[Predisposing and fostering change in addiction]. / Prédisposer et favoriser le changement dans l'addiction.

The model of addiction as a chronic and progressive brain disease has brought its share of progress. Nevertheless, the model reveals its limitation when it comes to remission. We outline here some factors of change that the disease model hinders, and suggest a different way to foster change.

Le modèle de l'addiction comme une maladie cérébrale chronique et progressive a apporté son lot de progrès, mais nous confronte à présent à ses limites en termes de rémission des individus qui en souffrent. Nous exposons ici certains facteurs du changement auxquels cette définition fait obstacle et proposons une manière différente de favoriser le changement.

[Addictions]. / Addictions.

This year, the actuality for addictions in this edition addresses four points. The disease model of addiction is criticized by the cognitive neurosciences which need to consider the agentivity of the persons. Regarding the societal actuality, clinical pharmacology review of cannabidiol presents an update on legal cannabis. The suicidality of excessive gamblers may be prevented specifically. Addiction and first psychotic episodes need an integrated care.

Cette année, l'actualité des addictions pour ce numéro concerne quatre points. Le modèle de la maladie de l'addiction est critiqué par les neurosciences cognitives qui demandent de reconnaître l'agentivité des personnes. Au vu de l'actualité sociétale, une revue pharmacologique clinique du cannabidiol vient mettre à jour nos connaissances sur le cannabis légal. La suicidalité des joueurs excessifs peut faire l'objet de prévention spécifique. L'addiction et le premier épisode psychotique nécessitent une prise en charge intégrée.

[Addictions]. / Addictions.

In 2016, the actuality for addictions in this edition addresses four points. Social neurosciences of addiction are of great importance regarding the vulnerabilities for addiction and for the recovery. Deep brain stimulation is emerging in the therapeutic panel coming from the clinical neurosciences for the addictions. Novelties in opioid agonists for the treatment of opiates dependence, with the apparition in the Swiss market of release morphine and of levomethadone. Cannabis and prison, a pilot study for the maintenance of abstinence in prison.

En 2016, l'actualité des addictions pour ce numéro concerne quatre points. Les neurosciences sociales de l'addiction, qui ont une grande importance en termes de vulnérabilité pour l'addiction mais aussi pour le rétablissement. La stimulation cérébrale profonde qui fait son apparition dans l'éventail thérapeutique issu des neurosciences cliniques pour les addictions. Les nouveautés du traitement agoniste opioïde de la dépendance aux opiacés avec l'apparition dans le marché suisse de la morphine retard puis de la lévométhadone. Des algorithmes sont proposés pour orienter le prescripteur. Cannabis et prison, une étude pilote pour le maintien de l'abstinence en prison.

Linking empathy to visuospatial perspective-taking in gambling addiction.

It has been demonstrated that people suffering from substance-related addictions are less empathic than their non-addicted counterparts. Our first aim was to verify if this is also true for behavioral addictions. We hypothesized that problem gamblers are less empathic than healthy controls. Our second aim was to identify a cognitive marker of empathy that could be targeted in cognitive rehabilitation strategies. We propose that a potential cognitive marker of empathy could be visuospatial perspective-taking. Specifically, we hypothesized that visuospatial perspective-taking performances are lower in problem gamblers compared to healthy controls and that these visuospatial performances predict empathy. Thirty-one non-gamblers, 24 healthy gamblers, and 21 problem gamblers performed a visuospatial perspective-taking task before completing the Interpersonal Reactivity Index (IRI; Davis, 1980; Davis, 1983). Problem gamblers had decreased empathy and lower performance at the visuospatial perspective-taking task than non-gamblers and healthy gamblers. Furthermore, we confirmed that visuospatial perspective-taking abilities predict empathy on the IRI dimensions of interpersonal perspective-taking and personal distress. The present study provides new evidence that reduced empathy is not limited to subjects with substance-related addictions; rather, it extends to behavioral addictions. Visuospatial perspective-taking may be a viable cognitive marker for use as a rehabilitation target of empathy.

[Addiction]. / Addictions.

This year, the actuality about addiction is on psychopharmacology, in the controversy about the prescription of baclofene to reduce the craving for alcohol. More results from controlled studies are expected. The development of smartphones to access toe-Health skills is questionable, especially in matterofevaluation of these programs. Despite of encouraging results, open questions are remaining for clinicians, to be compared with clinical practice. Finally, it is necessary to keep in touch with translational neurosciences; in fact, research is showing that populations of addicts present a deficit in matter of empathy. This is the cause of a handicap in the social relationships. At a lower level, a difficulty to take the other's place could be the cause of this deficit at a higher level. Rehabilitation perspectives could come out of this discovery.

