Changes In Neural Plasticity Research Articles

The Effects of GABAergic Polarity Changes on Episodic Neural Network Activity in Developing Neural Systems.

Early in development, neural systems have primarily excitatory coupling, where even GABAergic synapses are excitatory. Many of these systems exhibit spontaneous episodes of activity that have been characterized through both experimental and computational studies. As development progress the neural system goes through many changes, including synaptic remodeling, intrinsic plasticity in the ion channel expression, and a transformation of GABAergic synapses from excitatory to inhibitory. What effect each of these, and other, changes have on the network behavior is hard to know from experimental studies since they all happen in parallel. One advantage of a computational approach is that one has the ability to study developmental changes in isolation. Here, we examine the effects of GABAergic synapse polarity change on the spontaneous activity of both a mean field and a neural network model that has both glutamatergic and GABAergic coupling, representative of a developing neural network. We find some intuitive behavioral changes as the GABAergic neurons go from excitatory to inhibitory, shared by both models, such as a decrease in the duration of episodes. We also find some paradoxical changes in the activity that are only present in the neural network model. In particular, we find that during early development the inter-episode durations become longer on average, while later in development they become shorter. In addressing this unexpected finding, we uncover a priming effect that is particularly important for a small subset of neurons, called the “intermediate neurons.” We characterize these neurons and demonstrate why they are crucial to episode initiation, and why the paradoxical behavioral change result from priming of these neurons. The study illustrates how even arguably the simplest of developmental changes that occurs in neural systems can present non-intuitive behaviors. It also makes predictions about neural network behavioral changes that occur during development that may be observable even in actual neural systems where these changes are convoluted with changes in synaptic connectivity and intrinsic neural plasticity.

Association of contextual cues with morphine reward increases neural and synaptic plasticity in the ventral hippocampus of rats

Drug addiction is associated with aberrant memory and permanent functional changes in neural circuits. It is known that exposure to drugs like morphine is associated with positive emotional states and reward-related memory. However, the underlying mechanisms in terms of neural plasticity in the ventral hippocampus, a region involved in associative memory and emotional behaviors, are not fully understood. Therefore, we measured adult neurogenesis, dendritic spine density and brain-derived neurotrophic factor (BDNF) and TrkB mRNA expression as parameters for synaptic plasticity in the ventral hippocampus. Male Sprague Dawley rats were subjected to the CPP (conditioned place preference) paradigm and received 10mg/kg morphine. Half of the rats were used to evaluate neurogenesis by immunohistochemical markers Ki67 and doublecortin (DCX). The other half was used for Golgi staining to measure spine density and real-time quantitative reverse transcription-polymerase chain reaction to assess BDNF/TrkB expression levels. We found that morphine-treated rats exhibited more place conditioning as compared with saline-treated rats and animals that were exposed to the CPP without any injections. Locomotor activity did not change significantly. Morphine-induced CPP significantly increased the number of Ki67 and DCX-labeled cells in the ventral dentate gyrus. Additionally, we found increased dendritic spine density in both CA1 and dentate gyrus and an enhancement of BDNF/TrkB mRNA levels in the whole ventral hippocampus. Ki67, DCX and spine density were significantly correlated with CPP scores. In conclusion, we show that morphine-induced reward-related memory is associated with neural and synaptic plasticity changes in the ventral hippocampus. Such neural changes could underlie context-induced drug relapse.

