GABAergic inhibition shapes behavior and neural dynamics in human visual working memory.

Neuronal inhibition, primarily mediated by GABAergic neurotransmission, is crucial for brain development and healthy cognition. Gamma-aminobutyric acid concentration levels in sensory areas have been shown to correlate with hemodynamic and oscillatory neuronal responses. How these measures relate to one another during working memory, a higher-order cognitive process, is still poorly understood. We address this gap by collecting magnetoencephalography, functional magnetic resonance imaging, and Flumazenil positron emission tomography data within the same subject cohort using an n-back working-memory paradigm. By probing the relationship between GABAA receptor distribution, neural oscillations, and Blood Oxygen Level Dependent (BOLD) modulations, we found that GABAA receptor density in higher-order cortical areas predicted the reaction times on the working-memory task and correlated positively with the peak frequency of gamma power modulations and negatively with BOLD amplitude. These findings support and extend theories linking gamma oscillations and hemodynamic responses to gamma-aminobutyric acid neurotransmission and to the excitation-inhibition balance and cognitive performance in humans. Considering the small sample size of the study, future studies should test whether these findings also hold for other, larger cohorts as well as to examine in detail how the GABAergic system and neural fluctuations jointly support working-memory task performance.

Subject-Specific Activation of Central Respiratory Centers during Breath-Holding Functional Magnetic Resonance Imaging.

BACKGROUND: Voluntary breath-holding (BH) triggers responses from central neural control and respiratory centers in order to restore breathing. Such responses can be observed using functional MRI (fMRI). OBJECTIVES: We used this paradigm in healthy volunteers with the view to develop a biomarker that could be used to investigate disorders of the central control of breathing at the individual patient level. METHOD: In 21 healthy human subjects (mean age±SD, 32.8 ± 9.9 years old), fMRI was used to determine, at both the individual and group levels, the physiological neural response to expiratory and inspiratory voluntary apneas, within respiratory control centers in the brain and brainstem. RESULTS: Group analysis showed that expiratory BH, but not inspiratory BH, triggered activation of the pontine respiratory group and raphe nuclei at the group level, with a significant relationship between the levels of activation and drop in SpO2. Using predefined ROIs, expiratory BH, and to a lesser extent, inspiratory BH were associated with activation of most respiratory centers. The right ventrolateral nucleus of the thalamus, right pre-Bötzinger complex, right VRG, right nucleus ambiguus, and left Kölliker-Fuse-parabrachial complex were only activated during inspiratory BH. Individual analysis identified activations of cortical/subcortical and brainstem structures related to respiratory control in 19 out of 21 subjects. CONCLUSION: Our study shows that BH paradigm allows to reliably trigger fMRI response from brainstem and cortical areas involved in respiratory control at the individual level, suggesting that it might serve as a clinically relevant biomarker to investigate conditions associated with an altered central control of respiration.

Wearable devices for sudden unexpected death in epilepsy prevention.

Sudden unexpected death in epilepsy (SUDEP) is most often associated with the occurrence of generalized tonic-clonic seizures (GTCS), a seizure type that can now be detected with high sensitivity and specificity by wearable or bed devices. The recent development in such devices and their performance offer multiple opportunities to tackle SUDEP and its prevention. Reliable GTCS detection might help physicians optimize antiepileptic treatment, which could in turn reduce the risk of SUDEP. GTCS-triggered alarms can lead to immediate intervention by caregivers that are also likely to decrease the odd of SUDEP. The biosignals used to detect GTCS might provide novel SUDEP biomarkers, in particular, by informing on several important characteristics of the ictal and postictal periods (type of GTCS, duration of tonic phase, rotation in the prone position, presence and duration of postictal immobility and bradycardia, rise in electrodermal activity). Other biosensors not yet used for detecting GTCS might provide complementary information, such as the presence and intensity of ictal/postictal hypoxemia. The above biomarkers, if strongly predictive, could help identify patients at very high risk of SUDEP, enabling better assessment of individual risk, as well as selection of appropriate patients for clinical studies aiming at preventing SUDEP. The same biosignals could also be used as ancillary biomarkers to test the impact of various interventions before moving to highly challenging randomized controlled trials with SUDEP as a primary outcome.

