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The main objective of this work was to study the impact of repetitive Transcranial Magnetic Stimulation (rTMS) treatment on brain activity in 8 patients with major depressive disorder (MDD) and 10 patients with bipolar disorder (BP). Changes due to rTMS stimulation of the left dorsolateral prefrontal cortex (DLPFC) were investigated considering separately responders and non-responders to therapy in each of both groups. The aim of the research is to determine whether non-responders differ from responders suffered from both diseases, as well as if any change occurred due to rTMS across consecutive rTMS sessions. The graph-theory-based connectivity analysis of non-linearity measure of phase interdependencies-Phase Locking Value (PLV)-was examined from EEG data. The approximately 15-min EEG recordings from each of participants were recorded before and after 1st, 10th, and 20th session, respectively. PLV calculated from data was analyzed using principal graph theory indices (strength and degree) within five physiological frequency bands and in individual channels separately. The impact of rTMS on the EEG connectivity in every group of patients evaluated by PLV was assessed. Each of four groups reacted differently to rTMS treatment. The strength and degree of PLV increased in gamma band in both groups of responders. Moreover, an increase of indices in beta band for BP-responders was observed. While, in MDD-non-responders the indices decreased in gamma band and increased in beta band. Moreover, the index strength was lower in alpha band for BP- non-responders. The rTMS stimulation caused topographically specific changes, i.e., the increase of the activity in the left DLPFC as well as in other brain regions such as right parieto-occipital areas. The analysis of PLV allowed for evaluation of the rTMS impact on the EEG activity in each group of patients. The changes of PLV under stimulation might be a good indicator of response to depression treatment permitting to improve the effectiveness of therapy.

Repetitive transcranial magnetic stimulation (rTMS) modulates brain activity in different ways according to the stimulation parameters. Although the after-effects of rTMS over motor cortex are well documented in healthy individuals, less is known about the stimulation of dorso-lateral prefrontal cortex (DLPFC). Here, we studied in 20 healthy subjects how cortical oscillations are modulated by four different active rTMS protocols (1Hz, 10Hz, continuous and intermittent theta bursts — cTBS and iTBS) of the left DLPFC, and by a sham protocol used as a control condition, by comparing the spectral power of pre- and post-rTMS electroencephalographic (EEG) recordings of 15min duration. EEG spectrum was estimated with the fast Fourier transform (FFT) and partitioned using the common physiological frequency bands: delta (1–4Hz), theta (3.5–7Hz), alpha (7.5–13Hz), low beta (14–22Hz), high beta (22–30Hz) and gamma (30–45Hz). Statistical analyses of EEG changes induced by rTMS were computed with Statistical Parametric Mapping (SPM) for EEG, in every frequency band, at the scalp level and at the cortex level. We found for every active protocol a significant decrease of delta and theta power on left prefrontal electrodes, mainly localised in the left DLPFC. In higher frequency bands (beta and gamma), the decrease of power in the DLPFC was also observed contralaterally. Protocol-specific amplitude effects were found in the prefrontal cortex bilaterally in all frequency bands, but also in parietal and temporal regions in low EEG frequencies. In high frequencies, EEG power in the prefrontal cortex increased after rTMS for 10Hz and iTBS protocols, but this effect did not survive the comparison to Sham responses. Because large delta and theta activity is usually associated with cortical inhibition, observed rTMS-induced EEG changes in low frequencies suggest that rTMS of DLPFC transiently decreases local cortical inhibition. Importantly, local responses take place in association with other unknown mechanisms that modulate inter-hemispheric connectivity between homologous regions, resulting in the increase or decrease of fast activity in each prefrontal lobe, depending on the stimulation protocol. Only decreases of fast activity following active rTMS could be detected as significant when compared to Sham stimulation. •First comparison of EEG after effects between 5 rTMS protocols of left DLPFC•Decrease of EEG power in low frequencies found in the left DLPFC for all protocols•Decrease of EEG power in high frequencies found in the left and right DLPFC