Role of microglia in mechanical allodynia in the anterior cingulate cortex

Plastic changes that increase nociceptive transmission are observed in several brain regions under conditions of chronic pain. Synaptic plasticity in the anterior cingulate cortex (ACC) is particularly associated with neuropathic pain. Glial cells are considered candidates for the modulation of neural plastic changes in the central nervous system. In this study, we aimed to investigate the role of ACC glial cells in the development of neuropathic pain. First, we examined the expression of glial cells in the ACC of nerve-ligated mice. The expression of astrocytes and microglia was increased in the ACC of nerve-ligated mice, which was reversed by intracerebroventricular (i.c.v) treatment with the microglia inhibitor minocycline. Then, we examined the effect of minocycline on mechanical allodynia in nerve-ligated mice. I.c.v. and intra-ACC treatment with minocycline partially inhibited mechanical allodynia in the nerve-ligated mice. The expression of phosphorylated alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluR1 subunit at Ser831, but not at Ser845, was increased in the ACC of the nerve-ligated mice compared to sham-operated mice, which was attenuated by minocycline administration. These results suggest that the activation of microglia in the ACC is involved in the development of hyperalgesia in mice with neuropathic pain.

Modulating phonemic fluency performance in healthy subjects with transcranial magnetic stimulation over the left or right lateral frontal cortex.

A growing body of evidence have suggested that non-invasive brain stimulation techniques, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), can improve the performance of aphasic patients in language tasks. For example, application of inhibitory rTMS or tDCs over the right frontal lobe of dysphasic patients resulted in improved naming abilities. Several studies have also reported that in healthy controls (HC) tDCS application over the left prefrontal cortex (PFC) improve performance in naming and semantic fluency tasks. The aim of this study was to investigate in HC, for the first time, the effects of inhibitory repetitive TMS (rTMS) over left and right lateral frontal cortex (BA 47) on two phonemic fluency tasks (FAS or FPL). 44 right-handed HCs were administered rTMS or sham over the left or right lateral frontal cortex in two separate testing sessions, with a 24h interval, followed by the two phonemic fluency tasks. To account for possible practice effects, an additional 22 HCs were tested on only the phonemic fluency task across two sessions with no stimulation. We found that rTMS-inhibition over the left lateral frontal cortex significantly worsened phonemic fluency performance when compared to sham. In contrast, rTMS-inhibition over the right lateral frontal cortex significantly improved phonemic fluency performance when compared to sham. These results were not accounted for practice effects. We speculated that rTMS over the right lateral frontal cortex may induce plastic neural changes to the left lateral frontal cortex by suppressing interhemispheric inhibitory interactions. This resulted in an increased excitability (disinhibition) of the contralateral unstimulated left lateral frontal cortex, consequently enhancing phonemic fluency performance. Conversely, application of rTMS over the left lateral frontal cortex may induce a temporary, virtual lesion, with effects similar to those reported in left frontal patients.

RTMS Ameliorates PTSD Symptoms in Rats by Enhancing Glutamate Transmission and Synaptic Plasticity in the ACC via the PTEN/Akt Signalling Pathway.

Repetitive transcranial magnetic stimulation (rTMS) is a novel physiological therapy that has been adopted to clinically treat psychiatric disorders. Our previous study indicated the potential therapeutic effect of rTMS on posttraumatic stress disorder (PTSD). However, the exact molecular mechanism is elusive. Currently, using the single prolonged stress (SPS) rat model for PTSD, we investigated the glutamatergic transmission and neural plasticity changes in the anterior cingulate cortex (ACC) after SPS induction and explored the protective effects and mechanism of rTMS treatment. We found that high-frequency rTMS (HrTMS, 15Hz) treatment significantly relieved the impaired glutamatergic receptors in the ACC after SPS treatment by significantly increasing NMDAR and AMPAR expression. Simultaneously, HrTMS blocked inhibited neuronal phosphatase and tensin homologue on chromosome 10 (PTEN)/Akt signalling in the ACC after SPS treatment by decreasing PTEN expression and increasing Akt phosphorylation, which is critically involved in the regulation of memory and synaptic plasticity. The PTEN inhibitors bpV and small interfering RNA and the Akt inhibitor wortmannin were stereotaxically administered to the ACC after SPS treatment to advance the mechanistic study. Analysis by Western blot, double immunofluorescence, Golgi staining and behavioural tests demonstrated that the effects of rTMS on PTEN/Akt activation, glutamatergic receptor expression, neuronal synaptic plasticity and PTSD-related behaviours induced by SPS treatment were enhanced by PTEN inhibition and blocked by Akt inhibition in the ACC. Our study provides convincing evidence for the effectiveness of rTMS treatment on PTSD and suggests that its potential mechanism involves remodelling neuronal synaptic plasticity via the PTEN/Akt signalling pathway.

