Quantitative brainstem and spinal MRI in amyotrophic lateral sclerosis: implications for predicting noninvasive ventilation needs.

BACKGROUND: Respiratory complications resulting from motor neurons degeneration are the primary cause of death in amyotrophic lateral sclerosis (ALS). Predicting the need for non-invasive ventilation (NIV) in ALS is important for advance care planning and clinical trial design. The aim of this study was to assess the potential of quantitative MRI at the brainstem and spinal cord levels to predict the need for NIV during the first six months after diagnosis. METHODS: Forty-one ALS patients underwent MRI and spirometry shortly after diagnosis. The need for NIV was monitored according to French health guidelines for 6 months. The performance of four regression models based on: clinical variables, brainstem structures volumes, cervical spinal measurements, and combined variables were compared to predict the need for NIV within this period. RESULTS: Both the clinical model (R2 = 0.28, AUC = 0.85, AICc = 42.67, BIC = 49.8) and the brainstem structures' volumes model (R2 = 0.30, AUC = 0.85, AICc = 40.13, BIC = 46.99) demonstrated good predictive performance. In addition, cervical spinal cord measurements model similar performance (R2 = 0.338, AUC = 0.87, AICc = 37.99, BIC = 44.49). Notably, the combined model incorporating predictors from all three models yielded the best performance (R2 = 0.60, AUC = 0.959, AICc = 36.38, BIC = 44.8). These findings are supported by observed positive correlations between brainstem volumes, cervical (C4/C7) cross-sectional area, and spirometry-measured lung volumes. CONCLUSIONS: Our study shows that brainstem volumes and spinal cord area are promising measures to predict respiratory intervention needs in ALS.

Comparison of spinal magnetic resonance imaging and classical clinical factors in predicting motor capacity in amyotrophic lateral sclerosis.

BACKGROUND: Motor capacity is crucial in amyotrophic lateral sclerosis (ALS) clinical trial design and patient care. However, few studies have explored the potential of multimodal MRI to predict motor capacity in ALS. This study aims to evaluate the predictive value of cervical spinal cord MRI parameters for motor capacity in ALS compared to clinical prognostic factors. METHODS: Spinal multimodal MRI was performed shortly after diagnosis in 41 ALS patients and 12 healthy participants as part of a prospective multicenter cohort study, the PULSE study (NCT00002013-A00969-36). Motor capacity was assessed using ALSFRS-R scores. Multiple stepwise linear regression models were constructed to predict motor capacity at 3 and 6 months from diagnosis, based on clinical variables, structural MRI measurements, including spinal cord cross-sectional area (CSA), anterior-posterior, and left-to-right cross-section diameters at vertebral levels from C1 to T4, and diffusion parameters in the lateral corticospinal tracts (LCSTs) and dorsal columns. RESULTS: Structural MRI measurements were significantly correlated with the ALSFRS-R score and its sub-scores. And as early as 3 months from diagnosis, structural MRI measurements fit the best multiple linear regression model to predict the total ALSFRS-R (R2 = 0.70, p value = 0.0001) and arm sub-score (R2 = 0.69, p value = 0.0002), and combined with DTI metric in the LCST and clinical factors fit the best multiple linear regression model to predict leg sub-score (R2 = 0.73, p value = 0.0002). CONCLUSIONS: Spinal multimodal MRI could be promising as a tool to enhance prognostic accuracy and serve as a motor function proxy in ALS.

Increased cortico-striatal connectivity during motor practice contributes to the consolidation of motor memory in writer's cramp patients.

Sensorimotor representations of movements are created in the sensorimotor network through repeated practice to support successful and effortless performance. Writer's cramp (WC) is a disorder acquired through extensive practice of finger movements, and it is likely associated with the abnormal acquisition of sensorimotor representations. We investigated (i) the activation and connectivity changes in the brain network supporting the acquisition of sensorimotor representations of finger sequences in patients with WC and (ii) the link between these changes and consolidation of motor performance 24 h after the initial practice. Twenty-two patients with WC and 22 age-matched healthy volunteers practiced a complex sequence with the right (pathological) hand during functional MRI recording. Speed and accuracy were measured immediately before and after practice (day 1) and 24 h after practice (day 2). The two groups reached equivalent motor performance on day 1 and day 2. During motor practice, patients with WC had (i) reduced hippocampal activation and hippocampal-striatal functional connectivity; and (ii) overactivation of premotor-striatal areas, whose connectivity correlated with motor performance after consolidation. These results suggest that patients with WC use alternative networks to reach equiperformance in the acquisition of new motor memories.

