Increase In Vestibulo-ocular Reflex Gain Research Articles

Effect of a differential training paradigm with varying frequencies and amplitudes on adaptation of vestibulo-ocular reflex in mice.

The vestibulo-ocular reflex (VOR) functions to maintain eye stability during head movement, and VOR gain can be dynamically increased or decreased by gain-up or gain-down adaptation. In this study, we investigated the impact of a differential training paradigm with varying frequencies and amplitudes on the level of VOR adaptation in mice. Training for gain-up (out of phase) or gain-down (in phase) VOR adaptation was applied for 60min using two protocols: (1) oscillation of a drum and turntable with fixed frequency and differing amplitudes (0.5Hz/2.5°, 0.5Hz/5° and 0.5Hz/10°). (2) Oscillation of a drum and turntable with fixed amplitude and a differing frequency (0.25Hz/5°, 0.5Hz/5° and 1Hz/5°). VOR adaptation occurred distinctively in gain-up and gain-down learning. In gain-up VOR adaptation, the learned increase in VOR gain was greatest when trained with the same frequency and amplitude as the test stimulation, and VOR gain decreased after gain-up training with too high a frequency or amplitude. In gain-down VOR adaptation, the decrease in VOR gain increased as the training frequency or amplitude increased. These results suggest that different mechanisms are, at least in part, involved in gain-up and gain-down VOR adaptation.

Expression of a Form of Cerebellar Motor Memory Requires Learned Alterations to the Activity of Inhibitory Molecular Layer Interneurons.

Procedural memories formed in the cerebellum in response to motor errors depend on changes to Purkinje cell (PC) spiking patterns that correct movement when the erroneous context is repeated. Because molecular layer interneurons (MLIs) inhibit PCs, learning-induced changes to MLI output may participate in reshaping PC spiking patterns. However, it remains unclear whether error-driven learning alters MLI activity and whether such changes are necessary for the memory engram. We addressed this knowledge gap by measuring and manipulating MLI activity in the flocculus of both sexes of mice before and after vestibulo-ocular reflex (VOR) adaptation. We found that MLIs are activated during vestibular stimuli and that their population response exhibits a phase shift after the instantiation of gain-increase VOR adaptation, a type of error-driven learning thought to require climbing-fiber-mediated instructive signaling. Although acute optogenetic suppression of MLI activity did not affect baseline VOR performance, it negated the expression of gain-increase learning, demonstrating a specific role of MLI activity changes in motor memory expression. This effect was transitory; after a multiday consolidation period, the expression of VOR gain-increase learning was no longer sensitive to MLI activity suppression. Together, our results indicate that error-driven alteration of MLI activity is necessary for labile, climbing-fiber-induced motor memory expression.SIGNIFICANCE STATEMENT In the cerebellum, motor learning induces an associative memory of the sensorimotor context of an erroneous movement that, when recalled, results in a new pattern of output that improves subsequent trials of performance. Our study shows that error-driven motor learning induces changes to the activity pattern of cerebellar molecular layer interneurons (MLIs) and that this new pattern of activity is required to express the corrective motor memory.

Interface entre as medidas de benefício após a reabilitação vestibular – relato de casos

ABSTRACT The purpose of this research is to characterize the vestibular rehabilitation (VR), vestibulo-ocular reflex (VOR) gain, the occurrence of compensatory saccades, the static and dynamic balance, and the impact on quality of life in three patients with peripheral vestibular hypofunction. This is a descriptive study, approved by the ethics in research committee, under number 4,462.519. Three female patients participated in the study, two aged 55 and one aged 67, with a medical diagnosis of peripheral vestibular dysfunction. The participants underwent anamnesis, Dizziness Handicap Inventory (DHI) questionnaire, clinical assessment of postural balance and Video Head Impulse Test (vHIT), pre and post VR. The VR was applied in a personalized manner, based on the Cawthorne and Cooksey protocol, associated with virtual reality stimuli. After VR, a reduction in the total score average of DHI was observed, suggesting a decrease in participation restriction. The clinical balance assessment results were within the normal range for the altered tests, pre VR. In the three evaluated cases, vHIT showed increased RVO gain for the previously affected semicircular ducts (SCDs), compatible with normality standards, and reduction or extinction in the occurrence of compensatory saccades. The increase in VOR gain and the reduction or suppression of compensatory saccades after VR are suggestive signs of vestibular compensation. These results were compatible with increased postural stability and less restricted quality of life. These findings demonstrate the benefit provided by VR in the three evaluated cases.