Neural Plasticity Is Involved in Physiological Sleep, Depressive Sleep Disturbances, and Antidepressant Treatments.

Depression, which is characterized by a pervasive and persistent low mood and anhedonia, greatly impacts patients, their families, and society. The associated and recurring sleep disturbances further reduce patient's quality of life. However, therapeutic sleep deprivation has been regarded as a rapid and robust antidepressant treatment for several decades, which suggests a complicated role of sleep in development of depression. Changes in neural plasticity are observed during physiological sleep, therapeutic sleep deprivation, and depression. This correlation might help us to understand better the mechanism underlying development of depression and the role of sleep. In this review, we first introduce the structure of sleep and the facilitated neural plasticity caused by physiological sleep. Then, we introduce sleep disturbances and changes in plasticity in patients with depression. Finally, the effects and mechanisms of antidepressants and therapeutic sleep deprivation on neural plasticity are discussed.

The Role of Neural Plasticity in Depression: From Hippocampus to Prefrontal Cortex.

Neural plasticity, a fundamental mechanism of neuronal adaptation, is disrupted in depression. The changes in neural plasticity induced by stress and other negative stimuli play a significant role in the onset and development of depression. Antidepressant treatments have also been found to exert their antidepressant effects through regulatory effects on neural plasticity. However, the detailed mechanisms of neural plasticity in depression still remain unclear. Therefore, in this review, we summarize the recent literature to elaborate the possible mechanistic role of neural plasticity in depression. Taken together, these findings may pave the way for future progress in neural plasticity studies.

Drug Addiction and Histone Code Alterations.

Acute and prolonged exposure to drugs of abuse induces changes in gene expression, synaptic function, and neural plasticity in brain regions involved in reward. Numerous genes are involved in this process, and persistent changes in gene expression coincide with epigenetic histone modifications and DNA methylation. Histone modifications are attractive regulatory mechanisms, which can encode complex environmental signals in the genome of postmitotic cells, like neurons. Recently, it has been demonstrated that specific histone modifications are involved in addiction-related gene regulatory mechanisms, by a diverse set of histone-modifying enzymes and readers. These histone modifiers and readers may prove to be valuable pharmacological targets for effective treatments for drug addiction.

Histone deacetylase 5 modulates the effects of social adversity in early life on cocaine-induced behavior

Psychostimulants induce stable changes in neural plasticity and behavior in a transcription-dependent manner. Further, stable cellular changes require transcription that is regulated by epigenetic mechanisms that alter chromatin structure, such as histone acetylation. This mechanism is typically catalyzed by enzymes with histone acetyltransferase or histone deacetylase (HDAC) activity. Class IIa HDACs are notable for their high expression in important regions of the brain reward circuitry and their neural activity-dependent shuttling in and out of the cell nucleus. In particular, HDAC5 has an important modulatory function in cocaine-induced behaviors and social defeat stress-induced effects. Although a mutation in HDAC5 has been shown to cause hypersensitive responses to chronic cocaine use whether this response worsens during chronic early life stress has not been examined yet.In this study, we exposed mouse pups to two different early life stress paradigms (social isolation, ESI, and social threat, EST) to determine whether the heterozygous null mutation in HDAC5 (HDAC5+/−) moderated the effects of exposure to stress in early life on adult cocaine-induced conditioned place preference (CPP). Notably, HDAC5+/− mice that had been exposed to ESI were more susceptible to developing cocaine-induced CPP and more resistant to extinguishing this behavior. The same effect was not observed for HDAC5+/− mice experiencing EST, suggesting that only ESI induces behavioral changes by acting precisely through HDAC5-related biological pathways.Finally, an analysis of c-Fos expression performed to discover the neurobiological substrates that mediated this phenotype, identified the dorsolateral striatum as an important structure that mediates the interaction between HDAC5 mutation and ESI. Our data demonstrate that decreased HDAC5 function is able to exacerbate the long-term behavioral effects of adverse rearing environment in mouse.

