Maurice Ptito

Orientationally invariant indices of axon diameter and density from diffusion MRI

This paper proposes and tests a technique for imaging orientationally invariant indices of axon diameter and density in white matter using diffusion magnetic resonance imaging. Such indices potentially provide more specific markers of white matter microstructure than standard indices from diffusion tensor imaging. Orientational invariance allows for combination with tractography and presents new opportunities for mapping brain connectivity and quantifying disease processes. The technique uses a four-compartment tissue model combined with an optimized multishell high-angular-resolution pulsed-gradient-spin-echo acquisition. We test the method in simulation, on fixed monkey brains using a preclinical scanner and on live human brains using a clinical 3T scanner. The human data take about one hour to acquire. The simulation experiments show that both monkey and human protocols distinguish distributions of axon diameters that occur naturally in white matter. We compare the axon diameter index with the mean axon diameter weighted by axon volume. The index differs from this mean and is protocol dependent, but correlation is good for the monkey protocol and weaker, but discernible, for the human protocol where greater diffusivity and lower gradient strength limit sensitivity to only the largest axons. Maps of axon diameter and density indices from the monkey and human data in the corpus callosum and corticospinal tract reflect known trends from histology. The results show orientationally invariant sensitivity to natural axon diameter distributions for the first time with both specialist and clinical hardware. This demonstration motivates further refinement, validation, and evaluation of the precise nature of the indices and the influence of potential confounds.

Alterations of the visual pathways in congenital blindness

We used whole brain MRI voxel-based morphometry (VBM) to study the anatomical organization of the visual system in congenitally blind (CB) adults. Eleven CB without a history of visual perception were compared with 21 age- and sex-matched normal-sighted controls (NS). CB showed significant atrophy of the geniculo-striate system, encompassing the optic nerves, the optic chiasm, the optic radiations and the primary visual cortex (BA17). The volume decrease in BA17 reached 25% in both hemispheres. The pulvinar and its projections to the associative visual areas were also dramatically altered, BA18/19 and the middle temporal cortex (MT) showing volume reductions of up to 20%. Additional significant white matter alterations were observed in the inferior longitudinal tract and in the posterior part of the corpus callosum, which links the visual areas of both hemispheres. Our data indicate that the afferent projections to the visual cortex in CB are largely atrophied. Despite the massive volume reductions in the occipital lobes, there is compelling evidence from the literature (reviewed in Noppeney 2007; Ptito and Kupers 2005) that blind subjects activate their visual cortex when performing tasks that involve somatosensory or auditory inputs, suggesting a reorganization of the neural pathways that transmit sensory information to the visual cortex.

Beyond visual, aural and haptic movement perception: hMT+ is activated by electrotactile motion stimulation of the tongue in sighted and in congenitally blind individuals

The motion-sensitive middle temporal cortex (hMT+ complex) responds also to non-visual motion stimulation conveyed through the tactile and auditory modalities, both in sighted and in congenitally blind individuals. This indicates that hMT+ is truly responsive to motion-related information regardless of visual experience and the sensory modality through which such information is carried to the brain. Here we determined whether the hMT+ complex responds to motion perception per se, that is, motion not perceived through the visual, haptic or aural modalities. Using functional magnetic resonance imaging (fMRI), we investigated brain responses in eight congenitally blind and nine sighted volunteers who had been trained to use the tongue display unit (TDU), a sensory substitution device which converts visual information into electrotactile pulses delivered to the tongue, to resolve a tactile motion discrimination task. Stimuli consisted of either static dots, dots moving coherently or dots moving in random directions. Both groups learned the task at the same rate and activated the hMT+ complex during tactile motion discrimination, although at different anatomical locations. Furthermore, the congenitally blind subjects showed additional activations within the dorsal extrastriate cortical pathway. These results extend previous data in support of the supramodal functional organization of hMT+ complex by showing that this cortical area processes motion-related information per se, that is, motion stimuli that are not visual in nature and that are administered to body structures that, in humans, are not primarily devoted to movement perception or spatial location, such as the tongue. In line with previous studies, the differential activations between sighted and congenitally blind individuals indicate that lack of vision leads to functional rearrangements of these supramodal cortical areas.

Transcranial magnetic stimulation of the visual cortex induces somatotopically organized qualia in blind subjects.

After loss of a particular sensory channel, the deprived cortex can be activated by inputs from other sensory modalities. It is not known whether activation of the rewired cortex evokes subjective experiences characteristic of that cortex or consistent with the rerouted sensory information. In a previous study, blind subjects were trained to perform visual tasks with a tongue display unit, a sensory substitution device that translates visual displays into electrotactile tongue stimulation. This cross-modal sensory stimulation activated their visual cortices. We now extend this finding by using transcranial magnetic stimulation to examine the perceptual correlates of training-induced plastic responses. We find that blind subjects proficient with the use of the tongue display unit report somatopically organized tactile sensations that are referred to the tongue when transcranial magnetic stimulation is applied over the occipital cortex. No such sensations were evoked in trained, blindfolded, seeing control subjects who performed the sensory substitution task equally well. These data show that the perceptual correlate of activity in a given cortical area reflects the characteristics of its novel sensory input source.

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.

