Michel Lacour

Posture control, aging, and attention resources: models and posture-analysis methods.

This paper reviews the literature on balance and cognitive function in normal aging. The first part provides a general background of dual tasking (postural performance under a concurrent cognitive activity) and summarizes the main relevant models capable of explaining the poorer postural performance of older-healthy adults compared to younger-healthy adults: the cross-domain competition model, the nonlinear interaction model, and the task-prioritization model. In the second part, we discuss the main limitations of the traditional-posturographic analyses used in most of the dual-task investigations and explain how these can account for some discrepancies found in the literature. New methods based on the stabilogram-diffusion analysis and the wavelet transform are proposed as better approaches to understand posture control. The advantages of these new methods are illustrated in young adults and elderly people performing a simple postural task (quiet standing) simultaneously with a mental or a spatial task.

Sensory strategies in human postural control before and after unilateral vestibular neurotomy

Abstract Vestibular inputs tonically activate the antigravitative leg muscles during normal standing in humans, and visual information and proprioceptive inputs from the legs are very sensitive sensory loops for body sway control. This study investigated the postural control in a homogeneous population of 50 unilateral vestibular-deficient patients (Ménière’s disease patients). It analyzed the postural deficits of the patients before and after surgical treatment (unilateral vestibular neurotomy) of their diseases and it focused on the visual contribution to the fine regulation of body sway. Static posturographic recordings on a stable force-plate were done with patients with eyes open (EO) and eyes closed (EC). Body sway and visual stabilization of posture were evaluated by computing sway area with and without vision and by calculating the percentage difference of sway between EC and EO conditions. Ménière’s patients were examined when asymptomatic, 1 day before unilateral vestibular neurotomy, and during the time-course of recovery (1 week, 2 weeks, 1 month, 3 months, and 1 year). Data from the patients were compared with those recorded in 26 healthy, age- and sex-matched participants. Patients before neurotomy exhibited significantly greater sway area than controls with both EO (+52%) and EC (+93%). Healthy participants and Ménière’s patients, however, displayed two different behaviors with EC. In both populations, 54% of the subjects significantly increased their body sway upon eye closure, whereas 46% exhibited no change or significantly swayed less without vision. This was statistically confirmed by the cluster analysis, which clearly split the controls and the patients into two well-identified subgroups, relying heavily on vision (visual strategy, V) or not (non-visual strategy, NV). The percentage difference of sway averaged +36.7%±10.9% and –6.2%±16.5% for the V and NV controls, respectively; +45.9%±16.8% and –4.2%±14.9% for the V and NV patients, respectively. These two distinct V and NV strategies seemed consistent over time in individual subjects. Body sway area was strongly increased in all patients with EO early after neurotomy (1 and 2 weeks) and regained preoperative values later on. In contrast, sway area as well as the percentage difference of sway were differently modified in the two subgroups of patients with EC during the early stage of recovery. The NV patients swayed more, whereas the V patients swayed less without vision. This surprising finding, indicating that patients switched strategies with respect to their preoperative behavior, was consistently observed in 45 out of the 50 Ménière’s patients during the whole postoperative period, up to 1 year. We concluded that there is a differential weighting of visual inputs for the fine regulation of posture in both healthy participants and Ménière’s patients before surgical treatment. This differential weighting was correlated neither with age or sex factors, nor with the clinical variables at our disposal in the patients. It can be accounted for by a different selection of sensory orientation references depending on the personal experience of the subjects, leading to a more or less heavy dependence on vision. The change of sensory strategy in the patients who had undergone neurotomy might reflect a reweighting of the visual and somatosensory cues controlling balance. Switching strategy by means of a new sensory selection of orientation references may be a fast adaptive response to the lesion-induced postural instability.

Walking performance of vestibular-defective patients before and after unilateral vestibular neurotomy

The present study investigated goal-directed linear locomotion in nine Menières patients before and after (1 week, 1 and 3 months) a curative unilateral vestibular neurotomy (UVN). Experiments were done using a 3D motion analysis system in subjects walking eyes open (EO) and eyes closed (EC) towards a real or memorized target, respectively. Locomotor pattern (velocity, step length, step frequency and walk ratio) and walking trajectory deviations were evaluated for normal and fast speeds of locomotion and compared to those recorded in 10 healthy subjects. Before UVN, patients showed no walking deviation but gait pattern changes characterized by slower walks compared to the controls, mainly due to step length and step frequency reductions for both visual conditions and locomotion speeds. In the acute stage after UVN, locomotor pattern impairments were significantly accentuated. On the other hand, patients showed strong walking deviations towards the lesioned side with EC. Opposite lateral deviation towards the intact side were observed with EO for normal speed only. Recovery from impaired locomotor pattern was achieved within 1 month for normal speed but remained uncompensated 3 months post-lesion for fast speed particularly in EC condition. Finally, the walking trajectory deviation towards the lesioned side in the dark was maintained up to 3 months after UVN. The results show that central processing of visual and vestibular cues contributes to an accurate locomotor pointing. They argue for an increased weight of visual reference frame on locomotor functions when vestibular function is unilaterally impaired.

