Visualizing the Neural Bases of a Disconnection Syndrome with Diffusion Tensor Imaging N. Molko1, L. Cohen1,2, J. F. Mangin3, F. Chochon2, S. Lehe´ricy 2, D. Le Bihan3, and S. Dehaene1 Downloaded from http://mitprc.silverchair.com/jocn/article-pdf/14/4/629/1757539/08989290260045864.pdf by guest on 18 May 2021 Abstract & Disconnection syndromes are often conceptualized exclu- hemifield words. Statistical analyses of diffusion images revealed sively within cognitive box-and-arrow diagrams unrelated to a damaged fiber tract linking the left ventral occipito-temporal brain anatomy. In a patient with alexia in his left visual field region to its right homolog across the lesioned area of corpus resulting from a posterior callosal lesion, we illustrate how callosum and stopping close to the areas found active in fMRI. diffusion tensor imaging can reveal the anatomical bases of a The behavioral disconnection syndrome could, thus, be related disconnection syndrome by tracking the degeneration of neural functionally to abnormal fMRI activations and anatomically to pathways and relating it to impaired fMRI activations and the absence of a connection between those activations. The behavior. Compared to controls, an abnormal pattern of brain present approach, based on the ‘‘negative tracking’’ of activity was observed in the patient during word reading, with a degenerated bundles, provides new perspectives on the under- lack of activation of the left visual word form area (VWFA) by left- standing of human brain connections and disconnections. & INTRODUCTION measured voxel. In particular, this anisotropy parameter The cognitive impairments that can be observed in has been shown to be highly sensitive to the degener- brain-lesioned patients are sometimes better explained ation of white matter tracts in brain-injured patients, in by a disconnection between two cerebral processes than whom focal decreases in anisotropy can be observed by primary damage to those processes themselves (Werring et al., 2000). Furthermore, the direction of (Geschwind, 1965). However, disconnections are often water diffusion itself can be measured with diffusion conceptualized exclusively within cognitive box-and- tensor MRI and can be used to infer the local orientation arrow diagrams unrelated to brain anatomy. Up to of fibers (Poupon et al., 2000; Conturo et al., 1999; Le now, the only way to identify the anatomical basis of Bihan, 1995). interarea connections was the postmortem histological In normal subjects, the local orientation vectors meas- visualization of fiber pathways. Diffusion tensor imaging, ured at each voxel location can then be connected a magnetic resonance technique, represents a new together using computer algorithms to infer the long- approach for the study of brain connectivity. This non- range trajectory of entire fiber tracts (Poupon et al., invasive technique allows the measurement of the 2000; Conturo et al., 1999). However, such tracking of Brownian motion of water molecules on a voxel-by-voxel neural pathways remains impeded by the insufficient basis, thus providing quantitative information on the spatial resolution, which results in tracing ambiguities microstructure of biological tissues. The motion of water due to the crossing of fiber bundles within the same molecules is modified by local tissue components such voxel. Here, we describe a different approach, based on as cell membranes, organelles, and macromolecules. In the ‘‘negative tracking’’ of degenerated bundles, which particular, within cerebral white matter, the coherent may circumvent some of these problems. The method orientation of axons constrains water molecules to move consists in isolating a fiber tract by identifying, in a preferentially along the main direction of neural fibers. patient with a focal brain lesion, the set of voxels that This introduces a measurable anisotropy in the diffu- present a statistically significant decrease in anisotropy sion, which can be quantified and gives information and which presumably reflect the degeneration of an about the local density and coherence of axons in the entire fiber tract. Like classical histological methods based on the tracking of degenerated axons after le- sions, this method can be used to isolate a neural 1INSERM, Service Hospitalier Fre´de´ric Joliot, 2Hoˆpital de la pathway within the otherwise complex and intermingled Salpeˆtrie`re, 3UNAF, Service Hospitalier Fre´de´ric Joliot, Com- connections of the normal human brain. The trajectory misariat` a l’Energie Atanique of the degenerated pathway can then be compared with D 2002 Massachusetts Institute of Technology Journal of Cognitive Neuroscience 14:4, pp. 629–636 Downloaded from http://www.mitpressjournals.org/doi/pdf/10.1162/08989290260045864 by guest on 29 September 2021 the outcome of computerized tracking algorithms in In particular, patients with lesions affecting the splenium normal subjects. of their corpus callosum are unable to read words pre- Whether used in normals or patients, diffusion tensor sented in the left half of their visual field, a deficit that is imaging allows for