Bilateral Transcranial Magnetic Stimulation of the Prefrontal Cortex Reduces Cocaine Intake: A Pilot Study

Background: Chronic cocaine consumption is associated with a decrease in mesolim- bic dopamine transmission that maintains drug intake. transcranial magnetic stimulation (TMS) is gaining reliability, a useful therapeutic tool in drug addiction, since it can modu- late cortico-limbic activity resulting in reduction of drug craving. Aims: In the present study, we investigated the therapeutic effect of bilateral TMS of prefrontal cortex (PFC) in reducing cocaine intake, in a sample of treatment-seeking patients with current cocaine use disorder (DSM-V). Methods: Ten cocaine addicts (DSM-V) were randomly assigned to the active or sham stimulation protocol in a double-blind experimental design. Twelve repetitive TMS (rTMS) sessions were administered three times a week for 4 weeks at 100% of motor threshold, over bilateral PFC. Cocaine intake (ng/mg) was assessed by hair analysis at baseline (before treatment, T0), after 1 month (end of treatment, T1), 3 (T2), and 6 (T3) months later. All subjects received psychological support weekly. Results: The two-way ANOVA for repeated measures did not show a signi cant effect of the interaction between time and treatment (F4,32 = 0.35; p = 0.87). Despite that result indicated no difference in the effect of the two conditions (active vs. sham) along time, a decreasing trend in cocaine consumption in active TMS group (F3,23 = 3.42; p = 0.04) vs. sham (F3,15 = 1.88; p = 0.20) was observed when we performed exploratory analysis with time as factor. Indeed, Post hoc comparisons showed a signi cant reduction in the amount of cocaine detected from the onset to 3 months later (T0–T2; p = 0.02) and to the end of treatment (T0–T3; p = 0.01) in addicts from the active group. Conclusion: Bilateral rTMS of PFC at 10 Hz did not show a signi cant effect on cocaine intake compared to sham. However, a long-term reduction on cocaine intake in active TMS-treated patients was observed when we considered the time as factor. Further studies are required to con rm these encouraging but preliminary ndings, in order to consolidate rTMS as a valid tool to treat cocaine addiction

Type-II Colloidal Quantum Wells: CdSe/CdTe Core/Crown Heteronanoplatelets

Solution-processed quantum wells, also known as colloidal nanoplatelets (NPLs), are emerging as promising materials for colloidal optoelectronics. In this work, we report the synthesis and characterization of CdSe/CdTe core/crown NPLs exhibiting a Type-II electronic structure and Type-II specific optical properties. Here, based on a core-seeded approach, the CdSe/CdTe core/crown NPLs were synthesized with well-controlled CdTe crown coatings. Uniform and epitaxial growth of CdTe crown region was verified by using structural characterization techniques including transmission electron microscopy (TEM) with quantitative EDX analysis and X-ray diffraction (XRD). Also the optical properties were systematically studied in these Type-II NPLs that reveal strongly red-shifted photoluminescence (up to similar to 150 nm) along with 2 orders of magnitude longer fluorescence lifetimes (up to 190 ns) compared to the Type-I NPLs owing to spatially indirect excitons at the Type-II interface between the CdSe core and the CdTe crown regions. Photoluminescence excitation spectroscopy confirms that this strongly red-shifted emission actually arises from the CdSe/CdTe NPLs. In addition, temperature-dependent time-resolved fluorescence spectroscopy was performed to reveal the temperature-dependent fluorescence decay kinetics of the Type-II NPLs exhibiting interesting behavior. Also, water-soluble Type-II NPLs were achieved via ligand exchange of the CdSe/CdTe core/crown NPLs by using 3-mercaptopropionic acid (MPA), which allows for enhanced charge extraction efficiency owing to their shorter chain length and enables high quality film formation by layer-by-layer (LBL) assembly. With all of these appealing properties, the CdSe/CdTe core/crown heterostructures having Type-II electronic structure presented here are highly promising for light-harvesting applications

Relocation of a flow-shop, without interrupting the production : optimization by DEVS modelisation and simulation

International audienceno abstrac

Pilotage proactif des lignes de production kanban par modélisation DEVS et simulation temps réel

