Predisposition to repeat breeding in UK cattle and success of artificial insemination alone or in combination with embryo transfer.

To investigate whether there was a subpopulation of repeat breeders (cows or heifers that returned to oestrus after three inseminations) that were less fertile after a fourth artificial insemination (AI) with or without additional embryo transfer, and to estimate the efficacy of AI plus embryo transfer to overcome repeat breeding problems, a two-part investigation was carried out. Part 1 involved 85 repeat breeders and 85 controls subjected to AI alone. In part 2, 128 repeat breeders received AI on day 0 plus an embryo transfer seven days later, while controls received embryo transfer alone on day 7. In repeat breeders, the interval between calving and pregnancy was 80 days longer than in the controls (P=0.01), irrespective of previous fertility treatment which had mainly focused on the ovaries. The incidence of dystocia was similar in repeat breeders and in controls, but repeat breeders had a higher previous incidence of moderate uterine infection compared with controls (P=0.04). In repeat breeder cows, pregnancy rates for AI alone were 30 per cent after the fourth AI (controls: 45 to 64 per cent after one to three inseminations) compared with 52.6 per cent after a fourth AI with embryo transfer (controls with embryo transfer alone: 49 per cent). Successful pregnancies after a fourth AI plus embryo transfer produced a 6.25 per cent incidence of twins.

A direct projection from superior colliculus to substantia nigra pars compacta in the cat.

Dopaminergic neurons exhibit a short-latency, phasic response to unexpected, biologically salient stimuli. The midbrain superior colliculus also is sensitive to such stimuli, exhibits sensory responses with latencies reliably less than those of dopaminergic neurons, and, in rat, has been shown to send direct projections to regions of the substantia nigra and ventral tegmental area containing dopaminergic neurons (e.g. pars compacta). Recent electrophysiological and electrochemical evidence also suggests that tectonigral connections may be critical for relaying short-latency (<100 ms) visual information to midbrain dopaminergic neurons. By investigating the tectonigral projection in the cat, the present study sought to establish whether this pathway is a specialization of the rodent, or whether it may be a more general feature of mammalian neuroanatomy. Anterogradely and retrogradely transported anatomical tracers were injected into the superior colliculus and substantia nigra pars compacta, respectively, of adult cats. In the anterograde experiments, abundant fibers and terminals labeled with either biotinylated dextran amine or Phaseolus vulgaris leucoagglutinin were seen in close association with tyrosine hydroxylase-positive (dopaminergic) somata and processes in substantia nigra pars compacta and the ventral tegmental area. In the retrograde experiments, injections of biotinylated dextran amine into substantia nigra produced significant retrograde labeling of tectonigral neurons of origin in the intermediate and deep layers of the ipsilateral superior colliculus. Approximately half of these biotinylated dextran amine-labeled neurons were, in each case, shown to be immunopositive for the calcium binding proteins, parvalbumin or calbindin. Significantly, virtually no retrogradely labeled neurons were found either in the superficial layers of the superior colliculus or among the large tecto-reticulospinal output neurons. Taken in conjunction with recent data in the rat, the results of this study suggest that the tectonigral projection may be a common feature of mammalian midbrain architecture. As such, it may represent an additional route by which short-latency sensory information can influence basal ganglia function.

The MMN is a derivative of the auditory N100 response.

We argue that the mismatch negativity (MMN), elicited by rare auditory events, is generated by the same neural mechanisms as the N100, elicited by any audible stimulus. To date, the MMN has been considered to be a unique index of auditory sensory memory and a component which is functionally and spatially separate from the N100 response because: (i) MMN and N100 appear to have different generator locations; (ii) the MMN occurs too late to be an N100; (iii) the MMN, as opposed to the N100, is elicited by stimulus omissions. By utilizing neural modeling and EEG/MEG results, we show that the above reasoning relies on unwarranted assumptions and propose that the MMN is, essentially, an amplitude- and latency-modulated N100 response. This study offers a physiologically constrained and theoretically plausible framework whereby brain dynamics in terms of stimulus feature maps and their reorganization may be used to describe various memory- and learning-related effects of human auditory cognition.

The auditory n100m response reflects changes in speech fundamental frequency.