Comparison of Incremental Vestibulo-ocular Reflex Adaptation Training Versus x1 Training in Patients With Chronic Peripheral Vestibular Hypofunction: A Two-Year Randomized Controlled Trial.

A crossover, double-blinded randomized controlled trial to investigate once-daily incremental vestibulo-ocular reflex (VOR) adaptation (IVA) training over 2 years in people with stable and chronic peripheral vestibular hypofunction. Twenty-one patients with peripheral vestibular hypofunction were randomly assigned to intervention-then-control (n = 12) or control-then-intervention (n = 9) groups. The task consisted of either x1 (control) or IVA training, once daily every day for 15 minutes over 6-months, followed by a 6-month washout, then repeated for arm 2 of the crossover. Primary outcome: vestibulo-ocular reflex gain. Secondary outcomes: compensatory saccades, dynamic visual acuity, static balance, gait, and subjective symptoms. Multiple imputation was used for missing data. Between-group differences were analyzed using a linear mixed model with repeated measures. On average patients trained once daily 4 days per week. IVA training resulted in significantly larger VOR gain increase (active: 20.6% ± 12.08%, P = 0.006; passive: 30.6% ± 25.45%, P = 0.016) compared with x1 training (active: -2.4% ± 12.88%, P = 0.99; passive: -0.6% ± 15.31%, P = 0.68) (P < 0.001). The increased IVA gain did not significantly reduce with approximately 27% persisting over the washout period. x1 training resulted in greater reduction of compensatory saccade latency (P = 0.04) and increase in amplitude (P = 0.02) compared with IVA training. There was no difference between groups in gait and balance measures; however, only the IVA group had improved total Dizziness Handicap Inventory (P = 0.006). Our results suggest IVA improves VOR gain and reduces perception of disability more than conventional x1 training. We suggest at least 4 weeks of once-daily 4 days-per-week IVA training should be part of a comprehensive vestibular rehabilitation program.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A356).

Once-Daily Incremental Vestibular-Ocular Reflex Adaptation Training in Patients With Chronic Peripheral Vestibular Hypofunction: A 1-Week Randomized Controlled Study

This was a double-blinded randomized controlled study to investigate the effects of once-daily incremental vestibulo-ocular reflex (VOR) training over 1 week in people with chronic peripheral vestibular hypofunction. A total of 24 patients with peripheral vestibular hypofunction were randomly assigned to intervention (n = 13) or control (n = 11) groups. Training consisted of either x1 (control) or incremental VOR adaptation exercises, delivered once daily for 15 minutes over 4 days in 1 week. Primary outcome: VOR gain with video-oculography. Secondary outcomes: Compensatory saccades measured using scleral search coils, dynamic visual acuity, static balance, gait, and subjective symptoms. Between-group differences were analyzed with a linear mixed-model with repeated measures. There was a difference in the VOR gain increase between groups (P < 0.05). The incremental training group gain increased during active (13.4% ± 16.3%) and passive (12.1% ± 19.9%) head impulse testing (P < 0.02), whereas it did not for the control group (P = 0.59). The control group had reduced compensatory saccade latency (P < 0.02). Both groups had similarly improved dynamic visual acuity scores (P < 0.05). Both groups had improved dynamic gait index scores (P < 0.002); however, only the incremental group had improved scores for the 2 walks involving head oscillations at approximately 2 Hz (horizontal: P < 0.05; vertical: P < 0.02), increased gait speed (P < 0.02), and step length (P < 0.01) during normal gait, and improved total Dizziness Handicap Inventory (P < 0.05). Our results suggest incremental VOR adaptation significantly improves gain, gait with head rotation, balance during gait, and symptoms in patients with chronic peripheral vestibular hypofunction more so than conventional x1 gaze-stabilizing exercises.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A336).

How Good Are We in Evaluating a Bedside Head Impulse Test?

Clinicians performing a horizontal head impulse test (HIT) are looking for a corrective saccade. The detection of such saccades is a challenge. The aim of this study is to assess an expert's likelihood of detecting corrective saccades in subjects with vestibular hypofunction. In a prospective cohort observational study at a tertiary referral hospital, we assessed 365 horizontal HITs performed clinically by an expert neurootologist from a convenience sample of seven patients with unilateral or bilateral deficient vestibulo-ocular reflex (VOR). All HITs were recorded simultaneously by video-oculography, as a gold standard. We evaluated saccades latency and amplitude, head velocity, and gain. Saccade amplitude was statistically the most significant parameter for saccade detection (p < 0.001).The probability of saccade detection was eight times higher for HIT toward the pathological side (p = 0.029). In addition, an increase in saccade amplitude resulted in an increased probability of detection (odds ratio [OR] 1.77 [1.31 to 2.40] per degree, p < 0.001). The sensitivity to detect a saccade amplitude of 1 degree was 92.9% and specificity 79%. Saccade latency and VOR gain did not significantly influence the probability of the physician identifying a saccade (OR 1.02 [0.94 to 1.11] per 10-msec latency and OR 0.84 [0.60 to 1.17] per 0.1 VOR gain increase). The saccade amplitude is the most important factor for accurate saccade detection in clinically performed head impulse tests. Contrary to current knowledge, saccade latency and VOR gain play a minor role in saccade detection.

