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The blood oxygen level-dependent (BOLD) effect is extensively used for functional MRI (fMRI) but presents some limitations. Diffusion-weighted fMRI (DfMRI) has been proposed as a method more tightly linked to neuronal activity. This work proposes a protocol of DfMRI acquired for several b-values and diffusion directions that is compared to gradient-echo BOLD (GE-BOLD) and to repeated spin-echo BOLD (SE-BOLD, acquisitions performed with b=0s/mm2), which was also used to ensure the reproducibility of the response. A block stimulation paradigm of the primary visual system (V1) was performed in 12 healthy subjects with checkerboard alternations (2Hz frequency). DfMRI was performed at 3T with 5 b-values (b=1500, 1000, 500, 250, 0s/mm2) with TR/TE=1004/93ms, Δ/δ=45.4ms/30ms, and 6 spatial directions for diffusion measures. GE-BOLD was performed with a similar block stimulation design timing. Apparent Diffusion Coefficient (ADC)-fMRI was computed with all b-values used. An identical Z-score level was used for all fMRI modalities for the comparison of volumes of activation. ADC-fMRI and SE-BOLD fMRI activation locations were compared in a voxel-based analysis to a cytoarchitectural probability map of V1. SE-BOLD activation volumes represented only 55% of the GE-BOLD activation volumes (P

Skin-brain signalling in itch reactions has been demonstrated with neuroimaging techniques showing specific brain activation. With positron emission tomography (PET), the itch model used must be adapted to technical and practical constraints. The technique of itch induction by histamine iontophoresis enables modulation of the sensation via the electrical charge applied. This itch model was validated on normal forearm skin of 56 subjects, with itch visual analogue scores peaking to approximately 1.0 cm after 3-4 min, falling to 0.2 cm at 15 min, with no influence of sex, zone, or order. Subsequently, the model was used in a PET study on 14 male volunteers, comparing histamine with physiological saline (control). The results show that the brain is able to discriminate these two conditions, with activated areas similar to those described previously, with, in addition, the anterior cingulate cortex and the insula being positively correlated with the intensity of the sensation.

The Prader–Willi syndrome (PWS), a rare multisystem genetic disease, leads to severe disabilities, such as morbid obesity, endocrine dysfunctions, psychiatric disorders, and social disturbances. We explored the whole brain of patients with PWS to detect abnormalities that might explain the behavioral and social disturbances, as well as the psychiatric disorders of these patients. Nine patients with PWS (six males, three females; mean age 16.4 years) underwent a positron emission tomography (PET) scan with H215O as a tracer to measure regional cerebral blood flow (rCBF). The images were compared with those acquired from nine controls (six males, three females; mean age 21.2 years). A morphologic magnetic resonance imaging (MRI) was also performed in PWS patients, and their cognitive and behavioral skills were assessed with Wechsler Intelligence Scale for Children III and the Child Behavior Check List (CBCL). The MRI images showed no evident anatomic abnormalities, whereas PET scans revealed hypoperfused brain regions in PWS patients compared with controls, particularly in the anterior cingulum and superior temporal regions. We observed a significant relationship ( P

Magnetic resonance imaging (MRI) studies have highlighted the possibility to investigate brain iron content in vivo. In this study, we combined T2* relaxometry and automatic segmentation of basal ganglia based on T1-weighted images in healthy subjects, with the aim of characterizing age related changes in volume and iron-related relaxivity values (R2*) of these structures. Thirty healthy subjects underwent MR imaging at 3 Tesla. Mean R2* values and volumes were calculated for the selected subcortical structures (pallidum, putamen, thalamus and caudate nucleus). Our results showed a correlation between R2* values and iron concentration as calculated from published post-mortem data. Furthermore, we observed a shrinkage/iron increase with a different pattern in the anatomical regions selected in this work, suggesting that the age-related changes on these MR parameters are specific to the subcortical structure considered. In particular, the putamen demonstrated a decrease of volume and an increase of iron level, with the posterior region of this structure appearing more disposed to iron deposition. Our work suggests that combining volumetry and iron estimation in MRI permits to investigate in vivo neurophysiological and neuropathological changes of basal ganglia.

Brain atrophy measured by magnetic resonance structural imaging has been proposed as a surrogate marker for the early diagnosis of Alzheimer's disease. Studies on large samples are still required to determine its practical interest at the individual level, especially with regards to the capacity of anatomical magnetic resonance imaging to disentangle the confounding role of the cognitive reserve in the early diagnosis of Alzheimer's disease. One hundred and thirty healthy controls, 122 subjects with mild cognitive impairment of the amnestic type and 130 Alzheimer's disease patients were included from the ADNI database and followed up for 24 months. After 24 months, 72 amnestic mild cognitive impairment had converted to Alzheimer's disease (referred to as progressive mild cognitive impairment, as opposed to stable mild cognitive impairment). For each subject, cortical thickness was measured on the baseline magnetic resonance imaging volume. The resulting cortical thickness map was parcellated into 22 regions and a normalized thickness index was computed using the subset of regions (right medial temporal, left lateral temporal, right posterior cingulate) that optimally distinguished stable mild cognitive impairment from progressive mild cognitive impairment. We tested the ability of baseline normalized thickness index to predict evolution from amnestic mild cognitive impairment to Alzheimer's disease and compared it to the predictive values of the main cognitive scores at baseline. In addition, we studied the relationship between the normalized thickness index, the education level and the timeline of conversion to Alzheimer's disease. Normalized thickness index at baseline differed significantly among all the four diagnosis groups (P < 0.001) and correctly distinguished Alzheimer's disease patients from healthy controls with an 85% cross-validated accuracy. Normalized thickness index also correctly predicted evolution to Alzheimer's disease for 76% of amnestic mild cognitive impairment subjects after cross-validation, thus showing an advantage over cognitive scores (range 63–72%). Moreover, progressive mild cognitive impairment subjects, who converted later than 1 year after baseline, showed a significantly higher education level than those who converted earlier than 1 year after baseline. Using a normalized thickness index-based criterion may help with early diagnosis of Alzheimer's disease at the individual level, especially for highly educated subjects, up to 24 months before clinical criteria for Alzheimer's disease diagnosis are met.

