Gaining new insights into the anatomy of the human hypothalamus is crucial for the development of new treatment strategies involving functional stereotactic neurosurgery. Here, using anatomical comparisons between histology and magnetic resonance images of the human hypothalamus in the coronal plane, we show that discrete gray and white hypothalamic structures are consistently identifiable by MRI. Macroscopic and microscopic images were used to precisely annotate the MRI sequences realized in the coronal plane in twenty healthy volunteers. MRI was performed on a 1.5T scanner, using a protocol including T1-weighted 3D fast field echo, T1-weighted inversionrecovery, turbo spin echo and T2-weighted 2D fast field echo imaging. For each gray matter structure as well as for white matter bundles, the different MRI sequences were analyzed in comparison to each other. The anterior commissure and the fornix were often identifiable, while the mammillothalamic tract was more difficult to spot. Qualitative analyses showed that MRI could also highlight finer structures such as the paraventricular nucleus, the ventromedial nucleus of the hypothalamus and the infundibular (arcuate) nucleus, brain nuclei that play key roles in the regulation of food intake and energy homeostasis. The posterior hypothalamic area, a target for deep brain stimulation in the treatment of cluster headaches, was readily identified, as was the lateral hypothalamic area, which similar to the aforementioned hypothalamic nuclei, could be a putative target for deep brain stimulation in the treatment of obesity. Finally, each of the identified structures was mapped to Montreal Neurological Institute (MNI) space. Please find enclosed the revised version of our manuscript "MRI atlas of the human hypothalamus" which we have modified according to the minor comment made by the reviewer#3.We appreciated the careful and incisive evaluation of our data made by the reviewers throughout the reviewing process. We hope that the manuscript is now in suitable form for publication in Neuroimage.  New insights into the anatomy of the human hypothalamus  Specific 1.5T MRI sequences approach histological resolution within the hypothalamus  White matter bundles within the hypothalamus can be identified using 1.5T MRI  Hypothalamic gray structures can be identified using 1.5T MRI *4. HighlightsWe have revised our manuscript to address the minor point raised by reviewer 3.In the "Data analysis" paragraph of the materials and methods section it now reads: "Structures were identified visually based on our knowledge of specific landmarks obtained from anatomical-histological cross sections and with reference to previously published atlases (Swaab et al., 1993;Koutcherov et al., 2000Koutcherov et al., , 2004Koutcherov et al., 2007;Mai et al., 2008); the landmarks used, such as the optic tract, the floor of the diencephalon, the third ventricle, and the fornix, were readily and reliably identifiable in MR scans." AbstractGaining new insights into the anatomy of the hu...

The study of the links and interactions between development and motor learning has noticeable implications for the understanding and management of neurodevelopmental disorders. This is particularly relevant for the cerebellum which is critical for sensorimotor learning. The olivocerebellar pathway is a key pathway contributing to learning of motor skills. Its developmental maturation and remodeling are being unraveled. Advances in genetics have led to major improvements in our appraisal of the genes involved in cerebellar development, especially studies in mutant mice. Cerebellar neurogenesis is compartmentalized in relationship with neurotransmitter fate. The Engrailed-2 gene is a major actor of the specification of cerebellar cell types and late embryogenic morphogenesis. Math1, expressed by the rhombic lip, is required for the genesis of glutamatergic neurons. Mutants deficient for the transcription factor Ptf1a display a lack of Purkinje cells and gabaergic interneurons. Rora gene contributes to the developmental signaling between granule cells and Purkinje neurons. The expression profile of sonic hedgehog in postnatal stages determines the final size/shape of the cerebellum. Genes affecting the development impact upon the physiological properties of the cerebellar circuits. For instance, receptors are developmentally regulated and their action interferes directly with developmental processes. Another field of research which is expanding relates to very preterm neonates. They are at risk for cerebellar lesions, which may themselves impair the developmental events. Very preterm neonates often show sensori-motor deficits, highlighting another major link between impaired developments and learning deficiencies. Pathways playing a critical role in cerebellar development are likely to become therapeutical targets for several neurodevelopmental disorders.

IntroductionMagnetic resonance imaging (MRI) can be used to identify biomarkers in Parkinson’s disease (PD); R2* values reflect iron content related to high levels of oxidative stress, whereas volume and/or shape changes reflect neuronal death. We sought to assess iron overload in the nigrostriatal system and characterize its relationship with focal and overall atrophy of the striatum in the pivotal stages of PD.MethodsTwenty controls and 70 PD patients at different disease stages (untreated de novo patients, treated early-stage patients and advanced-stage patients with L-dopa-related motor complications) were included in the study. We determined the R2* values in the substantia nigra, putamen and caudate nucleus, together with striatal volume and shape analysis. We also measured R2* in an acute MPTP mouse model and in a longitudinal follow-up two years later in the early-stage PD patients.ResultsThe R2* values in the substantia nigra, putamen and caudate nucleus were significantly higher in de novo PD patients than in controls. Early-stage patients displayed significantly higher R2* values in the substantia nigra (with changes in striatal shape), relative to de novo patients. Measurements after a two-year follow-up in early-stage patients and characterization of the acute MPTP mouse model confirmed that R2* changed rapidly with disease progression. Advanced-stage patients displayed significant atrophy of striatum, relative to earlier disease stages.ConclusionEach pivotal stage in PD appears to be characterized by putative nigrostriatal MRI biomarkers: iron overload at the de novo stage, striatal shape changes at early-stage disease and generalized striatal atrophy at advanced disease.