Human vestibulo-ocular reflex adaptation is frequency selective

The vestibulo-ocular reflex (VOR) is the only system that maintains stable vision during rapid head rotations. The VOR gain (eye/head velocity) can be trained to increase using a vestibular-visual mismatch stimulus. We sought to determine whether low-frequency (sinusoidal) head rotation during training leads to changes in the VOR during high-frequency head rotation testing, where the VOR is more physiologically relevant. We tested eight normal subjects over three sessions. For training protocol 1, subjects performed active sinusoidal head rotations at 1.3 Hz while tracking a laser target, whose velocity incrementally increased relative to head velocity so that the VOR gain required to stabilize the target went from 1.1 to 2 over 15 min. Protocol 2 was the same as protocol 1, except that head rotations were at 0.5 Hz. For protocol 3, head rotation frequency incrementally increased from 0.5 to 2 Hz over 15 min, while the VOR gain required to stabilize the target was kept at 2. We measured the active and passive, sinusoidal (1.3Hz) and head impulse VOR gains before and after each protocol. Sinusoidal and head impulse VOR gains increased in protocols 1 and 3; however, although the sinusoidal VOR gain increase was ~20%, the related head impulse gain increase was only ~10%. Protocol 2 resulted in no-gain adaptation. These data show human VOR adaptation is frequency selective, suggesting that if one seeks to increase the higher-frequency VOR response, i.e., where it is physiologically most relevant, then higher-frequency head movements are required during training, e.g., head impulses.NEW & NOTEWORTHY This study shows that human vestibulo-ocular reflex adaptation is frequency selective at frequencies >0.3 Hz. The VOR in response to mid- (1.3 Hz) and high-frequency (impulse) head rotations were measured before and after mid-frequency sinusoidal VOR adaptation training, revealing that the mid-frequency gain change was higher than high-frequency gain change. Thus, if one seeks to increase the higher-frequency VOR response, where it is physiologically most relevant, then higher-frequency head movements are required during training.

Incremental Vestibulo-ocular Reflex Adaptation Training Dynamically Tailored for Each Individual.

Unilateral incremental vestibulo-ocular reflex (VOR) adaptation (IVA) increases the VOR gain (= eye/head velocity) for head rotations to one side by ∼10%. Prior IVA studies involved setting the initial VOR training gain demand at the subject's starting value (= 1 in a healthy subject), with the gain preset to increment by 0.1 every 90 seconds over 15 minutes, defined as Static IVA. We determined whether a dynamically calculated gain demand (= "actual gain" + 0.1) would result in greater adaptation, defined as Dynamic IVA. Using a hybrid video-oculography and StableEyes training system, we measured the active (self-generated head impulse) and passive (imposed, unpredictable head impulse) VOR gain in 8 healthy subjects before and after 15 minutes of Static (ie, preset) and Dynamic IVA training consisting of active, leftward and rightward, horizontal head impulses (peak amplitude 15°, peak velocity 150°/s, and peak acceleration 3000°/s). We also measured the active VOR gain during training. The VOR gain increase toward the adapting side was ∼5% larger after Dynamic compared with Static IVA training (Dynamic: 13.9% ± 5.2%, Static: 9.4% ± 7.3%; P < 0.05). Our data suggest that 17°/s retinal image slip (due to the 0.1 gain difference between demand and actual gain) is sufficient to drive robust VOR adaptation. The implications for vestibular rehabilitation are that Dynamic IVA training not only produces better VOR adaptation but also allows more flexible training, for example, training can be spread over several smaller time blocks, without undoing prior adaptation.

Postural and vestibular changes related to CPAP treatment in moderate-to-severe OSA patients: a 12-month longitudinal study.

