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PubMedDate not supplied

Instrumental cardiovascular conditioning: a review.

This paper reviews experiments, hypotheses, and current controversies about instrumental cardiovascular conditioning. Demonstrations of such conditioning in curarized animals challenged a differentiation between instrumental and classical learning on the basis of their respective effector systems but did not prove direct operant learning by the autonomic nervous system. In humans, ethical prohibition of curarization and lack of adequate controls for respiration and muscle tension have resulted in incomplete understanding of the roles of voluntary, somatic mediators. Despite a variety of potential clinical applications of biofeedback, the available literature lacks studies of its efficacy compared to more standard modes of therapy. The physiological mechanisms and central neural pathways involved in instrumental cardiovascular conditioning remain almost totally unknown.

Animals↗

PubMed1981

Autonomic hyperreflexia during upper extremity surgery.

A case is presented of autonomic hyperreflexia in a quadriplegic patient occurring during upper extremity surgery. Tourniquet ischaemia is proposed as the likely causative stimulus. An understanding of the afferent neural pathways involved in this physiological response may be useful in better understanding the subjective phenomena of tourniquet pain in neurologically intact individuals.

Adult↗

PubMed2005

Molecular targets of opiate drug abuse in neuroAIDS.

Opiate drug abuse, through selective actions at mu-opioid receptors (MOR), exacerbates the pathogenesis of human immunodeficiency virus-1 (HIV-1) in the CNS by disrupting glial homeostasis, increasing inflammation, and decreasing the threshold for pro-apoptotic events in neurons. Neurons are affected directly and indirectly by opiate-HIV interactions. Although most opiates drugs have some affinity for kappa (KOR) and/or delta (DOR) opioid receptors, their neurotoxic effects are largely mediated through MOR. Besides direct actions on the neurons themselves, opiates directly affect MOR-expressing astrocytes and microglia. Because of their broad-reaching actions in glia, opiate abuse causes widespread metabolic derangement, inflammation, and the disruption of neuron-glial relationships, which likely contribute to neuronal dysfunction, death, and HIV encephalitis. In addition to direct actions on neural cells, opioids modulate inflammation and disrupt normal intercellular interactions among immunocytes (macrophages and lymphocytes), which on balance further promote neuronal dysfunction and death. The neural pathways involved in opiate enhancement of HIV-induced inflammation and cell death, appear to involve MOR activation with downstream effects through PI3-kinase/Akt and/or MAPK signaling, which suggests possible targets for therapeutic intervention in neuroAIDS.

AIDS Dementia Complex↗

PubMedDate not supplied

Moebius syndrome in association with hypogonadotropic hypogonadism.

The association between hypogonadotropic hypogonadism and multiple CNS lesions in a variety of disorders suggests a possible causative link between these clinical findings. Neural afferent input into the hypothalamus from higher CNS centers modulates GnRH secretion and derangements of these neural pathways could potentially result in diminished gonadotropin secretion and hypogonadism. This report describes a patient with multiple CNS defects secondary to Moebius syndrome and hypogonadotropic hypogonadism whose clinical features support the hypothesis that his CNS and endocrine defects may be causally associated. Comprehensive clinical evaluation in this patient revealed severe mental retardation; cranial nerve palsies; motor, reflex, and gait disturbances; and sexual infantilism secondary to hypogonadotropic hypogonadism. An MRI of the brain revealed atrophy or hypoplasia of the third cranial nerve and the olfactory gyri. Numerous syndromes including the Moebius syndrome are now described in which hypogonadotropic hypogonadism and CNS defects are associated. Detailed neuroanatomic and embryologic studies have demonstrated the important functional interrelationships between higher central nervous system centers and the hypothalamus. Taken together, these findings provide support for the causative association of multiple CNS defects and hypogonadotropic hypogonadism.

Abnormalities, Multiple↗

PubMed2000

[Raeder- and Collet-Siccard-Syndrome. Acute pareses of cranial nerves symptomatic of a dissection of internal carotid artery].

Acute cerebral nerve paresis can be caused in many different ways. One of the more rare causes of paresis of one or more neural pathways is dissection of the internal carotid artery. Early diagnosis is important, even with atypical symptoms, since prompt anticoagulative therapy can hinder stroke from embolism due to the dissection. We report on two patients with Raeder's syndrome and Collet-Sicard syndrome resulting from dissection of the internal carotid artery. Besides the cranial and caudal nerves involved in our study, loss of function has also been reported with the sixth to eighth cranial nerves, so that any painful, sudden cranial nerve deficiency can indicate possible carotid dissection.

