Lionel Pazart

Pilot study of feasibility of the effect of treatment with tDCS in patients suffering from treatment-resistant depression treated with escitalopram

OBJECTIVE This double-blind, sham-controlled trial investigated the effects of two daily tDCS sessions over a 5-day period in treatment-resistant depression. METHOD Twenty-four treatment-resistant depressed patients received two daily sessions of active or sham anodal tDCS to the left prefrontal cortex (2 mA, 10 sessions over 1 week). Depression severity, psychomotor retardation and cognitive function were assessed. RESULTS Active tDCS was not significantly superior to sham tDCS on the HDRS at week 4, as well as on the MADRS and SRRS scales, and on neuropsychological tests. Response rates were not significantly higher with active tDCS. tDCS was well tolerated, with mild adverse events limited to transient scalp discomfort. CONCLUSION tDCS did not induce clinically relevant antidepressant effect in active and sham stimulation groups. There was no impact on psychomotor and neuropsychological functioning. SIGNIFICANCE tDCS efficacy on specific symptom profiles in pharmacotherapy-resistant depression is limited. The use of optimized stimulation protocol and longer period of follow up may valuably contribute to specify the place of tDCS in treatment-resistant depression.

A case report of daily left prefrontal repetitive transcranial magnetic stimulation (rTMS) as an adjunctive treatment for Alzheimer disease

Department of Clinical Psychiatry, University Hospital of Besancon, France EA 481 Neuroscience, IFR 133, University of Franche-Comt e, Besancon, France Clinical Investigation Center CIC-IT 808 INSERM, University Hospital of Besancon, France Department of Neurology, University Hospital of Besancon, France Memory Center of Research and Resources (MCRR), University Hospital of Besancon, France Rapid-Fr Network (Regional Network for Diagnostic Aid and Management of patients with Cognitive Impairment in the Franche-Comt e geographical area), Besancon, France

Substitute or complement? Defining the relative place of EEG and fMRI in the detection of voluntary brain reactions.

To improve the assessment of awareness in patients with disorders of consciousness, recent protocols using functional Magnetic Resonance Imaging (fMRI) have been developed, and led some specialized coma centers to use this method on a routine basis. Recently, promising results have also been observed with electroencephalography (EEG), a less expensive and widely available technique. However, since the spatiotemporal nature of the recorded signal differs between both EEG and fMRI, the question of whether one method could substitute or should complement the other method is a matter of debate. In this study, we compared the neural processes of two well-known EEG and fMRI mental imagery protocols to define the relative place of each method in the assessment of awareness. A group of 20 healthy volunteers performed both EEG and fMRI command-following and communication tasks. Distinct command following was found with both EEG and fMRI for five subjects, only with fMRI for 12 subjects, and only with EEG for one subject. In the communication task, neither EEG nor fMRI alone gave satisfactory results and no reliable communication could be established in approximately 1/3rd of the participants. If fMRI showed the best performance to detect volitional reactions in mental imagery tasks, our results provide evidence that the use of EEG must not be underestimated since a better detection was found with this method for at least one subject. More than being used as a substitute, EEG should complement fMRI to improve the detection of sign of awareness, and to reduce the risks of misjudgments.

Resting motor threshold changes and clinical response to prefrontal repetitive transcranial magnetic stimulation in depressed patients.

Aims:  Several variables are able to influence the antidepressant effects of repetitive transcranial magnetic stimulation (rTMS), particularly the intensity of stimulation, which is generally expressed according to the resting motor threshold (RMT). The aim of our study was to investigate whether or not RMT changes during the treatment of resistant depression by rTMS and whether these fluctuations could alter treatment outcome.