To assess whether vestibulo-ocular reflex (VOR) gain, posturography parameters and related clinical outcomes can improve in OSA patients after 12months of CPAP treatment, taking into consideration that a certain degree of vestibular dysfunction has been identified in these subjects. Vestibular, postural, clinical, and polygraphic parameters were assessed in 32 OSA patients before and after beneficial CPAP treatment by means of video head impulse test (vHIT), static posturography (SP), Dizziness Handicap Inventory (DHI), Epworth Sleepiness Scale (ESS), and Apnea-Hypopnea Index (AHI), respectively, and were compared by means of a "within-subject" ANOVA model and Spearman's rank correlation. After the 12-month period of treatment, OSA patients demonstrated a significant reduction in AHI values, in both opened and closed eyes conditions of surface and length as well as in power spectra recorded in low, middle, and high frequency interval. Although a significant improvement was also recorded among DHI and ESS scores, VOR gain increase did not survive to post-hoc corrections. Finally, positive correlations between the differences between pre- and post-treatment AHI, ESS, and PS values were found. The present work highlighted that postural instability and dizziness-related conditions due to OSA may improve after 12months of CPAP treatment. Although VOR gain did not demonstrate significant improvement, this study might open future perspectives directed to assessing VOR gain changes after longer periods of CPAP treatment.

Human Vestibulo-Ocular Reflex Adaptation: Consolidation Time Between Repeated Training Blocks Improves Retention.

We sought to determine if separating vestibulo-ocular reflex (VOR) adaptation training into training blocks with a consolidation (rest) period in between repetitions would result in improved VOR adaptation and retention. Consolidation of motor learning refers to the brain benefitting from a rest period after prior exposure to motor training. The role of consolidation on VOR adaptation is unknown, though clinicians often recommend rest periods as a part of vestibular rehabilitation. The VOR is the main gaze stabilising system during rapid head movements. The VOR is highly plastic and its gain (eye/head velocity) can be increased via training that induces an incrementally increasing retinal image slip error signal to drive VOR adaptation. The unilateral incremental adaptation technique typically consists of one 15-min training block leading to an increase in VOR gain of ~ 10% towards the training side. We tested nine normal subjects, each over six separate sessions/days. Three training protocols/sessions were 5min each (1 × 5-min training) and three training protocols/sessions were 55min each. Each 55-min protocol comprised 5-min training, 20-min rest, 5-min training, 20-min rest, 5-min training (3 × 5-min training). Active and passive VOR gains were measured before and after training. For training with consolidation breaks, VOR gain retention was measured over 1h. The VOR gain increase after 1 × 5-min training was 3.1 ± 2.1% (P < 0.01). One might expect that repeating this training three times would result in × 3 total increase of 9.3%; however, the gain increase after 3 × 5-min training was only 7.1 ± 2.8% (P < 0.001), suggesting that consolidation did not improve VOR adaptation for our protocols. However, retention was improved by the addition of consolidation breaks, i.e. gains did not decrease over 1h (P = 0.43). These data suggest that for optimal retention VOR adaptation exercises should be performed over shorter repeated blocks.

Core Body Temperature Effects on the Mouse Vestibulo-ocular Reflex.

Core body temperature has been shown to affect vestibular end-organ and nerve afferents so that their resting discharge rate and sensitivity increase with temperature. Our aim was to determine whether these changes observed in extracellular nerve recordings of anaesthetized C57BL/6 mice corresponded to changes in the behavioural vestibulo-ocular reflex (VOR) of alert mice. The VOR drives eye rotations to keep images stable on the retina during head movements. We measured the VOR gain (eye velocity/head velocity) and phase (delay between vestibular stimulus and response) during whole-body sinusoidal rotations ranging 0.5-12Hz with peak velocity 50 or 100°/s in nine adult C57BL/6 mice. We also measured the VOR during whole-body transient rotations with acceleration 3000 or 6000°/s2 reaching a plateau of 150 or 300°/s. These measures were obtained while the mouse's core body temperature was held at either 32 or 37°C for at least 35min before recording. The temperature presentation order and timing were pseudo-randomized. We found that a temperature increase from 32 to 37°C caused a significant increase in sinusoidal VOR gain of 17% (P<0.001). Temperature had no other effects on the behavioural VOR. Our data suggest that temperature effects on regularly firing afferents best correspond to the changes that we observed in the VOR gain.

VOR Gain Is Related to Compensatory Saccades in Healthy Older Adults.