We studied the cortical activation underlying perception of variations in speech fundamental frequency (F0) as indexed by the amplitude, latency and source location of the auditory N100m response registered with magnetoencephalography (MEG). Ten subjects were presented with Finnish vowels with either a constant or an ascending/descending F0. We found that the human auditory cortex is sensitive to these time-varying changes in the F0 of speech: vowels with a constant F0 elicited more prominent N100m responses than did vowels with ascending or descending changes in F0. These results suggest that the speech-related behavior of the N100m arises out of cortical sensitivity to variations in the F0 and its harmonics which underlie the perception of pitch and intonation. The present observations are interpreted in terms of the interrelatedness of speech production and perception.

Spectral characterization of ongoing and auditory event-related brain processes.

Brain processes phase-locked to stimuli can be readily observed with electro- and magnetoencephalography (EEG & MEG, respectively) using stimulus-triggered averaging of the measured signal. The detection of non-phase-locked brain processes depends on the method used for analyzing the unaveraged data. Here we introduce a technique, partition-referenced moment (PRM) power spectrum, which uses established spectral estimation algorithms but yields a power spectrum with sharp, easily distinguishable peaks in an otherwise level spectrum even when the signal (such as EEG & MEG) is of the one-over-frequency-slope type. Employing this method and wavelet transforms, we show that transient auditory brain responses are followed by dispersed small-magnitude power reductions. Power reductions occurred around 400-600 ms and were specific to ongoing 10 Hz-oscillations. The PRM-method also indicated ongoing oscillations in the 15-30 Hz frequency range where power reductions occurred at around 200-400 ms. Thus, the presented methods enable the straightforward detection of ongoing brain oscillations and their association with event-related power changes.

Periodic glottal excitation and formant frequencies in the perception of vowels.

Voiced speech is created by the fluctuating vocal folds generating the glottal pulseform. This excitation signal is the source of the speech fundamental frequency and its harmonic integer multiples. Periodic glottal excitation is required for the elicitation of speech-specific cortical processes indexed by the auditory N100m response. Here, we studied the cortical processing underlying the perception of the vowels /a/ and /u/ produced using normal and aperiodic phonation. The behavior of the N100m, registered with magnetoencephalography (MEG), was studied in 10 subjects. The amplitude and latency of the N100m as well as the center of gravity of the activated cortical areas varied as a function of stimulus periodicity. Further, the presence of glottal excitation had differential effects on the latency of the N100m elicited by the vowels /a/ and /u/. Thus, changes affecting the perceptual quality of speech signals without changing their phonetic content modify the dynamics of human auditory cortex.

Behavioral detection of spatial stimuli is reflected in auditory cortical dynamics.

We studied the cortical processing of spatial stimuli by magnetoencephalographic (MEG) measurements using broadband noise bursts presented from eight sound source directions in the horizontal plane. The stimuli were individually created for each subject by using three-dimensional (3D) sound techniques. The subjects carried out a behavioral task where their accuracy for localizing the 3D stimuli was established. We found that the auditory N100m response was sensitive to the sound source direction, exhibiting contralaterally more preponderant responses in both the left and the right hemisphere. Generally, responses were more prominent in the right hemisphere. The behavioral performance of the subjects correlated positively with N100m amplitude organization, showing that the dynamics of auditory cortex predict behavioral sound detection.

Auditory evoked responses are additive to brain oscillations.

The generation mechanism of stimulus-evoked electro- and magnetoencephalographic (EEG & MEG) responses has remained controversial. One view holds that evoked responses are independent components, additive to ongoing brain activity. The other view holds that evoked responses are generated via stimulus-induced phase reorganization of ongoing brain activity. This issue has been commonly addressed with signal processing techniques that assume a high level of stationarity (i.e., unchanging properties over time) of the measured signal. Here we used signal analysis methods suitable for analyzing non-stationary signals. We found that auditory stimulation leads to a large power increase of the poststimulus signal compared to prestimulus level. Linear superposition of the (time-domain) averaged response and the unaveraged prestimulus signal accounted for 90% of the power increase. Further, we found that auditory stimulation does not lead to a phase-coherent state of ongoing oscillations. Taken together our results show that auditory evoked responses are directly additive to ongoing oscillations and only 10% of the observed power increases are explained by non-phase-locked brain activity. When examining evoked brain activity with methods providing simultaneous frequency and time information, emphasizing temporal accuracy is likely to provide more accurate descriptions of non-stationary processes of the human brain.

