Optokinetic-vestibular interaction in patients with increased gain of the vestibulo-ocular reflex

We studied optokinetic nystagmus (OKN), optokinetic afternystagmus (OKAN) and visual-vestibular interaction in five patients with markedly elevated vestibulo-ocular reflex (VOR) gain due to cerebellar atrophy. All had impaired smooth pursuit, decreased initial slow phase velocity of OKN, and impaired ability to suppress the VOR with real or imagined targets. OKN slow phase velocity gradually built up over 25-45 s, reaching normal values for low stimulus velocities (< or = 30 deg/s). Initial velocity of OKAN was increased, but the rate of decay of OKAN was normal. These findings can be explained by models that include separate velocity storage and variable gain elements shared by the vestibular and optokinetic systems.     

Interpretation revealed in the blink of an eye: Depressive bias in the resolution of ambiguity.

Self-report measures of interpretation have been criticized on methodological grounds. An approach is introduced in this article that enables the assessment of interpretive bias with a greater degree of methodological rigor than previously has been the case. Psychophysiological researchers have established that the magnitude of the human blink reflex is augmented when elicited during negative rather than neutral imagery. The 1st experiment demonstrates that the blink reflex is sensitive to the emotional valence of imagery evoked by interpretations imposed on ambiguous stimuli. In the 2nd experiment, this measure is used to assess interpretations imposed on ambiguous stimuli by individuals who differ in depression levels. The findings are consistent with the hypothesis that depression is associated with a negative interpretive bias. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contributions of regularly and irregularly discharging vestibular-nerve inputs to the discharge of central vestibular neurons in the alert squirrel monkey

The discharge of neurons in the vestibular nuclei was recorded in alert squirrel monkeys while they were being sinusoidally rotated at 2 Hz. Type I position-vestibular-pause (PVP I) and vestibular-only (V I) neurons, as well as a smaller number of other type I and type II eye-plus-vestibular neurons were studied. Many of the neurons were monosynaptically related to the ipsilateral vestibular nerve. Eye-position and vestibular components of the rotation response were separated by multiple regression. Anodal currents, simultaneously delivered to both ears, were used to eliminate the head-rotation signals of irregularly discharging (I) vestibular-nerve afferents, presumably without affecting the corresponding signals of regularly discharging (R) afferents. R and I inputs to individual central neurons were determined by comparing rotation responses with and without the anodal currents. The bilateral currents, while reducing the background discharge of all types of neurons, did not affect the mean vestibular gain or phase calculated from a population of PVP I neurons or from a mixed population consisting of all type I units. From this result, it is concluded that I inputs are canceled at the level of secondary neurons. The cancellation may explain why the ablating currents do not affect the gain and phase of the vestibulo-ocular reflex. While cancellation was nearly perfect on a population basis, it was less so in individual neurons. For some neurons, the ablating currents decreased vestibular gain, while for other neurons the vestibular gain was increased. The former neurons are interpreted as receiving a net excitatory (I-EXC) I input, the latter neurons, a net inhibitory (I-INH) input. When compared with the corresponding R inputs, the I inputs were usually small and phase advanced. Phase advances were larger for I-EXC than for I-INH inputs. The sign and magnitude of the I inputs were unrelated to other discharge properties of individual neurons, including discharge regularity and the phase of vestibular responses measured in the absence of the ablating currents. Unilateral currents were used to assess the efficacy of ipsilateral and contralateral pathways. Ipsilateral pathways were responsible for almost all of the effects seen with bilateral currents. The results suggest that the vestibular signals carried by central neurons, even by those neurons receiving a monosynaptic vestibular-nerve input, are modified by polysynaptic pathways.     

