Dépendances [Addiction]

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. Les nouveautés en médecine 2009 concernant les dépendances confirment l'étendue du champ bio-psychosocial de la médecine et de la psychiatrie de l'addiction. Tout d'abord un point de situation est fait sur le risque d'arythmie cardiaque dans les traitements de substitution opiacée. Puis une revue de l'actualité du traitement de l'hépatite C dans la toxicodépendance en montre la pertinence. Sur le plan de la recherche plus fondamentale, les neurosciences cognitives progressent dans l'approche de la nature du craving et de ses composantes endophénotypiques. Les troubles liés aux médias électroniques illustrent les frontières de l'addiction : une étude de cas vient en explorer le contenu. Enfin, des données récentes sur les rapports entre cannabis et psychoses sont présentées.

Olfactory and/or visual cues for spatial navigation through ontogeny: olfactory cues enable the use of visual cues

This study analyzed the spatial memory capacities of rats in darkness with visual and/or olfactory cues through ontogeny. Tests were conducted with the homing board, where rats had to find the correct escape hole. Four age groups (24 days, 48 days, 3-6 months, and 12 months) were trained in 3 conditions: (a) 3 identical light cues; (b) 5 different olfactory cues; and (c) both types of cues, followed by removal of the olfactory cues. Results indicate that immature rats first take into account olfactory information but are unable to orient with only the help of discrete visual cues. Olfaction enables the use of visual information by 48-day-old rats. Visual information predominantly supports spatial cognition in adult and 12-month-old rats. Results point out cooperation between vision and olfaction for place navigation during ontogeny in rats.

Delineating Dementia with Lewy Bodies: Can Magnetic Resonance Imaging Help?

As future treatments increasingly target the protein chemistry underlying the different dementias, itbecomes crucially important to distinguish between the dementias during life. Neither specific proteinnor genetic markers are as yet available in clinical practice. However, neuroimaging is an obviouscandidate technique that may yield enhanced diagnostic accuracy when applied to thedementias. The physiopathology and anatomopathology is complex in dementia with Lewy bodies(DLB). Besides the relative sparing of medial temporal lobe structures in DLB in comparison toAlzheimer's disease, no clear signature pattern of cerebral atrophy associated with DLB has beenestablished so far. Among others, one reason may be the difficulty in visualizing the small brainnuclei that are differentially involved among the dementias. While we think that structural magneticresonance imaging neuroimaging should be part of the diagnostic workup of most dementia syndromesdue to its usefulness in the differential diagnosis, its contribution to a positive diagnosis ofDLB is as yet limited. The development of different neuroimaging techniques may help distinguishreliably DLB from other neurodegenerative disorders. However, in order to become accepted as partof standard care, these techniques must still prove their effectiveness under routine conditions suchas those encountered by the general practitioner.

Visual search in spatial neglect studied with a preview paradigm.

Impaired visual search is a hallmark of spatial neglect. When searching for an unique feature (e.g., color) neglect patients often show only slight visual field asymmetries. In contrast, when the target is defined by a combination of features (e.g., color and form) they exhibit a severe deficit of contralesional search. This finding suggests a selective impairment of the serial deployment of spatial attention. Here, we examined this deficit with a preview paradigm. Neglect patients searched for a target defined by the conjunction of shape and color, presented together with varying numbers of distracters. The presentation time was varied such that on some trials participants previewed the target together with same-shape/different-color distracters, for 300 or 600 ms prior to the appearance of additional different-shape/same-color distracters. On the remaining trials the target and all distracters were shown simultaneously. Healthy participants exhibited a serial search strategy only when all items were presented simultaneously, whereas in both preview conditions a pop-out effect was observed. Neglect patients showed a similar pattern when the target was presented in the right hemifield. In contrast, when searching for a target in the left hemifield they showed serial search in the no-preview condition, as well as with a preview of 300 ms, and partly even at 600 ms. A control experiment suggested that the failure to fully benefit from item preview was probably independent of accurate perception of time. Our results, when viewed in the context of existing literature, lead us to conclude that the visual search deficit in neglect reflects two additive factors: a biased representation of attentional priority in favor of ipsilesional information and exaggerated capture of attention by ipsilesional abrupt onsets.

Neuropathy after herniorrhaphy: indication for surgical treatment and outcome.

