Cognitive profile and brain morphological changes in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is accompanied by neurocognitive impairment, likely mediated by injury to various brain regions. We evaluated brain morphological changes in patients with OSA and their relationship to neuropsychological and oximetric data. Sixteen patients affected by moderate-severe OSA (age: 55.8±6.7 years, 13 males) and fourteen control subjects (age: 57.6±5.1 years, 9 males) underwent 3.0 Tesla brain magnetic resonance imaging (MRI) and neuropsychological testing evaluating short- and long-term memory, executive functions, language, attention, praxia and non-verbal learning. Volumetric segmentation of cortical and subcortical structures and voxel-based morphometry (VBM) were performed. Patients and controls differed significantly in Rey Auditory-Verbal Learning test (immediate and delayed recall), Stroop test and Digit span backward scores. Volumes of cortical gray matter (GM), right hippocampus, right and left caudate were smaller in patients compared to controls, with also brain parenchymal fraction (a normalized measure of cerebral atrophy) approaching statistical significance. Differences remained significant after controlling for comorbidities (hypertension, diabetes, smoking, hypercholesterolemia). VBM analysis showed regions of decreased GM volume in right and left hippocampus and within more lateral temporal areas in patients with OSA. Our findings indicate that the significant cognitive impairment seen in patients with moderate-severe OSA is associated with brain tissue damage in regions involved in several cognitive tasks. We conclude that OSA can increase brain susceptibility to the effects of aging and other clinical and pathological occurrences.

Clinical, genetic and magnetic resonance findings in an Italian patient affected by L-2-hydroxyglutaric aciduria.

L-2-Hydroxyglutaric aciduria (L-2-HGA) is a neurometabolic disease characterized by the presence of elevated levels of 2-hydroxyglutaric acid in the plasma, cerebrospinal fluid and urine. Clinical features in this inherited condition consist of mental deterioration, ataxia and motor deficits with pyramidal and extrapyramidal symptoms and signs. L-2-HGA is caused by mutations in the L-2-HGDH gene which most probably encodes for a L-2-hydroxyglutarate dehydrogenase, a putative mitochondrial protein converting L-2-hydroxyglutarate to alphaketoglutarate. Here, we report a pathogenic nonsense mutation in the L-2-HGDH gene found for the first time in an Italian patient affected by L-2-HGA, reinforcing the previously described phenotype of this rare metabolic disease and confirming the data indicating that mutations in the L-2-HGDH gene cause L-2-HGA.

Metabolic correlatives of brain activity in a FOS epilepsy patient.

The correlation and the interactions between neuronal activity and underlying metabolic dynamics are still a matter of debate, especially in pathological conditions. This study reports findings obtained on a subject suffering from fixation-off sensitivity (FOS) epilepsy, exploited as a model system of triggerable anomalous electrical activity. Functional Magnetic Resonance Spectroscopy was used to investigate the metabolic response to visual spike-inducing stimuli in a single voxel placed in the temporo-occipital lobe of a FOS epilepsy patient. MRS measurements were additionally performed on a control group of five healthy volunteers. The FOS patient also underwent an EEG session with the same stimulus paradigm. Uniquely in the FOS patient, glutamate and glutamine concentration increased during the first 10 min of stimulation and then returned to baseline. On the other hand, FOS-induced epileptic activity (spiking) endured throughout all the stimulation epoch. The observed metabolic dynamics may be likely linked to a complex interplay between alterations of the metabolic pathways of glutamate and modulation of the neuronal activity.

Characterization of the functional response in the human spinal cord: Impulse-response function and linearity.

