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PurposeThis study aimed to investigate usefulness of acoustic change complex (ACC) as an objective measure of difference limen for intensity (DLI) in auditory neuropathy spectrum disorders (ANSD) and cochlear hearing loss (CHL).MethodThe study used a multiple static group comparison research design. Twenty normal-hearing individuals (NH), 19 individuals with ANSD, and 23 individuals with CHL underwent DLI measurement using behavioral (psychoacoustic) techniques and ACC. For eliciting ACC, a 500-ms, 1,000-Hz pure tone was presented at 80 dB SPL. Additionally, six variants of this stimulus with intensity increments of 1, 3, 4, 5, 10, and 20 dB starting 250 ms after stimulus onset were used to elicit the ACC.ResultsThe lowest intensity change that produced replicable and clearly identifiable ACC was referred as objective DLI. In comparison to NH and CHL, the behavioral as well as the objective DLI were significantly larger (poorer) in ANSD (p< .05). Significantly strong positive correlation existed between DLI obtained using behavioral and objective measures (p< .05).ConclusionsACC could be a useful objective tool to measure DLI in the clinical population, provided the individuals of the clinical population fulfill the prerequisite of the presence of Auditory Long Latency Responses.Supplemental Materialhttps://doi.org/10.23641/asha.12560132

Research has shown that people who are instructed to volitionally respond to pitch-shifted feedback either produce responses that follow the shift direction with a short latency of 100–200 ms or oppose the shift direction with longer latencies of 300–400 ms. This difference in response latencies prompted a comparison of three groups of vocalists with differing abilities, non-trained English-speaking subjects, non-trained Mandarin-speaking subjects, and trained English-speaking singers. All subjects produced short latency following responses and long latency opposing responses, and in most cases the opposing responses were preceded by a shorter latency following response. Across groups, the magnitudes of the opposing and following responses were largest for the Mandarin speakers. Singers produced the smallest opposing response magnitudes, suggesting differences in the pitch goals of the two groups. Opposing response latencies were longest for the English and Mandarin speaking subjects and shortest for the trained singers, demonstrating that musical training increases the speed of producing the opposing responses. The presence of similar latencies of small following responses preceding larger opposing responses in all groups suggests that the tendency to mimic changes in sounds to which a person is attending are not influenced by vocal training or experience.Research has shown that people who are instructed to volitionally respond to pitch-shifted feedback either produce responses that follow the shift direction with a short latency of 100–200 ms or oppose the shift direction with longer latencies of 300–400 ms. This difference in response latencies prompted a comparison of three groups of vocalists with differing abilities, non-trained English-speaking subjects, non-trained Mandarin-speaking subjects, and trained English-speaking singers. All subjects produced short latency following responses and long latency opposing responses, and in most cases the opposing responses were preceded by a shorter latency following response. Across groups, the magnitudes of the opposing and following responses were largest for the Mandarin speakers. Singers produced the smallest opposing response magnitudes, suggesting differences in the pitch goals of the two groups. Opposing response latencies were longest for the English and Mandarin speaking subjects and shortest for the ...

Intrahepatic cholangiocarcinoma (iCCA) is a lethal malignant neoplasm with limited therapeutic options. Previous studies have found that Notch1 overexpression alone suffices to induce iCCA in the mouse, albeit after long latency. The current study found that activation of the Yes-associated protein (Yap) proto-oncogene occurs during Notch1-driven iCCA progression. After co-expressing activated Notch1 intracellular domain (Nicd) and Yap (YapS127A) in the mouse liver, rapid iCCA formation and progression occurred in Nicd/Yap mice. Mechanistically, an increased expression of amino acid transporters and activation of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway was detected in Nicd/Yap mouse liver tumors. Significantly, the genetic deletion of Raptor, the major mTORC1 component, completely suppressed iCCA development in Nicd/Yap mice. Elevated expression of Notch1, YAP, amino acid transporters, and members of the mTORC1 pathway was also detected ubiquitously in a collection of human iCCA specimens. Their levels were associated with a poor patient outcome. This study demonstrates that Notch and YAP concomitant activation is frequent in human cholangiocarcinogenesis. Notch and YAP synergize to promote iCCA formation by activating the mTORC1 pathway.

OBJECTIVE: Urgency–rash action during strong emotion–is a robust correlate of nonsuicidal self-injury (NSSI). This study tested whether urgency is associated with time between NSSI urges and NSSI, and sought to replicate the finding that urgency is associated with NSSI history. METHODS: Participants attending a partial hospitalization program (N = 669) completed self-report measures of urgency, NSSI history and latency, and psychiatric symptoms. RESULTS: Consistent with previous research in clinical samples, rates of lifetime engagement in NSSI were high. Using logistic regression to predict short vs. long latency between urges and NSSI, no significant relationship emerged between negative urgency and latency to self-injure. Negative urgency more than doubled the likelihood of NSSI history (p < .001, OR = 2.39). In addition, exploratory analyses revealed several links between NSSI latency and negative urgency. CONCLUSION: Results confirm that urgency is robustly related to NSSI, yet also suggest that more research is needed to understand how urgency relates to the parameters of NSSI within those who self-injure. Use of retrospective self-report measures may limit the ability to test links between urgency and latency of NSSI.

The aim of the present study was to investigate the role of wood dust exposure in intestinal (ITAC) and non-intestinal type (non-ITAC) nasal adenocarcinoma, so as to improve understanding of the oncogenic mechanisms in the light of the recent literature and of evo-devo concepts. Materials and methods All consecutive patients operated in our institution for nasal adenocarcinoma diagnosed on anatomopathology between May 2004 and February 2014 were included. Surgical specimens were examined twice by independent pathologists, blind to wood dust exposure status. Clinical and demographic data, including wood dust exposure, were collected for the two groups (ITAC and non-IATC). Results 90 patients (84 ITAC, 6 non-ITAC) were included. No non-ITAC patients had history of wood dust exposure, versus 83/84 cases (99%) in ITAC (mean exposure duration: 30 ± 16 years; range 2–65 years). Only 12 ITAC patients (18%) were still exposed at diagnosis. ITAC may develop long after the end of wood dust exposure (up to 60 years). Eight patients (12%) had exposure durations of less than 5 years. Latency between onset of exposure and onset of disease did not decrease with exposure duration. Conclusion Exposure to wood dust, even for short periods of time, incurs a risk of developing ITAC, usually after a long latency period. Any exposure requires lifetime follow-up, to ensure prompt treatment. Factors leading to the development of nasal ITAC and non-ITAC are probably different. The analogy with Barret's esophagus and esophageal adenocarcinoma may shed light on the oncogenesis of nasal ITAC.

