Burst firing induces a slow after hyperpolarization in rat auditory thalamus.

The Ca2+-activated slow after hyperpolarization (sAHP) is found in many CNS regions where it may induce post-spike suppression of neuronal firing over many seconds. Nevertheless, the presence of sAHP in sensory thalamus remains uncertain. Here we show that a robust sAHP could be evoked in the rat medial geniculate body of auditory thalamus in vitro following a low-threshold Ca2+ spike and burst firing. The evoked sAHP exhibited kinetic and pharmacological features similar to that found elsewhere in the CNS. The sAHP was resistant to TTX or apamin but eliminated by muscarine. Furthermore, activation of low-threshold Ca2+ conductance alone is sufficient to induce the sAHP. Therefore, the membrane conductance underlying sAHP is functionally expressed in lemniscal thalamic relay neurons which may be preferably activated during burst firing.

Distinct forms of cholinergic modulation in parallel thalamic sensory pathways.

Mammalian thalamus is a critical site where early perception of sensorimotor signals is dynamically regulated by acetylcholine in a behavioral state-dependent manner. In this study, we examined how synaptic transmission is modulated by acetylcholine in auditory thalamus where sensory relay neurons form parallel lemniscal and nonlemniscal pathways. The former mediates tonotopic relay of acoustic signals, whereas the latter is involved in detecting and transmitting auditory cues of behavioral relevance. We report here that activation of cholinergic muscarinic receptors had opposite membrane effects on these parallel synaptic pathways. In lemniscal neurons, muscarine induced a sustained membrane depolarization and tonic firing by closing a linear K(+) conductance. In contrast, in nonlemniscal neurons, muscarine evoked a membrane hyperpolarization by opening a voltage-independent K(+) conductance. Depending on the level of membrane hyperpolarization and the strength of local synaptic input, nonlemniscal neurons were either suppressed or selectively engaged in detecting and transmitting synchronized synaptic input by firing a high-frequency spike burst. Immunohistochemical and Western blotting experiments showed that nonlemniscal neurons predominantly expressed M2 muscarinic receptors, whereas lemniscal cells had a significantly higher level of M1 receptors. Our data indicate that cholinergic modulation in the thalamus is pathway-specific. Enhanced cholinergic tone during behavioral arousal or attention may render synaptic transmission in nonlemniscal thalamus highly sensitive to the context of local synaptic activities.

Neuronal response to local electrical stimulation in rat thalamus: physiological implications for mechanisms of deep brain stimulation.

High-frequency deep brain stimulation (DBS) of sensorimotor thalamus containing "tremor cells" leads to tremor arrest in humans with parkinsonian and essential tremor. To examine the possible underlying mechanism(s), we recorded in vitro intracellular responses of rat thalamic neurons to local intrathalamic stimulation. Such simulated DBS (sDBS) induced a sustained membrane depolarization accompanied by an increase in apparent membrane conductance in both motor and sensory neurons. With stimulation frequency above approximately 100 Hz, the sDBS-induced depolarization most typically led to repetitive neuronal firing or less frequently resulted in a complete blockade of action potential genesis. When regular intracellular current pulses were injected into cells to mimic "tremor" activity, such rhythmic discharges were invariably disrupted or abolished by the random spike firing induced during high-frequency sDBS. Low-frequency sDBS left rhythmicity unaffected.We conclude that clinical thalamic DBS may lead to a neuronal de-rhythmicity and tremor stoppage through masking and/or blocking rhythmic firing of tremor cells.

KIDSCARE: a network for children with special health care needs.

In December 1997, Arkansas Medicaid in cooperation with Title V and Children's Medical Services (CMS) implemented guidelines for the preauthorization of therapy services for Children with Special Health Care Needs (CSHCN). The University of Arkansas for Medical Sciences (UAMS) in partnership with Arkansas Medicaid (MCD), and Chidren's Medical Services (CMS) were given the charge of developing clinical practice guidelines for physical therapy (PT), occupational therapy (OT), and speech/language therapy (SLP) for this population based on primary diagnosis and age appropriateness. This process involved the implementation of a statewide, internet-based, clinical information support network. The objective of this article is to describe KIDSCARE, a clinical information support network, currently under development, for the determination of medical necessity and allocation of therapy services for CSHCN.

Temporal pattern and spectral complexity as stimulus parameters for eliciting a cardiac orienting reflex in human fetuses.

