Vestibular Network Research Articles

Neural correlates of disturbed perception of verticality

Perception of verticality can be perturbed after cortical stroke. However, a relationship between lesion location and pathologic perception of verticality is still a matter of debate since previous studies revealed contradictory results. Thus, the aim of the current study was to test whether specific cortical lesions were associated with tilts of subjective visual vertical (SVV) and to determine the critical brain areas that cause such tilts in the case of a lesion. SVV was systematically studied in 54 patients (22 patients with left-sided and 32 patients with right-sided lesions) with acute unilateral strokes, analyzed by modern voxel-wise lesion-behavior mapping techniques. The data give evidence for an association between tilt of SVV and the insular cortex (IC) and inferior frontal gyrus (IFG) in both hemispheres. Whereas the IC seems to be the prominent structure in the left hemisphere, the IFG is most affected in the right hemisphere. Furthermore, other cortical regions such as the superior temporal gyrus (STG) and the rolandic operculum as well as-subcortically-the inferior occipitofrontal fascicle and the superior longitudinal fascicle seem to be involved in the vestibulo-cortical network for the perception of verticality in the roll plane. Damage to these regions might lead to an imbalance within the vestibular network of one hemisphere due to a deficit in multimodal signal processing.

Vestibular and attractor network basis of the head direction cell signal in subcortical circuits.

Accurate navigation depends on a network of neural systems that encode the moment-to-moment changes in an animal's directional orientation and location in space. Within this navigation system are head direction (HD) cells, which fire persistently when an animal's head is pointed in a particular direction (Sharp et al., 2001a; Taube, 2007). HD cells are widely thought to underlie an animal's sense of spatial orientation, and research over the last 25+ years has revealed that this robust spatial signal is widely distributed across subcortical and cortical limbic areas. The purpose of the present review is to summarize some of the recent studies arguing that the origin of the HD signal resides subcortically, specifically within the reciprocal connections of the dorsal tegmental and lateral mammillary nuclei. Furthermore, we review recent work identifying “bursting” cellular activity in the HD cell circuit after lesions of the vestibular system, and relate these observations to the long held view that attractor network mechanisms underlie HD signal generation. Finally, we summarize anatomical and physiological work suggesting that this attractor network architecture may reside within the tegmento-mammillary circuit.

Meta-analytical definition and functional connectivity of the human vestibular cortex

Contrary to most other sensory systems, no consensus has been reached within the scientific community about the exact locations and functions of human cortical areas processing vestibular information. Metaanalytical modelling using activation likelihood estimation (ALE) for the integration of neuroimaging results has already been successfully applied to several distinct tasks, thereby revealing the cortical localization of cognitive functions. We used the same algorithm and technique with all available and suitable PET and fMRI studies employing a vestibular stimulus. Most consistently across 28 experiments vestibular stimuli evoked activity in the right hemispheric parietal opercular area OP 2 implicating it as the core region for vestibular processing. Furthermore, we took our primary results as a seeding point and fed them into a functional connectivity analysis based on resting-state oscillations in 100 healthy subjects. This subsequent calculation confirmed direct connections of the area OP 2 with every other region found in the meta-analysis, in particular temporo-parietal regions, premotor cortex, and the midcingulate gyrus. Thus revealing a joint vestibular network in accordance with a concept from animal literature termed the inner vestibular circle. Moreover, there was also a significant vestibular connectivity overlap with frontal but not parietal cortical centres responsible for the generation of saccadic eye movements, likely to be involved in nystagmus fast phase generation. This was shown in an additional ocular motor meta-analysis. We conclude that the cytoarchitectonic area OP 2 in the parietal operculum, embedded in a joint vestibular network, should be the primary candidate for the human vestibular cortex. This area may represent the human homologue to the vestibular area PIVC as proposed by Guldin and Grüsser in non-human primates.

