ReviewTop-down approach to vestibular compensation: Translational lessons from vestibular rehabilitation☆
Introduction
Recent decades of basic research into cellular and molecular mechanisms of vestibular compensation have produced important insights into functional plasticity of the central nervous system. For example, a considerable body of evidence indicates that vestibulo-ocular reflex plasticity is mediated by protein kinase C (PKC)-dependent mechanisms in modular vestibulocerebellar cortico-nuclear microcircuits termed microcomplexes, which are small networks involving the inferior olive, vestibular nuclei, nucleus prepositus hypoglossi and the flocculonodular lobe (Ito, 2001). Inhibition of flocculonodular lobe Purkinje cell PKC blocks adaptive modification of vestibulo-ocular (De Zeeuw et al., 1998) and optokinetic (Shutoh et al., 2003) responses. In this regard, it is significant that Purkinje cells in different flocculonodular lobe microcomplexes show transient molecular changes in specific PKC isoform expression during compensation for unilateral ablation of vestibular endorgans (Balaban and Romero, 1998, Balaban et al., 1999, Goto et al., 1997) and that PKC inhibition retards the resolution of spontaneous nystagmus in these animals (Balaban et al., 1999). Inhibition of flocculus PKC also prevented a compensatory increase in the intrinsic excitability of medial vestibular nucleus neurons during early vestibular compensation (Johnston et al., 2002). Although cerebellar long term depression (LTD) is induced in Purkinje cells by processes that require simultaneous parallel and climbing fiber activity and PKC activation (De Zeeuw et al., 1998, Ito, 2001, Leitges et al., 2004, Linden and Connor, 1995), the PKC-mediated effects on both cerebellar motor learning and oculomotor aspects of vestibular compensation likely include mechanisms in addition to LTD (Faulstich et al., 2006, Schonewille et al., 2011). A number of comprehensive reviews provide additional examples of the value of vestibular compensation as a model system for investigating dynamic neural reorganization of sensorimotor processes (Cullen et al., 2009, Dutia, 2010, Gliddon et al., 2005, Lacour and Tighilet, 2010).
Unfortunately, these advances in understanding of basic processes of vestibular compensation have found very little translational application into therapies that improve compensation outcomes in patients. By contrast, vestibular rehabilitation therapy has been a remarkable success story. This communication explores implications of Lacour's (Lacour, 2006) observation that vestibular compensation includes a rapid, ‘vestibulo-centric’ static process and a longer term, dynamic, distributed learning process. We suggest that the focus of the basic scientific approach on spontaneous compensation after peripheral vestibular ablation elucidates only mechanisms that bring a patient to the functional point of entry into rehabilitation therapy. Vestibular rehabilitation therapy improves dynamic performance by replacing systematically some previously compensatory strategies with new, learned strategies that enhance functional recovery. The therapy is guided by three implicit assumptions. Firstly, spontaneous compensation is not optimal. Secondly, compensation is viewed as a top-down, ordered process, proceeding from eye–head stabilization to dynamic gait stabilization. Thirdly, effective rehabilitation involves stepwise guidance of adaptive learning to achieve interim goals of increasing complexity. For example, a first goal in vestibular rehabilitation is to overcome the voluntary (‘adaptive’) limitations on head movements that patients often adopt to minimize precipitating disequilibrium and nausea (Herdman and Whitney, 2007); other interim goals may only be intermediate steps to enable further improvement. The implication is obvious: scientific paradigms for studying vestibular compensation should be expanded to elucidate mechanisms that are likely to be clinically meaningful for improving rehabilitation outcomes.
