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

The present study investigated goal-directed linear locomotion in nine Menière’s 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.     

Vestibular information is necessary for maintaining metric properties of representational space: evidence from mental imagery

The vestibular system contributes to a wide range of functions, from postural and oculomotor reflexes to spatial representation and cognition. Vestibular signals are important to maintain an internal, updated representation of the body position and movement in space. However, it is not clear to what extent they are also necessary to mentally simulate movement in situations that do not involve displacements of the body, as in mental imagery. The present study assessed how vestibular loss can affect object-based mental transformations (OMTs), i.e., imagined rotations or translations of objects relative to the environment. Participants performed one task of mental rotation of 3D-objects and two mental scanning tasks dealing with the ability to build and manipulate mental images that have metric properties. Menière's disease patients were tested before unilateral vestibular neurotomy and during the recovery period (1 week and 1 month). They were compared to healthy participants tested at similar time intervals and to bilateral vestibular-defective patients tested after the recovery period. Vestibular loss impaired all mental imagery tasks. Performance varied according to the extent of vestibular loss (bilateral patients were frequently the most impaired) and according to the time elapsed after unilateral vestibular neurotomy (deficits were stronger at the early stage after neurotomy and then gradually compensated). These findings indicate that vestibular signals are necessary to perform OMTs and provide the first demonstration of the critical role of vestibular signals in processing metric properties of mental representations. They suggest that vestibular loss disorganizes brain structures commonly involved in mental imagery, and more generally in mental representation.     

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 microm) 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 structures 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 functionally implicated in the dynamic aspects of vestibular compensation.     

Ageing effects on path integration and landmark navigation

Navigation abilities show marked decline in both normal ageing and dementia. Path integration may be particularly affected, as it is supported by the hippocampus and entorhinal cortex, both of which show severe degeneration with ageing. Age differences in path integration based on kinaesthetic and vestibular cues have been clearly demonstrated, but very little research has focused on visual path integration, based only on optic flow. Path integration is complemented by landmark navigation, which may also show age differences, but has not been well studied either. Here we present a study using several simple virtual navigation tasks to explore age differences in path integration both with and without landmark information. We report that, within a virtual environment that provided only optic flow information, older participants exhibited deficits in path integration in terms of distance reproduction, rotation reproduction, and triangle completion. We also report age differences in triangle completion within an environment that provided landmark information. In all tasks, we observed a more restricted range of responses in the older participants, which we discuss in terms of a leaky integrator model, as older participants showed greater leak than younger participants. Our findings begin to explain the mechanisms underlying age differences in path integration, and thus contribute to an understanding of the substantial decline in navigation abilities observed in ageing. © 2012 Wiley Periodicals, Inc.     

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 β subnuclei of the inferior olive (βIO) (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.     

Impairment and recovery on a food foraging task following unilateral vestibular deafferentation in rats

It has been suggested that the vestibular system may contribute to the development of higher cognitive function, especially spatial learning and memory that uses idiothetic cues (e.g., dead reckoning). However, few studies have been done using behavioral tasks that could potentially separate the animals' ability for dead reckoning from piloting. The food foraging task requires the animal to continuously monitor and integrate self-movement cues and generate an accurate return path. It has been shown that bilateral vestibular-lesioned rats were impaired on this task. The present study used the same task to further examine the contribution of vestibular information to spatial navigation by comparing unilateral and bilateral lesions and by testing the animals at different time points following the lesion. The results demonstrated that animals with unilateral vestibular deafferentation were impaired in performing the task in the dark at 3 months after the lesion, and this impairment disappeared at 6 months after the lesion. This supports the notion that vestibular information contributes to dead reckoning and suggests possible recovery of function over time after the lesion. Animals with bilateral vestibular deafferentation were not able to be tested on the foraging task because they exhibited behavior distinct from the unilateral-lesioned animals, with significant hesitation in leaving their home cage for as long as 6 months after the lesion.     