Pusher syndrome: its cortical correlate

Unilateral stroke can lead to a disorder of postural balance that manifests as a pushing away toward the contralesional side. It is called "pusher syndrome" (PS). The aims of this study were first to assess the anatomical cortical regions that induce PS and second to clarify whether tilt of the subjective visual vertical (SVV)--a sign of vestibular otolith dysfunction--is associated with PS. Sixty-six patients with acute unilateral strokes (28 left-sided lesions, 38 right-sided lesions) were tested for PS, for tilts of the SVV, for hemineglect and for the anatomical lesion site by magnetic resonance imaging (MRI)-based voxelwise lesion-behavior mapping analysis. Our data indicated no significant voxels; however, there was a trend towards an association between lesions of the posterior part of the insula, the operculum and the superior temporal gyrus--key areas of the multisensory vestibular cortical network--and the extent of pushing in patients with right-sided lesions, whereas the rather anterior part of the insula, the operculum as well as the internal capsule reaching to the lateral thalamus seemed to be involved in PS in left-sided lesion patients. These data might point toward a link between the systems responsible for postural control and for processing vestibular otolith information. These findings indicate that vestibular information might be fundamental in right-sided lesion patients for maintaining body posture in space.

F010 Functional status of hearing aids in bimodal (CI-HA) users

Short tone bursts trigger a vestibular evoked myogenic potential (VEMP), an inhibitory potential which reflects a component of the vestibulocollic reflex (VCR). These potentials arise as a result of activation of the sacculus and are expressed through the vestibulo-collic reflex (VCR). Up to now, the ascending projections of the sacculus are unknown in humans, only the representation of the semicircular canals or the entire vestibular nerve has been demonstrated. The aim of this study was to determine whether a sacculus stimulus that evoked VEMPs could activate vestibular cortical areas in fMRI.To determine this, we studied the differential effects of unilateral VEMP stimulation in 21 healthy right-handers in a clinical 1.5 T scanner while wearing piezo electric headphones. A unilateral VEMP stimulus and two auditory control stimuli were given in randomized order over the stimulated ear. A random effects statistical analysis was done with SPM2 (p < 0.05, corrected). After exclusion of the auditory effects, the major findings were as follows: (i) significant activations were located in the multisensory cortical vestibular network within both hemispheres, including the posterior insular cortex, the middle and superior temporal gyri, and the inferior parietal cortex. (ii) The activation pattern was elicited bilaterally with a predominance of the right hemisphere in right-handers. (iii) Saccular vestibular projection was predominantly ipsilateral, whereas (iv) pure acoustic stimuli were processed with a predominance of the respective contralateral and mainly in the left hemisphere.This is the first demonstration by means of fMRI of the cortical representation of the saccular input at cortical level. The activation pattern is similar to that known from the stimulation of the entire vestibular nerve or the horizontal semicircular canal. Our data give evidence of a task-dependent separation of the processing within the vestibular otolith and the auditory systems in the two hemispheres.

Neurologic bases for comorbidity of balance disorders, anxiety disorders and migraine: neurotherapeutic implications

The comorbidity among balance disorders, anxiety disorders and migraine has been studied extensively from clinical and basic research perspectives. From a neurological perspective, the comorbid symptoms are viewed as the product of sensorimotor, interoceptive and cognitive adaptations that are produced by afferent interoceptive information processing, a vestibulo–parabrachial nucleus network, a cerebral cortical network (including the insula, orbitofrontal cortex, prefrontal cortex and anterior cingulate cortex), a raphe nuclear–vestibular network, a coeruleo–vestibular network and a raphe–locus coeruleus loop. As these pathways overlap extensively with pathways implicated in the generation, perception and regulation of emotions and affective states, the comorbid disorders and effective treatment modalities can be viewed within the contexts of neurological and psychopharmacological sites of action of current therapies.

Does caloric vestibular stimulation modulate tinnitus?

Caloric vestibular stimulation (CVS) has been demonstrated to transiently modulate a variety of cognitive functions. These effects are associated with the brain activation induced by CVS, involving the temporal–parietal cortex, anterior cingulate cortex and insular cortex, which are thought to form a multimodal vestibular cortical network. The present study investigated the effect of CVS upon tinnitus. Twenty patients undergoing vestibular function tests for symptoms of imbalance and who reported tinnitus were asked to rate their tinnitus using visual analogue measures of pitch and intensity immediately before and after CVS (H 2O at 44 °C) in the ear ipsilateral to the tinnitus. One patient was excluded due to test findings indicative of a central vestibular abnormality. The mean VAS pitch (pre–post) changed from 5.65 to 5.28 (95% confidence interval (−0.87, 0.12), p-value 0.13) and the mean change in intensity changed from 5.21 to 4.43 (95% confidence interval (−1.60, 0.04), p-value 0.06). The findings indicate that there is no consistent influence of CVS upon tinnitus, and we propose that perceived pitch and intensity of tinnitus are independent of the multimodal vestibular network that is activated by CVS.

