We investigate over a 12-year period the association between regional cerebral blood flow (CBF) and cardiovascular risk factors in a prospective cohort of healthy older adults (81.96 ± 3.82 year-old) from the Cognitive REServe and Clinical ENDOphenotype (CRESCENDO) study. Cardiovascular risk factors were measured over 12 years, and gray matter CBF was measured at the end of the study from high-resolution magnetic resonance imaging using arterial spin labeling. The association between cardiovascular risk factors, their long-term change, and CBF was assessed using multivariate linear regression models. Women were observed to have higher CBF than men (p < 0.05). Increased mean arterial pressure (MAP) over the 12-year period was correlated with a low cerebral blood flow (p < 0.05, R(2) = 0.21), whereas no association was detected between CBF and MAP at the time of imaging. High levels of glycemia tended to be associated with low cerebral blood flow values (p < 0.05). Age, alcohol consumption, smoking status, body mass index, history of cardiovascular disease, and hypertension were not associated with CBF. Our main result suggests that change in MAP is the most significant predictor of future CBF in older adults.

To validate the functional relevance of resting state networks (RSNs) by means of a comparison of resting state connectivity (RSC) between language regions elicited by direct cortical stimulation versus RSC between random regions; and to evaluate the accuracy of resting state fMRI in surgical planning by assessing the overlap between RSNs and intraoperative functional mapping results. Sensorimotor and language eloquent sites were identified by direct electrical cortical stimulation in 98 patients with a diffuse low-grade glioma. A seed to voxel analysis with inter-language stimulation point connectivity versus inter-random ROIs connectivity was performed (19 patients). An independant component analysis (ICA) was also applied to rsfMRI data. Language and sensorimotor components were selected over 20 independent components and compared to the corresponding stimulation points and resected cortex masks (31 and 90 patients, respectively). The significantly higher RSC between language seeds than between random seeds validated the functional relevance of RSC. ICA partly succeeded to distinguish eloquent versus surgically removable areas and may be possibly used as a complementary tool to intraoperative mapping.

Hypometabolism has been observed in the contralesional cerebellar hemisphere after various supratentorial cortical lesions. It is unknown whether the consequences of the dee- and deafferentation subsequent to wide-awake surgery for brain diffuse low-grade glioma can be assessed within remote and unresected subcortical structures such as the cerebellum or thalamus. To answer this question, we have conducted several regional analyses. More specifically, we have performed amplitude of low-frequency fluctuations (neuronal activity magnitude) and regional homogeneity (local temporal correlations) analyses on resting state functional magnetic resonance imaging (rs-fMRI) data and at different time points, before and after surgery. Our main results demonstrated that it is possible to evaluate subtle subcortical changes using these tools dedicated to the analysis of rs-fMRI data. The observed variations of spontaneous neuronal activity were particularly significant within the cerebellum which showed altered regional homogeneity and neuronal activity intensity in very different, specialized and non-overlapping subregions, in accordance to its neuro-anatomo-functional topography. These variations were moreover observed in the immediate postoperative period and recovered after 3 months.

Hemidystonia is usually 'secondary' to structural lesions within the cortico-striato-pallido-thalamic or the cerebello-thalamo-cortical loops. Globus pallidus internus Deep Brain Stimulation (GPi DBS) is a validated technique in the treatment of primary dystonia and still under assessment for secondary dystonia. Results of DBS in hemidystonia are limited and heterogeneous. Further knowledge concerning motor network organization after focal brain lesions might contribute to the understanding of this mitigated response to DBS and to the refinement of DBS indications and techniques in secondary dystonia. This study aimed to identify movement-related functional magnetic resonance imaging (fMRI) activation patterns in a group of hemidystonic patients in comparison to healthy controls (HC). Further analysis assessed recruitment pattern in different patient subgroups defined according to clinical and radiological criteria relevant to GPi DBS eligibility (hyperkinetic/hypokinetic and prepallidal/postpallidal). Eleven patients and nine HC underwent fMRI with a block-design alternating active and rest conditions. The motor paradigm consisted of self-paced elbow flexion-extension movements. The main results were as follows: single-subject studies revealed several activation patterns involving motor-related network regions; both ipsilesional and contralesional hemispheres showed abnormal patterns of activity; compared with HC, hemidystonic patients showed decreased brain activity in ipsilesional thalamus, pallidal and temporal areas during affected arm task execution; 'hypokinetic' subgroup was commonly related to widespread bilateral overactivity. This study provides additional arguments for case-by-case assessment of DBS surgery indication and target selection in hemidystonia. Single-lead approach might be unable to modulate a highly disorganized network activity in certain patients with this clinical syndrome.