Evaluation of vestibular and visual oculomotor function

The visual system interacts synergistically with the vestibular system. A normally functioning vestibulo-ocular reflex is necessary but not sufficient for optimum visual acuity during head motion. Studies of dynamic visual acuity, the acuity achieved during relative motion of visual targets or of the observer, indicate that motion of images on the retina markedly compromises vision. The vestibulo-ocular reflex normally provides a substantial measure of stabilization of the retina during head movements, but purely vestibular compensatory eye movements are not sufficiently precise for optimal vision under all circumstances. Other mechanisms, including visual tracking, motor preprogramming, prediction, and mental set, interact synergistically to optimize the gain (eye velocity divided by head velocity) of compensatory head movements. All of these mechanisms are limited in their capacity to produce effective visual-vestibular interaction at higher rotational frequencies and velocities. It is under these conditions that vestibular deficits give rise to symptoms of oscillopsia. Patients having vestibular lesions exploit mechanisms of visual-vestibular interaction to compensate by substitution for deficient vestibular function. Thus, for accurate topographic clinical diagnosis of vestibular lesions, testing conditions should isolate purely vestibular responses. This may be done by testing reflex eye movements during passively generated rotations in darkness, or perhaps by testing during other types of motion under conditions of extreme frequency and velocity sufficient to attenuate the effects of visual-vestibular interaction. This article reviews clinical tests of vestibular function in relation to synergistic interactions with vision.     

Adapting reflexes controlling the human posture

Doubt about the role of stretch reflexes in movement and posture control has remained in part because the questions of reflex "usefulness" and the postural "set" have not been adequately considered in the design of experimental paradigms. The intent of this study was to discover the stabilizing role of stretch reflexes acting upon the ankle musculature while human subjects performed stance tasks requiring several different postural "sets". Task specific differences of reflex function were investigated by experiments in which the role of stretch reflexes to stabilize sway doing stance could be altered to be useful, of no use, or inappropriate. Because the system has available a number of alternate inputs to posture (e.g., vestibular and visual), stretch reflex responses were in themselves not necessary to prevent a loss of balance. Nevertheless, 5 out of 12 subjects in this study used long-latency (120 msec) stretch reflexes to help reduce postural sway. Following an unexpected change in the usefulness of stretch reflexes, the 5 subjects progressively altered reflex gain during the succeeding 3-5 trials. Adaptive changes in gain were always in the sense to reduce sway, and therefore could be attenuating or facilitating the reflex response. Comparing subjects using the reflex with those not during so, stretch reflex control resulted in less swaying when the task conditions were unchanging. However, the 5 subjects using reflex controls oftentimes swayed more during the first 3-5 trials after a change, when inappropriate responses were elicited. Four patients with clinically diagnosed cerebellar deficits were studied briefly. Among the stance tasks, their performance was similar to normal in some and significantly poorer in others. Their most significant deficit appeared to be the inability to adapt long-latency reflex gain following changes in the stance task. The study concludes with a discussion of the role of stretch reflexes within a hierarchy of controls ranging from muscle stiffness up to centrally initiated responses.     

Cyanobacterial tRNA(Leu)(UAA) group I introns have polyphyletic origin

Insecticide susceptibility of field populations of stable flies, Stomoxys calcitrans (L.), was assayed using 3 exposure techniques: treated filter papers, treated glass petri dishes, and topical applications. Both topical applications and residual exposure to treated glass surfaces were suitable for testing susceptibility of stable flies to permethrin, stirofos, or methoxychlor. Residues on filter papers yielded inconsistent results with stirofos and methoxychlor. Significant concentration-mortality regression lines were generated with permethrin residues on filter papers, but approximately 1,000 times more insecticide was required to produce a toxic response when compared with permethrin residues on glass. Because of higher variability in response and the greater amount of insecticide required, residues on filter papers do not appear appropriate to test insecticide susceptibility in stable flies. Paired comparisons of field (F) and susceptible (S) stable flies resulted in field to susceptible ratios significantly > 1.0 only when the flies were treated topically, which suggests that topical application is more sensitive than residues on glass for the insecticides tested. Topical treatment with permethrin resulted in one FS(LD90) of 1.8-fold. Topical treatment with methoxychlor resulted in one FS(LD90) of 3.4-fold. However, the magnitude of these ratios is not larger than the significant differences observed within the susceptible laboratory colony from one generation to another. Intense exposure to insecticides is not known to have occurred in these field populations, indicating that the observed differences are the result of natural variation among stable fly populations and unrelated to prior selection with insecticides.     

