Microstructural MRI basis of the cognitive functions in patients with Spinocerebellar ataxia type 2

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease involving the cerebellum. The particular atrophy pattern results in some typical clinical features mainly including motor deficits. In addition, the presence of cognitive impairments, involving language, visuospatial and executive functions, has been also shown in SCA2 patients and it is now widely accepted as a feature of the disease. The aim of the study is to investigate the microstructural patterns and the anatomo-functional substrate that could account for the cognitive symptomatology observed in SCA2 patients. In the present study, diffusion tensor imaging (DTI) based-tractography was performed to map the main cerebellar white matter (WM) bundles, such as Middle and Superior Cerebellar Peduncles, connecting cerebellum with higher order cerebral regions. Damage-related diffusivity measures were used to determine the pattern of pathological changes of cerebellar WM microstructure in patients affected by SCA2 and correlated with the patients' cognitive scores. Our results provide the first evidence that WM diffusivity is altered in the presence of the cerebellar cortical degeneration associated with SCA2 thus resulting in a cerebello-cerebral dysregulation that may account for the specificity of cognitive symptomatology observed in patients

Neural substrates of motor and cognitive dysfunctions in SCA2 patients: a network based statistics analysis

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease characterized by a progressive cerebellar syndrome, which can be isolated or associated with extracerebellar signs. It has been shown that patients affected by SCA2 present also cognitive impairments and psychiatric symptoms. The cerebellum is known to modulate cortical activity and to contribute to distinct functional networks related to higher-level functions beyond motor control. It is therefore conceivable that one or more networks, rather than isolated regions, may be dysfunctional in cerebellar degenerative diseases and that an abnormal connectivity within specific cerebello-cortical regions might explain the widespread deficits typically observed in patients. In the present study, the network-based statistics (NBS) approach was used to assess differences in functional connectivity between specific cerebellar and erebral “nodes” in SCA2 patients. Altered inter-nodal connectivity was found between more posterior regions in the cerebellum and regions in the cerebral cortex clearly related to cognition and emotion. Furthermore, more anterior cerebellar lobules showed altered inter-nodal connectivity with motor and somatosensory cerebral regions. The present data suggest that in SCA2 a cerebellar dysfunction affects long-distance cerebral regions and that the clinical symptoms may be specifically related with connectivity changes between motor and non-motor cerebello-cortical nodes

Structural cerebellar correlates of cognitive functions in spinocerebellar ataxia type 2

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease involving the cerebellum and characterized by a typical motor syndrome. In addition, the presence of cognitive impairment is now widely acknowledged as a feature of SCA2. Given the extensive connections between the cerebellum and associative cerebral areas, it is reasonable to hypothesize that cerebellar neurodegeneration associated with SCA2 may impact on the cerebellar modulation of the cerebral cortex, thus resulting in functional impairment. The aim of the present study was to investigate and quantitatively map the pattern of cerebellar gray matter (GM) atrophy due to SCA2 neurodegeneration and to correlate that with patients' cognitive performances. Cerebellar GM maps were extracted and compared between SCA2 patients (n = 9) and controls (n = 33) by using voxel-based morphometry. Furthermore, the relationship between cerebellar GM atrophy and neuropsychological scores of the patients was assessed. Specific cerebellar GM regions were found to be affected in patients. Additionally, GM loss in cognitive posterior lobules (VI, Crus I, Crus II, VIIB, IX) correlated with visuospatial, verbal memory and executive tasks, while additional correlations with motor anterior (V) and posterior (VIIIA, VIIIB) lobules were found for the tasks engaging motor and planning components. Our results provide evidence that the SCA2 neurodegenerative process affects the cerebellar cortex and that MRI indices of atrophy in different cerebellar subregions may account for the specificity of cognitive symptomatology observed in patients, as result of a cerebello-cerebral dysregulation

Casimir-Polder shift of ground-state hyperfine Zeeman sublevels of hydrogen isotopes in a micron-sized metallic cavity at finite temperature

The frequencies of transitions between hyperfine levels of ground-state atoms can be measured with exquisite precision using magnetic-resonance techniques. This makes hyperfine transitions ideal probes of QED effects originating from the interaction of atoms with the quantized electromagnetic field. One of the most remarkable effects predicted by QED is the Casimir-Polder shift experienced by the energy levels of atoms placed near one or more dielectric objects. Here we compute the Casimir-Polder shift and the width of hyperfine transitions between ground-state Zeeman sublevels of a hydrogen atom placed in a micron-sized metallic cavity, over a range of temperatures extending from cryogenic temperatures to room temperature. Results are presented also for deuterium and tritium. We predict shifts of the hyperfine transitions frequencies of a few tens of Hz that might be measurable with present-day magnetic resonance apparatus