There is a common fallacy that translational research is strictly a ‘bottom-up’ process from the laboratory bench, via animal model trials, to the clinic. To the contrary, the fundamental importance of the clinical to basic research path in experimental medicine was emphasized by Claude Bernard (Bernard, 1875, c1989) more than 130 years ago in the statement that experimental medicine “ …claims knowledge of the laws of healthy and diseased organisms, not only as to foresee phenomena, but also so as to be able to regulate and alter them within certain limits. Accordingly, we easily perceive that medicine tends to become experimental, and that every physician who gives his patients active medicine cooperates in building up experimental medicine.” Stated simply, basic investigators have the task of providing therapeutically relevant explanations for the outcomes of the patient-oriented and disease-oriented clinical research. Hence, this review focuses on lessons from procedures and outcomes of vestibular rehabilitation therapy that can inform the experimental analysis of vestibular compensation. Conversely, we discuss how principles from laboratory studies of vestibular compensation inform and are validated by clinical rehabilitation practice.
Section snippets
History and relationship with ‘stages of compensation’
Vestibular rehabilitation is a therapeutic approach to enhance functional vestibular compensation. Sir Terence Cawthorne and F.S. Cooksey (Cawthorne, 1945, Cawthorne, 1949, Cooksey, 1945) are credited with formalizing the concept of vestibular rehabilitation by developing a balance rehabilitation strategy for British soldiers injured in the Second World War. Despite the success of their work, vestibular rehabilitation was largely ignored until half a century later, when a number of
Therapeutic progression proceeds from head control to locomotion
Empirical principles for vestibular rehabilitation practice include an implicit top-down strategy for progression of exercises. The therapy progression can be summarized from the literature (Herdman and Whitney, 2007, Whitney and Sparto, 2011) as follows. If patient are incapable of standing safely, they remain seated and perform active eye and head movements while fixating on a point in a lighted room. If the patient is capable of standing safely, static postural control exercises are
Sensorimotor performance
Experience with vestibular rehabilitation indicates that outcomes are improved by stepwise achievement of interim goals, which may require replacing previously compensatory strategies with new, learned strategies that enhance functional recovery. The first benchmark, resolution of nausea, severe vertigo and spontaneous nystagmus, is typically achieved prior to initiating rehabilitation (Herdman and Whitney, 2007). It has long been recognized that this benchmark is a necessary but insufficient
Vestibular compensation is a life-long, trainable adaptive process
The term ‘vestibular compensation’ is used most commonly to describe phenomena that occur after unilateral impairment of the vestibular periphery (Curthoys and Halmagyi, 1999). The profound effects of compensatory processes on balance control were noted during the latter decades of the nineteenth century in some of the earliest descriptions of the phenomena. The most striking was von Bechterew's report (Bechterew, 1883) that unilateral, serial bilateral, and simultaneous bilateral damage to the
References (118)
- et al.
A role of climbing fibers in regulation of flocculonodular lobe protein kinase C expression during vestibular compensation
Brain Res.
(1998) - et al.
Protein kinase C inhibition blocks the early appearance of vestibular compensation
Brain Res.
(1999) - et al.
Behavior therapy for vestibular rehabilitation
J. Anxiety Disord.
(2001) - et al.
Expression of a protein kinase C inhibitor in Purkinje cells blocks cerebellar LTD and adaptation of the vestibulo-ocular reflex
Neuron
(1998) - et al.
Adaptation of the human vestibuloocular reflex to magnifying lenses
Brain Res.
(1975) - et al.
GABAergic systems in the vestibular nucleus and their contribution to vestibular compensation
Prog. Neurobiol.
(2005) - et al.
Anterograde tracing of projections from the dorsal raphe nucleus to the vestibular nuclei
Neuroscience
(2006) - et al.
Serotonergic and nonserotonergic neurons in the dorsal raphe nucleus send collateralized projections to both the vestibular nuclei and the central amygdaloid nucleus
Neuroscience
(2006) - et al.
Selective anterograde tracing of the individual serotonergic and nonserotonergic components of the dorsal raphe nucleus projection to the vestibular nuclei
Neuroscience
(2007) - et al.
Vestibular adaptation exercises and recovery: acute stage after acoustic neuroma resection
Otolaryngol.-Head Neck Surg.
(1995)
Identifying deficits in balance control following vestibular or proprioceptive loss using posturographic analysis of stance tasks
Clin. Neurophysiol.
