OCT-angiography: Regional reduced macula microcirculation in ocular hypertensive and pre-perimetric glaucoma patients.

PURPOSE: OCT-angiography (OCT-A) offers a non-invasive method to visualize retinochoroidal microvasculature. As glaucoma disease affects retinal ganglion cells in the macula, macular microcirculation is of interest. The purpose of the study was to investigate regional macular vascular characteristics in patients with ocular hypertension (OHT), pre-perimetric primary open-angle glaucoma (pre-POAG) and controls by OCT-A in three microvascular layers. MATERIAL AND METHODS: 180 subjects were recruited from the Erlangen Glaucoma Registry, the Department of Ophthalmology, University of Erlangen and residents: 38 OHT, 20 pre-POAG, 122 controls. All subjects received an ophthalmological examination including measurements of retinal nerve fibre layer (RNFL), retinal ganglion cell layer (RGC), inner nuclear layer (INL), and Bruch's Membrane Opening-Minimum Rim Width (BMO-MRW). Macular vascular characteristics (vessel density, VD, foveal avascular zone, FAZ) were measured by OCT-A (Spectralis OCT II) in superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). RESULTS: With age correction of VD data, type 3 tests on fixed effects showed a significant interaction between diagnosis and sectorial VD in SVP (p = 0.0004), ICP (p = 0.0073), and DCP (p = 0.0003). Moreover, a significance in sectorial VD was observed within each layer (p<0.0001) and for the covariate age (p<0.0001). FAZ differed significantly between patients' groups only in ICP (p = 0.03), not in SVP and DCP. For VD the AUC values of SVP, ICP, and DCP were highest among diagnostic modalities (AUC: 0.88, 95%-CI: 0.75-1.0, p<0.001). CONCLUSION: Regional reduced macula VD was observed in all three retinal vascular layers of eyes with OHT and pre-POAG compared to controls, indicating localized microvascular changes as early marker in glaucoma pathogenesis.

Topographic correlation between macular superficial microvessel density and ganglion cell-inner plexiform layer thickness in glaucoma-suspect and early normal-tension glaucoma.

BACKGROUND/AIMS: To investigate the topographic relationship between macular superficial microvessel density (SMD) and macular ganglion cell-inner plexiform layer (GCIPL) thickness in eyes with glaucoma-suspect (GS) and early normal-tension glaucoma (NTG). METHODS: A total of 86 eyes of 86 patients with early NTG (standard automated perimetry mean deviation >-5.5 decibels) and a total of 25 eyes of 25 patients with GS were retrospectively reviewed. All of the subjects underwent optical coherence tomography (OCT) and OCT angiography (OCTA) scan. On the OCTA scan images, macular SMD was analysed by customised software. RESULTS: In GS and patients with early NTG, macular GCIPL thickness showed significant correlations with macular SMD in the superotemporal (ST), inferotemporal (IT) and inferoinferior (II) sectors (r=0.191, 0.373 and 0.346 for ST, IT and II sector, respectively). Additionally, circumpapillary retinal nerve fibre layer (RNFL) thickness and macular SMD showed significant correlations between the ST sector of the macula and the 1, 9 clock-hour peripapillary regions and between the IT and II sectors of the macula and the 6, 7, 8 clock-hour peripapillary regions. The IT sector macular SMD showed fair diagnostic power (area under the receiver operating characteristic curve [AUROC] = 0.758) and showed high diagnostic power when combined with IT sector macular GCIPL thickness (AUROC=0.954). CONCLUSIONS: Sectoral macular SMD showed topographic correlations with macular GCIPL thickness and circumpapillary RNFL thickness in patients with GS and early-stage NTG. Macular SMD analysis is potentially useful in the clinical evaluation of early glaucoma.

Accuracy of peripapillary versus macular vessel density in diagnosis of early to advanced primary open angle glaucoma.