Evidence for modulation of opioidergic activity in central vestibular processing: A [18F] diprenorphine PET study

Animal and functional imaging studies had identified cortical structures such as the parieto-insular vestibular cortex, the retro-insular cortex, or the anterior cingulate cortex belonging to a vestibular cortical network. Basic animal studies revealed that endorphins might be important transmitters involved in cerebral vestibular processing. The aim of the present study was therefore to analyse whether the opioid system is involved in vestibular neurotransmission of humans or not. Changes in opioid receptor availability during caloric air stimulation of the right ear were studied with [(18)F] Fluoroethyl-diprenorphine ([(18)F]FEDPN) PET scans in 10 right-handed healthy volunteers and compared to a control condition. Decrease in receptor availability to [(18)F]FEDPN during vestibular stimulation in comparison to the control condition was significant at the right posterior insular cortex and the postcentral region indicating more endogenous opioidergic binding in these regions during stimulation. These data give evidence that the opioidergic system plays a role in the right hemispheric dominance of the vestibular cortical system in right-handers.

Evidence for cognitive vestibular integration impairment in idiopathic scoliosis patients

BackgroundAdolescent idiopathic scoliosis is characterized by a three-dimensional deviation of the vertebral column and its etiopathogenesis is unknown. Various factors cause idiopathic scoliosis, and among these a prominent role has been attributed to the vestibular system. While the deficits in sensorimotor transformations have been documented in idiopathic scoliosis patients, little attention has been devoted to their capacity to integrate vestibular information for cognitive processing for space perception. Seated idiopathic scoliosis patients and control subjects experienced rotations of different directions and amplitudes in the dark and produced saccades that would reproduce their perceived spatial characteristics of the rotations (vestibular condition). We also controlled for possible alteration of the oculomotor and vestibular systems by measuring the subject's accuracy in producing saccades towards memorized peripheral targets in absence of body rotation and the gain of their vestibulo-ocular reflex.ResultsCompared to healthy controls, the idiopathic scoliosis patients underestimated the amplitude of their rotations. Moreover, the results revealed that idiopathic scoliosis patients produced accurate saccades to memorized peripheral targets in absence of body rotation and that their vestibulo-ocular reflex gain did not differ from that of control participants.ConclusionOverall, results of the present study demonstrate that idiopathic scoliosis patients have an alteration in cognitive integration of vestibular signals. It is possible that severe spine deformity developed partly due to impaired vestibular information travelling from the cerebellum to the vestibular cortical network or alteration in the cortical mechanisms processing the vestibular signals.

Gray‐Matter Atrophy after Chronic Complete Unilateral Vestibular Deafferentation

It has been shown in blind patients that the abolition of sensory input can lead to changes in white- and cortical gray-matter volumes. Here the white- and gray-matter changes found with whole brain voxel-based morphometry in 16 patients with complete chronic unilateral vestibular deafferentation (UVD) due to vestibular schwannoma removal several years prior are reported on. Subtle deficits in spatial memory and navigation were previously shown in patients with right UVD. Images of the brains of right-UVD patients were flipped, standard preprocessing steps were performed, and the data were modulated. Patients showed a gray-matter volume reduction in the cerebellum due to schwannoma removal, in the supramarginal gyrus ipsilateral to the lesion, as well as in the postcentral and superior temporal gyrus, areas involved in the vestibular cortical network, and in the motion-sensitive area MT/V5. There was no correlation with behavioral navigational abilities. No gray-matter atrophy was found in the insular cortical vestibular region or the hippocampus, both of which receive bilateral vestibular projections. The thalamus and tegmentum of the mesencephalon showed gray-matter reduction on the opposite side; this was possibly due to reduced auditory input, which is known to cross at this level. In comparison to healthy controls, no regional increases in gray-matter volume were seen. No white-matter changes were detected at the selected threshold.

