rotating in depth, the other group with random sequences of the same views. In one condition, participants viewed the sequences of the views in rapid succession with a negligible interstimulus interval (ISI). This condition was characterized by three different presentation times. In another condition, participants were presented a sequence with a 1-sec. ISI among the views. That regular sequences of views with a negligible ISI and a shorter presentation time were hypothesized to give rise to better recognition, related to a stronger impression of face rotation. Analysis of data from 45 participants showed a shorter presentation time was associated with significantly better accuracy on the recognition task; however, differences between performances associated with regular and random sequences were not significant.

Abnormalities of the QT interval in primary disorders of autonomic failure.

PubMed

Choy, A M; Lang, C C; Roden, D M; Robertson, D; Wood, A J; Robertson, R M; Biaggioni, I

1998-10-01

Experimental evidence shows that activation of the autonomic nervous system influences ventricular repolarization and, therefore, the QT interval on the ECG. To test the hypothesis that the QT interval is abnormal in autonomic dysfunction, we examined ECGs in patients with severe primary autonomic failure and in patients with congenital dopamine beta-hydroxylase (DbetaH) deficiency who are unable to synthesize norepinephrine and epinephrine. Maximal QT and rate-corrected QT (QTc) intervals and adjusted QTc dispersion [(maximal QTc - minimum QTc on 12 lead ECG)/square root of the number of leads measured] were determined in blinded fashion from ECGs of 67 patients with primary autonomic failure (36 patients with multiple system atrophy [MSA], and 31 patients with pure autonomic failure [PAF]) and 17 age- and sex-matched healthy controls. ECGs of 5 patients with congenital DbetaH deficiency and 6 age- and sex-matched controls were also analyzed. Patients with MSA and PAF had significantly prolonged maximum QTc intervals (492+/-58 ms(1/2) and 502+/-61 ms(1/2) [mean +/- SD]), respectively, compared with controls (450+/-18 ms(1/2), P < .05 and P < .01, respectively). A similar but not significant trend was observed for QT. QTc dispersion was also increased in MSA (40+/-20 ms(1/2), P < .05 vs controls) and PAF patients (32+/-19 ms(1/2), NS) compared with controls (21+/-5 ms(1/2)). In contrast, patients with congenital DbetaH deficiency did not have significantly different RR, QT, QTc intervals, or QTc dispersion when compared with controls. Patients with primary autonomic failure who have combined parasympathetic and sympathetic failure have abnormally prolonged QT interval and increased QT dispersion. However, QT interval in patients with congenital DbetaH deficiency was not significantly different from controls. It is possible, therefore, that QT abnormalities in patients with primary autonomic failure are not solely caused by lesions of the sympathetic nervous system, and that the parasympathetic nervous system is likely to have a modulatory role in ventricular repolarization.

Discrimination of speech and non-speech sounds following theta-burst stimulation of the motor cortex

PubMed Central

Rogers, Jack C.; Möttönen, Riikka; Boyles, Rowan; Watkins, Kate E.

2014-01-01

Perceiving speech engages parts of the motor system involved in speech production. The role of the motor cortex in speech perception has been demonstrated using low-frequency repetitive transcranial magnetic stimulation (rTMS) to suppress motor excitability in the lip representation and disrupt discrimination of lip-articulated speech sounds (Möttönen and Watkins, 2009). Another form of rTMS, continuous theta-burst stimulation (cTBS), can produce longer-lasting disruptive effects following a brief train of stimulation. We investigated the effects of cTBS on motor excitability and discrimination of speech and non-speech sounds. cTBS was applied for 40 s over either the hand or the lip representation of motor cortex. Motor-evoked potentials recorded from the lip and hand muscles in response to single pulses of TMS revealed no measurable change in motor excitability due to cTBS. This failure to replicate previous findings may reflect the unreliability of measurements of motor excitability related to inter-individual variability. We also measured the effects of cTBS on a listener’s ability to discriminate: (1) lip-articulated speech sounds from sounds not articulated by the lips (“ba” vs. “da”); (2) two speech sounds not articulated by the lips (“ga” vs. “da”); and (3) non-speech sounds produced by the hands (“claps” vs. “clicks”). Discrimination of lip-articulated speech sounds was impaired between 20 and 35 min after cTBS over the lip motor representation. Specifically, discrimination of across-category ba–da sounds presented with an 800-ms inter-stimulus interval was reduced to chance level performance. This effect was absent for speech sounds that do not require the lips for articulation and non-speech sounds. Stimulation over the hand motor representation did not affect discrimination of speech or non-speech sounds. These findings show that stimulation of the lip motor representation disrupts discrimination of speech sounds in an articulatory feature-specific way. PMID:25076928

Discrimination of speech and non-speech sounds following theta-burst stimulation of the motor cortex.

PubMed

Rogers, Jack C; Möttönen, Riikka; Boyles, Rowan; Watkins, Kate E

2014-01-01

Perceiving speech engages parts of the motor system involved in speech production. The role of the motor cortex in speech perception has been demonstrated using low-frequency repetitive transcranial magnetic stimulation (rTMS) to suppress motor excitability in the lip representation and disrupt discrimination of lip-articulated speech sounds (Möttönen and Watkins, 2009). Another form of rTMS, continuous theta-burst stimulation (cTBS), can produce longer-lasting disruptive effects following a brief train of stimulation. We investigated the effects of cTBS on motor excitability and discrimination of speech and non-speech sounds. cTBS was applied for 40 s over either the hand or the lip representation of motor cortex. Motor-evoked potentials recorded from the lip and hand muscles in response to single pulses of TMS revealed no measurable change in motor excitability due to cTBS. This failure to replicate previous findings may reflect the unreliability of measurements of motor excitability related to inter-individual variability. We also measured the effects of cTBS on a listener's ability to discriminate: (1) lip-articulated speech sounds from sounds not articulated by the lips ("ba" vs. "da"); (2) two speech sounds not articulated by the lips ("ga" vs. "da"); and (3) non-speech sounds produced by the hands ("claps" vs. "clicks"). Discrimination of lip-articulated speech sounds was impaired between 20 and 35 min after cTBS over the lip motor representation. Specifically, discrimination of across-category ba-da sounds presented with an 800-ms inter-stimulus interval was reduced to chance level performance. This effect was absent for speech sounds that do not require the lips for articulation and non-speech sounds. Stimulation over the hand motor representation did not affect discrimination of speech or non-speech sounds. These findings show that stimulation of the lip motor representation disrupts discrimination of speech sounds in an articulatory feature-specific way.

Body Position Influences Which Neural Structures Are Recruited by Lumbar Transcutaneous Spinal Cord Stimulation

PubMed Central

Danner, Simon M.; Krenn, Matthias; Hofstoetter, Ursula S.; Toth, Andrea; Mayr, Winfried; Minassian, Karen

2016-01-01

Transcutaneous stimulation of the human lumbosacral spinal cord is used to evoke spinal reflexes and to neuromodulate altered sensorimotor function following spinal cord injury. Both applications require the reliable stimulation of afferent posterior root fibers. Yet under certain circumstances, efferent anterior root fibers can be co-activated. We hypothesized that body position influences the preferential stimulation of sensory or motor fibers. Stimulus-triggered responses to transcutaneous spinal cord stimulation were recorded using surface-electromyography from quadriceps, hamstrings, tibialis anterior, and triceps surae muscles in 10 individuals with intact nervous systems in the supine, standing and prone positions. Single and paired (30-ms inter-stimulus intervals) biphasic stimulation pulses were applied through surface electrodes placed on the skin between the T11 and T12 inter-spinous processes referenced to electrodes on the abdomen. The paired stimulation was applied to evaluate the origin of the evoked electromyographic response; trans-synaptic responses would be suppressed whereas direct efferent responses would almost retain their amplitude. We found that responses to the second stimulus were decreased to 14%±5% of the amplitude of the response to the initial pulse in the supine position across muscles, to 30%±5% in the standing, and to only 80%±5% in the prone position. Response thresholds were lowest during standing and highest in the prone position and response amplitudes were largest in the supine and smallest in the prone position. The responses obtained in the supine and standing positions likely resulted from selective stimulation of sensory fibers while concomitant motor-fiber stimulation occurred in the prone position. We assume that changes of root-fiber paths within the generated electric field when in the prone position increase the stimulation thresholds of posterior above those of anterior root fibers. Thus, we recommend conducting spinal reflex or neuromodulation studies with subjects lying supine or in an upright position, as in standing or stepping. PMID:26797502

A role of right middle frontal gyrus in reorienting of attention: a case study

PubMed Central

Japee, Shruti; Holiday, Kelsey; Satyshur, Maureen D.; Mukai, Ikuko; Ungerleider, Leslie G.

2015-01-01

The right middle fontal gyrus (MFG) has been proposed to be a site of convergence of the dorsal and ventral attention networks, by serving as a circuit-breaker to interrupt ongoing endogenous attentional processes in the dorsal network and reorient attention to an exogenous stimulus. Here, we probed the contribution of the right MFG to both endogenous and exogenous attention by comparing performance on an orientation discrimination task of a patient with a right MFG resection and a group of healthy controls. On endogenously cued trials, participants were shown a central cue that predicted with 90% accuracy the location of a subsequent peri-threshold Gabor patch stimulus. On exogenously cued trials, a cue appeared briefly at one of two peripheral locations, followed by a variable inter-stimulus interval (ISI; range 0–700 ms) and a Gabor patch in the same or opposite location as the cue. Behavioral data showed that for endogenous, and short ISI exogenous trials, valid cues facilitated responses compared to invalid cues, for both the patient and controls. However, at long ISIs, the patient exhibited difficulty in reverting to top-down attentional control, once the facilitatory effect of the exogenous cue had dissipated. When explicitly cued during long ISIs to attend to both stimulus locations, the patient was able to engage successfully in top-down control. This result indicates that the right MFG may play an important role in reorienting attention from exogenous to endogenous attentional control. Resting state fMRI data revealed that the right superior parietal lobule and right orbitofrontal cortex, showed significantly higher correlations with a left MFG seed region (a region tightly coupled with the right MFG in controls) in the patient relative to controls. We hypothesize that this paradoxical increase in cortical coupling represents a compensatory mechanism in the patient to offset the loss of function of the resected tissue in right prefrontal cortex. PMID:25784862

Motor Timing Deficits in Sequential Movements in Parkinson Disease Are Related to Action Planning: A Motor Imagery Study

PubMed Central

Avanzino, Laura; Pelosin, Elisa; Martino, Davide; Abbruzzese, Giovanni

2013-01-01

Timing of sequential movements is altered in Parkinson disease (PD). Whether timing deficits in internally generated sequential movements in PD depends also on difficulties in motor planning, rather than merely on a defective ability to materially perform the planned movement is still undefined. To unveil this issue, we adopted a modified version of an established test for motor timing, i.e. the synchronization–continuation paradigm, by introducing a motor imagery task. Motor imagery is thought to involve mainly processes of movement preparation, with reduced involvement of end-stage movement execution-related processes. Fourteen patients with PD and twelve matched healthy volunteers were asked to tap in synchrony with a metronome cue (SYNC) and then, when the tone stopped, to keep tapping, trying to maintain the same rhythm (CONT-EXE) or to imagine tapping at the same rhythm, rather than actually performing it (CONT-MI). We tested both a sub-second and a supra-second inter-stimulus interval between the cues. Performance was recorded using a sensor-engineered glove and analyzed measuring the temporal error and the interval reproduction accuracy index. PD patients were less accurate than healthy subjects in the supra-second time reproduction task when performing both continuation tasks (CONT-MI and CONT-EXE), whereas no difference was detected in the synchronization task and on all tasks involving a sub-second interval. Our findings suggest that PD patients exhibit a selective deficit in motor timing for sequential movements that are separated by a supra-second interval and that this deficit may be explained by a defect of motor planning. Further, we propose that difficulties in motor planning are of a sufficient degree of severity in PD to affect also the motor performance in the supra-second time reproduction task. PMID:24086534

Timing and Causality in the Generation of Learned Eyelid Responses

PubMed Central

Sánchez-Campusano, Raudel; Gruart, Agnès; Delgado-García, José M.

2011-01-01

The cerebellum-red nucleus-facial motoneuron (Mn) pathway has been reported as being involved in the proper timing of classically conditioned eyelid responses. This special type of associative learning serves as a model of event timing for studying the role of the cerebellum in dynamic motor control. Here, we have re-analyzed the firing activities of cerebellar posterior interpositus (IP) neurons and orbicularis oculi (OO) Mns in alert behaving cats during classical eyeblink conditioning, using a delay paradigm. The aim was to revisit the hypothesis that the IP neurons (IPns) can be considered a neuronal phase-modulating device supporting OO Mns firing with an emergent timing mechanism and an explicit correlation code during learned eyelid movements. Optimized experimental and computational tools allowed us to determine the different causal relationships (temporal order and correlation code) during and between trials. These intra- and inter-trial timing strategies expanding from sub-second range (millisecond timing) to longer-lasting ranges (interval timing) expanded the functional domain of cerebellar timing beyond motor control. Interestingly, the results supported the above-mentioned hypothesis. The causal inferences were influenced by the precise motor and pre-motor spike timing in the cause-effect interval, and, in addition, the timing of the learned responses depended on cerebellar–Mn network causality. Furthermore, the timing of CRs depended upon the probability of simulated causal conditions in the cause-effect interval and not the mere duration of the inter-stimulus interval. In this work, the close relation between timing and causality was verified. It could thus be concluded that the firing activities of IPns may be related more to the proper performance of ongoing CRs (i.e., the proper timing as a consequence of the pertinent causality) than to their generation and/or initiation. PMID:21941469

From comparison to classification: a cortical tool for boosting perception.

PubMed

Nahum, Mor; Daikhin, Luba; Lubin, Yedida; Cohen, Yamit; Ahissar, Merav

2010-01-20

Humans are much better in relative than in absolute judgments. This common assertion is based on findings that discrimination thresholds are much lower when measured with methods that allow interstimuli comparisons than when measured with methods that require classification of one stimulus at a time and are hence sensitive to memory load. We now challenged this notion by measuring discrimination thresholds and evoked potentials while listeners performed a two-tone frequency discrimination task. We tested various protocols that differed in the pattern of cross-trial tone repetition. We found that best performance was achieved only when listeners effectively used cross-trial repetition to avoid interstimulus comparisons with the repeated reference tone. Instead, they classified one tone, the nonreference tone, as either high or low by comparing it with a recently formed internal reference. Listeners were not aware of the switch from interstimulus comparison to classification. Its successful use was revealed by the conjunction of improved behavioral performance and an event-related potential component (P3), indicating an implicit perceptual decision, which followed the nonreference tone in each trial. Interestingly, tone repetition itself did not suffice for the switch, implying that the bottleneck to discrimination does not reside at the lower, sensory stage. Rather, the temporal consistency of repetition was important, suggesting the involvement of higher-level mechanisms with longer time constants. These findings suggest that classification is based on more automatic and accurate mechanisms than interstimulus comparisons and that the ability to effectively use them depends on a dynamic interplay between higher- and lower-level cortical mechanisms.

Event related aspects of somatosensory and auditory evoked potentials: noise or signals?

PubMed

Stowell, H

1985-05-01

The so-called Vertex Potential (VP) of human scalp-conducted and event related brain potential (ERBP), which occur as a slow and often large, biphasic sinusoid within the 100-400 msec time segment after transient stimulation in the three main sensory modalities, are the longest researched of all human evoked potential (EP) phenomena. Its variable amplitude has been directly correlated, in experiments expressly tailored for the purpose, with input/output variables such as the rate of acceleration of given stimulus parameters from a state of relative rest (RM function), interstimulus interval (ISI), stimulus intensity, skin potential and resistance changes (SPR and SRR), the peripheral electroneurogram (ENG), and experimentally isolated C-fiber afference; and with neuropsychological variables such as attention or vigilance, visual acuity, response time, subjective stimulus probability or expectancy, acute pain of both fast and slow kinds, intelligence quotient (IQ), and psychometric personality scores (e.g., extraversion versus introversion and neuroticism versus normality). Unfortunately, the cerebral, neural origins of the VP, if any, are unknown; it is reported as usually absent from cortex-surface EP in those primates and mammals hitherto studied, and also from human extracranial event related magnetic fields of the brain (ERMFb) insofar as these reveal only superficial tangential sources; but a possible analog has been recorded from deep subcortical electrodes during human neurosurgery. In view of the increasing published range and quantity of direct correlates of VP amplitude, and of the scarcity of data about its neuroanatomy and neurophysiology, it seemed a good idea to do some rudimentary signal analysis. Preliminary results from five subjects confirm earlier data: The VP of somatosensory (SEP) and auditory (AEP) evoked potentials, as obtained by scalp-conductance and either averaged or single-epoch, can be resolved into inconsistently stimulus synchronized frequency components which are also present as relatively unsynchronized waves in the theta and alpha bands (approx. 2-13 Hz) of the unstimulated or near-threshold-stimulated electroencephalogram (EEG). In averages of numerous single trials (20 less than N less than 102), initiated at interstimulus intervals longer than 2.5 sec and deliberately sequenced so that the initiator could learn to estimate the timing of stimulus onsets, the phase coherence of the power-dominant alpha and theta waves within the 100-400 msec time segment of ERBP is obvious when the stimulus is an intense transient and psychologically not "habituated".(ABSTRACT TRUNCATED AT 400 WORDS)

Underestimated and unreported prolonged QTc by automated ECG analysis in patients on methadone: can we rely on computer reading?

PubMed

Talebi, Soheila; Azhir, Alaleh; Zuber, Sam; Soman, Sandeep; Visco, Ferdinand; Totouom-Tangho, Holly; Kalantar, Hossein; Worku Hassen, Getaw

2015-04-01

Recognition of prolonged corrected QT (QTc) interval is of particular importance, especially when using medications known to prolong QTc interval. Methadone can prolong the QTc interval and has the potential to induce torsades de pointes. The objective of this study is to investigate the accuracy of computerized ECG analysis in correctly identifying and reporting QTc interval in patients on methadone. We conducted a retrospective review of ECGs in the Muse electronic database of patients on methadone who are above 18 years old between January 2012 and December 2013 at an urban community hospital. ECGs were analyzed by the Marquette 12SL ECG Analysis Program (GE'Healthcare) reviewed by a cardiologist. A total of 826 ECGs of patients on methadone were examined manually for the QTc interval, of which 625 (75.7%) had QTc less than 470 ms, 149 (18%) had QTc between 470-499 ms and 52 (6.3%) had QTc more than 499 ms. QTc between 470-499 ms was underestimated by machine in 19 (12.8%) ECGs and QTc more than 499 ms was underestimated in 10 (19.6%) when compared to manually calculated QTc. QTc prolongation was underreported in 63 ECGs (48.5%) of those whose QTc between 470-499 ms and in 1 ECG (2.4%) of those whose QTc was more than 499 ms. QTc can be underestimated or unreported by the computer analysis. Physicians not only should calculate QTc manually but also examine the actual QTc value displayed on the report before concluding that this parameter is normal, especially in patients who are at risk of QTc prolongation.

Abnormalities of the QT interval in primary disorders of autonomic failure

NASA Technical Reports Server (NTRS)

Choy, A. M.; Lang, C. C.; Roden, D. M.; Robertson, D.; Wood, A. J.; Robertson, R. M.; Biaggioni, I.

1998-01-01

BACKGROUND: Experimental evidence shows that activation of the autonomic nervous system influences ventricular repolarization and, therefore, the QT interval on the ECG. To test the hypothesis that the QT interval is abnormal in autonomic dysfunction, we examined ECGs in patients with severe primary autonomic failure and in patients with congenital dopamine beta-hydroxylase (DbetaH) deficiency who are unable to synthesize norepinephrine and epinephrine. SUBJECTS AND METHODS: Maximal QT and rate-corrected QT (QTc) intervals and adjusted QTc dispersion [(maximal QTc - minimum QTc on 12 lead ECG)/square root of the number of leads measured] were determined in blinded fashion from ECGs of 67 patients with primary autonomic failure (36 patients with multiple system atrophy [MSA], and 31 patients with pure autonomic failure [PAF]) and 17 age- and sex-matched healthy controls. ECGs of 5 patients with congenital DbetaH deficiency and 6 age- and sex-matched controls were also analyzed. RESULTS: Patients with MSA and PAF had significantly prolonged maximum QTc intervals (492+/-58 ms(1/2) and 502+/-61 ms(1/2) [mean +/- SD]), respectively, compared with controls (450+/-18 ms(1/2), P < .05 and P < .01, respectively). A similar but not significant trend was observed for QT. QTc dispersion was also increased in MSA (40+/-20 ms(1/2), P < .05 vs controls) and PAF patients (32+/-19 ms(1/2), NS) compared with controls (21+/-5 ms(1/2)). In contrast, patients with congenital DbetaH deficiency did not have significantly different RR, QT, QTc intervals, or QTc dispersion when compared with controls. CONCLUSIONS: Patients with primary autonomic failure who have combined parasympathetic and sympathetic failure have abnormally prolonged QT interval and increased QT dispersion. However, QT interval in patients with congenital DbetaH deficiency was not significantly different from controls. It is possible, therefore, that QT abnormalities in patients with primary autonomic failure are not solely caused by lesions of the sympathetic nervous system, and that the parasympathetic nervous system is likely to have a modulatory role in ventricular repolarization.

Androgen profiling by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in healthy normal-weight ovulatory and anovulatory late adolescent and young women.

PubMed

Fanelli, Flaminia; Gambineri, Alessandra; Belluomo, Ilaria; Repaci, Andrea; Di Lallo, Valentina Diana; Di Dalmazi, Guido; Mezzullo, Marco; Prontera, Olga; Cuomo, Gaia; Zanotti, Laura; Paccapelo, Alexandro; Morselli-Labate, Antonio Maria; Pagotto, Uberto; Pasquali, Renato

2013-07-01

Physiological transient imbalance typical of adolescence needs to be distinguished from hyperandrogenism-related dysfunction. The accurate determination of circulating androgens is the best indicator of hyperandrogenism. However, reliable reference intervals for adolescent and young women are not available. The aim of the study was to define androgen reference intervals in young women and to analyze the impact of the menstrual phase and ovulation efficiency over the androgen profile as assessed by reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique. Female high school students aged 16-19 years were included in the study. The study was performed on reference subjects properly selected among an unbiased population. Normal-weight, drug and disease free, eumenorrheic females with no signs of hyperandrogenism were included. The steroid hormone profile was determined by a validated in-house LC-MS/MS method. A statistical estimation of overall and menstrual phase-specific reference intervals was performed. A subgroup of anovulatory females was identified based on progesterone circulating levels. The impact of ovulation efficiency over hormonal profile was analyzed. A total of 159 females satisfied healthy criteria. Androgen levels did not vary according to menstrual phase, but a significantly higher upper reference limit was found for T in the luteal phase compared to the follicular phase. Higher T and androstenedione levels were observed in anovulatory compared to ovulatory females, paralleled by higher LH and FSH and lower 17-hydroxyprogesterone and 17β-estradiol levels. This is the first study providing LC-MS/MS-based, menstrual phase-specific reference intervals for the circulating androgen profile in young females. We identified a subgroup of anovulatory healthy females characterized by androgen imbalance.

Effect of posture on arterial baroreflex control of heart rate in humans

NASA Technical Reports Server (NTRS)

Harrison, M. H.; Rittenhouse, D.; Greenleaf, J. E.

1986-01-01

The effects of blood-volume redistribution induced by postural changes on baroreflex activity are investigated. The central blood volume and baroreceptor functions of ten males between 23-51 years old were examined while they were in the head-up tilt (HUT), head-down tilt (HDT), and supine positions. It is observed that during HDT at 15 deg the pulse interval over the first five cardiac cycles following neck suction onset is 51 + or - 18 ms longer, at 30 deg it is 61 + or - 20 ms longer, and at 45 deg it is 74 + or - 35 ms longer than at supine; during HUT at 15 deg the pulse interval is 25 + or - 9 ms shorter than when supine, but for the 30 and 45 deg there is no significant difference in pulse interval detected. The data reveal that posture does modify arterial baroreflex control of heart rate.

The effects of apremilast on the QTc interval in healthy male volunteers: a formal, thorough QT study

PubMed Central

Palmisano, Maria; Wu, Anfan; Assaf, Mahmoud; Liu, Liangang; Park, C. Hyung; Savant, Ishani; Liu, Yong; Zhou, Simon

2016-01-01

Objective: This study was conducted to evaluate the effect of apremilast and its major metabolites on the placebo-corrected change-from-baseline QTc interval of an electrocardiogram (ECG). Materials and methods: Healthy male subjects received each of 4 treatments in a randomized, crossover manner. In the 2 active treatment periods, apremilast 30 mg (therapeutic exposure) or 50 mg (supratherapeutic exposure) was administered twice daily for 9 doses. A placebo control was used to ensure double-blind treatment of apremilast, and an open-label, single dose of moxifloxacin 400 mg was administered as a positive control. ECGs were measured using 24-hour digital Holter monitoring. Results: The two-sided 98% confidence intervals (CIs) for ΔΔQTcI of moxifloxacin completely exceeded 5 ms 2 – 4 hours postdose. For both apremilast dose studies, the least-squares mean ΔΔQTcI was < 1 ms at all time points, and the upper limit of two-sided 90% CIs was < 10 ms. There were no QT/QTc values > 480 ms or a change from baseline > 60 ms. Exploratory evaluation of pharmacokinetic/pharmacodynamic data showed no trend between the changes in QT/QTc interval and the concentration of apremilast or its major metabolites M12 and M14. Conclusions: Apremilast did not prolong the QT interval and appears to be safe and well tolerated up to doses of 50 mg twice daily. PMID:27285466

Effect of intravenous amiodarone on QT and T peak-T end dispersions in patients with nonischemic heart failure treated with cardiac resynchronization-defibrillator therapy and electrical storm.

PubMed

Ogiso, Masataka; Suzuki, Atsushi; Shiga, Tsuyoshi; Nakai, Kenji; Shoda, Morio; Hagiwara, Nobuhisa

2015-02-01

The effect of intravenous amiodarone on spatial and transmural dispersion of ventricular repolarization in patients receiving cardiac resynchronization therapy (CRT) remains unclear. We studied 14 patients with nonischemic heart failure who received CRT with a defibrillator, experienced electrical storm and were treated with intravenous amiodarone. Each patient underwent 12-lead electrocardiography (ECG) and 187-channel repolarization interval-difference mapping electrocardiography (187-ch RIDM-ECG) before and during the intravenous administration of amiodarone infusion. A recurrence of ventricular tachyarrhythmia was observed in 2 patients during the early period of intravenous amiodarone therapy. Intravenous amiodarone increased the corrected QT interval (from 470±52 ms to 508±55 ms, P=0.003), but it significantly decreased the QT dispersion (from 107±35 ms to 49±27 ms, P=0.001), T peak-T end (Tp-e) dispersion (from 86±17 ms to 28±28 ms, P=0.001), and maximum inter-lead difference between corrected Tp-e intervals as measured by using the 187-ch RIDM-ECG (from 83±13 ms to 50±19 ms, P=0.001). Intravenous amiodarone suppressed the electrical storm and decreased the QT and Tp-e dispersions in patients treated by using CRT with a defibrillator.

Prevalence of the metabolic syndrome in a psychiatric hospital in Mexico.

PubMed

Díaz-Castro, Lina; Cabello-Rangel, Héctor; Cuevas-Pineda, Guillermo J; Reza-Garduño, Horacio; Castañeda-González, Carlos J

2011-01-01

The metabolic syndrome (MS) is formed by elevated blood pressure, hypercholesterolemia, hypertriglyceridemía, hyperglycemia and abdominal obesity. Mexico occupies the second place worldwide in prevalence of obesity. It has been reported that the use of psychopharmaceuticals increase the risk of MS. To detect prevalence of MS in patients with a psychiatric diagnosis with or without psychopharmaceutical treatment. An observational, descriptive study was designed. Informed consent was obtained, enrolling a sample of 216 patients in the six-month period, all of them over 18 years of age. The following variables were measured: blood pressure, weight, height, waist circumference, triglyceride, glucose and high-density lipoprotein serum levels, by colorimetric enzyme assay in Roche analyzer. Student's t-test, and Cochran-Mantel- Haenszel and Fisher's exact test. A total of 50% of the sample had a waist circumference >88 cm; 10% glycemia superior to 110 mg/dl, 30% triglycerides >150 mg/dl; 14% met the MS criteria. When patients with and without MS were grouped, and glucose and triglycerides were compared, a p 0.0001 was obtained. With a 93.4% confidence interval, the relationship between sedentary life and MS was accepted. Women, aged 40-59 years tended to have MS, with 98.4% CI. The only family background associated to MS was obesity (97.7% CI). There is a positive relationship between MS and the use of typical or atypical antipsychotics. SSRIs are significantly related with MS: p 0.072 and 91.5% confidence interval, benzodiazepines with p 0.073 and 92.7% confidence interval. Only 14% of the sample had MS. Psychopharmaceuticals were associated to MS, women between 40 to 59 years having a greater risk.

Associative spike timing-dependent potentiation of the basal dendritic excitatory synapses in the hippocampus in vivo.

PubMed

Fung, Thomas K; Law, Clayton S; Leung, L Stan

2016-06-01

Spike timing-dependent plasticity in the hippocampus has rarely been studied in vivo. Using extracellular potential and current source density analysis in urethane-anesthetized adult rats, we studied synaptic plasticity at the basal dendritic excitatory synapse in CA1 after excitation-spike (ES) pairing; E was a weak basal dendritic excitation evoked by stratum oriens stimulation, and S was a population spike evoked by stratum radiatum apical dendritic excitation. We hypothesize that positive ES pairing-generating synaptic excitation before a spike-results in long-term potentiation (LTP) while negative ES pairing results in long-term depression (LTD). Pairing (50 pairs at 5 Hz) at ES intervals of -10 to 0 ms resulted in significant input-specific LTP of the basal dendritic excitatory sink, lasting 60-120 min. Pairing at +10- to +20-ms ES intervals, or unpaired 5-Hz stimulation, did not induce significant basal dendritic or apical dendritic LTP or LTD. No basal dendritic LTD was found after stimulation of stratum oriens with 200 pairs of high-intensity pulses at 25-ms interval. Pairing-induced LTP was abolished by pretreatment with an N-methyl-d-aspartate receptor antagonist, 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), which also reduced spike bursting during 5-Hz pairing. Pairing at 0.5 Hz did not induce spike bursts or basal dendritic LTP. In conclusion, ES pairing at 5 Hz resulted in input-specific basal dendritic LTP at ES intervals of -10 ms to 0 ms but no LTD at ES intervals of -20 to +20 ms. Associative LTP likely occurred because of theta-rhythmic coincidence of subthreshold excitation with a backpropagated spike burst, which are conditions that can occur naturally in the hippocampus. Copyright © 2016 the American Physiological Society.

Associative spike timing-dependent potentiation of the basal dendritic excitatory synapses in the hippocampus in vivo

PubMed Central

Fung, Thomas K.; Law, Clayton S.

2016-01-01

Spike timing-dependent plasticity in the hippocampus has rarely been studied in vivo. Using extracellular potential and current source density analysis in urethane-anesthetized adult rats, we studied synaptic plasticity at the basal dendritic excitatory synapse in CA1 after excitation-spike (ES) pairing; E was a weak basal dendritic excitation evoked by stratum oriens stimulation, and S was a population spike evoked by stratum radiatum apical dendritic excitation. We hypothesize that positive ES pairing—generating synaptic excitation before a spike—results in long-term potentiation (LTP) while negative ES pairing results in long-term depression (LTD). Pairing (50 pairs at 5 Hz) at ES intervals of −10 to 0 ms resulted in significant input-specific LTP of the basal dendritic excitatory sink, lasting 60–120 min. Pairing at +10- to +20-ms ES intervals, or unpaired 5-Hz stimulation, did not induce significant basal dendritic or apical dendritic LTP or LTD. No basal dendritic LTD was found after stimulation of stratum oriens with 200 pairs of high-intensity pulses at 25-ms interval. Pairing-induced LTP was abolished by pretreatment with an N-methyl-d-aspartate receptor antagonist, 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), which also reduced spike bursting during 5-Hz pairing. Pairing at 0.5 Hz did not induce spike bursts or basal dendritic LTP. In conclusion, ES pairing at 5 Hz resulted in input-specific basal dendritic LTP at ES intervals of −10 ms to 0 ms but no LTD at ES intervals of −20 to +20 ms. Associative LTP likely occurred because of theta-rhythmic coincidence of subthreshold excitation with a backpropagated spike burst, which are conditions that can occur naturally in the hippocampus. PMID:27052581

Prevalence of QT interval prolongation in patients admitted to cardiac care units and frequency of subsequent administration of QT interval-prolonging drugs: a prospective, observational study in a large urban academic medical center in the US.

PubMed

Tisdale, James E; Wroblewski, Heather A; Overholser, Brian R; Kingery, Joanna R; Trujillo, Tate N; Kovacs, Richard J

2012-06-01

Cardiac arrest due to torsades de pointes (TdP) is a rare but catastrophic event in hospitals. Patients admitted to cardiac units are at higher risk of drug-induced QT interval prolongation and TdP, due to a preponderance of risk factors. Few data exist regarding the prevalence of QT interval prolongation in patients admitted to cardiac units or the frequency of administering QT interval-prolonging drugs to patients presenting with QT interval prolongation. The aim of this study was to determine the prevalence of Bazett's-corrected QT (QT(c)) interval prolongation upon admission to cardiac units and the proportion of patients presenting with QT(c) interval prolongation who are subsequently administered QT interval-prolonging drugs during hospitalization. This was a prospective, observational study conducted over a 1-year period (October 2008-October 2009) in 1159 consecutive patients admitted to two cardiac units in a large urban academic medical centre located in Indianapolis, IN, USA. Patients were enrolled into the study at the time of admission to the hospital and were followed daily during hospitalization. Exclusion criteria were age <18 years, ECG rhythm of complete ventricular pacing, and patient designation as 'outpatient' in a bed and/or duration of stay <24 hours. Data collected included demographic information, past medical history, daily progress notes, medication administration records, laboratory data, ECGs, telemetry monitoring strips and diagnostic reports. All patients underwent continuous cardiac telemetry monitoring and/or had a baseline 12-lead ECG obtained within 4 hours of admission. QT intervals were determined manually from lead II of 12-lead ECGs or from continuous lead II telemetry monitoring strips. QT(c) interval prolongation was defined as ≥470 ms for males and ≥480 ms for females. In both males and females, QT(c) interval >500 ms was considered abnormally high. A medication was classified as QT interval-prolonging if there were published data indicating that the drug causes QT interval prolongation and/or TdP. Study endpoints were (i) prevalence of QT(c) interval prolongation upon admission to the Cardiac Medical Critical Care Unit (CMCCU) or an Advanced Heart Care Unit (AHCU); (ii) proportion of patients admitted to the CMCCU/AHCU with QT(c) interval prolongation who subsequently were administered QT interval-prolonging drugs during hospitalization; (iii) the proportion of these higher-risk patients in whom TdP risk factor monitoring was performed; (iv) proportion of patients with QT(c) interval prolongation who subsequently received QT-prolonging drugs and who experienced further QT(c) interval prolongation. Of 1159 patients enrolled, 259 patients met exclusion criteria, resulting in a final sample size of 900 patients. mean (± SD) age, 65 ± 15 years; female, 47%; Caucasian, 70%. Admitting diagnoses: heart failure (22%), myocardial infarction (16%), atrial fibrillation (9%), sudden cardiac arrest (3%). QT(c) interval prolongation was present in 27.9% of patients on admission; 18.2% had QT(c) interval >500 ms. Of 251 patients admitted with QT(c) interval prolongation, 87 (34.7%) were subsequently administered QT interval-prolonging drugs. Of 166 patients admitted with QT(c) interval >500 ms, 70 (42.2%) were subsequently administered QT interval-prolonging drugs; additional QT(c) interval prolongation ≥60 ms occurred in 57.1% of these patients. QT(c) interval prolongation is common among patients admitted to cardiac units. QT interval-prolonging drugs are commonly prescribed to patients presenting with QT(c) interval prolongation.

Validation of PR interval length as a criterion for development of atrial fibrillation in non-Hispanic whites, African Americans and Hispanics.

PubMed

Shulman, Eric; Aagaard, Philip; Kargoli, Faraj; Hoch, Ethan; Zheng, Laura; Di Biase, Luigi; Fisher, John; Gross, Jay; Kim, Soo; Ferrick, Kevin; Krumerman, Andrew

2015-01-01

PR interval prolongation on electrocardiogram (ECG) increases the risk of atrial fibrillation (AF). Non-Hispanic Whites are at higher risk of AF compared to African Americans and Hispanics. However, it remains unknown if prolongation of the PR interval for the development of AF varies by race/ethnicity. Therefore, we determined whether race affects the PR interval length's ability to predict AF and if the commonly used criterion of 200 ms in AF prediction models can continue to be used for non-White cohorts. This is a retrospective epidemiological study of consecutive inpatient and outpatients. An ECG database was initially interrogated. Patients were included if their initial ECG demonstrated sinus rhythm and had two or more electrocardiograms and declared a race and/or ethnicity as non-Hispanic White, African American or Hispanic. Development of AF was stratified by race/ethnicity along varying PR intervals. Cox models controlled for age, gender, race/ethnicity, systolic blood pressure, BMI, QRS, QTc, heart rate, murmur, treatment for hypertension, heart failure and use of AV nodal blocking agents to assess PR interval's predictive ability for development of AF. 50,870 patients met inclusion criteria of which 5,199 developed AF over 3.72 mean years of follow-up. When the PR interval was separated by quantile, prolongation of the PR interval to predict AF first became significant in Hispanic and African Americans at the 92.5th quantile of 196-201 ms (HR: 1.42, 95% CI: 1.09-1.86, p=0.01; HR: 1.32, 95% CI: 1.07-1.64, p=0.01, respectively) then in non-Hispanic Whites at the 95th quantile at 203-212 ms (HR: 1.24, 95% CI: 1.24-1.53, p=0.04). For those with a PR interval above 200 ms, African Americans had a lower risk than non-Hispanic Whites to develop AF (HR: 0.80, 95% CI: 0.64-0.95, p=0.012), however, no significant difference was demonstrated in Hispanics. This is the first study to validate a PR interval value of 200 ms as a criterion in African Americans and Hispanics for the development of AF. However, a value of 200 ms may be less sensitive as a predictive measure for the development of AF in African Americans compared to non-Hispanic Whites. Copyright © 2015 Elsevier Inc. All rights reserved.

Atrial electromechanical coupling intervals in pregnant subjects.

PubMed

Altun, Burak; Tasolar, Hakan; Gazï, Emïne; Gungor, Aysenur Cakir; Uysal, Ahmet; Temïz, Ahmet; Barutcu, Ahmet; Acar, Gurkan; Colkesen, Yucel; Ozturk, Ufuk; Akkoy, Murat

2014-01-01

The aim of this study was to evaluate atrial conduction abnormalities obtained by tissue Doppler imaging (TDI) and electrocardiogram analysis in pregnant subjects. A total of 30 pregnant subjects (28 ± 4 years) and 30 controls (28 ± 3 years) were included. Systolic and diastolic left ventricular (LV) function was measured using conventional echocardiography and TDI. Inter-atrial, intraatrial and intra-left atrial electromechanical coupling (PA) intervals were measured with TDI. P-wave dispersion (PD) was calculated from a 12-lead electrocardiogram. Atrial electromechanical coupling at the septal and left lateral mitral annulus (PA septal, PA lateral) was significantly prolonged in pregnant subjects (62.1 ± 2.7 vs 55.3 ±3.2 ms, p < 0.001; 45.7 ± 2.5 vs 43.1 ± 2.7 ms, p < 0.001, respectively). Inter-atrial (PA lateral - PA tricuspid), intra-atrial (PA septum - PA tricuspid) and intra-left atrial (PA lateral - PA septum) electromechanical coupling intervals, maximum P-wave (Pmax) duration and PD were significantly longer in the pregnant subjects (26.4 ± 4.0 vs 20.2 ± 3.6 ms, p < 0.001; 10.0 ± 2.0 vs 8.0 ± 2.6 ms, p = 0.002; 16.4 ± 3.3 vs 12.2 ± 3.0 ms, p < 0.001; 103.1 ± 5.4 vs 96.8 ± 7.4 ms, p ± 0.001; 50.7 ± 6.8 vs 41.6 ± 5.5 ms, p < 0.001, respectively). We found a significant positive correlation between inter-atrial and intraleft atrial electromechanical coupling intervals and Pmax (r = 0.282, p = 0.029, r = 0.378, p = 0.003, respectively). This study showed that atrial electromechanical coupling intervals and PD, which are predictors of AF, were longer in pregnant subjects and this may cause an increased risk of AF in pregnancy.

Abnormal myocardial repolarisation in response to hypoxaemia and fenoterol.

PubMed Central

Kiely, D. G.; Cargill, R. I.; Grove, A.; Struthers, A. D.; Lipworth, B. J.

1995-01-01

BACKGROUND--Prolongation of the QTc interval has been associated with cardiac dysrhythmias and sudden death. QTc dispersion (interlead variability in QTc interval) has recently been proposed as being a more sensitive marker of repolarisation abnormalities and shown to be a more specific index of arrhythmia risk. Although hypoxaemia and fenoterol have previously been shown to prolong the QTc interval, this does not reflect regional myocardial repolarisation abnormalities. METHODS--Electrophysiological effects were measured at baseline and after 30 minutes steady state hypoxaemia at an arterial oxygen saturation (SaO2) of 75-80% (study 1) and at baseline then 30 minutes after inhaled fenoterol 2.4 mg (study 2). From the ECG, lead II corrected QT interval (QTc) and overall corrected QT dispersion were measured using a computer linked digitising tablet according to standard criteria. RESULTS--QTc dispersion was increased during hypoxia compared with baseline values (mean (SE) 69 (6) ms v 50 (5) ms) and after fenoterol compared with baseline (79 (13) v 46 (4) ms), respectively. There was also an increase in QTc interval and heart rate after fenoterol (493 (23) v 420 (6) ms and 98 (3) v 71 (6) bpm, respectively). The heart rate was increased during hypoxaemia compared with baseline (78 (3) v 64 (2) bpm), but no change occurred in the QTc interval. CONCLUSIONS--Both hypoxaemia and fenoterol cause myocardial repolarisation abnormalities in man in terms of increased QTc dispersion, but only fenoterol increased the QTc interval. This may be relevant in the aetiology of arrhythmias in patients with acute severe asthma where beta agonist therapy and hypoxaemia coexist. PMID:7491554

Pigeons (Columba livia) show change blindness in a color-change detection task.

PubMed

Herbranson, Walter T; Jeffers, Jacob S

2017-07-01

Change blindness is a phenomenon whereby changes to a stimulus are more likely go unnoticed under certain circumstances. Pigeons learned a change detection task, in which they observed sequential stimulus displays consisting of individual colors back-projected onto three response keys. The color of one response key changed during each sequence and pecks to the key that displayed the change were reinforced. Pigeons showed a change blindness effect, in that change detection accuracy was worse when there was an inter-stimulus interval interrupting the transition between consecutive stimulus displays. Birds successfully transferred to stimulus displays involving novel colors, indicating that pigeons learned a general change detection rule. Furthermore, analysis of responses to specific color combinations showed that pigeons could detect changes involving both spectral and non-spectral colors and that accuracy was better for changes involving greater differences in wavelength. These results build upon previous investigations of change blindness in both humans and pigeons and suggest that change blindness may be a general consequence of selective visual attention relevant to multiple species and stimulus dimensions.

Dissociating emotion-induced blindness and hypervision.

PubMed

Bocanegra, Bruno R; Zeelenberg, René

2009-12-01

Previous findings suggest that emotional stimuli sometimes improve (emotion-induced hypervision) and sometimes impair (emotion-induced blindness) the visual perception of subsequent neutral stimuli. We hypothesized that these differential carryover effects might be due to 2 distinct emotional influences in visual processing. On the one hand, emotional stimuli trigger a general enhancement in the efficiency of visual processing that can carry over onto other stimuli. On the other hand, emotional stimuli benefit from a stimulus-specific enhancement in later attentional processing at the expense of competing visual stimuli. We investigated whether detrimental (blindness) and beneficial (hypervision) carryover effects of emotion in perception can be dissociated within a single experimental paradigm. In 2 experiments, we manipulated the temporal competition for attention between an emotional cue word and a subsequent neutral target word by varying cue-target interstimulus interval (ISI) and cue visibility. Interestingly, emotional cues impaired target identification at short ISIs but improved target identification when competition was diminished by either increasing ISI or reducing cue visibility, suggesting that emotional significance of stimuli can improve and impair visual performance through distinct perceptual mechanisms.

Single-trial event-related potentials to significant stimuli.

PubMed

Rushby, Jacqueline A; Barry, Robert J

2009-11-01

The stimulus-response pattern of the skin conductance response (SCR) was used as a model of the Orienting Reflex (OR) to assess the P1, N1, P2, N2 and late positive complex (LPC/P300) components of the ERP in a simple habituation paradigm, in which a single series of 12 innocuous tones were presented at a very long interstimulus interval (2 min). To maintain their waking state during this boring task, participants were instructed to alternately close or open their eyes to each stimulus. None of the baseline-to-peak ERP measures showed trials effects comparable with the marked habituation over trials shown by the SCRs. Principal Components Analysis was used to decompose the ERP, yielding factors identified as the N1, N2, P3a, P3b and Novelty P3 components. An additional factor represented later eye-movement activity. No trial effects were apparent for the N1, N2, P3a or P3b components. The Novelty P3 showed marked response decrement over trials. These results are discussed in relation to current conceptualisations of the OR.

The effect of spatio-temporal distance between visual stimuli on information processing in children with Specific Language Impairment.

PubMed

Dispaldro, Marco; Corradi, Nicola

2015-01-01

The purpose of this study is to evaluate whether children with Specific Language Impairment (SLI) have a deficit in processing a sequence of two visual stimuli (S1 and S2) presented at different inter-stimulus intervals and in different spatial locations. In particular, the core of this study is to investigate whether S1 identification is disrupted due to a retroactive interference of S2. To this aim, two experiments were planned in which children with SLI and children with typical development (TD), matched by age and non-verbal IQ, were compared (Experiment 1: SLI n=19; TD n=19; Experiment 2: SLI n=16; TD n=16). Results show group differences in the ability to identify a single stimulus surrounded by flankers (Baseline level). Moreover, children with SLI show a stronger negative interference of S2, both for temporal and spatial modulation. These results are discussed in the light of an attentional processing limitation in children with SLI. Copyright © 2015 Elsevier Ltd. All rights reserved.

The role of dopamine in the timing of Pavlovian conditioned keypecking in ring doves.

PubMed

Ohyama, T; Horvitz, J C; Kitsos, E; Balsam, P D

2001-01-01

The effect of dopaminergic drugs on the timing of conditioned keypecking in ring doves was studied in two experiments. Subjects were given pairings of a keylight with food and the temporal distribution of keypecks was obtained during unreinforced probe trials. Experiment 1 demonstrated that injections of pimozide before each session immediately decreased response rates but shifted timing distributions gradually to the right over several days of treatment. Experiment 2 showed similar results using a longer interstimulus interval (ISI). No shifts were observed when the drug was injected after training sessions, or when a delay, identical to each subject's average latency to eat during the drug condition, was inserted between keylight offset and food presentation. Consequently, the shifts in timing were mediated neither by mere accumulation of the drug nor a delay from keylight offset to food presentation resulting from the drug's ability to slow motor processes. The results suggest that pimozide modulates response rate through its effect on motor processes or incentive value, and response timing through a conditioned response (CR) to injection-related cues established via their repeated pairings with the drug.

The ex-Gaussian distribution of reaction times in adolescents with attention-deficit/hyperactivity disorder.

PubMed

Gu, Shoou-Lian Hwang; Gau, Susan Shur-Fen; Tzang, Shyh-Weir; Hsu, Wen-Yau

2013-11-01

We investigated the three parameters (mu, sigma, tau) of ex-Gaussian distribution of RT derived from the Conners' continuous performance test (CCPT) and examined the moderating effects of the energetic factors (the inter-stimulus intervals (ISIs) and Blocks) among these three parameters, especially tau, an index describing the positive skew of RT distribution. We assessed 195 adolescents with DSM-IV ADHD, and 90 typically developing (TD) adolescents, aged 10-16. Participants and their parents received psychiatric interviews to confirm the diagnosis of ADHD and other psychiatric disorders. Participants also received intelligence (WISC-III) and CCPT assessments. We found that participants with ADHD had a smaller mu, and larger tau. As the ISI/Block increased, the magnitude of group difference in tau increased. Among the three ex-Gaussian parameters, tau was positively associated with omission errors, and mu was negatively associated with commission errors. The moderating effects of ISIs and Blocks on tau parameters suggested that the ex-Gaussian parameters could offer more information about the attention state in vigilance task, especially in ADHD. Copyright © 2013 Elsevier Ltd. All rights reserved.

The optimized V-V interval determined by interventricular conduction times versus invasive measurement by LVdP/dtMAX.

PubMed

van Gelder, Berry M; Meijer, Albert; Bracke, Frank A

2008-09-01

We compared the calculated optimal V-V interval derived from intracardiac electrograms (IEGM) with the optimized V-V interval determined by invasive measurement of LVdP/dt(MAX). Thirty-two patients with heart failure (six females, ages 68 +/- 7.8 years) had a CRT device implanted. After implantation of the atrial, right and a left ventricular lead, the optimal V-V interval was calculated using the QuickOpt formula (St. Jude Medical, Sylmar, CA, USA) applied to the respective IEGM recordings (V-V(IEGM)), and also determined by invasive measurement of LVdP/dt(MAX) (V-V(dP/dt)). The optimal V-V(IEGM) and V-V(dP/dt) intervals were 52.7 +/- 18 ms and 24.0 +/- 33 ms, respectively (P = 0.017), without correlation between the two. The baseline LVdP/dt(MAX) was 748 +/- 191 mmHg/s. The mean value of LVdP/dt(MAX) at invasive optimization was 947 +/- 198 mmHg/s, and at the calculated optimal V-V(IEGM) interval 920 +/- 191 mmHg/s (P < 0.0001). In spite of this significant difference, there was a good correlation between both methods (R = 0.991, P < 0.0001). However, a similarly good correlation existed between the maximum value of LVdP/dt(MAX) and LVdP/dt(MAX) at a fixed V-V interval of 0 ms (R = 0.993, P < 0.0001), or LVdP/dt(MAX) at a randomly selected V-V interval between 0 and +80 ms (R = 0.991, P < 0.0001). Optimizing the V-V interval with the IEGM method does not yield better hemodynamic results than simultaneous BiV pacing. Although a good correlation between LVdP/dt(MAX) determined with V-V(IEGM) and V-V(dP/dt) can be constructed, there is no correlation with the optimal settings of V-V interval in the individual patient.

Prolonged corrected QT interval is predictive of future stroke events even in subjects without ECG-diagnosed left ventricular hypertrophy.

PubMed

Ishikawa, Joji; Ishikawa, Shizukiyo; Kario, Kazuomi

2015-03-01

We attempted to evaluate whether subjects who exhibit prolonged corrected QT (QTc) interval (≥440 ms in men and ≥460 ms in women) on ECG, with and without ECG-diagnosed left ventricular hypertrophy (ECG-LVH; Cornell product, ≥244 mV×ms), are at increased risk of stroke. Among the 10 643 subjects, there were a total of 375 stroke events during the follow-up period (128.7±28.1 months; 114 142 person-years). The subjects with prolonged QTc interval (hazard ratio, 2.13; 95% confidence interval, 1.22-3.73) had an increased risk of stroke even after adjustment for ECG-LVH (hazard ratio, 1.71; 95% confidence interval, 1.22-2.40). When we stratified the subjects into those with neither a prolonged QTc interval nor ECG-LVH, those with a prolonged QTc interval but without ECG-LVH, and those with ECG-LVH, multivariate-adjusted Cox proportional hazards analysis demonstrated that the subjects with prolonged QTc intervals but not ECG-LVH (1.2% of all subjects; incidence, 10.7%; hazard ratio, 2.70, 95% confidence interval, 1.48-4.94) and those with ECG-LVH (incidence, 7.9%; hazard ratio, 1.83; 95% confidence interval, 1.31-2.57) had an increased risk of stroke events, compared with those with neither a prolonged QTc interval nor ECG-LVH. In conclusion, prolonged QTc interval was associated with stroke risk even among patients without ECG-LVH in the general population. © 2014 American Heart Association, Inc.

Acousto-Optical Vector Matrix Product Processor: Implementation Issues

DTIC Science & Technology

1989-04-25

power by a factor of 3.8. The acoustic velocity in longitudinal TeO2 is 4200 m/s, almost the same as the 4100 m/s acoustic velocity in dense flint glass ...field via an Interaction Model AOD150 dense flint glass Bragg Cell. The cell’s specifications are listed in the table below. BRAGG CELL SPECIFICATIONS...39 ns intervals). Since the speed of sound in dense flint glass is 4100 m/s, the acoustic field generated in a 10 As interval is distributed over a 4.1

QTc abnormalities in deliberate self-poisoning with moclobemide.

PubMed

Downes, M A; Whyte, I M; Isbister, G K

2005-07-01

Several medications have been found to prolong the QT interval in overdose. This can predispose to torsade de pointes-type ventricular tachycardia. To analyse the effects of moclobemide deliberate self-poisoning on the length of both QT and corrected QT (QTc) intervals. Electrocardiograms (ECG) of all patients presenting to a regional toxicology service with moclobemide ingestion were reviewed. Cases where a cardiotoxic agent was coingested were excluded. QT and QTc parameters were compared with a comparison group of patients ingesting paracetamol or benzodiazepines. Of 75 patients where ECG were available, the median ingested dose was 4.5 g (interquartile range (IQR): 2.4-7.5; range: 0.6-18 g) and the median age was 34 years (IQR: 26-44). The mean QT interval was 415 ms (standard deviation (SD): 51 ms) with a mean QTc of 459 ms (SD: 44 ms), and were prolonged compared with the comparison group. Twelve female patients had a QTc > 500 ms and in seven of these causality was established based on a pre- or post-ECG with a QTc < 500 ms. Only 10% of the moclobemide cases had a heart rate (HR) > 100 beats per minute, making overcorrection of HR by Bazett's formula an unlikely cause of the findings. No cardiac arrythmias were observed other than one case of first-degree heart block. Moclobemide prolongs the QT and QTc intervals in overdose and a 12-lead ECG should be done on all moclobemide deliberate self-poisonings. Continuous cardiac monitoring for what is otherwise a relatively benign overdose would appear to be an inappropriate use of resources but can be considered in patients with a QTc > 500 ms or with known risks for QT prolongation.

Effect of hyperventilation on rate corrected QT interval of children.

PubMed

Kannivelu, Arivalagan; Kudumula, Vikram; Bhole, Vinay

2013-02-01

Hyperventilation is known to cause ST segment changes and QT variability in adults, but this has not been systematically studied in children. To investigate the effect of hyperventilation on rate corrected QT interval (QTc) in children. 25 children (male=10) with a median age of 14 (range 8.3-17.6) years were asked to hyperventilate for 1 min before exercise testing using the modified Bruce protocol. Mean QTc at rest, after hyperventilation, at peak exercise and at 1 min of recovery was 425(±31), 460(±30), 446(±38) and 420(±32) ms, respectively. Mean increase (95% CI) in QTc after hyperventilation was 35(19 to 51) ms (p<0.001), while there was minimal difference between QT interval at rest and after hyperventilation (mean QT 352(±41) vs 357(±44) ms). In six children, there were abnormalities in T wave morphology following hyperventilation. The QTc increment following hyperventilation was more pronounced in children with resting QTc <440 ms (n=14, mean increment (95% CI): 55 (33 to 78) ms) compared to children with QTc ≥440 ms (n=11, mean increment (95% CI): 9 (-4 to 22) ms) (p=0.001). QTc prolongation following hyperventilation was seen in children with both low and intermediate probability of long QT syndrome (LQTS). Peak exercise and early recovery did not cause a statistically significant change in QTc in either of these groups. Hyperventilation produces repolarisation abnormalities, including prolongation of QTc and T wave abnormalities in children with low probability of LQTS. The likely mechanism is delayed adaptation of QT interval with increased heart rate. Thus, a hyperventilation episode can be misdiagnosed as LQTS, especially in an emergency department.

[Structure of maxillary sinus mucous membrane under normal conditions and in odontogenic perforative sinusitis].

PubMed

Baĭdik, O D; Logvinov, S V; Zubarev, S G; Sysoliatin, P G; Gurin, A A

2011-01-01

Methods of light, electron microscopy and immunohistochemistry were used to study the samples of maxillary sinus (MS) mucous membrane (MM) under normal conditions and in odontogenic sinusitis. To study the normal structure, the samples were obtained at autopsy from 26 human corpses 12-24 hours after death. Electron microscopic and immunohistochemical study was performed on biopsies of grossly morphologically unchanged MS MM, obtained during the operations for retention cysts in 6 patients. MS MM in perforative sinusitis was studied using the biopsies obtained from 43 patients. The material is broken into 4 groups depending on perforative sinusitis duration. Under normal conditions, MS MM is lined with a pseudostratified columnar ciliated epithelium. Degenerative changes of ciliated epithelial cells were already detected at short time intervals after MS perforations and become apparent due to reduction of specific volume of mitochondria and, rough endoplasmic reticulum, and increase of nuclear-cytoplasmic ratio. In the globlet cells, the reduction of nuclear-cytoplasmic ratio was associated with the disturbance of the secretory product release. At time intervals exceeding 3 months, epithelium underwent metaplasia into simple cuboidal and stratified squamous keratinized, while in MS MM lamina propria, cellular infiltration was increased. CD4+ cell content in sinus MM gradually increased, while at late periods after perforation occurrence it decreased. Low CD4+ cell count within the epithelium and the absence of muromidase on the surface of MS MM was detected. With the increase of the time interval since MS perforation, the number of CD8+ and CD20+ cells in MS MM was found to increase.

Drug-Induced QTc Interval Prolongation: A Multicenter Study to Detect Drugs and Clinical Factors Involved in Every Day Practice.

PubMed

Keller, Guillermo A; Alvarez, Paulino A; Ponte, Marcelo L; Belloso, Waldo H; Bagnes, Claudia; Sparanochia, Cecilia; Gonzalez, Claudio D; Villa Etchegoyen, M Cecilia; Diez, Roberto A; Di Girolamo, Guillermo

2016-01-01

The actual prevalence of drug induced QTc prolongation in clinical practice is unknown. Our objective was to determine the occurrence and characteristics of drug-induced QT prolongation in several common clinical practices. Additionally, a subgroup of patients treated with dextropropoxyphene of particular interest for the regulatory authority was analysed. Medical history and comorbidities predisposing to QT interval prolongation were registered for 1270 patient requiring medical assistance that involved drug administration. Three ionograms and ECGs were performed: baseline, intra- and after treatment; QT interval was corrected with Bazzet formula. Among patients, 9.9% presented QTc >450/470 ms, 3% QTc > 500 ms, 12.7% ΔQTc >30 ms and 5.2% ΔQTc >60 ms. QTc prolongation associated with congestive heart failure, ischemic cardiopathy, diabetes, renal failure, arrhythmias, hypothyroidism, and bradycardia. At univariate analysis, clarithromycin, haloperidol, tramadol, amiodarone, glyceryl trinitrate, amoxicillin + clavulanic acid, amoxicillin + sulbactam, ampicillin + sulbactam, fentanyl, piperacillin + tazobactam, and diazepam prolonged QTc. Prolongation remained significantly associated with furosemide, clarithromycin, glyceryl trinitrate and betalactamase inhibitors after multivariate analysis. QT interval prolongation in everyday practice is frequent, in association to clinical factors and drugs that can be easily identified for monitoring and prevention strategies.

Type 1 diabetes and multiple sclerosis: A Danish population-based cohort study.

