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Reconstruction of Purkinje cell SS FR during VF paradigm (bottom) by a multiple regression model consisting of retinal slip velocity (top), retinal slip acceleration (2nd), efference copy (3rd), and a dc term (not shown) for a typical cell. In the top 3 panels, gray lines are original traces including saccadic periods and black lines are after desaccade. In the bottom panel, the gray trace is the original Purkinje cell SS FR, and the black dots are the reconstruction by the model. Ten seconds of about 60 s of data are shown.
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The gain of the vertical vestibuloocular reflex (VVOR), defined as eye velocity/head velocity was adapted in squirrel monkeys by employing visual-vestibular mismatch stimuli. VVOR gain, measured in the dark, could be trained to values between 0.4 and 1.5. Single-unit activity of vertical zone Purkinje cells was recorded from the flocculus and ventr...
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Citations
... Synaptic plasticity"). Other input modalities to the artificial cerebellum via MFs are target speed, error, and the copy of motor command (efference copy) as in the real oculomotor control system (Noda, 1986;Hirata and Highstein, 2001;Blazquez et al., 2003;Huang et al., 2013). ...
The cerebellum plays a central role in motor control and learning. Its neuronal network architecture, firing characteristics of component neurons, and learning rules at their synapses have been well understood in terms of anatomy and physiology. A realistic artificial cerebellum with mimetic network architecture and synaptic plasticity mechanisms may allow us to analyze cerebellar information processing in the real world by applying it to adaptive control of actual machines. Several artificial cerebellums have previously been constructed, but they require high-performance hardware to run in real-time for real-world machine control. Presently, we implemented an artificial cerebellum with the size of 10⁴ spiking neuron models on a field-programmable gate array (FPGA) which is compact, lightweight, portable, and low-power-consumption. In the implementation three novel techniques are employed: (1) 16-bit fixed-point operation and randomized rounding, (2) fully connected spike information transmission, and (3) alternative memory that uses pseudo-random number generators. We demonstrate that the FPGA artificial cerebellum runs in real-time, and its component neuron models behave as those in the corresponding artificial cerebellum configured on a personal computer in Python. We applied the FPGA artificial cerebellum to the adaptive control of a machine in the real world and demonstrated that the artificial cerebellum is capable of adaptively reducing control error after sudden load changes. This is the first implementation and demonstration of a spiking artificial cerebellum on an FPGA applicable to real-world adaptive control. The FPGA artificial cerebellum may provide neuroscientific insights into cerebellar information processing in adaptive motor control and may be applied to various neuro-devices to augment and extend human motor control capabilities.
... This is consistent with a large number of studies suggesting that long-term depression (LTD) occurs at the excitatory parallel fiber synapses onto Purkinje cells in response to error signals carried by climbing fiber inputs, effectively implementing reinforcement learning through error-driven plasticity ('parallel fiber-Purkinje cell LTD'; Coesmans et al., 2004;Gilbert and Thach, 1977;Ito and Kano, 1982;Kimpo et al., 2014;Medina and Lisberger, 2008;Sakurai, 1987;Silva et al., 2023;Yang and Lisberger, 2013;Yang and Lisberger, 2014, but see Schonewille et al., 2011). In contrast, later experimental observations raised the possibility that the learning-related changes in Purkinje cell firing could instead be due to feedback of changes occurring outside of the cerebellar cortex ('Miles-Lisberger model', Figure 1D; Hirata and Highstein, 2001;Lisberger, 1994a;Lisberger et al., 1994c;Lisberger et al., 1994b;Miles and Lisberger, 1981). Furthermore, these experiments were interpreted as evidence that parallel fiber-Purkinje cell plasticity within the cerebellar cortex was in the opposite direction (long-term potentiation, LTP) from the LTD predicted by the Marr-Albus-Ito model. ...
... This is challenging because the vestibular, visual, and efference copy signals are tightly correlated due to feedforward and feedback interactions. Previous models have attempted to address this issue by assuming a particular strength of efference copy feedback, or have quantitatively fit simpler open-loop models to limited sets of data that may not fully eliminate the confounds stemming from strongly correlated predictor variables (Blazquez et al., 2003;Hirata and Highstein, 2001;Lisberger, 1994a;Tabata et al., 2002). Here, we fit an extensive set of Purkinje cell and eye movement data recorded in monkeys before and after learning, while systematically varying the strength of efference copy feedback (by setting the strength of filter k PE ) to separate the contributions of different, correlated pathways and enable solutions that have not previously been considered (see Materials and methods). ...