Background One out of three patients with schizophrenia failed to respond adequately to antipsychotics and continue to experience debilitating symptoms such as auditory hallucinations and negative symptoms. The development of additional therapeutic approaches for these persistent symptoms constitutes a major goal for patients. Here, we develop a randomized-controlled trial testing the efficacy of high-frequency transcranial random noise stimulation (hf-tRNS) for the treatment of resistant/persistent symptoms of schizophrenia in patients with various profiles of symptoms, cognitive deficits and illness duration. We also aim to investigate the biological and cognitive effects of hf-tRNS and to identify the predictors of clinical response. Methods In a randomized, double-blind, 2-arm parallel-group, controlled, multicentre study, 144 patients with schizophrenia and persistent symptoms despite the prescription of at least one antipsychotic treatment will be randomly allocated to receive either active ( n = 72) or sham ( n = 72) hf-tRNS. hf-tRNS (100–500 Hz) will be delivered for 20 min with a current intensity of 2 mA and a 1-mA offset twice a day on 5 consecutive weekdays. The anode will be placed over the left dorsolateral prefrontal cortex and the cathode over the left temporoparietal junction. Patients’ symptoms will be assessed prior to hf-tRNS (baseline), after the 10 sessions, and at 1-, 3- and 6-month follow-up. The primary outcome will be the number of responders defined as a reduction of at least 25% from the baseline scores on the Positive and Negative Syndrome Scale (PANSS) after the 10 sessions. Secondary outcomes will include brain activity and connectivity, source monitoring performances, social cognition, other clinical (including auditory hallucinations) and biological variables, and attitude toward treatment. Discussion The results of this trial will constitute a first step toward establishing the usefulness of hf-tRNS in schizophrenia whatever the stage of the illness and the level of treatment resistance. We hypothesize a long-lasting effect of active hf-tRNS on the severity of schizophrenia symptoms as compared to sham. This trial will also have implications for the use of hf-tRNS as a preventive intervention of relapse in patients with schizophrenia. Trial registration ClinicalTrials.gov NCT02744989. Prospectively registered on 20 April 2016

Major depressive disorder is a leading cause of disability worldwide, with treatment-resistant depression (TRD) affecting approximately one-third of patients and leading to increased morbidity and healthcare costs. Electroconvulsive therapy (ECT) remains a key treatment for TRD, but its efficacy is limited, and it is associated with cognitive side effects and delayed symptom relief. Repetitive transcranial magnetic stimulation (rTMS) shares action mechanisms with ECT and has shown potential in enhancing ECT efficacy in a previous trial. The STIMAGNECT 2 trial aims to evaluate whether an rTMS add-on protocol can improve ECT outcomes in TRD patients after 10 ECT sessions. Eighty patients with TRD will be enrolled in a prospective multicentric double-blind randomized controlled trial. All patients will receive a total of 10 ECT sessions. Patients will be randomly assigned to an active or sham rTMS arm. The rTMS protocol (either active or sham) consists of 5 rTMS sessions over 4 days before the beginning of the ECT protocol, with an additional rTMS session the day before each ECT session from the 6th ECT session onward. The main outcome is the response rate following 10 ECT sessions, defined as the proportion of patients achieving a ≥ 50% reduction in their Hamilton Depression Rating Scale (HAMD, 21 items). Secondary outcomes include changes in depression severity (HAMD and QIDS-SR-16) at baseline, during the protocol (Day 4, Day 19, Day 26) and at the end of the protocol, as well as assessment of side effects (adapted UKU), cognitive function (memory, attention, visuospatial abilities, subjective cognitive complaint), autobiographical memory (TEMPau), and ECT session parameters such as seizure characteristics and anesthetic doses. Additionally, potential changes in regional gray matter density, cortical thickness, brain connectivity, and GABA levels will be compared between groups using several magnetic resonance imaging (MRI) sequences (3D, resting-state functional MRI, magnetic resonance spectroscopy). The aim of this trial is to optimize neurostimulation protocols using the synergistic effects of rTMS and ECT in order to improve the treatment of TRD. ClinicalTrials.gov NCT06391723 Id RCB: 2023-A01813-42. The trial was registered on January 30, 2024.