PURPOSE: To evaluate macular and peripapillary vessel density (mVD, pVD) using optical coherence tomography angiography (OCT-A) in healthy subjects, patients with ocular hypertension (OHT) and primary open-angle glaucoma (POAG) patients. METHODS: In this prospective observational study, OCT-A images were obtained from 60 eyes of 36 healthy, ocular hypertension (OHT), preperimetric glaucoma (PPG), early glaucoma (EG) and moderate and advanced POAG subjects. Superficial mVD was acquired over a 6×6-mm cube centered on the foveal avascular zone and pVD over a 4.5×4.5-mm cube centered on the optic disc. Peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell complex (GCC) thickness was calculated using spectral-domain OCT. Correlations between vascular, structural and Humphrey VF indices were evaluated (Spearman's rank correlation coefficient). RESULTS: Median pVD and mVD in the PPG eyes were lower than in healthy eyes (51.87% and 47.23% versus 55.70% and 53.61%, respectively; P<0.001 and P=0.003), but higher than in mild glaucoma eyes (46.21% and 41.98%, P<0.001 compared to normal eyes) and moderate to advanced glaucoma eyes (37.45% and 39.89%, P<0.0001 compared to normal eyes). The highest correlations were found between structural parameters and pVD (r=0.87 and 0.86 for pRNFL and GCC, P<0.0001), followed by mVD (r=0.69 for both pRNFL and GCC, P<0.0001). Correlations with mean VF sensitivity were similar for pVD and mVD (r=0.61 and 0.56) and for GCC and pRNFL (r=0.60 and 0.52, P<0.0001 for all). CONCLUSIONS: VD measured with OCT-A shows reduction in POAG. Detection of this damage differentiates PPG from normal and perimetric POAG eyes with a high correlation with structural parameters. Peripapillary VD accuracy is higher than mVD in detecting the disease. These results suggest that OCT-A could improve POAG diagnosis and understanding of the pathophysiologic mechanisms behind glaucoma.

Early detection of macular and peripapillary changes with spectralis optical coherence tomography in patients with prediabetes.

PURPOSE: To compare the retina ganglion cell complex (GCC) layer and peripapillary nerve fibre layer thickness (pRNFL) in patients with prediabetes and healthy subjects analysed by spectral domain optical coherence tomography (SD-OCT). METHODS: This cross-sectional and comparative study included prediabetic patients and healthy subjects. All participants underwent SD-OCT measurement of pRNFL thickness, and GCC thickness. RESULTS: A total of 30 eyes of the 30 patients with prediabetes and 30 eyes of 30 controls were included. The overall calculated pRNFL thicknesses were similar between the prediabetic and control subjects. The GCC thickness was significantly lower in all quadrants of the inner macula, and outer nasal quadrant in the prediabetes group when compared to the control group. CONCLUSION: Our study demonstrated that inner macular GCC thickness was significantly thinner in prediabetic subjects. As a result neurodegeneration may play role in the thinning of GCC.

[Progression of nerve fiber layer defects in retrobulbar optic neuritis by the macular ganglion cell complex]. / Évolution des déficits des fibres optiques dans les névrites optiques rétrobulbaires par le complexe ganglionnaire maculaire.

INTRODUCTION: Recent studies with SD OCT had shown early axonal damage to the macular ganglion cell complex (which consists of the three innermost layers of the retina: Inner Plexiform Layer [IPL], Ganglion Cell Layer [GCL], Retinal Nerve Fibre layer [RNFL]) in optic nerve pathology. Retrobulbar optic neuritis (RBON), occurring frequently in demyelinating diseases, leads to atrophy of the optic nerve fibers at the level of the ganglion cell axons, previously described in the literature. The goal of this study is to evaluate the progression of optic nerve fiber defects and macular ganglion cell complex defects with the SPECTRALIS OCT via a reproducible method by calculating a mean thickness in each quadrant after an episode of retrobulbar optic neuritis. METHODS: This is a prospective monocentric observational study including 8 patients at the Clermont-Ferrand university medical center. All patients underwent ocular examination with macular and disc OCT analysis and a Goldmann visual field at the time of inclusion (onset or recurrence of RBON), at 3 months and at 6 months. RESULTS: Patients were 40-years-old on average at the time of inclusion. After 6 months of follow-up, there was progression of the atrophy of the macular ganglion cell complex in the affected eye on (11.5% or 11µm) predominantly inferonasally (13.9% or 16µm) and superonasally (12.9% or 14µm) while the other eye remained stable. The decrease in thickness occurred mainly in the most internal 3 layers of the retina. On average, the loss in thickness of the peripapillary RNFL was predominantly inferotemporal (24.9% or 39µm) and superotemporal (21.8% or 28µm). DISCUSSION: In 3 months of progression, the loss of optic nerve fibers is already seen on macular and disc OCT after an episode of RBON, especially in inferior quadrants in spite of the improvement in the Goldmann visual field and visual acuity. Segmentation by quadrant was used here to compare the progression of the defect by region compared to the fovea in a global and reproducible way. The loss of thickness, predominantly inferonasally and superonasally, appears to correspond to the temporal loss on optic nerve OCT according to the literature. CONCLUSION: The follow-up of these patients with retrobulbar neuritis is important as shown by the possibility of relapse, especially in multiple sclerosis. Monitoring of the macular ganglion cell complex by a global method of calculation could contribute to the detection and localization of early damage after an episode of retrobulbar neuritis. This could possibly lead to a discussion of treatment modification or increased surveillance in cases of early detection of nerve fiber atrophy, or to showing the importance of monitoring, since monitoring of RBON is not standardized.