Acute Disease↗

PubMed2005

The four-plates test-retest paradigm to discriminate anxiolytic effects.

RATIONALE: Animal models of anxiety such as the four-plates test (FPT) enable the detection of an anxiolytic effect not only of benzodiazepines (BZDs) but also of other non-BZD anxiolytic compounds such as the antidepressants paroxetine and venlafaxine. Retesting mice in animal models of anxiety markedly alters the behavioural profile of various drugs. OBJECTIVES: The aim of this study was first to investigate the function of GABA(A)/BZD receptor and passive avoidance acquisition in the FPT "test-retest". The second aim of this study was to evaluate the capacity of the FPT to discriminate BZDs from other non-BZD anxiolytics in experienced mice. METHODS: The FPT was performed in naive and experienced mice (submitted to the test 24 h previously). The drugs studied were two BZDs, diazepam (1 mg/kg) and alprazolam (0.25 mg/kg); flumazenil, a GABA(A) receptor antagonist (8 mg/kg); atropine sulphate, a muscarinic cholinergic receptor antagonist (4 mg/kg) known for its amnesic properties; paroxetine, a selective serotonin reuptake inhibitor (4 and 8 mg/kg); venlafaxine, a serotonin and noradrenalin reuptake inhibitor (4 and 16 mg/kg); and DOI, a 5-HT2A agonist (1 mg/kg). RESULTS: Our results reveal an increase of anxiety (decrease of punished passages) in saline-experienced mice. Diazepam, alprazolam, paroxetine and venlafaxine did not prevent the increase in anxiety during retest, revealing a passive avoidance acquisition. Flumazenil did not modify the anxiogenic-like behaviour of experienced mice. In contrast, atropine seems to oppose the increase of anxiety; however, its effect is weak and disputable. DOI was the only anxiolytic compound able to oppose the decrease of punished passages of experienced mice. CONCLUSION: Anxiogenic behaviour on retesting indicates aversive learning. The protocol test-retest is unable to discriminate between the anxiolytic effect of BZDs from that of paroxetine or venlafaxine. However, this modified model may constitute a new tool to investigate other neural pathways implicated in anxiety.

Adrenergic Uptake Inhibitors↗

PubMed1998

Duration of sensitization to the locomotor stimulant effects of ethanol in mice.

Behavioral sensitization to the psychomotor stimulant effects of some drugs can be quite persistent, lasting for weeks to months after cessation of drug exposure. We investigated the duration of sensitization to the locomotor stimulant effects of 2.0 g/kg ethanol (EtOH) and determined whether repeated EtOH administration would lead to alterations in blood EtOH clearance rates. Female mice were injected (IP) daily for up to 10 consecutive days with saline or EtOH. Baseline activity and acute EtOH locomotor responses were evaluated in Omnitech automated activity monitors (10-min test), with horizontal distance traveled as the measure of locomotion. Locomotor activity response to EtOH was reevaluated immediately after the final daily EtOH injection, and at 5-day intervals during which no EtOH was administered. Tail blood samples for determination of blood ethanol concentrations (BECs) were collected from EtOH-treated mice at the end of activity sessions. Sensitization lasted for up to 29 days, and in two of three of the behavioral sensitization studies, repeated EtOH treatment resulted in elevated BECs. There was no significant effect of repeated EtOH exposure on EtOH clearance rate in a study involving no behavioral testing. The demonstration of persistent behavioral sensitization may imply a lasting hypersensitivity of certain neural pathways to EtOH, thus increasing the reinforcing value of EtOH and the probability of relapse to EtOH drinking after abstinence.

Animals↗

PubMed2004

Excitability changes in human hand motor area dependent on afferent inputs induced by different motor tasks.

Using the technique of transcranial magnetic stimulation (TMS) with a figure-of-eight-shaped coil in 16 normal volunteers, we studied the extents of motor evoked potentials (MEPs) induced by remote facilitation of voluntary teeth clenching (VTC) and by motor imagery (MI). In particular, we examined whether different excitability changes in the primary motor cortex (M1) induced by both facilitation methods occur between early (I1 and I2) and late (I3 and I4) components of I-waves elicited from a first dorsal interosseous (FDI) muscle. Both components of I-waves were induced by anterior-medially (AM) directed currents or posterior-laterally (PL) directed currents. Our hypothesis was that facilitatory effects of VTC and MI on M1 differ because the neural pathways of these afferent inputs differ. The present results indicate that during MI MEP amplitudes of late components are significantly larger than those of early ones, although both MEP amplitudes are enhanced. On the other hand, during VTC MEP amplitudes of early components are significantly enhanced, but those of late ones are rather depressed. We conclude that recruitment of early and late components of I-waves differ depending on the afferent inputs to the motor cortex.