Mind the bend: cerebral activations associated with mental imagery of walking along a curved path

The use of functional magnetic resonance imaging (fMRI) to examine mental imagery of locomotion has become an attractive way to investigate supraspinal gait control in humans. Whereas cerebral activation patterns associated with walking along a straight line have already been investigated, data on activations associated with the initiation of turns and the maintenance of a curved path are sparse. Electrophysiological findings in animals show that electrical stimulation of the striatum induces a contraversive turn of eyes, head, and body. In the present study, fMRI was used to investigate brain activity in 12 healthy volunteers during mental imagery of walking along a curved path, walking straight ahead, and upright stance. The major findings were as follows: (1) A shift of activation to the hemisphere contralateral to the turn was found in the putamen, and-for initiation of the turn-in the caudate nucleus. These findings confirm the important role of the striatum in the initiation of movement and the execution of contraversive body turns. (2) Parahippocampal and fusiform gyri, known to be involved in visually guided navigation, showed more activity when walking along a curved path than when walking straight ahead. (3) Deactivations were found in the superior and medial temporal gyri, areas belonging to the multisensory and vestibular cortical network. This reduced activity may reflect the suppression of vestibular signal processing in favour of-potentially conflicting-visual input. (4) Mental imagery of walking along a curved path induced ipsiversive eye movements in most subjects, as did actually walking along a curve. These data complement earlier findings on the role of anticipatory eye movements during initiation of turns and suggest that there is a very close neurophysiologic relation between locomotion and its mental imagery.

Cortical representation of saccular vestibular stimulation: VEMPs in fMRI

Short tone bursts trigger a vestibular evoked myogenic potential (VEMP), an inhibitory potential which reflects a component of the vestibulocollic reflex (VCR). These potentials arise as a result of activation of the sacculus and are expressed through the vestibulo-collic reflex (VCR). Up to now, the ascending projections of the sacculus are unknown in humans, only the representation of the semicircular canals or the entire vestibular nerve has been demonstrated. The aim of this study was to determine whether a sacculus stimulus that evoked VEMPs could activate vestibular cortical areas in fMRI. To determine this, we studied the differential effects of unilateral VEMP stimulation in 21 healthy right-handers in a clinical 1.5 T scanner while wearing piezo electric headphones. A unilateral VEMP stimulus and two auditory control stimuli were given in randomized order over the stimulated ear. A random effects statistical analysis was done with SPM2 ( p < 0.05, corrected). After exclusion of the auditory effects, the major findings were as follows: (i) significant activations were located in the multisensory cortical vestibular network within both hemispheres, including the posterior insular cortex, the middle and superior temporal gyri, and the inferior parietal cortex. (ii) The activation pattern was elicited bilaterally with a predominance of the right hemisphere in right-handers. (iii) Saccular vestibular projection was predominantly ipsilateral, whereas (iv) pure acoustic stimuli were processed with a predominance of the respective contralateral and mainly in the left hemisphere. This is the first demonstration by means of fMRI of the cortical representation of the saccular input at cortical level. The activation pattern is similar to that known from the stimulation of the entire vestibular nerve or the horizontal semicircular canal. Our data give evidence of a task-dependent separation of the processing within the vestibular otolith and the auditory systems in the two hemispheres.

Changes in D‐serine levels and localization during postnatal development of the rat vestibular nuclei

The patterns of development of the vestibular nuclei (VN) and their main connections involving glutamate neurotransmission offer a good model for studying the function of the glial-derived neuromodulator D-serine in synaptic plasticity. In this study we show that D-serine is present in the VN and we analyzed its distribution and the levels of expression of serine racemase and D-amino acid oxidase (D-AAO) at different stages of postnatal (P) development. From birth to P21, high levels of D-serine were detected in glial cells and processes in all parts of the VN. This period corresponded to high expression of serine racemase and low expression of D-AAO. On the other hand, in the mature VN D-serine displayed very low levels and was mainly localized in neuronal cell bodies and dendrites. This drop of D-serine in adult stages corresponded to an increasing expression of D-AAO at mature stages. High levels of glial D-serine during the first 3 weeks of postnatal development correspond to an intense period of plasticity and synaptogenesis and maturation of VN afferents, suggesting that D-serine could be involved in these phenomena. These results demonstrate for the first time that changes in D-serine levels and distribution occur during postnatal development in the central nervous system. The strong decrease of D-serine levels and the glial-to-neuronal switch suggests that D-serine may have distinct functional roles depending on the developmental stage of the vestibular network.

