The CONNECT project: Combining macro- and micro-structure.

In recent years, diffusion MRI has become an extremely important tool for studying the morphology of living brain tissue, as it provides unique insights into both its macrostructure and microstructure. Recent applications of diffusion MRI aimed to characterize the structural connectome using tractography to infer connectivity between brain regions. In parallel to the development of tractography, additional diffusion MRI based frameworks (CHARMED, AxCaliber, ActiveAx) were developed enabling the extraction of a multitude of micro-structural parameters (axon diameter distribution, mean axonal diameter and axonal density). This unique insight into both tissue microstructure and connectivity has enormous potential value in understanding the structure and organization of the brain as well as providing unique insights to abnormalities that underpin disease states. The CONNECT (Consortium Of Neuroimagers for the Non-invasive Exploration of brain Connectivity and Tracts) project aimed to combine tractography and micro-structural measures of the living human brain in order to obtain a better estimate of the connectome, while also striving to extend validation of these measurements. This paper summarizes the project and describes the perspective of using micro-structural measures to study the connectome.

Does an oblique/slanted perspective during virtual navigation engage both egocentric and allocentric brain strategies?

Perspective (route or survey) during the encoding of spatial information can influence recall and navigation performance. In our experiment we investigated a third type of perspective, which is a slanted view. This slanted perspective is a compromise between route and survey perspectives, offering both information about landmarks as in route perspective and geometric information as in survey perspective. We hypothesized that the use of slanted perspective would allow the brain to use either egocentric or allocentric strategies during storage and recall. Twenty-six subjects were scanned (3-Tesla fMRI) during the encoding of a path (40-s navigation movie within a virtual city). They were given the task of encoding a segment of travel in the virtual city and of subsequent shortcut-finding for each perspective: route, slanted and survey. The analysis of the behavioral data revealed that perspective influenced response accuracy, with significantly more correct responses for slanted and survey perspectives than for route perspective. Comparisons of brain activation with route, slanted, and survey perspectives suggested that slanted and survey perspectives share common brain activity in the left lingual and fusiform gyri and lead to very similar behavioral performance. Slanted perspective was also associated with similar activation to route perspective during encoding in the right middle occipital gyrus. Furthermore, slanted perspective induced intermediate patterns of activation (in between route and survey) in some brain areas, such as the right lingual and fusiform gyri. Our results suggest that the slanted perspective may be considered as a hybrid perspective. This result offers the first empirical support for the choice to present the slanted perspective in many navigational aids.

A disconnection account of Gerstmann syndrome: functional neuroanatomy evidence.

OBJECTIVE: To examine the functional neuroanatomy that could account for pure Gerstmann syndrome, which is the selective association of acalculia, finger agnosia, left-right disorientation, and agraphia. METHODS: We used structural and functional neuroimaging at high spatial resolution in healthy subjects to seek a shared cortical substrate of the Grundstörung posited by Gerstmann, ie, a common functional denominator accounting for this clinical tetrad. We construed a functional activation paradigm that mirrors each of the four clinical deficits in Gerstmann syndrome and determined cortical activation patterns. We then applied fiber tracking to diffusion tensor images and used cortical activation foci in the four functional domains as seed regions. RESULTS: None of the subjects showed parietal overlap of cortical activation patterns from the four cognitive domains. In every subject, however, the parietal activation patterns across all four domains consistently connected to a small region of subcortical parietal white matter at a location that is congruent with the lesion in a well-documented case of pure Gerstmann syndrome. INTERPRETATION: Our functional neuroimaging findings are not in agreement with Gerstmann's postulate of damage to a common cognitive function underpinning clinical semiology. Our evidence from intact functional neuroanatomy suggests that pure forms of Gerstmann's tetrad do not arise from lesion to a shared cortical substrate but from intraparietal disconnection after damage to a focal region of subcortical white matter.

Brain structure predicts the learning of foreign speech sounds.