Adult↗

PubMed2005

The influence of perturbation duration and velocity on the long-latency response to stretch in the biceps muscle.

Different neural pathways are proposed to mediate the long-latency stretch reflex response (M2) in muscles spanning distal and proximal joints of the upper limb. The M2 at the wrist joint is present only if the duration of the perturbation exceeds a critical time. Lee and Tatton put forward a converging input hypothesis, requiring an interaction of excitatory volleys at the spinal cord, to account for this feature. The goal of the present study was to examine the influence of the duration of perturbation on M2 responses elicited in a muscle spanning the elbow joint. Reflex responses were induced in the biceps brachii muscle by applying ramp-and-hold position displacements to the elbow. It was found that the M2 was strongly dependent on the duration of the perturbation. On average, responses were not elicited following perturbations of less than 35+/-5 ms. Using a novel double-movement paradigm, we were unable to provide support for the converging input hypothesis. The effect of the duration of perturbation on the M2 may account for the conflicting characteristics of the M2 that have been provided by previous studies applying mechanical or electrical perturbations of varying time durations.

Adult↗

PubMed2006

Pursuit and saccadic tracking exhibit a similar dependence on movement preparation time.

Data from previous human and primate studies on saccadic and smooth pursuit eye movements suggest that there are shared internal inputs (for example, perception, attention, expectation, and memory) for the initiation of the two types of movements. Additional reports examining the effect of preparation time on movement responses have shown that when ample time is allowed subjects usually generate long-latency "reactive" responses. When the time allowed to prepare a movement is short, however, subjects respond with reduced latency and often anticipate the stimulus ("predictive" response). Based on these findings, we believe that the shared internal inputs at early stages of movement preparation may result in saccade and pursuit eye movements demonstrating the same dependence on preparation time despite acting through different neural pathways further downstream. Previously we demonstrated a behavioral "phase transition" when normal subjects tracked alternating targets with saccades. When preparation time was long (low-frequency pacing) subjects made reactive saccades (latency approximately 180 ms). As preparation time monotonically decreased (pacing frequency increased), there was an abrupt transition to a predictive response (latency <100 ms). In the present study we show that a similar transition exists in smooth pursuit tracking and that the point of transition between the two behaviors is the same for both systems. In other words, the same behavior (reactive versus predictive) is selected when pursuit and saccade tracking are tested under the same time constraints. This provides further evidence that the two types of movements are different motor outcomes of a common decision process.

Eye Movements↗

PubMed1998

Final posture of the upper limb depends on the initial position of the hand during prehension movements.

The question of knowing how the nervous system transforms a desired position and orientation of the hand into a set of arm and forearm angles has been widely addressed during the last few decades. Despite this fact, it still remains unclear as to whether a unique posture of the arm is associated with every location and orientation of the hand in space. The main objective of the present study a was to address this question. To this end, we studied a prehension task requiring human subjects to reach and grasp a cylindrical object presented at different locations, along variable orientations. In contrast to previous investigations, we considered the influence of the initial position of the hand. Results showed that the posture of the arm: (1) varied systematically as a function of the movement starting point; (2) was stereotyped for a particular subject given a configuration of the object and a movement starting location; (3) was altered at both the distal and proximal levels when the orientation of the object was changed; (4) was similarly influenced by the experimental factors in all the subjects, except one. When considered together, the previous results support three main conclusions: First, the nervous system solves the joint redundancy problem using fixed strategies. Second, these fixed strategies do not provide a single correspondence between hand configuration and arm posture. Third, the position and orientation of the hand in space are unlikely to be controlled through separate independent neural pathways.

Adult↗

PubMed2003

Enzymatic assay for perfluoro-tagged metabolites of l-DOPA using crude lysate from E. coli transformed with pKKAADCII.

Isomers of l-DOPA and dopamine with a nine-atom 19F atom tag were exposed to aromatic acid decarboxylase (AADC) in the lysate of Escherichia coli JM109 that had been transformed with the plasmid pKKAADCII. The resulting samples were analyzed with HPLC. The first study investigated the conversion of the tagged l-DOPA into tagged dopamine, using the tagged dopamine as a standard. A second study was undertaken to identify the source of peaks seen in the enzymatic assays. l-DOPA with the tag bonded at position 5 served as the best substrate for AADC. Isomers that fit into the active site of AADC are likely to follow the biosynthetic path for dopamine in vivo and are potentially useful in magnetic resonance studies. The enzymatic assay described here provides an efficient and cost-effective tool for screening new compounds for use in the fluorine imaging of neural pathways.

