Cross-modal Extinction Research Articles

Unimodal and crossmodal extinction of nociceptive stimuli in healthy volunteers

Nociception, the physiological mechanisms specifically processing information about noxious and potentially painful stimuli, has the double function to warn about potential body damages (interoception) and about the cause of such potential damages (exteroception). The exteroceptive function is thought to rely on multisensory integration between somatic and extra-somatic stimuli, provided that extra-somatic stimuli occur near the stimulated body area. To corroborate this hypothesis, we succeeded to show in healthy volunteers that the perception of nociceptive stimuli applied on one hand can be extinguished, as compared to single presentation, by the simultaneous application of nociceptive stimuli on the opposite hand, as well as by the presentation of visual stimuli near the opposite hand. On the contrary, visual stimuli presented near the same stimulated hand facilitated the perception of nociceptive stimuli. This nociceptive extinction phenomenon indicates that the perception of noxious events does not merely rely on the specific activation of the nociceptive system, but also depends on other sensory experiences about the body and the space around it.

An exploratory cohort study of sensory extinction in acute stroke: prevalence, risk factors, and time course

Most studies on sensory extinction have focused on selected patients with subacute and chronic right hemisphere lesions. In studies conducted on acute stroke patients, risk factors and time course were not evaluated. Our aim was to determine the prevalence, risk factors, and time course of sensory extinction in the acute stroke setting. Consecutive patients with acute stroke were tested for tactile, visual, auditory, and auditory-tactile cross-modal extinction, as well as for peripersonal visuospatial neglect (PVN). Tests were repeated at 2, 7, 15, 30, and 90 days after initial examination. A multivariable logistic regression analysis was performed to test the association between sensory extinction and demographic and clinical risk factors. Seventy-three patients (38.4% women) were recruited: 64 with ischemic stroke and nine with haemorrhagic stroke. Mean age was 62.3 years (95% CI 58.8–65.7), mean NIHSS score was 1.6 (95% CI 1.2–2.1), and mean time to first examination was 4.1 days (95% CI 3.5–4.8). The overall prevalence of all subtypes of sensory extinction was 13.7% (95% CI 6.8–23.8). Tactile extinction was the most frequent subtype with a prevalence of 8.2% (95% CI 3.1–17.0). No extinction was found beyond 15 days after the first examination. After adjustment for age, sex, lesion side, type of stroke, time to first examination and stroke severity, a lesion volume ≥2 mL (adjusted OR = 38.88, p = 0.04), and presence of PVN (adjusted OR = 24.27, p = 0.04) were independent predictors of sensory extinction. The insula, the putamen, and the pallidum were the brain regions most frequently involved in patients with sensory extinction. Extinction is a rare and transient phenomenon in patients with minor stroke. The presence of PVN and lesion volume ≥2 mL are independent predictors of sensory extinction in acute stroke.

Interactions between Senses: Updating on Neural Mechanisms and Behavioral Evidence

Interactions between Senses: Updating on Neural Mechanisms and Behavioral Evidence

Spatial dependency of action simulation

In this study, we investigated the spatial dependency of action simulation. From previous research in the field of single-cell recordings, grasping studies and from crossmodal extinction tasks, it is known that our surrounding space can be divided into a peripersonal space and extrapersonal space. These two spaces are functionally different at both the behavioral and neuronal level. The peripersonal space can be seen as an action space which is limited to the area in which we can grasp objects without moving the object or ourselves. The extrapersonal space is the space beyond the peripersonal space. Objects situated within peripersonal space are mapped onto an egocentric reference frame. This mapping is thought to be accomplished by action simulation. To provide direct evidence of the embodied nature of this simulated motor act, we performed two experiments, in which we used two mental rotation tasks, one with stimuli of hands and one with stimuli of graspable objects. Stimuli were presented in both peri- and extrapersonal space. The results showed increased reaction times for biomechanically difficult to adopt postures compared to more easy to adopt postures for both hand and graspable object stimuli. Importantly, this difference was only present for stimuli presented in peripersonal space but not for the stimuli presented in extrapersonal space. These results extend previous behavioral findings on the functional distinction between peripersonal- and extrapersonal space by providing direct evidence for the spatial dependency of the use of action simulation. Furthermore, these results strengthen the hypothesis that objects situated within the peripersonal space are mapped onto an egocentric reference frame by action simulation.