Functional magnetic resonance imaging (fMRI) has emerged during the last decade as the main non-invasive technique for the investigation of human brain function. More recently, fMRI was also proposed for functional studies of the human spinal cord, but with controversial results. In fact, the functional contrast is not well-characterized, and even its origin has been challenged. In the present work, we characterized the temporal features of the functional signal evoked in the human spinal cord by a motor task, studied with an approach based on time-locked averaging of functional time series of different durations. Based on the results here reported, we defined an impulse-response function (irf) able to explain the functional response for motor tasks in the interval of 15-42 s of duration, thus suggesting the linearity of the phenomenon in this interval. Conversely, with stimulation durations ranging between 3 and 9 s, the functional signal was not detectable, and was under the level predicted by a linear behavior, suggesting deviation from linearity during short stimulations. The impulse-response function appeared slower than in the brain, peaking at about 9 s after its beginning. The observed contrast was generally larger than in the brain, on the order of about 5.4% of baseline signal at 1.5 T. The findings further suggested that the physiological origin of T(2) weighted functional imaging is similar in the spinal cord and in the brain.

dB/dt Evaluation in MRI Sites: Is ICNIRP Threshold Limit (for Workers) Exceeded?

The Directive 2013/35/EU establishes standards for workers exposed to static and time varying magnetic fields. These limits are based on ICNIRP guidelines expressed in terms of the electric field induced in the body. The complexity of this measurement led to theoretical models being developed. In this study, the experimental evaluation included varying magnetic field exposures for two classes of MRI workers. The measurements are conducted on four different MRI Systems including one 0.35 T, two 1.5 T, and one 3.0 T. Pocket magnetic dosimeters were used and it was carried out during routine conditions, emergency conditions, and cold-head maintenance/substitution. The acquired data has been processed and the corresponding dB/dt curves have been computed as the first time derivative of the dataset. The weighted peak approach was also implemented for the compliance assessment with regulatory limits. The dB/dt peak values have been compared with the reference level (RL) proposed by ICNIRP. The results show that the RL always exceeds during measurements on the 3.0 T scanner and sometimes on 1.5 T. In light of the foregoing, the diffusion of ultra-high field MRI scanners involves the introduction of behavioral rules that could be more useful than a numerical action level.

Performances evaluation and optimization of brain computer interface systems in a copy spelling task.

The evaluation of the performances of brain-computer interface (BCI) systems could be difficult as a standard procedure does not exist. In fact, every research team creates its own experimental protocol (different input signals, different trial structure, different output devices, etc.) and this makes systems comparison difficult. Moreover, the great question is whether these experiments can be extrapolated to real world applications or not. To overcome some intrinsic limitations of the most used criteria a new efficiency indicator will be described and used. Its main advantages are that it can predict with a high accuracy the performances of a whole system, a fact that can be used to successfully improve its behavior. Finally, simulations were performed to illustrate that the best system is built by tuning the transducer (TR) and the control interface (CI), which are the two main components of a BCI system, so that the best TR and the best CI do not exist but just the best combination of them.

How the NPX data format handles EEG data acquired simultaneously with fMRI.

There is a growing interest in combining EEG and (f)MRI data as they provide complementary information: EEG is characterized by a high temporal resolution but poor spatial one, while fMRI is characterized by a high spatial resolution but low temporal one. However, while a standard file format for storing EEG data is available since over a decade, it does not fulfill the needs of modern protocols and devices such as those involved in simultaneous EEG and fMRI recordings. The main reasons are the limited bit resolution, some difficulties encountered in handling and storing acquisition events or trace markers for off-line analyses and the impossibility to add some protocol-specific information that is not considered in the actual data formats. This, among others, hinders the release of free analysis software and makes it difficult to share data across different laboratories as every research unit develops its own tools according to its needs, stores data in proprietary formats and a lot of time is spent building software applications for converting data from one format to another. The NPX (NeuroPhysiological signals in eXtensible Markup Language) data format was defined to overcome these and other limitations, and here its main characteristics are reported as well as how some typical problems occurring in simultaneous EEG-fMRI recordings are also treated. Many tools based on the NPX technology can be freely downloaded, including a tool for removing artifacts occurring during simultaneous EEG-fMRI recordings.

Identification of activated regions during a language task.

