Search

Background: The subthalamic nucleus (STN) is an efficient target for treating patients with Parkinson's disease as well as patients with obsessive-compulsive disorder (OCD) using high frequency stimulation (HFS). In both Parkinson's disease and OCD patients, STN-HFS can trigger abnormal behaviours, such as hypomania and impulsivity., Methods: To investigate if this structure processes emotional information, and whether it depends on motor demands, we recorded subthalamic local field potentials in 16 patients with Parkinson's disease using deep brain stimulation electrodes. Recordings were made with and without dopaminergic treatment while patients performed an emotional categorisation paradigm in which the response varied according to stimulus valence (pleasant, unpleasant and neutral) and to the instruction given (motor, non-motor and passive)., Results: Pleasant, unpleasant and neutral stimuli evoked an event related potential (ERP). Without dopamine medication, ERP amplitudes were significantly larger for unpleasant compared with neutral pictures, whatever the response triggered by the stimuli; and the magnitude of this effect was maximal in the ventral part of the STN. No significant difference in ERP amplitude was observed for pleasant pictures. With dopamine medication, ERP amplitudes were significantly increased for pleasant compared with neutral pictures whatever the response triggered by the stimuli, while ERP amplitudes to unpleasant pictures were not modified., Conclusions: These results demonstrate that the ventral part of the STN processes the emotional valence of stimuli independently of the motor context and that dopamine enhances processing of pleasant information. These findings confirm the specific involvement of the STN in emotional processes in human, which may underlie the behavioural changes observed in patients with deep brain stimulation.

The deep brain nuclei play an important role in many brain functions and particularly motor control. Damage to these structures result in movement disorders such as in Parkinson's disease or Huntington's disease, or behavioural disorders such as Tourette syndrome. In this paper, we propose to study the connectivity profile of the deep nuclei to the motor, associative or limbic areas and we introduce a novel tool to build a probabilistic atlas of these connections to the cortex directly on the surface of the cortical mantel, as it corresponds to the space of functional interest. The tool is then applied on two populations of healthy volunteers and patients suffering from severe Huntington's disease to produce two surface atlases of the connectivity of the basal ganglia to the cortical areas. Finally, robust statistics are used to characterize the differences of that connectivity between the two populations, providing new connectivity-based biomarkers of the pathology.

Deep brain stimulation (DBS) is a new neurosurgical method principally used for the treatment of Parkinson disease (PD). Many new applications of DBS are under development, including the treatment of intractable psychiatric diseases. Brain imaging is used for the selection of patients for DBS, to localize the target nucleus, to detect complications, and to evaluate the final electrode contact position. In patients with implanted DBS systems, there is a risk of electrode heating when MR imaging is performed. This contraindicates MR imaging unless specific precautions are taken. Involvement of neuroradiologists in DBS procedures is essential to optimize presurgical evaluation, targeting, and postoperative anatomic results. The precision of the neuroradiologic correlation with anatomic data and clinical outcomes in DBS promises to yield significant basic science and clinical advances in the future.

We introduce an anatomical and electrophysiological model of deep brain structures dedicated to magnetoencephalography (MEG) and electroencephalography (EEG) source imaging. So far, most imaging inverse models considered that MEG/EEG surface signals were predominantly produced by cortical, hence superficial, neural currents. Here we question whether crucial deep brain structures such as the basal ganglia and the hippocampus may also contribute to distant, scalp MEG and EEG measurements. We first design a realistic anatomical and electrophysiological model of these structures and subsequently run Monte-Carlo experiments to evaluate the respective sensitivity of the MEG and EEG to signals from deeper origins. Results indicate that MEG/EEG may indeed localize these deeper generators, which is confirmed here from experimental MEG data reporting on the modulation of alpha brain waves.

Object: The aim of this study was to correlate the clinical improvement in patients with Parkinson disease (PD) treated using deep brain stimulation (DBS) of the subthalamic nucleus (STN) with the precise anatomical localization of stimulating electrodes., Methods: Localization was determined by superimposing figures from an anatomical atlas with postoperative magnetic resonance (MR) images obtained in each patient. This approach was validated by an analysis of experimental and clinical MR images of the electrode, and the development of a three-dimensional (3D) atlas-MR imaging coregistration method. The PD motor score was assessed through two contacts for each of two electrodes implanted in 10 patients: the "therapeutic contact" and the "distant contact" (that is, the next but one to the therapeutic contact). Seventeen therapeutic contacts were located within or on the border of the STN, most of which were associated with significant improvement of the four PD symptoms tested. Therapeutic contacts located in other structures (zona incerta, lenticular fasciculus, or midbrain reticular formation) were also linked to a significant positive effect. Stimulation applied through distant contacts located in the STN improved symptoms of PD, whereas that delivered through distant contacts in the remaining structures had variable effects ranging from worsening of symptoms to their improvement., Conclusions: The authors have demonstrated that 3D atlas-MR imaging coregistration is a reliable method for the precise localization of DBS electrodes on postoperative MR images. In addition, they have confirmed that although the STN is the main target during DBS treatment for PD, stimulation of surrounding regions, particularly the zona incerta or the lenticular fasciculus, can also improve symptoms of PD.