The purpose of this study was to determine whether temporal pattern and/or spectral complexity were important stimulus parameters for eliciting a cardiac orienting reflex (OR) in low-risk human fetuses. Each of 28 term fetuses was exposed to four sounds formed from the four different combinations of temporal pattern (pulsed, continuous) and spectral complexity (sine wave, /â/). The fetal cardiac electrical signal was captured transabdominally at a rate of 1024 Hz, and fetal R-waves were extracted by using adaptive signal-processing techniques. We found that pulsed sounds elicited a significantly greater decrease in heart rate (HR) than did continuous sounds. However, the HR response was relatively unaffected by spectral complexity. For the pure tone and the phoneme used in this study, our results indicate that temporal characteristics were more effective at eliciting a cardiac OR in human fetuses than was spectral complexity.

Human fetuses have nonlinear cardiac dynamics.

Approximate entropy (ApEn) is a statistic that quantifies regularity in time series data, and this parameter has several features that make it attractive for analyzing physiological systems. In this study, ApEn was used to detect nonlinearities in the heart rate (HR) patterns of 12 low-risk human fetuses between 38 and 40 wk of gestation. The fetal cardiac electrical signal was sampled at a rate of 1,024 Hz by using Ag-AgCl electrodes positioned across the mother's abdomen, and fetal R waves were extracted by using adaptive signal processing techniques. To test for nonlinearity, ApEn for the original HR time series was compared with ApEn for three dynamic models: temporally uncorrelated noise, linearly correlated noise, and linearly correlated noise with nonlinear distortion. Each model had the same mean and SD in HR as the original time series, and one model also preserved the Fourier power spectrum. We estimated that noise accounted for 17.2-44.5% of the total between-fetus variance in ApEn. Nevertheless, ApEn for the original time series data still differed significantly from ApEn for the three dynamic models for both group comparisons and individual fetuses. We concluded that the HR time series, in low-risk human fetuses, could not be modeled as temporally uncorrelated noise, linearly correlated noise, or static filtering of linearly correlated noise.

Behavioral state affects heart rate response to low-intensity sound in human fetuses.

The cardiac orienting reflex is elicited by a low-intensity sound, it consists of a sustained heart rate (HR) deceleration, and it is a specific physiological correlate of cognitive processing. In this study we examined the relationship between behavioral state and the cardiac orienting reflex in 75 human fetuses between 36 and 40 weeks gestation. Each fetus was stimulated with a 30-s speech sound at an average intensity of 83 dB SPL in quiet sleep (QS) and active sleep (AS). The fetal cardiac electrical signal was captured transabdominally at a rate of 1024 Hz and fetal R-waves were extracted using adaptive signal processing. Fetal behavioral states were assigned based on HR pattern and the presence or absence of eye and general body movements. We found that a significant HR deceleration occurred, in both QS and AS, following stimulus onset. However, HR decelerations occurred more often in QS than AS; and for fetuses exhibiting a HR deceleration, the magnitude of the deceleration was greater in AS compared to QS. In addition, in AS female fetuses exhibited a larger, more sustained HR deceleratory response than male fetuses, but the seconds x gender interaction in QS was not significant. Based on these results, we concluded that behavioral state is an important determinant of the HR deceleratory response in human fetuses.

Heart rate dynamics in low risk human fetuses.

Evaluation of nonlinear heart rate (HR) dynamics has received considerable attention in the pediatric literature because such analyses not only provide insight into underlying control mechanisms, but may also help to differentiate between normal and abnormal infants. The purpose of this study was to determine, in eight low risk human fetuses, if nonlinear HR dynamics could be identified by analyzing the dispersion of interbeat intervals at slow (Ds) and fast (Df) HRs. The fetal cardiac electrical signal was captured transabdominally at a resolution of +/- 1 ms. To test the null hypothesis, that the time series is the result of a linear stochastic process, Ds and Df for the original time series were compared with the values calculated for three linear models. The linear models were constructed to preserve the major statistical properties of the original time series, including the mean, SD, and the Fourier power spectrum. For each fetus, there was no evidence of nonlinear cardiac dynamics based on analyses of Ds and Df. In contrast, the distribution of adjacent R-R intervals and the pattern of change across three successive interbeat intervals both revealed significant nonlinearities in HR control in each fetus. If the difference between normal and abnormal infants is the result of aberrant control of nonlinear processes, then our findings indicate that parameters which describe the nonlinearity may be more useful then Ds and Df in assigning a risk status.

The heart rate deceleratory response in low-risk human fetuses: effect of stimulus intensity on response topography.

The purpose of this study was to determine the effect of stimulus intensity on heart rate response in 18 low-risk human fetuses between 37 and 40 weeks gestation. Each fetus was stimulated in quiet sleep with a 30-s voice sound at intensities of 80 dB and 90 dB. The fetal cardiac electrical signal was captured transabdominally at a rate of 1024 Hz and fetal R-waves were extracted using adaptive signal-processing techniques. We found that fetuses generally exhibited a 5- to 10-s decrease in heart rate following stimulus onset at an intensity of 80 dB. The response pattern changed from deceleratory to acceleratory when stimulus intensity was increased to 90 dB. Our findings suggest that a heart rate deceleration at low-stimulus intensity may be a component of the orienting reflex in the human fetus.