Objective: Vestibulo-ocular reflex (VOR) gain is well-suited for identifying rotational vestibular dysfunction, but may miss partial progressive decline in age-related vestibular function. Since compensatory saccades might provide an alternative method for identifying subtle vestibular decline, we describe the relationship between VOR gain and compensatory saccades in healthy older adults.Methods: Horizontal VOR gain was measured in 243 subjects age 60 and older from the Baltimore Longitudinal Study of Aging using video head impulse testing (HIT). Saccades in each HIT were identified as either “compensatory” or “compensatory back-up,” i.e., same or opposite direction as the VOR response respectively. Saccades were also classified as “covert” (occurring during head movement) and “overt” (occurring after head movement). The relationship between VOR gain and percentage of HITs with saccades, as well as the relationship between VOR gain and saccade latency and amplitude, were evaluated using regression analyses adjusting for age, gender, and race.Results: In adjusted analyses, the percentage of HITs with compensatory saccades increased 4.5% for every 0.1 decrease in VOR gain (p < 0.0001). Overt compensatory saccade amplitude decreased 0.6° (p < 0.005) and latency increased 90 ms (p < 0.001) for every 0.1 increase in VOR gain. Covert back-up compensatory saccade amplitude increased 0.4° for every 0.1 increase in VOR gain.Conclusion: We observed significant relationships between VOR gain and compensatory saccades in healthy older adults. Lower VOR gain was associated with larger amplitude, shorter latency compensatory saccades. Compensatory saccades reflect underlying rotational vestibular hypofunction, and may be particularly useful at identifying partial vestibular deficits as occur in aging adults.

Applications of neuromodulation to explore vestibular cortical processing; new insights into the effects of direct current cortical modulation upon pursuit, VOR and VOR suppression.

Functional imaging, lesion studies and behavioural observations suggest that vestibular processing is lateralised to the non-dominant hemisphere. Moreover, disruption of interhemispheric balance via inhibition of left parietal cortex using transcranial direct current stimulation (tDCS) has been associated with an asymmetric suppression of the vestibulo-ocular reflex (VOR). However, the mechanism by which the VOR was modulated remains unknown. In this paper we review the literature on non-invasive brain stimulation techniques which have been used to probe vestibular function over the last decade. In addition, we investigate the mechanisms whereby tDCS may modulate VOR, e.g. by acting upon pursuit, VOR suppression mechanisms or direct VOR modulation. We applied bi-hemispheric parietal tDCS in 11 healthy subjects and only observed significant effects on VOR gain (tdcs * condition p=0.041) - namely a trend for VOR gain increase with right anodal/left cathodal stimulation, and a decrease with right cathodal/left anodal stimulation. Hence, we suggest that the modulation of the VOR observed both here and in previous reports, is directly caused by top-down cortical control of the VOR as a result of disruption to interhemispheric balance, likely parietal.

Visual contribution to the high-frequency human angular vestibulo-ocular reflex

The vestibulo-ocular reflex (VOR) acts to maintain images stable on the retina by rotating the eyes in exactly the opposite direction, but with equal magnitude, to head velocity. When viewing a near target, this reflex has an increased response to compensate for the translation of the eyes relative to the target that acts to reduce retinal image slip. Previous studies have shown that retinal velocity error provides an important visual feedback signal to increase the low-frequency (<1 Hz) VOR response during near viewing. We sought to determine whether initial eye position and retinal image position error could provide enough information to substantially increase the high-frequency VOR gain (eye velocity/head velocity) during near viewing. Ten human subjects were tested using the scleral search coil technique during horizontal head impulses under different lighting conditions (constant dark, strobe light at 0.5, 1, 2, 4, 10, 15 Hz, constant light) while viewing near (9.5 ± 1.3 cm) and far (104 cm) targets. Our results showed that the VOR gain increased during near viewing compared to far viewing, even during constant dark. For the near target, there was an increase in VOR gain with increasing strobe frequency from 1.17 ± 0.17 in constant dark to 1.36 ± 0.27 in constant light, a 21 ± 9 % increase. For the far target, strobe frequency had no effect. Presentation order of strobe frequency (i.e. 0.5-15 vs. 15-0.5 Hz) did not affect the gain, but it did affect the vergence angle (angle between the two eye's lines of sight). The VOR gain and vergence angles were constant during each trial. Our findings show that a retinal position error signal helps increase the vergence angle and could be invoking vestibular adaptation mechanisms to increase the high-frequency VOR response during near viewing. This is in contrast to the low-frequency VOR that depends more on retinal velocity error and predictive adaptation mechanisms.