The study assumed that the antisaccade (AS) task is a relevant psychophysical tool to assess (i) short-term neuromodulation of the dorsolateral prefrontal cortex (DLPFC) induced by intermittent theta burst stimulation (iTBS); and (ii) mood change occurring during the course of the treatment. Saccadic inhibition is known to strongly involve the DLPFC, whose neuromodulation with iTBS requires less stimulation time and lower stimulation intensity, as well as results in longer aftereffects than the conventional repetitive transcranial magnetic stimulation (rTMS). Active or sham iTBS was applied every day for 3 weeks over the left DLPFC of 12 drug-resistant bipolar depressed patients. To assess the iTBS-induced short-term neuromodulation, the saccadic task was performed just before (S1) and just after (S2) the iTBS session, the first day of each week. Mood was evaluated through Montgomery and Asberg Depression Rating Scale (MADRS) scores and the difference in scores between the beginning and the end of treatment was correlated with AS performance change between these two periods. As expected, only patients from the active group improved their performance from S1 to S2 and mood improvement was significantly correlated with AS performance improvement. In addition, the AS task also discriminated depressive bipolar patients from healthy control subjects. Therefore, the AS task could be a relevant and useful tool for clinicians to assess if the Transcranial magnetic stimulation (TMS)-induced short-term neuromodulation of the DLPFC occurs as well as a \"trait vs. state\" objective marker of depressive mood disorder.

Images of human erythrocytes from a healthy donor were recorded under differential interference contrast (DIC) microscopy; they were acquired rapidly (~336 Hz) and the intensity of the centermost pixel of each cell was recorded for ~60 s (20,000 values). Various techniques were used to analyze the data, including detrended fluctuation analysis (DFA) and multiscale entropy (MSE); however, power spectrum analysis was deemed the most appropriate for metrifying and comparing results. This analysis was used to compare cells from young and old populations, and after perturbing normal conditions, with changes in temperature, adenosine triphosphate (ATP) concentration (using NaF, an inhibitor of glycolysis, and α-toxin, a pore-forming molecule used to permeabilize red cells to ATP), and water transport rates [using glycerol, and p -chloromercuriphenylsulfonic acid (pCMBS) to inhibit aquaporins, AQPs]. There were measurable differences in the membrane fluctuation characteristics in populations of young and old cells, but there was no significant change in the flickering time series on changing the temperature of an individual cell, by depleting it of ATP, or by competing with the minor water exchange pathway via AQP3 using glycerol. However, pCMBS, which inhibits AQP1, the major water exchange pathway, inhibited flickering in all cells, and yet it was restored by the membrane intercalating species dibutyl phthalate (DBP). We developed a computer model to simulate acquired displacement spectral time courses and to evaluate various methods of data analysis, and showed how the flexibility of the membrane, as defined in the model, affects the flickering time course.

Mathematical modeling is an often used approach in biological science which, given some understanding of a system, is employed as a means of predicting future behavior and quantitative hypothesis testing. However, as our understanding of processes becomes more in depth, the models we use to describe them become correspondingly more complex. There is a paucity of effective methods available for sampling the vast objective surfaces associated with complex multiparameter models while at the same time maintaining the accuracy needed for local evaluation of minima—all in a practical time period. We have developed a series of modifications to the curvilinear gradient method for parameter optimization. We demonstrate the power and efficiency of our routine through fitting of a 22 parameter Markov state model to an electrophysiological recording of a cardiac ion channel. Our method efficiently and accurately locates parameter minima which would not be easily identified using the currently available means. While the computational overhead involved in implementing the curvilinear gradient method may have contributed to resistance to adopting this technique, the performance improvements allowed by our modifications make this an extremely valuable tool in development of models of complex biological systems.