Behavioral and fMRI responses to fearful faces are altered in benign childhood epilepsy with centrotemporal spikes (BCECTS).

OBJECTIVE: We hypothesized that children with benign childhood epilepsy with centrotemporal spikes (BCECTS) might have altered social cognitive skills and underlying neural networks. METHODS: We studied 13 patients with BCECTS and 11 age-matched controls using event-related functional magnetic resonance imaging (fMRI) with an emotional discrimination task consisting of viewing happy, fearful, scrambled, and neutral faces. Behavioral performance measured during the task was correlated with clinical variables and behavioral ratings. RESULTS: In comparison with age-matched controls, children with BCECTS performing a fearful faces detection task showed significantly reduced bilateral fMRI activation in the insular cortex, caudate, and lentiform nuclei, as well as increased response time. The percentage of errors made by children with BCECTS correlated negatively with age, a finding not observed in controls. In patients, accuracy positively correlated with time since the last seizure. The above abnormalities were not observed during happy faces detection task, except for a slower response in children with BCECTS as compared to controls. SIGNIFICANCE: Our study suggests that BCECTS is associated with altered social cognition network and function, particularly for the identification of fearful faces. The age dependency of some of these findings supports the view that a delayed maturation of spiking cortical regions might underlie the cognitive dysfunction observed in BCECTS.

White matter development in children with benign childhood epilepsy with centro-temporal spikes.

Benign childhood epilepsy with centro-temporal spikes (BCECTS) is a unique form of non-lesional age-dependent epilepsy with rare seizures, focal electroencepalographic abnormalities affecting the same well delineated cortical region in most patients, and frequent mild to moderate cognitive dysfunctions. In this condition, it is hypothesized that interictal electroencepalographic discharges might interfere with local brain maturation, resulting in altered cognition. Diffusion tensor imaging allows testing of this hypothesis by investigating the white matter microstructure, and has previously proved sensitive to epilepsy-related alterations of fractional anisotropy and diffusivity. However, no diffusion tensor imaging study has yet been performed with a focus on BCECTS. We investigated 25 children suffering from BCECTS and 25 age-matched control subjects using diffusion tensor imaging, 3D-T1 magnetic resonance imaging, and a battery of neuropsychological tests including Conner's scale and Wechsler Intelligence Scale for Children (fourth revision). Electroencephalography was also performed in all patients within 2 months of the magnetic resonance imaging assessment. Parametric maps of fractional anisotropy, mean-, radial-, and axial diffusivity were extracted from diffusion tensor imaging data. Patients were compared with control subjects using voxel-based statistics and family-wise error correction for multiple comparisons. Each patient was also compared to control subjects. Fractional anisotropy and diffusivity images were correlated to neuropsychological and clinical variables. Group analysis showed significantly reduced fractional anisotropy and increased diffusivity in patients compared with control subjects, predominantly over the left pre- and postcentral gyri and ipsilateral to the electroencephalographic focus. At the individual level, regions of significant differences were observed in 10 patients (40%) for anisotropy (eight reduced fractional anisotropy, one increased fractional anisotropy, one both), and 17 (56%) for diffusivity (13 increased, one reduced, three both). There were significant negative correlations between fractional anisotropy maps and duration of epilepsy in the precentral gyri, bilaterally, and in the left postcentral gyrus. Accordingly, 9 of 12 patients (75%) with duration of epilepsy>12 months showed significantly reduced fractional anisotropy versus none of the 13 patients with duration of epilepsy≤12 months. Diffusivity maps positively correlated with duration of epilepsy in the cuneus. Children with BCECTS demonstrate alterations in the microstructure of the white matter, undetectable with conventional magnetic resonance imaging, predominating over the regions displaying chronic interictal epileptiform discharges. The association observed between diffusion tensor imaging changes, duration of epilepsy and cognitive performance appears compatible with the hypothesis that interictal epileptic activity alters brain maturation, which could in turn lead to cognitive dysfunction. However, such cross-sectional association does not demonstrate causality, and other hitherto unidentified factors could represent the common cause to part or all of the observed findings.

Efficient "pop-out" visual search elicits sustained broadband γ activity in the dorsal attention network.

