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International audience; Giant axonal neuropathy (GAN), a severe childhood disorder affecting both the peripheral nerves and the central nervous system, is due to mutations in the GAN gene encoding gigaxonin, a protein implicated in the cytoskeletal functions and dynamics. In the majority of the GAN series reported to date, patients had the classical clinical phenotype characterized by a severe axonal neuropathy with kinky hair and early onset CNS involvement including cerebellar and pyramidal signs. We present 12 patients (6 families) with GAN mutations and different clinical phenotypes. Four families were harbouring an identical homozygous nonsense mutation but with different severe clinical phenotypes, one patient had a novel missense homozygous mutation with a peculiar moderate phenotype and prominent skeletal deformations. The last family (4 patients) harbouring a homozygous missense mutation had the mildest form of the disease. In contrast with recent reported series of patients with typical GAN clinical features, the present series demonstrate obvious clinical heterogeneity.

International audience; OBJECTIVE: To study the pyramidal tract side effects (PTSEs) induced by the spread of current from the subthalamic nucleus (STN) to the pyramidal tract (PT), in patients with parkinsonism undergoing STN stimulation. METHODS: 14 patients bilaterally implanted with tetrapolar electrodes were assessed. For each side separately, the threshold of adverse effects induced by monopolar stimulation delivered by the chronically used contact was detected. The voltage was progressively increased until the patient experienced discomfort. All the PTSEs induced at 130 Hz (high-frequency stimulation (HFS)) and 2 or 3 Hz (low-frequency stimulation (LFS)) were videotaped. By superimposing the preoperative and postoperative MR images, the minimum distance (R) from the centre of the used contact to the medial border of the PT were measured. RESULTS: The progressive increase in voltage at HFS induced tonic motor contractions, mainly located in the face, in 27/28 electrodes. LFS induced synchronous rhythmic myoclonus in the same territory. PTSEs induced at threshold voltage by HFS were observed in the upper face at 13/28 electrodes (bilaterally in six cases) and in the contralateral lower face at five electrodes. A positive correlation was found between the stimulus intensity capable of eliciting motor contractions at HFS and R. CONCLUSIONS: HFS of the STN preferentially activates the corticobulbar tract over the corticospinal tract. Therefore, cranial motor contractions need to be looked for during electrical parameter setting. The positive correlation between the electrical intensity threshold for PTSEs and R reflects the need for millimetre accuracy in electrode positioning.

Normal cognitive development in infants follows a well‐known temporal sequence, which is assumed to be correlated with the structural maturation of underlying functional networks. Postmortem studies and, more recently, structural MR imaging studies have described qualitatively the heterogeneous spatiotemporal progression of white matter myelination. However, in vivo quantification of the maturation phases of fiber bundles is still lacking. We used noninvasive diffusion tensor MR imaging and tractography in twenty‐three 1–4‐month‐old healthy infants to quantify the early maturation of the main cerebral fascicles. A specific maturation model, based on the respective roles of different maturational processes on the diffusion phenomena, was designed to highlight asynchronous maturation across bundles by evaluating the time‐course of mean diffusivity and anisotropy changes over the considered developmental period. Using an original approach, a progression of maturation in four relative stages was determined in each tract by estimating the maturation state and speed, from the diffusion indices over the infants group compared with an adults group on one hand, and in each tract compared with the average over bundles on the other hand. Results were coherent with, and extended previous findings in 8 of 11 bundles, showing the anterior limb of the internal capsule and cingulum as the most immature, followed by the optic radiations, arcuate and inferior longitudinal fascicles, then the spinothalamic tract and fornix, and finally the corticospinal tract as the most mature bundle. Thus, this approach provides new quantitative landmarks for further noninvasive research on brain‐behavior relationships during normal and abnormal development. Hum Brain Mapp, 2008. © 2007 Wiley‐Liss, Inc.

