Gestational diabetes exacerbates maternal immune activation effects in the developing brain.

Maternal inflammation and diabetes increase the risk for psychiatric disorders in offspring. We hypothesized that these co-occurring risk factors may potentiate each other. To test this, we maternally exposed developing mice in utero to gestational diabetes mellitus (GDM) and/or maternal immune activation (MIA). Fetal mouse brains were exposed to either vehicle, GDM, MIA or GDM+MIA. At gestational day (GD) 12.5, GDM produced a hyperglycemic, hyperleptinemic maternal state, whereas MIA produced significant increases in proinflammatory cytokines and chemokines. Each condition alone resulted in an altered, inflammatory and neurodevelopmental transcriptome profile. In addition, GDM+MIA heightened the maternal inflammatory state and gave rise to a new, specific transcriptional response. This exacerbated response was associated with pathways implicated in psychiatric disorders, including dopamine neuron differentiation and innate immune response. Based on these data, we hypothesize that children born to GDM mothers and exposed to midgestation infections have an increased vulnerability to psychiatric disorder later in life, and this should be tested in follow-up epidemiological studies.

Seasonality of suicide behavior in Northwest Alaska: 1990-2009.

OBJECTIVES: Suicide is a leading cause of death worldwide, and disproportionately affects Indigenous populations. Seasonal suicide patterns are variable in the literature, and could offer novel approaches to the timing and focus of prevention efforts if better understood. With a suicide surveillance system in place since 1989, this study offers an unprecedented opportunity to explore seasonal variations in both fatal and non-fatal suicide behavior in an Indigenous Arctic region. STUDY DESIGN: Cross-sectional. METHODS: In this descriptive study, we analyzed data collected from 1990 to 2009 in the rural northwest region of Alaska, both graphically and using the chi-squared test for multinomials. RESULTS: We found a significant monthly variation for suicide attempts, with a peak in suicide behavior observed between April and August (P = 0.0002). Monthly variation was more pronounced among individuals ≤29 years of age, and was present in both males and females, although the seasonal pattern differed by sex. CONCLUSIONS: Our findings of a significant seasonal pattern in suicide behavior, with monthly variation (summer peak) in non-fatal suicide behavior among younger age groups, and among both males and females can assist planners in targeting subpopulations for prevention at different times of the year.

Oculomotor response to linear acceleration as induced by counter-rotation in supine subjects.

BACKGROUND: Horizontal nystagmus occurs in response to sinusoidal linear accelerations directed along an upright subject's Y (interaural) axis, and is proposed to be mediated by an utricular otolith mechanism. HYPOTHESIS: The otolith organs, composed of the utricles and saccules, provide a unique set of signals for any linear acceleration in 3-dimensional space. A supine subject under alternate changing directions of linear acceleration as induced by counter-rotation will receive alternate stimulation along the Y as well as the Z (dorsoventral) axis. We hypothesized that alternate horizontal and vertical nystagmus would be elicited as a result of the changing direction of linear acceleration. METHODS: A group of eight subjects in the supine position were exposed to counter-rotation at 0.16, 0.25, and 0.33 Hz. Vertical and horizontal eye movements were recorded simultaneously using the El-Mar eye and head tracking system. RESULTS: Horizontal nystagmus was observed in all supine subjects. The direction of the slow phase of nystagmus changed with directional changes in linear acceleration. Reversals in the direction of eye movements lagged behind the reversals in the direction of the acceleration. However, only two subjects exhibited alternating horizontal and vertical nystagmus as a result of changing axis of linear acceleration, from "along the Y axis" to "along the Z axis." CONCLUSION: We propose that the nystagmus induced in the supine subject was provoked by linear acceleration and largely an otolith-mediated reflex. The lack of vertical response could be due to the relative paucity of vestibular afferents information along the dorsoventral axis.

Visual influence on head shaking using the vestibular autorotation test.