... Learned increases in the VOR can be induced by pairing a vestibular stimulus with oppositely directed motion of a visual stimulus so that larger-than-normal eye movements are required to stabilize the image on the retina. Following such learning, Purkinje cell responses to an ipsiversive vestibular stimulus alone (in the dark) decrease (Blazquez et al., 2003;Hirata and Highstein, 2001;Lisberger et al., 1994b;Miles et al., 1980;Watanabe, 1985), which disinhibits brainstem target neurons, thereby increasing the amplitude of eye movements. Whereas these changes in behavior and neural activity are well established, longstanding controversy concerns the sites and directions of plasticity underlying these changes. ...
Determining the sites and directions of plasticity underlying changes in neural activity and behavior is critical for understanding mechanisms of learning. Identifying such plasticity from neural recording data can be challenging due to feedback pathways that impede reasoning about cause and effect. We studied interactions between feedback, neural activity, and plasticity in the context of a closed-loop motor learning task for which there is disagreement about the loci and directions of plasticity: vestibulo-ocular reflex learning. We constructed a set of circuit models that differed in the strength of their recurrent feedback, from no feedback to very strong feedback. Despite these differences, each model successfully fit a large set of neural and behavioral data. However, the patterns of plasticity predicted by the models fundamentally differed, with the direction of plasticity at a key site changing from depression to potentiation as feedback strength increased. Guided by our analysis, we suggest how such models can be experimentally disambiguated. Our results address a long-standing debate regarding cerebellum-dependent motor learning, suggesting a reconciliation in which learning-related changes in the strength of synaptic inputs to Purkinje cells are compatible with seemingly oppositely directed changes in Purkinje cell spiking activity. More broadly, these results demonstrate how changes in neural activity over learning can appear to contradict the sign of the underlying plasticity when either internal feedback or feedback through the environment is present.
... The eye position data were resampled from 120 to 240 Hz using the MATLAB interp1 function (cubic interpolation), and the eye velocity data were calculated by applying a three-point low-pass differentiation once. Saccades were eliminated from the eye movements using an automated desaccading algorithm with a velocity threshold (Hirata & Highstein, 2001). Figure 3 illustrates an example of a desaccading vertical eye position while tracking the downward motion of a 1 G target. ...
Humans can accurately estimate and track object motion, even if it accelerates. Research shows that humans exhibit superior estimation and tracking performance for descending (falling) than ascending (rising) objects. Previous studies presented ascending and descending targets along the gravitational and body axes in an upright posture. Thus, it is unclear whether humans rely on congruent information between the direction of the target motion and gravity or the direction of the target motion and longitudinal body axes. Two experiments were conducted to explore these possibilities. In Experiment 1, participants estimated the arrival time at a goal for both upward and downward motion of targets along the longitudinal body axis in the upright (both axes of target motion and gravity congruent) and supine (both axes incongruent) postures. In Experiment 2, smooth pursuit eye movements were assessed while tracking both targets in the same postures. Arrival time estimation and smooth pursuit eye movement performance were consistently more accurate for downward target motion than for upward motion, irrespective of posture. These findings suggest that the visual experience of seeing an object moving along an observer's leg side in everyday life may influence the ability to accurately estimate and track the descending object's motion.
... In multiple species, populations of cerebellar Purkinje cells have been shown to alter their firing modulation in directions that would support VOR gain-up and down changes. (Nagao, 1979;Miles et al., 1980;Watanabe, 1984;Lisberger et al., 1994;Pastor et al., 1997;Hirata and Highstein, 2001). More specifically, Purkinje cell firing activities showing almost no modulation during VOR in the dark before training turned to a contraversive or ipsiversive modulation to head velocity after gain-up or gain-down training, respectively (Watanabe, 1984;Lisberger et al., 1994). ...
... Saccades and post-saccadic drifts, if present, were eliminated from eye velocity data by applying a custom made automatic desaccading algorithm using an acceleration threshold (Hirata and Highstein, 2001). In this study, the eliminated portions of the data were not used for later analyses. ...
... The parameters S R and > R were estimated by using a non-linear optimization method in MATLAB (lsqnonlin) by minimizing the squared sum of the residual %('). Sensitivities of Purkinje cell modulation to eye and head parameters were estimated by using the following multiple linear regression model assuming that vestibulo-cerebellar Purkinje cell modulation can be represented by the linear summation of eye acceleration, velocity, position, head acceleration, velocity, and a dc term as in previous studies (Shidara et al., 1993;Gomi et al., 1998;Hirata and Highstein, 2001;Blazquez et al., 2003). ...