Unilateral Adaptation of the Human Angular Vestibulo-Ocular Reflex

A recent study showed that the angular vestibulo-ocular reflex (VOR) can be better adaptively increased using an incremental retinal image velocity error signal compared with a conventional constant large velocity-gain demand (×2). This finding has important implications for vestibular rehabilitation that seeks to improve the VOR response after injury. However, a large portion of vestibular patients have unilateral vestibular hypofunction, and training that raises their VOR response during rotations to both the ipsilesional and contralesional side is not usually ideal. We sought to determine if the vestibular response to one side could selectively be increased without affecting the contralateral response. We tested nine subjects with normal vestibular function. Using the scleral search coil and head impulse techniques, we measured the active and passive VOR gain (eye velocity / head velocity) before and after unilateral incremental VOR adaptation training, consisting of self-generated (active) head impulses, which lasted ≈ 15 min. The head impulses consisted of rapid, horizontal head rotations with peak-amplitude 15°, peak-velocity 150°/s and peak-acceleration 3,000°/s(2). The VOR gain towards the adapting side increased after training from 0.92 ± 0.18 to 1.11 ± 0.22 (+22.7 ± 20.2 %) during active head impulses and from 0.91 ± 0.15 to 1.01 ± 0.17 (+11.3 ± 7.5 %) during passive head impulses. During active impulses, the VOR gain towards the non-adapting side also increased by ≈ 8 %, though this increase was ≈ 70 % less than to the adapting side. A similar increase did not occur during passive impulses. This study shows that unilateral vestibular adaptation is possible in humans with a normal VOR; unilateral incremental VOR adaptation may have a role in vestibular rehabilitation. The increase in passive VOR gain after active head impulse adaptation suggests that the training effect is robust.

Total sleep deprivation can increase vestibulo‐ocular responses

The effect of sleep deprivation on the vestibular function is largely unknown. Some studies have found that postural balance or vestibular reflexes are decreased in sleep-deprived subjects while others found no change. The aim of this study was to evaluate the effect of sleep deprivation on the vestibulo-ocular reflex (VOR). Horizontal eye movements were recorded in healthy subjects during earth vertical axis rotation in darkness once after an ordinary night sleep and once after 26-29 h of sleep deprivation. In the first experiment (n = 8), for which rotation was a 60 degrees s(-1) velocity step, sleep deprivation induced a significant increase in VOR gain. In the second experiment (n = 12), for which rotation was sinusoidal (0.2 Hz +/- 25 degrees s(-1)), sleep deprivation induced no significant modification in VOR gain. The difference between the two studies was the abrupt onset of the step stimulation in comparison with the sinusoidal rotation. Because of its unexpected onset and the potential threat to postural balance, the step stimulation may activate the system specialized in reorienting attention towards salient or behaviourally relevant events. This system includes the right temporoparietal cortex, an area also involved in VOR control. A number of studies have found that sleep deprivation alters the activity of this cortical area during attentional tasks. It is therefore our hypothesis that the difference between the effects of these two vestibular stimulations results from a sleep deprivation-induced modulation of the right temporoparietal cortex.

Selective Engagement of Plasticity Mechanisms for Motor Memory Storage

The number and diversity of plasticity mechanisms in the brain raises a central question: does a neural circuit store all memories by stereotyped application of the available plasticity mechanisms, or can subsets of these mechanisms be selectively engaged for specific memories? The uniform architecture of the cerebellum has inspired the idea that plasticity mechanisms like cerebellar long-term depression (LTD) contribute universally to memory storage. To test this idea, we investigated a set of closely related, cerebellum-dependent motor memories. In mutant mice lacking Ca(2+)/calmodulin-dependent protein kinase IV (CaMKIV), the maintenance of cerebellar LTD is abolished. Although memory for an increase in the gain of the vestibulo-ocular reflex (VOR) induced with high-frequency stimuli was impaired in these mice, memories for decreases in VOR gain and increases in gain induced with low-frequency stimuli were intact. Thus, a particular plasticity mechanism need not support all cerebellum-dependent memories, but can be engaged selectively according to the parameters of training.

Flexibility of vestibulo-ocular reflex adaptation to modified visual input in human

