Constructing calendars in the brain.

By studying an enigmatic condition called, "calendar synesthesia", we explored the elusive boundary between perception, visual imagery, and the manner in which we construct an internal mental calendar by mapping time-sequences onto spatial maps. We use a series of demonstrations to establish that these calendars act more like real objects activating sensory pathways rather than purely abstract symbolic descriptions that bear no resemblance to an actual calendar. We propose that the calendar is enshrined in acircuitry involving the hippocampal place-cells and entorhinal grid-cells, which are connected to the angular gyrus (involved with computing sequences) via the inferior longitudinal fasciculus.

Synesthesia and the McCollough Effect.

Synesthetes, who see printed black letters and numbers as being colored, are thought to have enhanced cross-activation between brain modules for color and form. Since the McCollough effect also results from oriented contours (i.e., form) evoking specific colors, we conjectured that synesthetes may experience an enhanced McCollough effect, and find that this is indeed true.

Hypothesis concerning embodied calendars: A case study of number form, color spreading, and taste-color synaesthesia.

We propose a hypothesis concerning the neural basis of the mental 'calendar' we all carry around in our brains, based on observations we made on a 25year old 'projector synaesthete', EA, who displays some novel and instructive features. In addition to her grapheme-color synaesthesia, she has a circular 'calendar line', laid out vividly in front of her in the horizontal plane with December 31st passing through the middle of her chest and other months arranged in clockwise sequence ending with December on her right (July was 3 feet in front of her). Her access to episodic memories felt, subjectively, as if it was facilitated by her calendar line. Intriguingly, if she turned her sideways to look to the right, the calendar remained 'stuck to the chest' - meaning that it was body centered rather than head centered. Even more surprising is how, when she rotated her head rightward, the left portion of her calendar became "fuzzy", and memories of February and March became less accessible; a striking example of embodied cognition - memories gated by information from neural networks representing the activity of neck muscles. We postulate that the human calendar is mediated by connections between the angular gyrus and hippocampal place and time cells-via the inferior longitudinal fasciculus. Other aspects of EA's synaesthesia were also explored. The colors evoked by graphemes spread outside the grapheme itself, but the spread could be blocked by real as well as illusory contours. These interactions might be mediated by cells signaling illusory contours (in V2) and color/texture sensitive cells in (V4). Tastes also evoked colors, but, intriguingly, the colors were experienced inside her mouth rather than out there in the world. We discuss the deeper implications of these findings for understanding the nature of quale, and the manner in which the self anchors itself in space and time.

Synesthetic colors induced by graphemes that have not been consciously perceived.

Grapheme-color synesthetes experience colors when they see printed letters of the alphabet. Currently, we tested four "projector" synesthetes, whose colors evoked by graphemes have sensory support or quale and appear to be restricted spatially to the letters like real colors. We use three different kinds of puzzle pictures that contained hidden letters, which require 30 s or more for nonsynesthetes to identify. Grapheme-color projector synesthetes recognize them three times faster and report that the colors were evoked before conscious letter recognition, clueing them as to what the letters were. Subjectively, the synesthetic subjects reported that they also saw mirror-reversed letters in the same colors as nonreversed letters which enabled them to read mirror-reversed text at thrice the normal speed. We conclude that in some synesthetes colors are evoked preconsciously early in sensory processing.

Primary somatosensory cortex hand representation dynamically modulated by motor output.

The brain's primary motor and primary somatosensory cortices are generally viewed as functionally distinct entities. Here we show by means of magnetoencephalography with a phantom-limb patient, that movement of the phantom hand leads to a change in the response of the primary somatosensory cortex to tactile stimulation. This change correlates with the described conscious perception and suggests a greater degree of functional unification between the primary motor and somatosensory cortices than is currently realized. We suggest that this may reflect the evolution of this part of the human brain, which is thought to have occurred from an undifferentiated sensorimotor cortex.

External self-representations improve self-awareness in a child with autism.

We have previously suggested that the social symptoms of autism spectrum disorder (ASD) could be caused in part by a dysfunctional mirror neuron system (MNS). Since the recursive activity of a functioning MNS might enable the brain to integrate visual and motor sensations into a coherent body schema, the deficits in self-awareness often seen in ASD might be caused by the same mirror neuron dysfunction. CL is an autistic adolescent who is profoundly fascinated with his reflection, looking in mirrors at every opportunity. We demonstrate that CL's abnormal gait improves significantly when using a mirror for visual feedback. We also show that both the fascination and the happiness that CL derives from looking at a computer-generated reflection diminish when a delay is introduced between the camera input and screen output. We believe that immediate, real-time visual feedback allows CL to integrate motor sensations with external visual ones into a coherent body schema that he cannot internally generate, perhaps due to a dysfunctional MNS.