Passive sustained turning of the head induces asymmetric gain of the vestibulo-ocular reflex in healthy subjects

In order to test the hypothesis of an interaction between neck proprioception and the vestibulo-ocular reflex (VOR), we rotated 16 healthy subjects both facing forward and with their heads passively turned 70 degrees to either side. We found that gain tended to be lower when the subjects were rotated with their heads turned opposite to the direction of rotation compared to when they were rotated in the same direction, but facing forward. Although our findings were not statistically significant, they suggest that there is a measurable interaction between neck proprioception and the VOR in subjects with normal vestibular function. Asymmetric neck muscle proprioceptive signals seem to give rise to asymmetric functioning of the VOR, which, at least in part, could be the pathogenesis of cervical dizziness. If so, this could lead to misinterpretation of vestibular assessments in patients with neck pain who also complain of dizziness.     

Changes in dorsal neck muscle activity related to imposed eye movement in the decerebrate pigeon

Movements of the head and eyes are known to be intimately related. Eye position has also been shown to be closely related to the electromyographic activity of dorsal neck muscles; however, extraocular muscle proprioception has not generally been considered to play a part in the control of such movements. We have previously shown that, in the pigeon, imposed movements of one eye modify the vestibular responses of several dorsal neck muscles in ways that are dependent on stimulus parameters such as the amplitude and velocity of imposed eye movement. The present study examines more closely the interactions between imposed eye movements and different muscle pairs. The three neck muscle pairs studied each responded to afferent signals from the extraocular muscles in discrete and specific ways which appeared to be correlated with their different actions. Complementary effects of imposed eye movements in the horizontal plane were seen for both the complexus and splenius muscle pairs, with imposed eye movements in one direction producing the largest inhibition of the ipsilateral muscle's vestibular response and imposed eye movements in the opposite direction the largest inhibition of the contralateral muscle's vestibular response. During roll tilt oscillation (ear-up/ear-down) in the frontal plane, similar complementary effects of imposed eye movement were seen in the complexus muscle pair, but the splenius muscle pair showed little tuning, with similar inhibition for imposed eye movement directed either upwards or downwards. In contrast to these complementary effects, the biventer cervicis muscle pair showed no vestibular modulation during vestibular stimulation in the horizontal plane and their spontaneous activity was not altered by imposed eye movement. During roll-tilt oscillation (ear-up/ear-down) in the frontal plane imposed eye movement directed vertically upwards increased both muscles' vestibular responses and imposed eye movement directed vertically downwards inhibited both muscles' vestibular responses. Section of the ophthalmic branch of the trigeminal nerve (deafferenting the eye muscles) abolished the effects of imposed eye movement on the neck muscle pairs. In conjunction with further control experiments these results provide compelling evidence that proprioceptive signals from the extraocular muscles reach the neck muscles and provide them with a functionally significant signal. We have previously shown that signals from the extraocular muscles appear to be involved in the control of the vestibulo-ocular reflex. It follows from the experiments reported here that proprioceptive signals from the extraocular muscles are also likely to be involved in the control of gaze.     

Temporal and spatial pattern of expression of the HDL receptor SR-BI during murine embryogenesis

Cerebellar long-term depression (LTD) is a model system for neuronal information storage that has an absolute requirement for activation of protein kinase C (PKC). It has been claimed to underlie several forms of cerebellar motor learning. Previous studies using various knockout mice (mGluR1, GluRdelta2, glial fibrillary acidic protein) have supported this claim; however, this work has suffered from the limitations that the knockout technique lacks anatomical specificity and that functional compensation can occur via similar gene family members. To overcome these limitations, a transgenic mouse (called L7-PKCI) has been produced in which the pseudosubstrate PKC inhibitor, PKC[19-31], was selectively expressed in Purkinje cells under the control of the pcp-2(L7) gene promoter. Cultured Purkinje cells prepared from heterozygous or homozygous L7-PKCI embryos showed a complete blockade of LTD induction. In addition, the compensatory eye movements of L7-PKCI mice were recorded during vestibular and visual stimulation. Whereas the absolute gain, phase, and latency values of the vestibulo-ocular reflex and optokinetic reflex of the L7-PKCI mice were normal, their ability to adapt their vestibulo-ocular reflex gain during visuo-vestibular training was absent. These data strongly support the hypothesis that activation of PKC in the Purkinje cell is necessary for cerebellar LTD induction, and that cerebellar LTD is required for a particular form of motor learning, adaptation of the vestibulo-ocular reflex.     