[Addiction]. / Addictions.

The news in addiction medicine in 2013 are presented according to the new version of the DSM (DSM-5); new data on cannabinoid, highlight hypotheses on self-medication; a current status about treatment of the addiction via the internet is shown; and new therapeutic perspectives emerge from the knowledge on traumatic antecedents in addictive populations.

Risk perception and emotional coping: a pathway for behavioural addiction?

This article summarizes current concepts of the working memory with regard to its role within emotional coping strategies. In particular, it focuses on the fact that the limited capacity of the working memory to process now-relevant information can be turned into an advantage, when the individual is occupied by dealing with unpleasant emotion. Based on a phenomenon known as dual-task interference (DTI), this emotion can be chased by intense arousal due to clearly identifiable external stressors. Thus, risk perception might be used as a 'DTI inductor' that allows avoidance of unpleasant emotion. Successful mastery of risk adds a highly relevant dopaminergic component to the overall experience. The resulting mechanism of implicit learning may contribute to the development of a behavioural addiction. Besides its putative effects in the development of a behavioural addiction, the use of DTI might be of a more general interest for the clinical practice, especially in the field of psychotherapy.

Progression of auditory discrimination based on neural decoding predicts awakening from coma.

Auditory evoked potentials are informative of intact cortical functions of comatose patients. The integrity of auditory functions evaluated using mismatch negativity paradigms has been associated with their chances of survival. However, because auditory discrimination is assessed at various delays after coma onset, it is still unclear whether this impairment depends on the time of the recording. We hypothesized that impairment in auditory discrimination capabilities is indicative of coma progression, rather than of the comatose state itself and that rudimentary auditory discrimination remains intact during acute stages of coma. We studied 30 post-anoxic comatose patients resuscitated from cardiac arrest and five healthy, age-matched controls. Using a mismatch negativity paradigm, we performed two electroencephalography recordings with a standard 19-channel clinical montage: the first within 24 h after coma onset and under mild therapeutic hypothermia, and the second after 1 day and under normothermic conditions. We analysed electroencephalography responses based on a multivariate decoding algorithm that automatically quantifies neural discrimination at the single patient level. Results showed high average decoding accuracy in discriminating sounds both for control subjects and comatose patients. Importantly, accurate decoding was largely independent of patients' chance of survival. However, the progression of auditory discrimination between the first and second recordings was informative of a patient's chance of survival. A deterioration of auditory discrimination was observed in all non-survivors (equivalent to 100% positive predictive value for survivors). We show, for the first time, evidence of intact auditory processing even in comatose patients who do not survive and that progression of sound discrimination over time is informative of a patient's chance of survival. Tracking auditory discrimination in comatose patients could provide new insight to the chance of awakening in a quantitative and automatic fashion during early stages of coma.

Sleep-deprivation regulates α-2 adrenergic responses of rat hypocretin/orexin neurons.

We recently demonstrated, in rat brain slices, that the usual excitation by noradrenaline (NA) of hypocretin/orexin (hcrt/orx) neurons was changed to an inhibition following sleep deprivation (SD). Here we describe that in control condition (CC), i.e. following 2 hours of natural sleep in the morning, the α(2)-adrenergic receptor (α(2)-AR) agonist, clonidine, had no effect on hcrt/orx neurons, whereas following 2 hours of SD (SDC), it hyperpolarized the neurons by activating G-protein-gated inwardly rectifying potassium (GIRK) channels. Since concentrations of clonidine up to a thousand times (100 µM) higher than those effective in SDC (100 nM), were completely ineffective in CC, a change in the availability of G-proteins is unlikely to explain the difference between the two conditions. To test whether the absence of effect of clonidine in CC could be due to a down-regulation of GIRK channels, we applied baclofen, a GABA(B) agonist known to also activate GIRK channels, and found that it hyperpolarized hcrt/orx neurons in that condition. Moreover, baclofen occluded the response to clonidine in SDC, indicating that absence of effect of clonidine in CC could not be attributed to down-regulation of GIRK channels. We finally tested whether α(2)-ARs were still available at the membrane in CC and found that clonidine could reduce calcium currents, indicating that α(2)-ARs associated with calcium channels remain available in that condition. Taken together, these results suggest that a pool of α(2)-ARs associated with GIRK channels is normally down-regulated (or desensitized) in hcrt/orx neurons to only become available for their inhibition following sleep deprivation.