Whereas many studies have considered the role of attention in prospective timing, fewer have established relations between movement complexity and prospective timing. The present study aims at assessing to what extent motion complexity interferes with prospective timing and at delineating a neuropsychophysical plausible model. We have thus designed a visual paradigm presenting stimuli in sequential pairs (reference comparison interval). Stimuli are motionless or moving according to different complexities, and stimulus complexities are intermixed within each pair. To prevent a possible attention-sharing effect, no concurrent task was required. Our study suggests that movement complexity is a key component of duration perception, and that the relative judgement of durations depends on spatio-temporal features of stimuli. In particular, it shows that movement complexity can bias subjects' perception and performance, and that subjects detect that comparison intervals are longer than reference before their end. In the discussion, we advocate that the classical internal clock model cannot easily account for our results. Consequently, we propose a model for time perception, based on a parallel processing between comparison interval perception and the reconstruction of the reference duration.

Background:Structural gray matter characteristics of anxiety remain unclear. The aim of this study was to assess the influence of current depressive symptoms and history of depression on the gray matter characteristics of trait anxiety.Methods:Structural magnetic resonance imaging (MRI) data from 393 individuals aged 65 years or older were used. Regions of interest (ROIs) included the amygdala, anterior cingulate cortex (ACC), insula, orbitofrontal cortex (OFC), and temporal cortex. Trait anxiety was measured by the State-Trait Anxiety Inventory (STAI). Depression and depressive symptoms were measured using DSM-IV criteria and the Center for Epidemiological Studies Depression Scale (CESD).Results:After adjustments for sociodemographics and health-related variables, anxiety had a significant influence on the gray matter characteristics in all cortical ROIs. First, in participants without depression antecedents, higher trait anxiety was associated with a larger cortical thickness in all cortical ROIs. Second, in participants with a previous history of depression, higher trait anxiety was associated with a smaller cortical thickness in all cortical ROIs.Conclusions:These results suggest that anxiety is related to cortical thickness differently in healthy older adults and in older adults with psychiatric antecedents. Anxiety associated with thinner cortical areas could reflect symptoms of a specific type of depression or a vulnerability to develop depression.

We previously showed that the farnesyl transferase inihibitor, Tipifarnib induced vascularization normalization, oxygenation and radiosensitization in a pre-clinical glioblastoma (GBM) model. The aim of this study was to assess by dynamic-susceptibility-contrast MRI (DSC-MRI) the effect of radiotherapy (RT) and Tipifarnib combination on tumor perfusion in GBM patients. Eighteen patients with newly diagnosed GBM, enrolled in a phase I-II clinical trial associating RT with Tipifarnib, underwent anatomical MR imaging and DSC-MRI before (M0) and two months after treatment (M2). Anatomic volumes of interest (VOIs) were delineated according to contrast-enhanced and hyper-intense signal areas on T1-Gd and T2 images, respectively. Perfusion variations between M0 and M2 were assessed with median relative cerebral blood volume (rCBV) inside these VOIs. Another voxel by voxel analysis of CBV values classified 405,117 tumor voxels into High_, Normal_ and Low_CBVTUMOR according to the distribution of CBV in the contralateral normal tissue. These three categories of CBVTUMOR voxels were color-coded over anatomical MRI. Variations of median rCBV were significantly different for two groups of patients (P 0.013): rCBV decreased when initial rCBV was ≥ 1.0 (Group_rCBV_M0 1) and rCBV increased when initial rCBV was 1.0 (Group_rCBV_M0 1). Mapping of color-coded voxels provided additional spatial and quantitative information about tumor perfusion: Group_rCBV_M0 1 presented a significant decrease of High_CBVTUMOR volume (P = 0.015) simultaneously with a significant increase of Normal_CBVTUMOR volume (P = 0.009) after treatment. Group_rCBV_M0 1 presented a decrease of Low_CBVTUMOR volume with an increase of Normal_ and High_CBV TUMOR volume after treatment. Pre and post-treatment CBV measurements with DSC-MRI characterized tumor perfusion evolution in GBM patients treated with RT combined to Tipifarnib; showing variations in favour of tumor perfusion normalization in agreement with our pre-clinical results of vascular normalization.

The lateral masking effect results in lower performance on letter recognition when items are flanked by other stimuli. Using a new paradigm based on discrimination (feature analysis) and categorization (memory access) tasks, we investigated the influence of level of processing (as addressed, respectively, by these two tasks) and stimulus type (Latin letters, Korean letters and geometrical figures) on lateral masking. In addition, performance of dyslexic and non-dyslexic adult readers was compared. The non-dyslexic participants demonstrated a classical lateral masking effect with lower performance for flanked items than isolated ones. In addition, lateral masking was stronger in the categorization than in the discrimination task and was restricted to familiar items, i.e., Latin letters and geometrical figures. Dyslexic participants showed poorer performance than non-dyslexics on processing isolated items, and the pattern of decrease in performance for lateral masking was similar to non-dyslexics. However, they also showed a stronger decrease in performance in categorization and a stronger decrease related to the lateral masking for this categorization task. Our results in normal readers suggest that lateral masking relies on the interference between the target and the flankers during feature integration that may result in marked impairment of memory access (categorization task). Poorer performance in dyslexic readers may reflect impaired parafoveal/peripheral low-level processing during feature integration that may have worsened during the flanked condition due to a target selection/spatial-attentional disorder. Moreover, dyslexic subjects presented an additional categorization deficit that may relate to a specific left-hemispheric disorder.

