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PubMed1992

Comparison of the relaxant effects of diazepam, flunitrazepam and midazolam on airway smooth muscle.

The mechanisms by which benzodiazepines produce muscle relaxation and respiratory depression are not known, but they may include actions on peripheral benzodiazepine receptors or central GABA receptors, or a direct action on airway smooth muscle may also be involved. We have compared, therefore, the effects of diazepam, flunitrazepam and midazolam on airway tone by measuring isometric tension of guineapig trachealis muscle. Cumulative concentrations of diazepam, flunitrazepam and midazolam caused concentration-dependent relaxation of resting tone in the tracheal smooth muscle with no significant differences in pD2 values (-log EC50--an index of potency) or intrinsic activities (% of maximum response) for relaxations for the three compounds. Pretreatment with propranolol 10(-6) mol litre-1, flumazenil 10(-7) and 10(-6) mol litre-1 or PK11195 10(-6) mol litre-1 had no effect on diazepam- or midazolam-induced relaxation. Diazepam 3 x 10(-6) mol litre-1 pretreatment shifted the concentration-response curves for acetylcholine, histamine and serotonin (5-HT) to the right by a factor of approximately 2. Flunitrazepam 3 x 10(-6) mol litre-1 pretreatment also shifted the curves for histamine and 5-HT similarly to the right, whereas midazolam pretreatment did not inhibit any agonist-induced contractions. These results suggest that benzodiazepines relax airway smooth muscle, not via neural pathways or central and peripheral benzodiazepine receptors, but by a direct action on airway smooth muscle.

Animals↗

PubMed1992

Effects of isoflurane anaesthesia on the median nerve somatosensory evoked potential in children.

Evoked potentials are used to determine the integrity of neural pathways during neurosurgical and orthopaedic procedures, but the extent to which they may be altered by anaesthetic agents has not been studied systematically in children. In this study we have recorded median nerve somatosensory evoked potentials (mnSSEP) in children during isoflurane anaesthesia to determine if there are changes similar to those seen in adults. We studied 10 patients using standardized anaesthetic and clinical neurophysiological techniques. Control mnSSEP were obtained with 70% nitrous oxide in oxygen and isoflurane was then administered at 0.25, 0.50 and 0.75 MAC. The latencies and amplitudes of the mnSSEP were subjected to repeated measures analysis of the variance (ANOVA) and linear regression. There were statistically significant increases in N20, P22 latencies and central conduction time (P < 0.001) and reductions in amplitude of the N20-P22 complex (P < 0.03) with increasing end-tidal isoflurane concentrations. These results are similar to the findings in adults.

Anesthesia, Inhalation↗

PubMed1979

Mapping of local cerebral functional activity by measurement of local cerebral glucose utilization with [14C]deoxyglucose.

A method has been developed to measure the rates of glucose utilization in the individual structural and functional components of the central nervous system. It can be applied to conscious as well as anaesthetized animals. The method is based on the use of [14C]deoxyglucose as a tracer for glucose consumption. [14C]Deoxyglucose-6-phosphate accumulates in the tissue in a mathematically definable relationship to the rate of the tissue's glucose utilization. The [14C]deoxyglucose-6-phosphate concentrations in the various tissues of the nervous system are measured by a quantitative autoradiographic technique. The autoradiographs themselves are pictorial representations of the relative rates of glucose consumption in these tissues. Application of this method to rats and monkeys in various states of altered function demonstrates a clear and close relationship between the local levels of functional activity and energy metabolism. The method appears to be useful for mapping functional neural pathways on the basis of evoked metabolic responses (Plum, Gjedde and Samson, 1976).

Animals↗

PubMed1985

Cerebral somatosensory potentials evoked by muscle stretch, cutaneous taps and electrical stimulation of peripheral nerves in the lower limbs in man.