An object that differs markedly from its surrounding-for example, a red cherry among green leaves-seems to pop out effortlessly in our visual experience. The rapid detection of salient targets, independently of the number of other items in the scene, is thought to be mediated by efficient search brain mechanisms. It is not clear, however, whether efficient search is actually an "effortless" bottom-up process or whether it also involves regions of the prefrontal cortex generally associated with top-down sustained attention. We addressed this question with intracranial EEG (iEEG) recordings designed to identify brain regions underlying a classic visual search task and correlate neural activity with target detection latencies on a trial-by-trial basis with high temporal precision recordings of these regions in epileptic patients. The spatio-temporal dynamics of single-trial spectral analysis of iEEG recordings revealed sustained energy increases in a broad gamma band (50-150 Hz) throughout the duration of the search process in the entire dorsal attention network both in efficient and inefficient search conditions. By contrast to extensive theoretical and experimental indications that efficient search relies exclusively on transient bottom-up processes in visual areas, we found that efficient search is mediated by sustained gamma activity in the dorsal lateral prefrontal cortex and the anterior cingulate cortex, alongside the superior parietal cortex and the frontal eye field. Our findings support the hypothesis that active visual search systematically involves the frontal-parietal attention network and therefore, executive attention resources, regardless of target saliency.

Effects of aripiprazole, risperidone, and olanzapine on 5-HT1A receptors in patients with schizophrenia.

To investigate the impact of various antipsychotic drugs on the 5-HT1A serotoninergic system, we performed a [F]4-(2-methoxyphenyl)-1-[2-(N-2-pirydynyl)-p-luorobenzamido]-ethyl-piperazine PET study in 19 schizophrenic patients treated with either aripiprazole, which has a partial agonist activity at 5-HT1A receptors, or second-generation antipsychotics (SGA) (olanzapine or risperidone), which do not demonstrate such property. We used a simplified reference tissue model to generate parametric images of [F]MPPF-binding potential (BPND). A significant reduction of [F]MPPF BPND was found in treated schizophrenic patients compared to age- and sex-matched healthy subjects. These modifications were mainly localized in the frontal and orbitofrontal cortex and may reflect either the pathophysiology of schizophrenia or medication effects. The schizophrenic patients treated with aripiprazole showed a reduction of global [F]MPPF BPND compared with healthy subjects and schizophrenic patients with SGA treatment. In addition, compared with matched controls, the reduction of regional [F]MPPF BPND was more marked in the schizophrenic patients treated with aripiprazole compared with those receiving SGA treatment, possibly reflecting the partial agonist of aripiprazole activity at 5-HT1A receptors.

Quantitative PET analyses of regional [11C]PE2I binding to the dopamine transporter--application to juvenile myoclonic epilepsy.

The dopamine transporter (DAT) is of central interest in research on the pathophysiology and treatment of neuro-psychiatric disorders. [(11)C]PE2I is an established radioligand that provides high-contrast delineation of brain regions that are rich in DAT. The aim of the present PET study in eight patients with juvenile myoclonic epilepsy (JME) was to evaluate the kinetics of [(11)C]PE2I in the brain and to compare binding parameters with those of age-matched control subjects (n = 6). Each patient participated in 90-minute PET measurements with [(11)C]PE2I. Data were analyzed using kinetic compartment analyses with metabolite-corrected arterial plasma input and reference tissue models using the cerebellum as a reference region. The time-activity curves were well described by the two-tissue compartment model (2TCM) for the DAT-rich regions. The 2TCM with fixed K(1)/k(2) ratio derived from the cerebellum provided robust and reliable estimates of binding potential (BP(ND)) and total distribution volume (V(T)). The reference tissue models also provided robust estimates of BP(ND), although they gave lower BP(ND) values than the kinetic analysis. Compared with those of control subjects, we found that BP(ND) values obtained by all approaches were reduced in the midbrain of the patients with JME. The finding indicates impaired dopamine uptake in the midbrain of JME patients. The three-tissue compartment model could best describe uptake in the cerebellum, indicating that two kinetically distinguishable compartments exist in cerebellar tissue, which may correspond to nonspecific binding and the blood-brain barrier passing metabolite. The reference tissue models should be applied with better understanding of the biochemical nature of the radioligand and the reliability of these approaches.

Disengagement and inhibition of visual-spatial attention are differently impaired in children with rolandic epilepsy and Panayiotopoulos syndrome.