Neuroimaging studies that look at reading processes using words, pseudowords, nonwords and letters frequently report specific left fusiform gyrus (BA37) activations. In the present study, we examined fMRI signal variations within the left and right BA37 for paired Latin letters, Korean letters and geometrical figures in discrimination and categorization tasks. Data of Pernet et al. (Pernet, C., Franceries, X., Basan, S., Cassol, E., Démonet, J.F., Celsis, P., 2004. Anatomy and time course of discrimination and categorization processes in vision: an fMRI study. NeuroImage 22, 1563-1577) were re-analyzed using a ROI methodology that highlights the selective response of the left BA37 to Latin letter categorization. First, differences according to stimulus type were observed for the categorization task only. Second, we found weaker activation for Latin letter categorization than for both geometrical figure and Korean letter categorization. Third, only Latin letter categorization elicited as left-sided activation, although the direct comparison between regions did not demonstrate a significant difference. These data suggest that the left fusiform gyrus sustains access to letter representations in memory; and results are discussed with reference to the relationship between letter categorization and word recognition and to selective vs. specific (i.e. task-independent) neural response.

Functional magnetic resonance imaging (fMRI) using paced auditory serial addition test (PASAT) as paradigm was used to study the functional connectivity in 18 patients at the very early stage of multiple sclerosis (MS) compared with 18 controls, to determine the existence of circuitry disturbance inside the working memory network and its relationship with white matter abnormalities assessed by conventional MRI and magnetization transfer ratio (MTR) imaging. The left BA 45/46 was selected as the seed region to compute correlation maps with other brain regions. After obtaining the correlation map for each subject, between-group comparisons were performed using random effect procedure. Compared with controls, patients did not show any greater functional connectivity between left BA 45/46 and other regions during PASAT. In contrast, decrease in functional connectivity was observed in patients between left BA 45/46 and left BA 9, right BA 3, and the anterior cingulate cortex (BA 24). In patients, no correlations were found between altered functional connectivity and clinical data. However, functional connectivity observed between left BA 45/46 and BA 24 in patients was correlated with the MTR of normal appearing white matter, and with brain T2 lesion load. Altered functional connectivity is present inside the working memory network of patients at the very early stage of MS and is related to the extent of diffuse white matter changes.

Studies investigating the cerebral areas involved in visual processes generally oppose either different tasks or different stimulus types. This work addresses, by fMRI, the interaction between the type of task (discrimination vs. categorization) and the type of stimulus (Latin letters, well-known geometrical figures, and Korean letters). Behavioral data revealed that the two tasks did not differ in term of percentage of errors or correct responses, but a delay of 185 ms was observed for the categorization task in comparison with the discrimination task. All conditions activated a common neural network that includes both striate and extrastriate areas, especially the fusiform gyri, the precunei, the insulae, and the dorsolateral frontal cortex. In addition, interaction analysis revealed that the right insula was sensitive to both tasks and stimuli, and that stimulus type induced several significant signal variations for the categorization task in right frontal cortex, the right middle occipital gyrus, the right cuneus, and the left and right fusiform gyri, whereas for the discrimination task, significant signal variations were observed in the right occipito-parietal junction only. Finally, analyzing the latency of the BOLD signal also revealed a differential neural dynamics according to tasks but not to stimulus type. These temporal differences suggest a parallel hemisphere processing in the discrimination task vs. a cooperative interhemisphere processing in the categorization task that may reflect the observed differences in reaction time.

Phonological developmental dyslexics remain impaired in phonetic categorical perception (CP) even in adulthood. We studied the brain correlates of CP in dyslexics and controls using a block design fMRI protocol and stimuli from an phonetic continuum between natural /Pa/ and /Ta/ syllables. Subjects performed a pseudo-passive listening task which does not imply voluntary categorical judgment. In the control group, categorical deviant stimuli elicited specific activations in the left angular gyrus, the right inferior frontal gyrus and the right superior cingulate cortex. These regions were not activated in the dyslexic group in which activation was observed for acoustic but not phonetic changes in stimuli. Failures to activate key regions for language perception and auditory attention in dyslexic might account for persistent deficits in phonological awareness and reading tasks.

In electroencephalography (EEG) and event related potentials (ERP), localizing the electrical sources at the origin of scalp potentials (inverse problem) imposes, in a first step, the computation of scalp potential distribution from the simulation of sources (forward problem). This article proposes an alternative method for mimicing both the electrical and geometrical properties of the head, including brain, skull, and scalp tissue with resistors. Two resistor mesh models have been designed to reproduce the three-sphere reference model (analytical model). The first one (spherical resistor mesh) closely mimics the geometrical and electrical properties of the analytical model. The second one (cubic resistor mesh) is designed to conveniently handle anatomical data from magnetic resonance imaging. Both models have been validated, in reference to the analytical solution calculated on the three-sphere model, by computing the magnification factor and the relative difference measure. Results suggest that the mesh...

Clinical and neuroimaging studies have shown that verb processing suggests a preferential participation of a prefrontal network, which is dysfunctional in Parkinson's disease (PD). To assess a verb processing deficit in PD, we compared noun- and verb-generation tasks for 34 nondemented PD patients (according to the Dementia Rating Scale) with 34 matched normal subjects, using two intracategory tasks (noun/noun and verb/verb generation) and two intercategory tasks (noun/verb and verb/noun generation). PD patients were significantly impaired in the two tasks involving verb production, i.e., verb/verb and noun/verb generation, whereas their performance was similar to those of controls in the two tasks requiring noun production. For the two impaired tasks, we assessed 1) the influence of lexical competition that corresponds to the presence of several candidate words for a given stimulus; 2) the influence of slight cognitive dysfunction; and 3) the influence of motor deficit. Significant correlations were found between DRS scores and performance on the noun/verb task, and no significant correlations were found between lexical competition or motor deficit and performance. The specific deficit for verb production in PD patients is discussed in relation to deficits affecting either action or grammatical representations. © 2002 Movement Disorder Society

In a previous event-related fMRI study, we showed that the left occipitotemporal cortex was specifically involved in the abstract categorization of visually presented alphabetic symbols. Here, we duplicate the fMRI study by measuring visual event-related potentials to verify whether the left posterior cortex supports the processing of graphemic representations at a perceptual, prelexical level. N170 amplitudes elicited by the categorically ambiguous stimulus 'O' were about twice as small in the left as in the right occipitotemporal region, and comparable to that of other letters on the left, and to that of other geometric figures on the right. The side asymmetry suggests that a graphemic module is unilaterally implemented in the left hemisphere, where it automatically processes heteromorphic representations that do not depend on the physical characteristics of the signal, whereas the difference in amplitude suggests that this left graphemic module is in series with, precedes and does not transmit information to, or inhibits a general shape-analysis module.