Sex differences in mental rotation: Top–down versus bottom–up processing

Functional MRI during performance of a validated mental rotation task was used to assess a neurobiological basis for sex differences in visuospatial processing. Between-sex group analysis demonstrated greater activity in women than in men in dorsalmedial prefrontal and other high-order heteromodal association cortices, suggesting women performed mental rotation in an effortful, “top–down” fashion. In contrast, men activated primary sensory cortices as well as regions involved in implicit learning (basal ganglia) and mental imagery (precuneus), consistent with a more automatic, “bottom–up” strategy. Functional connectivity analysis in association with a measure of behavioral performance showed that, in men (but not women), accurate performance was associated with deactivation of parieto-insular vestibular cortex (PIVC) as part of a visual–vestibular network. Automatic evocation by men to a greater extent than women of this network during mental rotation may represent an effective, unconscious, bottom–up neural strategy which could reasonably account for men's traditional visuospatial performance advantage.

Therapeutic Effects of Caloric Stimulation and Optokinetic Stimulation on Hemispatial Neglect

Hemispatial neglect refers to a cognitive disorder in which patients with unilateral brain injury cannot recognize or respond to stimuli located in the contralesional hemispace. Hemispatial neglect in stroke patients is an important predictor for poor functional outcome. Therefore, there is a need for effective treatment for this condition. A number of interventions for hemispatial neglect have been proposed, although an approach resulting in persistent improvement is not available. Of these interventions, our review is focused on caloric stimulation and optokinetic stimulation. These lateralized or direction-specific stimulations of peripheral sensory systems can temporarily improve hemispatial neglect. According to recent functional MRI and PET studies, this improvement might result from the partial (re)activation of a distributed, multisensory vestibular network in the lesioned hemisphere, which is a part of a system that codes ego-centered space. However, much remain unknown regarding exact signal timing and directional selectivity of the network.

Asymmetrical perception of body rotation after unilateral injury to human vestibular cortex

Vestibular information plays a key role in many perceptual and cognitive functions, but surprisingly little is known about how vestibular signals are processed at the cortical level in humans. To address this issue, we tested the ability of two patients, with damage to key components of the vestibular network in either the left or right hemisphere, to perceive passive whole-body rotations (25–125°) about the yaw axis. In both patients, the posterior insula, hippocampus, putamen, and thalamus were extensively damaged. The patients’ responses were compared with those of nine age- and sex-matched neurologically intact participants. The body rotations were conducted without vision and the peak angular velocities ranged from 40° to 90° per second. Perceived rotation was assessed by open-loop manual pointing. The right hemisphere patient exhibited poor sensitivity for body rotations toward the contralesional (left) hemispace and generally underestimated the rotations. By contrast, his judgments of rotations toward the ipsilesional (right) hemispace greatly overestimated the physical rotation by 50–70° for all tested magnitudes. The left hemisphere patient's responses were more appropriately scaled for both rotation directions, falling in the low-normal range. These findings suggest that there is some degree of hemispheric specialization in the cortical processing of dynamic head rotations in the yaw plane. In this view, right hemisphere structures play a dominant role, processing rotations in both directions, while left hemisphere structures process rotations only toward the contralesional hemispace.

Identifying human parieto‐insular vestibular cortex using fMRI and cytoarchitectonic mapping

The parieto-insular vestibular cortex (PIVC) plays a central role in the cortical vestibular network. Although this region was first defined and subsequently extensively studied in nonhuman primates, there is also ample evidence for a human analogue in the posterior parietal operculum. In this study, we functionally and anatomically characterize the putative human equivalent to macaque area PIVC by combining functional magnetic resonance imaging (fMRI) of the cortical response to galvanic vestibular stimulation (GVS) with probabilistic cytoarchitectonic maps of the human parietal operculum. Our fMRI data revealed a bilateral cortical response to GVS in posterior parieto-insular cortex. Based on the topographic similarity of these activations to primate area PIVC, we suggest that they constitute the functionally defined human equivalent to macaque area PIVC. The locations of these activations were then compared to the probabilistic cytoarchitectonic maps of the parietal operculum (Eickhoff et al. [2005a]: Cereb Cortex, in press; Eickhoff et al. [2005c]: Cereb Cortex, in press), whereby the functionally defined PIVC matched most closely the cytoarchitectonically defined area OP 2. This activation of OP 2 by vestibular stimulation and its cytoarchitectonic features, which are similar to other primary sensory areas, suggest that area OP 2 constitutes the human equivalent of macaque area PIVC.