Neural correlates of virtual route recognition in congenital blindness

Despite the importance of vision for spatial navigation, blind subjects retain the ability to represent spatial information and to move independently in space to localize and reach targets. However, the neural correlates of navigation in subjects lacking vision remain elusive. We therefore used functional MRI (fMRI) to explore the cortical network underlying successful navigation in blind subjects. We first trained congenitally blind and blindfolded sighted control subjects to perform a virtual navigation task with the tongue display unit (TDU), a tactile-to-vision sensory substitution device that translates a visual image into electrotactile stimulation applied to the tongue. After training, participants repeated the navigation task during fMRI. Although both groups successfully learned to use the TDU in the virtual navigation task, the brain activation patterns showed substantial differences. Blind but not blindfolded sighted control subjects activated the parahippocampus and visual cortex during navigation, areas that are recruited during topographical learning and spatial representation in sighted subjects. When the navigation task was performed under full vision in a second group of sighted participants, the activation pattern strongly resembled the one obtained in the blind when using the TDU. This suggests that in the absence of vision, cross-modal plasticity permits the recruitment of the same cortical network used for spatial navigation tasks in sighted subjects.

Contrast and stability of the axon diameter index from microstructure imaging with diffusion MRI.

The ActiveAx technique fits the minimal model of white matter diffusion to diffusion MRI data acquired using optimized protocols that provide orientationally invariant indices of axon diameter and density. We investigated how limitations of the available maximal gradient strength (Gmax) on a scanner influence the sensitivity to a range of axon diameters. Multishell high‐angular‐diffusion‐imaging (HARDI) protocols for Gmax of 60, 140, 200, and 300 mT/m were optimized for the pulsed‐gradient‐spin‐echo (PGSE) sequence. Data were acquired on a fixed monkey brain and Monte‐Carlo simulations supported the results. Increasing Gmax reduces within‐voxel variation of the axon diameter index and improves contrast beyond what is achievable with higher signal‐to‐noise ratio. Simulations reveal an upper bound on the axon diameter (∼10 μm) that pulsed‐gradient‐spin‐echo measurements are sensitive to, due to a trade‐off between short T2 and the long diffusion time needed to probe larger axon diameters. A lower bound (∼2.5 μm) slightly dependent on Gmax was evident, below which axon diameters are identifiable as small, but impossible to differentiate. These results emphasize the key‐role of Gmax for enhancing contrast between axon diameter distributions and are, therefore, relevant in general for microstructure imaging methods and highlight the need for increased Gmax on future commercial systems. Magn Reson Med 70:711–721, 2013.

Navigation with a sensory substitution device in congenitally blind individuals.

Vision allows for obstacle detection and avoidance. The compensatory mechanisms involved in maintaining these functions in blind people using their remaining intact senses are poorly understood. We investigated the ability of congenitally blind participants to detect and avoid obstacles using the tongue display unit, a sensory substitution device that uses the tongue as a portal to the brain. We found that congenitally blind were better than sighted control participants in detecting and avoiding obstacles using the tongue display unit. Obstacles size and avoidance strategy had a significant effect on performance: large obstacles were better detected than small ones and step-around obstacles were better avoided than step-over ones. These data extend our earlier findings that when using a sensory substitution device, blind participants outperform sighted controls not only in a virtual navigation task but also during effective navigation within a human-sized obstacle course.

TMS of the occipital cortex induces tactile sensations in the fingers of blind Braille readers

Various non-visual inputs produce cross-modal responses in the visual cortex of early blind subjects. In order to determine the qualitative experience associated with these occipital activations, we systematically stimulated the entire occipital cortex using single pulse transcranial magnetic stimulation (TMS) in early blind subjects and in blindfolded seeing controls. Whereas blindfolded seeing controls reported only phosphenes following occipital cortex stimulation, some of the blind subjects reported tactile sensations in the fingers that were somatotopically organized onto the visual cortex. The number of cortical sites inducing tactile sensations appeared to be related to the number of hours of Braille reading per day, Braille reading speed and dexterity. These data, taken in conjunction with previous anatomical, behavioural and functional imaging results, suggest the presence of a polysynaptic cortical pathway between the somatosensory cortex and the visual cortex in early blind subjects. These results also add new evidence that the activity of the occipital lobe in the blind takes its qualitative expression from the character of its new input source, therefore supporting the cortical deference hypothesis.

Tactile-'visual' acuity of the tongue in early blind individuals.

This study compares the ‘tactile–visual’ acuity of the tongue for 15 early blind participants with that of 24 age-matched and sex-matched sighted controls. Snellens tumbling E test was used to assess ‘visual’ acuity using the tongue display unit. The tongue display unit is a sensory substitution device that converts a visual stimulus grabbed by a camera into electro-tactile pulses delivered to the tongue via a grid made out of electrodes. No overall significant difference was found in thresholds between early blind (1/206) and sighted control (1/237) participants. We found, however, a larger proportion of early blind in the two highest visual acuity categories (1/150 and 1/90). These results extend earlier findings that it is possible to measure visual acuity in the blind individuals using the tongue. Moreover, our data demonstrate that a subgroup of early blind participants is more efficient than controls in conveying visual information through the tongue.