Changes in Macular Retinal Layers and Peripapillary Nerve Fiber Layer Thickness after 577-nm Pattern Scanning Laser in Patients with Diabetic Retinopathy.

PURPOSE: The aim of this study was to evaluate the changes in thickness of each macular retinal layer, the peripapillary retinal nerve fiber layer (RNFL), and central macular thickness (CMT) after 577-nm pattern scanning laser (PASCAL) photocoagulation in patients with diabetic retinopathy. METHODS: This retrospective study included 33 eyes with diabetic retinopathy that underwent 577-nm PASCAL photocoagulation. Each retinal layer thickness, peripapillary RNFL thickness, and CMT were measured by spectral-domain optical coherence tomography before 577-nm PASCAL photocoagulation, as well as at 1, 6, and 12 months after 577-nm PASCAL photocoagulation. Computerized intraretinal segmentation of optical coherence tomography was performed to identify the thickness of each retinal layer. RESULTS: The average thickness of the RNFL, ganglion cell layer, inner plexiform layer, inner nuclear layer, inner retinal layer, and CMT at each follow-up increased significantly from baseline (p < 0.001), whereas that of the retinal pigment epithelium at each follow-up decreased significantly from baseline (p < 0.001). The average thickness of the peripapillary RNFL increased significantly at one month (p < 0.001). This thickness subsequently recovered to 7.48 µm, and there were no significant changes at six or 12 months compared to baseline (p > 0.05). CONCLUSIONS: Each macular retinal layer and CMT had a tendency to increase for one year after 577-nm PASCAL photocoagulation, whereas the average thickness of retinal pigment epithelium decreased at one-year follow-up compared to the baseline. Although an increase in peripapillary RNFL thickness was observed one month after 577-nm PASCAL photocoagulation, there were no significant changes at the one-year follow-up compared to the baseline.

Effects of hemodialysis on macular and retinal nerve fiber layer thicknesses in non-diabetic patients with end stage renal failure.

OBJECTIVES: To evaluate the thicknesses of retinal nerve fiber layer (RNFL) and macula by fourier-domain (FD) optical coherence tomography (OCT) in non-diabetic patients with end-stage-renal-failure (ESRF) undergoing hemodialysis (HD). METHODS: This is a prospective and observational study. Both eyes of 20 patients receiving HD (group 1) and 34 control patients (group 2) were evaluated by FD-OCT. Macular and RNFL thicknesses were compared between groups and their correlation with age, duration of HD, and gender were examined. In group 1, macular and RNFL thicknesses were evaluated before and shortly after HD in the first day, first and sixth months.   RESULTS: In group 1, pre-HD temporal, inferior, average RNFL thicknesses were thinner than group 2. This thinning did not correlate with duration of HD, age and gender. Pre-HD macular thicknesses were thinner than group 2. These thinnings did not correlate with age, but the thinnings at superior, nasal and average thickness correlated negatively with duration of HD. Nasal, temporal, and average macular thicknesses were thinner in female patients. The thickenings of RNFL and macula that were observed in the after HD first day and first month did not showed consistency in the sixth month except superior quadrant RNFL. CONCLUSION: Macular and RNFL thicknesses of patients receiving HD were less than the normal population. Age has no effect on these thinnings. The duration of HD affects more than gender. Hemodialysis  session  causes a consistent increase in superior quadrant RNFL.

PREVALENCE AND ASSOCIATIONS OF MYELINATED RETINAL NERVE FIBERS: Results From the Population-Based Gutenberg Health Study.