Studying Multisensory Processing and Its Role in the Representation of Space through Pathological and Physiological Crossmodal Extinction

The study of crossmodal extinction has brought a considerable contribution to our understanding of how the integration of stimuli perceived in multiple sensory modalities is used by the nervous system to build coherent representations of the space that directly surrounds us. Indeed, by revealing interferences between stimuli in a disturbed system, extinction provides an invaluable opportunity to investigate the interactions that normally exist between those stimuli in an intact system. Here, we first review studies on pathological crossmodal extinction, from the original demonstration of its existence, to its role in the exploration of the multisensory neural representation of space and the current theoretical accounts proposed to explain the mechanisms involved in extinction and multisensory competition. Then, in the second part of this paper, we report recent findings showing that physiological multisensory competition phenomena resembling clinical crossmodal extinction exist in the healthy brain. We propose that the development of a physiological model of sensory competition is fundamental to deepen our understanding of the cerebral mechanisms of multisensory perception and integration. In addition, a similar approach to develop a model of physiological sensory competition in non-human primates should allow combining functional neuroimaging with more invasive techniques, such as transient focal lesions, in order to bridge the gap between works done in the two species and at different levels of analysis.

Crossmodal visual‐tactile extinction: Modulation by posture implicates biased competition in proprioceptively reconstructed space

Extinction is a common consequence of unilateral brain injury: contralesional events can be perceived in isolation, yet are missed when presented concurrently with competing events on the ipsilesional side. This can arise crossmodally, where a contralateral touch is extinguished by an ipsilateral visual event. Recent studies showed that repositioning the hands in visible space, or making visual events more distant, can modulate such crossmodal extinction. Here, in a detailed single-case study, we implemented a novel spatial manipulation when assessing crossmodal extinction. This was designed not only to hold somatosensory inputs and hand/arm-posture constant, but also to hold (retinotopic) visual inputs constant, yet while still changing the spatial relationship of tactile and visual events in the external world. Our right hemisphere patient extinguished left-hand touches due to visual stimulation of the right visual field (RVF) when tested in the usual default posture with eyes/head directed straight ahead. But when her eyes/head were turned to the far left (and any visual events shifted along with this), such that the identical RVF retinal stimulation now fell at the same external location as the left-hand touch, crossmodal extinction was eliminated. Since only proprioceptive postural cues could signal this changed spatial relationship for the critical condition, our results show for the first time that such postural cues alone are sufficient to modulate crossmodal extinction. Identical somatosensory and retinal inputs can lead to severe crossmodal extinction, or none, depending on current posture.

Visuotactile Representation of Peripersonal Space: A Neural Network Study

Neurophysiological and behavioral studies suggest that the peripersonal space is represented in a multisensory fashion by integrating stimuli of different modalities. We developed a neural network to simulate the visual-tactile representation of the peripersonal space around the right and left hands. The model is composed of two networks (one per hemisphere), each with three areas of neurons: two are unimodal (visual and tactile) and communicate by synaptic connections with a third downstream multimodal (visual-tactile) area. The hemispheres are interconnected by inhibitory synapses. We applied a combination of analytic and computer simulation techniques. The analytic approach requires some simplifying assumptions and approximations (linearization and a reduced number of neurons) and is used to investigate network stability as a function of parameter values, providing some emergent properties. These are then tested and extended by computer simulations of a more complex nonlinear network that does not rely on the previous simplifications. With basal parameter values, the extended network reproduces several in vivo phenomena: multisensory coding of peripersonal space, reinforcement of unisensory perception by multimodal stimulation, and coexistence of simultaneous right- and left-hand representations in bilateral stimulation. By reducing the strength of the synapses from the right tactile neurons, the network is able to mimic the responses characteristic of right-brain-damaged patients with left tactile extinction: perception of unilateral left tactile stimulation, cross-modal extinction and cross-modal facilitation in bilateral stimulation. Finally, a variety of sensitivity analyses on some key parameters was performed to shed light on the contribution of single-model components in network behaviour. The model may help us understand the neural circuitry underlying peripersonal space representation and identify its alterations explaining neurological deficits. In perspective, it could help in interpreting results of psychophysical and behavioral trials and clarifying the neural correlates of multisensory-based rehabilitation procedures.