Identification of the location of vestibular lesions on the basis of vestibulo-ocular reflex measurements

Quantitative analysis of electro-oculographic recordings of eye movement in response to precise visual and vestibular stimuli makes possible the differentiation of three categories of vestibular syndromes due to pathological changes in three different parts of the visual vestibulo-ocular reflex arc: (1) decreased vestibulo-ocular reflex gain (e.g., decrease in slow component velocity), but normal fast components and visual-vestibular interaction (labyrinth and eighth nerve); (2) normal slow component velocity but abnormal fast components to all stimuli (pontine or medullar reticular formation); and (3) normal slow component velocity to vestibulo-ocular stimulaton but abnormal visual-vestibular interaction as well as normal fast components (visual-motor pathways or cerebellum).     

Gain and delay of human vestibulo-ocular reflexes to oscillation and steps of the head by a reactive torque helmet. I. Normal subjects

Vestibulo-ocular reflexes (VOR) were evaluated with a reactive torque helmet that imposed high-frequency oscillation (2-20 Hz) or step displacements of the head in the horizontal plane. The present paper describes the results in patients with vestibular deficiencies (labyrinthine defective; LD); experimental and analytical techniques and results for normal subjects were described in Part 1 of this paper. The patient groups included: total unilateral LD (related to acoustic neuroma; n = 40); severe (clinically total) bilateral LD (n = 7); bilateral hyporeflexia (n = 14); unilateral hyporeflexia (n = 11); and patients with LD phenomena that had subsided (n = 3). Helmet-induced head steps provided the most specific information. Characteristically, gain was lowered in one direction or both directions after unilateral or bilateral vestibular lesions, respectively; in general, the magnitude of the gain reduction correlated well with the degree of complaints and disability. Surprisingly, delay was systematically prolonged (up to several tens of milliseconds) in all groups of subjects with manifest vestibular pathology. These results suggest that the determination of delay, in addition to gain of the VOR, is feasible and important in the evaluation of vestibular function. The results of head oscillation generally supported the results for steps, but were somewhat less specific. The responses to manually generated head steps roughly agreed with those to helmet-induced steps, but because of the non-uniform acceleration they allowed a less exact analysis of VOR function.     

Variations in learning reflect individual differences in sensory function and synaptic integration

With the invertebrate Hermissenda as subjects, variability in acquisition of a learned association between light and rotation was correlated with the magnitude of the unconditioned responses elicited by these stimuli. Moreover, learning was facilitated by increasing stimulus intensity. In the isolated nervous system, pairings of light and mechanical stimulation of the animal's vestibular hair cells resulted in an increase in the excitability of B photoreceptors (an in vitro index of learning) that was strongly correlated with the strength of the synaptic interaction between the hair cells and the photoreceptors and weakly correlated with the magnitude of the light response in the photoreceptors. Because these in vitro results are not attributable to motor or motivational variables, they suggest that the efficacy of synaptic integration between sensory systems and sensory transduction is the primary determinant of the variability in learning.     

Role of primate medial vestibular nucleus in long-term adaptive plasticity of vestibuloocular reflex