Internalizing and externalizing characteristics of sexually and/or physically abused children.

This study evaluates the behavioral consequences of childhood abuse (sexual, physical, or both), with particular focus on prevalence of posttraumatic stress disorder (PTSD). Three abuse type groups and nonabused controls were contrasted on behavioral rating scales and on structured psychiatric interview data. The participants (109 abused children and 16 normal control children) were recruited from Arkansas Children's Hospital and local agencies for abused children. As expected, proportionately more females than males were sexually abused. Overall, males were rated as more disturbed than females. Type of abuse did not consistently influence behavioral ratings. Externalizing scores were significantly higher than internalizing scores in all abused groups. PTSD was diagnosed in 50% of the abused children, with a higher rate for boys who had been sexually abused as opposed to physically abused only (58% versus 13%). The most frequent comorbid condition with PTSD was Separation Anxiety. Sexually abused boys were hospitalized for psychiatric treatment at a higher rate than were other abused children.

Muscarine induces an anomalous inhibition of synaptic transmission in rat auditory thalamic neurons in vitro.

Muscarinic receptor-mediated inhibition of central synaptic transmission was studied in a monosynaptic pathway connecting the inferior colliculus and the auditory thalamus in in vitro rat brain explants. Extra- and intracellular synaptic responses were recorded by sharp electrode and whole-cell patch clamp techniques in the ventral nucleus of the medial geniculate body after electrical stimulation of the brachium of the inferior colliculus. Stimulation of tectal afferents evoked either a high-frequency burst or a single-spike synaptic response in ventral geniculate neurons. Bath application of muscarinic receptor agonists abolished responses consisting of a high-frequency burst, but not responses consisting of a single spike. In the majority of single-spike cells muscarinic agonists often induced a synaptic facilitation. The burst blocking effect was mimicked by a moderate elevation of extracellular potassium. Intracellular recordings showed that the burst synaptic responses similar to that recorded extracellularly were induced by an excitatory postsynaptic potential. This synaptic potential, by first activating a low-threshold spike, was able to evoke a burst of sodium spike discharges. Muscarinic agonists caused a slow membrane depolarization that inactivated the low-threshold spike, leading to a blockade of the burst response. This mechanism is tentatively termed here as EPSP-LTS decoupling. Our results therefore support the hypothesis that part of the muscarinic receptor-mediated synaptic inhibition previously reported in anesthetized animal preparations in vivo represents a membrane depolarization rather than pre- or postsynaptic inhibition.

Vagal tone during quiet sleep in normal human term fetuses.

The purpose of this paper was to calculate vagal tone (V) for 17 normal human fetuses in quiet sleep (QS) between 36 and 40 weeks gestation. The fetal cardiac electrical signal was captured transabdominally in 3-min blocks at a rate of 833 times per second and fetal R-waves were extracted using adaptive signal processing techniques. Fetal R-wave interbeat intervals were converted to equally spaced, time-based data, and the low-frequency component was removed using a 21-point third-order moving polynomial. The parameter V was calculated by taking the natural logarithm of the sum of the power densities between 0.3 Hz and 1.3 Hz. We found that fetal breathing was associated with an approximately 25% increase in V as compared to nonbreathing, 3.33 +/- 0.48 versus 2.57 +/- 0.47, p < 0.0001. Furthermore, there was a significant linear relationship between the mean single-fetus V during spontaneous respiration and the mean single-fetus V during normally occurring apneic periods, r = 0.772, p < 0.002. We conclude that respiratory activity is associated with a significant increase in vagal tone for normal human fetuses in QS.

Early heart rate response of normal human term fetuses to vibroacoustic stimulation.

We examined cardiac reactivity in the first 45 seconds following a single 1 second vibroacoustic stimulus (VAS) to determine if the prestimulus fetal heart rate (FHR) pattern was predictive of the immediate post-VAS heart rate response. Forty-nine normal human fetuses between 37 and 41 weeks of gestation were observed to enter quiet sleep and remain in that state for 3 to 5 minutes before testing. In general, VAS elicited an initial acceleratory response of approximately 20 beats/min above the mean prestimulus heart rate followed by a deceleratory response to an average of approximately 4 beats/min below baseline values. Fetuses with different average prestimulus heart rate patterns generally differed in their early cardiac response to VAS: when compared to a high baseline FHR, a low resting heart rate was associated with a greater increase in heart rate above baseline (r = -0.401; P = 0.03), a greater decrease below prestimulus values (r = -0.312; P = 0.03), and a greater difference between maximum and minimum heart rates (r = -0.465; P = 0.001). Higher baseline heart rates were associated with lower FHR variability in the prestimulus period (r = -0.422; P = 0.009). When we examined the time course of the early response, we found that fetuses that achieved a maximum heart rate quickly exhibited less of an increase above prestimulus values (r = 0.894; P = 0.005), displayed a greater decrease below baseline (r = 0.507; P = 0.0002), and reached the minimum heart rate faster (r = 0.575; P = 0.0001) than fetuses that required longer to achieve a maximum cardiac response.(ABSTRACT TRUNCATED AT 250 WORDS)

Spectral analysis of heart rate variability during quiet sleep in normal human fetuses between 36 and 40 weeks of gestation.