PURPOSE: To determine the prevalence, ocular, and systemic associations of myelinated retinal nerve fibers (MRNF) in a Caucasian cohort. METHODS: The Gutenberg Health Study (GHS) is a population-based, prospective cohort study encompassing 15,010 subjects in Germany. Gutenberg Health Study participants, aged 35 to 74 years, stratified for gender, decades of age, and residence were examined for ophthalmologic and systemic conditions. Optic disc centered and macular photographs were reviewed for the presence of MRNF. RESULTS: In 25,728 eyes of 12,906 participants (86.0% of the cohort), the prevalence of MRNF was 0.4%. In a binary logistic regression analysis, MRNF was positively associated with history of stroke (OR, 6.8; 95% CI, 2.9-16.1; P < 0.001). Myelinated retinal nerve fibers was not associated with age, sex, cardiovascular conditions other than stroke or ocular parameters, such as refraction, visual acuity, intraocular pressure, or central corneal thickness. CONCLUSION: This population-based study provides novel data on the prevalence of MRNF in Western Europe. We report a positive association between history of stroke and MRNF. It adds an additional retinal sign for stroke and calls for further studying of the behavior of oligodendrocytes within cerebrovascular diseases.

Multivariable logistic regression model: a novel mathematical model that predicts visual field sensitivity from macular ganglion cell complex thickness in glaucoma.

PURPOSE: To design a mathematical model that can predict the relationship between the ganglion cell complex (GCC) thickness and visual field sensitivity (VFS) in glaucoma patients. DESIGN: Retrospective cross-sectional case series. METHOD: Within 3 months from VFS measurements by the Humphrey field analyzer 10-2 program, 83 eyes underwent macular GCC thickness measurements by spectral-domain optical coherence tomography (SD-OCT). Data were used to construct a multiple logistic model that depicted the relationship between the explanatory variables (GCC thickness, age, sex, and spherical equivalent of refractive errors) determined by a regression analysis and the mean VFS corresponding to the SD-OCT scanned area. Analyses were performed in half or 8 segmented local areas as well as in whole scanned areas. A simple logistic model that included GCC thickness as the single explanatory variable was also constructed. The ability of the logistic models to depict the real GCC thickness/VFS in SAP distribution was analyzed by the χ2 test of goodness-of-fit. The significance of the model effect was analyzed by analysis of variance (ANOVA). RESULTS: Scatter plots between the GCC thickness and the mean VFS showed sigmoid curves. The χ2 test of goodness-of-fit revealed that the multiple logistic models showed a good fit for the real GCC thickness/VFS distribution in all areas except the nasal-inferior-outer area. ANOVA revealed that all of the multiple logistic models significantly predicted the VFS based on the explanatory variables. Although simple logistic models also exhibited significant VFS predictability based on the GCC thickness, the model effect was less than that observed for the multiple logistic models. CONCLUSIONS: The currently proposed logistic models are useful methods for depicting relationships between the explanatory variables, including the GCC thickness, and the mean VFS in glaucoma patients.

Retinal architecture predicts pupillary reflex metrics in MS.

OBJECTIVE: To study the relation of retinal nerve fiber layer thinning to clinical and physiologic measures of visual function in patients with MS or neuromyelitis optica and unilateral optic neuropathy. METHODS: We studied a cohort of control subjects (n = 64) and patients (n = 24) with evidence of unilateral thinning of their average retinal nerve fiber layer as measured by optical coherence tomography in order to characterize the relationship between ganglion cell axonal degeneration and its impact upon vision and pupillary light reflex metrics using infrared pupillometry. RESULTS: When compared to the normal fellow eye, and with respect to normal subjects' eyes, we confirmed significant abnormalities in retinal nerve fiber layer thickness, total macular volume, low-contrast letter acuity, and pupillary reflex metrics in the eye with the thinner retinal nerve fiber layer. For each -5% change in pupil diameter, there was a corresponding 7.1 Amicrom reduction in the average retinal nerve fiber layer thickness. There was a significant difference between the pupillary metric of percent change in diameter and a decrease in low-contrast letter acuity (P < 0.001). Each -5% change in pupil diameter was associated with a substantial 3.4 line loss of low-contrast letter acuity (P < 0.001). Each -5% change in pupil diameter was associated with a 0.2 mm(2) decrease in total macular volume (P < 0.001). CONCLUSION: These findings further corroborate the hypothesis that the retina can be utilized as a model to advance our understanding of the mechanisms of axonal and neurodegeneration, and the corresponding impact of these processes upon the pathophysiology of MS and related disorders.

