Ron Kupers

Compensatory plasticity and cross-modal reorganization following early visual deprivation

For human and non-human primates, vision is one of the most privileged sensory channels used to interact with the environment. The importance of vision is strongly embedded in the organization of the primate brain as about one third of its cortical surface is involved in visual functions. It is therefore not surprising that the absence of vision from birth, or the loss of vision later in life, has huge consequences, both anatomically and functionally. Studies in animals and humans, conducted over the past few decades, have demonstrated that the absence of vision causes massive structural changes that take place not only in the visually deprived cortex but also in other brain areas. These studies have further shown that the visually deprived cortex becomes responsive to a wide variety of non-visual sensory inputs. Recent studies even showed a role of the visually deprived cortex in cognitive processes. At the behavioral level, increases in acuity for auditory and tactile processes have been reported. The study of the congenitally blind brain also offers a unique model to gain better insights into the functioning of the normal sighted brain and to understand to what extent visual experience is necessary for the brain to develop its functional architecture. Finally, the study of the blind brain allows us to investigate how consciousness develops in the absence of vision. How does the brain of someone who has never had any visual perception form an image of the external world? In this paper, we discuss recent findings from animal studies as well as from behavioural and functional brain imaging studies in sighted and blind individuals that address these questions.

Neuromodulation of pain. A consensus statement prepared in Brussels 16-18 January 1998 by the following task force of the European Federation of IASP Chapters (EFIC).

J. Gybels, Belgium (Chair); S. Erdine, Turkey (Vice-chairman); J. Maeyaert, Belgium (Vice-chairman); B. Meyerson, Sweden (Vice-chairman); W. Winkelmuller, Germany (Vice-chairman); L. Augustinsson, Sweden; C. Bonezzi, Italy; L. Brasseur, France; M. DeJongste, The Netherlands; R. Kupers, Denmark; P. Marchettini, Italy; G. Muller-Schwefe, Germany; P. Nitescu, Sweden; L. Plaghki, Belgium; E. Reig, Spain; G. Spincemaille, The Netherlands; S. Thomson, UK; V. Tronnier, Germany; J.-P. Van Buyten, Belgium

A model of transient hyperalgesia in the behaving monkey induced by topical application of capsaicin

Abstract The aim of this study was to develop a model of transient hyperalgesia in the awake monkey performing operant tasks. An adult male rhesus monkey was trained to press a lever to receive food reward for detecting a light or to escape mechanical or thermal stimuli applied in the maxillary region of the face. A small contact thermode was positioned on one side of the face and a mechanical stimulator was placed on the other side. Noxious and innocuous thermal (43, 47 and 51°C) or mechanical (245, 490, 736 and 1472 mN) stimuli of 4.5‐s duration were presented in a pseudo‐random order. The animal was tested before, 1 h and 24 h after topical capsaicin application (0.3 ml; 0.004 M). At the site of capsaicin application, the monkey escaped more thermal and mechanical stimuli 1 h after than before capsaicin, suggestive of thermal and mechanical hyperalgesia. At 24 h post‐capsaicin, mechanical escape behavior had returned to baseline, but thermal escapes were still slightly elevated. Capsaicin had no significant effect on either mechanical or thermal escape behavior for stimuli presented to the contralateral site. Seven human subjects tested with these procedures reported higher pain intensity for similar stimuli after capsaicin application, in accordance with the monkey escape behavior. It is concluded that topical application of capsaicin on the maxillary face of the awake behaving monkey produces a transient thermal and mechanical hyperalgesia. The procedure is repeatable and produces no overt signs of distress. Thus it could provide an important tool for studying neural mechanisms of hyperalgesia and for testing analgesic treatments in primates.

Morphometric changes of the corpus callosum in congenital blindness.

We examined the effects of visual deprivation at birth on the development of the corpus callosum in a large group of congenitally blind individuals. We acquired high-resolution T1-weighted MRI scans in 28 congenitally blind and 28 normal sighted subjects matched for age and gender. There was no overall group effect of visual deprivation on the total surface area of the corpus callosum. However, subdividing the corpus callosum into five subdivisions revealed significant regional changes in its three most posterior parts. Compared to the sighted controls, congenitally blind individuals showed a 12% reduction in the splenium, and a 20% increase in the isthmus and the posterior part of the body. A shape analysis further revealed that the bending angle of the corpus callosum was more convex in congenitally blind compared to the sighted control subjects. The observed morphometric changes in the corpus callosum are in line with the well-described cross-modal functional and structural neuroplastic changes in congenital blindness.

MEG reveals a fast pathway from somatosensory cortex to occipital areas via posterior parietal cortex in a blind subject

Cross-modal activity in visual cortex of blind subjects has been reported during performance of variety of non-visual tasks. A key unanswered question is through which pathways non-visual inputs are funneled to the visual cortex. Here we used tomographic analysis of single trial magnetoencephalography (MEG) data recorded from one congenitally blind and two sighted subjects after stimulation of the left and right median nerves at three intensities: below sensory threshold, above sensory threshold and above motor threshold; the last sufficient to produce thumb twitching. We identified reproducible brain responses in the primary somatosensory (S1) and motor (M1) cortices at around 20 ms post-stimulus, which were very similar in sighted and blind subjects. Time-frequency analysis revealed strong 45–70 Hz activity at latencies of 20–50 ms in S1 and M1, and posterior parietal cortex Brodmann areas (BA) 7 and 40, which compared to lower frequencies, were substantially more pronounced in the blind than the sighted subjects. Critically, at frequencies from α-band up to 100 Hz we found clear, strong, and widespread responses in the visual cortex of the blind subject, which increased with the intensity of the somatosensory stimuli. Time-delayed mutual information (MI) revealed that in blind subject the stimulus information is funneled from the early somatosensory to visual cortex through posterior parietal BA 7 and 40, projecting first to visual areas V5 and V3, and eventually V1. The flow of information through this pathway occurred in stages characterized by convergence of activations into specific cortical regions. In sighted subjects, no linked activity was found that led from the somatosensory to the visual cortex through any of the studied brain regions. These results provide the first evidence from MEG that in blind subjects, tactile information is routed from primary somatosensory to occipital cortex via the posterior parietal cortex.