Deafferentation in thalamic and pontine areas in severe traumatic brain injury.

PURPOSE: Severe traumatic brain injury (TBI) is characterized mainly by diffuse axonal injuries (DAI). The cortico-subcortical disconnections induced by such fiber disruption play a central role in consciousness recovery. We hypothesized that these cortico-subcortical deafferentations inferred from diffusion MRI data could differentiate between TBI patients with favorable or unfavorable (death, vegetative state, or minimally conscious state) outcome one year after injury. METHODS: Cortico-subcortical fiber density maps were derived by using probabilistic tractography from diffusion tensor imaging data acquired in 24 severe TBI patients and 9 healthy controls. These maps were compared between patients and controls as well as between patients with favorable (FO) and unfavorable (UFO) 1-year outcome to identify the thalamo-cortical and ponto-thalamo-cortical pathways involved in the maintenance of consciousness. RESULTS: Thalamo-cortical and ponto-thalamo-cortical fiber density was significantly lower in TBI patients than in healthy controls. Comparing FO and UFO TBI patients showed thalamo-cortical deafferentation associated with unfavorable outcome for projections from ventral posterior and intermediate thalamic nuclei to the associative frontal, sensorimotor and associative temporal cortices. Specific ponto-thalamic deafferentation in projections from the upper dorsal pons (including the reticular formation) was also associated with unfavorable outcome. CONCLUSION: Fiber density of cortico-subcortical pathways as measured from diffusion MRI tractography is a relevant candidate biomarker for early prediction of one-year favorable outcome in severe TBI.

Retinotopic coding of extraretinal pursuit signals in early visual cortex.

During smooth pursuit, the image of the target is stabilized on the fovea, implying that speed judgments made during pursuit must rely on an extraretinal signal providing precise eye speed information. To characterize the introduction of such extraretinal signal into the human visual system, we performed a factorial, functional magnetic resonance imaging experiment, in which we manipulated the factor eye movement, with "fixation" and "pursuit" as levels, and the factor task, with "speed" and "form" judgments as levels. We hypothesized that the extraretinal speed signal is reflected as an interaction between speed judgments and pursuit. Random effects analysis yielded an interaction only in dorsal early visual cortex. Retinotopic mapping localized this interaction on the horizontal meridian (HM) between dorsal areas visual 2 and 3 (V2/V3) at 1-2 degrees azimuth. This corresponded to the position the pursuit target would have reached, if moving retinotopically, at the time of the subject's speed judgment. Because the 2 V2/V3 HMs are redundant, both may be involved in speed judgments, the ventral one involving judgments based on retinal motion and the dorsal one judgments requiring an internal signal. These results indicate that an extraretinal speed signal is injected into early visual cortex during pursuit.

Activation of mirror-neuron system by erotic video clips predicts degree of induced erection: an fMRI study.

Although visually-induced erection is a common occurrence in human male behaviour, the cerebral underpinnings of this response are not well-known. We hypothesized that the magnitude of induced erection would be linearly correlated with the activation of the mirror-neuron system in response to sexually explicit films. When presented with sexual video clips, eight out of ten healthy subjects had an erectile response demonstrated through volumetric penile plethysmography. The level of activation of the left frontal operculum and of the inferior parietal lobules, areas which contain mirror neurons, predicted the magnitude of the erectile response. These results suggest that the response of the mirror-neuron system may not only code for the motor correlates of observed actions, but also for autonomic correlates of these actions.

Accurate anisotropic fast marching for diffusion-based geodesic tractography.