Learning-induced plasticity in human audition: objects, time, and space.

The human auditory system is comprised of specialized but interacting anatomic and functional pathways encoding object, spatial, and temporal information. We review how learning-induced plasticity manifests along these pathways and to what extent there are common mechanisms subserving such plasticity. A first series of experiments establishes a temporal hierarchy along which sounds of objects are discriminated along basic to fine-grained categorical boundaries and learned representations. A widespread network of temporal and (pre)frontal brain regions contributes to object discrimination via recursive processing. Learning-induced plasticity typically manifested as repetition suppression within a common set of brain regions. A second series considered how the temporal sequence of sound sources is represented. We show that lateralized responsiveness during the initial encoding phase of pairs of auditory spatial stimuli is critical for their accurate ordered perception. Finally, we consider how spatial representations are formed and modified through training-induced learning. A population-based model of spatial processing is supported wherein temporal and parietal structures interact in the encoding of relative and absolute spatial information over the initial ~300 ms post-stimulus onset. Collectively, these data provide insights into the functional organization of human audition and open directions for new developments in targeted diagnostic and neurorehabilitation strategies.

Dynamic calibration of our sense of time.

An accurate sense of time contributes to functions ranging from the perception and anticipation of sensory events to the production of coordinated movements. However, accumulating evidence demonstrates that time perception is subject to strong illusory distortion. In two experiments, we investigated whether the subjective speed of temporal perception is dependent on our visual environment. By presenting human observers with speed-altered movies of a crowded street scene, we modulated performance on subsequent production of "20s" elapsed intervals. Our results indicate that one's visual environment significantly contributes to calibrating our sense of time, independently of any modulation of arousal. This plasticity generates an assay for the integrity of our sense of time and its rehabilitation in clinical pathologies.

Rat hypocretin/orexin neurons are maintained in a depolarized state by TRPC channels.

In a previous study we proposed that the depolarized state of the wake-promoting hypocretin/orexin (hcrt/orx) neurons was independent of synaptic inputs as it persisted in tetrodotoxin and low calcium/high magnesium solutions. Here we show first that these cells are hyperpolarized when external sodium is lowered, suggesting that non-selective cation channels (NSCCs) could be involved. As canonical transient receptor channels (TRPCs) are known to form NSCCs, we looked for TRPCs subunits using single-cell RT-PCR and found that TRPC6 mRNA was detectable in a small minority, TRPC1, TRPC3 and TRPC7 in a majority and TRPC4 and 5 in the vast majority (∼90%) of hcrt/orx neurons. Using intracellular applications of TRPC antibodies against subunits known to form NSCCs, we then found that only TRPC5 antibodies elicited an outward current, together with hyperpolarization and inhibition of the cells. These effects were blocked by co-application of a TRPC5 antigen peptide. Voltage-clamp ramps in the presence or absence of TRPC5 antibodies indicated the presence of a current with a reversal potential close to -15 mV. Application of the non-selective TRPC channel blocker, flufenamic acid, had a similar effect, which could be occluded in cells pre-loaded with TRPC5 antibodies. Finally, using the same TRPC5 antibodies we found that most hcrt/orx cells show immunostaining for the TRPC5 subunit. These results suggest that hcrt/orx neurons are endowed with a constitutively active non-selective cation current which depends on TRPC channels containing the TRPC5 subunit and which is responsible for the depolarized and active state of these cells.

Brain dynamics underlying training-induced improvement in suppressing inappropriate action.

Inhibitory control, a core component of executive functions, refers to our ability to suppress intended or ongoing cognitive or motor processes. Mostly based on Go/NoGo paradigms, a considerable amount of literature reports that inhibitory control of responses to "NoGo" stimuli is mediated by top-down mechanisms manifesting ∼200 ms after stimulus onset within frontoparietal networks. However, whether inhibitory functions in humans can be trained and the supporting neurophysiological mechanisms remain unresolved. We addressed these issues by contrasting auditory evoked potentials (AEPs) to left-lateralized "Go" and right NoGo stimuli recorded at the beginning versus the end of 30 min of active auditory spatial Go/NoGo training, as well as during passive listening of the same stimuli before versus after the training session, generating two separate 2 × 2 within-subject designs. Training improved Go/NoGo proficiency. Response times to Go stimuli decreased. During active training, AEPs to NoGo, but not Go, stimuli modulated topographically with training 61-104 ms after stimulus onset, indicative of changes in the underlying brain network. Source estimations revealed that this modulation followed from decreased activity within left parietal cortices, which in turn predicted the extent of behavioral improvement. During passive listening, in contrast, effects were limited to topographic modulations of AEPs in response to Go stimuli over the 31-81 ms interval, mediated by decreased right anterior temporoparietal activity. We discuss our results in terms of the development of an automatic and bottom-up form of inhibitory control with training and a differential effect of Go/NoGo training during active executive control versus passive listening conditions.