BACKGROUND: Chronic neuropathy after hernia repair is a neglected problem as very few patients are referred for surgical treatment. The aim of the present study was to assess the outcome of standardized surgical revision for neuropathic pain after hernia repair. METHODS: In a prospective cohort study we evaluated all patients admitted to our tertiary referral center for surgical treatment of persistent neuropathic pain after primary herniorrhaphy between 2001 and 2006. Diagnosis of neuropathic pain was based on clinical findings and a positive Tinel's sign. Postoperative pain was evaluated by a visual analogue scale (VAS) and a pain questionnaire up to 12 months after revision surgery. RESULTS: Forty-three consecutive patients (39 male, median age 35 years) underwent surgical revision, mesh removal, and radical neurectomy. The median operative time was 58 min (range: 45-95 min). Histological examination revealed nerve entrapment, complete transection, or traumatic neuroma in all patients. The ilioinguinal nerve was affected in 35 patients (81%); the iliohypogastric nerve, in 10 patients (23%). Overall pain (median VAS) decreased permanently after surgery within a follow-up period of 12 months (preoperative 74 [range: 53-87] months versus 0 [range: 0-34] months; p<0.0001). CONCLUSIONS: The results of this cohort study suggest that surgical mesh removal with ilioinguinal and iliohypogastric neurectomy is a successful treatment in patients with neuropathic pain after hernia repair.

Oxytocin response to an experimental psychosocial challenge in adults exposed to traumatic experiences during childhood or adolescence.

Long-term implications of the exposure to traumatizing experiences during childhood or adolescence, such as sexual abuse, or cancer, have been documented, namely the subjects' response to an acute stress in adulthood. Several indicators of the stress response have been considered (e.g. cortisol, heart rate). Oxytocin (OT) response to an acute stress of individuals exposed to trauma has not been documented. Eighty subjects (n=26 women who had experienced episodes of child abuse, n=25 men and women healthy survivors of cancer in childhood or adolescence, and 29 controls) have been submitted to a laboratory session involving an experimental stress challenge, the Trier social stress test. Overall, there was a clear OT response to the psychosocial challenge. Subjects having experienced a childhood/adolescence life-threatening illness had higher mean levels of OT than both abused and control subjects. There was a moderate negative relationship between OT and salivary cortisol. It is suggested that an acute stress stimulates OT secretion, and that the exposure to enduring life-threatening experiences in childhood/adolescence has long-lasting consequences regarding the stress system and connected functions, namely the activation of OT secretion. Better knowledge of such long-term implications is important so that to prevent dysregulations of the stress responses, which have been shown to be associated to the individual's mental health.

Physically based walking simulation

Hem realitzat l’estudi de moviments humans i hem buscat la forma de poder crear aquests moviments en temps real sobre entorns digitals de forma que la feina que han de dur a terme els artistes i animadors sigui reduïda. Hem fet un estudi de les diferents tècniques d’animació de personatges que podem trobar actualment en l’industria de l’entreteniment així com les principals línies de recerca, estudiant detingudament la tècnica més utilitzada, la captura de moviments. La captura de moviments permet enregistrar els moviments d’una persona mitjançant sensors òptics, sensors magnètics i vídeo càmeres. Aquesta informació és emmagatzemada en arxius que després podran ser reproduïts per un personatge en temps real en una aplicació digital. Tot moviment enregistrat ha d’estar associat a un personatge, aquest és el procés de rigging, un dels punts que hem treballat ha estat la creació d’un sistema d’associació de l’esquelet amb la malla del personatge de forma semi-automàtica, reduint la feina de l’animador per a realitzar aquest procés. En les aplicacions en temps real com la realitat virtual, cada cop més s’està simulant l’entorn en el que viuen els personatges mitjançant les lleis de Newton, de forma que tot canvi en el moviment d’un cos ve donat per l’aplicació d’una força sobre aquest. La captura de moviments no escala bé amb aquests entorns degut a que no és capaç de crear noves animacions realistes a partir de l’enregistrada que depenguin de l’interacció amb l’entorn. L’objectiu final del nostre treball ha estat realitzar la creació d’animacions a partir de forces tal i com ho fem en la realitat en temps real. Per a això hem introduït un model muscular i un sistema de balanç sobre el personatge de forma que aquest pugui respondre a les interaccions amb l’entorn simulat mitjançant les lleis de Newton de manera realista.

Consequences of sleep deprivation on neurotransmitter receptor expression and function.

Several pieces of evidence suggest that sleep deprivation causes marked alterations in neurotransmitter receptor function in diverse neuronal cell types. To date, this has been studied mainly in wake- and sleep-promoting areas of the brain and in the hippocampus, which is implicated in learning and memory. This article reviews findings linking sleep deprivation to modifications in neurotransmitter receptor function, including changes in receptor subunit expression, ligand affinity and signal transduction mechanisms. We focus on studies using sleep deprivation procedures that control for side-effects such as stress. We classify the changes with respect to their functional consequences on the activity of wake-promoting and/or sleep-promoting systems. We suggest that elucidation of how sleep deprivation affects neurotransmitter receptor function will provide functional insight into the detrimental effects of sleep loss.