The representation of space near the body through touch and vision

This review discusses how visual and the tactile signals are combined in the brain to ensure appropriate interactions with the space around the body. Visual and tactile signals converge in many regions of the brain (e.g. parietal and premotor cortices) where multisensory input can interact on the basis of specific spatial constraints. Crossmodal interactions can modulate also unisensory visual and somatosensory cortices, possibly via feed-back projections from fronto-parietal areas. These processes enable attentional selection of relevant locations in near body space, as demonstrated by studies of spatial attention in healthy volunteers and in neuropsychological patients with crossmodal extinction. These crossmodal spatial effects can be flexibly updated taking into account the position of the eyes and the limbs, thus reflecting the spatial alignment of visuo-tactile stimuli in external space. Further, studies that manipulated vision of body parts (alien, real or fake limbs) have demonstrated that passive viewing of the body can influence the perception of somatosensory stimuli, again involving areas in the premotor and parietal cortices. Finally, we discuss how tool-use can expand the region of visuo-tactile integration in near body space, emphasizing the flexibility of this system at the single-neuron level in the monkey's parietal cortex, with corresponding multisensory effects in normals and neuropsychological patients. We conclude that visuo-tactile crossmodal links dominate the representation of near body space and that this is implemented functionally in parietal and premotor brain regions. These integration processes mediate the orienting of spatial attention and generate an efficient and flexible representation the space around the body.

Action-specific remapping of peripersonal space

Peripersonal space processing in monkeys’ brain relies on visuo-tactile neurons activated by objects near, not touching, the animal's skin. Multisensory interplay in peripersonal space is now well documented also in humans, in brain damaged patients presenting cross-modal extinction as well as in healthy subjects and typically takes the form of stronger visuo-tactile interactions in peripersonal than far space. We recently showed in healthy humans the existence of a functional link between voluntary object-oriented actions (Grasping) and the multisensory coding of the space around us (as indexed by visual–tactile interaction). Here, we investigated whether performing different actions towards the same object implies differential modulations of peripersonal space. Healthy subjects were asked to either grasp or point towards a target object. In addition, they discriminated whether tactile stimuli were delivered on their right index finger (up), or thumb (down), while ignoring visual distractors. Visuo-tactile interaction was probed in baseline Static conditions (before the movement) and in dynamic conditions (action onset and execution). Results showed that, compared to the Static baseline both actions similarly strengthened visuo-tactile interaction at the action onset, when Grasping and Pointing were kinematically indistinguishable. Crucially, Grasping induced further enhancement than Pointing in the execution phase, i.e., when the two actions kinematically diverged. These findings reveal that performing actions induce a continuous remapping of the multisensory peripersonal space as a function of on-line sensory–motor requirements, thus supporting the hypothesis of a role for peripersonal space in the motor control of voluntary actions.

Autism Overflows with Syntheses

Editor: We were surprised to find our case study “Cross-modal extinction in a boy with severely autistic behaviour and high verbal intelligence” (Bonneh et al. 2008) impugned by Professor Waterhouse (2008) as an example of “unsynthesized and hoc theories” cluttering autism research. Our article never purports to constitute a theory in itself, and from its very beginning relates our observations of singlechannel perception to an established theoretical context described in terms of stimulus overselectivity (Lovaas et al. 1979), monotropism (Murray et al. 2005), and impaired attention shifting (Allen and Courchesne 2001). Waterhouse misattributes to us a causal claim that “autism results from monochannel of [sic] winner-takes-all perceptual processing” when in fact all that we claim is that our case results support the existence of such winner-takes-all processing in autism. Our point is not to clutter and to contend with existing theory, but rather to extend such theory to ‘lowfunctioning’ cases in a way that might further the very synthesis to which Waterhouse and we all aspire— hence our unifying theme of perturbed neural interactions (Rubenstein and Merzenich 2003). Though integrative, cooperative autism research has a long way to go still, Waterhouse’s assertion that “the field has not made progress in creating a synthesized, standard predictive causal theory of autism” seems to assume that statements that do not explicitly cite or support each other must necessarily be in conflict and competition. This assumption of irreconcilability is a defeatist fallacy. As Waterhouse herself observes, ideas of weak central coherence (Happe and Frith 2006) and the various takes on abnormal connectivity (Castelli et al. 2002; Just et al. 2004; Neuropsychol Rev (2009) 19:273–274 DOI 10.1007/s11065-009-9099-9

Cross-modal extinction in a boy with severely autistic behaviour and high verbal intelligence

Anecdotal reports from individuals with autism suggest a loss of awareness to stimuli from one modality in the presence of stimuli from another. Here we document such a case in a detailed study of A.M., a 13-year-old boy with autism in whom significant autistic behaviours are combined with an uneven IQ profile of superior verbal and low performance abilities. Although A.M.'s speech is often unintelligible, and his behaviour is dominated by motor stereotypies and impulsivity, he can communicate by typing or pointing independently within a letter board. A series of experiments using simple and highly salient visual, auditory, and tactile stimuli demonstrated a hierarchy of cross-modal extinction, in which auditory information extinguished other modalities at various levels of processing. A.M. also showed deficits in shifting and sustaining attention. These results provide evidence for monochannel perception in autism and suggest a general pattern of winner-takes-all processing in which a stronger stimulus-driven representation dominates behaviour, extinguishing weaker representations.