Functional magnetic resonance imaging (fMRI) techniques are based on the assumption that changes in neural activity are accompanied by modulation in the blood-oxygenation-level-dependent (BOLD) signal. In addition to conventional increases in BOLD signals, sustained negative BOLD signal changes are occasionally observed in many fMRI experiments, which show regions of cortex that seem to respond in antiphase with primary stimulus. The existence of this so-called negative BOLD response (NBR) has been observed and investigated in many functional studies. Several theoretical mechanisms have been proposed to account for it, but its origin has never been fully explained. In this study, the variability of fMRI activation, including the sources of the negative BOLD signal, during phonological and semantic language tasks, was investigated in six right-handed healthy subjects. We found significant activations in the brain regions, mainly in the left hemisphere, involved in the language stimuli [prominent in the inferior frontal gyrus, approximately Brodmann Areas (BA)7, BA44, BA45 and BA47, and in the precuneus]. Moreover, we observed activations in motor regions [precentral gyrus and supplementary motor area (SMA)], a result that suggests a specific role of these areas (particularly the SMA) in language processing. Functional analysis have also shown that certain brain regions, including the posterior cingulate cortex and the anterior cingulate cortex, have consistently greater activity during resting states compared to states of performing cognitive tasks. In our study, we observed diffuse NBR at the cortical level and a stronger negative response in correspondence to the main sinuses. These phenomena seem to be unrelated to a specific neural activity, appearing to be expressions of a mechanical variation in hemodynamics. We discussed about the importance of these responses that are anticorrelated with the stimulus. Our data suggest that particular care must be considered in the interpretation of fMRI findings, especially in the case of presurgical studies.

Quantitative evaluation for brain CT/MRI coregistration based on maximization of mutual information in patients with focal epilepsy investigated with subdural electrodes.

Patients with drug-resistant focal epilepsy may require intracranial investigations with subdural electrodes. These must be correctly localized with respect to the brain cortical surface and require appropriate monitoring. For this purpose, coregistration techniques, which fuse preimplantation 3D magnetic resonance imaging scans with postimplantation computed tomography scans, have been implemented. In order to reduce localization errors due to the fusion process, we used a coregistration method based on the maximization of mutual information (MI) in 11 patients with extratemporal epilepsy who were invasively investigated. Our registration method is based on three processing steps: rigid-body transformation for coregistration, computation of MI as a similarity measure and the use of the Downhill Simplex optimization method. After consistency analysis, the shift of the registration method reached 0.14+/-0.27 mm in translation and 0.03+/-0.14 degrees in rotation, and the accuracies assessed on voxels of skull surface and voxels of the center of the brain volume were 1.42+/-0.61 and 1.15+/-0.53 mm, respectively. The accuracy of the fusion process reached submillimeter range, and results were considered reliable for surgical planning in all studied patients.

An independent component analysis-based approach on ballistocardiogram artifact removing.

Interest about simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data acquisition has rapidly increased during the last years because of the possibility that the combined method offers to join temporal and spatial resolution, providing in this way a powerful tool to investigate spontaneous and evoked brain activities. However, several intrinsic features of MRI scanning become sources of artifacts on EEG data. Noise sources of a highly predictable nature such as those related to the pulse MRI sequence and those determined by magnetic gradient switching during scanning do not represent a major problem and can be easily removed. On the contrary, the ballistocardiogram (BCG) artifact, a large signal visible on all EEG traces and related to cardiac activity inside the magnetic field, is determined by sources that are not fully stereotyped and causing important limitations in the use of artifact-removing strategies. Recently, it has been proposed to use independent component analysis (ICA) to remove BCG artifact from EEG signals. ICA is a statistical algorithm that allows blind separation of statistically independent sources when the only available information is represented by their linear combination. An important drawback with most ICA algorithms is that they exhibit a stochastic behavior: each run yields slightly different results such that the reliability of the estimated sources is difficult to assess. In this preliminary report, we present a method based on running the FastICA algorithm many times with slightly different initial conditions. Clustering structure in the signal space of the obtained components provides us with a new way to assess the reliability of the estimated sources.

A cluster-based quantitative procedure in an fMRI study of Parkinson's disease.