© 2020 American Physiological Society. All rights reserved. Time course of changes in the longlatency feedback response parallels the fast process of short-term motor adaptation Adapting to novel dynamics involves modifying both feedforward and feedback control. We investigated whether the motor system alters feedback responses during adaptation to a novel force field in a manner similar to adjustments in feedforward control. We simultaneously tracked the time course of both feedforward and feedback systems via independent probes during a force field adaptation task. Participants (n 35) grasped the handle of a robotic manipulandum and performed reaches to a visual target while the hand and arm were occluded. We introduced an abrupt counterclockwise velocity-dependent force field during a block of reaching trials. We measured movement kinematics and shoulder and elbow muscle activity with surface EMG electrodes. We tracked the feedback stretch response throughout the task. Using force channel trials, we measured overall learning, which was later decomposed into a fast and slow process. We found that the longlatency feedback response (LLFR) was upregulated in the early stages of learning and was correlated with the fast component of feedforward adaptation. The change in feedback response was specific to the long-latency epoch (50-100 ms after muscle stretch) and was observed only in the triceps muscle, which was the muscle required to counter the force field during adaptation. The similarity in time course for the LLFR and the estimated time course of the fast process suggests both are supported by common neural circuits. While some propose that the fast process reflects an explicit strategy, we argue instead that it may be a proxy for the feedback controller. NEW & NOTEWORTHY We investigated whether changes in the feedback stretch response were related to the proposed fast and slow processes of motor adaptation. We found that the long-latency component of the feedback stretch response was upregulated in the early stages of learning and the time course was correlated with the fast process. While some propose that the fast process reflects an explicit strategy, we argue instead that it may be a proxy for the feedback controller.

Cervical cancer screening was revolutionized in the early 1980s with the discovery of human papillomaviruses (HPVs) as the single causative agent of the disease. Viral infections contribute to ~12% of cancers worldwide, and two DNA viruses, Epstein-Barr virus and HPV, are associated with 38% of all virus-associated cancers. Most viral-associated cancers develop after a long latency period (15-40 yr).

Classical deprivation instruments use a factor analytical approach relying on a smaller number of dimensions, factors or components. Multi-dimensional deprivation models attempt classification in fine detail—even down to street level. Single-centre retrospective cohort study using routinely collected aggregated and anonymised data on emergency medical admissions (96,526 episodes in 50,731 patients; 2002–2016). We calculated admission/readmission rate incidences for the 74 small areas within the hospital catchment area. We compared a classical Small Area Health Research Unit (SAHRU) to the multi-dimensional POBAL Haase and Pratschke Deprivation Index for Small Areas (POBAL) deprivation instrument and their deprivation ranks for two Irish censuses (2006/ 2011). There was poor agreement between the instruments of the Deprivation Ranks by Quintile—with agreement in 46 and 42% of small areas for the respective 2006 and 2011 censuses. The classical model (SAHRU) suggested more areas with severe deprivation (Q5 66 and 55%) compared with POBAL (Q5 32 and 24%) from the respective censuses. SAHRU classical instrument had a higher prediction level incidence rate ratio (IRR) 1.48 (95% CI 1.47, 1.49)) compared with POBAL IRR 1.28 (95% CI 1.27, 1.28) and systematically lower estimates of hospital admission and readmission rate incidences. Earlier Census data modelled more powerfully, suggesting a long latency between social circumstances and the ultimate expression of the emergency medical admission. Deprivation influences hospital incidence rates for emergency medical admissions and readmissions; instruments focusing at the very small area (individual or street level) have a utility but appear inferior in terms of representing the population risk of environmental/socio-economic factors which seem best approximated at a larger scale.

Defective muscle coordination for balance recovery may contribute to stroke survivors’ propensity for falling. Thus, we investigated deficits in muscle coordination for postural control and their association to body sway following balance perturbations in people with stroke. Specifically, we compared the automatic postural responses of 8 leg and trunk muscles recorded bilaterally in unimpaired individuals and those with mild to moderate impairments after unilateral supratentorial lesions (>6 months). These responses were elicited by unexpected floor translations in 12 directions. We extracted motor modules (ie, muscle synergies) for each leg using nonnegative matrix factorization. We also determined the magnitude of perturbation-induced body sway using a single-link inverted pendulum model. Whereas the number of motor modules for balance was not affected by stroke, those formed by muscles with long latency responses were replaced by atypically structured paretic motor modules (atypical muscle groupings), which hints at direct cerebral involvement in long-latency feedback responses. Other paretic motor modules had intact structure but were poorly recruited, which is indicative of indirect cerebral control of balance. Importantly, these paretic deficits were strongly associated with postural instability in the preferred activation direction of the impaired motor modules. Finally, these deficiencies were heterogeneously distributed across stroke survivors with lesions in distinct locations, suggesting that different cerebral substrates may contribute to balance control. In conclusion, muscle coordination deficits in the paretic limb of stroke survivors result in direction-specific postural instability, which highlights the importance of targeted interventions to address patient-specific balance impairments.

Blood or marrow transplantation (BMT) is used with curative intent for hematologic malignancies. Conditional on surviving the first 2 years after BMT, 5-year survival generally exceeds 70%. However, the cumulative therapeutic exposures lead to premature onset of chronic health conditions, such that the 15-year cumulative incidence of severe or life-threatening chronic health conditions exceeds 40%, resulting in premature mortality. The high burden of morbidity, coupled with a long latency between BMT and the development of chronic health conditions necessitates life-long risk-based monitoring of the BMT survivors. The issues of how and when to screen BMT survivors for therapy-related complications and exacerbation of preexisting conditions are important and largely unanswered questions. For BMT survivors, screening recommendations must incorporate risks associated with pre-BMT therapy as well as risks related to transplant conditioning and graft-versus-host disease. Here, we describe our approach to monitoring BMT survivors for risk-based screening and early detection of key late-occurring or long-term complications using patient scenarios to illustrate our discussion.

Disturbances to balance arising from forces applied to the upper limb have received relatively little attention compared to disturbances arising from support surface perturbations. In this study we applied fast ramp perturbations to the hand in anterior, posterior, medial and lateral directions. The effects of perturbation predictability and amplitude on the postural response of upper limb, trunk and lower limb muscles were investigated. Perturbations were applied either in blocks of constant amplitude and direction (predictable) or with direction and amplitude varying randomly (random) from trial to trial. The spatial-temporal patterns of anticipatory muscle activation under the predictable condition and the reactionary responses following the perturbation under both conditions were similarly organized. The size of the response increased systematically with the perturbation magnitude for both anticipatory and reactionary changes in muscle activation. However, the slope of the relation between perturbation amplitude and the magnitude of the change in muscle activation was greater when perturbations were predictable than when they were randomly selected. The timing of both the anticipatory and reactionary increases in muscle activation was invariant across perturbation amplitudes. The characteristics of the reactionary responses have a similar organization to the long latency muscle responses to support surface perturbations.

Silicosis is usually a disease of long latency affecting mostly older workers; therefore, silicosis deaths in young adults (aged 15-44 years) suggests acute or accelerated disease.* To understand the circumstances surrounding silicosis deaths among young persons, CDC analyzed the underlying and contributing causes† of death using multiple cause-of-death data (1999-2015) and industry and occupation information abstracted from death certificates (1999-2013). During 1999-2015, among 55 pneumoconiosis deaths of young adults with International Classification of Diseases, Tenth Revision (ICD-10) code J62 (pneumoconiosis due to dust containing silica),§ 38 (69%) had code J62.8 (pneumoconiosis due to other dust containing silica), and 17 (31%) had code J62.0 (pneumoconiosis due to talc dust) listed on their death certificate. Decedents whose cause of death code was J62.8 most frequently worked in the manufacturing and construction industries and production occupations where silica exposure is known to occur. Among the 17 decedents who had death certificates listing code J62.0 as cause of death, 13 had certificates with an underlying or a contributing cause of death code listed that indicated multiple drug use or drug overdose. In addition, 13 of the 17 death certificates listing code J62.0 as cause of death had information on decedent's industry and occupation; among the 13 decedents, none worked in talc exposure-associated jobs, suggesting that their talc exposure was nonoccupational. Examining detailed information on causes of death (including external causes) and industry and occupation of decedents is essential for identifying silicosis deaths associated with occupational exposures and reducing misclassification of silicosis mortality.

