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Cognitive Neuroscience: Rewired or Crosswired Brains?

2006; Elsevier BV; Volume: 16; Issue: 22 Linguagem: Inglês

10.1016/j.cub.2006.10.017

1879-0445

Roi Cohen Kadosh, Vincent Walsh,

Neuroscience and Neural Engineering

A new study of congenitally blind participants has provided important insights into the neuronal mechanisms of brain reorganization after injury, with implications for our knowledge of other cross-modal phenomena, such as synaesthesia, and for the generation of qualia. A new study of congenitally blind participants has provided important insights into the neuronal mechanisms of brain reorganization after injury, with implications for our knowledge of other cross-modal phenomena, such as synaesthesia, and for the generation of qualia. The human brain retains a high level of plasticity into adulthood, making possible adaptive changes which can compensate for damage and at least partially restore abilities ranging from sensory to higher cognitive functions. This capacity for plasticity is now being exploited by numerous rehabilitation and active research programs within neuroscience, medicine, engineering, psychology and occupational therapy. It has been shown that a brain region that is normally dedicated to the processing of a given sensory modality can, if deprived of its normal sensory input, be recruited by another sensory modality. For example, the primary visual cortex, which is involved in visual processing in healthy humans, is activated when blind participants perform tactile tasks such as Braille reading [1Sadato N. Pascual-Leone A. Grafman J. Ibanez V. Deiber M.-P. Dold G. Hallett M. Activation of the primary visual cortex by Braille reading in blind subjects.Nature. 1996; 380: 526-528Crossref PubMed Scopus (874) Google Scholar]. Determining the neuronal mechanisms behind this type of cross-modal plasticity is a fundamental problem for understanding brain development and in the application of neuroscience to recovery from brain damage. One possibility, called the reorganization hypothesis, is that the reorganization of the deprived brain leads to the establishment of new mediating pathways. A second possibility, the unmasking hypothesis, is that damage induces unmasking and strengthening of existing neuronal connections [2Wittenberg G. Werhahn K. Wassermann E.M. Herscovitch P. Cohen L.G. Functional connectivity between somatosensory and visual cortex in early blind humans.Eur. J. Neurosci. 2004; 20: 1923-1927Crossref PubMed Scopus (120) Google Scholar]. In an innovative study, Kupers et al.[3Kupers R. Fumal A. de Nooedhout A.M. Gjedde A. Schoenen J. Ptito M. Transcranial magnetic stimulation of the visual cortex induces somatotopically organized qualia in blind subjects.Proc. Natl. Acad. Sci. USA. 2006; 103: 13256-13260Crossref PubMed Scopus (94) Google Scholar] shed light on the neuronal mechanism behind this key question. They trained three groups of visually deprived participants: people blind from an early period in life; people blind from a later period in life; and blindfolded healthy control participants. The blind participants had suffered peripheral damage and therefore had an intact primary visual cortex. A well-designed experiment avoided any manual task that might give an advantage to blind people, for example as a result of Braille reading. Instead, the participants were trained on a sophisticated tactile task using the tongue display unit [4Bach-y-Rita P. Kercel S. Sensory substitution and the human–machine interface.Trends Cogn. Sci. 2003; 7: 541-546Abstract Full Text Full Text PDF PubMed Scopus (506) Google Scholar]. In the tongue display unit, electrotactile stimulation is delivered by a three-by-three electrode array placed on the participant's tongue. With training, both the sighted and bind participants could discriminate patterns of tongue stimulation with at least 85% correct responses on two successive days. Before and after training participants received single pulse transcranial magnetic stimulation (TMS) over the visual cortex and adjacent areas in the occipitoparietal and occipitotemporal association cortices. TMS induces a current which depolarizes the cell membrane, which has consequences according to the site of stimulation: for example, it causes motor movement under motor cortex stimulation, or phosphenes when the visual cortex is stimulated. Although all three groups were asked to report any subjective sensation due to the TMS pulse, none of the