Somatosensory cerebral evoked potentials were recorded in man to natural forms of somatosensory stimulation of the lower extremity including stretching of the muscle tendons, tapping on muscle bellies and tapping on cutaneous surfaces. These potentials were compared with those evoked by electrical stimulation of peripheral nerves measuring the amplitudes and latencies of the evoked potential components and defining the effects of stimulus variables on these parameters. Spinal cord potentials could only be detected to electrical stimuli. Mechanical stimulation of tendons and muscle bellies evoked scalp potentials at latencies earlier than those evoked by electrical stimulation of the peripheral nerve and by cutaneous stimulation at the same level of the leg. Muscle receptors, most probably muscle spindles, are the source of the short latency components obtained by the stretching of tendons and tapping on muscle bellies. The proximal location of these receptors as well as very rapid spinal conduction account for the latency difference. The potentials were larger to electrical stimulation of nerve trunks than to mechanical stimulation of tendons or skin, suggesting the asynchronous activation of a smaller number of fibres by the latter. Individuals with the largest potentials to one form of stimulation usually had the largest potentials to the other modes of stimulation. The use of physiological stimuli such as muscle stretch to test the transmission in specific neural pathways might be useful in investigating the processing of relatively selective afferent volleys using noninvasive evoked potential recordings.

Adult↗

PubMed1989

Abnormalities of nonvisually-guided eye movements in Parkinson's disease.

Rapid eye movements (saccades) were examined in 7 patients with idiopathic Parkinson's disease (PD) and a matched group of normal control subjects. The effect of instructional and stimulus conditions used to elicit saccades was examined using 3 experimental paradigms. Eye movements directly elicited by a novel peripheral target were unimpaired in patients with PD as compared with control subjects. Saccades to a remembered target location, however, were dysmetric in the PD group and showed a characteristic multistepping pattern. The PD impairment was not caused by a loss of information on target location since their final eye position was close to the target at all eccentricities. Peak velocity, duration, and latency did not distinguish between PD patients and controls. These results support the view that for saccades which are not directly elicited by a visual target there is a neural pathway that can be distinguished from structures involved in the generation of visually elicited (or 'reflexive') saccades. The finding that in PD saccades to a remembered target are selectively impaired suggests that structures in the basal ganglia play a crucial role in this alternative pathway.

Aged↗

PubMed1993

Neurochemical substrates of rigidity and chorea in Huntington's disease.

Huntington's disease is a progressive degenerative neurological disorder which produces a characteristic movement disorder termed chorea. Although chorea is associated with dysfunction of the basal ganglia, the underlying mechanisms by which dyskinesias such as chorea are produced, are poorly understood. Recent studies in primates have led to experimental models of chorea with postulated involvement of specific neural pathways. In the present study we attempted to determine the validity of the experimental models by measuring concentrations of gamma-aminobutyric acid (GABA), glutamate, substance P and met-enkephalin in the basal ganglia of Huntington's disease patients who manifested either chorea or rigidity/bradykinesia within 6 months of death. We also characterized changes in the Huntington's disease patients according to pathological grade, since this may be a confounding factor. We analysed post-mortem brain tissue from 12 controls, and 11 grade 3 and 12 grade 4 Huntington's disease patients. The grade 3 and 4 cases consisted of eight adult-onset choreic, nine adult-onset rigid and six juvenile-onset rigid patients. We also analysed the putamen and globus pallidus from 11 grade 2 adult onset choreic Huntington's disease patients. A model of chorea based on experimental studies in primates proposes that a loss of striatal GABAergic inhibitory projections to the globus pallidus externa leads to increased activity of the inhibitory globus pallidus externa GABAergic neurons which project to the subthalamic nucleus. It is believed that the loss of GABAergic inputs to the globus pallidus externa precedes a loss of GABAergic input to the globus pallidus interna, which occurs later in the disease and is associated with the development of rigidity and bradykinesia. In the choreic Huntington's disease patients whom we studied, there was a greater loss of GABA in the globus pallidus externa than in the globus pallidus interna, and the globus pallidus interna: globus pallidus externa GABA ratio was significantly increased compared with rigid patients. There were also increases in GABA in the subthalamic nucleus in the choreic patients, although this did not reach significance. A differential loss of met-enkephalin in the globus pallidus externa compared with substance P loss in the globus pallidus interna was not observed in either the choreic patients with advanced disease or the grade II patients. There was a significant increase in GABA concentrations in the ventroanterior nucleus of the thalamus in the choreic patients compared with rigid/bradykinetic patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1997

Origin and propagation of interictal discharges in the acute electrocorticogram. Implications for pathophysiology and surgical treatment of temporal lobe epilepsy.