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We investigated the effects of an artificial menstrual cycle on brain structure and activity in young women using metabolic magnetic resonance imaging (MRI). We show that the activation of the hypothalamo-pituitary-gonadal axis during the pill-free interval of low-dose combined oral contraceptive use is associated with transient microstructural and metabolic changes in the female hypothalamus but not in the thalamus, a brain structure unrelated to reproductive control, as assessed by water diffusion and proton magnetic resonance spectra measurements. Our results provide neuroanatomical insights into the mechanism by which sex steroid hormones mediate their central effects and raise the intriguing possibility that specific regions of the neuroendocrine brain use ovarian cycle-dependent plasticity to control reproduction in humans. These MRI-based physiological studies may pave the way for the development of new diagnostic and treatment strategies in the central loss of reproductive competence in human syndromes, such as hypothalamic amenorrhea.

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A 24-year-old woman suffered from gait unsteadiness and tetraparesis since childhood. Her medical history was characterized by a normal delivery of non-consanguineous parents. Walking with support was acquired at 10 months. Childhood development was characterized by occurrence of a progressive cerebellar ataxia, short stature, mental development retardation (IQ = 46), and hypodontia (i.e., absence of deciduous teeth eruption and short tooth roots). Walking without support was never acquired. At the age of 14, a partial growth hormone (GH) deficit (insufficient peak of GH in standard condition and with stimulation tests) and an hypogonadotropic hypogonadism [absence of luteinizing hormone (LH) and follicle stimulating hormone (FSH), lack of response to LH-releasing hormone (LH-RH) injection with LH peak at 0.6 UI/l and FSH peak at 1.4 UI/l] were found. Dental panoramic radiographs showed short tooth roots and absence of dental pulp chamber ( Fig. 1). At the age of 24, neurological examination observed a severe static and kinetic cerebellar syndrome, spastic tetraparesis, multidirectional nystagmus, vertical down and up-gaze palsy, and mental retardation. Walking perimeter was 10 m with human assistance. Neuro-ophthalmologic examination confirmed vertical gaze palsy, and revealed amblyopia (with visual acuity of 4/10 on both sides), severe myopia, and bilateral temporal papillary atrophy. Nerve conduction studies and electromyography were normal.Neuroimaging performed at 3 Tesla (Philips, Best, The Netherlands) showed marked atrophy of the corpus callosum (reflecting the global white matter (WM) volume) and the cerebellum. In addition, spinal cord atrophy was moderate (data not shown). Myelinated areas including the pyramidal tracts, the internal capsule, the deep cerebellum, and the brainstem were hyperintense relative to cortical grey matter (CGM) on T1-WI and hypomyelinated areas (=rest of the white matter) were diffusely hypointense relative to CGM on T1-W1 (Fig. 2a-c). On T2-FLAIR images, the myelinated area appeared iso/hypointense relative to CGM and the hypomyelinated area appeared diffusively hyperintense relative to CGM (Fig. 2d-f). The pons appeared small with widening of the prepontine cystern, which was probably due to hypomyelinated corticopontine tracts as well as atrophy of crossing cerebellar tracts (Fig. 2a, c, d, f). Single voxel proton-magnetic resonance spectroscopy (HMRS) spectra showed low choline/creatine and N-acetylaspartate/creatine ratios within the left semi-ovale WM, left basal ganglia and pons. A prominent myo-inositol peak was also found within the pons (Fig. 2g). Tractography obtained from a Diffusion

Purpose Idiopathic scoliosis (IS) is a frequent 3D structural deformity of the spine with a multi-factorial aetiology which remains largely unclear. In the last decade, human magnetic resonance imaging (MRI) morphometry studies (e.g. cortical thickness, 2D shape of the corpus callosum) have aimed to investigate the potential contribution of the central nervous system in the etiopathogenesis of IS. Recent developments in diffusion tensor imaging (DTI) allow us to extend the previous work to the study of white matter microstructure. Here, we hypothesized that part of the corpus callosum could show a difference in white matter microstructure in IS patients as compared to healthy controls.Methods We acquired DTI in 10 girls with IS and in 49 gender-matched controls to quantify the fractional anisotropy (FA) along the corpus callosum. Results Despite a very similar pattern of FA along the corpus callosum (maxima in the splenium and the genu and minimum in the isthmus), we found a significantly lower FA in the body in patients with IS as compared to control subjects. This region is known to connect the motor and premotor cortices of the two hemispheres. Conclusion This first diffusion magnetic resonance imaging brain study in IS patients, suggests that differences in white matter development, such as synchronization of axonal myelination and pruning could be involved in the etiopathogenesis of IS.