The vestibulo-ocular reflex (VOR) serves to keep images relatively stable on the retina. To maintain appropriate performance and minimize image slip throughout life, VOR is subjected to long-term adaptive regulation by visual input. It has been reported that adaptive changes in VOR gain (eye velocity/head velocity) are evoked either by fitting subjects with magnifying, miniaturizing, or reversing spectacles during normal behavior, or by moving a large visual field in or out of phase relative to the subject's head movement. The changes in VOR gain are frequency selective. Here, we examine the extent of VOR gain flexibility by causing VORs of similar direction to undergo different behavioral gain changes. Nine healthy adults participated in the study, ranging in age from 24 to 38 years (mean: 26 years) and with no history of neurotological symptoms. All subjects were clinically normal according to a screening battery that included combined neurologic and otologic physical examinations. Horizontal and vertical eye positions were recorded by bitemporal DC-coupled electro-oculography (EOG). The subject sat in a rotating chair. The axis of rotation of the body was always earth-vertical, with the interaural axis crossing the axis of rotation of the chair. The head was pointed 20° downwards in all experiments and stabilized in this position using a chin rest. The chair was surrounded by a half-cylindrical optokinetic screen (78 cm in diameter) placed in front of the subject, onto which random dot patterns were projected. Goggles were used to ensure that the subject was in complete darkness during both pre- and postadaptation periods. The chair was rotated sinusoidally at maximum amplitude of 30° or 60°: for 30° the stimulation was at 0.1, 0.2, 0.3, and 0.4 Hz; for 60° it was at 0.1, 0.2, and 0.3 Hz. VOR adaptation was obtained by inducing a retinal slip velocity by short-term alteration of the visual input of the large field; this change was produced by a combination of sinusoidal head rotation and the random dot patterns. In each adaptation session, the sinusoidal head rotation was either at 0.1 or 0.3 Hz and the amplitude was 30°. The random dot pattern was synchronized with sinusoidal head rotation in the same direction (x0 experiment) to make the retinal slip zero, and in the opposite direction to make the retinal slip twofold (x2 experiment). Therefore, a total of four adaptation protocols were tested. The subjects were asked to fixate on a single dot with the eyes straight-ahead in the x0 experiment, and follow it within random dot patterns in the x2 experiment. Each adaptation session lasted for 30 min. Two adaptation experiments were performed on each subject once per day. The averages of VOR gain and phase lag were calculated using Fourier analysis. Seven of the subjects who participated in the x2 adaptation experiment at 0.3 Hz and 30° amplitude showed a steady increase of VOR gain within a couple of trials. One of the remaining two subjects showed a decrease in VOR gain in all the three trials, and the other subject showed a VOR gain increase in three trials and decrease in two trials. In the x2 adaptation experiment at 0.3 Hz and 30° amplitude (peak velocity: 28°/s), the percentage gain change ((post−pre)/pre) was 133% at the same stimulation and 100% at 0.4 Hz (peak velocity: 37°/s). The gain change was 65% at 0.1 Hz and 60° amplitude (peak velocity: 18°/s), and 64% at 0.2 Hz and 60° amplitude (peak velocity: 37°/s). In the x1 adaptation experiment (30° at 0.3 Hz), the percentage gain change was −62% under the same conditions, −50% at 0.1 Hz and 60° amplitude, and −30% at 0.2 Hz and 60° amplitude. No change of VOR gain was observed at other frequencies, and the subject was not adapted at 0.1 Hz and 30° amplitude. The larger VOR gain increase in the x2 adaptation experiment for the faster head angular acceleration leads to the conclusion that the VOR gain mechanism can set very different gain states for the VOR that are quite similar in terms of the head acceleration.

Flexibility in the adaptation of the vestibulo-ocular reflex to modified visual inputs in humans