Auditory scene analysis and sensory memory: the role of the auditory N100m.

We consider the neural dynamics underlying auditory streaming, the perceptual grouping of transient auditory events, by using neural modeling and magnetoencephalographic (MEG) measurements in humans. We demonstrate that spatial variations in the strength of feedback inhibition leads to differential amplitude modulation (AM) tuning resembling that found in animal models. In our model, neurons respond selectively to stimuli presented at different onset-to-onset interstimulus intervals (ISIs), and their summed activity (corresponding to the MEG signal) exhibits both transient and sustained responses (SRs) at fast ISIs. In MEG measurements utilizing 2-s trains of 50-ms stimuli presented at 0-1950 ms ISIs, we observed the transient N100m and SRs predicted by the model, with a prominent SR emerging for discrete stimuli at ISIs below 200 ms. Our results explain why, at fast stimulus rates, the amplitude of the auditory N100m appears to be strongly attenuated even though auditory cortex continues to respond vigorously to the stimuli. The results suggest that the longer and shorter forms of auditory sensory memory may be reflected in the N100m and the SR, respectively. As the emergence of the SR coincides with the stimuli being perceived as auditory streams, our study suggests that auditory sensory memory as indexed by transient and sustained cortical activity might underlie auditory scene analysis.

Cortical activity elicited by isolated vowels and diphthongs.

Cortical activity underlying speech perception has been studied mostly by using isolated vowels with constant formant frequencies. Speech, however, is characterized by formant transitions whereby formant frequencies change as a function of time. We used magnetoencephalography (MEG) to investigate cortical activity elicited by isolated vowels and diphthongs containing formant transitions. Ten subjects were presented with two isolated vowels /a/ and /u/ and diphthongs /au/ and /ua/. Stimulus duration was 200 ms, and the diphthongs started and ended with a 50-ms constant-formant period and included a 100-ms linear transition period. Apart from studying the auditory N100m response, we examined subsequent brain activity in a 500-ms poststimulus time window, as the transitions were expected to elicit activity also in later stages of cognitive processing. All the stimuli elicited prominent N100m responses. Thereafter, both the isolated vowels and diphthongs elicited sustained brain activity lasting up to 500 ms. The present observations indicate that identification of the speech sounds as well as changes in their identity are reflected in the auditory N100m. Notably, the stimuli appeared to elicit left-hemispheric activity resembling the N400, typically obtained by using more complicated speech stimuli such as words and sentences.

Agmatine crosses the blood-brain barrier.

The question of whether agmatine crosses the blood-brain barrier has not been directly addressed, even though peripheral injection of this compound has produced behavioral responses in drug withdrawal, antidepressant, and anti-anxiety paradigms. Two models were used in this investigation. In the first, mice were injected intraperitoneally (i.p.) with agmatine (10, 50, or 300 mg/kg body weight) or arginine (600 mg/kg). After 1 or 3 hours, the animals were killed under gas anesthesia by perfusing their brains with ice-cold saline, and whole-brain agmatine was measured by HPLC. In parallel studies, a rhesus monkey was injected under gas anesthesia either intravenously (i.v.) with agmatine (30 mg/kg) or arginine (150 mg/kg), or intracerebroventricularly (i.c.v.) with agmatine (0.3 mg/kg i.c.v.). At varying times thereafter, cisterna magna cerebrospinal fluid (CSF) and blood plasma were collected and analyzed for agmatine levels. A rise in mouse brain agmatine was apparent after doses of 50 and 300 mg/kg i.p. Monkey CSF agmatine peaked in parallel with plasma agmatine 15 minutes following intravenous (i.v.) agmatine injection and at one sixth the level of the plasma peak. Monkey CSF agmatine peaked 43 minutes after i.v. arginine injection. The ventricular injection of agmatine resulted in a threefold sustained rise in blood plasma agmatine for at least 24 hours after injection. Therefore, agmatine and its precursor, arginine, cross the blood-brain barrier. CSF agmatine may be newly synthesized from peripherally injected arginine.

[Treatment of spinal fracture in ankylosing spondylitis]. / Behandlung der Wirbelsäulenfraktur bei ankylosierender Spondylitis.