Aromatic-L-Amino-Acid Decarboxylases↗

PubMed2005

Fascicular anatomy and surgical access of the human pudendal nerve.

The ability to access selectively distal nerve branches at the level of the compound pudendal nerve (PN) would allow control of multiple neural pathways and genitourinary functions at a single location. Nerve cuff electrodes can selectively stimulate individual fascicles; however the PN fascicular anatomy is unknown. The fascicular representation of distal branches was identified and traced proximally to create fascicle maps of 12 compound PNs in seven cadavers. Distal nerves were represented as groups of individual fascicles in the PN. Fascicle maps were consistent between specimens and along the PN within specimens. PN branch free length was 26+/-7.7 mm. PN cross-sections were relatively flat with major and minor diameters of 4.3+/-0.90 and 1.7+/-0.45 mm, respectively. Placing a nerve cuff on the PN is anatomically and surgically feasible. The PN fascicular anatomy, branch free length, and cross-section geometry are conducive to selective stimulation of distal nerves with a single nerve cuff electrode.

Aged↗

PubMed2006

Anatomy of autonomic nerve component in the male pelvis: the new concept from a perspective for robotic nerve sparing radical prostatectomy.

The DaVinci Robot (Intuitive Surgical, Sunnyvale California) with its magnified 3-D vision and multi-jointed wristed instruments enabled us to perform radical prostatectomy with consideration for the pelvic anatomy. In the present paper, we review the pelvic autonomic neuroanatomy with respect to robotic prostatectomy and demonstrate the procedures and critical points of nerve-sparing robotic radical prostatectomy based on novel anatomic concepts. Microscopic and macroscopic data were acquired from 30 fresh and 25 fixed male cadavers. A video study of 205 surgeries was performed for establishing the anatomy relevant to robotic prostatectomy. From a practical standpoint, we could group the relevant neural tissue into three broad zones: (1) proximal neurovascular plate (PNP), (2) predominant neurovascular bundles (PNB), (3) accessory distal neural pathways (ANP). Autonomic ganglion cells existed widely not only in nerve components but also along the viscera. The critical areas of nerve sparing surgery were the distal end of PNP, the entire PNB, and the circumference of the apex. Interindividual differences of cell counts were evident in all sites. Based on these concepts, we established the Athermal Robotic Technique (ART) for nerve sparing prostatectomy. Surgical and oncological outcomes were not mature but feasible. These tri-zonal and ganglion cell concepts may be of benefit to new surgeons undertaking nerve-sparing robotic radical prostatectomy.

Autonomic Pathways↗

PubMed2002

Intraoperative neurophysiological monitoring in pediatric neurosurgery: why, when, how?

INTRODUCTION: This review is primarily based on peer-reviewed scientific publications and on the authors' experience in the field of intraoperative neurophysiology. The purpose is a critical analysis of the role of intraoperative neurophysiological monitoring (INM) during various neurosurgical procedures, emphasizing the aspects that mainly concern the pediatric population. Original papers related to the field of intraoperative neurophysiology were collected using medline. INM consists in monitoring (continuous "on-line" assessment of the functional integrity of neural pathways) and mapping (functional identification and preservation of anatomically ambiguous nervous tissue) techniques. We attempted to delineate indications for intraoperative neurophysiological techniques according to their feasibility and reliability (specificity and sensitivity). DISCUSSION AND CONCLUSIONS: In compiling this review, controversies about indications, methodologies and the usefulness of some INM techniques have surfaced. These discrepancies are often due to lack of familiarity with new techniques in groups from around the globe. Accordingly, internationally accepted guidelines for INM are still far from being established. Nevertheless, the studies reviewed provide sufficient evidence to enable us to make the following recommendations. (1) INM is mandatory whenever neurological complications are expected on the basis of a known pathophysiological mechanism. INM becomes optional when its role is limited to predicting postoperative outcome or it is used for purely research purposes. (2) INM should always be performed when any of the following are involved: supratentorial lesions in the central region and language-related cortex; brain stem tumors; intramedullary spinal cord tumors; conus-cauda equina tumors; rhizotomy for relief of spasticity; spina bifida with tethered cord. (3) Monitoring of motor evoked potentials (MEPs) is now a feasible and reliable technique that can be used under general anesthesia. MEP monitoring is the most appropriate technique to assess the functional integrity of descending motor pathways in the brain, the brain stem and, especially, the spinal cord. (4) Somatosensory evoked potential (SEP) monitoring is of value in assessment of the functional integrity of sensory pathways leading from the peripheral nerve, through the dorsal column and to the sensory cortex. SEPs cannot provide reliable information on the functional integrity of the motor system (for which MEPs should be used). (5) Monitoring of brain stem auditory evoked potentials remains a standard technique during surgery in the brain stem, the cerebellopontine angle, and the posterior fossa. (6) Mapping techniques (such as the phase reversal and the direct cortical/subcortical stimulation techniques) are invaluable and strongly recommended for brain surgery in eloquent cortex or along subcortical motor pathways. (7) Mapping of the motor nuclei of the VIIth, IXth-Xth and XIIth cranial nerves on the floor of the fourth ventricle is of great value in identification of "safe entry zones" into the brain stem. Techniques for mapping cranial nerves in the cerebellopontine angle and cauda equina have also been standardized. Other techniques, although safe and feasible, still lack a strong validation in terms of prognostic value and correlation with the postoperative neurological outcome. These techniques include monitoring of the bulbocavernosus reflex, monitoring of the corticobulbar tracts, and mapping of the dorsal columns. These techniques, however, are expected to open up new perspectives in the near future.