Neuronal coding of linear motion in the vestibular nuclei of the alert cat

SummaryThe aim of the present study was to investigate some aspects of the central processing of otolith information during linear motion. For this purpose, the response characteristics of 69 vestibular nuclei units to sinusoidal otolith stimulation in the vertical Z axis were analysed in the alert cat. Among this population of neurons which responded to a 0.05 Hz, 290 mm translation, 47 units (70%) displayed a firing rate modulation which followed the input frequency (H1 units). The majority of these neurons exhibited an increase in discharge rate during upward displacement, with a response phase close to the motion velocity or slightly leading downward acceleration. The acceleration related units were divided into two groups according to whether they showed clear increases or only a slight change in discharge rate when the stimulus frequency was increased. The former group was characterized by an average −16.3 dB drop in gain (from 43.9±1.8 dB, S.D. to 27.6±7 dB, S.D.) within the 0.05 Hz–0.5 Hz frequency range, while the latter group displayed an average −31.2 dB gain attenuation (from 45.1±1.1 dB, S.D. to 13.9±0 dB) within the same decade. In contrast to differences in response gain, all the units tested exhibited a relatively stable phase lead of about 20° with respect to downward peak acceleration. Conversely, units whose response was close to motion velocity in the lower frequency range (0.05 Hz–0.10 Hz) displayed a strong phase lead of about 100° when the stimulus frequency was increased (up to 0.50 Hz). These neurons were thus characterized by an acceleration related response in the higher frequency range. At the same time, an average −24.8 dB gain attenuation (from 47.7±3.4 dB to 22.9±3.7 dB) was found in the 0.05 Hz–0.5 Hz decade. The remaining 22 neurons (30%) were called H2 units since they displayed a response waveform double that of the input frequency, a response already described during sinusoidal rotation. Unit discharge reached a peak approximately in phase with maximum upward and downward velocity. Asymmetrical change in unit firing rate about the resting discharge level and different dynamic behavior of the upward and downward response components were usually found. These response characteristics suggest that the H2 patterns are centrally constructed and could result from convergence of otolith afferents having opposite polarization vectors. Other evidence suggests that these units which behave like motion-detectors can exert an influence on the neck musculature. Our results corroborate, at least in part, the findings of previous studies on the dynamic responses properties of otolith-dependent central neurons during roll tilt, or pure linear acceleration in the horizontal plane.

Fos expression in the rat brain after exposure to gravito-inertial force changes

The immediate-early genes constitute useful neurobiological tools for mapping brain functional activity after sensory stimulation. We immunohistochemically investigated Fos protein expression in the brain of rats exposed to gravito-inertial force changes. Experiments were performed in hypergravity rats born and housed for 60 days in terrestrian gravity (1xg) and thereafter exposed for 90 min to 2xg or 4xg in a centrifuge, and in hypogravity rats born and housed for 60 days at 2xg and submitted for 90 min to 1xg. Data from these two experimental groups were quantified by light microscopy and compared to those from two groups of control rats born and permanently housed in either 1xg or 2xg environments that never had to adapt to novel gravito-inertial environments. Results showed a low basal Fos expression in the controls and a strong Fos staining in the experimental rats. Only the hypergravity rats displayed Fos-positive cells in vestibular-related brainstem regions (medial, inferior, and superior vestibular nuclei (VN); group y; dorsomedial cell column (DMCC) of the inferior olive (IO)). By contrast, many suprabulbar areas were strongly labeled in both the hyper- and hypogravity rats, as shown by the numerous Fos-positive cells in mesencephalic (colliculus, laterodorsal periaqueductal gray, autonomic nuclei), diencephalic (hypothalamic and thalamic nuclei), and telencephalic (parietal, temporal, entorhinal and visual cortices) structures. These spatial patterns of Fos expression suggest that an increase in gravito-inertial force activates otolith-vestibulo-olivar pathways and various suprabulbar structures underlying the corticovestibular interactions, which govern the multiple representations of vestibular information in the cortex. A decrease in gravito-inertial force has the opposite effects on the vestibulo-olivar structures as a result of otolith system disfacilitation which, in turn, modifies the activity of complex neural pathways. Exposure to both hyper- and hypogravity environments likely induces neurovegetative and/or stress effects that could account for Fos labeling in autonomic nuclei and in nervous structures involved in the hypothalamo-pituitary-adrenal axis.