Development of a novel virtual reality gait intervention

IntroductionImproving gait speed and kinematics can be a time consuming and tiresome process. We hypothesize that incorporating virtual reality videogame play into variable improvement goals will improve levels of enjoyment and motivation and lead to improved gait performance. PurposeTo develop a feasible, engaging, VR gait intervention for improving gait variables. MethodsCompleting this investigation involved four steps: 1) identify gait variables that could be manipulated to improve gait speed and kinematics using the Microsoft Kinect and free software, 2) identify free internet videogames that could successfully manipulate the chosen gait variables, 3) experimentally evaluate the ability of the videogames and software to manipulate the gait variables, and 4) evaluate the enjoyment and motivation from a small sample of persons without disability. ResultsThe Kinect sensor was able to detect stride length, cadence, and joint angles. FAAST software was able to identify predetermined gait variable thresholds and use the thresholds to play free online videogames. Videogames that involved continuous pressing of a keyboard key were found to be most appropriate for manipulating the gait variables. Five participants without disability evaluated the effectiveness for modifying the gait variables and enjoyment and motivation during play. Participants were able to modify gait variables to permit successful videogame play. Motivation and enjoyment were high. SummaryA clinically feasible and engaging virtual intervention for improving gait speed and kinematics has been developed and initially tested. It may provide an engaging avenue for achieving thousands of repetitions necessary for neural plastic changes and improved gait.

Cervical spine disorders and its association with tinnitus: The “triple” hypothesis

Subjective tinnitus and cervical spine disorders (CSD) are among the most common complaints encountered by physicians. Although the relationship between tinnitus and CSD has attracted great interest during the past several years, the pathogenesis of tinnitus induced by CSD remains unclear. Conceivably, CSD could trigger a somatosensory pathway-induced disinhibition of dorsal cochlear nucleus (DCN) activity in the auditory pathway; furthermore, CSD can cause inner ear blood impairment induced by vertebral arteries hemodynamic alterations and trigeminal irritation. In genetically -predisposed CSD patients with reduced serotoninergic tone, signals from chronically stimulated DCNs could activate specific cortical neuronal networks and plastic neural changes resulting in tinnitus. Therefore, an early specific tailored CSD treatments and/or boosting serotoninergic activity may be required to prevent the creation of ‘tinnitus memory circuits’ in CSD patients.

Increase in PAS-induced neuroplasticity after a treatment course of intranasal ketamine for depression. Report of three cases from a placebo-controlled trial

BackgroundAnimal studies suggest that neural plasticity may play a role in the antidepressant effects of a single ketamine dose. However, the potential effects of repeated ketamine treatments on human neuroplasticity are unknown. MethodsThis pilot RCT study measured plasticity-induced changes before and after a ketamine course, in three treatment-resistant depressed subjects, who were randomized to receive 8 intranasal treatments of 100mg ketamine or 4.5mg midazolam. Mood ratings were performed by a trained blinded rater at baseline and 24h–48h after the ketamine course, using the Montgomery Asberg Depression Rating Scale (MADRS). Neuroplasticity was assessed in the motor cortex using a paired associative stimulation (PAS) paradigm at baseline and 24h–48h after the treatment course. No changes in current psychotropic medication or dosage were permitted for 4weeks prior to trial entry and throughout the trial. ResultsThe subject receiving ketamine, but not those receiving midazolam, presented a marked increase in neural plasticity after the treatment course. However, mood changes were not associated with changes in neural plasticity. LimitationsPilot study with small sample size. Concomitant antidepressant medications taken. Plasticity was tested in the motor cortex only, thus the generalizability of these findings to other brain areas cannot be assumed. ConclusionsThese results suggest that a course of intranasal ketamine may enhance synaptic plasticity in subjects with depression, but this was not associated with antidepressant effects. Further research on this topic is warranted.