The etiology of Parkinson's disease is unknown, but the gene involved in an autosomic recessive form of the disease with early onset has recently been identified. It codes for a protein with an unknown function called parkin. In the present study we produced a specific polyclonal antiserum against human parkin. Immunohistochemical analysis showed that parkin is expressed in neuronal perikarya and processes but also in glial and blood vessels in the primate brain (human and monkey). Electron microscopy indicated that parkin immunoreactivity is mostly located in large cytoplasmic vesicles and at the level of the endoplasmic reticulum. Parkin was expressed heterogeneously in various structures of the brain. It was detectable in the dopaminergic systems at the level of the perikarya in the mesencephalon but also in the striatum. However, parkin was also expressed by numerous nondopaminergic neurons. The staining intensity of parkin was particularly high in the hippocampal formation, the pallidal complex, the red nucleus, and the cerebellum. Comparison of control subjects with patients with Parkinson's disease and control animals with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated animals revealed a loss of parkin-immunoreactive neurons only in the substantia nigra pars compacta. Furthermore, the surviving dopaminergic neurons in the parkinsonian state continued to express parkin at a level similar to that observed in the control situation. These data indicate that parkin is a widely expressed protein. Thus, the degeneration of dopaminergic neurons in familial cases of Parkinson's disease with autosomal recessive transmission cannot be explained solely in terms of an alteration of this protein., (Copyright 2001 Wiley-Liss, Inc.)

Parkinson's disease is characterized by a selective loss of dopaminergic neurons in the nigrostriatal pathway. However, not all dopaminergic neurons degenerate in this disease, and calcium has been suspected of playing a role in this differential vulnerability. An overexpression of the calcium-dependent protease calpain II has recently been reported in the parkinsonian substantia nigra, suggesting that a rise in intracellular calcium concentrations may be involved in the mechanism leading to cell death. The proteasic activity of calpain is regulated by an endogenous inhibitory protein called calpastatin. Because little is known about the distribution of calpastatin in the primate brain, we first analyzed immunohistochemically the calpastatin expression in normal human and monkey brain. A ubiquitous distribution of calpastatin immunostaining was observed in both cases, but its expression was variable from one region to another. In the basal ganglia, staining was intense in the striatum, in the pallidal complex, and in some nuclei of the thalamus. The cerebellum was stained intensely, particularly in the granular and Purkinje cell layers. A dense, heterogeneous staining was observed in the hippocampal formation, mostly in the pyramidal and granular layers. The distribution of staining was similar in the different cerebral cortices studied, and it was most intense in layer V. In the brainstem, staining was particularly prominent in the substantia nigra pars reticulata and compacta, the central gray substance, the superior colliculus, and the cuneiform nucleus, and staining was moderate in the tegmenti pedonculopontinus nucleus and the griseum pontis. In the second part of the study, the authors compared calpastatin expression in the mesencephalon between patients with Parkinson's disease and control subjects. Sequential double staining revealed that some dopaminergic neurons coexpress calpastatin, the proportion of double-stained neurons ranging between 52% and 76% among the different dopaminergic cell groups. Quantitative analysis of the number of calpastatin-stained neurons evidenced a loss of both calpastatin-positive and calpastatin-negative neurons in the substantia nigra of patients with Parkinson's disease. These data suggest that calpain II overexpression in Parkinson's disease is not compensated for by a concomitant increase in calpastatin expression., (Copyright 2000 Wiley-Liss, Inc.)