We hypothesized that selective serotonin reuptake inhibitors (SSRIs) could modulate motor activity in healthy subjects in a dose-dependent manner. The effects of a single dose of paroxetine were tested in a double-blind, placebo-controlled study. Six randomized and counterbalanced subjects performed behavioral tests in three sessions 1 week apart (E1, E2 and E3) at peak plasma concentration (5 h after drug intake). Each subject was given 20 mg or 60 mg of the drug, or a placebo. Tasks were the Nine Peg Hole test (three trials), Moede dexteritymeter (two trials), and compatible and incompatible reaction time tasks. The results show that at the first trials, performance did not differ after placebo or paroxetine intake. However, 20 and 60 mg of paroxetine improved performance significantly at the third trial of the Nine Peg Hole test and subjects receiving the drug performed 7% faster than those under placebo. An amount of 20 mg, but not 60 mg, of paroxetine improved dexterity significantly at the second trial of the Moede test and subjects performed 30% faster. Conversely, the drug did not affect reaction time for the compatible task and subjects were 11% slower under 20 mg with the incompatible task. Thus, paroxetine decreased the ability to inhibit automatism. Thus, it was concluded that a single dose of paroxetine improved motor performance through practice. But negative effects occurred on tasks including the inhibition of an automatism. Paroxetine enhanced brain motor output (motor activity in S1M1) [NeuroImage, 15 (2002) 26]. This S1M1 hyperactivation is likely to be responsible for the better performance. The brain effect and motor improvement were dose dependent. For both, 20 mg was the optimal dose.

The effect of a language therapy in a group of eight anomic mild patients (the Lexical Therapy group) was assessed by using a 5-month long Lexical Therapy in comparison with an occupational program used in a matched control group (AD; n = 8). The Lexical Therapy group benefited significantly from a language therapy as shown by the naming improvement postintervention. The improvement reached significance only for items that were included in the language therapy protocol and no significant generalization to untreated items was observed. In mild AD patients with anomia and no severe semantic impairment, a reinforcement of the relationship between the form of the object and the corresponding lexical label in episodic long term memory during language therapy may account for the observed lexical improvement.

Purpose Because lactate accumulation is considered a surrogate for hypoxia and tumor radiation resistance, we studied the spatial distribution of the lactate-to- N -acetyl-aspartate ratio (LNR) before radiation therapy (RT) with 3D proton magnetic resonance spectroscopic imaging (3D- 1 H-MRSI) and assessed its impact on local tumor control in glioblastoma (GBM). Methods and Materials Fourteen patients with newly diagnosed GBM included in a phase 2 chemoradiation therapy trial constituted our database. Magnetic resonance imaging (MRI) and MRSI data before RT were evaluated and correlated to MRI data at relapse. The optimal threshold for tumor-associated LNR was determined with receiver-operating-characteristic (ROC) curve analysis of the pre-RT LNR values and MRI characteristics of the tumor. This threshold was used to segment pre-RT normalized LNR maps. Two spatial analyses were performed: ( 1 ) a pre-RT volumetric comparison of abnormal LNR areas with regions of MRI-defined lesions and a choline (Cho)-to- N -acetyl-aspartate (NAA) ratio ≥2 (CNR2); and ( 2 ) a voxel-by-voxel spatial analysis of 4,186,185 voxels with the intention of evaluating whether pre-RT abnormal LNR areas were predictive of the site of local recurrence. Results A LNR of ≥0.4 (LNR-0.4) discriminated between tumor-associated and normal LNR values with 88.8% sensitivity and 97.6% specificity. LNR-0.4 voxels were spatially different from those of MRI-defined lesions, representing 44% of contrast enhancement, 64% of central necrosis, and 26% of fluid-attenuated inversion recovery (FLAIR) abnormality volumes before RT. They extended beyond the overlap with CNR2 for most patients (median: 20 cm 3 ; range: 6-49 cm 3 ). LNR-0.4 voxels were significantly predictive of local recurrence, regarded as contrast enhancement at relapse: 71% of voxels with a LNR-0.4 before RT were contrast enhanced at relapse versus 10% of voxels with a normal LNR ( P Conclusions Pre-RT LNR-0.4 in GBM indicates tumor areas that are likely to relapse. Further investigations are needed to confirm lactate imaging as a tool to define additional biological target volumes for dose painting.

The aim of the current study was to assess the reproducibility of functional magnetic resonance imaging (fMRI) brain activation signals in a sensorimotor task in healthy subjects. Because random or systematic changes are likely to happen when movements are repeated over time, the authors searched for time-dependent changes in the fMRI signal intensity and the extent of activation within and between sessions. Reproducibility was studied on a sensorimotor task called “the active task” that includes a motor output and a sensory feedback, and also on a sensory stimulation called “the passive task” that assessed the sensory input alone. The active task consisted of flexion and extension of the right hand. The subjects had performed it several times before fMRI scanning so that it was well learned. The passive task consisted of a calibrated passive flexion and extension of the right wrist. Tasks were 1 Hz-paced. The control state was rest. Subjects naïve to the MRI environment and non–MRI-naïve subjects were studied. Twelve MRI-naïve subjects underwent 3 fMRI sessions separated by 5 hours and 49 days, respectively. During MRI scanning, they performed the active task. Six MRI-naïve subjects underwent 2 fMRI sessions with the passive task 1 month apart. Three non–MRI-naïve subjects performed twice an active 2-Hz self-paced task. The data were analyzed with SPM96 software. For within-session comparison, for active or passive tasks, good reproducibility of fMRI signal activation was found within a session (intra-and interrun reproducibility) whether it was the first, second, or third session. Therefore, no within-session habituation was found with a passive or a well-learned active task. For between-session comparison, for MRI-naïve or non–MRI-naïve subjects, and with the active or the passive task, activation was increased in the contralateral premotor cortex and in ispsilateral anterior cerebellar cortex but was decreased in the primary sensorimotor cortex, parietal cortex, and posterior supplementary motor area at the second session. The lower cortical signal was characterized by reduced activated areas with no change in maximum peak intensity in most cases. Changes were partially reversed at the third session. Part of the test–retest effect may come from habituation of the MRI experiment context. Less attention and stress at the second and third sessions may be components of the inhibition of cortical activity. Because the changes became reversed, the authors suggest that, beyond the habituation process, a learning process occurred that had nothing to do with procedural learning, because the tasks were well learned or passive. A long-term memory representation of the sensorimotor task, not only with its characteristics (for example, amplitude, frequency) but also with its context (fMRI), can become integrated into the motor system along the sessions. Furthermore, the pattern observed in the fMRI signal changes might evoke a consolidation process.