Introduction: Stuttering is a speech fluency disorder, and may be associated with neuroaudiological factors linked to central auditory processing, including changes in auditory processing skills and temporal resolution. Objective: To characterize the temporal processing and long-latency auditory evoked potential in stutterers and to compare them with non-stutterers. Methods: The study included 41 right-handed subjects, aged 18-46 years, divided into two groups: stutterers (n = 20) and non-stutters (n = 21), compared according to age, education, and sex. All subjects were submitted to the duration pattern tests, random gap detection test, and long-latency auditory evoked potential. Results: Individuals who stutter showed poorer performance on Duration Pattern and Random Gap Detection tests when compared with fluent individuals. In the long-latency auditory evoked potential, there was a difference in the latency of N2 and P3 components; stutterers had higher latency values. Conclusion: Stutterers have poor performance in temporal processing and higher latency values for N2 and P3 components. Resumo Introdução: A gagueira é um distúrbio da fluência da fala e pode estar associada a fatores neuroaudiológicos ligados ao processamento auditivo central, entre eles as alterações das habilidades auditivas de processamento e resolução temporal. Objetivo: Caracterizar o processamento temporal e o potencial evocado auditivo de longa latência em indivíduos gagos e compará-los com indivíduos sem gagueira. Método: Participaram do estudo 41 indivíduos destros, de 18 a 46 anos, distribuídos em dois grupos: 20 com gagueira e 21 sem gagueira, comparados segundo idade, escolaridade e gênero. Todos os indivíduos foram submetidos aos testes de padrão de duração, teste de identificação de intervalos aleatórios e o potencial evocado auditivo de longa latência. Resultados: Indivíduos com gagueira apresentaram pior desempenho nos testes de padrão de duração e Random Gap Detection, quando comparados com os indivíduos fluentes. No potencial evocado auditivo de longa latência, houve diferença na latência dos componentes N2 e P3, os indivíduos gagos apresentaram maiores valores de latência. Conclusão: Os indivíduos com gagueira apresentaram processamento temporal com desempenho abaixo do esperado e um maior valor de latência para os componentes N2 e P3.

The long-latency “reflexive” response (LLR) following an upper limb mechanical perturbation is generated by neural circuitry shared with voluntary control. This feedback response supports many task-dependent behaviors and permits the expression of goal-directed corrections at latencies shorter than voluntary reaction time. An extensive body of literature has demonstrated that the LLR shows flexibility akin to voluntary control, but it has not yet been tested whether instruction-dependent LLR changes can also occur in the absence of an overt voluntary response. The present study used kinesthetic motor imagery ( experiment 1) and instructed participants to execute movement with the unperturbed contralateral limb ( experiment 2) to explore the relationship between the overt production of a voluntary response and LLR facilitation. Activity in stretched right wrist flexors were compared with standard “do not-intervene” and “compensate” conditions. Our findings revealed that on ~40% of imagery and ~50% of contralateral trials, a response occurred during the voluntary epoch in the stretched right wrist flexors. On these “leaked” trials, the early portion of the LLR (R2) was facilitated and displayed a similar increase to compensate trials. The latter half of the LLR (R3) showed further modulation, mirroring the patterns of voluntary epoch activity. By contrast, the LLR on “non-leaked” imagery and contralateral trials did not modulate. We suggest that even though a hastened voluntary response cannot account for all instruction-dependent LLR modulation, the overt execution of a response during the voluntary epoch in the same muscle(s) as the LLR is a prerequisite for instruction-dependent facilitation of this feedback response. NEW & NOTEWORTHY Using motor imagery and contralateral responses, we provide novel evidence that facilitation of the long-latency reflex (LLR) requires the execution of a response during the voluntary epoch. A high proportion of overt response “leaks” were found where the mentally simulated or mirrored response appeared in stretched muscle. The first half of the LLR was categorically sensitive to the appearance of leaks, whereas the latter half displayed characteristics closely resembling activity in the ensuing voluntary period.

Unilateral condylar hyperplasia (UCH) is characterized by an overgrowth of the mandibular condyle responsible for a facial and dental asymmetry associated with temporomandibular joint function and maxillary growth consequences. The diagnosis is based on a body of clinical, radiological and histological arguments. A 38 years old woman with a reactivation of UCH after a latency period of 16 years following an orthognathic surgery performed for facial asymmetry normalization is presented. She was addressed to our department for a facial progressive asymmetry relapse and dental prosthetic consequences.The radiological images and the planar scintigraphy combined with single-photon emission computed tomography scans showed an active left unilateral condylar hyperplasia. A left proportional condylectomy was performed.The case presented highlights the possibility for the UCH to be reactivated after a long period of latency, leading to a relapse of the occlusal and facial disorders and so advocates the need for first condylectomy or at least a long-term follow-up if condylectomy is not performed as a first-line treatment.

Background Anaesthetized rodents are examined for their capacity to model human mismatch negativity (MMN). In the present study, oddball and deviant-alone control paradigms, with stimuli varying in frequency (ascending and descending) and intensity (louder and quieter), were presented to anaesthetized mice to determine whether they elicit a translational mismatch response (MMR). New method Resulting waveforms displayed long-latency (>200 ms post-stimulus) components, only made fully visible from oddball paradigm data by applying a double-epoch subtraction. In this approach, an extended epoch containing two consecutive standard evoked responses was subtracted from the response to an oddball followed by a standard (i.e. oddball:standard – standard:standard). Results The trailing standard responses effectively cancelled each other out, revealing biphasic long-latency components. These MMR waveforms correlated strongly with deviant-alone paradigm evoked potentials >200 ms post-stimulus, potentially indicative of shared underlying mechanisms. Interestingly, these components were absent from the quieter oddball MMR. Comparison with existing method(s) Classical mismatch negativity computation is incapable of fully characterizing the long-latency biphasic response observed from this study, due to the inbuilt constraint of a single stimulus epoch. These results also suggest that the deviant-alone paradigm may be considered akin to a positive control for sensory-memory disruption, widely thought to be at the root of MMN generation in humans. Conclusions Long-latency auditory evoked potential components are observed from anaesthetized mice in response to frequency and increasing intensity oddball stimuli. These display some congruencies with human MMN.

Previous studies have demonstrated a progression of function when healthy subjects counter a sudden mechanical load. Short-latency reflexes are linked to local stretch of the particular muscle and its antagonist. Long-latency reflexes integrate stretch information from both local sources and muscles crossing remote joints appropriate for a limb’s mechanical interactions. Unresolved is how sensory information is processed throughout the corrective response, since capabilities at some time can be produced by circuits acting at that delay and at briefer delays. One possibility is that local abilities are always expressed at a short-latency delay and integrative abilities are always expressed at a long-latency delay. Alternatively, the neural circuits may be altered over time, leading to a temporal shift in expressing certain abilities; a refractory period could retard integrative responses to a second perturbation, whereas priming could enable integrative responses at short latency. We tested between these three hypotheses in a shoulder muscle by intermixing trials of step torque with either torque pulses ( experiment 1) or double steps of torque ( experiment 2). The second perturbation occurred at 35, 60, and 110 ms after the first perturbation to probe processing throughout the corrective action. The second perturbation reliably evoked short-latency responses in the shoulder muscle linked to only shoulder motion and long-latency responses linked to both shoulder and elbow motion. This pattern is best accounted by the continuous action of controllers with fixed functions. NEW & NOTEWORTHY Sudden displacement of the limb evokes a short-latency reflex, 20–50 ms, based on local muscle stretch and a long-latency reflex based on integrating muscle stretch at different joints. A novel double-perturbation paradigm tested if these abilities are temporally conserved throughout the corrective response or are shifted (retarded or delayed) due to functional changes in the responsible circuits. Multi-joint integration was reliably expressed at a long-latency delay consistent with the continuous operation of circuits with fixed abilities.