The present review analyses a motor circuit which, starting from the cerebral cortex goes through the pontine nucleus, granule cells, Purkinje's neurons, the cerebellar nuclei, the motor thalamus, and back to the cortex. This system is analysed by resorting to informational neuromorphology which deduces particular properties of information processing from spatial features observed on neuronal arborisations or sets of arborisations. The main part of the cerebro-cerebellar circuit is fine grained with relatively small arborisations. Such a fine grain is not used here for the preservation of a simple somatotopic representation, as is the case for sensory systems, but instead for a processing using "patchy maps" which is a known mode of parallel processing. There is a major break of arborisations geometry which is situated in the cerebellar cortex between the granule and Purkinje cells. The grain cells axons, the parallel fibers, are numerous and almost unbranched while the dendritic arborisations of Purkinje's cells are flat, with a large surface and are perpendicular to the parallel fibers which leads to both a cardinal and a reception convergence. This is also observed in the striato-pallidal system. A significant difference between the two systems which are separated almost everywhere, notably at the thalamic relays level, is that the system passing through the cerebellum essentially processes sensorimotor information while the basal ganglia system receives information from almost the whole cortex. The return to the cortical targets causes complex interferences. It clearly appears that the two motor systems process information in different manners.

We present a methodology for measuring precisely defined morphological parameters on complete dendritic arborizations. Brains are sectioned through anatomical planes which are defined with reference to ventricular landmarks. For each neuron, drawn through the camera lucida, dendritic points are defined and identified by means of a numerical topological codification. The 3-dimensional coordinates of each point are measured on a video computer microscope with reference to a cartesian system of axes which are oriented with reference to the anatomical planes of the brain. The data points from several serial sections are stored section by section and re-ordered by a computer program. Quantitative data concerning the diameters of the dendrites and the number and the dimensions of their spines are also stored. From these data, various quantitative morphological parameters may be computed. The accuracy of the video computer microscope is measured. The different existing computerized systems and the contribution of computerized techniques are discussed.

Our study proposes an objective method of describing 3-dimensional dendritic arborizations of neurons in the best possible conditions. The method is based upon a particular exploitation of statistical "principal component analysis". For each arborization, 3 principal axes are calculated which are its axes of inertia. The first two axes define the "principal plane" of the arborization. The shape of the arborization is determined from the statistical distribution of its dendritic points along each of these axes. Shapes are quantified by using an "index of axialization" (a) and an "index of flatness" (p) both of which may vary from zero to 1. The dimensions of the arborization, "length" (1), "width" (w) and "thickness" (t) are also measured along the principal axes. Orientation of arborizations is quantified by considering the orientation of the first principal axis for axialized arborization (a close to 1) and/or the orientation of the principal plane for flattened arborizations (p close to 1). In both cases 2 angles (azimuth and polar angle) are calculated. For spherical arborizations (a and p close to 1), no orientation is significant. The significance level of the defined orientations is evaluated from the values of the shape indices. Several examples are illustrated and other existing methods are discussed.

The most widely used conventional stereotactic method utilizing the Horsley-Clarke coordinate system does not allow accurate intracerebral placements. Improving the precision of stereotactic surgery in monkeys has become imperative in neurological research to limit the waste of animals. This problem can be resolved with the use of a stereotactic technique based on ventricular landmarks utilizing "orthogonal teleradiography". The radiological devices and the stereotactic apparatus developed for the use with this technique are described. The apparatus allows the intercommissural plane of the animal to be placed parallel to the rails of the stereotactic frame by means of a head rotation around the ear bars. In addition, the technique uses metric reticles to make the interchange between ventricular and mechanical coordinates possible. The ventriculographic and stereotactic procedures are also described.

Abstract Cellular expression of cytochrome oxidase subunit I (COI) mRNA has recently been used as a metabolic marker for neuronal activity to study the functional changes in the subthalamic nucleus (STN) in parkinsonism. The previous experimental studies have been performed when the pathological state was stabilized at a maximal level. In order to determine the evolution of changes in neuronal activity in the STN after nigrostriatal denervation, we analysed by in situ hybridization the cellular expression of COI mRNA in the subthalamic neurons at different times, from 6 h to 14 days, after unilateral intranigral microinjection of 6-hydroxydopamine (6-OHDA) in rats. In parallel, the time-dependent changes of the unit neuronal activity of subthalamic neurons have been recorded. Levels of COI mRNA increased by 41% in subthalamic neurons from 24 h after 6-OHDA intoxication, to 14 days (+26%). Similarly, electrical activity started to increase slightly 24 h after lesion (+20%) and remained significantly higher at 14 days after the lesion (+189%). Changes in neuronal mean discharge rate were associated with changes in the pattern of spiking activity, from a regular firing pattern to an irregular one with a high bursting activity. These results show that: (i) the hyperactivity of the STN represents a very early phenomenon in the physiopathology of parkinsonian syndromes; and (ii) that changes in COI mRNA expression slightly precede changes in electrical neuronal activity. [ABSTRACT FROM AUTHOR]