In this study we investigated the vestibular system by recording eye movements in response to voluntary high-frequency head-only movements using the Vestibular Autorotation Test (VAT; Western System Research Inc., Los Angeles, California). Our objective was to evaluate if the VAT could be implemented as one of the screening tests for vestibular integrity in aircrews and potential pilots. We attempted to record horizontal and vertical eye movements using electrooculography and head velocity with calibrated rotational velocity sensors. The gain and phase of the input and output signals were computed by discrete Fourier analysis. Seated subjects were instructed to fixate on a real or imaginary target while making smooth head oscillations about the spinal axis in time to an audible cue from 0.5 to 6.0 Hz/during an 18-second test period. Test trials included two conditions in the light with subjects fixated on a real target (C1) or on an imaginary target on a blank screen (C2); three conditions in the dark in which subjects fixated on an imaginary target (C3), fixated on a remembered LED target in the dark after it was extinguished (C4), or fixated on a real target (C5). All the dark trials were performed after dark adaptation for 30 minutes. We were not able to obtain consistent vertical VOR response (when the subjects oscillated their head about the interaural axis) using the VAT. For horizontal eye movements from 2.0 to just over 4.7 Hz, when subjects fixated on an imaginary target, there was an unexpected and significant increase in the gain of the eye movement velocities in the dark as compared to the gain obtained in the light conditions. In the dark trials, the gain was significantly higher when the subjects fixated on an imaginary target as opposed to a real target. There was no difference in phase among all conditions. This test could potentially serve for preliminary screening for the integrity of the vestibular system as it is noninvasive and of short duration. However, caution must be exercised in controlling various variables. Extensive normative data are needed to properly assess this test as a screening tool for aircrews.

Spatial disorientation-implicated accidents in Canadian forces, 1982-92.

In a recent survey of CF18 aircrew human factors, 44% of pilots reported experience with spatial disorientation (SD), of whom 10% had experienced more than 3 episodes. In order to investigate further, we have completed a retrospective study of SD-implicated category A accidents (where an aircraft is destroyed, declared missing, or damaged beyond economic repair) in the Canadian Forces (CF) during 1982-92. An overview of all SD occurrences (including accidents and incidents) across aircraft types is also presented. Information was gathered concerning the genesis and severity of disorientation so that research effort and pilot training could be appropriately implemented. Mishap investigation summaries involving category A accidents where SD was implicated were obtained from the CF Directorate of Flight Safety and reviewed. We also examined in detail the Board of Inquiry Reports of these accidents. The role of disorientation in these accidents was assessed. There were 62 category A accidents between 1982-92 and, in 14, SD had been assigned as a possible cause factor in the accident records. When divided into the categories of Recognized SD (RSD), Unrecognized SD (USD), and Incapacitating SD (ISD), all but two fell into the category of USD (the pilots were unaware of the disorientation). Of the SD accidents, 11 involved a total loss of 24 lives. The majority of the accidents happened during the day, and pilots' cumulative flying experience did not appear to be a significant factor. According to our assessment, there were two episodes of vestibular origin, involving the somatogravic illusion. Three episodes of disorientation occurred over frozen lakes, one over glassy water, and one over ocean.(ABSTRACT TRUNCATED AT 250 WORDS)

Dynamics of torsional optokinetic nystagmus under altered gravitoinertial forces.

The purpose of the present study was to investigate the influence of varying gravitoinertial forces on torsional optokinetic nystagmus during parabolic flights. Using the scleral search-coil technique, we measured the gain and phase lag of torsional optokinetic nystagmus (OKN) induced by a hemispherical visual display rotating about the roll axis either at constant velocity or sinusoidally at various frequencies during level flight, hypogravity, and hypergravity. Compared with level flight, there was a significant increase in slow-phase eye velocity during hypogravity and an increase in nystagmic frequency. An absence of well-developed torsional optokinetic afternystagmus was observed in all three gravity conditions. Other characteristics included a lack of a slow rise component. These data suggest that otolith inputs do affect torsional optokinetic afternystagmus suggests that the velocity storage pathways do not contribute significantly to the torsional OKN system in humans.

Etiologic significance of arginine vasopressin in motion sickness.