We assessed voluntary orientation and reorientation of visuospatial attention in 313 healthy 6- to 22-year-old participants, 30 children suffering from benign epilepsy with centrotemporal spikes (BECTS) and 13 children with Panayiotopoulos syndrome (PS). The developmental section highlights the late development of reorienting skills. Only children with BECTS-R showed a strong tendency toward a rightward bias in attentional orientation. Additionally, a unilateral deficit of disengagement characterizes the patients with BECTS-R and comorbid ADHD. Right rolandic spikes seem to aggravate subclinical reorienting difficulties. Finally, children with PS failed to diffuse inhibition, except in the nearest area outside the attentional focus. This deficit could be attributed to the typical occipital-to-frontal spreading of the spikes in PS. By showing distinct attentional deficiencies according to the epileptic syndrome and the epileptic focus lateralization in BECTS, the results provide new evidence for alterations of attentional mechanisms by interictal epileptic activity, which probably contribute to learning difficulties.

fMRI studies evaluating central respiratory control in humans.

A plethora of neural centers in the central nervous system control the fundamental respiratory pattern. This control is ensured by neurons that act as pacemakers, modulating activity through chemical control driven by changes in the O2/CO2 balance. Most of the respiratory neural centers are located in the brainstem, but difficult to localize on magnetic resonance imaging (MRI) due to their small size, lack of visually-detectable borders with neighboring areas, and significant physiological noise hampering detection of its activity with functional MRI (fMRI). Yet, several approaches make it possible to study the normal response to different abnormal stimuli or conditions such as CO2 inhalation, induced hypercapnia, volitional apnea, induced hypoxia etc. This review provides a comprehensive overview of the majority of available studies on central respiratory control in humans.

The dopamine system in idiopathic generalized epilepsies: identification of syndrome-related changes.

The present study tests the hypothesis that the dopamine system is altered in idiopathic generalized epilepsy (IGE), and that the pattern of possible changes differs between juvenile myoclonic epilepsy (JME) and epilepsy with tonic-clonic seizures only (GTCS). The dopamine (DA) system was investigated with PET and a DA transporter (DAT) ligand [(11)C]PE2I in 13 patients with JME, 13 with GTCS, and 12 healthy controls. The binding potential (BP) to DAT was quantified in the caudate, putamen, and midbrain. The possible impact on function was evaluated by correlating regional BP with test performance in a battery of neuropsychological tests. Both patient groups showed a reduced BP compared to controls, albeit in different locations. JME patients had a lower tracer binding than controls in the midbrain (0.8+/-0.1 vs. 1.0+/-0.2, p=0.019), whereas GTCS patients had reduced tracer binding in the putamen (5.9+/-1.6 vs. 7.1+/-1.2, p=0.023). While GTCS patients showed impaired performance in motor functions and on one test of executive function, JME patients performed poorly also in tests of working memory and several tests of executive function. Alterations in the DA system seem to exist in both GTCS and JME. However, the regional distribution of these changes differs between the two syndromes, as does their association with psychomotor and working memory performance. The present data suggest that the two forms of IGE have different neuronal substrates.

Neural correlates of verbal working memory in children with epilepsy with centro-temporal spikes.

BACKGROUND: Previous functional magnetic resonance imaging (fMRI) studies have identified brain systems underlying different components of working memory (WM) in healthy subjects. The aim of this study was to compare the functional integrity of these neural networks in children with self-limited childhood epilepsy with centro-temporal spikes (ECTS) as compared to healthy controls, using a verbal working memory task (WMT). METHODS: Functional MRI of WM in seventeen 6-to-13 year-old children, diagnosed with ECTS, and 17 sex- and age-matched healthy controls were conducted at 3 T. To estimate BOLD responses during the maintenance of low, medium, and high WMT loads, we used a Sternberg verbal WMT. Neuropsychological testing prior to scanning and behavioral data during scanning were also acquired. RESULTS: Behavioral performances during WMT, in particular accuracy and response time, were poorer in children with ECTS than in controls. Increased WM load was associated with increased BOLD signal in all subjects, with significant clusters detected in frontal and parietal regions, predominantly in the left hemisphere. However, under the high load condition, patients showed reduced activation in the frontal, temporal and parietal regions as compared to controls. In brain regions where WM-triggered BOLD activation differed between groups, this activation correlated with neuropsychological performances in healthy controls but not in patients with ECTS, further suggesting WM network dysfunction in the latter. CONCLUSION: Children with ECTS differ from healthy controls in how they control WM processes during tasks with increasing difficulty level, notably for high WM load where patients demonstrate both reduced BOLD activation and behavioral performances.