Functional MRI of galvanic vestibular stimulation with alternating currents at different frequencies

Functional MRI was performed in 28 healthy volunteers to study the effects of galvanic vestibular stimulation with alternating currents (AC-GVS) of different frequencies on brain activation patterns. The aims of this study were (1) to identify specific areas within the vestibular cortical network that are involved in the processing of frequency-specific aspects by correlation analyses, (2) to determine the optimal frequency for stimulation of the vestibular system with respect to perception, and (3) to analyze whether different frequencies of AC-GVS are mediated in different cortical areas or different sites within the vestibular cortex. AC-GVS was performed using sinusoidal stimulation currents with an amplitude of ±2.5 mA, and frequencies of 0.1 Hz, 0.3 Hz, 0.8 Hz, 1.0 Hz, 2.0 Hz, and 5.0 Hz were applied. Regardless of the applied stimulation frequency, AC-GVS elicited activations within a network of multisensory areas similar to those described in earlier studies using direct currents. No mapping of different stimulation frequencies to different cortical locations was observed. Additional activations of somatosensory cortex areas were observed during stimulation with 5 Hz only. The strongest vestibular sensations were reported during stimulation with 1 Hz and 2 Hz. Correlation analyses between blood oxygenation level dependent (BOLD) signal changes and stimulation frequency revealed a positive dependency in areas of the supramarginal gyrus, posterolateral thalamus, cerebellar vermis, posterior insula, and in the hippocampal region/uncus. These regions represent areas involved in the processing of vestibular information for head and body orientation in space.

Representation of Visual Gravitational Motion in the Human Vestibular Cortex

How do we perceive the visual motion of objects that are accelerated by gravity? We propose that, because vision is poorly sensitive to accelerations, an internal model that calculates the effects of gravity is derived from graviceptive information, is stored in the vestibular cortex, and is activated by visual motion that appears to be coherent with natural gravity. The acceleration of visual targets was manipulated while brain activity was measured using functional magnetic resonance imaging. In agreement with the internal model hypothesis, we found that the vestibular network was selectively engaged when acceleration was consistent with natural gravity. These findings demonstrate that predictive mechanisms of physical laws of motion are represented in the human brain.

Modulation and rehabilitation of spatial neglect by sensory stimulation

After unilateral cortical or subcortical, often parieto-temporal lesions, patients exhibit a marked neglect of their contralateral space and/or body side. These patients are severely disabled in all daily activities, have a poor rehabilitation outcome and therefore require professional treatment. Unfortunately, effective treatments for neglect are just in the process of development. The present chapter reviews three aspects related to the rehabilitation of neglect. The first part summarizes findings about spontaneous recovery in patients and experimental animals with neglect. The second part deals with techniques and studies evaluating short-term sensory modulation effects in neglect. In contrast to many other neurological syndromes spatial neglect may be modulated transiently but dramatically in its severity by sensory (optokinetic, neck proprioceptive, vestibular, attentional, somatosensory-magnetic) stimulation. In part three, current treatment approaches are summarized, with a focus on three novel techniques: repetitive optokinetic stimulation, neck vibration training and peripheral somatosensory-magnetic stimulation. Recent studies of repetitive optokinetic as well as neck vibratory treatment both indicate significantly greater as well as multimodal improvements in neglect symptomatology as compared to the standard treatment of neglect. This clear superiority might result from the partial (re)activation of a distributed, multisensory vestibular network in the lesioned hemisphere. Somatosensory-magnetic stimulation of the neglected or extinguishing hand provides another feasible, non-invasive stimulation technique. It may be particularly suited for the rehabilitation of somatosensory extinction and unawareness of the contralesional body side. Finally, pharmacological approaches for the treatment of neglect are shortly addressed. Isolated drug treatment of neglect is currently no successful rehabilitation strategy due to inconsistent results as well as possible side effects. However, combined behavioural and drug treatments might yield better results. This has to be tested empirically in patient studies. In conclusion, the findings obtained in short-term sensory stimulation studies led to the development of effective techniques for the long-term rehabilitation of neglect. Future rehabilitation studies should evaluate effective treatment combinations considering all possible techniques and devices (behavioural, pharmacological, prosthetic or physiological).