With the promising development of effective treatment, significant improvement in the very early diagnosis of Alzheimer's disease (AD) is required. There is vast agreement that a decline in memory, especially in verbal episodic memory, is the earliest and perhaps the most sensitive sign of incipient AD at the preclinical stage. However, this review offers evidence that impairment in episodic memory can be observed in normal elderly people as well as in aged subjects with mild cognitive impairment (MCI), a large proportion of whom will, however, not convert to dementia. Quantitative measurement of atrophy and brain activation in the hippocampal-parahippocampal formation by using structural and functional magnetic resonance imaging may help to distinguish the MCI decliners from the nondecliners. Cerebrospinal fluid levels of tau protein and Abet1-42 peptide, together with the presence of an apolipoprotein (apo)E epsilon4 allele may also increase our confidence in the early positive diagnosis of AD. This review concludes, however, that while adequate for constituting groups of patients in a research perspective, the extensive diagnostic procedure based on specific cognitive testing, neuroimaging and biological investigations is still out of reach for the practitioner.

Fluoxetine inhibits the reuptake of serotonin, and dextroamphetamine enhances presynaptic release of monoamines. Although the excitatory effect of both noradrenaline and dopamine on motor behavior generally is accepted, the role of serotonin on motor output is under debate. In the current investigation, the authors evidenced a putative role of monoamines and, more specifically, of serotonin in the regulation of cerebral motor activity in healthy subjects. The effects on cerebral motor activity of a single dose of fluoxetine (20 mg), an inhibitor of serotonin reuptake, and fenozolone (20 mg/50 kg), an amphetamine-like drug, were assessed by functional magnetic resonance imaging. Subjects performed sensorimotor tasks with the right hand. Functional magnetic resonance imaging studies were performed in two sessions on two different days. The first session, with two scan experiments separated by 5 hours without any drug administration, served as time-effect control. A second, similar session but with drug administration after the first scan assessed drug effects. A large increase in evoked signal intensity occurred in the ipsilateral cerebellum, and a parallel, large reduction occurred in primary and secondary motor cortices (P < 10–3). These results are consistent with the known effects of habituation. Both drugs elicited comparable effects, that is, a more focused activation in the contralateral sensorimotor area, a greater involvement of posterior supplementary motor area, and a widespread decrease of bilateral cerebellar activation (P < 10–3). The authors demonstrated for the first time that cerebral motor activity can be modulated by a single dose of fluoxetine or fenozolone in healthy subjects. Drug effects demonstrated a direct or indirect involvement of monoamines and serotonin in the facilitation of cerebral motor activity.

To address the question of the existence of a phonetic module for speech perception, event-related potentials were recorded using a 32 channel system in subjects performing a detection task where the target was the ambiguous, noise-like phoneme /f/ presented either among syllables (speech context) or among environmental sounds (non-speech context). Significant context effects were observed on the N2/P3 complex elicited by the target. In particular, a well localized N2b (250-280 ms) appeared at the left temporoparietal sites on the difference wave between contexts as the result of an enhanced negativity when the target was presented among non-speech stimuli. These findings suggest the involvement of the left temporoparietal region in autonomous, modular processes of speech perception.

We have studied the frontal perfusion in the resting condition of two groups of patients with frozen gait: 10 patients with the syndrome of "isolated gait ignition failure" (IGIF) and 8 patients with idiopathic Parkinson's disease (PD) and severe "off" freezing. These patients were compared with two other groups: one including 20 age-matched volunteers as normal control subjects and the other one including 12 patients with progressive supranuclear palsy (PSP) as a positive control with expected frontal hypoperfusion. Frontal perfusion was assessed using single photon emission computed tomography (SPECT) regional cerebral blood flow measurement with intravenous 133Xenon. A significant frontal hypoperfusion was only present in the PSP group but not in the three others. These results do not support the hypothesis that start hesitations and freezing when walking are related to a frontal lobe dysfunction. However, it is possible that frontal neuronal dysfunction occurs without measurable cerebral blood flow changes in the resting condition.

cited By 34; International audience; We have synthesized gadolinium oxysulfide nanoparticles (NPs) doped with other lanthanides (Eu3+, Er3+, Yb3+) via a hydroxycarbonate precursor precipitation route followed by a sulfuration process under a H2S-Ar atmosphere at 750 °C in order to propose new multimodal nanoplatforms for Magnetic Resonance (MR), X-ray and photoluminescence imaging. Gd2O2S:Eu3+ NPs strongly absorb near UV (≈300-400 nm) and re-emit strong red light (624 nm). They can be easily internalized by cancer cells, and imaged by epifluorescence microscopy under excitation in the NUV (365 nm). They are not cytotoxic for living cells up to 100 μg mL-1. Consequently, they are well adapted for in vitro imaging on cell cultures. Gd2O 2S:Eu3+ NPs also show strong transverse relaxivity and strong X-ray absorption allowing their use as contrast agents for T 2-weighted MRI and X-ray tomography. Our study shows that Gd 2O2S:Eu3+ NPs are considerably better than commercial Ferumoxtran-10 NPs as negative contrast agents for MRI. Upconversion emission of Gd2O2S:Er; Yb (1; 8%) NPs under infrared excitation (λex = 980 nm) shows mainly red emission (≈650-680 nm). Consequently, they are more specifically designed for in vivo deep fluorescence imaging, because both excitation and emission are located inside the "transparency window" of biological tissues (650-1200 nm). Magnetic relaxivity and X-ray absorption behaviors of Gd2O 2S:Er; Yb NPs are almost similar to Gd2O 2S:Eu3+ NPs.