Social cognition, behaviour and therapy adherence in frontal lobe epilepsy: a study combining neuroeconomic and neuropsychological methods.

Social behaviour of healthy humans and its neural correlates have been extensively studied in social neuroscience and neuroeconomics. Whereas it is well established that several types of epilepsies, such as frontal lobe epilepsy, lead to social cognitive impairments, experimental evidence on how these translate into behavioural symptoms is scarce. Furthermore, it is unclear whether social cognitive or behavioural disturbances have an impact on therapy adherence, which is critical for effective disease management, but generally low in these patients. In order to investigate the relationship between social cognition, social behaviour, and therapy adherence in patients with frontal lobe epilepsies (FLE), we designed a study combining conventional neuropsychological with behavioural economic and functional magnetic resonance imaging (fMRI) methodology. Fifteen patients and 15 healthy controls played a prisoners' dilemma game (an established game to operationalize social behaviour) while undergoing fMRI. Additionally, social cognitive, basic neuropsychological variables, and therapy adherence were assessed. Our results implicate that social behaviour is indeed affected and can be quantified using neuroeconomic methods in patients with FLE. Impaired social behaviour in these patients might be a consequence of altered brain activation in the medial prefrontal cortex and play a role in low therapy adherence. Finally, this study serves as an example of how to integrate neuroeconomic methods in neurology.

Limited evidence of physical therapy on balance after stroke: A systematic review and meta-analysis.

BACKGROUND: Stroke results in balance disorders and these directly affect autonomy and quality of life. The purpose of this systematic review and meta-analysis was to determine the efficacy of physical therapy (PT) on balance and postural control after stroke. METHODS: We included all randomized controlled trials assessing the efficacy of PT on balance and postural control in adult patients after stroke without language restriction. Medline, Embase/Scopus, Cochrane Central Register of Controlled Trials, PEDro, Pascal, and Francis databases were searched until January 2019. Primary outcomes were balance (Berg Balance scale and Postural Assessment Scale for Stroke) and postural control with postural deviation or stability measurement in sitting or standing static evaluation. A pair of independent reviewers selected studies, extracted data, and assessed risk of bias. Meta-analyses with subgroups (categories of PT, time post-stroke, and lesion location) and meta-regression (duration of PT) were conducted. RESULTS: A total of 145 studies (n = 5912) were selected from the 13,123 records identified. For balance, evidence was found in favor of the efficacy of functional task-training alone (standardized mean difference 0.39, 95% confidence interval [0.09; 0.68], heterogeneity I2 = 63%) or associated with musculoskeletal intervention and/or cardiopulmonary intervention (0.37, [0.19; 0.55], I2 = 48%), electrostimulation (0.91, [0.49; 1.34], I2 = 52%) immediately after intervention, compared to sham treatment or usual care (ST/UC). For postural deviation eyes open, assistive devices were more effective than no treatment (-0.21, [-0.37; -0.05], I2 = 0%) immediately after intervention; for postural stability eyes open, functional task-training and sensory interventions were more effective than ST/UC (0.97, [0.35; 1.59], I2 = 65% and 0.80, [0.46; 1.13], I2 = 37% respectively) immediately after intervention. CONCLUSIONS: Functional task-training associated with musculoskeletal intervention and/or cardiopulmonary intervention and sensory interventions seem to be immediately effective in improving balance and postural stability, respectively. The heterogeneity of PT and the weak methodological quality of studies limited the interpretation and the confidence in findings.

Neural Activity Elicited by a Cognitive Task can be Detected in Single-Trials with Simultaneous Intracerebral EEG-fMRI Recordings.