PurposeThe purpose of this study was to measure magnitude changes of auditory steady-state responses (ASSRs) and respective transient middle- and long-latency responses as a function of stimulus intensity and carrier frequency. The literature lacks clear consensus, including relationship to loudness.MethodA cohort of 48 adults with normal hearing was examined from a companion study (Tlumak, Durrant, & Delgado, 2015) on effects of aging. ASSRs were elicited by repeated tone-burst stimuli presented at rates of 40 and 0.75 Hz at 3 frequencies and 5 levels of stimulus intensity. The design also permitted scrutiny of any gender bias to the results.ResultsSimilar to derived transient response findings, ASSR magnitude (harmonic sum) systematically increased with intensity. Input–output function only at 0.75 Hz approximated a log–log linear function. However, slopes fell well below that of doubling of loudness per 10 dB SPL. Results failed to demonstrate significance as a function of carrier frequency and gender for both repetition rates.ConclusionEffects of stimulus intensity, carrier frequency, and gender on ASSRs were similar to those of their transient counterparts. Findings remain disappointing for objective loudness estimation. Results suggest only a clear linkage to the long-latency response and the 0.75-Hz magnitude but require careful consideration of limitations/underlying mechanisms when measuring loudness-related effects.

The study aimed to track long latency responses over a period of hearing aid use in naïve hearing aid users, and study its relationship with change in speech perception abilities and perceived benefit.Thirty adults in the age range of 23-60 years with moderate sensorineural hearing loss participated in the study. Auditory late latency responses (ALLRs), signal-to-noise ratio - 50 (SNR-50), and scores of speech spatial and qualities questionnaire (SSQ) were measured three times over a period of 2 months of hearing aid use.ALLRs showed a significant decrease in the P1 and N1 latency across the three measurements. Significant increase in the scores of SSQ and significant decrease in the SNR-50 were also found. The change in ALLRs did not correlate with change in scores of either SSQ or SNR-50.The study provides evidence for improvements in neural processing of auditory cortical areas with hearing aid acclimatization. The improvements seen in perceived benefit and speech perception are not related to the improvements in ALLRs. This is the first study in the domain with a younger group compared to the previous studies and the results show evidence for neural plasticity influencing hearing aid acclimatization benefits.

Bilateral deficits in sensorimotor function have been observed in unilateral musculoskeletal pain conditions. Evidence suggests a reduction in interhemispheric inhibition (IHI) from the “affected” (contralateral to the side of pain) to the “unaffected” primary motor cortex (M1) could contribute. However, the effect of short-lasting acute muscle pain on IHI, and whether any changes are related to early sensorimotor changes in the unaffected limb, is unknown. Using a cross-sectional study design, IHI was investigated in 20 healthy individuals before, immediately after, and 30 minutes after the induction of acute muscle pain in the right first dorsal interosseous muscle via a bolus injection of hypertonic saline. Transcranial magnetic stimulation was used to assess corticomotor excitability and short and long latency IHI. Pain intensity and quality were recorded using an 11-point numerical rating scale and the McGill Pain Questionnaire. Pressure pain thresholds were assessed in the affected and unaffected first dorsal interosseous and both tibialis anterior muscles. Participants reported an average pain intensity of 4.8 points (standard deviation = 1.3 points). Compared with baseline, corticomotor excitability was decreased at all time points in the affected but not the unaffected M1. IHI was decreased at all time points from the affected to the unaffected M1. Pressure pain thresholds were decreased over both first dorsal interosseous muscles at 30 minutes of follow-up. These findings suggest a decrease in IHI from the affected to the unaffected M1 that occurs rapidly after the onset of acute pain and could contribute to the development of bilateral symptoms. Perspective The affected M1 (contralateral to the side of pain) releases inhibition over the unaffected M1 within minutes after the onset of acute muscle pain. This finding could have relevance for the development of bilateral sensorimotor symptoms in unilateral pain conditions.

Background Deviant stimuli within a standard, frequent stimulus train induce a cortical somatosensory mismatch response (SMMR). The SMMR reflects the brain’s automatic mechanism for the detection of change in a somatosensory domain. It is usually elicited by electrical stimulation, which activates nerve fibers and receptors in superficial and deep skin layers, whereas tactile stimulation is closer to natural stimulation and activates uniform fiber types. We recorded SMMRs after electrical and tactile stimuli. Method 306-channel magnetoencephalography recordings were made with 16 healthy adults under two conditions: electrical (eSMMR) and tactile (tSMMR) stimulations. The SMMR protocol consisted of 1000 stimuli with 10% deviants to fingers. Results Sensor-level analysis revealed stronger activation after deviant stimulation in bilateral channel locations approximately corresponding to parietal cortical areas within both stimulation conditions. Between conditions, deviant tSMMR showed stronger activation in the ipsilateral channels. Based on sensor-level results, two components, M50 and SMMR (40–58 and 110–185 ms), were compared at the source-level. Deviant stimulation elicited stronger contralateral SI activation during M50 component in both conditions. SMMR was observed with both conditions, activating contralateral SII after deviant stimulation. However, only tSMMR showed long latency activation in bilateral SI cortices. This suggests that there is an integration of both body sides during the automatic stages of tactile processing in SI cortices. Conclusions This study indicates that tactile stimulation (tSMMR) is a feasible method for investigating the brain’s mechanism for detecting somatosensory changes; this may extend the clinical utility of tSMMR for assessing disorders involving altered somatosensory processing.

Long-latency auditory event potentials (LLAEPs) involving local and global auditory processes have been investigated to examine the impact of low-frequency (LF) and high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) on the cortical excitability of the temporal cortex. We hypothesized that both stimulation frequencies have the same modulation effect, in accordance with clinical data showing a reduction in auditory verbal hallucinations (AVHs) after LF and HF temporal rTMS in patients with schizophrenia. With 30 right-handed healthy volunteer participants enrolled in a crossover trial, we analyzed LLAEPs before and after LF- and HF-rTMS of the left temporal cortex. While we observed no changes in latencies, we did observe a similar inhibitory action of both rTMS frequencies on LLAEP amplitudes. Analysis of surface potential maps and cortical generators revealed some differences regarding auditory processes: HF-rTMS produced earlier, more diffuse, and more right-lateralized effects than LF-rTMS. Beyond a local impact, rTMS exerted a remote modulation influence on the frontal cortex that might be involved in attentional processes. This association could explain the therapeutic effect of temporal HF-rTMS on AVH.