PubMed

Nielsen, Nete M; Westergaard, Tine; Frisch, Morten; Rostgaard, Klaus; Wohlfahrt, Jan; Koch-Henriksen, Nils; Melbye, Mads; Hjalgrim, Henrik

2006-07-01

Type 1 diabetes mellitus (T1D) and multiple sclerosis (MS) contribute considerably to the burden of autoimmune diseases in young adults. Although HLA patterns of T1D and MS are considered mutually exclusive, individual and familial co-occurrence of the 2 diseases has been reported. To assess the co-occurrence of T1D and MS by estimating the risk for MS in patients with T1D and the risk for T1D in first-degree relatives of patients with MS. Two population-based disease registers, the Danish Hospital Discharge Register and the Danish Multiple Sclerosis Register were used to identify patients with T1D, defined as patients in whom diabetes was diagnosed before age 20 years (N = 6078), and patients with MS (N = 11 862). First-degree relatives (N = 14,771) of patients with MS were identified from family information in the Danish Civil Registration System. Patients with T1D and first-degree relatives of patients with MS were followed up for occurrence of MS and T1D, respectively, and the relative risks were expressed as standardized incidence ratios, that is, ratios of observed to expected numbers of outcomes based on national age, sex, and period-specific MS and T1D incidence rates. Patients with T1D were at more than 3-fold increased risk for development of MS (relative risk, 3.26; 95% confidence interval, 1.80-5.88; n = 11). First-degree relatives of patients with MS were at 63% increased risk (relative risk, 1.63; 95% confidence interval, 1.26-2.12; n = 56) for development of T1D. However, adjusting for familial relationship to patients with T1D reduced the excess risk to 44% (relative risk, 1.44; 95% confidence interval, 1.11-1.88; n = 56). The present nationwide cohort study demonstrates an intraindividual and, to a lesser degree, an intrafamilial co-occurrence of MS and T1D.

Evaluation of inhomogeneities of repolarization in patients with psoriasis vulgaris

PubMed Central

İnci, Sinan; Aksan, Gökhan; Nar, Gökay; Yüksel, Esra Pancar; Ocal, Hande Serra; Çapraz, Mustafa; Yüksel, Serkan; Şahin, Mahmut

2016-01-01

Introduction The arrhythmia potential has not been investigated adequately in psoriatic patients. In this study, we assessed the ventricular repolarization dispersion, using the Tp-e interval and the Tp-e/QT ratio, and investigated the association with inflammation. Material and methods Seventy-one psoriasis vulgaris patients and 70 age- and gender-matched healthy individuals were enrolled in the study. The severity of the disease was calculated using Psoriasis Area and Severity Index scoring. The QTd was defined as the difference between the maximum and minimum QT intervals. The Tp-e interval was defined as the interval from the peak of the T wave to the end of the T wave. The Tp-e interval was corrected for heart rate. The Tp-e/QT ratio was calculated using these measurements. Results There were no significant differences between the groups with respect to basal clinical and laboratory characteristics (p > 0.05). The Tp-e interval, the corrected Tp-e interval (cTp-e) and the Tp-e/QT ratio were also significantly higher in psoriasis patients compared to the control group (78.5 ±8.0 ms vs. 71.4 ±7.6 ms, p < 0.001, 86.3 ±13.2 ms vs. 77.6 ±9.0 ms, p < 0.001 and 0.21 ±0.02 vs. 0.19 ±0.02, p < 0.001 respectively). A significant correlation was detected between the cTp-e time and the Tp-e/QT ratio and the PASI score in the group of psoriatic patients (r = 0.51, p < 0.001; r = 0.59, p < 0.001, respectively). Conclusions In our study, we detected a significant increase in the Tp-e interval and the Tp-e/QT ratio in patients with psoriasis vulgaris. The Tp-e interval and the Tp-e/QT ratio may be predictors for ventricular arrhythmias in patients with psoriasis vulgaris. PMID:27904512

Did I see your hand moving? The effect of movement-related information on the Corsi block tapping task.

PubMed

Brunetti, Riccardo; Del Gatto, Claudia; Cavallina, Clarissa; Farina, Benedetto; Delogu, Franco

2018-05-01

The Corsi Block Tapping Task is a widespread test used to assess spatial working memory. Previous research hypothesized that the discrepancy found in some cases between the traditional and the digital (touchscreen) version of the Corsi block tapping task may be due to a direct motor resonance between the experimenter's and the participant's hand movements. However, we hypothesize that this discrepancy might be due to extra movement-related information included in the traditional version, lacking in the digital one. We investigated the effects of such task-irrelevant information using eCorsi, a touchscreen version of the task. In Experiment 1, we manipulate timing in sequence presentation, creating three conditions. In the Congruent condition, the inter-stimulus intervals reflected the physical distance in which the stimuli were spatially placed: The longer the spatial distance, the longer the temporal interval. In the Incongruent condition the timing changed randomly. Finally, in the Isochronous condition every stimulus appeared after a fixed interval, independently from its spatial position. The results showed a performance enhancement in the Congruent condition, suggesting an incidental spatio-temporal binding. In Experiment 2, we added straight lines between each location in the sequences: In the Trajectories condition participants saw trajectories from one spatial position to the other during sequence presentation, while a condition without such trajectories served as control. Results showed better performances in the Trajectories condition. We suggest that the timing and trajectories information play a significant role in the discrepancies found between the traditional and the touchscreen version of the Corsi Block Tapping Task, without the necessity of explanations involving direct motor resonance (e.g. seeing an actual hand moving) as a causal factor.

Why trace and delay conditioning are sometimes (but not always) hippocampal dependent: A computational model

PubMed Central

Moustafa, Ahmed A.; Wufong, Ella; Servatius, Richard J.; Pang, Kevin C. H.; Gluck, Mark A.; Myers, Catherine E.

2013-01-01

A recurrent-network model provides a unified account of the hippocampal region in mediating the representation of temporal information in classical eyeblink conditioning. Much empirical research is consistent with a general conclusion that delay conditioning (in which the conditioned stimulus CS and unconditioned stimulus US overlap and co-terminate) is independent of the hippocampal system, while trace conditioning (in which the CS terminates before US onset) depends on the hippocampus. However, recent studies show that, under some circumstances, delay conditioning can be hippocampal-dependent and trace conditioning can be spared following hippocampal lesion. Here, we present an extension of our prior trial-level models of hippocampal function and stimulus representation that can explain these findings within a unified framework. Specifically, the current model includes adaptive recurrent collateral connections that aid in the representation of intra-trial temporal information. With this model, as in our prior models, we argue that the hippocampus is not specialized for conditioned response timing, but rather is a general-purpose system that learns to predict the next state of all stimuli given the current state of variables encoded by activity in recurrent collaterals. As such, the model correctly predicts that hippocampal involvement in classical conditioning should be critical not only when there is an intervening trace interval, but also when there is a long delay between CS onset and US onset. Our model simulates empirical data from many variants of classical conditioning, including delay and trace paradigms in which the length of the CS, the inter-stimulus interval, or the trace interval is varied. Finally, we discuss model limitations, future directions, and several novel empirical predictions of this temporal processing model of hippocampal function and learning. PMID:23178699

Severity of Vision Loss Interacts With Word-Specific Features to Impact Out-Loud Reading in Glaucoma

PubMed Central

Mathews, Priya M.; Rubin, Gary S.; McCloskey, Michael; Salek, Sherveen; Ramulu, Pradeep Y.

2015-01-01

Purpose. To assess the impact of glaucoma-related vision loss on measures of out-loud reading, including time to say individual words, interval time between consecutive words, lexical errors, skipped words, and repetitions. Methods. Glaucoma subjects (n = 63) with bilateral visual field loss and glaucoma suspect controls (n = 57) were recorded while reading a standardized passage out loud. A masked evaluator determined the start and end of each recorded word and identified reading errors. Results. Glaucoma subjects demonstrated longer durations to recite individual words (265 vs. 243 ms, P < 0.001), longer intervals between words (154 vs. 124 ms, P < 0.001), and longer word/post-word interval complexes (the time spanned by the word and the interval following the word; 419 vs. 367 ms, P < 0.001) than controls. In multivariable analyses, each 0.1 decrement in log contrast sensitivity (logCS) was associated with a 15.0 ms longer word/post-interval complex (95% confidence interval [CI] = 9.6–20.4; P < 0.001). Contrast sensitivity was found to significantly interact with word length, word frequency, and word location at the end of a line with regards to word/post-word interval complex duration (P < 0.05 for all). Glaucoma severity was also associated with more lexical errors (Odds ratio = 1.20 for every 0.1 logCS decrement; 95% CI = 1.02–1.39, P < 0.05), but not with more skipped or repeated words. Conclusions. Glaucoma patients with greater vision loss make more lexical errors, are slower in reciting longer and less frequently used words, and more slowly transition to new lines of text. These problem areas may require special attention when designing methods to rehabilitate reading in patients with glaucoma. PMID:25737150

Oral Contraceptives Attenuate Cardiac Autonomic Responses to Musical Auditory Stimulation: Pilot Study.

PubMed

Milan, Réveni Carmem; Plassa, Bruna Oliveira; Guida, Heraldo Lorena; de Abreu, Luiz Carlos; Gomes, Rayana L; Garner, David M; Valenti, Vitor E

2015-01-01

The literature presents contradictory results regarding the effects of contraceptives on cardiac autonomic regulation. The research team aimed to evaluate the effects of musical auditory stimulation on cardiac autonomic regulation in women who use oral contraceptives. The research team designed a transversal observational pilot study. The setting was the Centro de Estudos do Sistema Nervoso Autônomo (CESNA) in the Departamento de Fonoaudiologia at the Universidade Estadual Paulista (UNESP) in Marília, SP, Brazil. Participants were 22 healthy nonathletic and nonsedentary females, all nonsmokers and aged between 18 and 27 y. Participants were divided into 2 groups: (1) 12 women who were not taking oral contraceptives, the control group; and (2) 10 women who were taking oral contraceptives, the oral contraceptive group. In the first stage, a rest control, the women sat with their earphones turned off for 20 min. After that period, the participants were exposed to 20 min of classical baroque music (ie, "Canon in D Major," Johann Pachelbel), at 63-84 dB. Measurements of the equivalent sound levels were conducted in a soundproof room, and the intervals between consecutive heartbeats (R-R intervals) were recorded, with a sampling rate of 1000 Hz. For calculation of the linear indices, the research team used software to perform an analysis of heart rate variability (HRV). Linear indices of HRV were analyzed in the time domain: (1) the standard deviation of normal-to-normal R-R intervals (SDNN), (2) the root-mean square of differences between adjacent normal R-R intervals in a time interval (RMSSD), and (3) the percentage of adjacent R-R intervals with a difference of duration greater than 50 ms (pNN50). The study also analyzed the frequency domain-low frequency (LF), high frequency (HF), and LF/HF ratio. For the control group, the musical auditory stimulation reduced (1) the SDNN from 52.2 ± 10 ms to 48.4 ± 16 ms (P = .0034); (2) the RMSSD from 45.8 ± 22 ms to 41.2 ± 19 ms (P = .0128); (3) the pNN50 from 25.5 ± 19 to 22.0 ± 18 (P = .0211); and (4) the LF (ms2) from 954.8 ± 457 ms2 to 686.2 ± 491 ms2 (P = .0024). In the oral contraceptive group, no significant changes occurred for the HRV indices during exposure to music. Musical auditory stimulation had a greater influence on cardiac autonomic regulation in women who did not use oral contraceptives.

Substitution of (R,S)-methadone by (R)-methadone: Impact on QTc interval.

PubMed

Ansermot, Nicolas; Albayrak, Ozgür; Schläpfer, Jürg; Crettol, Séverine; Croquette-Krokar, Marina; Bourquin, Michel; Déglon, Jean-Jacques; Faouzi, Mohamed; Scherbaum, Norbert; Eap, Chin B

2010-03-22

Methadone is administered as a chiral mixture of (R,S)-methadone. The opioid effect is mainly mediated by (R)-methadone, whereas (S)-methadone blocks the human ether-à-go-go-related gene (hERG) voltage-gated potassium channel more potently, which can cause drug-induced long QT syndrome, leading to potentially lethal ventricular tachyarrhythmias. To investigate whether substitution of (R,S)-methadone by (R)-methadone could reduce the corrected QT (QTc) interval, (R,S)-methadone was replaced by (R)-methadone (half-dose) in 39 opioid-dependent patients receiving maintenance treatment for 14 days. (R)-methadone was then replaced by the initial dose of (R,S)-methadone for 14 days (n = 29). Trough (R)-methadone and (S)-methadone plasma levels and electrocardiogram measurements were taken. The Fridericia-corrected QT (QTcF) interval decreased when (R,S)-methadone was replaced by a half-dose of (R)-methadone; the median (interquartile range [IQR]) values were 423 (398-440) milliseconds (ms) and 412 (395-431) ms (P = .06) at days 0 and 14, respectively. Using a univariate mixed-effect linear model, the QTcF value decreased by a mean of -3.9 ms (95% confidence interval [CI], -7.7 to -0.2) per week (P = .04). The QTcF value increased when (R)-methadone was replaced by the initial dose of (R,S)-methadone for 14 days; median (IQR) values were 424 (398-436) ms and 424 (412-443) ms (P = .01) at days 14 and 28, respectively. The univariate model showed that the QTcF value increased by a mean of 4.7 ms (95% CI, 1.3-8.1) per week (P = .006). Substitution of (R,S)-methadone by (R)-methadone reduces the QTc interval value. A safer cardiac profile of (R)-methadone is in agreement with previous in vitro and pharmacogenetic studies. If the present results are confirmed by larger studies, (R)-methadone should be prescribed instead of (R,S)-methadone to reduce the risk of cardiac toxic effects and sudden death.

Comparison of automated measurements of electrocardiographic intervals and durations by computer-based algorithms of digital electrocardiographs.

PubMed

Kligfield, Paul; Badilini, Fabio; Rowlandson, Ian; Xue, Joel; Clark, Elaine; Devine, Brian; Macfarlane, Peter; de Bie, Johan; Mortara, David; Babaeizadeh, Saeed; Gregg, Richard; Helfenbein, Eric D; Green, Cynthia L

2014-02-01

Automated measurements of electrocardiographic (ECG) intervals are widely used by clinicians for individual patient diagnosis and by investigators in population studies. We examined whether clinically significant systematic differences exist in ECG intervals measured by current generation digital electrocardiographs from different manufacturers and whether differences, if present, are dependent on the degree of abnormality of the selected ECGs. Measurements of RR interval, PR interval, QRS duration, and QT interval were made blindly by 4 major manufacturers of digital electrocardiographs used in the United States from 600 XML files of ECG tracings stored in the US FDA ECG warehouse and released for the purpose of this study by the Cardiac Safety Research Consortium. Included were 3 groups based on expected QT interval and degree of repolarization abnormality, comprising 200 ECGs each from (1) placebo or baseline study period in normal subjects during thorough QT studies, (2) peak moxifloxacin effect in otherwise normal subjects during thorough QT studies, and (3) patients with genotyped variants of congenital long QT syndrome (LQTS). Differences of means between manufacturers were generally small in the normal and moxifloxacin subjects, but in the LQTS patients, differences of means ranged from 2.0 to 14.0 ms for QRS duration and from 0.8 to 18.1 ms for the QT interval. Mean absolute differences between algorithms were similar for QRS duration and QT intervals in the normal and in the moxifloxacin subjects (mean ≤6 ms) but were significantly larger in patients with LQTS. Small but statistically significant group differences in mean interval and duration measurements and means of individual absolute differences exist among automated algorithms of widely used, current generation digital electrocardiographs. Measurement differences, including QRS duration and the QT interval, are greatest for the most abnormal ECGs. © 2014.

L2-L1 Translation Priming Effects in a Lexical Decision Task: Evidence From Low Proficient Korean-English Bilinguals

PubMed Central

Lee, Yoonhyoung; Jang, Euna; Choi, Wonil

2018-01-01

One of the key issues in bilingual lexical representation is whether L1 processing is facilitated by L2 words. In this study, we conducted two experiments using the masked priming paradigm to examine how L2-L1 translation priming effects emerge when unbalanced, low proficiency, Korean-English bilinguals performed a lexical decision task. In Experiment 1, we used a 150 ms SOA (50 ms prime duration followed by a blank interval of 100 ms) and found a significant L2-L1 translation priming effect. In contrast, in Experiment 2, we used a 60 ms SOA (50 ms prime duration followed by a blank interval of 10 ms) and found a null effect of L2-L1 translation priming. This finding is the first demonstration of a significant L2-L1 translation priming effect with unbalanced Korean-English bilinguals. Implications of this work are discussed with regard to bilingual word recognition models. PMID:29599733

Effects of phenobarbital and levetiracetam on PR and QTc intervals in patients with post-stroke seizure.

PubMed

Siniscalchi, Antonio; Scaglione, Francesco; Sanzaro, Enzo; Iemolo, Francesco; Albertini, Giorgio; Quirino, Gianluca; Manes, Maria Teresa; Gratteri, Santo; Mercuri, Nicola Biagio; De Sarro, Giovambattista; Gallelli, Luca

2014-12-01

Sudden unexplained/unexpected death (SUDEP) is related to high mortality in patients with epilepsy. The prolongation of QT interval, involved in cardiac arrhythmia-related SUDEP, may be precipitated by antiepileptic drugs (AEDs). In this study, we evaluated the effects of phenobarbital and levetiracetam on PR-QTc intervals in patients with post-stroke seizures. We performed an open-label, parallel group, prospective, multicenter study between June 2009 and December 2013 in patients older than 18 years of age with a clinical diagnosis of post-stroke seizure and treated with phenobarbital or levetiracetam. In order to exclude a role of cerebral post-stroke injury on modulation of PR and QTc intervals, patients with cerebral post-stroke injury and without seizures were also enrolled as controls. Interictal electrocardiography analysis revealed no significant difference in PR interval between patients treated with an AED (n = 49) and control patients (n = 50) (181.25 ± 12.05 vs. 182.4 ± 10.3 ms; p > 0.05). In contrast, a significantly longer QTc interval was recorded in patients treated with an AED compared with control patients (441.2 ± 56.6 vs. 396.8 ± 49.3 ms; p < 0.01). Patients treated with phenobarbital showed a significantly longer QTc interval than patients treated with levetiracetam (460.0 ± 57.2 vs. 421.5 ± 50.1 ms; p < 0.05). The study reported that in patients with late post-stroke seizures, phenobarbital prolonged QTc interval more so than levetiracetam.

Prevalence and risk factors for prolonged QT interval and QT dispersion in patients with type 2 diabetes.

PubMed

Ninkovic, Vladan M; Ninkovic, Srdjan M; Miloradovic, Vanja; Stanojevic, Dejan; Babic, Marijana; Giga, Vojislav; Dobric, Milan; Trenell, Michael I; Lalic, Nebojsa; Seferovic, Petar M; Jakovljevic, Djordje G

2016-10-01

Prolonged QT interval is associated with cardiac arrhythmias and sudden death. The present study determined the prevalence of prolonged QT interval and QT dispersion and defined their clinical and metabolic predictors in patients with type 2 diabetes. Cross-sectional study included 501 patients with type 2 diabetes. A standard 12-lead electrocardiogram was recorded. QT corrected for heart rate (QTc) >440 ms and QT dispersion (QTd) >80 ms were considered abnormally prolonged. QTc ≥ 500 ms was considered a high-risk QTc prolongation. Demographic, clinical and laboratory data were collected. Independent risk factors for prolonged QTc and QTd were assessed using logistic regression analysis. Prevalence of QTc > 440 ms and QTd > 80 ms were 44.1 and 3.6 %, respectively. Prevalence of high-risk QTc (≥500 ms) was 2 % only. Independent risk factors for QTc prolongation >440 ms were mean blood glucose (β = 2.192, p < 0.001), treatment with sulphonylurea (β = 5.198, p = 0.027), female gender (β = 8.844, p < 0.001), and coronary heart disease (β = 8.636, p = 0.001). Independent risk factors for QTc ≥ 500 ms were coronary heart disease (β = 4.134, p < 0.001) and mean blood glucose level (β = 1.735, p < 0.001). The independent risk factor for prolonged QTd was only coronary heart disease (β = 5.354, p < 0.001). Although the prevalence of prolonged QTc > 440 ms is significant, the prevalence of high-risk QTc (≥500 ms) and QTd > 80 ms is very low in patients with type 2 diabetes. Hyperglycaemia and coronary heart disease are strong predictors of high-risk QTc.

Automated saliva processing for LC-MS/MS: Improving laboratory efficiency in cortisol and cortisone testing.

PubMed

Antonelli, Giorgia; Padoan, Andrea; Artusi, Carlo; Marinova, Mariela; Zaninotto, Martina; Plebani, Mario

2016-04-01

The aim of this study was to implement in our routine practice an automated saliva preparation protocol for quantification of cortisol (F) and cortisone (E) by LC-MS/MS using a liquid handling platform, maintaining the previously defined reference intervals with the manual preparation. Addition of internal standard solution to saliva samples and calibrators and SPE on μ-elution 96-well plate were performed by liquid handling platform. After extraction, the eluates were submitted to LC-MS/MS analysis. The manual steps within the entire process were to transfer saliva samples in suitable tubes, to put the cap mat and transfer of the collection plate to the LC auto sampler. Transference of the reference intervals from the manual to the automated procedure was established by Passing Bablok regression on 120 saliva samples analyzed simultaneously with the two procedures. Calibration curves were linear throughout the selected ranges. The imprecision ranged from 2 to 10%, with recoveries from 95 to 116%. Passing Bablok regression demonstrated no significant bias. The liquid handling platform translates the manual steps into automated operations allowing for saving hands-on time, while maintaining assay reproducibility and ensuring reliability of results, making it implementable in our routine with the previous established reference intervals. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Increased whole-body auditory startle reflex and autonomic reactivity in children with anxiety disorders

PubMed Central

Bakker, Mirte J.; Tijssen, Marina A.J.; van der Meer, Johan N.; Koelman, Johannes H.T.M.; Boer, Frits

2009-01-01

Background Young patients with anxiety disorders are thought to have a hypersensitive fear system, including alterations of the early sensorimotor processing of threatening information. However, there is equivocal support in auditory blink response studies for an enlarged auditory startle reflex (ASR) in such patients. We sought to investigate the ASR measured over multiple muscles (whole-body) in children and adolescents with anxiety disorders. Methods Between August and December 2006, we assessed ASRs (elicited by 8 consecutive tones of 104 dB, interstimulus interval of about 2 min) in 25 patients and 25 matched controls using a case–control design and in 9 nonaffected siblings. We recorded the electromyographic activity of 6 muscles and the sympathetic skin response. We investigated response occurrence (probability %) and response magnitude (area under the curve in μV × ms) of the combined response of 6 muscles and of the single blink response. Results In patients (17 girls, mean age 12 years; 13 social phobia, 9 generalized anxiety, 3 other), the combined response probability (p = 0.027) of all muscles, the combined area under the curve of all muscles (p = 0.011) and the sympathetic skin response (p = 0.006) were enlarged compared with matched controls. The response probability (p = 0.48) and area under the curve (p = 0.07) of the blink response were normal in patients compared with controls. The ASR pattern was normal with normal latencies in patients compared with controls. In nonaffected siblings, the sympathetic skin response (p = 0.038), but not the combined response probability of all muscles (p = 0.15), was enlarged compared with controls. Limitations Limitations are the sample size and restricted comparison to the psychophysiological ASR paradigm. Conclusion The results point toward a hypersensitive central nervous system (fear system), including early sensorimotor processing alterations and autonomic hyperreactivity. The multiple muscle (whole-body) ASR is suggested to be a better tool to detect ASR abnormalities in patients with anxiety disorders than the blink response alone. Abnormalities in ASR serve as a candidate endophenotype of anxiety disorders. PMID:19568483

Standardization of magnetocardiography in nonhuman primates

NASA Astrophysics Data System (ADS)

Seki, Yusuke; Muneyuki, Kenta; Kandori, Akihiko; Tsukada, Keiji; Terao, Keiji; Ageyama, Naohide

2008-03-01

To establish the electrophysiological mappings of nonhuman primates by using magnetocardiogram (MCG) data and obtain the normal values of MCG parameters, we used 64-channel superconducting quantum interference devices to measure 8 × 8 MCG data for 95 cynomolgus monkeys (Macaca fascicularis, 51 female and 44 male). The PQ interval, QRS duration, QT interval and QTc were respectively 79 ± 14 ms, 42 ± 7 ms, 222 ± 23 ms and 363 ± 25 (mean ± SD), and these parameters did not differ significantly between female and male monkeys. These results indicate the normal values of the MCG parameters of the cynomolgus monkey and should facilitate animal experiments in magnetocardiography.

Venetoclax does not prolong the QT interval in patients with hematological malignancies: an exposure-response analysis.

PubMed

Freise, Kevin J; Dunbar, Martin; Jones, Aksana K; Hoffman, David; Enschede, Sari L Heitner; Wong, Shekman; Salem, Ahmed Hamed

2016-10-01

Venetoclax (ABT-199/GDC-0199) is a selective first-in-class B cell lymphoma-2 inhibitor being developed for the treatment of hematological malignancies. The aim of this study was to determine the potential of venetoclax to prolong the corrected QT (QTc) interval and to evaluate the relationship between systemic venetoclax concentration and QTc interval. The study population included 176 male and female patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 105) or non-Hodgkin's lymphoma (n = 71) enrolled in a phase 1 safety, pharmacokinetic, and efficacy study. Electrocardiograms were collected in triplicate at time-matched points (2, 4, 6, and 8 h) prior to the first venetoclax administration and after repeated venetoclax administration to achieve steady state conditions. Venetoclax doses ranged from 100 to 1200 mg daily. Plasma venetoclax samples were collected after steady state electrocardiogram measurements. The mean and upper bound of the 2-sided 90 % confidence interval (CI) QTc change from baseline were <5 and <10 ms, respectively, at all time points and doses (<400, 400, and >400 mg). Three subjects had single QTc values >500 ms and/or ΔQTc > 60 ms. The effect of venetoclax concentration on both ΔQTc and QTc was not statistically significant (P > 0.05). At the mean maximum concentrations achieved with therapeutic (400 mg) and supra-therapeutic (1200 mg) venetoclax doses, the estimated drug effects on QTc were 0.137 (90 % CI [-1.01 to 1.28]) and 0.263 (90 % CI [-1.92 to 2.45]) ms, respectively. Venetoclax does not prolong QTc interval even at supra-therapeutic doses, and there is no relationship between venetoclax concentrations and QTc interval.

A 2:1 AV rhythm: an adverse effect of a long AV delay during DDI pacing and its prevention by the ventricular intrinsic preference algorithm in DDD mode.

PubMed

Minamiguchi, Hitoshi; Oginosawa, Yasushi; Kohno, Ritsuko; Tamura, Masahito; Takeuchi, Masaaki; Otsuji, Yutaka; Abe, Haruhiko

2012-07-01

A 91-year-old woman received a dual-chamber pacemaker for sick sinus syndrome and intermittently abnormal atrioventricular (AV) conduction. The pacemaker was set in DDI mode with a 350-ms AV delay to preserve intrinsic ventricular activity. She complained of palpitation during AV sequential pacing. The electrocardiogram showed a 2:1 AV rhythm from 1:1 ventriculoatrial (VA) conduction during ventricular pacing in DDI mode with a long AV interval. After reprogramming of the pacemaker in DDD mode with a 250-ms AV interval and additional 100-ms prolongation of the AV interval by the ventricular intrinsic preference function, VA conduction disappeared and the patient's symptom were alleviated without increasing unnecessary right ventricular pacing. ©2011, The Authors. Journal compilation ©2011 Wiley Periodicals, Inc.

Programming Cardiac Resynchronization Therapy for Electrical Synchrony: Reaching Beyond Left Bundle Branch Block and Left Ventricular Activation Delay.

PubMed

Varma, Niraj; O'Donnell, David; Bassiouny, Mohammed; Ritter, Philippe; Pappone, Carlo; Mangual, Jan; Cantillon, Daniel; Badie, Nima; Thibault, Bernard; Wisnoskey, Brian

2018-02-06

QRS narrowing following cardiac resynchronization therapy with biventricular (BiV) or left ventricular (LV) pacing is likely affected by patient-specific conduction characteristics (PR, qLV, LV-paced propagation interval), making a universal programming strategy likely ineffective. We tested these factors using a novel, device-based algorithm (SyncAV) that automatically adjusts paced atrioventricular delay (default or programmable offset) according to intrinsic atrioventricular conduction. Seventy-five patients undergoing cardiac resynchronization therapy (age 66±11 years; 65% male; 32% with ischemic cardiomyopathy; LV ejection fraction 28±8%; QRS duration 162±16 ms) with intact atrioventricular conduction (PR interval 194±34, range 128-300 ms), left bundle branch block, and optimized LV lead position were studied at implant. QRS duration (QRSd) reduction was compared for the following pacing configurations: nominal simultaneous BiV (Mode I: paced/sensed atrioventricular delay=140/110 ms), BiV+SyncAV with 50 ms offset (Mode II), BiV+SyncAV with offset that minimized QRSd (Mode III), or LV-only pacing+SyncAV with 50 ms offset (Mode IV). The intrinsic QRSd (162±16 ms) was reduced to 142±17 ms (-11.8%) by Mode I, 136±14 ms (-15.6%) by Mode IV, and 132±13 ms (-17.8%) by Mode II. Mode III yielded the shortest overall QRSd (123±12 ms, -23.9% [ P <0.001 versus all modes]) and was the only configuration without QRSd prolongation in any patient. QRS narrowing occurred regardless of QRSd, PR, or LV-paced intervals, or underlying ischemic disease. Post-implant electrical optimization in already well-selected patients with left bundle branch block and optimized LV lead position is facilitated by patient-tailored BiV pacing adjusted to intrinsic atrioventricular timing using an automatic device-based algorithm. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Factors associated with the development of atrial fibrillation in patients with rheumatic mitral stenosis.

PubMed

Ozaydin, Mehmet; Turker, Yasin; Varol, Ercan; Alaca, Sule; Erdogan, Dogan; Yilmaz, Nigar; Dogan, Abdullah

2010-06-01

The aim of this study was to evaluate the factors associated with the development of atrial fibrillation (AF) in patients with rheumatic mitral stenosis (MS). A total of 146 consecutive patients with rheumatic MS were screened. They were accepted to be in AF group and sinus rhythm group according to their rhythm in the baseline ECG. After screening, 38 patients were excluded due to hyperthyroidism (n = 13), chronic obstructive pulmonary disease (n = 22), malignancy (n = 2) and rheumatoid arthritis (n = 1). Therefore, remaining 108 patients, 74 of whom in sinus rhythm (MS-SR) and 34 of whom in AF (MS-AF) constituted study population. Fourty age- and gender-matched patients constituted control group. Factors associated with development of AF in multivariable analysis included High sensitivity C reactive protein (P = 0.005; odds ratio, 3.44; 95% confidence interval, 1.44-8.22), N-terminal of brain natriuretic peptide precursor (P < 0.0001; odds ratio, 1.03; 95% confidence interval, 1.02-1.06) and left atrial diameter (P < 0.0001; odds ratio, 1.68; 95% confidence interval, 1.32-2.14). Present study suggests that High sensitivity C reactive protein, N-terminal of brain natriuretic peptide precursor and left atrial diameter are associated with development AF in patients with MS.

Differentiating the origin of outflow tract ventricular arrhythmia using a simple, novel approach.

PubMed

Efimova, Elena; Dinov, Borislav; Acou, Willem-Jan; Schirripa, Valentina; Kornej, Jelena; Kosiuk, Jedrzej; Rolf, Sascha; Sommer, Philipp; Richter, Sergio; Bollmann, Andreas; Hindricks, Gerhard; Arya, Arash

2015-07-01

Numerous electrocardiographic (ECG) criteria have been proposed to identify localization of outflow tract ventricular arrhythmias (OT-VAs); however, in some cases, it is difficult to accurately localize the origin of OT-VA using the surface ECG. The purpose of this study was to assess a simple criterion for localization of OT-VAs during electrophysiology study. We measured the interval from the onset of the earliest QRS complex of premature ventricular contractions (PVCs) to the distal right ventricular apical signal (the QRS-RVA interval) in 66 patients (31 men aged 53.3 ± 14.0 years; right ventricular outflow tract [RVOT] origin in 37) referred for ablation of symptomatic outflow tract PVCs. We prospectively validated this criterion in 39 patients (22 men aged 52 ± 15 years; RVOT origin in 19). Compared with patients with RVOT PVCs, the QRS-RVA interval was significantly longer in patients with left ventricular outflow tract (LVOT) PVCs (70 ± 14 vs 33.4±10 ms, P < .001). Receiver operating characteristic analysis showed that a QRS-RVA interval ≥49 ms had sensitivity, specificity, and positive and negative predictive values of 100%, 94.6%, 93.5%, and 100%, respectively, for prediction of an LVOT origin. The same analysis in the validation cohort showed sensitivity, specificity, and positive and negative predictive values of 94.7%, 95%, 95%, and 94.7%, respectively. When these data were combined, a QRS-RVA interval ≥49 ms had sensitivity, specificity, and positive and negative predictive values of 98%, 94.6%, 94.1%, and 98.1%, respectively, for prediction of an LVOT origin. A QRS-RVA interval ≥49 ms suggests an LVOT origin. The QRS-RVA interval is a simple and accurate criterion for differentiating the origin of outflow tract arrhythmia during electrophysiology study; however, the accuracy of this criterion in identifying OT-VA from the right coronary cusp is limited. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Spatiotemporal brain dynamics of emotional face processing modulations induced by the serotonin 1A/2A receptor agonist psilocybin.

PubMed

Bernasconi, Fosco; Schmidt, André; Pokorny, Thomas; Kometer, Michael; Seifritz, Erich; Vollenweider, Franz X

2014-12-01

Emotional face processing is critically modulated by the serotonergic system. For instance, emotional face processing is impaired by acute psilocybin administration, a serotonin (5-HT) 1A and 2A receptor agonist. However, the spatiotemporal brain mechanisms underlying these modulations are poorly understood. Here, we investigated the spatiotemporal brain dynamics underlying psilocybin-induced modulations during emotional face processing. Electrical neuroimaging analyses were applied to visual evoked potentials in response to emotional faces, following psilocybin and placebo administration. Our results indicate a first time period of strength (i.e., Global Field Power) modulation over the 168-189 ms poststimulus interval, induced by psilocybin. A second time period of strength modulation was identified over the 211-242 ms poststimulus interval. Source estimations over these 2 time periods further revealed decreased activity in response to both neutral and fearful faces within limbic areas, including amygdala and parahippocampal gyrus, and the right temporal cortex over the 168-189 ms interval, and reduced activity in response to happy faces within limbic and right temporo-occipital brain areas over the 211-242 ms interval. Our results indicate a selective and temporally dissociable effect of psilocybin on the neuronal correlates of emotional face processing, consistent with a modulation of the top-down control. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Temporal structure in the light response of relay cells in the dorsal lateral geniculate nucleus of the cat.

PubMed Central

Funke, K; Wörgötter, F

1995-01-01

1. The spike interval pattern during the light responses of 155 on- and 81 off-centre cells of the dorsal lateral geniculate nucleus (LGN) was studied in anaesthetized and paralysed cats by the use of a novel analysis. Temporally localized interval distributions were computed from a 100 ms time window, which was shifted along the time axis in 10 ms steps, resulting in a 90% overlap between two adjacent windows. For each step the interval distribution was computed inside the time window with 1 ms resolution, and plotted as a greyscale-coded pixel line orthogonal to the time axis. For visual stimulation, light or dark spots of different size and contrast were presented with different background illumination levels. 2. Two characteristic interval patterns were observed during the sustained response component of the cells. Mainly on-cells (77%) responded with multimodal interval distributions, resulting in elongated 'bands' in the 2-dimensional time window plots. In similar situations, the interval distributions for most (71%) off-cells were rather wide and featureless. In those cases where interval bands (i.e. multimodal interval distributions) were observed for off-cells (14%), they were always much wider than for the on-cells. This difference between the on- and off-cell population was independent of the background illumination and the contrast of the stimulus. Y on-cells also tended to produce wider interval bands than X on-cells. 3. For most stimulation situations the first interval band was centred around 6-9 ms, which has been called the fundamental interval; higher order bands are multiples thereof. The fundamental interval shifted towards larger sizes with decreasing stimulus contrast. Increasing stimulus size, on the other hand, resulted in a redistribution of the intervals into higher order bands, while at the same time the location of the fundamental interval remained largely unaffected. This was interpreted as an effect of the increasing surround inhibition at the geniculate level, by which individual retinal EPSPs were cancelled. A changing level of adaptation can result in a mixed shift/redistribution effect because of the changing stimulus contrast and changing level of tonic inhibition. 4. The occurrence of interval bands is not directly related to the shape of the autocorrelation function, which can be flat, weakly oscillatory or strongly oscillatory, regardless of the interval band pattern. 5. A simple computer model was devised to account for the observed cell behaviour. The model is highly robust against parameter variations.(ABSTRACT TRUNCATED AT 400 WORDS) Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 15 PMID:7562612

Temporal prediction modulates the evaluative processing of "good" action feedback: An electrophysiological study.

PubMed

Kimura, Kenta; Kimura, Motohiro; Iwaki, Sunao

2016-10-01

The present study aimed to investigate whether or not the evaluative processing of action feedback can be modulated by temporal prediction. For this purpose, we examined the effects of the predictability of the timing of action feedback on an ERP effect that indexed the evaluative processing of action feedback, that is, an ERP effect that has been interpreted as a feedback-related negativity (FRN) elicited by "bad" action feedback or a reward positivity (RewP) elicited by "good" action feedback. In two types of experimental blocks, the participants performed a gambling task in which they chose one of two cards and received an action feedback that indicated monetary gain or loss. In fixed blocks, the time interval between the participant's choice and the onset of the action feedback was fixed at 0, 500, or 1,000 ms in separate blocks; thus, the timing of action feedback was predictable. In mixed blocks, the time interval was randomly chosen from the same three intervals with equal probability; thus, the timing was less predictable. The results showed that the FRN/RewP was smaller in mixed than fixed blocks for the 0-ms interval trial, whereas there was no difference between the two block types for the 500-ms and 1,000-ms interval trials. Interestingly, the smaller FRN/RewP was due to the modulation of gain ERPs rather than loss ERPs. These results suggest that temporal prediction can modulate the evaluative processing of action feedback, and particularly good feedback, such as that which indicates monetary gain. © 2016 Society for Psychophysiological Research.

Effects of auditory stimulation with music of different intensities on heart period

PubMed Central

do Amaral, Joice A.T.; Guida, Heraldo L.; de Abreu, Luiz Carlos; Barnabé, Viviani; Vanderlei, Franciele M.; Valenti, Vitor E.

2015-01-01

Various studies have indicated that music therapy with relaxant music improves cardiac function of patients treated with cardiotoxic medication and heavy-metal music acutely reduces heart rate variability (HRV). There is also evidence that white noise auditory stimulation above 50 dB causes cardiac autonomic responses. In this study, we aimed to evaluate the acute effects of musical auditory stimulation with different intensities on cardiac autonomic regulation. This study was performed on 24 healthy women between 18 and 25 years of age. We analyzed HRV in the time [standard deviation of normal-to-normal RR intervals (SDNN), percentage of adjacent RR intervals with a difference of duration >50 ms (pNN50), and root-mean square of differences between adjacent normal RR intervals in a time interval (RMSSD)] and frequency [low frequency (LF), high frequency (HF), and LF/HF ratio] domains. HRV was recorded at rest for 10 minutes. Subsequently, the volunteers were exposed to baroque or heavy-metal music for 5 minutes through an earphone. The volunteers were exposed to three equivalent sound levels (60–70, 70–80, and 80–90 dB). After the first baroque or heavy-metal music, they remained at rest for 5 minutes and then they were exposed to the other music. The sequence of songs was randomized for each individual. Heavy-metal musical auditory stimulation at 80–90 dB reduced the SDNN index compared with control (44.39 ± 14.40 ms vs. 34.88 ± 8.69 ms), and stimulation at 60–70 dB decreased the LF (ms2) index compared with control (668.83 ± 648.74 ms2 vs. 392.5 ± 179.94 ms2). Baroque music at 60–70 dB reduced the LF (ms2) index (587.75 ± 318.44 ms2 vs. 376.21 ± 178.85 ms2). In conclusion, heavy-metal and baroque musical auditory stimulation at lower intensities acutely reduced global modulation of the heart and only heavy-metal music reduced HRV at higher intensities. PMID:26870675

Cognitive aspects of haptic form recognition by blind and sighted subjects.

PubMed

Bailes, S M; Lambert, R M

1986-11-01

Studies using haptic form recognition tasks have generally concluded that the adventitiously blind perform better than the congenitally blind, implicating the importance of early visual experience in improved spatial functioning. The hypothesis was tested that the adventitiously blind have retained some ability to encode successive information obtained haptically in terms of a global visual representation, while the congenitally blind use a coding system based on successive inputs. Eighteen blind (adventitiously and congenitally) and 18 sighted (blindfolded and performing with vision) subjects were tested on their recognition of raised line patterns when the standard was presented in segments: in immediate succession, or with unfilled intersegmental delays of 5, 10, or 15 seconds. The results did not support the above hypothesis. Three main findings were obtained: normally sighted subjects were both faster and more accurate than the other groups; all groups improved in accuracy of recognition as a function of length of interstimulus interval; sighted subjects tended to report using strategies with a strong verbal component while the blind tended to rely on imagery coding. These results are explained in terms of information-processing theory consistent with dual encoding systems in working memory.

Modulations of the processing of line discontinuities under selective attention conditions?

PubMed

Giersch, Anne; Fahle, Manfred

2002-01-01

We examined whether the processing of discontinuities involved in figure-ground segmentation, like line ends, can be modulated under selective attention conditions. Subjects decided whether a gap in collinear or parallel lines was located to the right or left. Two stimuli were displayed in immediate succession. When the gaps were on the same side, reaction times (RTs) for the second stimulus increased when collinear lines followed parallel lines, or the reverse, but only when the two stimuli shared the same orientation and location. The effect did not depend on the global form of the stimuli or on the relative orientation of the gaps. A frame drawn around collinear elements affected the results, suggesting a crucial role of the "amodal" orthogonal lines produced when line ends are aligned. Including several gaps in the first stimulus also eliminated RT variations. By contrast, RT variations remained stable across several experimental blocks and were significant for interstimulus intervals from 50 to 600 msec between the two stimuli. These results are interpreted in terms of a modulation of the processing of line ends or the production of amodal lines, arising when attention is selectively drawn to a gap.

Reactive and anticipatory looking in 6-month-old infants during a visual expectation paradigm.

PubMed

Quan, Jeffry; Bureau, Jean-François; Abdul Malik, Adam B; Wong, Johnny; Rifkin-Graboi, Anne

2017-10-01

This article presents data from 278 six-month-old infants who completed a visual expectation paradigm in which audiovisual stimuli were first presented randomly (random phase), and then in a spatial pattern (pattern phase). Infants' eye gaze behaviour was tracked with a 60 Hz Tobii eye-tracker in order to measure two types of looking behaviour: reactive looking (i.e., latency to shift eye gaze in reaction to the appearance of stimuli) and anticipatory looking (i.e., percentage of time spent looking at the location where the next stimulus is about to appear during the inter-stimulus interval). Data pertaining to missing data and task order effects are presented. Further analyses show that infants' reactive looking was faster in the pattern phase, compared to the random phase, and their anticipatory looking increased from random to pattern phases. Within the pattern phase, infants' reactive looking showed a quadratic trend, with reactive looking time latencies peaking in the middle portion of the phase. Similarly, within the pattern phase, infants' anticipatory looking also showed a quadratic trend, with anticipatory looking peaking during the middle portion of the phase.

Saliency predicts change detection in pictures of natural scenes.

PubMed

Wright, Michael J

2005-01-01

It has been proposed that the visual system encodes the salience of objects in the visual field in an explicit two-dimensional map that guides visual selective attention. Experiments were conducted to determine whether salience measurements applied to regions of pictures of outdoor scenes could predict the detection of changes in those regions. To obtain a quantitative measure of change detection, observers located changes in pairs of colour pictures presented across an interstimulus interval (ISI). Salience measurements were then obtained from different observers for image change regions using three independent methods, and all were positively correlated with change detection. Factor analysis extracted a single saliency factor that accounted for 62% of the variance contained in the four measures. Finally, estimates of the magnitude of the image change in each picture pair were obtained, using nine separate visual filters representing low-level vision features (luminance, colour, spatial frequency, orientation, edge density). None of the feature outputs was significantly associated with change detection or saliency. On the other hand it was shown that high-level (structural) properties of the changed region were related to saliency and to change detection: objects were more salient than shadows and more detectable when changed.

Temporal orienting precedes intersensory attention and has opposing effects on early evoked brain activity.

PubMed

Keil, Julian; Pomper, Ulrich; Feuerbach, Nele; Senkowski, Daniel

2017-03-01

Intersensory attention (IA) describes the process of directing attention to a specific modality. Temporal orienting (TO) characterizes directing attention to a specific moment in time. Previously, studies indicated that these two processes could have opposite effects on early evoked brain activity. The exact time-course and processing stages of both processes are still unknown. In this human electroencephalography study, we investigated the effects of IA and TO on visuo-tactile stimulus processing within one paradigm. IA was manipulated by presenting auditory cues to indicate whether participants should detect visual or tactile targets in visuo-tactile stimuli. TO was manipulated by presenting stimuli block-wise at fixed or variable inter-stimulus intervals. We observed that TO affects evoked activity to visuo-tactile stimuli prior to IA. Moreover, we found that TO reduces the amplitude of early evoked brain activity, whereas IA enhances it. Using beamformer source-localization, we observed that IA increases neural responses in sensory areas of the attended modality whereas TO reduces brain activity in widespread cortical areas. Based on these findings we derive an updated working model for the effects of temporal and intersensory attention on early evoked brain activity. Copyright © 2017 Elsevier Inc. All rights reserved.

Impairment of willed actions and use of advance information for movement preparation in schizophrenia

PubMed Central

Fuller, R.; Jahanshahi, M.

1999-01-01

OBJECTIVES—To assess willed actions in patients with schizophrenia using reaction time (RT) tasks that differ in the degree to which they involve volitionally controlled versus stimulus driven responses.
METHODS—Ten patients diagnosed with schizophrenia and 13 normal controls of comparable age were tested. Subjects performed a visual simple RT (SRT), an uncued four choice reaction time (CRT), and a fully cued four choice RT task. A stimulus 1(S1)−stimulus 2(S2) paradigm was used. The warning signal/precue (S1) preceded the imperative stimulus (S2) by either 0 (no warning signal or precue) 200, 800, 1600, or 3200ms.
RESULTS—The patients with schizophrenia had significantly slower RTs and movement times than normal subjects across all RT tasks. The unwarned SRT trials were significantly faster than the uncued CRT trials for both groups. For both groups, fully cued CRTs were significantly faster than the uncued CRTs. However, the S1−S2 interval had a differential effect on CRTs in the two groups. For the normal subjects fully cued CRTs and SRTs were equivalent when S1-S2 intervals were 800 ms or longer. A similar pattern of effects was not seen in the patients with schizophrenia, for whom the fully cued CRT were unexpectedly equivalent to SRT for the 200 ms interval and expectedly for the 1600 ms S1-S2 interval, but not the 3200 or 800 ms intervals.
CONCLUSIONS—Patients with schizophrenia were able to use advance information inherent in SRT or provided by the precue in fully cued CRT to speed up RT relative to uncued CRT. However, in the latter task, in which the volitional demands of preprogramming are higher since a different response has to be prepared on each trial, patients showed some unusual and inconsistent interval effects suggesting instability of attentional set. It is possible that future studies using RT tasks with higher volitional demands in patients with predominance of negative signs may disclose greater deficits in willed action in schizophrenia.

 PMID:10201424

Patients with left bundle branch block and left axis deviation show a specific left ventricular asynchrony pattern: Implications for left ventricular lead placement during CRT implantation.

PubMed

Sciarra, Luigi; Golia, Paolo; Palamà, Zefferino; Scarà, Antonio; De Ruvo, Ermenegildo; Borrelli, Alessio; Martino, Anna Maria; Minati, Monia; Fagagnini, Alessandro; Tota, Claudia; De Luca, Lucia; Grieco, Domenico; Delise, Pietro; Calò, Leonardo

Left bundle branch block (LBBB) and left axis deviation (LAD) patients may have poor response to resynchronization therapy (CRT). We sought to assess if LBBB and LAD patients show a specific pattern of mechanical asynchrony. CRT candidates with non-ischemic cardiomyopathy and LBBB were categorized as having normal QRS axis (within -30° and +90°) or LAD (within -30° and -90°). Patients underwent tissue Doppler imaging (TDI) to measure time interval between onset of QRS complex and peak systolic velocity in ejection period (Q-peak) at basal segments of septal, inferior, lateral and anterior walls, as expression of local timing of mechanical activation. Thirty patients (mean age 70.6years; 19 males) were included. Mean left ventricular ejection fraction was 0.28±0.06. Mean QRS duration was 172.5±13.9ms. Fifteen patients showed LBBB with LAD (QRS duration 173±14; EF 0.27±0.06). The other 15 patients had LBBB with a normal QRS axis (QRS duration 172±14; EF 0.29±0.05). Among patients with LAD, Q-peak interval was significantly longer at the anterior wall in comparison to each other walls (septal 201±46ms, inferior 242±58ms, lateral 267±45ms, anterior 302±50ms; p<0.0001). Conversely, in patients without LAD Q-peak interval was longer at lateral wall, when compared to each other (septal 228±65ms, inferior 250±64ms, lateral 328±98ms, anterior 291±86ms; p<0.0001). Patients with heart failure, presenting LBBB and LAD, show a specific pattern of ventricular asynchrony, with latest activation at anterior wall. This finding could affect target vessel selection during CRT procedures in these patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Right Ventricular Pacing for Assessment of Cavo-Tricuspid Isthmus Block.

PubMed

Venkataraman, Ganesh; Wish, Marc; Friehling, Ted; Strickberger, S Adam

2016-01-01

Background: Cavo-tricuspid isthmus (CTI) dependent atrial flutter is typically treated with cardiac ablation. Standard techniques to assess CTI block after ablation can be technically challenging. Right ventricular (RV) pacing may allow for another technique to assess CTI block after ablation. Objective: The purpose of this study was to evaluate RV pacing as a method to assess CTI block after ablation of CTI dependent atrial flutter, and define endpoints of ablation using this technique. Methods: 28 patients undergoing ablation of CTI dependent atrial flutter with intact ventriculoatrial (VA) conduction were prospectively enrolled in this study and underwent the RV pacing protocol, as well as standard coronary sinus (CS) pacing techniques to assess CTI block. Results: The mean trans-isthmus conduction interval during CS pacing (TICI CS ) at 600 and 400ms after CTI ablation was 168 +/- 9ms and 175 +/- 18ms, respectively. The mean trans-isthmus conduction interval during RV pacing (TICI RV ) at 600ms and 400ms after CTI ablation was 109 +/- 5ms and 111 +/- 5ms, respectively. A TICI RV >100ms was associated with a successful outcome after CTI ablation. Conclusions: RV pacing may add incremental value in the assessment of CTI block in patients undergoing ablation of CTI dependent atrial flutter.

A modeling and simulation approach to characterize methadone QT prolongation using pooled data from five clinical trials in MMT patients.

PubMed

Florian, J; Garnett, C E; Nallani, S C; Rappaport, B A; Throckmorton, D C

2012-04-01

Pharmacokinetic (PK)-pharmacodynamic modeling and simulation were used to establish a link between methadone dose, concentrations, and Fridericia rate-corrected QT (QTcF) interval prolongation, and to identify a dose that was associated with increased risk of developing torsade de pointes. A linear relationship between concentration and QTcF described the data from five clinical trials in patients on methadone maintenance treatment (MMT). A previously published population PK model adequately described the concentration-time data, and this model was used for simulation. QTcF was increased by a mean (90% confidence interval (CI)) of 17 (12, 22) ms per 1,000 ng/ml of methadone. Based on this model, doses >120 mg/day would increase the QTcF interval by >20 ms. The model predicts that 1-3% of patients would have ΔQTcF >60 ms, and 0.3-2.0% of patients would have QTcF >500 ms at doses of 160-200 mg/day. Our predictions are consistent with available observational data and support the need for electrocardiogram (ECG) monitoring and arrhythmia risk factor assessment in patients receiving methadone doses >120 mg/day.

Reassessment of the Access Testosterone chemiluminescence assay and comparison with LC-MS method.

PubMed

Dittadi, Ruggero; Matteucci, Mara; Meneghetti, Elisa; Ndreu, Rudina

2018-03-01

To reassess the imprecision and Limit of Quantitation, to evaluate the cross-reaction with dehydroepiandrosterone-sulfate (DHEAS), the accuracy toward liquid chromatography-mass spectrometry (LC-MS) and the reference interval of the Access Testosterone method, performed by DxI immunoassay platform (Beckman Coulter). Imprecision was evaluated testing six pool samples assayed in 20 different run using two reagents lots. The cross-reaction with DHEAS was studied both by a displacement curve and by spiking DHEAS standard in two serum samples with known amount of testosterone. The comparison with LC-MS was evaluated by Passing-Bablock analysis in 21 routine serum samples and 19 control samples from an External Quality Assurance (EQA) scheme. The reference interval was verified by an indirect estimation on 2445 male and 2838 female outpatients. The imprecision study showed a coefficient of variation (CV) between 2.7% and 34.7% for serum pools from 16.3 and 0.27 nmol/L. The value of Limit of Quantitation at 20% CV was 0.53 nmol/L. The DHEAS showed a cross-reaction of 0.0074%. A comparison with LC-MS showed a trend toward a slight underestimation of immunoassay vs LC-MS (Passing-Bablock equations: DxI=-0.24+0.906 LCMS in serum samples and DxI=-0.299+0.981 LCMS in EQA samples). The verification of reference interval showed a 2.5th-97.5th percentile distribution of 6.6-24.3 nmol/L for male over 14 years and <0.5-2.78 nmol/L for female subjects, in accord with the reference intervals reported by the manufacturer. The Access Testosterone method could be considered an adequately reliable tool for the testosterone measurement. © 2017 Wiley Periodicals, Inc.

Electrocardiographic and blood pressure effects of energy drinks and Panax ginseng in healthy volunteers: A randomized clinical trial.

PubMed

Shah, Sachin A; Occiano, Andrew; Nguyen, Tinh An; Chan, Amanda; Sky, Joseph C; Bhattacharyya, Mouchumi; O'Dell, Kate M; Shek, Allen; Nguyen, Nancy N

2016-09-01

Energy drink usage has been linked to emergency room visits and deaths. The objective of the study is to assess the electrocardiographic and blood pressure effects of energy drinks, Panax ginseng and placebo in healthy individuals. This was a randomized, double blinded, placebo controlled, crossover study. Young healthy volunteers with no comorbid conditions consumed 32oz of an energy drink, control drink with 800mg of Panax ginseng or matching placebo-control drink over 45min. Primary endpoints were QTc interval and systolic blood pressure. Secondary endpoints included QT interval, PR interval, QRS duration, heart rate, and diastolic blood pressure. All endpoints were assessed at baseline, 1, 2, 3.5, and 5.5h. A significant increase in QTc interval 2h post energy drink consumption was evident when compared to placebo (3.37±10.7ms and -3.19±11.8ms respectively; p=0.030). Similarly, systolic blood pressure 2h post energy drink consumption increased when compared to placebo (2.00±6.37mmHg and -2.67±5.83mmHg respectively; p=0.014). The PR interval significantly reduced over a 2h period post energy drink use in a clinically non-meaningful manner. Heart rate at 2h was not significantly higher in the energy drink group when compared to others. The QT interval, QRS interval and diastolic blood pressure were not impacted at any time point. Certain energy drinks consumed at a high volume significantly increase the QTc interval and systolic blood pressure by over 6ms and 4mmHg respectively. Panax ginseng does not have a significant impact on ECG or blood pressure parameters. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Delta of the local ventriculo-atrial intervals at the septal location to differentiate tachycardia using septal accessory pathways from atypical atrioventricular nodal re-entry.

PubMed

Calvo, David; Pérez, Diego; Rubín, José; García, Daniel; Ávila, Pablo; Javier García-Fernández, F; Pachón, Marta; Bravo, Loreto; Hernández, Jesús; Miracle, Ángel L; Valverde, Irene; Gozalez-Vasserot, Mar; Árias, Miguel Ángel; Jimenez-Candíl, Javier; Morís, César

2018-01-02

Tachycardia mediated by septal accessory pathways (AP) and atypical atrioventricular nodal re-entry (AVNRT) require careful electrophysiologic evaluation for differential diagnosis. We aim to describe the differential behaviour of local ventriculo-atrial (VA) intervals which predicts the tachycardia mechanism. The local VA intervals at the para-Hisian septum were measured under three different situations: (i) tachycardia; (ii) sustained entrainment from the right ventricular apex (RVA); and (iii) continuous pacing from the RVA during sinus rhythm. Differences were computed as follows: Δ-VAentr = VA during entrainment - VA during tachycardia; and Δ-VApac = VA while pacing during sinus rhythm - VA during tachycardia. In contrast to AVNRT, we hypothesized that an invariable retrograde conduction through the septal AP will keep the result of the subtractions close to 0 ms in cases of ortodromic atrioventricular re-entrant tachycardia (AVRT). We analysed 55 atypical AVNRT (45% posterior type) and 82 AVRT (10 anteroseptal, 18 para-Hisian, 12 mid-septal, and 42 posteroseptal). Δ-VAentr was longer for AVNRT (98.5 ± 40.3 ms) compared with septal AP (-5.7 ± 19.3 ms; P < 0.001). A value of 50 ms showed 98.7% sensitivity and 92% specificity (AUC 0.99; 95% CI 0.98-1). According to physiological criteria, a negative Δ-VAentr remains unobserved in the case of AVNRT (positive predictive value 100% for septal AP). Δ-VApac was also longer for AVNRT (66.5 ± 14.6 ms) compared with septal AP (-9.7 ± 3.3 ms; P < 0.001). A value of 50 ms showed 100% sensitivity and 74% specificity (AUC 0.86; 95% CI 0.76-0.93). Delta of the local VA intervals enables distinction between atypical AVNRT and AVRT mediated by septal AP. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.

Emotion processing in the visual brain: a MEG analysis.

PubMed

Peyk, Peter; Schupp, Harald T; Elbert, Thomas; Junghöfer, Markus

2008-06-01

Recent functional magnetic resonance imaging (fMRI) and event-related brain potential (ERP) studies provide empirical support for the notion that emotional cues guide selective attention. Extending this line of research, whole head magneto-encephalogram (MEG) was measured while participants viewed in separate experimental blocks a continuous stream of either pleasant and neutral or unpleasant and neutral pictures, presented for 330 ms each. Event-related magnetic fields (ERF) were analyzed after intersubject sensor coregistration, complemented by minimum norm estimates (MNE) to explore neural generator sources. Both streams of analysis converge by demonstrating the selective emotion processing in an early (120-170 ms) and a late time interval (220-310 ms). ERF analysis revealed that the polarity of the emotion difference fields was reversed across early and late intervals suggesting distinct patterns of activation in the visual processing stream. Source analysis revealed the amplified processing of emotional pictures in visual processing areas with more pronounced occipito-parieto-temporal activation in the early time interval, and a stronger engagement of more anterior, temporal, regions in the later interval. Confirming previous ERP studies showing facilitated emotion processing, the present data suggest that MEG provides a complementary look at the spread of activation in the visual processing stream.

Effect of Moderate Versus High-Intensity Interval Exercise Training on Heart Rate Variability Parameters in Inactive Latin-American Adults: A Randomised Clinical Trial.

PubMed

Ramírez-Vélez, Robinson; Tordecilla-Sanders, Alejandra; Téllez-T, Luis Andrés; Camelo-Prieto, Diana; Hernández-Quiñonez, Paula Andrea; Correa-Bautista, Jorge Enrique; Garcia-Hermoso, Antonio; Ramírez-Campillo, Rodrigo; Izquierdo, Mikel

2017-02-01

We investigated the effect of moderate versus high-intensity interval exercise training on the HRV indices in physically inactive adults. Twenty inactive adults were randomly allocated to receive either moderate intensity training (MCT group) or high-intensity interval training (HIT group). The MCT group performed aerobic training at an intensity of 55-75%, which consisted of walking on a treadmill at 60-80% of the maximum heart rate (HRmax) until the expenditure of 300 kcal. The HIT group ran on a treadmill for 4 minutes at 85-95% peak HRmax and had a recovery of 4 minutes at 65% peak HRmax until the expenditure of 300 kcal. Supine resting HRV indices (time domain: SDNN, standard deviation of normal-to-normal intervals; rMSSD, Root mean square successive difference of RR intervals and frequency domain: HFLn, high-frequency spectral power; LF, low-frequency spectral power and HF/LF ratio) were measured at baseline and 12 weeks thereafter. The SDNN changes were 3.4 (8.9) ms in the MCT group and 29.1 (7.6) ms in the HIT group (difference between groups 32.6 [95% CI, 24.9 to 40.4 (P = 0.01)]. The LF/HFLn ratio change 0.19 (0.03) ms in the MCT group and 0.13 (0.01) ms in the HIT group (P between groups = 0.016). No significant group differences were observed for the rMSSD, HF and LF parameters. In inactive adults, this study showed that a 12-week HIT training program could increase short-term HRV, mostly in vagally mediated indices such as SDNN and HF/LFLn ratio power.