Previous work has shown a relationship between parietal lobe anatomy and nonnative speech sound learning. We scanned a new group of phonetic learners using structural magnetic resonance imaging and diffusion tensor imaging. Voxel-based morphometry indicated higher white matter (WM) density in left Heschl's gyrus (HG) in faster compared with slower learners, and manual segmentation of this structure confirmed that the WM volume of left HG is larger in the former compared with the latter group. This finding was replicated in a reanalysis of the original groups tested in Golestani and others (2002, Anatomical correlates of learning novel speech sounds. Neuron 35:997-1010). We also found that faster learners have a greater asymmetry (left > right) in parietal lobe volumes than slower learners and that the right insula and HG are more superiorly located in slower compared with faster learners. These results suggest that left auditory cortex WM anatomy, which likely reflects auditory processing efficiency, partly predicts individual differences in an aspect of language learning that relies on rapid temporal processing. It also appears that a global displacement of components of a right hemispheric language network, possibly reflecting individual differences in the functional anatomy and lateralization of language processing, is predictive of speech sound learning.

Inverse retinotopy: inferring the visual content of images from brain activation patterns.

Traditional inference in neuroimaging consists in describing brain activations elicited and modulated by different kinds of stimuli. Recently, however, paradigms have been studied in which the converse operation is performed, thus inferring behavioral or mental states associated with activation images. Here, we use the well-known retinotopy of the visual cortex to infer the visual content of real or imaginary scenes from the brain activation patterns that they elicit. We present two decoding algorithms: an explicit technique, based on the current knowledge of the retinotopic structure of the visual areas, and an implicit technique, based on supervised classifiers. Both algorithms predicted the stimulus identity with significant accuracy. Furthermore, we extend this principle to mental imagery data: in five data sets, our algorithms could reconstruct and predict with significant accuracy a pattern imagined by the subjects.

Functional segregation of cortical language areas by sentence repetition.

The functional organization of the perisylvian language network was examined using a functional MRI (fMRI) adaptation paradigm with spoken sentences. In Experiment 1, a given sentence was presented every 14.4 s and repeated two, three, or four times in a row. The study of the temporal properties of the BOLD response revealed a temporal gradient along the dorsal-ventral and rostral-caudal directions: From Heschl's gyrus, where the fastest responses were recorded, responses became increasingly slower toward the posterior part of the superior temporal gyrus and toward the temporal poles and the left inferior frontal gyrus, where the slowest responses were observed. Repetition induced a decrease in amplitude and a speeding up of the BOLD response in the superior temporal sulcus (STS), while the most superior temporal regions were not affected. In Experiment 2, small blocks of six sentences were presented in which either the speaker voice or the linguistic content of the sentence, or both, were repeated. Data analyses revealed a clear asymmetry: While two clusters in the left superior temporal sulcus showed identical repetition suppression whether the sentences were produced by the same speaker or different speakers, the homologous right regions were sensitive to sentence repetition only when the speaker voice remained constant. Thus, hemispheric left regions encode linguistic content while homologous right regions encode more details about extralinguistic features like speaker voice. The results demonstrate the feasibility of using sentence-level adaptation to probe the functional organization of cortical language areas.

Validation of q-ball imaging with a diffusion fibre-crossing phantom on a clinical scanner.

Magnetic resonance (MR) diffusion imaging provides a valuable tool used for inferring structural anisotropy of brain white matter connectivity from diffusion tensor imaging. Recently, several high angular resolution diffusion models were introduced in order to overcome the inadequacy of the tensor model for describing fibre crossing within a single voxel. Among them, q-ball imaging (QBI), inherited from the q-space method, relies on a spherical Radon transform providing a direct relationship between the diffusion-weighted MR signal and the orientation distribution function (ODF). Experimental validation of these methods in a model system is necessary to determine the accuracy of the methods and to optimize them. A diffusion phantom made up of two textile rayon fibre (comparable in diameter to axons) bundles, crossing at 90 degrees , was designed and dedicated to ex vivo q-ball validation on a clinical scanner. Normalized ODFs were calculated inside regions of interest corresponding to monomodal and bimodal configurations of underlying structures. Three-dimensional renderings of ODFs revealed monomodal shapes for voxels containing single-fibre population and bimodal patterns for voxels located within the crossing area. Principal orientations were estimated from ODFs and were compared with a priori structural fibre directions, validating efficiency of QBI for depicting fibre crossing. In the homogeneous regions, QBI detected the fibre angle with an accuracy of 19 degrees and in the fibre-crossing region with an accuracy of 30 degrees .

Neural network involved in time perception: an fMRI study comparing long and short interval estimation.