Although acute electrocorticography (ECoG) is routinely performed during epilepsy surgery there is little evidence that the extent of the discharging regions is a useful guide to tailoring the resection or that the findings are predictive of outcome or pathology. Patterns of discharge propagation have, however, rarely been considered in assessing the ECoG. We hypothesize that regions where discharges show earliest peaks ('leading regions') are located in the epileptogenic zone, whereas sites in which late, secondary, propagated activity occurs have less epileptogenic potential and do not need to be excised. To allow intraoperative topographic ECoG analysis, a computer program has been developed to identify leading regions and the sites showing greatest rates or amplitudes of spikes. Their topography has been compared retrospectively with pathology and seizure control in 42 consecutive patients following temporal lobe surgery. Leading regions were most often found in the hippocampus, the subtemporal cortex and the superior temporal gyrus. The most common propagation patterns were from hippocampus to subtemporal cortex and vice versa. There was no association between seizure outcome and the location of regions with greatest incidence or amplitude of spikes or location of leading regions. There was, however, a strong and significant association between poor outcome and non-removal of leading regions other than those in the posterior subtemporal cortex. All leading regions (other than posterior subtemporal) were resected in 27 patients of whom 25 had a favourable outcome. Leading regions (other than posterior subtemporal) remained in 14 patients of whom only four had a good outcome. One patient had no epileptiform activity in the ECoG and good outcome. Persistent posterior subtemporal leading regions remained in nine subjects; all had favourable outcome (Grades I or II) but only three were seizure free. These results suggest that: (i) interictal epileptiform discharges may originate from a complex interaction between separate regions, resulting in propagation and recruitment of neuronal activity along specific neural pathways; (ii) removal of all discharging areas appears unnecessary to achieve seizure control provided that leading regions (other than posterior subtemporal) are removed; and (iii) identification of such leading regions could be used to tailor resections in order to improve seizure control and reduce neurological, neuropsychological and psychiatric post-surgical morbidity.

Adolescent↗

PubMed1999

Direct comparison of the neural substrates of recognition memory for words and faces.

For the purpose of identifying the relatively specific brain regions related to word and face recognition memory on the one hand and the regions common to both on the other, regional cerebral blood flow associated with different cognitive tasks for recognition memory was examined using [H215O]PET in healthy volunteers. The tasks consisted of recognizing two types of stimuli (faces and words) in two conditions (novel and familiar), and two baseline tasks (reading words and gender classification). The statistical analyses used to identify the specific regions consisted of three subtractions: novel words minus novel faces, familiar words minus familiar faces, and reading words minus gender classification. These analyses revealed relative differences in the brain circuitry used for recognizing words and for recognizing faces within a defined level of familiarity. In order to find the regions common to both face and word recognition, overlapping areas in four subtractions (novel words minus reading words, novel faces minus gender classification, familiar words minus reading words, and familiar faces minus gender classification) were identified. The results showed that the activation sites in word recognition tended to be lateralized to the left hemisphere and distributed as numerous small loci, and particularly included the posterior portion of the left middle and inferior temporal gyri. These regions may be related to lexical retrieval during written word recognition. In contrast, the activated regions for face recognition tended to be lateralized to the right hemisphere and located in a large aggregated area, including the right lingual and fusiform gyri. These findings suggest that strikingly different neural pathways are engaged during recognition memory for words and for faces, in which a critical role in discrimination is played by semantic cueing and perceptual loading, respectively. In addition, the investigation of the regions common to word and face recognition indicates that the anterior and posterior cingulate have dissociable functions in recognition memory that vary with familiarity, and that the cerebellum may serve as the co-ordinator of all four types of recognition memory processes.

Adult↗

PubMed2002

The antalgic efficacy of chronic motor cortex stimulation is related to sensory changes in the painful zone.