There is abundant evidence implicating the role of arginine vasopressin in motion sickness. The effects of AVP analogs on motion sickness were investigated in squirrel monkeys. Two specific V1 antagonists (SK&F 100273 and SK&F 103561) and three mixed V1/V2 antagonists (SK&F 101926, SK&F 105494, and SK&F 104146-D) were tested on six highly susceptible monkeys. Intravenous injections of 200 ug of a V1 antagonist abolished emesis in all six monkeys, and few prodromal symptoms remained (latency to emesis > 120 minutes, P < .001). Mixed V1/V2 antagonists failed to abolish emesis in all monkeys. However, there was a slight increase in the latency to the first bout of emesis/retching with the mixed antagonists when compared with the baseline. The dose-response relationship and rate of onset of action of the V1 antagonists (SK&F 100273) were explored. Latency to the first bout of emesis/retching increased to about twice that of the baseline when half of the effective antiemetic dose was used. The efficacy demonstrated by the specific V1 antagonists indicates that V1 receptors may modulate emesis.

Human gaze instability during brief exposure to reduced gravity.

The stability of gaze in three dimensions (horizontal, vertical and torsional) was investigated with the electromagnetic scleral search-coil technique during the microgravity phase of parabolic flights under two visual fixation conditions: fixation on a real target and on an imagined target. Subjects were secured upright with the head immobilized by a dental bite. There were torsional eye movements in response to the imposition of reduced gravitoinertial forces under both visual fixation conditions. The pattern of these movements was consistent with our previous findings on six other subjects. No significant horizontal eye movements were observed in either fixation condition. Under the condition of fixation on an imagined target, direction-specific vertical nystagmus was observed with slow phase directed upwards during transition from hypergravity to microgravity. The slow phase was directed downwards during transition from microgravity to hypergravity, although the nystagmus was of lower frequency and the magnitude of the slow phase velocity appeared to be smaller than during transition from hypergravity to microgravity. The vertical eye movements could be attributed to a change of otolithic stimulation along the subject's z axis since the rate of pitch rotation of the aircraft during parabolic flight was too slow to produce an effective canal input. These kinds of reflex eye movements could degrade vision during manoeuvres or turbulence in flight.

Space vestibulo-neuroscience in the new century.

In the new century there will probably be more long spaceflights and fewer short spaceflights. There will probably be several flights to Mars, flights that (if chemical rockets are used) will involve one year to get there, a second year on Mars, and a third year to return. The three-year Mars scenario will probably include rotation of the spacecraft to provide artificial gravity. If nuclear thermal rockets are used, a manned exploration of Mars could be accomplished in less than one year. Vestibular research will be directed towards ensuring that astronauts, upon landing on Mars, will be able to walk with confidence and without delay. Research will be required to investigate vestibular adaptation in spaceflight, motion sickness, and the vestibular effects of rotation in spaceflight.

Accuracy of aimed arm movements in changed gravity.

We studied the accuracy of aimed arm movements in normal gravity, and during the hypergravity (hyper-G) and microgravity (micro-G) episodes of KC-135 parabolic flights. Subjects pointed at mirror-viewed targets without sight of their arm, and final pointing position was measured by a digitizing pad. Compared with the normal gravity (normal-G) baseline, subjects pointed consistently higher in hyper-G, and still higher in micro-G. Results were not different if subjects viewed targets only during normal-G and pointed at their memorized position under changed gravity (changed-G); this suggests that the "elevator illusion" played a minor role in our study. The observed impairments were attributed to degraded proprioceptive feedback and/or inappropriate motor programs in changed-G. Pointing accuracy improved movement-to-movement but not parabola-to-parabola, indicating that prolonged exposure is needed for sustained adaptation.

Investigation of anti-motion sickness drugs in the squirrel monkey.