A 19-year-old man with no relevant medical history except a high velocity head trauma a few years earlier was admitted in our institution for sudden onset binocular diplopia. Head-CT performed afteer the trauma was depicted as being normal. He complained of chronic headaches for about three years, with recent worsening and painkillers resistance. Clinical examination found binocular ophthalmoplegia with paresis of both abducens nerves. Non-contrast CT-scan and CT angiography of the circle of Willis were normal. Brain MRI acquisition was performed on a 3T magnet (Skyra, Siemens, Germany) with a 32-channel head coil and included a dual-echo Susceptibility Weighted Imaging (SWI), with the following parameters: TE1/TE2 = 20/40 ms, TR = 47 ms, GRAPPA = 2, voxel size = 1 × 1 × 1.5 mm, 88 slices). Conventional sequences showed a subtle distension of the perioptic subarachnoid spaces on coronal T2 sequence (not shown), and a linear loss of signal on pial surface of the lefte lateral fissure (Fig. 1a). Susceptibility-weighted imaging was performed in order to quantify the related susceptibility effeect, through the use of quantitative susceptibility mapping. Marked pial signal loss on T2-GRE and susceptibility-weighted imaging (SWI) was observed at the level of the brainstem, lefte lateral fissure, cerebellar folia (Fig. 1b-f). Phase image was retrieved from SWI acquisition and underwent laplacian unwrapping as well as background field removal using regularization-enabled SHARP algorithm. Finally, total variation using split Bregman [1] method enabled images conversion to quantitative susceptibility maps (QSM). Reported susceptibility values were standardized according to the observed cerebrospinal fluid susceptibility. In normal appearing gray matteer (Fig. 1g-h), the value was 0.009 ± 0.1 ppm, while in cortico-pial affeected areas, measured susceptibility was 0.24 ± 0.1 ppm (Fig. 1f), suggesting a paramagnetic effeect. Discrete atrophy of the superior cerebellar vermis was also noted (Fig. 1k). T2-weighted images of the spinal cord showed a low signal lining on the spinal cord, suggesting hemosiderin deposit (Fig. 1i-j). No acute subarachnoid bleeding was present. Neither MR angiography of the intracranial vessels nor spinal MRI revealed any vascular malformation. No intra-axial hemorrhage was found. Fundoscopic examination revealed bilateral papillary subedema that was confirmed by the fluorescein angiogra-phy showing late papillary dye leakage. Lumbar puncture was finally performed and showed severe intracranial hypertension (57 cmH 2 O, normal range 7-15 cmH 2 0). Neither erythrocytes nor xantochromia were present. The diagnosis of superficial siderosis of the central nervous system was made based on the symptoms that were supported by radiological findings. Discussion

Changes in working memory are sensitive indicators of both normal and pathological brain aging and associated disability. The present study aims to further understanding of working memory in normal aging using a large cohort of healthy elderly in order to examine three separate phases of information processing in relation to changes in task load activation. Using covariance analysis, increasing and decreasing neural activation was observed on fMRI in response to a delayed item recognition task in 337 cognitively healthy elderly persons as part of the CRESCENDO (Cognitive REServe and Clinical ENDOphenotypes) study. During three phases of the task (stimulation, retention, probe), increased activation was observed with increasing task load in bilateral regions of the prefrontal cortex, parietal lobule, cingulate gyrus, insula and in deep gray matter nuclei, suggesting an involvement of central executive and salience networks. Decreased activation associated with increasing task load was observed during the stimulation phase, in bilateral temporal cortex, parietal lobule, cingulate gyrus and prefrontal cortex. This spatial distribution of decreased activation is suggestive of the default mode network. These findings support the hypothesis of an increased activation in salience and central executive networks and a decreased activation in default mode network concomitant to increasing task load.

Background and PurposeThe etiologic diagnosis of parkinsonian syndromes is of particular importance when considering syndromes of vascular or degenerative origin. The purpose of this study is to find differences in the white-matter architecture between those two groups in elderly patients.Materials and MethodsThirty-five patients were prospectively included (multiple-system atrophy, n = 5; Parkinson's disease, n = 15; progressive supranuclear palsy, n = 9; vascular parkinsonism, n = 6), with a mean age of 76 years. Patients with multiple-system atrophy, progressive supranuclear palsy and Parkinson's disease were grouped as having parkinsonian syndromes of degenerative origin. Brain MRIs included diffusion tensor imaging. Fractional anisotropy and mean-diffusivity maps were spatially normalized, and group analyses between parkinsonian syndromes of degenerative origin and vascular parkinsonism were performed using a voxel-based approach.ResultsStatistical parametric-mapping analysis of diffusion tensor imaging data showed decreased fractional anisotropy value in internal capsules bilaterally in patients with vascular parkinsonism compared to parkinsonian syndromes of degenerative origin (p = 0.001) and showed a lower mean diffusivity in the white matter of the left superior parietal lobule (p = 0.01).Fractional anisotropy values were found decreased in the middle cerebellar peduncles in multiple-system atrophy compared to Parkinson's disease and progressive supranuclear palsy. The mean diffusivity was increased in those regions for these subgroups.ConclusionClinically defined vascular parkinsonism was associated with decreased fractional anisotropy in the deep white matter (internal capsules) compared to parkinsonian syndromes of degenerative origin. These findings are consistent with previously published neuropathological data.