Restoration of vestibular function: basic aspects and practical advances for rehabilitation.

ABSTRACT Background: Normal balanced functioning of the human vestibular system is required to achieve an upright stance and locomotion, head and eye stabilization and internal spatial representation; any lesion in this system will disrupt these functions. Scope: This review synthesizes previous work performed by the author and his research group in both animal models and vestibular defective patients over the last three decades. The author presents both an updated view on the basic mechanisms underlying the two main theories of vestibular compensation and his views on the principles that should guide management and rehabilitation of patients with vestibular loss. Findings: Static deficits, following the loss or disruption of vestibular functions, are fully compensated; this is explained by the vestibulo-centric theory that suggests different plastic changes occurring in the vestibular nuclei complexes. In contrast, dynamic deficits remain poorly compensated; the restoration of dynamic vestibular functions results from substitution processes and vicarious strategies. The practical advances in the rehabilitation of vestibular defective patients are as follows: (1) perform rehabilitation at an early stage; (2) favour active retraining; (3) do not use stereotyped rehabilitation programs but adapt exercises to the patients; (4) examine patients in standardized environments; (5) use both static and dynamic tests; and (6) avoid drugs with sedative effects (or limit them to the very acute stage only) and prescribe those accelerating the recovery process (e.g. betahistine dihydrochloride). Conclusion: Recovery of vestibular function is greatest when early active retraining and adequate pharmacological treatments are used in combination.

New neurons in the vestibular nuclei complex after unilateral vestibular neurectomy in the adult cat

Recent findings revealed a reactive neurogenesis after lesions and in several models of disease. After unilateral vestibular neurectomy (UVN), we previously reported γ‐aminobutyric acid (GABA)ergic neurons are upregulated in the vestibular nuclei (VN) in the adult cat. Here, we ask whether this upregulation of GABAergic neurons resulted from a reactive neurogenesis. To determine the time course of cell proliferation in response to UVN, 5‐bromo‐2′‐deoxyuridine (BrdU) was injected 3 h, 1, 3, 7, 15 and 30 days after UVN. We investigated the survival and differentiation in UVN cats injected with BrdU at 3 days and perfused 30 days after UVN. Results show a high number of BrdU‐immunoreactive nuclei in the deafferented VN with a peak at 3 days after UVN and a decrease at 30 days. Most of the newly generated cells survived up to 1 month after UVN and gave rise to a variety of cell types. Confocal analysis revealed three cell lineages: microglial cells (OX 42/BrdU‐immunoreactive cells); astrocytes [glial fibrillary acidic protein (GFAP)/BrdU‐immunoreactive cells]; and neurons (NeuN/BrdU‐immunoreactive cells). That UVN induced new neurons was confirmed by an additional marker (nestin) expressed by neural precursor cells. We show that most of the newly generated neurons have a GABAergic phenotype [glutamate decarboxylase (GAD)‐67/BrdU‐immunoreactive cells]. Morphological analysis showed two subtypes of GABAergic neurons: medium and small (30 vs. 10 µm, respectively). This is the first report of reactive neurogenesis in the deafferented VN in the adult mammalian CNS.

Gamma amino butyric acid (GABA) immunoreactivity in the vestibular nuclei of normal and unilateral vestibular neurectomized cats

Recent neurochemical investigations of the central vestibular pathways have demonstrated that several neurotransmitters are involved in various operations required for stabilizing posture and gaze. Neurons of the vestibular nuclei (VN) receive GABAergic inhibitory afferents, and GABAergic neurons distributed throughout the vestibular complex are implicated in inhibitory vestibulo‐ocular and vestibulo‐spinal pathways. The aim of this study was to analyse the modifications of GABA immunoreactivity (GABA‐ir) in the cat VN after unilateral vestibular neurectomy (UVN). Indeed, compensation of vestibular deficits is a good model for studying adult central nervous system (CNS) plasticity and the GABAergic system is involved in CNS plasticity. We studied GABA‐ir by using a purified polyclonal antibody raised against GABA. Light microscopic preparations of thin (20 µm) sections of cat VN were used to quantify GABA‐ir by an image analysing system measuring GABA‐positive punctate structures and the number of GABA‐positive neurons. Both the lesioned and intact sides were analysed in three populations of UVN cats killed at different times after injury (1 week, 3 weeks and 1 year). These data were compared to those collected in normal unlesioned and sham‐operated cats. Results showed a spatial distribution of GABA‐ir in the control cats that confirmed previous studies. GABA‐ir neurons, fibres and nerve terminals were scattered in all parts of the VN. A higher concentration of GABA‐positive neurons (small cells) was detected in the medial and inferior VN (MVN and IVN) and in the dorsal part of the lateral VN (LVNd). A higher level of GABA‐positive punctate strutures was observed in the MVN and in the prepositus hypoglossi (PH) nucleus. Lesion‐induced changes were found at each survival time. One week after injury the number of GABA‐positive neurons was significantly increased in the MVN, the IVN and the dorsal part of the LVN on the lesioned side and in the ventral part of the LVN on the intact side. One year later a bilateral increase in GABA‐positive neurons was detected in the MVN whilst a bilateral decrease was observed in both the SVN and the ventral part of the LVN. Changes in the GABA‐staining varicosities did not strictly coincide with the distribution of GABA‐ir cells, suggesting that GABA‐ir fibres and nerve terminals were also modified. One week and later after injury, higher GABA‐staining varicosities were seen unilaterally in the ipsilateral MVN. In contrast, bilateral increases (in PH) and bilateral decreases (in SVN and the ventral part of the LVN) were recorded in the nearly (3 weeks) or fully (1 year) compensated cats. At this stage GABA‐staining varicosities were significantly increased in the lesioned side of the MVN. These findings demonstrate the reorganization of the GABAergic system in the VN and its possible role in recovery process after UVN in the cat. The changes seen during the acute stage could be causally related to the VN neuron deafferentation, contributing to the static vestibular deficits. Those found in the compensated cats would be more functionaly implicated in the dynamic aspects of vestibular compensation.