Epidural motor cortex stimulation (MCS) could achieve good pain control in patients with drug-resistant chronic neurogenic pain. In the search for parameters associated with the favourable outcome of this surgical procedure, quantitative sensory testing was performed in a series of 31 patients treated by MCS for chronic pain. Non-nociceptive and nociceptive sensory thresholds were measured in the painful area and its contralateral homologous zone with the stimulator in 'off' and in 'on' position. All 13 patients who exhibited normal or quite normal non-nociceptive thermal thresholds within the painful area benefited from MCS. Of the remaining 18 patients with altered thermal sensory thresholds, eight patients nevertheless experienced good pain control by MCS. In these eight 'good responders', sensory thresholds were improved by switching 'on' MCS. In contrast, the last 10 patients showed abnormal thermal thresholds that were not modified by switching 'on' MCS, and did not respond clinically to MCS. Therefore, 'good responders' to MCS could be identified by the absence of alteration of non-nociceptive sensory modalities within the painful area, or by abnormal sensory thresholds that could be improved by MCS. These results additionally suggest that MCS acts on neural pathways involved in sensory discrimination that, in turn, are able to modulate the transmission of pain signals.

Adult↗

PubMed2000

Working memory of auditory localization.

To investigate brain mechanisms of sound location memory, we studied the distribution of brain activation with functional magnetic resonance imaging (fMRI) in subjects performing an audiospatial n-back task with three memory load levels. Working memory processing of audiospatial information activated areas in the superior, middle and inferior frontal gyri, and in the posterior parietal and middle temporal cortices. In a control experiment, fMRI during audio- and visuospatial 2-back task performances revealed only few differentially activated subregions between the two tasks. These results demonstrate that working memory processing of auditory locations involves a distributed network of brain areas and suggest that mnemonic processing of audio- and visuospatial information is directed along a common neural pathway in the posterior parietal and prefrontal cortices.

Acoustic Stimulation↗

PubMed2006

Cortical activity at rest predicts cochlear implantation outcome.

The functional status of central neural pathways, in particular their susceptibility to plasticity and functional reorganization, may influence speech performance of deaf cochlear implant users. In this paper, we sought to determine how brain metabolic activity measured before implantation relates to cochlear implantation outcome, that is, speech perception. In 22 prelingually deaf children between 1 and 11 years, we correlated preoperative glucose metabolism as measured by F-18 fluorodeoxyglucose positron emission tomography with individual speech perception performance assessed 3 years after implantation, while factoring out the confounding effect of age at implantation. Whereas age at implantation was positively correlated with increased activity in the right superior temporal gyrus, speech scores were selectively associated with enhanced metabolic activity in the left prefrontal cortex and decreased metabolic activity in right Heschl's gyrus and in the posterior superior temporal sulcus. These results reinforce the notion that implantation should be performed as early as possible to prevent cross-modal takeover of auditory regions and suggest that rehabilitation strategies may be more efficient if they capitalize on general cognitive functions instead of only targeting specialized circuits dedicated to auditory and audiovisual pattern recognition.

Auditory Cortex↗

PubMed2005

Laterality of human primary gustatory cortex studied by MEG.

We examined the laterality of the human gustatory neural pathway by measuring gustatory-evoked magnetic fields (GEMfs) and demonstrating the activation of the human primary gustatory cortex (PGC). In patients whose chorda tympani nerve had been severed unilaterally on the right side, we stimulated the normal side (i.e., left side) of the chorda tympani nerve with NaCl solution using a device developed for measuring GEMfs. We used the whole-head magnetoencephalography system for recording GEMfs and analyzed the frequency and latency of PGC activation in each hemisphere. "The transitional cortex between the insula and the parietal operculum" was identified as PGC with the base of the central sulcus in this experiment. Significant difference was found in frequencies among bilateral, only-ipsilateral, and only-contralateral responses by the Friedman test (P < 0.05), and more frequent bilateral responses were observed than only-ipsilateral (P < 0.05) or only-contralateral responses (P < 0.01) by the multiple comparison tests. In the bilateral responses, the averaged activation latencies of the transitional cortex between the insula and the parietal operculum were not significantly different in both hemispheres. These results suggest that unilateral gustatory stimulation will activate the transitional cortex between the insula and the parietal operculum bilaterally in humans.

Adult↗

PubMed2004

Neurobiology of Acupuncture: Toward CAM.

