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Motor representations in the human mirror neuron system are tuned to respond to specific observed actions. This ability is widely believed to be influenced by genetic factors, but no study has reported a genetic variant affecting this system so far. One possibility is that genetic variants might interact with visuomotor associative learning to configure the system to respond to novel observed actions. In this perspective, we conducted a candidate gene study on the Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, a genetic variant linked to motor learning in regions of the mirror neuron system, and tested the effect of this polymorphism on motor facilitation and visuomotor associative learning. In a single-pulse TMS study carried on 16 Met (Val/Met and Met/Met) and 16 Val/Val participants selected from a large pool of healthy volunteers, Met participants showed significantly less muscle-specific corticospinal sensitivity during action observation, as well as reduced visuomotor associative learning, compared to Val homozygotes. These results are the first evidence of a genetic variant tuning sensitivity to action observation and bring to light the importance of considering the intricate relation between genetics and associative learning in order to further understand the origin and function of the human mirror neuron system.

The use of non-invasive brain stimulation like repetitive transcranial magnetic stimulation (rTMS) is an increasingly popular set of methods with promising results for the treatment of neurological and psychiatric disorders. Despite great enthusiasm, the impact of non-invasive brain stimulation on its neuronal substrates remains largely unknown. Here we show that rTMS applied over the frontal cortex of awaken mice induces dopamine D2 receptor dependent persistent changes of CDK5 and PSD-95 protein levels specifically within the stimulated brain area. Importantly, these modifications were associated with changes of histone acetylation at the promoter of these genes and prevented by administration of the histone deacetylase inhibitor MS-275. These findings show that, like several other psychoactive treatments, repeated rTMS sessions can exert long-lasting effects on neuronal substrates. This underscores the need of understanding these effects in the development of future clinical applications as well as in the establishment of improved guidelines to use rTMS in non-medical settings.

Background: The application of low-intensity direct current electric fields has been experimentally used in the clinic to treat a number of brain disorders, predominantly using transcranial direct current stimulation approaches. However, the cellular and molecular changes induced by such treatment remain largely unknown. Methods: Here, we tested various intensities of direct current electric fields (0, 25, 50, and 100V/m) in a well-controlled in vitro environment in order to investigate the responses of neurons, microglia, and astrocytes to this type of stimulation. This included morphological assessments of the cells, viability, as well as shape and fiber outgrowth relative to the orientation of the direct current electric field. We also undertook enzyme-linked immunosorbent assays and western immunoblotting to identify which molecular pathways were affected by direct current electric fields. Results: In response to direct current electric field, neurons developed an elongated cell body shape with neurite outgrowth that was associated with a significant increase in growth associated protein-43. Fetal midbrain dopaminergic explants grown in a collagen gel matrix also showed a reorientation of their neurites towards the cathode. BV2 microglial cells adopted distinct morphological changes with an increase in cyclooxygenase-2 expression, but these were dependent on whether they had already been activated with lipopolysaccharide. Finally, astrocytes displayed elongated cell bodies with cellular filopodia that were oriented perpendicularly to the direct current electric field. Conclusion: We show that cells of the central nervous system can respond to direct current electric fields both in terms of their morphological shape and molecular expression of certain proteins, and this in turn can help us to begin understand the mechanisms underlying the clinical benefits of direct current electric field.

Craving is recognized as an important diagnosis criterion for substance use disorders (SUDs) and a predictive factor of relapse. Various methods to study craving exist; however, suppressing craving to successfully promote abstinence remains an unmet clinical need in SUDs. One reason is that social and environmental contexts recalling drug and alcohol consumption in the everyday life of patients suffering from SUDs often initiate craving and provoke relapse. Current behavioral therapies for SUDs use the cue-exposure approach to suppress salience of social and environmental contexts that may induce craving. They facilitate learning and cognitive reinforcement of new behavior and entrain craving suppression in the presence of cues related to drug and alcohol consumption. Unfortunately, craving often overweighs behavioral training especially in real social and environmental contexts with peer pressure encouraging the use of substance, such as parties and bars. In this perspective, virtual reality (VR) is gaining interest in the development of cue-reactivity paradigms and practices new skills in treatment. VR enhances ecological validity of traditional craving-induction measurement. In this review, we discuss results from (1) studies using VR and alternative virtual agents in the induction of craving and (2) studies combining cue-exposure therapy with VR in the promotion of abstinence from drugs and alcohol use. They used virtual environments, displaying alcohol and drugs to SUD patients. Moreover, some environments included avatars. Hence, some studies have focused on the social interactions that are associated with drug-seeking behaviors and peer pressure. Findings indicate that VR can successfully increase craving. Studies combining cue–exposure therapy with virtual environment, however, reported mitigated success so far.