Parkinson's disease is a neurological disorder associated with disfunction of dopaminergic pathways of the basal ganglia. In this study, we report the effects of decreasing plasma concentrations of the dopamine-agonist apomorphine on the size and extents of activity clusters observed with functional magnetic resonance imaging during a simple motor task. Eight patients at advanced disease stage and six healthy volunteers were studied during four consecutive sessions. We observed consistent activations in the primary sensorimotor area of the contralateral side and in the supplementary motor area of both patients and controls during the first session. During subsequent sessions, while the drug concentration gradually decreased in patients, they showed a fragmentation of the activity areas, with an overall decrease of involved volume and a decline of activity in the supplementary motor area. The appearing of activity in the ipsilateral motor area matched a partial recovery of supplementary motor area activation. During the last session, when patients showed severe dyskinesia, a widespread region of positive and negative correlations between signal and task was observed. We conclude that the lack of subcortical circuitry is partially reversible by apomorphine and that when the drug effects are reduced, there is a possible mechanism recruitment of alternate subcortical pathways.

A chemical shift imaging study on regional metabolite distribution in a CADASIL family.

A chemical shift imaging (CSI) study was performed to directly assess relative concentrations of N-acetylaspartate (NAA), Cho and Cr metabolites in normal- and abnormal-appearing brain tissue of asymptomatic and symptomatic members of a single family with a neuropathologic, genetic and electrophysiological confirmed diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. The aim of the investigation was to evaluate clinical findings and metabolite abnormalities as early appearance of axonal injury in this syndrome. The main findings related statistically significant decreases in the mean metabolite ratios for NAA/Cr, NAA/Cho and Cho/Cr in the anterior parts in comparison with the posterior parts of the centrum semiovale in symptomatic and asymptomatic patients. The effect was considerably greater in the symptomatic patients, indicating a strong correlation between CSI and pathology results. No differences were found between the two areas in the control group. Although lactate signals were hardly detectable in individual spectra, there was a trend toward increased Lac/Cr values in the anterior parts with respect to the posterior parts in the patient group, with the effect particularly evident in the asymptomatic subjects with the gene mutation.

BOLD signal and vessel dynamics: a hierarchical cluster analysis.

The aim of the present study was to analyze blood oxygenation level-dependent (BOLD) signal variation during an apnea-based task in order to assess the capability of a functional magnetic resonance imaging (fMRI) procedure to estimate cerebral vascular dynamic effects. We measured BOLD contrast by hierarchical cluster analysis in healthy subjects undergoing an fMRI experiment, in which the task paradigm was one phase of inspirational apnea (IA). By processing the time courses of the fMRI experiment, analysis was performed only on a subclass of all the possible signal patterns; basically, root mean square and absolute variation differences have been calculated. Considering the baseline value obtained by computing the mean value of the initial rest period as reference, particular voxels showed relative important variations during the IA task and during the recovery phase following the IA. We focused our interest on the signal response of voxels that would correspond mainly to white and gray matter regions and that also may be affected by the proximity of large venous vessels. The results are presented as maps of space-temporal distribution of time series variations with two levels of hierarchical clustering among voxels with low to high initial response. Furthermore, we have presented a clustering of the signal response delay, conducting to a partition and identification of specified brain sites.

Metabolic alteration transients during paroxysmal activity in an epileptic patient with fixation-off sensitivity: a case study.

The purpose of this study was to investigate short-time metabolic variations related to continuous epileptic activity elicited by fixation-off sensitivity (FOS). Time-resolved magnetic resonance spectroscopy was performed on a patient on whom previous clinical findings clearly indicated presence of FOS. The epileptic focus was localized with a simultaneous electroencephalographic and functional magnetic resonance imaging study. The results showed a linear increase of the sum of glutamate and glutamine with time of paroxysmal activity in epileptic focus and much greater concentration of choline-containing compounds in focus than in the contralateral side.

Temperature Values Variability in Piezoelectric Implant Site Preparation: Differences between Cortical and Corticocancellous Bovine Bone.

PURPOSE: Various parameters can influence temperature rise and detection during implant site preparation. The aim of this study is to investigate local temperature values in cortical and corticocancellous bovine bone during early stages of piezoelectric implant site preparation. MATERIALS AND METHODS: 20 osteotomies were performed using a diamond tip (IM1s, Mectron Medical Technology, Carasco, Italy) on two different types of bovine bone samples, cortical and corticocancellous, respectively. A standardized protocol was designed to provide constant working conditions. Temperatures were measured in real time at a fixed position by a fiber optic thermometer. RESULTS: Significantly higher drilling time (154.90 sec versus 99.00 sec; p < 0.0001) and temperatures (39.26°C versus 34.73°C; p = 0.043) were observed in the cortical group compared to the corticocancellous group. A remarkable variability of results characterized the corticocancellous blocks as compared to the blocks of pure cortical bone. CONCLUSION: Bone samples can influence heat generation during in vitro implant site preparation. When compared to cortical bone, corticocancellous samples present more variability in temperature values. Even controlling most experimental factors, the impact of bone samples still remains one of the main causes of temperature variability.