Parietal connectivity mediates multisensory facilitation.

Our senses interact in daily life through multisensory integration, facilitating perceptual processes and behavioral responses. The neural mechanisms proposed to underlie this multisensory facilitation include anatomical connections directly linking early sensory areas, indirect connections to higher-order multisensory regions, as well as thalamic connections. Here we examine the relationship between white matter connectivity, as assessed with diffusion tensor imaging, and individual differences in multisensory facilitation and provide the first demonstration of a relationship between anatomical connectivity and multisensory processing in typically developed individuals. Using a whole-brain analysis and contrasting anatomical models of multisensory processing we found that increased connectivity between parietal regions and early sensory areas was associated with the facilitation of reaction times to multisensory (auditory-visual) stimuli. Furthermore, building on prior animal work suggesting the involvement of the superior colliculus in this process, using probabilistic tractography we determined that the strongest cortical projection area connected with the superior colliculus includes the region of connectivity implicated in our independent whole-brain analysis.

Enhanced mental rotation ability in time-space synesthesia.

Time-space synesthesia is a variant of sequence-space synesthesia and involves the involuntary association of months of the year with 2D and 3D spatial forms, such as arcs, circles, and ellipses. Previous studies have revealed conflicting results regarding the association between time-space synesthesia and enhanced spatial processing ability. Here, we tested 15 time-space synesthetes, and 15 non-synesthetic controls matched for age, education, and gender on standard tests of mental rotation ability, spatial working memory, and verbal working memory. Synesthetes performed better than controls on our test of mental rotation, but similarly to controls on tests of spatial and verbal working memory. Results support a dissociation between visuo-spatial imagery and spatial working memory capacity, and suggest time-space synesthesia is associated only with enhanced visuo-spatial imagery. These data are consistent with the time-space connectivity thesis that time-space synesthesia results from enhanced connectivity in the parietal lobe between regions supporting the representation of temporal sequences and those underlying visuo-spatial imagery.

The appearance of new phantom fingers post-amputation in a phocomelus.

We report the unusual case of a woman with right upper limb phocomelia who, post-amputation of her right hand following trauma, sprouted a phantom hand that contained five digits, including a phantom thumb and index finger that had been absent since her birth. These two phantom digits were initially half normal size, however, more than three decades later, with mirror visual feedback treatment, she was able to elongate them to normal length. This suggests that a hardwired representation of a complete hand had always been present in her brain, but inhibited by the presence of afferents from the phocomelic hand. Amputation of the phocomelic hand then led to disinhibition of this dormant representation, and the emergence of a phantom hand with five fingers, which was then further enhanced by false visual feedback from a mirror. The case powerfully demonstrates the interaction of nature and nurture in creating and sustaining body image.

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

Synesthesia is a perceptual experience in which stimuli presented through one modality will spontaneously evoke sensations in an unrelated modality. The condition occurs from increased communication between sensory regions and is involuntary, automatic, and stable over time. While synesthesia can occur in response to drugs, sensory deprivation, or brain damage, research has largely focused on heritable variants comprising roughly 4% of the general population. Genetic research on synesthesia suggests the phenomenon is heterogeneous and polygenetic, yet it remains unclear whether synesthesia ever provided a selective advantage or is merely a byproduct of some other useful selected trait. Progress in uncovering the genetic basis of synesthesia will help us understand why synesthesia has been conserved in the population.

Xenomelia: a new right parietal lobe syndrome.

BACKGROUND: Damage to the right parietal lobe has long been associated with various disorders of body image. The authors have recently suggested that an unusual behavioural condition in which otherwise rational individuals desire the amputation of a healthy limb might also arise from right parietal dysfunction. METHODS: Four subjects who desired the amputation of healthy legs (two right, one left and one, at first, bilateral and then left only) were recruited and underwent magnetoencephalography (MEG) scans during tactile stimulation of sites above and below the desired amputation line. Regions of interest (ROIs) in each hemisphere (superior parietal lobule (SPL), inferior parietal lobule, S1, M1, insula, premotor cortex and precuneus) were defined using FreeSurfer software. RESULTS: Analysis of average MEG activity across the 40-140 ms post-stimulation timeframe was carried out using an unpaired t test. This revealed significantly reduced activation only in the right SPL ROI for the subjects' affected legs when compared with both subjects' unaffected legs and that of controls. CONCLUSIONS: The right SPL is a cortical area that appears ideally placed to unify disparate sensory inputs to create a coherent sense of having a body. The authors propose that inadequate activation of the right SPL leads to the unnatural situation in which the sufferers can feel the limb in question being touched without it actually incorporating into their body image, with a resulting desire for amputation. The authors introduce the term 'xenomelia' as a more appropriate name than apotemnophilia or body integrity identity disorder, for what appears to be an unrecognised right parietal lobe syndrome.