Rehabilitation can improve cognitive deficits observed in patients with traumatic brain injury (TBI). However, despite rehabilitation, the ability of making a choice often remains impaired. Risk taking is a daily activity involving numerous cognitive processes subserved by a complex neural network. In this work we investigated risk taking using the Balloon Analogue Risk Task (BART) in patients with acute TBI and healthy controls. We hypothesized that individuals with TBI will take less risk at the BART as compared to healthy individuals. We also predicted that within the TBI group factors such as the number of days since the injury, severity of the injury, and sites of the lesion will play a role in risk taking as assessed with the BART. Main findings revealed that participants with TBI displayed abnormally cautious risk taking at the BART as compared to healthy subjects. Moreover, healthy individuals showed increased risk taking throughout the task which is in line with previous work. However, individuals with TBI did not show this increased risk taking during the task. We also investigated the influence of three patients’ characteristics on their performance at the BART: Number of days post injury, Severity of the head injury, and Status of the frontal lobe. Results indicate that performance at the BART was influenced by the number of days post injury and the status of the frontal lobe, but not by the severity of the head injury. Reported findings are encouraging for risk taking seems to naturally improve with time postinjury. They support the need of conducting longitudinal prospective studies to ultimately identify impaired and intact cognitive skills that should be trained postinjury.

Despite numerous revisions and reformulations, dopamine (DA) hypothesis of schizophrenia remains a pivotal neurochemical hypothesis of this illness. The aim of this review is to expose and discuss findings from positron emission tomography (PET) or single-photon-emission computed tomography (SPECT) studies investigating DA function in the striatum of medicated, drug-naïve or drug-free patients with schizophrenia and in individuals at risk compared with healthy volunteers. DA function was studied at several levels: i) at a presynaptic level where neuroimaging studies investigating DOPA uptake capacity clearly show an increase of DA synthesis in patients with schizophrenia; ii) at a synaptic level where neuroimaging studies investigating dopamine transporter availability (DAT) does not bring any evidence of dysfunction; iii) and finally, neuroimaging studies investigating DA receptor density show a mild increase of D2 receptor density in basic condition and, an hyperreactivity of DA system in dynamic condition. These results are discussed regarding laterality, sub-regions of striatum and implications for the at-risk population. Striatal DA abnormalities are now clearly demonstrated in patients with schizophrenia and at risk population and could constitute an endophenotype of schizophrenia. Subtle sub-clinical striatal DA abnormalities in at risk population could be a biomarker of transition from a vulnerability state to the expression of frank psychosis.

For ages, we have been looking for ways to enhance our physical and cognitive capacities in order to augment our security. One potential way to enhance our capacities may be to externally stimulate the brain. Methods of non-invasive brain stimulation (NIBS), such as repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (tES), have been recently developed to modulate brain activity. Both techniques are relatively safe and can transiently modify motor and cognitive functions outlasting the stimulation period. The purpose of this paper is to review data suggesting that NIBS can enhance motor and cognitive performance in healthy volunteers. We frame these findings in the context of whether they may serve security purposes. Specifically, we review studies reporting that NIBS induces paradoxical facilitation in motor (precision, speed, strength, acceleration endurance, and execution of daily motor task) and cognitive functions (attention, impulsive behavior, risk-taking, working memory, planning, and deceptive capacities). Although transferability and meaningfulness of these NIBS-induced paradoxical facilitations into real-life situations are not clear yet, NIBS may contribute at improving training of motor and cognitive functions relevant for military, civil, and forensic security services. This is an enthusiastic perspective that also calls for fair and open debates on the ethics of using NIBS in healthy individuals to enhance normal functions.