Biological motions commonly contain multiple frequency components in which each fundamental has to be adjusted by motor learning to acquire a new motor skill or maintain acquired skills. At times during this motor performance one frequency component needs to be enhanced (gain-up) while another is suppressed (gain-down). This pattern of simultaneous gain-up and -down adjustments at different frequencies is called frequency competitive motor learning. Currently we investigated cerebellar roles in this behavior utilizing the goldfish vestibulo-ocular reflex (VOR). Previously, VOR motor learning was shown in primates to be frequency selective and exhibit frequency competitive motor learning. Here we demonstrate that the goldfish VOR performs frequency competitive motor learning when high and low frequency components are trained to gain-up and gain-down, respectively. However, when the two frequency components were trained in the opposite directions only gain-up component was observed. We also found that cerebellectomy precluded any frequency competitive VOR motor learning. Complementary single unit recordings from vestibulo-cerebellar Purkinje cells revealed changes in firing modulation along with gain-down learning, but not with gain-up learning irrespective of frequency. These results demonstrate that the cerebellum is required for all frequency competitive VOR motor learning and Purkinje cell activity therein is well correlated with all gain-down behaviors independent of frequency. However, frequency competitive gain-up learning requires intact, recursive brainstem/cerebellar pathways. Collectively these findings support the idea that VOR gain-up and gain-down learning utilize separate brainstem/cerebellar circuitry that, in turn, clearly underlies the unique ability of the oculomotor system to deal with multiple frequency components.
... www.nature.com/scientificreports/ using an acceleration threshold 28 . In this study, the eliminated portions of the data were not used for any other analyses. ...
Predictive motor control is ubiquitously employed in animal kingdom to achieve rapid and precise motor action. In most vertebrates large, moving visual scenes induce an optokinetic response (OKR) control of eye movements to stabilize vision. In goldfish, the OKR was found to be predictive after a prolonged exposure to temporally periodic visual motion. A recent study showed the cerebellum necessary to acquire this predictive OKR (pOKR), but it remained unclear as to whether the cerebellum alone was sufficient. Herein we examined different fish species known to share the basic architecture of cerebellar neuronal circuitry for their ability to acquire pOKR. Carps were shown to acquire pOKR like goldfish while zebrafish and medaka did not, demonstrating the cerebellum alone not to be sufficient. Interestingly, those fish that acquired pOKR were found to exhibit long-lasting optokinetic after nystagmus (OKAN) as opposed to those that didn’t. To directly manipulate OKAN vestibular-neurectomy was performed in goldfish that severely shortened OKAN, but pOKR was acquired comparable to normal animals. These results suggest that the neuronal circuitry producing OKAN, known as the velocity storage mechanism (VSM), is required to acquire pOKR irrespective of OKAN duration. Taken together, we conclude that pOKR is acquired through recurrent cerebellum-brainstem parallel loops in which the cerebellum adjusts VSM signal flow and, in turn, receives appropriately timed eye velocity information to clock visual world motion.
... Una característica especial es que esta ganancia es plástica y puede cambiar a lo largo de la vida, así como cuando el tamaño cefálico y las interacciones de los ojos y oídos cambian. (Lisberger et al., 1978a(Lisberger et al., , 1978bIto 1985Ito , 1987Ito , 1989Ito , 1993aIto , 1993bMiles et al. 1985;Nagao et al. 1991;Watanabe et al. 1993;Hirata et al., 2001) ...
SUMMARY
“Characterization of vestibulo ocular reflex by video head
impulse test – vHIT in patients with unilateral Menière’s disease”
Introduction: The study of the Vestibulo-Ocular Reflex (VOR) by
video head impulse test (vHIT) has been used for a few decades
(MacDougall et al., 2009) as part of the evaluation of the patient with
peripheral vestibular pathology (Weber et al., 2008; Halmagyi et al.,
2017). There are few studies on a large number of cases of patients with
unilateral Menière's disease.
Objectives: The aim of this study is to characterize the behavior of the
VOR in patients with unilateral Menière's disease through vHIT. To
assess the validity of the test in this disease, as well as its usefulness in
predicting the compromise and possible pathological evolution of the
contralateral ear.
Patients and Methodology: A prospective, non-randomized
observational study of cases and controls (pathological ears vs. nonpathological ears) was performed, assessing VOR using vHIT in 85
patients with unilateral Menière's disease seen in the otorhinolaryngology department of the Clínica Universidad de Navarra under the lab and supervision of Prof. Dr. Nicolas Perez Fernandez, from 2011 to 2014. The data were analyzed according to the results of the software of the system, calling it automatic vHIT, or after individual review of each impulse (vHIT manual review), comparing them with each other, with the clinical diagnosis, with the caloric test and with the VEMPs.