the estimation of the anatomical thought to reflect an impaired transfer of visual informa- trajectory of fiber tracts in a few minutes in a living tion from low-level right-hemispheric visual regions to subject using standard magnetic resonance equipment. left-hemispheric regions specialized in written language Thus, diffusion MRI can easily be combined with func- processing (Cohen et al., 2000; Suzuki et al., 1998). tional magnetic resonance imaging, which gives access We used functional and diffusion tensor MRI to study to information about the activation of brain areas in a the anatomical connectivity and reading circuitry in given cognitive task. The two methods are complemen- patient AC, a 26-year-old right-handed man. Surgery for Downloaded from http://mitprc.silverchair.com/jocn/article-pdf/14/4/629/1757539/08989290260045864.pdf by guest on 18 May 2021 tary. Potentially, diffusion MRI can give access to the a hemorrhage in his left mesial parietal lobe, due to a connectivity of the regions that are identified as coac- small arteriovenous malformation, left patient AC with a tivated during functional MRI. However, at present, this split of the posterior half of his corpus callosum (Figure approach has not been used beyond the description of 1) (Cohen et al., 2000; Intriligator, Henaff, & Michel, the projections from the lateral geniculate nucleus to 2000; Michel, He´naff, & Intriligator, 1996). At the time of occipital visual cortex (Conturo et al., 1999). testing, AC could read words normally when presented In the present article, we used this approach to study in his right hemifield, but was severely slowed and the connectivity underlying the early visual stages of occasionally failed whenever words were presented in reading. The goal of the initial stages of reading is to his left hemifield (Cohen et al., 2000; Michel et al., 1996) build up a representation of letter strings that is invariant (see Methods for further details). The pattern of reading for irrelevant perceptual dimensions, such as the loca- errors in patient AC can be explained by his callosal tion in the visual field, the color of the ink, the size and lesion, which created a disconnection between the right- type of characters, and so forth. This abstract represen- hemispheric retinotopic areas and the left-hemispheric tation has been termed the ‘‘visual word form’’ (VWF) by VWFA (Figure 1). In order to study the precise anatom- Warrington and Shallice (1980). In normal subjects, ical basis of this disconnection hypothesis, we first used words flashed within a single hemifield, either left or fMRI to identify the inferotemporal regions activated right of fixation, cause both hemifield-dependent occi- during reading words presented tachistoscopically in pital activations in contralateral retinotopic areas, and one or the other hemifield. We then collected whole- hemifield-independent activations in the left fusiform brain diffusion tensor images in both the patient and 11 gyrus and other lateral temporal, parietal, and frontal normal subjects. A statistical voxel-by-voxel comparison areas of the left hemisphere (Cohen et al., 2000; Fiez & of the anisotropy images of the patient compared to Petersen, 1998; Price, 1997). Within this extensive net- normals allowed us to localize the degenerated connec- work, converging evidence suggests that a subregion of tions. We then went back to the diffusion images of a the left fusiform gyrus, whose Talairach coordinates are normal subject to infer the premorbid direction of fibers approximately x = À43, y = À54, z = À12, contributes in this area, and showed that they correspond in part to crucially to the cerebral basis of the VWF (Cohen et al., a long-distance fiber tract connecting right-hemispheric 2000; Beauregard et al., 1997; Puce, Allison, Asgari, Gore, visual regions to the VWFA. & McCarthy, 1996). It is activated irrespective of the stimulated hemifield, thus achieving invariance for posi- RESULTS tion (Cohen et al., 2000). A study using masked repeti- tion priming indicates that the VWFA responds to Behavior specific words independently of the case in which they Patient AC’s reading behavior replicated earlier findings are presented (Dehaene et al., 2001). Finally, this area (Cohen et al., 2000; Michel et al., 1996). The patient seems to overlap with the critical lesion site for pure experienced no difficulty in reading right visual field alexia, a selective deficit of word reading with sparing of (RVF) words (2% errors, mean latency = 728 msec) and writing and of auditory word comprehension (Leff et al., in saying the word ‘‘consonant’’ to RVF consonant string 2001; Beversdorf, Ratcliffe, Rhodes, & Reeves, 1997; (0 errors, 1148 msec). However, he was significantly Binder & Mohr, 1992; Damasio & Damasio, 1983; Dejer- slower with LVF words than with RVF words, 2125 vs. ine, 1892). As a consequence of such converging evi- 728 msec; t(94 df ) = 7.67, p <10À4, though his error dence, we proposed to name this left fusiform region the rate remained almost at floor level (6% errors). There visual word form area (VWFA) (Cohen et al., 2000).