One the one hand, capillary permeability to water is a well-defined concept in microvascular physiology, and linearly relates the net convective or diffusive mass fluxes (by unit area) to the differences in pressure or concentration, respectively, that drive them through the vessel wall. On the other hand, the permeability coefficient is a central parameter introduced when modeling diffusible tracers transfer from blood vessels to tissue in the framework of compartmental models, in such a way that it is implicitly considered as being identical to the capillary permeability. Despite their simplifying assumptions, such models are at the basis of blood flow quantification by H215O Positron Emission Tomgraphy. In the present paper, we use fluid dynamic modeling to compute the transfers of H215O between the blood and brain parenchyma at capillary scale. The analysis of the so-obtained kinetic data by the Renkin–Crone model, the archetypal compartmental model, demonstrates that, in this framework, the permeability coefficient is highly dependent on both flow rate and capillary radius, contrarily to the central hypothesis of the model which states that it is a physiological constant. Thus, the permeability coefficient in Renkin–Crone׳s model is not conceptually identical to the physiologic permeability as implicitly stated in the model. If a permeability coefficient is nevertheless arbitrarily chosen in the computed range, the flow rate determined by the Renkin–Crone model can take highly inaccurate quantitative values. The reasons for this failure of compartmental approaches in the framework of brain blood flow quantification are discussed, highlighting the need for a novel approach enabling to fully exploit the wealth of information available from PET data.

Background To integrate 3D MR spectroscopy imaging (MRSI) in the treatment planning system (TPS) for glioblastoma dose painting to guide simultaneous integrated boost (SIB) in intensity-modulated radiation therapy (IMRT). Methods For sixteen glioblastoma patients, we have simulated three types of dosimetry plans, one conventional plan of 60-Gy in 3D conformational radiotherapy (3D-CRT), one 60-Gy plan in IMRT and one 72-Gy plan in SIB-IMRT. All sixteen MRSI metabolic maps were integrated into TPS, using normalization with color-space conversion and threshold-based segmentation. The fusion between the metabolic maps and the planning CT scans were assessed. Dosimetry comparisons were performed between the different plans of 60-Gy 3D-CRT, 60-Gy IMRT and 72-Gy SIB-IMRT, the last plan was targeted on MRSI abnormalities and contrast enhancement (CE). Results Fusion assessment was performed for 160 transformations. It resulted in maximum differences p Conclusions Delivering standard doses to conventional target and higher doses to new target volumes characterized by MRSI and CE is now possible and does not increase dose to organs at risk. MRSI and CE abnormalities are now integrated for glioblastoma SIB-IMRT, concomitant with temozolomide, in an ongoing multi-institutional phase-III clinical trial. Our method of MR spectroscopy maps integration to TPS is robust and reliable; integration to neuronavigation systems with this method could also improve glioblastoma resection or guide biopsies.

X. Franceries1,2,4, N. Chauveau1,2,*, A. Sors3, M. Masquere4 and P. Celsis1,2 1Inserm, Imagerie Cerebrale et Handicaps Neurologiques UMR 825, Toulouse 2Universite de Toulouse, UPS, Imagerie Cerebrale et Handicaps Neurologiques UMR 825, CHU Purpan, Place du Dr Baylac, Toulouse Cedex 9 3LU 48 LERISM Laboratoire d’Etudes et de Recherche en Imagerie Spatiale et Medicale, UPS, Toulouse Cedex 4 4Universite de Toulouse, UPS, INPT, LAPLACE (Laboratoire Plasma et Conversion d'Energie), Toulouse Cedex 9 France

We measured changes in regional cerebral blood flow (rCBF) induced by reading, naming, and the Stroop effect in 12 right-handed normal volunteers. rCBF was quantified with a single-photon emission computerized tomograph after intravenous injection of 133Xe. Data were analyzed using predetermined regions of interest and a linear model. A significant relative activation was revealed in the right superior mesial frontal region during the Stroop effect.

Task-induced changes in regional cerebral blood flow (rCBF) during memory activation were compared in 18 right-handed patients with early Parkinson's disease (PD) and 20 normal volunteers using the same activation paradigm. We used single-photon emission computed tomography and 133Xe in 21 regions of interest during rest, passive listening of a word list, and memorization of another word list, which was followed by a free recall test immediately after completion of the rCBF measurement. The average performance on free recall was not significantly lower in PD patients than in controls. In normal subjects, five left-sided regions (anterior middle frontal, posterior inferior frontal, superior middle temporal, thalamic, and lenticular) showed a significant increase in memorizing compared to passive listening. This pattern of activation suggests the existence of a verbal rehearsal strategy during the memorization task in normals. In PD patients, increases in these regions did not reach significance, whereas significant activations were noted in superior prefrontal regions. Such alterations in the pattern of activation in PD patients, despite a memory performance similar to that of controls are viewed as a consequence of an early dysfunction of the articulatory loop system and of compensatory mechanisms in other parts of the frontal lobe emerging in the early stages of the disease.

A brain activation study using SPECT and 133Xe in a deep dysphasic patient with left temporal lesion is presented. The activation paradigm consisted of a passive listening to foreign language as baseline, a phoneme monitoring condition and a semantic word monitoring condition. The specific activation of the right middle temporal cortex observed in the semantic condition is congruent with the hypothesis of a compensatory role of the right hemisphere in processing concrete words. This case illustrates the interest of functional imaging for a better understanding of neural mechanisms of functional recovery after brain injury.