Age-related decline in VIP-positive parasympathetic nerve fibers in the human submacular choroid.

PURPOSE: An age-related decline in macular choroidal blood flow (ChBF) occurs in humans. Vasodilatory nerve fibers containing vasoactive intestinal polypeptide (VIP) innervate choroidal blood vessels. The current study was conducted to examine the possibility that an age-related loss of these fibers might occur in the submacular choroid in humans, and thus contribute to a decline in ChBF. METHODS: Macular choroid punches were collected from 35 healthy human donors ranging from 21 to 93 years of age. Choroidal samples were immunolabeled using anti-VIP and the peroxidase-antiperoxidase METHOD: VIP-positive nerve fiber abundance was quantified in up to 12 fields per punch. Fifty macular punches were analyzed, and results for eye pairs were averaged. Choroidal vessel diameter (ChVD) was measured for these same fields. The relationship between age and vessel diameter or VIP-positive fiber abundance was analyzed. Multivariate statistical models were generated correcting for gender, variables related to the tissue specimens, and potential procedural sources of variability. RESULTS: The fully adjusted multivariate models showed a significant age-related reduction in both the VIP-positive fiber abundance (P = 0.0003, adjusted R(2) = 0.51) and ChVD (P < 0.0001, adjusted R(2) = 0.63), with slopes of -0.45 and -0.19, respectively. Adjusting for the same variables, VIP-positive fiber abundance showed a significant direct correlation with ChVD. CONCLUSIONS: The results indicate a significant age-related decline in VIP-positive nerve fibers and vessel diameter in the submacular choroid in disease-free human donor eyes. These findings suggest that a decline in the neural control of ChBF and vessel diameter may explain the reductions in ChBF and its adaptive control observed clinically with aging.

Macular nerve fibers temporal to fovea may have a greater potential to recover function in patients with Leber's hereditary optic neuropathy.

PURPOSE: It is known that even after visual loss, younger patients with Leber's hereditary optic neuropathy (LHON) can recover vision. The purpose of this study was to determine the mean age at onset for LHON patients with and without visual recovery who carried the 11778 mutation, and to determine the pattern of central vision recovery. METHODS: Thirty-five LHON patients with the 11778 mutation of mitochondrial DNA who had visited the Keio University Hospital between 1980 and 1999 and were followed for 2 to 20 years, were the subjects of this retrospective study. The patients who had recovered vision were tested by Goldmann perimetry, Humphrey perimetry, and landmark-driven fundus microperimetry with a scanning laser ophthalmoscope (SLO). The fixation status was assessed by SLO microperimetry. RESULTS: Nine of the 35 patients (14 of 70 eyes) demonstrated a recovery of visual acuity to better than 0.3 in at least one eye. The mean age of disease onset was 15.9 +/- 4.6 years in patients with visual recovery and 25.5 +/- 8.9 years in patients without visual recovery. This difference in the mean age at onset was significant (P =.0001; Welch t-test). These 9 patients (14 eyes) showed fenestrated central scotomas in testing by Humphrey 10-2 threshold and SLO microperimetry. The nasal side of the central visual fields had a higher sensitivity than the temporal side in 7 of the 9 patients in Humphrey 10-2 threshold testing. Areas insensitive to 0 dB were detected on the nasal side of the central retina in these patients by SLO microperimetry, and fixation stability was related to the degree of clinical visual acuity. CONCLUSION: The LHON patients with the 11778 mutation and a younger age of onset were more likely to show visual recovery. The findings made by perimetry suggest that the nerve fiber bundles in the nasal field (retina temporal to the fovea) may have a greater potential to recover function in LHON patients.

Homonymous defect of macular vision in ischemic stroke.