Similarly shaped letters evoke similar colors in grapheme-color synesthesia.

Grapheme-color synesthesia is a neurological condition in which viewing numbers or letters (graphemes) results in the concurrent sensation of color. While the anatomical substrates underlying this experience are well understood, little research to date has investigated factors influencing the particular colors associated with particular graphemes or how synesthesia occurs developmentally. A recent suggestion of such an interaction has been proposed in the cascaded cross-tuning (CCT) model of synesthesia, which posits that in synesthetes connections between grapheme regions and color area V4 participate in a competitive activation process, with synesthetic colors arising during the component-stage of grapheme processing. This model more directly suggests that graphemes sharing similar component features (lines, curves, etc.) should accordingly activate more similar synesthetic colors. To test this proposal, we created and regressed synesthetic color-similarity matrices for each of 52 synesthetes against a letter-confusability matrix, an unbiased measure of visual similarity among graphemes. Results of synesthetes' grapheme-color correspondences indeed revealed that more similarly shaped graphemes corresponded with more similar synesthetic colors, with stronger effects observed in individuals with more intense synesthetic experiences (projector synesthetes). These results support the CCT model of synesthesia, implicate early perceptual mechanisms as driving factors in the elicitation of synesthetic hues, and further highlight the relationship between conceptual and perceptual factors in this phenomenon.

Compensational strategies for a merchant after stroke with anosognosia for alexia without agraphia.

We report the first case, to our knowledge, of successful return to work of a patient with alexia without agraphia. This case is also interesting as it is the first report of which we are aware of anosognosia for alexia without agraphia: the patient confabulated when asked to read English text, but immediately stated that he could not read Chinese text because he did not know that language. The selective nature of this confabulation would not be inconsistent with anosognosia being one of the brain's responses to absence of afferent information.

Using mirror visual feedback and virtual reality to treat fibromyalgia.

Fibromyalgia is a condition characterized by long term body-wide pain and tender points in joints, muscles and soft tissues. Other symptoms include chronic fatigue, morning stiffness, and depression. It is well known that these symptoms are exacerbated under periods of high stress. When pain becomes severe enough, the mind can enter what is known as a dissociative state, characterized by depersonalization - the feeling of detachment from one's physical body and the illusion of watching one's physical body from outside. In evolutionary terms, dissociative states are thought to be an adaptive mechanism to mentally distance oneself from pain, often during trauma. Similar dissociative experiences are reported by subjects who have used psychoactive drugs such as ketamine. We have previously used non-invasive mirror visual feedback to treat subjects with chronic pain from phantom limbs and suggested its use for complex regional pain syndrome: once considered intractable pain. We wondered whether such methods would work to alleviate the chronic pain of fibromyalgia. We tested mirror visual feedback on one fibromyalgia patient. On 15 trials, the patient's lower limb pain rating (on a scale from 1 to 10) decreased significantly. These preliminary results suggest that non-invasive dissociative anesthetics such as VR goggles, ketamine, and mirror visual feedback could be used to alleviate chronic pain from fibromyalgia. This would furnish us with a better understanding of the mechanism by which external visual feedback interacts with the internal physical manifestation of pain.

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.

Olfactory bulb dysgenesis, mirror neuron system dysfunction, and autonomic dysregulation as the neural basis for autism.

Autism is a disorder characterized by social withdrawal, impoverished language and empathy, and a profound inability to adopt another's viewpoint - a failure to construct a "theory of mind" for interpreting another person's thoughts and intentions. We previously showed that these symptoms might be explained, in part, by a paucity of mirror neurons. Prompted by an MRI report of an individual with autism, we now suggest that there may be, in addition, a congenital aplasia/dysplasia of the olfactory bulbs with consequent reduction of vasopressin and oxytocin receptor binding. There may also be sub-clinical temporal lobe epilepsy affecting the recently discovered third visual system that is rich in "empathy" related mirror neurons (MNS) and projects (via the TOP junction - just below the inferior parietal lobule) to limbic structures that regulate autonomic outflow. This causes deranged autonomic feedback, resulting in additional deficiencies in MNS with loss of emotional empathy and introspection.