OBJECTIVE: The objective of this study was to compare long-latency auditory evoked potentials before and after hearing aid fittings in children with sensorineural hearing loss compared with age-matched children with normal hearing. METHODS: Thirty-two subjects of both genders aged 7 to 12 years participated in this study and were divided into two groups as follows: 14 children with normal hearing were assigned to the control group (mean age 9 years and 8 months), and 18 children with mild to moderate symmetrical bilateral sensorineural hearing loss were assigned to the study group (mean age 9 years and 2 months). The children underwent tympanometry, pure tone and speech audiometry and long-latency auditory evoked potential testing with speech and tone burst stimuli. The groups were assessed at three time points. RESULTS: The study group had a lower percentage of positive responses, lower P1-N1 and P2-N2 amplitudes (speech and tone burst), and increased latencies for the P1 and P300 components following the tone burst stimuli. They also showed improvements in long-latency auditory evoked potentials (with regard to both the amplitude and presence of responses) after hearing aid use. CONCLUSIONS: Alterations in the central auditory pathways can be identified using P1-N1 and P2-N2 amplitude components, and the presence of these components increases after a short period of auditory stimulation (hearing aid use). These findings emphasize the importance of using these amplitude components to monitor the neuroplasticity of the central auditory nervous system in hearing aid users.

By encoding acoustic regularities present in the environment, the human brain can generate predictions of what is likely to occur next. Recent studies suggest that deviations from encoded regularities are detected within 10–50 ms after stimulus onset, as indicated by electrophysiological effects in the middle latency response (MLR) range. This is upstream of previously known long-latency (LLR) signatures of deviance detection such as the mismatch negativity (MMN) component. In the present study, we created predictable and unpredictable contexts to investigate MLR and LLR signatures of the encoding of spatial auditory regularities and the generation of predictions from these regularities. Chirps were monaurally delivered in an either regular (predictable: left–right–left–right) or a random (unpredictable left/right alternation or repetition) manner. Occasional stimulus omissions occurred in both types of sequences. Results showed that the Na component (peaking at 34 ms after stimulus onset) was attenuated for regular relative to random chirps, albeit no differences were observed for stimulus omission responses in the same latency range. In the LLR range, larger chirp-and omission-evoked responses were elicited for the regular than for the random condition, and predictability effects were more prominent over the right hemisphere. We discuss our findings in the framework of a hierarchical organization of spatial regularity encoding. This article is part of a Special Issue entitled SI: Prediction and Attention.

Objective This study was designed to investigate the effects of open technique rhinoplasty on facial nerve terminal branches more concerned with mimicry via electroneurography (ENoG). Methods Twenty patients ages between 24 and 36 years were included in the study. Five nasal mimicry muscles were used to evaluate axonal loss of the facial nerve: bilateral transverse nasal, levator labii superioris alaeque nasi (LLSAN), and procerus muscles of all patients were evaluated preoperatively and postoperative third month by ENoG. The patients that have abnormalities regarding the amplitude and latency at third month were reevaluated at sixth month postoperatively. Results Mean latencies of the facial nerve were calculated to be increased for all muscles at third postoperative month, but this increase was significant only for left LLSAN (P = 0.002). Amplitudes of the facial nerve decreased in all of the groups, but this decrease was not significant (P > 0.05). Two patients with exceptionally long latency facial nerve response of transverse nasal muscle and 11 muscle recordings with abnormal low amplitudes of the facial nerve at the third month was reevaluated at sixth postoperative month and the values were improved. Conclusions This study demonstrated that facial nerve integrity is minimally affected after rhinoplasty, yet all affected muscles were recovered on the long term.

A number of studies have highlighted the sophistication of corrective responses in lengthened muscles during the long-latency epoch. However, in various contexts, unloading can occur, which requires corrective actions from a shortened muscle. Here, we investigate the sophistication of inhibitory responses in shortened muscles due to unloading. Our first experiment quantified the inhibitory responses following an unloading torque that displaced the hand either into or away from a peripheral target. We observed larger long-latency inhibitory responses when perturbed into the peripheral target compared with away from the target. In our second experiment, we characterized the degree of inhibition following unloading with respect to different levels of preperturbation muscle activity. We initially observed that the inhibitory activity during the short-latency epoch scaled with increased levels of preperturbation muscle activity. However, this scaling peaked early in the R2 epoch (∼50 ms) but then quickly diminished through the rest of the long-latency epoch. Finally, in experiment 3, we investigated whether inhibitory perturbation responses consider intersegmental dynamics of the limb. We quantified unloading responses for either pure shoulder or pure elbow torques that evoked similar motion at the shoulder but different elbow motion. The long-latency inhibitory response in the shoulder, unlike the short-latency, was greater for the shoulder torque compared with the response following an elbow torque, as previously observed for a loading response. Taken together, these results illustrate that the long-latency unloading response is capable of a similar level of complexity as observed when loads are applied to the limb.

A transcortical pathway helps support goal-directed reaching by processing somatosensory information to produce rapid feedback responses across multiple joints and muscles. Here we tested whether such feedback responses can account for changes in arm configuration and for arbitrary visuomotor transformations – two manipulations that alter how muscles at the elbow and wrist need to be coordinated to achieve task success. Participants used a planar three degree-of-freedom exoskeleton robot to move a cursor to a target following a mechanical perturbation that flexed the elbow. In our first experiment, the cursor was mapped to the veridical position of the robot handle, but participants grasped the handle with two different hand orientations (thumb pointing upward or thumb point downward). We found that large rapid feedback responses were evoked in wrist extensor muscles when wrist extension helped move the cursor to the target (i.e., thumb upward), and in wrist flexor muscles when wrist flexion helped move the cursor to the target (i.e., thumb downward). In our second experiment, participants grasped the robot handle with their thumb pointing upward, but the cursor’s movement was either veridical, or was mirrored such that flexing the wrist moved the cursor as if the participant extended their wrist, and vice versa. After extensive practice, we found that rapid feedback responses were appropriately tuned to the wrist muscles that supported moving the cursor to the target when the cursor was mapped to the mirrored movement of the wrist, but were not tuned to the appropriate wrist muscles when the cursor was remapped to the wrist’s veridical movement.New and NoteworthyWe show that rapid feedback responses were evoked in different wrist muscles depending on the arm’s orientation, and this muscle activity was appropriate to generate the wrist motion that supported a reaching action. Notably, we also show that these rapid feedback responses can be evoked in wrist muscles that are detrimental to a reaching action if a non-veridical mapping between wrist and hand motion is extensively learned.

We describe a case of lymphocytic thrombophilic arteritis in a 15-year-old girl who had previously taken minocycline for a year. Cutaneous polyarteritis nodosa and lymphocytic thrombophilic arteritis share many features and may both be triggered by minocycline. There may be a long latency between drug exposure to minocycline and development of disease.

Background Malignant Mesothelioma (MM) is so associated with (professional, familial or environmental) asbestos exposure that trends in incidence and mortality parallel, after 30–40 years, the trend in asbestos consumption. In recent decades, the industrialized countries have witnessed a steady growth of pleural MM (MPM), following a stabilization or decline in rates in the countries that first adopted restrictive policies. The aim of this study was to evaluate the temporal variations of pleural MM incidence in the Veneto Region of Italy in the period 1987–2010. Methods We included only MPM with histological or cytological diagnosis. Age-Period-Cohort (APC) models were used to assess the trend in the incidence of MPM in both genders. Future predictions were evaluated by using a Bayesian APC model. Results In the period 1987–2010, 1600 MPMs have occurred. We observe a positive trend in the incidence in the whole period considered. The APC model showed that in both genders the cohort at higher risk is the one born between the years 1940–1945. Future projections indicate that the trend will decrease after the incidence peak of 2010; yet 1234 men are expected to develop a mesothelioma between 2011 and 2026. Among women, the future MPM rates will be stable or slightly decreasing. Conclusions The asbestos ban introduced in Italy in the year 1992 as a prospective result will certainly determine a decreasing incidence. However, the extremely long latency of MPM means that its influence is not yet observable.