Cryotherapy decreases synovial Doppler activity and pain in knee arthritis: A randomized-controlled trial

OBJECTIVE To measure and compare the effects of 2 local cryotherapy techniques on synovial power Doppler activity (primary outcome) and pain in non-septic knee arthritis without any concurrent treatment. METHODS 30 patients were randomized (ice: 30min, n=15 or cold CO2: 2min, n=15 both applied twice at 8h interval). Contralateral non-treated arthritic knees were used as paired controls (n=11 and n=10 respectively). The PDUS semi-quantitative score (0-3) and pain visual analogic scale were evaluated before/after each cold application, 2min, 2h, 24h after the first application. PDUS scores were checked in double-blind by 2 ultrasonographists. RESULTS The inter-class effect size of local cryotherapy on the power Doppler score remained significant the day after treatment in local cryotherapy-treated compared to contralateral non-treated knees (Global difference: -1 [95% confidence interval: -1.23; -0.77]; ice: -0.73 [-1.06; -0.4]; CO2: -0.7 [-1.18; -0.22]). Both techniques significantly and to the same extent reduced the power Doppler score and pain visual analogic scale at all evaluation times and globally throughout the 24 hour-study period. No dropout nor adverse event was reported. In multivariate analysis, the Power Doppler score decrease was associated with pain decrease, while pain decrease was associated with the female sex and ice technique. CONCLUSION Local ice and cold CO2 applied twice equally reduced synovial Power Doppler activity and pain over 24h in knee arthritis. These effects remained significant the day after treatment. ClinicalTrials.gov identifier: NCT02573298.

Protocol Design Challenges in the Detection of Awareness in Aware Subjects Using EEG Signals

Recent studies have evidenced serious difficulties in detecting covert awareness with electroencephalography-based techniques both in unresponsive patients and in healthy control subjects. This work reproduces the protocol design in two recent mental imagery studies with a larger group comprising 20 healthy volunteers. The main goal is assessing if modifications in the signal extraction techniques, training-testing/cross-validation routines, and hypotheses evoked in the statistical analysis, can provide solutions to the serious difficulties documented in the literature. The lack of robustness in the results advises for further search of alternative protocols more suitable for machine learning classification and of better performing signal treatment techniques. Specific recommendations are made using the findings in this work.

Evaluation of the clinical benefit of an electromagnetic navigation system for CT-guided interventional radiology procedures in the thoraco-abdominal region compared with conventional CT guidance (CTNAV II): study protocol for a randomised controlled trial

BackgroundInterventional radiology includes a range of minimally invasive image-guided diagnostic and therapeutic procedures that have become routine clinical practice. Each procedure involves a percutaneous needle insertion, often guided using computed tomography (CT) because of its availability and usability. However, procedures remain complicated, in particular when an obstacle must be avoided, meaning that an oblique trajectory is required. Navigation systems track the operator’s instruments, meaning the position and progression of the instruments are visualised in real time on the patient’s images. A novel electromagnetic navigation system for CT-guided interventional procedures (IMACTIS-CT®) has been developed, and a previous clinical trial demonstrated improved needle placement accuracy in navigation-assisted procedures. In the present trial, we are evaluating the clinical benefit of the navigation system during the needle insertion step of CT-guided procedures in the thoraco-abdominal region.Methods/designThis study is designed as an open, multicentre, prospective, randomised, controlled interventional clinical trial and is structured as a standard two-arm, parallel-design, individually randomised trial. A maximum of 500 patients will be enrolled. In the experimental arm (navigation system), the procedures are carried out using navigation assistance, and in the active comparator arm (CT), the procedures are carried out with conventional CT guidance. The randomisation is stratified by centre and by the expected difficulty of the procedure. The primary outcome of the trial is a combined criterion to assess the safety (number of serious adverse events), efficacy (number of targets reached) and performance (number of control scans acquired) of navigation-assisted, CT-guided procedures as evaluated by a blinded radiologist and confirmed by an expert committee in case of discordance. The secondary outcomes are (1) the duration of the procedure, (2) the satisfaction of the operator and (3) the irradiation dose delivered, with (4) subgroup analysis according to the expected difficulty of the procedure, as well as an evaluation of (5) the usability of the device.DiscussionThis trial addresses the lack of published high-level evidence studies in which navigation-assisted CT-guided interventional procedures are evaluated. This trial is important because it addresses the problems associated with conventional CT guidance and is particularly relevant because the number of interventional radiology procedures carried out in routine clinical practice is increasing.Trial registrationClinicalTrials.gov identifier: NCT01896219. Registered on 5 July 2013.