Characterization of Myocardial Repolarization Reserve in Adolescent Females With Anorexia Nervosa.

PubMed

Padfield, Gareth J; Escudero, Carolina A; DeSouza, Astrid M; Steinberg, Christian; Gibbs, Karen; Puyat, Joseph H; Lam, Pei Yoong; Sanatani, Shubhayan; Sherwin, Elizabeth; Potts, James E; Sandor, George; Krahn, Andrew D

2016-02-09

Patients with anorexia nervosa exhibit abnormal myocardial repolarization and are susceptible to sudden cardiac death. Exercise testing is useful in unmasking QT prolongation in disorders associated with abnormal repolarization. We characterized QT adaptation during exercise in anorexia. Sixty-one adolescent female patients with anorexia nervosa and 45 age- and sex-matched healthy volunteers performed symptom-limited cycle ergometry during 12-lead ECG monitoring. Changes in the QT interval during exercise were measured, and QT/RR-interval slopes were determined by using mixed-effects regression modeling. Patients had significantly lower body mass index than controls; however, resting heart rates and QT/QTc intervals were similar at baseline. Patients had shorter exercise times (13.7±4.5 versus 20.6±4.5 minutes; P<0.001) and lower peak heart rates (159±20 versus 184±9 beats/min; P<0.001). The mean QTc intervals were longer at peak exercise in patients (442±29 versus 422±19 ms; P<0.001). During submaximal exertion at comparable heart rates (114±6 versus 115±11 beats/min; P=0.54), the QTc interval had prolonged significantly more in patients than controls (37±28 versus 24±25 ms; P<0.016). The RR/QT slope, best described by a curvilinear relationship, was more gradual in patients than in controls (13.4; 95% confidence interval, 12.8-13.9 versus 15.8; 95% confidence interval, 15.3-16.4 ms QT change per 10% change in RR interval; P<0.001) and steepest in patients within the highest body mass index tertile versus the lowest (13.9; 95% confidence interval, 12.9-14.9 versus 12.3; 95% confidence interval, 11.3-13.3; P=0.026). Despite the absence of manifest QT prolongation, adolescent anorexic females have impaired repolarization reserve in comparison with healthy controls. Further study may identify impaired QT dynamics as a risk factor for arrhythmias in anorexia nervosa. © 2016 American Heart Association, Inc.

Vibrotactile masking experiments reveal accelerated somatosensory processing in congenitally blind braille readers.

PubMed

Bhattacharjee, Arindam; Ye, Amanda J; Lisak, Joy A; Vargas, Maria G; Goldreich, Daniel

2010-10-27

Braille reading is a demanding task that requires the identification of rapidly varying tactile patterns. During proficient reading, neighboring characters impact the fingertip at ∼100 ms intervals, and adjacent raised dots within a character at 50 ms intervals. Because the brain requires time to interpret afferent sensorineural activity, among other reasons, tactile stimuli separated by such short temporal intervals pose a challenge to perception. How, then, do proficient Braille readers successfully interpret inputs arising from their fingertips at such rapid rates? We hypothesized that somatosensory perceptual consolidation occurs more rapidly in proficient Braille readers. If so, Braille readers should outperform sighted participants on masking tasks, which demand rapid perceptual processing, but would not necessarily outperform the sighted on tests of simple vibrotactile sensitivity. To investigate, we conducted two-interval forced-choice vibrotactile detection, amplitude discrimination, and masking tasks on the index fingertips of 89 sighted and 57 profoundly blind humans. Sighted and blind participants had similar unmasked detection (25 ms target tap) and amplitude discrimination (compared with 100 μm reference tap) thresholds, but congenitally blind Braille readers, the fastest readers among the blind participants, exhibited significantly less masking than the sighted (masker, 50 Hz, 50 μm; target-masker delays, ±50 and ±100 ms). Indeed, Braille reading speed correlated significantly and specifically with masking task performance, and in particular with the backward masking decay time constant. We conclude that vibrotactile sensitivity is unchanged but that perceptual processing is accelerated in congenitally blind Braille readers.

Vibrotactile masking experiments reveal accelerated somatosensory processing in congenitally blind Braille readers

PubMed Central

Bhattacharjee, Arindam; Ye, Amanda J.; Lisak, Joy A.; Vargas, Maria G.; Goldreich, Daniel

2010-01-01

Braille reading is a demanding task that requires the identification of rapidly varying tactile patterns. During proficient reading, neighboring characters impact the fingertip at about 100-ms intervals, and adjacent raised dots within a character at 50-ms intervals. Because the brain requires time to interpret afferent sensorineural activity, among other reasons, tactile stimuli separated by such short temporal intervals pose a challenge to perception. How, then, do proficient Braille readers successfully interpret inputs arising from their fingertips at such rapid rates? We hypothesized that somatosensory perceptual consolidation occurs more rapidly in proficient Braille readers. If so, Braille readers should outperform sighted participants on masking tasks, which demand rapid perceptual processing, but would not necessarily outperform the sighted on tests of simple vibrotactile sensitivity. To investigate, we conducted two-interval forced-choice vibrotactile detection, amplitude discrimination, and masking tasks on the index fingertips of 89 sighted and 57 profoundly blind humans. Sighted and blind participants had similar unmasked detection (25-ms target tap) and amplitude discrimination (compared to 100-micron reference tap) thresholds, but congenitally blind Braille readers, the fastest readers among the blind participants, exhibited significantly less masking than the sighted (masker: 50-Hz, 50-micron; target-masker delays ±50 and ±100 ms). Indeed, Braille reading speed correlated significantly and specifically with masking task performance, and in particular with the backward masking decay time constant. We conclude that vibrotactile sensitivity is unchanged, but that perceptual processing is accelerated in congenitally blind Braille readers. PMID:20980584

Dynamical analysis of the avian-human influenza epidemic model using the semi-analytical method

NASA Astrophysics Data System (ADS)

Jabbari, Azizeh; Kheiri, Hossein; Bekir, Ahmet

2015-03-01

In this work, we present a dynamic behavior of the avian-human influenza epidemic model by using efficient computational algorithm, namely the multistage differential transform method(MsDTM). The MsDTM is used here as an algorithm for approximating the solutions of the avian-human influenza epidemic model in a sequence of time intervals. In order to show the efficiency of the method, the obtained numerical results are compared with the fourth-order Runge-Kutta method (RK4M) and differential transform method(DTM) solutions. It is shown that the MsDTM has the advantage of giving an analytical form of the solution within each time interval which is not possible in purely numerical techniques like RK4M.

The combined effects of forward masking by noise and high click rate on monaural and binaural human auditory nerve and brainstem potentials.

PubMed

Pratt, Hillel; Polyakov, Andrey; Bleich, Naomi; Mittelman, Naomi

2004-07-01

To study effects of forward masking and rapid stimulation on human monaurally- and binaurally-evoked brainstem potentials and suggest their relation to synaptic fatigue and recovery and to neuronal action potential refractoriness. Auditory brainstem evoked potentials (ABEPs) were recorded from 12 normally- and symmetrically hearing adults, in response to each click (50 dB nHL, condensation and rarefaction) in a train of nine, with an inter-click interval of 11 ms, that followed a white noise burst of 100 ms duration (50 dB nHL). Sequences of white noise and click train were repeated at a rate of 2.89 s(-1). The interval between noise and first click in the train was 2, 11, 22, 44, 66 or 88 ms in different runs. ABEPs were averaged (8000 repetitions) using a dwell time of 25 micros/address/channel. The binaural interaction components (BICs) of ABEPs were derived and the single, centrally located equivalent dipoles of ABEP waves I and V and of the BIC major wave were estimated. The latencies of dipoles I and V of ABEP, their inter-dipole interval and the dipole magnitude of component V were significantly affected by the interval between noise and clicks and by the serial position of the click in the train. The latency and dipole magnitude of the major BIC component were significantly affected by the interval between noise and clicks. Interval from noise and the click's serial position in the train interacted to affect dipole V latency, dipole V magnitude, BIC latencies and the V-I inter-dipole latency difference. Most of the effects were fully apparent by the first few clicks in the train, and the trend (increase or decrease) was affected by the interval between noise and clicks. The changes in latency and magnitude of ABEP and BIC components with advancing position in the click train and the interactions of click position in the train with the intervals from noise indicate an interaction of fatigue and recovery, compatible with synaptic depletion and replenishing, respectively. With the 2 ms interval between noise and the first click in the train, neuronal action potential refractoriness may also be involved.

Cardiovascular Autonomic Dysfunction in Patients with Morbid Obesity

PubMed Central

de Sant Anna Junior, Maurício; Carneiro, João Regis Ivar; Carvalhal, Renata Ferreira; Torres, Diego de Faria Magalhães; da Cruz, Gustavo Gavina; Quaresma, José Carlos do Vale; Lugon, Jocemir Ronaldo; Guimarães, Fernando Silva

2015-01-01

Background Morbid obesity is directly related to deterioration in cardiorespiratory capacity, including changes in cardiovascular autonomic modulation. Objective This study aimed to assess the cardiovascular autonomic function in morbidly obese individuals. Methods Cross-sectional study, including two groups of participants: Group I, composed by 50 morbidly obese subjects, and Group II, composed by 30 nonobese subjects. The autonomic function was assessed by heart rate variability in the time domain (standard deviation of all normal RR intervals [SDNN]; standard deviation of the normal R-R intervals [SDNN]; square root of the mean squared differences of successive R-R intervals [RMSSD]; and the percentage of interval differences of successive R-R intervals greater than 50 milliseconds [pNN50] than the adjacent interval), and in the frequency domain (high frequency [HF]; low frequency [LF]: integration of power spectral density function in high frequency and low frequency ranges respectively). Between-group comparisons were performed by the Student’s t-test, with a level of significance of 5%. Results Obese subjects had lower values of SDNN (40.0 ± 18.0 ms vs. 70.0 ± 27.8 ms; p = 0.0004), RMSSD (23.7 ± 13.0 ms vs. 40.3 ± 22.4 ms; p = 0.0030), pNN50 (14.8 ± 10.4 % vs. 25.9 ± 7.2%; p = 0.0061) and HF (30.0 ± 17.5 Hz vs. 51.7 ± 25.5 Hz; p = 0.0023) than controls. Mean LF/HF ratio was higher in Group I (5.0 ± 2.8 vs. 1.0 ± 0.9; p = 0.0189), indicating changes in the sympathovagal balance. No statistical difference in LF was observed between Group I and Group II (50.1 ± 30.2 Hz vs. 40.9 ± 23.9 Hz; p = 0.9013). Conclusion morbidly obese individuals have increased sympathetic activity and reduced parasympathetic activity, featuring cardiovascular autonomic dysfunction. PMID:26536979

Impact of transforming growth factor-beta1 on atrioventricular node conduction modification by injected autologous fibroblasts in the canine heart.

PubMed

Bunch, T Jared; Mahapatra, Srijoy; Bruce, G Keith; Johnson, Susan B; Miller, Dylan V; Horne, Benjamin D; Wang, Xiao-Li; Lee, Hon-Chi; Caplice, Noel M; Packer, Douglas L

2006-05-30

Atrioventricular (AV) nodal ablation for management of atrial fibrillation (AF) is irreversible and requires permanent pacemaker implantation. We hypothesized that as an alternative, implantation of autologous fibroblasts in the perinodal region would focally modify AV nodal conduction and that this modulation would be enhanced by pretreatment with transforming growth factor-beta1 (TGF-beta1), a stimulant of fibroblasts. Skin biopsies were taken from 12 mongrel dogs, and derived fibroblasts were dissociated and grown in culture for 2 weeks. Multiple injections (0.25 mL) were made through an 8F NOGA catheter along the fast/slow AV nodal pathways as guided by an electroanatomic mapping system. Seven dogs received fibroblasts alone (1x10(6) cells/mL), 7 dogs received TGF-beta1 (5 microg), 4 dogs received fibroblasts and TGF-beta1 (1x10(6) cells/mL+5 microg), and 4 dogs received saline only. AV node function was assessed at baseline and after 4 weeks. Saline (80 mL) with assigned therapy (0.25 mL per injection) was injected into the peri-AV nodal region in each dog. At baseline, the AH interval (66+/-3 ms) and the average RR interval (331+/-17 ms) in pacing-induced AF were similar in each cohort. The increase in AH interval in normal sinus rhythm was longer after fibroblast (23+/-4 versus 5+/-5 ms; P=0.05) and fibroblast plus TGF-beta1 (50+/-5 versus 5+/-5 ms; P<0.001) injections than with saline alone, with similar findings during high right atrium and distal coronary sinus pacing. The AH interval was not significantly increased after TGF-beta1 injections. The AH interval was significantly longer after fibroblast plus TGF-beta1 injections than with either therapy (TGF-beta1 or fibroblasts) alone. The RR interval during AF was increased in dogs that received fibroblasts alone (110+/-36 versus -41+/-34 ms) and to a greater extent with the addition of TGF-beta1 (294+/-108 versus -41+/-34 ms). No AV block was seen in any cohort at 4 weeks. Labeled fibroblasts that expressed vimentin were identified in all dogs that received cell injections at 4 weeks. AV nodal modification can be achieved with injected fibroblasts without the creation of AV block. The effect on AV node conduction is substantially enhanced by pretreatment of fibroblasts with TGF-beta1. These data have therapeutic potential for the management of rapid ventricular rate during AF without pacemaker implantation.

[Estimation of the atrioventricular time interval by pulse Doppler in the normal fetal heart].

PubMed

Hamela-Olkowska, Anita; Dangel, Joanna

2009-08-01

To assess normative values of the fetal atrioventricular (AV) time interval by pulse-wave Doppler methods on 5-chamber view. Fetal echocardiography exams were performed using Acuson Sequoia 512 in 140 singleton fetuses at 18 to 40 weeks of gestation with sinus rhythm and normal cardiac and extracardiac anatomy. Pulsed Doppler derived AV intervals were measured from left ventricular inflow/outflow view using transabdominal convex 3.5-6 MHz probe. The values of AV time interval ranged from 100 to 150 ms (mean 123 +/- 11.2). The AV interval was negatively correlated with the heart rhythm (p<0.001). Fetal heart rate decreased as gestation progressed (p<0.001). Thus, the AV intervals increased with the age of gestation (p=0.007). However, in the same subgroup of the fetal heart rate there was no relation between AV intervals and gestational age. Therefore, the AV intervals showed only the heart rate dependence. The 95th percentiles of AV intervals according to FHR ranged from 135 to 148 ms. 1. The AV interval duration was negatively correlated with the heart rhythm. 2. Measurement of AV time interval is easy to perform and has a good reproducibility. It may be used for the fetal heart block screening in anti-Ro and anti-La positive pregnancies. 3. Normative values established in the study may help obstetricians in assessing fetal abnormalities of the AV conduction.

Effects of practice on variability in an isochronous serial interval production task: asymptotical levels of tapping variability after training are similar to those of musicians.

PubMed

Madison, Guy; Karampela, Olympia; Ullén, Fredrik; Holm, Linus

2013-05-01

Timing permeates everyday activities such as walking, dancing and music, yet the effect of short-term practice in this ubiquitous activity is largely unknown. In two training experiments involving sessions spread across several days, we examined short-term practice effects on timing variability in a sequential interval production task. In Experiment 1, we varied the mode of response (e.g., drumstick and finger tapping) and the level of sensory feedback. In Experiment 2 we varied the interval in 18 levels ranging from 500 ms to 1624 ms. Both experiments showed a substantial decrease in variability within the first hour of practice, but little thereafter. This effect was similar across mode of response, amount of feedback, and interval duration, and was manifested as a reduction in both local variability (between neighboring intervals) and drift (fluctuation across multiple intervals). The results suggest mainly effects on motor implementation rather than on cognitive timing processes, and have methodological implications for timing studies that have not controlled for practice. Copyright © 2013 Elsevier B.V. All rights reserved.

Motor Synchronization in Patients With Schizophrenia: Preserved Time Representation With Abnormalities in Predictive Timing.

PubMed

Wilquin, Hélène; Delevoye-Turrell, Yvonne; Dione, Mariama; Giersch, Anne

2018-01-01

Objective: Basic temporal dysfunctions have been described in patients with schizophrenia, which may impact their ability to connect and synchronize with the outer world. The present study was conducted with the aim to distinguish between interval timing and synchronization difficulties and more generally the spatial-temporal organization disturbances for voluntary actions. A new sensorimotor synchronization task was developed to test these abilities. Method: Twenty-four chronic schizophrenia patients matched with 27 controls performed a spatial-tapping task in which finger taps were to be produced in synchrony with a regular metronome to six visual targets presented around a virtual circle on a tactile screen. Isochronous (time intervals of 500 ms) and non-isochronous auditory sequences (alternated time intervals of 300/600 ms) were presented. The capacity to produce time intervals accurately versus the ability to synchronize own actions (tap) with external events (tone) were measured. Results: Patients with schizophrenia were able to produce the tapping patterns of both isochronous and non-isochronous auditory sequences as accurately as controls producing inter-response intervals close to the expected interval of 500 and 900 ms, respectively. However, the synchronization performances revealed significantly more positive asynchrony means (but similar variances) in the patient group than in the control group for both types of auditory sequences. Conclusion: The patterns of results suggest that patients with schizophrenia are able to perceive and produce both simple and complex sequences of time intervals but are impaired in the ability to synchronize their actions with external events. These findings suggest a specific deficit in predictive timing, which may be at the core of early symptoms previously described in schizophrenia.

Evaluating dedicated and intrinsic models of temporal encoding by varying context

PubMed Central

Spencer, Rebecca M.C.; Karmarkar, Uma; Ivry, Richard B.

2009-01-01

Two general classes of models have been proposed to account for how people process temporal information in the milliseconds range. Dedicated models entail a mechanism in which time is explicitly encoded; examples include clock–counter models and functional delay lines. Intrinsic models, such as state-dependent networks (SDN), represent time as an emergent property of the dynamics of neural processing. An important property of SDN is that the encoding of duration is context dependent since the representation of an interval will vary as a function of the initial state of the network. Consistent with this assumption, duration discrimination thresholds for auditory intervals spanning 100 ms are elevated when an irrelevant tone is presented at varying times prior to the onset of the test interval. We revisit this effect in two experiments, considering attentional issues that may also produce such context effects. The disruptive effect of a variable context was eliminated or attenuated when the intervals between the irrelevant tone and test interval were made dissimilar or the duration of the test interval was increased to 300 ms. These results indicate how attentional processes can influence the perception of brief intervals, as well as point to important constraints for SDN models. PMID:19487188

Single therapeutic and supratherapeutic doses of corifollitropin alfa, a sustained follicle stimulant, do not prolong the QTcF-interval in healthy postmenopausal volunteers.

PubMed

de Kam, Pieter-Jan; van Kuijk, Jacqueline H M; Zandvliet, Anthe S; Thomsen, Torben

2015-09-01

Corifollitropin alfa (Elonva®) is the first hybrid follicle-stimulating hormone molecule with demonstrated sustained follicle-stimulating activity after a single subcutaneous injection. This trial evaluated if corifollitropin alfa is associated with QT/QTc prolongation and/ or proarrhythmic potential as compared to placebo in healthy post-menopausal women. Participants were healthy, postmenopausal women. Study treatments were corifollitropin alfa 150 μg, corifollitropin alfa 240 μg, and moxifloxacin 400 mg with placebo. This randomized, double blind, double-dummy, 4-period crossover trial compared single doses of corifollitropin alfa 150 μg (therapeutic dose), corifollitropin alfa 240 μg (supratherapeutic dose), and moxifloxacin 400 mg (positive control) with placebo. Corifollitropin alfa was administered on day 1 and moxifloxacin on day 2. The largest time-matched mean QTcF difference versus placebo for the therapeutic dose of corifollitropin alfa was 1.4 ms (upper limit of 1-sided 95% confidence interval (UL 95% CI) = 3.4 ms), and for the supratherapeutic dose was 1.2 ms (UL 95% CI = 3.6 ms). For both the therapeutic and the supratherapeutic dose of corifollitropin alfa and at all time points, the UL 95% CI for the time matched QTcF differences compared with placebo was below 10 ms, the threshold of relevance defined by the ICH E14 guideline. Single therapeutic and supratherapeutic doses of corifollitropin alfa are not associated with clinically relevant QT/QTc-interval prolongation in healthy post-menopausal women.

The Effects of Continuous One-Arm Kettlebell Swing Training on Physiological Parameters in United States Air Force Personnel: A Pilot Study

DTIC Science & Technology

2016-11-01

collegiate soccer players . KB snatches were performed 3 days per week for 20 minutes with 15-second work-to-rest intervals, while the control group...10] used KB weights that were 18% of total body mass and reported a 6% improvement in aerobic capacity in women’s collegiate soccer players who...Force Personnel: A Pilot Study Molly Wade, MS; Reginald O’Hara, PhD; Lydia Caldwell, MS; Jason Ordway, MS; Darryn Bryant, MS

Assessment of atrial electromechanical interval and P wave dispersion in patients with polycystic ovary syndrome.

PubMed

Bayır, Pınar Türker; Güray, Ümit; Duyuler, Serkan; Demirkan, Burcu; Kayaalp, Oya; Kanat, Selçuk; Güray, Yeşim

2016-02-01

Polycystic ovary syndrome (PCOS) is associated with increased cardiovascular risk, including ischemic stroke. Prolonged atrial electromechanical interval (EMI) is related to increased atrial fibrillation (AF) risk. The aim of the study is to evaluate atrial EMI and electrocardiographic P-wave indices related to increased AF risk in patients with PCOS. Forty PCOS patients diagnosed on the basis of the Rotterdam criteria and 20 age-matched controls were prospectively included. patients with atrioventricular or intraventricular conduction abnormalities, dysrhythmia or taking antiarrhythmic drugs, atherosclerotic heart disease, cardiomyopathies, valvular lesions, pericardial disease, a history of pulmonary emboli or pulmonary hypertension, and abnormal thyroid function were excluded. Intra and interatrial EMI were measured by tissue Doppler imaging and P-wave dispersion (Pd) was calculated on 12-lead electrocardiography (ECG). The Isovolumetric relaxation time was the interval between the aortic valve closure artifact at the end of the LV outflow envelope and the mitral valve opening artifact at the beginning of the mitral E wave. Patients with PCOS had significantly higher interatrial [38 (24-65) ms vs. 16 (9-19) ms p<0.001], left-sided intra-atrial (14.8±6.1 vs. 7±1.7 ms, p<0.001), and right-sided intra-atrial (22.3±8.1 vs. 8.6±3.6 ms, p<0.001) EMI compared with the control group. Pd was significantly greater in the PCOS group compared with control group [45 (27-60) ms vs. 30 (26-38) ms, p<0.001]. Echocardiographic parameters of atrial EMI were significantly correlated with body mass index, Pd, and isovolumetric relaxation time in patients with PCOS. PCOS is associated with prolonged inter- and intra-atrial conduction times, which are related to increased AF risk.

Visual Working Memory Cannot Trade Quantity for Quality.

PubMed

Ramaty, Ayelet; Luria, Roy

2018-01-01

Two main models have been proposed to describe how visual working memory (WM) allocates its capacity: the slot-model and the continuous resource-model. The purpose of the current study was to test a direct prediction of the resource model suggesting that WM can trade-off between the quantity and quality of the encoded information. Previous research reported equivocal results, with studies that failed to find such a trade-off and other studies that reported a trade-off. Following the design of previous studies, in Experiment 1 we replicated this trade-off, by presenting the memory array for 1200 ms. Experiment 2 failed to observe a trade-off between quantity and quality using a memory array interval of 300 ms (a standard interval for visual WM). Experiment 3 again failed to find this trade-off, when reinstating the 1200 ms memory array interval but adding an articulatory suppression manipulation. We argue that while participants can trade quantity for quality, this pattern depends on verbal encoding and transfer to long-term memory processes that were possible to perform only during the long retention interval. When these processes were eliminated, the trade-off disappeared. Thus, we didn't find any evidence that the trade-off between quantity for quality can occur within visual WM.

Effect of maternal use of chewing gums containing xylitol on transmission of mutans streptococci in children: a meta-analysis of randomized controlled trials.

PubMed

Lin, Hsi-Kuei; Fang, Chia-En; Huang, Mao-Suan; Cheng, Hsin-Chung; Huang, Tsai-Wei; Chang, Hui-Ting; Tam, Ka-Wai

2016-01-01

Mutans streptococci (MS) are the major causative bacteria involved in human dental decay. Habitual consumption of xylitol has been proved to reduce MS levels in saliva and plaque. To evaluate the effect of the maternal use of xylitol gum on MS reduction in infants. A structured literature review and meta-analysis. A random effects model was used to assess the relative risks of the incidence of MS in the saliva or plaque of children who were 6, 9, 12, 18, and 24 months old. We reviewed 11 RCTs derived from 5 research teams that included 601 mothers. Our results indicated that the incidence of MS in the saliva or plaque of the infants was significantly reduced in the xylitol group (risk ratio: 0.54; 95% confidence interval: 0.39-0.73, at 12-18 months) and (risk ratio: 0.56; 95% confidence interval: 0.40-0.79, at 36 months) compared with the control groups. The long-term effect of maternal xylitol gum exposure on their children's dental caries was controversial. Habitual xylitol consumption by mothers with high MS levels was associated with a significant reduction in the mother-child transmission of salivary MS. © 2015 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Maternal Oral Bacterial Levels Predict Early Childhood Caries Development

PubMed Central

Chaffee, B.W.; Gansky, S.A.; Weintraub, J.A.; Featherstone, J.D.B.; Ramos-Gomez, F.J.

2014-01-01

Objective: To calculate the association of maternal salivary bacterial challenge (mutans streptococci [MS] and lactobacilli [LB]) from pregnancy through 24 months’ postpartum with child caries incidence (≥1 cavitated or restored teeth) at 36 months. Materials & Methods: Dental, salivary bacterial, sociodemographic, and behavioral measures were collected at three- to six-month intervals from a birth cohort of low-income Hispanic mother-child dyads (N = 243). We calculated the relative child caries incidence, adjusted for confounding, following higher maternal challenge of MS (>4500 colony-forming units per milliliter of saliva [CFU/mL]) and LB (>50 CFU/mL) based on multivariable models. Results: Salivary MS and LB levels were greater among mothers of caries-affected children versus caries-free children. Mothers with higher salivary MS challenge were more likely to have MS-positive children (>0 CFU/mL), but maternal LB challenge was not a statistically significant predictor of child LB-positive status. Adjusting for sociodemographics, feeding and care practices, and maternal dental status, higher maternal salivary challenge of both MS and LB over the study period predicted nearly double the child caries incidence versus lower MS and LB (cumulative incidence ratio: 1.9; 95% confidence interval: 1.1, 3.8). Conclusion: Maternal salivary bacterial challenge not only is associated with oral infection among children but also predicts increased early childhood caries occurrence. PMID:24356441

Scopolamine Impairs Appetitive But Not Aversive Trace Conditioning: Role of the Medial Prefrontal Cortex.

PubMed

Pezze, Marie-Astrid; Marshall, Hayley J; Cassaday, Helen J

2017-06-28

The muscarinic acetylcholine receptor is an important modulator of medial prefrontal cortex (mPFC) functions, such as the working memory required to bridge a trace interval in associative leaning. Aversive and appetitive trace conditioning procedures were used to examine the effects of scopolamine (0.1 and 0.5 mg/kg, i.p.) in male rats. Follow-up experiments tested the effects of microinfusion of 0.15 μg of scopolamine (0.075 μg of in 0.5 μl/side) in infralimbic (IL) versus prelimbic regions of rat mPFC, in appetitive trace and locomotor activity (LMA) procedures. Systemic scopolamine was without effect in an aversive trace conditioning procedure, but impaired appetitive conditioning at a 2 s trace interval. This effect was demonstrated as reduced responding during presentations of the conditioned stimulus (CS) and during the interstimulus interval (ISI). There was no such effect on responding during food (unconditioned stimulus, US) responding or in the intertrial interval (ITI). In contrast, systemic scopolamine dose-relatedly increased LMA. Trace conditioning was similarly impaired at the 2 s trace (shown as reduced responding to the CS and during the ISI, but not during US presentations or in the ITI) after infusion in mPFC, whereas LMA was increased (after infusion in IL only). Therefore, our results point to the importance of cholinergic modulation in mPFC for trace conditioning and show that the observed effects cannot be attributed to reduced activity. SIGNIFICANCE STATEMENT Events are very often separated in time, in which case working memory is necessary to condition their association in "trace conditioning." The present study used conditioning variants motivated aversively with foot shock and appetitively with food. The drug scopolamine was used to block muscarinic acetylcholine receptors involved in working memory. The results show that reduced cholinergic transmission in medial prefrontal cortex (mPFC) impaired appetitive trace conditioning at a 2 s trace interval. However, scopolamine was without effect in the aversive procedure, revealing the importance of procedural differences to the demonstration of the drug effect. The finding that blockade of muscarinic receptors in mPFC impaired trace conditioning shows that these receptors are critical modulators of short-term working memory. Copyright © 2017 Pezze et al.

Scopolamine Impairs Appetitive But Not Aversive Trace Conditioning: Role of the Medial Prefrontal Cortex

PubMed Central

Pezze, Marie-Astrid; Marshall, Hayley J.

2017-01-01

The muscarinic acetylcholine receptor is an important modulator of medial prefrontal cortex (mPFC) functions, such as the working memory required to bridge a trace interval in associative leaning. Aversive and appetitive trace conditioning procedures were used to examine the effects of scopolamine (0.1 and 0.5 mg/kg, i.p.) in male rats. Follow-up experiments tested the effects of microinfusion of 0.15 μg of scopolamine (0.075 μg of in 0.5 μl/side) in infralimbic (IL) versus prelimbic regions of rat mPFC, in appetitive trace and locomotor activity (LMA) procedures. Systemic scopolamine was without effect in an aversive trace conditioning procedure, but impaired appetitive conditioning at a 2 s trace interval. This effect was demonstrated as reduced responding during presentations of the conditioned stimulus (CS) and during the interstimulus interval (ISI). There was no such effect on responding during food (unconditioned stimulus, US) responding or in the intertrial interval (ITI). In contrast, systemic scopolamine dose-relatedly increased LMA. Trace conditioning was similarly impaired at the 2 s trace (shown as reduced responding to the CS and during the ISI, but not during US presentations or in the ITI) after infusion in mPFC, whereas LMA was increased (after infusion in IL only). Therefore, our results point to the importance of cholinergic modulation in mPFC for trace conditioning and show that the observed effects cannot be attributed to reduced activity. SIGNIFICANCE STATEMENT Events are very often separated in time, in which case working memory is necessary to condition their association in “trace conditioning.” The present study used conditioning variants motivated aversively with foot shock and appetitively with food. The drug scopolamine was used to block muscarinic acetylcholine receptors involved in working memory. The results show that reduced cholinergic transmission in medial prefrontal cortex (mPFC) impaired appetitive trace conditioning at a 2 s trace interval. However, scopolamine was without effect in the aversive procedure, revealing the importance of procedural differences to the demonstration of the drug effect. The finding that blockade of muscarinic receptors in mPFC impaired trace conditioning shows that these receptors are critical modulators of short-term working memory. PMID:28559376

Assessment of atrial electromechanical delay and P-wave dispersion in patients with psoriasis.

PubMed

Yildiz, Abdulkadir; Ucmak, Derya; Oylumlu, Mustafa; Akkurt, Meltem Z; Yuksel, Murat; Akil, Mehmet Ata; Acet, Halit; Polat, Nihat; Aydin, Mesut; Bilik, M Zihni

2014-10-01

In this study, we sought to evaluate atrial electromechanical properties and conduction homogeneity by tissue Doppler imaging and electrocardiography in patients with psoriasis. Thirty-four patients with psoriasis and 30 age- and gender-matched healthy controls were included in the study. Atrial electromechanical coupling intervals were assessed by means of tissue Doppler echocardiography and P-wave dispersion (Pd) was calculated from electrocardiogram. A total of 64 subjects (33 male) with a mean age of 36.8 ± 11.9 years were included in the study. Basal characteristics were similar between 2 groups. Intra-atrial (15 ± 7 ms vs. 12 ± 5 ms, P = 0.009) and inter-atrial (28 ± 7 ms vs. 23 ± 7 ms, P = 0.002) electromechanical delays were significantly higher in patients with psoriasis compared with control groups. P-maximum (112 ± 16 ms vs. 103 ± 8 ms, P = 0.006) and Pd (35 ± 9 ms vs. 20 ± 6 ms, P < 0.001) were also prolonged in patients with psoriasis. This study demonstrated that atrial electromechanical coupling intervals and P-wave dispersion were prolonged in patients with psoriasis, which may cause an increased risk of atrial fibrillation in this patient group. © 2014, Wiley Periodicals, Inc.

Electrocardiogram: his bundle potentials can be recorded noninvasively beat by beat on surface electrocardiogram.

PubMed

Wang, Gaopin; Liu, Renguang; Chang, Qinghua; Xu, Zhaolong; Zhang, Yingjie; Pan, Dianzhu

2017-03-15

The micro waveform of His bundle potential can't be recorded beat-to-beat on surface electrocardiogram yet. We have found that the micro-wavelets before QRS complex may be related to atrioventricular conduction system potentials. This study is to explore the possibility of His bundle potential can be noninvasively recorded on surface electrocardiogram. We randomized 65 patients undergoing radiofrequency catheter ablation of paroxysmal superventricular tachycardia (exclude overt Wolff-Parkinson-White syndrome) to receive "conventional electrocardiogram" and "new electrocardiogram" before the procedure. His bundle electrogram was collected during the procedure. Comparative analysis of PA s (PA interval recorded on surface electrocardiogram), AH s (AH interval recorded on surface electrocardiogram) and HV s (HV interval recorded on surface electrocardiogram) interval recorded on surface "new electrocardiogram" and PA, AH, HV interval recorded on His bundle electrogram was investigated. There was no difference (P > 0.05) between groups in HV s interval (49.63 ± 6.19 ms) and HV interval (49.35 ± 6.49 ms). Results of correlational analysis found that HV S interval was significantly positively associated with HV interval (r = 0.929; P < 0.01). His bundle potentials can be noninvasively recorded on surface electrocardiogram. Noninvasive His bundle potential tracing might represent a new method for locating the site of atrioventricular block and identifying the origin of a wide QRS complex.

Levofloxacin can be used effectively as a positive control in thorough QT/QTc studies in healthy volunteers

PubMed Central

Taubel, Jorg; Naseem, Asif; Harada, Tomohiko; Wang, Duolao; Arezina, Radivoj; Lorch, Ulrike; Camm, A John

2010-01-01

AIMS To characterize the effects of levofloxacin on QT interval in healthy subjects and the most appropriate oral positive control treatments for International Conference on Harmonization (ICH) E14 QT/QTc studies. METHODS Healthy subjects received a single dose of levofloxacin (1000 or 1500 mg), moxifloxacin (400 mg) or placebo in a four-period crossover design. Digital 12-lead ECGs were recorded in triplicate. Measurement of QT interval was performed automatically with subsequent manual onscreen over-reading using electronic callipers. Blood samples were taken for determination of levofloxacin and moxifloxacin concentrations. RESULTS Mean QTcI (QT interval corrected for heart rate using a correction factor that is applicable to each individual) was prolonged in subjects receiving moxifloxacin 400 mg compared with placebo. The largest time-matched difference in QTcI for moxifloxacin compared with placebo was observed to be 13.19 ms (95% confidence interval 11.21, 15.17) at 3.5 h post dose. Prolonged mean QTcI was also observed in subjects receiving levofloxacin 1000 mg and 1500 mg compared with placebo. The largest time-matched difference in QTcI compared with placebo was observed at 3.5 h post dose for both 1000 mg and 1500 mg of levofloxacin [mean (95%) 4.42 ms (2.44, 6.39) in 1000 mg and 7.44 ms (5.47, 9.42) in 1500 mg]. A small increase in heart rate was observed with levofloxacin during the course of the study. However, moxifloxacin showed a greater increase compared with levofloxacin. CONCLUSIONS Both levofloxacin and moxifloxacin can fulfil the criteria for a positive comparator. The ICH E14 guidelines recommend a threshold of around 5 ms for a positive QT/QTc study. The largest time-matched difference in QTc for levofloxacin suggests the potential for use in more rigorous QT/QTc studies. This study has demonstrated the utility of levofloxacin on the assay in measuring mean QTc changes around 5 ms. PMID:20406223

Dimension-based attention in visual short-term memory.

PubMed

Pilling, Michael; Barrett, Doug J K

2016-07-01

We investigated how dimension-based attention influences visual short-term memory (VSTM). This was done through examining the effects of cueing a feature dimension in two perceptual comparison tasks (change detection and sameness detection). In both tasks, a memory array and a test array consisting of a number of colored shapes were presented successively, interleaved by a blank interstimulus interval (ISI). In Experiment 1 (change detection), the critical event was a feature change in one item across the memory and test arrays. In Experiment 2 (sameness detection), the critical event was the absence of a feature change in one item across the two arrays. Auditory cues indicated the feature dimension (color or shape) of the critical event with 80 % validity; the cues were presented either prior to the memory array, during the ISI, or simultaneously with the test array. In Experiment 1, the cue validity influenced sensitivity only when the cue was given at the earliest position; in Experiment 2, the cue validity influenced sensitivity at all three cue positions. We attributed the greater effectiveness of top-down guidance by cues in the sameness detection task to the more active nature of the comparison process required to detect sameness events (Hyun, Woodman, Vogel, Hollingworth, & Luck, Journal of Experimental Psychology: Human Perception and Performance, 35; 1140-1160, 2009).

Participation of the Classical Speech Areas in Auditory Long-Term Memory

PubMed Central

Karabanov, Anke Ninija; Paine, Rainer; Chao, Chi Chao; Schulze, Katrin; Scott, Brian; Hallett, Mark; Mishkin, Mortimer

2015-01-01

Accumulating evidence suggests that storing speech sounds requires transposing rapidly fluctuating sound waves into more easily encoded oromotor sequences. If so, then the classical speech areas in the caudalmost portion of the temporal gyrus (pSTG) and in the inferior frontal gyrus (IFG) may be critical for performing this acoustic-oromotor transposition. We tested this proposal by applying repetitive transcranial magnetic stimulation (rTMS) to each of these left-hemisphere loci, as well as to a nonspeech locus, while participants listened to pseudowords. After 5 minutes these stimuli were re-presented together with new ones in a recognition test. Compared to control-site stimulation, pSTG stimulation produced a highly significant increase in recognition error rate, without affecting reaction time. By contrast, IFG stimulation led only to a weak, non-significant, trend toward recognition memory impairment. Importantly, the impairment after pSTG stimulation was not due to interference with perception, since the same stimulation failed to affect pseudoword discrimination examined with short interstimulus intervals. Our findings suggest that pSTG is essential for transforming speech sounds into stored motor plans for reproducing the sound. Whether or not the IFG also plays a role in speech-sound recognition could not be determined from the present results. PMID:25815813

Participation of the classical speech areas in auditory long-term memory.

PubMed

Karabanov, Anke Ninija; Paine, Rainer; Chao, Chi Chao; Schulze, Katrin; Scott, Brian; Hallett, Mark; Mishkin, Mortimer

2015-01-01

Accumulating evidence suggests that storing speech sounds requires transposing rapidly fluctuating sound waves into more easily encoded oromotor sequences. If so, then the classical speech areas in the caudalmost portion of the temporal gyrus (pSTG) and in the inferior frontal gyrus (IFG) may be critical for performing this acoustic-oromotor transposition. We tested this proposal by applying repetitive transcranial magnetic stimulation (rTMS) to each of these left-hemisphere loci, as well as to a nonspeech locus, while participants listened to pseudowords. After 5 minutes these stimuli were re-presented together with new ones in a recognition test. Compared to control-site stimulation, pSTG stimulation produced a highly significant increase in recognition error rate, without affecting reaction time. By contrast, IFG stimulation led only to a weak, non-significant, trend toward recognition memory impairment. Importantly, the impairment after pSTG stimulation was not due to interference with perception, since the same stimulation failed to affect pseudoword discrimination examined with short interstimulus intervals. Our findings suggest that pSTG is essential for transforming speech sounds into stored motor plans for reproducing the sound. Whether or not the IFG also plays a role in speech-sound recognition could not be determined from the present results.

Cerebellar theta burst stimulation modulates short latency afferent inhibition in Alzheimer's disease patients

PubMed Central

Di Lorenzo, Francesco; Martorana, Alessandro; Ponzo, Viviana; Bonnì, Sonia; D'Angelo, Egidio; Caltagirone, Carlo; Koch, Giacomo

2013-01-01

The dysfunction of cholinergic neurons is a typical hallmark in Alzheimer's disease (AD). Previous findings demonstrated that high density of cholinergic receptors is found in the thalamus and the cerebellum compared with the cerebral cortex and the hippocampus. We aimed at investigating whether activation of the cerebello-thalamo-cortical pathway by means of cerebellar theta burst stimulation (TBS) could modulate central cholinergic functions evaluated in vivo by using the neurophysiological determination of Short-Latency Afferent Inhibition (SLAI). We tested the SLAI circuit before and after administration of cerebellar continuous TBS (cTBS) in 12 AD patients and in 12 healthy age-matched control subjects (HS). We also investigated potential changes of intracortical circuits of the contralateral primary motor cortex (M1) by assessing short intracortical inhibition (SICI) and intracortical facilitation (ICF). SLAI was decreased in AD patients compared to HS. Cerebellar cTBS partially restored SLAI in AD patients at later inter-stimulus intervals (ISIs), but did not modify SLAI in HS. SICI and ICF did not differ in the two groups and were not modulated by cerebellar cTBS. These results demonstrate that cerebellar magnetic stimulation is likely to affect mechanisms of cortical cholinergic activity, suggesting that the cerebellum may have a direct influence on the cholinergic dysfunction in AD. PMID:23423358

Integrating TRPV1 Receptor Function with Capsaicin Psychophysics

PubMed Central

Smutzer, Gregory; Devassy, Roni K.

2016-01-01

Capsaicin is a naturally occurring vanilloid that causes a hot, pungent sensation in the human oral cavity. This trigeminal stimulus activates TRPV1 receptors and stimulates an influx of cations into sensory cells. TRPV1 receptors function as homotetramers that also respond to heat, proinflammatory substances, lipoxygenase products, resiniferatoxin, endocannabinoids, protons, and peptide toxins. Kinase-mediated phosphorylation of TRPV1 leads to increased sensitivity to both chemical and thermal stimuli. In contrast, desensitization occurs via a calcium-dependent mechanism that results in receptor dephosphorylation. Human psychophysical studies have shown that capsaicin is detected at nanomole amounts and causes desensitization in the oral cavity. Psychophysical studies further indicate that desensitization can be temporarily reversed in the oral cavity if stimulation with capsaicin is resumed at short interstimulus intervals. Pretreatment of lingual epithelium with capsaicin modulates the perception of several primary taste qualities. Also, sweet taste stimuli may decrease the intensity of capsaicin perception in the oral cavity. In addition, capsaicin perception and hedonic responses may be modified by diet. Psychophysical studies with capsaicin are consistent with recent findings that have identified TRPV1 channel modulation by phosphorylation and interactions with membrane inositol phospholipids. Future studies will further clarify the importance of capsaicin and its receptor in human health and nutrition. PMID:26884754

Does Working Memory Enhance or Interfere With Speech Fluency in Adults Who Do and Do Not Stutter? Evidence From a Dual-Task Paradigm.

PubMed

Eichorn, Naomi; Marton, Klara; Schwartz, Richard G; Melara, Robert D; Pirutinsky, Steven

2016-06-01

The present study examined whether engaging working memory in a secondary task benefits speech fluency. Effects of dual-task conditions on speech fluency, rate, and errors were examined with respect to predictions derived from three related theoretical accounts of disfluencies. Nineteen adults who stutter and twenty adults who do not stutter participated in the study. All participants completed 2 baseline tasks: a continuous-speaking task and a working-memory (WM) task involving manipulations of domain, load, and interstimulus interval. In the dual-task portion of the experiment, participants simultaneously performed the speaking task with each unique combination of WM conditions. All speakers showed similar fluency benefits and decrements in WM accuracy as a result of dual-task conditions. Fluency effects were specific to atypical forms of disfluency and were comparable across WM-task manipulations. Changes in fluency were accompanied by reductions in speaking rate but not by corresponding changes in overt errors. Findings suggest that WM contributes to disfluencies regardless of stuttering status and that engaging WM resources while speaking enhances fluency. Further research is needed to verify the cognitive mechanism involved in this effect and to determine how these findings can best inform clinical intervention.

Musical and linguistic listening modes in the speech-to-song illusion bias timing perception and absolute pitch memory.

PubMed

Graber, Emily; Simchy-Gross, Rhimmon; Margulis, Elizabeth Hellmuth

2017-12-01

The speech-to-song (STS) illusion is a phenomenon in which some spoken utterances perceptually transform to song after repetition [Deutsch, Henthorn, and Lapidis (2011). J. Acoust. Soc. Am. 129, 2245-2252]. Tierney, Dick, Deutsch, and Sereno [(2013). Cereb. Cortex. 23, 249-254] developed a set of stimuli where half tend to transform to perceived song with repetition and half do not. Those that transform and those that do not can be understood to induce a musical or linguistic mode of listening, respectively. By comparing performance on perceptual tasks related to transforming and non-transforming utterances, the current study examines whether the musical mode of listening entails higher sensitivity to temporal regularity and better absolute pitch (AP) memory compared to the linguistic mode. In experiment 1, inter-stimulus intervals within STS trials were steady, slightly variable, or highly variable. Participants reported how temporally regular utterance entrances were. In experiment 2, participants performed an AP memory task after a blocked STS exposure phase. Utterances identically matching those used in the exposure phase were targets among transposed distractors in the test phase. Results indicate that listeners exhibit heightened awareness of temporal manipulations but reduced awareness of AP manipulations to transforming utterances. This methodology establishes a framework for implicitly differentiating musical from linguistic perception.

Abnormal tactile temporal discrimination in psychogenic dystonia.

PubMed

Morgante, F; Tinazzi, M; Squintani, G; Martino, D; Defazio, G; Romito, L; Albanese, A; Di Matteo, A; Quartarone, A; Girlanda, P; Fiorio, M; Berardelli, A

2011-09-20

Neurophysiologic studies demonstrated that patients with primary torsion dystonia (PTD) and with psychogenic dystonia (Psy-D) share similar abnormalities in the motor system. In this study, we evaluated somatosensory function in Psy-D by testing temporal discrimination threshold (TDT), and compared the results with those obtained in patients with PTD. TDT of tactile stimuli was assessed in 10 patients with Psy-D, 10 patients with PTD, and 16 control subjects. The 2 groups of patients were matched for age, gender, disease duration, and distribution of dystonia. Tactile stimuli consisted of pairs of non-noxious electrical shocks delivered to the right or left hand at interstimulus interval increasing from 0 to 400 msec, in 10-msec steps. TDT was defined as the value at which subjects recognized the 2 stimuli as asynchronous. TDT was higher in Psy-D and PTD compared to control subjects, for both the right and the left hand. In a subgroup of patients with unilateral dystonia (Psy-D = 4, PTD = 5), TDT did not differ between the affected and the unaffected side in both groups of patients. Disease duration was not correlated to the increased TDT value. Our study suggests an impaired processing of somatosensory inputs in both Psy-D and PTD. These abnormalities might represent a neurophysiological trait predisposing to develop a dystonic posture triggered by psychiatric and psychological factors.

Learning to perceive differences in solid shape through vision and touch.

PubMed

Norman, J Farley; Clayton, Anna Marie; Norman, Hideko F; Crabtree, Charles E

2008-01-01

A single experiment was designed to investigate perceptual learning and the discrimination of 3-D object shape. Ninety-six observers were presented with naturally shaped solid objects either visually, haptically, or across the modalities of vision and touch. The observers' task was to judge whether the two sequentially presented objects on any given trial possessed the same or different 3-D shapes. The results of the experiment revealed that significant perceptual learning occurred in all modality conditions, both unimodal and cross-modal. The amount of the observers' perceptual learning, as indexed by increases in hit rate and d', was similar for all of the modality conditions. The observers' hit rates were highest for the unimodal conditions and lowest in the cross-modal conditions. Lengthening the inter-stimulus interval from 3 to 15 s led to increases in hit rates and decreases in response bias. The results also revealed the existence of an asymmetry between two otherwise equivalent cross-modal conditions: in particular, the observers' perceptual sensitivity was higher for the vision-haptic condition and lower for the haptic-vision condition. In general, the results indicate that effective cross-modal shape comparisons can be made between the modalities of vision and active touch, but that complete information transfer does not occur.

A study of adaptation mechanisms based on ABR recorded at high stimulation rate.

PubMed

Valderrama, Joaquin T; de la Torre, Angel; Alvarez, Isaac; Segura, Jose Carlos; Thornton, A Roger D; Sainz, Manuel; Vargas, Jose Luis

2014-04-01

This paper analyzes the fast and slow mechanisms of adaptation through a study of latencies and amplitudes on ABR recorded at high stimulation rates using the randomized stimulation and averaging (RSA) technique. The RSA technique allows a separate processing of auditory responses, and is used, in this study, to categorize responses according to the interstimulus interval (ISI) of their preceding stimulus. The fast and slow mechanisms of adaptation are analyzed by the separated responses methodology, whose underlying principles and mathematical basis are described in detail. The morphology of the ABR is influenced by both fast and slow mechanisms of adaptation. These results are consistent with previous animal studies based on spike rate. Both fast and slow mechanisms of adaptation are present in all subjects. In addition, the distribution of the jitter and the sequencing of the stimuli may be critical parameters when obtaining reliable ABRs. The separated responses methodology enables for the first time the analysis of the fast and slow mechanisms of adaptation in ABR obtained at stimulation rates greater than 100 Hz. The non-invasive nature of this methodology is appropriate for its use in humans. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

The fine temporal structure of the rat licking pattern: what causes the variabiliy in the interlick intervals and how is it affected by the drinking solution?

PubMed

Lin, Xiong Bin; Pierce, Dwight R; Light, Kim Edward; Hayar, Abdallah

2013-10-01

Licking is a repetitive behavior controlled by a central pattern generator. Even though interlick intervals (ILIs) within bursts of licks are considered fairly regular, the conditions that affect their variability are unknown. We analyzed the licking pattern in rats that licked water, 10% sucrose solution, or 10% ethanol solution, in 90-min recording sessions after 4h of water deprivation. The histograms of ILIs indicate that licking typically occurred at a preferred ILI of about 130-140ms with evidence of bimodal or multimodal distributions due to occasional licking failures. We found that the longer the pause between bursts of licks, the shorter was the first ILI of the burst. When bursts of licks were preceded by a pause >4 s, the ILI was the shortest (~110ms) at the beginning of the burst, and then it increased rapidly in the first few licks and slowly in subsequent licks. Interestingly, the first ILI of a burst of licks was not significantly different when licking any of the 3 solutions, but subsequent licks exhibited a temporal pattern characteristic of each solution. The rapid deceleration in intraburst licking rate was due to an increase from ~27ms to ~56ms in the tongue-spout contact duration while the intercontact interval was only slightly changed (80-90ms). Therefore, the contact duration seems to be the major factor that increases the variability in the ILIs and could be another means for the rat to adjust the amount of fluid ingested in each individual lick.

Estimated preejection period (PEP) based on the detection of the R-wave and dZ/dt-min peaks in ECG and ICG

NASA Astrophysics Data System (ADS)

van Lien, René; Schutte, Nienke M.; Meijer, Jan H.; de Geus, Eco J. C.

2013-04-01

The validity of estimating the PEP from a fixed value for the Q-wave onset to the R-wave peak (QR) interval and from the R-wave peak to the dZ/dt-min peak (ISTI) interval is evaluated. Ninety-one subjects participated in a laboratory experiment in which a variety of physical and mental stressors were presented and 31 further subjects participated in a sequence of structured ambulatory activities in which large variation in posture and physical activity was induced. PEP, QR interval, and ISTI were scored. Across the diverse laboratory and ambulatory conditions the QR interval could be approximated by a fixed interval of 40 ms but 95% confidence intervals were large (25 to 54 ms). Multilevel analysis showed that 79% to 81% of the within and between-subject variation in the RB interval could be predicted by the ISTI. However, the optimal intercept and slope values varied significantly across subjects and study setting. Bland-Altman plots revealed a large discrepancy between the estimated PEP and the actual PEP based on the Q-wave onset and B-point. It is concluded that the estimated PEP can be a useful tool but cannot replace the actual PEP to index cardiac sympathetic control.

Translating QT interval prolongation from conscious dogs to humans.

PubMed

Dubois, Vincent F S; Smania, Giovanni; Yu, Huixin; Graf, Ramona; Chain, Anne S Y; Danhof, Meindert; Della Pasqua, Oscar

2017-02-01

In spite of screening procedures in early drug development, uncertainty remains about the propensity of new chemical entities (NCEs) to prolong the QT/QTc interval. The evaluation of proarrhythmic activity using a comprehensive in vitro proarrhythmia assay does not fully account for pharmacokinetic-pharmacodynamic (PKPD) differences in vivo. In the present study, we evaluated the correlation between drug-specific parameters describing QT interval prolongation in dogs and in humans. Using estimates of the drug-specific parameter, data on the slopes of the PKPD relationships of nine compounds with varying QT-prolonging effects (cisapride, sotalol, moxifloxacin, carabersat, GSK945237, SB237376 and GSK618334, and two anonymized NCEs) were analysed. Mean slope estimates varied between -0.98 ms μM -1 and 6.1 ms μM -1 in dogs and -10 ms μM -1 and 90 ms μM -1 in humans, indicating a wide range of effects on the QT interval. Linear regression techniques were then applied to characterize the correlation between the parameter estimates across species. For compounds without a mixed ion channel block, a correlation was observed between the drug-specific parameter in dogs and humans (y = -1.709 + 11.6x; R 2  = 0.989). These results show that per unit concentration, the drug effect on the QT interval in humans is 11.6-fold larger than in dogs. Together with information about the expected therapeutic exposure, the evidence of a correlation between the compound-specific parameter in dogs and in humans represents an opportunity for translating preclinical safety data before progression into the clinic. Whereas further investigation is required to establish the generalizability of our findings, this approach can be used with clinical trial simulations to predict the probability of QT prolongation in humans. © 2016 The British Pharmacological Society.

Auditory Memory Decay as Reflected by a New Mismatch Negativity Score Is Associated with Episodic Memory in Older Adults at Risk of Dementia

PubMed Central

Laptinskaya, Daria; Thurm, Franka; Küster, Olivia C.; Fissler, Patrick; Schlee, Winfried; Kolassa, Stephan; von Arnim, Christine A. F.; Kolassa, Iris-Tatjana

2018-01-01

The auditory mismatch negativity (MMN) is an event-related potential (ERP) peaking about 100–250 ms after the onset of a deviant tone in a sequence of identical (standard) tones. Depending on the interstimulus interval (ISI) between standard and deviant tones, the MMN is suitable to investigate the pre-attentive auditory discrimination ability (short ISIs, ≤ 2 s) as well as the pre-attentive auditory memory trace (long ISIs, >2 s). However, current results regarding the MMN as an index for mild cognitive impairment (MCI) and dementia are mixed, especially after short ISIs: while the majority of studies report positive associations between the MMN and cognition, others fail to find such relationships. To elucidate these so far inconsistent results, we investigated the validity of the MMN as an index for cognitive impairment exploring the associations between different MMN indices and cognitive performance, more specifically with episodic memory performance which is among the most affected cognitive domains in the course of Alzheimer’s dementia (AD), at baseline and at a 5-year-follow-up. We assessed the amplitude of the MMN for short ISI (stimulus onset asynchrony, SOA = 0.05 s) and for long ISI (3 s) in a neuropsychologically well-characterized cohort of older adults at risk of dementia (subjective memory impairment, amnestic and non-amnestic MCI; n = 57). Furthermore, we created a novel difference score (ΔMMN), defined as the difference between MMNs to short and to long ISI, as a measure to assess the decay of the auditory memory trace, higher values indicating less decay. ΔMMN and MMN amplitude after long ISI, but not the MMN amplitude after short ISI, was associated with episodic memory at baseline (β = 0.38, p = 0.003; β = −0.27, p = 0.047, respectively). ΔMMN, but not the MMN for long ISIs, was positively associated with episodic memory performance at the 5-year-follow-up (β = 0.57, p = 0.013). The results suggest that the MMN after long ISI might be suitable as an indicator for the decline in episodic memory and indicate ΔMMN as a potential biomarker for memory impairment in older adults at risk of dementia. PMID:29456500

Auditory Memory Decay as Reflected by a New Mismatch Negativity Score Is Associated with Episodic Memory in Older Adults at Risk of Dementia.

PubMed

Laptinskaya, Daria; Thurm, Franka; Küster, Olivia C; Fissler, Patrick; Schlee, Winfried; Kolassa, Stephan; von Arnim, Christine A F; Kolassa, Iris-Tatjana

2018-01-01

The auditory mismatch negativity (MMN) is an event-related potential (ERP) peaking about 100-250 ms after the onset of a deviant tone in a sequence of identical (standard) tones. Depending on the interstimulus interval (ISI) between standard and deviant tones, the MMN is suitable to investigate the pre-attentive auditory discrimination ability (short ISIs, ≤ 2 s) as well as the pre-attentive auditory memory trace (long ISIs, >2 s). However, current results regarding the MMN as an index for mild cognitive impairment (MCI) and dementia are mixed, especially after short ISIs: while the majority of studies report positive associations between the MMN and cognition, others fail to find such relationships. To elucidate these so far inconsistent results, we investigated the validity of the MMN as an index for cognitive impairment exploring the associations between different MMN indices and cognitive performance, more specifically with episodic memory performance which is among the most affected cognitive domains in the course of Alzheimer's dementia (AD), at baseline and at a 5-year-follow-up. We assessed the amplitude of the MMN for short ISI (stimulus onset asynchrony, SOA = 0.05 s) and for long ISI (3 s) in a neuropsychologically well-characterized cohort of older adults at risk of dementia (subjective memory impairment, amnestic and non-amnestic MCI; n = 57). Furthermore, we created a novel difference score (ΔMMN), defined as the difference between MMNs to short and to long ISI, as a measure to assess the decay of the auditory memory trace, higher values indicating less decay. ΔMMN and MMN amplitude after long ISI, but not the MMN amplitude after short ISI, was associated with episodic memory at baseline ( β = 0.38, p = 0.003; β = -0.27, p = 0.047, respectively). ΔMMN, but not the MMN for long ISIs, was positively associated with episodic memory performance at the 5-year-follow-up ( β = 0.57, p = 0.013). The results suggest that the MMN after long ISI might be suitable as an indicator for the decline in episodic memory and indicate ΔMMN as a potential biomarker for memory impairment in older adults at risk of dementia.

Prognostic significance of fever-induced Brugada syndrome.