Recent studies have shown that it is feasible to record simultaneously intracerebral EEG (icEEG) and functional magnetic resonance imaging (fMRI) in patients with epilepsy. While it has mainly been used to explore the hemodynamic changes associated with epileptic spikes, this approach could also provide new insight into human cognition. However, the first step is to ensure that cognitive EEG components, that have lower amplitudes than epileptic spikes, can be appropriately detected under fMRI. We compared the high frequency activities (HFA, 50-150[Formula: see text]Hz) elicited by a reading task in icEEG-only and subsequent icEEG-fMRI in the same patients ([Formula: see text]), implanted with depth electrodes. Comparable responses were obtained, with 71% of the recording sites that responded during the icEEG-only session also responding during the icEEG-fMRI session. For all the remaining sites, nearby clusters (distant of 7[Formula: see text]mm or less) also demonstrated significant HFA increase during the icEEG-fMRI session. Significant HFA increases were also observable at the single-trial level in icEEG-fMRI recordings. Our results show that low-amplitude icEEG signal components such as cognitive-induced HFAs can be reliably recorded with simultaneous fMRI. This paves the way for the use of icEEG-fMRI to address various fundamental and clinical issues, notably the identification of the neural correlates of the BOLD signal.

Gamma oscillations in V1 are correlated with GABA(A) receptor density: A multi-modal MEG and Flumazenil-PET study.

High-frequency oscillations in the gamma-band reflect rhythmic synchronization of spike timing in active neural networks. The modulation of gamma oscillations is a widely established mechanism in a variety of neurobiological processes, yet its neurochemical basis is not fully understood. Modeling, in-vitro and in-vivo animal studies suggest that gamma oscillation properties depend on GABAergic inhibition. In humans, search for evidence linking total GABA concentration to gamma oscillations has led to promising -but also to partly diverging- observations. Here, we provide the first evidence of a direct relationship between the density of GABA(A) receptors and gamma oscillatory gamma responses in human primary visual cortex (V1). By combining Flumazenil-PET (to measure resting-levels of GABA(A) receptor density) and MEG (to measure visually-induced gamma oscillations), we found that GABA(A) receptor densities correlated positively with the frequency and negatively with amplitude of visually-induced gamma oscillations in V1. Our findings demonstrate that gamma-band response profiles of primary visual cortex across healthy individuals are shaped by GABA(A)-receptor-mediated inhibitory neurotransmission. These results bridge the gap with in-vitro and animal studies and may have future clinical implications given that altered GABAergic function, including dysregulation of GABA(A) receptors, has been related to psychiatric disorders including schizophrenia and depression.

Dendritic cells exposed to estrogen in vitro exhibit therapeutic effects in ongoing experimental allergic encephalomyelitis.

Immunomodulatory effects of estrogen have been demonstrated by clinical and experimental observations, but the mechanisms by which estrogen exhibits the effects remain to be defined. One possible mechanism by which estrogen inhibits the development of experimental allergic encephalomyelitis (EAE), a commonly used model of multiple sclerosis (MS) in humans, is over the functions of dendritic cells (DC). Here, we describe that splenic DC from Lewis rats obtained on day 12 post-immunization (p.i.) with myelin basic protein (MBP) encephalitogenic peptide 68-86+Freund's complete adjuvant (FCA), after being exposed in vitro 17beta-estradiol, exhibited therapeutic effects on acute EAE when injected subcutaneously on day 5 p.i. Blood mononuclear cells (MNC) were isolated from thus treated rats on day 12 p.i. Administration of estrogen-exposed DC prevented the expansion of CD4+ T cells and increased proportions of regulatory T cells producing IL-10 and CD4+CD28- suppressor T cells, accompanied with increased IL-10 and IFN-gamma, and reduced TNF-alpha production. Infiltrates of CD68+ macrophages within the central nervous system and MBP 68-86-induced T cell proliferation were inhibited in rats injected with estrogen-exposed DC compared to rats injected with naive DC. Estrogen up-regulated the expression of indoleamine 2,3-dioxygenase, which promotes tolerogenic properties of DC. The results suggest that in vitro exposure of DC to estrogen modulates DC functions and results in a therapeutic effect of DC.

A phantom and animal study of temperature changes during fMRI with intracerebral depth electrodes.