Clinical guidelines for the treatment of vertebral fractures associated with ankylosing spondylitis are derived from case reports and a review of literature. The coincidence of paravertebral calcifications and fracture formations leads to problems in the establishment of a proper initial diagnosis. Therefore computed tomography and magnetic resonance imaging have to be employed to define the extent of fracture and the presence of spinal lesions. As a rule vertebral fractures based upon spondylitic alterations are extremely unstable and tend to secondary dislocation with a high risk of spinal cord injuries. Operative osteosynthesis is the method of choice in the fracture treatment. A successful stabilization requires an extended spondylodesis comprising at least five vertebral segments by a dorsal or a combined ventral instrumentation.

The feedback circuit connecting the superior colliculus and central mesencephalic reticular formation: a direct morphological demonstration.

The central mesencephalic reticular formation (cMRF) has been distinguished from the surrounding reticular formation due to its involvement in the control of saccades. A role in saccade function has been proposed for this region based on electrical-stimulation experiments, its neuronal activity, and its pattern of connections. The present study was undertaken in an attempt to further characterize the location of the central mesencephalic reticular formation by anatomical methods and to examine its connections with the superior colliculus at the neuronal level. Biotinylated dextran amine (BDA) was injected into the superior colliculus of two cynomolgus monkeys (Macaca fascicularis). This resulted in the retrograde labeling of a large number of neurons in a restricted area of the mesencephalic reticular formation. They were distributed bilaterally, with an ipsilateral predominance, forming a cellular band in the ventral half of the midbrain reticular formation that was 2.7 mm in its rostrocaudal extent. Its rostral pole lay dorsolateral to the red nucleus and ventrolateral to, but not immediately adjacent to, the interstitial nucleus of Cajal. The cell band was widest caudally, where it occupied an area of approximately 2.7 mm wide and 2 mm in depth. Labeled neurons displayed a wide variety of multipolar somatic shapes and sizes, with long, slightly tapering, sparsely branched dendrites. Tectal terminal arbors were also labeled within the mesencephalic reticular formation. They were concentrated bilaterally, with an ipsilateral predominance, in the same areas that contained retrogradely labeled neurons. Numerous, primarily en passant labeled boutons of various sizes and shapes were seen in close association with both labeled and unlabeled neurons. They formed axosomatic and, more commonly, axodendritic relationships with labeled neurons. The extensive relationship of labeled terminals and labeled cells suggests the existence of a strong interconnection between the deeper layers of the colliculus and the central mesencephalic reticular formation neurons projecting back to the tectum. The bidirectional neural circuit directly demonstrated in this study presumably provides an anatomical substrate for feedback modification of gaze signals generated in the colliculus. However, the presence of tectal terminals around unlabeled reticular neurons suggests that the collicular signal may also be fed forward to the downstream targets of the central mesencephalic reticular formation.

The distribution of primary afferent terminals from the eyelids of macaque monkeys.

Trigeminal sensory afferents from the eyelids convey two types of information that are important for the blink reflex. Movement of the lashes activates low-threshold mechanoreceptors which evoke protective blinks. Information about eyelid position is also transmitted centrally and is used to adapt the metrics of the blink reflex to changing conditions over time. This study employed transganglionic transport of horseradish peroxidase conjugated to choleratoxin-B subunit or wheat-germ agglutinin to investigate trigeminal afferents supplying the eyelids of macaque monkeys. Ganglion cells labeled from upper- and lower-lid injections were located in the ophthalmic and maxillary portions of the trigeminal ganglion, respectively. In both cases, labeled terminals were observed ipsilateral to the injected eyelid in the principal and spinal trigeminal nuclei. However, only a few labeled terminals were present in the principal nucleus, and very sparse terminal labeling was confined to a few locations along the ventral border of the pars oralis and interpolaris of the spinal trigeminal nucleus. The main concentration of label was found in the pars caudalis at and immediately below the spinomedullary junction. The terminal field from the upper eyelid was located ventrally in the pars caudalis, and that from the lower eyelid was located more dorsally. In both cases, the labeled terminal field was densest within lamina II of the spinal trigeminal nucleus. The heavy concentration of eyelid central terminals at the spinomedullary junction is surprising in light of physiological studies indicating representation of all parts of the face throughout the trigeminal nucleus. The distribution of eyelid afferent terminals in the macaque is caudal to the main concentration of corneal afferent terminals at the pars interpolaris/caudalis border. This may be a basis for differences seen in blinks produced by corneal as opposed to supraorbital stimulation. The presence of a single major site of eyelid primary afferent terminals suggests that sensory input for both eyelid proprioception and blink-reflex activation passes through this segment of the spinal trigeminal nucleus. These results provide a basis for investigation of the central connections of pars caudalis neurons in order to better establish the pathways producing trigeminally evoked blinks and blink adaptation.