PubMed

Mizusawa, Yuka; Morita, Hiroshi; Adler, Arnon; Havakuk, Ofer; Thollet, Aurélie; Maury, Philippe; Wang, Dao W; Hong, Kui; Gandjbakhch, Estelle; Sacher, Frédéric; Hu, Dan; Amin, Ahmad S; Lahrouchi, Najim; Tan, Hanno L; Antzelevitch, Charles; Probst, Vincent; Viskin, Sami; Wilde, Arthur A M

2016-07-01

In Brugada syndrome (BrS), spontaneous type 1 electrocardiogram (ECG) is an established risk marker for fatal arrhythmias whereas drug-induced type 1 ECG shows a relatively benign prognosis. No study has analyzed the prognosis of fever-induced type 1 ECG (F-type1) in a large BrS cohort. The objectives of this study were to assess the prognosis of F-type1 in asymptomatic BrS and to compare the effects of fever and drugs on ECG parameters. One hundred twelve patients with BrS who developed F-type1 were retrospectively enrolled. Prognosis was evaluated in 88 asymptomatic patients. In a subgroup (n = 52), ECG parameters of multiple ECGs (at baseline, during fever, and after drug challenge) were analyzed. Eighty-eight asymptomatic patients had a mean age of 45.8 ± 18.7 years, and 71.6% (67 of 88) were men. Twenty-one percent (18 of 88) had a family history of sudden cardiac death, and 26.4% (14 of 53) carried a pathogenic SCN5A mutation. Drug challenge was positive in 29 of 36 patients tested (80.6%). The risk of ventricular fibrillation in asymptomatic patients was 0.9%/y (3 of 88; 43.6 ± 37.4 months). ST-segment elevation in lead V2 during fever and after drug challenge was not significantly different (0.41 ± 0.21 ms during fever and 0.40 ± 0.30 ms after drug challenge; P > .05). Fever shortened the PR interval compared to baseline, whereas drug challenge resulted in prolonged PR interval and QRS duration (PR interval: 169 ± 29 ms at baseline, 148 ± 45 ms during fever, and 202 ± 35 ms after drug challenge; QRS duration: 97 ± 18 ms at baseline, 92 ± 28 ms during fever, and 117 ± 21 ms after drug challenge). Patients with BrS who develop F-type1 are at risk of arrhythmic events. F-type1 appears to develop through a more complex mechanism as compared with drug-induced type 1 ECG. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Serial position effects in recognition memory for odors: a reexamination.

PubMed

Miles, Christopher; Hodder, Kathryn

2005-10-01

Seven experiments examined recognition memory for sequentially presented odors. Following Reed (2000), participants were presented with a sequence of odors and then required to identify an odor from the sequence in a test probe comprising 2 odors. The pattern of results obtained by Reed (2000, although statistically marginal) demonstrated enhanced recognition for odors presented at the start (primacy) and end (recency) of the sequence: a result that we failed to replicate in any of the experiments reported here. Experiments 1 and 3 were designed to replicate Reed (2000), employing five-item and seven-item sequences, respectively, and each demonstrated significant recency, with evidence of primacy in Experiment 3 only. Experiment 2 replicated Experiment 1, with reduced interstimulus intervals, and produced a null effect of serial position. The ease with which the odors could be verbally labeled was manipulated in Experiments 4 and 5. Nameable odors produced a null effect of serial position (Experiment 4), and hard-to-name odors produced a pronounced recency effect (Experiment 5); nevertheless, overall rates of recognition were remarkably similar for the two experiments at around 70%. Articulatory suppression reduced recognition accuracy (Experiment 6), but recency was again present in the absence of primacy. Odor recognition performance was immune to the effects of an interleaved odor (Experiment 7), and, again, both primacy and recency effects were absent. There was no evidence of olfactory fatigue: Recognition accuracy improved across trials (Experiment 1). It is argued that the results of the experiments reported here are generally consistent with that body of work employing hard-to-name visual stimuli, where recency is obtained in the absence of primacy when the retention interval is short.

Glued to Which Face? Attentional Priority Effect of Female Babyface and Male Mature Face

PubMed Central

Zheng, Wenwen; Luo, Ting; Hu, Chuan-Peng; Peng, Kaiping

2018-01-01

A more babyfaced individual is perceived as more child-like and this impression from babyface, as known as babyface effect, has an impact on social life among various age groups. In this study, the influence of babyfaces on visual selective attention was tested by cognitive task, demonstrating that the female babyface and male mature face would draw participants’ attention so that they take their eyes off more slowly. In Experiment 1, a detection task was applied to test the influence of babyfaces on visual selective attention. In this experiment, a babyface and a mature face with the same gender were presented simultaneously with a letter on one of them. The reaction time was shorter when the target letter was overlaid with a female babyface or male mature face, suggesting an attention capture effect. To explore how this competition influenced by attentional resources, we conducted Experiment 2 with a spatial cueing paradigm and controlled the attentional resources by cueing validity and inter-stimulus interval. In this task, the female babyface and male mature face prolonged responses to the spatially separated targets under the condition of an invalid and long interval pre-cue. This observation replicated the result of Experiment 1. This indicates that the female babyface and male mature face glued visual selective attention once attentional resources were directed to them. To further investigate the subliminal influence from a babyface, we used continuous flash suppression paradigm in Experiment 3. The results, again, showed the advantage of the female babyfaces and male mature faces: they broke the suppression faster than other faces. Our results provide primary evidence that the female babyfaces and male mature faces can reliably glue the visual selective attention, both supra- and sub-liminally. PMID:29559946

The effect of prenatal methamphetamine exposure on attention as assessed by continuous performance tests: results from the Infant Development, Environment, and Lifestyle study.

PubMed

Kiblawi, Zeina N; Smith, Lynne M; LaGasse, Linda L; Derauf, Chris; Newman, Elana; Shah, Rizwan; Arria, Amelia; Huestis, Marilyn; DellaGrotta, Sheri; Dansereau, Lynne M; Neal, Charles; Lester, Barry

2013-01-01

To assess for the increased risk of attention-deficit hyperactivity disorder (ADHD) in young children with prenatal methamphetamine exposure from the multicenter, longitudinal Infant Development, Environment, and Lifestyle (IDEAL) study. The IDEAL study enrolled 412 mother-infant pairs at 4 sites (Tulsa, OK; Des Moines, IA; Los Angeles, CA; and Honolulu, HI). Methamphetamine-exposed subjects (n = 204) were identified by self-report and/or gas chromatography/mass spectrometry confirmation of amphetamine and metabolites in infant meconium. Matched subjects (n = 208) denied methamphetamine use and had a negative meconium screen. This analysis included a subsample of 301 subjects who were administered the Conners' Kiddie Continuous Performance Test (K-CPT) at 5.5 years of age (153 exposed and 148 comparison). Hierarchical linear models adjusted for covariates tested exposure effects on K-CPT measures. Using the same covariates, logistic regression was used to determine the effect of exposure on the incidence of a positive ADHD confidence index score, defined as greater than 50%. There were no differences between the groups in omission or commission errors or reaction time for correct trials. However, methamphetamine exposure was associated with subtle differences in other outcomes predictive of ADHD, including increased slope of reaction time across blocks (p < .001), increased variability in reaction time with longer interstimulus intervals (p < .01), and increased likelihood of greater than 50% on the ADHD confidence index (odds ratio, 3.1; 95% confidence interval, 1.2-7.8; p = .02). Prenatal methamphetamine exposure was associated with subtle differences in K-CPT scores at 5.5 years of age. Even at this relatively young age, these children exhibit indicators of risk for ADHD and warrant monitoring.

Glued to Which Face? Attentional Priority Effect of Female Babyface and Male Mature Face.

PubMed

Zheng, Wenwen; Luo, Ting; Hu, Chuan-Peng; Peng, Kaiping

2018-01-01

A more babyfaced individual is perceived as more child-like and this impression from babyface, as known as babyface effect, has an impact on social life among various age groups. In this study, the influence of babyfaces on visual selective attention was tested by cognitive task, demonstrating that the female babyface and male mature face would draw participants' attention so that they take their eyes off more slowly. In Experiment 1, a detection task was applied to test the influence of babyfaces on visual selective attention. In this experiment, a babyface and a mature face with the same gender were presented simultaneously with a letter on one of them. The reaction time was shorter when the target letter was overlaid with a female babyface or male mature face, suggesting an attention capture effect. To explore how this competition influenced by attentional resources, we conducted Experiment 2 with a spatial cueing paradigm and controlled the attentional resources by cueing validity and inter-stimulus interval. In this task, the female babyface and male mature face prolonged responses to the spatially separated targets under the condition of an invalid and long interval pre-cue. This observation replicated the result of Experiment 1. This indicates that the female babyface and male mature face glued visual selective attention once attentional resources were directed to them. To further investigate the subliminal influence from a babyface, we used continuous flash suppression paradigm in Experiment 3. The results, again, showed the advantage of the female babyfaces and male mature faces: they broke the suppression faster than other faces. Our results provide primary evidence that the female babyfaces and male mature faces can reliably glue the visual selective attention, both supra- and sub-liminally.

Temporal dynamics underlying the modulation of social status on social attention.

PubMed

Dalmaso, Mario; Galfano, Giovanni; Coricelli, Carol; Castelli, Luigi

2014-01-01

Fixating someone suddenly moving the eyes is known to trigger a corresponding shift of attention in the observer. This phenomenon, known as gaze-cueing effect, can be modulated as a function of the social status of the individual depicted in the cueing face. Here, in two experiments, we investigated the temporal dynamics underlying this modulation. To this end, a gaze-cueing paradigm was implemented in which centrally-placed faces depicting high- and low-status individuals suddenly shifted the eyes towards a location either spatially congruent or incongruent with that occupied by a subsequent target stimulus. Social status was manipulated by presenting fictive Curriculum Vitae before the experimental phase. In Experiment 1, in which two temporal intervals (50 ms vs. 900 ms) occurred between the direct-gaze face and the averted-gaze face onsets, a stronger gaze-cueing effect in response to high-status faces than low-status faces was observed, irrespective of the time participants were allowed for extracting social information. In Experiment 2, in which two temporal intervals (200 ms vs. 1000 ms) occurred between the averted-gaze face and target onset, a stronger gaze cueing for high-status faces was observed at the shorter interval only. Taken together, these results suggest that information regarding social status is extracted from faces rapidly (Experiment 1), and that the tendency to selectively attend to the locations gazed by high-status individuals may decay with time (Experiment 2).

A novel device based on smart textile to control heart's activity during exercise.

PubMed

Romagnoli, Marco; Alis, Rafael; Guillen, Javier; Basterra, Javier; Villacastin, J P; Guillen, Sergio

2014-06-01

In recent years, several systems have been developed to control cardiac function during exercise, and some are also capable of recording RR data to provide heart rate variability (HRV) analyses. In this study we compare time between heart beats and HRV parameters obtained with a smart textile system (GOW; Weartech sl., Spain) and an electrocardiogram machine commonly used in hospitals during continuous cycling tests. Twelve cardiology patients performed a 30-min cycling test at stable submaximal intensity. RR interval data were recorded during the test by both systems. 3-min RR segments were taken to compare the time intervals between beats and HRV variables using Bland-Altman analyses and intraclass correlation coefficients. Limits of agreement (LoAs) on RR intervals were stable at around 3 ms (widest LoAs -5.754 to 6.094 ms, tightest LoAs -2.557 to 3.105 ms, medium LoAs -3.638 ± 0.812 to 3.145 ± 0.539 ms). HRV parameters related to short-term change presented wide LoAs (RMSSD -0.17 to 18.41 %, HF -17.64 to 33.21 %, SD1 -0.50 to 17.54 %) as an effect of the error measurement of the GOW system. The GOW system is a valid tool for controlling HR during physical activity, although its use as a clinical tool for HRV cannot be supported.

The Presence or Absence of QTc Prolongation in Buprenorphine-Naloxone Among Youth with Opioid Dependence

PubMed Central

Poole, Sabrina A.; Pecoraro, Anna; Subramaniam, Geetha; Woody, George; Vetter, Victoria L

2015-01-01

Objective To evaluate buprenorphine-naloxone effects on the QTc in youth with opioid dependence. Buprenorphine is a partial agonist that is an effective treatment for opioid dependence. Compared to methadone it has a lower risk of QTc prolongation in adults but is less well studied in youth. It may also reduce the risk for torsades de pointes (TdP) an uncommon variant of polymorphic ventricular tachycardia, that can result in syncope, ventricular fibrillation, and sudden death. Methods Secondary analysis of ECG data from 95 subjects who participated in a multi-site trial for youth with opioid dependence. Subjects were randomized to a 2-week (DETOX), or a 12-week course of buprenorphine-naloxone (BUP). 12-lead ECGs were done at baseline, weeks 4 and 12, and QTc intervals were hand measured and calculated using Bazett's formula. Increases > 60 milliseconds (ms) were considered clinically significant, and readings > 450 ms (males) and 470 ms (females) indicated a prolonged QTc. Results Mean QTc intervals were higher for BUP than DETOX participants at baseline, week 4, and week 12 (p = 0.045), and females had longer mean QTc intervals than males (p < 0.0005). Variations in QTc intervals were observed in some, however none were above 500 ms, the level at which risk for TdP becomes more significant. Conclusion In this randomized trial, the mean QTc at baseline, before randomization, was higher in BUP than DETOX patients. Minimal changes in the QTc were seen at 4 and 12-weeks in a few patients in both groups. There was no evidence that buprenorphine-naloxone alone increased the QTc to a level that increased the risk for TdP. PMID:26690291

Effects of anthracycline, cyclophosphamide and taxane chemotherapy on QTc measurements in patients with breast cancer.

PubMed

Veronese, Pedro; Hachul, Denise Tessariol; Scanavacca, Mauricio Ibrahim; Hajjar, Ludhmila Abrahão; Wu, Tan Chen; Sacilotto, Luciana; Veronese, Carolina; Darrieux, Francisco Carlos da Costa

2018-01-01

Acute and subacute cardiotoxicity are characterized by prolongation of the corrected QT interval (QTc) and other measures derived from the QTc interval, such as QTc dispersion (QTdc) and transmural dispersion of repolarization (DTpTe). Although anthracyclines prolong the QTc interval, it is unclear whether breast cancer patients who undergo the ACT chemotherapy regimen of anthracycline (doxorubicin: A), cyclophosphamide (C) and taxane (T) may present with QTc, QTdc and DTpTe prolongation. Twenty-three consecutive patients with breast cancer were followed prospectively during ACT chemotherapy and were analyzed according to their QT measurements. QTc, QTdc and DTpTe measurements were determined by a 12-lead electrocardiogram (EKG) prior to chemotherapy (baseline), immediately after the first phase of anthracycline and cyclophosphamide (AC) treatment, and immediately after T treatment. Serum troponin and B-type natriuretic peptide (BNP) levels were also measured. Compared to baseline values, the QTc interval was significantly prolonged after the AC phase (439.7 ± 33.2 ms vs. 472.5 ± 36.3 ms, p = 0.001) and after T treatment (439.7 ± 33.2 ms vs. 467.9 ± 42.6 ms, p < 0.001). Troponin levels were elevated after the AC phase (23.0 pg/mL [min-max: 6.0-85.0] vs. 6.0 pg/mL [min-max: 6.0-22.0], p < 0.001) and after T treatment (25.0 pg/mL [min-max: 6.0-80.0] vs. 6.0 pg/mL [min-max: 6.0-22.0], p < 0.001) compared to baseline values. In this prospective study of patients with non-metastatic breast cancer who underwent ACT chemotherapy, significant QTc prolongation and an elevation in serum troponin levels were observed.

Automatic attentional orienting to other people's gaze in schizophrenia.

PubMed

Langdon, Robyn; Seymour, Kiley; Williams, Tracey; Ward, Philip B

2017-08-01

Explicit tests of social cognition have revealed pervasive deficits in schizophrenia. Less is known of automatic social cognition in schizophrenia. We used a spatial orienting task to investigate automatic shifts of attention cued by another person's eye gaze in 29 patients and 28 controls. Central photographic images of a face with eyes shifted left or right, or looking straight ahead, preceded targets that appeared left or right of the cue. To examine automatic effects, cue direction was non-predictive of target location. Cue-target intervals were 100, 300, and 800 ms. In non-social control trials, arrows replaced eye-gaze cues. Both groups showed automatic attentional orienting indexed by faster reaction times (RTs) when arrows were congruent with target location across all cue-target intervals. Similar congruency effects were seen for eye-shift cues at 300 and 800 ms intervals, but patients showed significantly larger congruency effects at 800 ms, which were driven by delayed responses to incongruent target locations. At short 100-ms cue-target intervals, neither group showed faster RTs for congruent than for incongruent eye-shift cues, but patients were significantly slower to detect targets after direct-gaze cues. These findings conflict with previous studies using schematic line drawings of eye-shifts that have found automatic attentional orienting to be reduced in schizophrenia. Instead, our data indicate that patients display abnormalities in responding to gaze direction at various stages of gaze processing-reflected by a stronger preferential capture of attention by another person's direct eye contact at initial stages of gaze processing and difficulties disengaging from a gazed-at location once shared attention is established.

Differential Changes in Myocardial Performance Index and Its Time Intervals in Donors and Recipients of Twin-to-Twin Transfusion Syndrome before and after Laser Therapy.

PubMed

Ortiz, Javier U; Torres, Ximena; Eixarch, Elisenda; Bennasar, Mar; Cruz-Lemini, Monica; Gómez, Olga; Lobmaier, Silvia M; Martínez, Josep M; Gratacós, Eduard; Crispi, Fatima

2018-01-19

To evaluate left myocardial performance index (MPI) and time intervals in fetuses with twin-to-twin transfusion syndrome (TTTS) before and after laser surgery. Fifty-one fetal pairs with TTTS and 47 uncomplicated monochorionic twin pairs were included. Left ventricular isovolumetric contraction time (ICT), ejection time (ET), and isovolumetric relaxation time (IRT) were measured using conventional Doppler. Recipients showed prolonged ICT (46 ± 12 vs. 31 ± 8 vs. 30 ± 5 ms; p < 0.001) and IRT (51 ± 9 vs. 43 ± 8 vs. 43 ± 5 ms; p < 0.001) and higher MPI (0.57 ± 0.12 vs. 0.47 ± 0.09 vs. 0.44 ± 0.05; p < 0.001) than donors and controls. Donors showed shorter ET than recipients and controls (157 ± 12 vs. 169 ± 10 vs. 168 ± 10 ms; p < 0.001) and higher MPI than controls (0.47 ± 0.09 vs. 0.44 ± 0.05; p = 0.006). Preoperative MPI changes were observed in all TTTS stages. Time intervals partially improved after surgery. Donor and recipient twins had higher MPI due to different changes in the time intervals, possibly reflecting the state of hypovolemia in the donor and hypervolemia and pressure overload in the recipient. © 2018 S. Karger AG, Basel.

Within-Subject Testing of the Signaled-Reinforcement Effect on Operant Responding as Measured by Response Rate and Resistance to Change

ERIC Educational Resources Information Center

Reed, Phil; Doughty, Adam H.

2005-01-01

Response rates under random-interval schedules are lower when a brief (500 ms) signal accompanies reinforcement than when there is no signal. The present study examined this signaled-reinforcement effect and its relation to resistance to change. In Experiment 1, rats responded on a multiple random-interval 60-s random-interval 60-s schedule, with…

Tricaine (MS-222) is a safe anesthetic compound compared to benzocaine and pentobarbital to induce anesthesia in leopard frogs (Rana pipiens).

PubMed

Cakir, Yavuz; Strauch, Stephen M

2005-01-01

Tricaine (MS-222) is used commonly for sedation, immobilization, and anesthesia of poikilothermic animals. The anesthetic efficacy of different concentrations of MS-222 was compared to benzocaine and pentobarbital on the physiological changes, heart rate and ECG (electrocardiogram) parameters in the leopard frog, Rana pipiens. Loss of righting reflex (RR), loss of pain response (NR = nociceptor response) and recovery time were measured. Heart rate and ECG parameters were also tested before and during anesthesia. The time to loss of RR and NR decreased while recovery time markedly increased with the increasing concentration of MS-222. Benzocaine at 200 mg/l induced a rapid anesthesia, but all frogs needed resuscitation. Pentobarbital at 300 mg/l induced a slow anesthesia, however, all of the frogs also needed resuscitation. All anesthetics at the mentioned concentrations decreased heart rate significantly as well as altered the ECG parameters. All anesthetics prolonged the Q-T interval, and MS-222 at 800 mg/l and benzocaine at 200 mg/l were the most effective anesthetic concentrations in increasing the Q-T interval. Frogs anesthetized by benzocaine and pentobarbital and high concentrations of MS-222 required resuscitation due to hypoxia. Pentobarbital and benzocaine seem to be very effective compounds, but their safety margins are narrow because of ventilatory failure. Therefore, MS-222 at a concentration of 200 mg/l or less is highly recommended for leopard frogs because prolonged recovery, high mortality rate and significant ECG changes are observed with higher concentrations of MS-222.

Nocturnal heart rate variability is lower in temporomandibular disorder patients than in healthy, pain-free individuals.

PubMed

Eze-Nliam, Chete M; Quartana, Phillip J; Quain, Angela M; Smith, Michael T

2011-01-01

To determine whether patients with a painful myofascial temporomandibular disorder (TMD) have diminished nocturnal heart rate variability (HRV), a marker of autonomic nervous system (ANS) dysfunction, relative to healthy, pain-free controls. Participants with myofascial TMD and healthy, pain-free volunteers underwent nocturnal polysomnography studies during which HRV indices were measured. Multiple linear regression analyses were used to determine whether TMD status exerted unique effects on HRV. Ninety-five participants (n = 37 TMD; n = 58 controls) were included in the analyses. The TMD group had a lower standard deviation of R-R intervals (89.81 ± 23.54 ms versus 107.93 ± 34.42 ms, P ⋜ .01), a lower root mean squared successive difference (RMSSD) of R-R intervals (54.78 ± 27.37 ms versus 81.88 ± 46.43 ms, P < .01), and a lower high frequency spectral power (2336.89 ± 1224.64 ms² versus 2861.78 ± 1319 ms², P = .05) than the control group. The ratio of the low-frequency (LF) to the high-frequency (HF) spectral power was higher in the TMD group (2.47 ± 2 versus 1.38 ± 0.65, P < .01). The differences in RMSSD (91.21 ms versus 112.03 ms, P = .05) and LF:HF ratio (0.71 versus 0.32, P < .01) remained significant after controlling for age and psychological distress. Myofascial TMD patients revealed lower nocturnal HRV than healthy, pain-free controls. Further research should focus on processes that address this ANS imbalance, which may potentially lead to effective therapeutic interventions.

Evaluation of Tp-e interval and Tp-e/QT ratio in patients with non-dipper hypertension.

PubMed

Demir, Mehmet; Uyan, Umut

2014-01-01

Non-dipper hypertension is associated with increased cardiovascular morbidity and mortality. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the transmural dispersion of repolarization and that increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. The aim of this study was to evaluate ventricular repolarization by using Tp-e interval and Tp-e/QT ratio in patients with non-dipper hypertension. This study included 80 hypertensive patients. Hypertensive patients were divided into two groups: 50 dipper patients (29 male, mean age 51.5 ± 8 years) and 30 non-dipper patients (17 male, mean age 50.6 ± 5.4 years). Tp-e interval and Tp-e/QT ratio were measured from the 12-lead electrocardiogram. These parameters were compared between groups. No statistically significant difference was found between two groups in terms of basic characteristics. In electrocardiographic parameters analysis, QT dispersion (QTd) and corrected QTd were significantly increased in non-dipper patients compared to the dippers (39.4 ± 11.5 versus 27.3 ± 7.5 ms and 37.5 ± 9.5 versus 29.2 ± 6.5 ms, p = 0.001 and p = 0.01, respectively). Tp-e interval and Tp-e/QT ratio were also significantly higher in non-dipper patients (97.5 ± 11.2 versus 84.2 ± 8.3 ms and 0.23 ± 0.02 versus 0.17 ± 0.02, all p value <0.001). Our study revealed that QTd, Tp-e interval and Tp-e/QT ratio are prolonged in patients with non-dipper hypertension.

The time course of face processing: startle eyeblink response modulation by face gender and expression.

PubMed

Duval, Elizabeth R; Lovelace, Christopher T; Aarant, Justin; Filion, Diane L

2013-12-01

The purpose of this study was to investigate the effects of both facial expression and face gender on startle eyeblink response patterns at varying lead intervals (300, 800, and 3500ms) indicative of attentional and emotional processes. We aimed to determine whether responses to affective faces map onto the Defense Cascade Model (Lang et al., 1997) to better understand the stages of processing during affective face viewing. At 300ms, there was an interaction between face expression and face gender with female happy and neutral faces and male angry faces producing inhibited startle. At 3500ms, there was a trend for facilitated startle during angry compared to neutral faces. These findings suggest that affective expressions are perceived differently in male and female faces, especially at short lead intervals. Future studies investigating face processing should take both face gender and expression into account. © 2013.

Filtering Drifter Trajectories Sampled at Submesoscale Resolution

DTIC Science & Technology

2015-07-10

interval 5 min and a positioning error 1.5 m, the acceleration error is 4 10 m/s , a value comparable with the typical Coriolis acceleration of a water...10 ms , corresponding to the Coriolis acceleration experi- enced by a water parcel traveling at a speed of 2.2 m/s. This value corresponds to the...computed by integrating the NCOM velocity field contaminated by a random walk process whose effective dispersion coefficient (150 m /s) was specified as the

Lack of effect of perampanel on QT interval duration: Results from a thorough QT analysis and pooled partial seizure Phase III clinical trials.

PubMed

Yang, Haichen; Laurenza, Antonio; Williams, Betsy; Patten, Anna; Hussein, Ziad; Ferry, Jim

2015-08-01

Perampanel is a selective, noncompetitive AMPA receptor antagonist approved as adjunctive treatment for partial seizures. To assess potential for delayed cardiac repolarization, a Phase I thorough QT study was performed, supplemented by plasma concentration-QT data modeled from 3 pooled Phase III studies. The Phase I thorough QT study (double-blind, combined fixed-sequence, parallel-group) quantified the effect of perampanel (6 mg once daily for 7 days, followed by dose escalation to a single 8-mg dose, a single 10-mg dose, then 12 mg once daily for 7 days), moxifloxacin positive control (single 400-mg dose on Day 16), and placebo on QT interval duration in healthy subjects (N = 261). Electrocardiograms were recorded at baseline, Day 7 (post 6 mg dose), and Day 16 (post 12 mg dose). Statistical comparisons were between the highest approved perampanel dose (12 mg) versus placebo, a "mid-therapeutic" dose (6 mg) versus placebo, and moxifloxacin versus placebo. Acknowledging that the Phase I thorough QT study could not incorporate a true "supratherapeutic" dose due to length of titration and tolerability concerns in healthy subjects, Phase III studies of perampanel included expanded electrocardiogram safety evaluations specifically intended to support concentration-QT response modeling. The lack of effect of perampanel on the QT interval is shown from pooled analysis of 3 double-blind, placebo-controlled, 19-week, Phase III studies with perampanel doses ≤ 12 mg (N = 1038, total perampanel; and N=442, placebo) in patients with partial seizures. QT measures were corrected for heart rate using Fridericia's (QTcF; the primary endpoint) and Bazett's (QTcB) formulas. In the Phase I thorough QT study, the positive control moxifloxacin caused peak time-matched, baseline-adjusted, placebo-corrected (ΔΔ) QTcF of 12.15 ms at 4h postdose, confirming a drug effect on QTc interval and study assessment sensitivity. Mean baseline-adjusted (Δ) QTcF versus nominal time curves were comparable between perampanel 12 mg and placebo, with most ΔQTcF values being slightly negative. Healthy subjects receiving perampanel 6 and 12 mg doses for 7 days showed no evidence of effects on cardiac repolarization. Peak ΔΔQTcF was 2.34 ms at 1.5h postdose for perampanel 6 mg and 3.92 ms at 0.5h postdose for perampanel 12 mg. At every time point, the upper 95% confidence limit of ΔΔQTcF for perampanel 6 and 12 mg was <10 ms. Phase III studies revealed no clinically significant difference between patients with partial seizures treated with perampanel or placebo in QTcF and QTcB values >450 ms, with no dose-dependent increases or large incremental changes from baseline of >60 ms. Regression analysis of individual plasma perampanel concentrations versus corresponding QTc interval values in Phase I thorough QT and Phase III studies demonstrated no relationship between perampanel concentrations and QT interval duration. Treatment with perampanel 6 mg and 12 mg for 7 days did not delay cardiac repolarization in healthy volunteers. In a population analysis of 1480 patients with partial seizures treated with perampanel doses ≤ 12 mg or placebo, no clinically significant trends in QT interval data were noted. Based on the thorough QT study and evaluations from pooled Phase III studies, there is no evidence of prolonged QT interval duration with perampanel treatment. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Determination of eight pesticides in Lycium barbarum by LC-MS/MS and dietary risk assessment.

PubMed

Fu, Yan; Yang, Ting; Zhao, Jian; Zhang, Liang; Chen, Ruoxia; Wu, Yinliang

2017-03-01

A LC-MS/MS method for determination of eight pesticides (triadimefon, sulfoxaflor, flusilazole, tebuconazole, difenoconazole, amitraz, azoxystrobin, and thiophanate-methyl) in Lycium barbarum was established. The samples were extracted with acetonitrile, and then cleaned up by primary secondary amine. The extracts were diluted with 0.1% formic acid in water. The results showed that at the fortified levels of 0.01-10mg/kg, the average recoveries of these pesticides ranged from 82.1% to 96.2% with the relative standard deviations lower than 7%. The half-lives of eight pesticides were 1.3-5.0days in Lycium barbarum fruits. The pre-harvest interval of all pesticides mentioned above were investigated. Tebuconazole (14days), sulfoxaflor (14days) and flusilazole (28days) have longer pre-harvest interval than the others which have 7days. The dietary risks, assessed as hazard quotients, were far below 100%. The results showed that the eight pesticides applied to Lycium barbarum were comparably safe for the consumer. Copyright © 2016 Elsevier Ltd. All rights reserved.

Age effects on discrimination of timing in auditory sequences

NASA Astrophysics Data System (ADS)

Fitzgibbons, Peter J.; Gordon-Salant, Sandra

2004-08-01

The experiments examined age-related changes in temporal sensitivity to increments in the interonset intervals (IOI) of components in tonal sequences. Discrimination was examined using reference sequences consisting of five 50-ms tones separated by silent intervals; tone frequencies were either fixed at 4 kHz or varied within a 2-4-kHz range to produce spectrally complex patterns. The tonal IOIs within the reference sequences were either equal (200 or 600 ms) or varied individually with an average value of 200 or 600 ms to produce temporally complex patterns. The difference limen (DL) for increments of IOI was measured. Comparison sequences featured either equal increments in all tonal IOIs or increments in a single target IOI, with the sequential location of the target changing randomly across trials. Four groups of younger and older adults with and without sensorineural hearing loss participated. Results indicated that DLs for uniform changes of sequence rate were smaller than DLs for single target intervals, with the largest DLs observed for single targets embedded within temporally complex sequences. Older listeners performed more poorly than younger listeners in all conditions, but the largest age-related differences were observed for temporally complex stimulus conditions. No systematic effects of hearing loss were observed.

QTc prolongation after brain surgery.

PubMed

Capparelli, Federico J; Abello, Mauricio; Patricio Maskin, L; Arista, Eugenia; Hlavnicka, Alejandro; Diaz, Maria Fernanda; Varela, Daniel; Wainsztein, Nestor A

2013-03-01

Abnormalities observed in the electrocardiogram (ECG) after acute central nervous system (CNS) events have been reported. Our objective was to assess the incidence of heart rate-corrected QT interval (QTc) prolongation in patients admitted to the intensive care unit (ICU) after brain surgery. Admission standard 12-lead ECGs were analyzed blinded to patient data. The QT interval was measured and Bazzett's formula was used to obtain QTc. Prolonged QTc was defined as ≧450 ms. We included 114 patients in the study. The mean age was 49±17 years. Brain neoplasm was the surgical indication in 90% of the patients. The mean QTc was 470±42 ms. Prolonged QTc was found in 71% patients. The heart rate-corrected QT interval was between 450 ms and 500 ms in 52% and >500 ms in 19% of the patients. The heart rate and concentration of serum glucose were higher in the prolonged QTc group. Only 7·5% of all patients had hypokalemia (≤3 mEq/l). In the prolonged QTc group 9·2% had hypokalemia compared to 3·2% in normal QTc patients (P = 0·406). There were no significant associations between categories of QTc and the serum levels of creatinine, magnesium, calcium, sodium, or pH. Phenytoin and metoclopramide were not frequently used in patients with prolonged QTc. This study supports our hypothesis that prolonged QTc is frequently observed after a brain surgery. Hypokalemia, hypocalcaemia, and drugs such as metoclopramide or phenytoin could not explain the high incidence of prolonged QTc. Brain injury during a surgical procedure may be one of the primary causes of QTc prolongation after neurosurgery.

The Fine Temporal Structure of the Rat Licking Pattern: What Causes the Variabiliy in the Interlick Intervals and How is it Affected by the Drinking Solution?

PubMed Central

2013-01-01

Licking is a repetitive behavior controlled by a central pattern generator. Even though interlick intervals (ILIs) within bursts of licks are considered fairly regular, the conditions that affect their variability are unknown. We analyzed the licking pattern in rats that licked water, 10% sucrose solution, or 10% ethanol solution, in 90-min recording sessions after 4h of water deprivation. The histograms of ILIs indicate that licking typically occurred at a preferred ILI of about 130−140ms with evidence of bimodal or multimodal distributions due to occasional licking failures. We found that the longer the pause between bursts of licks, the shorter was the first ILI of the burst. When bursts of licks were preceded by a pause >4 s, the ILI was the shortest (~110ms) at the beginning of the burst, and then it increased rapidly in the first few licks and slowly in subsequent licks. Interestingly, the first ILI of a burst of licks was not significantly different when licking any of the 3 solutions, but subsequent licks exhibited a temporal pattern characteristic of each solution. The rapid deceleration in intraburst licking rate was due to an increase from ~27ms to ~56ms in the tongue-spout contact duration while the intercontact interval was only slightly changed (80−90ms). Therefore, the contact duration seems to be the major factor that increases the variability in the ILIs and could be another means for the rat to adjust the amount of fluid ingested in each individual lick. PMID:23902635

Effects of atomoxetine on the QT interval in healthy CYP2D6 poor metabolizers

PubMed Central

Loghin, Corina; Haber, Harry; Beasley, Charles M; Kothare, Prajakti A; Kauffman, Lynnette; April, John; Jin, Ling; Allen, Albert J; Mitchell, Malcolm I

2013-01-01

Aim The effects of atomoxetine (20 and 60 mg twice daily), 400 mg moxifloxacin and placebo on QTc in 131 healthy CYP2D6 poor metabolizer males were compared. Methods Atomoxetine doses were selected to result in plasma concentrations that approximated expected plasma concentrations at both the maximum recommended dose and at a supratherapeutic dose in CYP2D6 extensive metabolizers. Ten second electrocardiograms were obtained for time-matched baseline on days −2 and −1, three time points after dosing on day 1 for moxifloxacin and five time points on day 7 for atomoxetine and placebo. Maximum mean placebo-subtracted change from baseline model-corrected QT (QTcM) on day 7 was the primary endpoint. Results QTcM differences for atomoxetine 20 and 60 mg twice daily were 0.5 ms (upper bound of the one-sided 95% confidence interval 2.2 ms) and 4.2 ms (upper bound of the one-sided 95% confidence interval 6.0 ms), respectively. As plasma concentration of atomoxetine increased, a statistically significant increase in QTc was observed. The moxifloxacin difference from placebo met the a priori definition of non-inferiority. Maximum mean placebo-subtracted change from baseline QTcM for moxifloxacin was 4.8 ms and this difference was statistically significant. Moxifloxacin plasma concentrations were below the concentrations expected from the literature. However, the slope of the plasma concentration−QTc change observed was consistent with the literature. Conclusion Atomoxetine was not associated with a clinically significant change in QTc. However, a statistically significant increase in QTc was associated with increasing plasma concentrations. PMID:22803597

Cardiac repolarization during fingolimod treatment in patients with relapsing-remitting multiple sclerosis.

PubMed

Laiho, Aapo; Laitinen, Tiina M; Hartikainen, Päivi; Hartikainen, Juha E K; Laitinen, Tomi P; Simula, Sakari

2018-02-01

Fingolimod is a sphingosine-1-phosphate receptor modulator for the treatment of relapsing-remitting multiple sclerosis (RRMS). Despite an established effect on heart rate, the effect of fingolimod on cardiac repolarization is not completely known. Twenty-seven patients with RRMS underwent 24-hr ambulatory ECG before fingolimod (baseline), at the day of fingolimod initiation (1D) and after three-month treatment (3M). The mean values of RR-interval as well as QT-interval corrected by Bazzet's (QTcBaz) and Fridericia's (QTcFri) formula were compared between baseline, 1D, and 3M over 24-hr period as well as at daytime and nighttime. QTcBaz over 24-hr was shorter at 1D (414 ± 20 ms, p  < .001) and at 3M (414 ± 20 ms, p  < .001) than at baseline (418 ± 20 ms). In contrast, QTcFri over 24-hr was longer at 1D (410 ± 19 ms, p  < .001) but similar at 3M (406 ± 19 ms, p  = .355) compared to baseline (407 ± 19 ms). Daytime QTcBaz was shorter at 1D ( p  < .001) and at 3M ( p  = .007), whereas daytime QTcFri was longer at 1D ( p  < .05) but similar at 3M ( p  = ns) compared to baseline. During the night, changes were observed neither in QTcBaz nor in QTcFri between baseline, 1D, and 3M. Changes in cardiac repolarization after fingolimod initiation were mild and occurred at daytime. Ambiguously, QTcBaz demonstrated shortening, whereas QTcFri showed prolongation in cardiac repolarization after fingolimod initiation. The formula applied for QT-interval correction needs to be taken carefully into account as evaluating pharmacovigilance issues related to fingolimod.

Long QT interval in Turner syndrome--a high prevalence of LQTS gene mutations.

PubMed

Trolle, Christian; Mortensen, Kristian H; Pedersen, Lisbeth N; Berglund, Agnethe; Jensen, Henrik K; Andersen, Niels H; Gravholt, Claus H

2013-01-01

QT-interval prolongation of unknown aetiology is common in Turner syndrome. This study set out to explore the presence of known long QT mutations in Turner syndrome and to examine the corrected QT-interval (QTc) over time and relate the findings to the Turner syndrome phenotype. Adult women with Turner syndrome (n = 88) were examined thrice and 68 age-matched healthy controls were examined once. QTc was measured by one blinded reader (intra-reader variability: 0.7%), and adjusted for influence of heart rate by Bazett's (bQTc) and Hodges's formula (hQTc). The prevalence of mutations in genes related to Long QT syndrome was determined in women with Turner syndrome and a QTc >432.0 milliseconds (ms). Echocardiographic assessment of aortic valve morphology, 24-hour blood pressures and blood samples were done. The mean hQTc in women with Turner syndrome (414.0 ± 25.5 ms) compared to controls (390.4 ± 17.8 ms) was prolonged (p<0.001) and did not change over time (416.9 ± 22.6 vs. 415.6 ± 25.5 ms; p =0.4). 45,X karyotype was associated with increased hQTc prolongation compared to other Turner syndrome karyotypes (418.2 ± 24.8 vs. 407.6 ± 25.5 ms; p = 0.055). In women with Turner syndrome and a bQTc >432 ms, 7 had mutations in major Long QT syndrome genes (SCN5A and KCNH2) and one in a minor Long QT syndrome gene (KCNE2). There is a high prevalence of mutations in the major LQTS genes in women with TS and prolonged QTc. It remains to be settled, whether these findings are related to the unexplained excess mortality in Turner women. NCT00624949. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol/sid/S0001FLI/selectaction/View/ts/3/uid/U000099E.

A preliminary study on postmortem interval estimation of suffocated rats by GC-MS/MS-based plasma metabolic profiling.

PubMed

Sato, Takako; Zaitsu, Kei; Tsuboi, Kento; Nomura, Masakatsu; Kusano, Maiko; Shima, Noriaki; Abe, Shuntaro; Ishii, Akira; Tsuchihashi, Hitoshi; Suzuki, Koichi

2015-05-01

Estimation of postmortem interval (PMI) is an important goal in judicial autopsy. Although many approaches can estimate PMI through physical findings and biochemical tests, accurate PMI calculation by these conventional methods remains difficult because PMI is readily affected by surrounding conditions, such as ambient temperature and humidity. In this study, Sprague-Dawley (SD) rats (10 weeks) were sacrificed by suffocation, and blood was collected by dissection at various time intervals (0, 3, 6, 12, 24, and 48 h; n = 6) after death. A total of 70 endogenous metabolites were detected in plasma by gas chromatography-tandem mass spectrometry (GC-MS/MS). Each time group was separated from each other on the principal component analysis (PCA) score plot, suggesting that the various endogenous metabolites changed with time after death. To prepare a prediction model of a PMI, a partial least squares (or projection to latent structure, PLS) regression model was constructed using the levels of significantly different metabolites determined by variable importance in the projection (VIP) score and the Kruskal-Wallis test (P < 0.05). Because the constructed PLS regression model could successfully predict each PMI, this model was validated with another validation set (n = 3). In conclusion, plasma metabolic profiling demonstrated its ability to successfully estimate PMI under a certain condition. This result can be considered to be the first step for using the metabolomics method in future forensic casework.

Comparing neuronal spike trains with inhomogeneous Poisson distribution: evaluation procedure and experimental application in cases of cyclic activity.

PubMed

Fiore, Lorenzo; Lorenzetti, Walter; Ratti, Giovannino

2005-11-30

A procedure is proposed to compare single-unit spiking activity elicited in repetitive cycles with an inhomogeneous Poisson process (IPP). Each spike sequence in a cycle is discretized and represented as a point process on a circle. The interspike interval probability density predicted for an IPP is computed on the basis of the experimental firing probability density; differences from the experimental interval distribution are assessed. This procedure was applied to spike trains which were repetitively induced by opening-closing movements of the distal article of a lobster leg. As expected, the density of short interspike intervals, less than 20-40 ms in length, was found to lie greatly below the level predicted for an IPP, reflecting the occurrence of the refractory period. Conversely, longer intervals, ranging from 20-40 to 100-120 ms, were markedly more abundant than expected; this provided evidence for a time window of increased tendency to fire again after a spike. Less consistently, a weak depression of spike generation was observed for longer intervals. A Monte Carlo procedure, implemented for comparison, produced quite similar results, but was slightly less precise and more demanding as concerns computation time.

Ventricular repolarization alterations in women with angina pectoris and suspected coronary microvascular dysfunction.

PubMed

Dose, Nynne; Michelsen, Marie Mide; Mygind, Naja Dam; Pena, Adam; Ellervik, Christina; Hansen, Peter R; Kanters, Jørgen K; Prescott, Eva; Kastrup, Jens; Gustafsson, Ida; Hansen, Henrik Steen

CMD could be the explanation of angina pectoris with no obstructive CAD and may cause ventricular repolarization changes. We compared T-wave morphology and QTc interval in women with angina pectoris with a control group as well as the associations with CMD. Women with angina pectoris and no obstructive coronary artery disease (n=138) and age-matched controls were compared in regard to QTc interval and morphology combination score (MCS) based on T-wave asymmetry, flatness and presence of T-wave notch. CMD was assessed as a coronary flow velocity reserve (CFVR) by transthoracic echocardiography. Women with angina pectoris had significantly longer QTc intervals (429±20ms) and increased MCS (IQR) (0.73 [0.64-0.80]) compared with the controls (419±20ms) and (0.63 [(0.53-0.73]), respectively (both p<0.001). CFVR was associated with longer QTc interval (p=0.02), but the association was attenuated after multivariable adjustment (p=0.08). This study suggests that women with angina pectoris have alterations in T-wave morphology as well as longer QTc interval compared with a reference population. CMD might be an explanation. Copyright © 2017 Elsevier Inc. All rights reserved.

Adults' age-related differences in strategy perseveration are modulated by response-stimulus intervals and problem features.

PubMed

Lemaire, Patrick; Brun, Fleur

2014-10-01

Ageing results in the tendency of older adults to repeat the same strategy across consecutive problems more often than young adults, even when such strategy perseveration is not appropriate. Here, we examined how these age-related differences in strategy perseveration are modulated by response-stimulus intervals and problem characteristics. We asked participants to select the best strategy while accomplishing a computational estimation task (i.e., provide approximate sums to two-digit addition problems like 38 + 74). We found that participants repeated the same strategy across consecutive problems more often when the duration between their response and next problem display was short (300 ms) than when it was long (1300 ms). We also found more strategy perseverations in older than in young adults under short Response-Stimulus Intervals, but not under long Response-Stimulus Intervals. Finally, age-related differences in strategy perseveration decreased when problem features helped participants to select the best strategy. These modulations of age-related differences in strategy perseveration by response-stimulus intervals and characteristics of target problems are important for furthering our understanding of mechanisms underlying strategy perseveration and, more generally, ageing effects on strategy selection.

Tachycardia-dependent augmentation of "notched J waves" in a general patient population without ventricular fibrillation or cardiac arrest: not a repolarization but a depolarization abnormality?

PubMed

Aizawa, Yoshifusa; Sato, Masahito; Kitazawa, Hitoshi; Aizawa, Yoshiyasu; Takatsuki, Seiji; Oda, Eiji; Okabe, Masaaki; Fukuda, Keiichi

2015-02-01

J waves can be observed in individuals of the general population, but electrocardiographic characteristics are poorly understood. The purpose of this study was to examine the J-wave dynamicity in a general patient population. The responses of J waves (>0.1 mV above the isoelectric line in 2 contiguous leads) to varying RR intervals were analyzed. Patients with aborted sudden cardiac death, documented ventricular fibrillation, or a family history of sudden cardiac death were excluded. The J-wave amplitude was measured at baseline, in beats with short RR intervals in conducted atrial premature beats (APBs) or atrial stimulation during the electrophysiology study, and in the beats next to APBs with prolonged RR intervals. Mainly notched J waves were identified in 94 of 701 (24.5%) general patients (13.4%), and APBs were present in 23 of 94 (24.5%) patients. The mean baseline amplitude of J waves was 0.20 ± 0.06 mV at the baseline RR interval of 853 ± 152 ms, 0.25 ± 0.11 mV at the RR interval in the conducted APB of 545 ± 133 ms (P = .0018), and 0.19 ± 0.08 mV at the RR interval of 1146 ± 314 ms (P = .3102). The clinical characteristics were not different between patients with and without tachycardia-dependent augmentation of J waves. Augmentation of J waves was confirmed by the electrophysiology study: 0.28 ± 0.12 mV vs 0.42 ± 0.11 mV at baseline and in the beats of atrial stimulation, respectively (P = .0001). However, no bradycardia-dependent augmentation (>0.05 mV) was observed. Such tachycardia-dependent augmentation can represent depolarization abnormality rather than repolarization abnormality. J waves in a general patient population were augmented at shorter RR intervals, but not at prolonged RR intervals. Mechanistically, conduction delay is most likely responsible for this. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Characteristics in childhood and adolescence associated with future multiple sclerosis risk in men: cohort study.

PubMed

Gunnarsson, M; Udumyan, R; Bahmanyar, S; Nilsagård, Y; Montgomery, S

2015-07-01

Associations with multiple sclerosis (MS) of living conditions in childhood and characteristics in adolescence including physical fitness, cognitive function and psychological stress resilience were investigated. A cohort of male Swedish residents born 1952-1956 who were included in the Swedish Military Conscription Register was used to create a nested case-control study comprising 628 MS cases and 6187 controls matched on birth year, county of residence and vital status at time of diagnosis. Conscription examination records were linked with other national register data. Conditional logistic regression was used to evaluate associations with MS subsequent to the conscription examination. Men with MS were less likely to be from more crowded households in childhood (>two persons per room) with an adjusted odds ratio of 0.67 (95% confidence interval 0.51-0.86, P = 0.023). They had lower physical working capacity in adolescence with adjusted odds ratio of 0.94 (95% confidence interval 0.89-0.99, P = 0.026). Cognitive function and stress resilience scores displayed no significant differences between cases and controls. Parental occupation in childhood and body mass index in adolescence were not associated with future MS risk. The inverse association of MS risk with higher levels of household crowding may reflect environmental factors such as the pattern of exposure to microorganisms. Lower physical fitness in men at MS risk may indicate a protective effect of exercise or could be due to prodromal disease activity, although there was no association with cognitive function. Poor psychological stress resilience (and thus risk of chronic stress arousal) was not associated with MS. © 2015 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

Radioimmunoassay and tandem mass spectrometry measurement of bedtime salivary cortisol levels: a comparison of assays to establish hypercortisolism.

PubMed

Baid, Smita K; Sinaii, Ninet; Wade, Matt; Rubino, Domenica; Nieman, Lynnette K

2007-08-01

Although bedtime salivary cortisol measurement has been proposed as the optimal screening test for the diagnosis of Cushing's syndrome, its performance using commercially available assays has not been widely evaluated. Our objective was to compare RIA and tandem mass spectrometry (LC-MS/MS) measurement of salivary cortisol in obese subjects and healthy volunteers. We conducted a cross-sectional prospective study of outpatients. We studied 261 obese subjects (186 female) with at least two additional features of Cushing's syndrome and 60 healthy volunteers (30 female). Subjects provided split bedtime salivary samples for cortisol measurement by commercially available RIA and LC-MS/MS. Results were considered normal or abnormal based on the laboratory reference range. Subjects with abnormal results underwent evaluation for Cushing's syndrome. In paired samples, RIA gave a lower specificity than LC-MS/MS in obese subjects (86 vs. 94%, P = 0.008) but not healthy volunteers (86 vs. 82%, P = 0.71). Among subjects with at least one abnormal result, both values were abnormal in 44% (confidence interval 26-62%) of obese and 75% (confidence interval 33-96%) of healthy volunteers. In obese subjects, salivary cortisol concentrations were less than 4.0 to 643 ng/dl (<0.11-17.7 nmol/liter; normal, < or =100 ng/dl, 2.80 nmol/liter) by LC-MS/MS and less than 50 to 2800 ng/dl (1.4-77.3 nmol/liter; normal, < or =170 ng/dl, 4.7 nmol/liter) by RIA. Cushing's syndrome was not diagnosed in any subject. Salivary cortisol levels should not be used as the sole test to diagnose Cushing's syndrome if laboratory-provided reference ranges are used for diagnostic interpretation.

Pharmacokinetics and repolarization effects of intravenous and transdermal granisetron.

PubMed

Mason, Jay W; Selness, Daniel S; Moon, Thomas E; O'Mahony, Bridget; Donachie, Peter; Howell, Julian

2012-05-15

The need for greater clarity about the effects of 5-HT(3) receptor antagonists on cardiac repolarization is apparent in the changing product labeling across this therapeutic class. This study assessed the repolarization effects of granisetron, a 5-HT(3) receptor antagonist antiemetic, administered intravenously and by a granisetron transdermal system (GTDS). In a parallel four-arm study, healthy subjects were randomized to receive intravenous granisetron, GTDS, placebo, or oral moxifloxacin (active control). The primary endpoint was difference in change from baseline in mean Fridericia-corrected QT interval (QTcF) between GTDS and placebo (ddQTcF) on days 3 and 5. A total of 240 subjects were enrolled, 60 in each group. Adequate sensitivity for detection of QTc change was shown by a 5.75 ms lower bound of the 90% confidence interval (CI) for moxifloxacin versus placebo at 2 hours postdose on day 3. Day 3 ddQTcF values varied between 0.2 and 1.9 ms for GTDS (maximum upper bound of 90% CI, 6.88 ms), between -1.2 and 1.6 ms for i.v. granisetron (maximum upper bound of 90% CI, 5.86 ms), and between -3.4 and 4.7 ms for moxifloxacin (maximum upper bound of 90% CI, 13.45 ms). Day 5 findings were similar. Pharmacokinetic-ddQTcF modeling showed a minimally positive slope of 0.157 ms/(ng/mL), but a very low correlation (r = 0.090). GTDS was not associated with statistically or clinically significant effects on QTcF or other electrocardiographic variables. This study provides useful clarification on the effect of granisetron delivered by GTDS on cardiac repolarization. ©2012 AACR.

In-Hospital Haloperidol Use and Perioperative Changes in QTc-Duration.

PubMed

Blom, M T; Jansen, S; de Jonghe, A; van Munster, B C; de Boer, A; de Rooij, S E; Tan, H L; van der Velde, N

2015-05-01

Haloperidol may prolong ECG QTc-duration but is often prescribed perioperatively to hip-fracture patients. We aimed to determine (1) how QTc-duration changes perioperatively, (2) whether low-dose haloperidol-use influences these changes, and (3) which clinical variables are associated with potentially dangerous perioperative QTc-prolongation (PD-QTc; increase >50 ms or to >500 ms). Prospective cohort study. Tertiary university teaching-hospital. Patients enrolled in a randomized controlled clinical trial of melatonin versus placebo on occurrence of delirium in hip-fracture patients. Data from ECGs made before and after hip surgery (1-3 days and/or 4-6 days post-surgery) were analyzed. QTc-duration was measured by hand, blinded for haloperidol and pre/post-surgery status. Clinical variables were measured at baseline. Mixed model analysis was used to estimate changes in QTc-duration. Risk-factors for PD-QTc were estimated by logistic regression analysis. We included 89 patients (mean age 84 years, 24% male); 39 were treated with haloperidol. Patients with normal pre-surgery QTc-duration (male ≤430 ms, female ≤450 ms) had a significant increase (mean 12 ms, SD 28) in QTc-duration. A significant decrease (mean 19 ms, SD 34) occurred in patients with prolonged pre-surgery QTc-duration (male >450ms, female >470 ms). Haloperidol-use did not influence the perioperative course of the QTc-interval (p=0.351). PD-QTc (n=8) was not associated with any of the measured risk-factors. QTc-duration changed differentially, increasing in patients with normal, but decreasing in patients with abnormal baseline QTc-duration. PD-QTc was not associated with haloperidol-use or other risk-factors. Low-dose oral haloperidol did not affect perioperative QTc-interval.

Low proarrhythmic potential of citalopram and escitalopram in contrast to haloperidol in an experimental whole-heart model.

PubMed

Frommeyer, Gerrit; Brücher, Benedict; von der Ahe, Henning; Kaese, Sven; Dechering, Dirk G; Kochhäuser, Simon; Bogossian, Harilaos; Milberg, Peter; Eckardt, Lars

2016-10-05

In several case reports proarrhythmic effects of citalopram and escitalopram have been reported. Systematic analyses on prorarrhythmic effects of these drugs are not yet available. The aim of the present study was to investigate if application of citalopram, escitalopram or haloperidol provokes polymorphic ventricular tachycardia in a sensitive model of proarrhythmia. In isolated rabbit hearts monophasic action potentials and ECG showed a significant QT-prolongation after application of citalopram (2µM: +47ms, 4µM: +56ms, P<0.05) accompanied by an increase of action potential duration (APD) but not dispersion of repolarization. Reduced potassium concentration in bradycardic AV-blocked hearts provoked early afterdepolarizations (EAD) in 2 of 12 hearts but no polymorphic ventricular tachycardia (pVT). Application of escitalopram also increased QT-interval (2µM: +3ms, 4µM: +30ms, P<0.05) and APD without effects on dispersion. 3 of 10 hearts showed EAD and pVT in 2 of 10 hearts (32 episodes). The results were compared to 12 rabbits treated with haloperidol which led to an increase in QT-interval (1µM:+62ms; 2µM:+96ms; P<0.01), APD and dispersion (1µM:+15ms, 2µM:+40ms; P<0.01) and induced EAD in all 12 and pVT in 10 of 12 hearts (152 episodes). Citalopram and escitalopram demonstrated a rather safe electrophysiologic profile despite significant QT prolongation. In contrast, haloperidol led to significant increase of dispersion of repolarization while this parameter remained stable under the influence of citalopram or escitalopram. These results imply that application of citalopram or escitalopram is not as proarrhythmic as some case reports might suggest while haloperidol is torsadogenic. Copyright © 2016 Elsevier B.V. All rights reserved.

Early life stress impairs social recognition due to a blunted response of vasopressin release within the septum of adult male rats.

PubMed

Lukas, Michael; Bredewold, Remco; Landgraf, Rainer; Neumann, Inga D; Veenema, Alexa H

2011-07-01

Early life stress poses a risk for the development of psychopathologies characterized by disturbed emotional, social, and cognitive performance. We used maternal separation (MS, 3h daily, postnatal days 1-14) to test whether early life stress impairs social recognition performance in juvenile (5-week-old) and adult (16-week-old) male Wistar rats. Social recognition was tested in the social discrimination test and defined by increased investigation by the experimental rat towards a novel rat compared with a previously encountered rat. Juvenile control and MS rats demonstrated successful social recognition at inter-exposure intervals of 30 and 60 min. However, unlike adult control rats, adult MS rats failed to discriminate between a previously encountered and a novel rat after 60 min. The social recognition impairment of adult MS rats was accompanied by a lack of a rise in arginine vasopressin (AVP) release within the lateral septum seen during social memory acquisition in adult control rats. This blunted response of septal AVP release was social stimulus-specific because forced swimming induced a rise in septal AVP release in both control and MS rats. Retrodialysis of AVP (1 μg/ml, 3.3 μl/min, 30 min) into the lateral septum during social memory acquisition restored social recognition in adult MS rats at the 60-min interval. These studies demonstrate that MS impairs social recognition performance in adult rats, which is likely caused by blunted septal AVP activation. Impaired social recognition may be linked to MS-induced changes in other social behaviors like aggression as shown previously. Copyright © 2010 Elsevier Ltd. All rights reserved.

Accessory pathway location affects brain natriuretic peptide level in patients with Wolff-Parkinson-White syndrome.

PubMed

Nakatani, Yosuke; Kumagai, Koji; Naito, Shigeto; Nakamura, Kohki; Minami, Kentaro; Nakano, Masahiro; Sasaki, Takehito; Kinugawa, Koichiro; Oshima, Shigeru

2017-01-01

The purpose of this study was to investigate the relationship between the accessory pathway location and brain natriuretic peptide (BNP) level in patients with Wolff-Parkinson-White (WPW) syndrome. We divided 102 WPW syndrome patients with normal left ventricular systolic function into four groups: those with manifest right (MR, n = 14), manifest septal (MS, n = 11), manifest left (ML, n = 30), and concealed (C, n = 47) accessory pathways. BNP level and electrophysiological properties, including difference in timing of the ventricular electrogram between the His bundle area and the distal coronary sinus area (His-CS delay), which indicate intraventricular dyssynchrony, were compared. BNP levels (pg/dl) were higher in the MR and MS groups than in the ML and C groups (MR, 64 ± 58; MS, 55 ± 45; ML, 17 ± 15; C, 25 ± 21; P < 0.001). AV intervals (ms) were shorter in the MR and MS groups than in the ML and C groups (MR, 76 ± 16; MS, 83 ± 6; ML, 101 ± 19; C, 136 ± 20; P < 0.001). His-CS delay (ms) was longer in the MR group than in the other groups (MR, 50 ± 15; MS, 21 ± 7; ML, 23 ± 10; C, 19 ± 8; P < 0.001). The AV interval (P < 0.01) and the His-CS delay (P < 0.001) were negatively and positively correlated, respectively, with the BNP level. Anterograde conduction with a right or septal accessory pathway increased the BNP level in WPW syndrome patients with normal cardiac function.

Factors associated with recently transmitted Mycobacterium tuberculosis strain MS0006 in Hinds County, Mississippi.

PubMed

Temple, Brian; Kwara, Awewura; Sunesara, Imran; Mena, Leandro; Dobbs, Thomas; Henderson, Harold; Holcomb, Mike; Webb, Risa

2011-12-01

The objective of this study was to investigate risk factors associated with tuberculosis (TB) transmission that was caused by Mycobacterium tuberculosis strain MS0006 from 2004 to 2009 in Hinds County, Mississippi. DNA fingerprinting using spoligotyping, mycobacterial interspersed repetitive unit, and IS6110-based restriction fragment length polymorphism of culture-confirmed cases of TB was performed. Clinical and demographic factors associated with strain MS0006 were analyzed by univariate and multivariate analysis. Of the 144 cases of TB diagnosed during the study period, 117 were culture positive with fingerprints available. There were 48 different strains, of which 6 clustered strains were distributed among 74 patients. The MS0006 strain accounted for 46.2% of all culture-confirmed cases. Risk factors for having the MS0006 strain in a univariate analysis included homelessness, HIV co-infection, sputum smear negativity, tuberculin skin test negativity, and noninjectable drug use. Multivariate analysis identified homelessness (odds ratio 7.88, 95% confidence interval 2.90-21.35) and African American race (odds ratio 5.80, 95% confidence interval 1.37-24.55) as independent predictors of having TB caused by the MS0006 strain of M. tuberculosis. Our findings suggest that a majority of recently transmitted TB in the studied county was caused by the MS0006 strain. African American race and homelessness were significant risk factors for inclusion in the cluster. Molecular epidemiology techniques continue to provide in-depth analysis of disease transmission and play a vital role in effective contact tracing and interruption of ongoing transmission.