Oscillations of the intracellular concentration of Ca²⁺ in cultured HEK-293 cells, which heterologously expressed the calcium-sensing receptor, were recorded with the fluorophore Fura-2 using fluorescence microscopy. HEK-293 cells are extremely sensitive to small perturbations in extracellular calcium concentrations. Resting cells were attached to cover slips and perifused with saline solution containing physiologically relevant extracellular Ca²⁺ concentrations in the range 0.5-5 mM. Acquired digitized images of the cells showed oscillatory fluctuations in the intracellular Ca²⁺ concentration over the time course, and were processed as a function of the change in Fura-2 excitation ratio and frequency at 12-37°C. Newly developed data processing techniques with wavelet analysis were used to estimate the frequency at which the rectified sinusoidal oscillations occurred; we estimated ~4 min⁻¹ under normal conditions. Temperature variations revealed an Arrhenius relationship in oscillation frequency. A critical Ca²⁺ concentration of ~2 mM was estimated, below which oscillations did not occur. These data were used to develop a kinetic model of the system that was simulated using Mathematica; kinetic parameter values were adjusted to match the experimentally observed oscillations of intracellular Ca²⁺ concentration as a function of extracellular Ca²⁺ concentration, and temperature; and from these, limit cycles were obtained and control coefficients were estimated for all parameters.

In this dissertation, I challenge the presuppositions of certain dualist approaches that result in an impoverished conception of music, in which music is taken to be at once ubiquitous and abstract, contextual and autonomous, and fulfilling both an ordinary and transcendent role in our social lives. I argue for what I call a more immanent approach, in which music is intimately involved in some of the central discoveries and relations we make and explore in life on various levels in the social, cultural, political, aesthetic, and ethical domains. Music's immanence lies in its ability to blur lines and bridge gaps in these realms. As a heuristic framework, this dissertation focuses on the implications of composition, a term given by Jacques Attali to what he believed to be a coming stage with respect to the increasingly changing nature of the relationship between music and society. In Attali's forecast, this change would be largely the result of significant developments in cultural, artistic, and technical production—from small, self-produced concert series and festivals to local and global underground networks of musicians, from sampling and multi-tracking to downloading, file-sharing, and sensor-wearing. In this dissertation, I explore various ways in which Attali's prediction has apparently been fulfilled, especially in light of how our experience and practice of music, as well as our discourses surrounding music, have effected changes in both the roles of the various participants involved in musical cultures and the codes and uses of music they employ.

Locomotion has been shown to impact aspects of visual processing in both humans and animal models. In the current study, we assess the impact of locomotion on the dynamics of binocular rivalry. We presented orthogonal gratings, one contrast-modulating at 0.8 Hz (matching average step frequency) and the other at 3.2 Hz, to participants using a virtual reality headset. We compared two conditions: stationary and walking. We continuously monitored participants’ foot position using tracking devices to measure the step cycle. During the walking condition, participants viewed the rivaling gratings for 60-second trials while walking on a circular path in a virtual reality environment. During the stationary condition, observers viewed the same stimuli and environment while standing still. The task was to continuously indicate the dominant percept via button press using handheld controllers. We found no significant differences between walking and standing for normalized dominance duration distributions, mean normalized dominance distributions, mean alternation rates, or mean fitted frequencies. Although our findings do not align with prior research highlighting distinctions in normalized dominance distributions between walking and standing, our study contributes unique evidence indicating that alternation rates vary across the step cycle. Specifically, we observed that the number of alternations is at its lowest during toe-off phases and reaches its peak at heel strike. This novel insight enhances our understanding of the dynamic nature of alternation patterns throughout the step cycle.