Interhemispheric coupling between the posterior sylvian regions impacts successful auditory temporal order judgment.

Accurate perception of the temporal order of sensory events is a prerequisite in numerous functions ranging from language comprehension to motor coordination. We investigated the spatio-temporal brain dynamics of auditory temporal order judgment (aTOJ) using electrical neuroimaging analyses of auditory evoked potentials (AEPs) recorded while participants completed a near-threshold task requiring spatial discrimination of left-right and right-left sound sequences. AEPs to sound pairs modulated topographically as a function of aTOJ accuracy over the 39-77ms post-stimulus period, indicating the engagement of distinct configurations of brain networks during early auditory processing stages. Source estimations revealed that accurate and inaccurate performance were linked to bilateral posterior sylvian regions activity (PSR). However, activity within left, but not right, PSR predicted behavioral performance suggesting that left PSR activity during early encoding phases of pairs of auditory spatial stimuli appears critical for the perception of their order of occurrence. Correlation analyses of source estimations further revealed that activity between left and right PSR was significantly correlated in the inaccurate but not accurate condition, indicating that aTOJ accuracy depends on the functional decoupling between homotopic PSR areas. These results support a model of temporal order processing wherein behaviorally relevant temporal information--i.e. a temporal 'stamp'--is extracted within the early stages of cortical processes within left PSR but critically modulated by inputs from right PSR. We discuss our results with regard to current models of temporal of temporal order processing, namely gating and latency mechanisms.

[Addiction]. / Dépendances.

The 2009 news in medicine regarding dependence confirm the bio-psycho-social field of addiction medicine and psychiatry. First a statement is made about the risk of cardiac arythmy in opioid substitution treatments. Then a review of the treatment of C hepatitis shows its importance in an addicted population. In the field of cognitive neuroscience, progress has been made in the knowledge of "craving" and of its endophenotypical components. Electronic medias related disorders are on the border of addiction: a case study is exploring this new domain. At last, recent datas are presented on the relationship between cannabis and psychosis.

Plastic brain mechanisms for attaining auditory temporal order judgment proficiency.

Accurate perception of the order of occurrence of sensory information is critical for the building up of coherent representations of the external world from ongoing flows of sensory inputs. While some psychophysical evidence reports that performance on temporal perception can improve, the underlying neural mechanisms remain unresolved. Using electrical neuroimaging analyses of auditory evoked potentials (AEPs), we identified the brain dynamics and mechanism supporting improvements in auditory temporal order judgment (TOJ) during the course of the first vs. latter half of the experiment. Training-induced changes in brain activity were first evident 43-76 ms post stimulus onset and followed from topographic, rather than pure strength, AEP modulations. Improvements in auditory TOJ accuracy thus followed from changes in the configuration of the underlying brain networks during the initial stages of sensory processing. Source estimations revealed an increase in the lateralization of initially bilateral posterior sylvian region (PSR) responses at the beginning of the experiment to left-hemisphere dominance at its end. Further supporting the critical role of left and right PSR in auditory TOJ proficiency, as the experiment progressed, responses in the left and right PSR went from being correlated to un-correlated. These collective findings provide insights on the neurophysiologic mechanism and plasticity of temporal processing of sounds and are consistent with models based on spike timing dependent plasticity.

The wake-promoting hypocretin/orexin neurons change their response to noradrenaline after sleep deprivation.

Sleep deprivation is accompanied by the progressive development of an irresistible need to sleep, a phenomenon whose mechanism has remained elusive. Here, we identified for the first time a reflection of that phenomenon in vitro by showing that, after a short 2 h period of total sleep deprivation, the action of noradrenaline on the wake-promoting hypocretin/orexin neurons changes from an excitation to an inhibition. We propose that such a conspicuous modification of responsiveness should contribute to the growing sleepiness that accompanies sleep deprivation.