Palbociclib has no clinically relevant effect on the QTc interval in patients with advanced breast cancer.

PubMed

Durairaj, Chandrasekar; Ruiz-Garcia, Ana; Gauthier, Eric R; Huang, Xin; Lu, Dongrui R; Hoffman, Justin T; Finn, Richard S; Joy, Anil A; Ettl, Johannes; Rugo, Hope S; Zheng, Jenny; Wilner, Keith D; Wang, Diane D

2018-03-01

The aim of this study was to assess the potential effects of palbociclib in combination with letrozole on QTc. PALOMA-2, a phase 3, randomized, double-blind, placebo-controlled trial, compared palbociclib plus letrozole with placebo plus letrozole in postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. The study included a QTc evaluation substudy carried out as a definitive QT interval prolongation assessment for palbociclib. Time-matched triplicate ECGs were performed at 0, 2, 4, 6, and 8 h at baseline (Day 0) and on Cycle 1 Day 14. Additional ECGs were collected from all patients for safety monitoring. The QT interval was corrected for heart rate using Fridericia's correction (QTcF), Bazett's correction (QTcB), and a study-specific correction factor (QTcS). In total, 666 patients were randomized 2 : 1 to palbociclib plus letrozole or placebo plus letrozole. Of these, 125 patients were enrolled in the QTc evaluation substudy. No patients in the palbociclib plus letrozole arm of the substudy (N=77) had a maximum postbaseline QTcS or QTcF value of ≥ 480 ms, or a maximum increase from clock time-matched baseline for QTcS or QTcF values of ≥ 60 ms. The upper bounds of the one-sided 95% confidence interval for the mean change from time-matched baseline for QTcS, QTcF, and QTcB at all time points and at steady-state Cmax following repeated administration of 125 mg palbociclib were less than 10 ms. Palbociclib, when administered with letrozole at the recommended therapeutic dosing regimen, did not prolong the QT interval to a clinically relevant extent.

Capture of activation during ventricular arrhythmia using distributed stimulation.

PubMed

Meunier, Jason M; Ramalingam, Sanjiv; Lin, Shien-Fong; Patwardhan, Abhijit R

2007-04-01

Results of previous studies suggest that pacing strength stimuli can capture activation during ventricular arrhythmia locally near pacing sites. The existence of spatio-temporal distribution of excitable gap during arrhythmia suggests that multiple and timed stimuli delivered over a region may permit capture over larger areas. Our objective in this study was to evaluate the efficacy of using spatially distributed pacing (DP) to capture activation during ventricular arrhythmia. Data were obtained from rabbit hearts which were placed against a lattice of parallel wires through which biphasic pacing stimuli were delivered. Electrical activity was recorded optically. Pacing stimuli were delivered in sequence through the parallel wires starting with the wire closest to the apex and ending with one closest to the base. Inter-stimulus delay was based on conduction velocity. Time-frequency analysis of optical signals was used to determine variability in activation. A decrease in standard deviation of dominant frequencies of activation from a grid of locations that spanned the captured area and a concurrence with paced frequency were used as an index of capture. Results from five animals showed that the average standard deviation decreased from 0.81 Hz during arrhythmia to 0.66 Hz during DP at pacing cycle length of 125 ms (p = 0.03) reflecting decreased spatio-temporal variability in activation during DP. Results of time-frequency analysis during these pacing trials showed agreement between activation and paced frequencies. These results show that spatially distributed and timed stimulation can be used to modify and capture activation during ventricular arrhythmia.

Astronomical timescale calibration for the Permian-Triassic boundary transition interval from global correlation of cyclic marine sequences

NASA Astrophysics Data System (ADS)

Huang, C.; Hinnov, L. A.; Tong, J.; Chen, Z.

2011-12-01

The mass extinctions near the Permian-Triassic boundary (PTB) resulted in the greatest dying of life on Earth. The cause of this catastrophe remains enigmatic. High-resolution chronology is crucial to understanding the recorded pattern of biotic evolution and possible causes for the extinctions. Magnetic susceptibility (MS) data from Shangsi, South China shows evidence for astronomical forcing through the PTB interval, with strong 405-kyr cycling. This allows development of an astrochronology for the PTB interval based on the 405-kyr orbital eccentricity metronome that has been proposed for the Mesozoic timescale. Radioisotope dating combined with the 405-kyr tuned MS series from Shangsi shows that the 405-kyr-cycle predominates throughout the PTB interval. In the Permian segment, ~100-kyr cyclicity dominates, and the 100-kyr-scale MS maxima correlate with high-amplitude precession-scale MS variations. Minima in the ~1.5-Myr, 405-kyr and ~100-kyr cycles converge at 252.6 Ma, approximately 200 kyr before the onset of the main mass extinction near the PTB. In the Triassic aftermath, the recorded astronomical signal is different, with predominant 405-kyr cycles and loss of 100 kyr cyclicity, and appearance of ~33 kyr (obliquity scale) cyclicity; 100-kyr cyclicity strengthens again 2 Myr later. This pattern indicates a change in the response of the depositional environment (or magnetic susceptibility) to astronomical forcing before and after the mass extinction interval. The astrochronology interpolates the timescale between the radioisotopically determined absolute dates; this facilitates estimation of ages for specific events in the PTB crisis, including magnetic reversals, biozone boundaries, and the mass extinctions. An estimated ~700 kyr duration for the Mass Extinction Interval (MEI) at Shangsi based on the 405-kyr tuning is supported by eccentricity-tuned estimates of three other sections in China (Meishan, Huangzhishan, and Heping), and two Alpine sections (Gartnerkofel, Austria and Bulla, Italy) from the eastern and western margins of the Palaeo-Tethys Ocean during PTB time. This suggests that the PTB mass extinctions were not the result of a single catastrophic event. Siberian trap volcanism was largely synchronous with the MEI and appears to be the most likely cause of the mass extinctions; astronomically paced climate change may also have played a role.

Temporal Ventriloquism in a Purely Temporal Context

ERIC Educational Resources Information Center

Hartcher-O'Brien, Jessica; Alais, David

2011-01-01

This study examines how audiovisual signals are combined in time for a temporal analogue of the ventriloquist effect in a purely temporal context, that is, no spatial grounding of signals or other spatial facilitation. Observers were presented with two successive intervals, each defined by a 1250-ms tone, and indicated in which interval a brief…

Measurement of Phonated Intervals during Four Fluency-Inducing Conditions

ERIC Educational Resources Information Center

Davidow, Jason H.; Bothe, Anne K.; Andreatta, Richard D.; Ye, Jun

2009-01-01

Purpose: Previous investigations of persons who stutter have demonstrated changes in vocalization variables during fluency-inducing conditions (FICs). A series of studies has also shown that a reduction in short intervals of phonation, those from 30 to 200 ms, is associated with decreased stuttering. The purpose of this study, therefore, was to…

[Evaluation of autonomic nervous system function with heart rate variability analysis in patients with hyperthyroidism and during euthyroidism after pharmacologic and surgical treatment].

PubMed

Barczyński, M; Tabor, S; Thor, P

1997-01-01

The aim of the present study was both to estimate autonomic nervous system (ANS) function in patients with hyperthyroidism by the heart rate variability (HRV) analysis and to evaluate the impact of pharmacological and surgical treatment on the ANS function. Analysis of the HRV underwent 10 female patients in course of thyreotoxicosis and after reaching full clinical and biochemical euthyroidism, after pharmacological therapy and in month after surgical treatment. The 10 minutes records at rest, in horizontal position were evaluated. The HRV parameters like mean of the heart rate, mean of RR intervals, standard deviation of all normal RR intervals (SDNN), range of the heart rate variability, low frequency (LF), high frequency (HF) components of the heart rate power spectral density and LF/HF ratio were assessed. The results were compared to those obtained from 10 age-, sex-, and body mass index-matched control subjects. The statistical significance (p < 0.05) was found in reduction of range of RR intervals, in increase of LF/HF ratio and in decrease of SDNN in hyperthyroidism in comparison to the control group (151.6/346.8 ms; 2.4/0.74; 24.4/57.2 ms2). In course of pharmacological euthyroidism there were statistically significant (p < 0.05) increase of range of RR intervals, reduction of LF/HF ratio and increase of SDNN in comparison to hyperthyroidism (270/151.6 ms; 0.995/2.4; 39/24.4 ms2). In euthyroidism after surgical treatment all the above parameters kept the similar levels as in pharmacological euthyroidism (no statistical significance for p < 0.05). On the base of the outcomes it was considered that in hyperthyroid patients there is advantage of sympathetic part of ANS over parasympathetic one which is due to sharp reduction of parasympathetic system activity. Pharmacological therapy with thyreostatics normalises balance of ANS to the level of the control group and after surgical treatment the balance keeps the same. Moreover, in the estimation of ANS as important as LF/HF ratio is the mean range of RR intervals.

Grand average ERP-image plotting and statistics: A method for comparing variability in event-related single-trial EEG activities across subjects and conditions

PubMed Central

Delorme, Arnaud; Miyakoshi, Makoto; Jung, Tzyy-Ping; Makeig, Scott

2014-01-01

With the advent of modern computing methods, modeling trial-to-trial variability in biophysical recordings including electroencephalography (EEG) has become of increasingly interest. Yet no widely used method exists for comparing variability in ordered collections of single-trial data epochs across conditions and subjects. We have developed a method based on an ERP-image visualization tool in which potential, spectral power, or some other measure at each time point in a set of event-related single-trial data epochs are represented as color coded horizontal lines that are then stacked to form a 2-D colored image. Moving-window smoothing across trial epochs can make otherwise hidden event-related features in the data more perceptible. Stacking trials in different orders, for example ordered by subject reaction time, by context-related information such as inter-stimulus interval, or some other characteristic of the data (e.g., latency-window mean power or phase of some EEG source) can reveal aspects of the multifold complexities of trial-to-trial EEG data variability. This study demonstrates new methods for computing and visualizing grand ERP-image plots across subjects and for performing robust statistical testing on the resulting images. These methods have been implemented and made freely available in the EEGLAB signal-processing environment that we maintain and distribute. PMID:25447029

The role of iconic memory in change-detection tasks.

PubMed

Becker, M W; Pashler, H; Anstis, S M

2000-01-01

In three experiments, subjects attempted to detect the change of a single item in a visually presented array of items. Subjects' ability to detect a change was greatly reduced if a blank interstimulus interval (ISI) was inserted between the original array and an array in which one item had changed ('change blindness'). However, change detection improved when the location of the change was cued during the blank ISI. This suggests that people represent more information of a scene than change blindness might suggest. We test two possible hypotheses why, in the absence of a cue, this representation fails to produce good change detection. The first claims that the intervening events employed to create change blindness result in multiple neural transients which co-occur with the to-be-detected change. Poor detection rates occur because a serial search of all the transient locations is required to detect the change, during which time the representation of the original scene fades. The second claims that the occurrence of the second frame overwrites the representation of the first frame, unless that information is insulated against overwriting by attention. The results support the second hypothesis. We conclude that people may have a fairly rich visual representation of a scene while the scene is present, but fail to detect changes because they lack the ability to simultaneously represent two complete visual representations.

Neonatal and fetal response decrement of evoked responses – a MEG study

PubMed Central

Sheridan, Carolin J.; Preissl, Hubert; Siegel, Eric R.; Murphy, Pam; Ware, Maureen; Lowery, Curtis L.; Eswaran, Hari

2008-01-01

Objective To investigate the response decrements of visual evoked responses (VER) in newborns and assess the applicability of this paradigm to fetuses in magnetoencephalographic (MEG) recordings. Methods Twelve newborns with no known risks or complications participated at chronological ages between six and 22 days. They constituted the follow-up group to a prenatal study conducted on a sample of 25 fetuses whose gestational age (GA) varied between 29 and 37 weeks at the time of recording. Trains of four light flashes with an interstimulus interval of 2 s followed by 10 s without stimulation were delivered to record VER. Results Nine of the 12 newborns responded to the stimulation and showed response decrements in amplitude from the first to the last light flash. Furthermore, the response latency increased significantly from the first to the last stimulus. The remaining three recordings were discontinued early. Even though the prenatal visual evoked response rate was only 29%, the fetuses exhibited a response decrement after the first stimulus. Conclusions The amplitude of VERs can be used to elicit a response decrement in newborns and, with limitations, even in fetuses. This paradigm might be a useful tool for a direct non-invasive assessment of neonatal and prenatal brain development and CNS functioning. Significance The proposed method might be a first step towards an early detection of developmental deficits in newborns and fetuses. PMID:18226946

Effects of Passive Finger Movement on Cortical Excitability

PubMed Central

Nakagawa, Masaki; Sasaki, Ryoki; Tsuiki, Shota; Miyaguchi, Shota; Kojima, Sho; Saito, Kei; Inukai, Yasuto; Onishi, Hideaki

2017-01-01

This study examined the effects of joint angle and passive movement direction on corticospinal excitability. The subjects were 14 healthy adults from whom consent could be obtained. We performed two experiments. In Experiment 1, we measured motor evoked potential (MEP) amplitude, F-wave and M-wave at 0° and 20° adduction during adduction or abduction movement, in the range of movement from 10° abduction to 30° adduction. In Experiment 2, MEPs were measured at static 0° and 20° adduction during passive adduction from 10° adduction to 30° adduction and static 20° adduction. MEP, F-waves and M-waves were recorded from the right first dorsal interosseous (FDI) muscle. Experiment 1 revealed significantly increased MEP amplitude at 0° during passive adduction compared to static 0° (p < 0.01). No other significant differences in MEP, M-wave and F-wave parameters were observed. In Experiment 2, MEP amplitude was significantly higher at 20° adduction during passive adduction compared with static 0° (p < 0.01). Based on these findings, it appears that fluctuations in MEP amplitude values during passive movement are not influenced by joint angle, but rather it is possible that it is due to intracortical afferent facilitation (AF) dependent on afferent input due to the start of movement and interstimulus interval (ISI) of transcranial magnetic stimulation (TMS). PMID:28515687

Goal neglect, fluid intelligence and processing speed: Manipulating instruction load and inter-stimulus interval.

PubMed

Iveson, Matthew H; Della Sala, Sergio; Anderson, Mike; MacPherson, Sarah E

2017-05-01

Goal maintenance is the process where task rules and instructions are kept active to exert their control on behavior. When this process fails, an individual may ignore a rule while performing the task, despite being able to describe it after task completion. Previous research has suggested that the goal maintenance system is limited by the number of concurrent rules which can be maintained during a task, and that this limit is dependent on an individual's level of fluid intelligence. However, the speed at which an individual can process information may also limit their ability to use task rules when the task demands them. In the present study, four experiments manipulated the number of instructions to be maintained by younger and older adults and examined whether performance on a rapid letter-monitoring task was predicted by individual differences in fluid intelligence or processing speed. Fluid intelligence played little role in determining how frequently rules were ignored during the task, regardless of the number of rules to be maintained. In contrast, processing speed predicted the rate of goal neglect in older adults, where increasing the presentation rate of the letter-monitoring task increased goal neglect. These findings suggest that goal maintenance may be limited by the speed at which it can operate. Copyright © 2017. Published by Elsevier B.V.

Encoding vs. retention: differential effects of cue manipulation on working memory performance in schizophrenia.

PubMed

Javitt, Daniel C; Rabinowicz, Esther; Silipo, Gail; Dias, Elisa C

2007-03-01

Deficits in working memory performance are among the most widely replicated findings in schizophrenia. Roles of encoding vs. memory retention in working memory remain unresolved. The present study evaluated working memory performance in schizophrenia using an AX-type continuous performance test (AX-CPT) paradigm. Participants included 48 subjects with schizophrenia and 27 comparison subjects. Behavior was obtained in 3 versions of the task, which differed based upon ease of cue interoperability. In a simple cue version of the task, cue letters were replaced with red or green circles. In the complex cue version, letter/color conjunctions served as cues. In the base version of the task, patients showed increased rates of false alarms to invalidly cued targets, similar to prior reports. However, when the cue stimuli were replaced with green or red circles to ease interpretation, patients showed similar false alarm rates to controls. When feature conjunction cues were used, patients were also disproportionately affected relative to controls. No significant group by interstimulus interval interaction effects were observed in either the simple or complex cue conditions, suggesting normal retention of information even in the presence of overall performance decrements. These findings suggest first, that cue manipulation disproportionately affects AX-CPT performance in schizophrenia and, second, that substantial behavioral deficits may be observed on working memory tasks even in the absence of disturbances in mnemonic retention.

Side Effects of Being Blue: Influence of Sad Mood on Visual Statistical Learning

PubMed Central

Bertels, Julie; Demoulin, Catherine; Franco, Ana; Destrebecqz, Arnaud

2013-01-01

It is well established that mood influences many cognitive processes, such as learning and executive functions. Although statistical learning is assumed to be part of our daily life, as mood does, the influence of mood on statistical learning has never been investigated before. In the present study, a sad vs. neutral mood was induced to the participants through the listening of stories while they were exposed to a stream of visual shapes made up of the repeated presentation of four triplets, namely sequences of three shapes presented in a fixed order. Given that the inter-stimulus interval was held constant within and between triplets, the only cues available for triplet segmentation were the transitional probabilities between shapes. Direct and indirect measures of learning taken either immediately or 20 minutes after the exposure/mood induction phase revealed that participants learned the statistical regularities between shapes. Interestingly, although participants from the sad and neutral groups performed similarly in these tasks, subjective measures (confidence judgments taken after each trial) revealed that participants who experienced the sad mood induction showed increased conscious access to their statistical knowledge. These effects were not modulated by the time delay between the exposure/mood induction and the test phases. These results are discussed within the scope of the robustness principle and the influence of negative affects on processing style. PMID:23555797

Overcoming residual interference in mental set switching: Neural correlates and developmental trajectory

PubMed Central

Witt, Suzanne T.; Stevens, Michael C.

2012-01-01

Mental set switching is a key facet of executive control measured behaviorally through reaction time or accuracy (i.e., ‘switch costs’) when shifting among task types. One of several experimentally-dissociable influences on switch costs is ‘task set inertia’, conceptualized as the residual interference conferred when a previous stimulus-response tendency interferes with subsequent stimulus processing on a new task. Task set inertia is thought to represent the passive decay of the previous stimulus-response set from working memory, and its effects decrease with increased interstimulus interval. Closely spaced trials confer high task set inertia, while sparsely spaced trials confer low task set inertia. This functional magnetic resonance imaging (fMRI) study characterized, for the first time, two opposing brain systems engaged to resolve task set inertia: 1) a frontoparietal ‘cortical control’ network for overcoming high task set inertia interference and 2) a subcortical-motor network more active during trials with low task set inertia. These networks were distinct from brain regions showing general switching effects (i.e., switch > non-switch) and from other previously-characterized interference effects. Moreover, there were ongoing maturational effects throughout adolescence for the brain regions engaged to overcome high task set inertia not seen for generalized switching effects. These novel findings represent a new avenue of exploration of cognitive set switching neural function. PMID:22584223

Impaired semantic inhibition during lexical ambiguity repetition in Parkinson's disease.

PubMed

Copland, David A; Sefe, Gameli; Ashley, Jane; Hudson, Carrie; Chenery, Helen J

2009-09-01

Impairments of semantic processing and inhibition have been observed in Parkinson's disease (PD), however, the consequences of faulty meaning selection and suppression have not been considered in terms of subsequent lexical processing. The present study employed a lexical ambiguity repetition paradigm where the first presentation of an ambiguity paired with a target biasing its dominant or subordinate meaning (e.g., bank - money or bank - river) was followed after several intervening trials by a presentation of the same ambiguity paired with a different target that biases the same (congruent) or a different (incongruent) meaning to that biased on the first presentation. Meaning dominance (dominant or subordinate weaker meanings) and interstimulus interval (ISI) were manipulated. Analyses conducted on the second presentation indicated priming of congruent meanings and no priming for the incongruent meanings at both short and long ISIs in the healthy controls, consistent with suppression of meanings competing with the representation biased in the first presentation. In contrast, the PD group failed to dampen activation for the incongruent meaning at the long ISI when the first presentation was subordinate. This pattern is consistent with an impairment of meaning suppression which is observed under controlled processing conditions and varies as a function of meaning dominance of the first presentation. These findings further refine our understanding of lexical-semantic impairments in PD and suggest a mechanism that may contribute to discourse comprehension impairments in this population.

Tremor pattern differentiates drug-induced resting tremor from Parkinson disease.

PubMed

Nisticò, R; Fratto, A; Vescio, B; Arabia, G; Sciacca, G; Morelli, M; Labate, A; Salsone, M; Novellino, F; Nicoletti, A; Petralia, A; Gambardella, A; Zappia, M; Quattrone, A

2016-04-01

DAT-SPECT, is a well-established procedure for distinguishing drug-induced parkinsonism from Parkinson's disease (PD). We investigated the usefulness of blink reflex recovery cycle (BRrc) and of electromyographic parameters of resting tremor for the differentiation of patients with drug-induced parkinsonism with resting tremor (rDIP) from those with resting tremor due to PD. This was a cross-sectional study. In 16 patients with rDIP and 18 patients with PD we analysed electrophysiological parameters (amplitude, duration, burst and pattern) of resting tremor. BRrc at interstimulus intervals (ISI) of 100, 150, 200, 300, 400, 500 and 750 msec was also analysed in patients with rDIP, patients with PD and healthy controls. All patients and controls underwent DAT-SPECT. Rest tremor amplitude was higher in PD patients than in rDIP patients (p < 0.001), while frequency and burst duration were higher in rDIP than in PD (p < 0.001, p < 0.003, respectively). Resting tremor showed a synchronous pattern in all patients with rDIP, whereas it had an alternating pattern in all PD patients (p < 0.001). DAT-SPECT was normal in rDIP patients while it was markedly abnormal in patients with PD. In the absence of DAT-SPECT, the pattern of resting tremor can be considered a useful investigation for differentiating rDIP from PD. Copyright © 2016. Published by Elsevier Ltd.

Schedule-induced masseter EMG in facial pain subjects vs. no-pain controls.

PubMed

Gramling, S E; Grayson, R L; Sullivan, T N; Schwartz, S

1997-02-01

Empirical reports suggest that oral habits (e.g., teeth clenching) may be behavioral mediators linking stress to muscle hyperreactivity and the development of facial pain. Another report suggests that excessive behavioral adjuncts develop in conjunction with fixed-time stimulus presentation. The present study assessed the extent to which the oral habits exhibited by facial pain patients are schedule-induced. Subjects with Temporomandibular Disorder (TMD) symptomatology (n = 15) and pain-free controls (n = 15) participated in a 4-phase experiment (adaptation, baseline, task, recovery) designed to elicit schedule-induced behaviors. Self-report of oral habits and negative affect were recorded after each phase. Objective measures of oral habits were obtained via behavioral observation and masseter EMG recordings. Results revealed that negative arousal significantly increased during the fixed-time (FT) task and was also associated with increased oral habits among the TMD subjects. Moreover, 40% of the TMD subjects and none of the controls exhibited a pattern of EMG elevations in the early part of the inter-stimulus interval that met a strict criteria for scheduled-induced behavior per se. Taken together, these results suggest that the TMD subjects were engaging in schedule-induced oral habits. The adjunctive behavior literature seems to provide a plausible explanation as to how oral habits develop and are maintained in TMD patients, despite their painful consequences.

Intra-individual reaction time variability based on ex-Gaussian distribution as a potential endophenotype for attention-deficit/hyperactivity disorder.

PubMed

Lin, H-Y; Hwang-Gu, S-L; Gau, S S-F

2015-07-01

Intra-individual variability in reaction time (IIV-RT), defined by standard deviation of RT (RTSD), is considered as an endophenotype for attention-deficit/hyperactivity disorder (ADHD). Ex-Gaussian distributions of RT, rather than RTSD, could better characterize moment-to-moment fluctuations in neuropsychological performance. However, data of response variability based on ex-Gaussian parameters as an endophenotypic candidate for ADHD are lacking. We assessed 411 adolescents with clinically diagnosed ADHD based on the DSM-IV-TR criteria as probands, 138 unaffected siblings, and 138 healthy controls. The output parameters, mu, sigma, and tau, of an ex-Gaussian RT distribution were derived from the Conners' continuous performance test. Multi-level models controlling for sex, age, comorbidity, and use of methylphenidate were applied. Compared with unaffected siblings and controls, ADHD probands had elevated sigma value, omissions, commissions, and mean RT. Unaffected siblings formed an intermediate group in-between probands and controls in terms of tau value and RTSD. There was no between-group difference in mu value. Conforming to a context-dependent nature, unaffected siblings still had an intermediate tau value in-between probands and controls across different interstimulus intervals. Our findings suggest IIV-RT represented by tau may be a potential endophenotype for inquiry into genetic underpinnings of ADHD in the context of heterogeneity. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Repetitive muscle compression reduces vascular mechano-sensitivity and the hyperemic response to muscle contraction.

PubMed

Messere, A; Turturici, M; Millo, G; Roatta, S

2017-06-01

Animal studies have shown that the rapid hyperemic response to external muscle compression undergoes inactivation upon repetitive stimulation, but this phenomenon has never been observed in humans. The aim of the present study was to determine whether 1) the vascular mechano-sensitivity underlying muscle compression-induced hyperemia is inactivated in an inter-stimulus interval (ISI)-dependent fashion upon repetitive stimulation, as suggested by animal studies, and 2) whether such inactivation also attenuates contraction-induced hyperemia. Brachial artery blood flow was measured by echo Doppler sonography in 13 healthy adults in response to 1) single and repetitive cuff muscle compression (CMC) of the forearm (20 CMCs, 1 s ISI); 2) a sequence of CMC delivered at decreasing ISI from 120 to 2 s; and 3) electrically-stimulated contraction of the forearm muscles before and after repetitive CMC. The peak amplitude of hyperemia in response to CMC normalized to baseline decreased from 2.2 ± 0.6 to 1.4 ± 0.4 after repetitive CMC and, in general, was decreased at ISI < 240 s. The peak amplitude of contraction-induced hyperemia was attenuated after as compared to before repeated CMC (1.7 ± 0.4 and 2.6 ± 0.6, respectively). Mechano-sensitivity of the vascular network can be conditioned by previous mechanical stimulation, and such preconditioning may substantially decrease contraction-induced hyperemia.

Gender identity disorders and multiple sclerosis risk: A national record-linkage study.

PubMed

Pakpoor, Julia; Wotton, Clare J; Schmierer, Klaus; Giovannoni, Gavin; Goldacre, Michael J

2016-11-01

An altered balance of gonadal hormones in males with gender identity disorders (GIDs) may increase multiple sclerosis (MS) risk both inherently and secondary to treatment in undergoing male-to-female conversion. We investigated any association between GIDs and MS through analysis of record-linked hospital statistics. Analysis of English Hospital Episode Statistics, 1999-2012. The adjusted rate ratio (RR) of MS following GIDs in males was 6.63 (95% confidence interval (95% CI) = 1.81-17.01, p = 0.0002). The RR of MS following GIDs in females was 1.44 (95% CI = 0.47-3.37, p = 0.58). We report a strong association between GIDs and MS in male-to-females, supporting a potential role for low testosterone and/or feminising hormones on MS risk in males. © The Author(s), 2016.

The DPP-4 inhibitor linagliptin does not prolong the QT interval at therapeutic and supratherapeutic doses

PubMed Central

Ring, Arne; Port, Andreas; Graefe-Mody, E Ulrike; Revollo, Ivette; Iovino, Mario; Dugi, Klaus A

2011-01-01

AIM To evaluate the potential effects of therapeutic and supratherapeutic doses of linagliptin (BI 1356) on the QT/QTc interval in healthy subjects. METHODS The study was a randomized, double-blind, placebo-controlled, four-period crossover study using single oral doses of linagliptin (5 mg and 100 mg), moxifloxacin (400 mg) and placebo. Electrocardiogram (ECG) profiles using triplicates of 12-lead 10-s ECGs were digitally recorded pre-dose and after drug administration. The mean change from baseline (MCfB) of the individually heart rate corrected QT interval (QTcI) between 1 and 4 h postdrug administration was the primary end point. Blood samples to measure plasma concentrations of linagliptin and its main metabolite were also obtained. RESULTS Forty-four Caucasian subjects (26 male) entered the study and 43 subjects completed the study as planned in the protocol. Linagliptin was not associated with an increase in the baseline-adjusted mean QTcI, at any time point. The placebo-corrected MCfB of QTcI was −1.1 (90% CI −2.7, 0.5) ms and −2.5 (–4.1, –0.9) ms for linagliptin 5 mg and 100 mg, respectively, thus within the non-inferiority margin of 10 ms according to ICH E14. Linagliptin was well tolerated; the assessment of ECGs and other safety parameters gave no clinically relevant findings at either dose tested. Maximum plasma concentrations after administration of 100-mg linagliptin were ∼24-fold higher than those observed previously for chronic treatment with the therapeutic 5-mg dose. Assay sensitivity was confirmed by a placebo-corrected MCfB of QTcI with moxifloxacin of 6.9 (90% CI 5.4, 8.5) ms. CONCLUSIONS Therapeutic and significantly supratherapeutic exposure to linagliptin is not associated with QT interval prolongation. PMID:21306414

Obstructive sleep apnea is associated with increased QT corrected interval dispersion: the effects of continuous positive airway pressure.

PubMed

Bilal, Nagihan; Dikmen, Nursel; Bozkus, Fulsen; Sungur, Aylin; Sarica, Selman; Orhan, Israfil; Samur, Anil

2017-03-31

Severe obstructive sleep apnea (OSA) is associated with increased QT corrected interval dispersion (QTcd) and continuous positive airway pressure (CPAP) is thought to improve this arrhythmogenic marker. The aim of the study was to determine the decrease of ratio of cardiovascular risk in patients with obstructive sleep apnea. The study included 65 patients with severe OSA who had an apnea-hypopnea index (AHI) score of >30. Each patient underwent 12-channel electrocardiogram (ECG) monitoring and polysomnography. Patients with an AHI score of <5 were used as the control group. The control group also underwent ECG monitoring and polysomnography testing. The QTcd levels of both groups were calculated. Three months after CPAP treatment, ECG recordings were obtained from the 65 patients with severe OSA again, and their QTcd values were calculated. There were 44 male and 21 female patients with severe OSA syndrome. The age, gender, body mass index, initial saturation, minimum saturation, average saturation, and desaturation index were determined in both groups. The QTc intervals of the OSA patients (62.48±16.29ms) were significantly higher (p=0.001) than those of the control group (29.72±6.30ms). There were statistically significant differences between the QTc values before and after the CPAP treatment, with pretreatment QTc intervals of 62.48±16.29ms and 3-month post-treatment values of 41.42±16.96ms (p=0.001). There was a positive and significant correlation between QTcd periods and the AHI and hypopnea index (HI) in OSA patients (p=0.001; r=0.71; p=0.001; r=0.679, respectively). CPAP treatment reduced the QTcd in patients with severe OSA. In addition, shortening the QTcd periods in patients with severe OSA may reduce their risk of arrhythmias and cardiovascular disease. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Influence of gender and types of sports training on QT variables in young elite athletes.

PubMed

Omiya, Kazuto; Sekizuka, Hiromitsu; Kida, Keisuke; Suzuki, Kengo; Akashi, Yoshihiro J; Ohba, Haruo; Musha, Haruki

2014-01-01

Influence of gender and sports training on QT variables such as QT interval and dispersion (QT dispersion: QTD) in young elite athletes were evaluated. Subjects included 104 male and 97 female Japanese elite athletes (mean age 21.6 years). Sports included basketball, fencing, gymnastics, judo, swimming, tennis, track and field and volleyball. Age-matched healthy non-athletes (32 men and 20 women) were enrolled as controls. QT measurements were manually obtained from a 12-lead resting electrocardiogram and QTD was calculated as the difference between the longest and shortest QT intervals. A corrected QT interval (QTc) was obtained using Bazett's formula. Subjects were divided into two groups; an endurance training group and a static training group on the basis of their training types. Maximum and minimum QTc were significantly longer in female athletes than in male athletes (max: 414.2 vs. 404.5 ms, min: 375.1 vs. 359.2 ms, p<0.0001 respectively), whereas QTc dispersion (QTcD) was shorter in female athletes than in male athletes (39.2 vs. 45.3 ms, p<0.0001). QTcD was significantly shorter in female athletes than in the female control group (39.2 vs. 45.2 ms, p<0.05). However, no statistically significant difference was observed between male athletes and the male control group. Male gymnasts exhibited significantly longer QTcD than the control group (p<0.01), but female gymnasts had significantly shorter QTcD than the control group (p<0.05). Maximum QTc intervals were prolonged in the male static training group compared with non-athletes, and QTcDs in the static training group were prolonged compared with the endurance training group. However, no significant difference was observed in the female group. In conclusion, both gender and different characteristics of sports training may affect QT variables even in young elite athletes. Vigorous static exercise training may independently prolong QT variables.

High-intensity interval training improves inflammatory and adipokine profiles in postmenopausal women with metabolic syndrome.

PubMed

Steckling, Flávia Mariel; Farinha, Juliano Boufleur; Figueiredo, Felipe da Cunha; Santos, Daniela Lopes Dos; Bresciani, Guilherme; Kretzmann, Nélson Alexandre; Stefanello, Sílvio Terra; Courtes, Aline Alves; Beck, Maristela de Oliveira; Sangoi Cardoso, Manuela; Duarte, Marta Maria Medeiros Frescura; Moresco, Rafael Noal; Soares, Félix Alexandre Antunes

2018-02-12

This study investigate the effects of high-intensity interval training (HIIT) on systemic levels of inflammatory and hormonal markers in postmenopausal women with metabolic syndrome (MS). Fifteen postmenopausal women with MS completed the training on treadmills. Functional, body composition parameters, maximal oxygen uptake (VO 2 max), and lipid profile were assessed before and after HIIT. Serum or plasma levels of cytokines and hormonal markers were measured along the intervention. The analysis of messenger RNA (mRNA) expression of these cytokines was performed in peripheral blood mononuclear cells (PBMC). VO 2 max and some anthropometric parameters were improved after HIIT, while decreased levels of proinflammatory markers and increased levels of interleukin-10 (IL-10) were also found. Adipokines were also modulated after 12 weeks or training. The mRNA expression of the studied genes was unchanged after HIIT. In conclusion, HIIT benefits inflammatory and hormonal axis on serum or plasma samples, without changes on PBMC of postmenopausal MS patients.

Onset of multiple sclerosis before adulthood leads to failure of age-expected brain growth

PubMed Central

Aubert-Broche, Bérengère; Fonov, Vladimir; Narayanan, Sridar; Arnold, Douglas L.; Araujo, David; Fetco, Dumitru; Till, Christine; Sled, John G.; Collins, D. Louis

2014-01-01

Objective: To determine the impact of pediatric-onset multiple sclerosis (MS) on age-expected brain growth. Methods: Whole brain and regional volumes of 36 patients with relapsing-remitting MS onset prior to 18 years of age were segmented in 185 longitudinal MRI scans (2–11 scans per participant, 3-month to 2-year scan intervals). MRI scans of 25 age- and sex-matched healthy normal controls (NC) were also acquired at baseline and 2 years later on the same scanner as the MS group. A total of 874 scans from 339 participants from the NIH-funded MRI study of normal brain development acquired at 2-year intervals were used as an age-expected healthy growth reference. All data were analyzed with an automatic image processing pipeline to estimate the volume of brain and brain substructures. Mixed-effect models were built using age, sex, and group as fixed effects. Results: Significant group and age interactions were found with the adjusted models fitting brain volumes and normalized thalamus volumes (p < 10−4). These findings indicate a failure of age-normative brain growth for the MS group, and an even greater failure of thalamic growth. In patients with MS, T2 lesion volume correlated with a greater reduction in age-expected thalamic volume. To exclude any scanner-related influence on our data, we confirmed no significant interaction of group in the adjusted models between the NC and NIH MRI Study of Normal Brain Development groups. Conclusions: Our results provide evidence that the onset of MS during childhood and adolescence limits age-expected primary brain growth and leads to subsequent brain atrophy, implicating an early onset of the neurodegenerative aspect of MS. PMID:25378667

Application of liquid chromatography-tandem mass spectrometry in the diagnosis and follow-up of maple syrup urine disease in a Chinese population.

PubMed

Lin, Na; Ye, Jun; Qiu, Wenjuan; Han, Lianshu; Zhang, Huiwen; Gu, Xuefan

2013-01-01

Maple syrup urine disease (MSUD) is an inherited disorder caused by a deficiency of the mitochondrial branched-chain keto acid dehydrogenase complex. We investigated whether liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a more reliable and accurate method than MS/MS in the diagnosis and management of patients with MSUD in a Chinese population. A total of 370 dried blood spots (DBS) from healthy neonates, 44 DBS specimens from phenylketonuria neonates, and 38 DBS samples from 10 MSUD patients were retrospectively tested using the LC-MS/MS method. The results were compared with those obtained by the MS/MS method. The reference intervals of branched-chain amino acids (BCAAs) and alloiosleucine (Allo-Ile) were estimated for both sexes. In classic MSUD patients, Allo-Ile was markedly elevated (average of 136 μmol/L, which was significantly higher than the normal value, <5 μmol/L). The averages of BCAAs were also markedly elevated continually during the treatment. The application of the LC-MS/MS method in the measurement of Allo-Ile and BCAAs in DBS is more useful for diagnosing and managing classic MSUD than the MS/MS method.

Effect of PR Interval on Outcomes Following Cardiac Resynchronization Therapy: A Secondary Analysis of the COMPANION Trial.

PubMed

Lin, Jeffrey; Buhr, Kevin A; Kipp, Ryan

2017-02-01

Prolonged PR intervals may impair atrioventricular mechanical coupling and adversely affect cardiac performance. We hypothesize that patients with advanced systolic heart failure, wide QRS complexes, and prolonged PR intervals will have improved survival from CRT-D regardless of whether left bundle branch block (LBBB) or non-LBBB is present. A total of 308 patients enrolled in the optimal pharmacologic therapy (OPT) and 595 patients in the cardiac resynchronization therapy with defibrillation (CRT-D) arms of the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure trial were stratified according to normal (≤230 ms) or prolonged PR interval (>230 ms). The incidence of all-cause mortality (ACM) or hospitalization (primary endpoint) and ACM (secondary endpoint) was compared using Kaplan-Meier curves. Cox proportional hazards models for the primary and secondary endpoints were fit with LBBB status and baseline PR interval. CRT-D treatment reduced both hospitalization/ACM (P = 0.002) and ACM (P = 0.003) compared to OPT. However, CRT-D was increasingly more effective in reducing ACM hazard in patients with longer baseline PR intervals (P = 0.002) regardless of LBBB status. In particular, in the prolonged baseline PR interval subgroup, ACM was reduced with CRT-D compared to OPT (P = 0.001) with little evidence of ACM reduction in the normal PR subgroup (P = 0.07). In patients with advanced systolic heart failure, wide QRS complexes, and prolonged PR intervals, restoration of atrioventricular mechanical coupling with CRT-D may improve survival regardless of LBBB status. In patients with non-LBBB, a benefit from CRT-D may occur with prolonged PR intervals. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Detection of tissue coagulation by decorrelation of ultrasonic echo signals in cavitation-enhanced high-intensity focused ultrasound treatment.

PubMed

Yoshizawa, Shin; Matsuura, Keiko; Takagi, Ryo; Yamamoto, Mariko; Umemura, Shin-Ichiro

2016-01-01

A noninvasive technique to monitor thermal lesion formation is necessary to ensure the accuracy and safety of high-intensity focused ultrasound (HIFU) treatment. The purpose of this study is to ultrasonically detect the tissue change due to thermal coagulation in the HIFU treatment enhanced by cavitation microbubbles. An ultrasound imaging probe transmitted plane waves at a center frequency of 4.5 MHz. Ultrasonic radio-frequency (RF) echo signals during HIFU exposure at a frequency of 1.2 MHz were acquired. Cross-correlation coefficients were calculated between in-phase and quadrature (IQ) data of two B-mode images with an interval time of 50 and 500 ms for the estimation of the region of cavitation and coagulation, respectively. Pathological examination of the coagulated tissue was also performed to compare with the corresponding ultrasonically detected coagulation region. The distribution of minimum hold cross-correlation coefficient between two sets of IQ data with 50-ms intervals was compared with a pulse inversion (PI) image. The regions with low cross-correlation coefficients approximately corresponded to those with high brightness in the PI image. The regions with low cross-correlation coefficients in 500-ms intervals showed a good agreement with those with significant change in histology. The results show that the regions of coagulation and cavitation could be ultrasonically detected as those with low cross-correlation coefficients between RF frames with certain intervals. This method will contribute to improve the safety and accuracy of the HIFU treatment enhanced by cavitation microbubbles.

Excess close burst pairs in FRB 121102

NASA Astrophysics Data System (ADS)

Katz, J. I.

2018-05-01

The repeating FRB 121102 emitted a pair of apparently discrete bursts separated by 37 ms and another pair, 131 d later, separated by 34 ms, during observations that detected bursts at a mean rate of ˜2 × 10-4 s-1. While FRB 121102 is known to produce multipeaked bursts, here I assume that these `burst pairs' are truly separate bursts and not multicomponent single bursts, and consider the implications of that assumption. Their statistics are then non-Poissonian. Assuming that the emission comes from a narrow range of rotational phase, then the measured burst intervals constrain any possible periodic modulation underlying the highly episodic emission. If more such short intervals are measured a period may be determined or periodicity may be excluded. The excess of burst intervals much shorter than their mean recurrence time may be explained if FRB emit steady but narrow beams that execute a random walk in direction, perhaps indicating origin in a black hole's accretion disc.

Effects of bilastine on T-wave morphology and the QTc interval: a randomized, double-blind, placebo-controlled, thorough QTc study.

PubMed

Graff, Claus; Struijk, Johannes J; Kanters, Jørgen K; Andersen, Mads P; Toft, Egon; Tyl, Benoît

2012-05-01

The International Conference of Harmonisation (ICH) E14 guideline for thorough QT studies requires assessing the propensity of new non-antiarrhythmic drugs to affect cardiac repolarization. The present study investigates whether a composite ECG measure of T-wave morphology (Morphology Combination Score [MCS]) can be used together with the heart rate corrected QT interval (QTc) in a fully ICH E14-compliant thorough QT study to exclude clinically relevant repolarization effects of bilastine, a novel antihistamine. Thirty participants in this crossover study were randomly assigned to receive placebo, moxifloxacin 400 mg, bilastine at therapeutic and supratherapeutic doses (20 and 100 mg) and bilastine 20 mg co-administered with ketoconazole 400 mg. Resting ECGs recorded at 12 nominal time points before and after treatments were used to determine Fridericia corrected QTc (QTcF) and MCS from the T-wave characteristics: asymmetry, flatness and notching. There were no effects of bilastine monotherapy (20 and 100 mg) on MCS or QTcF at those study times where the bilastine plasma concentrations were highest. MCS changes for bilastine monotherapy did not exceed the normal intrasubject variance of T-wave shapes for triplicate ECG recordings. Maximum QTcF prolongation for bilastine monotherapy was 5 ms or less: 3.8 ms (90% CI 0.3, 7.3 ms) for bilastine 20 mg and 5.0 ms (90% CI 2.0, 8.0 ms) for bilastine 100 mg. There were no indications of bilastine inducing larger repolarization effects on T-wave morphology as compared with the QTcF interval, as evidenced by the similarity of z-score equivalents for placebo-corrected changes in MCS and QTcF values. This study shows that bilastine, at therapeutic and supratherapeutic dosages, does not induce any effects on T-wave morphology or QTcF. These results confirm the absence of an effect for bilastine on cardiac repolarization.

The influence of type 2 diabetes and gender on ventricular repolarization dispersion in patients with sub-clinic left ventricular diastolic dysfunction

PubMed Central

Jani, Ylber; Kamberi, Ahmet; Xhunga, Sotir; Pocesta, Bekim; Ferati, Fatmir; Lala, Dali; Zeqiri, Agim; Rexhepi, Atila

2015-01-01

Objective: To assess the influence of type 2 DM and gender, on the QT dispersion, Tpeak-Tend dispersion of ventricular repolarization, in patients with sub-clinic left ventricular diastolic dysfunction of the heart. Background: QT dispersion, that reflects spatial inhomogeneity in ventricular repolarization, Tpeak-Tend dispersion, this on the other hand reflects transmural inhomogeneity in ventricular repolarization, that is increased in an early stage of cardiomyopathy, and in patients with left ventricular diastolic dysfunction, as well. The left ventricular diastolic dysfunction, a basic characteristic of diabetic heart disease (diabetic cardiomyopathy), that developes earlier than systolic dysfunction, suggests that diastolic markers might be sensitive for early cardiac injury. It is also demonstrated that gender has complex influence on indices of myocardial repolarization abnormalities such as QT interval and QT dispersion. Material and methods: We performed an observational study including 300 diabetic patients with similar epidemiological-demographic characteristics recruited in our institution from May 2009 to July 2014, divided into two groups. Demographic and laboratory echocardiographic data were obtained, twelve lead resting electrocardiography, QT, QTc, Tpeak-Tend-intervals and dispersion, were determined manually, and were compared between various groups. For statistical analysis a t-test, X2 test, and logistic regression are used according to the type of variables. A p value <0.05 was considered statistically significant for a confidence interval of 95%. Results: QTc max. interval, QTc dispersion and Tpeak-Tend dispersion, were significantly higher in diabetic group with subclinical LV (left ventricular) diastolic dysfunction, than in diabetic group with normal left ventricular diastolic function (445.24±14.7 ms vs. 433.55±14.4 ms, P<0.000; 44.98±18.78 ms vs. 32.05±17.9 ms, P<0.000; 32.60±1.6 ms vs. 17.46±2.0 ms, P<0.02. Prolonged QTc max. interval was found in 33% of patients, indiabetic group with subclinical left ventricular diastolic dysfunction vs. 13.3% of patients in diabetic group with normal left ventricular diastolic function, (Chi-square: 16.77, P<0.0001). A prolonged QTc dispersion, was found in 40.6% of patients, in diabetic group with subclinical left ventricular diastolic dysfunction vs. 20% of patients in diabetic group with normal left ventricular diastolic function Chi-square: 14.11, P<0.0002). A prolonged dispersion of Tpeak-Tend interval was found in 24% of patients in diabetic group with subclinical left ventricular diastolic dysfunction vs. 13.3% of patients in diabetic group with normal left ventricular diastolic function (Chi-square: 12.00, P<0.005). Females in diabetic group with subclinical left ventricular diastolic dysfunction in comparison with males in diabetic group with subclinical left ventricular diastolic dysfunction, have a significantly prolonged: mean QTc max. interval (23.3% vs. 10%, Chisquare: 12.0, P<0.005), mean QTc dispersion (27.3% vs. 13.3%, Chi-square: 10.24, P<0.001), mean Tpeak-Tend interval (10% vs. 3.3%, Chi-square: 5.77, P<0.01), mean Tpek-Tend dispersion (16.6% vs. 6.6%, Chi-square: 8.39, P<0.003). Conclusion: The present study has shown that influences of type 2 diabetes and gender in diabetics with sub-clinical left-ventricular diastolic dysfunction are reflected in a set of electrophysiological parameters that indicate a prolonged and more heterogeneous repolarization than in diabetic patients with normal diastolic function. In addition, it demonstrates that there exist differences between diabetic females with sub-clinic LV dysfunction and those with diabetes and normal LV function in the prevalence of increased set of electrophysiological parameters that indicate a prolonged and more heterogeneous repolarization. PMID:26550530

The influence of type 2 diabetes and gender on ventricular repolarization dispersion in patients with sub-clinic left ventricular diastolic dysfunction.

PubMed

Jani, Ylber; Kamberi, Ahmet; Xhunga, Sotir; Pocesta, Bekim; Ferati, Fatmir; Lala, Dali; Zeqiri, Agim; Rexhepi, Atila

2015-01-01

To assess the influence of type 2 DM and gender, on the QT dispersion, Tpeak-Tend dispersion of ventricular repolarization, in patients with sub-clinic left ventricular diastolic dysfunction of the heart. QT dispersion, that reflects spatial inhomogeneity in ventricular repolarization, Tpeak-Tend dispersion, this on the other hand reflects transmural inhomogeneity in ventricular repolarization, that is increased in an early stage of cardiomyopathy, and in patients with left ventricular diastolic dysfunction, as well. The left ventricular diastolic dysfunction, a basic characteristic of diabetic heart disease (diabetic cardiomyopathy), that developes earlier than systolic dysfunction, suggests that diastolic markers might be sensitive for early cardiac injury. It is also demonstrated that gender has complex influence on indices of myocardial repolarization abnormalities such as QT interval and QT dispersion. We performed an observational study including 300 diabetic patients with similar epidemiological-demographic characteristics recruited in our institution from May 2009 to July 2014, divided into two groups. Demographic and laboratory echocardiographic data were obtained, twelve lead resting electrocardiography, QT, QTc, Tpeak-Tend-intervals and dispersion, were determined manually, and were compared between various groups. For statistical analysis a t-test, X(2) test, and logistic regression are used according to the type of variables. A p value <0.05 was considered statistically significant for a confidence interval of 95%. QTc max. interval, QTc dispersion and Tpeak-Tend dispersion, were significantly higher in diabetic group with subclinical LV (left ventricular) diastolic dysfunction, than in diabetic group with normal left ventricular diastolic function (445.24±14.7 ms vs. 433.55±14.4 ms, P<0.000; 44.98±18.78 ms vs. 32.05±17.9 ms, P<0.000; 32.60±1.6 ms vs. 17.46±2.0 ms, P<0.02. Prolonged QTc max. interval was found in 33% of patients, indiabetic group with subclinical left ventricular diastolic dysfunction vs. 13.3% of patients in diabetic group with normal left ventricular diastolic function, (Chi-square: 16.77, P<0.0001). A prolonged QTc dispersion, was found in 40.6% of patients, in diabetic group with subclinical left ventricular diastolic dysfunction vs. 20% of patients in diabetic group with normal left ventricular diastolic function Chi-square: 14.11, P<0.0002). A prolonged dispersion of Tpeak-Tend interval was found in 24% of patients in diabetic group with subclinical left ventricular diastolic dysfunction vs. 13.3% of patients in diabetic group with normal left ventricular diastolic function (Chi-square: 12.00, P<0.005). Females in diabetic group with subclinical left ventricular diastolic dysfunction in comparison with males in diabetic group with subclinical left ventricular diastolic dysfunction, have a significantly prolonged: mean QTc max. interval (23.3% vs. 10%, Chisquare: 12.0, P<0.005), mean QTc dispersion (27.3% vs. 13.3%, Chi-square: 10.24, P<0.001), mean Tpeak-Tend interval (10% vs. 3.3%, Chi-square: 5.77, P<0.01), mean Tpek-Tend dispersion (16.6% vs. 6.6%, Chi-square: 8.39, P<0.003). The present study has shown that influences of type 2 diabetes and gender in diabetics with sub-clinical left-ventricular diastolic dysfunction are reflected in a set of electrophysiological parameters that indicate a prolonged and more heterogeneous repolarization than in diabetic patients with normal diastolic function. In addition, it demonstrates that there exist differences between diabetic females with sub-clinic LV dysfunction and those with diabetes and normal LV function in the prevalence of increased set of electrophysiological parameters that indicate a prolonged and more heterogeneous repolarization.

Temporal prediction restores the evaluative processing of delayed action feedback: an electrophysiological study.

PubMed

Kimura, Kenta; Kimura, Motohiro

2016-09-28

The evaluative processing of the valence of action feedback is reflected by an event-related brain potential component called feedback-related negativity (FRN) or reward positivity (RewP). Recent studies have shown that FRN/RewP is markedly reduced when the action-feedback interval is long (e.g. 6000 ms), indicating that an increase in the action-feedback interval can undermine the evaluative processing of the valence of action feedback. The aim of the present study was to investigate whether or not such undermined evaluative processing of delayed action feedback could be restored by improving the accuracy of the prediction in terms of the timing of action feedback. With a typical gambling task in which the participant chose one of two cards and received an action feedback indicating monetary gain or loss, the present study showed that FRN/RewP was significantly elicited even when the action-feedback interval was 6000 ms, when an auditory stimulus sequence was additionally presented during the action-feedback interval as a temporal cue. This result suggests that the undermined evaluative processing of delayed action feedback can be restored by increasing the accuracy of the prediction on the timing of the action feedback.

Benthic foraminiferal paleoecology and depositional patterns during the Albian at DSDP Site 327 (Falkland Plateau)

NASA Astrophysics Data System (ADS)

Lopes, Fernando M.; Koutsoukos, Eduardo A. M.; Kochhann, Karlos G. D.; Savian, Jairo F.; Fauth, Gerson

2017-10-01

The present paleoenvironmental study uses a spectrum of analytical methods, such as benthic foraminiferal assemblages, total organic carbon (TOC), calcium carbonate (CaCO3) contents and magnetic susceptibility (MS), to monitor variations in primary productivity, bottom-water oxygenation and depositional patterns within the Albian interval recovered at DSDP Site 327, Hole A, Falkland Plateau. Thirty-three benthic foraminiferal species were identified in the studied section and, based on the abundances of morphogroups (epifaunal and shallow infaunal), two distinct associations were identified. Stratigraphic intervals dominated by the epifaunal morphogroup can be interpreted as indicative of bottom-waters with low-oxygen content. However, these decreases in oxygenation were not vigorous enough to establish a dominance of deep-infaunal morphotypes, as supported by the low TOC values. Intervals dominated by the shallow infaunal morphogroup were interpreted as subjected to moderate to high nutrient flux to the ocean floor. These intervals are associated with high MS values and low CaCO3 content, suggesting that dissolution processes, rather than increased primary productivity, controlled CaCO3 accumulation in the studied section. Furthermore, faunal analysis points to deposition in an outer neritic to upper bathyal paleoenvironment.

Timing matters: the processing of pitch relations

PubMed Central

Weise, Annekathrin; Grimm, Sabine; Trujillo-Barreto, Nelson J.; Schröger, Erich

2014-01-01

The human central auditory system can automatically extract abstract regularities from a variant auditory input. To this end, temporarily separated events need to be related. This study tested whether the timing between events, falling either within or outside the temporal window of integration (~350 ms), impacts the extraction of abstract feature relations. We utilized tone pairs for which tones within but not across pairs revealed a constant pitch relation (e.g., pitch of second tone of a pair higher than pitch of first tone, while absolute pitch values varied across pairs). We measured the mismatch negativity (MMN; the brain’s error signal to auditory regularity violations) to second tones that rarely violated the pitch relation (e.g., pitch of second tone lower). A Short condition in which tone duration (90 ms) and stimulus onset asynchrony between the tones of a pair were short (110 ms) was compared to two conditions, where this onset asynchrony was long (510 ms). In the Long Gap condition, the tone durations were identical to Short (90 ms), but the silent interval was prolonged by 400 ms. In Long Tone, the duration of the first tone was prolonged by 400 ms, while the silent interval was comparable to Short (20 ms). Results show a frontocentral MMN of comparable amplitude in all conditions. Thus, abstract pitch relations can be extracted even when the within-pair timing exceeds the integration period. Source analyses indicate MMN generators in the supratemporal cortex. Interestingly, they were located more anterior in Long Gap than in Short and Long Tone. Moreover, frontal generator activity was found for Long Gap and Long Tone. Thus, the way in which the system automatically registers irregular abstract pitch relations depends on the timing of the events to be linked. Pending that the current MMN data mirror established abstract rule representations coding the regular pitch relation, neural processes building these templates vary with timing. PMID:24966823

Comparison of yoga and walking-exercise on cardiac time intervals as a measure of cardiac function in elderly with increased pulse pressure.

PubMed

Patil, Satish Gurunathrao; Patil, Shankargouda S; Aithala, Manjunatha R; Das, Kusal Kanti

Arterial aging along with increased blood pressure(BP) has become the major cardiovascular(CV) risk in elderly. The aim of the study was to compare the effects of yoga program and walking-exercise on cardiac function in elderly with increased pulse pressure (PP). An open label, parallel-group randomized controlled study design was adopted. Elderly individuals aged ≥60 years with PP≥60mmHg were recruited for the study. Yoga (study) group (n=30) was assigned for yoga training and walking (exercise) group (n=30) for walking with loosening practices for one hour in the morning for 6days in a week for 3 months. The outcome measures were cardiac time intervals derived from pulse wave analysis and ECG: resting heart rate (RHR), diastolic time(DT), ventricular ejection time(LVET), upstroke time(UT), ejection duration index (ED%), pre-ejection period (PEP), rate pressure product (RPP) and percentage of mean arterial pressure (%MAP). The mean within-yoga group change in RHR(bpm) was 4.41 (p=0.031), PD(ms): -50.29 (p=0.042), DT(ms): -49.04 (p=0.017), ED%: 2.107 (p=0.001), ES(mmHg/ms): 14.62 (p=0.118), ET(ms): -0.66 (p=0.903), UT(ms): -2.54 (p=0.676), PEP(ms): -1.25 (p=0.11) and %MAP: 2.08 (p=0.04). The mean within-control group change in HR (bpm) was 0.35 (p=0.887), PD (ms): 11.15(p=0.717), DT (ms): 11.3 (p=0.706), ED%: -0.101 (p=0.936), ES (mmHg/ms): 0.75 (p=0.926), ET(ms): 2.2 (p=0.721), UT(ms):4.7(p=455), PEP (ms): 2.1(p=0.11), %MAP: 0.65 (p=0.451). A significant difference between-group was found in RHR (p=0.036), PD (p=0.02), ED% (p=0.049), LVET (p=0.048), DT (p=0.02) and RPP (p=0.001). Yoga practice for 3 months showed a significant improvement in diastolic function with a minimal change in systolic function. Yoga is more effective than walking in improving cardiac function in elderly with high PP. Copyright © 2017 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Evidence for a neural signature of musical preference during silence.

PubMed

Joucla, Coralie; Nicolier, Magali; Giustiniani, Julie; Brunotte, Gaelle; Noiret, Nicolas; Monnin, Julie; Magnin, Eloi; Pazart, Lionel; Moulin, Thierry; Haffen, Emmanuel; Vandel, Pierre; Gabriel, Damien

2018-03-01

One of the most basic and person-specific affective responses to music is liking. The present investigation sought to determine whether liking was preserved during spontaneous auditory imagery. To this purpose, we inserted two-second silent intervals into liked and disliked songs, a method known to automatically recreate a mental image of these songs. Neural correlates of musical preference were measured by high-density electroencephalography in twenty subjects who had to listen to a set of five pre-selected unknown songs the same number of times for two weeks. Time frequency analysis of the two most liked and the two most disliked songs confirmed the presence of neural responses related to liking. At the beginning of silent intervals (400-900 ms and 1000-1300 ms), significant differences in theta activity were originating from the inferior frontal and superior temporal gyrus. These two brain structures are known to work together to process various aspects of music and are also activated when measuring liking while listening to music. At the end of silent intervals (1400-1900 ms), significant alpha activity differences originating from the insula were observed, whose exact role remains to be explored. Although exposure was controlled for liked and disliked songs, liked songs were rated as more familiar, underlying the strong relationship that exists between liking, exposure, and familiarity. Copyright © 2018 Elsevier B.V. All rights reserved.

Cardiovascular effects of fenoterol under conditions of hypoxaemia.

PubMed Central

Bremner, P; Burgess, C D; Crane, J; McHaffie, D; Galletly, D; Pearce, N; Woodman, K; Beasley, R

1992-01-01

BACKGROUND: The reason for the association of increased risk of death with fenoterol in patients with asthma in New Zealand is unknown but may relate to its cardiovascular effects. Most deaths from asthma occur outside hospital, where hypoxaemia is likely to be a complicating factor. The cardiovascular effects of fenoterol have been investigated therefore under conditions of normoxaemia and hypoxaemia. METHOD: Eight healthy men were studied on two occasions. Measurements of heart rate, blood pressure, total electromechanical systole (QS2I), electrocardiographic QTc interval, cardiac index, stroke volume, and ejection fraction were made under conditions of normoxaemia and hypoxaemia (arterial oxygen saturation 90%) before and after administration of 800 micrograms of fenoterol by a metered dose inhaler. The order in which treatments were applied was according to a Latin square design. RESULTS: Before inhalation of fenoterol hypoxaemia was associated with a significant increase in heart rate (8 beats/min) and QTc interval (15.6 ms). Under conditions of normoxaemia fenoterol caused a significant increase in heart rate (14.3 beats/min), systolic blood pressure (7.7 mm Hg), stroke volume (27.7 ml), cardiac index (1.6 1/min/m2), ejection fraction (11.48), and QTc interval (32.9 ms) and a fall in QS2I (-23.2 ms) and diastolic blood pressure (-8.4 mm Hg). Under conditions of hypoxaemia the changes after inhalation of fenoterol were similar to those recorded during normoxaemia; thus the effects of hypoxaemia and fenoterol were additive (heart rate 21.9 beats/min, QTc 43.5 ms with fenoterol and hypoxaemia). CONCLUSION: The chronotropic and electrophysiological effects of fenoterol were enhanced by conditions of hypoxaemia. PMID:1481183

Explosive Strength of the Knee Extensors: The Influence of Criterion Trial Detection Methodology on Measurement Reproducibility.