Structural brain changes are associated with response of negative symptoms to prefrontal repetitive transcranial magnetic stimulation in patients with schizophrenia.

Impaired neural plasticity may be a core pathophysiological process underlying the symptomatology of schizophrenia. Plasticity-enhancing interventions, including repetitive transcranial magnetic stimulation (rTMS), may improve difficult-to-treat symptoms; however, efficacy in large clinical trials appears limited. The high variability of rTMS-related treatment response may be related to a comparably large variation in the ability to generate plastic neural changes. The aim of the present study was to determine whether negative symptom improvement in schizophrenia patients receiving rTMS to the left dorsolateral prefrontal cortex (DLPFC) was related to rTMS-related brain volume changes. A total of 73 schizophrenia patients with predominant negative symptoms were randomized to an active (n=34) or sham (n=39) 10-Hz rTMS intervention applied 5 days per week for 3 weeks to the left DLPFC. Local brain volume changes measured by deformation-based morphometry were correlated with changes in negative symptom severity using a repeated-measures analysis of covariance design. Volume gains in the left hippocampal, parahippocampal and precuneal cortices predicted negative symptom improvement in the active rTMS group (all r⩽-0.441, all P⩽0.009), but not the sham rTMS group (all r⩽0.211, all P⩾0.198). Further analyses comparing negative symptom responders (⩾20% improvement) and non-responders supported the primary analysis, again only in the active rTMS group (F(9, 207)=2.72, P=0.005, partial η 2=0.106). Heterogeneity in clinical response of negative symptoms in schizophrenia to prefrontal high-frequency rTMS may be related to variability in capacity for structural plasticity, particularly in the left hippocampal region and the precuneus.

Perceptual learning leads to long lasting visual improvement in patients with central vision loss.

Macular Degeneration (MD), a visual disease that produces central vision loss, is one of the main causes of visual disability in western countries. Patients with MD are forced to use a peripheral retinal locus (PRL) as a substitute of the fovea. However, the poor sensitivity of this region renders basic everyday tasks very hard for MD patients. We investigated whether perceptual learning (PL) with lateral masking in the PRL of MD patients, improved their residual visual functions. Observers were trained with two distinct contrast detection tasks: (i) a Yes/No task with no feedback (MD: N = 3; controls: N = 3), and (ii) a temporal two-alternative forced choice task with feedback on incorrect trials (i.e., temporal-2AFC; MD: N = 4; controls: N = 3). Observers had to detect a Gabor patch (target) flanked above and below by two high contrast patches (i.e., lateral masking). Stimulus presentation was monocular with durations varying between 133 and 250 ms. Participants underwent 24- 27 training sessions in total. Both PL procedures produced significant improvements in the trained task and learning transferred to visual acuity. Besides, the amount of transfer was greater for the temporal-2AFC task that induced a significant improvement of the contrast sensitivity for untrained spatial frequencies. Most importantly, follow-up tests on MD patients trained with the temporal-2AFC task showed that PL effects were retained between four and six months, suggesting long-term neural plasticity changes in the visual cortex. The results show for the first time that PL with a lateral masking configuration has strong, non-invasive and long lasting rehabilitative potential to improve residual vision in the PRL of patients with central vision loss.

Long-Term Motor Recovery After Severe Traumatic Brain Injury: Beyond Established Limits.