Comparison of the distribution and somatodendritic morphology of tectotectal neurons in the cat and monkey.

The presence of a commissure connecting the two superior colliculi suggests they do not act independently, but the function of the tectotectal connection has never been firmly identified. To develop a better understanding of this commissural system, the present study determined the distribution and morphology of tectotectal neurons in the cat and macaque monkey, two animals with well-studied, but different orienting strategies. First, we compared the distribution of tectotectal cells retrogradely labeled following WGA-HRP injections into the contralateral superior colliculus. In monkeys, labeled tectotectal cells were found in all layers, but were concentrated in the intermediate gray layer (75%), particularly dorsally, and the adjacent optic layer (12%). Tectotectal cells were distributed throughout nearly the entire rostrocaudal extent of the colliculus. In cats, tectotectal cells were found in all the layers beneath the superficial gray, but the intermediate gray layer contained the greatest concentration (56%). Labeled cells were almost exclusively located in the rostral half of the cat superior colliculus, in contrast to the monkey distribution. In the context of the representation of visuomotor space in the colliculus, the distribution of monkey and cat tectotectal cells suggests a correspondence with oculomotor range. So these neurons may be involved in directing orienting movements performed within the oculomotor range. The somatodendritic morphology of tectotectal cells in these two species was revealed by homogeneous retrograde labeling from injections of biocytin or biotinylated dextran amine into the contralateral colliculus. The cell classes contributing to this pathway are fairly consistent across the two species. A variety of neuronal morphologies were observed, so there is no single tectotectal cell type. Instead, cell types similar to those found in each layer, excepting the largest neurons, were present among tectotectal cells. This suggests that a sample of each layer's output is sent to the contralateral colliculus.

Reciprocal connections between the zona incerta and the pretectum and superior colliculus of the cat.

The goal of the present experiments was to examine the relationships of the zona incerta with two structures associated with visuomotor behavior, the superior colliculus and pretectum. The experiments were carried out in the cat, a species commonly used in studies of visuomotor integration, and utilized wheat germ agglutinin horseradish peroxidase and biocytin as retrograde and anterograde neuronal tracers. Retrograde axonal transport demonstrated that most cells in the ventral subdivision of the zona incerta project to the superior colliculus. Anterograde tracers demonstrated that the incertotectal terminal field is most dense in the intermediate gray layer, which is the primary source of the descending pathway from the superior colliculus to brainstem gaze centers. Further experiments showed that scattered cells within the intermediate gray layer give rise to a reciprocal pathway that terminates in both the dorsal and ventral subdivisions of the zona incerta. The distribution of both labeled incertotectal cells and tectoincertal terminals extends dorsolateral to the zona incerta proper, between the reticular thalamic nucleus and the external medullary lamina. Electron microscopic examination of labeled tectoincertal terminals demonstrated that they contain mainly spherical vesicles and have slightly asymmetric to symmetric synaptic densities. Labeled terminals were observed contacting labeled cells in the zona incerta, suggesting that the reciprocal pathway may be monosynaptic. The zona incerta is also reciprocally interconnected with the pretectum. The anterior pretectal nucleus provides a dense projection to the ventral part of the zona incerta and receives a sparse reciprocal projection. The posterior pretectal nucleus and nucleus of the optic tract may also project to the zona incerta. The pretectoincertal fibers form terminals that contain primarily spherical vesicles and make distinctly asymmetric synaptic contacts. In summary, these results indicate that the deep layers of the superior colliculus, which are important for controlling saccades, are the target of a projection from the ventral subdivision of the zona incerta. Like the substantia nigra, the zona incerta may play a permissive role in the tectal initiation of saccadic eye movements. The incertotectal terminal field in the cat is less dense than that observed previously in the rat, suggesting species differences in the development of this pathway. An additional finding of this study is that one of the main sources of input to these incertotectal cells is the anterior pretectal nucleus. This pretectal incertal tectal pathway is likely to play a role in the guidance of tectally initiated saccades by somatosensory stimuli.