PubMed

Dirnberger, Johannes; Wiesinger, Hans-Peter; Wiemer, Nicolas; Kösters, Alexander; Müller, Erich

2016-04-01

The present study was conducted to assess test-retest reproducibility of explosive strength measurements during single-joint isometric knee extension using the IsoMed 2000 dynamometer. Thirty-one physically active male subjects (mean age: 23.7 years) were measured on two occasions separated by 48-72 h. The intraclass correlation coefficient (ICC 2,1) and the coefficient of variation (CV) were calculated for (i) maximum torque (MVC), (ii) the peak rate of torque development (RTD peak ) as well as for (iii) the average rate of torque development (RTD) and the impulse taken at several predefined time intervals (0-30 to 0-300 ms); thereby explosive strength variables were derived in two conceptually different versions: on the one hand from the MVC-trial (version I), on the other hand from the trial showing the RTD peak (version II). High ICC-values (0.80-0.99) and acceptable CV-values (1.9-8.7%) could be found for MVC as well as for the RTD and the impulse taken at time intervals of ≥100 ms, regardless of whether version I or II was used. In contrast, measurements of the RTD peak as well as the RTD and the impulse taken during the very early contraction phase (i.e. RTD/impulse 0-30ms and RTD/impulse 0-50ms ) showed clearly weaker reproducibility results (ICC: 0.53-0.84; CV: 7.3-16.4%) and gave rise to considerable doubts as to clinical usefulness, especially when derived using version I. However, if there is a need to measure explosive strength for earlier time intervals in practice, it is, in view of stronger reproducibility results, recommended to concentrate on measures derived from version II, which is based on the RTD peak -trial.

The effects of prepulse-blink reflex trial repetition and prepulse change on blink reflex modification at short and long lead intervals.

PubMed

Lipp, O V; Siddle, D A

1998-01-01

Prepulse inhibition and facilitation of the blink reflex are said to reflect different responses elicited by the lead stimulus, transient detection and orienting response respectively. Two experiments investigated the effects of trial repetition and lead stimulus change on blink modification. It was hypothesized that these manipulations will affect orienting and thus blink facilitation to a greater extent than they will affect transient detection and thus blink inhibition. In Experiment 1 (N = 64), subjects were trained with a sequence of 12 lead stimulus and 12 blink stimulus alone presentations, and 24 lead stimulus-blink stimulus pairings. Lead interval was 120 ms for 12 of the trials and 2000 ms for the other 12. For half the subjects this sequence was followed by a change in pitch of the lead stimulus. In Experiment 2 (N = 64), subjects were trained with a sequence of 36 blink alone stimuli and 36 lead stimulus-blink stimulus pairings. The lead interval was 120 ms for half the subjects and 2000 ms for the other half. The pitch of the lead stimulus on prestimulus trials 31-33 was changed for half the subjects in each group. In both experiments, the amount of blink inhibition decreased during training whereas the amount of blink facilitation remained unchanged. Lead stimulus change had no effect on blink modification in either experiment although it resulted in enhanced skin conductance responses and greater heart rate deceleration in Experiment 2. The present results are not consistent with the notion that blink facilitation is linked to orienting whereas blink inhibition reflects a transient detection mechanism.

Effect of mental challenge induced by movie clips on action potential duration in normal human subjects independent of heart rate.

PubMed

Child, Nicholas; Hanson, Ben; Bishop, Martin; Rinaldi, Christopher A; Bostock, Julian; Western, David; Cooklin, Michael; O'Neil, Mark; Wright, Matthew; Razavi, Reza; Gill, Jaswinder; Taggart, Peter

2014-06-01

Mental stress and emotion have long been associated with ventricular arrhythmias and sudden death in animal models and humans. The effect of mental challenge on ventricular action potential duration (APD) in conscious healthy humans has not been reported. Activation recovery intervals measured from unipolar electrograms as a surrogate for APD (n=19) were recorded from right and left ventricular endocardium during steady-state pacing, whilst subjects watched an emotionally charged film clip. To assess the possible modulating role of altered respiration on APD, the subjects then repeated the same breathing pattern they had during the stress, but without the movie clip. Hemodynamic parameters (mean, systolic, and diastolic blood pressure, and rate of pressure increase) and respiration rate increased during the stressful part of the film clip (P=0.001). APD decreased during the stressful parts of the film clip, for example, for global right ventricular activation recovery interval at end of film clip 193.8 ms (SD, 14) versus 198.0 ms (SD, 13) during the matched breathing control (end film left ventricle 199.8 ms [SD, 16] versus control 201.6 ms [SD, 15]; P=0.004). Respiration rate increased during the stressful part of the film clip (by 2 breaths per minute) and was well matched in the respective control period without any hemodynamic or activation recovery interval changes. Our results document for the first time direct recordings of the effect of a mental challenge protocol on ventricular APD in conscious humans. The effect of mental challenge on APD was not secondary to emotionally induced altered respiration or heart rate. © 2014 American Heart Association, Inc.

Timing of repetition suppression of event-related potentials to unattended objects.

PubMed

Stefanics, Gabor; Heinzle, Jakob; Czigler, István; Valentini, Elia; Stephan, Klaas Enno

2018-05-26

Current theories of object perception emphasize the automatic nature of perceptual inference. Repetition suppression (RS), the successive decrease of brain responses to repeated stimuli, is thought to reflect the optimization of perceptual inference through neural plasticity. While functional imaging studies revealed brain regions that show suppressed responses to the repeated presentation of an object, little is known about the intra-trial time course of repetition effects to everyday objects. Here we used event-related potentials (ERP) to task-irrelevant line-drawn objects, while participants engaged in a distractor task. We quantified changes in ERPs over repetitions using three general linear models (GLM) that modelled RS by an exponential, linear, or categorical "change detection" function in each subject. Our aim was to select the model with highest evidence and determine the within-trial time-course and scalp distribution of repetition effects using that model. Model comparison revealed the superiority of the exponential model indicating that repetition effects are observable for trials beyond the first repetition. Model parameter estimates revealed a sequence of RS effects in three time windows (86-140ms, 322-360ms, and 400-446ms) and with occipital, temporo-parietal, and fronto-temporal distribution, respectively. An interval of repetition enhancement (RE) was also observed (320-340ms) over occipito-temporal sensors. Our results show that automatic processing of task-irrelevant objects involves multiple intervals of RS with distinct scalp topographies. These sequential intervals of RS and RE might reflect the short-term plasticity required for optimization of perceptual inference and the associated changes in prediction errors (PE) and predictions, respectively, over stimulus repetitions during automatic object processing. This article is protected by copyright. All rights reserved. © 2018 The Authors European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

The Relationship between MOC Reflex and Masked Threshold

PubMed Central

Garinis, Angela; Werner, Lynne; Abdala, Carolina

2011-01-01

Otoacoustic emission (OAE) amplitude can be reduced by acoustic stimulation. This effect is produced by the medial olivocochlear (MOC) reflex. Past studies have shown that the MOC reflex is related to listening in noise and attention. In the present study, the relationship between strength of the contralateral MOC reflex and masked threshold was investigated in 19 adults. Detection thresholds were determined for a 1000-Hz, 300-ms tone presented simultaneously with one repetition of a 300-ms masker in an ongoing train of 300-ms masker bursts at 600-ms intervals. Three masking conditions were tested: 1) broadband noise 2) a fixed-frequency 4-tone complex masker and 3) a random-frequency 4-tone complex masker. Broadband noise was expected to produce energetic masking and the tonal maskers were expected to produce informational masking in some listeners. DPOAEs were recorded at fine frequency interval from 500 to 4000 Hz, with and without contralateral acoustic stimulation. MOC reflex strength was estimated as a reduction in baseline level and a shift in frequency of DPOAE fine-structure maxima near 1000-Hz. MOC reflex and psychophysical testing were completed in separate sessions. Individuals with poorer thresholds in broadband noise and in random-frequency maskers were found to have stronger MOC reflexes. PMID:21878379

The relative contributions of processing speed and cognitive load to working memory accuracy in multiple sclerosis.

PubMed

Leavitt, Victoria M; Lengenfelder, Jean; Moore, Nancy B; Chiaravalloti, Nancy D; DeLuca, John

2011-06-01

Cognitive symptoms of multiple sclerosis (MS) include processing-speed deficits and working memory impairment. The precise manner in which these deficits interact in individuals with MS remains to be explicated. We hypothesized that providing more time on a complex working memory task would result in performance benefits for individuals with MS relative to healthy controls. Fifty-three individuals with clinically definite MS and 36 matched healthy controls performed a computerized task that systematically manipulated cognitive load. The interval between stimuli presentations was manipulated to provide increasing processing time. The results confirmed that individuals with MS who have processing-speed deficits significantly improve in performance accuracy when given additional time to process the information in working memory. Implications of these findings for developing appropriate cognitive rehabilitation interventions are discussed.

Reverse causality behind the association between reproductive history and MS.

PubMed

Hedström, A K; Hillert, J; Olsson, T; Alfredsson, L

2014-04-01

Possible associations between childbearing patterns and multiple sclerosis (MS) risk have been studied for a long time, with conflicting results. We aimed to investigate the influence of reproductive history on MS risk. Using a Swedish population-based case-control study involving incident cases of MS (1798 cases, 3907 controls), we calculated odds ratios (OR) for MS comparing parents with childless subjects together with 95% confidence intervals (CI) employing logistic regression. Overall, there was an association between having children and reduced MS risk among both sexes. Subjects who had become parents within five years prior to the index year had a substantially reduced risk of developing MS (OR 0.6, 95% CI 0.5-0.8 for women, and OR 0.4, 95% CI 0.3-0.6 for men). No association between having children and MS risk was observed when more than 10 years had passed since the birth of the last child. We found no association between increasing offspring number and MS risk. The observed association between reproductive history and MS risk is restricted to a limited time period preceding the index year, with similar findings in both sexes, which contradicts biologic impact of pregnancy on MS risk and argues in favor of reverse causality, i.e. that fecundity is affected by yet-undiagnosed MS.

A novel predictive pharmacokinetic/pharmacodynamic model of repolarization prolongation derived from the effects of terfenadine, cisapride and E-4031 in the conscious chronic av node--ablated, His bundle-paced dog.

PubMed

Nolan, Emily R; Feng, Meihua Rose; Koup, Jeffrey R; Liu, Jing; Turluck, Daniel; Zhang, Yiqun; Paulissen, Jerome B; Olivier, N Bari; Miller, Teresa; Bailie, Marc B

2006-01-01

Terfenadine, cisapride, and E-4031, three drugs that prolong ventricular repolarization, were selected to evaluate the sensitivity of the conscious chronic atrioventricular node--ablated, His bundle-paced Dog for defining drug induced cardiac repolarization prolongation. A novel predictive pharmacokinetic/pharmacodynamic model of repolarization prolongation was generated from these data. Three male beagle dogs underwent radiofrequency AV nodal ablation, and placement of a His bundle-pacing lead and programmable pacemaker under anesthesia. Each dog was restrained in a sling for a series of increasing dose infusions of each drug while maintained at a constant heart rate of 80 beats/min. RT interval, a surrogate for QT interval in His bundle-paced dogs, was recorded throughout the experiment. E-4031 induced a statistically significant RT prolongation at the highest three doses. Cisapride resulted in a dose-dependent increase in RT interval, which was statistically significant at the two highest doses. Terfenadine induced a dose-dependent RT interval prolongation with a statistically significant change occurring only at the highest dose. The relationship between drug concentration and RT interval change was described by a sigmoid E(max) model with an effect site. Maximum RT change (E(max)), free drug concentration at half of the maximum effect (EC(50)), and free drug concentration associated with a 10 ms RT prolongation (EC(10 ms)) were estimated. A linear correlation between EC(10 ms) and HERG IC(50) values was identified. The conscious dog with His bundle-pacing detects delayed cardiac repolarization related to I(Kr) inhibition, and detects repolarization change induced by drugs with activity at multiple ion channels. A clinically relevant sensitivity and a linear correlation with in vitro HERG data make the conscious His bundle-paced dog a valuable tool for detecting repolarization effect of new chemical entities.

Atrial Premature Depolarization-Induced Changes in QRS and T Wave Morphology on Resting Electrocardiograms in Horses.

PubMed

Broux, B; De Clercq, D; Decloedt, A; Van Der Vekens, N; Verheyen, T; Ven, S; Pardon, B; van Loon, G

2016-07-01

The electrocardiographic differentiation between atrial (APDs) and ventricular (VPDs) premature depolarizations is important. P wave prematurity and normal QRS and T wave morphology generally are used as discriminating criteria for APDs. The aim of this study was to determine whether P, Q, R, S, and T wave amplitude, PQ interval, QRS and P wave duration and P and T wave morphology differ between APDs and sinus beats. To determine the relationship between the RR coupling interval and the change in S wave amplitude between sinus beats and APDs. Case-control study. From a modified base-apex configuration of 30 horses with APDs at rest, sinus beat and APD associated preceding RR interval, P, PQ and QRS duration and P, R, S, and T wave amplitudes were measured. Linear mixed models and logistic regression were used to determine the effect of APDs on the ECG variables studied. In comparison to sinus beats, APDs were associated with a significant (P < .001) change in P amplitude (-0.03 ± 0.01 mV) and increase in S (0.20 ± 0.02 mV) and T (0.08 ± 0.03 mV) amplitude. PQ (-20.3 ± 5.2 ms) and RR (-519 ± 14 ms) interval and P duration (-21.1 ± 3.0 ms) decreased (P < .001). APDs were significantly associated with a singular positive P wave (OR: 11.0, P < .001) and were more likely to have a monophasic positive T wave (OR: 9.2, P < .001). A smaller RR coupling interval was associated with an increased relative difference in S amplitude (P < .01). Atrial premature depolarizations may lead to changes in QRS and T wave morphology. Knowledge of these changes is important to avoid interpreting certain APDs as VPDs. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

"J waves" induced after short coupling intervals: a manifestations of latent depolarization abnormality?

PubMed

Aizawa, Yoshifusa; Nakayama, Masafumi; Sato, Masahito; Okabe, Masaaki; Aizawa, Yoshiyasu; Takatsuki, Seiji; Fukuda, Keiichi

2017-04-24

To confirm the presence of tachycardia-induced slur or notch in the terminal portion of the QRS complexes in a general patient population. A tachycardia-induced J wave was defined as a slur or notch in the terminal portion of the QRS complexes newly induced at short RR intervals during atrial premature contractions (APCs) or atrial electrical stimulation in the electrophysiological study (EPS). Twenty-three out of 2000 patients with general diseases were involved. All patients with aborted sudden cardiac death, ventricular fibrillation or a family history of sudden cardiac death were excluded. The mean age was 72 ± 9 years, and 11 patients were male (47.8%). When the RR interval was shortened from 821 ± 142 ms to 464 ± 52 ms in the conducted APCs (P < 0.0001), J waves became diagnostic (0.02 ± 0.03 mV to 0.20 ± 0.07 mV, P < 0.0001). J waves were confined to the inferior leads in 22 (95.7%) patients and were notched in 11 (47.8%) and slurred in 12 (52.2%) patients. The induction of J waves was accompanied by visible changes of the QRS morphology. When the post-APC RR interval was prolonged to 992 ± 305 ms (P = 0.0154 vs. baseline), the J waves were similar to baseline levels. During the EPS, J wave induction was confirmed during atrial stimulation. There were no characteristic clinical or ECG features in the patients with tachycardia-induced J waves. J waves can be newly induced by short RR intervals in a general patient population, and a conduction delay is the likely mechanism causing such J waves. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For Permissions, please email: journals.permissions@oup.com.

Male vocal competition is dynamic and strongly affected by social contexts in music frogs.

PubMed

Fang, Guangzhan; Jiang, Fan; Yang, Ping; Cui, Jianguo; Brauth, Steven E; Tang, Yezhong

2014-03-01

Male-male vocal competition in anuran species is critical for mating success; however, it is also highly time-consuming, energetically demanding and likely to increase predation risks. Thus, we hypothesized that changes in the social context would cause male vocal competition to change in real time in order to minimize the costs and maximize the benefits of competition. To test this hypothesis, we assessed the effect of repeating playbacks of either white noise (WN) or male advertisement calls on male call production in the Emei music frog (Babina daunchina), a species in which males build mud-retuse burrows and call from within these nests. Previous studies have shown that calls produced from inside burrows are highly sexually attractive (HSA) to females while those produced outside nests are of low sexual attractiveness (LSA). Results showed that most subjects called responsively after the end of WN playbacks but before the onset of conspecific call stimuli although call numbers were similar, indicating that while males adjusted competitive patterns according to the biological significance of signals, their competitive motivation did not change. Furthermore, these data indicate that the frogs had evolved the ability of interval timing. Moreover, when the inter-stimulus interval (ISI) between playbacks was varied, the subjects preferentially competed with HSA calls when the ISI was short (<4 s) but responded equally to HSA and LSA calls if the ISI was long (≥4 s), suggesting that males allocate competitive efforts depending on both the perceived sexual attractiveness of rivals and the time available for calling. Notably, approximately two-thirds of male calls occurred in response to HSA calls, a preference rate comparable to that previously found for females in phonotaxis experiments and consistent with the idea that the mechanisms underlying both the male's competitive responses to rivals and the female's preferences toward potential mates coevolved under the same selective pressure.

Effect of PR interval prolongation on long-term outcomes in patients with left bundle branch block vs non-left bundle branch block morphologies undergoing cardiac resynchronization therapy.

PubMed

Rickard, John; Karim, Mohammad; Baranowski, Bryan; Cantillon, Daniel; Spragg, David; Tang, W H Wilson; Niebauer, Mark; Grimm, Richard; Trulock, Kevin; Wilkoff, Bruce; Varma, Niraj

2017-10-01

Although the influence of QRS duration (QRSd) and/or bundle branch block morphology on outcomes of cardiac resynchronization therapy (CRT) have been well studied, the effect of PR interval remains uncertain. The purpose of this study was to evaluate the impact of PR prolongation (PRp) before CRT on long-term outcomes, specifically taking into account bundle branch block morphology and QRSd. We extracted clinical data on consecutive patients undergoing CRT. Multivariate models were constructed to analyze the effect of PRp (≥200 ms) on the combined endpoint of death, heart transplant, or left ventricular assist device. Kaplan-Meier curves were constructed stratifying patients based on bundle branch block and QRSd (dichotomized by 150 ms). Of the 472 patients who met inclusion criteria, 197 (41.7%) had PR interval ≥200 ms. During follow-up (mean 5.1 ± 2.6 years) there were 214 endpoints, of which 109 (23.1%) occurred in patients with PRp. In multivariate analysis, PRp was independently associated with worsened outcomes (hazard ratio 1.34, 95% confidence interval 1.01-1.77, P = .04). When stratified by bundle branch block morphology, PRp was significantly associated with worsened outcomes (log-rank P <.001) in patients with LBBB but not in those with non-LBBB (log-rank P = .55). Among patients with LBBB, stratified by QRSd, patients without PRp had improved outcomes compared to those with PRp independent of QRSd (log-rank P <.001). PRp is an independent predictor of impaired long-term outcome after CRT among patients with LBBB but not in non-LBBB patients. Notably, among LBBB patients, PRp is a more important predictor than QRSd in assessing long-term outcomes. Copyright © 2017. Published by Elsevier Inc.

A thorough QT study to evaluate the effects of therapeutic and supratherapeutic doses of delafloxacin on cardiac repolarization.

PubMed

Litwin, Jeffrey S; Benedict, Michael S; Thorn, Michael D; Lawrence, Laura E; Cammarata, Sue K; Sun, Eugene

2015-01-01

A randomized, double-blind, placebo-controlled, 4-period crossover study was conducted in 52 healthy adults to assess the effect of delafloxacin on the corrected QT (QTc) interval. The QT interval, corrected for heart rate using Fridericia's formula (QTcF), was determined predose and at 0.5, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 12, 18, and 24 h after dosing with delafloxacin at 300 mg intravenously (i.v.; therapeutic), delafloxacin at 900 mg i.v. (supratherapeutic), moxifloxacin at 400 mg orally (p.o.; positive control), and placebo. The pharmacokinetic profile of delafloxacin was also evaluated. At each time point after delafloxacin administration, the upper limit of the 90% confidence interval (CI) for the placebo-corrected change from the predose baseline in QTcF (ΔΔQTcF) was less than 10 ms (maximum, 3.9 ms at 18 h after dosing), indicating an absence of a clinically meaningful increase in the QTc interval. The lower limit of the 90% CI of ΔΔQTcF for moxifloxacin versus placebo was longer than 5 ms at all 5 time points selected for assay sensitivity analysis, demonstrating that the study was adequately sensitive to assess QTc prolongation. There was no positive relationship between delafloxacin plasma concentrations and ΔΔQTcF. Treatment-emergent adverse events (AEs) were more frequent among subjects receiving a single supratherapeutic dose of 900 mg delafloxacin. There were no deaths, serious AEs, or AEs leading to study discontinuation and no clinically meaningful abnormalities in laboratory values or vital signs observed at any time point after any dose of the study drug. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Automated Algorithm for J-Tpeak and Tpeak-Tend Assessment of Drug-Induced Proarrhythmia Risk

DOE PAGES

Johannesen, Lars; Vicente, Jose; Hosseini, Meisam; ...

2016-12-30

Prolongation of the heart rate corrected QT (QTc) interval is a sensitive marker of torsade de pointes risk; however it is not specific as QTc prolonging drugs that block inward currents are often not associated with torsade. Recent work demonstrated that separate analysis of the heart rate corrected J-T peakc (J-T peakc) and T peak-T end intervals can identify QTc prolonging drugs with inward current block and is being proposed as a part of a new cardiac safety paradigm for new drugs (the “CiPA” initiative). In this work, we describe an automated measurement methodology for assessment of the J-T peakcmore » and T peak-T end intervals using the vector magnitude lead. The automated measurement methodology was developed using data from one clinical trial and was evaluated using independent data from a second clinical trial. Comparison between the automated and the prior semi-automated measurements shows that the automated algorithm reproduces the semi-automated measurements with a mean difference of single-deltas <1 ms and no difference in intra-time point variability (p for all > 0.39). In addition, the time-profile of the baseline and placebo-adjusted changes are within 1 ms for 63% of the time-points (86% within 2 ms). Importantly, the automated results lead to the same conclusions about the electrophysiological mechanisms of the studied drugs. We have developed an automated algorithm for assessment of J-T peakc and T peak-T end intervals that can be applied in clinical drug trials. Under the CiPA initiative this ECG assessment would determine if there are unexpected ion channel effects in humans compared to preclinical studies. In conclusion, the algorithm is being released as open-source software.« less

Automated Algorithm for J-Tpeak and Tpeak-Tend Assessment of Drug-Induced Proarrhythmia Risk

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johannesen, Lars; Vicente, Jose; Hosseini, Meisam

Prolongation of the heart rate corrected QT (QTc) interval is a sensitive marker of torsade de pointes risk; however it is not specific as QTc prolonging drugs that block inward currents are often not associated with torsade. Recent work demonstrated that separate analysis of the heart rate corrected J-T peakc (J-T peakc) and T peak-T end intervals can identify QTc prolonging drugs with inward current block and is being proposed as a part of a new cardiac safety paradigm for new drugs (the “CiPA” initiative). In this work, we describe an automated measurement methodology for assessment of the J-T peakcmore » and T peak-T end intervals using the vector magnitude lead. The automated measurement methodology was developed using data from one clinical trial and was evaluated using independent data from a second clinical trial. Comparison between the automated and the prior semi-automated measurements shows that the automated algorithm reproduces the semi-automated measurements with a mean difference of single-deltas <1 ms and no difference in intra-time point variability (p for all > 0.39). In addition, the time-profile of the baseline and placebo-adjusted changes are within 1 ms for 63% of the time-points (86% within 2 ms). Importantly, the automated results lead to the same conclusions about the electrophysiological mechanisms of the studied drugs. We have developed an automated algorithm for assessment of J-T peakc and T peak-T end intervals that can be applied in clinical drug trials. Under the CiPA initiative this ECG assessment would determine if there are unexpected ion channel effects in humans compared to preclinical studies. In conclusion, the algorithm is being released as open-source software.« less

A thorough QT study to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine and escitalopram, in healthy volunteers.

PubMed

Kim, Anhye; Lim, Kyoung Soo; Lee, Howard; Chung, Hyewon; Yoon, Seo Hyun; Yu, Kyung-Sang; Cho, Joo-Youn; Jang, In-Jin; Chung, Jae-Yong

2016-07-01

Prolongation of the QT interval on an ECG is a surrogate marker for predicting the proarrhythmic potential of a drug under development. The aim of this study was to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine immediate release (IR) and escitalopram, in healthy individuals. This was a randomized, open-label, 4×4 Williams crossover study, with four single-dose treatments [placebo, 400 mg moxifloxacin (positive control), 20 mg escitalopram, and 100 mg quetiapine IR], conducted in 40 healthy volunteers. Serial blood samples for pharmacokinetics and ECG were collected. Individually, RR-corrected QTc intervals (QTcI) and placebo-adjusted changes from baseline values of QTcI (ΔΔQTcI) were evaluated. Lower-bound values of the one-sided 95% confidence interval for ΔΔQTcI of moxifloxacin with more than 5 ms confirmed the sensitivity of the assay. The maximum upper bound 95% confidence interval for the ΔΔQTcI of quetiapine IR and escitalopram was 13.7 and 10.5 ms, with mean estimates of 10.2 and 6.9 ms, respectively. Peak effects of moxifloxacin and quetiapine IR on ΔΔQTcI were observed at approximately time to maximum concentration (Tmax), whereas that of escitalopram was observed 3 h after Tmax. The concentration-ΔΔQTcI relationships of quetiapine IR and escitalopram were relatively flat, as compared with that of moxifloxacin. The results demonstrated the validity of trial methodology and that quetiapine IR and escitalopram caused QT prolongation in healthy individuals. In addition, hysteresis of escitalopram-induced QTc prolongation. These results indicate that higher doses of these drugs could lead to greater QT prolongation in a dose-response manner.

A Thorough QT Study To Evaluate the Effects of Therapeutic and Supratherapeutic Doses of Delafloxacin on Cardiac Repolarization

PubMed Central

Benedict, Michael S.; Thorn, Michael D.; Lawrence, Laura E.; Cammarata, Sue K.; Sun, Eugene

2015-01-01

A randomized, double-blind, placebo-controlled, 4-period crossover study was conducted in 52 healthy adults to assess the effect of delafloxacin on the corrected QT (QTc) interval. The QT interval, corrected for heart rate using Fridericia's formula (QTcF), was determined predose and at 0.5, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 12, 18, and 24 h after dosing with delafloxacin at 300 mg intravenously (i.v.; therapeutic), delafloxacin at 900 mg i.v. (supratherapeutic), moxifloxacin at 400 mg orally (p.o.; positive control), and placebo. The pharmacokinetic profile of delafloxacin was also evaluated. At each time point after delafloxacin administration, the upper limit of the 90% confidence interval (CI) for the placebo-corrected change from the predose baseline in QTcF (ΔΔQTcF) was less than 10 ms (maximum, 3.9 ms at 18 h after dosing), indicating an absence of a clinically meaningful increase in the QTc interval. The lower limit of the 90% CI of ΔΔQTcF for moxifloxacin versus placebo was longer than 5 ms at all 5 time points selected for assay sensitivity analysis, demonstrating that the study was adequately sensitive to assess QTc prolongation. There was no positive relationship between delafloxacin plasma concentrations and ΔΔQTcF. Treatment-emergent adverse events (AEs) were more frequent among subjects receiving a single supratherapeutic dose of 900 mg delafloxacin. There were no deaths, serious AEs, or AEs leading to study discontinuation and no clinically meaningful abnormalities in laboratory values or vital signs observed at any time point after any dose of the study drug. PMID:25845864

Lacosamide cardiac safety: clinical trials in patients with partial-onset seizures.

PubMed

Rudd, G D; Haverkamp, W; Mason, J W; Wenger, T; Jay, G; Hebert, D; Doty, P; Horstmann, R

2015-11-01

To evaluate the cardiac safety of adjunctive lacosamide in a large pool of adults with partial-onset seizures (POS). Post-randomization changes from baseline for electrocardiographic (ECG) measurements, diagnostic findings, and relevant adverse events (AEs) were compared for pooled data from three randomized, placebo-controlled trials of adjunctive lacosamide for the treatment of POS. Lacosamide did not prolong the QTc interval or affect heart rate as determined by an analysis of data from patients randomized to lacosamide 200, 400, or 600 mg/day (n = 944) compared with placebo (n = 364). After 12-week maintenance treatment, mean changes from baseline for QRS duration were similar between the placebo and lacosamide 200 and 400 mg/day groups (0.0, -0.2, and 0.4 ms), but slightly increased for lacosamide 600 mg/day (2.3 ms). A small, dose-related mean increase in PR interval was observed (-0.3, 1.4, 4.4, and 6.6 ms for the placebo and lacosamide 200, 400, and 600 mg/day groups, respectively). First-degree atrioventricular (AV) block was reported as a non-serious AE in 0.0%, 0.7%, 0.2%, and 0.5% of patients in the same respective groups. Second- or higher degree AV block was not observed. There was no evidence of a PR-interval-related pharmacodynamic interaction of lacosamide with either carbamazepine or lamotrigine. Evaluation of the pooled cardiac safety data from patients with POS showed that adjunctive lacosamide at the maximum recommended dose (400 mg/day) was not clearly associated with any cardiac effect other than a small, dose-related increase in PR interval that had no evident symptomatic consequence. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The BUMP model of response planning: intermittent predictive control accounts for 10 Hz physiological tremor.

PubMed

Bye, Robin T; Neilson, Peter D

2010-10-01

Physiological tremor during movement is characterized by ∼10 Hz oscillation observed both in the electromyogram activity and in the velocity profile. We propose that this particular rhythm occurs as the direct consequence of a movement response planning system that acts as an intermittent predictive controller operating at discrete intervals of ∼100 ms. The BUMP model of response planning describes such a system. It forms the kernel of Adaptive Model Theory which defines, in computational terms, a basic unit of motor production or BUMP. Each BUMP consists of three processes: (1) analyzing sensory information, (2) planning a desired optimal response, and (3) execution of that response. These processes operate in parallel across successive sequential BUMPs. The response planning process requires a discrete-time interval in which to generate a minimum acceleration trajectory to connect the actual response with the predicted future state of the target and compensate for executional error. We have shown previously that a response planning time of 100 ms accounts for the intermittency observed experimentally in visual tracking studies and for the psychological refractory period observed in double stimulation reaction time studies. We have also shown that simulations of aimed movement, using this same planning interval, reproduce experimentally observed speed-accuracy tradeoffs and movement velocity profiles. Here we show, by means of a simulation study of constant velocity tracking movements, that employing a 100 ms planning interval closely reproduces the measurement discontinuities and power spectra of electromyograms, joint-angles, and angular velocities of physiological tremor reported experimentally. We conclude that intermittent predictive control through sequential operation of BUMPs is a fundamental mechanism of 10 Hz physiological tremor in movement. Copyright © 2010 Elsevier B.V. All rights reserved.

Salivary testosterone measurement by liquid chromatography tandem mass spectrometry in adult males and females.

PubMed

Keevil, B G; MacDonald, P; Macdowall, W; Lee, D M; Wu, F C W

2014-05-01

Salivary testosterone (Sal-T) may be a useful surrogate of serum free testosterone. The study aims were to use a novel liquid chromatography tandem mass spectrometry (LC-MS/MS) assay to determine whether Sal-T concentrations accurately reflect Sal-T concentrations in both sexes and to investigate practical aspects of sample collection. Saliva and serum samples were collected in 104 male and 91 female subjects. A more sensitive LC-MS/MS assay was developed to enable Sal-T quantitation in the low concentrations found in females. Saliva (200 µL) was extracted with 1 mL of methyl-tert-butyl ether following the addition of D5-testosterone. Quantitation was performed using a Waters TQ-S mass spectrometer. The assay achieved a lower limit of quantification of 5 pmol/L, sufficiently sensitive to measure testosterone in female saliva. Sal-T showed a diurnal variation but samples taken at weekly and monthly intervals showed no significant differences. Sal-T was stable at ambient temperature for up to 5 days, after freeze-thawing and 3 years frozen storage. Reference intervals for Sal-T were 93-378 pmol/L in males and 5-46 pmol/L in females. Sal-T correlated significantly with serum calculated free-T in males (r = 0.71, P < 0.001) and in females (r = 0.39, P < 0.001). These results confirm that testosterone can be reliably and accurately measured by LC-MS/MS in both adult male and female saliva samples. These results lay the foundation for further exploration of the clinical application of Sal- T as a reliable alternative to serum testosterone in the diagnosis and management of androgen disorders and assessment of androgen status in clinical research.

Association between serum uric acid, metabolic syndrome and microalbuminuria in previously untreated essential hypertensive patients.

PubMed

Rodilla, Enrique; Pérez-Lahiguera, Francisco; Costa, José A; González, Carmen; Miralles, Amparo; Moral, Desamparados; Pascual, José María

2009-01-17

The aim of the study was to assess the association of serum uric acid levels with microalbuminuria -urinary albumin excretion (UAE)> or = 30mg/24h-. Cross-sectional study in 429 (220 women) hypertensive, non diabetic, never treated patients (mean age: 47 years) with glomerular filtration rate > or =60ml/min/1.73m(2). The prevalence of microalbuminuria was 20.5%; 18% had hyperuricemia and 47% fulfilled the criteria for metabolic syndrome (MS). Baseline UAE correlated in the unvaried analysis to diastolic blood pressure, waist circumference, high-density lipoprotein cholesterol and uric acid. In multiple linear regression models, only MS (beta=0.113; p=0.03), and serum uric acid values (beta=0.04; p=0.05) were independently associated with logUAE, after adjustment for age and sex. Hyperuricemia (serum uric acid level > or =7.0mg/dl for men and > or =6.5mg/dl for women; odds ratio=2.18; 95% confidence interval, 1.21-3.92; p=0.010), and MS (odds ratio=2.16; 95% confidence interval, 1.32-3.53; p=0.002) were independently associated with a higher risk of microalbuminuria in multiple logistic regression analyses. The prevalence of microalbuminuria was 45.8% in patients with coexistent MS and hyperuricemia, as compared to 13.6% in hypertensive patients without it (p<0.001). In patients with concomitant MS and hyperuricemia the probability of being microalbuminuric was 3.7 times higher than in patients without those factors. Serum uric acid level is associated with microalbuminuria. Coexistence of MS and hyperuricemia in hypertensive patients increases almost 4 times the odds of being microalbuminuric.

Towards assessing corticospinal excitability bilaterally: Validation of a double-coil TMS method.

PubMed

Grandjean, Julien; Derosiere, Gerard; Vassiliadis, Pierre; Quemener, Louise; Wilde, Ysaline de; Duque, Julie

2018-01-01

For several decades, Transcranial magnetic stimulation (TMS) has been used to monitor corticospinal excitability (CSE) changes in various contexts. Habitually, single-coil TMS is applied over one primary motor cortex (M1), eliciting motor-evoked potentials (MEPs) in a contralateral limb muscle, usually a hand effector. However, in many situations, it would be useful to obtain MEPs in both hands simultaneously, to track CSE bilaterally. Such an approach requires stimulating both M1 concurrently while avoiding interference between the two descending stimuli. We examined MEPs obtained at rest using a double-coil TMS approach where the two M1 are stimulated with a 1ms inter-pulse interval (double-coil 1ms ). MEPs were acquired using double-coil 1ms (MEP double ) or single-coil (MEP single ) TMS, at five different intensities of stimulation (100, 115, 130, 145 or 160% of the resting motor threshold, rMT). Given the 1ms inter-pulse interval in double-coil 1ms trials, MEP double were either evoked by a 1st (MEP double-1 ) or a 2nd (MEP double-2 ) TMS pulse. All MEP TYPE (MEP TYPE =MEP single , MEP double-1 and MEP double-2 ) were equivalent, regardless of the hand within which they were elicited, the intensity of stimulation or the pulse order. This method allows one to observe state-related CSE changes for the two hands simultaneously on a trial-by-trial basis. These results infer the absence of any neural interactions between the two cortico-spinal volleys with double-coil 1ms TMS. Hence, this technique can be reliably used to assess CSE bilaterally, opening new research perspectives for scientists interested in physiological markers of activity in the motor output system. Copyright © 2017 Elsevier B.V. All rights reserved.

Prolonged QRS Widening After Aripiprazole Overdose.

PubMed

Mazer-Amirshahi, Maryann; Porter, Robert; Dewey, Kayla

2018-05-05

Aripiprazole is an atypical antipsychotic with a long half-life. Overdose can result in protracted somnolence and cardiac disturbances, particularly QT interval prolongation. This is a single case report of a 14-year-old boy who took an overdose of aripiprazole and developed QRS widening. A 14-year-old boy intentionally ingested 20 tablets of aripiprazole (5 mg). He was brought to the emergency department when his ingestion was discovered. The patient's vital signs were as follows: temperature, 37.7°C; heart rate, 108 beats/min; blood pressure, 138/98 mm Hg; and respirations, 16 breaths/min. Activated charcoal was administered within 90 minutes of ingestion. Initial electrocardiogram (EKG) showed sinus tachycardia, with a QRS of 138 ms and QT interval of 444 ms. QRS duration was 90 ms on an EKG performed 3 months earlier. A bolus of sodium bicarbonate was administered, and the patient was transferred to the pediatric intensive care unit. Repeat EKG demonstrated a QRS of 156 ms, and a sodium bicarbonate infusion was initiated. The patient continued to have QRS prolongation for the next 8 days, reaching a peak of 172 ms 3 days postingestion. Despite aggressive treatment with sodium bicarbonate, there was persistent QRS prolongation; however, the patient did not have any dysrhythmias and remained hemodynamically stable. The patient was discharged 9 days postingestion when the QRS duration normalized to 82 ms. Genetic testing revealed that the patient was a CYP2D6 poor metabolizer. This case suggests that aripiprazole toxicity may possibly be associated with QRS prolongation without associated dysrhythmias or cardiovascular compromise. In addition, toxicity may be prolonged in patients who are CYP2D6 poor metabolizers.

Gender differences in the electrocardiogram screening of athletes.

PubMed

Bessem, Bram B; de Bruijn, Matthijs M C; Nieuwland, Wybe W

2017-02-01

Gender-related differences are frequently used in medicine. Electrocardiograms are also subject to such differences. This study evaluated gender differences in ECG parameters of young athletes, discussing the possible implications of these differences for ECG criteria used in the cardiovascular screening of young athletes. Observational cross-sectional study. In 2013 and 2014 all the ECGs from the cardiovascular screenings performed at University Sports Medical Centre in Groningen of the student athletes who wanted to participate in a college sports program were collected. The ECG characteristics were scored using computer-based measurements and the Seattle ECG criteria. The study population included 1436 athletes, of which 72% were male. Male athletes were older (19.3 years vs. 18.6 years), participated in sports more frequently (4.0/week vs. 3.8/week) and spent more hours per week practising sports (6.4h/week vs. 5.8h/week) than female athletes. Male athletes had significantly higher PR intervals (149ms vs. 141ms), lead voltages and QRS duration (98ms vs. 88ms). Female athletes had significantly higher resting heart rates (69/min vs. 64/min) and QTc intervals (407ms vs. 400ms). Male athletes also had significantly higher amounts of sinus bradycardia (38.3% vs. 23.0%), incomplete RBBB (15.0% vs. 3.7%), early repolarisation (4.5% vs. 1.0%) and isolated QRS voltage criteria for LVH (26.3% vs. 4.6%). All P-values were ≤0.001. ECGs of young athletes demonstrate gender-related differences. These differences could be considered in their cardiovascular screening. For the Seattle ECG criteria we advise additional research into the clinical implications of using gender-based cut-off values for the QRS duration in the intraventricular conduction delay criterion. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Mental stress test: a rapid, simple, and efficient test to unmask long QT syndrome.

PubMed

Etienne, Pauline; Huchet, François; Gaborit, Nathalie; Barc, Julien; Thollet, Aurélie; Kyndt, Florence; Guyomarch, Béatrice; Le Marec, Hervé; Charpentier, Flavien; Schott, Jean-Jacques; Redon, Richard; Probst, Vincent; Gourraud, Jean-Baptiste

2018-04-20

QT prolongation during mental stress test (MST) has been associated with familial idiopathic ventricular fibrillation. In long QT syndrome (LQTS), up to 30% of mutation carriers have normal QT duration. Our aim was to assess the QT response during MST, and its accuracy in the diagnosis of concealed LQTS. All patients who are carrier of a KCNQ1 or KCNH2 mutations without QT prolongation were enrolled. A control group was constituted of patients with negative exercise and epinephrine tests. Electrocardiogram were recorded at rest and at the maximum heart rate during MST and reviewed by two physicians. Among the 70 patients enrolled (median age 41±2.1 years, 46% male), 36 were mutation carrier for LQTS (20 KCNQ1 and 16 KCNH2), and 34 were controls. KCNQ1 and KCNH2 mutation carriers presented a longer QT interval at baseline [405(389; 416) and 421 (394; 434) ms, respectively] compared with the controls [361(338; 375)ms; P < 0.0001]. QT duration during MST varied by 9 (4; 18) ms in KCNQ1, 3 (-6; 16) ms in KCNH2, and by -22 (-29; -17) ms in controls (P < 0.0001). These QT variations were independent of heart rate (P < 0.3751). Receiver operating characteristic curve analysis identified a cut-off value of QT variation superior to -11 ms as best predictor of LQTS. It provided 97% sensitivity and 97% specificity of QT prolongation in the diagnosis of LQTS. We identified a paradoxical response of the QT interval during MST in LQTS. Easy to assess, MST may be efficient to unmask concealed LQTS in patients at risk of this pathology.

Effect of Left Cardiac Sympathetic Denervation on the Electromechanical Window in Patients with either Type 1 or Type 2 Long QT Syndrome: A Pilot Study.

PubMed

Schneider, Andrew E; Bos, J Martijn; Ackerman, Michael J

2016-09-01

Left cardiac sympathetic denervation (LCSD) exerts significant antifibrillatory effects in patients with long QT syndrome (LQTS). Recently, electromechanical window (EMW) has emerged as a novel torsadogenic marker in LQTS, superior to QT interval (QTc) in distinguishing symptomatic from asymptomatic patients. To explore the hypothesis that LCSD improves EMW most favorably in patients with LQT1. From September 2006 to July 2015, 44 LQT1 and 25 LQT2 patients underwent LCSD. Subset analysis was performed on the six LQT1 and seven LQT2 patients who had echocardiograms both pre-LCSD and ≥3 months post-LCSD. EMW is defined as the time difference (ms) between aortic valve closure and the end of the QT interval, measured from an ECG on the concurrent echocardiogram. Compared to published normal EMW values of 22 ± 19 ms, pre-LCSD EMW mean values were -78 ± 36 ms in LQT1 and -71 ± 35 ms in LQT2 (P < .001). Following LCSD, there was a 57 ± 35 ms decrease in QTc in LQT1 (P = .16) and 23 ± 21 ms decrease in QTc in LQT2 (P = .3). Overall, there was a 35 ± 57 ms mean improvement in EMW post-LCSD (P = .04). Five of the 6 (83%) LQT1 subjects had a favorable EMW change post-LCSD (mean improvement 56 ± 25 ms, P = .04). Five of the 7 (71%) LQT2 subjects had a favorable EMW change post-LCSD (mean improvement 18 ± 19 ms, P = .2). The precise mechanism of the LCSD therapeutic effect in LQTS patients is not fully understood. This pilot study raises the possibility that LCSD's antitorsadogenic effect in patients with LQT1 could be conferred in part by restoration of electromechanical order, evidenced by normalization of the EMW. © 2016 Wiley Periodicals, Inc.

Compendium of the FY1990 and FY1992 Research Reviews for the Research Methods Branch

DTIC Science & Technology

1994-09-01

the perfusion technique, the perfusion was not done in situ. Trout were anesthetized with MS-222 (3-aminobenzoic acid ethyl ester, Sigma Chemical...by a trypan blue exclusion test. Medaka Medaka were anesthetized with MS-222, transferred to a dissecting tray, and incised from the urogenital pore...Histology General histology was compared at intervals of 20 days. Fish were anesthetized , fixed, and processed for paraffin embedment, and sections

Duty factor variation possibility from 1% to 100% with PKU microwave driven Cs-free volume H{sup −} sources

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peng, S. X., E-mail: sxpeng@pku.edu.cn; Zhang, T.; Ren, H. T.

Microwave driven cesium-free volume H{sup −} sources, that have the ability to deliver tens of mA H{sup −} at 35 keV both in CW and 10% duty factor (100 Hz/1 ms), were developed at Peking University (PKU) [S. X. Peng et al., in Proceeding of IPAC 2015, WEPWA027, Richmond, Virginia, USA, 3–8 May 2015]. Recently, special efforts were paid on the investigation of duty factor variation possibility from 1% to 100% with them. Most of the experiments were carried out with a pulsed length (τ) of 1 ms and different intervals of 99 ms, 49 ms, 39 ms, 29 ms,more » 19 ms, 9 ms, 4 ms, 2 ms, 1 ms, 0.5 ms, and 0 ms, respectively. Other experiments were focused on CW operation and fixed duty factor of 1%. Experimental results prove that PKU H{sup −} sources can deliver tens of mA H{sup −} at duty factor from 1% to 100%. The RF power efficiency increases steadily with the increasing of duty factor from 1% to CW at a fixed pulsed length. Under a given duty factor and pulsed length, RF power efficiency keeps constant and the H{sup −} current increases with RF power linearly. Details will be presented in the paper.« less

Thunderstorm vertical velocities and mass flux estimated from satellite data

NASA Technical Reports Server (NTRS)

Adler, R. F.; Fenn, D. D.

1979-01-01

Infrared geosynchronous satellite data with an interval of five minutes between images are used to estimate thunderstorm top ascent rates on two case study days. A mean vertical velocity of 3.5/ms for 19 clouds is calculated at a height of 8.7 km. This upward motion is representative of an area of approximately 10km on a side. Thunderstorm mass flux of approximately 2x10 to the 11th power/gs is calculated, which compares favorably with previous estimates. There is a significant difference in the mean calculated vertical velocity between elements associated with severe weather reports (w bar=4.6/ms) and those with no such reports (2.5/ms). Calculations were made using a velocity profile for an axially symmetric jet to estimate the peak updraft velocity. For the largest observed w value of 7.8/ms the calculation indicates a peak updraft of approximately 50/ms.

Evaluation of Tp-e interval and Tp-e/QT ratio in patients with ankylosing spondylitis.

PubMed

Acar, Gurkan; Yorgun, Hikmet; Inci, Mehmet Fatih; Akkoyun, Murat; Bakan, Betul; Nacar, Alper Bugra; Dirnak, Imran; Cetin, Gozde Yildirim; Bozoglan, Orhan

2014-03-01

Ankylosing spondylitis (AS) is a chronic multi-systemic inflammatory rheumatic disorder. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the transmural dispersion of repolarization and that increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. The aim of this study was to evaluate ventricular repolarization by using Tp-e interval and Tp-e/QT ratio in patients with AS, and to assess the relation with inflammation. Sixty-two patients with AS and 50 controls were included. Tp-e interval and Tp-e/QT ratio were measured from a 12-lead electrocardiogram, and the Tp-e interval corrected for heart rate. The plasma level of high sensitive C-reactive protein (hsCRP) was measured. These parameters were compared between groups. In electrocardiographic parameters analysis, QT dispersion (QTd) and corrected QTd were significantly increased in AS patients compared to the controls (31.7 ± 9.6 vs 28.2 ± 7.4 and 35.8 ± 11.5 vs 30.6 ± 7.9 ms, P = 0.03 and P = 0.007, respectively). cTp-e interval and Tp-e/QT ratio were also significantly higher in AS patients (92.1 ± 10.2 vs 75.8 ± 8.4 and 0.22 ± 0.02 vs 0.19 ± 0.02 ms, all P values <0.001). cTp-e interval and Tp-e/QT ratio were significantly correlated with hsCRP (r = 0.63, P < 0.001 and r = 0.49, P < 0.001, respectively). Our study revealed that Tp-e interval and Tp-e/QT ratio were increased in AS patients. These electrocardiographic ventricular repolarization indexes were significantly correlated with the plasma level of hsCRP.

Evaluation of Tp-e interval and Tp-e/QT ratio in patients with ankylosing spondylitis.

PubMed

Acar, Gurkan; Yorgun, Hikmet; Inci, Mehmet Fatih; Akkoyun, Murat; Bakan, Betul; Nacar, Alper Bugra; Dirnak, Imran; Cetin, Gozde Yildirim; Bozoglan, Orhan

2013-04-12

OBJECTIVES: Ankylosing spondylitis (AS) is a chronic multi-systemic inflammatory rheumatic disorder. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the transmural dispersion of repolarization and that increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. The aim of this study was to evaluate ventricular repolarization by using Tp-e interval and Tp-e/QT ratio in patients with AS, and to assess the relation with inflammation. METHODS: Sixty-two patients with AS and 50 controls were included. Tp-e interval and Tp-e/QT ratio were measured from a 12-lead electrocardiogram, and the Tp-e interval corrected for heart rate. The plasma level of high sensitive C-reactive protein (hsCRP) was measured. These parameters were compared between groups. RESULTS: In electrocardiographic parameters analysis, QT dispersion (QTd) and corrected QTd were significantly increased in AS patients compared to the controls (31.7 ± 9.6 vs 28.2 ± 7.4 and 35.8 ± 11.5 vs 30.6 ± 7.9 ms, P = 0.03 and P = 0.007, respectively). cTp-e interval and Tp-e/QT ratio were also significantly higher in AS patients (92.1 ± 10.2 vs 75.8 ± 8.4 and 0.22 ± 0.02 vs 0.19 ± 0.02 ms, all P values <0.001). cTp-e interval and Tp-e/QT ratio were significantly correlated with hsCRP (r = 0.63, P < 0.001 and r = 0.49, P < 0.001, respectively). CONCLUSIONS: Our study revealed that Tp-e interval and Tp-e/QT ratio were increased in AS patients. These electrocardiographic ventricular repolarization indexes were significantly correlated with the plasma level of hsCRP.

Habituation of LG-mediated tailflip in the crayfish.

PubMed

Nagayama, Toshiki; Araki, Makoto

2015-06-01

Crayfish escape from threatening stimuli by tailflipping. If a stimulus is applied to the rear, crayfish escape up and forwards in a summersault maneuver that is mediated by the activation of lateral giant (LG) interneurons. The occurrence probability of LG-mediated tailflip, however, diminishes and habituates if a stimulus is repeatedly applied. Since crayfish have a relatively simple CNS with many identifiable neurons, crayfish represent a good animal to analyze the cellular basis of habituation. A reduction in the amplitude of the EPSP in the LGs, caused by direct chemical synaptic connection from sensory afferents by repetitive stimulations, is essential to bring about an inactivation of the LGs. The spike response of the LGs recovers within several minutes of habituation, but the LGs subsequently fail to spike when an additional stimulus is applied after specific periods following habituation. These results indicate that a decline in synaptic efficacy from the mechanosensory afferents recovers readily after a short delay, but then the excitability of the LGs themselves decreases. Furthermore, the processes underlying habituation are modulated depending on a social status. When two crayfish encounter each other, a winner-loser relationship is established. With a short interstimulus interval of 5 s, the rate of habituation of the LG in both socially dominant and subordinate crayfish becomes lower than in socially isolated animals. Serotonin and octopamine affect this social status-dependent modulation of habituation by means of activation of downstream second messenger system of cAMP and IP3 cascades, respectively.

A Concealed Information Test with multimodal measurement.

PubMed

Ambach, Wolfgang; Bursch, Stephanie; Stark, Rudolf; Vaitl, Dieter

2010-03-01

A Concealed Information Test (CIT) investigates differential physiological responses to deed-related (probe) vs. irrelevant items. The present study focused on the detection of concealed information using simultaneous recordings of autonomic and brain electrical measures. As a secondary issue, verbal and pictorial presentations were compared with respect to their influence on the recorded measures. Thirty-one participants underwent a mock-crime scenario with a combined verbal and pictorial presentation of nine items. The subsequent CIT, designed with respect to event-related potential (ERP) measurement, used a 3-3.5s interstimulus interval. The item presentation modality, i.e. pictures or written words, was varied between subjects; no response was required from the participants. In addition to electroencephalogram (EEG), electrodermal activity (EDA), electrocardiogram (ECG), respiratory activity, and finger plethysmogram were recorded. A significant probe-vs.-irrelevant effect was found for each of the measures. Compared to sole ERP measurement, the combination of ERP and EDA yielded incremental information for detecting concealed information. Although, EDA per se did not reach the predictive value known from studies primarily designed for peripheral physiological measurement. Presentation modality neither influenced the detection accuracy for autonomic measures nor EEG measures; this underpins the equivalence of verbal and pictorial item presentation in a CIT, regardless of the physiological measures recorded. Future studies should further clarify whether the incremental validity observed in the present study reflects a differential sensitivity of ERP and EDA to different sub-processes in a CIT. Copyright 2009 Elsevier B.V. All rights reserved.

Effect of acoustic similarity on short-term auditory memory in the monkey

PubMed Central

Scott, Brian H.; Mishkin, Mortimer; Yin, Pingbo

2013-01-01

Recent evidence suggests that the monkey’s short-term memory in audition depends on a passively retained sensory trace as opposed to a trace reactivated from long-term memory for use in working memory. Reliance on a passive sensory trace could render memory particularly susceptible to confusion between sounds that are similar in some acoustic dimension. If so, then in delayed matching-to-sample, the monkey’s performance should be predicted by the similarity in the salient acoustic dimension between the sample and subsequent test stimulus, even at very short delays. To test this prediction and isolate the acoustic features relevant to short-term memory, we examined the pattern of errors made by two rhesus monkeys performing a serial, auditory delayed match-to-sample task with interstimulus intervals of 1 s. The analysis revealed that false-alarm errors did indeed result from similarity-based confusion between the sample and the subsequent nonmatch stimuli. Manipulation of the stimuli showed that removal of spectral cues was more disruptive to matching behavior than removal of temporal cues. In addition, the effect of acoustic similarity on false-alarm response was stronger at the first nonmatch stimulus than at the second one. This pattern of errors would be expected if the first nonmatch stimulus overwrote the sample’s trace, and suggests that the passively retained trace is not only vulnerable to similarity-based confusion but is also highly susceptible to overwriting. PMID:23376550

Evidence for increased glutamatergic cortical facilitation in children and adolescents with major depressive disorder.

PubMed

Croarkin, Paul E; Nakonezny, Paul A; Husain, Mustafa M; Melton, Tabatha; Buyukdura, Jeylan S; Kennard, Betsy D; Emslie, Graham J; Kozel, F Andrew; Daskalakis, Zafiris J

2013-03-01

Converging lines of evidence implicate the glutamate and γ-aminobutyric acid neurotransmitter systems in the pathophysiology of major depressive disorder. Transcranial magnetic stimulation cortical excitability and inhibition paradigms have been used to assess cortical glutamatergic and γ-aminobutyric acid-mediated tone in adults with major depressive disorder, but not in children and adolescents. To compare measures of cortical excitability and inhibition with 4 different paradigms in a group of children and adolescents with major depressive disorder vs healthy controls. Cross-sectional study examining medication-free children and adolescents (aged 9-17 years) with major depressive disorder compared with healthy controls. Cortical excitability was assessed with motor threshold and intracortical facilitation measures. Cortical inhibition was measured with cortical silent period and intracortical inhibition paradigms. University-based child and adolescent psychiatry clinic and neurostimulation laboratory. Twenty-four participants with major depressive disorder and 22 healthy controls matched for age and sex. Patients with major depressive disorder were medication naive and had moderate to severe symptoms based on an evaluation with a child and adolescent psychiatrist and scores on the Children's Depression Rating Scale-Revised. Motor threshold, intracortical facilitation, cortical silent period, and intracortical inhibition. Compared with healthy controls, depressed patients had significantly increased intracortical facilitation at interstimulus intervals of 10 and 15 milliseconds bilaterally. There were no significant group differences in cortical inhibition measures. These findings suggest that major depressive disorder in children and adolescents is associated with increased intracortical facilitation and excessive glutamatergic activity.

Differential effects of uncertainty on LPP responses to emotional events during explicit and implicit anticipation.

PubMed

Lin, Huiyan; Liang, Jiafeng; Jin, Hua; Zhao, Dongmei

2018-07-01

Previous studies have investigated whether uncertainty influences neural responses to emotional events. The findings of such studies, particularly with respect to event-related potentials (ERPs), have been controversial due to several factors, such as the stimuli that serve as cues and the emotional content of the events. However, it is still unknown whether the effects of uncertainty on ERP responses to emotional events are influenced by anticipation patterns (e.g., explicit or implicit anticipation). To address this issue, participants in the present study were presented with anticipatory cues and then emotional (negative and neutral) pictures. The cues either did or did not signify the emotional content of the upcoming picture. In the inter-stimulus intervals between cues and pictures, participants were asked to estimate the expected probability of the occurrence of a specific emotional category of the subsequent picture based on a scale in the explicit anticipation condition, while in the implicit condition, participants were asked to indicate, using a number on a scale, which color was different from the others. The results revealed that in the explicit condition, uncertainty increased late positive potential (LPP) responses, particularly for negative pictures, whereas LPP responses were larger for certain negative pictures than for uncertain negative pictures in the implicit condition. The findings in the present study suggest that the anticipation pattern influences the effects of uncertainty when evaluation of negative events. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of physiological aging on mismatch negativity: a meta-analysis.

PubMed

Cheng, Chia-Hsiung; Hsu, Wan-Yu; Lin, Yung-Yang

2013-11-01

Mismatch negativity (MMN) is a promising window on how the functional integrity of auditory sensory memory and change discrimination is modulated by age and relevant clinical conditions. However, the effects of aging on MMN have remained somewhat elusive, particularly at short interstimulus intervals (ISIs). We performed a meta-analysis of peer-reviewed MMN studies that had targeted both young and elderly adults to estimate the mean effect size. Nine studies, consisting of 29 individual investigations, were included and the final total study population consisted of 182 young and 165 elderly subjects. The effects of different deviant types and duration of ISIs on the effect size were assessed. The overall mean effect size was 0.63 (95% CI at 0.43-0.82). The effect sizes for long ISI (>2s, effect size 0.68, 95% CI at 0.31-1.06) and short ISI (<2s, effect size 0.61, 95% CI at 0.39-0.84) were both considered moderate. A further analysis showed a prominent aging-related decrease in MMN responses to duration and frequency changes at short ISIs. It was also interesting to note that the effect size was about 25% larger for duration deviant condition compared to the frequency deviant condition. In conclusion, a reduced MMN response to duration and frequency deviants is a robust feature among the aged adults, which suggests that there has been a decline in the functional integrity of central auditory processing in this population. © 2013.

Dysrhythmia of timed movements in Parkinson's disease and freezing of gait.