Left spatial hemineglect: An unmanageable explosion of dissociations? no

Abstract

The term “spatial hemineglect” refers to the defective ability of patients with unilateral cerebral lesions (more frequently in the right hemisphere) to explore the side of space contralateral to the lesion, and to report stimuli presented in this portion of space. The differential diagnosis of hemineglect from global disorders of space exploration and perception is based on the presence of a contra-ipsilateral gradient, whereby performance is comparatively preserved in the ipsilateral side (right in right brain-damaged patients). In the more widely used diagnostic tasks, such as target cancellation and line bisection, patients can use the unaffected ipsilesional arm and are free to move their head and eyes, to compensate for associated visual half-field deficits. A defective performance in these tasks, therefore, cannot be attributed to primary sensory or motor deficits, which may occur in the absence of spatial hemineglect (see Bisiach & Vallar, 1988).     

Auditory deficits in visuospatial neglect patients

Since the pioneering experimental work of Bisiach et al. (1984) on deficits in sound localisation associated with unilateral brain lesions and visual neglect, a number of systematic investigations have examined auditory processing in visuospatial neglect patients. Evidence from a variety of experimental paradigms has revealed some auditory deficits in detection and identification tasks, during bilateral stimulation; plus localisation deficits for single sounds. These deficits emerge predominantly for contra-lesional sounds, although some auditory disturbances applying to both contra- and ipsilesional sounds have also been documented. Here we review evidence suggesting that some of these auditory deficits arise in relatively high-level stages of spatial processing. In addition, we present new analyses showing that auditory deficits in identification and localisation tasks often correlate with clinical measures of visual neglect, across a variety of different studies and tasks. This empirical relation suggests that a disturbance of multisensory spatial processing may often account for the joint auditory and visual spatial deficits in neglect patients, although rarer dissociations between the modalities should also be considered.     

Cognitive requirements for vestibular and ocular motor processing in healthy adults and patients with unilateral vestibular lesions

This study investigated the role of cognition in the vestibulo-ocular reflex (VOR) and ocular pursuit using a dual-task paradigm in patients with unilateral peripheral vestibular loss and healthy adults. We hypothesized that cognitive resources are involved in successful processing and integration of vestibular and ocular motor sensory information, and this requirement would be greater in patients with vestibular dysfunction. Sixteen well-compensated patients with surgically confirmed absent unilateral peripheral vestibular function and 16 healthy age- and sex-matched controls underwent seven combinations of vestibular-only, visual-only, and visual-vestibular stimuli while performing three different information processing tasks. Visual-vestibular stimuli included a semicircular canal and an otolith stimulus provided through seated chair rotations; fixation on a laser target and sinusoidal smooth pursuit while still; and fixation on a head-fixed laser target during chair rotations. The information processing tasks were three different auditory reaction time (RT) tasks: (1) simple RT, (2) disjunctive RT, and (3) choice RT. Our results showed increases in RTs in both patients and controls under all vestibular-only stimulation conditions and during ocular pursuit. Patients showed greater increases in RTs during vestibular stimulation and the more complex disjunctive and choice RT tasks. No differences between the groups were found during the visual-only or visual-vestibular interaction conditions. These results reveal interference between vestibulo-ocular processing and a concurrent RT task, suggesting that the VOR and the ocular motor system are dependent upon cognitive resources to some extent, and thus, are not fully automatic systems. We speculate that this interference with cognition occurs as a result of the sensory integration required for resolving inputs from multiple sensory streams. The particularly large decrement in information processing task performance of the patients compared with controls during vestibular stimulation suggests that compensation for unilateral vestibular loss requires continued cognitive resources.     

