David Brang

The cross-activation theory at 10

In 2001, Ramachandran and Hubbard introduced the cross-activation model of grapheme-colour synaesthesia. On the occasion of its 10-year anniversary, we review the evidence from experiments that have been conducted to test the model to assess how it has fared. We examine data from behavioural, functional magnetic resonance imaging (fMRI), anatomical studies (diffusion tensor imaging and voxel-based morphometry), and electroencephalography (EEG) and magnetoencephalography (MEG) studies of grapheme-colour synaesthesia. Although much of this evidence has supported the basic cross-activation hypothesis, our growing knowledge of the neural basis of synaesthesia, grapheme, and colour processing has necessitated two specific updates and modifications to the basic model: (1) our original model assumed that binding and parietal cortex functions were normal in synaesthesia; we now recognize that parietal cortex plays a key role in synaesthetic binding, as part of a two-stage model. (2) Based on MEG data we have recently collected demonstrating that synaesthetic responses begin within 140 ms of stimulus presentation, and an updated understanding of the neural mechanisms of reading as hierarchical feature extraction, we present a revised and updated version of the cross-activation model, the cascaded cross-tuning model. We then summarize data demonstrating that the cross-activation model may be extended to account for other forms of synaesthesia and discuss open questions about how learning, development, and cortical plasticity interact with genetic factors to lead to the full range of synaesthetic experiences. Finally, we outline a number of future directions needed to further test the cross-activation theory and to compare it with alternative theories.

Magnetoencephalography reveals early activation of V4 in grapheme-color synesthesia

Grapheme-color synesthesia is a neurological phenomenon in which letters and numbers (graphemes) consistently evoke particular colors (e.g. A may be experienced as red). The cross-activation theory proposes that synesthesia arises as a result of cross-activation between posterior temporal grapheme areas (PTGA) and color processing area V4, while the disinhibited feedback theory proposes that synesthesia arises from disinhibition of pre-existing feedback connections. Here we used magnetoencephalography (MEG) to test whether V4 and PTGA activate nearly simultaneously, as predicted by the cross-activation theory, or whether V4 activation occurs only after the initial stages of grapheme processing, as predicted by the disinhibited feedback theory. Using our high-resolution MEG source imaging technique (VESTAL), PTGA and V4 regions of interest (ROIs) were separately defined, and activity in response to the presentation of achromatic graphemes was measured. Activation levels in PTGA did not significantly differ between synesthetes and controls (suggesting similar grapheme processing mechanisms), whereas activation in V4 was significantly greater in synesthetes. In synesthetes, PTGA activation exceeded baseline levels beginning 105-109ms, and V4 activation did so 5ms later, suggesting nearly simultaneous activation of these areas. Results are discussed in the context of an updated version of the cross-activation model, the cascaded cross-tuning model of grapheme-color synesthesia.

Apotemnophilia: a neurological disorder

Apotemnophilia, a disorder that blurs the distinction between neurology and psychiatry, is characterized by the intense and longstanding desire for amputation of a specific limb. Here we present evidence from two individuals suggestive that this condition, long thought to be entirely psychological in origin, actually has a neurological basis. We found heightened skin conductance response to pinprick below the desired line of amputation. We propose apotemnophilia arises from congenital dysfunction of the right superior parietal lobule and its connection with the insula.

Size reduction using Mirror Visual Feedback (MVF) reduces phantom pain

Following limb amputation patients continue to feel the vivid presence of a phantom limb. A majority of patients also experience pain in the phantom and sometimes (as in our case DS) the pain is severe. Remarkably we find that optically ‘resurrecting’ the phantom with a mirror and using a lens to make the phantom appear to shrink caused the pain to ‘shrink’ as well.

Is the sky 2? Contextual priming in grapheme-color synaesthesia

Grapheme-color synaesthesia is a neurological phenomenon in which particular graphemes, such as the numeral 9, automatically induce the simultaneous perception of a particular color, such as the color red. To test whether the concurrent color sensations in grapheme-color synaesthesia are treated as meaningful stimuli, we recorded event-related brain potentials as 8 synaesthetes and 8 matched control subjects read sentences such as “Looking very clear, the lake was the most beautiful hue of 7.” In synaesthetes, but not control subjects, congruous graphemes, compared with incongruous graphemes, elicited a more negative N1 component, a less positive P2 component, and a less negative N400 component. Thus, contextual congruity of synaesthetically induced colors altered the brain response to achromatic graphemes beginning 100 ms postonset, affecting pattern-recognition, perceptual, and meaning-integration processes. The results suggest that grapheme-color synaesthesia is automatic and perceptual in nature and also suggest that the connections between colors and numbers are bidirectional.