PubMed

Tolleson, Christopher M; Dobolyi, David G; Roman, Olivia C; Kanoff, Kristen; Barton, Scott; Wylie, Scott A; Kubovy, Michael; Claassen, Daniel O

2015-10-22

A well-established motor timing paradigm, the Synchronization-Continuation Task (SCT), quantifies how accurately participants can time finger tapping to a rhythmic auditory beat (synchronization phase) then maintain this rhythm after the external auditory cue is extinguished, where performance depends on an internal representation of the beat (continuation phase). In this study, we investigated the hypothesis that Parkinson's disease (PD) patients with clinical symptoms of freezing of gait (FOG) exhibit exaggerated motor timing deficits. We predicted that dysrhythmia is exacerbated when finger tapping is stopped temporarily and then reinitiated under the guidance of an internal representation of the beat. Healthy controls and PD patients with and without FOG performed the SCT with and without the insertion of a 7-s cessation of motor tapping between synchronization and continuation phases. With no interruption between synchronization and continuation phases, PD patients, especially those with FOG, showed pronounced motor timing hastening at the slowest inter-stimulus intervals during the continuation phase. The introduction of a gap prior to the continuation phase had a beneficial effect for healthy controls and PD patients without FOG, although patients with FOG continued to show pronounced and persistent motor timing hastening. Ratings of freezing of gait severity across the entire sample of PD tracked closely with the magnitude of hastening during the continuation phase. These results suggest that PD is accompanied by a unique dysrhythmia of measured movements, with FOG reflecting a particularly pronounced disruption to internal rhythmic timing. Copyright © 2015 Elsevier B.V. All rights reserved.

Stimulus-specific adaptation in a recurrent network model of primary auditory cortex

PubMed Central

2017-01-01

Stimulus-specific adaptation (SSA) occurs when neurons decrease their responses to frequently-presented (standard) stimuli but not, or not as much, to other, rare (deviant) stimuli. SSA is present in all mammalian species in which it has been tested as well as in birds. SSA confers short-term memory to neuronal responses, and may lie upstream of the generation of mismatch negativity (MMN), an important human event-related potential. Previously published models of SSA mostly rely on synaptic depression of the feedforward, thalamocortical input. Here we study SSA in a recurrent neural network model of primary auditory cortex. When the recurrent, intracortical synapses display synaptic depression, the network generates population spikes (PSs). SSA occurs in this network when deviants elicit a PS but standards do not, and we demarcate the regions in parameter space that allow SSA. While SSA based on PSs does not require feedforward depression, we identify feedforward depression as a mechanism for expanding the range of parameters that support SSA. We provide predictions for experiments that could help differentiate between SSA due to synaptic depression of feedforward connections and SSA due to synaptic depression of recurrent connections. Similar to experimental data, the magnitude of SSA in the model depends on the frequency difference between deviant and standard, probability of the deviant, inter-stimulus interval and input amplitude. In contrast to models based on feedforward depression, our model shows true deviance sensitivity as found in experiments. PMID:28288158

Task-dependent activation of distinct fast and slow(er) motor pathways during motor imagery.

PubMed

Keller, Martin; Taube, Wolfgang; Lauber, Benedikt

2018-02-22

Motor imagery and actual movements share overlapping activation of brain areas but little is known about task-specific activation of distinct motor pathways during mental simulation of movements. For real contractions, it was demonstrated that the slow(er) motor pathways are activated differently in ballistic compared to tonic contractions but it is unknown if this also holds true for imagined contractions. The aim of the present study was to assess the activity of fast and slow(er) motor pathways during mentally simulated movements of ballistic and tonic contractions. H-reflexes were conditioned with transcranial magnetic stimulation at different interstimulus intervals to assess the excitability of fast and slow(er) motor pathways during a) the execution of tonic and ballistic contractions, b) motor imagery of these contraction types, and c) at rest. In contrast to the fast motor pathways, the slow(er) pathways displayed a task-specific activation: for imagined ballistic as well as real ballistic contractions, the activation was reduced compared to rest whereas enhanced activation was found for imagined tonic and real tonic contractions. This study provides evidence that the excitability of fast and slow(er) motor pathways during motor imagery resembles the activation pattern observed during real contractions. The findings indicate that motor imagery results in task- and pathway-specific subliminal activation of distinct subsets of neurons in the primary motor cortex. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Differential brain activations in adult attention-deficit/ hyperactivity disorder subtypes: a counting Stroop functional MRI study.

PubMed

Shang, Chi-Yung; Sheng, Chia; Yang, Li-Kuang; Chou, Tai-Li; Gau, Susan Shur-Fen

2018-06-01

Although previous functional neuroimaging studies have found abnormal brain activations in individuals with attention deficit hyperactivity disorder (ADHD), little was known about distinct brain dysfunctions across different ADHD subtypes. The objective of the present study was to investigate the abnormal brain activations associated with two ADHD subtypes, predominantly inattentive (ADHD-PI) and combined (ADHD-C) subtypes. Twenty-five adults with ADHD-PI, 25 with ADHD-C, and 30 healthy controls (HC) participated in this study. The brain function of the participants were assessed by using the counting Stroop task inside the scanner and the Conners' Continuous Performance Test (CCPT) outside the scanner. The HC group showed greater activations in the caudate nucleus and inferior frontal gyrus (IFG) than the ADHD-PI and ADHD-C groups. The ADHD-PI group showed greater activations in the superior parietal lobule (SPL) than the ADHD-C group. In all participants with ADHD, we found negative correlations of activation in the left caudate and the left IFG with the standard deviation of the reaction time of the CCPT, and negative correlations of activation in the left SPL with the reaction time changes across different inter-stimulus intervals. Our results demonstrated altered brain activity in the frontostriatal networks of adults with ADHD-PI and the fronto-striato-parietal networks of adults with ADHD-C. Abnormalities in the parietal areas may represent the main difference between the ADHD-PI and ADHD-C subtypes.

Changes in complex spike activity during classical conditioning

PubMed Central

Rasmussen, Anders; Jirenhed, Dan-Anders; Wetmore, Daniel Z.; Hesslow, Germund

2014-01-01

The cerebellar cortex is necessary for adaptively timed conditioned responses (CRs) in eyeblink conditioning. During conditioning, Purkinje cells acquire pause responses or “Purkinje cell CRs” to the conditioned stimuli (CS), resulting in disinhibition of the cerebellar nuclei (CN), allowing them to activate motor nuclei that control eyeblinks. This disinhibition also causes inhibition of the inferior olive (IO), via the nucleo-olivary pathway (N-O). Activation of the IO, which relays the unconditional stimulus (US) to the cortex, elicits characteristic complex spikes in Purkinje cells. Although Purkinje cell activity, as well as stimulation of the CN, is known to influence IO activity, much remains to be learned about the way that learned changes in simple spike firing affects the IO. In the present study, we analyzed changes in simple and complex spike firing, in extracellular Purkinje cell records, from the C3 zone, in decerebrate ferrets undergoing training in a conditioning paradigm. In agreement with the N-O feedback hypothesis, acquisition resulted in a gradual decrease in complex spike activity during the conditioned stimulus, with a delay that is consistent with the long N-O latency. Also supporting the feedback hypothesis, training with a short interstimulus interval (ISI), which does not lead to acquisition of a Purkinje cell CR, did not cause a suppression of complex spike activity. In contrast, observations that extinction did not lead to a recovery in complex spike activity and the irregular patterns of simple and complex spike activity after the conditioned stimulus are less conclusive. PMID:25140129

Effect of acoustic similarity on short-term auditory memory in the monkey.

PubMed

Scott, Brian H; Mishkin, Mortimer; Yin, Pingbo

2013-04-01

Recent evidence suggests that the monkey's short-term memory in audition depends on a passively retained sensory trace as opposed to a trace reactivated from long-term memory for use in working memory. Reliance on a passive sensory trace could render memory particularly susceptible to confusion between sounds that are similar in some acoustic dimension. If so, then in delayed matching-to-sample, the monkey's performance should be predicted by the similarity in the salient acoustic dimension between the sample and subsequent test stimulus, even at very short delays. To test this prediction and isolate the acoustic features relevant to short-term memory, we examined the pattern of errors made by two rhesus monkeys performing a serial, auditory delayed match-to-sample task with interstimulus intervals of 1 s. The analysis revealed that false-alarm errors did indeed result from similarity-based confusion between the sample and the subsequent nonmatch stimuli. Manipulation of the stimuli showed that removal of spectral cues was more disruptive to matching behavior than removal of temporal cues. In addition, the effect of acoustic similarity on false-alarm response was stronger at the first nonmatch stimulus than at the second one. This pattern of errors would be expected if the first nonmatch stimulus overwrote the sample's trace, and suggests that the passively retained trace is not only vulnerable to similarity-based confusion but is also highly susceptible to overwriting. Copyright © 2013 Elsevier B.V. All rights reserved.

Autonomic adaptation after traditional and reverse swimming training periodizations.

PubMed

Clemente-Suárez, Vicente Javier; Fernandes, R J; Arroyo-Toledo, J J; Figueiredo, P; González-Ravé, J M; Vilas-Boas, J P

2015-03-01

The objective of the present study was to analyze the autonomic response of trained swimmers to traditional and reverse training periodization models. Seventeen swimmers were divided in two groups, performing a traditional periodization (TPG) or a reverse periodization (RPG) during a period of 10 weeks. Heart rate variability and 50 m swimming performance were analyzed before and after the training programs. After training, the TPG decreased the values of the high frequency band (HF), the number of differences between adjacent normal R-R intervals longer than 50 ms (NN50) and the percentage of differences between adjacent normal R-R intervals more than 50 ms (pNN50), and the RPG increased the values of HF and square root of the mean of the sum of the squared differences between adjacent normal R-R intervals (RMSSD). None of the groups improved significantly their performance in the 50-m test. The autonomic response of swimmers was different depending on the periodization performed, with the reverse periodization model leading to higher autonomic adaption. Complementary, the data suggests that autonomic adaptations were not critical for the 50-m swimming performance.

Kinetics of fast short-term depression are matched to spike train statistics to reduce noise.

PubMed

Khanbabaie, Reza; Nesse, William H; Longtin, Andre; Maler, Leonard

2010-06-01

Short-term depression (STD) is observed at many synapses of the CNS and is important for diverse computations. We have discovered a form of fast STD (FSTD) in the synaptic responses of pyramidal cells evoked by stimulation of their electrosensory afferent fibers (P-units). The dynamics of the FSTD are matched to the mean and variance of natural P-unit discharge. FSTD exhibits switch-like behavior in that it is immediately activated with stimulus intervals near the mean interspike interval (ISI) of P-units (approximately 5 ms) and recovers immediately after stimulation with the slightly longer intervals (>7.5 ms) that also occur during P-unit natural and evoked discharge patterns. Remarkably, the magnitude of evoked excitatory postsynaptic potentials appear to depend only on the duration of the previous ISI. Our theoretical analysis suggests that FSTD can serve as a mechanism for noise reduction. Because the kinetics of depression are as fast as the natural spike statistics, this role is distinct from previously ascribed functional roles of STD in gain modulation, synchrony detection or as a temporal filter.

Dual mechanisms in the perceptual processing of click train temporal regularity.

PubMed

Phillips, Dennis P; Dingle, Rachel N; Hall, Susan E; Jang, Moragh

2012-07-01

Two experiments measured human sensitivity to temporal jitter in 25-click trains with inter-click intervals (ICIs) between 5 and 100 ms. In a naturalistic experiment using wideband clicks, jitter thresholds were a nonmonotonic function of ICI, peaking for ICIs near 40-60 ms. In a subsequent experiment, clicks were high-passed and presented against a low-frequency noise masker. Jitter threshold vs ICI functions lost the positive slope over short ICIs but retained the negative slope at long ICIs. The same behavior was seen in click rate discrimination tasks. Different processes mediate regularity analysis for click trains with ICIs above and below 40-60 ms.

Multiple sclerosis in North African migrants to France.

PubMed

Kurtzke, J F; Delasnerie-Lauprêtre, N; Wallin, M T

1998-11-01

Among some 7500 respondents with known place of birth who had completed a nationwide questionnaire survey for multiple sclerosis (MS) in France in 1986, there were 260 born in former French North Africa (Algeria, Morocco, Tunisia). They had migrated to France between 1923 and 1986, but 66% came between 1956 and 1964. Two-thirds were from Algeria, where virtually the entire European population had emigrated in 1962 at the end of the Algerian war for independence. The migrants were younger at prevalence day (mean 43.4 years) and at onset (29.4 years) than the French-born MS (46.6; 31.3 years). Eight migrants lacked age information. The 225 migrants with onset more than 1 year after immigration presumably acquired their MS in France. They provided an age adjusted (US 1960) MS prevalence rate 1.54 times that for all France. If the latter is taken at 50 per 100,000 population their estimated adjusted rate is 76.8 with 95% confidence interval of 67.1 to 87.5. The other 27 with presumed acquisition in North Africa gave an estimated adjusted prevalence of 16.6 per 100,000 (95% CI 10.9-24.1). For those migrants with acquisition in France there was a mean interval of 13 years between immigration or age 11 and clinical onset, with a minimum of 3 years. This series provides further support for the theses: 1) that MS is primarily an environmental disease acquired after childhood; 2) that acquisition requires prolonged or repeated exposure (here 3 years for these medium-to-high MS risk migrants) followed by a prolonged latent or incubation period between acquisition and symptom onset (here 10 years); and 3) that this disease is most likely a widespread but unknown persistent infection which results in clinical MS in only a small proportion of those affected.

Effects of ATX-MS-1467 immunotherapy over 16 weeks in relapsing multiple sclerosis.

PubMed

Chataway, Jeremy; Martin, Keith; Barrell, Kevin; Sharrack, Basil; Stolt, Pelle; Wraith, David C

2018-03-13

To assess safety, tolerability, and efficacy of the antigen-specific immunotherapy ATX-MS-1467 in participants with relapsing multiple sclerosis using different treatment protocols to induce tolerance. Two open-label trials in adult participants with relapsing multiple sclerosis were conducted. Study 1 was a multicenter, phase 1b safety evaluation comparing intradermal (i.d.) (cohort 1) with subcutaneous (cohort 2) administration in 43 participants. Both cohorts received ATX-MS-1467 dosed at 25, 50, 100, 400, and 800 μg at 14-day intervals over 8 weeks, followed by 8 weeks with 4 additional 800-μg doses at 14-day intervals and 32 weeks off study medication. Study 2 was a phase 2a, multicenter, single-arm trial enrolling 37 participants. ATX-MS-1467 was titrated from 50 μg i.d. on day 1 to 200 μg on day 15 and 800 μg on day 29 followed by biweekly administration of 800 μg for 16 weeks and 16 weeks off study medication. Efficacy was evaluated on MRI parameters and clinical variables. Safety endpoints included treatment-emergent adverse events and injection-site reactions. In study 1, there was a significant decrease in new/persisting T1 gadolinium-enhanced (GdE) lesions in cohort 1 from baseline to week 16, returning to baseline values at week 48. In study 2, the number of T1 GdE lesions were significantly reduced on treatment and remained reduced at study completion. Safety results were unremarkable in both studies. Relatively slow ATX-MS-1467 titration and a longer full-dose i.d. treatment period is associated with reduction in GdE lesions and a sustained effect post treatment. Further trials of ATX-MS-1467 are warranted. This work provides Class IV evidence that for patients with relapsing multiple sclerosis, slow ATX-MS-1467 titration and a longer full-dose i.d. treatment period is associated with reduction in GdE lesions. © 2018 American Academy of Neurology.

A case-control study of risk factors for multiple sclerosis in Iran.

PubMed

Alonso, Alvaro; Cook, Stuart D; Maghzi, Amir-Hadi; Divani, Afshin A

2011-05-01

Numerous studies have assessed risk factors for multiple sclerosis (MS), although none have been conducted previously in Iran. The objective of this study was to study lifestyle and environmental risk factors of MS in the Iranian population. A case-control study, including 394 MS cases and 394 matched controls, was conducted in MS clinics in different Iranian cities. Information on lifestyles, environmental exposures, and past medical history was obtained from medical charts and phone interviews. In multivariable analysis, sunlight exposure was associated with a lower risk of MS: the odds ratio (OR) and 95% confidence interval (CI) of MS associated with a 1-h increment in daily sunlight was 0.62 (0.53-0.73). Smoking was associated with MS risk in women (OR: 6.48, 95% CI: 1.46-28.78), but not in men (OR: 0.72, 95% CI: 0.31-1.68) (p=0.002 for interaction). Finally, past history of common surgical procedures, infectious disorders, or exposure to pets and farm animals was not associated with MS risk. Different modifiable lifestyles, including sunlight exposure and smoking, were associated with lower MS risk in Iran. Interventions aimed at promoting smoking cessation and, more importantly, at increasing exposure to sunlight might contribute to the prevention of MS.

Interaction of paired cortical and peripheral nerve stimulation on human motor neurons.

PubMed

Poon, David E; Roy, Francois D; Gorassini, Monica A; Stein, Richard B

2008-06-01

This paper contrasts responses in the soleus muscle of normal human subjects to two major inputs: the tibial nerve (TN) and the corticospinal tract. Paired transcranial magnetic stimulation (TMS) of the motor cortex at intervals of 10-25 ms strongly facilitated the motor evoked potential (MEP) produced by the second stimulus. In contrast, paired TN stimulation produced a depression of the reflex response to the second stimulus. Direct activation of the pyramidal tract did not facilitate a second response, suggesting that the MEP facilitation observed using paired TMS occurred in the cortex. A TN stimulus also depressed a subsequent MEP. Since the TN stimulus depressed both inputs, the mechanism is probably post-synaptic, such as afterhyperpolarization of motor neurons. Presynaptic mechanisms, such as homosynaptic depression, would only affect the pathway used as a conditioning stimulus. When TN and TMS pulses were paired, the largest facilitation occurred when TMS preceded TN by about 5 ms, which is optimal for summation of the two pathways at the level of the spinal motor neurons. A later, smaller facilitation occurred when a single TN stimulus preceded TMS by 50-60 ms, an interval that allows enough time for the sensory afferent input to reach the sensory cortex and be relayed to the motor cortex. Other work indicates that repetitively pairing nerve stimuli and TMS at these intervals, known as paired associative stimulation, produces long-term increases in the MEP and may be useful in strengthening residual pathways after damage to the central nervous system.

Prognostic value of free light chains lambda and kappa in early multiple sclerosis.

PubMed

Voortman, Margarete M; Stojakovic, Tatjana; Pirpamer, Lukas; Jehna, Margit; Langkammer, Christian; Scharnagl, Hubert; Reindl, Markus; Ropele, Stefan; Seifert-Held, Thomas; Archelos, Juan-Jose; Fuchs, Siegrid; Enzinger, Christian; Fazekas, Franz; Khalil, Michael

2017-10-01

Cerebrospinal fluid (CSF) immunoglobulin free light chains (FLC) have been suggested as quantitative alternative to oligoclonal bands (OCB) in the diagnosis of multiple sclerosis (MS). However, little is known on their role in predicting clinical and paraclinical disease progression, particularly in early stages. To assess the prognostic value of FLC in OCB-positive patients with clinically isolated syndrome (CIS) suggestive of MS and early MS. We determined FLC kappa (KFLC) and lambda (LFLC) in CSF and serum by nephelometry in 61 patients (CIS ( n = 48), relapsing-remitting multiple sclerosis ( n = 13)) and 60 non-inflammatory neurological controls. Median clinical follow-up time in CIS was 4.8 years (interquartile range (IQR), 1.5-6.5 years). Patients underwent 3T magnetic resonance imaging (MRI) at baseline and follow-up (median time interval, 2.2 years; IQR, 1.0-3.7 years) to determine T2 lesion load (T2LL) and percent brain volume change (PBVC). CSF FLC were significantly increased in CIS/MS compared to controls (all p < 0.001). A lower KFLC/LFLC CSF ratio was associated with CIS-clinically definite multiple sclerosis (CDMS) conversion (hazard ratio (HR) = 2.89; 95% confidence interval (CI) = 1.17-7.14; p < 0.05). No correlations were found for FLC variables with T2LL or PBVC. Our study confirms increased intrathecal synthesis of FLC in CIS/MS which supports their diagnostic contribution. The KFLC/LFLC CSF ratio appears to have a prognostic value in CIS beyond OCB.

An increasing electromechanical window is a predictive marker of ventricular fibrillation in anesthetized rabbit with ischemic heart.

PubMed

Limprasutr, Vudhiporn; Pirintr, Prapawadee; Kijtawornrat, Anusak; Hamlin, Robert L

2018-05-10

The QTc interval is widely used in Safety Pharmacological studies to predict arrhythmia risk, and the electromechanical window (EMW) and short-term variability of QT intervals (STV QT ) have been studied as new biomarkers for drug-induced Torsades de Pointes (TdP). However, the use of EMW and STV QT to predict ventricular fibrillation (VF) has not been elucidated. This study aimed to evaluate EMW and STV QT to predict VF in anesthetized rabbit model of VF. VF was induced by ligation of the left anterior descending and a descending branch of the left circumflex coronary arteries in a sample population of rabbits (n=18). VF was developed 55.6% (10/18). In rabbit with VF, the EMW was significantly higher than in rabbits without VF (96.3 ± 15.6 ms and 49.5 ± 5.6 ms, respectively, P<0.05). STV QT had significantly increased before the onset of VF in rabbits that experienced VF, but not in rabbits that did not experience VF (11.7 ± 1.8 ms and 3.7 ± 0.4 ms, respectively, P<0.05). The EMW and STV QT had better predictive power for VF with higher sensitivity and specificity than the QTc measure. The result suggested that the increasing of EMW, as well as the elevation of STV QT , can potentially be used as biomarkers for predicting of VF.

A sensitive LC-MS/MS method for the quantification of urinary 8-iso-prostaglandin F2α (8-iso-PGF2α) including pediatric reference interval.

PubMed

Xiao, Yi; Fu, Xiaowei; Pattengale, Paul; Dien Bard, Jennifer; Xu, Yan-Kang; O'Gorman, Maurice R

2016-09-01

Oxidative stress has been implicated in numerous diseases, including arthritis, atherosclerosis, Alzheimer's disease, cancer, diabetes, hypertension, and inflammation. 8-iso-prostaglandin F2α, a member of the F2 isoprostane family, has been well-accepted as a valuable biomarker for the assessment of oxidative stress. We report the development and validation of an ultra-sensitive LC-MS/MS assay for urinary 8-iso-PGF2α measurements in pediatric population. The assay was linear from 0.024 to 20nmol/l (R(2)=0.99). Recoveries were above 85% and matrix effects were below 5%. The variability was determined at nmol/l concentration: the intra-day variability (%CV) ranged from 3.9% to 4.5% (n=20); and the inter-day variability ranged from 4.3% to 5.7% (n=20). The accuracy of our laboratory developed test was evaluated with a clinical reference laboratory (n=39), and a correlation coefficient of 0.9257 was observed. Reference interval were established to be <0.5ng/mg creatinine in a group of pediatric population (2months-18years, n=123). The precision of the assay will allow for accurate assessment of oxidative stress, and is acceptable for patient testing, particularly in pediatric population. Copyright © 2016 Elsevier B.V. All rights reserved.

The contribution of waveform interactions to the perception of concurrent vowels.

PubMed

Assmann, P F; Summerfield, Q

1994-01-01

Models of the auditory and phonetic analysis of speech must account for the ability of listeners to extract information from speech when competing voices are present. When two synthetic vowels are presented simultaneously and monaurally, listeners can exploit cues provided by a difference in fundamental frequency (F0) between the vowels to help determine their phonemic identities. Three experiments examined the effects of stimulus duration on the perception of such "double vowels." Experiment 1 confirmed earlier findings that a difference in F0 provides a smaller advantage when the duration of the stimulus is brief (50 ms rather than 200 ms). With brief stimuli, there may be insufficient time for attentional mechanisms to switch from the "dominant" member of the pair to the "nondominant" vowel. Alternatively, brief segments may restrict the availability of cues that are distributed over the time course of a longer segment of a double vowel. In experiment 1, listeners did not perform better when the same 50-ms segment was presented four times in succession (with 100-ms silent intervals) rather than only once, suggesting that limits on attention switching do not underlie the duration effect. However, performance improved in some conditions when four successive 50-ms segments were extracted from the 200-ms double vowels and presented in sequence, again with 100-ms silent intervals. Similar improvements were observed in experiment 2 between performance with the first 50-ms segment and one or more of the other three segments when the segments were presented individually. Experiment 3 demonstrated that part of the improvement observed in experiments 1 and 2 could be attributed to waveform interactions that either reinforce or attenuate harmonics that lie near vowel formants. Such interactions were beneficial only when the difference in F0 was small (0.25-1 semitone). These results are compatible with the idea that listeners benefit from small differences in F0 by performing a sequence of analyses of different time segments of a double vowel to determine where the formants of the constituent vowels are best defined.

Metabolic syndrome and C-reactive protein in bank employees.

PubMed

Cattafesta, Monica; Bissoli, Nazaré Souza; Salaroli, Luciane Bresciani

2016-01-01

The ultrasensitive C-reactive protein (us-CRP) is used for the diagnosis of cardiovascular disease, but it is not well described as a marker for the diagnosis of metabolic syndrome (MS). An observational and transversal study of bank employees evaluated anthropometric, hemodynamic, and biochemical data. CRP values were determined using commercial kits from Roche Diagnostics Ltd, and MS criteria were analyzed according to National Cholesterol Education Program's - Adult Treatment Panel III (NCEP/ATP III). A total of 88 individuals had MS, and 77.3% (n=68) of these showed alterations of us-CRP (P=0.0001, confidence interval [CI] 0.11-0.34). Individuals with MS had higher mean values of us-CRP in global measures (P=0.0001) and stratified by sex (P=0.004) than individuals without the syndrome. This marker exhibited significant differences with varying criteria for MS, such as waist circumference (P=0.0001), triglycerides (P=0.002), and diastolic blood pressure (P=0.007), and the highest levels of us-CRP were found in individuals with more MS criteria. us-CRP was strongly associated with the presence of MS and MS criteria in this group of workers. us-CRP is a useful and effective marker for identifying the development of MS and may be used as a reference in routine care.

Magnitude of increase in QTc interval after initiation of dofetilide in patients with persistent atrial fibrillation is associated with increased rates of pharmacological cardioversion and long-term freedom from recurrent atrial fibrillation.

PubMed

Huang, Henry D; Waks, Jonathan W; Steinhaus, Daniel A; Zimetbaum, Peter

2016-07-01

Dofetilide is a class III antiarrhythmic drug approved for the treatment of atrial fibrillation (AF). Dofetilide-induced corrected QT (QTc) interval prolongation is a surrogate for the degree of drug effect, but the relationships between drug-induced QTc interval prolongation, pharmacological cardioversion (PCV), and freedom from recurrent AF are unclear. The purpose of this study was to assess associations between QTc interval change during dofetilide initiation and PCV and long-term AF recurrence. We performed retrospective analyses of a prospective cohort of patients with AF admitted for dofetilide initiation between 2001 and 2014. Clinical characteristics and electrocardiographic variables were assessed. We evaluated outcomes of successful PCV in patients with persistent AF and time to recurrence of AF in patients with paroxysmal and persistent AF. During the study, 243 patients with persistent AF and 176 patients with paroxysmal AF initiated dofetilide. PCV occurred in 93/243 (41.7%) patients with persistent AF. After multivariable adjustment, QTc interval change was associated with PCV (adjusted odds ratio 1.21; P = .003 per 10-ms QTc increase). Inhospital QTc interval change was associated with long-term freedom from AF in patients with persistent AF (adjusted hazard ratio 0.92; P = .011 at 4 years per 10-ms QTc increase), but not in patients with paroxysmal AF. In patients with persistent AF, PCV was also associated with long-term freedom from recurrent AF (adjusted hazard ratio 0.62; P = .009 at 4 years). The magnitude of QTc interval prolongation during dofetilide initiation is an independent predictor of successful PCV and long-term freedom from arrhythmia in patients with persistent AF. QTc interval change had no association with AF recurrence in patients with paroxysmal AF, suggesting that different mechanisms of arrhythmogenesis may be operant in different AF types. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Simultaneous determination of radionuclides separable into natural decay series by use of time-interval analysis.

PubMed

Hashimoto, Tetsuo; Sanada, Yukihisa; Uezu, Yasuhiro

2004-05-01

A delayed coincidence method, time-interval analysis (TIA), has been applied to successive alpha- alpha decay events on the millisecond time-scale. Such decay events are part of the (220)Rn-->(216)Po ( T(1/2) 145 ms) (Th-series) and (219)Rn-->(215)Po ( T(1/2) 1.78 ms) (Ac-series). By using TIA in addition to measurement of (226)Ra (U-series) from alpha-spectrometry by liquid scintillation counting (LSC), two natural decay series could be identified and separated. The TIA detection efficiency was improved by using the pulse-shape discrimination technique (PSD) to reject beta-pulses, by solvent extraction of Ra combined with simple chemical separation, and by purging the scintillation solution with dry N(2) gas. The U- and Th-series together with the Ac-series were determined, respectively, from alpha spectra and TIA carried out immediately after Ra-extraction. Using the (221)Fr-->(217)At ( T(1/2) 32.3 ms) decay process as a tracer, overall yields were estimated from application of TIA to the (225)Ra (Np-decay series) at the time of maximum growth. The present method has proven useful for simultaneous determination of three radioactive decay series in environmental samples.

Depressed heart rate variability as an independent predictor of death in chronic congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

PubMed

Ponikowski, P; Anker, S D; Chua, T P; Szelemej, R; Piepoli, M; Adamopoulos, S; Webb-Peploe, K; Harrington, D; Banasiak, W; Wrabec, K; Coats, A J

1997-06-15

After acute myocardial infarction, depressed heart rate variability (HRV) has been proven to be a powerful independent predictor of a poor outcome. Although patients with chronic congestive heart failure (CHF) have also markedly impaired HRV, the prognostic value of HRV analysis in these patients remains unknown. The aim of this study was to investigate whether HRV parameters could predict survival in 102 consecutive patients with moderate to severe CHF (90 men, mean age 58 years, New York Heart Association [NYHA] class II to IV, CHF due to idiopathic dilated cardiomyopathy in 24 patients and ischemic heart disease in 78 patients, ejection fraction [EF], 26%; peak oxygen consumption, 16.9 ml/kg/min) after exclusion of patients in atrial fibrilation with diabetes or with chronic renal failure. In the prognostic analysis (Cox proportional-hazards model, Kaplan-Meier survival analysis), the following factors were investigated: age, CHF etiology, NYHA class, EF, peak oxygen consumption, presence of ventricular tachycardia on Holter monitoring, and HRV measures derived from 24-hour electrocardiography monitoring, calculated in the time (standard deviation of all normal RR intervals [SDNN], standard deviation of 5-minute RR intervals [SDANN], mean of all 5-minute standard deviations of RR intervals [SD], root-mean-square of difference of successive RR intervals [rMSSD], and percentage of adjacent RR intervals >50 ms different [pNN50]) and frequency domain (total power [TP], power within low-frequency band [LF], and power within high-frequency band [HF]). During follow-up of 584 +/- 405 days (365 days in all who survived), 19 patients (19%) died (mean time to death: 307 +/- 315 days, range 3 to 989). Cox's univariate analysis identified the following factors to be predictors of death: NYHA (p = 0.003), peak oxygen consumption (p = 0.01), EF (p = 0.02), ventricular tachycardia on Holter monitoring (p = 0.05), and among HRV measures: SDNN (p = 0.004), SDANN (p = 0.003), SD (p = 0.02), and LF (p = 0.003). In multivariate analysis, HRV parameters (SDNN, SDANN, LF) were found to predict survival independently of NYHA functional class, EF, peak oxygen consumption, and ventricular tachycardia on Holter monitoring. The Kaplan-Meier survival curves revealed SDNN < 100 ms to be a useful risk factor; 1-year survival in patients with SDNN < 100 ms was 78% when compared with 95% in those with SDNN > 100 ms (p = 0.008). The coexistence of SDNN < 100 ms and a peak oxygen consumption < 14 ml/kg/min allowed identification of a group of 18 patients with a particularly poor prognosis (1-year survival 63% vs 94% in the remaining patients, p <0.001). We conclude that depressed HRV on 24-hour ambulatory electrocardiography monitoring is an independent risk factor for a poor prognosis in patients with CHF. Whether analysis of HRV could be recommended in the risk stratification for better management of patients with CHF needs further investigation.

LC-MS/MS imaging with thermal film-based laser microdissection.

PubMed

Oya, Michiko; Suzuki, Hiromi; Anas, Andrea Roxanne J; Oishi, Koichi; Ono, Kenji; Yamaguchi, Shun; Eguchi, Megumi; Sawada, Makoto

2018-01-01

Mass spectrometry (MS) imaging is a useful tool for direct and simultaneous visualization of specific molecules. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is used to evaluate the abundance of molecules in tissues using sample homogenates. To date, however, LC-MS/MS has not been utilized as an imaging tool because spatial information is lost during sample preparation. Here we report a new approach for LC-MS/MS imaging using a thermal film-based laser microdissection (LMD) technique. To isolate tissue spots, our LMD system uses a 808-nm near infrared laser, the diameter of which can be freely changed from 2.7 to 500 μm; for imaging purposes in this study, the diameter was fixed at 40 μm, allowing acquisition of LC-MS/MS images at a 40-μm resolution. The isolated spots are arranged on a thermal film at 4.5-mm intervals, corresponding to the well spacing on a 384-well plate. Each tissue spot is handled on the film in such a manner as to maintain its spatial information, allowing it to be extracted separately in its individual well. Using analytical LC-MS/MS in combination with the spatial information of each sample, we can reconstruct LC-MS/MS images. With this imaging technique, we successfully obtained the distributions of pilocarpine, glutamate, γ-aminobutyric acid, acetylcholine, and choline in a cross-section of mouse hippocampus. The protocol we established in this study is applicable to revealing the neurochemistry of pilocarpine model of epilepsy. Our system has a wide range of uses in fields such as biology, pharmacology, pathology, and neuroscience. Graphical abstract Schematic Indication of LMD-LC-MS/MS imaging.

Discovery of 4ms and 7 MS Pulsars in M15 (F & H)

NASA Astrophysics Data System (ADS)

Middleditch, J.

1992-12-01

Observations of M15 taken during Oct. 23-Nov. 1 1991 with the Arecibo 305-m telescope at 430 MHz, which were analyzed using 2-billion point Fourier transforms on supercomputers at Los Alamos National Laboratory, reveal two new ms pulsars in the globular cluster, M15. The sixth and fastest yet discovered in this cluster, M15F, has a spin rate of 248.3 Hz, while the eighth and latest to be discovered in this cluster has a spin rate of 148.3 Hz, the only one known so far in the frequency interval of 100-200 Hz. Further details and implications of these discoveries will be discussed.

The sodium glucose cotransporter 2 inhibitor empagliflozin does not prolong QT interval in a thorough QT (TQT) study

PubMed Central

2013-01-01

Background Empagliflozin is a potent, selective sodium glucose cotransporter 2 (SGLT2) inhibitor in development as an oral antidiabetic treatment. This QT interval study assessed potential effects of empagliflozin on ventricular repolarisation and other electrocardiogram (ECG) parameters. Methods A randomised, placebo-controlled, single-dose, double-blind, five-period crossover study incorporating a novel double-placebo period design to reduce sample size, while maintaining full statistical power. Treatments: single empagliflozin doses of 25 mg (therapeutic) and 200 mg (supratherapeutic), matching placebo and open-label moxifloxacin 400 mg (positive control). Triplicate 12-lead ECGs of 10 second duration were recorded at baseline and during the first 24 hours after dosing. The primary endpoint was mean change from baseline (MCfB) in the population heart rate-corrected QT interval (QTcN) between 1–4 hours after dosing. Results Thirty volunteers (16 male, 14 female, mean [range] age: 34.5 [18–52] years) were randomised. The placebo-corrected MCfB in QTcN 1–4 hours after dosing was 0.6 (90% CI: -0.7, 1.9) ms and -0.2 (-1.4, 0.9) ms for empagliflozin 25 mg and 200 mg, respectively, below the ICH E14 defined threshold of regulatory concern 10 ms. Assay sensitivity was confirmed by a placebo-corrected MCfB in QTcN 2–4 hours post-dose of 12.4 (10.7, 14.1) ms with moxifloxacin 400 mg. Empagliflozin tolerability was good for all volunteers; 23.3% experienced adverse events (AEs) with empagliflozin and 27.6% with placebo. The most frequent AE was nasopharyngitis. Conclusions/interpretation Single doses of empagliflozin 25 mg and 200 mg were not associated with QTcN prolongation and were well tolerated in healthy volunteers. Trial registration ClinicalTrials.gov: NCT01195675 PMID:23617452

Intravenous sotalol decreases transthoracic cardioversion energy requirement for chronic atrial fibrillation in humans: assessment of the electrophysiological effects by biatrial basket electrodes.

PubMed

Lai, L P; Lin, J L; Lien, W P; Tseng, Y Z; Huang, S K

2000-05-01

This study was undertaken to assess the effects of sotalol on the transthoracic cardioversion energy requirement for chronic atrial fibrillation (AF) and on the atrial electrograms during AF recorded by two basket electrodes. The effects of sotalol infusion on transthoracic electrical cardioversion for chronic atrial fibrillation in humans have not been well investigated. We included 18 patients with persistent AF for more than three months. Atrial electrograms were recorded by two basket electrodes positioned in each atrium respectively. Transthoracic cardioversion was performed before and after sotalol 1.5 mg/kg i.v. infusion. In the 14 patients whose AF could be terminated by cardioversion before sotalol infusion, the atrial defibrillation energy was significantly reduced after sotalol infusion (236 +/- 74 jules [J] vs. 186 +/- 77 J; p < 0.01). Atrial fibrillation was refractory to cardioversion in four patients at baseline and was converted to sinus rhythm by cardioversion after sotalol infusion in two of them. We further divided the patients into two groups. Group A consisted of 10 patients in whom the energy requirement was decreased by sotalol while group B consisted of eight patients in whom the energy requirement was not decreased. The mean A-A (atrial local electrogram) intervals during AF were significantly increased after sotalol infusion in both groups, but the increment of A-A interval was significantly larger in group A than it was in group B patients (36 +/- 13 ms vs. 22 +/- 8 ms for the right atrium; 19 +/- 7 ms vs. 9 +/- 7 ms for the left atrium; both p < 0.05). The spatial and temporal dispersions of A-A intervals were not significantly changed after sotalol infusion in both atria in both groups. Sotalol decreases the atrial defibrillation energy requirement by increasing atrial refractoriness but not by decreasing the dispersion of refractoriness.

Normal standards for computer-ECG programs for prognostically and diagnostically important ECG variables derived from a large ethnically diverse female cohort: the Women's Health Initiative (WHI).

PubMed

Rautaharju, Pentti M; Zhang, Zhu-ming; Gregg, Richard E; Haisty, Wesley K; Z Vitolins, Mara; Curtis, Anne B; Warren, James; Horaĉek, Milan B; Zhou, Sophia H; Soliman, Elsayed Z

2013-01-01

Substantial new information has emerged recently about the prognostic value for a variety of new ECG variables. The objective of the present study was to establish reference standards for these novel risk predictors in a large, ethnically diverse cohort of healthy women from the Women's Health Initiative (WHI) study. The study population consisted of 36,299 healthy women. Racial differences in rate-adjusted QT end (QT(ea)) and QT peak (QT(pa)) intervals as linear functions of RR were small, leading to the conclusion that 450 and 390 ms are applicable as thresholds for prolonged and shortened QT(ea) and similarly, 365 and 295 ms for prolonged and shortened QT(pa), respectively. As a threshold for increased dispersion of global repolarization (T(peak)T(end) interval), 110 ms was established for white and Hispanic women and 120 ms for African-American and Asian women. ST elevation and depression values for the monitoring leads of each person with limb electrodes at Mason-Likar positions and chest leads at level of V1 and V2 were first computed from standard leads using lead transformation coefficients derived from 892 body surface maps, and subsequently normal standards were determined for the monitoring leads, including vessel-specific bipolar left anterior descending, left circumflex artery and right coronary artery leads. The results support the choice 150 μV as a tentative threshold for abnormal ST-onset elevation for all monitoring leads. Body mass index (BMI) had a profound effect on Cornell voltage and Sokolow-Lyon voltage in all racial groups and their utility for left ventricular hypertrophy classification remains open. Common thresholds for all racial groups are applicable for QT(ea), and QT(pa) intervals and ST elevation. Race-specific normal standards are required for many other ECG parameters. Copyright © 2013 Elsevier Inc. All rights reserved.

Explosive Strength of the Knee Extensors: The Influence of Criterion Trial Detection Methodology on Measurement Reproducibility

PubMed Central

Wiesinger, Hans-Peter; Wiemer, Nicolas; Kösters, Alexander; Müller, Erich

2016-01-01

Abstract The present study was conducted to assess test-retest reproducibility of explosive strength measurements during single-joint isometric knee extension using the IsoMed 2000 dynamometer. Thirty-one physically active male subjects (mean age: 23.7 years) were measured on two occasions separated by 48–72 h. The intraclass correlation coefficient (ICC 2,1) and the coefficient of variation (CV) were calculated for (i) maximum torque (MVC), (ii) the peak rate of torque development (RTDpeak) as well as for (iii) the average rate of torque development (RTD) and the impulse taken at several predefined time intervals (0–30 to 0–300 ms); thereby explosive strength variables were derived in two conceptually different versions: on the one hand from the MVC-trial (version I), on the other hand from the trial showing the RTDpeak (version II). High ICC-values (0.80–0.99) and acceptable CV-values (1.9–8.7%) could be found for MVC as well as for the RTD and the impulse taken at time intervals of ≥100 ms, regardless of whether version I or II was used. In contrast, measurements of the RTDpeak as well as the RTD and the impulse taken during the very early contraction phase (i.e. RTD/impulse0–30ms and RTD/impulse0–50ms) showed clearly weaker reproducibility results (ICC: 0.53–0.84; CV: 7.3–16.4%) and gave rise to considerable doubts as to clinical usefulness, especially when derived using version I. However, if there is a need to measure explosive strength for earlier time intervals in practice, it is, in view of stronger reproducibility results, recommended to concentrate on measures derived from version II, which is based on the RTDpeak-trial. PMID:28149337

Electrocardiographic measures of repolarization dispersion and their relationships with echocardiographic indices of ventricular remodeling and premature ventricular beats in hypertension

PubMed Central

Ciobanu, Ana; Tse, Gary; Liu, Tong; Deaconu, Maria V; Gheorghe, Gabriela S; Ilieşiu, Adriana M; Nanea, Ioan T

2017-01-01

Objective To examine the relationship between Tpeak- Tend interval (Tpe) and Tpe/QT ratio with occurrence of ventricular premature beats (VPBs) and left ventricular remodeling in hypertension. Methods A total of 52 patients with mild to moderate essential hypertension were included, undergoing echocardiography and 24-hours Holter monitoring. Ventricular remodeling was assessed by left ventricular mass index (LVMI) using the Devereux formula and diastolic function by transmitral E and A wave velocities and E/A ratio. Tpe was measured in the precordial leads. The end of the T wave was set by the method of the tangent to the steepest descending slope of the T wave. Results Tpe and Tpe/QT in leads V2 (r = 0.33, P = 0.01; r = 0.27, P = 0.04 respectively) and V3 (r = 0.40, P = 0.002; r = 0.40, P = 0.003, respectively) correlated significantly with LVMI. A significant inverse relationship was observed between E/A ratio and QT (r = −0.33, P = 0.01), Tpe in V3 (r = −0.39, P = 0.003) and Tpe/QT in V3 (r = −0.31, P = 0.02). Tpe in V3, V5, mean Tpe and maximum Tpe with cut-off values of 60 ms, 59 ms, 62 ms and 71 ms, respectively, associated with the occurrence of ventricular premature beats. Conclusions The repolarization parameters Tpe interval and Tpe/QT ratio correlate with LVMI and indices of left ventricular diastolic function and show better predictive values than traditional parameters such as QT interval and QT dispersion. Lead V3 is the best lead for measuring Tpe and Tpe/QT. These ECG indices can therefore be used in clinical practice to monitor LV remodeling and predict occurrence of VPBs. PMID:29581710

Microvolt T-wave alternans and beat-to-beat variability of repolarization during early postischemic remodeling in a pig heart.

PubMed

Floré, Vincent; Claus, Piet; Antoons, Gudrun; Oosterhoff, Peter; Holemans, Patricia; Vos, Marc A; Sipido, Karin R; Willems, Rik

2011-07-01

Repolarization variability is considered to predict sudden cardiac death. T-wave alternans (TWA) has been the subject of exhaustive research, whereas beat-to-beat variability of repolarization (BVR) is a new parameter that possibly predicts proarrhythmia. How these parameters interact has not been tested. The purpose of this study was to compare TWA and BVR as predictors of proarrhythmic substrate early after myocardial infarction (MI). In nine pigs, MI was induced by 1-hour occlusion of the left anterior descending coronary artery. Cardiac magnetic resonance imaging was performed at day 21. Six sham pigs served as control. Spectral TWA was tested during right atrial pacing before induction of MI and after 21 days. BVR was calculated from 60 consecutive QT intervals. Magnetic resonance imaging showed transmural MI. TWA was negative in all pigs at clinical threshold rate and equally present in MI versus sham pigs at higher rates (170 bpm: 55% vs 50% positive TWA). In MI pigs, BVR of QT intervals increased significantly during acute ischemia (2.44 ± 0.43 ms vs 3.55 ± 0.41 ms, P <.01) and even more on day 21 (5.80 ± 1.12 ms), but it differed significantly from sham (2.14 ± 0.54 ms, P <.01). A clinical ventricular tachycardia induction protocol was positive in 2 of 8 MI pigs and in none of 6 shams. In early remodeling after MI, BVR at intrinsic heart rate was a consistent phenomenon, whereas TWA during atrial pacing or baseline QT-interval changes were not. TWA and BVR could reflect different post-MI remodeling processes. BVR may be a new technique for predicting a potentially proarrhythmic substrate in the early postinfarction period. Copyright © 2011 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Transformation of temporal sequences in the zebra finch auditory system

PubMed Central

Lim, Yoonseob; Lagoy, Ryan; Shinn-Cunningham, Barbara G; Gardner, Timothy J

2016-01-01

This study examines how temporally patterned stimuli are transformed as they propagate from primary to secondary zones in the thalamorecipient auditory pallium in zebra finches. Using a new class of synthetic click stimuli, we find a robust mapping from temporal sequences in the primary zone to distinct population vectors in secondary auditory areas. We tested whether songbirds could discriminate synthetic click sequences in an operant setup and found that a robust behavioral discrimination is present for click sequences composed of intervals ranging from 11 ms to 40 ms, but breaks down for stimuli composed of longer inter-click intervals. This work suggests that the analog of the songbird auditory cortex transforms temporal patterns to sequence-selective population responses or ‘spatial codes', and that these distinct population responses contribute to behavioral discrimination of temporally complex sounds. DOI: http://dx.doi.org/10.7554/eLife.18205.001 PMID:27897971

Significant variations in Weber fraction for changes in inter-onset interval of a click train over the range of intervals between 5 and 300 ms.

PubMed

Ungan, Pekcan; Yagcioglu, Suha

2014-01-01

It is a common psychophysical experience that a train of clicks faster than ca. 30/s is heard as one steady sound, whereas temporal patterns occurring on a slower time scale are perceptually resolved as individual auditory events. This phenomenon suggests the existence of two different neural mechanisms for processing of auditory sequences with fast and slow repetition rates. To test this hypothesis we used Weber's law, which is known to be valid for perception of time intervals. Discrimination thresholds and Weber fractions (WFs) for 12 base inter-click intervals (ICIs) between 5 and 300 ms were measured from 10 normal hearing subjects by using an "up-down staircase" algorithm. The mean WF, which is supposed to be constant for any perceptual mechanism according to Weber's law, displayed significant variation with click rate. WFs decreased sharply from an average value of around 5% at repetition rates below 20 Hz to about 0.5% at rates above 67 Hz. Parallel to this steep transition, subjects reported that at rates below 20 Hz they perceived periodicity as a fast tapping rhythm, whereas at rates above 50 Hz the perceived quality was a pitch. Such a dramatic change in WF indicated the existence of two separate mechanisms for processing the click rate for long and short ICIs, based on temporal and spectral features, respectively. A range of rates between 20 and 33 Hz, in which the rate discrimination threshold was maximum, appears to be a region where both of the presumed time and pitch mechanisms are relatively insensitive to rate alterations. Based on this finding, we speculate that the interval-based perception mechanism ceases to function at around 20 Hz and the spectrum-based mechanism takes over at around 33 Hz; leaving a transitional gap in between, where neither of the two mechanisms is as sensitive. Another notable finding was a significant drop in WF for ICI = 100 ms, suggesting a connection of time perception to the electroencephalography alpha rhythm.

Adipokines, insulin resistance, and adiposity as a predictors of metabolic syndrome in child survivors of lymphoma and acute lymphoblastic leukemia of a developing country.

PubMed

Barbosa-Cortés, Lourdes; López-Alarcón, Mardia; Mejía-Aranguré, Juan Manuel; Klünder-Klünder, Miguel; Del Carmen Rodríguez-Zepeda, María; Rivera-Márquez, Hugo; de la Vega-Martínez, Alan; Martin-Trejo, Jorge; Shum-Luis, Juan; Solis-Labastida, Karina; López-Aguilar, Enrique; Matute-González, Guadalupe; Bernaldez-Rios, Roberto

2017-02-13

There is a growing body of evidence indicating that pediatric survivors of cancer are at a greater risk of developing metabolic syndrome. This study evaluated some probable predictors of metabolic syndrome (MS), such as leptin and adiponectin concentrations, the leptin/adiponectin ratio, insulin resistance, and adiposity, in a sample of child survivors of lymphoma and leukemia in Mexico City. Fifty two children (leukemia n = 26, lymphoma n = 26), who were within the first 5 years after cessation of therapy, were considered as eligible to participate in the study. Testing included fasting insulin, glucose, adipokines and lipids; body fat mass was measured by DXA. The MS components were analyzed according to tertiles of adipokines, insulin resistance, and adiposity. Comparisons between continuous variables were performed according to the data distribution. The MS components were analyzed according to tertiles of adipokines, insulin resistance, and adiposity. With the purpose of assessing the risk of a present MS diagnosis, odds ratios (OR) with a 95% confidence interval (95% IC) were obtained using logistic regression analysis according to the various metabolic markers. The median children age was 12.1 years, and the interval time from the completion of therapy to study enrollment was 4 years. Among the MS components, the prevalence of HDL-C low was most common (42%), followed by central obesity (29%). The HOMA-IR (OR 9.0, 95% CI 2.0; 41.1), body fat (OR 5.5, 95% CI 1.6; 19.3), leptin level (OR 5.7, 95% CI 1.6; 20.2) and leptin/adiponectin ratio (OR 9.4, 95% CI 2.0; 49.8) in the highest tertile, were predictive factors of developing MS; whereas the lowest tertile of adiponectin was associated with a protective effect but not significant. Biomarkers such as HOMA-IR, leptin and leptin/adiponectin are associated with each of the components of the MS and with a heightened risk of suffering MS among children survivors of cancer. Given the close relationship between MS with risk of developing type 2 diabetes and cardiovascular disease, it is imperative to implement prevention measures in this population and especially in developing countries where these pathologies have become the leading cause of death.

The development of an MRI lesion quantifying system for multiple sclerosis patients undergoing treatment

NASA Astrophysics Data System (ADS)

Moin, Paymann; Ma, Kevin; Amezcua, Lilyana; Gertych, Arkadiusz; Liu, Brent

2009-02-01

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that affects approximately 2.5 million people worldwide. Magnetic resonance imaging (MRI) is an established tool for the assessment of disease activity, progression and response to treatment. The progression of the disease is variable and requires routine follow-up imaging studies. Currently, MRI quantification of multiple sclerosis requires a manual approach to lesion measurement and yields an estimate of lesion volume and interval change. In the setting of several prior studies and a long treatment history, trends related to treatment change quickly become difficult to extrapolate. Our efforts seek to develop an imaging informatics based MS lesion computer aided detection (CAD) package to quantify and track MS lesions including lesion load, volume, and location. Together, with select clinical parameters, this data will be incorporated into an MS specific e- Folder to provide decision support to evaluate and assess treatment options for MS in a manner tailored specifically to an individual based on trends in MS presentation and progression.

The effects of associative and semantic priming in the lexical decision task.

PubMed

Perea, Manuel; Rosa, Eva

2002-08-01

Four lexical decision experiments were conducted to examine under which conditions automatic semantic priming effects can be obtained. Experiments 1 and 2 analyzed associative/semantic effects at several very short stimulus-onset asynchronies (SOAs), whereas Experiments 3 and 4 used a single-presentation paradigm at two response-stimulus intervals (RSIs). Experiment 1 tested associatively related pairs from three semantic categories (synonyms, antonyms, and category coordinates). The results showed reliable associative priming effects at all SOAs. In addition, the correlation between associative strength and magnitude of priming was significant only at the shortest SOA (66 ms). When prime-target pairs were semantically but not associatively related (Experiment 2), reliable priming effects were obtained at SOAs of 83 ms and longer. Using the single-presentation paradigm with a short RSI (200 ms, Experiment 3), the priming effect was equal in size for associative + semantic and for semantic-only pairs (a 21-ms effect). When the RSI was set much longer (1,750 ms, Experiment 4), only the associative + semantic pairs showed a reliable priming effect (23 ms). The results are interpreted in the context of models of semantic memory.

Validating the Accuracy of Reaction Time Assessment on Computer-Based Tablet Devices.

PubMed

Schatz, Philip; Ybarra, Vincent; Leitner, Donald

2015-08-01

Computer-based assessment has evolved to tablet-based devices. Despite the availability of tablets and "apps," there is limited research validating their use. We documented timing delays between stimulus presentation and (simulated) touch response on iOS devices (3rd- and 4th-generation Apple iPads) and Android devices (Kindle Fire, Google Nexus, Samsung Galaxy) at response intervals of 100, 250, 500, and 1,000 milliseconds (ms). Results showed significantly greater timing error on Google Nexus and Samsung tablets (81-97 ms), than Kindle Fire and Apple iPads (27-33 ms). Within Apple devices, iOS 7 obtained significantly lower timing error than iOS 6. Simple reaction time (RT) trials (250 ms) on tablet devices represent 12% to 40% error (30-100 ms), depending on the device, which decreases considerably for choice RT trials (3-5% error at 1,000 ms). Results raise implications for using the same device for serial clinical assessment of RT using tablets, as well as the need for calibration of software and hardware. © The Author(s) 2015.

Reference intervals for plasma concentrations of adrenal steroids measured by LC-MS/MS: Impact of gender, age, oral contraceptives, body mass index and blood pressure status.

PubMed

Eisenhofer, Graeme; Peitzsch, Mirko; Kaden, Denise; Langton, Katharina; Pamporaki, Christina; Masjkur, Jimmy; Tsatsaronis, George; Mangelis, Anastasios; Williams, Tracy A; Reincke, Martin; Lenders, Jacques W M; Bornstein, Stefan R

2017-07-01

Mass spectrometric-based measurements of the steroid metabolome have been introduced to diagnose disorders featuring abnormal steroidogenesis. Defined reference intervals are important for interpreting such data. Liquid chromatography-tandem mass spectrometry was used to establish reference intervals for 16 steroids (pregnenolone, progesterone, 11-deoxycorticosterone, corticosterone, aldosterone, 18-oxocortisol, 18-hydroxycortisol, 17-hydroxyprogesterone, 21-deoxycortisol, 11-deoxycortisol, cortisol, cortisone, dehydroepiandrosterone, dehydroepiandrosterone-sulfate, androstenedione, testosterone) measured in plasma from 525 volunteers with (n=227) and without (n=298) hypertension, including 68 women on oral contraceptives. Women showed variable plasma concentrations of several steroids associated with menstrual cycle phase, menopause and oral contraceptive use. Progesterone was higher in females than males, but most other steroids were higher in males than females and almost all declined with advancing age. Using models that corrected for age and gender, body mass index showed weak negative relationships with corticosterone, 21-deoxycortisol, cortisol, cortisone, testosterone, progesterone, 17-hydroxyprogesterone and 11-deoxycorticosterone, but a positive relationship with 18-hydroxycortisol. Hypertensives and normotensives showed negligible differences in plasma concentrations of steroids. Age and gender are the most important variables for plasma steroid reference intervals, which have been established here according to those variables for a panel of 16 steroids primarily useful for diagnosis and subtyping of patients with endocrine hypertension. Copyright © 2017. Published by Elsevier B.V.

Pericardial Fat is Associated With Atrial Conduction: The Framingham Heart Study

PubMed Central

Friedman, Daniel J.; Wang, Na; Meigs, James B.; Hoffmann, Udo; Massaro, Joseph M.; Fox, Caroline S.; Magnani, Jared W.

2014-01-01

Background Obesity is associated with altered atrial electrophysiology and a prominent risk factor for atrial fibrillation. Body mass index, the most widely used adiposity measure, has been related to atrial electrical remodeling. We tested the hypothesis that pericardial fat is independently associated with electrocardiographic measures of atrial conduction. Methods and Results We performed a cross‐sectional analysis of 1946 Framingham Heart Study participants (45% women) to determine the relation between pericardial fat and atrial conduction as measured by P wave indices (PWI): PR interval, P wave duration (P‐duration), P wave amplitude (P‐amplitude), P wave area (P‐area), and P wave terminal force (P‐terminal). We performed sex‐stratified linear regression analyses adjusted for relevant clinical variables and ectopic fat depots. Each 1‐SD increase in pericardial fat was significantly associated with PR interval (β=1.7 ms, P=0.049), P‐duration (β=2.3 ms, P<0.001), and P‐terminal (β=297 μV·ms, P<0.001) among women; and P‐duration (β=1.2 ms, P=0.002), P‐amplitude (β=−2.5 μV, P<0. 001), and P‐terminal (β=160 μV·ms, P=0.002) among men. Among both sexes, pericardial fat was significantly associated with P‐duration in analyses additionally adjusting for visceral fat or intrathoracic fat; a similar but non‐significant trend existed with P‐terminal. Among women, pericardial fat was significantly associated with P wave area after adjustment for visceral and intrathoracic fat. Conclusions Pericardial fat is associated with atrial conduction as quantified by PWI, even with adjustment for extracardiac fat depots. Further studies are warranted to identify the mechanisms through which pericardial fat may modify atrial electrophysiology and promote subsequent risk for arrhythmogenesis. PMID:24595189

Clinically observed chickenpox and the risk of childhood-onset multiple sclerosis.

PubMed

Mikaeloff, Yann; Caridade, Guillaume; Suissa, Samy; Tardieu, Marc

2009-05-15

The authors conducted a population-based case-control study to investigate whether clinically observed chickenpox, linked with a level of intensity for clinical expression, increases the risk of multiple sclerosis (MS) in childhood. The cases were MS patients whose disease onset occurred between 1994 and 2003, before age 16 years, in France. Each case was matched for age, sex, and geographic origin with as many as 12 controls randomly selected from the general population. Information about clinically observed chickenpox in cases and controls before the index date regarding onset of MS was collected with a standardized questionnaire and was checked against health certificates. Conditional logistic regression was used to estimate the odds ratio for an association between MS and chickenpox. The 137 MS cases were matched with 1,061 controls. Clinically observed chickenpox had occurred in 76.6% of the cases and 84.9% of their matched controls. The adjusted odds ratio of MS onset associated with chickenpox occurrence was 0.58 (95% confidence interval: 0.36, 0.92). The authors concluded that clinically observed chickenpox was associated with a lower risk of childhood-onset MS in a French population.

An Updated Meta-Analysis of Risk of Multiple Sclerosis following Infectious Mononucleosis

PubMed Central

Handel, Adam E.; Williamson, Alexander J.; Disanto, Giulio; Handunnetthi, Lahiru; Giovannoni, Gavin; Ramagopalan, Sreeram V.

2010-01-01

Background Multiple sclerosis (MS) appears to develop in genetically susceptible individuals as a result of environmental exposures. Epstein-Barr virus (EBV) infection is an almost universal finding among individuals with MS. Symptomatic EBV infection as manifested by infectious mononucleosis (IM) has been shown in a previous meta-analysis to be associated with the risk of MS, however a number of much larger studies have since been published. Methods/Principal Findings We performed a Medline search to identify articles published since the original meta-analysis investigating MS risk following IM. A total of 18 articles were included in this study, including 19390 MS patients and 16007 controls. We calculated the relative risk of MS following IM using a generic inverse variance with random effects model. This showed that the risk of MS was strongly associated with IM (relative risk (RR) 2.17; 95% confidence interval 1.97–2.39; p<10−54). Discussion Our results establish firmly that a history of infectious mononucleosis significantly increases the risk of multiple sclerosis. Future work should focus on the mechanism of this association and interaction with other risk factors. PMID:20824132

On the Time Course of Vocal Emotion Recognition

PubMed Central

Pell, Marc D.; Kotz, Sonja A.