Inhibitory feedback from sensory pathways is important for controlling movement. Here, we characterize, for the first time, a long-latency, inhibitory spinal pathway to ankle flexors that is activated by low-threshold homonymous afferents. To examine this inhibitory pathway in uninjured, healthy participants, we suppressed motor-evoked potentials (MEPs), produced in the tibialis anterior (TA), by a prior stimulation to the homonymous common peroneal nerve (CPN). The TA MEP was suppressed by a triple-pulse stimulation to the CPN, applied 40, 50, and 60 ms earlier and at intensities of 0.5–0.7 times motor threshold (average suppression of test MEP was 33%). Whereas the triple-pulse stimulation was below M-wave and H-reflex threshold, it produced a long-latency inhibition of background muscle activity, approximately 65–115 ms after the CPN stimulation, a time period that overlapped with the test MEP. However, not all of the MEP suppression could be accounted for by this decrease in background muscle activity. Evoked responses from direct activation of the corticospinal tract, at the level of the brain stem or thoracic spinal cord, were also suppressed by low-threshold CPN stimulation. Our findings suggest that low-threshold muscle and cutaneous afferents from the CPN activate a long-latency, homonymous spinal inhibitory pathway to TA motoneurons. We propose that inhibitory feedback from spinal networks, activated by low-threshold homonymous afferents, helps regulate the activation of flexor motoneurons by the corticospinal tract.

PURPOSE: To characterize the findings obtained in the long latency auditory evoked potentials in malnourished children, as well as to compare them to the results obtained for children at the same age who present typical development. METHODS: Sixty-five children aged between 7 and 12 years old, of both genders, were evaluated. The control group consisted of 34 children with normal development and the study group consisted of 31 children diagnosed with malnutrition. All children underwent conventional pure tone audiometry, acoustic impedance measurement, dichotic digit test and long latency auditory evoked potentials. RESULTS: The study group presented a statistically significant difference for latencies of the components P1, N1 and P300. The latencies of these components were higher than those of the control group. Concerning the types of alterations found in the study group, increased latency for P1 and P300 and the absence of response in N1 were predominant. The control group showed a statistically significant difference in the amplitude of P300 when compared to the right and left ears. CONCLUSION: Malnourished children present with changes in the long latency auditory evoked potentials, suggesting a deficit in central auditory pathways and alterations in the processing of acoustic information.

Modulation of the long-latency reflex (LLR) is important for sensorimotor control during interaction with different mechanical loads. Transcortical pathways usually contribute to LLR modulation, but the integrity of pathways projecting to the paretic and non-paretic arms of stroke survivors is compromised. We hypothesize that disruption of transcortical reflex pathways reduces the capacity for stroke survivors to appropriately regulate the LLR bilaterally.Elbow perturbations were applied to the paretic and non-paretic arms of persons with stroke, and the dominant arm of age-matched controls as subjects interacted with Stiff or Compliant environments rendered by a linear actuator. Reflexes were quantified using surface electromyograms, recorded from biceps.LLR amplitude was significantly larger during interaction with the Compliant load compared to the Stiff load in controls. However, there was no significant change in LLR amplitude for the paretic or non-paretic arm of stroke survivors.Modulation of the LLR is altered in the paretic and non-paretic arms after stroke.Our results are indicative of bilateral sensorimotor impairments following stroke. The inability to regulate the LLR may contribute to bilateral deficits in tasks that require precise control of limb mechanics and stability.

The long-latency stretch response (muscle activity 50–100 ms after a mechanical perturbation) can be coordinated across multiple joints to support goal-directed actions. Here we assessed the flexibility of such coordination and whether it serves to counteract intersegmental dynamics and exploit kinematic redundancy. In three experiments, participants made planar reaches to visual targets after elbow perturbations and we assessed the coordination of long-latency stretch responses across shoulder, elbow, and wrist muscles. Importantly, targets were placed such that elbow and wrist (but not shoulder) rotations could help transport the hand to the target—a simple form of kinematic redundancy. In experiment 1 we applied perturbations of different magnitudes to the elbow and found that long-latency stretch responses in shoulder, elbow, and wrist muscles scaled with perturbation magnitude. In experiment 2 we examined the trial-by-trial relationship between long-latency stretch responses at adjacent joints and found that the magnitudes of the responses in shoulder and elbow muscles, as well as elbow and wrist muscles, were positively correlated. In experiment 3 we explicitly instructed participants how to use their wrist to move their hand to the target after the perturbation. We found that long-latency stretch responses in wrist muscles were not sensitive to our instructions, despite the fact that participants incorporated these instructions into their voluntary behavior. Taken together, our results indicate that, during reaching, the coordination of long-latency stretch responses across multiple joints counteracts intersegmental dynamics but may not be able to exploit kinematic redundancy.

Summary Center-surround antagonism has been used as the canonical model to describe receptive fields of retinal ganglion cells (RGCs) for decades. We describe a newly identified RGC type in the mouse, called the ON delayed (OND) RGC, with receptive field properties that deviate from center-surround organization. Responding with an unusually long latency to light stimulation, OND RGCs respond earlier as the visual stimulus increases in size. Furthermore, OND RGCs are excited by light falling far beyond their dendrites. We unravel details of the circuit mechanisms behind these phenomena, revealing new roles for inhibition in controlling both temporal and spatial receptive field properties. The non-canonical receptive field properties of the OND RGC—integration of long temporal and large spatial scales—suggest that unlike typical RGCs, it may encode a slowly varying, global property of the visual scene.

Visual Overview, Suppose that someone bumps into your arm at a party while you are holding a glass of wine. Motion of the disturbed arm will engage rapid and goal-directed feedback responses in the upper-limb., Suppose that someone bumps into your arm at a party while you are holding a glass of wine. Motion of the disturbed arm will engage rapid and goal-directed feedback responses in the upper-limb. Although such responses can rapidly counter the perturbation, it is also clearly desirable not to destabilize your grasp and/or spill the wine. Here we investigated how healthy humans maintain a stable grasp following perturbations by using a paradigm that requires spatial tuning of the motor response dependent on the location of a virtual target. Our results highlight a synchronized expression of target-directed feedback in shoulder and hand muscles occurring at ∼60 ms. Considering that conduction delays are longer for the more distal hand muscles, these results suggest that target-directed responses in hand muscles were initiated before those for the shoulder muscles. These results show that long-latency feedback can coordinate upper limb and hand muscles during object manipulation tasks.

In a voluntary movement, the nervous system specifies not only the motor commands but also the gains associated with reaction to sensory feedback. For example, suppose that, during reaching, a perturbation tends to push the hand to the left. With practice, the brain not only learns to produce commands that predictively compensate for the perturbation but also increases the long-latency reflex gain associated with leftward displacements of the arm. That is, the brain learns a feedback controller. Here, we wondered whether, during the preparatory period before the reach, the brain engaged this feedback controller in anticipation of the upcoming movement. If so, its signature might be present in how the motor system responds to perturbations in the preparatory period. Humans trained on a reach task in which they adapted to a force field. During the preparatory period before the reach, we measured how the arm responded to a pulse to the hand that was either in the direction of the upcoming field, or in the opposite direction. Reach adaptation produced an increase in the long-latency (45-100 ms delay) feedback gains with respect to baseline, but only for perturbations that were in the same direction as the force field that subjects expected to encounter during the reach. Therefore, as the brain prepares for a reach, it loads a feedback controller specific to the upcoming reach. With adaptation, this feedback controller undergoes a change, increasing the gains for the expected sensory feedback.