International audience; BACKGROUND AND PURPOSE: The early postnatal period is perhaps the most dynamic phase of white matter development. We hypothesized that the early postnatal development of the corpus callosum and corticospinal tracts could be studied in unsedated healthy neonates by using novel approaches to diffusion tensor imaging (DTI) and quantitative tractography. MATERIALS AND METHODS: Isotropic 2 x 2 x 2 mm(3) DTI and structural images were acquired from 47 healthy neonates. DTI and structural images were coregistered and fractional anisotropy (FA), mean diffusivity (MD), and normalized T1-weighted (T1W) and T2-weighted (T2W) signal intensities were determined in central midline and peripheral cortical regions of the white matter tracts of the genu and splenium of the corpus callosum and the central midbrain and peripheral cortical regions of the corticospinal tracts by using quantitative tractography. RESULTS: We observed that central regions exhibited lower MD, higher FA values, higher T1W intensity, and lower T2W intensity than peripheral cortical regions. As expected, MD decreased, FA increased, and T2W signal intensity decreased with increasing age in the genu and corticospinal tract, whereas there was no significant change in T1W signal intensity. The central midline region of the splenium fiber tract has a unique pattern, with no change in MD, FA, or T2W signal intensity with age, suggesting different growth trajectory compared with the other tracts. FA seems to be more dependent on tract organization, whereas MD seems to be more sensitive to myelination. CONCLUSIONS: Our novel approach may detect small regional differences and age-related changes in the corpus callosum and corticospinal white matter tracts in unsedated healthy neonates and may be used for future studies of pediatric brain disorders that affect developing white matter.

International audience; The human infant is particularly immature at birth and brain maturation, with the myelination of white matter fibers, is protracted until adulthood. Diffusion tensor imaging offers the possibility to describe non invasively the fascicles spatial organization at an early stage and to follow the cerebral maturation with quantitative parameters that might be correlated with behavioral development. Here, we assessed the feasibility to study the organization and maturation of major white matter bundles in eighteen 1- to 4-month-old healthy infants, using a specific acquisition protocol customized to the immature brain (with 15 orientations of the diffusion gradients and a 700 s mm(-2)b factor). We were able to track most of the main fascicles described at later ages despite the low anisotropy of the infant white matter, using the FACT algorithm. This mapping allows us to propose a new method of quantification based on reconstructed tracts, split between specific regions, which should be more sensitive to specific changes in a bundle than the conventional approach, based on regions-of-interest. We observed variations in fractional anisotropy and mean diffusivity over the considered developmental period in most bundles (corpus callosum, cerebellar peduncles, cortico-spinal tract, spino-thalamic tract, capsules, radiations, longitudinal and uncinate fascicles, cingulum). The results are in good agreement with the known stages of white matter maturation and myelination, and the proposed approach might provide important insights on brain development.

The purpose of this study was to investigate the time-course of corticospinal excitability during reaction time (RT), and compare the excitability when a precue provided information regarding both the direction and extent of the upcoming movement ('Full' condition), specified the direction of the upcoming movement only ('Direction' condition), or provided no information at all ('None' condition). Ten healthy, right-handed subjects performed a four-choice RT task that involved flexion and extension of dominant wrist. Transcranial magnetic stimulation (TMS) was presented at random intervals over a period of 120 ms prior to the subject's average non-stimulated voluntary electromyography (EMG) activity onset. We found that there was a significant relationship between motor-evoked potential (MEP) amplitude and TMS onset when both the flexor carpi radialis (FCR) and extensor carpi radialis (ECR) acted as an agonist. This relationship could be explained using the sigmoidal Boltzmann equation. The slope for the relationship did not differ between the Full and Direction conditions, suggesting that corticospinal excitability is not altered in the specification of movement extent. Both these conditions differed significantly from the None condition. The modulation of corticospinal excitability appeared greater in the FCR than in the ECR. There was a significant delay in RT the closer in time TMS was presented with respect to EMG onset. During extension, there was no difference in slope between the three conditions, whereas during flexion the slope was greater in the None condition than in the Direction condition, which was in turn greater than in the Full condition. This was mirrored in the relationship between agonist MEP amplitude and TMS onset for both muscles. It is possible that the gain of the corticospinal tract is increased in the conditions in which less information is provided in the precue to partly compensate for the increase in RT, which comes as a result of the additional processing required in those conditions.