It has long been accepted that acupuncture, puncturing and scraping needles at certain points on the body, can have analgesic and anesthetic effects, as well as therapeutic effects in the treatment of various diseases. This therapy, including acupuncture anesthesia, has drawn the attention of many investigators and become a research subject of international interest around the world. Numerous studies have demonstrated that the nervous system, neurotransmitters, endogenous substances and Jingluo (meridians) may respond to needling stimulation and electrical acupuncture. An abundance of information has now accumulated concerning the neurobiological mechanisms of acupuncture, in relation to both neural pathways and neurotransmitters/hormonal factors that mediate autonomic regulation, pain relief and other therapeutics. Early studies demonstrated that the analgesic effects of electroacupuncture (EA) are mediated by opioid peptides in the periaqueductal gray. Recent evidence shows that nitric oxide plays an important role in mediating the cardiovascular responses to EA stimulation through the gracile nucleus-thalamic pathway. Other substances, including serotonin, catecholamines, inorganic chemicals and amino acids such as glutamate and alpha-aminobutyric acid (GABA), are proposed to mediate certain cardiovascular and analgesic effects of acupuncture, but at present their role is poorly understood. The increased interest in acupuncture health care has led to an ever-growing number of investigators pursuing research in the processes of the sense of needling touch, transduction of needling stimulation signals, stimulation parameters and placebos. In this Review, the evidence and understanding of the neurobiological processes of acupuncture research have been summarized with an emphasis on recent developments of nitric oxide mediating acupuncture signals through the dorsal medulla-thalamic pathways.

Journal Article↗

PubMed2026

Molecular Drivers of Mutualistic Association Between Anemone and Anemonefish.

The anemone-anemonefish mutualism is one of the most iconic in the marine environment. While the evolution of this mutualistic relationship has contributed to the ecological success of both partners, the underlying molecular processes that establish and maintain it remain poorly understood, particularly how anemonefish tolerate anemone venom. Here, we characterize the transcriptional dynamics in both the anemonefish Amphiprion clarkii and its host anemone Entacmaea quadricolor 48 h after association, providing a rare insight into the coordinated molecular processes in both partners that underlie symbiosis establishment. Upon acclimation with an anemone, anemonefish showed differential regulation of sensory perception and memory genes in key brain regions, indicating activation of neural pathways that may facilitate host recognition and mutualism establishment. In the fish's skin, altered expression of genes involved in neurotransmitter release, cytoskeleton organization, and venom receptor proteins points to mechanisms of resistance to anemone venom. This resistance is particularly remarkable since anemone hosting fish exhibited increased expression of genes encoding mechanoreceptors, putative venom-associated proteins, and ion channels involved in nematocyst discharge, indicating the anemone does indeed mount an active response to their mutualistic partner. By simultaneously capturing the molecular responses of both symbiotic partners, our results reveal the complex, coordinated interplay of molecular events in both species that play a pivotal role in establishing this mutualistic relationship.

Symbiosis↗

PubMed1984

Circadian temperature variation in healthy aged and in Alzheimer's disease.

Circadian temperature variation was monitored in healthy older adults and in health-, age-, and sex-matched Alzheimer's dementia patients. Oral and rectal temperatures were analyzed for mean level, amplitude, and phase using cosinor analyses. Mean 24-hour temperature level was not altered by dementia. A significant sex effect, however, was observed among dementia patients with women exceeding men in mean 24-hour temperatures and across daytime time periods. Cosinor-derived phase and amplitude measures were unaffected by dementia or by sex. This indicates that the primary neuronal degeneration characteristic of Alzheimer's disease in its early stages does not disable the neural pathway(s) controlling circadian temperature regulation. Some impairment in temperature homeostatic regulation may be present, however, because a greater intrasubject temperature variability was observed in Alzheimer men than in control men.

Age Factors↗

PubMedDate not supplied

Diphtheria and hearing loss.