participants reported a subjective feeling from the tongue before the training started. In contrast, after the training, three early blind and one late blind participant reported a sensation on the tongue after TMS. This sensation was described as short lasting tingling, which varied in intensity, extent and topography. Moreover, the characteristics of these qualia were somatotopically organised as a function of the occipital cortex stimulation. Importantly, while the amount of training and performance was similar between the different groups, none of the healthy, non-blind, participants reported similar tactile sensations; rather, as would be expected after stimulation of the occipital cortex, they reported phosphenes [5Cowey A. Walsh V. Magnetically induced phosphenes in sighted, blind and blindsighted observers.NeuroReport. 2000; 11: 3269-3273Crossref PubMed Scopus (197) Google Scholar]. Coming back to the key question of the neuronal mechanisms behind cross-modal plasticity, the time frame of the cross-modal plasticity observed by Kupers et al. [3Kupers R. Fumal A. de Nooedhout A.M. Gjedde A. Schoenen J. Ptito M. Transcranial magnetic stimulation of the visual cortex induces somatotopically organized qualia in blind subjects.Proc. Natl. Acad. Sci. USA. 2006; 103: 13256-13260Crossref PubMed Scopus (94) Google Scholar] is critical. The plasticity was observed in less than a week, a time-frame which excludes the possibility of the establishment of new anatomical connections [6Pascual-Leone A. Amedi A. Fregni F. Merabet L.B. The plastic human brain cortex.Annu. Rev. Neurosci. 2005; 28: 377-401Crossref PubMed Scopus (1062) Google Scholar]. This would tend to support the unmasking hypothesis. This view receives further support from earlier studies that have questioned the standard view of sensory cortical parcellation by demonstrating multi-modal neurons in a supposedly modality-specific area in rats [7Wallace M.T. Ramachandran R. Stein B.E. A revised view of sensory cortical parcellation.Proc. Natl. Acad. Sci. USA. 2004; 101: 2167-2172Crossref PubMed Scopus (242) Google Scholar], while others have shown that tactile processing can be disrupted by interfering with the visual cortex of healthy participants [8Zangaladze A. Epstein C.M. Grafton S.T. Sathian K. Involvement of visual cortex in tactile discrimination of orientation.Nature. 1999; 401: 587-590Crossref PubMed Scopus (353) Google Scholar]. These observations suggest there are latent non-visual inputs to the visual cortex, but these might not give rise to conscious visual sensations because of masking by the dominating visual input which constitutes the majority of the neuronal population in visual cortex. Previous studies have supported the reorganization hypothesis by observing that early blind, in comparison to late blind, subjects exhibit larger activity in the visual cortex evoked by tactile stimulation [9Cohen L.G. Weeks R.A. Sadato N. Celnik P. Ishii K. Hallett M. Period of susceptibility for cross-modal plasticity in the blind.Ann. Neurol. 1999; 45: 451-460Crossref PubMed Scopus (226) Google Scholar]. It is important to note, however, that the difference between early and late blind participants in previous studies was investigated by using Braille reading as the experimental task. This tactile task clearly involves several confounding factors, which Kupers et al.[3Kupers R. Fumal A. de Nooedhout A.M. Gjedde A. Schoenen J. Ptito M. Transcranial magnetic stimulation of the visual cortex induces somatotopically organized qualia in blind subjects.Proc. Natl. Acad. Sci. USA. 2006; 103: 13256-13260Crossref PubMed Scopus (94) Google Scholar] successfully avoided, such as experience with fingertip tactile stimulation that resulted in an increased activation in the visual cortex. The riddle of the neuronal mechanism behind cross-modal sensation is not limited to the cases of negative symptoms, such as complete loss of a sense. Similar inquiries about the source of cross-modal sensation in healthy people with positive symptoms are stimulated by the phenomenon of synaesthesia [10Mulvenna C. Walsh V. Synaesthesia.Curr. Biol. 2005; 15: R399-R400Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar]. In synaesthesia, sensory experiences, such as tastes, or concepts, such as numbers, automatically evoke additional percepts, such as color. For example, a grapheme–colour synaesthete will experience colour when seeing a digit or letter, and a vision–touch synaesthete will experience being touched when seeing other people touched [11Blakemore S.