In humans a substantial part of corticospinal excitation to upper limb motoneurons is mediated through cervical premotoneurons located rostral to motoneurons, analogous to the feline system of C3-C4 propriospinal neurons. The indirect (disynaptic) component of the corticospinal command passing through the propriospinal relay may be updated by the extensive convergence at this level of afferent inputs (both excitatory and inhibitory) from the moving limb. Propriospinal neurons are potently inhibited by feedback inhibitory interneurons facilitated from the motor cortex, and this explains why artificial volleys delivered to the pyramidal system by itself have failed to demonstrate this indirect corticospinal projection. The strength of this indirect corticospinal projection may be estimated in routine practice by the amount of suppression elicited by a cutaneous volley on the ongoing electromyogram of extensor carpi radialis, and is increased in patients recovering from hemiplegia and in early Parkinson's disease.

Peripheral stimuli facilitate, at a pre-motoneuronal level, the responses elicited in human upper limb motoneurons (MNs) by transcranial magnetic stimulation over the motor cortex (TMS). Several features indicate that the relevant premotoneurones are distinct from segmental interneurones and located rostral to MNs. Thus, corticospinal volleys would have an indirect (propriospinal) pathway to upper limb MNs, in addition to the direct cortico-motoneuronal pathway. Slightly increasing the corticospinal input causes the facilitation to be reversed to inhibition. This is consistent with a well-developed system of inhibitory intemeurones activated by corticospinal and afferent inputs inhibiting propriospinal neurones (PNs). Corticospinal activation of these inhibitory interneurones would explain why propriospinally-mediated corticospinal EPSPs are weak in primate MNs after artificial (electrical or magnetic) activation of the corticospinal system by itself. However, indirect evidence for descending facilitation of PNs can be provided during normal voluntary contractions, while using the modulation of the ongoing EMG or of the H reflex.

We sought to determine why a given muscle appears represented in widespread loci in the motor cortex (MCx). To this end, we microstimulated every 500 microm along medio-lateral rows and recorded the evoked electromyographic (EMG) responses of up to a dozen forelimb muscles of the cat. A consistent finding in all animals studied was that along a given row, distal muscle responses could be elicited from medially situated cortical loci and conversely, proximal muscles responses from laterally situated cortical loci. In many such cases, the evoked EMG responses were such that the largest responses from a distal muscle were obtained by stimulation at a medially situated point and those of a proximal muscle from a laterally situated point. A Spearman correlation analysis showed that there was no correlation between cortical position and where the peak response of a given muscle occurred. These quantitative results strongly support the view that in the forelimb area of the cat MCx there exists widespread 'colonies' of corticospinal neurons with common spinal cord targets.

International audience; This paper will discuss experiments dedicated to the exploration of pathways linking the sensorimotor cortex (SMC) and the main bulbar nuclei involved in cardiovascular control: the nucleus tractus solitarius (NTS), the dorsal nucleus of the vagus (DMV) and the rostral ventrolateral medulla (RVLM). Results obtained through neurofunctional and neuroanatomical methods are presented in order to bring new answers to relevant points concerning somato-cardiovascular integration: firstly to show the ability of the SMC to influence neurons in bulbar cardiovascular nuclei, and secondly to identify pathways that transmit such influences. The neurofunctional approach, based on the identification of Fos-like immunoreactive neurons, indicated that the SMC has functional connections with cardiovascular bulbar nuclei. The neuroanatomical approach, which employed retrograde and anterograde axonal tracing methods, provided evidence of direct projections from the SMC to NTS/DMV and RVLM. Furthermore, experiments showed clearly that corticospinal neurons sent collaterals to bulbar cardiovascular nuclei, especially to the RVLM. Direct cortical projections to the NTS/DMV and the RVLM provide the anatomical basis for cortical influences on the baroreceptor reflex and sympathetic vasomotor mechanisms for blood pressure control, and support the hypothesis of cortical commands coupling somatic and cardiovascular outputs for action.