Gilles de la Tourette syndrome and voluntary movement: a functional MRI study.

Tourette syndrome (TS) is hypothesised to be caused by an abnormal organization of movement control. The aim of this study was to use functional magnetic resonance imaging to study motor cortex activation in a TS patient. Usual and unusual self-paced voluntary movements were performed. The TS patient displayed supplementary motor area (SMA) activation during both tasks. This activation reflects a continuous use of the SMA to perform the voluntary motor movements required in both tasks. Moreover, the absence of tics during the execution of these voluntary motor tasks suggests that tic activity may be suppressed by additional mental effort.

In vivo quantitative 1H MRS of cerebellum and evaluation of quantitation reproducibility by simulation of different levels of noise and spectral resolution.

A quantitative analysis of cerebellar metabolites in normal subjects has been performed by proton MR spectroscopy (MRS) with relaxation time correction. Quantitation was carried out in seven healthy human subjects with the well-established LCModel program. The prior knowledge utilized for quantitation was obtained from solutions containing the major brain metabolites and MRS investigated under the same experimental conditions. The tissue water signal was used as an internal standard for the in vivo studies. Both in vitro (for the prior knowledge template) and in vivo data were acquired separately at 1.5 T by PRESS sequence (TR, 1500 ms; TE, 30 ms). The absolute concentration of main cerebellar metabolites was corrected for relaxation time effects. Different noise and line broadening conditions were considered and simulated in the spectral processing in order to evaluate the effect of spectral quality on the concentration estimates.

Issues about the fMRI of the human spinal cord.

Noninvasive functional studies on human spinal cord by means of magnetic resonance imaging (MRI) are gaining attention because of the promising applications in the study of healthy and injured central nervous system. The findings obtained are generally consistent with the anatomic knowledge based on invasive methods, but the origin and specificity of functional contrast is still debated. In this paper, a review of current knowledge and major issues about functional MRI (fMRI) in the human spinal cord is presented, with emphasis on the main methodological and technical problems and on forthcoming applications as clinical tool.

Simultaneous EEG-fMRI acquisition: how far is it from being a standardized technique?

Simultaneous EEG-fMRI is a powerful tool to study spontaneous and evoked brain activity because of the complementary advantages of the two techniques in terms of temporal and spatial resolution. In recent years, a significant number of scientific works have been published on this subject. However, many technical problems related to the intrinsic incompatibility of EEG and MRI methods are still not fully solved. Furthermore, simultaneous acquisition of EEG and event-related fMRI requires precise synchronization of all devices involved in the experimental setup. Thus, timing issue must be carefully considered in order to avoid significant methodological errors. The aim of the present work is to highlight and discuss some of technical and methodological open issues associated with the combined use of EEG and fMRI. These issues are presented in the context of preliminary data regarding simultaneous acquisition of event-related evoked potentials and BOLD images during a visual odd-ball paradigm.

Hemodynamic response (BOLD/fMRI) in focal epilepsy with reference to benzodiazepine effect.

We studied a new procedure of BOLD/fMRI acquisition in epilepsy. They use the benzodiazepine effect to achieve a more reliable baseline for statistical analysis. The method works only in the MR domain without EEG correlation. It compares the EPI images during interictal epileptic discharges and the images "inactivated" by benzodiazepine. The results in five out of eight patients show that this procedure in comparison with the EEG/fMRI method gives a net improvement of spatial definition of BOLD areas. These preliminary results seem to confirm the hypothesis that the better BOLD/fMRI procedure in epilepsy is to make use of physical features of MR that, unlike EEG, is not influenced by the distance of intercerebral sources and consequently allows a more complete and undistorted display of BOLD areas.