Using geodesics for inferring white matter fibre tracts from diffusion-weighted MR data is an attractive method for at least two reasons: (i) the method optimises a global criterion, and hence is less sensitive to local perturbations such as noise or partial volume effects, and (ii) the method is fast, allowing to infer on a large number of connexions in a reasonable computational time. Here, we propose an improved fast marching algorithm to infer on geodesic paths. Specifically, this procedure is designed to achieve accurate front propagation in an anisotropic elliptic medium, such as DTI data. We evaluate the numerical performance of this approach on simulated datasets, as well as its robustness to local perturbation induced by fiber crossing. On real data, we demonstrate the feasibility of extracting geodesics to connect an extended set of brain regions.

Neuroanatomical correlates of penile erection evoked by photographic stimuli in human males.

The objective of this study was to identify the cerebral correlates of the early phase, and of low to moderate levels, of penile tumescence using for the first time a volumetric measure of the penile response. We hypothesized that (i) regions whose response had been found correlated with circumferential penile responses in previous studies would be identified with volumetric plethysmography and (ii) that other brain regions, including the amygdalae, would be found using the more sensitive volumetric measurement. In ten healthy males, functional magnetic resonance imaging (fMRI) was used to study brain responses to sexually stimulating photographs and to various categories of control photographs. Both ratings of perceived erection and penile plethysmography demonstrated an erectile response to the presentation of sexually stimulating photographs. Regions where the BOLD signal was correlated with penile volumetric responses included the right medial prefrontal cortex, the right and left orbitofrontal cortices, the insulae, the paracentral lobules, the right ventral lateral thalamic nucleus, the right anterior cingulate cortex and regions involved in motor imagery and motor preparation (supplementary motor areas, left ventral premotor area). This study suggests that the development of low levels of penile tumescence in response to static sexual stimuli is controlled by a network of frontal, parietal, insular and cingulate cortical areas and that penile tumescence reciprocally induces activation in somatosensory regions of the brain.

Federating distributed and heterogeneous information sources in neuroimaging: the NeuroBase Project.

The NeuroBase project aims at studying the requirements for federating, through the Internet, information sources in neuroimaging. These sources are distributed in different experimental sites, hospitals or research centers in cognitive neurosciences, and contain heterogeneous data and image processing programs. More precisely, this project consists in creating of a shared ontology, suitable for supporting various neuroimaging applications, and a computer architecture for accessing and sharing relevant distributed information. We briefly describe the semantic model and report in more details the architecture we chose, based on a media-tor/wrapper approach. To give a flavor of the future deployment of our architecture, we de-scribe a demonstrator that implements the comparison of distributed image processing tools applied to distributed neuroimaging data.

[Functional amblyopia: a functional MRI evaluation of the visual cortex response after treatment]. / Amblyopie fonctionnelle : évaluation en IRM fonctionnelle de la réponse corticale visuelle après traitement.

PURPOSE: Functional MRI evaluation of the cortical response in treated amblyopic patients. MATERIAL AND METHODS: Clinical and functional MRI exploration of ten patients, seven men and three women aged from 21 to 59 years, with strabismus management during childhood. Functional evaluations were performed on a 1.5 Tesla MR device, with four monocular functional sessions, two stimulations per eye. Alternating rest and active phases displayed still and flickering black and white checkerboards with spatial and temporal frequencies of 1 degree/8Hz and 15'/4Hz. Anatomical realignment and statistical analysis were performed using SPM99 (Statistical Parametric Mapping) to compare the four sessions in individuals. RESULTS AND DISCUSSION: In patients presenting a visual acuity of the amblyopic eye less than 0.7, stimulation of this eye induced lower response in V1, V3, and V5 in comparison with the contralateral eye stimulation. Unexpectedly, in patients recovering normal or subnormal acuity, the amblyopic eye gave comparable or enhanced response in these areas. Additional response was found in the secondary visual cortex, the cuneus, the lingual gyrus, and in parietal, frontal, and orbitofrontal areas. These results suggest a variation in cortical response depending on the efficacy of the treatment. Recovered amblyopic eye, even with acuity less than the contralateral eye, may induce a reinforced cortical sensitivity to visual stimulus. Secondary visual areas may contribute to an attentional process in image perception and analysis. Cortical plasticity may be observed several years after amblyopia treatment. CONCLUSION: Our study substantiates the importance of an effective and early treatment of functional amblyopia, inducing cortical plasticity with reinforced attention and sensitivity to visual perception.