Early attempts to develop an animal model for anti-motion sickness drugs, using dogs and cats; were unsuccessful. Dogs did not show a beneficial effect of scopolamine (probably the best single anti-motion sickness drug for humans thus far) and the findings in cats were not definitive. The authors have developed an animal model using the squirrel monkey (Saimiri sciureus) of the Bolivian phenotype. Unrestrained monkeys in a small lucite cage were tested in an apparatus that induces motion sickness by combining vertical oscillation and horizontal rotation in a visually unrestricted laboratory environment. Signs of motion sickness were scored using a rating scale. Ten susceptible monkeys (weighing 800-1000 g) were given a total of five tests each, to establish the baseline susceptibility level. Based on the anticholinergic activity of scopolamine, the sensitivity of squirrel monkey to scopolamine was investigated, and the appropriate dose of scopolamine for this species was determined. Then various anti-motion sickness preparations were administered in subsequent tests: 100 ug scopolamine per monkey; 140 ug dexedrine; 50 ug scopolamine plus 70 ug dexedrine; 100 ug scopolamine plus 140 ug dexedrine; 3 mg promethazine; 3 mg promethazine plus 3 mg ephedrine. All these preparations were significantly effective in preventing motion sickness in the monkeys. Ephedrine, by itself, which is marginally effective in humans, was ineffective in the monkeys at the doses tried (0.3-6.0 mg). The squirrel monkey appears to be a good animal model for antimotion sickness drugs. Peripherally acting antihistamines such as astemizole and terfenadine were found to be ineffective, whereas flunarizine, and an arginine vasopressin V1 antagonist, showed significant activity in preventing motion sickness.

Human ocular torsion during parabolic flights: an analysis with scleral search coil.

Rotation of the eyes about the visual axis is known as ocular torsion. A lateral inclination (a "roll") of the head induces ocular torsion in the opposite direction, a response known as ocular counterrolling. For six subjects, we recorded the static (head still) and dynamic (head in oscillatory roll motion) ocular torsion in normal 1 g condition and also during the microgravity and hypergravity periods of parabolic flight, using the electromagnetic scleral search coil technique. With the head still, the direction and magnitude of torsion that occurred in response to microgravity and hypergravity differed substantially from one individual to another, but there was a significant difference in torsional magnitude between the microgravity and hypergravity periods, for all static head positions including the upright position. Under normal 1 g conditions, counterrolling compensated for about 16% of (voluntary) static head roll, while dynamic counterroll was much larger, up to 36% of head roll at 0.55 Hz. With increasing frequency of head oscillation between 0.33 Hz and 0.55 Hz, the gain of counterrolling increased and there was no change in the phase relationship. The gain of dynamic counterroll (in response to voluntary head rolling) was not significantly less in hypogravity, suggesting that on the ground at these frequencies the contribution of gravity and gravity receptors to this reflex is redundant: this reflex is probably driven by the semicircular canals. In some subjects, the torsional displacement in microgravity is accompanied by micro-torsional oscillatory motion.

The influence of age on susceptibility to motion sickness in monkeys.

A longitudinal study on the effects of age on the susceptibility to motion sickness in the squirrel monkey was carried out over a 10-year period (1982 to 1991). The typical life span of squirrel monkeys is 15 years. Ten mature male squirrel monkeys of the Bolivian subspecies were found to be susceptible to motion sickness induced by a combination of vertical oscillation at 0.5 Hz and rotation in the horizontal plane at 25 rotations per minute (RPM) in a visually unrestricted environment. Signs of motion sickness were quantified according to a rating scale based on Graybiel's diagnostic criteria. Latency to vomiting/retching and severity of sickness obtained from year 1 (baseline), 3, 5, 7 and 10 were subjected to repeated-measures design analysis. There were no significant differences in the susceptibility level (as measured by latency to vomiting/retching and cumulative sickness scores) in the monkeys throughout the 10-year period. The habituation to 7 consecutive daily exposures remained the same throughout the same period. We conclude that, in the squirrel monkeys from maturity to near the end of their life span, there is no change in susceptibility to motion sickness with aging.

Visually-induced sickness in normal and bilaterally labyrinthine-defective subjects.

A group of nine normal subjects (with no overt vestibular dysfunction) and a group of 6 bilaterally labyrinthine-defective subjects were exposed to a visual field rotating about an Earth-horizontal axis (orthogonal to the gravity axis). The visual stimulus was provided by a 3-m diameter sphere with random dots rotating at 30, 45, and 60 degrees per second (degree/s) about the stationary subject's roll, pitch and yaw axes. The subject's head was positioned at the center of the sphere such that it experienced apparent motion in all three axes. Results indicated that in the normal group, symptoms of motion sickness were reported in 21 of 27 test-trials. When labyrinthine-defective subjects were exposed to the roll and pitch stimulus, no sickness symptoms were reported or observed. These results strongly suggest that the vestibular system is necessary for sickness induced by moving visual fields.