In this study, long ( approximately 1,300 ms) and short duration ( approximately 450 ms) estimation trials in an event-related functional MRI (fMRI) study were contrasted in order to reveal the regions within a time estimation network yielding increased activation with the increase of the duration to be estimated. In accordance with numerous imaging studies, our results showed that the presupplementary motor area (preSMA), the anterior cingulate, the prefrontal and parietal cortices, and the basal ganglia were involved in the estimation trials whatever the duration to be estimated. Moreover, only a subset of the regions within this distributed cortical and subcortical network yielded increased activation with increasing time, namely, the preSMA, the anterior cingulate cortex, the right inferior frontal gyrus (homolog to Broca's area), the bilateral premotor cortex, and the right caudate nucleus. This suggests that these regions are directly involved in duration estimation. We propose that the caudate-preSMA circuit, the anterior cingulate, and the premotor-inferior frontal regions may support a clock mechanism, decision and response-related processes, and active maintenance of temporal information, respectively.

Reference frames for spatial cognition: different brain areas are involved in viewer-, object-, and landmark-centered judgments about object location.

Functional magnetic resonance imaging was used to compare the neural correlates of three different types of spatial coding, which are implicated in crucial cognitive functions of our everyday life, such as visuomotor coordination and orientation in topographical space. By manipulating the requested spatial reference during a task of relative distance estimation, we directly compared viewer-centered, object-centered, and landmark-centered spatial coding of the same realistic 3-D information. Common activation was found in bilateral parietal, occipital, and right frontal premotor regions. The retrosplenial and ventromedial occipital-temporal cortex (and parts of the parietal and occipital cortex) were significantly more activated during the landmark-centered condition. The ventrolateral occipital-temporal cortex was particularly involved in object-centered coding. Results strongly demonstrate that viewer-centered (egocentric) coding is restricted to the dorsal stream and connected frontal regions, whereas a coding centered on external references requires both dorsal and ventral regions, depending on the reference being a movable object or a landmark.

Phonological grammar shapes the auditory cortex: a functional magnetic resonance imaging study.

Languages differ depending on the set of basic sounds they use (the inventory of consonants and vowels) and on the way in which these sounds can be combined to make up words and phrases (phonological grammar). Previous research has shown that our inventory of consonants and vowels affects the way in which our brains decode foreign sounds (Goto, 1971; Näätänen et al., 1997; Kuhl, 2000). Here, we show that phonological grammar has an equally potent effect. We build on previous research, which shows that stimuli that are phonologically ungrammatical are assimilated to the closest grammatical form in the language (Dupoux et al., 1999). In a cross-linguistic design using French and Japanese participants and a fast event-related functional magnetic resonance imaging (fMRI) paradigm, we show that phonological grammar involves the left superior temporal and the left anterior supramarginal gyri, two regions previously associated with the processing of human vocal sounds.

Monitoring disease progression in CADASIL with diffusion magnetic resonance imaging: a study with whole brain histogram analysis.

BACKGROUND AND PURPOSE: In cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a large increase in water diffusion has been found both inside and outside the cerebral lesions as detected on conventional MRI. The aim of the present study was to assess the sensitivity of diffusion tensor imaging for monitoring the progression of cerebral tissue damage during the course of CADASIL. METHODS: With the use of diffusion tensor imaging, whole brain trace of the diffusion tensor [Trace(D)] histograms were obtained in 22 CADASIL patients and 12 age-matched controls at baseline, in 14 patients after a mean delay of 21 months, and in 5 controls after a mean delay of 29 months. Parameters derived from these histograms (mean value, peak height, and peak location) were analyzed at baseline and during the follow-up. RESULTS: At baseline, all the histogram parameters differed between patients and controls and were found to be significantly correlated with both the Mini-Mental State Examination score and Rankin Scale score in the patient group. The follow-up study showed a decrease in the peak height associated with an increase in the mean value of whole brain Trace(D) histograms in the 14 CADASIL patients scanned twice. The diffusion changes appeared larger in the patients whose Rankin score increased during the study period. CONCLUSIONS: These results suggest that the measurement of water diffusion over time is a sensitive marker for the progression of tissue damage in the brain. Thus, quantitative diffusion MRI can be used to monitor disease progression in CADASIL and possibly in other types of small-vessel brain disorders.