1. Fifteen hundred and thirty cells were recorded in the medial vestibular nucleus (MVN) of alert monkeys whose vestibuloocular reflex (VOR) had been adapted to one of two kinds of spectacles. The "high-gain" sample was recorded from monkeys that had worn 2.0 x telescopic spectacles; the gain of the VOR in the dark (eye velocity divided by head velocity) was greater than 1.5. The "low-gain" sample was recorded from monkeys that had worn goggles providing a visual field that was fixed with respect to the freely turning head; the gain of the VOR was less than 0.4. 2. Cells showing modulation of firing rate related to imposed head velocity were grouped into four categories: pure vestibular (10), vestibular-plus-saccade (10), vestibular-plus-position (10), and vestibular-plus-head/body (24). Sensitivity to head velocity was measured from averaged responses to sinusoidal, 0.4-Hz whole-body oscillation in the horizontal plane. Almost all cells (98%) having increased firing during ipsilateral head rotation received inputs from the horizontal semicircular canals. Conversely, 82% of cells having increased firing during contralateral head rotation received inputs from the vertical canals. 3. There were no statistically significant differences in resting discharge rate, phase shift, or sensitivity to head velocity between the high- and low-gain samples of any of the cell types. Nonetheless, there was a consistent tendency, evident in all the functionally defined cell groups, for the sensitivity to be about 20% greater in the high-gain samples. However, this difference is small by comparison with the fourfold difference in VOR gain. 4. Detailed scrutiny of the response properties of individual cells suggested that the small differences in sensitivity reflect small changes distributed throughout the population, rather than large and potentially significant changes within a small sub-population. 5. Our data indicate that large, adaptive changes in the gain of the VOR are accompanied by only minor changes in the vestibular sensitivity and no changes in the phase shift or resting discharge rates of cells in the MVN. It remains possible that large changes in vestibular sensitivity occurred in cells we did not sample or in subgroups we could not identify. We argue that this is unlikely and that the major changes underlying VOR plasticity occur after the first central synapse in the VOR pathways.     

Inbred mouse strains differ in the regulation of startle and prepulse inhibition of the startle response.

The startle response and adaptability of the startle response (prepulse inhibition and habituation) have been observed in animals. The studies reported here screened 8 inbred mouse strains to determine whether genetic factors influence these behaviors. Strain differences were found in both the sensitivity to acoustic startle and the magnitude of both the auditory and tactile startle as well as the magnitude of prepulse inhibition (PPI) of both tactile and acoustic startle. Neither the 2 startle responses nor the 2 forms of PPI were significantly correlated with one another, suggesting that different genes regulate these 2 forms of startle and PPI. Acoustic-acoustic PPI was significantly correlated, however, with hippocampal auditory gating (TC ratio) suggesting an overlap in the genes that regulate these 2 forms of sensory gating. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

COMT genetic variation affects fear processing: Psychophysiological evidence.

Emotional dysregulation is a core characteristic of many psychiatric diseases, including the anxiety disorders. Although heritable influences account for a significant degree of variation in risk for such disorders, relatively few candidate susceptibility factors have been identified. A coding variant in one such gene, encoding the dopamine catabolic enzyme catechol-O-methyltransferase (COMT Val158Met), has previously been associated with anxiety and with anxiety-related temperament and altered neural responses to affective stimuli in healthy individuals. In 96 healthy women recruited from a sample of 800 participants according to genotype, the authors tested for an association between the DRD2/ANKK1 Taq Ia, the COMT Val158Met, and a psychophysiological measure of emotion processing, the acoustic affective startle reflex modulation (ASRM) paradigm, and found that COMT genotype significantly affected startle reflex modulation by aversive stimuli, with Met158 homozygotes exhibiting a markedly potentiated startle reflex compared with Val158 carriers. A trait measure of anxiety (Gray's Behavioral Inhibition System; J. A. Gray & N. McNaughton, 2000) was also associated with ASRM. The functional polymorphism in the dopamine D2 receptor (DRD2/ANKK1 Taq Ia) had no effect on startle modulation. The findings support prior genetic and neuroimaging associations of the COMT 158Met allele to affective psychopathology and alterations in neural systems for emotional arousal and regulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of myelin basic protein and proteolipid protein genes in multiple sclerosis: single strand conformation polymorphism analysis of the human sequences

Susceptibility to multiple sclerosis (MS) is widely held to have a strong genetic component. While the identities of genes conferring susceptibility are currently unknown, possible candidates include those genes coding for proteins which function in central nervous system (CNS) myelin. Two such genes are the human myelin basic protein (MBP) and proteolipid protein (PLP) genes, whose products make up approximately 80% of the total protein in CNS myelin. The association of a variable number tandem repeat (VNTR) 5' to the human MBP gene with MS has been the subject of conflicting reports. Here we test the hypothesis that mutations in the human MBP and PLP genes might be associated with MS by examining the entire expressed sequence of both genes by single strand conformation polymorphism (SSCP) analysis, using a panel of 71 MS patients and 71 controls. We have also re-examined the VNTR region in patients and controls. Three base changes were found in the human PLP gene and nine base changes in the human MBP gene; these were essentially equally distributed between patients and controls. No preferential distribution of various alleles of the VNTR between patients and controls was found. Although intronic and regulatory regions have not been examined, it would appear unlikely that mutations in these genes coding for the two major CNS myelin proteins contribute significantly to genetic susceptibility to MS.     