Aberrant reinnervation of facial musculature in a subhuman primate: a correlative analysis of eyelid kinematics, muscle synkinesis, and motoneuron localization.

A macaque monkey with a preexisting facial nerve injury showed a synkinesis of perioral muscles with blinking and thus provided a serendipitous model for a multiphasic analysis of this common neurologic syndrome. The amplitude of the paretic eyelid in spontaneous and air-puff-induced blinks was about one-third that of the normal eyelid. Despite the blink hypometria, induced blink durations remained matched for the two lids. EMG confirmed co-contraction of the zygomaticus and orbicularis oculi muscles on the affected side during blinking, with silence of the zygomaticus on the normal side. Neuroanatomic investigation showed that, on the affected side, some zygomaticus motoneurons were in the somatotopically correct nuclear subdivisions but that the majority were in the dorsal subdivision, which normally innervates the orbicularis oculi. This study supports the contention that some orbicularis oculi motoneurons are incorrectly rerouted to supply the perioral musculature following recovery from a peripheral seventh-nerve injury. This same pattern of relative weakness in eyelid muscles and the stereotyped co-contraction of lid and perioral muscles with blinking occurs in humans, suggesting that aberrant reinnervation may be the mechanism for this clinical phenomenon.

NADPH-diaphorase reactivity in ciliary ganglion neurons: a comparison of distributions in the pigeon, cat, and monkey.

Ciliary ganglia from the pigeon, cat, and monkey were investigated for the presence of NADPH-diaphorase reactivity by use of a standard histochemical method. In the pigeon, where the ganglion is known to control lens and pupil function, and the choroidal vasculature, about one-third of the ganglion cells were densely stained and most other somata were lightly stained. In some cases, preganglionic terminals with a cap-like morphology were also darkly stained. The pattern of NADPH-diaphorase staining in mammals was very different from that seen in pigeons. In both mammalian species, where the ganglion is known to control lens and pupil function, a small number (less than 2%) of the ganglion cells were shown to be densely NADPH-diaphorase positive, revealing their neuronal processes. The presence of NADPH-diaphorase positive cells in pigeon, cat, and monkey ciliary ganglia suggests that nitric oxide may be used for intercellular communication in this ganglion, or in light of the known importance of nitric oxide in vascular control, some of these positive neurons may participate in the control of choroidal vasodilation.

Ultrastructure of the macaque ciliary ganglion.

The primate ciliary ganglion is an obligatory relay in the pathways that control the lens and pupil for the near response and the light reflex, two functions which have been the target of increasing inquiry in behavioural physiology paradigms. This investigation provides a comprehensive description of the ultrastructure of the ciliary ganglion in the rhesus monkey (Macaca mulatta). The results indicate that the ciliary ganglion contains a heterogeneous population of neurons in terms of somatic size, cytoplasmic contents and somatodendritic distribution of terminals. Variations in the clear and dense-cored vesicle content of the synaptic profiles present in the ganglion suggest that the synaptic inputs are also heterogeneous and may mediate separate functions. Several characteristic ultrastructural features of the macaque ciliary ganglion are noteworthy. Despite the large size of the neuronal somata, most cells do not exhibit contacts directly onto the somatic membrane. However, the few somata that do receive direct input often display several axosomatic contacts. The vast majority of synaptic interactions occur in the perisomatic neuropil, where the postsynaptic elements consist of simple and complex somatic appendages, as well as dendrites with their appendages. There is little neuropil independent of these immediately perisomatic regions. In some cases, axonal terminals form the central element of complex glomeruli, in which they are presynaptic to numerous spine-like profiles. In other cases, axon terminals and their postsynaptic targets are found within shallow depressions in the somatic membrane or, occasionally, deeply embedded within the borders of the postganglionic neuron. The somata and all the non-myelinated neuronal elements are surrounded by interdigitating, electron-dense processes of satellite cells. These glial cells are sometimes found in shallow recesses, or deeply embedded within the borders of the neuronal somata. The complexity of the ultrastructure of the ciliary ganglion in the macaque suggests that this ganglion may not be a simple relay in the parasympathetic outflow to the eye, but may instead be the site of neuronal processing of the preganglionic input.