Long‐term deficits on a foraging task after bilateral vestibular deafferentation in rats

Animal studies have shown that bilateral vestibular deafferentation (BVD) causes deficits in spatial memory that may be related to electrophysiological and neurochemical changes in the hippocampus. Recently, human studies have also indicated that human patients can exhibit spatial memory impairment and hippocampal atrophy even 8–10 yr following BVD. Our previous studies have shown that rats with unilateral vestibular deafferentation (UVD) showed an impairment at 3 months after the surgery on a food foraging task that relies on hippocampal integration of egocentric cues, such as vestibular information; however, by 6 months postop, they showed a recovery of function. By contrast, the long‐term effects of BVD on spatial navigation have never been well studied. In this study, we tested BVD or sham rats on a food foraging task at 5 months postop. Under light conditions, BVD rats were able to use visual cues to guide themselves home, but did so with a significantly longer homing time. However, in darkness, BVD rats were severely impaired in the foraging task, as indicated by a significantly longer homing distance and homing time, with more errors and larger heading angles when compared with sham rats. These results suggest that, unlike UVD, BVD causes long‐term deficits in spatial navigation that are unlikely to recover, even with repeated T‐maze training. © 2008 Wiley‐Liss, Inc.     

Visual and cross-modal cues increase the identification of overlapping visual stimuli in Balint’s syndrome

Introduction: Cross-modal interactions improve the processing of external stimuli, particularly when an isolated sensory modality is impaired. When information from different modalities is integrated, object recognition is facilitated probably as a result of bottom-up and top-down processes. The aim of this study was to investigate the potential effects of cross-modal stimulation in a case of simultanagnosia. Method: We report a detailed analysis of clinical symptoms and an ¹⁸F-fluorodeoxyglucose (FDG) brain positron emission tomography/computed tomography (PET/CT) study of a patient affected by Balint’s syndrome, a rare and invasive visual–spatial disorder following bilateral parieto-occipital lesions. An experiment was conducted to investigate the effects of visual and nonvisual cues on performance in tasks involving the recognition of overlapping pictures. Four modalities of sensory cues were used: visual, tactile, olfactory, and auditory. Results: Data from neuropsychological tests showed the presence of ocular apraxia, optic ataxia, and simultanagnosia. The results of the experiment indicate a positive effect of the cues on the recognition of overlapping pictures, not only in the identification of the congruent valid-cued stimulus (target) but also in the identification of the other, noncued stimuli. All the sensory modalities analyzed (except the auditory stimulus) were efficacious in terms of increasing visual recognition. Conclusions: Cross-modal integration improved the patient’s ability to recognize overlapping figures. However, while in the visual unimodal modality both bottom-up (priming, familiarity effect, disengagement of attention) and top-down processes (mental representation and short-term memory, the endogenous orientation of attention) are involved, in the cross-modal integration it is semantic representations that mainly activate visual recognition processes. These results are potentially useful for the design of rehabilitation training for attentional and visual–perceptual deficits.     

Visual scanning in patients with unilateral visual neglect due to right-sided cerebro-vascular lesion

The characteristics of visual scanning in patients with unilateral visual neglect (UVN) were studied. Forty-one patients who showed UVN in the figure finding test and 21 patients who showed to UVN in the test were selected from 176 patients with the right-sided cerebro-vascular lesion. They ranged in age from 46 to 78 years. The severity of UVN in each subject was determined by the number of the figures neglected unilaterally in the figure finding test in which a subject was asked to circle the designated figures scattered among the other figures on the test paper. The following two tests were administered to each subject. Test 1 examined binocular peripheral vision by tachistoscopic method in which a white circle of 1 degree was presented for 1/8 sec at 15 degrees from the central fixation point either unilaterally or bilaterally. Test 2 investigated the movement of gazing point while a subject was searching a target on a screen with his or her head stabilized. It was recorded on 16 mm movie film with Eye-Mark Recorder Model IV (Nac Co.) and converted into a series of position coordinates from which a visual scan path was reproduced and values of variables representing characteristics of visual scanning were computed. Six of 19 subjects who demonstrated "mild" UVN were found their peripheral vision intact. The characteristics of their visual scan path did not differ from the ones of the other 9 subjects who demonstrated "no" UVN as well as intact peripheral vision.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sensory and memory properties of hippocampal place cells