The vestibulo-ocular reflex (VOR) serves to stabilize images on the retina. To maintain appropriate performance and minimize image slippage throughout life, the VOR is subject to long-term adaptive regulation in response to visual input. Adaptive changes in VOR gain (eye velocity/head velocity) can be evoked either by fitting subjects with magnifying, miniaturizing, or reversing spectacles during normal behavior or by moving a large visual field in or out of phase relative to the subject's head movement. These changes exhibit frequency-selectivity. Here, we examine the flexibility of VOR gains by causing VOR in similar directions to undergo different behavioral gain changes. Nine healthy adults, ranging in age from 24 to 38 (mean 28.5) with no history of neurotological symptoms participated in the study. All subjects demonstrated clinically normal functioning on a screening battery of tests that included combined neurologic and otologic physical examinations. Horizontal and vertical eye positions were recorded by bitemporal DC coupled electrooculography (EOG). The subject sat in a rotating chair. The axis of rotation of the body was always earth-vertical, the interaural axis crossing the axis of rotation of the chair. The head was positioned at 20 degrees down in all experiments and was stabilized in this position using a chin rest. The chair was 78 cm in diameter and was shielded by a half-cylindrical optokinetic screen positioned in front of the subjects. Random dot patterns were projected onto this screen. During per- and post-adaptation periods, goggles were fitted to ensure that the subject was in complete darkness and the chair was rotated sinusoidally. The amplitude of the rotating chair was 30 degrees and 60 degrees. Frequencies of rotation were 0.1 Hz, 0.2 Hz, 0.3 Hz and 0.4 Hz for amplitudes of 30 degrees and 0.1 Hz, 0.2 Hz, and 0.3 Hz for amplitudes of 60 degrees. To induce VOR adaptation, the retinal slippage velocity caused by the visual input of a large field was changed for short-term; the change was produced by a combination of sinusoidal head rotation and random dot patterns. During each adaptation session, the frequencies of sinusoidal head rotation were either 0.1 Hz or 0.3 Hz and the amplitude was 30 degrees. The random dot patterns were synchronized with the sinusoidal head rotation in the same direction to make the retinal slippage zero (x0 experiment) and in the opposite direction to double the retinal slippage (x2 experiment). Therefore, a total of four adaptation protocols were tested. The subjects were asked to fix their eyes on a single dot by looking straight ahead in the x0 experiment and to follow the dot in the random dot pattern in the x2 experiment. Each adaptation session lasted for 30 minutes. Each subject participated in couple of adaptation experiments everyday. The average VOR gain and phase lag were calculated using a Fourier transformation. Out of all the subjects who participated in the x2 adaptation experiment at 0.3 Hz with an amplitude of 30 degrees, seven subjects showed a steady increase in VOR gain during a couple of the trials. One out of the remaining two subjects showed a decrease in VOR gain in all three trials. Another subject showed an increase in VOR gain during three trials and a decrease in two trials. In the x2 adaptation experiment with a range of 30 degrees at 0.3 Hz (peak velocity: 28 degrees/s), the percent change in gain (post-pre/pre) was 133% at the same stimulation and 100% at 0.4 Hz (peak velocity: 37 degrees/s). The percent change in gain was 65% for amplitudes of 60 degrees at 0.1 Hz (peak velocity: 18 degrees/s) and 64% for amplitudes 60 degrees at 0.2 Hz (peak velocity: 37 degrees/s). In the x1 adaptation experiment (30 degrees at 0.3 Hz), the percent change in gain was -62% for the same conditions and -50% for amplitude of 60 degrees at 0.1 Hz and -30% for amplitudes of 60 degrees at 0.2 Hz. No change, in VOR gain was observed at the other frequencies. The

Effect of adaptation to telescopic spectacles on the initial human horizontal vestibuloocular reflex.

Gain of the vestibuloocular reflex (VOR) not only varies with target distance and rotational axis, but can be chronically modified in response to prolonged wearing of head-mounted magnifiers. This study examined the effect of adaptation to telescopic spectacles on the variation of the VOR with changes in target distance and yaw rotational axis for head velocity transients having peak accelerations of 2,800 and 1,000 degrees /s(2). Eye and head movements were recorded with search coils in 10 subjects who underwent whole body rotations around vertical axes that were 10 cm anterior to the eyes, centered between the eyes, between the otoliths, or 20 cm posterior to the eyes. Immediately before each rotation, subjects viewed a target 15 or 500 cm distant. Lighting was extinguished immediately before and was restored after completion of each rotation. After initial rotations, subjects wore 1.9x magnification binocular telescopic spectacles during their daily activities for at least 6 h. Test spectacles were removed and measurement rotations were repeated. Of the eight subjects tolerant of adaptation to the telescopes, six demonstrated VOR gain enhancement after adaptation, while gain in two subjects was not increased. For all subjects, the earliest VOR began 7-10 ms after onset of head rotation regardless of axis eccentricity or target distance. Regardless of adaptation, VOR gain for the proximate target exceeded that for the distant target beginning at 20 ms after onset of head rotation. Adaptation increased VOR gain as measured 90-100 ms after head rotation onset by an average of 0.12 +/- 0.02 (SE) for the higher head acceleration and 0.19 +/- 0.02 for the lower head acceleration. After adaptation, four subjects exhibited significant increases in the canal VOR gain only, whereas two subjects exhibited significant increases in both angular and linear VOR gains. The latencies of linear and early angular target distance effects on VOR gain were unaffected by adaptation. The earliest significant change in angular VOR gain in response to adaptation occurred 50 and 68 ms after onset of the 2,800 and 1,000 degrees /s(2) peak head accelerations, respectively. The latency of the adaptive increase in linear VOR gain was approximately 50 ms for the peak head acceleration of 2,800 degrees /s(2), and 100 ms for the peak head acceleration of 1,000 degrees /s(2). Thus VOR gain changes and latency were consistent with modification in the angular VOR in most subjects, and additionally in the linear VOR in a minority of subjects.