A unique PDZ ligand in PKCa confers induction of cerebellar long-term synaptic depression
Neuron
Effect of oculo-motor and gaze stability exercises on postural stability and dynamic visual acuity in healthy young adults
Gait Posture
Reevaluating the role of LTD in cerebellar motor learning
Neuron
Organization of the coeruleo-vestibular pathway in rats, rabbits and monkeys
Brain Res. Rev.
Long-term modifications of vertical and horizontal vestibulo-ocular reflex dynamics in man. I. After acute unilateral vestibular paralysis
Acta Oto-Laryngol.
Recover of vestibulo-ocular reflex function in subjects with an acute unilateral vestibular deficit
J. Vestib. Res.
Improvements in trunk sway observed for stance and gait tasks during recovery from an acute unilateral peripheral vestibular deficit
Audiol. Neuro-Otol.
Stress signalling pathways that impair prefrontal cortex structure and function
Nat. Rev. Neurosci.
A factor analytic study of the dizziness handicap inventory: does it assess phobi avoidance in vestibular referrals?
J. Vestib. Res.
Vestibulo-autonomic interactions: a teleologic perspective
Neurologic bases for comorbidity of balance disorders, anxiety disorders and migraine: neurotherapeutic implications
Expert Rev. Neurother.
Generalization of gait adaptation for fall prevention: from movable platform to slippery floor
J. Neurophysiol.
Deficits and recovery of head and trunk orientation and stabilization after unilateral vestibular loss
Brain
Voluntary movement strategies of individuals with unilateral peripheral vestibular hypofunction
J. Vestib. Res.
Cerebral representations for egocentric space. Functional-anatomical evidence from caloric vestibular stimulation and neck vibration
Brain
Vestibular loss causes hippocampal atrophy and impaired spatial memory in humans
Brain
The moving platform after-effect reveals dissociation between what we know and how we walk
J. Neural Transm.
What the “broken escalator” phenomenon teaches us about balance
Ann. N. Y. Acad. Sci.
Cerebral functional magnetic resonance imaging of vestibular, auditory, and nociceptive areas during galvanic stimulation
Ann. Neurol.
Vestibular injuries
Proc. R. Soc. Med.
Rehabilitation in vestribular injuries
Proc. R. Soc. Med.
Some observations on the pathology and surgical treatment of labyrinthine vertigo of non-infective origin
Ann. R. Coll. Surg. Engl.
Balance control in very old adults with and without visual impairment
Eur. J. Appl. Physiol.
Disability and rehabilitation in the dizzy patient
Curr. Opin. Neurol.
The effects of visual input on open-loop and closed-loop postural control mechanisms
Exp. Brain Res.
Human horizontal vestibulo-ocular reflex initiation: effects of acceleration, target distance and unilateral deafferentation
J. Neurophysiol.
Neural substrates underlying vestibular compensation: contribution of peripheral versus central processing
J. Vestib. Res.
Vestibular compensation
Unilateral vestibular failure suppresses cortical visual motion processing
Brain
Dominance for vestibular cortical function in the non-dominant hemisphere
Cereb. Cortex
Functional brain imaging of peripheral and central vestibular disorders
Brain
Mechanisms of vestibular compensation: recent advances
Curr. Opin. Otolaryngol. Head Neck Surg.
Transfer of podokinetic adaptation from stepping to hopping
J. Neurophysiol.
Identifying human parieto-insular vestibular cortex using fMRI and cytoarchitectonic mapping
Hum. Brain Mapp.
Effects of bilateral vestibulo-ocular reflex exercises on vestibular compensation after vestibular schwannoma surgery
Otol. Neurotol.
Human vestibular cortex identified with caloric stimulation in functional magnetic resonance imaging
NeuroImage
Oculomotor plasticity during vestibular compensation does not depend upon cerebellar LTD
J. Neurophysiol.
Cited by (0)
- ☆
Disclaimer: The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the U.S. Government.