The rat hippocampus contains place cells whose firing is location-specific. These cells fire only when the rat enters a restricted region of the environment called the firing field. In this review, we examine the sensory information that is fundamental to the place cell system for producing spatial firing. While visual information takes precedence in the control of firing fields when it is available, local (olfactory and/or tactile) cues combined with motion-related cues can permit stable spatial firing. Motion-related cues are integrated by hippocampal place cells, but in the absence of external cues do not support stable firing over long periods. While firing fields are based on a variety of sensory cues, they do not strictly depend on such cues. Rather, sensory information is important for activating the representation appropriate to the current environment as reflected by the firing properties of place cell ensembles. Specific sensory channels as well as the memory properties of place cells can support ongoing firing under manipulations of the environment. These memory features raise the question of the role of the place cell system in the acquisition, storage and retrieval of spatial information. Based on the existing literature about the effects of hippocampal lesions and about the metabolic activations in spatial memory tasks, we suggest that a function of the place cell system is to automatically provide the organism with information about its current location so as to allow for the rapid acquisition of novel information.     

Cortical modulation of whole body movements in brain-damaged patients

The aim of the present study was to assess whether the consistent bias in reproducing distances and lengths on visual tasks that characterizes hemispatial neglect is also present when whole body displacements have to be calculated and reproduced. Two different experiments were proposed to participants with right brain lesions and neglect syndrome (RN+), right (RN-) and left brain lesions (LN-) without neglect and to participants without brain damage (C). In Experiment 1, participants actively reproduced passive linear displacements in the same or in a different direction. This task could be performed using only vestibular and somatosensory input, since no relevant visual input was available. In Experiment 2, relevant visual information had to be integrated with vestibular and somatosensory information in order to make the active reproduction. In Experiment 1, all brain-damaged groups reproduced the horizontal displacements similarly to the control group and without any spatial asymmetry. In Experiment 2, when vestibular, somatosensory and visually remembered information was required to produce an integrated mental representation, RN+ processed contralesional displacements differently from ipsilesional ones. Rectilinear displacements of the whole body in space were not affected by focal left and right brain lesions, suggesting that the computation of nonvisual information can be accomplished by brain structures different from those involved in spatial visual processes. However, when body displacements in space required a mental representation based on visual and nonvisual sensory information, a significant asymmetry appeared only in patients with hemispatial neglect. Some attempts are made to identify the neural substrates involved in this integration.     

Selective hippocampal cholinergic deafferentation impairs self-movement cue use during a food hoarding task

Investigations using selective lesion techniques suggest that the septohippocampal cholinergic system may not be critical for spatial orientation. These studies employ spatial tasks that provide the animal with access to both environmental and self-movement cues; therefore, intact performance may reflect spared spatial orientation or compensatory mechanisms associated with one class of spatial cues. The present study investigated the contribution of the septohippocampal cholinergic system to spatial behavior by examining performance in foraging tasks in which cue availability was manipulated. Thirteen female Long-Evans rats received selective lesions of the medial septum/vertical band with 192 IgG saporin, and 11 received sham surgeries. Rats were trained to forage for hazelnuts in an environment with access to both environmental and self-movement cues (cued condition). Manipulations include altering availability of environmental cues associated with the refuge (uncued probe), removing all visual environmental cues (dark probe), and placing environmental and self-movement cues into conflict (reversal probe). Medial septum lesions disrupted homeward segment topography only under conditions in which self-movement cues were critical for organizing food hoarding behavior (dark and reversal). These results are consistent with medial septum lesions producing a selective impairment in self-movement cue processing and suggest that these rats were able to compensate for deficits in self-movement cue processing when provided access to environmental cues.     