International audienceno abstrac

TRANSCRANICAL MAGNETIC STIMULATION IN COCAINE ADDICTION:PRELIMINARY FINDINGS

Drug addiction is a brain disease which leads to profound disturbances in an individual’s behaviour. In spite of the progress made in the understanding of the neurobiological mechanisms underlying addiction, expectations from a therapeutic point of view have not been satisfying. Given the modest efficacy of therapeutic tools available, Transcranial Magnetic Stimulation (TMS) seems to be a promising “non-pharmacologic” aid in various neuropathologies including addiction which is characterized by a decrease of dopaminergic activity (DA). Thus, ‘restoring’ pre-pathology DA activity may yield clinical benefits in addicts. In particular, it has been reported that TMS reduces the craving for cocaine in cocaine addicts. Thus, the main aims of the present project is to apply bilateral dTMS to the Dorso-Lateral Pre-frontal Cortices of cocaine abusers in order to deepen understanding the neural correlates of addiction; to identify optimal parameters of stimulation; and, above all, to evaluate short/long term therapeutic effects of dTMS. Wee applied dTMS in nineteen cocaine abusers (average age: 34,57; F: 2; M: 17) selected on DSM IV criteria and randomly assigned to real/sham stimulation protocols. Fourteen of them are currently included in the study while four abandoned due to personal problems (4 drop-out) and one has been excluded because he did not satisfy inclusion criteria. We assessed the intake of cocaine through self-reports and hair analysis at different times pre- (T0) and post-treatment (T1 T2 T3..). We considered the psycho-social impact of Addiction behaviour by assessing the anxiety (STAY-1; STAY-2 ) and the several dimension of hostility (BDHI ) before and after stimulation (T0, T1,T2,T3.. ). The interim analysis shows that all subjects have reduced intake of cocaine regardless of the frequency (1 Hz n. = 6 or 10 Hz n. = 8) of the stimulation protocol applied (sham condition was administered in six subjects). Six months after treatment (T3) all subjects show a reduction in cocaine intake with no distinction among groups (real vs sham nor 10 vs 1 Hz). More cases are needed in 1 Hz and sham conditions to “balance” the groups. The follow-up data, however, shows a strong persistence of the effect in the real group, and decidedly weaker maintenance in sham group. An analogues trend has been observed also in psychological dimensions. We hypothesize an initial placebo/sham effect which disappears over time in the sham patients group. Nevertheless these preliminary data encourage further investigation to evaluate the potential effects of dTMS in the treatment of cocaine abusers and in the prevention of relapses

D-TMS IN COCAINE ADDICTION: PRELIMINARY FINDINGS

Cocaine addiction is a phatological state characterized by a marked decrease in the levels of D2 receptors and in the amount of Dopamine (DA) released by DA cells [1]. This perturbations lead to neuroadpatations in several other circuits involved in motivation, inhibitory control, and memory which finally determ compulsive-impulsive drug self-administration [2]. Thus ‘restoring’ pre-pathology DA activity may yield clinical benefits [3]. There is a substantial need for therapeutic tools in addictive states, and TMS appears to be a promising “non-pharmacologic” candidate, since it can modulate the DA system and the function of related areas [4] . In the cocaine addict there is a disregulation of the mesolimbic dopaminergic system (AVT, NaC, COF, CCA, CPFvm) which in turn result inhibits [5; 6]. We hypothesize that bilateral TMS application over the Dorsolateral Prefrontal-cortex may ‘indirectly’ stimulate DA physiological activity by increasing DA level in the human brain [7] thereby producing a reduction in cocaine intake. Considering that TMS parameters are pivotal in the resilience of its neural effects, (2) the project aims at identifying stimulation parameters with higher chance to resemble long term effects. Principles [8; 9] • Deep Transcranial Magnetic Stimulation (dTMS) • Depolarization of target neurons • Excitatory Effects Fr > 5Hz • Inhibitory Effects Fr ≤ 1Hz Protocol A double-blind randomized control study • Subject: - 30 Cocaine Addicts (CA) (DSM-IV); - 2 SG CA (Real 10Hz)/CA (Real 1Hz) - 1 CG CA sham dTMS • Treatment: - 12 sessions dTMS: 3 sessions/week, for 4 weeks - Parameters (%): Motor Threshold (MT) 110% - Frequency (Hz): 10 Hz or 1Hz randomly assigned - Duration of Stimulation: 8 minutes - Follow Up (FU): 3/6/12 months. Although preliminary, the data show a trend toward a significant reduction in cocaine intake. At the 2FU (six month after treatment) all treated subjects show a reduction in cocaine intake. More cases are needed in the 1 Hz and SHAM group. Nevertheless further investigation is encouraged by this ad interim analysis. [1] Volkow et al., 2010 Bioessays 32(9):748-755 [2] Volkow et al.,2004 Neurophar 47:3-13 [3] Diana, 2 011 Front Psychi 2:64 [4] Feil et al., 2010 Neurosci&Biobe 35:248-275 [5] Melis et al., 2005 Inter Rev Neurob 63:101-154 [6] Koob et al., 2010Neuropsychoph 35 (1):217-38 [7] Strafella et al., 2003 Brain 126:2609-2615 [8] Miniussi et al., 2011 Psychology Press 1-23 [9] Rossi et al., 2009 Clini Neurophysiol 120 (12):2008-3