Computational quest for understanding the role of astrocyte signaling in synaptic transmission and plasticity.

The complexity of the signaling network that underlies astrocyte-synapse interactions may seem discouraging when tackled from a theoretical perspective. Computational modeling is challenged by the fact that many details remain hitherto unknown and conventional approaches to describe synaptic function are unsuitable to explain experimental observations when astrocytic signaling is taken into account. Supported by experimental evidence is the possibility that astrocytes perform genuine information processing by means of their calcium signaling and are players in the physiological setting of the basal tone of synaptic transmission. Here we consider the plausibility of this scenario from a theoretical perspective, focusing on the modulation of synaptic release probability by the astrocyte and its implications on synaptic plasticity. The analysis of the signaling pathways underlying such modulation refines our notion of tripartite synapse and has profound implications on our understanding of brain function.

Reduction of the hand representation in the ipsilateral primary motor cortex following unilateral section of the corticospinal tract at cervical level in monkeys.

BACKGROUND: After sub-total hemi-section of cervical cord at level C7/C8 in monkeys, the ipsilesional hand exhibited a paralysis for a couple of weeks, followed by incomplete recovery of manual dexterity, reaching a plateau after 40-50 days. Recently, we demonstrated that the level of the plateau was related to the size of the lesion and that progressive plastic changes of the motor map in the contralesional motor cortex, particularly the hand representation, took place following a comparable time course. The goal of the present study was to assess, in three macaque monkeys, whether the hand representation in the ipsilesional primary motor cortex (M1) was also affected by the cervical hemi-section.¦RESULTS: Unexpectedly, based on the minor contribution of the ipsilesional hemisphere to the transected corticospinal (CS) tract, a considerable reduction of the hand representation was also observed in the ipsilesional M1. Mapping control experiments ruled out the possibility that changes of motor maps are due to variability of the intracortical microstimulation mapping technique. The extent of the size reduction of the hand area was nearly as large as in the contralesional hemisphere in two of the three monkeys. In the third monkey, it represented a reduction by a factor of half the change observed in the contralesional hemisphere. Although the hand representation was modified in the ipsilesional hemisphere, such changes were not correlated with a contribution of this hemisphere to the incomplete recovery of the manual dexterity for the hand affected by the lesion, as demonstrated by reversible inactivation experiments (in contrast to the contralesional hemisphere). Moreover, despite the size reduction of M1 hand area in the ipsilesional hemisphere, no deficit of manual dexterity for the hand opposite to the cervical hemi-section was detected.¦CONCLUSION: After cervical hemi-section, the ipsilesional motor cortex exhibited substantial reduction of the hand representation, whose extent did not match the small number of axotomized CS neurons. We hypothesized that the paradoxical reduction of hand representation in the ipsilesional hemisphere is secondary to the changes taking place in the contralesional hemisphere, possibly corresponding to postural adjustments and/or re-establishing a balance between the two hemispheres.

Triiodothyronine exerts a trophic action on rat sensory neuron survival and neurite outgrowth through different pathways.

Apart from several growth factors which play a crucial role in the survival and development of the central and peripheral nervous systems, thyroid hormones can affect different processes involved in the differentiation and maturation of neurons. The present study was initiated to determine whether triiodothyronine (T3) affects the survival and neurite outgrowth of primary sensory neurons in vitro. Dorsal root ganglia (DRG) from 19-day-old embryos or newborn rats were plated in explant or dissociated cell cultures. The effect of T3 on neuron survival was tested, either in mixed DRG cell cultures, where neurons grow with non-neuronal cells, or in neuron-enriched cultures where non-neuronal cells were eliminated at the outset. T3, in physiological concentrations, promoted the growth of neurons in mixed DRG cell cultures as well as in neuron-enriched cultures without added nerve growth factor (NGF). Since neuron survival in neuron-enriched cultures cannot be promoted by endogenous neurotrophic factors synthesized by non-neuronal cells, the increased number of surviving neurons was due to a direct trophic action of T3. Another trophic effect was revealed in this study: T3 sustained the neurite outgrowth of sensory neurons in DRG explants. The stimulatory effect of T3 on nerve fibre outgrowth was considerably reduced when non-neuronal cell proliferation was inhibited by the antimitotic agent cytosine arabinoside, and was completely suppressed when the great majority of non-neuronal cells were eliminated in neuron-enriched cultures. These results indicate that the stimulatory effect of T3 on neurite outgrowth is mediated through non-neuronal cells. It is conceivable that T3 up-regulates Schwann cell expression of a neurotrophic factor, which in turn stimulates axon growth of sensory neurons. Together, these results demonstrate that T3 promotes both survival and neurite outgrowth of primary sensory neurons in DRG cell cultures. The trophic actions of T3 on neuron survival and neurite outgrowth operate under two different pathways.