Brain Mapping↗

PubMed1998

Comparison of beta-protein/A4 deposits and Alz-50-stained cytoskeletal changes in the hypothalamus and adjoining areas of Alzheimer's disease patients: amorphic plaques and cytoskeletal changes occur independently.

Alzheimer's disease is characterized neuropathologically by senile plaques and cytoskeletal changes. It has been proposed that amorphic plaques would locally induce anterograde propagation of cytoskeletal changes in consecutive neurons followed by amorphic plaque deposition at their axonal terminals. The Alzheimer changes would spread in this way along neural pathways. To test the 'primary amyloid anatomical cascade hypothesis', Congo red staining, beta-protein/A4 (Abeta) antiserum and Alz-50, which recognizes cytoskeletal changes, were applied to the hypothalamus and adjoining brain areas of five Alzheimer's disease patients of 40-90 years of age and five age- and sex-matched controls. The results showed that (1) virtually all Abeta plaques in the hypothalamus were of the Congo red-negative amorphic type; (2) amorphic plaques and Alz-50-stained cytokeletal changes were observed not only in all Alzheimer's disease patients but also in a non-demented, 90-year-old control subject; (3) the density of amorphic plaques in the hypothalamus was unrelated to the duration of the dementia; (4) the density of amorphic plaques was unrelated to that of Alz-50-stained cytoskeletal changes; (5) double-labeling with anti-Abeta and Alz-50 did not show an evident topical relationship between amorphic plaque deposition and the occurrence of cytoskeletal changes; and (6) the distribution of Abeta and Alz-50 staining in five brain areas, for which essential anatomical information is available, did not support the primary amyloid anatomical cascade hypothesis. Amorphic plaques and cytoskeletal changes rather occur independently.

Adult↗

PubMed2006

A binocular pupil model for simulation of relative afferent pupil defects and the swinging flashlight test.

Many important intracranial neural pathways are involved in the control of the two muscles of the human pupil and the observation and analysis of pupil responses to light or other stimuli is of great interest in many clinical procedures. The binocular pupil model presented in this document has a topology encompassing much of the complexity of the pupil system neurophysiology. The dynamic parameters of the model were matched against pupil experiments under multiple conditions. It is employed here to simulate responses to the swinging flashlight test, a procedure which is routinely practiced in ophthalmology to diagnose different degrees of relative afferent pupil defects often a consequence of severe optic nerve diseases or retinal dysfunctions. Other, not light-dependent, pupil stimuli are briefly discussed.

Computer Simulation↗

PubMed2000

Spatial cognition and neuro-mimetic navigation: a model of hippocampal place cell activity.

A computational model of hippocampal activity during spatial cognition and navigation tasks is presented. The spatial representation in our model of the rat hippocampus is built on-line during exploration via two processing streams. An allothetic vision-based representation is built by unsupervised Hebbian learning extracting spatio-temporal properties of the environment from visual input. An idiothetic representation is learned based on internal movement-related information provided by path integration. On the level of the hippocampus, allothetic and idiothetic representations are integrated to yield a stable representation of the environment by a population of localized overlapping CA3-CA1 place fields. The hippocampal spatial representation is used as a basis for goal-oriented spatial behavior. We focus on the neural pathway connecting the hippocampus to the nucleus accumbens. Place cells drive a population of locomotor action neurons in the nucleus accumbens. Reward-based learning is applied to map place cell activity into action cell activity. The ensemble action cell activity provides navigational maps to support spatial behavior. We present experimental results obtained with a mobile Khepera robot.

Animals↗