Dynamic size‐change of peri‐hand space through tool‐use: Spatial extension or shift of the multi‐sensory area

Several studies in humans and non-human primates have shown that tool-use can expand near peripersonal space (Farnè & Làdavas, 2000; Iriki, Tanaka, & Iwamura, 1996). In humans, the extension of the near peripersonal space is revealed by an increase in the severity of cross-modal extinction caused by visual stimulation at the distal edge of a rake after its use as a reaching tool. The crucial question addressed here concerns whether the dynamic re-sizing of the peri-hand space in humans constitutes a real spatial expansion of visual-tactile peri-hand area along the tool axis. Alternatively, it could constitute a shift of the integrative area from the hand towards the distal edge of the tool, or the formation of a novel visual-tactile integrative area at the same distal location (Holmes, Calvert, & Spence, 2004). We contrasted the alternative predictions made by these hypotheses in a group of RBD patients by probing, at different locations along the tool axis, the changes induced by tool-use on cross-modal extinction. By assessing the visual-tactile extinction near the hand, midway along the tool, and at the distal edge of the tool we found an increase in visual-tactile extinction after tool-use both at the middle and the distal location along the tool axis. In contrast, no change intervened at the hand proximity. These findings support the view that the tool-use dependent re-mapping of peri-hand space in humans consists of a continuous elongation of visual-tactile peri-hand area from the hand towards the tip of the tool.

Neural correlates of crossmodal visual-tactile extinction and of tactile awareness revealed by fMRI in a right-hemisphere stroke patient

We used fMRI to study the neural correlates of crossmodal, visual-tactile extinction in a single case (patient GK). GK has chronic extinction after a lesion centred on right inferior parietal cortex, and has previously been investigated extensively in purely visual fMRI studies [e.g. Rees, G., Wojciulik, E., Clarke, K., Husain, M., Frith, C., & Driver, J. (2000). Unconscious activation of visual cortex in the damaged right hemisphere of a parietal patient with extinction. Brain, 123(Pt 8), 1624–1633; Rees, G., Kreiman, G., & Koch, C. (2002). Neural correlates of consciousness in humans. Nature Reviews Neuroscience, 3(4), 261–270]. With concurrent stimulation of the right visual field plus left index finger, GK showed crossmodal extinction of left touch on approximately half of such trials here (reflecting impaired sensitivity, i.e. lowered d-prime), albeit becoming aware of left touch on the other half. fMRI revealed activation of contralateral primary somatosensory cortex on crossmodal trials when touch was extinguished from awareness, suggesting unconscious residual processing there. When GK became aware of the left touch, additional activation was found in surviving right parietal cortex, and in frontal regions; moreover, functional coupling was enhanced with a region of frontal cortex implicated in awareness by previous work. Finally, on trials where crossmodal extinction arose, surviving right parietal cortex showed stronger functional coupling with the left visual and right somatosensory regions driven by the competing stimuli, indicating that crossmodal extinction arises when inputs to separate modalities interact competitively via multimodal cortex.

Neuropsychological evidence of modular organization of the near peripersonal space

The space closely surrounding the body, near peripersonal space, is represented through multisensory coding, as witnessed by the spatial distribution of visual-tactile extinction in brain-damaged patients. Typically, tactile stimuli delivered on the contralesional hand are more severely extinguished by visual stimuli presented near to than far from the ipsilesional hand. To investigate whether the near peripersonal space is a unitary multisensory representation of the peribody space or is organized in a modular fashion, separately representing different body parts. Cross-modal extinction was used to assess right brain-damaged patients with left tactile extinction by presenting a combination of ipsilesional visual and contralesional tactile stimuli, both between homologous body parts (i.e., the two hands and sides of the face) and between nonhomologous body parts (i.e., right hand + left face and right face + left hand). Visual-tactile extinction observed in the near peripersonal space of homologous body parts was more severe than that obtained between nonhomologous body parts. In contrast, cross-modal extinction observed in the far peripersonal space was overall weak and comparable when stimulating homologous or nonhomologous body sectors. In addition, a clear near-far modulation of visual-tactile extinction was obtained only when stimulating homologous, but not nonhomologous, body parts. These findings were observed irrespective of the severity of unisensory tactile extinction. Near peripersonal space is not unitary but is functionally organized in modules and consists of at least two different spatial representations, one around the hand and another around the face, which might be selectively affected in patients with extinction.