Purpose The effects of type of stimuli (i.e., nonspeech vs. speech), speech (i.e., natural vs. synthetic), gender of speaker and listener, speaker (i.e., self vs. other), and frequency alteration in self-produced speech on the late auditory cortical evoked potential were examined. Method Young adult men ( n = 15) and women ( n = 15), all with normal hearing, participated. P1–N1–P2 components were evoked with the following stimuli: 723-Hz tone bursts; naturally produced male and female /a/ tokens; synthetic male and female /a/ tokens; an /a/ token self-produced by each participant; and the same /a/ token produced by the participant but with a shift in frequency. Results In general, P1–N1–P2 component latencies were significantly shorter when evoked with the tonal stimulus versus speech stimuli and natural versus synthetic speech ( p < .05). Women had significantly shorter latencies for only the P2 component ( p < .05). For the tonal versus speech stimuli, P1 amplitudes were significantly smaller, and N1 and P2 amplitudes were significantly larger ( p < .05). There was no significant effect of gender on the P1, N1, or P2 amplitude ( p > .05). Conclusion These findings are consistent with the notion that spectrotemporal characteristics of nonspeech and speech stimuli affect P1–N1–P2 latency and amplitude components.

We estimated the past and future age-standardised incidence rates of mesothelioma by birth cohort and by period of diagnosis in South East England. We extracted data on patients diagnosed with mesothelioma (International Classification of Diseases-10 C45) between 1960 and 2009 from the Thames Cancer Registry. We calculated the age-standardised incidence rates using the European standard population. We used age-cohort and age-period modelling to estimate the age-specific incidence rates for the 1900 to 1950 birth cohorts and the 1935 to 2034 calendar periods. A much more pronounced increase in mesothelioma incidence between 1972 and 2007 was observed in males than in females. In both sexes, the incidence rates increased in successive generations up to the 1945 birth cohort. Projection of rates in the future showed an increase in incidence in males until 2022 and a decrease thereafter. Among females, the incidence rate was predicted to increase gradually until reaching its maximum around 2027, and to remain stable thereafter. The occurrence of mesothelioma is closely linked to occupational exposure to asbestos in the 1960s and 1970s and, due to the long latency period, the incidence of mesothelioma is projected to increase until the 2020s.

Objective: To understand the practices medical care providers and health care staff utilize in managing and preventing Adverse Drug Reactions of Long Latency (ADRLLs) among their patients on medications such as glucocorticoids. Design: Qualitative study of key informant interviews. Setting: Denver Department of Veterans Affairs (VA) Medical Center. Participants: Fourteen physician providers and health care staff (nurses and pharmacists) in primary care and rheumatology. Methods: A trained interviewer conducted semi-structured interviews in which providers and health care staff were asked about their processes for tracking and averting ADRLLs. Participants were asked about barriers and facilitators to monitoring ADRLLs and solicited for suggestions to improve existing processes. Interviews were analyzed using ATLAS.ti software. Results: Providers overwhelmingly commented on barriers, rather than facilitators. Six core themes emerged regarding ADRLL management barriers: patient noncompliance, provider workload, complications coordinating care, provider unfamiliarity with ADRLLs, lack of a standardized monitoring system, and communication failures. Ideas to improve the monitoring of ADRLLs fell into two domains: improving automated computer generated reminders or assigning a specific person to monitor potential ADRLLs. Conclusions: Interviewees strongly endorsed a more systematic approach to ADRLL management, either through less intrusive computer-generated system reminders or through a dedicated staff person, such as a pharmacist, who could more closely monitor potential ADRLLs. There was disagreement among interviewees about who is responsible for monitoring ADRLLs (specialists versus primary care providers, VA versus non-VA providers, residents versus attending physicians).

Leprosy is a chronic infectious disorder caused by Mycobacterium leprae, which mainly affects skin and peripheral nerves. It is classified as either paucibacillary or multibacillary based upon clinical manifestations and slit-skin smear results. It is speculated that leprosy develops after a long latency period following M. leprae infection. However, the actual time of infection and the duration of latency have never been proven in human patients. To date, four cases of spontaneous leprosy have been reported in chimpanzees who were caught in West Africa in infancy and used for medical research in the USA and Japan. One of these chimpanzees was extensively studied in Japan, and single-nucleotide polymorphism analysis for the M. leprae genome was conducted. This analysis revealed that the chimpanzee was infected with M. leprae during infancy in West Africa and the pathognomonic signs of leprosy appeared after at least 30 years of incubation. Analysis of leprosy in chimpanzees can contribute not only to medical research but also to the understanding of the pathoetiology of leprosy.

The purpose of this study was to investigate whether rhythmic arm swing modulates the long latency effect of transcranial magnetic stimulation (TMS) on soleus motoneuron pool excitability. Ten healthy humans rhythmically swung the left arm back and forth in a sitting position. The soleus H-reflex was evoked when the arm was in the backward swing phase. Conditioning TMS was delivered over the motor cortex 8 ms before the soleus H-reflex was evoked. The soleus H-reflex amplitude in both legs was depressed by the rhythmic arm swing. In contrast, rhythmic arm swing enhanced the facilitatory effect of conditioning TMS over the motor cortex contralateral to the arm swing side on the soleus H-reflex ipsilateral to the arm swing side. This finding indicates that rhythmic arm swing enhances some polysynaptic facilitatory pathways from the motor cortex contralateral to the arm swing side to the soleus motoneuron pool ipsilateral to the arm swing side.

Exposure to ionizing radiation has clearly been established as one of the risk factors for the development of breast cancer. Much data on the relationship between radiation exposures and subsequent breast cancer are derived from atomic bomb survivors and women who received medical exposures either for diagnostic or therapeutic purposes. Although these populations differ in background breast cancer risks and the dose, quality, and timing of radiation, consistent findings include an increased risk with younger age at exposure, long latency to breast cancer development, and increasing risk with increasing radiation dose. Although therapeutic radiation is rarely used to treat benign conditions, it remains an important and effective treatment modality for a wide range of cancers. Increased knowledge of radiation-related breast cancer and modifying influences plays an important role in guiding the initial treatment approach for young women and optimizing long-term follow-up care.

Sudden stretch of active muscle typically results in two characteristic electromyographic responses: the short latency M1 and the long latency M2. The M1 response originates from the monosynaptic Ia afferent reflex pathway. The M2 response is less well understood and is likely a compound response to different afferent inputs mediated by spinal and transcortical pathways. In this study the possible contribution of the Ia afferent pathway to the M2 response was investigated. A mechanism was hypothesized in which the M1 response synchronizes the motoneurons, and therewith their refractory periods. Stretch perturbation experiments were performed on the wrist and results were compared with a computational model of a pool of motoneurons receiving tonic and Ia afferent input. The simulations showed the same stretch amplitude, velocity, and duration-dependent characteristics on the M2 as found experimentally. It was concluded that the stretch duration effect of the M2 likely originates from the proposed Ia afferent mediated mechanism.