Superior Orthonasal but Not Retronasal Olfactory Skills in Congenital Blindness

Sight is undoubtedly important for finding and appreciating food, and cooking. Blind individuals are strongly impaired in finding food, limiting the variety of flavours they are exposed to. We have shown before that compared to sighted controls, congenitally blind individuals have enhanced olfactory but reduced taste perception. In this study we tested the hypothesis that congenitally blind subjects have enhanced orthonasal but not retronasal olfactory skills. Twelve congenitally blind and 14 sighted control subjects, matched in age, gender and body mass index, were asked to identify odours using grocery-available food powders. Results showed that blind subjects were significantly faster and tended to be better at identifying odours presented orthonasally. This was not the case when odorants were presented retronasally. We also found a significant group x route interaction, showing that although both groups performed better for retronasally compared to orthonasally presented odours, this gain was less pronounced for blind subjects. Finally, our data revealed that blind subjects were more familiar with the orthonasal odorants and used the retronasal odorants less often for cooking than their sighted counterparts. These results confirm that orthonasal but not retronasal olfactory perception is enhanced in congenital blindness, a result that is concordant with the reduced food variety exposure in this group.

Pain perception is increased in congenital but not late onset blindness.

There is now ample evidence that blind individuals outperform sighted individuals in various tasks involving the non-visual senses. In line with these results, we recently showed that visual deprivation from birth leads to an increased sensitivity to pain. As many studies have shown that congenitally and late blind individuals show differences in their degree of compensatory plasticity, we here address the question whether late blind individuals also show hypersensitivity to nociceptive stimulation. We therefore compared pain thresholds and responses to supra-threshold nociceptive stimuli in congenitally blind, late blind and normally sighted volunteers. Participants also filled in questionnaires measuring attention and anxiety towards pain in everyday life. Results show that late blind participants have pain thresholds and ratings of supra-threshold heat nociceptive stimuli similar to the normally sighted, whereas congenitally blind participants are hypersensitive to nociceptive thermal stimuli. Furthermore, results of the pain questionnaires did not allow to discriminate late blind from normal sighted participants, whereas congenitally blind individuals had a different pattern of responses. Taken together, these results suggest that enhanced sensitivity to pain following visual deprivation is likely due to neuroplastic changes related to the early loss of vision.

Neural correlates of taste perception in congenital blindness

Sight is undoubtedly important for the perception and the assessment of the palatability of tastants. Although many studies have addressed the consequences of visual impairment on food selection, feeding behavior, eating habits and taste perception, nothing is known about the neural correlates of gustation in blindness. In the current study we examined brain responses during gustation using functional magnetic resonance imaging (fMRI). We scanned nine congenitally blind and 14 age- and sex-matched blindfolded sighted control subjects, matched in age, gender and body mass index (BMI), while they made judgments of either the intensity or the (un)pleasantness of different tastes (sweet, bitter) or artificial saliva that were delivered intra-orally. The fMRI data indicated that during gustation, congenitally blind individuals activate less strongly the primary taste cortex (right posterior insula and overlying Rolandic operculum) and the hypothalamus. In sharp contrast with results of multiple other sensory processing studies in congenitally blind subjects, including touch, audition and smell, the occipital cortex was not recruited during taste processing, suggesting the absence of taste-related compensatory crossmodal responses in the occipital cortex. These results underscore our earlier behavioral demonstration that congenitally blind subjects have a lower gustatory sensitivity compared to normal sighted individuals. We hypothesize that due to an underexposure to a variety of tastants, training-induced crossmodal sensory plasticity to gustatory stimulation does not occur in blind subjects.

Sleep structure in blindness is influenced by circadian desynchrony

We examined the structure, duration and quality of sleep, including non‐rapid eye movement sleep and rapid eye movement sleep, in 11 blind individuals without conscious light perception and 11 age‐ and sex‐matched sighted controls. Because blindness is associated with a greater incidence of free‐running circadian rhythms, we controlled for circadian phase by a measure of melatonin onset timing. When circadian rhythm was entrained and melatonin onset occurred at normal times, sleep structure did not differ between blind and sighted individuals. On the other hand, an abnormal timing of the circadian phase, including delayed, shifted and unclassifiable melatonin onsets, led to larger rapid eye movement sleep latencies and increased wake times. No differences were observed for stages of non‐rapid eye movement sleep, either between congenital and late blind and sighted individuals, or across the different circadian phases. Moreover, abnormal circadian phases were more common in the blind (n = 5) than the sighted (n = 2) sample. Our findings suggest that the sleep structure of blind individuals depends on entrainment of circadian phase, rather than on the absence of vision.

Pain hypersensitivity in congenital blindness is associated with faster central processing of C-fibre input

We have recently shown that visual deprivation from birth exacerbates responses to painful thermal stimuli. However, the mechanisms underlying pain hypersensitivity in congenital blindness are unclear.