Electro-cortical modulations and fronto-parietal activity during motor transitions in the elderly

With aging, bimanual movements are performed with increased cerebral activity in frontal and parietal areas. In contrast, motor switching is poorly documented and is expected to engage increasing resources in the elderly. In this study, spontaneous electroencephalographic activity (EEG) was recorded while 39 young participants (YP) and 37 elderly (EP) performed motor transitions from unimanual tapping to symmetric bimanual tapping (= Activation), and opposite (= Inhibition). We measured the delay of switching using the mean and standard deviation of transition time (meanTT and sdTT). Task-related power (TRPow) in alpha frequency band (8-12Hz) was used to measure electro-cortical changes, negative values corresponding to increased cerebral activity. A balance index (BI) was computed between frontal and parietal regions, values non-significantly different from "zero" representing a comparable level of cerebral activity in these regions. The results reveal higher sdTT 1) in EP compared to YP in both transitions, 2) in Activation compared to Inhibition in both groups. TRPow tends to reach greater negative values (p=0.052) in EP compared to YP in both tapping modes and both motor transitions. Furthermore, the results show more negative TRPow 1) in both motor transitions compared to the tapping movements and 2) in frontal region for YP compared to EP during Inhibition only. BI values differ significantly from "zero" for YP in Inhibition only. In conclusion, motor transitions are more variable and tend to be resource-consuming in the elderly. Moreover, the cerebral activity spreading in EP characterized by similar level of activity between frontal and parietal regions suggest reduced capacity to recruit specialized neural mechanisms during motor inhibition.

Roles of mGluR5 in synaptic function and plasticity of the mouse thalamocortical pathway.

The group I metabotropic glutamate receptor 5 (mGluR5) has been implicated in the development of cortical sensory maps. However, its precise roles in the synaptic function and plasticity of thalamocortical (TC) connections remain unknown. Here we first show that in mGluR5 knockout (KO) mice bred onto a C57BL6 background cytoarchitectonic differentiation into barrels is missing, but the representations for large whiskers are identifiable as clusters of TC afferents. The altered dendritic morphology of cortical layer IV spiny stellate neurons in mGluR5 KO mice implicates a role for mGluR5 in the dendritic morphogenesis of excitatory neurons. Next, in vivo single-unit recordings of whisker-evoked activity in mGluR5 KO adults demonstrated a preserved topographical organization of the whisker representation, but a significantly diminished temporal discrimination of center to surround whiskers in the responses of individual neurons. To evaluate synaptic function at TC synapses in mGluR5 KO mice, whole-cell voltage-clamp recording was conducted in acute TC brain slices prepared from postnatal day 4-11 mice. At mGluR5 KO TC synapses, N-methyl-D-aspartate (NMDA) currents decayed faster and synaptic strength was more easily reduced, but more difficult to strengthen by Hebbian-type pairing protocols, despite a normal developmental increase in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated currents and presynaptic function. We have therefore demonstrated that mGluR5 is required for synaptic function/plasticity at TC synapses as barrels are forming, and we propose that these functional alterations at the TC synapse are the basis of the abnormal anatomical and functional development of the somatosensory cortex in the mGluR5 KO mouse.

Connexin 30 sets synaptic strength by controlling astroglial synapse invasion.

Astrocytes play active roles in brain physiology by dynamic interactions with neurons. Connexin 30, one of the two main astroglial gap-junction subunits, is thought to be involved in behavioral and basic cognitive processes. However, the underlying cellular and molecular mechanisms are unknown. We show here in mice that connexin 30 controls hippocampal excitatory synaptic transmission through modulation of astroglial glutamate transport, which directly alters synaptic glutamate levels. Unexpectedly, we found that connexin 30 regulated cell adhesion and migration and that connexin 30 modulation of glutamate transport, occurring independently of its channel function, was mediated by morphological changes controlling insertion of astroglial processes into synaptic clefts. By setting excitatory synaptic strength, connexin 30 plays an important role in long-term synaptic plasticity and in hippocampus-based contextual memory. Taken together, these results establish connexin 30 as a critical regulator of synaptic strength by controlling the synaptic location of astroglial processes.