OBJECTIVE: To determine if infectious diseases usually experienced in childhood have an effect on hearing ability later in life. METHODS: The Epidemiology of Hearing Loss Study (N = 3,753) is a population-based study of age-related hearing loss in adults aged 48 to 92 years in Beaver Dam, Wisconsin. As part of this study, infectious disease history was obtained and hearing was tested using pure-tone audiometry. Hearing loss was defined as a pure-tone average of thresholds at 500 Hz, 1,000 Hz, 2,000 Hz, and 4,000 Hz greater than 25 decibels hearing level in either ear. RESULTS: After adjusting for confounders, only a history of diphtheria (n = 37) was associated with hearing loss (odds ratio [OR] 2.79; 95% confidence interval [CI] 1.05, 7.36). There was no relationship between hearing loss and history of chickenpox, measles, mumps, pertussis, polio, rheumatic fever, rubella, or scarlet fever. Only two participants with a history of diphtheria and hearing loss reported having a hearing loss before age 20. CONCLUSIONS: Diphtheria in childhood may have consequences for hearing that do not become apparent until later in life. A possible biological mechanism for a diphtheria effect on hearing ability exists: The toxin produced by the Corynebacterium diphtheriae bacteria can cause damage to cranial nerves and therefore may affect the auditory neural pathway. These data may have important implications for areas facing a resurgence of diphtheria cases.

Adult↗

PubMed2003

Genetic regulation of feed intake and energy balance in poultry.

Intensive selection by poultry breeders over many generations for economically important production traits such as growth rate and meat production has been accompanied by significant changes in feed intake and energy balance. For example, the modern commercial broiler, selected for rapid growth and enhanced muscle mass, does not adequately regulate voluntary feed intake to achieve energy balance. When given unrestricted access to feed, broilers exhibit hyperphagia leading to an excessive accumulation of energy (fat) stores, making these birds prone to obesity and other health-related problems. Humoral and neural pathways have been identified and studied in mammals that link appetite and energy balance. A series of highly integrated regulatory mechanisms exists for both of these processes involving complex interactions between peripheral tissues and the central nervous system. Within the central nervous system, the brainstem and the hypothalamus play critical roles in the regulation of feed intake and energy balance. Genes encoding key regulatory factors such as hormones, neuropeptides, receptors, enzymes, transcription factors, and binding/transport proteins constitute the molecular basis for regulatory systems that derive from integrated sensing, signaling, and metabolic pathways. However, we do not yet have a complete understanding of the genetic basis for this regulation in poultry. This review examines what is currently known about the regulation of feed intake and energy balance in poultry. A better understanding of the genes associated with controlling feed intake and energy balance and how their expression is regulated by nutritional and hormonal stimuli will offer new insights into current poultry breeding and management practices.

Animal Husbandry↗

PubMed1987

Soleus muscle electromyographic activity and ankle dorsiflexion range of motion during four stretching procedures.

Volitional muscle contractions are used frequently in some combination with muscle stretching to promote muscle relaxation and to increase range of motion. In this study, muscle lengthening procedures were evaluated in the ankle plantar flexors. Four soleus muscle stretching procedures--static stretch (SS), hold relax (HR) (isometric plantar flexor contraction before stretch), agonist contract (AC) (dorsiflexor contraction assisting stretch), and hold relax-agonist contraction (HR-AC)--were performed in the sagittal plane by 12 physically active adults. The dorsiflexion angle, soleus muscle electromyogram, and soleus muscle motoneuron excitability as determined by the Hoffmann-reflex (H-reflex) amplitude were measured throughout the duration of each stretch. The range of dorsiflexion achieved at the end of the stretch did not differ significantly between stretching procedures, although in 8 of the 12 subjects and in the subject group as a whole, the AC and HR-AC procedures were associated with higher levels of soleus muscle EMG than the levels in the SS and HR procedures (p less than .01). The H-reflex amplitudes during the AC and HR-AC procedures were smaller than the amplitudes during the SS and HR procedures (p less than .001), suggesting the possibility of reciprocal inhibition during the agonist contraction. Increased tonic EMG levels produced by input from other neural pathways affecting alpha motoneurons in the AC and HR-AC procedures may have masked this inhibitory reflex. In healthy adults, a complicated procedure, involving muscle contractions for decreasing active resistance to stretch, may be unnecessary because active resistance to stretch is minimal and muscle relaxation during stretch appears to have little or no direct effect on the ROM achieved.

Adult↗