We have used single photon emission computed tomography to study cerebral blood flow (CBF), CBF reactivity to acetazolamide, and cerebral blood volume (CBV) in 15 subjects presenting widespread leukoaraiosis, with the aim of answering the question if chronic ischaemia or hypo metabolism is associated with leukoaraiosis. We compared these subjects to 9 controls presenting no leukoaraiosis but with similarly distributed factors for leukoaraiosis. The subjects with leukoaraiosis showed a low regional (r)CBF in their white matter, while CBV and CBF reactivity to acetazolamide were not significantly affected. rCBF, rCBV and rCBF reactivity to acetazolamide did not differ between the cortex of patients and controls. Our results suggest that the low white matter CBF of the patients with leukoaraiosis was related mainly to hypometabolism and not to oligaemia. The capacity of the cerebral vessels to vasodilate does not appear to be affected by leukoaraiosis.

One objective of modern neuroimaging is to identify markers that can aid in diagnosis, disease progression monitoring and long-term drug impact analysis. In this study, Parkinson-associated physiopathological modifications were characterized in six subcortical structures by simultaneously measuring quantitative magnetic resonance parameters sensitive to complementary tissue characteristics (i.e. volume atrophy, iron deposition and microstructural damage). Thirty patients with Parkinson's disease and 22 control subjects underwent 3-T magnetic resonance imaging with T₂*-weighted, whole-brain T₁-weighted and diffusion tensor imaging scans. The mean R₂* value, mean diffusivity and fractional anisotropy in the pallidum, putamen, caudate nucleus, thalamus, substantia nigra and red nucleus were compared between patients with Parkinson's disease and control subjects. Comparisons were also performed using voxel-based analysis of R₂*, mean diffusivity and fractional anisotropy maps to determine which subregion of the basal ganglia showed the greater difference for each parameter. Averages of each subregion were then used in a logistic regression analysis. Compared with control subjects, patients with Parkinson's disease displayed significantly higher R₂* values in the substantia nigra, lower fractional anisotropy values in the substantia nigra and thalamus, and higher mean diffusivity values in the thalamus. Voxel-based analyses confirmed these results and, in addition, showed a significant difference in the mean diffusivity in the striatum. The combination of three markers was sufficient to obtain a 95% global accuracy (area under the receiver operating characteristic curve) for discriminating patients with Parkinson's disease from controls. The markers comprising discriminating combinations were R₂* in the substantia nigra, fractional anisotropy in the substantia nigra and mean diffusivity in the putamen or caudate nucleus. Remarkably, the predictive markers involved the nigrostriatal structures that characterize Parkinson's physiopathology. Furthermore, highly discriminating combinations included markers from three different magnetic resonance parameters (R₂*, mean diffusivity and fractional anisotropy). These findings demonstrate that multimodal magnetic resonance imaging of subcortical grey matter structures is useful for the evaluation of Parkinson's disease and, possibly, of other subcortical pathologies.

It is suggested that resting state networks reflecting correlated neural regional activities participate significantly in brain functioning. A fundamental issue is to understand how these networks interact and how their activities change during behavioral transitions. Our aim was to understand better with functional MRI connectivity how the brain switched from a “resting” to a movement-related state by exploring the transitory readiness state for an intended movement of the right hand. Our study does not address movement preparation occurring in a time scale of milliseconds before movement which has been widely studied but movement-readiness which can last longer. At rest, in the absence of overt goal-directed behavior, a “default-mode” network, whose main areas are the posterior cingulate cortex and precuneus (PCC/Pcu), shows high activity interpreted as day dreaming, free association, stream of consciousness, and inner rehearsal. We found that, during rest, the “default-mode” network and the sensorimotor network were not functionally correlated. During movement-readiness, the two networks were functionally correlated through an interaction between the PCC/Pcu and the medial superior parietal cortex in the upper precuneus. The complex PCC/Pcu has been shown to be involved in retrieval and/or setting up spatial attributes for motor imagery, and thus, would be a key region in the movement-readiness phase. It might functionally connect to the medial superior parietal cortex to initiate the movement programming through retrieval of suited movement parameters. The anterior cingulum, functionally correlated to the primary sensorimotor cortex during movement-readiness would have a motivational role or could generate predictions about the movement.

Cognitive and cerebral blood flow (CBF) lateral asymmetries have been quantified in 23 right handed patients with lateralised idiopathic Parkinson's disease. Thirteen patients who had predominant right-sided symptoms (RPD) were compared with ten who had predominant left-sided symptoms (LPD). The patient subgroups were matched for age, education, duration of illness, disease severity and medication. Normalised asymmetries scores were calculated from the data obtained with a test battery and SPECT. No correlation was found between laterality of motor Parkinsonian symptoms and cognitive or haemodynamic asymmetry scores.

1. We have measured regional cerebral blood flow (rCBF) and motor function before and after the subcutaneous (s.c.) injection of apomorphine in parkinsonian patients deprived of their usual treatment for at least 48 h. 2. Nineteen patients, pretreated with domperidone (20 mg three times daily for 48 h), received a mean dose of 5.8 mg s.c. apomorphine. All patients switched 'on'. The mean motor score was significantly improved (-65%, P less than 0.01) but no significant change in rCBF was observed. 3. Seven other patients, not pretreated with domperidone, received a lower dose (0.3 mg) of s.c. apomorphine. No change in motor score was observed while the mean rCBF significantly increased (+12%, P less than 0.05). 4. We conclude that s.c. apomorphine increases rCBF in parkinsonian patients. This effect is independent of the central therapeutic effects of the drug. It is mediated by the stimulation of dopaminergic receptors of the cerebral vessels. These receptors are located outside the cerebral blood brain barrier and can be considered as 'peripheral' ones.