Survival of the synesthesia gene: why do people hear colors and taste words?

This Unsolved Mystery reviews the biological evidence for why synesthesia, a condition in which stimuli presented through one modality spontaneously evoke sensations in an unrelated modality, may have been conserved in the population.

Contextual Priming in Grapheme–Color Synesthetes and Yoked Controls: 400 msec in the Life of a Synesthete

Grapheme–color synesthesia is a heritable trait where graphemes (“2”) elicit the concurrent perception of specific colors (red). Researchers have questioned whether synesthetic experiences are meaningful or simply arbitrary associations and whether these associations are perceptual or conceptual. To address these fundamental questions, ERPs were recorded as 12 synesthetes read statements such as “The Coca-Cola logo is white and 2,” in which the final grapheme induced a color that was either contextually congruous (red) or incongruous (“…white and 7,” for a synesthetes who experienced 7 as green). Grapheme congruity was found to modulate the amplitude of the N1, P2, N300, and N400 components in synesthetes, suggesting that synesthesia impacts perceptual as well as conceptual aspects of processing. To evaluate whether observed ERP effects required the experience of colored graphemes versus knowledge of grapheme–color pairings, we ran three separate groups of controls on a similar task. Controls trained to a synesthetes associations elicited N400 modulation, indicating that knowledge of grapheme–color mappings was sufficient to modulate this component. Controls trained to synesthetic associations and given explicit visualization instructions elicited both N300 and N400 modulations. Lastly, untrained controls who viewed physically colored graphemes (“2” printed in red) elicited N1 and N400 modulations. The N1 grapheme congruity effect began earlier in synesthetes than colored grapheme controls but had similar scalp topography. Data suggest that, in synesthetes, achromatic graphemes engage similar visual processing networks as colored graphemes in nonsynesthetes and are in keeping with models of synesthesia that posit early feed-forward connections between form and color processing areas in extrastriate cortex. The P2 modulation was unique to the synesthetes and may reflect neural activity that underlies the conscious experience of the synesthetic induction.

Dynamic reorganization of referred sensations by movements of phantom limbs

After amputation of an arm the sensory map of the body changes radically, causing the sensory input from face to ‘invade’ the original hand area in the brain. As a result, touching the face of the amputee evokes tactile sensations on the phantom. These sensory referrals from the face to phantom hand occur in a stable, topographically organized manner. We now find that volitional movements of the phantom cause striking, systematic shifts in the map along the direction of movement. We conclude that the reorganization of maps is based partly on reversible inhibition of ordinarily silent synapses, not entirely on new anatomical connections. This finding further highlights the dynamic nature of the brain on remarkably short-time scales.

Visual field heterogeneity, laterality, and eidetic imagery in synesthesia

JS was a grapheme-color synesthete in whom numerals and letters of the alphabet consistently evoked colors. In the first set of experiments we showed that the color – in a consistent and reliable manner – was most pronounced in the left visual field and in central vision. In the second experiment we devised a novel test for eidetic imagery and showed that his self-report of enhanced imagery could be verified experimentally. The implications of these findings for the level at which synesthesia occurs, the ‘enhanced cross-activation’ model, and the mechanisms of visual memory are discussed.

Sexual and Food Preference in Apotemnophilia and Anorexia: Interactions between ‘Beliefs' and ‘Needs' Regulated by Two-Way Connections between Body Image and Limbic Structures

Apotemnophilia straddles the boundary between neurology and psychiatry. It is a condition in which individuals experience the strong and specific desire for amputation of a healthy limb. Research suggests this disorder may be of neurological origin, specifically that the body image centers of the brain lack a cortical representation for a particular limb. A curious aspect of this condition is that sufferers often report an attraction to amputees in addition to desiring their own limb be removed. We postulate that sexual ‘aesthetic preference’ for certain body morphology is dictated in all individuals in part by the cortical representation of ones body image.