Results: 2855 head impulses were studied (an average of 17 impulses
per patient), finding no significant difference of gain in healthy ears
(1.01) and in pathological ones (0.9); only 13% of patients presented a
gain <0.8. In the pathological ears, was presented an average of 4% of covert type catch-up saccades, associated with early stages; 34% overt type and 14% of both types of saccades, of the latter 40% had pathological gains and are associated with longer disease and late stages. According to automatic vHIT, 18 bilateral cases were found and 4 cases where the pathological ear was the contralateral one; according to vHIT after manual review 7 bilateral cases and 3 on the contralateral ear.
The mean peak angular velocities of the head impulses and the aRVO
were 156°/sec, 126°/sec in the covert saccades, 88°/sec in the overt
saccades and 178°/sec in those presenting both types of saccades.
According to diagnostic criteria of the American Academy of
Otolaryngology and Head and Neck Surgery (AAO-HNS) 1995, the
pathological side corresponded in 49% and 62% of cases according to
automatic vHIT and manual revision respectively, giving a sensitivity
to the 49% vHIT automatic test and 62% after manual revision, a
specificity of 74% and 88%, according to automatic vHIT or manual
revision respectively. The automatic vHIT and manual revision did not differ significantly. In 63% of cases the pathological result of the vHIT correspond to the positive caloric test, and in 76% with the pathological result of the VEMPc, only in 54% with the positive HIT. The 16% of pathological cases in the caloric test and 13% of the VEMPc presented a gain in the vHIT <0.8, the latter with higher values of canal paresis and IAD increased compare to the cases with normal gains.
Discussion: The demographic characteristics corresponded to those
described in the literature. Regarding the own study of vHIT, the gain
is similar to that published for this type of patient with an average close
to the unit. It was considered that an impulse with presence of more than 50% of catch-up saccades is pathological. The gain and the refixed saccades of VOR were related to the stage and status of the disease, to the time of evolution and to the number of times it received intratympanic gentamicin. No relationship was found between the velocity of the impulse and the gain. The RVO is not altered by the presence of spontaneous nystagmus. Gains less than 0.8 are observed during acute crises, values greater than the unit appear in symptomatic patients or with severe status. Both the gains lower than 0.8 and greater than 1.2 are related to higher caloric paresis and increase of the IAD in the VEMPc. The greatest disparity of results vHIT, caloric test and VEMPc is found in post-crisis patients (0-7 days after the last acute crisis).
The number of contralateral ears considered pathological by the test
corresponds to that described in patients with this same pathology.
Conclusions: Through the vHIT test we have been able to characterize
the VOR in patients with unilateral Menière's disease, determining the
normal values of gain and percentage of saccades, as well as the
association with disease-dependent variables that modify the VOR.
We can also evaluate the asymptomatic contralateral ear, and in case of
positivity MRI-FLAIR is recommended for a more directed and less
aggressive treatment.
Keywords:
vHIT, video head impulse test, Menière's disease, Vestibulo-Ocular
Reflex, gain, refixation saccades, catch-up saccades, vestibular
compensation.
... Specifically, vertical and horizontal VOR velocities were characterised by head pitch and yaw velocity, respectively. These results are consistent with other studies demonstrating that VOR velocity during sinusoidal head rotation is proportional to head angular velocity (Gauthier et al. 1984;Hirata and Highstein 2001;Paige 1994;Tabak et al. 1997;Tweed et al. 1994). More importantly, even though the vibration was presented along a translational axis, in head-free conditions, the head rotates relative to the body and thus rotational VOR plays a dominant role in ocular stability. ...
The vestibulo-ocular reflex (VOR) plays a crucial role in ocular stability. However, VOR characteristics under realistic whole-body vibration conditions, particularly without head restriction, remain unclear. The aim of this study was to characterise the VOR over a wide range of whole-body vibration frequencies (0.7–10 Hz), such as occur when driving a car. Eye and head movements were measured in response to unidirectional translational whole-body vibration that resembled actual vehicle vibrations. The VOR was then modelled by regressing eye velocity data on multiple head movement components. Results showed that the VOR was explained by angular velocity, linear acceleration, and linear jerk components of the head movements. Because the VOR in response to head linear-jerk components disrupted ocular stability in the current experimental setup, our results suggest that degraded vision in whole-body vibratory environments might be partially attributable to jerky head movements.