Deceptive abilities have long been studied in relation to personality traits. More recently, studies explored the neural substrates associated with deceptive skills suggesting a critical role of the prefrontal cortex. Here we investigated whether non-invasive brain stimulation over the dorsolateral prefrontal cortex (DLPFC) could modulate generation of untruthful responses about subject’s personal life across contexts (i.e., deceiving on guilt-free questions on daily activities; generating previously memorized lies about past experience; and producing spontaneous lies about past experience), as well as across modality responses (verbal and motor responses). Results reveal that real, but not sham, transcranial direct current stimulation (tDCS) over the DLPFC can reduce response latency for untruthful over truthful answers across contexts and modality responses. Also, contexts of lies seem to incur a different hemispheric laterality. These findings add up to previous studies demonstrating that it is possible to modulate some processes involved in generation of untruthful answers by applying non-invasive brain stimulation over the DLPFC and extend these findings by showing a differential hemispheric contribution of DLPFCs according to contexts.

Patients suffering from various neurological and psychiatric disorders show different levels of facial emotion recognition (FER) impairment, sometimes from the early phases of the disease. Investigating the relative severity of deficits in FER across different clinical and high-risk populations has potential implications for the diagnosis and treatment of these diseases, and could also allow us to understand the neurobiological mechanisms of emotion perception itself. To investigate the role of the dopaminergic system and of the frontotemporal network in FER, we reanalyzed and compared data from four of our previous studies investigating FER performance in patients with frontotemporal dysfunctions and/or dopaminergic system abnormalities at different stages. The performance of patients was compared to the performance obtained by a specific group of matched healthy controls using Cohen’s d effect size. We thus compared emotion and gender recognition in patients with frontotemporal dementia (FTD), amnestic mild cognitive impairment (aMCI), Alzheimer’s disease (AD) at the mild dementia stage, major depressive disorder, Parkinson’s disease treated by l-DOPA (PD-ON) or not (PD-OFF), remitted schizophrenia (SCZ-rem), first-episode schizophrenia treated by antipsychotic medication (SCZ-ON), and drug-naïve first-episode schizophrenia (SCZ-OFF), as well as in unaffected siblings of patients with schizophrenia (SIB). The analyses revealed a pattern of differential impairment of emotion (but not gender) recognition across pathological conditions. On the one hand, dopaminergic medication seems not to modify the moderate deficits observed in SCZ and PD groups (ON vs. OFF), suggesting that the deficit is independent from the dopaminergic system. On the other hand, the observed increase in effect size of the deficit among the aMCI, AD, and FTD groups (and also among the SIB and SCZ-rem groups) suggests that the deficit is dependent on neurodegeneration of the frontotemporal neural networks. Our transnosographic approach combining clinical and high-risk populations with the impact of medication provides new information on the trajectory of impaired emotion perception in neuropsychiatric conditions, and on the role of the dopaminergic system and the frontotemporal network in emotion perception.

Background: The two human cerebral hemispheres are continuously interacting, through excitatory and inhibitory influences and one critical structure subserving this interhemispheric balance is the corpus callosum. Interhemispheric neurophysiological abnormalities and intrahemispheric behavioral impairments have been reported in individuals lacking the corpus callosum. The aim of this study was to examine intrahemispheric neurophysiological function in primary motor cortex devoid of callosal projections. Methods: Intracortical excitatory and inhibitory systems were tested in three individuals with complete agenesis of the corpus callosum and sixteen healthy individuals. These systems were assessed using transcranial magnetic stimulation (TMS) protocols: motor threshold at rest, paired-pulse curve, and cortical silent period. Results: TMS revealed no difference between the patient and control groups on the motor threshold measure, as well as intracortical facilitation and intracortical inhibition systems as tested by paired stimulation. However, intrahemispheric inhibitory function was found to be abnormal in participants without callosal projections, as the cortical silent period duration was significantly increased in the patient group. Conclusion: These data suggest that in addition to previously reported impaired interhemispheric function, patients lacking the entire corpus callosum also display abnormal intrahemispheric excitability of the primary motor cortex.