Multivariate source prelocalization (MSP): use of functionally informed basis functions for better conditioning the MEG inverse problem.

Spatially characterizing and quantifying the brain electromagnetic response using MEG/EEG data still remains a critical issue since it requires solving an ill-posed inverse problem that does not admit a unique solution. To overcome this lack of uniqueness, inverse methods have to introduce prior information about the solution. Most existing approaches are directly based upon extrinsic anatomical and functional priors and usually attempt at simultaneously localizing and quantifying brain activity. By contrast, this paper deals with a preprocessing tool which aims at better conditioning the source reconstruction process, by relying only upon intrinsic knowledge (a forward model and the MEG/EEG data itself) and focusing on the key issue of localization. Based on a discrete and realistic anatomical description of the cortex, we first define functionally Informed Basis Functions (fIBF) that are subject specific. We then propose a multivariate method which exploits these fIBF to calculate a probability-like coefficient of activation associated with each dipolar source of the model. This estimated distribution of activation coefficients may then be used as an intrinsic functional prior, either by taking these quantities into account in a subsequent inverse method, or by thresholding the set of probabilities in order to reduce the dimension of the solution space. These two ways of constraining the source reconstruction process may naturally be coupled. We successively describe the proposed Multivariate Source Prelocalization (MSP) approach and illustrate its performance on both simulated and real MEG data. Finally, the better conditioning induced by the MSP process in a classical regularization scheme is extensively and quantitatively evaluated.

[Cortical response in age-related macular degeneration (part I). Methodology and subject specificities]. / Réponse corticale dans la DMLA (Première partie). Méthodologie et spécificités des sujets.

PURPOSE: To evaluate the cortical response to visual stimulation in patients with age-related macular degeneration (ARMD). MATERIAL AND METHODS: We conducted a prospective functional MRI study at 1.5 Testa in ten patients presenting with unilateral or bilateral ARMD and five age-matched controls. The visual stimulus was a sequence of resting phase (presentation of a fixation point on a black background) followed by an activation phase (flashes at 2 Hz). Functional data were recorded with anatomy; significant hemodynamic response secondary to neuronal activation was statistically determined using the SPM 99 software. RESULTS: The first objective was to estimate the feasibility of a functional study in the elderly. Controls and patients complained about the duration of the examination, although each of the two active functional sessions lasted only 4.5 min. The central point fixation was impaired for the patients; some deviated their gaze to center the fixation point on a perimacular retinal area. Because of substantial movement during MRI acquisitions, the data from two patients and one control were withdrawn from statistic processing. DISCUSSION AND CONCLUSION: This study is one of the few evaluations reported on functional MRI in the elderly, because of technical constraints, patient fragility and their ophthalmologic pathology. Optimizing the visual stimulus and the paradigm of stimulation, repeating patient information and support have helped demonstrate significant cortical hemodynamic response in most subjects, even in the most affected patients. Evaluation of the visual cortex by functional MRI appears feasible in the ophthalmologic pathology of the elderly, providing an adapted management of the subject's conditions.

[Cortical response to age-related macular degeneration (Part II). Functional MRI study]. / Réponse corticale dans la DMLA (Deuxième partie). Etude en IRM fonctionnelle.