Techniques of brain functional assessment have contributed to information about the localization and organization of cerebral areas involved in higher brain functions. Nevertheless, few studies have concentrated on the organization of neural networks supporting verbal memory. In the present study, regional cerebral blood flow (rCBF) was measured by single photon emission computerized tomography and IV Xenon 133 in 20 normal volunteers. Measurements were made within 20 regions of interest (ROI) during three experimental conditions: rest, word passive binaural listening and word list learning. A list of 12 words, all differing from the 36 words used for the passive listening, was presented three times to the subjects, in the sarne order. Word characteristics and mode of presentation were as for the passive listening. Compared with the rest, passive listening significantly increased rCBF in the cerebellar hemispheres (+8 m/100 g/min). Learning condition increased rCBF in predominantly three left-sided conical [the anterior-middle frontal ( +6 ml/100 g/min), the posterior—inferior frontal ( +7 ml/100 g/min) and the superior-middle temporal ( +7 ml/100 g/min) and two leftsided subcortical (the subcortical thalamic ( +6 ml/100 g/min) and lenticular regions (+7 ml/100 g/min)] areas. Two regions (the superior—middle temporal and the posterior—inferior frontal regions) showed significant changes in lateral asymmetry (left > right) between listening and learning. Eleven subjects performed at the maximum level (12 words over 12 with no false positive). Whereas CBF tended to be slightly higher on the average in these subjects who performed at maximal level compared to the remaining subjects (67 vs 64 ml/100 g/min, NS), none of the regional differences reached significance. The 11 subjects who tried or perfectly succeeded in learning in the order of presentation all the words of the list showed marked left lateral asymmetry in thalamus (p The present results confirm the predominant involvement of certain left cortical and subcortical regions in regulation and control of verbal memory and suggest that these same regions would participate in the processing of learning and memorizing of verbal material by short or long-term memory systems.

This paper presents a correlative study between phonological and semantic verbal fluency performances and SPECT data obtained at rest in a group of dementia of Alzheimer type (DAT) patients. In both verbal fluency tasks, normals were superior to DAT patients, but in the majority of our patients, phonological verbal fluency appeared more resistant than semantic verbal fluency. The only significant result we found was between good performances on semantic verbal fluency and relative preserved left anterior cerebral blood flow. Results are discussed first in terms of cognitive strategies required for verbal fluency and second in terms of predominant lateralized hypoperfusion in relation with both verbal fluency tasks.

Based on a previous work on a large group of aphasics with subcortical lesions, we propose a pathophysiological hypothesis according to which (1) in most cases, subcortical lesions generate a pathological status so that a left perisylvian cortical system, which is involved in the processing of phonological aspects of language, is not affected; (2) two systems are disturbed: (a) a subcortico-frontal system which is implicated in the dynamics of speech production and (b) a complex subcortico-cortical system which processes the lexico-semantic aspects of language production and comprehension; (3) compensatory processes account for the absence of comprehension impairments in many cases; (4) in some cases, non-thalamic subcortical lesions are associated with standard aphasic syndromes including phonemic disorders which correspond to a disturbance of the phonological information processing system. The present SPECT study of regional cerebral blood flow (rCBF) was performed in order to test this hypothesis. The rCBF was assessed in 14 patients with subcortical aphasia at the acute stage, in 11 patients with cortical aphasia and in 23 normal volunteers. Results partly supported our hypothesis. In the subcortical group, the severity aphasia score was correlated with rCBF ratios in three left cortical regions and in a right posterior temporal region. Phonological disorders were associated with a hypoperfusion in some left cortical regions. Auditory comprehension disorders were associated with hypoperfusion in both left and right posterior temporal regions. The rLCR in these homologous regions were highly correlated and this correlation was more marked in the subcortical patient group than in the normal group. We propose that compensatory neural mechanisms in these interconnected homologous posterior temporal areas account for preserved comprehension capacities in many cases of subcortical aphasia, especially the thalamic cases.

grey matter (GM) probability in the MTL were obtained. Neuropsychological testing was performed at baseline for all subjects, and during follow-up between 1-3.5 years in MCI patients. Conversion to AD was defined based upon clinical and neuropsychological evaluation and change in Clinical Dementia Rating (CDR) scale score from 0.5 to 1.0. Subjects were reclassified to four cognitive status levels: 1 control, 2 MCI-Nonconverter, 3 MCI-Converter, and 4 AD. An ordinal regression model was created with MTL structural and PMC fMRI measures, age and MMSE as the independent variables. Results: Both imaging and follow-up data were available in 32 MCI subjects, 10 of whom converted to AD (total sample 28 controls, 22 MCI-Nonconverters, 10 MCI-Converters, and 13 AD). In our regression model, the main effects of all four factors were statistically significant (p 0.05), independent of one another. Contributions to model variance (highest to lowest) were as follows: MTL GM probability, MMSE, Age, and PMC signal change. Conclusions: PMC deactivation and MTL GM probability measures contribute independently to diagnostic classification, including prognosis in MCI patients. Combined use of structural and functional MRI information may serve as adjuncts to neuropsychological testing in early identification and monitoring of disease progression.

The T1 head template model used in Statistical Parametric Mapping Version 2000 (SPM2), was segmented into five layers (scalp, skull, CSF, grey and white matter) and implemented in 2 mm voxels. We designed a resistor mesh model (RMM), based on the finite volume method (FVM) to simulate the electrical properties of this head model along the three axes for each voxel. Then, we introduced four dipoles of high eccentricity (about 0.8) in this RMM, separately and simultaneously, to compute the potentials for two sets of conductivities. We used the direct cortical imaging technique (CIT) to recover the simulated dipoles, using 60 or 107 electrodes and with or without addition of Gaussian white noise (GWN). The use of realistic conductivities gave better CIT results than standard conductivities, lowering the blurring effect on scalp potentials and displaying more accurate position areas when CIT was applied to single dipoles. Simultaneous dipoles were less accurately localized, but good qualitative and stable quantitative results were obtained up to 5% noise level for 107 electrodes and up to 10% noise level for 60 electrodes, showing that a compromise must be found to optimize both the number of electrodes and the noise level. With the RMM defined in 2 mm voxels, the standard 128-electrode cap and 5% noise appears to be the upper limit providing reliable source positions when direct CIT is used. The admittance matrix defining the RMM is easy to modify so as to adapt to different conductivities. The next step will be the adaptation of individual real head T2 images to the RMM template and the introduction of anisotropy using diffusion imaging (DI).