2011-01-01

How quickly do listeners recognize emotions from a speaker's voice, and does the time course for recognition vary by emotion type? To address these questions, we adapted the auditory gating paradigm to estimate how much vocal information is needed for listeners to categorize five basic emotions (anger, disgust, fear, sadness, happiness) and neutral utterances produced by male and female speakers of English. Semantically-anomalous pseudo-utterances (e.g., The rivix jolled the silling) conveying each emotion were divided into seven gate intervals according to the number of syllables that listeners heard from sentence onset. Participants (n = 48) judged the emotional meaning of stimuli presented at each gate duration interval, in a successive, blocked presentation format. Analyses looked at how recognition of each emotion evolves as an utterance unfolds and estimated the “identification point” for each emotion. Results showed that anger, sadness, fear, and neutral expressions are recognized more accurately at short gate intervals than happiness, and particularly disgust; however, as speech unfolds, recognition of happiness improves significantly towards the end of the utterance (and fear is recognized more accurately than other emotions). When the gate associated with the emotion identification point of each stimulus was calculated, data indicated that fear (M = 517 ms), sadness (M = 576 ms), and neutral (M = 510 ms) expressions were identified from shorter acoustic events than the other emotions. These data reveal differences in the underlying time course for conscious recognition of basic emotions from vocal expressions, which should be accounted for in studies of emotional speech processing. PMID:22087275

On the role of attention for the processing of emotions in speech: sex differences revisited.

PubMed

Schirmer, Annett; Kotz, Sonja A; Friederici, Angela D

2005-08-01

In a previous cross-modal priming study [A. Schirmer, A.S. Kotz, A.D. Friederici, Sex differentiates the role of emotional prosody during word processing, Cogn. Brain Res. 14 (2002) 228-233.], we found that women integrated emotional prosody and word valence earlier than men. Both sexes showed a smaller N400 in the event-related potential to emotional words when these words were preceded by a sentence with congruous compared to incongruous emotional prosody. However, women showed this effect with a 200-ms interval between prime sentence and target word whereas men showed the effect with a 750-ms interval. The present study was designed to determine whether these sex differences prevail when attention is directed towards the emotional content of prosody and word meaning. To this end, we presented the same prime sentences and target words as in our previous study. Sentences were spoken with happy or sad prosody and followed by a congruous or incongruous emotional word or pseudoword. The interval between sentence offset and target onset was 200 ms. In addition to performing a lexical decision, participants were asked to decide whether or not a word matched the emotional prosody of the preceding sentence. The combined lexical and congruence judgment failed to reveal differences in emotional-prosodic priming between men and women. Both sexes showed smaller N400 amplitudes to emotionally congruent compared to incongruent words. This suggests that the presence of sex differences in emotional-prosodic priming depends on whether or not participants are instructed to take emotional prosody into account.

Validity of the Polar V800 monitor for measuring heart rate variability in mountain running route conditions.

PubMed

Caminal, Pere; Sola, Fuensanta; Gomis, Pedro; Guasch, Eduard; Perera, Alexandre; Soriano, Núria; Mont, Lluis

2018-03-01

This study was conducted to test, in mountain running route conditions, the accuracy of the Polar V800™ monitor as a suitable device for monitoring the heart rate variability (HRV) of runners. Eighteen healthy subjects ran a route that included a range of running slopes such as those encountered in trail and ultra-trail races. The comparative study of a V800 and a Holter SEER 12 ECG Recorder™ included the analysis of RR time series and short-term HRV analysis. A correction algorithm was designed to obtain the corrected Polar RR intervals. Six 5-min segments related to different running slopes were considered for each subject. The correlation between corrected V800 RR intervals and Holter RR intervals was very high (r = 0.99, p < 0.001), and the bias was less than 1 ms. The limits of agreement (LoA) obtained for SDNN and RMSSD were (- 0.25 to 0.32 ms) and (- 0.90 to 1.08 ms), respectively. The effect size (ES) obtained in the time domain HRV parameters was considered small (ES < 0.2). Frequency domain HRV parameters did not differ (p > 0.05) and were well correlated (r ≥ 0.96, p < 0.001). Narrow limits of agreement, high correlations and small effect size suggest that the Polar V800 is a valid tool for the analysis of heart rate variability in athletes while running high endurance events such as marathon, trail, and ultra-trail races.

Reduced Baroreflex Sensitivity in Cluster Headache Patients.

PubMed

Barloese, Mads C J; Mehlsen, Jesper; Brinth, Louise; Lundberg, Helena I S; Jennum, Poul J; Jensen, Rigmor H

2015-06-01

Important elements of cluster headache (CH) pathophysiology may be seated in the posterior hypothalamus. Cranial autonomic features are inherent, but involvement of systemic autonomic control is still debated. We aimed to characterize autonomic function as investigated by baroreflex sensitivity (BRS) in CH patients. Twenty-six active CH patients and an equal number of age-, sex-, and BMI-matched controls underwent head-up tilt table test and BRS was determined by the sequence method. Compared with controls, patients exhibited a blunted reactivity of RR intervals in response to falls and increases in systolic blood pressure (SBP) (15.3 vs. 20.0 ms/mmHg, P = .0041) in the supine position. Also, compared with controls, BRS was lower in patients having suffered an attack within the past 12 hours (n = 13, 12.5 vs. 22.3 ms/mmHg, P = .0091), opposed to those patients who had not (n = 13, 16.0 ms/mmHg, P = .1523). In the tilted position, the drop in SBP at the carotid sinuses was higher in patients who had recently suffered an attack. Despite this, they exhibited a less marked shortening of RR intervals when compared with patients who had been attack free for longer. CH patients exhibit a subclinical blunting of BRS that may be affected by the attacks themselves. The fast RR interval fluctuations used in this method reflects cardiovagal responses, thus the blunted responses are suggestive of dysfunction in the parasympathetic division of the autonomic nervous system or in the central relay of impulses from the baroreceptors. © 2015 American Headache Society.

The relationship between atrial electromechanical delay and left atrial mechanical function in stroke patients

PubMed Central

Akıl, Mehmet Ata; Akıl, Eşref; Bilik, Mehmet Zihni; Oylumlu, Mustafa; Acet, Halit; Yıldız, Abdülkadir; Akyüz, Abdurrahman; Ertaş, Faruk; Toprak, Nizamettin

2015-01-01

Objective: The aim of this study was to evaluate the relationship between atrial electromechanical delay (EMD) measured with tissue Doppler imaging (TDI) and left atrial (LA) mechanical functions in patients with ischemic stroke and compare them with healthy controls. Methods: Thirty patients with ischemic stroke were enrolled into this cross-sectional, observational study. The control group consisted of 35 age- and gender-matched apparently healthy individuals patients. Acute cerebral infarcts of probable embolic origin were diagnosed via imaging and were confirmed by a neurologist. Echocardiographically, time intervals from the beginning of P wave to beginning of A wave from the lateral and septal mitral and right ventricular tricuspid annuli in TDI were recorded. The differences between these intervals gave the mechanical delays (inter- and intra-atrial). Left atrial (LA) volumes were measured using the biplane area-length method, and LA mechanical function parameters were calculated. Statistical analysis was performed using student’s t-test, chi-squared test, and Pearson’s test. Results: The laboratory and clinical characteristics were similar in the two groups. Increased left atrial EMD (21.36±10.38 ms versus 11.74±6.06 ms, p<0.001), right atrial EMD (13.66±8.62 ms versus 9.66±6.81 ms, p=0.040), and interatrial EMD (35.03±9.95 ms versus 21.40±8.47 ms, p<0.001) were observed in stroke patients as compared to controls. Active LA emptying volume and fraction and passive LA emptying volumes and fraction were similar between controls and stroke patients. Total LA emptying volumes were significantly increased in stroke patients as compared to healthy controls (33.19±11.99 mL/m2 versus 27.48±7.08 mL/m2, p=0.021). Conclusion: According to the results of our study, interatrial electromechanical delay may be a new predictor for ischemic stroke. PMID:25537998

[The characteristics of VEMP in patients with acoustic neuroma].

PubMed

Xue, Bin; Yang, Jun

2008-01-01

To establish the normal value of the vestibular evoked myogenic potential (VEMP), and to determine the characteristics of VEMP in patients with acoustic neuroma (AN) and to explore the significance of VEMP in diagnosis of AN. Click-evoked VEMP was recorded with surface electrodes attached on the sternocleidomastoid muscle. Latencies and amplitudes of specific waveform of VEMP were measured. The hearing normal subjects including 26 males and 20 females were chosen to establish the normal value of VEMP. VEMP was investigated in 14 patients with AN who underwent surgery during the period of 2006-2007 as well as auditory brainstem response (ABR) and vestibular caloric test. Of 46 subjects with normal hearing, VEMP was present in both ears in 43 subjects, absent in either ear in three subjects. The reducible rate is 93.5% (86/92). The nor-mal value obtained from 86 reducible ears were as follows (means +/- standard deviation): latency of p13 (11.86 +/- 2.11) ms, latency of n23 (18.57 +/- 2.19) ms, interval time between p13 and n23 (6.71 +/- 1.69) ms, amplitude of p13n23 (24.18 +/- 8.22) microV. Interaural variances in 43 subjects whose VEMP were available were as follows (means +/- standard deviation): /deltap13 (0.64 +/- 0.61) ms, /deltan23/(1.05 +/- 0.97) ms, interval time between /delta13n23/ (0.84 +/- 0.81) ms, amplitude ratio (max/min) 1.32 +/- 0. 37, interaural asymmetric ratio of VEMP 0.12 +/- 0.11. Of the 14 patients with AN, VEMP was absent on the affected side in eight patients, absent on either side in three patients, and present on the unaffected side in 11 patients. VEMP presented on the affected side in three patients was significantly prolonged in /deltapl3/ and /deltap13n23/. Patients with AN characterized with VEMP could be useful in the diagnosis of AN combined together with other tests.

Gait Speed Predicts 30-Day Mortality After Transcatheter Aortic Valve Replacement: Results From the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry.

PubMed

Alfredsson, Joakim; Stebbins, Amanda; Brennan, J Matthew; Matsouaka, Roland; Afilalo, Jonathan; Peterson, Eric D; Vemulapalli, Sreekanth; Rumsfeld, John S; Shahian, David; Mack, Michael J; Alexander, Karen P

2016-04-05

Surgical risk scores do not include frailty assessments (eg, gait speed), which are of particular importance for patients with severe aortic stenosis considering transcatheter aortic valve replacement. We assessed the association of 5-m gait speed with outcomes in a cohort of 8039 patients who underwent transcatheter aortic valve replacement (November 2011-June 2014) and were included in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. We evaluated the association between continuous and categorical gait speed and 30-day all-cause mortality before and after adjustment for Society of Thoracic Surgeons-predicted risk of mortality score and key variables. Secondary outcomes included in-hospital mortality, bleeding, acute kidney injury, and stroke. The overall median gait speed was 0.63 m/s (25th-75th percentile, 0.47-0.79 m/s), with the slowest walkers (<0.5 m/s) constituting 28%, slow walkers (0.5-0.83 m/s) making up 48%, and normal walkers (>0.83 m/s) constituting 24% of the population. Thirty-day all-cause mortality rates were 8.4%, 6.6%, and 5.4% for the slowest, slow, and normal walkers, respectively (P<0.001). Each 0.2-m/s decrease in gait speed corresponded to an 11% increase in 30-day mortality (adjusted odds ratio, 1.11; 95% confidence interval, 1.01-1.22). The slowest walkers had 35% higher 30-day mortality than normal walkers (adjusted odds ratio, 1.35; 95% confidence interval, 1.01-1.80), significantly longer hospital stays, and a lower probability of being discharged to home. Gait speed is independently associated with 30-day mortality after transcatheter aortic valve replacement. Identification of frail patients with the slowest gait speeds facilitates preprocedural evaluation and anticipation of a higher level of postprocedural care. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01737528. © 2016 American Heart Association, Inc.

Permanent pacemaker implantation in octogenarians with unexplained syncope and positive electrophysiologic testing.

PubMed

Giannopoulos, Georgios; Kossyvakis, Charalampos; Panagopoulou, Vasiliki; Tsiachris, Dimitrios; Doudoumis, Konstantinos; Mavri, Maria; Vrachatis, Dimitrios; Letsas, Konstantinos; Efremidis, Michael; Katsivas, Apostolos; Lekakis, John; Deftereos, Spyridon

2017-05-01

Syncope is a common problem in the elderly, and a permanent pacemaker is a therapeutic option when a bradycardic etiology is revealed. However, the benefit of pacing when no association of symptoms to bradycardia has been shown is not clear, especially in the elderly. The aim of this study was to evaluate the effect of pacing on syncope-free mortality in patients aged 80 years or older with unexplained syncope and "positive" invasive electrophysiologic testing (EPT). This was an observational study. A positive EPT for the purposes of this study was defined by at least 1 of the following: a corrected sinus node recovery time of >525 ms, a basic HV interval of >55 ms, detection of infra-Hisian block, or appearance of second-degree atrioventricular block on atrial decremental pacing at a paced cycle length of >400 ms. Among the 2435 screened patients, 228 eligible patients were identified, 145 of whom were implanted with a pacemaker. Kaplan-Meier analysis determined that time to event (syncope or death) was 50.1 months (95% confidence interval 45.4-54.8 months) with a pacemaker vs 37.8 months (95% confidence interval 31.3-44.4 months) without a pacemaker (log-rank test, P = .001). The 4-year time-dependent estimate of the rate of syncope was 12% vs 44% (P < .001) and that of any-cause death was 41% vs 56% (P = .023), respectively. The multivariable odds ratio was 0.25 (95% confidence interval 0.15-0.40) after adjustment for potential confounders. In patients with unexplained syncope and signs of sinus node dysfunction or impaired atrioventricular conduction on invasive EPT, pacemaker implantation was independently associated with longer syncope-free survival. Significant differences were also shown in the individual components of the primary outcome measure (syncope and death from any cause). Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Urinary iodine: comparison of a simple method for its determination in microplates with measurement by inductively-coupled plasma mass spectrometry

PubMed Central

Haap, Michael; Roth, Heinz Jürgen; Huber, Thomas; Dittmann, Helmut; Wahl, Richard

2017-01-01

The aim of our study was to develop and validate an inexpensive, rapid, easy to use quantitative method to determine urinary iodine without major procurement costs for equipment. The rationale behind introducing this method is the increasing demand for urinary iodine assessments. Our study included 103 patients (76 female, 27 male), age (arithmetic mean) 52 ± 17.3 years. Urinary iodine was determined in microplates by a modification of the Sandell-Kolthoff reaction. The results were compared with inductively-coupled plasma mass spectrometry (ICP-MS) for iodine, considered as reference method. Geometric mean of urinary iodine determined by the Sandell-Kolthoff reaction method was 62.69 μg/l (95% confidence interval 53.16–73.92) whereas by the ICP-MS method it was 65.53 μg/l (95% confidence interval 54.77–78.41). Passing-Bablok regression equations for both methods gave y = 3.374 + 0.873x (y: Sandell-Kolthoff method, x: ICP-MS). Spearman´s correlation coefficient was 0.981, indicating a very high degree of agreement between the two methods. Bland-Altman plots showed no significant systematic difference between the two methods. The modified Sandell-Kolthoff method using microtiter plate technique presented here is a simple, inexpensive semi-automated method to determine urinary iodine with very little toxic waste. Comparison with the ICP-MS-technique yielded a good agreement between the two methods. PMID:28045077

Aerobic interval exercise improves parameters of nonalcoholic fatty liver disease (NAFLD) and other alterations of metabolic syndrome in obese Zucker rats.

PubMed

Kapravelou, Garyfallia; Martínez, Rosario; Andrade, Ana M; Nebot, Elena; Camiletti-Moirón, Daniel; Aparicio, Virginia A; Lopez-Jurado, Maria; Aranda, Pilar; Arrebola, Francisco; Fernandez-Segura, Eduardo; Bermano, Giovanna; Goua, Marie; Galisteo, Milagros; Porres, Jesus M

2015-12-01

Metabolic syndrome (MS) is a group of metabolic alterations that increase the susceptibility to cardiovascular disease and type 2 diabetes. Nonalcoholic fatty liver disease has been described as the liver manifestation of MS. We aimed to test the beneficial effects of an aerobic interval training (AIT) protocol on different biochemical, microscopic, and functional liver alterations related to the MS in the experimental model of obese Zucker rat. Two groups of lean and obese animals (6 weeks old) followed a protocol of AIT (4 min at 65%-80% of maximal oxygen uptake, followed by 3 min at 50%-65% of maximal oxygen uptake for 45-60 min, 5 days/week, 8 weeks of experimental period), whereas 2 control groups remained sedentary. Obese rats had higher food intake and body weight (P < 0.0001) and suffered significant alterations in plasma lipid profile, area under the curve after oral glucose overload (P < 0.0001), liver histology and functionality, and antioxidant status. The AIT protocol reduced the severity of alterations related to glucose and lipid metabolism and increased the liver protein expression of PPARγ, as well as the gene expression of glutathione peroxidase 4 (P < 0.001). The training protocol also showed significant effects on the activity of hepatic antioxidant enzymes, although this action was greatly influenced by rat phenotype. The present data suggest that AIT protocol is a feasible strategy to improve some of the plasma and liver alterations featured by the MS.

Magnitude and Temporal Variability of Inter-stimulus EEG Modulate the Linear Relationship Between Laser-Evoked Potentials and Fast-Pain Perception

PubMed Central

Li, Linling; Huang, Gan; Lin, Qianqian; Liu, Jia; Zhang, Shengli; Zhang, Zhiguo

2018-01-01

The level of pain perception is correlated with the magnitude of pain-evoked brain responses, such as laser-evoked potentials (LEP), across trials. The positive LEP-pain relationship lays the foundation for pain prediction based on single-trial LEP, but cross-individual pain prediction does not have a good performance because the LEP-pain relationship exhibits substantial cross-individual difference. In this study, we aim to explain the cross-individual difference in the LEP-pain relationship using inter-stimulus EEG (isEEG) features. The isEEG features (root mean square as magnitude and mean square successive difference as temporal variability) were estimated from isEEG data (at full band and five frequency bands) recorded between painful stimuli. A linear model was fitted to investigate the relationship between pain ratings and LEP response for fast-pain trials on a trial-by-trial basis. Then the correlation between isEEG features and the parameters of LEP-pain model (slope and intercept) was evaluated. We found that the magnitude and temporal variability of isEEG could modulate the parameters of an individual's linear LEP-pain model for fast-pain trials. Based on this, we further developed a new individualized fast-pain prediction scheme, which only used training individuals with similar isEEG features as the test individual to train the fast-pain prediction model, and obtained improved accuracy in cross-individual fast-pain prediction. The findings could help elucidate the neural mechanism of cross-individual difference in pain experience and the proposed fast-pain prediction scheme could be potentially used as a practical and feasible pain prediction method in clinical practice. PMID:29904336

Comparison of the docetaxel concentration in human plasma measured with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and a nanoparticle immunoassay and clinical applications of that assay.

PubMed

Geng, Chunmei; Li, Pingli; Chen, Xuwang; Yuan, Guiyan; Guo, Nan; Liu, Huanjun; Zhang, Rui; Guo, Ruichen

2017-05-23

To determine the feasibility of using a nanoparticle immunoassay for clinical therapeutic drug monitoring (TDM) of docetaxel concentrations, a sensitive and simple method of liquid chromatography-tandem mass spectrometry (LC-MS/MS) was established to measure the docetaxel concentration in human plasma and the results of LC-MS/MS and the immunoassay were compared. Docetaxel and paclitaxel (the internal standard, or IS) in human plasma were extracted through protein precipitation, separated on a Diamonsil C18 column (150 mm × 4.6 mm, 5 μm), ionized with positive ions, and detected with LC-MS/MS in multi-reaction monitoring (MRM) mode. Plasma samples from 248 cancer patients were assayed with LC-MS/MS and a nanoparticle immunoassay. Data from the samples were analyzed with the statistical software SPSS and the software MedCalc. Results indicated that the calibration curve of the validated method of LC-MS/MS was linear over the range of 10-2,000 ng/mL, with an lowest limit of quantitation (LLOQ) of 10 ng/mL, and the intra- and inter- day precision and accuracy were both < ± 15%. Comparison of the two methods indicated that results of the LC-MS/MS were closely related to those of the nanoparticle immunoassay, with a correlation coefficient (R) of 0.965 and acceptable 95% confidence intervals (CI) of ‒ 231.7-331.1 ng/mL. Overall, the established method of LC-MC/MS and the nanoparticle immunoassay were both suitable for measurement of the docetaxel concentration in human plasma, and the immunoassay was far more cost-effective and better at clinical TDM of docetaxel in clinical practice.

Risk Factors for Permanent Pacemaker after Implantation of Surgical or Percutaneous Self-Expanding Aortic Prostheses.

PubMed

Villa, Emmanuel; Clerici, Alberto; Messina, Antonio; Testa, Luca; Bedogni, Francesco; Moneta, Andrea; Donatelli, Francesco; Troise, Giovanni

2016-11-01

The use of transcatheter aortic valve implantation (TAVI) following the introduction of Nitinol autoexpandable devices has spread rapidly during recent years. In addition, cardiac surgery has been revolutionized due to the use of Nitinol-based sutureless prostheses for aortic valve replacement (AVR). During the same period, however, permanent pacemaker (PPM) implantation has emerged as a frequent complication. The study aim was to identify the risk factors of PPM following the implantation of a Nitinol self-expanding prosthesis (for AVR or TAVI). A study group was created between two institutions experienced in the use of nitinol devices, and a pool of 336 patients (56.6% CoreValve - Medtronic; 43.4% Perceval - Sorin) was available for a retrospective analysis. Pre-procedural clinical and electrocardiography (ECG) variables and postprocedural ECG variables were compared between the PPM group and control patients who had not received a PPM during their index hospitalization. A PPM was required in 12.8% of patients (TAVI 17.5% versus AVR 6.8%, p = 0.007). PPM patients had a higher logistical EuroSCORE (median 20.77% versus 15.59%, p = 0.015), a lower use of statins (18.6% versus 34.2%, p = 0.04), a pre-procedural longer QRS interval (median 117 ms versus 98 ms, p = 0.002), and a higher incidence of conduction disturbances (29.3% versus 16.8%, p = 0.034), with a prevalence of right bundle branch block. At the first postprocedural ECG, non-stimulated PPM patients had a longer QRS interval (median 150 ms versus 113 ms, p<0.001) and a longer QTc interval (487.3 ± 46 ms versus 510.8 ± 53.8 ms, p = 0.005). Prevalent intra-ventricular conduction disorders in both groups included left bundle branch block. AVR patients received a PPM later than the TAVI group (median 6 days versus 3 days, p = 0.01). TAVI was an independent predictor of PPM at logistic regression analysis (OR 3.18; 95% CI 1.19-8.48, p = 0.021), but the significance disappeared after incorporating post-procedural ECG variables. Nitinol technology is a ground-breaking option for aortic valve procedures. However, the radial forces of the self-expandable mechanism may be implicated in the increased need for PPM, mostly in cases of TAVI compared to AVR, that most likely are due to displacement of the stent provoked by in situ calcium clusters. Given the clinical and economic impact of PPM, new parameters are required to understand the stent/tissue interaction and to help with device selection.

The effect of anesthetization and urinary bladder catheterization on renal function of rainbow trout

USGS Publications Warehouse

Hunn, J.B.; Willford, W.A.

1970-01-01

1. Rainbow trout were anesthetized with MS-222 (Sandoz) or methylpentynol and catheterized. Urine was collected at selected intervals up to 48 hr. 2. Effects of MS-222 anesthesia on urine flow and composition were isolated from the stress of catheterization by re-anesthetizing the fish 18 to 20 hr post catheterization. 3. Urine output patterns were similar following MS-222 or methylpentynol anesthesia and catheterization. Highest urine flows were measured 4 to 8 hr post treatment. The highest urine output after re-anesthetization with MS-222 was observed 2 to 4 hr post-anesthesia. 4. Highest concentrations of Na2+, K+, Ca2+, Cl- and inorganic PO4 in the urine were measured in the first 2 hr after anesthesia and catheterization. 5. Flow rates and chemical composition of urine indicate that "normal" renal function is re-established 12 to 24 hr post-treatment.

Metabolic syndrome and C-reactive protein in bank employees

PubMed Central

Cattafesta, Monica; Bissoli, Nazaré Souza; Salaroli, Luciane Bresciani

2016-01-01

Background The ultrasensitive C-reactive protein (us-CRP) is used for the diagnosis of cardiovascular disease, but it is not well described as a marker for the diagnosis of metabolic syndrome (MS). Methods An observational and transversal study of bank employees evaluated anthropometric, hemodynamic, and biochemical data. CRP values were determined using commercial kits from Roche Diagnostics Ltd, and MS criteria were analyzed according to National Cholesterol Education Program’s – Adult Treatment Panel III (NCEP/ATP III). Results A total of 88 individuals had MS, and 77.3% (n=68) of these showed alterations of us-CRP (P=0.0001, confidence interval [CI] 0.11–0.34). Individuals with MS had higher mean values of us-CRP in global measures (P=0.0001) and stratified by sex (P=0.004) than individuals without the syndrome. This marker exhibited significant differences with varying criteria for MS, such as waist circumference (P=0.0001), triglycerides (P=0.002), and diastolic blood pressure (P=0.007), and the highest levels of us-CRP were found in individuals with more MS criteria. Conclusion us-CRP was strongly associated with the presence of MS and MS criteria in this group of workers. us-CRP is a useful and effective marker for identifying the development of MS and may be used as a reference in routine care. PMID:27274294

High prevalence of sickness absence and disability pension among multiple sclerosis patients: a nationwide population-based study.

PubMed

Tinghög, Petter; Hillert, Jan; Kjeldgård, Linnea; Wiberg, Michael; Glaser, Anna; Alexanderson, Kristina

2013-12-01

Although multiple sclerosis (MS) often implies substantial disability, there is little knowledge about sick leave and disability pension among MS patients. The purpose of this study was to estimate the prevalence rates of sick leave and disability pension among MS patients and to explore how socio-demographics are associated with such rates. The register data of all people who lived in Sweden in 2005 and were 16-64 years old was used to identify 9721 MS patients and matched controls. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated and effect modifications were evaluated with Wald X(2) tests. In 2005, 61.7% of the MS patients were on partial or full disability pension compared to 14.2% among the controls. Of the others, 36.8% had ≥ 1 sick-leave spell for >14 days during that year. Socio-demographics were similarly associated with sick leave and disability pension among MS patients and controls, with the noteworthy exceptions that female gender and immigration status were less potent risk factors in the MS population (p<0.05). In spite of widespread access to modern health care including disease-modifying drugs, the majority of MS patients of working ages were on a disability pension. Strategies enabling MS patients to retain their footing in the labour market are needed.

[Influence of pacing site on myocardial transmural dispersion of repolarization in intact normal and dilated cardiomyopathy dogs].

PubMed

Bai, Rong; Pu, Jun; Liu, Nian; Lu, Jia-Gao; Zhou, Qiang; Ruan, Yan-Fei; Niu, Hui-Yan; Wang, Lin

2003-12-25

In order to verify the hypothesis that left ventricular epicardial (LV-Epi) pacing and biventricular (BiV) pacing unavoidably influence the myocardial electrophysiological characters and may result in high risk of malignant ventricular arrhythmia, we calculated, in both normal mongrel dogs and dog models with rapid-right-ventricular-pacing induced dilated cardiomyopathy congestive heart failure (DCM-CHF), the monophasic action potential duration (MAPD) and the transmural dispersion of repolarization (TDR) in intracardiac electrogram together with the QT interval and T(peak)-T(end) (T(p(-T(e)) interval in surface electrocardiogram (ECG) during LV-Epi and BiV pacing, compared with those during right ventricular endocardial (RV-Endo) pacing. To prepare the DCM-CHF dog model, rapid right ventricular pacing (250 bpm) was performed for 23.6+/-2.57 days to the dog. All the normal and DCM-CHF dogs were given radio frequency catheter ablation (RFCA) to His bundle with the guide of X-ray fluoroscopy. After the RFCA procedures, the animals were under the situation of complete atrioventricular block so that the canine heart rates could be voluntarily controlled in the following experiments. After a thoracotomy, ECG and monophasic action potentials (MAP) of subendocardial, subepicardial and mid-layer myocardium were recorded synchronously in 8 normal and 5 DCM-CHF dogs during pacing from endocardium of RV apex (RV-Endo), epicardium of LV anterior wall (LV-Epi) and simultaneously both of the above (biventricular, BiV), the later was similar to the ventricular resynchronization therapy to congestive heart failure patients in clinic. The Tp-Te) meant the interval from the peak to the end of T wave, which was a representative index of TDR in surface ECG. The TDR was defined as the difference between the longest and the shortest MAPD of subendocardial, subepicardial and mid-layer myocardium. Our results showed that in normal dogs, pacing participating of LV (LV-Epi, BiV) prolonged MAPD of all the three layers of the myocardium (P<0.05) with the character that mid-layer MAPD was the longest and subepicardial MAPD was the shortest following subendocardial MAPD. At the same time, TDR prolonged from 26.75 ms at RV-Endo pacing to 37.54 ms at BiV pacing and to 47.16 ms at LV-Epi pacing (P<0.001). Meanwhile in surface ECG, BiV and LV-Epi pacing resulted in a longer Tp-Te) interval compared with RV-Endo pacing (P<0.01), without parallel QT interval prolongation. Furthermore, all the DCM-CHF model dogs showed manifestations of congestive heart failure and enlargement of left ventricles. Based on the lengthening of mid-layer MAPD from 257.35 ms to 276.30 ms (P<0.0001) and increase of TDR from 27.58 ms to 33.80 ms (P equals;0.002) in DCM-CHF model due to the structural disorders of myocardium compared with the normal dog, LV-Epi and BiV pacing also led to the effect of prolonging MAPD of three layers of the myocardium and enlarging TDR. From these results we make the conclusions that prolongation of MAPD of subendocardial, subepicardial and mid-layer myocardium and increase in TDR during pacing participating of LV (LV-Epi, BiV) may contribute to the formation of unidirectional block and reentry, which play roles or at least are the high risk factors in the development of malignant ventricular arrhythmia, especially in case of structural disorders of myocardium. These findings must be considered seriously when ventricular resynchronization therapy is performed to congestive heart failure patients.

Mortality and comorbidities in patients with multiple sclerosis compared with a population without multiple sclerosis: An observational study using the US Department of Defense administrative claims database.

PubMed

Capkun, Gorana; Dahlke, Frank; Lahoz, Raquel; Nordstrom, Beth; Tilson, Hugh H; Cutter, Gary; Bischof, Dorina; Moore, Alan; Simeone, Jason; Fraeman, Kathy; Bancken, Fabrice; Geissbühler, Yvonne; Wagner, Michael; Cohan, Stanley

2015-11-01

Data are limited for mortality and comorbidities in patients with multiple sclerosis (MS). Compare mortality rates and event rates for comorbidities in MS (n=15,684) and non-MS (n=78,420) cohorts from the US Department of Defense (DoD) database. Comorbidities and all-cause mortality were assessed using the database. Causes of death (CoDs) were assessed through linkage with the National Death Index. Cohorts were compared using mortality (MRR) and event (ERR) rate ratios. All-cause mortality was 2.9-fold higher in the MS versus non-MS cohort (MRR, 95% confidence interval [CI]: 2.9, 2.7-3.2). Frequent CoDs in the MS versus non-MS cohort were infectious diseases (6.2, 4.2-9.4), diseases of the nervous (5.8, 3.7-9.0), respiratory (5.0, 3.9-6.4) and circulatory (2.1, 1.7-2.7) systems and suicide (2.6, 1.3-5.2). Comorbidities including sepsis (ERR, 95% CI: 5.7, 5.1-6.3), ischemic stroke (3.8, 3.5-4.2), attempted suicide (2.4, 1.3-4.5) and ulcerative colitis (2.0, 1.7-2.3), were higher in the MS versus non-MS cohort. The rate of cancers was also higher in the MS versus the non-MS cohort, including lymphoproliferative disorders (2.2, 1.9-2.6) and melanoma (1.7, 1.4-2.0). Rates of mortality and several comorbidities are higher in the MS versus non-MS cohort. Early recognition and management of comorbidities may reduce premature mortality and improve quality of life in patients with MS. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Analysis Concerning the Inspection Threshold for Multi-Site Damage.

DOT National Transportation Integrated Search

1993-12-01

Periodic inspections, at a prescribed interval, for Multi-Site Damage (MS) in longitudinal fuselage lap-joints start when the aircraft has accumulated a certain number of flights, the inspection threshold. The work reported here was an attempt to obt...

Cardiac Repolarization Abnormalities and Potential Evidence for Loss of Cardiac Sodium Currents on ECGs of Patients with Chagas' Heart Disease

NASA Technical Reports Server (NTRS)

Schlegel, T. T.; Medina, R.; Jugo, D.; Nunez, T. J.; Borrego, A.; Arellano, E.; Arenare, B.; DePalma, J. L.; Greco, E. C.; Starc, V.

2007-01-01

Some individuals with Chagas disease develop right precordial lead ST segment elevation in response to an ajmaline challenge test, and the prevalence of right bundle branch block (RBBB) is also high in Chagas disease. Because these same electrocardiographic abnormalities occur in the Brugada syndrome, which involves genetically defective cardiac sodium channels, acquired damage to cardiac sodium channels may also occur in Chagas disease. We studied several conventional and advanced resting 12-lead/derived Frank-lead ECG parameters in 34 patients with Chagas -related heart disease (mean age 39 14 years) and in 34 age-/gender-matched healthy controls. All ECG recordings were of 5-10 min duration, obtained in the supine position using high fidelity hardware/software (CardioSoft, Houston, TX). Even after excluding those Chagas patients who had resting BBBs, tachycardia and/or pathologic arrhythmia (n=8), significant differences remained in multiple conventional and advanced ECG parameters between the Chagas and control groups (n=26/group), especially in their respective QT interval variability indices, maximal spatial QRS-T angles and low frequency HRV powers (p=0.0006, p=0.0015 and p=0.0314 respectively). In relation to the issue of potential damage to cardiac sodium channels, the Chagas patients had: 1) greater than or equal to twice the incidence of resting ST segment elevation in leads V1-V3 (n=10/26 vs. n=5/26) and of both leftward (n=5/26 versus n=0/26) and rightward (n=7/26 versus n=3/26) QRS axis deviation than controls; 2) significantly increased filtered (40-250 Hz) QRS interval durations (92.1 8.5 versus 85.3 plus or minus 9.0 ms, p=0.022) versus controls; and 3) significantly decreased QT and especially JT interval durations versus controls (QT interval: 387.5 plus or minus 26.4 versus 408.9 plus or minus 34.6 ms, p=0.013; JT interval: 290.5 plus or minus 26.3 versus 314.8 plus or minus 31.3 ms; p=0.0029). Heart rates and Bazett-corrected QTc/JTc intervals were not significantly different between groups. Patients with Chagas heart disease have increased cardiac repolarization abnormalities, especially by advanced ECG. Moreover, as a group, they have decreased uncorrected JT and QT interval durations and increased filtered QRS interval durations (versus age/gender-matched controls), all suggesting a potential loss of cardiac sodium channel function that might be mediated, in part, by cardiac autonomic damage. Overall findings support Brugada et al's recent hypothesis that the pathway leading to sudden death may often be similar in Chagas' disease and Brugada syndrome i.e., damage to the sodium channel (infectious/immunologic/autonomic in Chagas' genetic in Brugada) with consequent loss of sodium currents may facilitate a phase II-reentry based arrhythmic substrate for ventricular fibrillation in both conditions. In general, JT interval-related results have been underreported in the Chagas literature.

Kinetics and components of the flash photocurrent of isolated retinal rods of the larval salamander, Ambystoma tigrinum.

PubMed Central

Cobbs, W H; Pugh, E N

1987-01-01

1. Membrane currents initiated by intense, 20 microseconds flashes (photocurrents) were recorded from isolated salamander rods by combined extracellular suction electrodes and intracellular tight-seal electrodes either in current or voltage clamp mode. The magnitudes (mean +/- 2 S.E.M.) of the maximal photoresponses recorded by the suction and by the intracellular electrode respectively were 40 +/- 5 pA (n = 18) and 35 +/- 7 mV (n = 8) for current clamp at zero current; 43 +/- 9 pA and 66 +/- 13 (n = 11) pA for voltage clamp at the zero-current holding potential, -24 +/- 3 mV. 2. Photocurrents initiated by flashes isomerizing 0.1% or more of the outer segment's rhodopsin achieved a saturated velocity and were 95% complete in less than 50 ms. The effect of incrementing flash intensity above 0.1% isomerization can be described as a translation of the photocurrent along the time axis towards the origin. Within the interval 0-50 ms the latter two-thirds of the velocity-saturated photocurrent is well described as a single-exponential decay. The decay was much faster in voltage clamp (2.8 +/- 1.2 ms, n = 11) than in current clamp mode (17 +/- 5 ms, n = 17). 3. The initial third of the velocity-saturated photocurrent, occurring over the interval from the flash to the onset of exponential decay, followed about the same time course in current and voltage clamp. The time interval occupied by this initial 'latent' phase decreased with increasing flash intensity and attained an apparent minimum of about 7 ms in response to flashes isomerizing 10% or more of the rhodopsin at ca. 22 degrees C. 4. The hypothesis that the decay of outer segment light-sensitive membrane current is the same in current and voltage clamp was supported by an analysis of the difference between outer segment currents measured successively in the two recording modes. First, the tail of the difference current decayed exponentially with a time constant approximately equal to R x C, where R and C are independently estimated slope resistance and capacitance of the rod. Secondly, the integral of the difference current, when divided by outer segment capacitance, closely approximated the hyperpolarizing light response measured under current clamp. Thus, displacement current accounted for the difference between photocurrents measured in current and voltage clamp.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2832596

Semantic processing of unattended parafoveal words.

PubMed

Di Pace, E; Longoni, A M; Zoccolotti, P

1991-08-01

The influence that a context word presented either foveally or parafoveally, may exert on the processing of a subsequent target word was studied in a semantic decision task. Fourteen subjects participated in the experiment. They were presented with word-nonword pairs (prime). One member of the pair (which the subjects had to attend to) appeared centrally, the other parafoveally. The prime was followed by a target at two inter-stimulus intervals (ISI; 200 and 2000 msec). The word stimulus of the pair could be semantically related or unrelated to the target. The subjects' task was to classify the target as animal or not animal by pressing one of two buttons as quickly as possible. When the target word was semantically associated with the foveal (attended) word the reaction times were faster for both ISIs; when it was associated with the parafoveal (unattended) word in the prime pair, there were facilitatory effects only in the short ISI condition. A second experiment was run in order to evaluate the possibility that the obtained results were due to identification of the parafoveal stimulus. The same prime-target pairs of experiment 1 (without the target stimuli) were used. The prime-target pairs were presented to fourteen subjects who were requested to name the foveal (attended) stimulus and subsequently, if possible, the parafoveal (unattended) one. Even in this condition, percentage of identification of the unattended word was only 15%, suggesting that previous findings were not due to identification of unattended stimuli. Results are discussed in relation to Posner and Snyder's (1975) dual coding theory.

The retention and disruption of color information in human short-term visual memory.

PubMed

Nemes, Vanda A; Parry, Neil R A; Whitaker, David; McKeefry, Declan J

2012-01-27

Previous studies have demonstrated that the retention of information in short-term visual perceptual memory can be disrupted by the presentation of masking stimuli during interstimulus intervals (ISIs) in delayed discrimination tasks (S. Magnussen & W. W. Greenlee, 1999). We have exploited this effect in order to determine to what extent short-term perceptual memory is selective for stimulus color. We employed a delayed hue discrimination paradigm to measure the fidelity with which color information was retained in short-term memory. The task required 5 color normal observers to discriminate between spatially non-overlapping colored reference and test stimuli that were temporally separated by an ISI of 5 s. The points of subjective equality (PSEs) on the resultant psychometric matching functions provided an index of performance. Measurements were made in the presence and absence of mask stimuli presented during the ISI, which varied in hue around the equiluminant plane in DKL color space. For all reference stimuli, we found a consistent mask-induced, hue-dependent shift in PSE compared to the "no mask" conditions. These shifts were found to be tuned in color space, only occurring for a range of mask hues that fell within bandwidths of 29-37 deg. Outside this range, masking stimuli had little or no effect on measured PSEs. The results demonstrate that memory masking for color exhibits selectivity similar to that which has already been demonstrated for other visual attributes. The relatively narrow tuning of these interference effects suggests that short-term perceptual memory for color is based on higher order, non-linear color coding. © ARVO

A behavioural investigation of human visual short term memory for colour.

PubMed

Nemes, V A; Parry, N R A; McKeefry, D J

2010-09-01

We examined visual short term memory (VSTM) for colour using a delayed-match-to-sample paradigm. In these experiments we measured the effects of increasing inter-stimulus interval (ISI), varying between 0 and 10 s, on the ability of five colour normal human observers to make colour matches between a reference and subsequently presented test stimuli. The coloured stimuli used were defined by different chromatic axes on the isoluminant plane of DKL colour space. In preliminary experiments we used a hue scaling procedure to identify a total of 12 colour stimuli which served as reference hues in the colour memory experiments: four stimuli were exemplars of red, green, blue and yellow colour appearance categories, four were located between these categories and a further four were located on the cardinal axes that isolated the activity of the cone-opponent mechanisms. Our results demonstrate that there is a reduction in the ability of observers to make accurate colour matches with increasing ISIs and that this reduced performance was similar for all colour stimuli. However, the shifts in hue that were measured between the reference and matched test stimuli were significantly greater for the cardinal stimuli compared to those measured for the stimuli defined by the hue scaling procedure. This deterioration in the retention of hue in VSTM for stimuli that isolate cone-opponent mechanisms may be a reflection of the reorganisation of colour processing that occurs in the cortex where colour appearance mechanisms become more prominent. © 2010 The Authors, Ophthalmic and Physiological Optics © 2010 The College of Optometrists.

Statistical parametric mapping of LORETA using high density EEG and individual MRI: application to mismatch negativities in schizophrenia.

PubMed

Park, Hae-Jeong; Kwon, Jun Soo; Youn, Tak; Pae, Ji Soo; Kim, Jae-Jin; Kim, Myung-Sun; Ha, Kyoo-Seob

2002-11-01

We describe a method for the statistical parametric mapping of low resolution electromagnetic tomography (LORETA) using high-density electroencephalography (EEG) and individual magnetic resonance images (MRI) to investigate the characteristics of the mismatch negativity (MMN) generators in schizophrenia. LORETA, using a realistic head model of the boundary element method derived from the individual anatomy, estimated the current density maps from the scalp topography of the 128-channel EEG. From the current density maps that covered the whole cortical gray matter (up to 20,000 points), volumetric current density images were reconstructed. Intensity normalization of the smoothed current density images was used to reduce the confounding effect of subject specific global activity. After transforming each image into a standard stereotaxic space, we carried out statistical parametric mapping of the normalized current density images. We applied this method to the source localization of MMN in schizophrenia. The MMN generators, produced by a deviant tone of 1,200 Hz (5% of 1,600 trials) under the standard tone of 1,000 Hz, 80 dB binaural stimuli with 300 msec of inter-stimulus interval, were measured in 14 right-handed schizophrenic subjects and 14 age-, gender-, and handedness-matched controls. We found that the schizophrenic group exhibited significant current density reductions of MMN in the left superior temporal gyrus and the left inferior parietal gyrus (P < 0. 0005). This study is the first voxel-by-voxel statistical mapping of current density using individual MRI and high-density EEG. Copyright 2002 Wiley-Liss, Inc.

Real-time cerebellar neuroprosthetic system based on a spiking neural network model of motor learning.

PubMed

Xu, Tao; Xiao, Na; Zhai, Xiaolong; Kwan Chan, Pak; Tin, Chung

2018-02-01

Damage to the brain, as a result of various medical conditions, impacts the everyday life of patients and there is still no complete cure to neurological disorders. Neuroprostheses that can functionally replace the damaged neural circuit have recently emerged as a possible solution to these problems. Here we describe the development of a real-time cerebellar neuroprosthetic system to substitute neural function in cerebellar circuitry for learning delay eyeblink conditioning (DEC). The system was empowered by a biologically realistic spiking neural network (SNN) model of the cerebellar neural circuit, which considers the neuronal population and anatomical connectivity of the network. The model simulated synaptic plasticity critical for learning DEC. This SNN model was carefully implemented on a field programmable gate array (FPGA) platform for real-time simulation. This hardware system was interfaced in in vivo experiments with anesthetized rats and it used neural spikes recorded online from the animal to learn and trigger conditioned eyeblink in the animal during training. This rat-FPGA hybrid system was able to process neuronal spikes in real-time with an embedded cerebellum model of ~10 000 neurons and reproduce learning of DEC with different inter-stimulus intervals. Our results validated that the system performance is physiologically relevant at both the neural (firing pattern) and behavioral (eyeblink pattern) levels. This integrated system provides the sufficient computation power for mimicking the cerebellar circuit in real-time. The system interacts with the biological system naturally at the spike level and can be generalized for including other neural components (neuron types and plasticity) and neural functions for potential neuroprosthetic applications.

A Gap in Time: Extending our Knowledge of Temporal Processing Deficits in the HIV-1 Transgenic Rat.

PubMed

McLaurin, Kristen A; Moran, Landhing M; Li, Hailong; Booze, Rosemarie M; Mactutus, Charles F

2017-03-01

Approximately 50 % of HIV-1 seropositive individuals develop HIV-1 associated neurocognitive disorders (HAND), which commonly include alterations in executive functions, such as inhibition, set shifting, and complex problem solving. Executive function deficits in HIV-1 are fairly well characterized, however, relatively few studies have explored the elemental dimensions of neurocognitive impairment in HIV-1. Deficits in temporal processing, caused by HIV-1, may underlie the symptoms of impairment in higher level cognitive processes. Translational measures of temporal processing, including cross-modal prepulse inhibition (PPI), gap-prepulse inhibition (gap-PPI), and gap threshold detection, were studied in mature (ovariectomized) female HIV-1 transgenic (Tg) rats, which express 7 of the 9 HIV-1 genes constitutively throughout development. Cross-modal PPI revealed a relative insensitivity to the manipulation of interstimulus interval (ISI) in HIV-1 Tg animals in comparison to control animals, extending previously reported temporal processing deficits in HIV-1 Tg rats to a more advanced age, suggesting the permanence of temporal processing deficits. In gap-PPI, HIV-1 Tg animals exhibited a relative insensitivity to the manipulation of ISI in comparison to control animals. In gap-threshold detection, HIV-1 Tg animals displayed a profound differential sensitivity to the manipulation of gap duration. Presence of the HIV-1 transgene was diagnosed with 91.1 % accuracy using gap threshold detection measures. Understanding the generality and permanence of temporal processing deficits in the HIV-1 Tg rat is vital to modeling neurocognitive deficits observed in HAND and provides a key target for the development of a diagnostic screening tool.

Relationships between skin temperature and temporal summation of heat and cold pain.

PubMed

Mauderli, Andre P; Vierck, Charles J; Cannon, Richard L; Rodrigues, Anthony; Shen, Chiayi

2003-07-01

Temporal summation of heat pain during repetitive stimulation is dependent on C nociceptor activation of central N-methyl-d-aspartate (NMDA) receptor mechanisms. Moderate temporal summation is produced by sequential triangular ramps of stimulation that control skin temperature between heat pulses but do not elicit distinct first and second pain sensations. Dramatic summation of second pain is produced by repeated contact of the skin with a preheated thermode, but skin temperature between taps is not controlled by this procedure. Therefore relationships between recordings of skin temperature and psychophysical ratings of heat pain were evaluated during series of repeated skin contacts. Surface and subcutaneous recordings of skin temperatures revealed efficient thermoregulatory compensation for heat stimulation at interstimulus intervals (ISIs) ranging from 2 to 8 s. Temporal summation of heat pain was strongly influenced by the ISIs and cannot be explained by small increases in skin temperature between taps or by heat storage throughout a stimulus series. Repetitive brief contact with a precooled thermode was utilized to evaluate whether temporal summation of cold pain occurs, and if so, whether it is influenced by skin temperature. Surface and subcutaneous recordings of skin temperature revealed a sluggish thermoregulatory compensation for repetitive cold stimulation. In contrast to heat stimulation, skin temperature did not recover between cold stimuli throughout ISIs of 3-8 s. Psychophysically, repetitive cold stimulation produced an aching pain sensation that progressed gradually and radiated beyond the site of stimulation. The magnitude of aching pain was well related to skin temperature and thus appeared to be established primarily by peripheral factors.

Neurophysiological correlates of abnormal somatosensory temporal discrimination in dystonia.

PubMed

Antelmi, Elena; Erro, Roberto; Rocchi, Lorenzo; Liguori, Rocco; Tinazzi, Michele; Di Stasio, Flavio; Berardelli, Alfredo; Rothwell, John C; Bhatia, Kailash P

2017-01-01

Somatosensory temporal discrimination threshold is often prolonged in patients with dystonia. Previous evidence suggested that this might be caused by impaired somatosensory processing in the time domain. Here, we tested if other markers of reduced inhibition in the somatosensory system might also contribute to abnormal somatosensory temporal discrimination in dystonia. Somatosensory temporal discrimination threshold was measured in 19 patients with isolated cervical dystonia and 19 age-matched healthy controls. We evaluated temporal somatosensory inhibition using paired-pulse somatosensory evoked potentials, spatial somatosensory inhibition by measuring the somatosensory evoked potentials interaction between simultaneous stimulation of the digital nerves in thumb and index finger, and Gamma-aminobutyric acid-ergic (GABAergic) sensory inhibition using the early and late components of high-frequency oscillations in digital nerves somatosensory evoked potentials. When compared with healthy controls, dystonic patients had longer somatosensory temporal discrimination thresholds, reduced suppression of cortical and subcortical paired-pulse somatosensory evoked potentials, less spatial inhibition of simultaneous somatosensory evoked potentials, and a smaller area of the early component of the high-frequency oscillations. A logistic regression analysis found that paired pulse suppression of the N20 component at an interstimulus interval of 5 milliseconds and the late component of the high-frequency oscillations were independently related to somatosensory temporal discrimination thresholds. "Dystonia group" was also a predictor of enhanced somatosensory temporal discrimination threshold, indicating a dystonia-specific effect that independently influences this threshold. Increased somatosensory temporal discrimination threshold in dystonia is related to reduced activity of inhibitory circuits within the primary somatosensory cortex. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Does the sight of physical threat induce a tactile processing bias? Modality-specific attentional facilitation induced by viewing threatening pictures.

PubMed

Van Damme, Stefaan; Gallace, Alberto; Spence, Charles; Crombez, Geert; Moseley, G Lorimer

2009-02-09

Threatening stimuli are thought to bias spatial attention toward the location from which the threat is presented. Although this effect is well-established in the visual domain, little is known regarding whether tactile attention is similarly affected by threatening pictures. We hypothesised that tactile attention might be more affected by cues implying physical threat to a person's bodily tissues than by cues implying general threat. In the present study, participants made temporal order judgments (TOJs) concerning which of a pair of tactile (or auditory) stimuli, one presented to either hand, at a range of inter-stimulus intervals, had been presented first. A picture (showing physical threat, general threat, or no threat) was presented in front of one or the other hand shortly before the tactile stimuli. The results revealed that tactile attention was biased toward the side on which the picture was presented, and that this effect was significantly larger for physical threat pictures than for general threat or neutral pictures. By contrast, the bias in auditory attention toward the side of the picture was significantly larger for general threat pictures than for physical threat pictures or neutral pictures. These findings therefore demonstrate a modality-specific effect of physically threatening cues on the processing of tactile stimuli, and of generally threatening cues on auditory information processing. These results demonstrate that the processing of tactile information from the body part closest to the threatening stimulus is prioritized over tactile information from elsewhere on the body.

Peripheral vision and perceptual asymmetries in young and older martial arts athletes and nonathletes.

PubMed

Muiños, Mónica; Ballesteros, Soledad

2014-11-01

The present study investigated peripheral vision (PV) and perceptual asymmetries in young and older martial arts athletes (judo and karate athletes) and compared their performance with that of young and older nonathletes. Stimuli were dots presented at three different eccentricities along the horizontal, oblique, and vertical diameters and three interstimulus intervals. Experiment 1 showed that although the two athlete groups were faster in almost all conditions, karate athletes performed significantly better than nonathlete participants when stimuli were presented in the peripheral visual field. Experiment 2 showed that older participants who had practiced a martial art at a competitive level when they were young were significantly faster than sedentary older adults of the same age. The practiced sport (judo or karate) did not affect performance differentially, suggesting that it is the practice of martial arts that is the crucial factor, rather than the type of martial art. Importantly, older athletes lose their PV advantage, as compared with young athletes. Finally, we found that physical activity (young and older athletes) and age (young and older adults) did not alter the visual asymmetries that vary as a function of spatial location; all participants were faster for stimuli presented along the horizontal than for those presented along the vertical meridian and for those presented at the lower rather than at the upper locations within the vertical meridian. These results indicate that the practice of these martial arts is an effective way of counteracting the processing speed decline of visual stimuli appearing at any visual location and speed.

Neural Correlates of Subjective Awareness for Natural Scene Categorization of Color Photographs and Line-Drawings.

PubMed

Fu, Qiufang; Liu, Yong-Jin; Dienes, Zoltan; Wu, Jianhui; Chen, Wenfeng; Fu, Xiaolan

2017-01-01

It remains controversial whether visual awareness is correlated with early activation indicated by VAN (visual awareness negativity), as the recurrent process hypothesis theory proposes, or with later activation indicated by P3 or LP (late positive), as suggested by global workspace theories. To address this issue, a backward masking task was adopted, in which participants were first asked to categorize natural scenes of color photographs and line-drawings and then to rate the clarity of their visual experience on a Perceptual Awareness Scale (PAS). The interstimulus interval between the scene and the mask was manipulated. The behavioral results showed that categorization accuracy increased with PAS ratings for both color photographs and line-drawings, with no difference in accuracy between the two types of images for each rating, indicating that the experience rating reflected visibility. Importantly, the event-related potential (ERP) results revealed that for correct trials, the early posterior N1 and anterior P2 components changed with the PAS ratings for color photographs, but did not vary with the PAS ratings for line-drawings, indicating that the N1 and P2 do not always correlate with subjective visual awareness. Moreover, for both types of images, the anterior N2 and posterior VAN changed with the PAS ratings in a linear way, while the LP changed with the PAS ratings in a non-linear way, suggesting that these components relate to different types of subjective awareness. The results reconcile the apparently contradictory predictions of different theories and help to resolve the current debate on neural correlates of visual awareness.

Neural Correlates of Subjective Awareness for Natural Scene Categorization of Color Photographs and Line-Drawings

PubMed Central

Fu, Qiufang; Liu, Yong-Jin; Dienes, Zoltan; Wu, Jianhui; Chen, Wenfeng; Fu, Xiaolan

2017-01-01

It remains controversial whether visual awareness is correlated with early activation indicated by VAN (visual awareness negativity), as the recurrent process hypothesis theory proposes, or with later activation indicated by P3 or LP (late positive), as suggested by global workspace theories. To address this issue, a backward masking task was adopted, in which participants were first asked to categorize natural scenes of color photographs and line-drawings and then to rate the clarity of their visual experience on a Perceptual Awareness Scale (PAS). The interstimulus interval between the scene and the mask was manipulated. The behavioral results showed that categorization accuracy increased with PAS ratings for both color photographs and line-drawings, with no difference in accuracy between the two types of images for each rating, indicating that the experience rating reflected visibility. Importantly, the event-related potential (ERP) results revealed that for correct trials, the early posterior N1 and anterior P2 components changed with the PAS ratings for color photographs, but did not vary with the PAS ratings for line-drawings, indicating that the N1 and P2 do not always correlate with subjective visual awareness. Moreover, for both types of images, the anterior N2 and posterior VAN changed with the PAS ratings in a linear way, while the LP changed with the PAS ratings in a non-linear way, suggesting that these components relate to different types of subjective awareness. The results reconcile the apparently contradictory predictions of different theories and help to resolve the current debate on neural correlates of visual awareness. PMID:28261141

Laurentide Ice Sheet Meltwater Geochemistry During the MIS 3 Warm Phase from Single-Shell Trace Element and Isotope Measurements

NASA Astrophysics Data System (ADS)

Branson, O.; Vetter, L.; Fehrenbacher, J. S.; Spero, H. J.

2016-12-01

The geochemical variability between individual foraminifera within single core intervals records both palaeo-oecanographic conditions and ecology. Within the biological context of foraminiferal species, this population variability may be interpreted to provide unparalleled paleoenvironmental information. For example, coupled trace element and stable isotope analyses of single O. universa offer a powerful tool for reconstructing the δ18O of Laurentide Ice Sheet (LIS) meltwater, by calculating the intercept between temperature-corrected δ18O water and Ba/Ca salinity estimates (Vetter et al., in review). This offers valuable insights into the dynamics of ice sheet melting at the end of the last glacial maximum. Here we apply similar coupled single-shell laser ablation (LA-ICP-MS) and isotope ratio mass spectrometry (IRMS) techniques to explore the δ18O of Laurentide meltwater during H4 and bracketing intervals. The application of these methods to down-core samples requires the development of robust LA-ICP-MS data processing techniques to identify primary signals within Ba contaminated samples, and careful consideration of palaeo Ba/Ca-salinity relationships. Our analyses offer a significant advance in systematic LA-ICP-MS data processing methods, offer constraints on the variability of riverine Ba fluxes, and ultimately provide δ18O estimates of LIS meltwater during H4.

The modulation rate transfer function of a harbour porpoise (Phocoena phocoena).

PubMed

Linnenschmidt, Meike; Wahlberg, Magnus; Damsgaard Hansen, Janni

2013-02-01

During echolocation, toothed whales produce ultrasonic clicks at extremely rapid rates and listen for the returning echoes. The auditory brainstem response (ABR) duration was evaluated in terms of latency between single peaks: 5.5 ms (from peak I to VII), 3.4 ms (I-VI), and 1.4 ms (II-IV). In comparison to the killer whale and the bottlenose dolphin, the ABR of the harbour porpoise has shorter intervals between the peaks and consequently a shorter ABR duration. This indicates that the ABR duration and peak latencies are possibly related to the relative size of the auditory structures of the central nervous system and thus to the animal's size. The ABR to a sinusoidal amplitude modulated stimulus at 125 kHz (sensitivity threshold 63 dB re 1 μPa rms) was evaluated to determine the modulation rate transfer function of a harbour porpoise. The ABR showed distinct envelope following responses up to a modulation rate of 1,900 Hz. The corresponding calculated equivalent rectangular duration of 263 μs indicates a good temporal resolution in the harbour porpoise auditory system similar to the one for the bottlenose dolphin. The results explain how the harbour porpoise can follow clicks and echoes during echolocation with very short inter click intervals.

Switching between univalent task-sets in schizophrenia: ERP evidence of an anticipatory task-set reconfiguration deficit.

PubMed

Karayanidis, Frini; Nicholson, Rebecca; Schall, Ulrich; Meem, Lydia; Fulham, Ross; Michie, Patricia T

2006-10-01

The present study used behavioral and event-related potential (ERP) indices of task-switching to examine whether schizophrenia patients have a specific deficit in anticipatory task-set reconfiguration. Participants switched between univalent tasks in an alternating runs paradigms with blocked response-stimulus interval (RSI) manipulation (150, 300, 600, and 1200ms). Nineteen high functioning people with schizophrenia were compared to controls that were matched for age, gender, education and premorbid IQ estimate. Schizophrenia patients had overall increased RT, but no increase in corrected RT switch cost. In the schizophrenia group, ERPs showed reduced activation of the differential positivity in anticipation of switch trial at the optimal 600ms RSI and reduced activation of the frontal post-stimulus switch negativity at both 600 and 1200ms RSI compared to the control group. Despite no behavioral differences in task switching performance, anticipatory and stimulus-triggered ERP indices of task-switching suggest group differences in processing of switch and repeat trials, especially at longer RSI conditions that for control participants provide opportunity for anticipatory activation of task-set reconfiguration processes. These results are compatible with impaired implementation of endogenously driven processes in schizophrenia and greater reliance on external task cues, especially at long preparation intervals.