-J. Bristow D. Bird G. Frith C. Ward J. Somatosensory activations during the observation of touch and a case of vision–touch synesthesia.Brain. 2005; 128: 1571-1583Crossref PubMed Scopus (426) Google Scholar]. In the case of E.S., a hearing–taste synaesthete, a musical interval induces a taste on the tongue: for example, major sixth tastes like low-fat cream [12Beeli G. Esslen M. Jancke L. When coloured sounds taste sweet.Nature. 2005; 434: 38Crossref PubMed Scopus (81) Google Scholar]. In line with this phenomenology, brain imaging studies have found that, in synaesthetes, in contrast to non-synaesthetes, visual areas can be activated by sound [13Nunn J.A. Gregory L.J. Brammer M. Williams S.C.R. Parslow D.M. Morgan M.J. Morris R.G. Bullmore E.T. Baron-Cohen S. Gray J.A. Functional magnetic resonance imaging of synesthesia: activation of V4/V8 by spoken words.Nat. Neurosci. 2002; 5: 371-375Crossref PubMed Scopus (276) Google Scholar], and the somatosensory cortex can be activated by visual input [11Blakemore S.-J. Bristow D. Bird G. Frith C. Ward J. Somatosensory activations during the observation of touch and a case of vision–touch synesthesia.Brain. 2005; 128: 1571-1583Crossref PubMed Scopus (426) Google Scholar] (Figure 1). Whether synaesthesia is a result of abnormal neuronal connections, due to a failure of pruning at an early developmental stage, or a malfunction in inhibition, is a point of dispute [14Hubbard E.M. Ramachandran V.S. Neurocognitive mechanisms of synesthesia.Neuron. 2005; 48: 509-520Abstract Full Text Full Text PDF PubMed Scopus (258) Google Scholar]. In the latter view, synaesthesia would be mediated by the same neuronal connections that exist in non-synaesthetes' brains, and the unusual experience would be induced by disinhibition of feedback signals, probably from a 'multisensory nexus'. These hypotheses have a striking similarity to those drawn by researchers working on compensatory changes in the deprived brain, with failed pruning corresponding to the reorganization hypothesis and disinhibition to the unmasking hypothesis. The similarity does not end here. Both cross modal phenomena show a wide range of individual differences [14Hubbard E.M. Ramachandran V.S. Neurocognitive mechanisms of synesthesia.Neuron. 2005; 48: 509-520Abstract Full Text Full Text PDF PubMed Scopus (258) Google Scholar] and both are bidirectional. That is, previous studies found that tactile tasks activate the occipital cortex in blind participants [1Sadato N. Pascual-Leone A. Grafman J. Ibanez V. Deiber M.-P. Dold G. Hallett M. Activation of the primary visual cortex by Braille reading in blind subjects.Nature. 1996; 380: 526-528Crossref PubMed Scopus (874) Google Scholar, 2Wittenberg G. Werhahn K. Wassermann E.M. Herscovitch P. Cohen L.G. Functional connectivity between somatosensory and visual cortex in early blind humans.Eur. J. Neurosci. 2004; 20: 1923-1927Crossref PubMed Scopus (120) Google Scholar, 6Pascual-Leone A. Amedi A. Fregni F. Merabet L.B. The plastic human brain cortex.Annu. Rev. Neurosci. 2005; 28: 377-401Crossref PubMed Scopus (1062) Google Scholar]. Moreover, Kupers et al.[3Kupers R. Fumal A. de Nooedhout A.M. Gjedde A. Schoenen J. Ptito M. Transcranial magnetic stimulation of the visual cortex induces somatotopically organized qualia in blind subjects.Proc. Natl. Acad. Sci. USA. 2006; 103: 13256-13260Crossref PubMed Scopus (94) Google Scholar] showed that, after training to discriminate motion based tongue stimulation, stimulation to the visual cortex resulted in tactile sensation on the tongue. Similarly, it has been shown that in grapheme–colour synaesthesia not only does number activate colour but also colour activates a numerical magnitude [15Cohen Kadosh R. Sagiv N. Linden D.E.J. Robertson L.C. Elinger G. Henik A. When blue is larger than red: Colors influence numerical cognition in synesthesia.J. Cogn. Neurosci. 2005; 17: 1766-1773Crossref PubMed Scopus (63) Google Scholar]. Might it be that finding the source for one of them will supply critical information for the other? And more fundamentally, might the 'extra' qualia experienced by these two groups of people show that the basis of awareness is in modality-specific cortices rather than in higher order control centres? Answering these questions will make a valuable contribution to the understanding of the mechanisms behind these interesting phenomena, and provide further clues as to why some people perceive information consciously while others do not.