Instability of ocular torsion in zero gravity: possible implications for space motion sickness.

Inherent asymmetries of the gravity-sensitive otolith organs of the inner ear may be well-compensated in ordinary 1 G, but rendered unstable in novel gravitational states. Several aspects of ocular counterrolling and spontaneous eye torsion, reflexes governed by the otoliths, were examined during the hypo- and hypergravity in parabolic flight on the NASA KC-135 aircraft. Among the subjects were two astronauts, one who had suffered space motion sickness during his mission and one who had not. Using an observed separation of scores of torsional instability at 0 G as the criterion, we divided our 10 subjects into the 5 highest and 5 lowest scorers, reminiscent of the approximately 50% who do and the 50% who do not experience space motion sickness (SMS). The astronaut who had had SMS was in the high group; and the one who had not was in the low group. At 1.8 G, the groups defined at 0 G were significantly different in the instability measure. They were also significantly different at both 0 G and 1.8 G in another measure, that of torsional variability. There were no differences between the groups in amplitude of eye torsion in 0 G or 1.8 G. None of the tests were significantly different in 1 G. The results suggest that these tests of eye torsion on the KC-135 might differentiate those who would experience SMS from those who would not. Proof of this speculation awaits replication of the study using only astronaut subjects.

Motion sickness susceptibility and aerobic fitness: a longitudinal study.

A longitudinal study evaluated the susceptibility to motion sickness in initially unfit subjects before and after an endurance training program. Motion stimulation was provided by the Precision Angular Mover, in which the subject was tumbled head over heels about an Earth-horizontal axis at 20 cycles per minute in darkness. Maximal aerobic power and the blood lactate response to submaximal exercise were evaluated with cycle ergometry. The training program caused significant improvements in VO2max and endurance capacity, and a significant decrease in percent body fat. There was a significant (p less than 0.0125) increase in motion sickness susceptibility after the physical training, suggesting that increased physical fitness caused increased susceptibility to motion sickness in some individuals.

Visually-induced tilt during parabolic flights.

A helmet-mounted visual display system was used to study visually induced sensations of self-motion (vection) about the roll, pitch and yaw axes under normal gravity condition (1g) and during the microgravity and hypergravity phases of parabolic flights aboard the NASA KC-135 aircraft. Under each gravity condition, the following parameters were investigated: (1) the subject's perceived body vertical with eyes closed and with eyes open gazing at a stationary random dot display; (2) the magnitude of sensations of body tilt with respect to the subjective vertical, while the subject viewed displays rotating about the roll, pitch and yaw axes; (3) the magnitude of vection; (4) latency of vection. All eleven subjects perceived a definite "up and down" orientation throughout the course of the flight. During the microgravity phase, the average magnitudes of perceived body tilt and self-motion increased significantly, and there was no significant difference in vection latency. These results show that there is a rapid onset of increased dependence on visual inputs for perception of self-orientation and self-motion in weightlessness, and a decreased dependence on otolithic and somatosensory graviceptive information. Anti-motion sickness drugs appear not to affect the parameters measured.

An illusion of reversed direction in hyperopes.

If a subject who is sufficiently farsighted removes his corrective, positive, lenses and looks with one eye from a distance of one or a few meters, at a small lighted area such as the (continuously "on") indicator light of an electric toothbrush, razor, or smoke detector, and if a small object such as a pin is then moved slowly from above to below the subject's eyes (in a plane close to the eye), the subject will perceive the object moving normally from above to below until it encroaches on his view of the lighted area. The object will then be seen to encroach first on the bottom of the lighted area, and as the object continues to move down it will be seen to be moving up across the lighted area, exiting the lighted area at the top. Similarly, an object moved in front of the eye from the subject's left to his right will be seen by the subject to traverse the lighted area in the reverse direction, right to left, even though the subject moves the object himself. Also, while the object is in front of the lighted area, it is perceived as an upside down silhouette having surprisingly clear and sharp edges, and it appears to be located on the lighted area rather than close to the eye where it really is.