Neurogenesis and astrogenesis contribution to recovery of vestibular functions in the adult cat following unilateral vestibular neurectomy: cellular and behavioral evidence

In physiological conditions, neurogenesis occurs in restricted regions of the adult mammalian brain, giving rise to integrated neurons into functional networks. In pathological or postlesional conditions neurogenesis and astrogenesis can also occur, as demonstrated in the deafferented vestibular nuclei after immediate unilateral vestibular neurectomy (UVN) in the adult cat. To determine whether the reactive cell proliferation and beyond neurogenesis and astrogenesis following UVN plays a functional role in the vestibular functions recovery, we examined the effects of an antimitotic drug: the cytosine-beta-d arabinofuranoside (AraC), infused in the fourth ventricle after UVN. Plasticity mechanisms were evidenced at the immunohistochemical level with bromodeoxyuridine, GAD67 and glial fibrillary acidic protein (GFAP) stainings. Consequences of immediate or delayed AraC infusion on the behavioral recovery processes were evaluated with oculomotor and posturo-locomotor tests. We reported that after UVN, immediate AraC infusion blocked the cell proliferation and decreased the number of GFAP-immunoreactive cells and GABAergic neurons observed in the vestibular nuclei of neurectomized cats. At the behavioral level, after UVN and immediate AraC infusion the time course of posturo-locomotor function recovery was drastically delayed, and no alteration of the horizontal spontaneous nystagmus was observed. In contrast, an infusion of AraC beginning 3 weeks after UVN had no influence neither on the time course of the behavioral recovery, nor on the reactive cell proliferation and its differentiation. We conclude that the first 3 weeks after UVN represent a possible critical period in which important neuroplasticity mechanisms take place for promoting vestibular function recovery: reactive neurogenesis and astrogenesis might contribute highly to vestibular compensation in the adult cat.

Fos expression in the cat brainstem after unilateral vestibular neurectomy

Immediate early genes are generally expressed in response to sensory stimulation or deprivation and can be used for mapping brain functional activity and studying the molecular events underlying CNS plasticity. We immunohistochemically investigated Fos protein induction in the cat brainstem after unilateral vestibular neurectomy (UVN), with special reference to the vestibular nuclei (VN) and related structures. Fos-like immunoreactivity was analyzed at 2, 8, and 24 h, and 1 and 3 weeks after UVN. Data from these subgroups of cats were quantified in light microscopy and compared to those recorded in control and sham-operated animals submitted to anesthesia and anesthesia plus surgery, respectively. Results showed a very low level of Fos expression in the control and sham conditions. By contrast, Fos was consistently induced in the UVN cats. Asymmetrical labeling was found in the medial, inferior, and superior VN (ipsilateral predominance) and in the prepositus hypoglossi (PH) nuclei and the beta subnuclei of the inferior olive (betaIO) (contralateral predominance). Symmetrical staining was observed in the autonomic, tegmentum pontine, pontine gray, locus coeruleus and other reticular-related nuclei. As a rule, Fos expression peaked early (2 h) and declined progressively. However, some brainstem structures including the ipsilateral inferior VN and the bilateral pontine gray nuclei displayed a second peak of Fos expression (24 h-1 week). By comparing these data to the behavioral recovery process, we conclude that the early Fos expression likely reflects the activation of neural pathways in response to UVN whereas the delayed Fos expression might underlie long-term plastic changes involved in the recovery process.