The purpose of this study was to develop and implement a new technique for repeated monitoring of spinal mid- to long-latency somatosensory evoked potentials (SpSEPs) during sciatic nerve stimulation following recovery from spinal cord injury (SCI) in rats. Results of this study showed significant reproducibility of SpSEP components between specimens (analysis of variance [ANOVA], p0.05) and recording days (ANOVA, p0.700) using this technique. SpSEP amplitudes were significantly reduced (approximately 50% of uninjured amplitude, ANOVA, p0.001) following SCI and remained depressed for 10 weeks post-injury. SpSEP amplitude following high-intensity stimuli (1 mA) correlated with BBB locomotor score (Pearson, R0.353, P0.001). Characteristics of the mid- to long-latency SpSEPs suggest these components may reflect the integrity of the lateral pain pathway within the spinothalamic tract (STT). The technique and data presented in this study may be useful in future studies aimed at quantifying spinal cord integrity following injury and treatment using the rat model of SCI.

Background Although a long latency period of toxicity after exposure to methylmercury (MeHg) is known to exist in humans, few animal studies have addressed this issue. Substantiation of delayed MeHg toxicity in animals would affect the risk evaluation of MeHg. Objectives Our goal in this study was to demonstrate the existence of a latency period in a rodent model in which the toxicity of perinatal MeHg exposure becomes apparent only later in life. Our study included metallothionein (MT) knockout mice because studies have suggested the potential susceptibility of this strain to the neurodevelopmental toxicity of MeHg. Methods Pregnant MT-null and wild-type C57Bl/6J mice were exposed to MeHg through their diet containing 5 μg Hg/g during gestation and early lactation. We examined behavioral functions of the offspring using frequently used paradigms, including open field behavior (OPF), passive avoidance (PA), and the Morris water maze (MM), at ages of 12–13 and 52–53 weeks. Results At 12 weeks of age, behavioral effects of MeHg were not detected, except for OPF performance in MeHg-exposed MT-null females. At 52 weeks of age, the MeHg-exposed groups showed poorer performance both in PA and MM, and their OPF activity differed from controls. These effects of MeHg appeared exaggerated in the MT-null strain. The brain Hg concentration had leveled off by 13 weeks of age. Conclusions The results suggest the existence of a long latency period after perinatal exposure to low-level MeHg, in which the behavioral effects emerged long after the leveling-off of brain Hg levels. Hence, the initial toxicologic event responsible for the late effects should have occurred before this leveling-off of brain Hg.

Adult T-cell leukemia/lymphoma is a T-cell malignancy caused by the human T-cell lymphotropic virus-I. Adult T-cell leukemia/lymphoma is primarily a disease of adults due to the long latency period between initial infection and development of leukemia. We present a case of acute adult T-cell leukemia/lymphoma in an adolescent. Skin lesions had appeared 3 years earlier and were the initial sign of human T-cell lymphotropic virus-I infection and T-cell malignancy. Her disease failed to respond to both intensive chemotherapy and antiviral therapy. Cutaneous lesions are sometimes the initial sign of adult T-cell leukemia/lymphoma and early recognition is imperative.

Many studies have demonstrated that muscle activity 50–100 ms after a mechanical perturbation (i.e., the long-latency stretch response) can be modulated in a manner that reflects voluntary motor control. These previous studies typically assessed modulation of the long-latency stretch response from individual muscles rather than how this response is concurrently modulated across multiple muscles. Here we investigated such concurrent modulation by having participants execute goal-directed reaches to visual targets after mechanical perturbations of the shoulder, elbow, or wrist while measuring activity from six muscles that articulate these joints. We found that shoulder, elbow, and wrist muscles displayed goal-dependent modulation of the long-latency stretch response, that the relative magnitude of participants' goal-dependent activity was similar across muscles, that the temporal onset of goal-dependent muscle activity was not reliably different across the three joints, and that shoulder muscles displayed goal-dependent activity appropriate for counteracting intersegmental dynamics. We also observed that the long-latency stretch response of wrist muscles displayed goal-dependent modulation after elbow perturbations and that the long-latency stretch response of elbow muscles displayed goal-dependent modulation after wrist perturbations. This pattern likely arises because motion at either joint could bring the hand to the visual target and suggests that the nervous system rapidly exploits such simple kinematic redundancy when processing sensory feedback to support goal-directed actions.

Object. The authors analyzed the factors involved in determining prolonged survival (≥ 24 months) in patients with brain metastases treated by gamma knife surgery (GKS). Methods. Between 1995 and 2003, a total of 116 patients underwent 167 GKS procedures for brain metastases. There was no special case selection. Smaller and larger lesions were treated with different protocols. The mean patient age was 56.9 years, the mean number of initial lesions was 3.15, and the mean lesion volume was 10.45 cm.3 The mean follow-up time was 9.2 months. The median patient survival was 8.68 months. One-, 2-, 3-, 4-, and 5-year actuarial survival rates were 31.8%, 19.8%, 14.6%, 7.7%, and 6.9%, respectively. Patient age, number of lesions at presentation, and lesion volume had no influence on patient survival. Twenty-three (19.8%) patients survived for 24 months or more. Certain factors were associated with increased survival time. These were stable primary disease (21 of 23 patients), a long latency between diagnosis of the primary tumor and the occurrence of brain metastases (mean 28.4 months, median 16 months), absence of third-organ involvement, and repeated local procedures. Ten patients underwent repeated GKS (mean 3.4 per patient). Seven patients required open surgery for local treatment failures (recurrence or radiation necrosis). Two patients had both. Fifteen patients underwent repeated procedures. Conclusions. Aggressive local therapy with GKS, repeated GKS, and GKS plus surgery can achieve increased survival in a subgroup of patients with stable primary disease, no third-organ involvement, and long primary-brain secondary intervals.

Mismatch negativity (MMN) is thought to represent a neurophysiological index of auditory information processing that is independent of attention. Because this measure does not require an overt behavioral response, MMN has potential to evaluate higher order perceptual abilities in infants, young children and difficult-to-test populations, thereby extending results obtained from more basic physiologic and electroacoustic measures (auditory brainstem responses, ABRs; otoacoustic emissions, OAEs). Whereas the basic tenet of MMN is appealing, several issues-of-contention remain to be solved before this event related potential (ERP) can be applicable for routine clinical use. These issues include the consistent identification of MMN within individuals (vs. groups), its stability over time, and its reportedly poor signal-to-noise ratio (SNR). Herein, we focus on the issue of SNR, by comparing and contrasting SNR of MMN with other long latency auditory ERPs.

To evaluate the gamma-band activity related to somatosensory processing, we recorded neuromagnetic signals from seven healthy subjects. The source power changes evoked by electrical stimulation of the median nerve were estimated with synthetic aperture magnetometry (SAM). Source power in the low gamma band (40 Hz) decreased in the contralateral primary somatosensory cortex (SI) for a few hundred milliseconds (i.e. middle and long latency) and then increased inversely. Source power in the high gamma band (70-90 Hz) increased simultaneously both in the contralateral SI and contra/ipsilateral secondary somatosensory cortex (SII) in 80-180 ms. These results suggest that low and high gamma oscillations work under independent mechanisms during somatosensory processing. In particular, high gamma oscillations may play an essential role in making a functional connection between SI and SII.