Practitioner summary: The vestibulo-ocular reflex (VOR) during unidirectional translational whole-body vibration without head restriction was modelled using multiple head movement components, with the aim of characterising the VOR. Results showed that the VOR was explained by angular velocity, linear acceleration, and linear jerk components of head movements.
... VOR adaptation alters the activity of both floccular PCs and floccular target neurons (FTNs) in the VN; however, the latency of firing change in PCs was too late to explain changes in VOR [35,36]. Additionally, the observed change in PC activity was insufficient to describe the learning [20,36]. The altered responses of FTNs after VOR adaptation were not totally lost when the flocculus was chemically inactivated [30,42,43,[46][47][48], supporting the view that memory is stored outside of the cerebellum. ...
In memory research, studying cerebellum-dependent memory is advantageous due to its relatively simple neural architecture compared with that of other memory circuits. To understand how cerebellum-dependent memory develops and is stored in this circuit, numerous hypotheses have been proposed. These hypotheses are generally able to adequately explain most learning and memory processes; however, several reported results are still poorly understood. Recently, the importance of intrinsic plasticity (i.e., plasticity of intrinsic excitability) has been highlighted in several studies. Because the classical view of cerebellum-dependent eye movement learning was focused on synaptic plasticity, it is valuable to consider the intrinsic plasticity for deeper understanding. In the present review, we re-examine the utility and limitations of previous hypotheses, from classic to recent, and propose an updated hypothesis. Integrating intrinsic plasticity into current models of the vestibulo-ocular reflex (VOR) circuit may facilitate deeper understanding of the VOR adaptation process. In particular, during the period of memory transfer, dynamic changes in excitability in both cerebellar Purkinje cells and vestibular nuclear neurons illuminate the role of intrinsic plasticity in the circuit.
... Consistent with previous work (Lisberger and Fuchs, 1978;Lisberger et al., 1994;Pastor et al., 1997;Raymond and Lisberger, 1998;Hirata and Highstein, 2001;Katoh et al., 2015), the spike rate of Purkinje cells in our samples was highly correlated with gaze velocity. Gaze velocity is defined as the angular velocity of the eye in world coordinates, which is equal to the sum of eye velocity in the head, plus head velocity in the world. ...
The rate and temporal pattern of neural spiking each have the potential to influence computation. In the cerebellum, it has been hypothesized that the irregularity of interspike intervals in Purkinje cells affects their ability to transmit information to downstream neurons. Accordingly, during oculomotor behavior in mice and rhesus monkeys, mean irregularity of Purkinje cell spiking varied with mean eye velocity. However, moment-to-moment variations revealed a tight correlation between eye velocity and spike rate, with no additional information conveyed by spike irregularity. Moreover, when spike rate and irregularity were independently controlled using optogenetic stimulation, the eye movements elicited were well-described by a linear population rate code with 3-5 ms temporal precision. Biophysical and random-walk models identified biologically realistic parameter ranges that determine whether spike irregularity influences responses downstream. The results demonstrate cerebellar control of movements through a remarkably rapid rate code, with no evidence for an additional contribution of spike irregularity.
... The cerebellum does not control movement directly, but it plays a modulatory role of the motor output. In support, movement onset usually precedes PC responses (Hirata and Highstein, 2001;Sánchez-Campusano et al., 2007). Moreover, the relation between cerebellar output and motor behavior varies depending on the behavioral state and the behavioral task. ...
The central nervous system (CNS) achieves fine motor control by generating predictions of the consequences of the motor command, often called forward models of the movement. These predictions are used centrally to detect not-self generated sensations, to modify ongoing movements, and to induce motor learning. However, finding a neuronal correlate of forward models has proven difficult. In the oculomotor system, we can identify neuronal correlates of forward models vs. neuronal correlates of motor commands by examining neuronal responses during smooth pursuit at eccentric eye positions. During pursuit, torsional eye movement information is not present in the motor command, but it is generated by the mechanic of the orbit. Importantly, the directionality and approximate magnitude of torsional eye movement follow the half angle rule. We use this rule to investigate the role of the cerebellar flocculus complex (FL, flocculus and ventral paraflocculus) in the generation of forward models of the eye. We found that mossy fibers (input elements to the FL) did not change their response to pursuit with eccentricity. Thus, they do not carry torsional eye movement information. However, vertical Purkinje cells (PCs; output elements of the FL) showed a preference for counter-clockwise (CCW) eye velocity [corresponding to extorsion (outward rotation) of the ipsilateral eye]. We hypothesize that FL computes an estimate of torsional eye movement since torsion is present in PCs but not in mossy fibers. Overall, our results add to those of other laboratories in supporting the existence in the CNS of a predictive signal constructed from motor command information.