To report neural plasticity changes after severe traumatic brain injury. Case-control study. Canadian soldier, Captain Trevor Greene survived a severe open-traumatic brain injury during a 2006 combat tour in Afghanistan. Longitudinal follow-up for more than 6 years. Twelve longitudinal functional magnetic imaging (fMRI) examinations were conducted to investigate lower limb activation changes in association with clinical examination. Trevor Greene's lower limb fMRI activation was compared with control fMRI activation of (1) mental imagery of similar movement and (2) matched control subject data. Trevor Greene's motor recovery and corresponding fMRI activation increased significantly over time (F = 32.54, P < .001). Clinical measures of functional recovery correlated strongly with fMRI motor activation changes (r = 0.81, P = .001). By comparison, while Trevor Greene's mental imagery activated similar motor regions, there was no evidence of fMRI activation change over time. While comparable, control motor activation did not change over time and there was no significant mental imagery activation. Motor function recovery can occur beyond 6 years after severe traumatic brain injury, both in neural plasticity and clinical outcome. This demonstrates that continued benefits in physical function due to rehabilitative efforts can be achieved for many years following injury. The finding challenges current practices and assumptions in rehabilitation following traumatic brain injury.

Sleep Drive Is Encoded by Neural Plastic Changes in a Dedicated Circuit

Prolonged wakefulness leads to an increased pressure for sleep, but how this homeostatic drive is generated and subsequently persists is unclear. Here, from a neural circuit screen in Drosophila, we identify a subset of ellipsoid body (EB) neurons whose activation generates sleep drive. Patch-clamp analysis indicates these EB neurons are highly sensitive to sleep loss, switching from spiking toburst-firing modes. Functional imaging and translational profiling experiments reveal that elevated sleep need triggers reversible increases in cytosolic Ca(2+) levels, NMDA receptor expression, and structural markers of synaptic strength, suggesting theseEB neurons undergo "sleep-need"-dependent plasticity. Strikingly, the synaptic plasticity of these EB neurons is both necessary and sufficient for generating sleep drive, indicating that sleep pressure is encoded by plastic changes withinthis circuit. These studies define an integrator circuit for sleep homeostasis and provide a mechanism explaining the generation and persistence of sleep drive.

Sex differences in impulsive and compulsive behaviors: a focus on drug addiction.

Sex differences in inhibition and self-regulation at a behavioral level have been widely described. From an evolutionary point of view, the different selection pressures placed on male and female hominids led them to differ in their behavioral strategies that allowed our species to survive during natural selection processes. These differences reflect changes in neural and structural plasticity that might be the core of sex differences, and of the susceptibility towards one psychiatric condition rather than another. The goal of the present review is to summarize current evidence for such a dichotomy in impulsive and compulsive behavior with a focus on drug addiction. Sex-dependent differences in drug abuse and dependence will be examined in the context of pathophysiological regulation of impulse and motivation by neuromodulators (i.e. gonadal hormones) and neurotransmitters (i.e. dopamine). Advances in the understanding of the sex differences in the capability to control impulses and motivational states is key for the determination of efficacious biologically based intervention and prevention strategies for several neuropsychiatric disorders where loss of impulse control and compulsivity are the core symptoms.

Neuromagnetic correlates of adaptive plasticity across the hand-face border in human primary somatosensory cortex.

It is well established that permanent or transient reduction of somatosensory inputs, following hand deafferentation or anesthesia, induces plastic changes across the hand-face border, supposedly responsible for some altered perceptual phenomena such as tactile sensations being referred from the face to the phantom hand. It is also known that transient increase of hand somatosensory inputs, via repetitive somatosensory stimulation (RSS) at a fingertip, induces local somatosensory discriminative improvement accompanied by cortical representational changes in the primary somatosensory cortex (SI). We recently demonstrated that RSS at the tip of the right index finger induces similar training-independent perceptual learning across the hand-face border, improving somatosensory perception at the lips (Muret D, Dinse HR, Macchione S, Urquizar C, Farnè A, Reilly KT.Curr Biol24: R736-R737, 2014). Whether neural plastic changes across the hand-face border accompany such remote and adaptive perceptual plasticity remains unknown. Here we used magnetoencephalography to investigate the electrophysiological correlates underlying RSS-induced behavioral changes across the hand-face border. The results highlight significant changes in dipole location after RSS both for the stimulated finger and for the lips. These findings reveal plastic changes that cross the hand-face border after an increase, instead of a decrease, in somatosensory inputs.