Shaping multisensory action–space with tools: evidence from patients with cross-modal extinction

Recent findings from neurophysiology, neuropsychology and psychology have shown that peri-personal space is represented through an integrated multisensory processing. In humans, the interaction between peri-personal space representation and action execution can be revealed through the use of tools that, by extending the reachable space, modify the strength of visual–tactile extinction. We have previously shown that the peri-hand space whereby vision and touch are integrated can be expanded, and contracted, depending upon tool-use. Here, we show that these dynamic changes critically depend upon active tool-use, as they are not found after an equally long, but passive exposure to an elongated (hand + tool) body configuration. We also show that the extent of the peri-hand space elongation, as assessed at fixed far location (60 cm from the hand), varies according to the tool length such that a 30 cm long tool produced less elongation than a 60 cm long tool. This reveals for the first time that the distal border of elongated area is not sharply limited to the tool length, but extends beyond its physical size to include a peri-tool space whereby the strength of visual–tactile integration seems to fade. Remarkably, a similar amount of peri-hand space elongation was found when the effects of using a 30 cm long tool were compared with those produced by using a tool that was physically 60 cm long, but operationally 30 cm long. By dissociating with this ‘hybrid’ tool, the amount of space that is globally added to the hand (60 cm) from the one that is actually reachable (30 cm), we provide here the first evidence that the extent of peri-hand space elongation after tool use is tightly related to the functionally effective length of the tool, and not merely to its absolute length.

Cross-modal extinction in autism: A case report

Cross-modal extinction in autism: A case report

Active Tool Use with the Contralesional Hand Can Reduce Cross-modal Extinction of Touch on that Hand

After a unilateral brain lesion, patients may show cross-modal, visual-tactile extinction. Such patients may fail to report tactile stimuli on the contralesional hand when presented together with competing visual stimuli near the ipsilesional hand. In this work we tested the hypothesis that this cross-modal extinction may be reduced when a patient has used a tool with the contralesional hand to reach for objects in the ipsilesional visual field. Consistent with previous work, we hypothesize that active use of a tool may extend cross-modal interactions between visual stimuli at the tip of the tool and tactile stimuli on the hand wielding the tool. In the new situation of a tool connecting the contralesional hand with ipsilesional visual space, competition between stimuli on these opposite sides may be reduced, so that extinction decreases. We studied patient BV, who showed reliable cross-modal, visual-tactile extinction after right-hemisphere stroke. In two separate sessions we showed that prolonged tool use (10-20 min) with the contralesional hand in ipsilesional space reduced cross-modal extinction for up to 60-90 min post-training. We propose that an actively used tool may be effective in linking cross-modal stimuli presented along its extension. This can then overcome competition between stimuli presented on opposite sides of the body midline, thus modulating extinction.

Active tool use with the contralesional hand can reduce cross-modal extinction of touch on that hand

Active tool use with the contralesional hand can reduce cross-modal extinction of touch on that hand

Active Tool Use with the Contralesional Hand Can Reduce Cross-modal Extinction of Touch on that Hand

Active Tool Use with the Contralesional Hand Can Reduce Cross-modal Extinction of Touch on that Hand

Auditory Peripersonal Space in Humans: a Case of Auditory-Tactile Extinction

Animal experiments have shown that the spatial correspondence between auditory and tactile receptive fields of ventral pre-motor neurons provides a map of auditory peripersonal space around the head. This allows neurons to localize a near sound with respect to the head. In the present study, we demonstrated the existence of an auditory peripersonal space around the head in humans. In a right-brain damaged patient with tactile extinction, a sound delivered near the ipsilesional side of the head extinguished a tactile stimulus delivered to the contralesional side of the head (cross-modal auditory-tactile extinction). In contrast, when an auditory stimulus was presented far from the head, cross-modal extinction was dramatically reduced. This spatially specific cross-modal extinction was found only when a complex sound like a white noise burst was presented; pure tones did not produce spatially specific cross-modal extinction. These results show a high degree of functional similarity between the characteristics of the auditory peripersonal space representation in humans and monkeys. This similarity suggests that analogous physiological substrates might be responsible for coding this multisensory integrated representation of peripersonal space in human and non-human primates.