On the difficulty to communicate with fMRI-based protocols used to identify covert awareness

Assessment of awareness in patients with disorders of consciousness such as patients in a vegetative state (unresponsive wakefulness syndrome, UWS) and patients in a minimally conscious state (MCS) remains difficult, with a high rate of misdiagnosis (around 40%). While patients with UWS have no awareness, patients with MCS have partial preservation of conscious awareness. To improve the assessment of awareness in these patients, recent functional neuroimaging protocols have been developed. However, does the complexity of realizing and interpreting these functional magnetic resonance imaging (fMRI) investigation protocols, which are currently carried out by only a few specialist teams, permit generalizable use in clinical routine? In this study, 32 healthy volunteers, by definition perfectly conscious and able to efficiently communicate, performed the protocol proposed by Monti et al. in 2010. Four methods (comprising the method proposed by Monti et al., a mean squared error-based method, a correlation-based method, and a support vector machine-based method) were tested for correctly and accurately interpreting the communication task. Firstly, the different instructions for the localizer and the communication tasks had no effect on activations. Secondly, 25% of participants (8/32) did not provide the expected patterns of activations during fMRI tasks (four for each imagery task). However, this did not necessarily prevent the classification methods from correctly guessing the answers during the communication task. Conversely, these classification methods may fail to detect the correct answers even though participants activated the expected brain areas. None of the four methods produced 100% correct detection during the communication phases. The correlation-based method obtained the best results with an error rate of 4.2%. The results of this study demonstrate that fMRI-based communication paradigms may not be robust enough to reliably detect awareness in all aware patients. There is still a need to develop new statistical and analytical methods before considering their generalization in clinical routine.

Microsensors and image processing for single oocyte qualification: toward multiparametric determination of the best time for fertilization

During intracytoplasmic sperm injection (ICSI) attempts, oocytes reaching metaphase II are microinjected. A morphological examination under a microscope is the usual method for determining oocyte maturity. The level of oocyte maturity is based on the meiotic status (Germinal Vesicle, metaphase I and metaphase II) of the oocytes with respect to their increasing maturity. In this letter, we summarize the studies conducted to analyze cytoplasm maturity using various microsystems and image processing. Optical microsystems are used to measure the transmission spectra and refractive index of the oocytes. We compared the transmission spectra measurements to the transmission electron microscopy results. Karhunen–Loeve transform is also used to evaluate the maturity of the oocytes. To summarize, optical analysis techniques are a minimally invasive technology allowing cytoplasm maturity to be assessed. Oocytes should not only be qualified in terms of GV, MI or MII, but also regarding their temporal evolution over the course of these maturation stages. The ultimate aim of this work is to describe the maturation of the oocytes by a trajectory in a multidimensional space and to determine when would be the best time for successful fertilization.

Don't forget the lyrics! Spatiotemporal dynamics of neural mechanisms spontaneously evoked by gaps of silence in familiar and newly learned songs.

The vast majority of people experience musical imagery, the sensation of reliving a song in absence of any external stimulation. Internal perception of a song can be deliberate and effortful, but also may occur involuntarily and spontaneously. Moreover, musical imagery is also involuntarily used for automatically completing missing parts of music or lyrics from a familiar song. The aim of our study was to explore the onset of musical imagery dynamics that leads to the automatic completion of missing lyrics. High-density electroencephalography was used to record the cerebral activity of twenty healthy volunteers while they were passively listening to unfamiliar songs, very familiar songs, and songs previously listened to for two weeks. Silent gaps inserted into these songs elicited a series of neural activations encompassing perceptual, attentional and cognitive mechanisms (range 100-500ms). Familiarity and learning effects emerged as early as 100ms and lasted 400ms after silence occurred. Although participants reported more easily mentally imagining lyrics in familiar rather than passively learnt songs, the onset of neural mechanisms and the power spectrum underlying musical imagery were similar for both types of songs. This study offers new insights into the musical imagery dynamics evoked by gaps of silence and on the role of familiarity and learning processes in the generation of these dynamics. The automatic and effortless method presented here is a potentially useful tool to understand failure in the familiarity and learning processes of pathological populations.