Intra-Aortic Balloon Counterpulsation for the Treatment of Ischemic Stroke

Colloid volume expansion has been shown to increase cerebral blood flow to ischemic brain in an animal stroke model and improve recovery in patients. It is, however, potentially hazardous to use in older patients because of frequently associated cardiovascular disease. Intra-Aortic Balloon Counterpulsation might reduce the risks of using volume expansion therapy in the elderly patient. This study was designed to see if Intra-Aortic Balloon Counterpulsation (without volume expansion), in an animal with a normal heart, would increase cerebral blood flow and EEG activity in the ischemic brain. Unilateral cerebral ischemia was produced in baboons (n = 9) after right middle cerebral artery occlusion. A 12 ml intra-aortic balloon catheter was introduced into the descending aorta via the femoral artery prior to middle cerebral artery occlusion. The balloon was positioned distal to the origin of the left subclavian artery and following middle cerebral artery occlusion was inflated with each R wave on the ECG. Cardiac output, cerebral blood flow (by Hydrogen wash-out), computer-mapped EEG, and hemodynamic data were collected prior to middle cerebral artery occlusion and following occlusion both before and during counterpulsation. Intra-Aortic Balloon Counterpulsation produced a significant increase in pulse pressure from 54.7 ± 21 to 70.6 ± 33 mmHg (p = .043). No significant change was seen in cardiac output, mean arterial pressure, or cerebral blood flow. Although the computer- mapped EEG improved and the right (ischemic) hemisphere cerebral blood flow did increase slightly from 16.9 ± 6.5 to 18.3 ± 8.3 ml/100 gm/min, the cerebral blood flow changes were not significant (p=.295). It is possible that the desired increase in cerebral blood flow was not achieved partly because the animals were only 3-4 years old and were difficult to stroke. We believe that there is merit to a follow-up study in older primates with colloid volume expansion where Intra-Aortic Balloon Counterpulsation is used to protect the heart from the deleterious effects of volume expansion and where the cardiac effects of volume expansion and counterpulsation are quantified. Perhaps volume expansion with Intra-Aortic Balloon Counterpulsation will be safer and more effective than either treatment modality alone. (All data reported as mean ± standard deviation

Positivity Conditions for Generalised Schwarzschild Space-Times

International audienceWe analyse the impact of positivity conditions on static spherically symmetric deformations of the Schwarzschild space-time. The metric is taken to satisfy, at least asymptotically, the Einstein equation in the presence of a non-trivial stress-energy tensor, on which we impose various physicality conditions. We systematically study and compare the impact of these conditions on the space-time deformations. The universal nature of our findings applies to both classical and quantum metric deformations with and without event horizons. We further discuss minimal realisations of the asymptotic stress energy tensor in terms of physical fields. Finally, we illustrate our results by discussing concrete models of quantum black holes

IGF-1 as a possible marker of early cognitive impairment: A pilot study

Insulin-like growth factor (IGF)-1 is an important neurotrophic hormone. Disregulation of this hormone has been reported to influence the genesis of cognitive impairment and dementia in the elderly patients. We evaluated IGF-1 serum values and cognitive status in elder subjects. Primary endpoint was finding a possible link between IGF-1 values and MMSE scores, adjusted for age and sex. Elder patients (range 55–71 ys) were followed for up to 4 years (median 3.2 years). Cognitive status was assessed by Mini Mental State Examination (MMSE). A total of 210 subjects were enrolled. Yearly evaluation included routine laboratory tests, a complete physical examination and cognitive state measurement. At baseline evaluation, patients were divided into three groups: Healthy (MMSE > 26), Borderline (MMSE 24–26), Cognitive impairment (MMSE < 24). We used multiple linear regression with a scatter plot to compare IGF-1 and MMSE, adjusted for diagnosis of hypertension. Then, we checked the ROC curve, analyzing the AUC of our marker. At the baseline evaluation, no differences were found in the three groups for therapy and other diseases. Borderline subjects differed from other two groups, with a significant elevation of IGF-1 values (P < 0.05). The AUC curve of the yearly evaluation showed significant values (0.86 ± 0,02). This trial showed IGF-1 elevation in borderline subjects. Further studies will be performed in order to demonstrate the efficacy and sensibility of this serum marker

Reverse engineering a mouse embryonic stem cell-specific transcriptional network reveals a new modulator of neuronal differentiation

Gene expression profiles can be used to infer previously unknown transcriptional regulatory interaction among thousands of genes, via systems biology ‘reverse engineering’ approaches. We ‘reverse engineered’ an embryonic stem (ES)-specific transcriptional network from 171 gene expression profiles, measured in ES cells, to identify master regulators of gene expression (‘hubs’). We discovered that E130012A19Rik (E13), highly expressed in mouse ES cells as compared with differentiated cells, was a central ‘hub’ of the network. We demonstrated that E13 is a protein-coding gene implicated in regulating the commitment towards the different neuronal subtypes and glia cells. The overexpression and knock-down of E13 in ES cell lines, undergoing differentiation into neurons and glia cells, caused a strong up-regulation of the glutamatergic neurons marker Vglut2 and a strong down-regulation of the GABAergic neurons marker GAD65 and of the radial glia marker Blbp. We confirmed E13 expression in the cerebral cortex of adult mice and during development. By immuno-based affinity purification, we characterized protein partners of E13, involved in the Polycomb complex. Our results suggest a role of E13 in regulating the division between glutamatergic projection neurons and GABAergic interneurons and glia cells possibly by epigenetic-mediated transcriptional regulation

Reverse engineering a mouse embryonic stem cell-specific transcriptional network reveals a new modulator of neuronal differentiation

Gene expression profiles can be used to infer previously unknown transcriptional regulatory interaction among thousands of genes, via systems biology 'reverse engineering' approaches. We 'reverse engineered' an embryonic stem (ES)-specific transcriptional network from 171 gene expression profiles, measured in ES cells, to identify master regulators of gene expression ('hubs'). We discovered that E130012A19Rik (E13), highly expressed in mouse ES cells as compared with differentiated cells, was a central 'hub' of the network. We demonstrated that E13 is a protein-coding gene implicated in regulating the commitment towards the different neuronal subtypes and glia cells. The overexpression and knock-down of E13 in ES cell lines, undergoing differentiation into neurons and glia cells, caused a strong up-regulation of the glutamatergic neurons marker Vglut2 and a strong down-regulation of the GABAergic neurons marker GAD65 and of the radial glia marker Blbp. We confirmed E13 expression in the cerebral cortex of adult mice and during development. By immuno-based affinity purification, we characterized protein partners of E13, involved in the Polycomb complex. Our results suggest a role of E13 in regulating the division between glutamatergic projection neurons and GABAergic interneurons and glia cells possibly by epigenetic-mediated transcriptional regulation