Réflexion théorique sur la place des mécanismes cognitifs mnésiques et temporels dans l’addiction

IntroductionAddictions can be regarded as cognitive disorders related to neurobiological impairments. On the one hand, some cognitive impairments occur as a result of substance intake and withdrawal upon stopping intake, while, on the other hand, cognitive mechanisms are responsible for initiating and maintaining addiction. In this review, we detail the memory and temporal mechanisms involved in this pathology. MethodologyWe reviewed the literature dedicated to the mechanisms of conditioning association between a substance and a context, and the memory and temporal mechanisms involved in the maintenance of addiction. Cognitive impairments in this context are accompanied by both short-term and long-term neurobiological disorders. ResultsDrug-context conditioning is dependent on learning abilities in rats and humans, and it is the first step towards the development of an addiction. In fact, with the beginning of an addiction, it is the context associated with the substance intake, which determines the reinforcing factors (such as pleasure in the case of drug consumption) for the development of an addiction. Maintenance of addiction is related to the persistence of this association between context and substance. Furthermore, the impulsiveness of patients renders them unable to delay their gratification. Consequently, even if delayed gratifications are more valuable, patients prefer immediate gratification such as substance use. DiscussionThe memory and temporal mechanisms of addiction are central to the initiation and maintenance of drug addiction. They also affect patients’ ability to develop projects for the future. The salience of the memory association between drug and context is accompanied by a decline in autobiographical memories, which become poor and lacking in detail. It is probably these impairments which are responsible for the difficulty that the patients have while investigating their story during psychotherapy. On the other hand, given that even though delayed gratification is greater patients prefer immediate gratification, they have difficulty making plans for the future and constructing their own personality. These cognitive impairments are sustained by neurobiological correlates such as dopamine dysregulation in the short-term and changes in neural plasticity in the cortico-meso-limbic system in the long term. ConclusionWe reviewed full arguments which highlight that addiction is mediated by cognitive mechanisms which are related on the one hand to clinical symptoms and, on the other hand, to neurobiological alterations. According to the literature, memory and time mechanisms seem to be central to the initiation and maintenance of addictive behaviours. More research is needed to improve our knowledge of the cognitive mechanisms of addiction and to develop new tools for treating patients.

Correlations between arm motor behavior and brain function following bilateral arm training after stroke: a systematic review.

Bilateral training (BT) of the upper limb (UL) might enhance recovery of arm function after stroke. To better understand the therapeutic potential of BT, this study aimed to determine the correlation between arm motor behavior and brain structure/function as a result of bilateral arm training poststroke. A systematic review of quantitative studies of BT evaluating both UL motor behavior and neuroplasticity was conducted. Eleven electronic databases were searched. Two reviewers independently selected studies, extracted data and assessed methodological quality, using the Effective Public Health Practice Project (EPHPP) tool. Eight studies comprising 164 participants met the inclusion criteria. Only two studies rated "strong" on the EPHPP tool. Considerable heterogeneity of participants, BT modes, comparator interventions and measures contraindicated pooled outcome analysis. Modes of BT included: in-phase and anti-phase; functional movements involving objects; and movements only. Movements were mechanically coupled, free, auditory-cued, or self-paced. The Fugl-Meyer Assessment (UL section) was used in six of eight studies, however, different subsections were used by different studies. Neural correlates were measured using fMRI and TMS in three and five studies, respectively, using a wide variety of variables. Associations between changes in UL function and neural plasticity were inconsistent and only two studies reported a statistical correlation following BT. No clear pattern of association between UL motor and neural response to BT was apparent from this review, indicating that the neural correlates of motor behavior response to BT after stroke remain unknown. To understand the full therapeutic potential of BT and its different modes, further investigation is required.