D-TMS IN COCAINE ADDICTION: preliminary findings

Cocaine-related disorders are currently among the most devastating mental disease as they leads to profound disturbances in an individual\u2019s behaviour resulting in tremendous economic, social, and moral costs. Imaging studies in human have shown a reduction of dopamine (DA) receptors accompanied by a lesser release of endogenous DA in the ventral striatum (AVT) of cocaine subjects thereby resulting in a \u2018dopamine-impoverished\u2019 brain[1-2]. This perturbations lead to neuroadpatations in several other circuits which are related to motivation, inhibitory control, and memory which finally determ compulsive-impulsive self drug administration[3]. The lasting reduction in physiological activity of the DA system leads to the idea that an increment on its activity, to restore pre-drug levels, may yield significant clinical improvements[2]. There is a substantial need for therapeutic tools in addictive states and TMS appears to be a promising \u2018non-pharmacologic\u2019 candidate, since it can modulate the DA system and the function of related areas[4]. It has been just reported[5] that rTMS over the left dorso-lateral prefrontal cortices (DLPfcx) temporarily reduces the craving for cocaine in cocaine addicts but there are no studies which have investigated the TMS effects in the cocaine intake. Considering that we applied bilateral deep-rTMS to the DLPfcx of cocaine abusers, in order (1) to evaluate the short/long term therapeutic effects of TMS in cocaine intake trough hair analysis during the time line (T0,T1,T2,T3.. ), (2) to identify optimal parameters of stimulation (1HZ/10HZ), (3) to highlight possible correlation between cocaine intake and clinical parameters. 20 cocaine abusers have been recruited selected on the DSM-IV criteria and randomly assigned to real rTMS group (100% of motor threshold, 10 HZ/1 HZ, 5 second per train, 20 trains, 15 seconds of inter-stimulus) or to sham stimulation one. In order to investigate the effect of TMS on cocaine dependence we assessed the cocaine intake trough hair analysis before (T0) and after treatment (T1) and every 3 months for the follow-up data. The interim analysis shows that all subjects have reduced the intake of cocaine regardless of the frequency (10 Hz or sham condition) of the stimulation protocol applied. Six months after the treatment (T2) all treated subjects show a reduction in cocaine intake with no distinction among groups (real vs sham). More cases are needed in 1 Hz and sham conditions to \u201cbalance\u201d the groups. The follow-up data, however, shows a strong persistence of the effect in the real group, and decidedly weaker maintenance in sham. We hypothesize an initial placebo/sham effect which disappears over time in the sham patients group. More cases are needed in 1 hz and sham condition to balance the groups. Nevertheless these preliminary data encourage further investigation to evaluate the potential effects of dTMS in the treatment of cocaine abusers and in the prevention of relapses. References 1 Volkow et al., 2010 Bioessays 32(9):748-755 2 Diana, 2011 Front Psychi 2:64 3 Volkow et al., 2004 Neurophar 47:3-13 4 Feil et al., 2010 Neurosci&Biobe 35:248-275 5 Politi et al., 2008 Am J on Add, Vol.17(4): 345-34

Morphology-induced phonon spectra of CdSe/CdS nanoplatelets: core/shell vs. core–crown

Recently developed two-dimensional colloidal semiconductor nanocrystals, or nanoplatelets (NPLs), extend the palette of solution-processable free-standing 2D nanomaterials of high performance. Growing CdSe and CdS parts subsequently in either side-by-side or stacked manner results in core–crown or core/shell structures, respectively. Both kinds of heterogeneous NPLs find efficient applications and represent interesting materials to study the electronic and lattice excitations and interaction between them under strong one-directional confinement. Here, we investigated by Raman and infrared spectroscopy the phonon spectra and electron–phonon coupling in CdSe/CdS core/shell and core–crown NPLs. A number of distinct spectral features of the two NPL morphologies are observed, which are further modified by tuning the laser excitation energy Eexc between in- and off-resonant conditions. The general difference is the larger number of phonon modes in core/shell NPLs and their spectral shifts with increasing shell thickness, as well as with Eexc. This behaviour is explained by strong mutual influence of the core and shell and formation of combined phonon modes. In the core–crown structure, the CdSe and CdS modes preserve more independent behaviour with only interface modes forming the phonon overtones with phonons of the core.Dieser Beitrag ist aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich

Spectroscopy of Colloidal Semiconductor Core/Shell Nanoplatelets with High Quantum Yield

Free standing two-dimensional materials appear as a novel class of structures. Recently, the first colloidal two-dimensional heterostructures have been synthesized. These core/shell nanoplatelets are the first step toward colloidal quantum wells. Here, we study in detail the spectroscopic properties of this novel generation of colloidal nanoparticles. We show that core/shell CdSe/CdZnS nanoplatelets with 80% quantum yield can be obtained. The emission time trace of single core/shell nanoplatelets exhibits reduced blinking compared to core nanoplatelets with a two level emission time trace. At cryogenic temperatures, these nanoplatelets have a quantum yield close to 100% and a stable emission time trace. A solution of core/shell nanoplatelets has emission spectra with a full width half-maximum close to 20 nm, a value much lower than corresponding spherical or rod-shaped heterostructures. Using single particle spectroscopy, we show that the broadening of the emission spectra upon the shell deposition is not due to dispersity between particles but is related to an intrinsic increased exciton–phonon coupling in the shell. We also demonstrate that optical spectroscopy is a relevant tool to investigate the presence of traps induced by shell deposition. The spectroscopic properties of the core/shell nanoplatelets presented here strongly suggest that this new generation of objects will be an interesting alternative to spherical or rod-shaped nanocrystals