It is generally believed that a homonymous defect of macular vision (HMV) is caused by a small lesion restricted to the occipital lobe tip and rarely results from ischemic stroke. The incidence of HMV was studied retrospectively in 54 patients with infarction of the posterior cerebral artery territory who underwent Goldmann's visual field test. HMV was found in 6 patients (11%). In all of them, HMV was first dismissed due to a confrontation test of visual fields at the bedside and later detected by Goldmann's visual field test. All had a relatively large infarction extending from the occipital lobe tip to the posterior part of the calcarine cortex and/or the neighboring subcortical regions. Stroke-induced HMV can be caused by a large lesion involving the occipital pole and may not be so rare as generally considered.

Evaluation of the retinal nerve fiber layer thickness in eyes with idiopathic macular holes.

PURPOSE: To compare the retinal nerve fiber layer thickness in eyes with idiopathic macular holes and age-matched normal controls using scanning laser polarimeter. METHODS: The retinal nerve fiber layer thickness was measured in 40 eyes of 40 consecutive patients with idiopathic macular hole (stage 1, 10 eyes; stage 2, eight eyes; stage 3, 15 eyes; stage 4, seven eyes) and 40 eyes of 40 age-matched normal controls with a scanning laser polarimeter. The retinal nerve fiber layer thickness within a 10-pixel-wide ellipse located concentrically with the disk and located 1.5-disk diameters from the center of the disk was measured. The mean overall retinal nerve fiber layer thickness of the peripapillary retina, four 90-degree quadrants, and 16 equal sectors of every 22.5 degrees was calculated for both groups. The retinal nerve fiber layer thickness in the two groups was statistically compared. RESULTS: The mean retinal nerve fiber layer thickness measurement for the overall peripapillary retina and for three of the four 90-degree quadrants was not significantly different between the two groups. However, the temporal 90-degree quadrant was significantly thinner in the macular hole group (47.2 versus 54.6 microm, P =.026). For the 16 sectors of 22.5 degrees, the lower three sectors of the four sectors in the temporal quadrant were thinner in the macular hole group (P <.05). CONCLUSIONS: The retinal nerve fiber layer thickness of the papillomacular area is thinner in eyes with idiopathic macular hole than that in normal eyes. The progressive thinning of the retinal nerve fiber layer thickness as the stage of the macular hole advances may suggest that surgery should be done at the earliest stage.

Convergence and interaction of neck and macular vestibular inputs on reticulospinal neurons.

Extracellular recordings were obtained in decerebrate cats from neurons located in the inhibitory area of the medullary reticular formation, namely in the medial aspects of the nucleus reticularis gigantocellularis, magnocellularis and ventralis. Of 127 medullary reticular units examined, 77 were reticulospinal neurons antidromically identified following stimulation of the spinal cord at T12-L1; the remaining 50 neurons were not activated antidromically. Unit firing rate was analyzed under separate stimulation of macular vestibular, neck, or combined receptors by using sinusoidal rotations about the longitudinal axis at 0.026 Hz, 10 peak amplitude. Among the 127 reticular units, 84 (66.1%) responded with a periodic modulation of their firing rate to roll tilt of the animal and 93 (73.2%) responded to neck rotation. Convergence of macular and neck inputs was found in 71/127 (55.9%) reticular neurons; in these units, the gain as well as the sensitivity of the first harmonic of response corresponded on the average to 0.49 +/- 0.41, SD imp/s/deg and 5.10 +/- 4.27, SD %/deg for the neck responses and to 0.40 +/- 0.39, SD imp/s/deg and 3.90 +/- 3.80, SD %/deg for the macular responses, respectively. Most of the convergent reticular units were maximally excited by the direction of stimulus orientation, the first hormonic or responses showing an average phase lead of about +42.7 with respect to neck position and +24.9 with respect to animal position. Two populations of convergent neurons were observed. The first group of units (58/71, i.e. 81.7%) showed reciprocal ("out of phase") responses to the two inputs in that they were mainly excited during side-down neck rotation, but inhibited during side-down animal tilt. The remaining group of units (13/71, i.e. 18.3%) showed parallel ("in phase") responses to the two inputs and they were mainly excited by side-down neck rotation and animal tilt. The response characteristics of medullary reticular neurons to the combined neck and macular inputs, elicited during head rotation, closely corresponded to those predicted by a vectorial summation of the individual neck and macular responses. In particular, "out of phase" units displayed small amplitudes and large phase leads of the responses with respect to head position, when both types of receptors were costimulated. In contrast, "in phase" units displayed large amplitude and small phase leads during head rotation.(ABSTRACT TRUNCATED AT 400 WORDS)