BACKGROUND: MRI is routinely used in patients undergoing intracerebral electroencephalography (icEEG) in order to precisely locate the position of intracerebral electrodes. In contrast, fMRI has been considered unsafe due to suspected greater risk of radiofrequency-induced (RF) tissue heating at the vicinity of intracerebral electrodes. We determined the possible temperature change at the tip of such electrodes during fMRI sessions in phantom and animals. METHODS: A human-shaped torso phantom and MRI-compatible intracerebral electrodes approved for icEEG in humans were used to mimic a patient with four intracerebral electrodes (one parasagittal and three coronal). Six rabbits were implanted with one or two coronal electrodes. MRI-induced temperature changes at the tip of electrodes were measured using a fibre-optic thermometer. All experiments were performed on Siemens Sonata 1.5T scanner. RESULTS: For coronally implanted electrodes with wires pulled posteriorly to the magnetic bore, temperature increase recorded during EPI sequences reached a maximum of 0.6°C and 0.9°C in phantom and animals, respectively. These maximal figures were decreased to 0.2°C and 0.5°C, when electrode wires were connected to cables and amplifier. When electrode wires were pulled anteriorly to the magnetic bore, temperature increased up to 1.3°C in both phantom and animals. Greater temperature increases were recorded for the single electrode implanted parasagitally in the phantom. CONCLUSION: Variation of the temperature depends on the electrode and wire position relative to the transmit body coil and orientation of the constant magnetic field (B0). EPI sequence with intracerebral electrodes appears as safe as standard T1 and T2 sequence for implanted electrodes placed perpendicular to the z-axis of the magnetic bore, using a 1.5T MRI system, with the free-end wires moving posteriorly, in phantom and animals.

Magnetic resonance imaging in clinical trials.

PURPOSE OF REVIEW: The aim of this article is to review the latest clinical trials in neurological diseases where magnetic resonance imaging was used to assess treatment outcome. RECENT FINDINGS: The unique sensitivity of magnetic resonance imaging for detecting disorders in the brain has made it an attractive noninvasive tool for assessing treatment efficacy in several diseases. Volumetric and functional magnetic resonance imaging have proved to represent robust biomarkers for the evaluation of anti-Alzheimer treatments, and have demonstrated a significant impact of cholinesterase inhibitors. The optimization of thrombolytic therapy in acute ischemic stroke has concentrated on the quantification of the ischemic penumbra, using perfusion-weighted and diffusion-weighted imaging. Standard assessment of T2 or fluid-attenuated inversion recovery lesion load remains the method of choice to evaluate new therapeutic strategy in multiple sclerosis. Other nonconventional quantitative magnetic resonance imaging techniques such as magnetic resonance volumetry, magnetization transfer imaging, diffusion-weighted imaging, or magnetic resonance spectroscopy are increasingly used in the field. SUMMARY: Magnetic resonance imaging has become a major surrogate marker of treatment response in clinical trials of neurological disorders, offering the possibility to reduce the required sample size or to shorten the duration of the trial.

Imaging of odor perception delineates functional disintegration of the limbic circuits in mesial temporal lobe epilepsy.

Metabolic and neuro-receptor abnormalities within the extrafocal limbic circuits are established in mesial temporal lobe epilepsy (MTLE). However, very little is known about how these circuits process external stimuli. We tested whether odor activation can help delineate limbic functional disintegration in MTLE, and measured cerebral blood flow with PET during birhinal smelling of familiar and unfamiliar odors, using smelling of odorless air as the baseline condition. Patients with MTLE (13 left-sided, 10 right-sided) and 21 controls were investigated. In addition to odor activation, the analysis included functional connectivity, using right and left piriform cortex as seed regions. Healthy controls activated the amygdala, piriform, anterior insular, and cingulate cortices on both sides. Smelling of familiar odors engaged, in addition, the right parahippocampus, and the left Brodmann Area (BA) 44, 45, 47. Patients failed to activate the amygdala, piriform and the anterior insular cortex in the epileptogenic hemisphere. Furthermore, those with left MTLE did not activate the left BA 44, 45 and 47 with familiar odors, which they perceived as less familiar than controls. Congruent with the activation data each seed region was in patients functionally disconnected with the contralateral amygdala+piriform+insular cortex. The functional disintegration in patients exceeded the reduced activation, and included the contralateral temporal neocortex, and in subjects with right MTLE also the right orbitofrontal cortex. Imaging of odor perception may be used to delineate functional disintegration of the limbic networks in MTLE. It shows an altered response in several regions, which may underlie some interictal behavioral problems associated with this condition.