Clinical application of dynamic posturography for evaluating sensory integration and vestibular dysfunction

The assessment of sensory organization in balance control by dynamic posturography is unique compared with clinical maneuvers and other vestibular or neurologic testing. It was designed to isolate the relative contributions of visual, somatosensory, and vestibular feedback, and thus to assess the overall function of the balance control system in adaptively selecting between available sensory information for orientation cues to serve as a reference to earth vertical. Rather than serving as a test for specific pathologic conditions, the utility of posturography is in screening for balance disorders and in functionally defining different types of sensory deficits or central disorders. This functional information can be used to define restrictions or high-risk environments for patients, to guide rehabilitative balance therapy, and to monitor progression of recovery from a disease process.     

Conjunctive effects of reward and behavioral episodes on hippocampal place-differential neurons of rats on a mobile treadmill

Previous studies reported context (or behavior)-dependent activities of hippocampal place cells, which are suggested to be the neural basis of episodic memory. However, it remains unclear what distinctive items these context-dependent activities encode. We investigated separately the effects of space, locomotion, and episodes with positive/negative reinforcements on activity of place-differential neurons in the hippocampal CA1 area. Rats were placed on a treadmill affixed to a motion stage translocated along a figure 8-shaped track. The track could be navigated by two different routes that shared a common central stem. The stage was paused at the start and end of the routes, where conditioned response tasks with different reinforcements were imposed. As the rats passed the common central stem, some neurons fired differently depending on the route. Comparison of hippocampal spatial firing patterns across different conditions with and without treadmill operation and/or the tasks indicated that these route-dependent spatial firing patterns were sensitive to locomotion, the tasks, and vestibular sensation or visual cues such as optic flow. The results suggest that external sensory inputs, path integration, and reinforcement context are all integrated in the hippocampus, which might provide the neural basis of episodic memory.     

Trajectory estimation in schizophrenia

Two experiments were conducted to investigate the ability of schizophrenia patients to maintain internal representation over time and space. It has been hypothesized that the ability to guide behavior by internal representation, mediated by the dorsolateral prefrontal cortex (DLPFC), is impaired in schizophrenia [e.g. Goldman-Rakic, P.S., 1996. The functional parcellation of dorsolateral prefrontal cortex and the heterogeneous facets of schizophrenia. In: Matthysse, S., Levy, D.L. (Eds.), Psychopathology: Evolution of a New Science. Cambridge University Press, Cambridge]. In Experiment 1, subjects observed a target, which traveled behind an opaque wall during a part of its trajectory. The task was to accurately assess the speed of the target by predicting when the target would re-emerge on the other side of the wall. In Experiment 2, subjects were asked to estimate the spatial trajectory of an established target path when it was partially occluded from view by another object. Schizophrenia patients were impaired in estimating the speed of a moving target and in estimating the spatial trajectory, without showing deficits in the control tasks. These results suggest that schizophrenia patients may not be able to accurately maintain the internal representation of a target over time and space. Such deficits may have deleterious consequences in goal-directed behavior.     

Number processing in posterior cortical atrophy--a neuropsycholgical case study

Posterior cortical atrophy (PCA) is an uncommon syndrome of dementia with early onset, characterised by disorders of higher visual function, variable symptoms of Balint's syndrome, visual agnosia, alexia, agraphia, finger agnosia, right-left disorientation and dyscalculia [Benson D. F., Davis R. J., & Snyder B. D. (1988). Posterior cortical atrophy. Archives of Neurology, 45, 789-793]. In a single case study specific numerical deficits were observed which may be predicted by parietal neurodegeneration (more pronounced on the right side; verified by SPECT). Besides impairments in all tasks involving visuo-spatial abilities (e.g., dot counting, analog number scale task), deficits appeared in tasks requiring access to an internal representation of numbers such as mental number bisection, approximation, estimation and semantic facts. In number comparison an increased distance effect was found. In simple arithmetic, a striking dissociation between operations was found-multiplication and addition facts being preserved at a superficial level, subtraction and division being severely impaired. The study confirms the close relation between spatial and numerical processing and highlights the modular organisation of the semantic system (number semantics impaired). Moreover, the study adds evidence about the clinical manifestation of the particular degenerative syndrome.