Rx for hand pieces: preventive maintenance key to long life

Patients with hemispheric lesions frequently suffer from equilibrium impairment that may be prolonged and may interfere with rehabilitation. In an effort to clarify whether this phenomenon is related to vestibular dysfunction, we examined the relationship of the horizontal vestibulo-ocular reflex (VOR) with stability in 15 patients with unilateral hemispheric stroke. The study included electro-oculographic recording of the VOR while the patients were rotated in a vestibular chair. Stability was scored in accordance with the patients' ability to maintain equilibrium in six graded positions. The findings demonstrated relationship between VOR gain (eye/head displacement) and equilibrium. It is suggested that the "loss of balance" after stroke may be related to an impairment of the corticovestibular modulation of the vestibular function.     

Studies on Neisseria gonorrhoeae strains from test-of-cure specimens. Correlation between the in vitro susceptibility to penicillin and the sensitivity to the complement-dependent bactericidal activity of normal and convalescent human serum

Sixty-seven out of 88 Neisseria gonorrhoeae strains isolated from test-of-cure (TOC) specimens during a five-months' period were included in the study. For 62 patients sufficient information was obtained in order to distinguish between relapse (34 ptt) and re-infection (28 ptt). For comparison with strains from these two groups of patients, 63 urogenital and 21 pharyngeal gonococcal strains isolated during the same period of time were randomly selected. The distributions according to susceptibility to penicillin for TOC strains and control strains corresponded to those found for the total number of TOC strains (275) and other strains (3,345) tested in 1979, respectively. The TOC strains did not differ from the control strains in sensitivity to the complement-dependent. The TOC strains did not differ from the control strains in sensitivity to the complement-dependent bactericidal activity of normal human serum. However, gonococcal strains less susceptible to penicillin in vitro (MIC values within the range 0.1-2.0 microgram/ml) were significantly more sensitive to the complement-dependent activity of normal human serum (P less than 0.01) than strains fully susceptible to penicillin (MIC less than 0.01 microgram/ml.) Penicillin-resistant strains (MIC greater than 2.0 microgram/ml) did not differ from strains susceptible to less than 0.1 microgram penicillin/ml and were slightly more serum-resistant than the less susceptible strains (P less than 0.05). No difference in serum-sensitivity of urogenital and pharyngeal isolates could be demonstrated. The level of bactericidal activity of homologous convalescent serum was unrelated to the presence of antibodies either to gonococcal pili or crude gonococcal antigen preparations. The sensitivity to normal human serum of a certain strain was not correlated with sensitivity to homologous convalescent serum.     

Genetic factors in multiple sclerosis

OBJECTIVE: To evaluate the role of candidate genes in the susceptibility to multiple sclerosis (MS) and describe the role of T-cell receptor (TCR) gene rearrangements in the MS brain lesion in identifying a major target of the immune response in this disease. DATA SOURCES: MEDLINE, bibliography review of published data, and unpublished studies. STUDY SELECTION: Published studies using novel molecular approaches to analyze the role of the major histocompatibility complex (MHC) and TCR gene complexes, as well as other candidate genes, in susceptibility to MS. We analyze epigenetic events involving TCR genes in individuals with MS and describe recent clinical trials in which immunotherapy has been attempted. DATA SYNTHESIS: Consistent with a polygenic model for disease predisposition, MHC and TCR gene associations with MS are relatively weak. Despite intensive research, no other putative "MS genes" have been firmly established. The analysis of TCR rearrangements in the brain lesion has helped to identify a major target of the immune response in MS. CONCLUSION: Understanding the genetic basis for autoimmune demyelination will offer new possibilities for the treatment of this illness.