Respiratory sinus arrhythmia (RSA) is a clinical manifestation of the parasympathetic nervous system which can be identified in the high-frequency region of the heart rate variability (HRV) power spectrum. The purpose of this study was to determine the relative contribution of RSA to overall HRV for human fetuses in quiet sleep. The study population consisted of 13 normal human fetuses between 36 and 40 weeks of gestation for whom data were collected during spontaneous breathing and normally occurring apneic periods. Fetal breathing was monitored continuously using real-time sonography. The fetal electrocardiogram was captured transabdominally in 3-min blocks at a rate of 833 Hz and fetal R-waves were extracted from the raw signal using adaptive signal processing techniques. Fetal behavioral state was determined at the beginning and end of each 3-min data collection period. The fetal R-wave interbeat intervals (IBIs) were converted to equally-spaced, time-based data, and linear detrending of the time series was accomplished by subtracting the mean heart period from each weighted IBI. Total power (TP, 0.0-2.5 Hz) was divided into RSA (0.4-1.0 Hz), high-frequency (HF, 0.2-2.5 Hz), low-frequency (LF, 0.04-0.2 Hz), and very-low-frequency (VLF, 0.0-0.04 Hz) regions, and the power densities were summed to determine the absolute power for each frequency component. A total of 81 3-min blocks (mean per subject 6.3, range 2-14) were available for analysis. Eleven (85%) of 13 fetuses demonstrated a HF peak during fetal breathing, and RSA accounted for approximately 20% of the TP.(ABSTRACT TRUNCATED AT 250 WORDS)

Motor and cardiac response during habituation testing: demonstration of exaggerated cardiac reactivity in a subgroup of normal human fetuses.

In this study we wanted to determine: (1) whether or not a relationship existed between the rate of habituation of the fetal motor response and changes in the fetal heart rate (FHR), and (2) if this relationship could be used to identify a subgroup of fetuses who exhibited exaggerated cardiac reactivity during habituation testing. Thirty-nine normal human fetuses between 34 and 40 weeks of gestation were evaluated. Habituation testing consisted of a 1 second vibroacoustic stimulus with a 10 second interstimulus interval for eight trials. The motor response was observed using real-time sonography, and a score of 0 to 10 was assigned for each trial based on subjective assessment of the fetal response. Motor habituation was evaluated in terms of the rate of response decrement in movement over trials (Re). Subjects were initially divided into slow and fast motor habituators based on the median of Re, and it was found that fetuses whose motor response habituated slowly displayed a significantly greater increase in heart rate compared with fetuses who habituated more rapidly (F1,37 = 8.61; P = 0.0057). Cardiac reactivity was then defined as "the average increase in FHR above the mean prestimulus value during the last half of the testing period." When the data were divided into quadrants based on medians, we identified seven (18%) fetuses who habituated rapidly but who also displayed high cardiac reactivity. We conclude that there is a significant relationship between the magnitude of the increase in FHR above baseline and the rate of motor habituation in normal human fetuses.

Behavioural state change in normal human fetuses following a single vibroacoustic stimulus: effect of duration of quiet sleep prior to stimulation.

We examined 96 normal human fetuses between 37 and 41 weeks of gestation to determine the relationship between the duration of the active state following a single vibroacoustic stimulus (VAS) and the time spent in prestimulus state 1F, i.e. quiet sleep (QS). All fetuses were observed to enter state 1F prior to testing. After remaining in this state for 3 min, each fetus was randomized into one of three groups: no stimulation (Group I, N = 32); a single 1-s VAS delivered after 3-5 min of QS (Group II, N = 33); and a single 1-s VAS delivered after 18-20 min of QS (Group III, N = 31). Fetuses in Groups I, II, and III were otherwise behaviourally indistinguishable. Heart rate and eye and body movements were monitored until the fetus either returned to state 1F and remained in that state for 3 min or did not return to state 1F within 60 min. Of the 64 fetuses who were stimulated, 62 responded, indicating that there was no effect of prestimulus state duration on the sensitivity to VAS. Fetuses stimulated after 18-20 min of QS behaved similarly to fetuses who entered an active period spontaneously.(ABSTRACT TRUNCATED AT 250 WORDS)