UNLABELLED: PURPOSE AND MATERIALS: To evaluate the cortical response to visual stimulation in patients with age-related macular degeneration (ARMD), we conducted a functional MRI study in ten patients presenting unilateral or bilateral ARMD and five age-matched controls, using white flashes during activation phases (see Part I). RESULTS: After anatomical conformation, eight patients and four controls showed significant cortical hemodynamic response to monocular stimulations. Individual analysis was preferred to group evaluation, because of the differences in visual loss in a small number of patients. In controls, we observed cortical response in the primary visual cortex, especially at occipital poles corresponding to the macula. Patients showed a qualitative and quantitative restriction in cortical response and exclusion of occipital poles after stimulation of the affected eye, whereas activation was found in the peripheral striate and peristriate cortex. Cortical response showed hemispheric asymmetry in some patients. DISCUSSION: Our study demonstrated an activation defect in the macular projected striate cortex, corresponding to visual impairment in ARMD patients. Nevertheless, at a given visual acuity, cortical response may vary among subjects. Patients' subjective apprehension may account for such variations, as well as objective visual capacity stemming from residual functional retinal areas within the affected macula. The hemispheric asymmetry in cortical activation may result from gaze deviation onto the new fixation area in the perimacular retina, thus altering the global visual field. Enhancement in the peripheral striate and peristriate areas suggests changes in cortical interactions, possibly by a lowering of the feedback from macular projected V1. Finally, cortical evaluations must take into account degenerative phenomena delaying the hemodynamic response in the elderly. CONCLUSION: Aiming at a specific population of weakened patients with a serious visual impairment, we obtained significant results concerning cortical plasticity for visual perception in central vision deletion. Our preliminary findings must be confirmed in a larger population and correlated with other techniques exploring vision, in particular with multifocal electroretinography for retinal evaluation.

Dynamics of parietofrontal networks underlying visuospatial short-term memory encoding.

Brain imaging studies in TEP, functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) have shown that visuospatial short-term memory tasks depend on dorsal parietofrontal networks. Knowing the spatiotemporal dynamics of this network would provide further understanding of the neural bases of the encoding process. We combined magnetoencephalography (MEG) with EEG and fMRI techniques to study this network in a task, in which participants had to judge the symmetry in position of two dots, presented either simultaneously ("immediate comparison") or successively ("memorization" of a first dot and "delayed comparison", after 3 s, with a second dot). With EEG, larger amplitude was observed in the parietocentral P3b component (350-500 ms) in the immediate and "delayed comparisons" than in "memorization" condition, where topography at this time was more anterior and right lateralized. MEG provided a more accurate localization and temporal variations of sources, revealing a strong M4 component at 450 ms in the "memorization" condition, with two sources localized in parietal and right premotor regions. These localizations are consistent with both fMRI foci and EEG cortical current source densities (CSD), but only MEG revealed the strong increase in premotor region at 450 ms related to "memorization". These combined results suggest that EEG P3B and MEG M4 components reflect two different dynamics in parietofrontal networks: the parietocentral P3b indexes a decision mechanism during the immediate and "delayed comparisons", whereas the MEG M4 component, with a larger right premotor source, reflects the encoding process in visuospatial short-term memory.

Individual differences in prefrontal cortical activation on the Tower of London planning task: implication for effortful processing.

Solving challenging ('effortful') problems is known to involve the dorsal and dorsolateral prefrontal cortex in normal volunteers, although there is considerable individual variation. In this functional magnetic resonance imaging study, we show that healthy subjects with different levels of performance in the Tower of London planning task exhibit different patterns of brain activation. All subjects exhibited significant bilateral activation in the dorsolateral prefrontal cortex, the anterior and posterior cingulate areas and the parietal cortex. However, 'standard performers' (performance < 70% correct) and 'superior performers' (performance >70% correct) differed in the patterns of activation exhibited. Superior performers showed a significantly more spatially extended activation in the left dorsolateral prefrontal cortex than did standard performers, whereas the latter group tended to show increased activation of the anterior cingulate region.

Estimating the effective degrees of freedom in univariate multiple regression analysis.

The general linear model provides the most widely applied statistical framework for analyzing functional MRI (fMRI) data. With the increasing temporal resolution of recent scanning protocols, and more elaborate data preprocessing schemes, data independency is no longer a valid assumption. In this paper, we revise the statistical background of the general linear model in the presence of temporal autocorrelations. First, when detecting the activation signal, we explicitly account for the temporal autocorrelation structure, which yields a generalized F-test and the associated corrected (or effective) degrees of freedom (DOF). The proposed approach is data driven and thus independent of any specific preprocessing method. Then, for event-related protocols, we propose a new model for the temporal autocorrelations ("damped oscillator" model) and compare this model to another, previously used in the field (first-order autoregressive model, or AR(1) model). In the case of long fMRI time series, an efficient approximation for the number of effective DOF is provided for both models. Finally, the validity of our approach is assessed using simulated and real fMRI data and is compared with more conventional methods.